
1: Ophthalmic Surg Lasers Imaging. 2009 Jan-Feb;40(1):68-70.

Acute visual acuity loss following intravitreal bevacizumab for diabetic macular 
edema.

Chen E, Hsu J, Park CH.

Retina Service, Wills Eye Institute, Philadelphia, Pennsylvania, USA.

A 58-year-old woman with non-proliferative diabetic retinopathy presented with
decreased visual acuity from chronic macular edema. She had undergone multiple
treatments previously, including focal laser treatment and intravitreal
triamcinolone acetonide. Within 2 days of treatment with intravitreal
bevacizumab, the patient noted a significant decrease in visual acuity.
Fluorescein angiogram demonstrated an enlargement of the foveal avascular zone
and persistent late leakage following intravitreal bevacizumab; optical coherence
tomography performed before and after treatment revealed persistent cystoid
macular edema. The use of intravitreal bevacizumab in chronic, refractory
diabetic macular edema may cause acute visual acuity loss by disrupting an
already fragile vascular perfusion status, leading to macular ischemia.

Publication Types: 
    Case Reports

PMID: 19205502 [PubMed - indexed for MEDLINE]

2: Ophthalmic Surg Lasers Imaging. 2009 Jan-Feb;40(1):65-7.

Resolution of macular edema in idiopathic juxtafoveal telangiectasis using PDT.

Kotoula MG, Chatzoulis DZ, Karabatsas CH, Tsiloulis A, Tsironi EE.

Department of Ophthalmology, University of Thessaly School of Medicine, Larissa, 
Greece.

A 57-year-old woman was treated by photodynamic therapy for macular edema due to 
idiopathic juxtafoveal telangiectasis (presumed type 1A) without subretinal
neovascularization. Initial visual acuity of the treated eye was 20/200 and it
improved to 20/40 by 3 months after the photodynamic therapy session. Visual
acuity remained stable 32 months after the treatment. Color photographs and
fundus fluorescein angiography before and after photodynamic therapy revealed
regression of hemorrhages, exudates, and fluorescein leakage. Photodynamic
therapy has long-term benefits for the patient with idiopathic juxtafoveal
telangiectasis, presumed type 1A, because it can improve visual acuity and
macular edema.

Publication Types: 
    Case Reports

PMID: 19205501 [PubMed - indexed for MEDLINE]

3: Ophthalmic Surg Lasers Imaging. 2009 Jan-Feb;40(1):6-12.

Vitrectomy alone versus vitrectomy with simultaneous intravitreal injection of
triamcinolone for macular edema associated with branch retinal vein occlusion.

Uemura A, Yamamoto S, Sato E, Sugawara T, Mitamura Y, Mizunoya S.

Department of Ophthalmology and Visual Science, Chiba University Graduate School 
of Medicine, Chiba, Japan.

BACKGROUND AND OBJECTIVE: To evaluate the efficacy of vitrectomy with
simultaneous intravitreal injection of triamcinolone acetonide for macular edema 
associated with branch retinal vein occlusion. PATIENTS AND METHODS: A
retrospective study of 45 eyes with macular edema associated with branch retinal 
vein occlusion. A posterior vitreous detachment was created and the vitreous
cortex was completely removed, after which 23 eyes immediately had an
intravitreal injection of triamcinolone acetonide (triamcinolone acetonide group)
and 22 eyes did not (no triamcinolone acetonide group). Visual acuity,
fluorescein angiograms, and foveal thickness determined by optical coherence
tomography were examined preoperatively and postoperatively. RESULTS: Mean
postoperative visual acuity at 12 months was significantly better than the
preoperative visual acuity in both groups. The fovea was significantly thinner 1 
month postoperatively in both groups. Foveal thickness gradually decreased until 
12 months in the no triamcinolone acetonide group; however, foveal thickness
increased for 12 months in the triamcinolone acetonide group. A recurrence of
macular edema was more frequent in the triamcinolone acetonide group than in the 
no triamcinolone acetonide group (P = .006). CONCLUSIONS: Because there was no
significant difference in the improvement of best-corrected visual acuity between
the groups 12 months postoperatively, there may be no benefit in the use of
intraoperative intravitreal triamcinolone acetonide.

PMID: 19205489 [PubMed - indexed for MEDLINE]

4: Arch Ophthalmol. 2009 Feb;127(2):193-9.

Serum cystatin C level, kidney disease markers, and incidence of age-related
macular degeneration: the Beaver Dam Eye Study.

Klein R, Knudtson MD, Lee KE, Klein BE.

Department of Ophthalmology and Visual Sciences, University of Wisconsin School
of Medicine and Public Health, 610 N Walnut St, Room 417 WARF, Madison, WI
53726-2336, USA. kleinr@epi.ophth.wisc.edu

OBJECTIVE: To examine the associations of the serum cystatin C level and chronic 
kidney disease with the incidence of age-related macular degeneration (AMD) over 
15 years. METHODS: In this population-based cohort study of 4926 individuals aged
43 to 86 years at baseline, 3779 participated in 1 or more follow-up
examinations. Age-related macular degeneration was determined by grading
photographs of the macula. Individuals were defined as having mild or moderate to
severe chronic kidney disease based on a value of more than 45 mL/min/1.73 m(2)
to 60 mL/min/1.73 m(2) or less and 45 mL/min/1.73 m(2) or less, respectively,
according to the Modification of Diet in Renal Disease Study equation. RESULTS:
While controlling for age and other risk factors, the level of serum cystatin C
at baseline was associated with the incidence of early AMD (odds ratio per log
standard deviation [95% confidence interval], 1.16 [1.01-1.35]) and exudative AMD
(1.42 [1.03-1.96]) but not geographic atrophy (0.89 [0.56-1.41]) or progression
of AMD (1.02 [0.88-1.18]). Mild chronic kidney disease was associated with the
15-year cumulative incidence of early AMD (odds ratio per log standard deviation,
1.36 [95% confidence interval, 1.00-1.86]) but not the incidence of other AMD end
points. CONCLUSION: There is a relationship between the level of serum cystatin C
and chronic kidney disease with the incidence of AMD. The underlying biological
processes remain to be determined.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 19204238 [PubMed - indexed for MEDLINE]

5: Arch Ophthalmol. 2009 Feb;127(2):132-40.

Observational study of the development of diabetic macular edema following
panretinal (scatter) photocoagulation given in 1 or 4 sittings.

Diabetic Retinopathy Clinical Research Network, Brucker AJ, Qin H, Antoszyk AN,
Beck RW, Bressler NM, Browning DJ, Elman MJ, Glassman AR, Gross JG, Kollman C,
Wells JA 3rd.

Collaborators: Browning D, Antoszyk AN, Brooks DR, Cowen MK, Stallings AH, Helms 
JV, Price AK, Murphy HL, Pierce RE, Ruiz KA, George RJ, McOwen MD,
Balasubramaniam UM, Powers ME, McClain D, Clark LM, Davis LM, Braverman JM,
Ciardella AP, Ryman LS, Dixon BF, Stillberger MA, Zapata JD, Rhodes RC, Brown DM,
Elman MJ, Raden RZ, Sloan MD, Butcher TM, Starr J, Salfer-Firestone D, Coffey T, 
Singletary PV, Gore N, Cain T, Sotirakos P, Shabi G, Lazarus HS, Bunch DP, Ridge 
AD, Booth K, Davis LC, Trimble M, Moore J, Fish GE, Wang RC, Arnwine J, Arceneaux
S, Sanchez B, Gray K, Cummings K, Aguado H, Jaramillo D, Gross JG, Fishburne BC, 
Magee MA, Flowers AM, Cummings PW, Gabriel RA, Bland KK, Lovit HK, Mallet CN,
Price RL, Christoff R, Edwards PA, Ober MD, Rock SM, Monk MK, Murphy J, Wilson
DF, Croswell M, Rusinek BA, Schillace LM, Troszak TA, Stern BA, Wells JA, Clark
WL, Gridine MD, Cahill CP, Hickman AB, Spivey R, Kim JE, Han DP, Wirostko WJ,
Alvarez D, Drescher TS, Knapp RJ, Barwick V, Flanders J, Backes DB, Selchert KJ, 
Beringer JR, Keller KL, Chan CK, Salib DM, Lin SG, Nuthi AS, Dickerson ED, Keith 
TL, Sage KE, Andresen TA, Aldana I, Wiskirchen TB, Castillo SU, Warren S, Rollins
K, Huff KM, Chesbrough DJ, Bretz SE, Sharuk GS, Schlossman DK, Kopple A, Stockman
ME, Cavicchi RW, Casazza EL, Fan JT, Rauser ME, Rollins KE, Corliss CJ, Osuna SL,
Kiernan WH, Cloud JD, Milam W, Saldana G, Hampton GR, Spalding SC, Torrisi PF,
Rutledge BK, Grinnell CJ, DiSano FM, Kwasniewski LM, Czajak TC, Capone LA, Corey 
B, Hay PB, Martinez JA, Montesclaros CA, Odean CE, Sabo RA, Garcia CA, McCrary J,
Garibay E, Lessieur EM, Villeda PR, Paz HL, Montoya JP, Nguyen CV, Santisbon E,
Cerda SM, Lopez RA, Ramirez A, Friedman SM, Blackmer KA, Key JS, Carlton S, Fagan
DA, Gregory V, Aaberg TM, Scott S, Markus D, Kronlein S, Lewis S, Shami M, Pusser
P, Tarter CL, Squires L, Wentlandt TF, Hartnett ME, Garg S, Barnhart CJ, Cantrell
D, Esquejo RL, Shields KD, Lyon AT, Kaminski LA, Ackatz LE, O'Donnell LM, Shankle
J, Davidorf FH, Green AM, Perry JG, Chaudhuri CG, Savage SJ, Drouilhet JH, Pelke 
S, Nobler D, Batlle IR, Batlle KA, Williams GM, Parks M, Googe J, McMillan TA,
Anderson NG, Perkins SL, Higdon CT, Hunt C, Whetstone JK, Jacobus M, Moore M,
Blais PA, Cooney MJ, Sorenson JA, Maranan L, Sco M, Agresta EI, Smith CW, DuCoty 
CL, Varadian S, Salinas C, Banalewicz E, Hamel M, Nagle AL, Chen M, Wong KL,
Holland C, Hagin K, Sneath M, Miller R, Beck RW, Glassman AR, Barros J, Dale BB, 
Constantine SR, Dupre SS, Edwards AR, Hutton M, Johnson PA, Kollman C, Lester LA,
Loggins BL, McClellan SL, Murtaugh P, Moke PS, Qin H, Pritchard R, Ramirez H,
Scott E, Stockdale CR, Davis MD, Danis RP, Hubbard L, Reimers J, Vargo P, Moeller
E, Myers D, Daywalt M, Bressler NM, Aiello LP, Everett DF, Miskala PH, Brucker
AJ, Browning D, Chew EY, Danis RP, Haller JA, Aiello LP, Baker CW, Bressler NM,
Bunch DP, Everett DF, Ferris F, Glassman AR, Marcus DM, Anderson G, Carlton S,
Gardner T, Gross JG, Li HK, Price AK, Miskala P, Fong DS, Bressler NM, Aiello LP,
Beck RW, Bhavsar A, Danis RP, Davis MD, Everett DF, Ferris FL, Fish J, Friedman
S, Glassman AR, Lauer A, Brown DM, Browning DJ, Elman MJ, McLead K, Miskala PH,
Grinnell CJ, Connett J, Barnbaum D, Flynn HW Jr, Frank RN, Genuth S, Jampol L,
Wisniewski S, Resnick J.

OBJECTIVE: To compare the effects of single-sitting vs 4-sitting panretinal
photocoagulation (PRP) on macular edema in subjects with severe nonproliferative 
or early proliferative diabetic retinopathy with relatively good visual acuity
and no or mild center-involved macular edema. METHODS: Subjects were treated with
1 sitting or 4 sittings of PRP in a nonrandomized, prospective, multicentered
clinical trial. Main Outcome Measure Central subfield thickness on optical
coherence tomography (OCT). RESULTS: Central subfield thickness was slightly
greater in the 1-sitting group (n = 84) than in the 4-sitting group (n = 71) at
the 3-day (P = .01) and 4-week visits (P = .003). At the 34-week primary outcome 
visit, the slight differences had reversed, with the thickness being slightly
greater in the 4-sitting group than in the 1-sitting group (P = .06). Visual
acuity differences paralleled OCT differences. CONCLUSIONS: Our results suggest
that clinically meaningful differences are unlikely in OCT thickness or visual
acuity following application of PRP in 1 sitting compared with 4 sittings in
subjects in this cohort. More definitive results would require a large randomized
trial. Application to Clinical Practice These results suggest PRP costs to some
patients in terms of travel and lost productivity as well as to eye care
providers could be reduced. TRIAL REGISTRATION: clinicaltrials.gov Identifier:
NCT00687154.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Research Support, N.I.H., Extramural

PMID: 19204228 [PubMed - indexed for MEDLINE]

6: Vasc Health Risk Manag. 2008;4(5):1137-40.

Severe macular edema induced by pioglitazone in a patient with diabetic
retinopathy: a case study.

Oshitari T, Asaumi N, Watanabe M, Kumagai K, Mitamura Y.

Department of Ophthalmology, Kimitsu Central Hospital, Kisarazu City, Chiba,
Japan. tarii@aol.com

We report a case of severe diabetic macular edema (DME) that developed after
pioglitazone was used by a patient with proliferative diabetic retinopathy. A
30-year-old woman with poorly controlled type 2 diabetes mellitus visited our
clinic in 2004. She had moderate pre-proliferative diabetic retinopathy OU.
Because of the rapid progression of the diabetic retinopathy, she received
pan-retinal photocoagulation in both eyes. Two weeks before using pioglitazone,
her visual acuity was 0.9 OD and 0.7 OS. On October 2007, pioglitazone was
prescribed by her internist because of poorly controlled blood glucose level. Two
weeks later, her body weight increased, and her face became edematous. Her visual
acuity decreased to 0.5 OU, and ophthlamoscopy showed severe DME in both eyes.
Two weeks after stopping pioglitazone, her visual acuity improved to 0.8 OD and
0.5 OS, but the DME was still severe in the optical coherence tomographic images.
Then, one half the usual dose (25 mg) of spironolactone, a diuretic, was given
and her macular edema was resolved. Her final visual acuity improved to 0.9 OD
and 0.7 OS. We recommend that when a patient taking pioglitazone complains of
decreased vision, the physician should promptly consult an ophthalmologist.

Publication Types: 
    Case Reports

PMID: 19183764 [PubMed - indexed for MEDLINE]

7: Postgrad Med. 2009 Jan;121(1):136-40.

Current trends in age-related macular degeneration.

Kravitz D, Gariano RF.

Department of Ophthalmology, Stanford University School of Medicine, Palo Alto,
CA 94305, USA.

Age-related macular degeneration is the leading cause of irreversible blindness
in older persons of the developed world. Addressing treatable risk factors
reduces the incidence and progression of this condition. Recent advances in
understanding and treating macular degeneration have dramatically improved the
visual prognosis.

PMID: 19179822 [PubMed - indexed for MEDLINE]

8: Coll Antropol. 2008 Oct;32 Suppl 2:9-10.

Appearance of age related maculopathy after cataract surgery.

Kovacević D, Miljenović T, Njirić S, Mikulicić M, Vojniković B.

Department of Ophthalmology, University Hospital Rijeka, Rijeka, Croatia.
damir.kovacevic@ri.t-com.hr

The pathogenesis of age-related maculopathy (ARM), the most common cause of
visual loss after the age of 60 years, involves a variety of hereditary and
environmental factors. When the cataractous lens is removed and replaced by clear
intraocular lens, a significant increase in ocular transmittance of optical
radiation occurs. The aim of this study was to assess whether cataract surgery in
older persons may increase the risk for development of ARM. This is a
retrospective study. Medical records of 307 patients, aged 43 to 96 years, (163
male and 144 female) were randomly evaluated. They had undergone cataract
extraction (phacoemulsification or extracapsular lens extraction) with clear
intraocular lens implantation from January 2001 to December 2005 at the
Department of Ophthalmology, University Hospital Rijeka. Patients were examined
two weeks after surgery and followed up for at least two years. Based on the
exclusion criteria, only patients without any sign of AMD at the first
postoperative check up were included. A total of 80 patients (26%) showed
development of ARM at the last check up, which was at least 2 years after
surgery. Our results indicate that pseudophakia is a risk factor for development 
of ARM.

PMID: 19140270 [PubMed - indexed for MEDLINE]

9: Coll Antropol. 2008 Oct;32 Suppl 2:3-4.

Development and progression of age-related macular degeneration after cataract
surgery--in the near future it could become a forensic medicine problem.

Vojniković B, Coklo M, Bosnar A.

After testing all types of implanted IOLs with spectrophotometer, author
estimated that filtering of sun light is not successful, leaving open the
possibility of development of AMD after cataract surgery. This is especially
serious problem in implantation of IOLs to children. Until recently, implantation
of intraocular lenses without or with inappropriate UV protection was not
considered a serious problem. Nowadays we know that, especially in children, such
treatment is no longer acceptable and results in AMD. It is only a matter of time
when the first lawsuit will appear on it. We suggest obligatory eye protection
after cataract surgery (aphakic and pseudophakic eyes) with Medical filters
(Yellow-Green: 550-600 nm) and regular ophthalmic controls.

Publication Types: 
    Editorial

PMID: 19140269 [PubMed - indexed for MEDLINE]

10: Arch Ophthalmol. 2009 Jan;127(1):13-21.

Improved vision-related function after ranibizumab vs photodynamic therapy: a
randomized clinical trial.

Bressler NM, Chang TS, Fine JT, Dolan CM, Ward J; Anti-VEGF Antibody for the
Treatment of Predominantly Classic Choroidal Neovascularization in Age-Related
Macular Degeneration (ANCHOR) Research Group.

Department of Ophthalmology, Retina Division, Wilmer Eye Institute, The Johns
Hopkins University School of Medicine, Baltimore, Maryland 21205-2002, USA.
nmboffice@jhmi.edu

OBJECTIVE: To compare patient-reported visual function in those with neovascular 
age-related macular degeneration treated with ranibizumab or verteporfin
photodynamic therapy (PDT). DESIGN: Multicenter, double-masked, phase 3 trial
(ANCHOR). Participants were randomized in a 1:1:1 ratio to receive 0.3 or 0.5 mg 
of intravitreal ranibizumab plus sham verteporfin or sham injections plus active 
verteporfin monthly. The National Eye Institute Visual Function Questionnaire-25 
(NEI VFQ-25) was administered at baseline and 1, 2, 3, 6, 9, 12, 18, and 24
months. MAIN OUTCOME MEASURE: Mean change from baseline in NEI VFQ-25 scores at
12 months. RESULTS: At 12 months, patients treated with ranibizumab (0.3 mg [n = 
137] or 0.5 mg [n = 139]) had mean improvements in NEI VFQ-25 composite scores of
5.9 (95% confidence interval [CI], 3.6 to 8.3) and 8.1 (95% CI, 5.3 to 10.8)
points, respectively; patients treated with PDT (n = 142) had a mean improvement 
of 2.2 points (95% CI, -0.3 to 4.7; vs 0.5 mg of ranibizumab, P < .001; vs 0.3 mg
of ranibizumab, P = .003). At each dose through 24 months, patients treated with 
ranibizumab were more likely to improve in most subscales, including the
prespecified subscales (near activities, distance activities, and vision-specific
dependency). CONCLUSIONS: Patients treated with ranibizumab were more likely to
report clinically meaningful improvements in visual function through 24 months
compared with those treated with verteporfin PDT. Application to Clinical
Practice Ranibizumab treatment in neovascular age-related macular degeneration
can improve patient-reported visual function. Trial Registration
clinicaltrials.gov Identifier: NCT00061594.

Publication Types: 
    Clinical Trial, Phase III
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 19139332 [PubMed - indexed for MEDLINE]

11: Coll Antropol. 2008 Oct;32 Suppl 2:11-4.

Chronic diabetic macular oedema, pars plana vitrectomy or combination of PPV and 
laser?

Synek S, Synkova M.

Department of Ophthalmology and Optometry, Medical Faculty, Masaryk University,
Teaching Hospital St. Anne, Brno, Czech Republic. svatopluk.synek@fnusa.cz

Diabetic cystoid macular oedema (DME) is a common cause of visual acuity (VA)
decrease. Good anatomical results and VA of pars plana vitrectomy (PPV) in cases 
of macular hole internal limiting membrane (ILM) peeling leads to usage of this
technique in DME. A favorable result even in a case without vitreoretinal
traction leads to conclusion that pathogenesis of this disease is different. We
analyzed retrospectively 20 eyes from 20 patients with DME that had undergone PPV
and ILM peeling. Half of them were laser treated 6 months before surgery. All
eyes had an attached posterior hyaloids membrane in the macular region, but
without thickening and without traction. Median duration of DME at the time of
PPV was 18 months (range 12-24 months). The median preoperative best-corrected VA
of 0.4 (range 0.01-1.0), improved to a median postoperative VA of 0.55 (range
0.01-1.0). Ten eyes without preoperative laser coagulation had a median VA
improvement of 77%, while 10 eyes with preoperative macular laser treatment had a
median VA improvement of 14.8%. In all 20 eyes DME was no longer visible on
microscopic examination after a median period of 3 months after PPV. PPV and ILM 
peeling resulted in the resolution of oedema, with an improvement in VA in the
majority of cases. Eyes without preoperative macular photocoagulation had a
significantly higher visual improvement than eyes with preoperative laser
treatment. A randomized controlled prospective trial of PPV versus laser is
needed to determine the role of PPV as a treatment modality for DME.

Publication Types: 
    Clinical Trial
    Comparative Study

PMID: 19137999 [PubMed - indexed for MEDLINE]

12: Coll Antropol. 2008 Oct;32 Suppl 2:5-7.

Intravitreal bevacizumab for the management of age-related macular degeneration.

Kovacević D, Caljkusić-Mance T, Misljenović T, Mikulicić M, Alpeza-Dunato Z.

Department of Ophthalmology, University Hospital Rijeka, Rijeka, Croatia.
damir.kovacevic@ri.t-com.hr

The aim of this study is to report short-term effect of the treatment of "wet"
ARMD (age-related macular degeneration) with intravitreal bevacizumab (Avastin). 
Prospective study included 36 patients (36 eyes) with "wet' form of ARMD. All
patients were over 60 year old (22 female, 14 male). Changes of macula included
minimally classic CNV (choroidal neovascularisation) (24), occult subfoveal CNV
(10) and first stage of cicatrial CNV (2). Bevacizumab 1.25 mg was administered
intravitreally through pars plana using a 27-gauge needle. Patients had no
previous eye treatment. Ophthalmic exam before and after the treatment included: 
Snellen VA (visual acuity) and examination including measurement of IOP
(intraocular pressure), FA (fluorescein angiography) and interview with patients.
After 4-6 weeks 28 (78%) patients had significant improvement of VA. Median VA
improved from 0.083 to 0.200 (p<0.01). Eight patients (22%) had no significant
improvement in VA but three of them reported to see more light. FA showed
complete resolution of macular edema in 6 patients (17%), partially resolved in
23 patients (64%) and no change in 7 patients (19%). No systemic side-effect was 
found. Short-term results suggest that intravitreally administered bevacizumab is
well tolerated treatment for ARMD with very high number of patients showing
improvement in VA.

Publication Types: 
    Clinical Trial

PMID: 19137998 [PubMed - indexed for MEDLINE]

13: PLoS ONE. 2009;4(1):e4160. Epub 2009 Jan 8.

Autophagy and exosomes in the aged retinal pigment epithelium: possible relevance
to drusen formation and age-related macular degeneration.

Wang AL, Lukas TJ, Yuan M, Du N, Tso MO, Neufeld AH.

Department of Ophthalmology, Forsythe Laboratory for the Investigation of the
Aging Retina, Northwestern University School of Medicine, Chicago, Illinois,
United States of America.

Age-related macular degeneration (AMD) is a major cause of loss of central vision
in the elderly. The formation of drusen, an extracellular, amorphous deposit of
material on Bruch's membrane in the macula of the retina, occurs early in the
course of the disease. Although some of the molecular components of drusen are
known, there is no understanding of the cell biology that leads to the formation 
of drusen. We have previously demonstrated increased mitochondrial DNA (mtDNA)
damage and decreased DNA repair enzyme capabilities in the rodent RPE/choroid
with age. In this study, we found that drusen in AMD donor eyes contain markers
for autophagy and exosomes. Furthermore, these markers are also found in the
region of Bruch's membrane in old mice. By in vitro modeling increased mtDNA
damage induced by rotenone, an inhibitor of mitochondrial complex I, in the RPE, 
we found that the phagocytic activity was not altered but that there were: 1)
increased autophagic markers, 2) decreased lysosomal activity, 3) increased
exocytotic activity and 4) release of chemoattractants. Exosomes released by the 
stressed RPE are coated with complement and can bind complement factor H,
mutations of which are associated with AMD. We speculate that increased autophagy
and the release of intracellular proteins via exosomes by the aged RPE may
contribute to the formation of drusen. Molecular and cellular changes in the old 
RPE may underlie susceptibility to genetic mutations that are found in AMD
patients and may be associated with the pathogenesis of AMD in the elderly.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 19129916 [PubMed - indexed for MEDLINE]

14: Ophthalmology. 2009 Jan;116(1):87-93.

Vitreous levels of interleukin-6 and vascular endothelial growth factor in
macular edema with central retinal vein occlusion.

Noma H, Funatsu H, Mimura T, Harino S, Hori S.

Department of Ophthalmology, Yachiyo Medical Center, Tokyo Women's Medical
University, Chiba, Japan. nomahide@tymc.twmu.ac.jp

OBJECTIVE: To investigate whether interleukin (IL)-6 or vascular endothelial
growth factor (VEGF) influences macular edema in patients with central retinal
vein occlusion (CRVO). DESIGN: Retrospective case-control study. PARTICIPANTS:
Twenty-seven patients who had macular edema with CRVO and 16 patients with
nonischemic ocular diseases (control group). METHODS: Retinal ischemia was
evaluated by measuring the area of capillary nonperfusion using fluorescein
angiography and the public domain Scion Image program, and macular edema was
examined by optical coherence tomography. Vitreous fluid samples were obtained at
pars plana vitrectomy. VEGF and IL-6 levels in vitreous fluid and plasma were
determined with enzyme-linked immunosorbent assay kits. MAIN OUTCOME MEASURES:
Vitreous fluid levels of IL-6 and VEGF. RESULTS: The vitreous fluid levels of
VEGF (median: 435 pg/ml) and IL-6 (median: 51.2 pg/ml) were significantly higher 
in the patients with CRVO than in the control group (median: 62.4 pg/ml and 1.07 
pg/ml, respectively; P = 0.0046 and P<0.0001, respectively). The vitreous fluid
level of VEGF was significantly correlated with that of IL-6 (P = 0.0029).
Vitreous fluid levels of both VEGF and IL-6 were significantly higher in patients
with CRVO who had retinal ischemia than in those without ischemia (P<0.0001 and P
= 0.0003, respectively). Vitreous fluid levels of VEGF and IL-6 were also
significantly correlated with the severity of macular edema (P = 0.0014 and P =
0.0047, respectively). CONCLUSIONS: Both IL-6 and VEGF were elevated in the
vitreous fluid of patients with ischemic CRVO and macular edema. VEGF may
increase vascular permeability in patients with macular edema and CRVO, whereas
IL-6 may also contribute by acting together with or via VEGF. FINANCIAL
DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any
materials discussed in this article.

PMID: 19118700 [PubMed - indexed for MEDLINE]

15: Ophthalmology. 2009 Jan;116(1):80-6.

Effect of intravitreal bevacizumab injection on aqueous humor cytokine levels in 
clinically significant macular edema.

Roh MI, Kim HS, Song JH, Lim JB, Kwon OW.

The Institute of Vision Research, Department of Ophthalmology, Yonsei University 
College of Medicine, Seoul, Korea.

PURPOSE: To determine the effect of intravitreal bevacizumab (Avastin, Genentech,
Inc., San Francisco, CA) injection on aqueous humor cytokine levels in clinically
significant macular edema (CSME). DESIGN: Retrospective, comparative study.
PARTICIPANTS: Seventeen eyes undergoing intravitreal injection for CSME and 11
eyes undergoing cataract surgery as negative controls. Nine patients with CSME
were naïve to intravitreal bevacizumab injection (CSME group 1), and 8 patients
previously received 1 intravitreal bevacizumab injection at a mean of 9.6+/-1.4
weeks earlier (CSME group 2). METHODS: Aqueous humor samples were collected
before performing intravitreal injection in the CSME group and during cataract
surgery in the control group. Aqueous cytokine levels were determined by
immunoassay using multianalyte biochip array technology. MAIN OUTCOME MEASURES:
The concentration of cytokines in the aqueous humor was recorded as a mean (+/-
standard deviation) in CSME groups 1 and 2 and the control group. Correlations of
aqueous humor cytokine levels were evaluated. RESULTS: Significantly higher
levels of interleukin (IL)-6, IL-8, and monocyte chemoattractant protein (MCP)-1 
were noted in patients with CSME compared with controls. Although higher vascular
endothelial growth factor (VEGF) levels were noted in CSME group 1 (P = 0.001), a
lower level of VEGF was noted after intravitreal bevacizumab injection in CSME
group 2 (P = 0.004) compared with the control group. VEGF levels were also lower 
in CSME group 2 compared with CSME group 1 (P = 0.001). In CSME group 2, a
significant negative correlation was observed between VEGF and IL-6 (rho =
-0.833, P = 0.01) and VEGF and MCP-1 (rho = -0.736, P = 0.037). CONCLUSIONS:
Significantly higher levels of IL-6, IL-8, VEGF, and MCP-1 were noted in the
aqueous humor of CSME. However, recurrence of macular edema was noted with
significantly lower concentrations of VEGF after a single intravitreal injection 
of bevacizumab. This suggests the potential importance of IL-6 and MCP-1 in the
pathogenesis of CSME. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary 
or commercial interest in any materials discussed in this article.

Publication Types: 
    Comparative Study

PMID: 19118699 [PubMed - indexed for MEDLINE]

16: Ophthalmology. 2009 Jan;116(1):73-9.

Association of vitreous inflammatory factors with diabetic macular edema.

Funatsu H, Noma H, Mimura T, Eguchi S, Hori S.

Department of Ophthalmology, Yachiyo Medical Center, Tokyo Women's Medical
University, Yachiyo, Japan. hfunatsu@tymc.twmu.ac.jp

PURPOSE: To evaluate the association between vitreous inflammatory factors and
the severity of diabetic macular edema (DME). DESIGN: Retrospective case-control 
study. PARTICIPANTS: Fifty-three patients with DME, 15 patients with nondiabetic 
ocular disease, and 8 diabetic patients without retinopathy. METHODS: Vitreous
fluid samples were obtained during vitreoretinal surgery, and the levels of
vascular endothelial growth factor (VEGF), intercellular adhesion molecule
(ICAM)-1, interleukin (IL)-6, monocyte chemotactic protein (MCP)-1, and pigment
epithelium-derived factor (PEDF) were measured by enzyme-linked immunosorbent
assay. Multivariate analysis was performed to assess the association of these
factors with the severity of DME. MAIN OUTCOME MEASURES: Vitreous fluid levels of
inflammatory factors. RESULTS: Vitreous fluid levels of VEGF, ICAM-1, IL-6, and
MCP-1 were significantly higher in patients with DME than in nondiabetic patients
(P<0.05, all respectively) or diabetic patients without retinopathy (P<0.05, all 
respectively). In contrast, the PEDF level was significantly lower in patients
with DME than in nondiabetic patients (P<0.05) or diabetic patients without
retinopathy (P<0.05). Vitreous levels of VEGF, ICAM-1, IL-6, and MCP-1 were
significantly higher in patients with hyperfluorescent DME than in those with
minimally fluorescent DME (P = 0.0018, P = 0.0022, P = 0.0032, and P = 0.0053,
respectively). Conversely, the vitreous level of PEDF was significantly lower in 
hyperfluorescent DME than in minimally fluorescent DME (P = 0.0134). Vitreous
levels of VEGF, ICAM-1, IL-6, MCP-1, and PEDF were significantly correlated with 
the retinal thickness at the central fovea (P<0.0001, P<0.0001, P = 0.0282, P =
0.0009, and P = 0.0466, respectively). VEGF and ICAM-1 had a stronger influence
on the severity of DME than the other factors (P = 0.0004 and P = 0.0372,
respectively). CONCLUSIONS: Vitreous fluid levels of VEGF, ICAM-1, IL-6, MCP-1,
and PEDF were related to retinal vascular permeability and the severity of DME.
VEGF and ICAM-1 had a stronger influence than the other factors. FINANCIAL
DISCLOSURE(S): The authors have no proprietary or commercial interest in any
materials discussed in this article.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 19118698 [PubMed - indexed for MEDLINE]

17: Ophthalmology. 2009 Jan;116(1):66-72.

A systematic correlation of angiography and high-resolution optical coherence
tomography in diabetic macular edema.

Bolz M, Ritter M, Schneider M, Simader C, Scholda C, Schmidt-Erfurth U.

Department of Ophthalmology, Medical University of Vienna, Vienna, Austria.

PURPOSE: To correlate leakage patterns in fluorescein angiography (FA) images and
retinal morphologic features in high-definition optical coherence tomography (HD 
OCT) images in diabetic macular edema. DESIGN: Prospective pilot study and case
series. PARTICIPANTS: Nine consecutive patients (10 eyes) with diabetic macular
edema. METHODS: All patients were examined using FA (HRA 2; Heidelberg
Engineering) and HD OCT (Carl Zeiss Meditec; resolution, 512x128 pixels, 5.8x5.8 
mm, and high-resolution scans consisting of 4096 A scans) on the same day. Using 
Adobe Photoshop (CS2 Version 9.0; Adobe Systems Incorporated, San Jose, CA) a
grid containing 15x7 fields was superimposed on the HD OCT en face image and a
late-phase FA image according to retinal landmarks. In each patient, a
standardized analysis of 105 subfields was performed to provide a
characterization of the type of vascular leakage in FA and the associated retinal
morphologic changes in corresponding locations. MAIN OUTCOME MEASURES:
Angiographic leakage type and structural alteration in retinal morphologic
features in OCT. RESULTS: There was a high consistency between FA and OCT in the 
petaloid pattern of hyperfluorescence that correlated with the presence of large 
cystic spaces in the outer nuclear layer (ONL) and the outer plexiform layer
(OPL) with or without subretinal fluid in 30.4% and 69.6% of graded fields,
respectively. A honeycomblike pattern of hyperfluorescence was associated with
swelling and cystic spaces in ONL, OPL, the inner nuclear, and the inner
plexiform layer in 71.4% of graded fields. Diffuse patterns of hyperfluorescence 
did not correlate with characteristic retinal changes in HD OCT, but rather
showed diversity in the type of morphologic alteration. The presence of central
fluid pooling, such as subretinal fluid, could be identified only by HD OCT and
not by FA. CONCLUSIONS: In the examined patients, a petaloid pattern and a
honeycomb pattern of hyperfluorescence observed in FA were found to correlate to 
characteristic changes in HD OCT, whereas a diffuse leakage pattern was
associated with nonuniform changes in retinal morphologic features. FINANCIAL
DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any
materials discussed in this article.

Publication Types: 
    Comparative Study

PMID: 19118697 [PubMed - indexed for MEDLINE]

18: Ophthalmology. 2009 Jan;116(1):57-65.e5.

Ranibizumab versus verteporfin photodynamic therapy for neovascular age-related
macular degeneration: Two-year results of the ANCHOR study.

Brown DM, Michels M, Kaiser PK, Heier JS, Sy JP, Ianchulev T; ANCHOR Study Group.

Collaborators: Aaberg T, Abraham P, Akduman L, Alfaro DV 3rd, Antoszyk A, Arnold 
J, Awh C, Beer P, Belmont J, Berger B, Berinstein D, Bhisitkul R, Boyer D,
Bridges W, Brooks HL Jr, Brown D, Ciulla T, Clark WL, Connor T, Cousins S, Devin 
F, Dunn W, Eaton A, Fekrat DS, Foja C, Foster B, Gaudric A, Gilles M, Glaser D,
Godley B, Gonzalez V, Goodart R, Guymer R, Halperin L, Heier J, Holz F, Hubbard
B, Hudson H, Le D, Johnson M, Joussen A, Kaiser P, Kuppermann B, Lomeo M,
MacDonald C, Marcus D, Martidis A, Martinez J, Maxwell D Jr, McMillan T, Michels 
M, Miller D, Michell P, Orgel I, Park R, Paul M, Pavan P, Petersen M, Prensky J, 
Raskauskas P, Reichel E, Reid D, Richmond P, Rodden W, Rosenfeld PJ, Runge P,
Sadda S, Sanislo S, Schwartz SG, Seres AI, Singer M, Soubrane G, Soucek P, Stern 
W, Stoller G, Thompson J, Tom D, Torti R, Trese M, van Kuijk E, Verstaeten T,
Warren K, Weiss H, Weiss J, Wells C, Wolf S, Zhang K.

Vitreoretinal Consultants, Methodist Hospital, Houston, Texas 77030, USA.
dmbmd@houstonretina.com

OBJECTIVE: The 2-year, phase III trial designated Anti-vascular endothelial
growth factor (VEGF) Antibody for the Treatment of Predominantly Classic
Choroidal Neovascularization (CNV) in Age-related Macular Degeneration (ANCHOR)
compared ranibizumab with verteporfin photodynamic therapy (PDT) in treating
predominantly classic CNV. DESIGN: Multicenter, international, randomized,
double-masked, active-treatment-controlled clinical trial. PARTICIPANTS: Patients
with predominantly classic, subfoveal CNV not previously treated with PDT or
antiangiogenic drugs. INTERVENTION: Patients were randomized 1:1:1 to verteporfin
PDT plus monthly sham intraocular injection or to sham verteporfin PDT plus
monthly intravitreal ranibizumab (0.3 mg or 0.5 mg) injection. The need for PDT
(active or sham) retreatment was evaluated every 3 months using fluorescein
angiography (FA). MAIN OUTCOME MEASURES: The primary, intent-to-treat efficacy
analysis was at 12 months, with continued measurements to month 24. Key measures 
included the percentage losing <15 letters from baseline visual acuity (VA) score
(month 12 primary efficacy outcome measure), percentage gaining >or=15 letters
from baseline, and mean change over time in VA score and FA-assessed lesion
characteristics. Adverse events were monitored. RESULTS: Of 423 patients (143
PDT, 140 each in the 2 ranibizumab groups), the majority (>or=77% in each group) 
completed the 2-year study. Consistent with results at month 12, at month 24 the 
VA benefit from ranibizumab was statistically significant (P<0.0001 vs. PDT) and 
clinically meaningful: 89.9% to 90.0% of ranibizumab-treated patients had lost
<15 letters from baseline (vs. 65.7% of PDT patients); 34% to 41.0% had gained
>or=15 letters (vs. 6.3% of PDT group); and, on average, VA was improved from
baseline by 8.1 to 10.7 letters (vs. a mean decline of 9.8 letters in PDT group).
Changes in lesion anatomic characteristics on FA also favored ranibizumab (all
comparisons P<0.0001 vs. PDT). Overall, there was no imbalance among groups in
rates of serious ocular and nonocular adverse events. In the pooled ranibizumab
groups, 3 of 277 (1.1%) patients developed presumed endophthalmitis in the study 
eye (rate per injection = 3/5921 [0.05%]). CONCLUSIONS: In this 2-year study,
ranibizumab provided greater clinical benefit than verteporfin PDT in patients
with age-related macular degeneration with new-onset, predominantly classic CNV. 
Rates of serious adverse events were low. FINANCIAL DISCLOSURE(S): Proprietary or
commercial disclosure may be found after the references.

Publication Types: 
    Clinical Trial, Phase III
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 19118696 [PubMed - indexed for MEDLINE]

19: BMC Ophthalmol. 2008 Dec 22;8:25.

Novel measures of cardiovascular health and its association with prevalence and
progression of age-related macular degeneration: the CHARM Study.

McCarty CA, Dowrick A, Cameron J, McGrath B, Robman LD, Dimitrov P, Tikellis G,
Nicolas C, McNeil J, Guymer R.

Center for Human Genetics, Marshfield Clinic Research Foundation, Marshfield, MA,
USA. mccarty.catherine@mcrf.mfldclin.edu

BACKGROUND: To determine if novel measures of cardiovascular health are
associated with prevalence or progression of age-related macular degeneration
(AMD). METHODS: Measures of the cardiovascular system: included intima media
thickness (IMT), pulse wave velocity (PWV), systemic arterial compliance (SAC),
carotid augmentation index (AI). For the prevalence study, hospital-based AMD
cases and population-based age- and gender-matched controls with no signs of AMD 
in either eye were enrolled. For the progression component, participants with
early AMD were recruited from two previous studies; cases were defined as
progression in one or both eyes and controls were defined as no progression in
either eye. RESULTS: 160 cases and 160 controls were included in the prevalence
component. The upper two quartiles of SAC, implying good cardiovascular health,
were significantly associated with increased risk of AMD (OR = 2.54, 95% CL =
1.29, 4.99). High PWV was associated with increased prevalent AMD. Progression
was observed in 82 (32.3%) of the 254 subjects recruited for the progression
component. Higher AI (worse cardiovascular function) was protective for AMD
progression (OR = 0.30, 95%CL = 0.13, 0.69). Higher aortic PWV was associated
with increased risk of AMD progression; the highest risk was seen with the second
lowest velocity (OR = 6.22, 95% CL = 2.35, 16.46). CONCLUSION: The results were
unexpected in that better cardiovascular health was associated with increased
risk of prevalent AMD and progression. Inconsistent findings between the
prevalence and progression components could be due to truly different disease
etiologies or to spurious findings, as can occur with inherent biases in case
control studies of prevalence. Further investigation of these non-invasive
methods of characterizing the cardiovascular system should be undertaken as they 
may help to further elucidate the role of the cardiovascular system in the
etiology of prevalent AMD and progression.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 19102747 [PubMed - indexed for MEDLINE]

20: Ophthalmology. 2009 Feb;116(2):297-303. Epub 2008 Dec 16.

Risk of advanced age-related macular degeneration after cataract surgery in the
Age-Related Eye Disease Study: AREDS report 25.

Chew EY, Sperduto RD, Milton RC, Clemons TE, Gensler GR, Bressler SB, Klein R,
Klein BE, Ferris FL 3rd.

National Eye Institute, Bethesda, Maryland, USA.

PURPOSE: To assess the risk of advanced age-related macular degeneration (AMD)
developing after cataract surgery. DESIGN: Cohort study. PARTICIPANTS: Four
thousand five hundred seventy-seven participants (8050 eyes) from a multicenter, 
controlled, randomized clinical trial, the Age-Related Eye Disease Study (AREDS).
METHODS: Development of advanced AMD, either neovascular (NV) AMD or geographic
atrophy (GA), was evaluated with annual fundus photographs, and history of
cataract surgery was assessed every 6 months. Cox proportional hazard models with
time-dependent covariates were conducted for NV AMD and GA separately. MAIN
OUTCOME MEASURES: Neovascular AMD, GA, and central GA (CGA; involving the center 
of the macula). RESULTS: The Cox proportional hazards model of right eyes showed 
nonsignificant hazard ratios of 1.20 (95% confidence interval [CI], 0.82-1.75)
for NV AMD, 0.80 (95% CI, 0.61-1.06) for GA, and 0.87 (95% CI, 0.64-1.18) for
CGA. Similar results were obtained for left eyes: 1.07 (95% CI, 0.72-1.58) for NV
AMD, 0.94 (95% CI, 0.71-1.25) for GA, and 0.86 (95% CI, 0.63-1.19) for CGA. For
participants with advanced AMD in 1 eye (AREDS category 4), the hazard ratios for
fellow eyes were 1.08 (95% CI, 0.65-1.72) for NV AMD and 0.98 (95% CI, 0.64-1.49)
for CGA. CONCLUSIONS: The AREDS results showed no clear effect of cataract
surgery on the risk of progression to advanced AMD. FINANCIAL DISCLOSURE(S): The 
author(s) have no proprietary or commercial interest in any materials discussed
in this article.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial
    Research Support, N.I.H., Extramural

PMID: 19091420 [PubMed - indexed for MEDLINE]

21: Ophthalmology. 2009 Feb;116(2):286-96. Epub 2008 Dec 16.

Applying the CONSORT and STROBE statements to evaluate the reporting quality of
neovascular age-related macular degeneration studies.

Fung AE, Palanki R, Bakri SJ, Depperschmidt E, Gibson A.

Pacific Eye Associates, California Pacific Medical Center, San Francisco,
California 94115, USA. annefungmd@yahoo.com

PURPOSE: To evaluate the quality of reporting in the neovascular age-related
macular degeneration (nvAMD) literature by applying the Consolidated Standards
for Reporting Trials (CONSORT) and Strengthening the Reporting of Observational
Studies in Epidemiology (STROBE) statement writing standards. DESIGN: CONSORT and
STROBE impact analysis; literature review. PARTICIPANTS: Phase III randomized
controlled trials (RCTs) of verteporfin photodynamic therapy, pegaptanib, and
ranibizumab, and interventional case studies of bevacizumab for nvAMD. METHODS: A
literature search identified eligible articles published before October 31, 2007.
We assessed the report quality of Phase III RCTs using the CONSORT statement and 
case series publications using the STROBE statement, both with indicators
relevant to nvAMD. MAIN OUTCOME MEASURES: Presence or absence of CONSORT or
STROBE statement indicators. RESULTS: Seven publications of Phase III RCTs and 29
publications on bevacizumab interventional case studies for nvAMD met our
inclusion criteria. Of 37 possible CONSORT writing guideline items, the mean
report quality for RCTs was 30.6 (83%), with a range from 23 to 35 (65%-95%). Of 
35 possible STROBE writing guideline items, the mean report quality grade for
intravitreal bevacizumab case series was 23 (70%), with a range from 16 to 31
(46%-94%). Among the bevacizumab studies, more than 90% reported scientific
background, drug dose and administration, baseline characteristics, unadjusted
results, and adverse events. Fewer than 20% reported study size calculations,
handling of missing data, or a discussion of bias. CONCLUSIONS: Since the
adoption of the CONSORT standards by Ophthalmology and other journals in 1996,
the reporting quality for RCTs has further improved among this cohort of nvAMD
articles. On the other hand, no reporting standards for case series have existed 
until the recent publication of the STROBE statement. In this first application
of the STROBE standards to ophthalmology, we found that the small interventional 
studies in our series had an average reporting score lower than the RCTs, but
also that some individual scores were higher than the RCTs. This outcome
demonstrates that good, useful articles can be written about small studies.
Although not a direct measure of the quality of a study, good reporting allows a 
reader to assess the validity and applicability of the study's findings.
FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after 
the references.

PMID: 19091408 [PubMed - indexed for MEDLINE]

22: Acta Ophthalmol. 2008 Dec;86(8):930-1.

Uveal melanoma and macular degeneration: molecular biology and potential
therapeutic applications.

Economou MA.

Cellular and Molecular Tumour Pathology, Department of Oncology and Pathology,
Cancer Center Karolinska, Karolinska Institute, Sweden.
mario-alexander.economou@sankterik.se

Uveal melanoma is the most common primary intraocular malignant tumor in adults
with 30% to 50% of patients that ultimately succumb to metastatic disease, mainly
to the liver. (Shields et al. 1991) Although new diagnostic and therapeutic tools
have been developed during the most recent years, only the eye conservation rate 
has been achieved, while the survival rate remains poor. The reason for this
liver-homing is largely unknown, but it is conceivable that hepatic environmental
factors may be implicated in the growth, dissemination, and progression of this
malignancy. The insulin-like growth factor (IGF-1) that binds to the IGF-1
receptor (IGF-1R) is mainly produced in the liver. It has been shown to be
crucial for tumor transformation, maintenance of malignant phenotype, promotion
of cell growth, and prevention of apoptosis. (Baserga 1995) The hepatocyte growth
factor/scatter factor (HGF/SF) is another growth factor produced in the liver and
exerts its biological effects through binding to the plasma membrane receptor
c-Met. The activation of this receptor by HGF/SF ligand can induce proliferation,
motility, adhesion, and invasion of tumor cells. (Cruz et al. 2003) Metastasis is
a process involving many components, including tumor cell adhesion, migration,
extracellular matrix (ECM) proteolysis, and invasion. The tumor cells undergo
intravasation, disperse via the vascular and the lymphatic systems, and finally
extravasate to invade the secondary sites. In all these steps, proteolytic enzyme
systems are involved, including the matrix metalloproteinase (MMP) system and the
plasminogen activation system. The migration of a malignant cell through the ECM 
and the basement membrane requires proteolytic activities. (Stetler-Stevenson et 
al. 1993). Efforts to target the IGF-I system has been made with different types 
of cancer but not with uveal melanoma.

PMID: 19086934 [PubMed - indexed for MEDLINE]

23: Indian J Ophthalmol. 2009 Jan-Feb;57(1):55-7.

Cystoid macular edema after bone marrow transplantation.

Khetan V, Chaudhary SP, Gopal L.

Bhagwan Mahavir Vitreoretinal Services, Vision and Medical Research Foundation,
Sankara Nethralaya, Nungambakkam, Chennai - 600 006, India.

We report a case of cystoid macular edema in a patient who underwent bone marrow 
transplant for aplastic anemia. After having ruled out all the other causes of
cystoid macular edema, we concluded that it was secondary to the bone marrow
transplant. The patient had mild visual impairment and did not recover the lost
vision. In this case report, we describe in detail the clinical presentation,
follow-up, and course of medication that this patient had. It is an illustrated
case report of cystoid macular edema after bone marrow transplant with mild
visual impairment and no recovery.

Publication Types: 
    Case Reports

PMID: 19075413 [PubMed - indexed for MEDLINE]

24: Am J Epidemiol. 2009 Mar 1;169(5):633-41. Epub 2008 Dec 13.

Combined effects of complement factor H genotypes, fish consumption, and
inflammatory markers on long-term risk for age-related macular degeneration in a 
cohort.

Wang JJ, Rochtchina E, Smith W, Klein R, Klein BE, Joshi T, Sivakumaran TA,
Iyengar S, Mitchell P.

Vision Research, Department of Ophthalmology and the Westmead Millennium
Institute, University of Sydney, Sydney, New South Wales, Australia.
jiejin_wang@wmi.usyd.edu.au

At baseline in 1992-1994, the authors assessed the combined effects of complement
factor H (CFH) genotypes with smoking, fish consumption, and inflammatory markers
on the risk of age-related macular degeneration (AMD) in 3,654 persons aged > or 
=49 years. They reexamined 75% of the survivors after 5 and 10 years, confirming 
incident AMD by side-by-side photographic grading. Of the 2,452 persons followed 
in the Blue Mountains Eye Study, 1,881 were genotyped (rs1061170), with CC, CT,
and TT identified in 13.6%, 46.7%, and 39.7%, respectively. AMD risk increased
with each additional C allele (early AMD: age- and sex-adjusted relative risk
(RR) = 1.6, 95% confidence interval (CI): 1.2, 1.9; late AMD: RR = 2.3, 95% CI:
1.5, 3.6). Late AMD risk among current smokers with the CC/CT genotypes (RR =
10.7, 95% CI: 3.4, 33.9) was 5-fold that for genotypically similar nonsmokers (RR
= 2.2, 95% CI: 0.9, 5.5) versus current nonsmokers with TT genotypes. Weekly
compared with less than weekly consumption of fish was associated with reduced
late AMD risk in participants with the CC genotype (RR = 0.15, 95% CI: 0.03, 0.8)
but not the CT (RR = 0.7, 95% CI: 0.3, 2.0) or TT (RR = 1.3, 95% CI: 0.2, 7.2)
genotypes. This study documents joint contributions from genetic and systemic
factors in determining the progression of AMD.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 19074778 [PubMed - indexed for MEDLINE]

25: Med Phys. 2008 Nov;35(11):5151-60.

Dosimetry characterization of a multibeam radiotherapy treatment for age-related 
macular degeneration.

Lee C, Chell E, Gertner M, Hansen S, Howell RW, Hanlon J, Bolch WE.

Department of Nuclear and Radiological Engineering, University of Florida,
Gainesville, Florida 32611, USA.

Age-related macular degeneration (ARMD) is a major health problem worldwide.
Advanced ARMD, which ultimately leads to profound vision loss, has dry and wet
forms, which account for 20% and 80% of cases involving severe vision loss,
respectively. A new device and approach for radiation treatment of ARMD has been 
recently developed by Oraya Therapeutics, Inc. (Newark, CA). The goal of the
present study is to provide a initial dosimetry characterization of the proposed 
radiotherapy treatment via Monte Carlo radiation transport simulation. A 3D eye
model including cornea, anterior chamber, lens, orbit, fat, sclera, choroid,
retina, vitreous, macula, and optic nerve was carefully designed. The eye model
was imported into the MCNPX2.5 Monte Carlo code and radiation transport
simulations were undertaken to obtain absorbed doses and dose volume histograms
(DVH) to targeted and nontargeted structures within the eye. Three different
studies were undertaken to investigate (1) available beam angles that maximized
the dose to the macula target tissue, simultaneously minimizing dose to normal
tissues, (2) the energy dependency of the DVH for different x-ray energies (80,
100, and 120 kVp), and (3) the optimal focal spot size among options of 0.0, 0.4,
1.0, and 5.5 mm. All results were scaled to give 8 Gy to the macula volume, which
is the current treatment requirement. Eight beam treatment angles are currently
under investigation. In all eight beam angles, the source-to-target distance is
13 cm, and the polar angle of entry is 300 from the geometric axis of the eye.
The azimuthal angle changes in eight increments of 45 degrees in a clockwise
fashion, such that an azimuthal angle of 0 degreee corresponds to the 12 o'clock 
position when viewing the treated eye. Based on considerations of nontarget
tissue avoidance, as well as facial-anatomical restrictions on beam delivery,
treatment azimuthal angles between 135 degrees and 225 degrees would be available
for this treatment system (i.e., directly upward and entering the eye from
below). At beam directions approaching 225 degrees and higher, some dose
contribution to the optic nerve would result under the assumption that the optic 
nerve is tilted cranially above the geometric axis in a given patient, a feature 
not typically seen in past studies. A total treatment dose of 24 Gy would be
delivered in three 8 Gy treatments at these selected azimuthal angles. Dose
coefficients, defined as the macula radiation absorbed dose per unit air kerma in
units of Gy/Gy, were 16% higher for 120 kVp x-ray beams in comparison to those at
80 kVp, thus requiring only 86% of the integrated tube current (mAs) for
equivalent dose delivery. When 0.0, 0.4, and 1.0 mm focal spot sizes were used,
the dose profiles in the macula are very similar and relatively uniform, whereas 
a 5.5 mm focal spot size produced a more nonuniform dose profile. The results of 
this study dem onstrate the therapeutic promise of this device and provide
important information for further design and clinical implementation for
radiotherapy treatments for ARMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 19070249 [PubMed - indexed for MEDLINE]

26: Ophthalmic Surg Lasers Imaging. 2008 Nov-Dec;39(6):460-5.

Risk factors for severe vision loss immediately after transpupillary
thermotherapy for occult subfoveal choroidal neovascularization.

Mason JO 3rd, Colagross CC, Feist RM, White MF, Thomley ML, Vail RS, McGwin G Jr.

Department of Ophthalmology, University of Alabama at Birmingham School of
Medicine, Callahan Eye Foundation Hospital, Birmingham, Alabama 35233, USA.

BACKGROUND AND OBJECTIVE: To determine risk factors for immediate severe vision
loss in patients with age-related macular degeneration after transpupillary
thermotherapy for occult subfoveal choroidal neovascularization. PATIENTS AND
METHODS: Retrospective review of 84 consecutive patients with age-related macular
degeneration who received transpupillary thermotherapy for occult subfoveal
choroidal neovascularization. Seven cases had severe vision loss and 77 were
controls. All patients were treated with a diode infrared laser. Follow-up was
completed on all patients 1, 3, and 6 months after treatment with transpupillary 
thermotherapy. RESULTS: Pretreatment visual acuity ranged from 20/40 to 1/200.
Seven of 84 consecutive eyes had an immediate visual acuity loss of 6 or more
Snellen lines after transpupillary thermotherapy. CONCLUSION: Transpupillary
thermotherapy has a small but significant risk of immediate severe vision loss in
patients with age-related macular degeneration with occult subfoveal choroidal
neovascularization. Statistically significant risk factors include a subretinal
hemorrhage 5 disc areas or greater in size, 9 disc areas or greater of subretinal
fluid, and a laser power greater than 550 mW.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 19065975 [PubMed - indexed for MEDLINE]

27: Mol Vis. 2008;14:2263-71. Epub 2008 Dec 8.

Sequence variants in HTRA1 and LOC387715/ARMS2 and phenotype and response to
photodynamic therapy in neovascular age-related macular degeneration in
populations from Israel.

Chowers I, Meir T, Lederman M, Goldenberg-Cohen N, Cohen Y, Banin E, Averbukh E, 
Hemo I, Pollack A, Axer-Siegel R, Weinstein O, Hoh J, Zack DJ, Galbinur T.

Department of Ophthalmology, Hadassah-Hebrew University Medical Center,
Jerusalem, Israel. chowers@hadassah.org.il

PURPOSE: Single nucleotide polymorphisms (SNPs) in the tightly linked
LOC387715/ARMS2 and HTRA1 genes have been associated with age-related macular
degeneration (AMD). We tested whether these SNPs are associated with AMD in
Israeli populations, if they underlie variable phenotype and response to therapy 
in neovascular AMD (NVAMD), and if HTRA1 expression in vivo is associated with
its promoter variant. METHODS: Genotyping for the rs10490924 SNP in
LOC387715/ARMS2 and the rs11200638 SNP in HTRA1 was performed on 255 NVAMD
patients and 119 unaffected controls from Ashkenazi and Sephardic Jewish, and
from Arab origins which are the main ethnic groups composing the Israeli
population. Genotyping was correlated with phenotype and response to therapy
among 143 patients who underwent photodynamic therapy (PDT). HTRA1 mRNA levels in
white blood cells (WBCs), measured by quantitative PCR, were correlated with
genotype in 27 participants. RESULTS: Both SNPs were in almost complete linkage
disequilibrium (D'=0.96-1). Homozygotes for the T allele of rs10490924 had an
odds ratio (OR) of 8.6, with a 95% confidence interval (CI) of 3.5-20.8, and
homozygotes for the A allele of rs11200638 had an OR of 10.7, with a 95% CI of
3.2-35.7, for having AMD (p<0.00001). There was no association among these SNPs
and phenotype or response to PDT. HTRA1 mRNA levels in WBCs were not associated
with rs11200638 genotypes. CONCLUSIONS: The rs10490924 SNP in LOC387715/ARMS2 and
the rs11200638 SNP in HTRA1 are strongly associated with NVAMD in this Israeli
population. These variants do not have a major contribution to the variable
phenotype and response to PDT which characterize NVAMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 19065273 [PubMed - indexed for MEDLINE]

28: Arch Ophthalmol. 2008 Dec;126(12):1748-54.

Resource use and costs associated with diabetic macular edema in elderly persons.

Shea AM, Curtis LH, Hammill BG, Kowalski JW, Ravelo A, Lee PP, Sloan FA, Schulman
KA.

Center for Clinical and Genetic Economics, Duke Clinical Research Institute,
Durham, NC 27715, USA.

OBJECTIVE: To examine trends in resource use and the effect of incident diabetic 
macular edema (DME) on 1- and 3-year total direct medical costs in elderly
patients. METHODS: We used a nationally representative 5% sample of Medicare
beneficiaries from 2000 through 2004 to identify patients with incident DME and a
control cohort of patients with diabetes mellitus but no history of retinal
disease. We summed Medicare reimbursement amounts for all claims and applied
generalized linear models to estimate the effect of DME on 1- and 3-year costs.
We also examined the use of select imaging techniques and treatments. RESULTS:
After adjusting for demographic characteristics and baseline comorbid conditions,
DME was associated with 31% higher 1-year costs and 29% higher 3-year costs.
There were significant shifts in the use of testing and treatment modalities.
From 2000 to 2004, use of intravitreal injection increased from 1% to 13% of
patients; use of optical coherence tomography increased from 2.5% to more than
40%. Use of laser photocoagulation decreased over time. CONCLUSIONS: After
adjusting for demographic variables and baseline comorbid conditions, new-onset
DME was a significant independent predictor of total medical costs after 1 and 3 
years. Diagnostic and treatment modalities used for DME have changed
significantly.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 19064859 [PubMed - indexed for MEDLINE]

29: Am J Ophthalmol. 2009 Mar;147(3):406-12. Epub 2008 Dec 3.

Comparison between intravitreal and orbital floor triamcinolone acetonide after
phacoemulsification in patients with endogenous uveitis.

Roesel M, Tappeiner C, Heinz C, Koch JM, Heiligenhaus A.

Department of Ophthalmology, St Franziskus-Hospital, Muenster, Germany.

PURPOSE: To compare the effect of intravitreal and orbital floor triamcinolone
acetonide (TA) on macular edema, visual outcome, and course of postoperative
inflammation after cataract surgery in uveitis patients. DESIGN: Prospective,
randomized clinical trial. METHODS: Monocenter study (40 patients) with chronic
endogenous uveitis who underwent phacoemulsification with intraocular lens
implantation with either 4 mg intravitreal TA (n = 20) or 40 mg orbital floor TA 
(n = 20). The primary outcome was influence on cystoid macular edema (CME).
Secondary outcome measures were best-corrected visual acuity (BCVA), anterior
chamber cell grade, laser flare photometry, giant cell deposition, posterior
capsule opacification (PCO), and intraocular pressure. RESULTS: Mean central
foveal thickness decreased in the intravitreal TA group and increased in the
orbital floor TA group (P < .001 at one and three months). CME improved in 50% of
patients after intravitreal TA, whereas it was unchanged after orbital floor TA
(difference between the groups at three months, P = .049). Mean BCVA (logarithm
of the minimal angle of resolution) improved postoperatively (P < .001) from 0.76
and 0.74 to 0.22 and 0.23 in the intravitreal TA and orbital floor TA group,
respectively. Anterior chamber cell count at one month was lower in the
intravitreal TA than in the orbital floor TA group (P = .02). Laser flare
photometry values and giant cell numbers were slightly higher after orbital floor
TA than after intravitreal TA. The groups did not differ with respect to PCO rate
and ocular hypertension. CONCLUSIONS: The CME improvement and anti-inflammatory
effect after intravitreal TA was better than after orbital floor TA injection in 
cataract surgery in uveitis patients.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial

PMID: 19054496 [PubMed - indexed for MEDLINE]

30: PLoS ONE. 2008;3(12):e3833. Epub 2008 Dec 2.

Multifactor effects and evidence of potential interaction between complement
factor H Y402H and LOC387715 A69S in age-related macular degeneration.

Seitsonen SP, Onkamo P, Peng G, Xiong M, Tommila PV, Ranta PH, Holopainen JM,
Moilanen JA, Palosaari T, Kaarniranta K, Meri S, Immonen IR, Järvelä IE.

Department of Ophthalmology, University of Helsinki, Helsinki, Finland.
sanna.seitsonen@hus.fi

BACKGROUND: Variants in the complement cascade genes and the LOC387715/HTRA1,
have been widely reported to associate with age-related macular degeneration
(AMD), the most common cause of visual impairment in industrialized countries.
METHODS/PRINCIPAL FINDINGS: We investigated the association between the LOC387715
A69S and complement component C3 R102G risk alleles in the Finnish case-control
material and found a significant association with both variants (OR 2.98, p =
3.75 x 10(-9); non-AMD controls and OR 2.79, p = 2.78 x 10(-19), blood donor
controls and OR 1.83, p = 0.008; non-AMD controls and OR 1.39, p = 0.039; blood
donor controls), respectively. Previously, we have shown a strong association
between complement factor H (CFH) Y402H and AMD in the Finnish population. A
carrier of at least one risk allele in each of the three susceptibility loci
(LOC387715, C3, CFH) had an 18-fold risk of AMD when compared to a non-carrier
homozygote in all three loci. A tentative gene-gene interaction between the two
major AMD-associated loci, LOC387715 and CFH, was found in this study using a
multiplicative (logistic regression) model, a synergy index
(departure-from-additivity model) and the mutual information method (MI),
suggesting that a common causative pathway may exist for these genes. Smoking
(ever vs. never) exerted an extra risk for AMD, but somewhat surprisingly, only
in connection with other factors such as sex and the C3 genotype. Population
attributable risks (PAR) for the CFH, LOC387715 and C3 variants were 58.2%, 51.4%
and 5.8%, respectively, the summary PAR for the three variants being 65.4%.
CONCLUSIONS/SIGNIFICANCE: Evidence for gene-gene interaction between two major
AMD associated loci CFH and LOC387715 was obtained using three methods, logistic 
regression, a synergy index and the mutual information (MI) index.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 19048105 [PubMed - indexed for MEDLINE]

31: PLoS ONE. 2008;3(11):e3813. Epub 2008 Nov 26.

Evaluation of clustering and genotype distribution for replication in genome wide
association studies: the age-related eye disease study.

Edwards AO, Fridley BL, James KM, Sharma AS, Cunningham JM, Tosakulwong N.

Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota, United States of 
America. edwardslab@mayo.edu

Genome-wide association studies (GWASs) assess correlation between traits and DNA
sequence variation using large numbers of genetic variants such as single
nucleotide polymorphisms (SNPs) distributed across the genome. A GWAS produces
many trait-SNP associations with low p-values, but few are replicated in
subsequent studies. We sought to determine if characteristics of the genomic loci
associated with a trait could be used to identify initial associations with a
higher chance of replication in a second cohort. Data from the age-related eye
disease study (AREDS) of 100,000 SNPs on 395 subjects with and 198 without
age-related macular degeneration (AMD) were employed. Loci highly associated with
AMD were characterized based on the distribution of genotypes, level of
significance, and clustering of adjacent SNPs also associated with AMD suggesting
linkage disequilibrium or multiple effects. Forty nine loci were highly
associated with AMD, including 3 loci (CFH, C2/BF, LOC387715/HTRA1) already known
to contain important genetic risks for AMD. One additional locus (C3) reported
during the course of this study was identified and replicated in an additional
study group. Tag-SNPs and haplotypes for each locus were evaluated for
association with AMD in additional cohorts to account for population differences 
between discovery and replication subjects, but no additional clearly significant
associations were identified. Relying on a significant genotype tests using a
log-additive model would have excluded 57% of the non-replicated and none of the 
replicated loci, while use of other SNP features and clustering might have missed
true associations.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 19043567 [PubMed - indexed for MEDLINE]

32: Home Health Care Serv Q. 2008;27(3):167-86.

Home care as a complex experience: a chronological case study.

Porter EJ.

School of Nursing, University of Missouri-Columbia, Columbia, MO 65211, USA.
PorterEJ@missouri.edu

This case study of an older woman with macular degeneration describes her
experience of dispensing daily medications over a 3-year period, during which a
home care nurse began and continued visits. Using a phenomenological method, I
analyzed data of 9 interviews, discerning the structure of her experience and
depicting it in 7 diagrams. The home care experience can have unintended outcomes
influenced by family and provider perceptions of clients' abilities, especially
when family members and practitioners assume tasks that older women have managed 
alone. Minimizing intergenerational ambivalence about the need for home care and 
maximizing client agency should be preeminent foci of home care providers.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 19042236 [PubMed - indexed for MEDLINE]

33: Lancet. 2008 Nov 22;372(9652):1835-45.

Age-related macular degeneration.

Coleman HR, Chan CC, Ferris FL 3rd, Chew EY.

Division of Epidemiology and Clinical Research, National Eye Institute, National 
Institutes of Health, Bethesda, MD, USA.

Age-related macular degeneration is the leading cause of blindness in elderly
populations of European descent. The most consistent risk factors associated with
this ocular condition are increasing age and cigarette smoking. Genetic
investigations have shown that complement factor H, a regulator of the
alternative complement pathway, and LOC387715/HtrA1 are the most consistent
genetic risk factors for age-related macular degeneration. Although the
pathogenesis of this disease is unknown, oxidative stress might have an important
role. Treatment with antioxidant vitamins and zinc can reduce the risk of
developing advanced age-related macular degeneration by about a quarter in those 
at least at moderate risk. Intravitreal injections of ranibizumab, a monoclonal
antibody that inhibits all forms of vascular endothelial growth factor, have been
shown to stabilise loss of vision and, in some cases, improve vision in
individuals with neovascular age-related macular degeneration. These findings,
combined with assessments of possible environmental and genetic interactions and 
new approaches to modulate inflammatory pathways, will hopefully further expand
our ability to understand and treat age-related macular degeneration.

PMID: 19027484 [PubMed - indexed for MEDLINE]

34: Oligonucleotides. 2008 Dec;18(4):305-19.

Chemical modification of siRNAs for in vivo use.

Behlke MA.

Integrated DNA Technologies, Inc., Coralville, Iowa 52241, USA.
mbehlke@idtdna.com

Well over a hundred reports have been published describing use of synthetic
small-interfering RNAs (siRNAs) in animals. The majority of these reports
employed unmodified RNA duplexes. While unmodified RNA is the natural effector
molecule of RNA interference, certain problems arise with experimental or
therapeutic use of RNA duplexes in vivo, some of which can be improved or solved 
through use of chemical modifications. Judicious use of chemical modifications
can improve the nuclease stability of an RNA duplex, decrease the likelihood of
triggering an innate immune response, lower the incidence of off-target effects
(OTEs), and improve pharmacodynamics. This review will examine studies that
document the utility of various chemical modifications for use in siRNAs, both in
vitro and in vivo, with close attention given to reports demonstrating actual
performance in animal model systems.

Publication Types: 
    Review

PMID: 19025401 [PubMed - indexed for MEDLINE]

35: Adv Exp Med Biol. 2008;632:117-42.

Complement factor H: using atomic resolution structure to illuminate disease
mechanisms.

Barlow PN, Hageman GS, Lea SM.

School of Chemistry and Biological Sciences, Joseph Black Chemistry Building,
University of Edinburgh, Edinburgh EH9 2PB, UK. Paul.Barlow@ed.ac.uk

Complement Factor H has recently come to the fore with variant forms implicated
in a range of serious disease states. This review aims to bring together recent
data concerning the structure and biological activity of this molecule to
highlight the way in which a molecular understanding of function may open novel
therapeutic possibilities. In particular we examine the evidence for and against 
the hypothesis that sequence variations in factor H may predispose to disease if 
they perturb its ability to recognise and respond appropriately to polyanionic
carbohydrates on host surfaces that require protection from complement-mediated
damage.

Publication Types: 
    Review

PMID: 19025119 [PubMed - indexed for MEDLINE]

36: Can J Ophthalmol. 2008 Dec;43(6):678-82.

Use of fluorescein and indocyanine green angiography in polypoidal choroidal
vasculopathy patients following photodynamic therapy.

Windisch R, Windisch BK, Cruess AF.

Department of Ophthalmology and Visual Sciences, Eye Center, Dalhousie
University, Halifax, NS.

BACKGROUND: Exudative age-related macular degeneration (AMD) is a
sight-threatening event in many elderly people. Some patients have a much better 
outcome in visual acuity (VA) than others after treatment with photodynamic
therapy (PDT) with verteporfin. The combination of fluorescein angiography (FA)
and indocyanine green (ICG) angiography using the Heidelberg Retina Angiograph II
(HRA 2) should make a delineation of distinct pattern(s) possible in order to
better select and assess therapy. METHODS: This is a retrospective, case-control,
single-centre study. We identified a total of 168 eyes of 168 patients from July 
2003 to June 2006, including 30 eyes of 30 patients with better visual outcome,
defined in this study as VA < or = 0.48 logMAR (> or =20/60 Snellen chart) at the
end of the study. Best-corrected VA, maximal central retinal thickness as
measured by optical coherence tomography, and results of the FA/ICG angiography
using the HRA 2 were analyzed. In this article, we discuss patients with
polypoidal choroidal vasculopathy (PCV) and their characteristics. RESULTS: The
average follow-up time was 15.3 months (range 4-28 months). Seventeen (57%) of
the 30 patients with better visual outcome had PCV. All patients in the group
with better visual outcome needed fewer PDT treatments compared with our control 
group of patients with an exudative AMD. INTERPRETATION: Simultaneous FA/ICG
angiography using the HRA 2 allowed delineation of a subgroup of patients with
PCV who showed a better visual outcome compared with those with other types of
exudative AMD, after treatment with PDT.

PMID: 19020634 [PubMed - indexed for MEDLINE]

37: Nutr Rev. 2008 Dec;66(12):695-702.

Possible role for dietary lutein and zeaxanthin in visual development.

Hammond BR Jr.

Vision Sciences Laboratory, University of Georgia, Athens, Georgia 30602, USA.

The possibility that the macular carotenoids, lutein (L), and zeaxanthin (Z),
could retard age-related changes in the eye and prevent the eye diseases that
result from such changes (namely, cataract and macular degeneration) has been
carefully studied. A role for the carotenoids very early in life, however, has
received far less attention. Nevertheless, an influence on visual development is 
likely. Retinal L and Z, for instance, would influence the development of the
visual system if they 1) altered input during a critical/sensitive period of
visual development and/or 2) influenced maturation and/or 3) protected the retina
during a period when it was particularly vulnerable. The available evidence
indicates that the pigments may play a role in all three of these areas.

Publication Types: 
    Review

PMID: 19019038 [PubMed - indexed for MEDLINE]

38: Folia Med (Plovdiv). 2008 Jul-Sep;50(3):30-8.

Types of diabetic macular edema assessed by optical coherence tomography.

Koleva-Georgieva DN, Sivkova NP.

Department of Ophthalmology, Medical University, Plovdiv, Bulgaria.

AIM: To assess the types of diabetic macular edema (DME) in patients with type 2 
diabetes mellitus by analyzing retinal thickness, morphology and presence of
macular traction using optical coherence tomography (OCT). PATIENTS AND METHODS: 
This prospective study included 74 diabetics with diabetic retinopathy (DR) (141 
eyes), 29 diabetics without DR (57 eyes) and 25 healthy volunteers (39 eyes). The
ophthalmic examination included best corrected visual acuity,
stereo-ophthalmoscopy, fluorescein angiography and OCT. DME assessment was based 
on the analysis of several OCT features: macular thickness, retinal morphology
and presence of macular traction--vitreomacular and/or from epiretinal membranes.
Four OCT types of DME were suggested: type 1--early, type 2--simple, type
3--cystoid (3a--mild, 3b--intermediate, 3c--severe) and type 4--serous macular
detachment. The distribution of the DME types and their correlation with retinal 
thickness and visual acuity were analyzed. RESULTS: The distribution of eyes with
DME was: type 1--14.1%, type 2--30.4%, type 3--45.7% (3a--14.1%, 3b--12%,
3c--19.6%) and type 4--9.8%. Macular traction with retinal distortion was
detected in 31.5% of the eyes with DME. Retinal thickness at the fixation point
was 176 +/- 16.8 microm (116 microm / 210 microm) in healthy eyes and 182.2 +/-
19.6 microm (138 microm / 212 microm) in eyes without DR. There was no
statistically significant difference between the two groups (Independent samples 
test, P > 0.05). The retina was significantly thicker in eyes with early DME
(232.9 +/- 7.9 microm) than in healthy eyes and eyes without DR (Independent
samples test, F = 16.274 and F = 13.100, P < 0.0001). Increasing retinal
thickness was significantly correlated with worse visual acuity (ANOVA, F =
16.692, P < 0.0001). CONCLUSION: OCT precisely differentiated 4 types of DME:
early, simple, cystoid and serous macular detachment, as well as determined the
presence of macular traction. The early diagnosis, high precision in retinal
thickness measurement, assessment of the morphologic types and macular traction
are of uppermost importance in determining the therapeutic approach, prognosis
and the effect of treatment.

PMID: 19009748 [PubMed - indexed for MEDLINE]

39: J Cataract Refract Surg. 2008 Nov;34(11):1953-7.

Foveal thickness after phacoemulsification in patients with pseudoexfoliation
syndrome, pseudoexfoliation glaucoma, or primary open-angle glaucoma.

Yüksel N, Doğu B, Karabaş VL, Cağlar Y.

Kocaeli University, Medical Faculty, Ophthalmology Department, Kocaeli, Turkey.
nursencemre@e-kolay.net

PURPOSE: To use optical coherence tomography (OCT) to assess changes in foveal
thickness after uneventful phacoemulsification in eyes with pseudoexfoliation
syndrome (PXF), pseudoexfoliation glaucoma (PXG), or primary open-angle glaucoma 
(POAG). SETTING: Department of Ophthalmology, University of Kocaeli, Kocaeli,
Turkey. METHODS: This prospective observational case series comprised 87 eyes (87
patients) that had phacoemulsification. Thirty-three were control eyes with
cataract and no ocular disease, 15 eyes had POAG, 22 eyes had PXF, and 17 eyes
had PXG. Foveal thickness was measured by OCT preoperatively and 1, 2, 4, and 8
weeks postoperatively. Intraocular pressure was recorded preoperatively and 8
weeks postoperatively. RESULTS: In all groups, the mean foveal thickness was
statistically significantly greater at all postoperative visits than
preoperatively. The mean change in foveal thickness was higher in the POAG group 
than in the PXF and control groups at 2 and 8 weeks. The mean increase in foveal 
thickness was greater in the PXG group than in the control group and the PXF
group at 2 and 4 weeks. Three patients (1 patient in each group except PXF)
developed clinically significant cystoid macular edema (CME); the incidence of
CME was not statistically significant. CONCLUSION: Foveal thickness measured by
OCT increased in patients with POAG and PXG and was higher than in the control
group and the PXF group after uneventful phacoemulsification.

PMID: 19006744 [PubMed - indexed for MEDLINE]

40: Expert Opin Pharmacother. 2008 Dec;9(17):3045-52.

Pharmacotherapy of age-related macular degeneration.

Ahmadi MA, Lim JI.

University of Illinois at Chicago, Department of Ophthalmology and Visual
Sciences, Illinois Eye and Ear Infirmary, IL 60612, Chicago USA.

BACKGROUND: Age-related macular degeneration is the leading cause of blindness in
the developed world. The number of persons with vision loss from age-related
macular degeneration is projected to increase dramatically over the next few
decades. Therefore, effective therapeutic and prophylactic agents are greatly
needed. OBJECTIVE: This article will discuss some of the newer treatment
strategies that may help to reduce the incidence of visual loss from age-related 
macular degeneration. Some of these therapies and strategies can be implemented
today, while many are hypothetical based on current laboratory data and ongoing
clinical trials. METHODS: A review of the literature and ongoing clinical trials 
was undertaken. CONCLUSION: Current therapies using antioxidants for prevention
of the progression of age-related macular degeneration and anti-vascular
endothelial growth factor therapies for neovascular age-related macular
degeneration have given us tools for tackling this disease better and reducing
the number of patients with vision loss. Combinations of some of the existing
treatments and new forms of therapy may yet further decrease the treatment burden
in the future.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 19006477 [PubMed - indexed for MEDLINE]

41: Arch Ophthalmol. 2008 Nov;126(11):1562-6.

Analysis of major alleles associated with age-related macular degeneration in
patients with multifocal choroiditis: strong association with complement factor
H.

Ferrara DC, Merriam JE, Freund KB, Spaide RF, Takahashi BS, Zhitomirsky I, Fine
HF, Yannuzzi LA, Allikmets R.

LuEsther T. Mertz Retinal Research Center, New York, New York, USA.

OBJECTIVE: To analyze the frequency of major age-related macular degeneration
(AMD)-associated alleles in patients with multifocal choroiditis (MFC). METHODS: 
A cohort of 48 patients with MFC was compared with previously characterized
cohorts of patients with advanced AMD (368 samples) and matched unaffected
controls (368 samples). Allele and genotype frequencies of single nucleotide
polymorphisms for the following AMD-associated alleles were evaluated: risk
alleles in complement factor H (CFH) gene (Y402H and IVS14) and LOC387715/HTRA1
gene on 10q26 (A69S) and protective alleles in CFH (IVS1, IVS6, and delCFHR1-3)
and complement factor B loci (H9L and R32Q). RESULTS: Frequencies of all major
AMD-associated alleles in the CFH locus indicate a strong, statistically
significant association of CFH gene single nucleotide polymorphisms and MFC.
However, the same analysis for the single nucleotide polymorphisms in complement 
factor B and 10q26 loci matched the results in the control group. CONCLUSIONS:
Like AMD, the MFC phenotype is strongly associated with the major
alleles/haplotypes in the CFH locus. Clinical Relevance We report compelling
evidence of a strong association between CFH polymorphisms and MFC, which
contributes to the understanding of MFC pathogenesis and suggests new potential
therapeutic targets.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 19001225 [PubMed - indexed for MEDLINE]

42: Arch Ophthalmol. 2008 Nov;126(11):1554-60.

Changes in abdominal obesity and age-related macular degeneration: the
Atherosclerosis Risk in Communities Study.

Peeters A, Magliano DJ, Stevens J, Duncan BB, Klein R, Wong TY.

Department of Epidemiology and Preventive Medicine, Monash University, Victoria, 
Australia.

OBJECTIVE: To examine the association between changes in waist-hip ratio (WHR), a
measure of abdominal obesity, and age-related macular degeneration (AMD).
METHODS: A total of 12 515 persons from a population-based cohort study, aged 45 
to 64 years in 1987 to 1989, were followed up over 6 years. The percentage change
in WHR during follow-up was ranked into sex-specific deciles; an increase in WHR 
was defined as the top 10% of change and a decrease in WHR as the bottom 10%. The
association of increased or decreased WHR and presence of AMD at follow-up was
determined using logistic regression adjusting for potential confounders.
RESULTS: The average change in WHR was an increase of 2%, ranging from a decrease
of 44% to an increase of 102%. A decrease in WHR of 3% or more was associated
with 29% lower odds of any AMD (odds ratio = 0.71; 95% confidence interval,
0.52-0.97). This effect was most pronounced among obese participants at baseline,
where a decrease in WHR was associated with 59% lower odds of AMD (odds ratio =
0.41; 95% confidence interval, 0.20-0.82). CONCLUSIONS: Middle-aged persons who
had a 3% or greater reduction in WHR over time were less likely to have AMD,
particularly among those who were initially obese.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 19001224 [PubMed - indexed for MEDLINE]

43: Retina. 2008 Nov-Dec;28(10):1463-77.

Automated diagnosis of retinopathy by content-based image retrieval.

Chaum E, Karnowski TP, Govindasamy VP, Abdelrahman M, Tobin KW.

Department of Ophthalmology, University of Tennessee Health Science Center,
Memphis, Tennessee, USA. echaum@utmem.edu

PURPOSE: To describe a novel computer-based image analysis method that is being
developed to assist and automate the diagnosis of retinal disease. METHODS:
Content-based image retrieval is the process of retrieving related images from
large database collections using their pictorial content. The content feature
list becomes the index for storage, search, and retrieval of related images from 
a library based upon specific visual characteristics. Low-level analyses use
feature description models and higher-level analyses use perceptual organization 
and spatial relationships, including clinical metadata, to extract semantic
information. RESULTS: We defined, extracted, and tested a large number of region-
and lesion-based features from a dataset of 395 retinal images. Using a
statistical hold-one-out method, independent queries for each image were
submitted to the system and a diagnostic prediction was formulated. The
diagnostic sensitivity for all stratified levels of age-related macular
degeneration ranged from 75% to 100%. Similarly, the sensitivity of detection and
accuracy for proliferative diabetic retinopathy ranged from 75% to 91.7% and for 
nonproliferative diabetic retinopathy, ranged from 75% to 94.7%. The overall
purity of the diagnosis (specificity) for all disease states in the dataset was
91.3%. CONCLUSIONS: The probabilistic nature of content-based image retrieval
permits us to make statistically relevant predictions regarding the presence,
severity, and manifestations of common retinal diseases from digital images in an
automated and deterministic manner.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, Non-P.H.S.

PMID: 18997609 [PubMed - indexed for MEDLINE]

44: Retina. 2008 Nov-Dec;28(10):1443-50.

Retinal fixation impairment in diabetic macular edema.

Vujosevic S, Pilotto E, Bottega E, Benetti E, Cavarzeran F, Midena E.

Fondazione G. B Bietti per l'Oftalmologia, IRCCS, Roma, Italy.

PURPOSE: To evaluate the characteristics of retinal fixation in patients with
diabetic macular edema using microperimetry. METHODS: One hundred seventy nine
eyes (98 patients) with untreated diabetic macular edema underwent best corrected
visual acuity determination (Early Treatment Diabetic Retinopathy Study charts), 
digital color stereoscopic fundus photos, fluorescein angiography and Optical
Coherence Tomography assessment of macula. Fixation and retinal thresholds were
determined with an automatic microperimeter. RESULTS: Best corrected visual
acuity (approximate Snellen equivalent) was: 20/25 or better in 90 (52%) eyes,
20/50 to 20/32 in 39 (22.5%) eyes, 20/200 to 20/62.5 in 35 (20.2%) eyes and
inferior to 20/200 in 9 (5.2%) eyes. Fixation was central in 128 (71.51%), poor
central in 26 (14.53%) and predominantly eccentric in 25 (13.97%) eyes; stable in
133 (74.3%), relatively unstable in 42 (23.46%) and unstable in 4 (2.23%) eyes.
Both fixation location and stability were not significantly influenced by edema
characteristics (diffuse, focal, cystoid, spongelike, with or without subfoveal
neuroretinal detachment), (P > 0.05), whereas they were significantly influenced 
by the presence of subfoveal hard exudates, (P = 0.004 and P = 0.0046,
respectively). Site and stability of fixation were significantly associated, (P <
0.0001). Retinal pseudofovea would have been covered by laser photocoagulation in
24 (47%) eyes with poorly central and predominantly eccentric fixation and in 29 
(63%) eyes with relatively unstable and unstable fixation. CONCLUSION:
Microperimetry shows that fixation location and stability in patients with
diabetic macular edema are independent of edema characteristics, except when
subfoveal hard exudates are present. Location of pseudofovea may influence
treatment strategy.

PMID: 18997608 [PubMed - indexed for MEDLINE]

45: Eur J Ophthalmol. 2008 Nov-Dec;18(6):1017-9.

Changes of vascular endothelial growth factor after vitrectomy for macular edema 
secondary to retinal vein occlusion.

Noma H, Funatsu H, Mimura T, Hori S.

Department of Ophthalmology, Yachiyo Medical Center, Tokyo Women's Medical
University, Chiba - Japan. nomahide@tymc.twmu.ac.jp

PURPOSE.To examine whether vitrectomy combined with retinal photocoagulation
reduces the vitreous level of vascular endothelial growth factor (VEGF) in
patients with macular edema associated with retinal vein occlusion (RVO).
METHODS. The authors measured VEGF levels in vitreous samples from four eyes of
four patients with RVO during vitrectomy and fluid samples obtained during
revitrectomy 3 to 9 months postoperatively for complications: an epiretinal
membrane in two patients, macular holes in one patient, and vitreous hemorrhage
in one patient. During vitrectomy, retinal photocoagulation was performed on the 
ischemic region of the retina in all cases (mean of 510 shots). RESULTS. In four 
eyes with RVO, there was a difference in the vitreous VEGF levels between the
vitreous samples obtained during vitrectomy (mean of 2692 pg/mL, range of
15.6-9040 pg/mL) and the fluid samples obtained at the time of revitrectomy (mean
of 947 pg/mL, range of 15.6-3430 pg/mL). CONCLUSIONS. The results suggest that
the vitreous levels of VEGF may be reduced by vitrectomy combined with retinal
photocoagulation for macular edema with RVO. It may be important to reduce the
vitreous levels of VEGF by vitrectomy and retinal photocoagulation for ischemic
retina in macular edema with RVO.

Publication Types: 
    Case Reports

PMID: 18988180 [PubMed - indexed for MEDLINE]

46: Eur J Ophthalmol. 2008 Nov-Dec;18(6):1014-6.

Serous detachment of macula in cystoid macular edema associated with latanoprost.

Ozdemir H, Karacorlu M, Karacorlu SA.

The Istanbul Retina Institute Inc., Istanbul - Turkey.

PURPOSE. To report serous macular detachment in two patients with cystoid macular
edema (CME) associated with latanoprost. METHODS. Two eyes of two patients with
CME associated with latanoprost underwent an ophthalmoscopic examination,
fluorescein angiography, and optical coherence tomography (OCT). RESULTS. In both
patients, besides CME, OCT showed serous macular detachment composed of retinal
elevation over a nonreflective cavity with minimal shadowing of the underlying
tissues. CONCLUSIONS. This is the first case report that shows an association
between serous macular detachment and CME associated with latanoprost.

Publication Types: 
    Case Reports

PMID: 18988179 [PubMed - indexed for MEDLINE]

47: Eur J Ophthalmol. 2008 Nov-Dec;18(6):1011-3.

Pseudophakic macular edema and oral acetazolamide: an optical coherence
tomography measurable, dose-related response.

Ismail RA, Sallam A, Zambarakji HJ.

Whipps Cross University Hospital, London - UK. rehab.ismail@yahoo.co.uk

PURPOSE. Although uncommon after phacoemulsification surgery, cystoid macular
edema (CME) is an important cause of postoperative reduction of vision after
cataract surgery. To demonstrate an optical coherence tomography (OCT)
measurable, dose-related response to orally administered acetazolamide in a
patient presenting with pseudophakic CME. METHODS. A 76-year-old woman with
reduced vision in right eye due to cataract had uneventful phacoemulsification.
Surgery was complicated by early onset endophthalmitis that was treated with
intravitreal antibiotics with good visual recovery. At 6 months follow-up, she
presented with further reduction of vision (0.5 LogMAR) due to CME and a central 
foveal thickness (CFT) of 587 microm. RESULTS. Acetazolamide treatment was
started in combination with topical ketorolac. At a daily dose of 500 mg, CFT and
visual acuity were 262 microm and 0.34 LogMAR, respectively. Dose reduction of
acetazolamide to 250 mg/day was associated with worsening of the CFT to 335
microm. CFT was subsequently measured at 230 microm on increasing the
acetazolamide dose to 500 mg/day and measured 353 microm when acetazolamide dose 
was halved. CFT was 478 microm when acetazolamide was ceased.CONCLUSIONS. In this
report, the authors have shown a dose-related response of pseudophakic CME to
oral acetazolamide. This would suggest that the clinical response to oral
acetazolamide may be titrated to the extent of CME and monitored by OCT.

Publication Types: 
    Case Reports

PMID: 18988178 [PubMed - indexed for MEDLINE]

48: Eur J Ophthalmol. 2008 Nov-Dec;18(6):949-54.

Age related maculopathy and diabetes.

Borrone R, Saravia M, Bar D.

Department of Ophthalmology, Retina Center, Diabetes Section, University of
Buenos Aires, School of Medicine, Buenos Aires - Argentina.
rborrone@intramed.net.ar

PURPOSE. To compare the prevalence of age-related maculopathy (ARM) in a sample
of diabetic patients with the general population. METHODS. Binocular indirect
ophthalmoscopy, biomicroscopy, and fluorescein angiography. Retrospective
prevalence study; descriptive-observational case-control type. Two different
groups were analyzed from a sample of 1000 consecutive files of diabetic
patients: 1) 65 to 74 years old (n = 263) and 2) 75 years and older (n = 199).
Prevalence was compared to that of the general population in a control group and 
the following epidemiologic studies: Beaver Dam Eye Study, Framingham Eye Study, 
Blue Mountains Study, and Rotterdam Eye Study. RESULTS. In diabetic patients aged
75 or older, prevalence of ARM was as follows: early lesions 2.51% (5/199), late 
lesions (ARMD) 2.51% (5/199). In comparison, the risk in patients 75 or older is 
as follows: control group (ARMD): OR 4.79, 95% CI 1.778-12.033, p (Fisher)
0.0005; Beaver Dam Eye Study (ARMD): OR 2.93, 95% CI 1.152-7.450, p (Fisher): 0; 
Blue Mountains Eye Study (ARMD): OR 3.06, 95% CI 1.208-7.754, p (Fisher): 0;
Framingham Eye Study (ARM): OR 6.73, 95% CI 3.041-14.880, p (Fisher): 0;
Rotterdam Eye Study: p (Fisher) 0.133. CONCLUSIONS. 1) A lower prevalence of ARM 
was found in the sample of diabetic patients aged 75 or older than in the general
population (with the exception of the Rotterdam study). 2) Prevalence of ARM was 
even lower in diabetic patients presenting diabetic retinopathy, whether or not
they had been treated with photocoagulation. 3) In diabetic patients, the
exudative form was more frequent than the atrophic form, in an inverse ratio to
that of the general population.

Publication Types: 
    Comparative Study

PMID: 18988167 [PubMed - indexed for MEDLINE]

49: Eur J Ophthalmol. 2008 Nov-Dec;18(6):941-8.

Intravitreal bevacizumab versus combined bevacizumab-triamcinolone versus macular
laser photocoagulation in diabetic macular edema.

Faghihi H, Roohipoor R, Mohammadi SF, Hojat-Jalali K, Mirshahi A, Lashay A, Piri 
N, Faghihi Sh.

Eye Research Center, Farabi Eye Hospital, Medical Sciences/University of Tehran
and Ophthalmic Research Center, Noor Eye Hospital, Tehran - Iran.

PURPOSE. To evaluate the additive effect of triamcinolone to bevacizumab in
comparison to standard macular laser photocoagulation versus bevacizumab in the
management of diabetic macular edema (DME). METHODS. In a prospective, randomized
clinical trial, 130 eyes of 110 patients with type 2 diabetes with DME were
included. Eligible eyes were randomly assigned to 1.25 mg intravitreal
bevacizumab (42 eyes) (IVB group) or combination of 1.25 mg bevacizumab and 2 mg 
triamcinolone acetonide (41 eyes) (IVB+IVT group) or macular laser
photocoagulation (47 eyes) (MPC). Central macular thickness (CMT) and visual
acuity changes at week 6 and 16 were assessed. RESULTS. The mean age of the
patients was 57 -/+7 years. Patients were followed 16 weeks. At week 6, all the
three groups showed significant reduction in CMT but the reductions for IVB and
IVB+IVT were significantly more than MPC (p<0.001). At week 16, the response was 
not stable for IVB (p<0.001), but IVB+IVT maintained its superior status to MPC
(p<0.001). At week 16, visual acuities were essentially unchanged for the two
groups of MPC and IVB and improvement for IVB+IVT was marginal and at most was
0.1 log MAR. No patient developed uveitis, endophthalmitis, or thromboembolic
event. CONCLUSIONS. Single intravitreal bevacizumab or triamcinolone plus
bevacizumab injection brought about significantly greater macular thickness
reduction in diabetic patients in comparison to standard laser treatment.
However, the response for bevacizumab alone was short-lived. Reduction in macular
thickness was only marginally associated with visual acuity improvement in the
triamcinolone plus bevacizumab injection group.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial

PMID: 18988166 [PubMed - indexed for MEDLINE]

50: Clin Interv Aging. 2008;3(3):581-93.

Can HMG Co-A reductase inhibitors ("statins") slow the progression of age-related
macular degeneration? The age-related maculopathy statin study (ARMSS).

Guymer RH, Dimitrov PN, Varsamidis M, Lim LL, Baird PN, Vingrys AJ, Robman L.

Centre for Eye Research Australia, University of Melbourne, Melbourne, Victoria, 
Australia.

Age-related macular degeneration (AMD) is responsible for the majority of visual 
impairment in the Western world. The role of cholesterol-lowering medications,
HMG Co-A reductase inhibitors or statins, in reducing the risk of AMD or of
delaying its progression has not been fully investigated. A 3-year prospective
randomized controlled trial of 40 mg simvastatin per day compared to placebo in
subjects at high risk of AMD progression is described. This paper outlines the
primary aims of the Age-Related Maculopathy Statin Study (ARMSS), and the
methodology involved. Standardized clinical grading of macular photographs and
comparison of serial macular digital photographs, using the International grading
scheme, form the basis for assessment of primary study outcomes. In addition,
macular function is assessed at each visit with detailed psychophysical
measurements of rod and cone function. Information collected in this study will
assist in the assessment of the potential value of HMG Co-A reductase inhibitors 
(statins) in reducing the risk of AMD progression.

Publication Types: 
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18982929 [PubMed - indexed for MEDLINE]

51: Clin Interv Aging. 2008;3(3):473-82.

Age-related macular degeneration and the aging eye.

Ehrlich R, Harris A, Kheradiya NS, Winston DM, Ciulla TA, Wirostko B.

Indiana University School of Medicine, Department of Ophthalmology, Indianapolis,
IN 46202, USA.

Age-related macular degeneration (AMD) is an ocular disease that causes damage to
the retinal macula, mostly in the elderly. Normal aging processes can lead to
structural and blood flow changes that can predispose patients to AMD, although
advanced age does not inevitably cause AMD. In this review, we describe changes
that occur in the macular structure, such as the retinal pigment epithelium and
Bruch's membrane, with advancing age and in AMD. The role of genetics in AMD and 
age-related changes in ocular blood flow that may play a role in the pathogenesis
of AMD are also discussed. Understanding the pathophysiology of AMD development
can help guide future research to further comprehend this disease and to develop 
better treatments to prevent its irreversible central vision loss in the elderly.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18982917 [PubMed - indexed for MEDLINE]

52: Med Image Comput Comput Assist Interv Int Conf Med Image Comput Comput Assist
Interv. 2008;11(Pt 1):883-91.

Geometric deformable model driven by CoCRFs: application to optical coherence
tomography.

Tsechpenakis G, Lujan B, Martinez O, Gregori G, Rosenfeld PJ.

Dept. of Electrical and Computer Engineering, University of Miami, USA.
gavriil@miami.edu

We present a geometric deformable model driven by dynamically updated probability
fields. The shape is defined with the signed distance function, and the internal 
(smoothness) energy consists of a C1 continuity constraint, a shape prior, and a 
term that forces the zero-level of the shape distance function towards a
connected form. The image probability fields are estimated by our collaborative
Conditional Random Field (CoCRF), which is updated during the evolution in an
active learning manner: it infers class posteriors in pixels or regions with
feature ambiguities by assessing the joint appearance of neighboring sites and
using the classification confidence. We apply our method to Optical Coherence
Tomography fundus images for the segmentation of geographic atrophies in dry
age-related macular degeneration of the human eye.

Publication Types: 
    Evaluation Studies

PMID: 18979829 [PubMed - indexed for MEDLINE]

53: J Mol Biol. 2008 Dec 31;384(5):1341-52. Epub 2008 Oct 19.

Uncontrolled zinc- and copper-induced oligomerisation of the human complement
regulator factor H and its possible implications for function and disease.

Nan R, Gor J, Lengyel I, Perkins SJ.

Institute of Structural and Molecular Biology, Division of Biosciences, and
Department of Ocular Biology and Therapeutics, Darwin Building, University
College London, Gower Street, London WC1E 6BT, UK.

Polymorphisms in factor H (FH), a major regulator of complement activation, and
the accumulation of high zinc concentrations in the outer retina are both
associated with age-related macular degeneration. FH is inhibited by zinc, which 
causes FH to aggregate. To investigate this, we quantitatively studied
zinc-induced FH self-association by X-ray scattering and analytical
ultracentrifugation to demonstrate uncontrolled FH oligomerisation in conditions 
corresponding to physiological levels of FH and pathological levels of zinc in
the outer retina. By scattering, FH at 2.8-7.0 microM was unaffected until [Zn]
increased to 20 microM, whereupon the radius of gyration, RG, values increased
from 9 to 15 nm at [Zn]=200 microM. The maximum dimension of FH increased from 32
to 50 nm, indicating that compact oligomers had formed. By ultracentrifugation,
size-distribution analyses showed that monomeric FH at 5.57 S was the major
species at [Zn] up to 60 microM. At [Zn] above 60 microM, a series of large
oligomers were formed, ranging up to 100 S in size. Oligomerisation was reversed 
by ethylenediaminetetraacetic acid. Structurally distinct large oligomers were
observed for Cu, while Ni, Cd and Fe showed low amounts of oligomers and Mg and
Ca showed no change. Fluid-phase assays showed reduced FH activities that
correlated with increased oligomer formation. The results were attributed to
different degrees of stabilisation of weak self-dimerisation sites in FH by
transition metals. The relevance of metal-induced FH oligomer formation to
complement regulation and age-related macular degeneration is discussed.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18976665 [PubMed - indexed for MEDLINE]

54: Clin Experiment Ophthalmol. 2008 Aug;36(6):514-20.

Visual function and performance with blue-light blocking filters in age-related
macular degeneration.

Kiser AK, Deschler EK, Dagnelie G.

Lions Vision Center, Wilmer Eye Institute, Johns Hopkins University, Baltimore,
Maryland 21205-2020, USA. abittne1@jhmi.edu

PURPOSE: Some dispute has occurred over the use of blue-light-attenuating
intraocular lenses in age-related macular degeneration (AMD), as they may reduce 
scotopic vision. This study aimed to determine if a blue blocking filter would
affect performance during eye-hand coordination and mobility tasks in scotopic
illumination, psychophysically measured scotopic sensitivity or colour
discrimination in AMD patients. METHODS: Scotopic measures performed with and
without a blue-attenuating filter included a mobility obstacle course,
manipulation of cylindrical blocks and a psychophysical dark-adapted full-field
flash test. A navy and blue sock colour sorting task evaluated photopic colour
discrimination. Subjects were 22 bilateral pseudophakes with early AMD and visual
acuity >6/24. RESULTS: On average with the filter, there was a 13% increase in
time during the block test. The differences in time and number of bumps with
versus without the filter were not significant for the mobility course.
Performance with and without the filter was well correlated for the blocks (r =
0.70), flash test (r = 0.83) and mobility (r = 0.66), and the regression slopes
were not significantly different from unity. 77% of subjects misidentified at
least one navy sock as black with the filter compared with 9% without, with a
significant increase in such misidentifications with the filter. CONCLUSIONS: The
difference in scotopic visual function or performance with versus without a
blue-blocking filter most likely does not produce a clinically significant effect
or risk; however, detection of navy colour may be impaired.

Publication Types: 
    Comparative Study

PMID: 18954312 [PubMed - indexed for MEDLINE]

55: Br J Ophthalmol. 2008 Dec;92(12):1581-90. Epub 2008 Oct 24.

Interventions for diabetic macular oedema: a systematic review of the literature.

O'Doherty M, Dooley I, Hickey-Dwyer M.

Limerick Regional Hospital, Limerick, Ireland. maeveodoherty@gmail.com

OBJECTIVES: This review discusses the evolution of the treatment of diabetic
macular oedema and gives helpful guidelines in the treatment of diabetic macular 
oedema based on available evidence to date. METHODS: A literature search of all
English articles from the Medline and Cochrane database was performed. The search
was limited to only English randomised controlled clinical trials in humans.
Overall, 93 articles were cited from 1979 to 2007. Of these, 31 articles
corresponded to subject matter. Studies were evaluated on a standardised data
extraction form and tabulated for easy review. RESULTS: There is good evidence
that laser treatment preserves vision in eyes with diabetic macular oedema (DMO).
However, laser is a potentially destructive form of treatment which may be of
greater benefit in combination with newer forms of treatment such as intravitreal
steroid or intravitreal antiangiogenic agents. Current evidence does not support 
a clear benefit for surgical intervention in DMO. CONCLUSIONS: Although laser
treatment remains the cornerstone of treatment in diabetic macular oedema, the
literature is beginning to support combination therapy. Using one or two
intravitreal injections to reduce central macular thickness followed by focal or 
grid laser to give a sustained response may offer an alternative to treatment in 
DMO.

Publication Types: 
    Review

PMID: 18952646 [PubMed - indexed for MEDLINE]

56: Br J Ophthalmol. 2009 Jan;93(1):91-5. Epub 2008 Oct 24.

Effect of 308 nm excimer laser irradiation on retinal pigment epithelium cell
viability in vitro.

Krohne TU, Hunt S, Holz FG.

Department of Ophthalmology, University of Bonn, Ernst-Abbe-Str. 2, D-53127 Bonn,
Germany. krohne@uni-bonn.de

BACKGROUND: Translocation of an autologous retinal pigment epithelium (RPE) sheet
under the macula is currently under investigation as a treatment for exudative
AMD. Excimer laser-assisted RPE sheet translocation (EST) employs intraocular
excimer ablation of excess graft choroidal tissue as a measure to enhance RPE
sheet functionality. This study assessed potential adverse effects of excimer
irradiation on RPE cells in vitro. METHODS: Human RPE cells (ARPE-19) received
308 nm XeCl excimer laser treatment or 311-312 nm UV-B irradiation. Cell death
was visualised with Trypan Blue and quantified by LDH release assay. Apoptosis
was detected by DNA fragmentation assay. RESULTS: Laser treatment of 0.175-0.25
J/cm(2) resulted in delayed cell death within 48 h. Time course and dose response
paralleled the effect of UV-B irradiation. Cytotoxicity was mediated by
apoptosis. Human choroid/Bruch membrane tissue sheets covering the cells during
laser irradiation reduced cytotoxicity by 87-95%. CONCLUSION: Cultured human RPE 
cells are susceptible to apoptotic cell death induced by 308 nm excimer laser
irradiation. Absorption by choroid/Bruch membrane tissue can largely prevent the 
cytotoxic effect. In clinical application, the residual adverse effect of laser
ablation on graft RPE cell viability needs to be outweighed by potential
advantageous effects on graft survival and functionality to allow for a sensible 
application of excimer ablation in RPE translocation surgery.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18952645 [PubMed - indexed for MEDLINE]

57: Clin Experiment Ophthalmol. 2008 Jul;36(5):437-42.

Correlation between CFH Y402H and HTRA1 rs11200638 genotype to typical exudative 
age-related macular degeneration and polypoidal choroidal vasculopathy phenotype 
in the Japanese population.

Gotoh N, Yamada R, Nakanishi H, Saito M, Iida T, Matsuda F, Yoshimura N.

Department of Ophthalmology, Fukushima Medical University School of Medicine,
Fukushima, Japan.

BACKGROUND: Typical exudative age-related macular degeneration (AMD) and
polypoidal choroidal vasculopathy (PCV) are two of the major macular diseases
found in Asians. Although genomic studies have shown a contribution by CFH and
LOC387715/HTRA1 polymorphisms to the development of these two diseases, the
correlation of the clinical phenotypes to these genotypes has not been determined
in Asian patients. METHODS: The prevalence of the CFH Y402H and HTRA1 rs11200638 
genotypes was determined in 116 patients with typical exudative AMD and in 204
patients with PCV. Potential correlations of these polymorphisms were tested
retrospectively and cross-sectionally for bilaterality of the disease, final
visual acuity and the greatest linear dimension of the choroidal neovascular
(CNV) lesion. RESULTS: There was no significant difference in the incidence of
CFH Y402H (P = 0.598) and HTRA1 rs11200638 (P = 0.290) between eyes with typical 
exudative AMD and with PCV. There was a significant association between the
lesion size and HTRA1 rs11200638. For eyes with typical AMD, the size of the
lesion (6363 +/- 2837 microm) was significantly larger in the high-risk
homozygous group (AA), than in the low-risk homozygous group (GG) (3866 +/- 1947 
microm; P = 0.0003). The same tendency was observed for the size of the lesion in
PCV cases (homozygous group: 6347 +/- 2673 microm, non-risk homozygous group:
4405 +/- 2066 microm, P = 1.3 x 10(-5). CONCLUSIONS: A common genetic background 
may exist between typical exudative AMD and PCV patients. Among the patients with
these two clinical entities, those with a homozygous HTRA1 rs11200638 risk allele
had larger CNV lesions.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18939352 [PubMed - indexed for MEDLINE]

58: Invest Ophthalmol Vis Sci. 2009 Feb;50(2):586-91. Epub 2008 Oct 20.

Peripheral retinal drusen and reticular pigment: association with CFHY402H and
CFHrs1410996 genotypes in family and twin studies.

Seddon JM, Reynolds R, Rosner B.

Ophthalmic Epidemiology and Genetics Service, Department of Ophthalmology, Tufts 
University School of Medicine and Tufts Medical Center, New England Eye Center,
Boston, Massachusetts 02111, USA. jseddon@tuftsmedicalcenter.org

PURPOSE: To evaluate the relationship between peripheral retinal drusen and
reticular pigment changes and genotypes associated with age-related macular
degeneration (AMD). METHODS: Using standard protocols, 2103 family members and
twins were examined. Clinical and photographic data were graded according to the 
Clinical Age-Related Maculopathy Grading System (CARMS) as grade 1 (no AMD),
grade 2 (small drusen and/or pigment irregularities), grade 3 (intermediate AMD),
grade 4 (central or noncentral geographic atrophy), or grade 5 (neovascular
disease). Peripheral drusen and reticular pigment were assessed with a
standardized examination. Associations between six AMD genetic variants and
retinal phenotypes were analyzed. RESULTS: AMD grade was associated with
peripheral drusen and reticular pigment (odds ratio [OR] 1.9 for advanced AMD;
P<0.001). Both peripheral retinal phenotypes were associated with AMD related
genotypes. For CFHY402H, the OR was 2.8 for the CC genotype versus TT (P for
trend<0.001, with increase in peripheral drusen with each additional risk [C]
allele). Similar results were seen for CFHrs1410996. Reticular pigment was
related to CFHY402H, with OR 2.0 for the CC genotype versus TT (P for
trend<0.001, for increase in pigment with each risk allele) and to CFHrs1410996
(P for trend=0.006). These findings were not seen for the LOC387715 A69S gene
region, CFB, C2, or C3. Among individuals with no or minimal maculopathy, CFH
variants were associated with more than a twofold increased risk of drusen and
reticular pigment. CONCLUSIONS: Peripheral retinal drusen and reticular pigment
are associated with AMD and with CFHY402H and CFHrs1410996 genotypes, adjusting
for AMD grade. These phenotypes may be a marker of genetic susceptibility for
patients with or without AMD.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Twin Study

PMID: 18936151 [PubMed - indexed for MEDLINE]

59: Ophthalmology. 2008 Dec;115(12):2192-8. Epub 2008 Oct 18.

Computerized model of cost-utility analysis for treatment of age-related macular 
degeneration.

Fletcher EC, Lade RJ, Adewoyin T, Chong NV.

King's College Hospital, London, United Kingdom. emily_cfletcher@yahoo.co.uk

PURPOSE: To present a computerized model assessing individualized cost utility
for current treatments for neovascular age-related macular degeneration (AMD) to 
enhance discussion regarding treatment options. DESIGN: Case- and eye-specific
cost-utility analysis using individual case scenarios. PARTICIPANTS: Visual
acuity data from published randomized controlled trials are incorporated into
this analysis. METHODS: Computerized model (Microsoft Visual Basic 6.0
programming) to establish preference-based cost-utility analysis in association
with individual cost of treatment and blindness for neovascular AMD for both the 
better and worst seeing eye, with extrapolation of results over a 5-year term.
MAIN OUTCOME MEASURES: Cost per quality-adjusted life-year (QALY) and cost per
QALY gained for comparison of treatments for specific visual acuities. RESULTS:
All treatments show an increase in utility in comparison with best supportive
care (BSC) if the better-seeing eye is treated. Ranibizumab, using the Phase
IIIb, Multicenter, Randomized, Double-Masked, Sham Injection-Controlled Study of 
the Efficacy and Safety of Ranibizumab in Subjects with Subfoveal Choroidal
Neovascularisation (CNV) with or without Classic CNV Secondary to AMD (PIER)
regimen, is the most cost effective at $626 938 per QALY gained for treatment of 
the better seeing eye. To increase utility value when treating the worst seeing
eye, the vision must improve to such a degree that it becomes the better seeing
eye. This level of improvement is only possible if there is <9 letters difference
between the 2 eyes and treated with ranibizumab. Over 5 years, increasing
influence from the cost of blindness results in increasing costs for those
treatments unable to stabilize vision. Within 5 years, the cost per QALY for the 
BSC is greater than all treatments except monthly ranibizumab injections.
CONCLUSIONS: Assessment of cost of treatment incorporates both effectiveness of
treatment, cost of treatment, and cost of blindness. Cost analysis enables
incorporation of these aspects of treatment with the quality of life data to
provide a better comparison of treatments over time. This analysis has provided a
method for individual analysis and therefore can provide the structure for
resource allocation. FINANCIAL DISCLOSURE(S): The authors have no proprietary or 
commercial interest in any materials discussed in this article.

PMID: 18930556 [PubMed - indexed for MEDLINE]

60: Ophthalmology. 2008 Dec;115(12):2199-205. Epub 2008 Oct 18.

Is there tachyphylaxis to intravitreal anti-vascular endothelial growth factor
pharmacotherapy in age-related macular degeneration?

Schaal S, Kaplan HJ, Tezel TH.

Department of Ophthalmology and Visual Sciences, Kentucky Lions Eye Center,
University of Louisville School of Medicine, Louisville, Kentucky 40202, USA.

PURPOSE: To determine whether repetitive injections of intravitreal bevacizumab
and/or triamcinolone acetate in patients with exudative age-related macular
degeneration (AMD) results in a decrease in biological response. DESIGN:
Retrospective comparative case series. PARTICIPANTS: Forty-three eyes of 43
patients with exudative AMD. METHODS: Pre- and postinjection optical coherence
tomography (OCT) sections of 43 patients with AMD were analyzed to determine the 
change in the biologic response after each subsequent injection of intravitreal
bevacizumab (2.5 mg/100 microL), preservative-free triamcinolone acetonide (pfTA)
(4.0 mg/100 microL), or a combination of bevacizumab (1.25 mg/50 microL) and pfTA
(2.0 mg/50 microL). The retinal thickness of each OCT sector was determined and
expressed as volume. Standardized volumetric change index (SVCI) was determined
to identify a statistically significant change. Pre- and postinjection (6 weeks) 
SVCI differences were plotted as a function of time to determine the biological
response after each intravitreal treatment. MAIN OUTCOME MEASURES: Change in SVCI
after intravitreal injections and the number of injections required to decrease
the biological response by 50% (INJ(50)). RESULTS: There was no difference in the
age, gender, and preinjection thickness of the retina in each of the 3 groups.
The SVCI after intravitreal bevacizumab injections decreased, indicating a
possible tachyphylactic response to bevacizumab. This decrease in biological
response was partially alleviated with the addition of pfTA. Combination of pfTA 
and bevacizumab increased the INJ(50) from 2.9 with bevacizumab alone to 5.1
injections. A biphasic biologic response was observed with pfTA characterized by 
a rapid increase in efficacy with the second injection, peaking at the third
injection and gradually decreasing afterward. CONCLUSIONS: Repeated intravitreal 
injections of bevacizumab in exudative AMD seemed to be associated with decreased
bioefficacy. However, combined pharmacotherapy with triamcinolone acetate
lessened this effect. Thus, multitargeted pharmacotherapy in exudative AMD may
have a therapeutic benefit. FINANCIAL DISCLOSURE(S): Proprietary or commercial
disclosure may be found after the references.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18930553 [PubMed - indexed for MEDLINE]

61: Ophthalmology. 2008 Dec;115(12):2206-14. Epub 2008 Oct 18.

Relationship between optical coherence tomography retinal parameters and visual
acuity in neovascular age-related macular degeneration.

Keane PA, Liakopoulos S, Chang KT, Wang M, Dustin L, Walsh AC, Sadda SR.

Doheny Image Reading Center, Doheny Eye Institute, Keck School of Medicine of the
University of Southern California, Los Angeles, California 90033, USA.

PURPOSE: To investigate the relationship between optical coherence tomography
(OCT)-derived measurements of retinal morphology and visual acuity in patients
with neovascular age-related macular degeneration (AMD). DESIGN: Retrospective
cross-sectional study. PARTICIPANTS: A total of 216 consecutive patients (216
eyes) newly diagnosed with neovascular AMD who underwent StratusOCT imaging at
the time of diagnosis. METHODS: Best-corrected Snellen visual acuity was recorded
for each patient. Raw exported StratusOCT images for each patient were analyzed
using publicly available custom software entitled "OCTOR," which allows the
precise positioning of prespecified boundaries on individual B-scans. Thickness
and volume were calculated for morphologic parameters of interest: neurosensory
retina, subretinal fluid, subretinal tissue (SRT), and pigment epithelial
detachment. MAIN OUTCOME MEASURES: OCT-derived measurements of retinal morphology
and visual acuity. RESULTS: An increased total volume of SRT was correlated with 
decreased visual acuity (r = 0.370, P<0.0001). Decreased visual acuity was also
modestly correlated with increased thickness of the neurosensory retina at the
foveal center point (r = 0.245, P = 0.0004). No statistically significant
association was detected between visual acuity and the total volume of subretinal
fluid or pigment epithelial detachment. The association between visual acuity and
both the neurosensory retina and the SRT was stronger for lesions classified as
minimally classic or occult on fluorescein angiography. For occult lesions, 20%
of the variation in visual acuity could be predicted by a multiple regression
model that incorporated age and SRT volume, whereas, for minimally classic
lesions, 62% of the variation in visual acuity could be predicted by a multiple
regression model that incorporated age, total neurosensory retinal volume, and
total SRT volume. CONCLUSIONS: The presence of increased SRT thickness and volume
on OCT, and to a lesser extent increased neurosensory retinal thickness and
volume, is associated with decreased visual acuity in neovascular AMD. However,
because of the complex pathophysiology of neovascular AMD and, in part, the
limitations of StratusOCT, these factors only account for a small degree of the
variation in visual acuity that these patients exhibit. The detection of stronger
correlations between retinal anatomy and visual acuity is likely to require the
use of more advanced imaging modalities. FINANCIAL DISCLOSURE(S): Proprietary or 
commercial disclosure may be found after the references.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 18930551 [PubMed - indexed for MEDLINE]

62: Am J Ophthalmol. 2009 Feb;147(2):267-275.e2. Epub 2008 Oct 17.

Prospective comparison of cirrus and stratus optical coherence tomography for
quantifying retinal thickness.

Kiernan DF, Hariprasad SM, Chin EK, Kiernan CL, Rago J, Mieler WF.

University of Chicago Hospitals, Ophthalmology and Visual Sciences, Chicago,
Illinois, USA.

PURPOSE: To compare Cirrus Fourier-domain optical coherence tomography (OCT) with
Stratus time-domain OCT for imaging retinal diseases and quantifying retinal
thickness (RT) of all nine OCT zones, central macular thickness, and average
macular thickness in eyes with and without macular edema. DESIGN: Prospective
comparison between two OCT systems. METHODS: RT measurements were performed in
120 eyes of 60 patients suspected of having increased retina thickness using both
Stratus and Cirrus OCT on the same day. Twenty-one eyes had both 512 x 128 and
200 x 200 Cirrus cube scans done. RESULTS: Data from 101 eyes (53 patients) were 
analyzed; 46 eyes (45.5%) had macular edema on clinical examination (Group 1),
whereas 55 eyes (54.4%) had no clinical evidence of macular edema (Group 2).
There was modest correlation between all thickness measurements in 909 zones and 
each group (range of Pearson correlation, 0.51 to 0.89) and average value was
significantly greater when measured with Cirrus OCT for all eyes (mean
difference, 43.2 microm; P < .0001). There were few measurement differences
between different resolution Cirrus cube scans. CONCLUSIONS: Cirrus OCT measures 
RT approximately 43 microm greater than Stratus OCT, which is likely attributable
to Cirrus OCT detection of the outer band of the retinal pigment epithelium vs
Stratus OCT detection of the inner/outer segment photoreceptor junction. All
zones showed a wide degree of variability in correlation. Both Cirrus cube scans 
provide similar data. Future studies comparing these systems might consider
utilizing average macular thickness values, which reflect macular volume and may 
provide more consistent measurements.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 18929353 [PubMed - indexed for MEDLINE]

63: Am J Ophthalmol. 2009 Feb;147(2):291-297.e2. Epub 2008 Oct 17.

Combined laser and intravitreal triamcinolone for proliferative diabetic
retinopathy and macular edema: one-year results of a randomized clinical trial.

Maia OO Jr, Takahashi BS, Costa RA, Scott IU, Takahashi WY.

Department of Ophthalmology, Hospital São Rafael, Monte Tabor Foundation,
Salvador, BA, Brazil. omaiausp@uol.com.br

PURPOSE: To evaluate laser combined with intravitreal triamcinolone acetonide
(IVTA) for the management of patients with proliferative diabetic retinopathy
(PDR) and clinically significant macular edema (CSME). DESIGN: Randomized
clinical trial. METHODS: settings: Single center. study population: Twenty-two
patients with bilateral treatment-naïve moderate PDR and CSME. intervention:
Laser (panretinal and macular) photocoagulation was performed in each eye,
followed by IVTA in one randomly assigned eye. Best-corrected visual acuity
(BCVA), fundus photography, and optical coherence tomography were performed at
baseline and at months 1, 3, 6, 9, and 12. main outcome measures: Changes in
BCVA, central macular thickness (CMT), and total macular volume (TMV). RESULTS:
The mean logarithm of the minimal angle of resolution (logMAR) BCVA improved
significantly, and mean CMT and TMV were significantly reduced in the IVTA group 
compared with the laser-only group (controls) at all study follow-up visits (P < 
.001). The mean logMAR BCVA (Snellen equivalent) was 0.44 (20/50(-2)) for the
IVTA group and 0.38 (20/50(+1)) for the controls at baseline, and 0.12
(20/25(-1)) for the IVTA group and 0.32 (20/40(-1)) for the controls at 12 months
(P < .001). The mean CMT and TMV were, respectively, 360 microm and 8.59 mm(3)
for the IVTA group and 331 microm and 8.44 mm(3) for the controls at baseline,
and 236 microm and 7.32 mm(3) for the IVTA group and 266 microm and 7.78 mm(3)
for the controls at 12 months (P < .001). CONCLUSIONS: The combination of laser
photocoagulation with IVTA was associated with improved BCVA and decreased CMT
and TMV when compared with laser photocoagulation alone for the treatment of
moderate PDR with CSME.

Publication Types: 
    Randomized Controlled Trial

PMID: 18929352 [PubMed - indexed for MEDLINE]

64: Ophthalmology. 2008 Oct;115(10):1837-46.

Anti-vascular endothelial growth factor pharmacotherapy for age-related macular
degeneration: a report by the American Academy of Ophthalmology.

Ip MS, Scott IU, Brown GC, Brown MM, Ho AC, Huang SS, Recchia FM; American
Academy of Ophthalmology.

American Academy of Ophthalmology, Box 7424, San Francisco, CA 94120, USA.

OBJECTIVE: To examine the evidence about the safety and efficacy of anti-vascular
endothelial growth factor (VEGF) pharmacotherapies for the treatment of
neovascular age-related macular degeneration (AMD). DESIGN: Literature searches
were conducted in May and October 2007 in PubMed with no date restrictions,
limited to articles published in English, and in the Cochrane Central Register of
Controlled Trials without a language limitation and yielded 310 citations. The
first author reviewed the abstracts of these articles and selected 73 articles of
possible clinical relevance for review by the panel. The panel deemed 64 of these
articles sufficiently clinically relevant to review in full text and assigned
ratings of level of evidence to each of the selected articles with the guidance
of the panel methodologists. RESULTS: Eleven studies provided level I evidence
for intravitreal pegaptanib and ranibizumab for neovascular AMD; there were no
studies rated level I for bevacizumab for neovascular AMD. Five studies were
rated as level II, which included studies of ranibizumab and bevacizumab, and the
remaining 38 articles retrieved were rated as level III. The studies do not
provide information about long-term results or the value (comparative
effectiveness) and cost-effectiveness of combined therapies. CONCLUSIONS: Review 
of the available literature to date suggests that anti-VEGF pharmacotherapy,
delivered by intravitreal injection, is a safe and effective treatment for
neovascular AMD for up to 2 years. There is level I evidence to support this
conclusion for pegaptanib and ranibizumab, but none for bevacizumab at this time.

Publication Types: 
    Meta-Analysis
    Research Support, Non-U.S. Gov't

PMID: 18929163 [PubMed - indexed for MEDLINE]

65: Exp Neurol. 2008 Dec;214(2):347-61. Epub 2008 Sep 27.

Elucidating the phenomenon of HESC-derived RPE: anatomy of cell genesis,
expansion and retinal transplantation.

Vugler A, Carr AJ, Lawrence J, Chen LL, Burrell K, Wright A, Lundh P, Semo M,
Ahmado A, Gias C, da Cruz L, Moore H, Andrews P, Walsh J, Coffey P.

Department of Ocular Biology and Therapeutics, Institute of Ophthalmology,
University College London, 11-43 Bath Street, London, EC1V 9EL, UK.
a.vugler@ucl.ac.uk

Healthy Retinal Pigment Epithelium (RPE) cells are required for proper visual
function and the phenomenon of RPE derivation from Human Embryonic Stem Cells
(HESC) holds great potential for the treatment of retinal diseases. However,
little is known about formation, expansion and expression profile of RPE-like
cells derived from HESC (HESC-RPE). By studying the genesis of pigmented foci we 
identified OTX1/2-positive cell types as potential HESC-RPE precursors. When
pigmented foci were excised from culture, HESC-RPE expanded to form extensive
monolayers, with pigmented cells at the leading edge assuming a precursor role:
de-pigmenting, proliferating, expressing keratin 8 and subsequently
re-differentiating. As they expanded and differentiated in vitro, HESC-RPE
expressed markers of both developing and mature RPE cells which included OTX1/2, 
Pax6, PMEL17 and at low levels, RPE65. In vitro, without signals from a
developing retinal environment, HESC-RPE could produce regular, polarised
monolayers with developmentally important apical and basal features. Following
transplantation of HESC-RPE into the degenerating retinal environment of Royal
College of Surgeons (RCS) dystrophic rats, the cells survived in the subretinal
space, where they maintained low levels of RPE65 expression and remained out of
the cell cycle. The HESC-RPE cells responded to the in vivo environment by
downregulating Pax6, while maintaining expression of other markers. The presence 
of rhodopsin-positive material within grafted HESC-RPE indicates that in the
future, homogenous transplants of this cell type may be capable of supporting
visual function following retinal dystrophy.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18926821 [PubMed - indexed for MEDLINE]

66: Pharmacogenomics. 2008 Oct;9(10):1547-50.

CFH and LOC387715/ARMS2 genotypes and antioxidants and zinc therapy for
age-related macular degeneration.

Lee AY, Brantley MA Jr.

Department of Ophthalmology and Visual Sciences, Campus Box 8096, Washington
University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA.

EVALUATION OF: Klein ML, Francis PJ, Rosner B et al.: CFH and LOC387715/ARMS2
genotypes and treatment with antioxidants and zinc for age-related macular
degeneration. Ophthalmology 115(6), 1019-1025 (2008). The late form of
age-related macular degeneration (AMD) is a leading cause of irreversible vision 
loss in the elderly, with a complex etiology involving genetic and environmental 
factors. Recently, multiple distinct genetic susceptibility loci for AMD have
been identified. Specifically, variations in the Complement Factor H (CFH) gene
as well as the LOC387715/ARMS2 gene have been shown to be strongly associated
with AMD. The Age-Related Eye Disease Study (AREDS) is a large multicenter,
placebo-controlled, randomized clinical trial that showed that a combination of
zinc and antioxidants reduced progression to late-stage AMD. In the present
study, the authors found that within AREDS there was a significant interaction
between zinc and CFH genotypes, indicating that CFH genotypes may be predictive
of treatment response to zinc supplementation.

PMID: 18855541 [PubMed - indexed for MEDLINE]

67: Mol Vis. 2008;14:1829-34. Epub 2008 Oct 8.

Association of complement factor H Y402H polymorphism with phenotype of
neovascular age related macular degeneration in Israel.

Chowers I, Cohen Y, Goldenberg-Cohen N, Vicuna-Kojchen J, Lichtinger A, Weinstein
O, Pollack A, Axer-Siegel R, Hemo I, Averbukh E, Banin E, Meir T, Lederman M.

Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Hebrew
University School of Medicine, Jerusalem, Israel. chowers@hadassah.org.il

PURPOSE: The Tyr402His variant of complement factor H (CFH) is associated with
age-related macular degeneration (AMD) in several populations. Our aim was to
evaluate if this single nucleotide polymorphism (SNP) is associated with AMD in
the Israeli population and see if it underlies heterogeneity in clinical
manifestation and responses to photodynamic therapy (PDT), which characterize
neovascular AMD (NVAMD). METHODS: Genotyping for the Tyr402His variant was
performed in 240 NVAMD patients (78.1+/-7 age range) and 118 controls (70.8+/-8.2
age range). Genotyping was correlated with clinical characteristics and treatment
parameters in sequential 131 NVAMD patients who underwent PDT. RESULTS:
TheTyr402His coding allele was associated with NVAMD in the Israeli population:
odds ratio (OR)=1.9; 95% confidence interval (CI)=1.3-2.6; p=0.0002. Homozygosity
for this variant was associated with an OR of 3.4 (95% CI: 1.7-6.8) for having
AMD. There was no association among this SNP and age of onset of NVAMD, gender,
neovascular lesion size, initial or final visual acuity, and number of PDT
sessions required. CONCLUSIONS: In accordance with findings from the majority of 
previous study populations, the Tyr402His variant of CFH is associated with NVAMD
in Israel. However, heterogeneity in clinical manifestations of NVAMD and in its 
response to PDT is not underlined by this CFH variant and may be accounted for by
other genetic and environmental factors.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18852870 [PubMed - indexed for MEDLINE]

68: Arch Ophthalmol. 2008 Oct;126(10):1396-403.

Sunlight exposure, antioxidants, and age-related macular degeneration.

Fletcher AE, Bentham GC, Agnew M, Young IS, Augood C, Chakravarthy U, de Jong PT,
Rahu M, Seland J, Soubrane G, Tomazzoli L, Topouzis F, Vingerling JR, Vioque J.

Department of Epidemiology and Population Health, London School of Hygiene &
Tropical Medicine, Keppel Street, London, England. astrid.fletcher@lshtm.ac.uk

OBJECTIVE: To examine the association of sunlight exposure and antioxidant level 
with age-related macular degeneration (AMD). METHODS: Four thousand seven hundred
fifty-three participants aged 65 years or older in the European Eye Study
underwent fundus photography, were interviewed for adult lifetime sunlight
exposure, and gave blood for antioxidant analysis. Blue light exposure was
estimated by combining meteorologic and questionnaire data. RESULTS: Data on
sunlight exposure and antioxidants were available in 101 individuals with
neovascular AMD, 2182 with early AMD, and 2117 controls. No association was found
between blue light exposure and neovascular or early AMD. Significant
associations were found between blue light exposure and neovascular AMD in
individuals in the quartile of lowest antioxidant level-vitamin C, zeaxanthin,
vitamin E, and dietary zinc-with an odds ratio of about 1.4 for 1 standard
deviation unit increase in blue light exposure. Higher odds ratios for blue light
were observed with combined low antioxidant levels, especially vitamin C,
zeaxanthin, and vitamin E (odds ratio, 3.7; 95% confidence interval, 1.6-8.9),
which were also associated with early stages of AMD. CONCLUSIONS: Although it is 
not possible to establish causality between sunlight exposure and neovascular
AMD, our results suggest that people in the general population should use ocular 
protection and follow dietary recommendations for the key antioxidant nutrients.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18852418 [PubMed - indexed for MEDLINE]

69: Arch Ophthalmol. 2008 Oct;126(10):1367-74.

Combination of photodynamic therapy and intraocular triamcinolone for exudative
age-related macular degeneration and long-term chorioretinal macular atrophy.

Piermarocchi S, Sartore M, Lo Giudice G, Maritan V, Midena E, Segato T.

Department of Ophthalmology, University of Padova, Padova, Italy.
stefano.piermarocchi@unipd.it

OBJECTIVE: To evaluate the long-term effect of intravitreal triamcinolone
acetonide (IVT) treatment combined with photodynamic therapy (PDT) vs PDT alone
for neovascular age-related macular degeneration. METHODS: Prospective randomized
study. Eighty-four patients were enrolled to receive PDT (n = 41) or IVT
treatment followed by PDT (n = 43) within approximately a 7- to 15-day interval. 
All patients were naive to treatment. At baseline and each follow-up visit at 3, 
6, 12, and 24 months, measurement of best-corrected visual acuity (VA),
fluorescein angiography, indocyanine green angiography, and optical coherence
tomography were performed. Mean changes in VA and retreatment rate were
considered as primary outcome indicators. Analysis of vascular choroidal changes 
documented by indocyanine green angiography and fundus autofluorescence
measurements were also performed. RESULTS: Mean VA increased at 1 month of
follow-up but decreased progressively by the 24-month point in both groups (P =
.74). The retreatment rate was significantly lower (P < .001) in the combined
therapy group. Choroidal hypoperfusion/nonperfusion (P < .001) and areas with
decreased/absent fundus autofluorescence within the PDT spot area were
significantly greater with combined therapy (P < .001). CONCLUSIONS: Combination 
IVT treatment with PDT seemed to be more effective for managing neovascular
age-related macular degeneration, but long-term analysis failed to demonstrate
functional benefits.

Publication Types: 
    Randomized Controlled Trial

PMID: 18852414 [PubMed - indexed for MEDLINE]

70: Eur J Ophthalmol. 2008 Sep-Oct;18(5):831-3.

Spectral domain OCT documented resolution of recalcitrant macular edema after
intravitreal bevacizumab in branch retinal vein occlusion.

Chalam KV, Keshavamurthy R, Brar VS.

University of Florida College of Medicine, Department of Ophthalmology,
Jacksonville, FL 32204, USA. kchalam@jax.ufl.edu

PURPOSE: Cystoid macular edema is one of the important causes of visual loss in
branch retinal vein occlusion. Proximity of the cyst to the external limiting
membrane and disruption of the layer on time domain optical coherence tomography 
is associated with poor final visual outcomes. The authors describe pre- and
post-intravitreal bevacizumab spectral domain optical coherence tomography
features in a case of cystoid macular edema associated with branch retinal vein
occlusion that was resolved after treatment with intravitreal bevacizumab.
METHODS: A 50-year-old woman was diagnosed with cystoid macular edema due to
branch retinal vein occlusion and underwent intravitreal injection with
bevacizumab after the primary treatment with laser photocoagulation failed.
RESULTS: The patient's visual acuity recovered from 20/40 to 20/20. Spectral
domain optical coherence tomography documented complete resolution of a large
foveal cyst (150 micronm by 280 micronm) and recovery of the discontinuity of the
external limiting membrane 1 week after treatment. CONCLUSIONS: Spectral domain
optical coherence tomography is a useful tool in identifying the ultrastructural 
changes associated with cystoid macular edema associated with branch retinal vein
occlusion and identifying the possible factors involved in prognosticating visual
outcome after effective treatment.

Publication Types: 
    Case Reports

PMID: 18850569 [PubMed - indexed for MEDLINE]

71: Ophthalmic Epidemiol. 2008 Sep-Oct;15(5):308-16.

Postmenopausal hormone therapy and age-related maculopathy in older women.

Seitzman RL, Mangione C, Ensrud KE, Cauley JA, Stone KL, Cummings SR, Hochberg
MC, Hillier TA, Yu F, Coleman AL.

Department of Ophthalmology, David Geffen School of Medicine, UCLA, Los Angeles, 
California, USA. seitzman@ucla.edu

PURPOSE: To examine the association between postmenopausal hormone therapy and
Age-Related Maculopathy (ARM) in older women and to determine if these
associations vary by smoking status. METHODS: A cross-sectional analysis of 1065 
women of European origin aged > or = 74 years attending the year-10 examination
of the Study of Osteoporotic Fractures was performed. Fundus photographs were
graded for ARM using a modification of the Wisconsin Age-Related Maculopathy
Grading System used in NHANES III. Multiple imputation methods were used to
examine the associations of type and duration of postmenopausal hormone therapy
use with early and late ARM as well as interactions with smoking history.
RESULTS: Compared to never users, Neither estrogen alone (E), Estrogen plus
progestin (E+P), nor duration of use was significantly associated with early ARM 
[odds ratio (OR) E = 1.01, 95% confidence interval (CI) 0.77-1.34; OR E+P = 0.85,
95% CI 0.55-1.35; OR < or = 3 years use = 1.04, 95% CI 0.74-1.47; OR > 3-12 years
use = 0.93, 95% CI 0.64-1.35; OR > 12 years use = 0.95, 95% CI 0.65-1.37] or late
ARM (OR any E/E+P = 0.59, 95% CI 0.29-1.19; OR < or = 3 years use = 0.73, 95% CI 
0.30-1.77; OR > 3 years of use = 0.51, 95% CI 0.22-1.17), though power for late
ARM was limited. Tests for smoking interactions were not significant.
CONCLUSIONS: This study found no evidence to support an association between use
of E, E+P, or duration of use and ARM risk.

Publication Types: 
    Multicenter Study
    Research Support, N.I.H., Extramural

PMID: 18850467 [PubMed - indexed for MEDLINE]

72: Am J Ophthalmol. 2009 Feb;147(2):276-282.e1. Epub 2008 Oct 9.

Reduced zinc and copper in the retinal pigment epithelium and choroid in
age-related macular degeneration.

Erie JC, Good JA, Butz JA, Pulido JS.

Department of Ophthalmology Mayo Clinic, Rochester, Minnesota, USA.
erie.jay@mayo.edu

PURPOSE: To measure zinc and copper levels in the retinal pigment epithelium
(RPE) and choroid complex and in the neural retina in subjects with and without
age-related macular degeneration (AMD). DESIGN: Laboratory investigation.
METHODS: Eighty-eight donor eyes (44 subjects) were analyzed. After retinal
dissection, the RPE and choroid complex was photographed. Using the Minnesota
Grading System (MGS), the RPE and choroid complex was classified into 1 of 4
stages as defined by the Age-Related Eye Disease Study. Subjects without AMD were
defined as both eyes having MGS stage 1; subjects with AMD were defined as both
eyes having MGS stages 2 through 4. Zinc and copper levels were determined by
using an inductively coupled plasma-mass spectrometer. Metal levels from two eyes
of the same subject were averaged and treated as one observation. Differences in 
metal levels were examined by using Wilcoxon rank-sum tests. RESULTS: The mean
RPE and choroid complex zinc level in subjects with AMD (+/- standard deviation, 
223.7 +/- 94.0 microg/g; n = 15) was reduced 24% when compared with that of
subjects without AMD (292.1 +/- 98.5 microg/g; n = 29; P = .01). The mean RPE and
choroid complex copper level in subjects with AMD (5.1 +/- 1.1 microg/g) was
reduced 23% when compared with that of subjects without AMD (6.6 +/- 1.4
microg/g; P = .002). No difference was detected in retinal zinc and copper levels
in subjects with and without AMD (P > .09). CONCLUSIONS: Reduced RPE and choroid 
complex zinc and copper levels in AMD eyes combined with previous information
that oral supplementation of zinc plus copper reduces the risk of progression of 
AMD suggests that metal homeostasis plays a role in AMD and in retinal health.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18848316 [PubMed - indexed for MEDLINE]

73: Cochrane Database Syst Rev. 2008 Oct 8;(4):CD006928.

Macular translocation for neovascular age-related macular degeneration.

Eandi CM, Giansanti F, Virgili G.

Department of Clinical Physiopathology, Eye Clinic, University of Torino, Via
Juvarra 19, Torino, Italy, 10122. chiara.eandi@unito.it

BACKGROUND: Macular translocation has been proposed by vitreoretinal surgeons to 
displace the neuroretinal tissue onto healthy retinal pigment epithelium and
choroid when the macula has been invaded by subretinal neovascularisation.
OBJECTIVES: This review aims at assessing the effectiveness of macular
translocation for preserving or improving vision in patients with neovascular
age-related macular degeneration (AMD). SEARCH STRATEGY: We searched the Cochrane
Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE,
EMBASE and Caribbean Literature on Health Sciences (LILACS). There were no
language or date restrictions in the search for trials.The electronic databases
were last searched on 21 July 2008. SELECTION CRITERIA: We included randomised or
quasi randomised controlled trials comparing macular translocation with any other
treatment or observation. DATA COLLECTION AND ANALYSIS: Two authors independently
extracted the data. The risk ratio (RR) of visual loss and visual gain was
estimated at one year after treatment. MAIN RESULTS: Only one small unblinded
study on 50 people compared full macular translocation with photodynamic therapy 
(PDT) in AMD patients with predominantly classic subfoveal choroidal
neovascularisation (CNV). At the last examination, performed in most of the cases
after one year, there was no difference in the rate of visual loss of 3 or more
lines (translocation versus PDT: RR 0.56, 95% confidence interval (CI) 0.22 to
1.43), as well as in the mean change of contrast sensitivity (1 letter favouring 
translocation; 95% CI -3.51 to 5.51) and the rate of recurrence of CNV
(translocation versus PDT: RR 1.56, 95% CI 0.83 to 2.91). Other outcomes
significantly favoured translocation, such as the gain of 3 or more ETDRS lines
(RR 21, 95% CI 1.30 to 340.02), the mean change of visual acuity (mean difference
(MD) 14.60, 95% CI 5.39 to 23.81) and the mean change of near visual acuity score
(MD 17.80, 95% CI 3.98 to 31.62) which is obtained with an algorithm. Serious
complications reported after macular translocation were retinal detachment in
6/25 patients and diplopia requiring prismatic correction in 5/25 patients.
AUTHORS' CONCLUSIONS: There is insufficient evidence from randomised controlled
trials on the effectiveness of macular translocation, which is also not free of
important risks. Furthermore, this technique is difficult to perform and a long
surgical training is required. Future studies might include patients with small
neovascular lesions that failed to respond to current pharmacological therapies
and are willing to accept the risks associated with surgery to try to improve
visual acuity.

Publication Types: 
    Review

PMID: 18843739 [PubMed - indexed for MEDLINE]

74: Am J Clin Nutr. 2008 Oct;88(4):1104-10.

Dietary glycemic index and the risk of age-related macular degeneration.

Kaushik S, Wang JJ, Flood V, Tan JS, Barclay AW, Wong TY, Brand-Miller J,
Mitchell P.

Centre for Vision Research, Department of Ophthalmology and Westmead Millennium
Institute, University of Sydney, Sydney, Australia.

BACKGROUND: Dietary factors are known risk factors for age-related macular
degeneration (AMD) -- the leading cause of visual loss among persons aged > or
=65 y. High-glycemic-index diets have been hypothesized as a risk factor for AMD,
but prospective data are unavailable. OBJECTIVE: The objective was to examine the
association between dietary glycemic index and the 10-y incidence of AMD in the
Blue Mountain Eye Study population. DESIGN: This was a population-based cohort
study with 3,654 participants (> or =49 y) examined at baseline (1992-1994);
2,335 patients were reexamined after 5 y and 1952 after 10 y. The Wisconsin
System was used to grade 10-y incident early and late AMD from retinal
photographs. A food-frequency questionnaire was used to collect dietary
information at baseline, and an Australian database was used to calculate the
mean glycemic index. RESULTS: Over 10 y, 208 of 1,810 persons (cumulative
incidence: 14.1%) developed early AMD. After age, smoking, other risk factors,
and dietary constituents were adjusted for, a higher mean dietary glycemic index 
was associated with an increased 10-y risk of early AMD in a comparison of
quartiles 1 and 4 [relative risk (RR): 1.77; 95% CI: 1.13, 2.78; P for trend =
0.03]. Conversely, a greater consumption of cereal fiber (RR: 0.68; 95% CI: 0.44,
1.04; P for trend = 0.05) and breads and cereals (predominantly lower glycemic
index foods such as oatmeal) (RR: 0.67; 95% CI: 0.44, 1.02; P for trend = 0.03)
was associated with a reduced risk of incident early AMD. No relation was
observed with late AMD. CONCLUSIONS: A high-glycemic-index diet is a risk factor 
for early AMD -- the recognized precursor of sight-threatening late AMD.
Low-glycemic-index foods such as oatmeal may protect against early AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18842800 [PubMed - indexed for MEDLINE]

75: Lancet. 2008 Nov 22;372(9652):1828-34. Epub 2008 Oct 6.

Comment in:
    Lancet. 2008 Nov 22;372(9652):1788-9.    Lancet. 2009 Feb 7;373(9662):461-2.

Association between the SERPING1 gene and age-related macular degeneration: a
two-stage case-control study.

Ennis S, Jomary C, Mullins R, Cree A, Chen X, Macleod A, Jones S, Collins A,
Stone E, Lotery A.

Genetic Epidemiology and Bioinformatics Group, University of Southampton, Human
Genetics Division (Mp 808), Southampton General Hospital, Southampton, UK.

BACKGROUND: Age-related macular degeneration is the most prevalent form of visual
impairment and blindness in developed countries. Genetic studies have made
advancements in establishing the molecular cause of this disease, identifying
mutations in the complement factor H (CFH) gene and a locus on chromosome 10
encompassing the HTRA1/LOC387715/ARMS2 genes. Variants in complement 3 (C3) and
an HLA locus containing both factor B and C2 genes have also been implicated. We 
aimed to identify further genetic risk factors for this disease. METHODS: We used
a case-control study design in a UK sample of patients with age-related macular
degeneration (n=479) and controls (n=479) and undertook a low-density screen of
32 genes using 93 single nucleotide polymorphisms (SNPs). Genes were selected as 
candidates on the basis of potential functional relevance to age-related macular 
degeneration. Significant initial findings were confirmed by replication in an
independent US cohort of 248 unrelated patients with disease and 252 controls,
and by high-density genotyping around association signals. FINDINGS: The SNP
variant rs2511989, located within intron six of the SERPING1 gene, showed highly 
significant genotypic association with age-related macular degeneration
(uncorrected p=4.0x10(-5), corrected p=0.00372). We detected no evidence for
association between disease and the other 31 candidate genes. The odds ratio for 
age-related macular degeneration in rs2511989 G/A heterozygotes compared with
wild type G/G homozygotes was 0.63 (95% CI 0.47-0.84). A similar comparison of
the A/A homozygotes with the wild type yielded an odds ratio of 0.44 (0.31-0.64).
We replicated the observed genotypic association in a US cohort (p=0.008).
Furthermore, a secondary high-density genotyping study across the SERPING1 gene
region identified five additional SNP variants similarly associated with
age-related macular degeneration (rs2244169, rs2511990, rs2509897, rs1005510, and
rs2511988). INTERPRETATION: Genetic variation in SERPING1 significantly alters
susceptibility to age-related macular degeneration. SERPING1 encodes the C1
inhibitor, which has a crucial role in inhibition of complement component 1 (C1) 
and might implicate the classic pathway of complement activation in this disease.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18842294 [PubMed - indexed for MEDLINE]

76: J Nurs Scholarsh. 2008;40(3):212-8.

Genetic association studies in nursing practice and scholarship.

Underwood PC, Read CY.

Boston College Connell School of Nursing, Chestnut Hill, MA 02467, USA.
underwpa@bc.edu

PURPOSE: To explore the role of genetic association studies in risk assessment
for common complex diseases. ORGANIZING FRAMEWORK: An introduction to the types
of genetic association studies is followed by a discussion of their potential use
in risk assessment for age-related macular degeneration and type 2 diabetes
mellitus. The benefits and limitations of this burgeoning technology are explored
and related to nursing practice and scholarship. CONCLUSIONS: Nurses in practice 
must be prepared to assist clients with decisions about seeking and interpreting 
results from genetic association studies and nurse researchers must apply current
guidelines for conducting robust studies and applying the results of such studies
in clinical practice. CLINICAL RELEVANCE: Data collected from genetic association
studies will increasingly be used to identify novel prevention and treatment
strategies for many complex diseases. An understanding of the principles that
underlie this new science is essential for nurses in all areas of clinical
practice as they design, test, and implement appropriate intervention and
prevention strategies based on genetic association studies.

Publication Types: 
    Review

PMID: 18840203 [PubMed - indexed for MEDLINE]

77: Am J Clin Oncol. 2008 Oct;31(5):488-92.

Assessment of central vision and macular structure in patients undergoing
iodine-125 brachytherapy for ciliochoroidal melanoma.

Oliver SC, Young TA, Kobe LH, Leu MY, Lee SP, Chun MW, Straatsma BR.

Department of Ophthalmology, David Geffen School of Medicine at UCLA, Los
Angeles, CA 90095-7000, USA.

OBJECTIVES: To prospectively report standardized visual function and macular
structural assessment in patients undergoing iodine-125 brachytherapy for
choroidal and ciliary body melanoma. MATERIALS AND METHODS: Patients were
enrolled for pretreatment and annual posttreatment assessment. Evaluations
included ophthalmic history; standardized refraction; visual acuity, contrast
sensitivity, and color vision measurement; comprehensive ophthalmic examination; 
fundus photography; fluorescein angiography; optical coherence tomography; and
ultrasonography. Radiation doses to the foveola and optic disc margin were
calculated. RESULTS: Forty-two patients were enrolled. Melanoma location included
3 in the ciliary body, 7 anterior, 11 equatorial, 13 posterior, and 8 macular
tumors. Mean apical tumor height was 4.45 mm (range 1.79-9.83 mm) and mean
longitudinal tumor diameter was 9.41 mm (range 4.52-4.73 mm).Pretreatment mean
best-corrected Ferris-Bailey early treatment diabetic retinopathy study visual
acuity was 50 (standard deviation +/- 15) letters (Snellen equivalent 20/32,
range 20/15 to hand motions). The mean Pelli-Robson contrast threshold percentage
was 4.1% (+/- 2.5%). The mean Hardy-Rand-Rittler color vision score was 13/14
(+/- 2.7). Mean distances from the posterior edge of the tumor to the foveola and
the optic disc margin were 6.99 mm (+/- 6.22 mm) and 7.28 mm (+/- 5.98 mm),
respectively. At the foveola, median total radiation dose was 36.2 Gy (+/-50.6
Gy) and median dose rate was 31.6 cGy/h (+/- 39.8 cGy/h). At the optic nerve,
median total radiation dose was 42.8 Gy (+/- 30.8 Gy) and median dose rate was
36.2 cGy/h (+/- 21.4 cGy/h). CONCLUSION: This prospective assessment of macular
structure and function will provide more complete understanding of the ocular
effects of radiation therapy for ocular melanoma.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18838887 [PubMed - indexed for MEDLINE]

78: Optom Vis Sci. 2008 Oct;85(10):947-50.

Anti-inflammatory drug use and age-related macular degeneration.

Swanson MW, McGwin G Jr.

University of Alabama at Birmingham School of Optometry, 1716 University
Boulevard, Birmingham, AL 35294-0010, USA. mswanson@uab.edu

PURPOSE: Basic research has shown that early processes in the development of
age-related macular degeneration (ARMD) are related to inflammation. The purpose 
of this manuscript is to evaluate the association of ARMD and the use of
anti-inflammatory medications. METHODS: A nested case control study was carried
out among male patients at the Veteran's Medical Center in Birmingham, Alabama
(BVAMC). Cases were 614 patients with incident ARMD diagnosed between 1997 and
2001 by International Classification of Disease, Ninth Revision code. Controls
(4526) were individuals with no diagnosis of ARMD by International Classification
of Disease, Ninth Revision coding and matched on age. Formulary records of all
medications dispensed through the Veteran's Administration Medical Center were
accessed. All oral or injectable drugs with anti-inflammatory properties were
considered anti-inflammatory medications for study purposes. Topical ophthalmic
and dermatologic preparations were not considered anti-inflammatory. RESULTS:
Among veterans with a diagnosis of ARMD 24% (150/614) patients had filled a
prescription for any of the anti-inflammatory medications compared with 60%
(3051/4526) individuals in the control population. Individuals who had filled a
prescription for anti-inflammatory drugs had an 85% reduced odds of having a
diagnosis of ARMD (odds ratio 0.15, 95% confidence interval 0.12-0.18).
CONCLUSIONS: The results of this study suggest that veterans who had filled a
prescription for anti-inflammatory medications had a reduced risk of ARMD.
Further studies are needed to confirm this result.

PMID: 18832975 [PubMed - indexed for MEDLINE]

79: Curr Opin Mol Ther. 2008 Oct;10(5):506-15.

NT-501: an ophthalmic implant of polymer-encapsulated ciliary neurotrophic
factor-producing cells.

Emerich DF, Thanos CG.

InCytu Inc, Lincoln, RI 02865, USA. emerich@incytu.com

Neurotech Pharmaceuticals Inc is developing NT-501, an implantable polymeric
device containing a genetically modified cell line that secretes ciliary
neurotrophic factor, for the potential treatment of retinitis pigmentosa (RP) and
age-related macular degeneration (AMD). Phase III clinical trials for RP and a
phase II clinical trial for dry AMD are ongoing. A phase I clinical trial showed 
that NT-501 treatment was well tolerated with variable, but positive improvements
in visual acuity.

Publication Types: 
    Review

PMID: 18830926 [PubMed - indexed for MEDLINE]

80: Retina. 2008 Nov-Dec;28(10):1522-9.

Central and pericentral retinal sensitivity after macular translocation surgery.

Chieh JJ, Stinnett SS, Toth CA.

Department of Ophthalmology, Duke University Medical Center, Durham, North
Carolina, USA.

PURPOSE: To evaluate the separate contribution of the retina versus retinal
pigment epithelium (RPE)-choriocapillaris to visual function after treatment of
neovascular age-related macular degeneration by measuring retinal sensitivity
across three areas after macular translocation surgery. METHODS: Using the Nidek 
microperimeter-1, we tested retinal sensitivity across three areas in 35 patients
after macular translocation surgery. Microperimetry scores ranged from -2 (no
response to brightest stimulus) to 20 (response with 20 dB neutral density
filtering). Median retinal sensitivity score (MRSS) for the central 10-degrees
(Area 1, fovea translocated over healthier RPE) was compared with acuity, reading
speed and MRSS of adjacent areas: Area 2, retina over site of choroidal
neovascularization removal and Area 3, retina over undisturbed RPE. RESULTS: In
27 of 35 eyes in this study (77%), the MRSS for Area 1, was greater than Area 2. 
Area 1 was a median of 3.0 decibels (dB) greater in sensitivity (range, 16
greater-2 lower) than Area 2 (P < or = 0.001), and 5.0 dB lower (range, 2
greater-12 lower) than Area 3 (P < or = 0.001). The median of the MRSS (25th/75th
percentile) for Areas 1, 2 and 3 were 2.0 (0.0/6.0), -2.0 (-2.0/-2.0) and 9
(4.0/12.0), respectively. The MRSS for Area 1 correlated with reading speed more 
than with acuity. CONCLUSIONS: Sensitivity of the translocated macula was
significantly greater than in Area 2, retina over abnormal RPE-choriocapillaris, 
suggesting that disturbed RPE-choriocapillaris significantly limits retinal
function. Area 1 sensitivity was lower than in retina unaffected by age-related
macular degeneration over undisturbed RPE, suggesting that persisting retinal
dysfunction can limit vision recovery.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18827740 [PubMed - indexed for MEDLINE]

81: Retina. 2008 Nov-Dec;28(10):1387-94.

Primary intravitreal bevacizumab for subfoveal choroidal neovascularization in
age-related macular degeneration: results of the Pan-American Collaborative
Retina Study Group at 12 months follow-up.

Arevalo JF, Fromow-Guerra J, Sanchez JG, Maia M, Berrocal MH, Wu L, Saravia MJ,
Costa RA; Pan-American Collaborative Retina Study Group.

Collaborators: Wu L, Evans T, Arevalo JF, Sanchez JG, Garcia-Amaris RA, Zeballos 
DG, Espinoza JV, Farah M, Maia M, Aggio FB, Quiroz-Mercado H, Fromow-Guerra J,
Morales-Canton V, Guerrero-Naranjo JL, Rodriguez FJ, Infante R, Flores S, Medina 
D, Berrocal MH, Cruz-Villegas V, Graue-Wiechers F, Lozano-Rechy D, Robledo V,
Rodriguez-Loaiza JL, Roca JA, Reategui G, Saravia MJ, Martinez-Cartier M, Avila
M, Costa RA, Cardillo J, Verdaguer J, Carpentier C, Verdaguer JI, Filsecker L,
Sepúlveda G.

Retina and Vitreous Service, Clinica Oftalmológica Centro Caracas, Caracas,
Venezuela. arevalojf2020@gmail.com

PURPOSE: To report the 12-month anatomic and Early Treatment Diabetic Retinopathy
Study best-corrected visual acuity (BCVA) response after primary intravitreal
bevacizumab (Avastin, Genentech Inc., San Francisco, CA) (1.25 mg or 2.5 mg) in
patients with subfoveal choroidal neovascularization secondary to age-related
macular degeneration. METHODS: Sixty-three eyes of 63 consecutive patients with
subfoveal choroidal neovascularization secondary to age-related macular
degeneration, a mean age of 73.7 +/- 7.5 years and a minimum of 12 months (mean
55.5 +/- 6.2 weeks) of follow-up participated in this interventional
retrospective multicenter case series in 7 centers from 6 countries. Patients
were treated with at least 1 intravitreal injection of 1.25 mg or 2.5 mg of
bevacizumab. Patients underwent Early Treatment Diabetic Retinopathy Study BCVA
testing, ophthalmoscopic examination, optical coherence tomography, and
fluorescein angiography at baseline and follow-up visits. Repeated measures
analysis of variance was used to compare mean values. RESULTS: The mean number of
intravitreal bevacizumab injections per eye was 3.5 (range, 1-8). Mean baseline
BCVA was 20/320, logarithm of the minimum angle of resolution = 1.2, and mean
final BCVA was 20/200, logarithm of the minimum angle of resolution = 1.0 (P <
0.001). Central macular thickness at baseline by optical coherence tomography had
a mean of 389.2 +/- 149.6 microm which was significantly reduced to a mean of
281.0 +/- 96.1 microm, 268.2 +/- 82.6 microm, 262.6 +/- 92.3 microm, and 241.3
+/- 76.7 microm at 1, 3, 6, and 12 months after initial treatment, respectively
(P < 0.0001). Ocular adverse events included transient increased intraocular
pressure in 2 (3.1%) eyes, endophthalmitis in 2 (3.1%) eyes, and transient
hypotony in 1 eye (1.1%). No systemic adverse events were observed. CONCLUSION:
Primary intravitreal bevacizumab at doses of 1.25 mg or 2.5 mg seems to provide
stability or improvement in BCVA, optical coherence tomography, and fluorescein
angiography in subfoveal choroidal neovascularization secondary to age-related
macular degeneration at 12 months.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 18827735 [PubMed - indexed for MEDLINE]

82: BMC Ophthalmol. 2008 Sep 29;8:18.

Treatment of branch retinal vein occlusion induced macular edema with
bevacizumab.

Abegg M, Tappeiner C, Wolf-Schnurrbusch U, Barthelmes D, Wolf S, Fleischhauer J.

Department of Ophthalmology, Inselspital, University of Bern, Switzerland.
mhabegg@hispeed.ch

BACKGROUND: Branch retinal vein occlusion is a frequent cause of visual loss with
currently insufficient treatment options. We evaluate the effect of Bevacizumab
(Avastin) treatment in patients with macular edema induced by branch retinal vein
occlusion. METHODS: Retrospective analysis of 32 eyes in 32 patients with
fluorescein angiography proven branch retinal vein occlusion, macular edema and
Bevacizumab treatment. Outcome measures were best corrected visual acuity in
logMAR and central retinal thickness in OCT. RESULTS: Visual acuity was
significantly better 4 to 6 weeks after Bevacizumab treatment compared to visual 
acuity prior to treatment (before 0.7 +/- 0.3 and after 0.5 +/- 0.3; mean +/-
standard deviation; p < 0.01, paired t-test). Gain in visual acuity was
accompanied by a significant decrease in retinal thickness (454 +/- 117 to 305
+/- 129 microm, p < 0.01, paired t-test). Follow up (170, 27 - 418 days; median, 
range) shows that improvement for both visual acuity and retinal thickness last
for several months after Bevacizumab use. CONCLUSION: We present evidence that
intravitreal Bevacizumab is an effective and lasting treatment for macular edema 
after branch retinal vein occlusion.

PMID: 18823536 [PubMed - indexed for MEDLINE]

83: Br J Ophthalmol. 2008 Oct;92(10):1424-8.

Immunohistochemical localisation of intravitreally injected bevacizumab at the
posterior pole of the primate eye: implication for the treatment of retinal vein 
occlusion.

Julien S, Heiduschka P, Hofmeister S, Schraermeyer U.

Section of Experimental Vitreoretinal Surgery, Centre of Ophthalmology, Institute
for Ophthalmic Research, Tuebingen, Germany. sylvie.julien@med.uni-tuebingen.de

AIM: To locate bevacizumab in the posterior pole within 1-14 days after
intravitreal injection in the primate eye. METHODS: Four Cynomolgus monkeys
received an intravitreal injection of 1.25 mg of bevacizumab. The eyes were
enucleated on days 1, 4, 7 and 14 for immunohistochemistry using donkey
anti-human Cy3-IgG. Control eyes remained untreated. RESULTS: In the optic nerve,
immunoreactivity for bevacizumab was most prominent on day 1 after injection and 
diminished rapidly. In the blood vessels of the nerve fibre layer, the staining
was intense in the walls and weak in the lumen from day 1 to 4, and was only
localised in the lumen thereafter. In the macula, an accumulation of bevacizumab 
was observed 1 day after injection in the nerve fibre layer, the ganglion cell
layer and in the photoreceptors at the level of the outer nuclear layer in the
fovea centralis. CONCLUSION: Bevacizumab penetrates quickly into the macula, the 
retinal veins and the optic nerve after intravitreal injection in the primate
eye, and accumulates preferentially and specifically on the vessel walls and
inside the photoreceptors localised in the fovea centralis 1 day after injection.
Our finding supports the clinically observed rapid effect in the treatment of
retinal vein occlusion and macular oedema.

PMID: 18815425 [PubMed - indexed for MEDLINE]

84: IEEE Trans Med Imaging. 2008 Oct;27(10):1495-505.

Intraretinal layer segmentation of macular optical coherence tomography images
using optimal 3-D graph search.

Garvin MK, Abramoff MD, Kardon R, Russell SR, Wu X, Sonka M.

Department of Electrical and Computer Engineering, The University of Iowa, Iowa
City, IA 52242, USA. mona-garvin@uiowa.edu

Current techniques for segmenting macular optical coherence tomography (OCT)
images have been 2-D in nature. Furthermore, commercially available OCT systems
have only focused on segmenting a single layer of the retina, even though each
intraretinal layer may be affected differently by disease. We report an automated
approach for segmenting (anisotropic) 3-D macular OCT scans into five layers.
Each macular OCT dataset consisted of six linear radial scans centered at the
fovea. The six surfaces defining the five layers were identified on each 3-D
composite image by transforming the segmentation task into that of finding a
minimum-cost closed set in a geometric graph constructed from edge/regional
information and a priori determined surface smoothness and interaction
constraints. The method was applied to the macular OCT scans of 12 patients (24
3-D composite image datasets) with unilateral anterior ischemic optic neuropathy 
(AION). Using the average of three experts' tracings as a reference standard
resulted in an overall mean unsigned border positioning error of 6.1 +/- 2.9
microm, a result comparable to the interobserver variability (6.9 +/- 3.3
microm). Our quantitative analysis of the automated segmentation results from
AION subject data revealed that the inner retinal layer thickness for the
affected eye was 24.1 microm (21%) smaller on average than for the unaffected eye
(p < 0.001), supporting the need for segmenting the layers separately.

Publication Types: 
    Evaluation Studies
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, Non-P.H.S.

PMID: 18815101 [PubMed - indexed for MEDLINE]

85: Invest Ophthalmol Vis Sci. 2009 Feb;50(2):533-9. Epub 2008 Sep 20.

Further assessment of the complement component 2 and factor B region associated
with age-related macular degeneration.

McKay GJ, Silvestri G, Patterson CC, Hogg RE, Chakravarthy U, Hughes AE.

Centre for Vision Sciences, Queen's University of Belfast, Belfast, Northern
Ireland, United Kingdom. g.j.mckay@qub.ac.uk

PURPOSE: Polymorphic variation in genes involved in regulation of the complement 
system has been implicated as a major cause of genetic risk, in addition to the
LOC387715/HTRA1 locus and other environmental influences. Previous studies have
identified polymorphisms in the complement component 2 (CC2) and factor B (CFB)
genes, as potential functional variants associated with AMD, in particular CFB
R32Q and CC2 rs547154, both of which share strong linkage disequilibrium (LD).
METHODS: Data derived from the HapMap Project were used to select 18
haplotype-tagging SNPs across the extended CC2/CFB region for genotyping, to
measure the strength of LD in 318 patients with neovascular AMD and 243
age-matched control subjects to identify additional potential functional variants
in addition to those originally reported. RESULTS: Strong LD was measured across 
this region as far as the superkiller viralicidic activity 2-like gene (SKIV2L). 
Nine SNPs were identified to be significantly associated with the genetic effect 
observed at this locus. Of these, a nonsynonymous coding variant SKIV2L R151Q
(rs438999; OR, 0.48; 95% confidence interval [CI], 0.31-0.74; P<0.001), was in
strong LD with CFB R32Q, rs641153 (r(2)=0.95) and may exert a functional effect. 
When assessed within a logistic regression model measuring the effects of genetic
variation at the CFH and LOC387715/HTRA1 loci and smoking, the effect remained
significant (OR, 0.38; 95% CI, 0.22-0.65; P<0.001). Additional variation
identified within this region may also confer a weaker but independent effect and
implicate additional genes within the pathogenesis of AMD. CONCLUSIONS: Because
of the high level of LD within the extended CC2/CFB region, variation within
SKIV2L may exert a functional effect in AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18806297 [PubMed - indexed for MEDLINE]

86: Invest Ophthalmol Vis Sci. 2009 Feb;50(2):540-3. Epub 2008 Sep 20.

Analysis of rare variants in the complement component 2 (C2) and factor B (BF)
genes refine association for age-related macular degeneration (AMD).

Richardson AJ, Islam FM, Guymer RH, Baird PN.

Centre for Eye Research Australia, University of Melbourne, East Melbourne,
Victoria, Australia. andreajr@unimelb.edu.au

PURPOSE: Several single-nucleotide polymorphisms (SNPs) in the C2 and BF genes
have been associated with age-related macular degeneration (AMD) in Caucasian
populations from the United States. The study was conducted to evaluate whether
these SNPs are also associated with AMD in persons of Anglo-Celtic ethnicity in
an Australian population. METHODS: Included in the study were 565 persons with
AMD and 204 ethnically matched control subjects. All participants completed a
standard health questionnaire, were given a fundus examination, and provided a
blood sample for DNA extraction. Alleles were determined by a matrix-assisted
desorption ionization-time of flight (MALDI-TOF)-based approach followed by
statistical analysis. RESULTS: The C2 and BF genes indicated significant
association with AMD of only two SNPs; rs547154 (IVS10) in the C2 gene (P=9.1 x
10(-5)) and rs641153 (R32Q) in the BF gene (P=7.0 x 10(-5)). No association with 
AMD was found for SNP rs9332739 (E318D) in the C2 gene or for rs4151667 (L9H),
rs1048709 (R150R), rs4151659 (K565E), or rs2072633 (IVS17) in the BF gene. A
protective haplotype of variants IVS10 and R32Q was associated with AMD (OR 0.29,
95% CI 0.20-0.42). CONCLUSIONS: In this study, the association of the IVS10 and
R32Q variants in the C2 and BF genes in AMD was replicated. Haplotype analysis
indicated association of these variants with AMD in an Australian population.
Both IVS10 and R32Q variants were in strong linkage disequilibrium with each
other (r(2)=0.96). Although the E318D and L9H variants have shown association
with AMD in previous studies, the findings were not in agreement. This
demonstrates a refined pattern of association of these rare variants with AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18806293 [PubMed - indexed for MEDLINE]

87: Ophthalmology. 2008 Nov;115(11):1904-10. Epub 2008 Sep 18.

Age-related macular degeneration and complement activation-related diseases: a
population-based case-control study.

Nitsch D, Douglas I, Smeeth L, Fletcher A.

Department of Epidemiology and Population Health, London School of Hygiene &
Tropical Medicine, London, United Kingdom.

OBJECTIVE: Recent evidence suggests an important role for the complement system
in the etiology of age-related macular degeneration (AMD). We aimed to
investigate whether other diseases known to be associated with complement
activation are associated with AMD. DESIGN: Case-control study. PARTICIPANTS: We 
reviewed medical records from the United Kingdom General Practice Research
Database (GPRD). Cases (n = 18 007) were defined as people aged >/=50 years with 
a first diagnosis of AMD while registered with a practice included in the GPRD
between 1987 and 2002. For each case, 5 controls with no record of AMD (n = 86
169) were matched by gender, practice, and age (within 5 years). METHODS: Records
were searched for diagnoses of systemic lupus erythematosus (SLE),
glomerulonephritis, and diabetic nephropathy occurring before the AMD diagnosis
date (or equivalent date for controls). MAIN OUTCOME MEASURES: Diagnosis of AMD. 
RESULTS: A diagnosis of SLE was found in 0.07% of controls and 0.13% of AMD cases
(confounder-adjusted odds ratio [OR], 1.69; 95% confidence interval [CI],
1.05-2.72). Glomerulonephritis was diagnosed in 0.13% of controls and 0.2% of
cases (adjusted OR 1.46; 95% CI, 0.99-2.13). Diabetic nephropathy was strongly
associated with AMD with an adjusted OR of 3.00 and a 95% CI of 1.55-5.97, which 
was independent of the association of diabetes with AMD. CONCLUSIONS: Specific
diseases that are associated with complement activation are also associated with 
AMD. The impact of diabetic nephropathy on AMD may be larger than previously
recognized.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18801575 [PubMed - indexed for MEDLINE]

88: J Med Invest. 2008 Aug;55(3-4):279-82.

Efficacy of sub-Tenon's capsule injection of triamcinolone acetonide for
refractory diabetic macular edema after vitrectomy.

Sato H, Naito T, Matsushita S, Takebayashi M, Shiota H.

Department of Ophthalmology, Institute of Health Biosciences, University of
Tokushima Graduate School, Tokushima, Japan.

PURPOSE: To determine whether or not a sub-Tenon's capsule injection of
triamcinolone acetonide(TA) is an effective treatment for refractory diabetic
macular edema after vitrectomy. METHODS: Thirty-nine eyes of 26 patients with
diabetic macular edema were injected with 20 mg TA into the sub-Tenon's capsule. 
The central macular thickness (CMT) measured by an optical coherence tomography
(OCT) and visual acuities were compared between pre-treatment and 1, 3 months
post-treatment. RESULTS: The decrease in the mean CMT between the baseline (435
microm) and 1 month (326 microm) or 3 months (303 microm) time points was
statistically significant. Seven eyes (70%) at 1 month and 3 months
post-treatment in the vitrectomized eyes or PPV(pars plana vitrectomy)(+) group, 
15 eyes(52%) at 1 month, and 19 eyes (66%) at 3 months in the non-vitrectomized
eyes or PPV(-)group maintained 20% reduction in CMT from pre-treatment with a
single injection of TA. The recurrence of macular edema was observed in 1 eye
(14%) in the PPV(+)group, and 3 eyes (16%) in the PPV(-)group. CONCLUSION: The
sub-Tenon's capsule injection of TA was effective for refractory diabetic macular
edema after vitrectomy. In addition, it was suggested that the treatment of
vitrectomized eyes was more effective than that of non-vitrectomized eyes.

PMID: 18797143 [PubMed - indexed for MEDLINE]

89: J Med Invest. 2008 Aug;55(3-4):211-5.

Results of submacular surgery to remove diabetic submacular hard exudates.

Naito T, Matsushita S, Sato H, Katome T, Nagasawa T, Shiota H.

Department of Ophthalmology, Institute of Health Biosciences, University of
Tokushima Graduate School, Tokushima, Japan.

PURPOSE: To evaluate outcomes of submacular surgery to remove massive submacular 
hard exudates with diabetic macular edema. DESIGN: Retrospective,
non-comparative, interventional consecutive case series. Participants: Fifty-six 
eyes of 40 patients with massive submacular hard exudates with diabetic macular
edema. INTERVENTION: Submacular surgery was performed to remove massive
submacular hard exudates. MAIN OUTCOME MEASURES: Preoperative and postoperative
visual acuities and clinical findings. All patients were followed for more than 1
year postoperatively. RESULTS: The macular hard exudates underlying the fovea
almost disappeared, and macular edema remarkably reduced following surgery.
Visual acuities ranged from 0.01 to 0.3 before surgery, and from 0.04 to 1.0
after surgery. Visual acuity improved by two lines or more in 45 eyes (80.4%),
remained unchanged in 8 eyes (14.3%) and worsened in 3 eyes (5.3%). Visual acuity
improved to 0.3 or more in 24 eyes (42.9%). Better postoperative visual acuity
(0.3 or better) was related to hemoglobin A1C (HbA1C) and the size of hard
exudates. CONCLUSIONS: Results showed the efficacy of submacular surgery to
remove massive hard exudates with diabetic macular edema, and outcomes were
satisfactory.

PMID: 18797133 [PubMed - indexed for MEDLINE]

90: Am J Health Syst Pharm. 2008 Oct 1;65(19):1805-14.

Ranibizumab for neovascular age-related macular degeneration.

Hernandez-Pastor LJ, Ortega A, Garcia-Layana A, Giraldez J.

Pharmacy Department, University Clinic, University of Navarra, Pamplona, Spain.
luisjaher@unav.es

PURPOSE: The pharmacology, pharmacokinetics, clinical efficacy, safety,
pharmacoeconomics, and place in therapy of ranibizumab are reviewed. SUMMARY:
Ranibizumab is the humanized fragment of the murine monoclonal antibody that
binds all the active forms of the vascular endothelial growth factor, leading to 
the inhibition of the neovascular process underlying age-related macular
degeneration (AMD). In animal studies, intravitreal administration of ranibizumab
resulted in penetration of the drug into all layers of the retina and subsequent 
slow absorption into the systemic circulation. Improvement in visual acuity by 15
or more letters has been observed in 33.8-40.3% of patients treated with
ranibizumab in pivotal clinical trials, compared with 5% of patients treated with
sham injections and photodynamic therapy (PDT). The addition of PDT to
ranibizumab has not been shown to offer any benefit in terms of efficacy and has 
been found to worsen ocular adverse reactions. The most common adverse ocular
reactions reported in patients receiving ranibizumab during clinical trials
include conjunctival hemorrhage, eye pain, vitreous floaters, increased
intraocular pressure, and intraocular inflammation. Ranibizumab's efficacy in the
treatment of neovascular AMD is well established; however, questions remain
regarding the drug's optimal dosing strategy, duration of therapy, and combined
therapy with other agents. While ranibizumab has been defined as the best
available weapon against AMD, it is also the most expensive. CONCLUSION: The
efficacy of ranibizumab in the treatment of AMD is well established, but more
studies are needed to determine ranibizumab's optimal dosage interval, duration
of therapy, and combined use with other agents.

Publication Types: 
    Review

PMID: 18796421 [PubMed - indexed for MEDLINE]

91: Invest Ophthalmol Vis Sci. 2009 Jan;50(1):482-7. Epub 2008 Sep 12.

Postural stability and gait among older adults with age-related maculopathy.

Wood JM, Lacherez PF, Black AA, Cole MH, Boon MY, Kerr GK.

School of Optometry, Queensland University of Technology, Brisbane, Australia.
j.wood@qut.edu.au

PURPOSE: To assess the postural stability and gait characteristics of adults with
age-related maculopathy (ARM) and to identify the visual factors associated with 
postural stability and gait in this clinical population. METHODS: Participants
included 80 individuals with a range of severity of ARM (mean age, 77.2 years).
Binocular visual function measures included visual acuity, contrast sensitivity, 
and merged binocular visual fields. Postural stability was assessed on both a
firm and a foam surface using center-of-pressure measures derived from a force
platform. Forty three of the participants underwent a three-dimensional motion
analysis to quantify gait characteristics, including walking velocity, proportion
of time spent with both feet in contact with the ground (double-support time),
stride length, and step width. RESULTS: After adjustment for age, sex,
self-reported physical function, and cataract severity, all the vision measures
were significantly associated with postural stability on the foam surface, with
contrast sensitivity being the strongest correlate. In the analysis of the gait
measures, only contrast sensitivity was significantly associated with walking
velocity, step width, or stride length, whereas contrast sensitivity and visual
field loss were both significantly associated with double-support time.
CONCLUSIONS: Impaired contrast sensitivity was associated with postural
instability, slower walking velocity, increased step width, and reduced stride
length. Impairments in either contrast sensitivity or visual fields were
associated with increased double-support time. This result suggests that loss of 
contrast sensitivity and visual fields in patients with ARM can lead to balance
and mobility problems.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18791170 [PubMed - indexed for MEDLINE]

92: Am J Ophthalmol. 2009 Jan;147(1):11-21.e1. Epub 2008 Sep 13.

Etiology and treatment of macular edema.

Johnson MW.

Department of Ophthalmology and Visual Sciences, University of Michigan Medical
School, W. K. Kellogg Eye Center, Ann Arbor, Michigan, USA. markwj@umich.edu

PURPOSE: To summarize current concepts and recent literature regarding the
pathogenesis, clinical substrates, and treatment of macular edema, in light of
evolving pharmacologic and surgical approaches to this prevalent cause of vision 
loss. DESIGN: Interpretive essay. METHODS: Review and synthesis of selected
recent literature, with interpretation and perspective. RESULTS: Macular edema
occurs in a wide variety of pathologic conditions and represents the final common
phenotype of several basic pathophysiologic processes. A variety of pharmacologic
agents targeting inflammatory and vasopermeability molecules have been shown to
reduce macular edema and improve visual function over the short-term. Vitreous
surgery effectively addresses the tractional components of macular edema, where
present. Despite recent advances, laser photocoagulation remains the treatment of
choice for macular edema associated with nondiffuse patterns of vascular leakage.
CONCLUSIONS: Effective management of macular edema is based on recognizing and
addressing the pathogenic factors that are operative in a given disease setting. 
Although treatment options are expanding with the development of new drugs and
surgical procedures, the long-term efficacy and safety of most new approaches
have yet to be established in controlled clinical trials.

Publication Types: 
    Review

PMID: 18789796 [PubMed - indexed for MEDLINE]

93: Retina. 2008 Nov-Dec;28(10):1416-20.

Complement factor H variant increases the risk for early age-related macular
degeneration.

Lin JM, Tsai YY, Wan L, Lin HJ, Tsai Y, Lee CC, Tsai CH, Tsai FJ, Tseng SH.

Department of Ophthalmology, China Medical University Hospital, Taichung, Taiwan.

PURPOSE: To investigate whether a polymorphism in the complement factor H gene
determines the risk for the development of early age-related macular degeneration
(AMD). METHODS: In this retrospective case-control study, we enrolled 133
unrelated Taiwan Chinese patients with early AMD and 180 age- and sex-matched
control subjects. Early AMD was defined as the presence of extensive intermediate
drusen or any large, soft drusen (> or = 125 microm), possibly accompanied by
drusenoid retinal pigment epithelial detachment, and the absence of signs of late
AMD. Genomic DNA was extracted from peripheral blood obtained from all the AMD
patients and control subjects. Polymerase chain reaction was performed to analyze
the complement factor H polymorphism (Y402H, rs1061170). RESULTS: The genotype
distribution differed significantly between the early AMD patients (TT 80%; TC
14%; and CC 6%) and controls (TT 91%; TC 9%; CC 0%; P = 9 x 10(-4)). The C allele
frequency was significantly higher in the early AMD patients than in the controls
(13% vs. 4%, P = 1 x 10(-4), odds ratios = 3.26, 95% confidence intervals =
1.76-6.02). CONCLUSIONS: Our study demonstrated that the presence of the Y402H
polymorphism in complement factor H is significantly associated with increased
susceptibility to early AMD in Taiwan Chinese populations and that the C allele
frequency is low in these populations.

PMID: 18784628 [PubMed - indexed for MEDLINE]

94: Retina. 2008 Nov-Dec;28(10):1375-86.

Comparison of 2.5 mg/kg and 5 mg/kg systemic bevacizumab in neovascular
age-related macular degeneration: twenty-four week results of an uncontrolled,
prospective cohort study.

Geitzenauer W, Michels S, Prager F, Rosenfeld PJ, Kornek G, Vormittag L,
Schmidt-Erfurth U.

Department of Ophthalmology, Medical University of Vienna, Austria.

BACKGROUND: To compare safety, visual acuity (VA), and anatomic outcomes of 2.5
mg/kg and 5 mg/kg intravenous bevacizumab in patients with neovascular
age-related macular degeneration. METHODS: In an institutional cohort study, 16
patients (2 cohorts, 27 eyes) with neovascular age-related macular degeneration
were treated with 5 mg/kg intravenous bevacizumab and 2.5 mg/kg, respectively.
All patients received 3 initial intravenous infusions at 2-week intervals. The
main outcome measures were VA, optical coherence tomography, and fluorescein
angiography. RESULTS: No serious systemic or ocular adverse events were
identified. By Day 7, mean VA increased from 56 letters (20/80(+1)) at baseline
to 60 letters (20/63) in the 5 mg/kg group and mean central retinal thickness
decreased by 83 microm. In the 2.5 mg/kg group, mean VA increased from 55 letters
(20/80) to 66 letters (20/50(+1)) and mean central retinal thickness decreased by
93 microm. By Month 3, VA improved by 10 letters compared to baseline in the 5
mg/kg group and by 9 letters in the 2.5 mg/kg group. Central retinal thickness
was reduced by 128 microm in the 5 mg/kg group and by 127 microm in the 2.5 mg/kg
group. These benefits were sustained through 6 months. No statistically
significant difference was found between both treatment groups regarding safety, 
VA, and anatomic outcomes. CONCLUSION: Similar VA, optical coherence tomography, 
and angiographic improvements were observed in both treatment groups up to 6
months. Further follow-up is required to evaluate the long-term durability and
safety of both treatment regimens.

Publication Types: 
    Clinical Trial
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 18784625 [PubMed - indexed for MEDLINE]

95: Korean J Ophthalmol. 2008 Sep;22(3):190-3.

Resolution of severe macular edema in adult coats' disease with intravitreal
triamcinolone and bevacizumab injection.

Jun JH, Kim YC, Kim KS.

Department of Ophthalmology, School of Medicine, Dongsan Medical Center, Keimyung
University, Daegu, Korea.

A 47 year old male patient visited our hospital with the chief complaint of
deterioration of the visual acuity in the left eye. The fundus examination
revealed thick hard exudates, multiple aneurysms and telangiectasias of the
retinal vessels in the posterior pole. Fluorescein angiography demonstrated
massive leakage over an area of the aneurysms. Optical coherence tomography
(Stratus OCT; Zeiss-Humphrey, Dubin, CA) revealed diffuse and marked thickening
of the retina. Laser photocoagulation was performed under the diagnosis of Coats'
disease. However, the treatment could not be performed satisfactorily. On the
first and 6th weeks, an intravitreal injection of bevacizumab and triamcinolone
acetonide was administered, and laser photocoagulation was again attempted. The
effectiveness of eachagent on retinal edema was evaluated at the follow-up
performed at 1, 2, 5, 7, 10 weeks and 6 months after the injection. At one week
after the intravitreal bevacizumab injection, there was no improvement. An
intravitreal injection of triamcinolone acetonide was performed 6 weeks after the
initial diagnosis,which resulted in a reduction in the thickness of the macular
edema. Therefore, laser photocoagulation was performed sufficiently on
telangiectasias. The follow-up at 6 months showed a relative increase in the
macular edema, but there was reduced leakage from the telangiectasias compared
with the previous angiograph.

Publication Types: 
    Case Reports

PMID: 18784449 [PubMed - indexed for MEDLINE]

96: Br J Ophthalmol. 2008 Dec;92(12):1636-41. Epub 2008 Sep 9.

A study comparing two protocols of treatment with intravitreal bevacizumab
(Avastin) for neovascular age-related macular degeneration.

Arias L, Caminal JM, Casas L, Masuet C, Badia MB, Rubio M, Pujol O, Arruga J.

Department of Ophthalmology, Hospital Universitari de Bellvitge, C/Feixa Llarga, 
sn, 08907-L'Hospitalet de Llobregat, Barcelona, Spain. luisarias@telefonica.net

AIMS: The aim of this study was to compare two treatment options for choroidal
neovascularisation (CNV) secondary to age-related macular degeneration (AMD): (1)
bevacizumab administered once a month for 3 months and thereafter as needed
(loading dose (LD)); and (2) bevacizumab administered as needed, after the first 
injection (pro re nata (as needed) (PRN)). METHODS: Fifty consecutive patients
were enrolled in this prospective study. The first 25 patients were included in
the LD group and the last 25 patients in the PRN group. In both groups, the need 
for re-treatment was based on the presence of persistent or recurrent macular
oedema, subretinal fluid or pigment epithelial detachment on optical coherence
tomography scans. RESULTS: At the 6-month follow-up, mean visual acuity improved 
by 13.7 letters (p<0.001) in the LD group and 4.6 in the PRN group (p<0.001).
Thirty-six per cent of patients in the LD group compared with 12% in the PRN
group gained 15 or more letters (p = 0.04). Mean foveal thickness decreased by
91.3 microm (p<0.001) in the LD group and 48.2 microm in the PRN group (p<0.001).
No ocular or systemic side effects were observed. CONCLUSION: Patients with CNV
secondary to AMD treated with a LD protocol had better results than patients
treated with a PRN protocol with intravitreal bevacizumab.

Publication Types: 
    Comparative Study

PMID: 18782803 [PubMed - indexed for MEDLINE]

97: Br J Ophthalmol. 2008 Dec;92(12):1642-7. Epub 2008 Sep 9.

Photodynamic therapy with verteporfin for age-related macular degeneration or
polypoidal choroidal vasculopathy: comparison of the presence of serous retinal
pigment epithelial detachment.

Saito M, Iida T, Nagayama D.

Department of Ophthalmology, Fukushima Medical University School of Medicine, 1
Hikarigaoka, Fukushima 960-1295, Japan. smasaaki@fmu.ac.jp

AIM: To evaluate outcomes after photodynamic therapy (PDT) with verteporfin in
Japanese patients with age-related macular degeneration (AMD) or polypoidal
choroidal vasculopathy (PCV) and compare results with the presence/absence of a
retinal pigment epithelial detachment (PED). METHODS: We retrospectively reviewed
183 eyes with subfoveal choroidal neovascularisation secondary to AMD with more
than 3 months' follow-up (range 3 to 36; mean 15.6). A serous PED developed in 44
of 183 eyes. RESULTS: A total of 124 eyes (67.8%) completed 12 months' follow-up.
In 49 eyes with typical AMD, the best-corrected visual acuity (BCVA) improved a
mean of 0.48 line. A significant (p<0.05 to p<0.0005) decline in VA occurred in
eyes with a serous PED during any 3-month period. In 75 eyes with PCV, the BCVA
at 12 months improved a mean of 1.79 lines. There was no significant difference
between the BCVA in 22 eyes with a PED and 53 eyes without a PED during any 3
months. CONCLUSIONS: In eyes with typical AMD, a serous PED was associated with a
significant decline in BCVA compared with eyes without a serous PED. In eyes with
PCV, the visual outcomes were unaffected by a serous PED. When PDT is
administered, differentiating PCV from typical AMD using indocyanine green
angiography is important.

Publication Types: 
    Comparative Study

PMID: 18782798 [PubMed - indexed for MEDLINE]

98: Retina. 2008 Oct;28(8):1132-7.

Combination photodynamic therapy and intravitreal ranibizumab in neovascular AMD 
in a north Indian population: a pilot study.

Kumar A, Gopalakrishnan K, Sinha S.

India Institute of Medical Sciences, New Delhi, India. akum66mm@yahoo.co.in

PURPOSE: To evaluate photodynamic therapy (PDT) with verteporfin along with
intravitreal Ranibizumab in treatment of neovascular age related macular
degeneration. METHODS: This prospective interventional care series included 16
patients (17 eyes) of choroidal neovascularization secondary to neovascular AMD, 
who were treated with PDT with verteporfin followed by an injection of 0.5mg
Ranibuzimab on the same day. The main outcome measures were best corrected visual
acuity (VA) as recorded by both Snellen's and ETDRS charts (logMAR), contrast
sensitivity (Pelli-Robson Chart), retreatment frequency and frequency of side
effects. RESULTS: Seventeen eyes underwent PDT with verteporfin and intravitreal 
0.5mg Ranibizumab, following PDT. Patients were followed up every month for a
total period of 6 months. Initial VA ranged from CF to 20/32 and final acuity
ranged from CF to 20/20. VA stabilizes (gain/loss <2 lines) in 14 out of 17 eyes 
(82.24%) and improved in 3 out of 17 (17.65%). Contrast sensitivity improved in
15 out of 17 eyes (82.24%) Lesion type, patient age had no influence on the
outcome. There were no cases of ocular/systematic adverse events. Retreatment was
required in only 2 out of 17 cases (11.76%) with only a single injection of
ranibizumab. CONCLUSION: The combination of PDT with intravitreal Ranibizumab
improves contrast sensitivity and stabilizes vision and reduces the number of
retreatments, without significant ocular and/or systematic risks.

PMID: 18779720 [PubMed - indexed for MEDLINE]

99: Retina. 2008 Oct;28(8):1097-103.

Correlation between microaneurysms and retinal thickness in diabetic macular
edema.

Blair NP, Shahidi M, Lai WW, Zelkha R.

Department of Ophthalmology and Visual Sciences, University of Illinois, Chicago,
Illinois 60612, USA. npblair@uic.edu

PURPOSE: Microaneurysms commonly are believed to be related causally to retinal
thickening in diabetic retinopathy, especially by leaking. The hypothesis that
thicker areas of retina in diabetic retinopathy have more microaneurysms per unit
area than areas that are not as thick was tested. METHODS: Retinal thickness
analysis was performed with a prototype instrument for 27 eyes of 27 diabetic
patients and 22 normal eyes of 22 healthy subjects. Maps of retinal thickness
were created, and microaneurysms were counted in zones having four levels of
retinal thickness. RESULTS: There was no increase in either total microaneurysms 
or apparent leaking microaneurysms per unit area with increasing levels of
retinal thickness (P = 0.77 and 0.87, respectively). CONCLUSION: Some
microaneurysms may not cause thickening, or other factors may contribute to
retinal thickening in diabetic retinopathy. The results may have implications on 
the pathogenesis of diabetic macular edema.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, U.S. Gov't, Non-P.H.S.

PMID: 18779716 [PubMed - indexed for MEDLINE]

100: Retina. 2008 Oct;28(8):1053-60.

Long-term effect of intravitreal bevacizumab (avastin) in patients with chronic
diffuse diabetic macular edema.

Kook D, Wolf A, Kreutzer T, Neubauer A, Strauss R, Ulbig M, Kampik A, Haritoglou 
C.

From the Department of Ophthalmology, Ludwig-Maximilians-Universität, Munich,
Germany.

PURPOSE: To evaluate the long-term efficacy of bevacizumab for the treatment of
chronic diffuse diabetic macular edema after various previous treatments.
METHODS: A total of 126 patients (mean age: 66 years) with chronic diffuse
diabetic macular edema were consecutively incorporated in this prospective,
noncomparative case series. Inclusion was performed independently from the size
of edema, retinal thickness, visual acuity (VA), age, metabolic control, type of 
diabetes, or type of previous treatments. The patients underwent a complete eye
examination including best-corrected VA with ETDRS charts, slit lamp examination,
intraocular pressure measurement, stereoscopic biomicroscopy of the macula,
retinal thickness measurement using optical coherence tomography (OCT),
fluorescein angiography, and fundus photography. All patients were treated with
repeated intravitreal injections of bevacizumab (1.25 mg). Patients were observed
in intervals of 4-12 weeks for a period of up to 6-12 months. RESULTS: All
patients had received various previous treatments such as laser treatment (62%
focal laser treatment, 38% panretinal laser treatment), vitrectomy (11%), or
intravitreal injection of triamcinolone (41%). All patients completed 6 months
and 59 patients (47%) completed 12 months of follow-up; within this period 48%
had received at least three intravitreal injections of bevacizumab. Mean diameter
of foveal avascular zone was 858 +/- 341 microm. At baseline mean VA was 40.3
ETDRS letters (0.82 logMAR Snellen VA) and mean central retinal thickness on OCT 
was 463 microm. Throughout follow-up VA changes were not significant with a mean 
change of -1.6 ETDRS letters after 6 months, but significant with +5.1 ETDRS
letters after 12 months. Mean central retinal thickness (OCT) decreased to 374
microm after 6 months (P < 0.001) and to 357 microm after 12 months (P < 0.001). 
Changes of retinal thickness and visual acuity did not correlate. No other
factors investigated, such as age, central retinal thickness, or previous
treatments, were predictive for a change of VA. Macular ischemia was not
exacerbated as a result of the treatment. CONCLUSION: Even in cases with chronic 
diffuse ischemic diabetic macular edema, a long-term decrease of central retinal 
thickness can be observed following repeated intravitreal injections of
bevacizumab. In these patients, mean decrease in retinal thickness is aligned
with a gain in mean VA. Treatment with bevacizumab at an earlier stage of
diabetic macular edema without ischemia may be associated with an even better
functional outcome.

PMID: 18779710 [PubMed - indexed for MEDLINE]

101: Arch Ophthalmol. 2008 Sep;126(9):1280-6.

Hospitalized cardiovascular diseases in neovascular age-related macular
degeneration.

Nguyen-Khoa BA, Goehring EL Jr, Werther W, Gower EW, Do DV, Jones JK.

The Degge Group, Ltd, Arlington, Virginia, USA. bnguyen@deggegroup.com

OBJECTIVE: To compare the incidence rate of hospitalized myocardial infarctions
(MIs) and cerebrovascular accidents (CVAs) in subjects with and without
neovascular age-related macular degeneration (AMD). METHODS: A retrospective
database cohort study was performed in subjects with neovascular AMD and controls
matched for age, sex, geography, and enrollment duration. Healthcare claims for
the study period from January 1, 2002, to June 30, 2005, were used to identify
subjects and outcomes. Incidence of hospitalized MI and CVA events and rate
ratios adjusted for 11 risk factors were calculated. RESULTS: In 7203 subjects
with neovascular AMD and 20,208 controls, the rate of MI was 16.2 events per 1000
subjects with neovascular AMD and 23.1 events per 1000 controls. The adjusted
rate ratio for MI was 0.58 (95% confidence interval, 0.48-0.72; P < .001) for
subjects with neovascular AMD vs controls. The rate of CVA was 14.3 events per
1000 subjects with neovascular AMD and 22.1 events per 1000 controls. The
adjusted rate ratio for CVA was 0.56 (95% confidence interval, 0.45-0.70; P <
.001). CONCLUSIONS: Rates of MI or CVA were significantly lower in subjects with 
neovascular AMD than in controls. These findings could not be explained by
systematic differences in case selection, health care use, or comorbidities,
although other possible biases cannot be ruled out.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 18779491 [PubMed - indexed for MEDLINE]

102: Arch Ophthalmol. 2008 Sep;126(9):1274-9.

The relationship of dietary omega-3 long-chain polyunsaturated fatty acid intake 
with incident age-related macular degeneration: AREDS report no. 23.

SanGiovanni JP, Chew EY, Agrón E, Clemons TE, Ferris FL 3rd, Gensler G, Lindblad 
AS, Milton RC, Seddon JM, Klein R, Sperduto RD; Age-Related Eye Disease Study
Research Group.

National Eye Institute, Bethesda, Maryland, USA.

OBJECTIVE: To examine the association of dietary omega-3 long-chain
polyunsaturated fatty acid and fish intake with incident neovascular age-related 
macular degeneration (AMD) and central geographic atrophy (CGA). METHODS:
Multicenter clinic-based prospective cohort study from a clinical trial including
Age-Related Eye Disease Study (AREDS) participants with bilateral drusen at
enrollment. Main outcome measures were incident neovascular AMD and CGA,
ascertained from annual stereoscopic color fundus photographs (median follow-up, 
6.3 years). We estimated nutrient and food intake from a validated food frequency
questionnaire (FFQ) at baseline, with intake of docosahexaenoic acid (DHA),
eicosapentaenoic acid (EPA), combined EPA and DHA, and fish as primary exposures.
RESULTS: After controlling for known covariates, we observed a reduced likelihood
of progression from bilateral drusen to CGA among people who reported the highest
levels of EPA (odds ratio [OR], 0.44; 95% confidence interval [CI], 0.23-0.87)
and EPA+DHA (OR, 0.45; 95% CI, 0.23-0.90) consumption. Levels of DHA were
associated with CGA in age-, sex-, and calorie-adjusted models (OR, 0.51; 95% CI,
0.26-1.00); however, this statistical relationship did not persist in
multivariable models. CONCLUSIONS: Dietary lipid intake is a modifiable factor
that may influence the likelihood of developing sight-threatening forms of AMD.
Our findings suggest that dietary omega-3 long-chain polyunsaturated fatty acid
intake is associated with a decreased risk of progression from bilateral drusen
to CGA.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Research Support, N.I.H., Extramural

PMID: 18779490 [PubMed - indexed for MEDLINE]

103: Ophthalmic Surg Lasers Imaging. 2008 Jul-Aug;39(4 Suppl):S15-20.

Calibration of fundus images using spectral domain optical coherence tomography.

Lujan BJ, Wang F, Gregori G, Rosenfeld PJ, Knighton RW, Puliafito CA, Danis RP,
Hubbard LD, Chang RT, Budenz DL, Seider MI, Knight O.

Bascom Palmer Eye Institute, University of Miami Miller School of Medicine,
Miami, Florida 33136, USA.

BACKGROUND AND OBJECTIVE: Measurements performed on fundus images using current
software are not accurate. Accurate measurements can be obtained only by
calibrating a fundus camera using measurements between fixed retinal landmarks,
such as the dimensions of the optic nerve, or by relying on a calibrated model
eye provided by a reading center. However, calibrated spectral domain OCT
(SD-OCT) could offer a convenient alternative method for the calibration of any
fundus image. PATIENTS AND METHODS: The ability to measure exact distances on
SD-OCT fundus images was tested by measuring the distance between the center of
the fovea and the optic nerve. Calibrated SD-OCT scans measuring 6 X 6 X 2 mm
centered on the fovea and the optic nerve were analyzed in 50 healthy right eyes.
The foveal center was identified using cross-sectional SD-OCT images, and the
center of the optic nerve was identified manually. The SD-OCT scans were
registered to each other, and the distances between the center of the optic nerve
and fovea were calculated. The overlay of these SD-OCT fundus images on
photographic fundus images was performed. RESULTS: Any image of the fundus could 
be calibrated by overlaying the SD-OCT fundus image, and the measurements were
consistent with previously defined calibration methods. The mean distance between
the center of the fovea and the center of the optic nerve was 4.32 +/-0.32 mm.
The line from the center of the optic nerve to the foveal center had a mean
declination of 7.67 +/- 3.88 degrees. Mean horizontal displacement and vertical
displacement were 4.27 +/- 0.29 mm and 0.58 +/- 0.29 mm, respectively.
CONCLUSIONS: The overlay of the SD-OCT fundus image provides a convenient method 
for calibrating any image of the fundus. This approach should provide a uniform
standard when comparing images from different devices and from different reading 
centers.

Publication Types: 
    Comparative Study
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18777875 [PubMed - indexed for MEDLINE]

104: Invest Ophthalmol Vis Sci. 2008 Dec;49(12):5553-60. Epub 2008 Sep 4.

Retinal function in best macular dystrophy: relationship between
electrophysiological, psychophysical, and structural measures of damage.

Maia-Lopes S, Silva ED, Reis A, Silva MF, Mateus C, Castelo-Branco M.

Visual Neuroscience Laboratory, IBILI, Faculty of Medicine, University of
Coimbra, Coimbra, Portugal.

PURPOSE: To establish structure-function correlations across the visual field, to
investigate disease progression in Best macular dystrophy (BMD), by correlating
structural damage with retinal function as assessed by the combination of
psychophysics and multifocal electrophysiology. METHODS: Spatial achromatic and
chromatic contrast sensitivities (probing red-green and blue-yellow pathways)
were assessed using custom-made psychophysical software to evaluate retinal
damage in BMD and age-matched control eyes (n = 19 and n = 22, respectively).
Neurosensory retinal dysfunction was also evaluated by means of multifocal
electroretinography (mfERG). Correlation analysis was performed between
functional parameters in BMD, clinical measures, and morphologic data obtained by
optical coherence tomography (OCT). RESULTS: Significant peripheral impairment of
retinal function, as measured by mfERG and spatial achromatic contrast
sensitivity (CS) methods, was found in BMD. Furthermore, changes in thickness of 
the neurosensory retina, as measured by OCT, and reduced mfERG responses were
also indicators of early loss in BMD and often occurred even with preserved
visual acuity. Disease duration was significantly correlated with psychophysical 
deterioration in chromatic and achromatic tasks but not with mfERG measures.
Interestingly, partial correlation analysis revealed a significant independent
correlation with our CS measures. CONCLUSIONS: Novel topographic achromatic and
chromatic CS methods can detect and quantify functional impairment in early
stages of BMD, including the involvement of the peripheral retina and the central
chromatic pathway, and can provide new pathophysiological information with added 
value in relation to electrophysiological and structural measures of damage.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18775865 [PubMed - indexed for MEDLINE]

105: Am J Ophthalmol. 2008 Nov;146(5):649-55, 655.e1-6. Epub 2008 Sep 5.

Diabetic macular edema: what is focal and what is diffuse?

Browning DJ, Altaweel MM, Bressler NM, Bressler SB, Scott IU; Diabetic
Retinopathy Clinical Research Network.

Jaeb Center for Health Research, Tampa, FL 33647, USA. DRCR.netX4@jaeb.org

PURPOSE: To review the available information on classification of diabetic
macular edema (DME) as focal or diffuse. DESIGN: Interpretive essay. METHODS:
Literature review and interpretation. RESULTS: The terms focal diabetic macular
edema and diffuse diabetic macular edema frequently are used without clear
definitions. Published definitions often use different examination methods and
often are inconsistent. Evaluating published information on the prevalence of
focal and diffuse DME, the responses of focal and diffuse DME to treatments, and 
the importance of focal and diffuse DME in assessing prognosis is hindered
because the terms are used inconsistently. A newer vocabulary may be more
constructive, one that describes discrete components of the concepts such as
extent and location of macular thickening, involvement of the center of the
macula, quantity and pattern of lipid exudates, source of fluorescein leakage,
and regional variation in macular thickening and that distinguishes these terms
from the use of the term focal when describing one type of photocoagulation
technique. Developing methods for assessing component variables that can be used 
in clinical practice and establishing reproducibility of the methods are
important tasks. CONCLUSIONS: Little evidence exists that characteristics of DME 
described by the terms focal and diffuse help to explain variation in visual
acuity or response to treatment. It is unresolved whether a concept of focal and 
diffuse DME will prove clinically useful despite frequent use of the terms when
describing management of DME. Further studies to address the issues are needed.

Publication Types: 
    Research Support, N.I.H., Extramural
    Review

PMID: 18774122 [PubMed - indexed for MEDLINE]

106: Jpn J Ophthalmol. 2008 Jul-Aug;52(4):265-8. Epub 2008 Sep 5.

Erratum in:
    Jpn J Ophthalmol. 2008 Sep-Oct;52(5):426. Yoshikawa, Tadanori [corrected to
Yoshikawa, Tadanobu].

Posterior sub-Tenon injection of triamcinolone acetonide as pretreatment for
focal laser photocoagulation in diabetic macular edema patients.

Shima C, Ogata N, Minamino K, Yoshikawa T, Matsuyama K, Matsumura M.

Department of Ophthalmology, Kansai Medical University, Moriguchi, Osaka, Japan.

PURPOSE: To determine whether a posterior sub-Tenon injection of triamcinolone
acetonide (TA) before focal photocoagulation is safe and effective in patients
with diabetic macular edema. METHODS: Sixteen eyes of 11 diabetic patients with
unresolved diffuse macular edema were treated with a 20-mg sub-Tenon injection of
TA 1 to 2 months before focal photocoagulation. Focal photocoagulation was
applied only to microaneurysms, and grid laser photocoagulation was not
performed. The main outcome measures used were visual acuity (VA), central
macular thickness (CMT) determined by optical coherence tomography (OCT), and the
fluorescein angiographic appearance of the retina. Patients were followed for at 
least 6 months. RESULTS: One month after the sub-Tenon injection of TA, the
macular edema was resolved with a significant reduction of the CMT on OCT. VA
improved slightly. Subsequent focal photocoagulation of the microaneurysms
maintained the significant reduction of CMT for up to 6 months. A significant
improvement of VA was observed in 37.5% patients at 6 months, and there was no
decrease in VA in any of the patients. CONCLUSIONS: A 20-mg sub-Tenon TA
injection prior to focal laser photocoagulation is a safe and beneficial
treatment in patients with diabetic macular edema.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18773263 [PubMed - indexed for MEDLINE]

107: Optom Vis Sci. 2008 Sep;85(9):827-33.

Reading speed does not benefit from increased line spacing in AMD patients.

Chung ST, Jarvis SH, Woo SY, Hanson K, Jose RT.

College of Optometry, University of Houston, Houston, Texas, USA.
s.chung@berkeley.edu

PURPOSE: Crowding, the adverse spatial interaction due to the proximity of
adjacent targets, has been suggested as an explanation for slow reading in
peripheral vision. Previously, we showed that increased line spacing, which
presumably reduces crowding between adjacent lines of text, improved reading
speed in the normal periphery (Chung, Optom Vis Sci 2004;81:525-35). The purpose 
of this study was to examine whether or not individuals with age-related macular 
degeneration (AMD) would benefit from increased line spacing for reading.
METHODS: Experiment 1: Eight subjects with AMD read aloud 100-word passages
rendered at five line spacings: the standard single spacing, 1.5x, 2x, 3x, and 4x
the standard spacing. Print sizes were 1x and 2x of the critical print size.
Reading time and number of reading errors for each passage were measured to
compute the reading speed. Experiment 2: Four subjects with AMD read aloud
sequences of six 4-letter words, presented on a computer monitor using the rapid 
serial visual presentation (RSVP) paradigm. Target words were presented singly,
or flanked above and below by two other words that changed in synchrony with the 
target word, at various vertical word separations. Print size was 2x the critical
print size. Reading speed was calculated based on the RSVP exposure duration that
yielded 80% of the words read correctly. RESULTS: Averaged across subjects,
reading speeds for passages were virtually constant for the range of line
spacings tested. For sequences of unrelated words, reading speeds were also
virtually constant for the range of vertical word separations tested, except at
the smallest (standard) separation at which reading speed was lower. CONCLUSIONS:
Contrary to the previous finding that reading speed improved in normal peripheral
vision, increased line spacing in passages, or increased vertical separation
between words in RSVP, did not lead to improved reading speed in people with AMD.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 18772718 [PubMed - indexed for MEDLINE]

108: Br J Ophthalmol. 2008 Dec;92(12):1628-35. Epub 2008 Sep 4.

Same-day administration of verteporfin and ranibizumab 0.5 mg in patients with
choroidal neovascularisation due to age-related macular degeneration.

Schmidt-Erfurth U, Wolf S; PROTECT Study Group.

Collaborators: Aue A, Bartz-Schmidt KU, Bornfeld N, Engelmann K, Foerster MH,
Gabel VP, Gamulescu A, Holz FG, Inhoffen W, Kruse F, Lohmann CP, Michels R,
Pauleikhoff D, Sander D, Schmidt-Erfurth U, Uhlig CE, Wolf S.

Department of Ophthalmology, Universitätsklinik fur Augenheilkunde und
Optometrie, University of Vienna, AKH Vienna, Währinger Gürtel 18-20, A-1090
Vienna, Austria. ursula.schmidt-erfurth@meduniwien.ac.at

OBJECTIVE: To evaluate safety of same-day administration of verteporfin and
ranibizumab. METHODS: Prospective, open-label, multicentre study; patients with
predominantly classic (n = 13) or occult (n = 19) choroidal neovascularisation
secondary to age-related macular degeneration received standard-fluence
verteporfin at baseline and months 3, 6 and 9, based on fluorescein angiography
(FA). Ranibizumab 0.5 mg was administered at baseline and months 1, 2 and 3. MAIN
OUTCOME MEASURE: The incidence of severe vision loss (best-corrected visual
acuity (BCVA) loss > or = 30 letters; primary safety assessment). RESULTS: No
severe vision loss due to ocular inflammation or uveitis occurred. One patient
had moderate vision loss (BCVA loss > or = 15 letters). Three patients had
mild/moderate uveitis. Two serious ocular adverse events occurred (retinal
pigment epithelial tear and moderate BCVA decrease). No systemic adverse events
occurred. At 9 months, all lesions were inactive with no recurrent leakage on FA 
and optical coherence tomography; macular oedema and subretinal fluid resolved.
The mean BCVA measured at 2 m improved by 6.9 letters at 4 months and 2.4 letters
at 9 months. CONCLUSIONS/APPLICATION TO CLINICAL PRACTICE: Same-day verteporfin
and ranibizumab was safe and not associated with severe vision loss or severe
ocular inflammation. Lesions stabilized, with minimal treatment required after
month 3.

Publication Types: 
    Clinical Trial, Phase II
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 18772178 [PubMed - indexed for MEDLINE]

109: PLoS ONE. 2008 Sep 1;3(9):e3119.

Chronic cigarette smoke causes oxidative damage and apoptosis to retinal
pigmented epithelial cells in mice.

Fujihara M, Nagai N, Sussan TE, Biswal S, Handa JT.

Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, Maryland,
United States of America.

The purpose of this study was to determine whether mice exposed to chronic
cigarette smoke develop features of early age-related macular degeneration (AMD).
Two month old C57Bl6 mice were exposed to either filtered air or cigarette smoke 
in a smoking chamber for 5 h/day, 5 days/week for 6 months. Eyes were fixed in
2.5% glutaraldehyde/2% paraformaldehyde and examined for ultrastructural changes 
by transmission electron microscopy. The contralateral eye was fixed in 2%
paraformaldehyde and examined for oxidative injury to the retinal pigmented
epithelium (RPE) by 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-OHdG) immunolabeling
and apoptosis by TUNEL labeling. Mice exposed to cigarette smoke had
immunolabeling for 8-OHdG in 85+/-3.7% of RPE cells counted compared to
9.5+/-3.9% in controls (p<0.00001). Bruch membrane was thicker in mice exposed to
smoke (1086+/-332 nm) than those raised in air (543+/-132 nm; p = 0.0069). The
two most pronounced ultrastructural changes (severity grading scale from 0-3)
seen were a loss of basal infoldings (mean difference in grade = 1.98; p<0.0001),
and an increase in intracellular vacuoles (mean difference in grade = 1.7;
p<0.0001). Ultrastructural changes to Bruch membrane in cigarette-smoke exposed
mice were smaller in magnitude but consistently demonstrated significantly higher
grade injury in cigarette-exposed mice, including basal laminar deposits (mean
difference in grade = 0.54; p<0.0001), increased outer collagenous layer deposits
(mean difference in grade = 0.59; p = 0.002), and increased basal laminar deposit
continuity (mean difference in grade = 0.4; p<0.0001). TUNEL assay showed a
higher percentage of apoptotic RPE from mice exposed to cigarette smoke (average 
8.0+/-1.1%) than room air (average 0+/-0%; p = 0.043). Mice exposed to chronic
cigarette smoke develop evidence of oxidative damage with ultrastructural
degeneration to the RPE and Bruch membrane, and RPE cell apoptosis. This model
could be useful for studying the mechanism of smoke induced changes during early 
AMD.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18769672 [PubMed - indexed for MEDLINE]

110: Ophthalmic Genet. 2008 Sep;29(3):139-44.

Mutation analysis of the VMD2 gene in thai families with best macular dystrophy.

Atchaneeyasakul LO, Jinda W, Sakolsatayadorn N, Trinavarat A, Ruangvoravate N,
Thanasombatskul N, Thongnoppakhun W, Limwongse C.

Department of Ophthalmology, Faculty of Medicine, Siriraj Hospital Mahidol
University, Bangkok, Thailand. atchanee@hotmail.com

BACKGROUND: To identify genetic mutations of the VMD2 gene in two Thai families
with Best macular dystrophy. MATERIALS AND METHODS: Ophthalmic examination
including best-corrected visual acuity (BCVA), dilated fundus examination and
fundus photography, and electro-oculography (EOG) was performed in two probands
and their family members. Mutation screening of the VMD2 gene was performed by
single-strand conformation polymorphism (SSCP) analysis followed by direct DNA
sequencing of the abnormal exons. RESULTS: The 58-year-old male proband
demonstrated typical egg yolk-like macular lesion in both eyes. Mutational
screening of VMD2 identified a band shift in exon 7, which was confirmed by
direct DNA sequencing to be a G to A transition at position 724 bp. This novel
missense mutation resulted in the change of an amino acid valine to methionine
and was responsible for the abnormal Arden ratio in the proband's daughter. The
second male proband age 25 had a characteristic egg yolk-like macular lesion in
the left eye and a scrambled egg appearance in the right. Mutation analysis
identified a C to T transition at position 652 bp in exon 6. This reported
missense mutation led to an amino acid substitution of cysteine for arginine. The
mutation was documented in the maternal grandmother, the mother, as well as the
elder sister of the proband. CONCLUSIONS: The Val-242-Met mutation is associated 
with a late-onset visual disturbance and the Arg-218-Cys mutation was associated 
with marked intra-familial clinical variability of expression. Presymptomatic
testing will be available to the family members at risk with high accuracy.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 18766995 [PubMed - indexed for MEDLINE]

111: Ophthalmic Genet. 2008 Sep;29(3):117-9.

The frequency of the H402 allele of CFH and its involvement with age-related
maculopathy in an aged Black African Xhosa population.

Ziskind A, Bardien S, van der Merwe L, Webster AR.

Division of Ophthalmology, Faculty of Health Sciences, University of
Stellenbosch, Cape Town, South Africa. az@sun.ac.za

The H402 allele of the CFH gene is an established risk factor for age-related
maculopathy (ARMD) in Caucasians, accounting for approximately 60% of the genetic
risk at the population level. In general, the advanced forms of ARMD are rare in 
Black populations in Africa, as well as Black populations who have lived for
generations in the United States or the West Indies, although there are reports
that the earlier forms such as drusen may not be all that uncommon. The aim of
the present study was to estimate the frequency of the C allele of the CFH Y402H 
variant in an aged South African Black Xhosa population and to describe the
evidence of ARMD found.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18766990 [PubMed - indexed for MEDLINE]

112: Ophthalmology. 2008 Sep;115(9):1460-7.

Age-period-cohort effect on the incidence of age-related macular degeneration:
the Beaver Dam Eye Study.

Klein R, Knudtson MD, Lee KE, Gangnon RE, Klein BE.

Department of Ophthalmology and Visual Sciences, University of Wisconsin School
of Medicine and Public Health, Madison, Wisconsin 53726-2336, USA.
kleinr@epi.ophth.wisc.edu

OBJECTIVE: To examine relationships of age, period, and birth cohort with the
5-year incidence of age-related macular degeneration (AMD). DESIGN:
Population-based cohort study with 4 examination visits 5 years apart from 1988
through 1990, 1993 through 1995, 1998 through 2000, and 2003 through 2005.
PARTICIPANTS: Two thousand nine hundred sixty-eight persons (6603 participant
visits) and 3588 persons (8184 participant visits) 43 to 86 years of age at
baseline contributing to the incidence of early and late AMD, respectively.
METHODS: Grading of stereoscopic fundus photographs using the Wisconsin
Age-Related Maculopathy Grading System. MAIN OUTCOME MEASURES: Five-year
incidence of early AMD. RESULTS: While controlling for age, there was a lower
5-year incidence of early AMD in later rather than in earlier birth cohorts (odds
ratio per increasing category, 0.70; 95% confidence interval, 0.62-0.78;
P<0.001). This remained while controlling for smoking, blood pressure, and other 
related factors. There was no evidence for a period or birth cohort effect with
late AMD. CONCLUSIONS: Lower incidence of early AMD in more recent birth cohorts 
is likely the result of unmeasured risk factors for early AMD. Further study of
possible unmeasured risk factors that may have caused this cohort effect may help
to identify new modifiable risk factors for AMD. Diminishing incidence of early
AMD in later birth cohorts would be expected to result in lower long-term
estimates of future incidence of AMD than do current estimates that do not take
this effect into account.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18762073 [PubMed - indexed for MEDLINE]

113: Am J Ophthalmol. 2008 Nov;146(5):664-673. Epub 2008 Aug 30.

Implantable telescope for end-stage age-related macular degeneration: long-term
visual acuity and safety outcomes.

Hudson HL, Stulting RD, Heier JS, Lane SS, Chang DF, Singerman LJ, Bradford CA,
Leonard RE; IMT002 Study Group.

Retina Centers, P.C., Tucson, Arizona, USA. henhud@msn.com

PURPOSE: To evaluate long-term safety and best-corrected visual acuity (BCVA)
results of a telescope prosthesis in patients with end-stage age-related macular 
degeneration (AMD). DESIGN: Prospective, open-label clinical trial with
fellow-eye controls. METHODS: Patients with end-stage AMD (bilateral geographic
atrophy or disciform scars; BCVA, 20/80 to 20/800) received the telescope
prosthesis at 28 centers. Methods were similar to those described in the one-year
results, with follow-up visits continuing at 18 and 24 months. Main outcome
measures included BCVA change from baseline, endothelial cell density (ECD) and
morphometry, and incidence of complications. RESULTS: At two years, data from 174
(92.6%) of 188 available patients were analyzed. Overall, 103 (59.5%) of 173
telescope-implanted eyes gained three lines or more (doubling of visual angle) of
BCVA compared with 18 (10.3%) of 174 fellow control eyes (P < .0001). Mean BCVA
improved 3.6 lines (standard deviation [SD], 1.9 lines) and 2.8 lines (SD, 2.3
lines) from baseline in eyes with the 3X and 2.2X device models, respectively.
Mean ECD stabilized through two years, with 2.4% mean cell loss occurring from
one to two years. There was no significant change in coefficient of variation or 
percentage of hexagonal endothelial cells from within six months to two years
after surgery. The most common complication was inflammatory deposits.
CONCLUSIONS: Long-term results of this telescope prosthesis show the substantial 
BCVA improvement at one year is maintained at two years. Key indicators of
corneal health demonstrate ECD change that reflects remodeling of the endothelium
associated with the implantation procedure. ECD stabilizes over time, and there
is no evidence of any ongoing endothelial trauma.

Publication Types: 
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 18760765 [PubMed - indexed for MEDLINE]

114: Am J Ophthalmol. 2008 Dec;146(6):954-9.e1. Epub 2008 Aug 30.

Retinal vascular caliber and age-related macular degeneration: the Singapore
Malay Eye Study.

Jeganathan VS, Kawasaki R, Wang JJ, Aung T, Mitchell P, Saw SM, Wong TY.

Centre for Eye Research Australia, University of Melbourne, Melbourne, Victoria, 
Australia.

PURPOSE: To investigate the relationship between retinal vascular caliber and
age-related macular degeneration (AMD). DESIGN: Population-based cross-sectional 
study. METHODS: Three thousand two hundred and eighty (78.7% response rate) Malay
Singaporeans aged 40 to 80 years residing in 15 districts of Singapore underwent 
retinal photography. Retinal vessel caliber was measured from retinal photographs
using a validated computer-based technique. AMD was assessed following a modified
Wisconsin Age-Related Maculopathy Grading System. RESULTS: Retinal data were
available from 3,265 subjects (99.5% of 3,280) for this study. Early and late AMD
prevalence were 4.9% (n = 160) and 0.7% (n = 23) of the population, respectively,
or in 205 (3.1%) and 30 (0.5%) eyes examined, respectively. After controlling for
age and arteriolar caliber, wider venular caliber was associated with higher
prevalence of early AMD (odds ratio [OR] per one standard deviation [SD]
increment in venular caliber, 1.53; 95% confidence interval [CI], 1.13 to 2.09). 
This association remained significant after further adjustment for gender,
smoking, hypertension, diabetes, and body mass index (OR per one SD, 1.52; 95%
CI, 1.11 to 2.09). There was no significant association between retinal
arteriolar caliber and early AMD, or between arteriolar or venular caliber and
late AMD. CONCLUSIONS: Wider venular caliber was associated independently with
early AMD. This finding may suggest that pathogenic processes linking to wider
venular caliber be shared by early AMD and common cardiovascular risk factors
such as inflammation, dyslipidemia, and endothelial dysfunction.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18760764 [PubMed - indexed for MEDLINE]

115: Coll Antropol. 2008 Jun;32(2):351-3.

Long term results of age-related macular degeneration therapy with prednisolone
acetate--special refer to peripheral visual field changes.

Vojniković B, Kovacević D, Njirić S, Coklo M.

Eye Polyclinic Dr. B. Vojniković, Rijeka, Croatia. decv@decv.com

In the north Croatian Adriatic area in the period of seven years (from January
2001 to September 2007) 475 patients (39 to 80 years of age) with dry form of age
related macular degeneration (AMD) were diagnosed. Complete ophthalmologic
examination with special reference to visual field testing (Perimetric analysis) 
was performed. Peripheral visual field defects were found in 85% of patients.
Elderly patients with more advanced forms of macular degeneration had more
peripheral visual field defects. In 400 patients corticosteroid therapy (5 mg
Prednisolonacetate, anterior H-inject, Winthorp) was administered via parabulbar 
injections every day/five days. Control group consisted of 75 patients treated
with regular polyvitamine therapy (Lutein, Beta Karoten, Vitamin E). Patients
treated with corticosteroids had peripheral visual field improvements from 10 to 
25 degrees and central field improvements from 5 to 20%. In the control group
treated with vitamins, central visual field showed improvements from 0.5 to 1% in
43 patients but without peripheral visual field improvements after 6 months.

Publication Types: 
    Controlled Clinical Trial

PMID: 18756880 [PubMed - indexed for MEDLINE]

116: Expert Opin Drug Deliv. 2008 Sep;5(9):1039-46.

Iluvien: a new sustained delivery technology for posterior eye disease.

Kane FE, Burdan J, Cutino A, Green KE.

Alimera Sciences, Inc., 6120 Windward Pkwy, Suite 290, Alpharetta, GA 30005, USA.
fran.kane@alimerasciences.com

Iluvien (fluocinolone acetonide intravitreal insert, Alimera Sciences, Inc.), a
novel injectable intravitreal insert, is being studied to deliver a very low dose
of a corticosteroid to the retina for up to 3 years as a treatment for diabetic
macular edema. Using a proprietary 25-gauge injector system, an ophthalmologist
injects the Iluvien insert, which uses the Medidur (Alimera Sciences, Inc.)
technology, into the vitreous through a minimally invasive procedure in an
out-patient setting. The placement of the device in the inferior vitreous has the
potential to maximize drug at the retina while reducing exposure of the anterior 
chamber. Phase III studies are underway to test the safety and efficacy of
Iluvien. This article offers a specific review of the Iluvien technology rather
than an overview of the various intravitreal methods of treating posterior eye
disease.

Publication Types: 
    Review

PMID: 18754752 [PubMed - indexed for MEDLINE]

117: N Engl J Med. 2008 Oct 2;359(14):1456-63. Epub 2008 Aug 27.

Erratum in:
    N Engl J Med. 2008 Oct 23;359(17):1859.

Toll-like receptor 3 and geographic atrophy in age-related macular degeneration.

Yang Z, Stratton C, Francis PJ, Kleinman ME, Tan PL, Gibbs D, Tong Z, Chen H,
Constantine R, Yang X, Chen Y, Zeng J, Davey L, Ma X, Hau VS, Wang C, Harmon J,
Buehler J, Pearson E, Patel S, Kaminoh Y, Watkins S, Luo L, Zabriskie NA,
Bernstein PS, Cho W, Schwager A, Hinton DR, Klein ML, Hamon SC, Simmons E, Yu B, 
Campochiaro B, Sunness JS, Campochiaro P, Jorde L, Parmigiani G, Zack DJ,
Katsanis N, Ambati J, Zhang K.

Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital,
Chengdu, China.

BACKGROUND: Age-related macular degeneration is the most common cause of
irreversible visual impairment in the developed world. Advanced age-related
macular degeneration consists of geographic atrophy and choroidal
neovascularization. The specific genetic variants that predispose patients to
geographic atrophy are largely unknown. METHODS: We tested for an association
between the functional toll-like receptor 3 gene (TLR3) variant rs3775291
(involving the substitution of phenylalanine for leucine at amino acid 412) and
age-related macular degeneration in Americans of European descent. We also tested
for the effect of TLR3 Leu and Phe variants on the viability of human retinal
pigment epithelial cells in vitro and on apoptosis of retinal pigment epithelial 
cells from wild-type mice and Tlr3-knockout (Tlr3(-/-)) mice. RESULTS: The Phe
variant (encoded by the T allele at rs3775291) was associated with protection
against geographic atrophy (P=0.005). This association was replicated in two
independent case-control series of geographic atrophy (P=5.43x10(-4) and
P=0.002). No association was found between TLR3 variants and choroidal
neovascularization. A prototypic TLR3 ligand induced apoptosis in a greater
fraction of human retinal pigment epithelial cells with the Leu-Leu genotype than
those with the Leu-Phe genotype and in a greater fraction of wild-type mice than 
Tlr3(-/-) mice. CONCLUSIONS: The TLR3 412Phe variant confers protection against
geographic atrophy, probably by suppressing the death of retinal pigment
epithelial cells. Since double-stranded RNA (dsRNA) can activate TLR3-mediated
apoptosis, our results suggest a role of viral dsRNA in the development of
geographic atrophy and point to the potential toxic effects of
short-interfering-RNA therapies in the eye. 2008 Massachusetts Medical Society

Publication Types: 
    In Vitro
    Multicenter Study
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, Non-P.H.S.

PMID: 18753640 [PubMed - indexed for MEDLINE]

118: Acta Ophthalmol. 2008 Aug;86(5):504-9.

Subretinal surgery and transplantation of autologous pigment epithelial cells in 
retinal angiomatous proliferation.

Krebs I, Binder S, Stolba U, Kellner L, Glittenberg C, Goll A.

Department of Ophthalmology, Rudolf Foundation Clinic, Vienna, Austria.
Ilse.Krebs@wienkav.at

PURPOSE: The aim of this study was to examine whether the presence of retinal
angiomatous proliferation (RAP) is a prognostic factor in subretinal surgery with
transplantation of a suspension of autologous retinal pigment epithelial (RPE)
cells. METHODS: Eyes that had been followed for at least 12 months after
subretinal surgery were reviewed retrospectively and assigned to group 1
(presence of RAP) or group 2 (lesions without RAP). Main outcome measures were
logMAR distance acuity and lesion size at 12 months. RESULTS: A total of 68 eyes 
of 68 patients were included; 28 were assigned to group 1 and 40 to group 2. A
total of 43% of patients were male and 57% were female. Their mean age was 77.8
years. Mean distance acuity was 1.02 logMAR at baseline and 1.06 logMAR at month 
12. Mean lesion size was 27.9 mm(2) at baseline and 29.9 mm2 at month 12. The
differences between the groups were not significant. CONCLUSIONS: The presence of
RAP did not significantly influence the outcome after subretinal surgery with
transplantation of autologous RPE cells. Other than age, preoperative lesion size
and distance acuity were the only predictive factors for postoperative results.

PMID: 18752526 [PubMed - indexed for MEDLINE]

119: Proc Natl Acad Sci U S A. 2008 Sep 2;105(35):12843-8. Epub 2008 Aug 26.

Role of Stargardt-3 macular dystrophy protein (ELOVL4) in the biosynthesis of
very long chain fatty acids.

Agbaga MP, Brush RS, Mandal MN, Henry K, Elliott MH, Anderson RE.

Department of Cell Biology, University of Oklahoma Health Sciences Center,
Oklahoma City, USA.

Stargardt-like macular dystrophy (STGD3) is a dominantly inherited juvenile
macular degeneration that eventually leads to loss of vision. Three independent
mutations causing STGD3 have been identified in exon six of a gene named
Elongation of very long chain fatty acids 4 (ELOVL4). The ELOVL4 protein was
predicted to be involved in fatty acid elongation, although evidence for this and
the specific step(s) it may catalyze have remained elusive. Here, using a
gain-of-function approach, we provide direct and compelling evidence that ELOVL4 
is required for the synthesis of C28 and C30 saturated fatty acids (VLC-FA) and
of C28-C38 very long chain polyunsaturated fatty acids (VLC-PUFA), the latter
being uniquely expressed in retina, sperm, and brain. Rat neonatal cardiomyocytes
and a human retinal epithelium cell line (ARPE-19) were transduced with
recombinant adenovirus type 5 carrying mouse Elovl4 and supplemented with 24:0,
20:5n3, or 22:5n3. The 24:0 was elongated to 28:0 and 30:0; 20:5n3 and 22:5n3
were elongated to a series of C28-C38 PUFA. Because retinal degeneration is the
only known phenotype in STGD3 disease, we propose that reduced VLC-PUFA in the
retinas of these patients may be the cause of photoreceptor cell death.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18728184 [PubMed - indexed for MEDLINE]

120: Am J Ophthalmol. 2008 Dec;146(6):960-7.e1. Epub 2008 Aug 23.

Smoking, cardiovascular risk factors, and age-related macular degeneration in
Asians: the Singapore Malay Eye Study.

Cackett P, Wong TY, Aung T, Saw SM, Tay WT, Rochtchina E, Mitchell P, Wang JJ.

Singapore Eye Research Institute, Singapore; Singapore National Eye Center,
Singapore.

PURPOSE: To assess associations between smoking and cardiovascular risk factors
and prevalent age-related macular degeneration (AMD) in the Singapore Malay
population. DESIGN: Population-based, cross-sectional study. METHODS: A total of 
3,280 Malay adults age 40 to 80 years were included in the study. Early and late 
AMD signs were graded from retinal photographs following Wisconsin system. All
participants had interview, systemic examination, and laboratory investigations
to determine smoking status and cardiovascular risk factors. RESULTS: A total of 
3,265 participants had gradable photos, 21 (0.6%) with late AMD and 169 (5.2%)
with early AMD. After adjusting for age and gender, current smokers were
significantly more likely to have late AMD (odds ratio [OR], 3.79; 95% confidence
interval [CI], 1.40 to 10.23). This association was stronger among those who
currently smoked >5 packs of cigarettes per week (OR, 9.35; 95% CI, 2.49 to
35.08). CONCLUSIONS: Smoking was associated with a higher late AMD prevalence in 
Malays, consistent with findings from studies in White populations.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18723144 [PubMed - indexed for MEDLINE]

121: Ophthalmology. 2008 Nov;115(11):1883-90. Epub 2008 Aug 22.

Drusen ultrastructure imaging with spectral domain optical coherence tomography
in age-related macular degeneration.

Khanifar AA, Koreishi AF, Izatt JA, Toth CA.

Duke University Medical Center, Department of Ophthalmology, Durham, North
Carolina, USA.

PURPOSE: To categorize drusen ultrastructure in age-related macular degeneration 
(AMD) using spectral domain optical coherence tomography (SDOCT) and correlate
the tomographic and photographic drusen appearances. DESIGN: Prospective case
series. PARTICIPANTS: Thirty-one eyes of 31 patients with non-neovascular AMD.
METHODS: Subjects with drusen and a clinical diagnosis of AMD were enrolled in an
SDOCT imaging study from August of 2005 to May of 2007. Foveal linear scans were 
acquired, and the image data were processed for analysis. Drusen were scored by 4
morphologic categories: shape, predominant internal reflectivity, homogeneity,
and presence of overlying hyper-reflective foci. The prevalences of each
morphologic pattern and combinations of morphologic patterns observed were
calculated. The photographic appearance of each druse was compared with the
tomographic classification. Interobserver and intraobserver agreement analysis
was performed. MAIN OUTCOME MEASURES: Prevalence of morphologic parameters using 
SDOCT. RESULTS: Twenty-one eyes of 21 patients had SDOCT B-scans of adequate
quality for analysis. On the basis of the above morphologic categories, 17
different drusen patterns were found in 120 total drusen. The most common was
convex, homogeneous, with medium internal reflectivity, and without overlying
hyper-reflective foci, present in 17 of 21 eyes (81%). Of the 16 eyes (76%) with 
nonhomogeneous drusen, 5 had a distinct hyper-reflective core. Hyper-reflective
foci overlying drusen were in 7 eyes (33%). Although half of the photographically
soft-indistinct drusen were convex with medium internal reflectivity and
homogeneous without overlying hyper-reflective foci, the other half had
significant variability in their tomographic appearance. Both interobserver and
intraobserver agreement in drusen grading were high. Readers agreed the most when
grading drusen shape and reflectivity, whereas the least agreement was for drusen
homogeneity. CONCLUSIONS: Drusen ultrastructure can be imaged with SDOCT and
characterized with a simple grading system. Photographic appearance may predict
some but not all tomographic appearances. Trained observers have a high level of 
agreement with this grading system. These in vivo morphologic characteristics
imaged with SDOCT may be distinct subclasses of drusen types, may relate closely 
to ultrastructural drusen elements identified in cadaveric eyes, and may be
useful imaging biomarkers for disease severity or risk of progression. This will 
require validation from further studies.

Publication Types: 
    Comparative Study
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18722666 [PubMed - indexed for MEDLINE]

122: J Cataract Refract Surg. 2008 Sep;34(9):1571-7.

Clinical magnification and residual refraction after implantation of a double
intraocular lens system in patients with macular degeneration.

Amselem L, Diaz-Llopis M, Felipe A, Artigas JM, Navea A, García-Delpech S.

Hospital General Universitario, Departamento de Optica, Facultad de Física,
Universitat de València, C/Dr Moliner 50, Burjassot, Valencia, Spain.

PURPOSE: To evaluate the efficacy of a standard double intraocular lens (IOL)
system (IOL-Vip) in patients with low vision and central scotoma due to macular
degeneration and assess the predictability of the residual refraction and
magnification. SETTING: Ophthalmology Department, Hospital General Universitario,
Valencia, Spain. METHODS: This interventional prospective noncomparative case
series comprised 13 consecutive surgical procedures in 10 patients with central
scotoma. Follow-up was 12 months. Evaluation included the difference between
preoperative and postoperative best corrected visual acuity (BCVA), refraction,
position of the IOLs, endothelial cell density, and occurrence of postoperative
complications. Residual refraction and eye magnification were calculated using a 
theory developed in a previous study, and the values were compared with the
clinical results. RESULTS: The mean BCVA was 1.37 logMAR preoperatively and 0.68 
logMAR 1 year postoperatively. The mean best corrected clinical gain was 44%.
There was no statistically significant difference between the clinically
evaluated and theoretically calculated residual refractions (P = .17). No
intraoperative or postoperative complications occurred. CONCLUSIONS: Implantation
of the double IOL system improved BCVA in patients with low vision due to
advanced maculopathy. The results were best in myopic patients (long eyes);
patients with hyperopia (short eyes) had high residual refraction. The
postoperative clinical gain and residual refraction were predictable, showing the
feasibility of implanting a customized double IOL.

PMID: 18721722 [PubMed - indexed for MEDLINE]

123: Ophthalmology. 2008 Nov;115(11):1891-8. Epub 2008 Aug 21.

The HtrA1 promoter polymorphism, smoking, and age-related macular degeneration in
multiple case-control samples.

Tuo J, Ross RJ, Reed GF, Yan Q, Wang JJ, Bojanowski CM, Chew EY, Feng X, Olsen
TW, Ferris FL 3rd, Mitchell P, Chan CC.

Laboratory of Immunology, National Eye Institute, National Institutes of Health, 
Bethesda, Maryland, USA.

OBJECTIVE: To assess the association and combined effect on the risk of
age-related macular degeneration (AMD) by the HtrA1 and complement factor H (CFH)
polymorphisms, smoking, and serum cholesterol. DESIGN: Clinic-based and
population-based case control study. PARTICIPANTS: A total of 805 AMD cases and
921 controls from The Eye Clinic of National Eye Institute, Age-Related Eye
Diseases Study, Blue Mountain Eye Study Cohort, and Minnesota Lions Eye Bank.
METHODS: DNA samples were genotyped for polymorphisms of rs11200638 in HtrA1
promoter and rs380390 in CFH. HtrA1 protein in ocular tissue was measured.
Interactions of the HtrA1 risk allele with the CFH risk variant, smoking status, 
and cholesterol were assessed. MAIN OUTCOME MEASURES: AMD was evaluated by
retinal specialists, and AMD subtypes (geographic atrophy and neovascularization)
were determined. RESULTS: Strong associations of the HtrA1 risk allele (A) with
AMD were present in all sample sets. A similar magnitude of association was
observed for central geographic atrophy and neovascular AMD. The combination of
the HtrA1 and CFH risk alleles increased AMD susceptibility, as did the
combination of the HtrA1 risk allele with smoking. No combined effect of HtrA1
risk allele and cholesterol level was found. Enhanced expression of HtrA1 protein
was detected in retina with AMD. CONCLUSIONS: Findings from multiple samples
support an AMD genetic variant harbored within HtrA1. The risk of advanced AMD
increased when the presence of risk alleles from HtrA1 was combined with either
CFH risk alleles or history of smoking.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18718667 [PubMed - indexed for MEDLINE]

124: Ophthalmic Surg Lasers Imaging. 2008 Jul-Aug;39(4):294-8.

Treatment of neovascular age-related macular degeneration with pegaptanib and
boosting with bevacizumab or ranibizumab as needed.

Farah SE.

Department of Ophthalmology and Visual Sciences, The Albert Einstein College of
Medicine, Pelham Bay, New York, USA.

BACKGROUND AND OBJECTIVE: Neovascular age-related macular degeneration presents a
therapeutic challenge. The efficacy of pegaptanib sodium, a selective inhibitor
of vascular endothelial growth factor 165, was examined as a therapeutic mainstay
combined with "as needed" boosts of nonselective vascular endothelial growth
factor blockade with bevacizumab or ranibizumab. PATIENTS AND METHODS: A
retrospective chart review of outcomes of patients treated with pegaptanib and
later boosted with bevacizumab or ranibizumab was conducted. Visual acuity,
optical coherence tomography, and fluorescein angiography findings were recorded 
and assessed. RESULTS: During a mean follow-up of 12.1 months, an average of 7.8 
injections of pegaptanib 0.3 mg, 1.4 injections of bevacizumab 1.25 mg, and 0.9
injections of ranibizumab 0.5 mg were administered to 17 eyes. In all, 47% of
eyes gained 3 or more lines of visual acuity and 76% gained 0 or more lines.
CONCLUSION: Pegaptanib as a mainstay of neovascular age-related macular
degeneration therapy with an occasional boost of bevacizumab or ranibizumab
appears to be an effective treatment option.

PMID: 18717434 [PubMed - indexed for MEDLINE]

125: Ocul Immunol Inflamm. 2008 Jul-Aug;16(4):181-3.

Pathergy-like reaction following intravitreal triamcinolone acetonide injection
in a patient with Behçet disease.

Yalçindağ FN, Batioğlu F.

Faculty of Medicine, Ophthalmology Department, Ankara University, Ankara, Turkey.
yalcinda@medicine.ankara.edu.tr

PURPOSE: To describe a patient with Behcet disease who developed a pathergy-like 
reaction following intravitreal triamcinolone acetonide injection. METHODS: Case 
report. RESULTS: A 30-year-old man with a history of Behçet disease received an
intravitreal injection of triamcinolone acetonide for the treatment of cystoid
macular edema. The following day, he was noted to have erythematous swelling
around the injection site. The lesion disappeared spontaneously within 2 weeks.
CONCLUSION: Pathergy-like reaction to minor trauma may develop not only on the
skin but also in the mucous membranes such as conjunctiva in patients with Behçet
disease.

Publication Types: 
    Case Reports

PMID: 18716954 [PubMed - indexed for MEDLINE]

126: Ocul Immunol Inflamm. 2008 Jul-Aug;16(4):155-60.

Optical coherence tomography for classification and clinical evaluation of
macular edema in patients with uveitis.

Iannetti L, Accorinti M, Liverani M, Caggiano C, Abdulaziz R, Pivetti-Pezzi P.

Department of Ophthalmology, Ocular Immunovirology Service, La Sapienza
University of Rome, Rome, Italy.

PURPOSE: To study use of optical coherence tomography (OCT) for macular edema in 
uveitis. METHODS: In total, 44 patients with uveitis and macular edema underwent 
OCT. Data obtained were correlated with anatomic type, duration of uveitis, and
visual acuity (VA). RESULTS: Both cystoid macular edema (CME) and diffuse macular
edema (DME) correlate negatively with VA, although statistically CME showed
stronger correlation (p = .02). Also CME had higher mean foveal thickness than
DME (p < .01). Negative correlation between foveal thickness and VA (p < .05) was
observed. CME correlates with uveitis duration (p < .01). CONCLUSIONS: CME and
macular thickening correlate with VA reduction and uveitis duration.

PMID: 18716950 [PubMed - indexed for MEDLINE]

127: Graefes Arch Clin Exp Ophthalmol. 2008 Oct;246(10):1395-402. Epub 2008 Aug
16.

Drusenoid maculopathy in rhesus monkeys (Macaca mulatta): effects of age and
gender.

Gouras P, Ivert L, Landauer N, Mattison JA, Ingram DK, Neuringer M.

Department of Ophthalmology, Columbia University, New York, NY, USA.
pg10@columbia.edu

PURPOSE: To compare drusenoid maculopathy in monkeys with human age-related
macular degeneration, and evaluate the influence of age, gender and caloric
restriction. METHODS: Examination by indirect ophthalmoscopy, slit-lamp
biomicroscopy and fundus photography, including in some cases fluorescein
angiography, was performed on 61 male and 60 female rhesus macaques of ages 10-39
years. Fifty-four of the monkeys were maintained on a calorically restricted diet
(approximately 30% lower than control levels) and 67 on an approximately ad
libitum diet for 2-19 years, with all other environmental factors held constant. 
Maculopathies were graded on a 5-point scale and the effects of age, sex, and
diet on prevalence and severity were examined. The retinas of six monkeys with
macular drusen, 19-28 years old, were examined histologically. RESULTS: Rhesus
monkeys showed a high prevalence (61%) of drusenoid maculopathy. The prevalence
and severity of the maculopathy increased with age (p = 0.012). Fully half of all
monkeys aged 10-12 years had some detectable degree of drusen. This high
prevalence in young adulthood indicates that drusen develop much earlier in
rhesus monkeys than in humans, who develop early maculopathy most rapidly at
50-60 years of age, even when correcting for the 3-fold difference in lifespan.
No neovascularization or geographic atrophy was found. Females had a higher
prevalence and severity than males (p = 0.019). Calorically restricted monkeys
had a slightly lower prevalence and severity at 10-12 years than controls, but
the difference was not statistically significant. This is an on-going project,
and differences between the caloric restricted and ad-lib groups may emerge as
the animals age. Some monkeys developed severe maculopathy in their 20s, with
others unaffected in their 30s. The histology of drusen resembled those in human 
retina. CONCLUSION: Drusenoid maculopathy is common in rhesus monkeys, even in
young adult life. Half of the rhesus monkeys examined have drusen at a much
younger age than in humans. Severity of maculopathy was greater in female
monkeys, a gender difference not consistently found in humans. No differences
were detected due to caloric restriction, but a definitive test of this
intervention will require a larger sample, longer period of observation, and/or
an earlier institution of caloric restriction. Genetic factors are implied
because with similar environments, some monkeys are affected at an early age,
while older ones are not.

Publication Types: 
    Comparative Study

PMID: 18709381 [PubMed - indexed for MEDLINE]

128: Invest Ophthalmol Vis Sci. 2009 Jan;50(1):1-4. Epub 2008 Aug 15.

Effect of ruboxistaurin on the visual acuity decline associated with
long-standing diabetic macular edema.

Davis MD, Sheetz MJ, Aiello LP, Milton RC, Danis RP, Zhi X, Girach A, Jimenez MC,
Vignati L; PKC-DRS2 Study Group.

Department of Ophthalmology and Visual Sciences, University of Wisconsin,
Madison, Wisconsin, USA.

PURPOSE: To compare relationships between severity and duration of diabetic
macular edema (DME) and visual acuity (VA) observed in the PKC-DRS2 with those
from the Early Treatment Diabetic Retinopathy Study (ETDRS) and to assess the
effect of the orally administered PKC beta inhibitor ruboxistaurin (RBX) on these
parameters. METHODS: In the PKC-DRS2, patients with moderately severe to very
severe nonproliferative diabetic retinopathy (n = 685) were randomly assigned to 
32 mg/d RBX or placebo and followed up for 36 months with ETDRS VA measurements
and fundus photographs (FP) every 3 to 6 months. Mean VA was calculated across
all FP visits for eyes in each level of the ETDRS DME severity scale at those
visits. For eyes with baseline VA > or = 20/40, relationships between change in
VA from baseline to last visit and duration of severe DME were analyzed with
linear regression. RESULTS: Mean VA decreased by approximately 22 letters between
the mildest and most severe levels of the DME scale in the PKC-DRS2, compared
with 27 letters in the ETDRS. In the placebo group, the rate of decrease in VA
over time associated with duration of severe DME was 0.67 letters per month (24
letters over 36 months, compared with 20 letters over 28-36 months in the ETDRS).
This rate was 30% less in the RBX group (0.47 letter per month, P = 0.022).
CONCLUSIONS: The VA decrease in the PKC-DRS2 associated with long-standing DME
agrees well with estimates from the ETDRS. RBX appears to ameliorate this
decrease, an effect that could be important clinically. (ClinicalTrials.gov
number, NCT00604383.).

Publication Types: 
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18708615 [PubMed - indexed for MEDLINE]

129: Invest Ophthalmol Vis Sci. 2008 Dec;49(12):5574-80. Epub 2008 Aug 15.

Elastin-mediated choroidal endothelial cell migration: possible role in
age-related macular degeneration.

Skeie JM, Mullins RF.

Center for Macular Degeneration, Department of Ophthalmology and Visual Science, 
University of Iowa, Iowa City, Iowa 52242, USA.

PURPOSE: Endothelial cell (EC) migration is a key event in angiogenesis, and is
likely to play an important role in choroidal neovascularization in age-related
macular degeneration (AMD). Altered elastin metabolism has been described in AMD,
and the present study sought to determine the effects of elastin-derived peptides
(EDPs) on choroidal EC migration and proliferation. METHODS: Migration of the
chorioretinal EC line Rf/6a and a primary culture of human choroidal ECs through 
polycarbonate membrane inserts was quantified in the presence of elastin
bioactive hexapeptides (BPs), EDPs, bovine serum albumin (BSA), or balanced salt 
solution. Proliferation assays and in vitro wound closure experiments were also
performed in the presence of elastin fragments or balanced salt solution
(control). Elastin overlay experiments were performed on sections of human eyes. 
RESULTS: For both Rf/6a and human primary choroidal ECs exposed to EDPs or BPs,
the number of ECs that migrated through the polycarbonate membrane was
significantly higher than ECs exposed to balanced salt solution alone or to BSA
(P < 0.05) in all experiments. In contrast, the rate of EC proliferation did not 
significantly change in comparison to controls. Elastin binding sites were
identified on choroidal ECs in human eyes. CONCLUSIONS: Elastin fragments
increase choroidal EC migration, whereas they do not appear to increase or
decrease EC proliferation. Local or systemic abnormalities in elastin physiology 
may participate in pathologic neovascular membrane formation in AMD.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18708613 [PubMed - indexed for MEDLINE]

130: Ophthalmology. 2008 Oct;115(10):e47-54. Epub 2008 Aug 16.

Ranibizumab for the treatment of macular edema associated with perfused central
retinal vein occlusions.

Pieramici DJ, Rabena M, Castellarin AA, Nasir M, See R, Norton T, Sanchez A,
Risard S, Avery RL.

California Retina Consultants and Research Foundation, Santa Barbara, California 
93103, USA. dpieramici@yahoo.com

PURPOSE: Assessment of biological effect, visual acuity changes, and safety of
intravitreal (IVT) ranibizumab in patients with macular edema associated with
perfused central retinal vein occlusion (CRVO). DESIGN: Ongoing, prospective,
open-label, single-center, uncontrolled study. PARTICIPANTS: Ten adult patients
with macular edema associated with perfused CRVO. METHODS: Patients were randomly
assigned to receive 3 monthly IVT injections of either 0.3 or 0.5 mg ranibizumab 
(n = 5 at each dose). Additional injections were administered quarterly as needed
over the ensuing 21 months at the physician's discretion for recurrent or
persistent macular edema. MAIN OUTCOME MEASURES: The predetermined primary
endpoint was the percentage of patients gaining >or=15 letters of best-corrected 
Early Treatment of Diabetic Retinopathy Study visual acuity (BCVA). The secondary
endpoints include the mean change in BCVA and central retinal thickness (CRT)
measured by optical coherence tomography, the rate of progression to ischemic
CRVO, extent of intraocular hemorrhage, retinal vein diameter, optic nerve head
swelling, and the incidence and severity of ocular and nonocular adverse events. 
RESULTS: After 3, 6, and 9 months of follow-up, 40%, 10%, and 30% of patients,
respectively, gained >or=15 letters in BCVA; mean BCVA improved by 12+/-20
letters, 3+/-21 letters, and 1+/-24 letters, respectively, compared with
baseline; CRT showed a mean decrease of 272+/-244 microm, 88+/-178 microm, and
119+/-153 microm, compared with baseline. No significant differences were
observed between the 0.3- and 0.5-mg doses. Most patients experienced decreases
in the extent of retinal hemorrhage, retinal vein diameter, and optic nerve head 
swelling at months 3 and 6 compared with baseline. No patients progressed to
ischemic CRVO or experienced a severe adverse event that was attributed to
ranibizumab. CONCLUSIONS: Ranibizumab is generally well-tolerated and may improve
BCVA and decrease CRT. The improvements in BCVA and CRT observed during the
initial monthly injection period (0 to 3 months) were possibly lost to the
recurrence of macular edema in between ranibizumab injection during the quarterly
treatments (3 to 9 months). The extent of retinal hemorrhage, retinal vein
diameter, and nerve swelling continued to normalize for most of the patients from
baseline to 6 months. Follow-up is ongoing, and alternative dosing regimens are
being evaluated.

Publication Types: 
    Case Reports
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18708258 [PubMed - indexed for MEDLINE]

131: Ophthalmology. 2008 Nov;115(11):1899-903. Epub 2008 Aug 16.

Polymorphisms in the vascular endothelial growth factor gene and risk of
age-related macular degeneration: the Rotterdam Study.

Boekhoorn SS, Isaacs A, Uitterlinden AG, van Duijn CM, Hofman A, de Jong PT,
Vingerling JR.

Department of Epidemiology & Biostatistics, Erasmus Medical Center, Rotterdam,
The Netherlands.

PURPOSE: Vascular endothelial growth factor (VEGF) is an important regulator of
angiogenesis and a target for inhibition therapy in wet age-related macular
degeneration (AMD). The purpose of this study was to examine whether genetic
variation in the VEGF gene is associated with AMD and, especially, with its wet
end stage. DESIGN: Prospective population-based cohort study. PARTICIPANTS: Four 
thousand two hundred twenty-eight participants aged 55 years and older. METHODS: 
AMD was classified according to a modified International Classification System
using fundus color images. Genotypes and haplotypes were determined for 3
functional VEGF single nucleotide polymorphisms (SNPs): C-2578A, G-1154A, and
G-634C. Cox proportional hazards regression analyses were used to investigate
possible associations between the individual SNPs and incident AMD. The
Haplo.Stats program was used to test the associations between VEGF gene
haplotypes and incident AMD. MAIN OUTCOME MEASURE: AMD RESULTS: Of 4228
participants at risk for incident early and late AMD for whom blood specimens
were available for VEGF genotyping, incident early AMD developed in 514 and
incident late AMD developed in 89 (35 dry and 54 wet) after a mean follow-up of
7.4 years. None of the SNPs showed a significant association with incident early 
or late AMD, especially not with incident wet AMD. Haplotype analyses also
detected no associations. CONCLUSIONS: The a priori hypothesis that 3 common SNPs
in the VEGF gene would be a risk factor for AMD, especially the wet form, could
not be confirmed.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18708255 [PubMed - indexed for MEDLINE]

132: BMC Ophthalmol. 2008 Aug 17;8:15.

The ChromaTest, a digital color contrast sensitivity analyzer, for diabetic
maculopathy: a pilot study.

Wong R, Khan J, Adewoyin T, Sivaprasad S, Arden GB, Chong V.

Ophthalmology Department, Retinal Research Unit, King's College Hospital NHS
Trust, Denmark Hill, London, UK. drrogerwong@gmail.com

BACKGROUND: To assess the ability of the Chromatest in investigating diabetic
maculopathy. METHOD: Patients with Type 2 diabetes and no concurrent ocular
pathology or previous laser photocoagulation were recruited. Visual acuities were
assessed followed by colour contrast sensitivity testing of each eye using
Chromatest. Dilated fundoscopy with slit lamp biomicroscopy with 78 D lens was
then performed to confirm the stage of diabetic retinopathy according to the
Early Treatment Diabetic Retinopathy Study. RESULTS: 150 eyes in 150 patients
were recruited into this study. 35 eyes with no previous laser photocoagulation
were shown to have clinically significant macular oedema (CSMO) and 115 eyes with
untreated non-proliferative diabetic retinopathy (NPDR) on fundus biomicroscopy. 
Statistical significant difference was found between CSMO and NPDR eyes for
protan colour contrast threshold (p = 0.01). Statistical significance was found
between CSMO and NPDR eyes for tritan colour contrast threshold (p = 0.0002).
Sensitivity and specificity for screening of CSMO using pass-fail criterion for
age matched TCCT results achieved 71% (95% confidence interval: 53-85%) and 70%
(95% confidence interval: 60-78%), respectively. However, threshold levels were
derived using the same data set for both training and testing the effectiveness
since this was the first study of NPDR using the Chromatest CONCLUSION: The
ChromaTest is a simple, cheap, easy to use, and quick test for colour contrast
sensitivity. This study did not achieve results to justify use of the Chromatest 
for screening, but it reinforced the changes seen in tritan colour vision in
diabetic retinopathy.

Publication Types: 
    Evaluation Studies

PMID: 18706104 [PubMed - indexed for MEDLINE]

133: Mol Vis. 2008 Aug 11;14:1487-95.

Comprehensive analysis of CRP, CFH Y402H and environmental risk factors on risk
of neovascular age-related macular degeneration.

Kim IK, Ji F, Morrison MA, Adams S, Zhang Q, Lane AM, Capone A, Dryja TP, Ott J, 
Miller JW, DeAngelis MM.

Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear
Infirmary, Boston, MA 02114, USA.

PURPOSE: To examine if the gene encoding C-reactive protein (CRP), a biomarker of
inflammation, confers risk for neovascular age-related macular degeneration (AMD)
in the presence of other modifiers of inflammation, including body mass index
(BMI), diabetes, smoking, and complement factor H (CFH) Y402 genotype.
Additionally we examined the degree to which CRP common variation was in linkage 
disequilibrium (LD) within our cohort. METHODS: We ascertained 244 individuals
from 104 families where at least one member had neovascular AMD, and a sibling
had normal maculae and was past the age of the index patient's diagnosis of
neovascular AMD. We employed a direct sequencing approach to analyze the
5'-promoter region as well as the entire coding region and the 3'-untranslated
region of the CRP gene. CFH Y402 genotype data was available for all
participants. Lifestyle and medical factors were obtained via administration of a
standardized questionnaire. The family-based association test, haplotype
analysis, McNemar's test, and conditional logistic regression were used to
determine significant associations and interactions. Haploview was used to
calculate the degree of LD (r2) between all CRP variants identified. RESULTS: Six
single nucleotide polymorphisms (SNPs; rs3091244, rs1417938, rs1800947,
rs1130864, rs1205, and rs3093068) comprised one haplotype block of which only
rs1130864 and rs1417938 were in high LD (r2=0.94). SNP rs3093068 was in LD but
less so with rs3093059 (r2=0.83), which is not part of the haplotype block. Six
SNPs made up six different haplotypes with > or = 5% frequency, none of which
were significantly associated with AMD risk. No statistically significant
association was detected between any of the nine common variants in CRP and
neovascular AMD when considering disease status alone or when controlling for
smoking exposure, BMI, diabetes, or CFH genotype. Significant interactions were
not found between CRP genotypes and any of the risk factors studied. No novel CRP
variation was identified. CONCLUSIONS: We provide evidence that if elevated
serum/plasma levels of CRP are associated with neovascular AMD, it is likely not 
due to genetic variation within CRP, but likely due to variations in some other
genetic as well as epidemiological factors.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18704199 [PubMed - indexed for MEDLINE]

134: Br J Ophthalmol. 2008 Nov;92(11):1492-7. Epub 2008 Aug 14.

Features of age-related macular degeneration assessed with three-dimensional
Fourier-domain optical coherence tomography.

Menke MN, Dabov S, Sturm V.

Department of Ophthalmology, University of Zürich, USZ, Zürich, Switzerland.
marcel.menke@gmail.com

BACKGROUND/AIMS: Age-related macular degeneration (AMD) is among the leading
causes of severe visual loss in individuals over 60 years old. Retinal changes
associated with AMD were previously studied by time-domain optical coherence
tomography (OCT). Recently, Fourier-domain OCT (FD-OCT) has been introduced.
FD-OCT provides increased scan resolution and scanning speed, and generates
three-dimensional (3D) OCT images. The purpose of this study was to demonstrate
features of AMD assessed with high-density scanning 3D-FD-OCT (Topcon
3D-OCT1000). METHODS: The study was designed as a prospective, observational case
series. Five patients with typical morphological changes due to AMD were chosen
based on funduscopic findings. Eyes with non-exudative- and exudative AMD were
included. 3D-FD-OCT images were obtained, and typical morphological changes
associated with AMD were presented. RESULTS: FD-OCT provided detailed 3D-images
of retinal structure. In addition, FD-OCT showed improved retinal coverage and
image quality. FD-OCT B-scan imaging identified typical retinal changes
associated with AMD. In addition, FD-OCT imaging revealed information about the
extent and the 3D shape of retinal lesions. CONCLUSION: 3D-FD-OCT imaging is
useful for diagnosing and following patients with AMD. In addition, 3D-FD-OCT
provided information about the extent and 3D shape of retinal pathologies and
showed improved retinal coverage.

Publication Types: 
    Evaluation Studies

PMID: 18703554 [PubMed - indexed for MEDLINE]

135: Retina. 2008 Jul-Aug;28(7):1008-12.

Posterior cystoid retinal degeneration in central serous chorioretinopathy.

Piccolino FC, De La Longrais RR, Manea M, Cicinelli S.

Fondazione per la Macula Onlus, Genova, Italy. felice.cardillopiccolino@unito.it

PURPOSE: To study the pattern of cystoid retinal changes in the posterior fundi
of eyes with chronic central serous chorioretinopathy (CSC) using optical
coherence tomography (OCT). METHODS: We retrospectively studied 34 eyes with
chronic CSC and cystoid retinal changes at the posterior pole documented by OCT. 
We analyzed the distribution of cystoid retinal changes with respect to the fovea
and chorioretinal lesions. RESULTS: Generally, cystoid retinal changes occurred
in the papillomacular region (21 eyes); foveal involvement was observed in 20
eyes. Large cystoid changes in the central macula with concentric perifoveal
lesion extension were detected in three eyes. Cystoid changes tended to occur
where the retina adhered to subretinal fibrosis, large laser scars, or
spontaneous atrophy of the retinal pigment epithelium and the choroid. Visual
acuity ranged from 20/20 to 20/400. In nine eyes in which the cystoid changes
spared the foveal center, visual acuity was 20/40 or better. CONCLUSION: Cystoid 
retinal degeneration in eyes with chronic CSC was distributed outside of the
fovea and was not necessarily associated with severely reduced visual acuity.
"Posterior cystoid retinal degeneration" defines this pathologic pattern
appropriately. OCT findings suggest that intraretinal exudation and cystoid
changes in chronic CSC develop through the formation of chorioretinal adherences.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18698305 [PubMed - indexed for MEDLINE]

136: Retina. 2008 Jul-Aug;28(7):987-95.

Periocular triamcinolone for prevention of macular edema after iodine 125 plaque 
radiotherapy of uveal melanoma.

Horgan N, Shields CL, Mashayekhi A, Teixeira LF, Materin MA, O'Regan M, Shields
JA.

Ocular Oncology Service, Wills Eye Institute, Thomas Jefferson University,
Philadelphia, Pennsylvania 19107, USA.

OBJECTIVE: To investigate the potential benefit of periocular depot triamcinolone
in the prevention of macular edema after iodine 125 plaque radiotherapy for uveal
melanoma. METHODS: This comparative, nonrandomized, interventional study included
87 patients with uveal melanoma who underwent plaque radiotherapy. The
triamcinolone group included 55 consecutive patients who were treated with 40 mg 
of periocular triamcinolone at the time of plaque application and 4 months and 8 
months later. The comparison group comprised 32 consecutive patients treated with
plaque radiotherapy without triamcinolone. Patients were evaluated at 4 months, 8
months, 12 months, 18 months, and 24 months after plaque application with
clinical examination, fundus photography, and optical coherence tomography (OCT).
The associations of clinical variables with the development of OCT-evident
macular edema (the main outcome measure) were investigated using Cox proportional
hazards analysis. RESULTS: By multivariate analysis, eyes treated with periocular
triamcinolone had a significant reduction in the risk of radiation-induced
macular edema (P = 0.002; hazard estimate = 0.49; 95% confidence interval, 0.17- 
0.80). Adverse effects associated with periocular triamcinolone treatment
included elevation of intraocular pressure (7% of cases) and blepharoptosis (5%
of cases). CONCLUSIONS: Periocular triamcinolone treatment significantly lowered 
the risk of macular edema after plaque radiotherapy for uveal melanoma in this
series but did not significantly alter the rate of vision loss at 24 months of
follow-up.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 18698302 [PubMed - indexed for MEDLINE]

137: Retina. 2008 Jul-Aug;28(7):976-80.

Pegaptanib combined with intravitreal injection of moxifloxacin as treatment of
wet macular degeneration.

Bennett MD, Yee W, Bryan JS.

Retina Institute of Hawaii, Honolulu, Hawaii 96815, USA.
mbennett@retinahawaii.com

PURPOSE: To evaluate the effectiveness of pegaptanib combined with intravitreal
injection of moxifloxacin as treatment of wet macular degeneration. METHODS: This
retrospective review included patients who received pegaptanib combined with 165 
microg of moxifloxacin every 6 weeks. Ophthalmic examination was performed, and
adverse events were recorded at each visit; additional assessments (e.g., optical
coherence tomography) were performed when indicated. RESULTS: Eighty eyes of 65
patients were identified; the median length of follow-up was 13.2 months (range, 
10-16 months), and eyes received an average of 6 injections (range, 4-9 months). 
Seventy eyes of 80 patients have been followed for >or=1 year; 80% (65/70) had
stable or improved vision, and 97% (68/70) lost <15 letters of vision.
CONCLUSION: Pegaptanib combined with intravitreal injection of moxifloxacin
appears to be effective treatment of wet macular degeneration.

PMID: 18698300 [PubMed - indexed for MEDLINE]

138: Retina. 2008 Jul-Aug;28(7):957-63.

Effects of macular ischemia on the outcome of intravitreal bevacizumab therapy
for diabetic macular edema.

Chung EJ, Roh MI, Kwon OW, Koh HJ.

Department of Opthalmology, NHIC Ilsan Hospital, Gyounggi-do, Korea.

PURPOSE: To evaluate the effects of macular ischemia on visual outcomes in
patients with diabetic macular edema (DME), after intravitreal bevacizumab
injections. METHODS: Data on 59 eyes of 53 consecutive patients treated with
intravitreal bevacizumab for DME were retrospectively reviewed. Data from
preoperative fluorescein angiography (FA) tests were examined. Patients with an
enlarged foveal avascular zone (FAZ), >or=1000 microm, or a broken perifoveal
capillary ring at the border of the FAZ, with a distinct area of capillary
nonperfusion within one disk diameter of the foveal center in the transit phase
of fluorescein angiography, were defined as having macular ischemia. The patients
were thus divided into two groups: with or without macular ischemia. Early
Treatment Diabetic Retinopathy Study (ETDRS) scores, and foveal thicknesses
measured using third generation ocular coherence tomography (OCT), were evaluated
at baseline and at 1 month and 3 months after treatment. RESULTS: At 3 months
after treatment, the mean visual acuity (VA) score decreased from a baseline VA
of 0.52 +/- 0.27 (approximate Snellen equivalent, 20/63) to 0.57 +/- 0.21 (20/80)
in the ischemic group. In the nonischemic group, by contrast, the VA improved
from 0.66 +/- 0.34 (20/100) at baseline to 0.59 +/- 0.33 (20/80) at 3 months
post-treatment. Nine of 18 eyes (50%) in the ischemic group, but only 9 of 41
eyes (21%) in the nonischemic group, experienced visual losses of >or=1 line on
the ETDRS chart (P = 0.031, Pearson chi-square test). Four eyes (22%) in the
ischemic group, but only 2 eyes (5%) in the nonischemic group, lost >or=3 lines
(P = 0.042, Pearson chi-square test). CONCLUSION: Macular ischemia may have a
negative effect on short term visual outcomes after intravitreal bevacizumab
injections in patients with DME.

PMID: 18698297 [PubMed - indexed for MEDLINE]

139: Retina. 2008 Jul-Aug;28(7):947-56.

25-gauge vitrectomy and triamcinolone acetonide-assisted internal limiting
membrane peeling for chronic cystoid macular edema associated with branch retinal
vein occlusion.

Ma J, Yao K, Zhang Z, Tang X.

Eye Center of Affiliated Second Hospital School of Medicine, Zhejiang University,
Hangzhou, PR China. zjhzqz@yahoo.com.cn

PURPOSE: To evaluate the efficacy of 25-gauge vitrectomy and triamcinolone
acetonide (TA)-assisted internal limiting membrane (ILM) peeling for chronic
cystoid macular edema (CCME) in branch retinal vein occlusion (BRVO). METHODS:
Thirty-four patients (38 eyes) presenting with CCME in BRVO were treated
prospectively by 25-gauge vitrectomy and ILM peeling. Change in best-corrected
visual acuity (BCVA) and CCME status were evaluated preoperatively and
postoperatively at 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, and
7 months. RESULTS: Mean postoperative logMAR BCVAs +/- SD were 0.69 +/- 0.42,
0.65 +/- 0.41, 0.59 +/- 0.32, 0.39 +/- 0.27, 0.35 +/- 0.31, 0.32 +/- 0.28, and
0.32 +/- 0.31 at the seven follow-up months, respectively. Mean foveal
thicknesses +/- SD were 443 +/- 60 microm, 212 +/- 67 microm, 188 +/- 41 microm, 
176 +/- 53 microm, 173 +/- 41 microm, 171 +/- 39 microm, and 170 +/- 41 microm at
the 7 follow-up months, respectively. Compared with before surgery, BCVA
improved, and CCME was absorbed significantly (P < 0.01, Dunnett test). Foveal
thickness and logMAR BCVA 7 months after surgery had a significant negative
linear correlation (r = -0.81, P < 0.01; Spearman rank correlation). CONCLUSIONS:
Twenty-five-gauge vitrectomy with TA-assisted ILM peeling is generally effective 
in reducing macular edema and improving BCVA for CCME in BRVO for at least 7
months.

PMID: 18698296 [PubMed - indexed for MEDLINE]

140: Retina. 2008 Jul-Aug;28(7):919-30.

A randomized trial comparing intravitreal triamcinolone and focal/grid
photocoagulation for diabetic macular edema: baseline features.

Ip MS, Bressler SB, Antoszyk AN, Flaxel CJ, Kim JE, Friedman SM, Qin H; Diabetic 
Retinopathy Clinical Research Network.

University of Wisconsin Fundus Photograph Reading Center, Madison, WI, USA.

PURPOSE: To compare baseline demographic, systemic, and ocular characteristics
within age and racial subgroups among participants in this Diabetic Retinopathy
Clinical Research Network clinical trial and to compare this cohort with other
cohorts enrolled in phase 3 clinical trials for diabetic retinopathy. METHODS:
Thirty-six month, randomized, controlled, multicenter clinical trial of 693
participants with diabetic macular edema enrolled at 88 clinical sites in the
United States. Participants were categorized into self-reported race/ethnicity
subgroups and into one of three age groups: 18 to <60, 60 to <70, and 70 and
older. RESULTS: Mean age of participants was 63 years, 72% were white, and median
visual acuity letter score was 62 (approximately 20/63). No substantial
difference was identified between racial subgroups for any baseline variable.
Older participants were more likely to have Type 2 diabetes mellitus and longer
duration disease. The most frequent levels of diabetic retinopathy among 840
study eyes were moderate (level 43) to moderately severe (level 47)
nonproliferative disease. CONCLUSION: While the racial composition of this cohort
does not differ from other cohorts in large phase 3 trials that have evaluated
participants with diabetic retinopathy, the inclusion of many subjects over age
70 and a better level of glycemic control are distinguishing features.

Publication Types: 
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, N.I.H., Extramural

PMID: 18698292 [PubMed - indexed for MEDLINE]

141: Curr Eye Res. 2008 Aug;33(8):701-7.

Constancy of ERp29 expression in cultured retinal pigment epithelial cells in the
Ccl2/Cx3cr1 deficient mouse model of age-related macular degeneration.

Verma V, Sauer T, Chan CC, Zhou M, Zhang C, Maminishkis A, Shen D, Tuo J.

Immunopathology Section, Laboratory of Immunology, National Eye Institute,
National Institutes of Health, Bethesda, Maryland 20892-1857, USA.

PURPOSE: Given the critical role of the retinal pigment epithelium (RPE) in the
pathogenesis of age-related macular generation (AMD) and the links drawn between 
chaperone proteins and neurodegenerative disease, we aimed to culture RPE from
the Ccl2(-/-)/Cx3cr1(-/-) mouse model of AMD and evaluate expression of chaperone
protein ERp29. MATERIALS AND METHODS: Murine RPE cells were surgically and
chemically isolated and cultured. ERp29 mRNA and protein expression were
evaluated by real-time RT-PCR, immunohistochemistry, and Western blot. RESULTS:
Ccl2(-/-)/Cx3cr1(-/-) RPE was successfully isolated and cultured. They presented 
a decreased but statistically insignificant difference in ERp29 transcript and
protein expression compared to C57B6/L wild type mouse RPE. CONCLUSIONS: The
effective murine RPE culture described here enables future investigation into RPE
biology and AMD pathogenesis. Although we found a decrease in ERp29 expression in
the Ccl2(-/-)/Cx3cr1(-/-) RPE, the difference was less than we previously
observed in the whole retina. This suggests that the RPE may not contribute to
the greater differential expression and ERp29 might have a more significant role 
in the neuroretina than in the RPE during AMD pathogenesis.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 18696346 [PubMed - indexed for MEDLINE]

142: Graefes Arch Clin Exp Ophthalmol. 2008 Oct;246(10):1403-11. Epub 2008 Aug
12.

Drusenoid maculopathy in rhesus monkeys: autofluorescence, lipofuscin and drusen 
pathogenesis.

Gouras P, Ivert L, Mattison JA, Ingram DK, Neuringer M.

Department of Ophthalmology, Columbia University, New York, NY, USA.
pg10@columbia.edu

PURPOSE: To examine patterns of retinal pigment epithelial autofluorescence and
lipofuscin accumulation in relation to drusen and to explore the pathogenesis of 
drusen in rhesus monkeys. METHODS: The macular areas of six rhesus monkeys,
euthanized at 19 to 28 years of age, were studied by bright field and
fluorescence light microscopy and transmission electron microscopy. RESULTS:
There was strong autofluorescence in the retinal epithelium that tended to
diminish over drusen. Electron microscopy revealed that all retinal epithelial
cells had large concentrations of lipofuscin bodies. The epithelial cells
overlying drusen, however, tended to have less lipofuscin than epithelial cells
not associated with drusen. Electron microscopy revealed that the epithelial
cells overlying drusen were losing segments of cytoplasm containing lipofuscin
bodies. Macrophage-like cells were consistently present in Bruch's membrane
microns away from this lipofuscin-containing cytoplasmic material. CONCLUSIONS:
Retinal epithelial cells overlying drusen have less lipofuscin than neighboring
epithelial cells. The loss of lipofuscin seems due to a loss of cytoplasm
containing lipofuscin that contributes to drusen formation. Macrophages in
Bruch's membrane may be responsible for removing this lipofuscin debris. The
results support in vivo studies showing reduced autofluorescence over drusen and 
support the "budding" of epithelial cytoplasm as a source of drusen material.

PMID: 18696097 [PubMed - indexed for MEDLINE]

143: Ann Acad Med Singapore. 2008 Jul;37(7):591-3.

Effects on the contralateral eye after intravitreal bevacizumab and ranibizumab
injections: a case report.

Wu Z, Sadda SR.

Doheny Retina Institute, Doheny Eye Institute, Los Angeles, CA 90033, USA.

INTRODUCTION: We report a case in which intravitreal bevacizumab and ranibizumab 
appeared to have effects in the contralateral, uninjected eye. CLINICAL PICTURE: 
An 83-year-old man with macular oedema from branch retinal vein occlusion (BRVO) 
in the right eye developed neovascular macular degeneration in the left eye.
Intravitreal bevacizumab in the left eye improved macular oedema in the right eye
temporarily before it recurred. Subsequently, intravitreal ranibizumab in the
left eye also resulted in significant reduction of macular oedema in the right
eye. OUTCOME: Vision and macular oedema in the right eye improved. CONCLUSION:
Bevacizumab and ranibizumab may have therapeutic effects in the uninjected eye,
possibly because they may escape from the eye into the systemic circulation.

Publication Types: 
    Case Reports

PMID: 18695773 [PubMed - indexed for MEDLINE]

144: Curr Drug Saf. 2008 Jan;3(1):24-6.

Use of statins and angiotensin converting enzyme inhibitors (ACE-Is) and the risk
of age-related macular degeneration: nested case-control study.

Etminan M, Brophy JM, Maberley D.

Centre for Clinical Epidemiology and Evaluation, Vancouver General Hospital, 7
Floor - 828 West 10 Ave., Vancouver, British Columbia, Canada. metminan@shaw.ca

BACKGROUND: Age related macular degeneration (AMD) is a progressive degenerative 
disease affecting central vision. Recent studies have shown that that statins may
lower the risk of AMD potentially due to statins' anti-inflammatory and
anti-oxidative properties. We sought to further explore this association and also
explore the role of angiotensin-converting enzyme inhibitors (ACE-Is) with
respect to the development of AMD. METHODS: We conducted a nested case-control
study within a cardiovascular cohort that had undergone revascularization
interventions in the Province of Quebec, Canada. Cases were identified as those
with an ICD-9 code for AMD. For each case, four controls were randomly chosen
from the cohort and matched to the cases by age and calendar time. Conditional
logistic regression was used to estimate rate ratios and adjust for potential
confounders. RESULTS: Our nested case-control study consisted of 2,867 cases and 
11,468. Current users of ACE-Is or statins were at a slightly higher risk of
developing AMD (1.19 [1.07-1.33]) and (1.30 [1.17-1.44]) respectively. The
results were similar for those using these drugs in the year prior. CONCLUSIONS: 
Based on the results of our study, statin and ACE-I use may be associated with an
increase in the risk of AMD. Given that our study is an observational study,
further studies are required to confirm or refute these findings.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18690977 [PubMed - indexed for MEDLINE]

145: Am J Clin Nutr. 2008 Aug;88(2):398-406.

Oily fish consumption, dietary docosahexaenoic acid and eicosapentaenoic acid
intakes, and associations with neovascular age-related macular degeneration.

Augood C, Chakravarthy U, Young I, Vioque J, de Jong PT, Bentham G, Rahu M,
Seland J, Soubrane G, Tomazzoli L, Topouzis F, Vingerling JR, Fletcher AE.

Department of Epidemiology & Population Health, London School of Hygiene &
Tropical Medicine, London, United Kingdom.

BACKGROUND: Fish intake, the major source of docosahexaenoic acid (DHA) and
eicosapentaenoic acid (EPA), may reduce the risk of age-related macular
degeneration (AMD). OBJECTIVE: We investigated the association of oily fish and
dietary DHA and EPA with neovascular AMD (NV-AMD). DESIGN: Participants aged
>/=65 y in the cross-sectional population-based EUREYE study underwent fundus
photography and were interviewed by using a food-frequency questionnaire. Fundus 
images were graded by the International Classification System for Age Related
Maculopathy. Questionnaire data were converted to nutrient intakes with the use
of food-composition tables. Survey logistic regression was used to calculate odds
ratios (ORs) and 95% CIs of energy-adjusted quartiles of EPA or DHA with NV-AMD, 
taking into account potential confounders. RESULTS: Dietary intake data and
fundus images were available for 105 cases with NV-AMD and for 2170 controls
without any features of early or late AMD. Eating oily fish at least once per
week compared with less than once per week was associated with a halving of the
odds of NV-AMD (OR = 0.47; 95% CI: 0.33, 0.68; P = 0.002). Compared with the
lowest quartile, there was a significant trend for decreased odds with increasing
quartiles of either DHA or EPA. ORs in the highest quartiles were 0.32 (95% CI:
0.12, 0.87; P = 0.03) for DHA and 0.29 (95% CI: 0.11, 0.73; P = 0.02) for EPA.
CONCLUSIONS: Eating oily fish at least once per week compared with less than once
per week was associated with a halving of the OR for NV-AMD.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 18689376 [PubMed - indexed for MEDLINE]

146: Eur J Hum Genet. 2009 Jan;17(1):100-4. Epub 2008 Aug 6.

Variation near complement factor I is associated with risk of advanced AMD.

Fagerness JA, Maller JB, Neale BM, Reynolds RC, Daly MJ, Seddon JM.

Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA,
USA.

A case-control association study for advanced age-related macular degeneration
was conducted to explore several regions of interest identified by linkage. This 
analysis identified a single nucleotide polymorphism just 3' of complement factor
I on chromosome 4 showing significant association (P<10(-7)). Sequencing was
performed on coding exons in linkage disequilibrium with the detected
association. No obvious functional variation was discovered that could be the
proximate cause of the association, suggesting a noncoding regulatory mechanism.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18685559 [PubMed - indexed for MEDLINE]

147: Mol Vis. 2008 Jul 28;14:1373-81.

Association of CFH, LOC387715, and HTRA1 polymorphisms with exudative age-related
macular degeneration in a northern Chinese population.

Xu Y, Guan N, Xu J, Yang X, Ma K, Zhou H, Zhang F, Snellingen T, Jiao Y, Liu X,
Wang N, Liu N.

Beijing Tongren Eye Center, Capital Medical University, Beijing, China.

PURPOSE: Variants in complement factor H (CFH), the hypothetical LOC387715, and
the high-temperature requirement A-1 (HTRA1) genes have been reported to be
associated with age-related macular degeneration (AMD). The purpose of this study
was to investigate the association of reported common single-nucleotide
polymorphisms (SNPs) in CFH, LOC387715, and HTRA1 with exudative AMD in a
northern Chinese population. METHODS: A cohort of 121 unrelated patients with
exudative AMD and 132 control subjects were enrolled in this study. Genomic DNA
was extracted from blood leukocytes. Genotyping for SNPs rs1061170:T>C in CFH
(Y402H), rs10490924:G>T in LOC387715 (A69S), and rs11200638:G>A in the promoter
of HTRA1 was performed using a polymerase chain reaction (PCR) method followed by
allele-specific restriction enzyme digestion and direct sequencing. RESULTS: The 
Y402H variant in CFH was not associated with exudative AMD in our study
population. Frequencies of Y402H was 10.3% in AMD cases and 8.0% in controls
(p=0.353). Significant associations were detected for exudative AMD with SNPs
rs10490924:G>T in LOC387715 (A69S), and rs11200638:G>A in the promoter of HTRA1. 
The risk T-allele frequency of rs10490924 in LOC387715 was 64.9% in cases versus 
43.2% in controls (p<0.001). The odds ratio for risk of AMD was 1.56 (95% CI;
0.80-3.03) for the GT genotype and 5.45 (95% CI; 2.59-11.49) for the TT genotype.
The A allele frequency of rs11200638 in the HTRA1 promoter was 67.8% in cases
versus 42.4% in controls (p<0.001). The odds ratio was 2.75 (95% CI; 1.34-5.64)
for the GA genotype and 7.90 (95% CI; 3.61-17.26) for the AA genotype. An odds
ratio of 7.94 (95% CI; 3.49-18.04) was obtained for carriers with both TT
genotype in LOC387715 and AA genotype in the HTRA1 promoter. CONCLUSIONS: Our
data suggest that the LOC387715 and HTRA1 polymorphisms are associated with a
higher risk of exudative AMD in northern Chinese. We found no association of CFH 
Y402H with exudative AMD. The low frequency of CFH Y402H variant was further
confirmed in this study population.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18682812 [PubMed - indexed for MEDLINE]

148: Mol Vis. 2008 Aug 4;14:1395-400.

Joint effects of polymorphisms in the HTRA1, LOC387715/ARMS2, and CFH genes on
AMD in a Caucasian population.

Francis PJ, Zhang H, Dewan A, Hoh J, Klein ML.

Macular Degeneration Center, Casey Eye Institute, Oregon Health & Science
University, Portland, OR, USA.

PURPOSE: To estimate the joint effects of single nucleotide polymorphisms (SNPs) 
in the genes complement factor H (CFH), HtrA serine peptidase 1 (HTRA1), and
age-related maculopathy susceptibility 2 (LOC387715/ARMS2) in a Caucasian age
related macular degeneration (AMD) case-control cohort. METHODS: We genotyped
three SNPs, rs1061170 (exon 9, CFH), rs11200638 (HTRA1 promoter, -512 bp), and
rs10490924 (6.6 kb upstream of HTRA1 in LOC387715/ARMS2) in 333 cases with
advanced AMD (choroidal neovascularization [CNV] and geographic atrophy) and 171 
age-matched examined controls. Association tests were performed for individual
SNPs and jointly with the CFH SNP Y402H. Analyses for interaction were also
performed. RESULTS: The linkage disequilibrium measure for two SNPs on 10q26,
rs10490924 and rs11200638, is D'=0.8 and all four possible haplotypes of the two 
SNPs were detected in the samples. The allelic association test for rs11200638 on
the promoter of HTRA1 yielded p-values less than 10(-10) for geographic atrophy, 
less than 10(-16) for neovascularization, and less than 10(-19) for the pooled
phenotypes (with an odds ration [OR] of 3.973; 95% confidence interval [CI]
2.928, 5.390). Disease risk is conferred in a dosage-dependent fashion. Similar
figures were observed for the LOC387715/ARMS2 SNP. No interaction was detected
between either between the 10q26 SNPs or the CFH SNP. CONCLUSIONS: This is the
first analysis to show that the two 10q26 SNPs are not in complete linkage
disequilibrium. Our studies however show that both the HTRA1 and LOC387715/ARMS2 
SNP appear to contribute equally to disease risk (both geographic atrophy and
choroidal neovascularization) with no evidence of interaction with CFH.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 18682806 [PubMed - indexed for MEDLINE]

149: Invest Ophthalmol Vis Sci. 2009 Jan;50(1):399-404. Epub 2008 Aug 1.

Segmentation error in Stratus optical coherence tomography for neovascular
age-related macular degeneration.

Patel PJ, Chen FK, da Cruz L, Tufail A.

Moorfields Eye Hospital, London, United Kingdom.

PURPOSE: To describe the rate of automated segmentation error in Stratus optical 
coherence tomography (OCT) scans in consecutive patients with neovascular
age-related macular degeneration (nAMD) receiving treatment and to investigate
the effect of the segmentation error on automated retinal thickness measures and 
whether further imaging reduces the rate of segmentation error. METHODS: A
retrospective analysis of fast macular thickness map (FMTM) protocol OCT scans of
50 eyes of 50 consecutive patients with nAMD. Each line scan was analyzed for
segmentation error with manual measurement of the center-point retinal thickness 
allowing calculation of the percentage error in automated thickness. OCT scanning
was repeated to overcome segmentation error. RESULTS: Segmentation error was
detected in 45 (90%) of the 50 patients with 37 (74%) patients having an error
affecting the central 1-mm subfield. Scan sets with a high central segmentation
error score (two or more line scans affected of six) had a significantly greater 
error in automated center-point retinal thickness than scan sets with a low error
score (20% compared with 3%, P < 0.000005). Central subfield segmentation error
persisted in 30 (60%) patients despite repeat scanning. CONCLUSIONS: There is a
high rate of segmentation error in OCT scans of patients with nAMD who are
undergoing treatment, leading to errors in automated central retinal thickness
measurement. The authors recommend manual measurement of central macular
thickness when two or more line scans are affected by segmentation error in the
central 1-mm subfield. Repeated scanning reduced the rate of error but did not
eliminate the problem.

PMID: 18676631 [PubMed - indexed for MEDLINE]

150: Invest Ophthalmol Vis Sci. 2009 Jan;50(1):405-13. Epub 2008 Aug 1.

Visualization of sub-retinal pigment epithelium morphologies of exudative macular
diseases by high-penetration optical coherence tomography.

Yasuno Y, Miura M, Kawana K, Makita S, Sato M, Okamoto F, Yamanari M, Iwasaki T, 
Yatagai T, Oshika T.

Computational Optics Group, Institute of Applied Physics, University of Tsukuba, 
Tennodai 1-1-1, Tsukuba, Ibaraki, 305-8573, Japan.
yasuno@optlab2.bk.tsukuba.ac.jp

PURPOSE: To evaluate the clinical significance of the newly developed
long-wavelength probe optical coherence tomography (LP-OCT) for the diagnosis of 
exudative macular diseases. METHODS: Fourteen eyes of 13 participants were
prospectively enrolled in the study. There were seven type I and five type II
choroidal neovascularization (CNV) cases associated with age-related macular
degeneration and idiopathic neovascularization and one case of polypoidal
choroidal vasculopathy (PCV). A custom-built LP-OCT based on swept-source OCT
(SS-OCT) technology was used. This new OCT uses a probe beam with a wavelength of
1060 nm that provides deeper penetration into the choroid and higher image
contrast to the structures beneath the retinal pigment epithelium (RPE) and
pathologic tissues than does conventional OCT. The depth resolution is 10.4
microm in tissue and the measurement speed is 28,000 depth scans/s. All the eyes 
were also examined by standard short wavelength probe OCT (SP-OCT). The image
contrasts of the LP- and SP-OCT were qualitatively evaluated and analyzed by
Wilcoxon's paired signed rank test and Spearman's rank correlation test. RESULTS:
In 10 of 14 eyes, high-contrast visualization of the diseases beneath the RPE,
CNV, or fibrin was attained. These diseases were almost invisible in the SP-OCT
images. The LP-OCT of the remaining eyes also revealed significant improvement in
the image contrasts beneath the RPE and CNV. Qualitative evaluation of the image 
contrasts and subsequent statistical test indicated statistically significant
improvement in the image penetration to the choroid of LP-OCT to that of SP-OCT. 
CONCLUSIONS: LP-OCT provided significant improvement in the image contrast of
exudative macular diseases.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18676629 [PubMed - indexed for MEDLINE]

151: Invest Ophthalmol Vis Sci. 2008 Dec;49(12):5274-8. Epub 2008 Aug 1.

Documenting fixation at an extrafoveal locus with a modified slit lamp in
age-related macular degeneration.

Leinonen MT, Hyvärinen L.

Department of Ophthalmology Turku University Hospital, Turku, Finland.
leinonen@iki.fi .

PURPOSE: To develop a simple and clinically useful technique for observing
fixation at an extrafoveal locus (preferred retinal locus [PRL]) with different
targets and texts in age-related macular degeneration (AMD). METHODS: A standard 
slit lamp was modified by adding several fixation targets in the illumination
pathway for direct observation and documentation of fixation during fundus
examination. Fixation patterns were analyzed in 30 subjects with AMD. RESULTS:
The location and stability of fixation with various stimuli was possible to
record in each subject. In 23 subjects, there was no difference between the
fixations at star and wagon wheel stimuli; in seven subjects, they were in
clearly different retinal locations. Fixation was unstable in three subjects. The
PRL for reading words was detectable in all subjects. CONCLUSIONS: The present
assessment technique seems to offer a simple, clinically available technique to
record fixation patterns to different targets and texts.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18676623 [PubMed - indexed for MEDLINE]

152: Ophthalmology. 2008 Aug;115(8):1366-71, 1371.e1.

Optical coherence tomography measurements and analysis methods in optical
coherence tomography studies of diabetic macular edema.

Browning DJ, Glassman AR, Aiello LP, Bressler NM, Bressler SB, Danis RP, Davis
MD, Ferris FL, Huang SS, Kaiser PK, Kollman C, Sadda S, Scott IU, Qin H; Diabetic
Retinopathy Clinical Research Network.

Collaborators: Safar A, Kim NM, Walsh AC, Sadda S, Schwartz SD, Gonzales CR, Chen
S, Daniels SA, Leong CJ, Ray SK, Ting TD, Verne AZ, Kuppermann BD, Tu ES, Fong D,
Pince KJ, Pieramici DJ, Castellarin AA, Nasir MA, Jumper JM, Fu AD, Johnson RN,
McDonald HR, Fan JT, Rauser ME, Suthar MB, Chan CK, Lin SG, Nuthi AS, Salib DM,
Novack RL, Boyer DS, Hopkins JJ, Rahhal FM, Tabandeh H, Teasley LA, Lansing M,
Braverman JM, Larrison WI, Mathura JR Jr, Jones BE, Chen M, Niffenegger JH, Wing 
G, Ghuman AT, Grodin RW, Raskauskas PA, Walker JP, Glatzer RJ, Dhalla MS,
Thompson WS, Perez Ortiz DJ, Friedman SM, Plous OZ, Richmond PP, Barnes CD, Okun 
NJ, Olson JC, Shaikh SA, Tolentino M, Berger A, Hamilton RS, Moon SJ, Chalam KV, 
Grover S, Gupta SK, Marcus DM, Singh H, Drouilhet JH, Kokame GT, Scott MH,
MacCumber MW, Lyon AT, Gill MK, Mirza RG, Pollack JS, Civantos JM, Flood TP,
MacCumber MW, Lim JI, Blair NP, Blair MP, Ulanski LJ 2nd, Maturi RK, Ciulla T,
Hrisomalos NF, Minturn JT, Maturi RK, Lazarus HS, Baker CW, Stone TW, Isernhagen 
RD, Kitchens JW, Wood WJ, Gitter KA, Willson RL, Sharuk GS, Aiello LP, Arrigg PG,
Murtha TJ, Schlossman DK, Shah ST, Sun JK, Topping TM, Cleary TA, Heier JS,
Krzystolik MG, Phillips WB 2nd, Berinstein D, Garfinkel R, Kaplan G, Von Fricken 
MA, Bressler S, Bressler NM, Do DV, Finkelstein D, Solomon SD, Sung JU,
Zimmer-Galler I, Elman MJ, Benner JD, Butler JW, Hoffert D, Flynn TE, Edwards PA,
Abrams GW, Mahmoud T, Trese MT, Ruby AJ, Aaberg TM, Margherio AR, Raphaelian PV, 
Garber FW, Glazer LC, Zheutlin JD, Sarrafizadeh R, Noffke AS, Klesert TR, Bhavsar
A, Emerson GG, Feman SS, Akduman L, Apte RS, Blinder KJ, Engelbrecht NE, Rao PK, 
Batlle IR, Greven CM, Kurup SK, Slusher MM, Browning D, Antoszyk AN, Brown JC,
Ridley ME, Hartnett ME, Garg S, Houghton OM, Meredith TA, Chace R, Ie D,
Lipkowitz JL, Beer PM, Falk N, Hampton GR, Rutledge BK, Spalding SC, Torrisi PF, 
Gentile RC, Ponce EA, DiLoreto DA Jr, Chung MM, Cooney MJ, Sorenson JA, Singerman
LJ, Coney JM, Miller DG, Novak MA, Huang SS, Tang J, Davidorf FH, Chang S,
Christoforidis JB, Kingsley RM, Leonard RE 2nd, Lauer AK, Flaxel CJ, Francis PJ, 
Hwang TS, Peters MA, Dreyer RF, Handelman IL, Lee MS, Lemley CA, Ma C, Gardner
TW, Neely KA, Scott IU, Brucker AJ, Kaufman SR, Estafanous MF, Wenz RE, Smith CW,
Woodcome HA Jr, Wells JA 3rd, Clark WL, Gross JG, Fishburne BC, Magee MA, Abraham
P, Googe J Jr, Anderson NG, McMillan TA, Perkins SL, Recchia FM, Agarwal A,
Sternberg P Jr, Cummings HL, Couch DA, Gunn JM, Davis GH, Berger BB, Fish GE,
Wang RC, Shami M, Smith SR, Lambert HM, Diaz-Rohena R, Khawly JA, Willis AW,
Callanan DG, Solley WA, Brown DM, Benz MS, Chen E, Fish RH, Kim RY, Wong TP,
Garcia CA, McCrary J, Pons ME, Patel SS, Lee SY, Gonzalez VH, Patel NR, Su YT,
Goodart RA, Faber DW, Kinyoun JL, Kim JE, Connor TB Jr, Han DP, Stepien KE,
Weinberg DV, Wirostko WJ, Gottlieb J, Altaweel MM, Blodi BA, Ip MS, Nork TM.

Jaeb Center for Health Research, 15310 Amberly Drive, Suite 350, Tampa, FL 33647,
USA. drcrnetX1@jaeb.org

OBJECTIVE: To evaluate optical coherence tomography (OCT) measurements and
methods of analysis of OCT data in studies of diabetic macular edema (DME).
DESIGN: Associations of pairs of OCT variables and results of 3 analysis methods 
using data from 2 studies of DME. PARTICIPANTS: Two hundred sixty-three subjects 
from a study of modified Early Treatment of Diabetic Retinopathy Study (mETDRS)
versus modified macular grid (MMG) photocoagulation for DME and 96 subjects from 
a study of diurnal variation of DME. METHODS: Correlations were calculated for
pairs of OCT variables at baseline and for changes in the variables over time.
Distribution of OCT measurement changes, predictive factors for OCT measurement
changes, and treatment group outcomes were compared when 3 measures of change in 
macular thickness were analyzed: absolute change in retinal thickness, relative
change in retinal thickness, and relative change in retinal thickening. MAIN
OUTCOME MEASURES: Concordance of results using different OCT variables and
analysis methods. RESULTS: Center point thickness correlated highly with central 
subfield mean thickness (CSMT) at baseline (0.98-0.99). The distributions of
changes in CSMT were approximately normally distributed for absolute change in
retinal thickness and relative change in retinal thickness, but not for relative 
change in retinal thickening. Macular thinning in the mETDRS group was
significantly greater than in the MMG group when absolute change in retinal
thickness was used, but not when relative change in thickness and relative change
in thickening were used. Relative change in macular thickening provides unstable 
data in eyes with mild degrees of baseline thickening, unlike the situation with 
absolute or relative change in retinal thickness. CONCLUSIONS: Central subfield
mean thickness is the preferred OCT measurement for the central macula because of
its higher reproducibility and correlation with other measurements of the central
macula. Total macular volume may be preferred when the central macula is less
important. Absolute change in retinal thickness is the preferred analysis method 
in studies involving eyes with mild macular thickening. Relative change in
thickening may be preferable when retinal thickening is more severe.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 18675696 [PubMed - indexed for MEDLINE]

153: Ophthalmology. 2008 Aug;115(8):e39-46.

Time course of morphologic effects on different retinal compartments after
ranibizumab therapy in age-related macular degeneration.

Ahlers C, Golbaz I, Stock G, Fous A, Kolar S, Pruente C, Schmidt-Erfurth U.

Medical University of Vienna, Vienna, Austria.

PURPOSE: To analyze the effect of ranibizumab therapy on retinal and subretinal
compartments in age-related macular degeneration and to compare the time course
of compartment specific effects to visual function. DESIGN: Prospective
noncomparative case series. PARTICIPANTS: Fourteen patients with changes in 3
major compartments owing to neovascular age-related macular degeneration.
METHODS: Standard treatment with 3 monthly doses of intravitreal ranibizumab was 
performed. Eyes were examined at baseline and weeks 1, 4, and 12 using a
standardized protocol. Manual segmentation was applied to all 128 B-scans
contained in a macular raster scan (MRS). MAIN OUTCOME MEASURES: Morphology and
time course of different retinal and subretinal compartments. RESULTS:
High-definition optical coherence tomography and manual segmentation allowed for 
precise identification of volumes within individual compartments. All morphologic
parameters responded positively to therapy, but demonstrated a specific time
course. Subretinal fluid was identified as the most relevant factor for visual
function, whereas changes in retinal and subpigment epithelial volumes did not
correlate with the time course of functional rehabilitation. CONCLUSION: Analysis
of MRS identified a characteristic impact of therapy on retinal and subretinal
morphology.

PMID: 18675694 [PubMed - indexed for MEDLINE]

154: Ophthalmology. 2008 Nov;115(11):1876-82. Epub 2008 Jul 31.

Night vision symptoms and progression of age-related macular degeneration in the 
Complications of Age-related Macular Degeneration Prevention Trial.

Ying GS, Maguire MG, Liu C, Antoszyk AN; Complications of Age-related Macular
Degeneration Prevention Trial Research Group.

Department of Ophthalmology, School of Medicine, University of Pennsylvania,
Philadelphia, Pennsylvania, USA.

OBJECTIVE: To describe baseline night vision symptoms and their association with 
>/=3-lines loss in visual acuity (VA), choroidal neovascularization (CNV), and
geographic atrophy (GA). DESIGN: Cohort study within a multicenter randomized
clinical trial. PARTICIPANTS: A total of 1052 participants with >/=10 large (>125
mu) drusen and VA >/=20/40 in each eye. METHODS: At baseline, participants
self-administered a 10-item Night Vision Questionnaire (NVQ-10). VA testing was
performed at baseline, 6 months, and annually. One eye of each participant was
randomly assigned to laser treatment, and the contralateral eye was assigned to
observation. During follow-up, trained readers identified CNV on the basis of
fluorescein angiograms and end point GA, defined as >1 disc area of new GA, based
on color photographs. Evaluation was performed by repeated-measures logistic
regression for NVQ-10 score as a risk factor for >/=3-lines loss in VA and by
survival analysis for CNV and GA, with and without adjustment for participant and
ocular characteristics. Evaluations were based on observed eyes and treated eyes,
considered separately and combined. MAIN OUTCOME MEASURES: A >/=3-lines loss in
VA, development of CNV and end point GA. RESULTS: At baseline, NVQ-10 scores
ranged from 3 to 100 with a mean of 70 (100 corresponds to no night vision
symptoms). Compared with participants with the best night vision (fourth quartile
of scores), participants with the worst night vision (first quartile of scores)
were at increased risk of >/=3-lines loss in VA in both observed and treated
eyes; odds ratios (95% confidence interval) were 2.85 (1.85-4.39) and 2.00
(1.27-3.14), respectively. The relative risk for the first quartile versus the
fourth quartile for development of GA was 4.18 (1.80-9.68) in observed eyes and
2.59 (1.13-5.95) in treated eyes. The relative risk for CNV incidence was 1.99
(1.12-3.54) in observed eyes and 1.33 (0.81-2.19) in treated eyes. These
relationships were maintained after adjustment for baseline participant and
ocular characteristics. CONCLUSIONS: Participants who perceived the most problems
in their night vision at baseline had an increased risk of >/=3-lines loss in VA,
CNV, and GA. These associations are independent of established risk factors.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial
    Research Support, N.I.H., Extramural

PMID: 18672295 [PubMed - indexed for MEDLINE]

155: Ophthalmology. 2008 Nov;115(11):1911-5. Epub 2008 Jul 31.

Acute intraocular inflammation after intravitreous injections of bevacizumab for 
treatment of neovascular age-related macular degeneration.

Wickremasinghe SS, Michalova K, Gilhotra J, Guymer RH, Harper CA, Wong TY,
Qureshi S.

Medical Retina Unit, Royal Victorian Eye and Ear Hospital, Melbourne, Australia.

PURPOSE: Bevacizumab is an inhibitor of vascular endothelial growth factor widely
used as an "off-label" treatment of neovascular age-related macular degeneration 
(AMD), despite the lack of clinical trial data on efficacy or safety of this
drug. We describe acute intraocular inflammation after intravitreous injection of
bevacizumab for the treatment of neovascular AMD. DESIGN: A retrospective case
series. PARTICIPANTS: Patients with neovascular AMD treated with intravitreous
injection of bevacizumab from clinical practices in 2 states (Victoria and South 
Australia) in Australia. METHODS: We retrospectively reviewed cases of acute
intraocular inflammation after intravitreous injection of bevacizumab for the
treatment of neovascular AMD. MAIN OUTCOME MEASURES: The detection and
description of inflammation in a large cohort of patients. RESULTS: There were 14
cases (11 women and 3 men), from a total of 1278 injections given. The mean age
of patients was 83.7 years (range, 74-98). The majority had a prior injection of 
bevacizumab, with a mean number of injections of 2.7 (range, 1-6). Most patients 
presented within 24 hours of intravitreous injection, with rapid reduction in
vision, but minimal discomfort. There were associated signs of ocular
inflammation in the anterior and posterior segments of the eye. Visual acuity at 
presentation was substantially reduced compared with the preinjection acuity,
although the vision rapidly improved with treatment over a period of 7-25 days
toward preinjection visual acuity. CONCLUSIONS: Intravitreous injection of
bevacizumab for the treatment of neovascular AMD may be associated with acute
intraocular inflammation. Differentiation from infectious endophthalmitis is
important for appropriate management of this condition.

Publication Types: 
    Case Reports
    Multicenter Study

PMID: 18672291 [PubMed - indexed for MEDLINE]

156: Am J Ophthalmol. 2008 Nov;146(5):692-9. Epub 2008 Jul 30.

The epidemiology of progression of pure geographic atrophy: the Beaver Dam Eye
Study.

Klein R, Meuer SM, Knudtson MD, Klein BE.

Department of Ophthalmology and Visual Sciences, University of Wisconsin School
of Medicine and Public Health, Madison, Wisconsin 53726, USA.
kleinr@epi.ophth.wisc.edu

PURPOSE: To examine the change in size and location of pure geographic atrophy
(GA). DESIGN: Population-based cohort study. METHODS: Ninety-five persons with GA
either at baseline or at the one of the three five-year follow-up examinations,
or both, were identified. Using computer-assisted software, the lesion area and
greatest linear dimension (GLD) were calculated. Thirty-two persons (53 multiple 
eye-visit pairs) were seen at multiple visits five years apart with GA in the
same eye to evaluate changes in total area and GLD. RESULTS: At the first
occasion when pure GA was identified (n = 95), 45% had a single GA lesion, 18%
had multifocal GA lesions, and 37% had a merged GA lesion. Of 53 eyes with
multiple visits, the overall increase in atrophy was 6.4 mm(2) over a five-year
period. The atrophy progressed to involve the foveal center in 47% of 19 eyes,
and there was a mean decrease of 17 letters read correctly. Eyes with multifocal 
GA were most likely to have the area of atrophy increase (mean, 12 mm(2)), to
have atrophy progress to the foveal center (83%), and to have a decrease in
vision (mean, 22 letters), whereas eyes with a single GA lesion were least likely
to have the area of atrophy increase (mean, 2 mm(2)), to have the lesion progress
to the foveal center (22%), and to have a decrease in vision (mean, 10 letters). 
CONCLUSIONS: These are the first population-based data describing the five-year
change in eyes with pure GA. Information on progression of GA will be useful for 
clinical trials of new interventions for GA.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18672224 [PubMed - indexed for MEDLINE]

157: Br J Ophthalmol. 2008 Sep;92(9):1163-8. Epub 2008 Jul 31.

The rationale and evidence base for a protective role of macular pigment in
age-related maculopathy.

Loane E, Kelliher C, Beatty S, Nolan JM.

Macular Pigment Research Group, Waterford Institute of Technology, Cork Road,
Waterford, Ireland.

Age-related maculopathy (ARM) remains the most common cause of blind registration
in people aged 50 years or over in the developed world, and its prevalence
continues to rise. Although effective new treatments have become available in the
recent past, these are expensive and cumbersome to the healthcare provider and to
the patient, and many cases remain resistant to such therapy. There is a
biologically plausible rationale whereby macular pigment, which is entirely of
dietary origin, may prevent or delay the onset, or ameliorate the clinical
course, of ARM. In this article, we review this rationale, and critically
appraise the current evidence base germane to the use of supplements containing
the macular carotenoids in patients with, or at risk of developing, ARM.

Publication Types: 
    Review

PMID: 18669545 [PubMed - indexed for MEDLINE]

158: Retina. 2008 Nov-Dec;28(10):1421-6.

Agreement among Canadian retina specialists in the determination of treatment
eligibility for photodynamic therapy in age-related macular degeneration.

Muni RH, Altaweel M, Tennant M, Weaver B, Kertes PJ.

Department of Ophthalmology and Vision Sciences, University of Toronto,
Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.

OBJECTIVES: To determine inter- and intraobserver agreement among Canadian retina
specialists in their angiographic classification of choroidal neovascularization 
and their decision to treat with photodynamic therapy. Agreement was also
determined between retina specialists and a Reading Center. METHODS: Forty retina
specialists graded 24 cases of exudative age-related macular degeneration on two 
occasions separated by 6 months. Participants were asked to categorize the
choroidal neovascularization and indicate if they would treat with photodynamic
therapy. Agreement was determined for decision to treat and for interpretation of
the fluorescein angiogram. Angiographic interpretation by participants was
compared with that of the Reading Center. RESULTS: The kappas among the 40
participants for lesion categorization and treatment decision were 0.43 (95%
confidence interval: 0.36-0.52) and 0.29 (95% confidence interval: 0.18-0.42),
respectively. The kappa for intraobserver agreement was 0.57 (95% confidence
interval: 0.50-0.64) for lesion categorization and 0.58 (95% confidence interval:
0.43-0.74) for treatment decision. The mean percent agreement with the Reading
Center for lesion categorization was 65.4%. CONCLUSIONS: There was moderate
interobserver agreement for choroidal neovascularization categorization and poor 
agreement among Canadian retina specialists for decision to treat with
photodynamic therapy. There was moderate intraobserver agreement for both
treatment decision and lesion categorization. There was moderate agreement
between observers and the Reading Center for angiographic choroidal
neovascularization categorization.

PMID: 18667952 [PubMed - indexed for MEDLINE]

159: Retina. 2008 Nov-Dec;28(10):1427-34.

Topical nepafenac as an alternate treatment for cystoid macular edema in steroid 
responsive patients.

Warren KA, Fox JE.

Department of Ophthalmology, University of Kansas School of Medicine, Kansas
City, USA. kwarren@warrenretina.com

PURPOSE: To evaluate the use of nepafenac 0.1% in patients with cystoid macular
edema who are known steroid responders. METHODS: Patients (N = 15) with clinical 
and angiographic cystoid macular edema (> or = 2 months) and a history of
increased intraocular pressure following administration of topical
corticosteroids participated in this prospective, open-label, pilot study. All
patients were treated with nepafenac 0.1% four times daily for 6 weeks and the
dose was tapered off over the ensuing 6 weeks. The total treatment duration was
12 weeks. Visual acuity and retinal thickness were measured. RESULTS: For the
entire population, there was a mean significant improvement in visual acuity and 
retinal thickness at 4 weeks and 12 weeks posttreatment compared with baseline (P
< 0.0001). A subgroup analysis revealed that patients with pseudophakic cystoid
macular edema (n = 11) had a mean significant improvement in visual acuity and
retinal thickness compared with baseline at 4 weeks and 12 weeks posttreatment (P
< 0.0001). Although the improvement in the vitreoretinal interface disorders
group was not statistically different from baseline (probably due to the
outlier), three of the four patients with vitreoretinal interface disorders had
improvement in visual acuity and retinal thickness. Nepafenac was well tolerated.
CONCLUSION: Nepafenac may be an effective and safe therapy for treating chronic
cystoid macular edema in patients who are steroid responders.

Publication Types: 
    Clinical Trial

PMID: 18664937 [PubMed - indexed for MEDLINE]

160: Br J Ophthalmol. 2008 Oct;92(10):1312-5. Epub 2008 Jul 29.

Education, socio-economic status and age-related macular degeneration in Asians: 
the Singapore Malay Eye Study.

Cackett P, Tay WT, Aung T, Wang JJ, Shankar A, Saw SM, Mitchell P, Wong TY.

Singapore Eye Research Institute, Singapore.

BACKGROUND/AIMS: Low socio-economic status is increasingly being identified as a 
risk marker for chronic diseases, but few studies have investigated the link
between socio-economic factors and age-related macular degeneration (AMD). The
present study aimed to assess the association between socio-economic status and
the prevalence of AMD. METHODS: A population-based cross-sectional study of 3280 
(78.7% response rate) Malay adults aged 40-80 years residing in 15 south-western 
districts of Singapore. AMD was graded from retinal photographs at a central
reading centre using the modified Wisconsin AMD scale. Early and late AMD signs
were graded from retinal photographs following the Wisconsin grading system.
Socio-economic status including education, housing type and income were
determined from a detailed interview. RESULTS: Of the participants, 3265 had
photographs of sufficient quality for grading of AMD. Early AMD was present in
168 (5.1%) and late AMD in 21 (0.6%). After adjusting for age, gender, smoking,
hypertension, diabetes and body mass index, participants with lower educational
levels were significantly more likely to have early AMD (multivariate OR 2.2, 95%
CI 1.2 to 4.0). This association was stronger in persons who had never smoked
(multivariate OR 3.6, 95% confidence CI 1.4 to 9.4). However, no association with
housing type or income was seen. CONCLUSIONS: Low educational level is associated
with a higher prevalence of early AMD signs in our Asian population, independent 
of age, cardiovascular risk factors and cigarette smoking.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18664503 [PubMed - indexed for MEDLINE]

161: Br J Ophthalmol. 2008 Oct;92(10):1352-6. Epub 2008 Jul 28.

Photodynamic therapy combined with low-dose intravitreal triamcinolone acetonide 
for age-related macular degeneration refractory to photodynamic therapy alone.

Iwama D, Otani A, Sasahara M, Yodoi Y, Gotoh N, Tamura H, Tsujikawa A, Yoshimura 
N.

Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School
of Medicine, Kyoto, Japan.

AIM: To examine the effects of photodynamic therapy (PDT) with verteporfin
combined with low-dose intravitreal triamcinolone acetonide (IVTA) for exudative 
age-related macular degeneration (AMD) that is resistant to PDT alone. DESIGN:
Retrospective case series. METHODS: A retrospective review was performed, using
the medical records of 22 eyes of 21 patients who consecutively received combined
PDT and 2 mg of IVTA for exudative AMD with a suspected chorioretinal anastomosis
or for AMD that was resistant to prior PDT alone. Only those patients who could
be followed up for more than 12 months after this combined therapy were enrolled 
in the study. Best corrected visual acuity and intraocular pressure measurements 
were taken during each examination. Colour photography, fluorescein/indocyanine
green angiography and optical coherence tomography were carried out at baseline
and every 3 months thereafter. Need for retreatment was based on dye leakage and 
the presence of serous retinal detachement (SRD) seen by optical coherence
tomography. RESULTS: Visual acuity improved or was maintained in the majority of 
patients, with the mean change between baseline and the last visit being an
improvement of 0.94 lines (p = 0.45). Seventeen (77%) of the 22 eyes showed
improved or maintained visual acuity after 12 months of follow-up. Eight (36%) of
the 22 eyes continued to show an SRD at the 12-month follow-up; this corresponded
to unchanged or even decreased leakage of dye. The mean number of retreatments
was 1.36, but the incidence of side effects accompanying treatment was not as
high as that reported previously for combined therapy that utilised higher-dose
IVTA. CONCLUSIONS: PDT combined with low-dose IVTA for exudative AMD seems to be 
as effective and safe as combined therapy with the higher-dose IVTA that was
reported previously.

PMID: 18662914 [PubMed - indexed for MEDLINE]

162: Ophthalmology. 2008 Sep;115(9):1447-9, 1449.e1-10. Epub 2008 Jul 26.

Comment in:
    Ophthalmology. 2008 Sep;115(9):1445-6.

A randomized trial comparing intravitreal triamcinolone acetonide and focal/grid 
photocoagulation for diabetic macular edema.

Diabetic Retinopathy Clinical Research Network.

Collaborators: Elman MJ, Raden RZ, Sloan MD, Butcher TM, Starr J,
Salfer-Firestone D, Singletary PV, Coffey T, Gore N, Shabi G, Cain T, Sotirakos
P, Stone TW, Wood WJ, Isernhagen RD, Kitchens JW, Heath WR, Holcomb DM, Cruz JL, 
Van Arsdall J, Buck M, Millett C, Slade EA, Blevins ST, Friedman SM, Plous OZ,
Blackmer KA, Key JS, Carlton SD, Sjoblom KL, Fagan DA, Gregory V, Maldonado J,
Gostischa KA, McKinney A, Glatzer RJ, Thompson WS, Brady-Lopez JA, Fernandez CV, 
Tardif AA, Sherley CM, Quinchia E, Birth JA, Bolet A, Benton-Murray J, Aramayo P,
Fernandez BM, Earl M, McHugh KL, Hampton GR, Spalding SC, Torrisi PF, Rutledge
BK, Grinnell CJ, DiSano FM, Kwasniewski LM, Czajak TC, Hay PB, Burke JL, Fyles
KB, Corey B, Capone LA, Browning D, Antoszyk AN, Brooks DR, Cowen MK, Helms JV,
Price AK, Murphy HL, Chatari LB, Walker RO, Pierce RE, McClain D, Ruiz KA, Davis 
LM, Balasubramaniam UM, Lutman B, McOwen MD, George RJ, Clark LM, Pieramici DJ,
Castellarin AA, Rabena MD, Smith R, Magana LD, Sterling AL, Norton TA, Davies SK,
Robbins EA, Tramel L, Basefsky JC, Avery K, Hernandez D, Kruzel ML, Boyer K,
Giust M, Lauer AK, Flaxel CJ, Hwang TS, Pope SI, Hanel SA, Toomey MD, Vahrenwald 
DR, Nolte SK, Ira SD, Wallace PR, Rice PB, West KL, Redenbo EF, Steinkamp PN,
Gaultney JM, Howell CS, Singerman LJ, Novak MA, Miller DG, Nitzsche TM, McNamara 
E, Schach KL, Weiss DE, Tanner V, Dubois KA, Cunningham TL, Greanoff GA,
Smith-Brewer SK, DuBois JC, Gottlieb J, Blodi BA, Altaweel MM, Ip MS, Nork TM,
Burke KF, Soderling BH, Perry-Raymond JR, Wealti AM, Soderling ED, Pohlman AJ,
Dietzman KA, Somers GF, Olson SR, Peterson JC, Krolnik DA, Knutson GE, Brown DM, 
Kim RY, Wong TP, Benz MS, Fish RH, Hallett JE, Rodriguez MA, De La Garza R,
Hutchinson C, Tang XS, Norris JB, Kubecka D, Hay S, Mutz KA, Kimbrough AD,
Williamson A, Kegley EN, Skelly ML, Evans MA, Fan JT, Suthar MB, Rauser ME,
Rollins KE, Chakrabarty AK, Quesada CG, Osuna SL, Corliss CJ, Kiernan WH, Ortega 
AM, Saldana G, Milam W, Cloud JD, Lazarus HS, Bunch DP, Ridge AD, Booth K, Davis 
LC, Moore J, Trimble M, Smith CW, Woodcome HA, Krzystolik MG, Greenberg PB,
Janigian RH, DuCoty CL, Varadian S, Salinas C, Henriques S, Banalewicz E, Hamel
M, Nagle AL, Benner JD, Butler JW, Scott H, Hamill K, McCrorey JM, Hurley RL,
Welch L, Carbaugh C, Goodwin AE, Richmond PP, Olson JC, Lieb DF, Barnes CD,
Shaikh SA, Okun NJ, Bell G, Davila LD, Treutel JA, Huertas C, Diaz CR, Thornton
TE, Jarrett R, Patel SS, Lee SY, Garcia KL, Jaimes A, Arrington BK, Dunn BL, Nafe
GR, Jones T, Adams LD, Bartlett TA, Hoffert D, Flynn TE, Sutherland D, Wilbur LR,
Forni T, Betterley P, Shorey ML, Frazier KA, Novack RL, Boyer DS, Rahhal FM,
Mukarram S, Gasparyan T, Sierra J, Sanguinet J, Smucker A, Kessinger J, Sharuk
GS, Murtha TJ, Arrigg PG, Sun JK, Kopple A, Stockman ME, Bestourous L,
Cavallerano JD, Strong J, Casazza EL, Cavicchi RW, Schlossman DK, Shah ST, Aiello
LP, Braverman JM, Ciardella AP, Ryman LS, Stillberger MA, Zapata JD, Montalvo SI,
Rhodes RC, Brown DM, Googe J, Anderson NG, Higdon CT, Morris CD, Evans S, Strong 
TE, Seitz VL, Hunt C, Cimino DJ, Blais PA, Jacobus M, Shami M, Pusser P, Tarter
CL, Gutierrez NR, Squires L, Anderson EM, Wentlandt TF, Kingsley RM, Leonard RE, 
Youngberg MD, Ogilbee LM, Dwiggins CJ, Hart JS, Richmond WR, Burris R, Baker CW, 
Caldwell TM, Martin TR, Palmer MJ, Lambert LF, Travis AB, Smith DD, Gross JG,
Fishburne BC, Magee MA, Flowers AM, Cummings PW, Henry KL, Gabriel RA, Bland KK, 
Lovit HK, Mallet CN, Price RL, Fish GE, Wang RC, Arnwine J, Sanchez B, Arceneaux 
S, Hendrix BL, Cummings K, Ellenich P, Jaramillo D, Gray K, Aguado H, Davis GH,
Li HK, Spillar H, Seitz VL, Zertuche AD, Nolen RR, Bourg JM, Garcia-Garza GA,
Krason Z, Horna J, Crocker A, Kelso C, Aaberg TM, Raphaelian PV, Scott S,
Kronlein S, Markus D, Lewis S, Scott IU, Gardner TW, Neely KA, Chobanoff SM,
Walter LE, Wilmarth M, Frawley ML, Strong JD, Bennett TJ, Brucker AJ, Stoltz RA, 
Drossner S, DuPont JC, Boxley SL, McRay M, Devine C, Weeney L, Berger JM, Nyberg 
W, Aleman TS, Clark WL, Wells JA, Gridine MD, Bearden RT, Cahill CP, McDougal PD,
Henderson ML, Hickman AB, Spivey R, Greven CM, Slusher MM, Fish J, Ledbetter FM, 
Clark MD, Miller DT, Tyler M, Callanan DG, Solley WA, Bradley PJ, Elmore GJ,
Grimes CA, Creighton JR, Garcia Y, Boleman B, Gray K, Huang SS, Chattah NM,
Karpinecz LL, Buckholz KB, Norell MA, Clow C, Carlton K, Burke S, Harrod MA,
Pankhurst G, Benetz BA, Wing G, Raskauskas PA, Ghuman AT, Walker JP, Kiesel C,
Knips E, Dyshanowitz D, Banks JM, Garcia CA, Patel K, Foster WJ, McCrary J,
Garibay E, Lessieur EM, Martinez O, Banda D, Montoya JP, Vi Nguyen C, Paz HL,
Santisbon E, Ramirez A, Cerda SM, Salinas LR, Stoever CA, Livas B, Cummings E,
Calderon EE, Pollack JS, Civantos JM, Ciscato BJ, Mikota RA, Kosinski BM, Muir
DW, Bhavsar AR, Olson TM, Chan C, Ries J, Carli WB, Pearson SL, Hager CH,
Spike-Kivel M, Jodell J, Taylor-Reetz L, Ortiz DJ, Perez BR, Alvarez M, Johnson
RL, Montoya SE, Jarrett R, Davidorf FH, Chambers RB, Elliott RJ, Milliron JD,
Chaudhuri CG, Perry JG, Halk AC, Savage SJ, Keating MJ, Cummings HL, Couch DA,
Gunn JM, Long DJ, Darnell G, Vermillion JJ, Mallard R, Berry JP, Carpenter S,
Schwartz SD, Gonzales CR, Gupta A, Ostrick R, Khwarg JW, Rosman ML, Shokouh B,
Chun M, Kageyama J, Moral J, Tetreault M, Le Beck DL, Lipka KM, Kim JE, Wirostko 
WJ, Han DP, Alvarez D, Drescher TS, Lange CY, Reiter KM, Graf J, Flanders J,
Barwick V, Selchert KJ, Backes DB, Beringer JR, Daniels SA, Ray SK, Leong CJ,
Ting TD, Moreci CM, Takahara S, Dowell KJ, Combs WM, Tejada RJ, Hom N, Williams
M, Hughes MD, Hanamoto F, Berger BB, Manhart GJ, Rodriguez M, Durham EA, Jeffers 
SA, Clevenger-Smith TL, Scrivner EN, Callen N, Talbert MA, Dorn DS, Gallia B,
Gartner MT, Ren Y, Ostrander B, Maturi RK, Minturn JT, Bleau LA, Agugliaro D,
Storie M, Novak CK, Samaniego DL, Morrow SJ, Maple A, Poston JL, Steele T, Ie D, 
Lipkowitz JL, Geraghty S, Sannazzaro BR, Harper M, Polanco L, Napoli D, McCall L,
Gonzalez VH, Vann VR, Guel DA, McNames RL, Herrera J, Ramirez D, Rodriguez G,
Lopez M, Garza G, Martinez MM, Herrera A, Trevino MG, Cuellar D, Garza C, Corona 
RM, Chan CK, Nuthi AS, Salib DM, Lin SG, Tarasewicz DG, Walther KS, Koch W,
Campbell CM, Sage KE, Dickerson ED, Andresen TA, Wiskirchen TB, Keith TL, Warren 
S, Sandra S, Rollins K, Huff KM, Evans R, Chesbrough DJ, Chen M, Holland C, Hagin
K, Miller R, Sneath M, Beer PM, Falk N, Olmeda E, Newton AL, Garza D, Whitney C, 
Fischer J, Faulhammer LA, Davis R, Feman SS, Akduman L, Anderson JS, Anderson KL,
Willerton RJ, Ghadban R, Burke P, Porter TI, Salvalaggio DD, Breeding L, Kleber
CJ, Apte RS, Blinder KJ, Engelbrecht NE, Rao PK, Nobel GS, Light PA, Weeks RF,
Walters CL, Sgorlon MK, Boyd LK, Vaughn AM, Wright TL, Gabel DL, Raeber ML,
Wehmeier J, Solomon SD, Finkelstein D, Bressler S, Frey M, Doll W, Donohue D,
Jurao R, Sheehan SE, Shah SM, Cain D, Falk R, Graul J, McDonald J, Herring C,
Belt J, Emmert D, MacCumber MW, Merrill PT, Sheth ND, Levine SJ, Voskuil-Marre D,
Gaynes BI, Pappas L, Hulvey P, Pleskovich JM, Lyon AT, Mathura JR, Kaminski L,
Ackatz L, O'Donnell LM, Rozenbajgier Z, Shankle J, Ryan DM, Simjanoski E, Edwards
PA, Ober MD, Rock SM, Monk MK, Murphy J, Wilson DF, Croswell M, Troszak TA, Stern
BA, Rusinek BA, Smith AL, Schillace LM, Phillips WB, Berinstein D, Garfinkel R,
Kaplan G, Oliver D, Byank LS, Haziminas JC, Kruzel M, Bickhart E, Frantz R, Ayyad
A, Flory M, Walker Y, Peters MA, Handelman IL, Ma C, Hobbs S, Reichenberger KJ,
Raunig W, Kramer SM, Durbin G, Kopfer M, Logan J, Daniel H, Wohlsein H, Johnson
M, Jumper JM, McDonald HR, Fu AD, Rose JM, Fiermonte P, Stolarczuk M, Teske B,
Linares SC, Ryan DM, Grout ST, Esquejo RL, Bye AJ, Huggans S, Chen S, You TT,
Casiano ME, Agustin EB, Zimmer N, Vazquez A, Topping TM, Heier JS, Morley MG,
Williams L, Hurley VM, Tyler LA, Zand PP, Daniel PE, Yenyil HL, Chong SG, Howard 
TN, Marino K, Graham M, Jones M, Hartnett ME, Landers MB, Meredith TA, Garg S,
Barnhart CJ, Vallar CD, Esquejo RL, Shields KD, Cantrell D, Kuppermann BD,
Grijalva J, Magallon R, Trump B, Safar A, Kim NM, Hankins SK, Troillett DL, Brown
AK, Aletter K, Troillett CJ, Brummett SK, Walsh AC, Lim JI, Flaxel CJ, Chong LP, 
Padilla M, Garcia JM, Richine LS, Dougall JA, Lansing M, Fox LB, Ross JE,
Alexander KA, Smith RK, Roussel DJ, Goodart RA, Faber DW, Mehr DS, Murphy HJ,
Perkins TL, Osguthorpe RW, Knight D, Kinyoun JL, Saperstein DA, Rath SA,
Pettingill J, Lawrence BS, Ernst PK, Clifton BC, Leslie JD, Stephens C, Kokame
GT, Shen J, Yuen A, Klesert TR, Olsen TW, Rath P, Walski JM, Cook S, Rolfer SM,
Patterson PK, Philiph D, Cohen MJ, Harvey PS, Recchia FM, Agarwal A, Sternberg P,
Owings S, Kinder KM, Franklin CC, Mofield GG, Taylor-Ward MB, Munn GE, Recchia
CC, Adkins T, Ou A, Guerrero P, Kapoor S, Gallardo JM, Tai KW, Paa JA, Boyd K,
Gonzalez N, Masini R, Vallet N, DiLoreto DA, Chung MM, Stoutenburg AM, Fedick N, 
Schaefer T, Goole MM, Addams LM, Fischer WS, Tutko J, Marcus DM, Singh H, Zapata 
GR, McAteer MC, Benson J, Hill CM, Overton KY, Hendrickson J, Freeman B, Ivey K, 
Oldag VL, Ridley ME, Schafer ML, Munoz D, Brogdon AA, Lummis JT, Peterson DC,
Cisco JK, Abrams GW, Puklin JE, Schulz LL, Milanovic C, Krzeminski VR, Silvis B, 
Morehead KM, Sadikovic Z, Lambert HM, Miller PS, Busch SK, Lazarte VN,
Fredrickson D, Morales JA, Schmidt AW, Gitter KA, Willson RL, Batlle IR, Marvel
CB, Schomaker K, Trese MT, Williams GA, Capone A, Ruby AJ, Zajechowski M,
Mitchell BL, Huckabone C, Treuter TF, Bridges CD, Szydlowski LD, Streasick P,
Guenther ML, Drouilhet JH, Pelke S, Nobler D, Bell T, Larrison WI, Karnolt A,
Abraham P, Livermont K, Green BL, Potter E, Parks D, Tu ES, Pince KJ, Fong DS,
Chase P, Moore BA, Krzystolik MG, Henriques S, German E, Bache JE, Beck RW,
Glassman AR, Barros J, Dale BB, Constantine SR, Dupre SS, Edwards AR, Hutton M,
Johnson PA, Kollman C, Lester LA, Loggins BL, McClellan SL, Murtaugh P, Moke PS, 
Qin H, Pritchard R, Ramirez H, Scott E, Stockdale CR, Davis MD, Danis RP, Hubbard
L, Reimers J, Vargo P, Moeller E, Myers D, Daywalt M, Bressler NM, Aiello LP,
Everett DF, Miskala PH, Ip MS, Aiello LP, Beck RW, Bressler NM, Clark WL, Daniels
SA, Davis MD, Everett DF, Ferris F, Glassman AR, Greven CM, Starr J, Browning D, 
Danis RP, Elman MJ, Grinnell CJ, Hampton GR, Heath WR, Krzystolik MG, Lauer A,
McLeod K, Miskala P, Ortiz DJ, Callanan D, Stone TW, Wong KL, Bressler NM, Aiello
LP, Beck RW, Bhavsar A, Danis RP, Davis MD, Everett DF, Ferris FL, Fish J,
Friedman S, Glassman AR, Lauer A, Brown DM, Browning DJ, Elman MJ, McLeod K,
Miskala PH, Grinnell CJ, Connett J, Barnbaum D, Flynn HW Jr, Frank RN, Genuth S, 
Jampol L, Wisniewski S, Resnick J.

Jaeb Center for Health Research, Tampa, FL 33647, USA. drcrnetB3@jaeb.org

OBJECTIVE: To evaluate the efficacy and safety of 1-mg and 4-mg doses of
preservative-free intravitreal triamcinolone in comparison with focal/grid
photocoagulation for the treatment of diabetic macular edema (DME). DESIGN:
Multicenter, randomized clinical trial. PARTICIPANTS: Eight hundred forty study
eyes of 693 subjects with DME involving the fovea and with visual acuity of 20/40
to 20/320. METHODS: Eyes were randomized to focal/grid photocoagulation (n =
330), 1 mg intravitreal triamcinolone (n = 256), or 4 mg intravitreal
triamcinolone (n = 254). Retreatment was given for persistent or new edema at
4-month intervals. The primary outcome was evaluated at 2 years. MAIN OUTCOME
MEASURES: Visual acuity measured with the electronic Early Treatment Diabetic
Retinopathy Study method (primary), optical coherence tomography-measured retinal
thickness (secondary), and safety. RESULTS: At 4 months, mean visual acuity was
better in the 4-mg triamcinolone group than in either the laser group (P<0.001)
or the 1-mg triamcinolone group (P = 0.001). By 1 year, there were no significant
differences among groups in mean visual acuity. At the 16-month visit and
extending through the primary outcome visit at 2 years, mean visual acuity was
better in the laser group than in the other 2 groups (at 2 years, P = 0.02
comparing the laser and 1-mg groups, P = 0.002 comparing the laser and 4-mg
groups, and P = 0.49 comparing the 1-mg and 4-mg groups). Treatment group
differences in the visual acuity outcome could not be attributed solely to
cataract formation. Optical coherence tomography results generally paralleled the
visual acuity results. Intraocular pressure increased from baseline by 10 mmHg or
more at any visit in 4%, 16%, and 33% of eyes in the 3 treatment groups,
respectively, and cataract surgery was performed in 13%, 23%, and 51% of eyes in 
the 3 treatment groups, respectively. CONCLUSIONS: Over a 2-year period,
focal/grid photocoagulation is more effective and has fewer side effects than
1-mg or 4-mg doses of preservative-free intravitreal triamcinolone for most
patients with DME who have characteristics similar to the cohort in this clinical
trial. The results of this study also support that focal/grid photocoagulation
currently should be the benchmark against which other treatments are compared in 
clinical trials of DME.

Publication Types: 
    Clinical Trial, Phase III
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, N.I.H., Extramural

PMID: 18662829 [PubMed - indexed for MEDLINE]

163: Br J Ophthalmol. 2008 Oct;92(10):1304-10. Epub 2008 Jul 25.

Environmental tobacco smoke exposure and eye disease.

Lois N, Abdelkader E, Reglitz K, Garden C, Ayres JG.

Ophthalmology Department, Grampian University Hospitals-NHS Trust, Aberdeen, UK. 
noemilois@aol.com

AIM: To undertake a systematic review of the literature on the effect of
environmental tobacco smoke (ETS) and eye disease. METHODS: Medline (1950-January
Week 2 2007), EMBASE (1980 to 2007 Week 07), SCOPUS and Science Direct were
searched on ETS exposure and eye disease using various combinations of the
following terms: passive smoking, environmental tobacco smoke, sidestream smoke, 
involuntary smoking, secondhand smoke; with eye, conjunctiva, sclera, episclera, 
cornea, lens, iris, retina, choroid, uvea, optic nerve, uveitis, iritis,
blindness, visual loss, cataract, thyroid eye disease, conjunctivitis,
age-related macular degeneration, dry eye, tears. The above terms were also used 
to search abstracts published on The Association for Research in Vision and
Ophthalmology Annual Meeting abstracts, from 1995 to 2006, and the grey
literature, including PhD and MSc theses/dissertations. A search was further
conducted specifically on eye diseases where active smoking has been proposed to 
be a risk factor, including age-related macular degeneration, Graves
ophthalmology, glaucoma, uveitis, refractive errors, strabismus, tobacco-alcohol 
amblyopia, non-arteritic ischaemic optic neuropathy, Leber optic neuropathy and
diabetic retinopathy. Given the scarce number of studies found through the above 
search, all articles found on ETS and eye disease were included in this review.
RESULTS: Seven studies evaluated the possible relationship between ETS and an eye
disease. These studies referred to refractive errors in children (n = 2),
cataract (n = 1), age-related macular degeneration (n = 3) and Grave
ophthalmopathy (n = 1). The data available were insufficient to establish
conclusive relationships between ETS and these eye diseases. CONCLUSION: Very
scarce data exist in the literature on the effect of ETS on diseases of the eye. 
It seems appropriate that ETS should be included in future studies addressing the
effect of smoking on eye disease.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18658170 [PubMed - indexed for MEDLINE]

164: Klin Oczna. 2008;110(4-6):183-7.

Exudative age-related macular degeneration or Best vitelliform macular
dystrophy?--A case report.

Kubicka-Trzaska A, Filemonowicz-Skoczek A, Karska-Basta I, Romanowska-Dixon B.

Department of Ophthalmology, Clinic of Ophthalmology and Ocular Oncology, Medical
College, Jagiellonian University, Kraków, Poland.

PURPOSE: To report a case of Best vitelliform macular dystrophy referred to the
Department Ophthalmology in Krakow with a diagnosis of exudative age-related
macular degeneration (AMD). MATERIALS AND METHODS: 70-years old man was diagnosed
in our clinic because of a two years history of slow, progressive visual acuity
worsening in both eyes with the presence of metamorphopsia. The basic ophthalmic 
examination was performed with additional diagnostic methods including: colour
vision test (Panel D-15), Amsler grid test, contrast sensitivity test
(Pelli-Robson chart), fluorescein angiography (FA), indocyanine green angiography
(ICGA), electroretinogram (ERG), electrooculogram (EOG) and optical coherence
tomography (OCT). RESULTS: Visual acuity in the right eye was: 0.16 and in the
left: 0.25. Amsler grid test revealed the presence of bilateral mild
etamorphopsia with the relative central scotoma. Pelli-Robson test showed
decreased contrast sensitivity perception in both eyes; PO > LO. On fundoscopy in
macula of both eyes the symmetrical round, elevated lesions of 1.5 dd with the
meniscus of subretinal creamy-yellow masses were present. The early frames of FA 
showed the presence of round lesions with distinct borders, unchanged in size and
shape throught the examination, hypofluorescent in the lower and hyperfluorescent
in the upper half of the lesions. Late frames of FA revealed the irregular
hyperfluorescence also in lower aspects of the lesions. ICGA showed: round
hypofluorescent lesions with isofluorescence in the upper part of the lesions.
ERG--revealed no pathology, EOG--showed decreased light response and depressed
Arden ratio in both eyes. OCT demonstrated hiperreflectivity of the retinal
pigment epithelium with elevation of retina and deletion of the foveolar
depression in both eyes. CONCLUSIONS: Based on the results of performed tests the
diagnosis of the Best vitelliform macular dystrophy was established. In some
cases various pathologies involving the macula may mimic the exudative AMD. The
basic ophthalmic examination supported by additional diagnostic methods allow to 
establish the definitive diagnosis in most cases of macular disorders.

Publication Types: 
    Case Reports

PMID: 18655458 [PubMed - indexed for MEDLINE]

165: J Clin Invest. 2008 Aug;118(8):2908-16.

Comment in:
    J Clin Invest. 2008 Aug;118(8):2681-4.

Mutant prominin 1 found in patients with macular degeneration disrupts
photoreceptor disk morphogenesis in mice.

Yang Z, Chen Y, Lillo C, Chien J, Yu Z, Michaelides M, Klein M, Howes KA, Li Y,
Kaminoh Y, Chen H, Zhao C, Chen Y, Al-Sheikh YT, Karan G, Corbeil D, Escher P,
Kamaya S, Li C, Johnson S, Frederick JM, Zhao Y, Wang C, Cameron DJ, Huttner WB, 
Schorderet DF, Munier FL, Moore AT, Birch DG, Baehr W, Hunt DM, Williams DS,
Zhang K.

Department of Ophthalmology and Visual Science, Eccles Institute of Human
Genetics, University of Utah, Salt Lake City, Utah, USA.

Familial macular degeneration is a clinically and genetically heterogeneous group
of disorders characterized by progressive central vision loss. Here we show that 
an R373C missense mutation in the prominin 1 gene (PROM1) causes 3 forms of
autosomal-dominant macular degeneration. In transgenic mice expressing R373C
mutant human PROM1, both mutant and endogenous PROM1 were found throughout the
layers of the photoreceptors, rather than at the base of the photoreceptor outer 
segments, where PROM1 is normally localized. Moreover, the outer segment disk
membranes were greatly overgrown and misoriented, indicating defective disk
morphogenesis. Immunoprecipitation studies showed that PROM1 interacted with
protocadherin 21 (PCDH21), a photoreceptor-specific cadherin, and with actin
filaments, both of which play critical roles in disk membrane morphogenesis.
Collectively, our results identify what we believe to be a novel complex involved
in photoreceptor disk morphogenesis and indicate a possible role for PROM1 and
PCDH21 in macular degeneration.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, Non-P.H.S.

PMID: 18654668 [PubMed - indexed for MEDLINE]

166: Br J Ophthalmol. 2008 Aug;92(8):1065-8.

The prevalence of cystoid macular oedema in retinitis pigmentosa patients
determined by optical coherence tomography.

Hajali M, Fishman GA, Anderson RJ.

Department of Ophthalmology and Visual Sciences (MC 648), Room 3.85, Eye and Ear 
Infirmary, 1855 W Taylor Street, Chicago, IL 60612-7234, USA.

AIMS: To determine the prevalence of cystoid macular oedema (CMO) in retinitis
pigmentosa (RP) patients of various genetic subtypes using optical coherence
tomography (OCT). METHODS: We performed a complete ocular examination on 124 RP
patients including best corrected visual acuity, intraocular pressure
measurement, anterior segment and a detailed fundus exam. OCT images were then
acquired using two different units. The presence of hypo-reflective lacunae was
used to diagnose CMO. RESULTS: Of the 124 patients, 47 showed CMO in at least one
eye (38%), while 34 showed CMO in both eyes (27%). The prevalence of CMO in at
least one eye for autosomal dominant (AD) patients was 52%, for autosomal
recessive (AR) 39%, isolated 39%, Usher II 35% and none in the X linked recessive
(XL) group. Using a chi-square analysis, no statistical significant difference
was found for the prevalence of "bilateral CMO" (p = 0.60) or "CMO in at least
one eye" (p = 0.59) among the AD, AR, isolated and Usher II genetic subtypes.
CONCLUSION: Because of its notable prevalence, it would seem prudent to screen RP
patients by OCT for the possible presence of CMO, to identify those amenable to
treatment and also for future treatment trials when monitoring visual acuity.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18653601 [PubMed - indexed for MEDLINE]

167: Ann Epidemiol. 2008 Aug;18(8):647-56.

Smoking and the risk of age-related macular degeneration: a meta-analysis.

Cong R, Zhou B, Sun Q, Gu H, Tang N, Wang B.

Department of Pharmacology, Key Laboratory of Reproductive Medicine, Nanjing
Medical University, Nanjing, China.

PURPOSE: Some studies were undertaken to evaluate the association between
cigarette smoking and age-related macular degeneration (AMD). This meta-analysis 
summarized the risk estimate of smoking and AMD and provided robust evidence for 
the association. METHODS: Relevant studies were identified by searching PubMed
and MEDLINE (from 1966 to June 2007) and reviewing the reference lists of key
articles. The summary relative risk ratio (RR) or odds ratio (OR) and 95%
confidence interval (CI) were calculated. Study-specific risk estimates were
pooled using a random-effects model. RESULTS: Five prospective cohort and eight
case-control studies met our inclusion criteria. Ever smoking was statistically
significant associated with increased risk of AMD among cohort studies (RR, 1.61;
95% CI, 1.01-2.57) or case-control studies (RR, 1.76; 95% CI, 1.56-1.99). Current
smokers were at higher risk of AMD than past smokers. Both geographic atrophy
(GA) and neovascular AMD (NV) are subtypes of AMD. A significant relationship was
found between smoking and GA risk. Smoking increased the risk of NV, with
marginal nonsignificance (RR, 1.47; 95% CI, 0.92-2.37) in cohort studies and
significance in case-control studies (RR, 1.96; 95% CI, 1.69-2.27). CONCLUSIONS: 
This meta-analysis indicated smoking, especially current smoking, was
significantly associated with increased risks of AMD and its subtypes.

Publication Types: 
    Meta-Analysis

PMID: 18652983 [PubMed - indexed for MEDLINE]

168: Clin Chem Lab Med. 2008;46(9):1250-5.

Are microarrays useful in the screening of ABCA4 mutations in Italian patients
affected by macular degenerations?

Stenirri S, Alaimo G, Manitto MP, Brancato R, Ferrari M, Cremonesi L.

Genomic Unit for the Diagnosis of Human Pathologies, San Raffaele Scientific
Institute, Milan, Italy.

BACKGROUND: Recessive Stargardt disease is due to mutation in the retina-specific
ABC transporter gene. Established strategies for molecular characterization of
this gene include direct detection by a microarray interrogating approximately
500 DNA variations and a scanning denaturing HPLC methodology. METHODS: Because
11 mutations were recorded to account for approximately 50% of molecular defects 
in the Italian population, we evaluated an alternative open microchip-based assay
for a fast and simplified level 1 screening for these mutations. RESULTS: This
approach allowed the characterization of both mutated alleles in 4% and one
mutated allele in 43% of cases when applied to a cohort of 47 Stargardt patients.
In the same patients, further investigation by denaturing HPLC for complete
characterization identified both mutated allele in 51% and one mutated allele in 
19% of cases, allowing the detection of 38 different mutations, five of which had
never been described. Notably, new mutations account for a high proportion (13%) 
of molecular defects in our patient cohort. CONCLUSION: The findings raises the
question about the choice of the optimal diagnostic strategy for complete
genotyping of the ABCA4 gene, as new mutations could not be identified by any
direct detection technology, irrespective of the total number of variations
screened.

PMID: 18652558 [PubMed - indexed for MEDLINE]

169: Diabet Med. 2008 Jul;25(7):860-2.

Spontaneous resolution of diabetic macular oedema after discontinuation of
thiazolidenediones.

Liazos E, Broadbent DM, Beare N, Kumar N.

St Paul's Eye Unit, Royal Liverpool University Hospital, Liverpool, UK.
stliazos@hotmail.com

AIM: To report a case of spontaneous resolution of diabetic maculopathy with
cystoid macular oedema in a diabetic patient after discontinuation of
rosiglitazone, documented with serial ocular computed tomography (OCT) images.
METHODS: A 59-year-old male with a 6-year history of well-controlled diabetes
mellitus presented with reduced visual acuity (VA) attributed to clinically
significant macular oedema (CSMO). The patient had been started on rosiglitazone 
8 months previously. Glitazone treatment was stopped and the patient
prospectively followed up. RESULTS: The patient demonstrated CSMO on OCT at
presentation. Three months after cessation of rosiglitazone, CSMO had completely 
resolved and VA improved. Resolution of CSMO was confirmed on OCT examination.
The patient required no interventional treatment, i.e. no laser or intravitreal
therapy, for his CSMO. CONCLUSIONS: To the best of our knowledge, this is the
first case to document spontaneous resolution of CSMO and improvement in VA on
discontinuation of a glitazone. Glitazones have a definitive role in the
management of diabetic patients and ophthalmologists and physicians should both
be aware that there may be an association with weight gain, peripheral oedema and
CSMO. We recommend that ophthalmologists consider discontinuing glitazones in
consultation with the diabetologist before embarking on interventional management
such as laser or intravitreal injections.

Publication Types: 
    Case Reports

PMID: 18644073 [PubMed - indexed for MEDLINE]

170: Graefes Arch Clin Exp Ophthalmol. 2008 Oct;246(10):1391-4. Epub 2008 Jul 19.

Association of beta zone of parapapillary atrophy with age-related macular
degeneration in adult Chinese. The Beijing Eye Study.

Wang YX, Xu L, Li YB, Jonas JB.

Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital University 
of Medical Sciences, Beijing, China.

BACKGROUND: Since parapapillary atrophy and age-related macular degeneration
(AMD) share features of their ophthalmoscopic and histological appearance, such
as irregular pigmentation, proliferation and loss of the retinal pigment
epithelium, it was the purpose of the study to assess whether parapapillary
atrophy, particularly beta zone of parapapillary atrophy, is associated with AMD 
in a population-based investigation. METHODS: The Beijing Eye Study included 4439
subjects out of 5324 subjects invited to participate (response rate 83.4%) with
an age of 40 + years. The present investigation consisted of 3874 (82.3%)
subjects for whom readable fundus photographs of at least one eye were available 
with normal intraocular pressure, a refractive error of >- 8 diopters, and no
signs of glaucomatous optic neuropathy. RESULTS: In a multivariate analysis, beta
zone of parapapillary atrophy was significantly associated with age (P < 0.001), 
optic disc size (P < 0.001) and myopic refractive error (P < 0.001). It was not
significantly associated with presence of retinal pigment depigmentation (P =
0.20) or hyperpigmentation (P = 0.99), drusen size (P = 0.27), and presence of
early AMD (P = 0.72) or late AMD (P = 0.99). CONCLUSIONS: Although beta zone of
parapapillary atrophy and age-related macular degeneration have a similar
histology with irregularities of the retinal pigment epithelium and eventual
closure of the choriocapillaris and loss of retinal pigment epithelium cells, the
entities are clinically not significantly associated with each other.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18642022 [PubMed - indexed for MEDLINE]

171: Clin Exp Optom. 2008 Sep;91(5):427-37. Epub 2008 Jul 10.

Inhibitors of vascular endothelial growth factor (VEGF) in the management of
neovascular age-related macular degeneration: a review of current practice.

van Wijngaarden P, Qureshi SH.

The Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia.

We review the fundamental changes that are now occurring to the management of
neovascular (wet) age-related macular degeneration (AMD). An improved
understanding of the role of vascular endothelial growth factor (VEGF) in the
genesis of choroidal neovascular membranes has led to the creation and use of
intravitreous anti-VEGF antibodies (bevacizumab and ranubizumab) and an aptamer
(pegaptanib) in the treatment of these lesions. These new intravitreous
injections for AMD have supplanted previous treatments in both efficacy and
safety and are now the standard of care for neovascular AMD. We discuss the
biochemistry of the anti-VEGF pathway. While there is substantial evidence for
the use of ranubizumab and pegaptanib, the intravitreous administration of
bevacizumab has not been tested in randomised controlled clinical trials. We
review the evidence base for all three agents and the patho-physiological basis
for adverse reactions to intravitreous VEGF blockade.

Publication Types: 
    Review

PMID: 18637105 [PubMed - indexed for MEDLINE]

172: Curr Diab Rep. 2008 Aug;8(4):263-9.

Novel potential mechanisms for diabetic macular edema: leveraging new
investigational approaches.

Gardner TW, Antonetti DA.

Department of Ophthalmology, Penn State College of Medicine, HU19, 500 University
Drive, Hershey, PA 17033, USA. tgardner@psu.edu

This article evaluates the current knowledge of the molecular mechanisms by which
diabetes ocular and systemic inflammation induce breakdown of the blood-retinal
barrier resulting in macular edema. We also summarize the relationship between
molecular targets and the use of therapeutic inhibitors in preclinical studies
and clinical trials. Further studies are needed to understand the regulation of
normal blood-retinal barrier physiology and the relationship between events in
animal models of diabetic retinopathy and humans with diabetes.

Publication Types: 
    Review

PMID: 18631437 [PubMed - indexed for MEDLINE]

173: Retina. 2008 Nov-Dec;28(10):1435-42.

Posterior hyaloid changes following intravitreal triamcinolone and macular laser 
for diffuse diabetic macular edema.

Sivaprasad S, Ockrim Z, Massaoutis P, Ikeji F, Hykin PG, Gregor ZJ.

Moorfields Eye Hospital, 162, City Road, London, EC1V 2PD, United Kingdom.
senswathi@aol.com

PURPOSE: To compare the effects of intravitreal triamcinolone and macular grid
laser photocoagulation on the vitreomacular relationship in diffuse diabetic
macular edema. METHODS: Review of optical coherence tomography images gathered in
a prospective, interventional randomized clinical trial. SETTING: Institutional
Practice. PROCEDURES: Seventy-seven optical coherence tomography images of 88
consecutive patients entered into a randomized clinical trial of the treatment of
persistent diffuse diabetic macular edema were reviewed by two independent
observers. All patients in the trial had diabetic macular edema following at
least two macular grid laser treatments and were randomized to intravitreal
injections of 4 mg triamcinolone or to further macular grid laser. Optical
coherence tomography images were recorded at baseline, 4, 8, and 12 months and
the patterns of vitreomacular relationship were classified into six categories.
MAIN OUTCOME MEASURES: The patterns of vitreomacular relationship in the two
groups were compared and correlated with the response to treatment. Outcome
measures were defined as changes in best-corrected visual acuity Early Treatment 
Diabetic Retinopathy Study letters and central macular thickness on optical
coherence tomography. RESULTS: Six eyes had peri-foveal vitreous detachment with 
or without traction in each group at baseline. At 12 months, the prevalence of
peri-foveal vitreous detachment was significantly higher after intravitreal
triamcinolone (n = 11) than macular grid laser (n = 8). These patients had poorer
visual outcome (P = 0.01) and increased central macular thickness (P = 0.002).
The development of complete posterior vitreous detachment was associated with
significantly decreased central macular thickness (P = 0.001) but not better
visual outcome (P = 0.72). CONCLUSION: These results suggest that posterior
hyaloid changes may play a more influential role in the response to intravitreal 
triamcinolone than laser treatment for diffuse diabetic macular edema.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial

PMID: 18628722 [PubMed - indexed for MEDLINE]

174: J Ocul Pharmacol Ther. 2008 Aug;24(4):403-7.

Intravitreal bevacizumab treatment for refractory diabetic macular edema.

Ornek K, Ornek N.

Department of Ophthalmology, Krkkale University, School of Medicine, Krkkale,
Turkey. kemalornek@hotmail.com

AIMS: The aim of this study was to report the short-term clinical and
angiographic outcomes after an intravitreal injection of bevacizumab in eyes with
refractory diabetic macular edema. METHODS: Patients who had been treated with
both grid-laser photocoagulation and intravitreal trimacinolone acetonide
injections for diabetic macular edema received intravitreal bevacizumab (0.125
mg/0.05 mL). Snellen visual acuity testing and fluorescien angiography were
performed before and 1 month after the injection for each patient. RESULTS:
Seventeen (17) eyes of 16 patients were included in the study. All patients
completed 6 weeks of follow-up. Visual acuity improved in 12 eyes (70%) and
remained the same in 5 eyes (30%). Eight (8) eyes (47%) revealed a marked
improvement of macular edema, 6 eyes (35%) revealed mild improvement, and 3 eyes 
(18%) had no change. None of the patients developed local or systemic adverse
events. CONCLUSIONS: Intravitreal injection of bevacizumab may be effective in
the treatment of refractory diabetic edema unresponsive to laser photocoagulation
and an intravitreal triamcinolone injection.

Publication Types: 
    Comparative Study

PMID: 18627339 [PubMed - indexed for MEDLINE]

175: Jpn J Ophthalmol. 2008 Mar-Apr;52(2):122-6. Epub 2008 Apr 30.

Efficacy and retention times of intravitreal triamcinolone acetonide for macular 
edema.

Kogure A, Ohkoshi K, Kogure S, Yamaguchi T, Kishi S.

Ophthalmology Department, St. Luke's International Hospital, Tokyo, Japan.
sahkuin@gmail.com

PURPOSE: To evaluate the retention of intravitreal triamcinolone acetonide (TA)
particles and the efficacy of TA therapy for patients with cystoid macular edema 
in branch retinal vein occlusion (BRVO) or diabetic macular edema (DME). We
monitored the TA particles until absorption from the vitreous cavity was
complete. The correlation between the intravitreal retention time of TA and its
efficacy was evaluated based on central macular thickness (CMT). RESULTS: The
intravitreal TA retention time was a mean 141.8 +/- 139.6 days in BRVO patients
and 114.5 +/- 59.6 days in DME patients. Patient age and retention time were
negatively correlated (r = -0.46; P = 0.013). At 6 months posttreatment the mean 
CMT decreased from 544.1 +/- 143.7 to 322.4 +/- 131.9 mum in BRVO patients and
from 454.5 +/- 119.0 to 371.2 +/- 209.4 mum in DME patients. Retention time and
CMT reduction were positively correlated in BRVO patient (r = 0.56, P = 0.02) but
not in DME patients (P = 0.06). CONCLUSIONS: Intravitreal TA reduced the CMT in
BRVO and DME patients over 6 months. The retention time was longer in younger
individuals. The efficacy of the therapy depended on the intravitreal TA
retention time observed clinically in BRVO patients. Biomicroscopic examination
of intravitreal TA is useful for evaluation of its efficacy.

PMID: 18626735 [PubMed - indexed for MEDLINE]

176: Jpn J Ophthalmol. 2008 Mar-Apr;52(2):99-107. Epub 2008 Apr 30.

Photodynamic therapy with verteporfin in Japanese patients with subfoveal
choroidal neovascularization secondary to age-related macular degeneration (AMD):
results of the Japanese AMD Trial (JAT) extension.

Japanese Age-Related Macular Degeneration Trial (JAT) Study Group.

Collaborators: Tano Y, Bressler NM, Ishibashi T, Ohji M, Shiraga F, Takahashi K, 
Weisberger A, Yuzawa M.

PURPOSE: To evaluate the longer term safety of verteporfin therapy in Japanese
patients with subfoveal classic choroidal neovascularization (CNV) due to
age-related macular degeneration (AMD). METHODS: Patients completing 12 months of
the Japanese AMD Trial (JAT) were eligible to enter the extension phase if the
investigator judged they would potentially benefit from further verteporfin
therapy. Patients had follow-up visits every 3 months, receiving verteporfin
therapy in the study eye if leakage from CNV was observed on fluorescein
angiography. Mean change from baseline in best-corrected visual acuity was a
safety variable in the extension. RESULTS: Of the 51 patients entering the study 
extension, 46 (90%) completed 24 months. Adverse events were similar to those in 
the first 12 months of JAT; no cumulative toxic effect of verteporfin therapy was
identified. Mean visual acuity letter score in the study eye increased from 50.8 
(20/100(+1) at baseline to 54.0 (20/80(-1)) at month 24. At month 24, six
patients (13%) had lost 15 or more letters of visual acuity, of whom four (9%)
had lost 30 or more letters. CONCLUSION: Verteporfin therapy was shown to be safe
and effective through 24 months in Japanese patients with subfoveal CNV due to
AMD, supporting its long-term use in these patients.

Publication Types: 
    Clinical Trial, Phase III
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 18626732 [PubMed - indexed for MEDLINE]

177: Arch Ophthalmol. 2008 Jul;126(7):986-9.

Identification of patients with diabetic macular edema from claims data: a
validation study.

Bearelly S, Mruthyunjaya P, Tzeng JP, Suñer IJ, Shea AM, Lee JT, Kowalski JW,
Curtis LH, Schulman KA, Lee PP.

Duke University Eye Center, Durham, NC 27715, USA.

OBJECTIVE: To assess the validity of an algorithm for identifying patients with
diabetic macular edema (DME) using International Classification of Diseases,
Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes in
administrative billing data from a convenience sample of physician offices.
METHODS: A convenience sample of 12 general ophthalmologists and 10 retina
specialists applied prespecified algorithms based on ICD-9-CM diagnosis codes to 
the billing claims of their practices and selected the associated medical
records. Four ophthalmologists abstracted data from the medical records, which
were then compared with the coded diagnoses. Main outcome measures were
sensitivity, specificity, and the kappa statistic for the DME algorithm (a
combination of codes 250.xx and 362.53), treating medical record documentation of
DME as the standard criterion. RESULTS: The DME algorithm had a sensitivity of
0.88 and a specificity of 0.96 for identifying DME. Excellent agreement was noted
between the algorithm and the medical records (kappa = 0.84). The algorithm
performed less well in identifying patients with a diagnosis of clinically
significant DME (sensitivity, 0.86; specificity, 0.84; kappa = 0.64).
CONCLUSIONS: The results of this pilot study suggest that patients with DME can
be identified accurately in claims data using ICD-9-CM diagnosis codes.
Application of this algorithm could improve investigations of disease prevalence 
and disease burden and provide an efficient means of assessing care and
interventions.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't
    Validation Studies

PMID: 18625948 [PubMed - indexed for MEDLINE]

178: Prog Retin Eye Res. 2008 Jul;27(4):372-90. Epub 2008 Jul 14.

The role of vascular endothelial growth factor and other endogenous interplayers 
in age-related macular degeneration.

Grisanti S, Tatar O.

Department of Ophthalmology at the University of Luebeck, Ratzeburger Allee 160, 
23538 Luebeck, Germany. Salvatore.Grisanti@uk-sh.de

Age-related macular degeneration (AMD) is a multifaceted disease characterized by
early subclinical changes at the choroidea-retinal pigment epithelium interface. 
Both the causal and formal pathogenesis of the disease is still puzzling.
Similarly, the reason for progression into two distinct late forms which are
"geographic atrophy" and "choroidal neovascularization" remains enigmatic. Late
changes are usually responsible for the dramatic loss in central function that
has a devastating effect on quality of life. In industrialized countries the
disease is a major cause for visual disability among persons over 60 years of
age. Due to demographic right-shift and increased life expectancy, AMD is not
only a medical problem but will have a pronounced socio-economic effect.
Neovascular AMD with the development of choroidal neovascularization in the
macular area accounts for 80% of the severe loss of visual acuity due to AMD. In 
the last decades, treatment modes were merely based on the destruction or
surgical removal of the neovascular complex. In the present, however, the
philosophical approach to treat the disease is changing to a pathology modifying 
manner. Intelligent targeting of the involved relevant factors and pathways
should stop disease progression, reduce complications and improve vision. The
first step into this new era has been accomplished with the introduction of
antiangiogenic agents. The new agents act either directly on vascular endothelial
growth factor (VEGF) or indirectly on its functional cascade. VEGF makes a
fundamental contribution to neovascular processes but it also acts in
physiological pathways. The main purpose of this review is to summarize its
physiological role especially within the eye, the role in the development of AMD 
and to understand and foresee both the benefits and potential side-effects of the
anti-VEGF-based therapy.

Publication Types: 
    Review

PMID: 18621565 [PubMed - indexed for MEDLINE]

179: Vision Res. 2008 Aug;48(18):1910-9. Epub 2008 Jul 11.

Reorganization of visual processing in macular degeneration: replication and
clues about the role of foveal loss.

Baker CI, Dilks DD, Peli E, Kanwisher N.

Laboratory of Brain and Cognition, National Institute of Mental Health, NIH, 10
Center Drive, Building 10, Room 4C104, Bethesda, MD 20892, USA.
bakerchris@mail.nih.gov

We previously reported large-scale reorganization of visual processing (i.e.,
activation of "foveal" cortex by peripheral stimuli) in two individuals with loss
of foveal input from macular degeneration [Baker, C.I., Peli, E., Knouf, N., &
Kanwisher, N. G. (2005). Reorganization of visual processing in macular
degeneration. Journal of Neuroscience, 25(3), 614-618]. Here, we replicate this
result in three new individuals. Further, we test the hypothesis that this
reorganization is dependent on complete loss of foveal input. In two other
individuals with extensive retinal lesions but some foveal sparing we found no
evidence for reorganization. We conclude that large-scale reorganization of
visual processing in MD occurs only in the complete absence of functional foveal 
vision.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 18620725 [PubMed - indexed for MEDLINE]

180: Am J Ophthalmol. 2008 Oct;146(4):501-507. Epub 2008 Jul 10.

High-definition optical coherence tomography features in vitelliform macular
dystrophy.

Querques G, Regenbogen M, Quijano C, Delphin N, Soubrane G, Souied EH.

Department of Ophthalmology, Centre Hospitalier Intercommunal de Creteil,
University Paris XII, Paris, France. giuseppe.querques@hotmail.it

PURPOSE: To correlate high-definition optical coherence tomography (HD OCT) and
fundus examination findings at different phases of vitelliform macular dystrophy 
and to determine the anatomic location of vitelliform material. DESIGN:
Prospective, noncomparative, observational case series. METHODS: A complete
ophthalmologic examination, including fundus biomicroscopy and HD OCT, was
performed in 11 consecutive patients with a diagnosis of vitelliform macular
dystrophy. RESULTS: Using HD OCT, we were able to demonstrate for the first time 
the presence of previtelliform lesions, characterized by a thicker layer between 
the retinal pigment epithelium (RPE) and the inner segment and outer segment
(IS/OS) interface. At this stage, a normal-appearing RPE and IS/OS interface were
found in two of four eyes. In all progressive stages from the vitelliform to the 
vitelliruptive, the vitelliform material was visualized by HD OCT as an highly
reflective lesion located between the hyporeflective outer nuclear layer and the 
hyperreflective RPE layer, associated or not to an optically empty lesion. At
these stages, a disrupted IS/OS interface and an almost normal appearance of all 
major intraretinal layers was detected. At the vitelliruptive and atrophic
stages, on some parts, the HD OCT scan revealed hyperreflective mottling on the
RPE layer, probably representing areas of focal RPE hypertrophy. The atrophic
stage and the fibrotic stage were characterized by thinning of all the retinal
layers and diffuse loss of the IS/OS interface. In our series, mean
best-corrected visual acuity impairment showed a statistically significant
correlation to the presence of focal disruption or diffuse loss of the IS/OS
interface (P = .002), as well as to a more advanced stage of the disease (P =
.01). A more advanced stage of the disease showed a strong statistically
significant correlation to the presence of diffuse loss of the IS/OS interface (P
< .001). CONCLUSIONS: Based on the HD OCT findings, we hypothesize that early
changes in vitelliform macular dystrophy involve the layer between the RPE and
the IS/OS interface, first with accumulation of material beneath the sensory
retina, and then with disruption and attenuation of IS and OS; late changes seem 
to affect the RPE, which undergoes hypertrophy, disruption, and attenuation.

Publication Types: 
    Comparative Study

PMID: 18619572 [PubMed - indexed for MEDLINE]

181: Am J Ophthalmol. 2008 Oct;146(4):520-526. Epub 2008 Jul 10.

Interobserver and intraobserver reliability of detecting age-related macular
degeneration using a nonmydriatic digital camera.

Le Tien V, Strého M, d'Athis P, Taillandier-Heriche E, Paillaud E, Mahiddine H,
Coscas G, Lejonc JL, Soubrane G, Souied EH.

Department of Ophthalmology, Centre Hospitalier Intercommunal, Université Paris
12-Henri-Mondor, Créteil, France.

PURPOSE: To evaluate the interobserver and intraobserver reliability of detecting
early and late age-related macular degeneration (AMD) using a nonmydriatic
digital camera in two distinct groups of older people. DESIGN: Prospective study.
METHODS: The two groups consisted of a series of patients older than 70 years
hospitalized in a geriatric unit and a younger series of people older than 55
years. In both groups, nonmydriatic color fundus photographs were obtained and
graded independently by two ophthalmologists (V.L. and M.S.). No ophthalmic
examination was performed. Main outcome measures were frequencies of early and
late AMD and interobserver and intraobserver agreement. RESULTS: Among 233
patients in group 1 (mean age, 84.6 years), only 119 patients (51%) could undergo
photography because of associated multiple morbidities. Mean age of group 2 was
63.8 years. In group 1, 35 (14.5%) of 238 pictures were ungradable. In series 2, 
65 (9.1%) of 716 pictures were ungradable. Frequencies of early and late AMD were
30.3% and 5.9% vs 12.6% and 2.6% in series 1 and 2, respectively. Interobserver
and intraobserver agreement was good or excellent (kappa > 0.6) in both groups.
CONCLUSIONS: In the entire geriatric cohort, 43% of the patients had gradable
pictures allowing a diagnosis. These patients would otherwise have had no access 
to any form of funduscopy. In the younger population, nonmydriatic pictures
permitted a diagnosis in 90% of the individuals. Detection of AMD with a
nonmydriatic digital camera may lead to large-scale screening and specific
management.

PMID: 18619569 [PubMed - indexed for MEDLINE]

182: Ophthalmologica. 2008;222(5):321-3. Epub 2008 Jul 11.

Early clinical experience with ranibizumab for occult and minimally classic
neovascular membranes in age-related macular degeneration.

Mantel I, Zografos L, Ambresin A.

Ophthalmology Department, University of Lausanne, Lausanne, Switzerland.
irmela.mantel@ophtal.vd.ch

BACKGROUND: In large randomized multicenter trials, ranibizumab has shown its
therapeutic efficacy for exudative age-related macular degeneration (AMD). The
aim of this paper is to report the real-life clinical experience with this
treatment for occult and minimally classic membranes without pigment epithelium
detachment. METHODS: We conducted a retrospective chart review of 37 patients
with occult and minimally classic neovascular membranes in AMD, without pigment
epithelium detachment. RESULTS: The mean visual improvement of 2 lines at 3, 6
and 9 months corresponds well with the results of the large trials. A mean number
of 5 reinjections was reached by month 8. It may potentially exceed the mean 5.5 
injections of the PrONTO study (prospective optical coherence tomography imaging 
of patients with neovascular AMD treated with intraocular ranibizumab). At months
6-8 recurrence was frequently observed. CONCLUSION: The early experience of
ranibizumab in clinical practice brings similarly good results as the large-scale
trials. However, interrupting the treatment too early may be a disadvantage.
Copyright 2008 S. Karger AG, Basel.

PMID: 18617755 [PubMed - indexed for MEDLINE]

183: Br J Ophthalmol. 2008 Sep;92(9):1248-52. Epub 2008 Jul 10.

Electrophysiological effects of intravitreal Avastin (bevacizumab) in the
treatment of exudative age-related macular degeneration.

Karanjia R, Eng KT, Gale J, Sharma S, ten Hove MW.

Department of Ophthalmology, Queen's University, Hotel Dieu Hospital, 166 Brock
Street, Kingston, ON, Canada, K7L 5G2; tenhove@queensu.ca.

OBJECTIVE: To examine the sensitivity of the multifocal electroretinogram
(mf-ERG) at measuring changes in retinal electrical activity in response to
Avastin (bevacizumab) treatment for age-related macular degeneration (ARMD).
METHODS: Nine subjects with exudative ARMD, not previously treated with
bevacizumab in the investigated eye, underwent pretreatment testing with mf-ERG
and intravenous fluorescein angiography (IVFA). A second mf-ERG test was
conducted post-treatment. The P1 response amplitudes were examined for the
hexagons corresponding to areas of pathology on the IVFA. Intertest variability
was accounted for by examining areas without pathology. Aggregate responses were 
also generated for central and lesion-associated responses. RESULTS: Changes in
P1 response amplitude correlated with changes in visual acuity (R(2)>0.96). An
improvement in Snellen visual acuity correlated with a significant improvement in
P1 response amplitude from lesion associated recordings (p<0.03). Changes in P1
response amplitudes were not observed when aggregate responses were generated.
CONCLUSION: This study represents a novel method for assessing an improvement of 
mf-ERG responses. This is the first study to demonstrate a statistically
significant change in retinal electrical activity postbevacizumab in patients
with ARMD. This study demonstrates a method for utilising mf-ERG to assess
changes in retinal electrical activity and to assess the effectiveness of
treatments such as bevacizumab.

Publication Types: 
    Evaluation Studies
    Research Support, Non-U.S. Gov't

PMID: 18617547 [PubMed - indexed for MEDLINE]

184: Br J Ophthalmol. 2008 Dec;92(12):1606-11. Epub 2008 Jul 9.

Comment in:
    Br J Ophthalmol. 2008 Dec;92(12):1573-4.

Pegaptanib sodium for neovascular age-related macular degeneration: third-year
safety results of the VEGF Inhibition Study in Ocular Neovascularisation (VISION)
trial.

Singerman LJ, Masonson H, Patel M, Adamis AP, Buggage R, Cunningham E, Goldbaum
M, Katz B, Guyer D.

Retina Associates of Cleveland, 3401 Enterprise Parkway, Suite 300, Cleveland, OH
44122, USA. lsingerman@retina-assoc.com

AIMS: To evaluate the safety of up to 3 years of pegaptanib sodium therapy in the
treatment of neovascular age-related macular degeneration (NV-AMD). METHODS: Two 
concurrent, prospective, multicentre, double-masked studies randomised subjects
with all angiographic lesion compositions of NV-AMD to receive intravitreous
pegaptanib sodium (0.3, 1 and 3 mg) or sham injections every 6 weeks for 54
weeks. Those initially assigned to pegaptanib were rerandomised to continue or
discontinue therapy for 48 more weeks; sham-treated subjects continued sham,
discontinued or received pegaptanib. At 102 weeks, subjects receiving pegaptanib 
0.3 mg or 1 mg in years 1 or 2 continued; those receiving pegaptanib 3 mg or who 
did not receive treatment in years 1 and 2 were rerandomised to 0.3 mg or 1 mg
for year 3. RESULTS: As in years 1 and 2, pegaptanib was well tolerated in year
3. Adverse events were mainly ocular in nature, mild, transient and
injection-related. Serious adverse events were rare. No evidence of systemic
safety signals attributed to vascular endothelial growth factor inhibition arose 
in year 3. There were no findings in relation to vital signs or electrocardiogram
results suggesting a relationship to pegaptanib treatment. CONCLUSION: The 3-year
safety profile of pegaptanib sodium was favourable in patients with NV-AMD.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial

PMID: 18614570 [PubMed - indexed for MEDLINE]

185: Eur J Ophthalmol. 2008 Jul-Aug;18(4):609-13.

Prognostic prediction ability of postoperative multifocal ERG after vitrectomy
for diabetic macular edema.

Leozappa M, Micelli Ferrari T, Grossi T, Pace V, Rinaldi ML, Battista D, Micelli 
Ferrari L.

UOC Oculistica, Ospedale Generale Regionale F. Miulli, Acquaviva delle Fonti,
Bari, Italy.

PURPOSE: Diabetic macular edema (DME) causes visual loss in diabetic patients.
Multifocal electroretinograms (mfERGs) have been used to assess macular function 
pre- and postvitrectomy for DME. METHODS: A standard three-port pars plana
vitrectomy with peeling of inner limiting membrane was performed in 25 eyes of 21
patients (13 male, 8 female) with DME. For each patient, visual acuity
examination, measure of retinal thickness (using optical coherence tomography),
and mfERGs were performed before and 1 week, 1 month, 3 months, and 6 months
after vitrectomy. RESULTS: Mean postoperative visual acuity was significantly
improved (p<0.05, t test), with mean increase of 0.17 logMAR units; mean retinal 
thickness was significantly (p<0.001) decreased after surgery (from 537 microm to
298 microm). The increase of normalized amplitude of central ring was not
significant; the mean P1 wave-amplitude increased from 0.33 to 0.40 mV; mean P1
wave-implicit time decreased 2.88 ms. We divided the patients into two groups:
Group 1 (13 eyes), in which the visual recovery was less than 0.20 logMAR, and
Group 2 (12 eyes), in which the visual recovery was greater than 0.20 logMAR. ERG
results were statistically significantly different between the groups (p<0.025), 
when we consider the response recorded from the central ring. In Group 2 there is
a marked reduction in implicit time of both ERGs waves, which was statistically
significant for N1 wave (p=0.01). The changes of parameters of mfERG observed 6
months after surgery were consistent with those recorded just 1 week after
surgery. CONCLUSIONS: Multifocal electroretinogram can be useful to predict
functional prognosis in patients with diabetes who underwent vitrectomy for
diabetic macular edema.

PMID: 18609483 [PubMed - indexed for MEDLINE]

186: Eur J Ophthalmol. 2008 Jul-Aug;18(4):601-8.

Macular function by multifocal electroretinogram in diabetic macular edema after 
intravitreal triamcinolone acetonide injection.

Karacorlu M, Ozdemir H, Senturk F, Arf Karacorlu S, Uysal O.

The Istanbul Retina Institute Inc., Istanbul, Turkey. retina@pobox.com

PURPOSE: The purpose of this study was to assess macular function by multifocal
electroretinography (mfERG) in eyes with diabetic macular edema (DME) after
intravitreal triamcinolone acetonide (IVTA) injection. METHODS: Fifteen eyes of
15 patients with DME scheduled for 4 mg IVTA injection were prospectively
recruited. The response to treatment was monitored functionally by visual acuity 
(VA) measurement and mfERG and anatomically by foveal thickness measured by
optical coherence tomography (OCT). The first-order kernel P1 mfERG responses
from 0 to 7 degrees (central) and 7 to 25 degrees (peripheral) were grouped and
analyzed. Changes in functional parameters (VAs and the P1 mfERG response
amplitudes and peak latencies) and morphometric parameters (OCT foveal thickness)
in eyes with DME 1 and 3 months after IVTA injection were compared with baseline 
values by Student t test. RESULTS: The mean baseline logMAR value for VAs of the 
patients before treatment was 0.49+/-0.26. After treatment, it was 0.27+/-0.23 at
1 month and 0.26+/-0.18 at 3 months, and differences from pretreatment values
were significant (for each, p<0.001). There were statistically significant
decreases in the mean foveal thickness at 1 and 3 months after treatment compared
with pretreatment values (for each, p<0.001). There were also statistically
significant increases in the mean P1 response amplitude for both central and
peripheral groups at all examinations compared with pretreatment (for each,
p<0.001). The mean P1 peak latencies for both the central and peripheral groups
were shortened, but not significantly. CONCLUSIONS: As well as the reduction in
DME and improvement in VA, IVTA injection improves macular function as assessed
by mfERG in diabetic patients.

PMID: 18609482 [PubMed - indexed for MEDLINE]

187: Eur J Ophthalmol. 2008 Jul-Aug;18(4):595-600.

Assessment of macular function by microperimetry in intermediate age-related
macular degeneration.

Dinc UA, Yenerel M, Gorgun E, Oncel M.

Yeditepe University Eye Hospital, Istanbul, Turkey. umutdinc@yahoo.com

PURPOSE: To evaluate retrospectively macular function by microperimetry (MP) in
intermediate age-related macular degeneration (AMD). METHODS: Thirty eyes of 30
patients with intermediate AMD and a visual acuity of 20/32 or better were
enrolled in the study. Macular function in patients with intermediate AMD and
age-matched control group were carried out with MP1 microperimeter. Mean
sensitivity (MS), mean defect (MD) parameters, fixation patterns, and
localizations were evaluated. Mann-Whitney U test was used for the comparison of 
macular function parameters between the intermediate AMD group and the control
group. RESULTS: MS was 12.7+/-2.8 dB and MD was detected as -6.2+/-2.2 dB in the 
intermediate AMD group by MP. Fixation patterns were stable in 22 eyes,
relatively unstable in 7 eyes, and unstable in 1 eye. Fixation location was
predominantly central in 19 eyes, poor central in 5 eyes, and predominantly
eccentric in 6 eyes. In the control group MS was 18.0+/-0.6 dB and MD was
-1.9+/-0.6 dB. When compared with control group, the decrease in MS and the
increase in MD were statistically significant in the intermediate AMD group
(p=0.001 and p=0.001, respectively). CONCLUSIONS: Assessment of retinal
sensitivity with MP1 microperimeter is a rapid, safe and noninvasive diagnostic
method. Early macular function loss in intermediate AMD can be precisely detected
by MP1 microperimeter before significant visual impairment is established and it 
is also useful for demonstrating the shift in the localization and the stability 
of fixation prior to progression of intermediate AMD to advanced and exudative
stage.

PMID: 18609481 [PubMed - indexed for MEDLINE]

188: Eur J Ophthalmol. 2008 Jul-Aug;18(4):591-4.

Can intravitreal tissue plasminogen activator and SF6 gas facilitate management
of macular degeneration with photodynamic therapy?

Muqit MM, Ghanchi FD.

Medical Retina Service, Department of Ophthalmology, Bradford Teaching Hospitals,
NHS Foundation Trust, Bradford, Yorkshire, UK. mmmk3@aol.com

PURPOSE: To describe the safety and efficacy of intravitreal tissue plasminogen
activator (tPA) and sulfur hexafluoride (SF6) gas with sequential photodynamic
therapy (PDT) in the management of submacular hemorrhage (SMH) associated with
macular degeneration (MD). METHODS: Consecutive case series of five patients
presenting with acute SMH from neovascular MD between May 2004 and January 2006
in a UK Eye Centre. Duration of visual loss was less than 7 weeks. Treatment
involved intravitreal injections of tPA, SF6 gas to achieve pneumatic
displacement of SMH, and 24 hours prone posturing. Displacement of SMH was
assessed by digital photography, and choroidal neovascularization (CNV) was
reclassified using angiography. PDT was applied when indicated within 1 to 12
days postoperatively. RESULTS: Adequate displacement of SMH allowed visualization
of CNV within 24 hours in three of five patients. One patient with large SMH of 7
weeks duration had partial displacement of SMH. Three patients were reclassified 
with classic CNV after tPA-SF6 injection, and successfully underwent PDT.
CONCLUSIONS: Intravitreal tPA and SF6 assisted pneumatic displacement of SMH is a
safe and effective intervention. This technique facilitates more accurate
angiographic classification of CNV. PDT may be sequentially and rapidly applied
as early as 1 day after injections. The technique may be offered to patients with
neovascular MD presenting with acute SMH.

PMID: 18609480 [PubMed - indexed for MEDLINE]

189: Trends Immunol. 2008 Aug;29(8):380-7. Epub 2008 Jul 2.

Factor H family proteins and human diseases.

Józsi M, Zipfel PF.

Junior Research Group Cellular Immunobiology, Leibniz Institute for Natural
Product Research and Infection Biology-Hans Knöll Institute, Jena D-07745,
Germany.

Complement is a major defense system of innate immunity and aimed to destroy
microbes. One of the central complement regulators is factor H, which belongs to 
a protein family that includes CFHL1 and five factor H-related (CFHR) proteins.
Recent evidence shows that factor H family proteins (factor H and CFHRs) are
associated with diverse and severe human diseases and are also used by human
pathogenic microbes for complement evasion. Therefore, dissecting the exact
functions of the individual CFHR proteins will provide insights into the
pathophysiology of such inflammatory and infectious diseases and will define the 
therapeutic potential of these proteins.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18602340 [PubMed - indexed for MEDLINE]

190: Curr Eye Res. 2008 Jul;33(7):591-8.

A randomized, prospective, placebo-controlled clinical trial of a novel
zinc-monocysteine compound in age-related macular degeneration.

Newsome DA.

Retinal Institute of Louisiana, New Orleans, Louisiana, USA.
doctordave1618@aol.com

PURPOSE: To test the hypothesis that daily use of zinc-monocysteine (ZMC)
supplement will be well tolerated and result in improved macular function in
persons with dry age-related macular degeneration (AMD). METHODS: Eligible,
consenting subjects were randomized to either ZMC 25 mg or placebo twice daily
for 6 months. Both ZMC and placebo groups enrolled 40 participants, with best
corrected visual acuity 20/25 to 20/70, macular drusen, and pigment changes.
Masked personnel determined baseline, 3- and 6-month best-corrected visual
acuity, contrast sensitivity, and light flash recovery time. Differences between 
ZMC and placebo were analyzed by a one-sided unpaired t-test of the paired
differences between baseline and 3- and 6-month timepoints for right and left
eyes separately. RESULTS: By 6 months the ZMC group showed improved visual acuity
(p < 0.0001) and contrast sensitivity (p < 0.0001). Macular light flash recovery 
time shortened in the ZMC group at 3 months by 2.1 sec (left eye, p = 0.0001) to 
3.6 sec (right eye, p < 0.0001), and at 6 months by 7.2 sec (left eye, p <
0.0001) to 7.4 sec (right eye, p < 0.0001). This variable had no improvement in
the placebo group. ZMC had a gastrointestinal irritation rate of under 2%.
CONCLUSION: ZMC 25 mg twice daily was well tolerated and was associated with
improved macular function in comparison to a placebo in persons with dry AMD.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18600492 [PubMed - indexed for MEDLINE]

191: Invest Ophthalmol Vis Sci. 2008 Nov;49(11):4795-800. Epub 2008 Jul 3.

Cataract surgery and the risk of aging macula disorder: the rotterdam study.

Ho L, Boekhoorn SS, Liana, van Duijn CM, Uitterlinden AG, Hofman A, de Jong PT,
Stijnen T, Vingerling JR.

Department of Epidemiology and Biostatistics, Erasmus Medical Center, Rotterdam, 
The Netherlands.

PURPOSE: To investigate still-controversial associations between prior cataract
surgery and aging macula disorder (AMD) in a general population. METHODS:
Baseline lens status and risk of incident AMD (iAMD) were examined in
participants of the prospective population-based Rotterdam Study at risk for AMD 
(n = 6032). Slit lamp examination was used to determine lens status and
stereoscopic color fundus photography to determine the presence of AMD. Odds
ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated with
generalized estimating equation (GEE) models. Stratified analyses were also
performed for CFH Y402H genotype. RESULTS: After adjusting for age, sex,
follow-up time, and the correlation between eyes, a history of cataract surgery
was associated with incident dry late AMD (OR, 3.43; 95% CI, 1.82-6.49). This
association remained significant after additional adjustment for smoking status
and AMD stage at baseline (OR, 3.44; 95% CI, 1.68-7.08). No statistically
significant association was found between prior cataract surgery and the
incidence of wet late AMD or early AMD. Homozygous CFH Y402H carriers had higher 
risks for all types of AMD compared to heterozygotes and noncarriers after
cataract surgery, particularly for dry AMD. CONCLUSIONS: The findings imply that 
cataract surgery increases the risk of dry AMD, particularly in homozygous CFH
Y402H carriers. The risk of AMD progression should be considered before
recommending cataract surgery to patients with cataract and early AMD.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 18599571 [PubMed - indexed for MEDLINE]

192: Invest Ophthalmol Vis Sci. 2008 Nov;49(11):4707-11. Epub 2008 Jul 3.

Retinal vascular caliber changes after intravitreal triamcinolone treatment for
diabetic macular edema.

Wickremasinghe SS, Rogers SL, Gillies MC, Zhu M, Wong TY.

Centre for Eye Research Australia, University of Melbourne, Melbourne, Australia.

PURPOSE: To describe the changes in retinal vascular caliber in response to a
single injection of intravitreal triamcinolone (IVTA) in patients with refractory
diabetic macular edema. METHODS: Prospective data from a randomized clinical
trial were used. The effects of IVTA versus sham injections in patients with
refractory diabetic macular edema were evaluated in a randomized clinical trial
involving 69 eyes of 43 patients. Of these, 28 eyes (15 IVTA and 13 sham) of 21
patients had gradable retinal photographs at the baseline and 3-month follow-up
visit for analysis in the present study. Retinal vascular caliber was measured
from digital fundus photographs and summarized as central retinal artery (CRAE)
and vein (CRVE) equivalents in all eyes at baseline and at the 3-month follow-up 
visit. RESULTS: Over the 3 months of the study, there was a significant reduction
compared to baseline in retinal arteriolar (147.8 microm vs. 140.0 microm, P =
0.047) and venular (219.5 microm vs. 198 microm, P = 0.039) caliber in eyes
treated with IVTA. There was no change in retinal arteriolar (139.9 microm vs.
139.2 microm, P = 0.878) or venular (220.3 microm vs. 217.6 microm, P = 0.534)
caliber in those treated with sham injections. CONCLUSIONS: IVTA has a
significant narrowing effect on both retinal arteriolar and venular diameter in
eyes with diabetic macular edema (ClinicalTrials.gov number, NCT00148330).

Publication Types: 
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18599569 [PubMed - indexed for MEDLINE]

193: Am J Ophthalmol. 2008 Oct;146(4):554-560. Epub 2008 Jul 2.

Comment in:
    Am J Ophthalmol. 2008 Oct;146(4):483-5.

A randomized, masked comparison of topical ketorolac 0.4% plus steroid vs steroid
alone in low-risk cataract surgery patients.

Wittpenn JR, Silverstein S, Heier J, Kenyon KR, Hunkeler JD, Earl M; Acular LS
for Cystoid Macular Edema (ACME) Study Group.

Collaborators: Wittpenn J, Silverstein S, Hunkeler J, Schechter B, Price F, Chu
R, Wallace B, Trattler W, Dougherty P, Goldberg D, Perry H, Solomon K, Donnenfeld
E, Kenyon K, Roberts C.

State University of New York at Stony Brook, Stony Brook, New York 11790, USA.
jrwittpenn@aol.com

PURPOSE: To evaluate whether adding perioperative topical ketorolac tromethamine 
0.4% improves cataract surgery outcomes relative to topical steroids alone in
patients without known risk factors for cystoid macular edema (CME). DESIGN:
Prospective, randomized, investigator-masked, multicenter clinical trial.
METHODS: Patients scheduled to undergo phacoemulsification and with no recognized
CME risks (diabetic retinopathy, retinal vascular disease, or macular
abnormality) were randomized to receive either prednisolone acetate 1% 4 times
daily (QID) alone (steroid group; n = 278) or prednisolone 1% QID plus ketorolac 
0.4% QID (ketorolac/steroid group; n = 268) for approximately four weeks
postoperatively. In the ketorolac/steroid group, patients also received topical
ketorolac 0.4% QID for three days preoperatively. In both groups, patients
received four doses of ketorolac 0.4% one hour before surgery. Patients with
capsular disruption or vitreous loss intraoperatively were exited from the study.
Outcome measures included CME incidence, retinal thickness as measured by optical
coherence tomography (OCT), best-corrected visual acuity, and contrast
sensitivity. RESULTS: No patients in the ketorolac/steroid group and five
patients in the steroid group had clinically apparent CME (P = .032). Based on
OCT, no ketorolac/steroid patient had definite or probable CME, compared with six
steroid patients (2.4%; P = .018). In the ketorolac/steroid group, mean retinal
thickening was less (3.9 microm vs 9.6 microm; P = .003), and fewer patients had 
retinal thickening of more than 10 microm as compared with the steroid group (26%
vs 51%; P < .001). CONCLUSIONS: This study suggests that adding perioperative
ketorolac to postoperative prednisolone significantly reduces the incidences of
CME and macular thickening in cataract surgery patients already at low risk for
this condition.

Publication Types: 
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18599019 [PubMed - indexed for MEDLINE]

194: Eye. 2008 Jun;22(6):855-9.

Plasma levels of matrix metalloproteinase-2 and -9 (MMP-2 and MMP-9) in
age-related macular degeneration.

Chau KY, Sivaprasad S, Patel N, Donaldson TA, Luthert PJ, Chong NV.

Institute of Ophthalmology, University College, London, UK.

BACKGROUND: Several studies indicate that age-related macular degeneration (AMD) 
and atherosclerosis may share common pathogenetic pathways. The aim of this study
was to determine the role of systemic matrix metalloproteinases (MMPs) in AMD,
given that MMPs are implicated in the pathogenesis of atherosclerosis. METHODS:
This study determined the plasma matrix metalloproteinases (MMP-2 and MMP-9)
levels in three groups of subjects: group 1 included subjects with age-related
maculopathy (ARM), group 2 included subjects with choroidal neovascularization
(CNV) owing to AMD and group 3 consisted of age-matched controls. RESULTS: The
mean plasma levels of MMP-2 were not significantly different in the three groups.
In contrast, the mean plasma MMP-9 levels were significantly higher in ARM and
CNV groups compared to that of the control group. However, there was no
significant difference in MMP-9 levels between ARM and CNV groups. CONCLUSION:
This is the first study that reveals a link between raised plasma MMP-9 levels
with AMD. Further studies are required to identify the factors that contribute to
this association.

PMID: 18597988 [PubMed - indexed for MEDLINE]

195: Am J Hum Genet. 2008 Jul;83(1):120-6.

Genotype-specific recurrence risks as indicators of the genetic architecture of
complex diseases.

Slatkin M.

Department of Integrative Biology, University of California, Berkeley, CA
94720-3140, USA. slatkin@berkeley.edu

A statistic is introduced that relates discoveries made in genome-wide
association (GWA) studies to patterns of disease risks among relatives. The
genotype-specific recurrence risk (GSR) is the genotype-specific risk to
relatives of known relationship to affected probands. The GSRs can be used for
three purposes. (1) They can provide an independent test of whether an allele
identified in a GWA study is associated with the disease. (2) They can provide a 
test of whether interactions among loci affecting the disease are multiplicative.
(3) They can be used by genetic counselors to incorporate information from GWA
studies for predicting the risk to relatives of known genotype. Under a
multiplicative model of disease causation, the GSRs for a locus are the genotypic
risks in probands for that locus multiplied by lambda(R)/lambda(jR), where
lambda(R) is Risch's recurrence risk ratio and lambda(jR) is the contribution to 
lambda(R) from the locus of interest. If there is saturation of risk with
increasing numbers of causative alleles, then observed GSRs for individuals with 
high-risk genotypes will be lower than predicted by the multiplicative model.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 18597734 [PubMed - indexed for MEDLINE]

196: PLoS ONE. 2008 Jul 2;3(7):e2593.

Systemic complement activation in age-related macular degeneration.

Scholl HP, Charbel Issa P, Walier M, Janzer S, Pollok-Kopp B, Börncke F, Fritsche
LG, Chong NV, Fimmers R, Wienker T, Holz FG, Weber BH, Oppermann M.

Department of Ophthalmology, University of Bonn, Bonn, Germany.

Dysregulation of the alternative pathway (AP) of complement cascade has been
implicated in the pathogenesis of age-related macular degeneration (AMD), the
leading cause of blindness in the elderly. To further test the hypothesis that
defective control of complement activation underlies AMD, parameters of
complement activation in blood plasma were determined together with
disease-associated genetic markers in AMD patients. Plasma concentrations of
activation products C3d, Ba, C3a, C5a, SC5b-9, substrate proteins C3, C4, factor 
B and regulators factor H and factor D were quantified in patients (n = 112) and 
controls (n = 67). Subjects were analyzed for single nucleotide polymorphisms in 
factor H (CFH), factor B-C2 (BF-C2) and complement C3 (C3) genes which were
previously found to be associated with AMD. All activation products, especially
markers of chronic complement activation Ba and C3d (p<0.001), were significantly
elevated in AMD patients compared to controls. Similar alterations were observed 
in factor D, but not in C3, C4 or factor H. Logistic regression analysis revealed
better discriminative accuracy of a model that is based only on complement
activation markers Ba, C3d and factor D compared to a model based on genetic
markers of the complement system within our study population. In both the
controls' and AMD patients' group, the protein markers of complement activation
were correlated with CFH haplotypes.This study is the first to show systemic
complement activation in AMD patients. This suggests that AMD is a systemic
disease with local disease manifestation at the ageing macula. Furthermore, the
data provide evidence for an association of systemic activation of the
alternative complement pathway with genetic variants of CFH that were previously 
linked to AMD susceptibility.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18596911 [PubMed - indexed for MEDLINE]

197: J AAPOS. 2008 Jun;12(3):309-11.

Combined intravitreal bevacizumab and triamcinolone injection in a child with
Coats disease.

Cakir M, Cekiç O, Yilmaz OF.

Beyoğlu Eye Training and Research Hospital, Istanbul, Turkey.
drmcakir@hotmail.com

We report a child with Coats disease who demonstrated a rapid response to
intravitreal bevacizumab and triamcinolone injection. A 14-year-old boy presented
with stage 3A Coats disease unresponsive to initial argon laser treatment and was
injected with intravitreal bevacizumab and triamcinolone acetonide. Following
intravitreal injection, a superior bullous exudative retinal detachment and
subfoveal serous fluid collection dramatically improved. Additional argon laser
photocoagulation resulted in complete regression of telangiectatic vessels as
well as decrease in macular exudation. Visual acuity improved from 20/400 to
20/125 after treatment, and the boy remained stable 6 months after injection.

Publication Types: 
    Case Reports

PMID: 18589387 [PubMed - indexed for MEDLINE]

198: Photomed Laser Surg. 2008 Jun;26(3):241-5.

Low-level laser therapy improves vision in patients with age-related macular
degeneration.

Ivandic BT, Ivandic T.

University of Heidelberg, Otto-Meyerhof Centre, Heidelberg.
boris.ivandic@med.uni-heidelberg.de

OBJECTIVE: The objective of this study of a case series was to examine the
effects of low-level laser therapy (LLLT) in patients with age-related macular
degeneration (AMD). BACKGROUND DATA: AMD affects a large proportion of the
elderly population; current therapeutic options for AMD are limited, however.
PATIENTS AND METHODS: In total, 203 patients (90 men and 113 women; mean age 63.4
+/- 5.3 y) with beginning ("dry") or advanced ("wet") forms of AMD (n = 348 eyes)
were included in the study. One hundred ninety-three patients (mean age 64.6 +/- 
4.3 y; n = 328 eyes) with cataracts (n = 182 eyes) or without cataracts (n = 146 
eyes) were treated using LLLT four times (twice per week). A semiconductor laser 
diode (780 nm, 7.5 mW, 292 Hz, continuous emission) was used for
transconjunctival irradiation of the macula for 40 sec (0.3 J/cm2) resulting in a
total dose of 1.2 J/cm2. Ten patients (n = 20 eyes) with AMD received mock
treatment and served as controls. Visual acuity was measured at each visit. Data 
were analyzed retrospectively using a t-test. RESULTS: LLLT significantly
improved visual acuity (p < 0.00001 versus baseline) in 162/182 (95%) of eyes
with cataracts and 142/146 (97%) of eyes without cataracts. The prevalence of
metamorphopsia, scotoma, and dyschromatopsia was reduced. In patients with wet
AMD, edema and bleeding improved. The improved vision was maintained for 3-36 mo 
after treatment. Visual acuity in the control group remained unchanged. No
adverse effects were observed in those undergoing therapy. CONCLUSION: In
patients with AMD, LLLT significantly improved visual acuity without adverse side
effects and may thus help to prevent loss of vision.

PMID: 18588438 [PubMed - indexed for MEDLINE]

199: Br J Ophthalmol. 2008 Aug;92(8):1081-5. Epub 2008 Jun 27.

Comparison of the optical coherence tomographic features of choroidal neovascular
membranes in pathological myopia versus age-related macular degeneration, using
quantitative subanalysis.

Keane PA, Liakopoulos S, Chang KT, Heussen FM, Ongchin SC, Walsh AC, Sadda SR.

Doheny Image Reading Center, Doheny Eye Institute, Keck School of Medicine of the
University of Southern California, 1450 San Pablo Street, DEI 3623, Los Angeles, 
CA 90033, USA.

AIM: To compare the retinal morphological characteristics of eyes with choroidal 
neovascularisation (CNV) secondary to pathological myopia versus eyes with CNV
secondary to age-related macular degeneration (AMD), using quantitative optical
coherence tomography (OCT) subanalysis. METHODS: Twenty-one eyes of 21 patients
newly diagnosed as having CNV secondary to pathological myopia, and 43
consecutive cases of eyes with newly diagnosed subfoveal CNV secondary to AMD
were retrospectively collected. In all patients, StratusOCT images and
fluorescein angiograms (FA) were available for analysis. StratusOCT images were
analysed using custom software (termed "OCTOR"), which allowed calculation of the
thickness/volume of the neurosensory retina, subretinal fluid (SRF), subretinal
tissue (SRT) and pigment epithelial detachments (PEDs). FA images were used to
calculate CNV leakage area and CNV lesion size for each eye. RESULTS: The total
volume of neurosensory retina in the pathological myopia group was significantly 
less than in the AMD group (7.10 (SD 0.50) mm3 vs 7.76 (0.93) mm3, p = 0.004).
The total volume of SRF in the pathological myopia group was less than in the AMD
group, but the difference was not statistically significant (0.33 (1.38) mm3 vs
0.55 (0.82) mm3, p = 0.434). The total volume of SRT in the pathological myopia
group was less than in the AMD group, but the difference was not statistically
significant (0.16 (0.15) mm3 vs 0.36 (0.60) mm3, p = 0.144). The total volume of 
PED in the pathological myopia group was markedly less than in the AMD group
(0.01 (0.03) mm3 vs 1.09 (1.89) mm3, p<0.001). On FA, the total leakage of CNV in
the AMD group was significantly greater than in the pathological myopia group
(4.17 (3.29) DAs vs 0.53 (0.58) DAs, p<0.001). CONCLUSIONS: CNV lesions in
pathological myopia were associated with considerably less retinal oedema, SRF
and SRT compared with CNV associated with AMD. PEDs were almost negligible in
myopic lesions compared with AMD. These findings are consistent with previous
clinical and angiographic descriptions of myopic CNV as relatively small lesions 
with modest exudation.

Publication Types: 
    Comparative Study
    Research Support, N.I.H., Extramural

PMID: 18586903 [PubMed - indexed for MEDLINE]

200: Br J Ophthalmol. 2008 Oct;92(10):1347-51. Epub 2008 Jun 27.

Reduced fluence versus standard photodynamic therapy in combination with
intravitreal triamcinolone: short-term results of a randomised study.

Sacu S, Varga A, Michels S, Weigert G, Polak K, Vécsei-Marlovits PV,
Schmidt-Erfurth U.

Medical University of Vienna, Department of Ophthalmology, Vienna, Austria.
stefan.sacu@meduniwien.ac.at

BACKGROUND: To compare early treatment effect of reduced fluence versus standard 
photodynamic therapy (rPDT, sPDT, respectively) in combination with intravitreal 
triamcinolone (IVTA) in neovascular age-related macular degeneration. METHODS:
Forty patients received either sPDT (group A, n = 20) or rPDT (group B, n = 20)
each followed by same-day 4 mg IVTA. Patients were examined at baseline, day 1,
week 1, 4 and 12. Main outcomes were visual acuity, central retinal thickness
(CRT), choroidal perfusion and macular sensitivity (MS). RESULTS: Baseline
characteristics were well balanced in both groups (p>0.05). At week 12, patients 
in group A had a mean loss of -3.7 letters compared with a gain of 3.4 letters in
group B (p = 0.04, between both groups). Both treatment groups showed a similar
course regarding CRT as well as MS (p>0.05). In 70% (14/20) of group A and 15%
(3/20) of group B, a choroidal hypoperfusion in the area of treatment was
observed after treatment (p<0.001). In 70% of group A and 55% of group B, a
repeat treatment was indicated at week 12 (p = 0.55). CONCLUSIONS: At month 3,
the rPDT+IVTA group showed a significantly better visual outcome, less alteration
of the choroid and a trend for lower recurrence rate than the sPDT+IVTA group.
Further follow-up of this study will provide information on long-term functional 
results and treatment durability.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial

PMID: 18586901 [PubMed - indexed for MEDLINE]

201: Diabetes Metab. 2008 Sep;34(4 Pt 1):389-91. Epub 2008 Jun 30.

Macular pattern dystrophy in MIDD: long-term follow-up.

Ambonville C, Meas T, Lecleire-Collet A, Laloi-Michelin M, Virally M, Kevorkian
JP, Paques M, Massin P, Guillausseau PJ.

Department of Internal Medicine B, hôpital Lariboisière, 2, rue Ambroise-Paré,
AP-HP, université Paris-7 Denis-Diderot, 75010 Paris, France.

A case of maternally inherited diabetes and deafness (MIDD)-associated macular
pattern dystrophy with a 15-year follow-up is reported. On initial examination at
age 37, visual acuity was normal, but chorioretinal atrophy at the posterior pole
was already present in both eyes. At age 52, visual acuity remained normal in the
right eye and was only slightly decreased in the left eye despite notable
extension of the areas of chorioretinal atrophy in that eye. No evidence of
diabetic retinopathy was present at any time. This case shows that visual acuity 
can remain stable in the long term despite extensive lesions of macular pattern
dystrophy.

Publication Types: 
    Case Reports

PMID: 18586543 [PubMed - indexed for MEDLINE]

202: Can J Clin Pharmacol. 2008 Winter;15(1):e22-35. Epub 2008 Jan 9.

The depletion of susceptibles effect in the assessment of burden-of-illness: the 
example of age-related macular degeneration in the community-dwelling elderly
population of Quebec.

Tournier M, Moride Y, Lesk M, Ducruet T, Rochon S.

Center for Clinical Epidemiology and Community Studies, SMBD Jewish General
Hospital, Montreal, Canada.

BACKGROUND: With the aging of the population, age-related macular degeneration
(AMD) is becoming a public health concern. Few studies have assessed its
consequences on morbidity and mortality, and the findings are conflicting.
OBJECTIVES: To assess the risk of depression, fracture, institutionalization, and
death among elderly patients with suspected exudative AMD and the impact of the
depletion of susceptibles effect in a burden-of-illness study. METHODS: A
population-based retrospective cohort study was conducted in the
community-dwelling elderly population of Quebec. The cohort was assembled through
the Quebec medical claims database (RAMQ). Among patients age 65 and older with a
claim involving a diagnosis of AMD over the years 2000 to 2004, those with
suspected exudative AMD (n=2,071) were retained, using fluorescein angiography as
a marker. The reference cohort consisted of a sample of 16,932 elderly without a 
claim involving AMD or visual impairment. RESULTS: Suspected exudative AMD was
associated with an increased risk of depression (hazard ratio HR=1.3, 95%CI
1.18-1.43) and fracture (HR=1.19, 95%CI 1.03-1.37), but a decreased risk of
institutionalization (HR=0.55, 95%CI 0.42-0.71) and death (HR=0.68, 95%CI
0.59-0.78). After adjustment for the incident/prevalent status of the AMD, the
association between suspected exudative AMD and institutionalization was no
longer statistically significant (HR=0.75, 95%CI 0.5-1.12). CONCLUSIONS: These
findings enhance the need to detect visual loss and to consider patients' ability
to adapt to AMD, to maintain their quality of life. Failure to account for
duration of illness and the depletion of susceptibles effect may bias results of 
burden-of-illness studies.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18579928 [PubMed - indexed for MEDLINE]

203: Br J Ophthalmol. 2008 Jul;92(7):976-80.

Immune cells in the human choroid.

Ezzat MK, Hann CR, Vuk-Pavlovic S, Pulido JS.

Department of Ophthalmology, Mayo Clinic Cancer Center, Mayo Clinic, Rochester,
MN 55905, USA.

AIM: To characterise the leucocytes in human macular choroid with and without
drusen, and in eyes with advanced age-related macular degeneration (AMD) with
fibrovascular scarring (FVS). METHODS: Ten eyes from nine donors (range 55-91
years of age) were obtained from an eye bank within 38 h post mortem. Fixed
macular biopsies were sectioned, stained immunochemically and examined for the
presence of leucocyte antigens CD45, CD4, CD8, CD14 and CD83. RESULTS: Four eyes 
without drusen, four eyes with drusen and two eyes with FVS contained 23.9 (SD
6.2)%, 27.5 (7.2)%, and 19.3 (11.3)% CD45-positive cells, respectively. The
corresponding percentages for CD4-positive cells were 5.4 (4.3), 8.9 (3.0) and
7.5 (8.1); for CD8-positive cells, 3.8 (0.7), 6.8 (2.2) and 6.3 (2.1); and for
CD14-positive cells, 3.7 (3.7), 3.6 (1.6) and 2.6 (3.6), respectively. The
authors found CD83-positive cells solely in one of the two FVS eyes examined that
had the more severe form of scarring. CONCLUSION: Human choroid contains similar 
amounts of CD4-positive cells and monocytes irrespective of the presence of
drusen, but CD8-positive cells are more abundant in macular choroid with drusen. 
The presence of haematopoietic cells in the macular choroid provides further
evidence for the possible participation of inflammatory cells in pathogenesis of 
AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18577650 [PubMed - indexed for MEDLINE]

204: Br J Ophthalmol. 2008 Jul;92(7):946-9.

Fundus autofluorescence in the diagnosis of cystoid macular oedema.

McBain VA, Forrester JV, Lois N.

Department of Ophthalmology, University of Aberdeen, Foresterhill, Aberdeen AB25 
2ZD, UK.

AIM: To determine the sensitivity and specificity of the non-invasive imaging
technique, fundus autofluorescence (AF), in the diagnosis of cystoid macular
oedema (CMO), using fluorescein angiography as the reference standard. DESIGN:
Retrospective, consecutive, observational case series. METHODS: Ninety-six
consecutive patients with CMO suspected clinically were selected from the AF
database of the Retina Unit, Ophthalmology Department, Grampian University
Hospitals-NHS Trust, between August 2004 and June 2006. Only patients in whom CMO
was secondary to (1) cataract extraction, (2) inherited retinopathies, (3)
inflammatory eye disease or (4) idiopathic cases were included in this study.
Only patients in whom AF images had been performed within 2 weeks of FFA and,
when obtained following FFA, there was a minimum gap of 4 days ("washing out"
period), were considered eligible for this study. A total of 34 eyes from 34
patients were eligible and were included in this study. FFA was used as the
reference test to confirm the presence of CMO, and, based on fluorescein
angiography (FFA), CMO was graded as either mild or florid. AF images were
examined in a masked fashion for the presence or absence of CMO. The sensitivity 
and specificity of AF in detecting CMO were then calculated. RESULTS: CMO was
seen on AF imaging as round or oval areas at the fovea with an AF signal similar 
to that of background levels. At this site (fovea), the AF signal is usually
reduced compared with background, due to the blockage caused by luteal pigment.
The diagnosis of CMO based on AF imaging had 81% sensitivity and 69% specificity 
when compared with the reference standard FFA. Based on the FFA, there were 12
cases of florid CMO and eight of mild CMO. Of the former, CMO was detected with
AF imaging in 100% (12/12 eyes), and of the latter, in 50% (4/8 eyes).
CONCLUSIONS: AF imaging can be used as a rapid, non-invasive technique in the
diagnosis of CMO.

Publication Types: 
    Evaluation Studies

PMID: 18577647 [PubMed - indexed for MEDLINE]

205: Br J Ophthalmol. 2008 Jul;92(7):933-5.

Optical coherence tomography: limits of the retinal-mapping program in
age-related macular degeneration.

Krebs I, Haas P, Zeiler F, Binder S.

Department of Ophthalmology, Rudolf Foundation Clinic, Juchgasse 25, 1030 Vienna,
Austria. Ilse.Krebs@wienkav.at

AIM: The retinal-mapping program of Stratus optical coherence tomography (Carl
Zeiss Meditec, Dublin, CA, USA) calculates the retinal volume of the central
region between the retinal surface and the retinal pigment epithelium (RPE). This
study evaluates the retinal-mapping program for studies dealing with AMD.
METHODS: The scans of both eyes of patients examined from August to October 2006 
because of macular degeneration were evaluated retrospectively. Independent
examiners tested whether the two lines indicating the retinal surface and the RPE
were positioned correctly by the threshold algorithm that corresponded with
correct measurements. RESULTS: The scans of 233 eyes of 117 patients were
evaluated (39.3% were men and 60.7% women, with a mean age of 76.9 years).
Overall, in 57.1% both lines were positioned correctly. False-positioned lines
were recorded in 9.0% due to low scan quality and in 33.9% due to a doubled or
interrupted hyper-reflective band of the RPE. Threshold algorithm
misinterpretation was significantly more frequent in occult lesions with and
without fibrosis than in non-exudative lesions, and were significantly correlated
to distance acuity (p<0.0001). CONCLUSION: The retinal-mapping program for
examination of AMD provided correct results in only 57.1% of eyes. A manual
correction of false-positioned lines would be needed to improve accuracy.

PMID: 18577644 [PubMed - indexed for MEDLINE]

206: Br J Ophthalmol. 2008 Jul;92(7):922-7.

Uveitic macular oedema: correlation between optical coherence tomography patterns
with visual acuity and fluorescein angiography.

Tran TH, de Smet MD, Bodaghi B, Fardeau C, Cassoux N, Lehoang P.

Department of Ophthalmology, Groupe Hospitalier Pitié Salpêtrière, Paris, France.
tranhachau@hotmail.com

AIMS: (1) To associate optical coherence tomography (OCT) patterns with
particular fluorescein angiography (FA) findings in uveitis patients with macular
oedema. (2) To investigate the correlation between tomographic features and
visual acuity (VA). (3) To determine the impact of OCT patterns on visual
improvement over time. METHODS: 129 eyes of 90 patients followed for uveitis with
macular oedema and adequate media clarity were consecutively included from
February to November 2004. We examined the relationship between VA, the
fluorescein angiograms grading and central thickness. RESULTS: Mean retinal
thickness at the central fovea was 357 (SD 128) microm. The mean VA was 0.5
(logMAR). There was agreement between OCT and FA in 112 eyes (86.8%). In eight
eyes (6.2%), serous retinal detachment (SRD) was detected on OCT but not on FA.
Nine eyes (7%) had perifoveal leakage on FA without macular thickening on OCT.
There were three patterns of macular oedema on OCT: diffuse macular oedema (DMO),
cystoid macular oedema (CMO) and SRD. CMO was detected in 61 eyes (50.8%), and in
18 of these eyes (15%), CMO was associated with SRD. DMO was detected in 45 eyes 
(37.5%), and in eight (6.7%) of these eyes, DMO was associated with SRD. SRD
without retinal thickening was present in 14 eyes (11%). Epiretinal membrane was 
detected by OCT in 27 eyes (21%). Six eyes demonstrated vitreomacular traction
(4.7%). There was a correlation between VA and central thickness on OCT (r =
0.407, p = 0.000001). Correlation between VA and central thickness is significant
in the group with CMO (r = 0.401, p = 0.001) but not significant in the group
with DMO. Furthermore, vision recovery was observed in patients with CMO but was 
limited in patients with DMO. SRD did not have a significant impact on visual
recovery, but its presence reduced the correlation between vision and central
thickness. CONCLUSION: OCT is effective in detection of macular oedema. It allows
determination of the distribution of fluid and quantification of retinal
thickness particularly in patients with CMO. In these patients, a potential for
vision recovery was also identified. DMO was associated with a poor visual
prognosis and a poor prognosis for vision recovery. SRD is associated with a high
probability of vision recovery when observed alone or underlying CMO eyes. It
should be substracted from the central thickness measurement when attempting to
correlate central thickness with vision in patients with macular oedema in
uveitis.

Publication Types: 
    Comparative Study

PMID: 18577643 [PubMed - indexed for MEDLINE]

207: BMC Med Res Methodol. 2008 Jun 25;8:40.

Integrated analysis of incidence, progression, regression and disappearance
probabilities.

Huang GH.

Institute of Statistics, National Chiao Tung University, Hsinchu, Taiwan.
ghuang@stat.nctu.edu.tw

BACKGROUND: Age-related maculopathy (ARM) is a leading cause of vision loss in
people aged 65 or older. ARM is distinctive in that it is a disease which can
transition through incidence, progression, regression and disappearance. The
purpose of this study is to develop methodologies for studying the relationship
of risk factors with different transition probabilities. METHODS: Our framework
for studying this relationship includes two different analytical approaches. In
the first approach, one can define, model and estimate the relationship between
each transition probability and risk factors separately. This approach is similar
to constraining a population to a certain disease status at the baseline, and
then analyzing the probability of the constrained population to develop a
different status. While this approach is intuitive, one risks losing available
information while at the same time running into the problem of insufficient
sample size. The second approach specifies a transition model for analyzing such 
a disease. This model provides the conditional probability of a current disease
status based upon a previous status, and can therefore jointly analyze all
transition probabilities. Throughout the paper, an analysis to determine the
birth cohort effect on ARM is used as an illustration. RESULTS AND CONCLUSION:
This study has found parallel separate and joint analyses to be more enlightening
than any analysis in isolation. By implementing both approaches, one can obtain
more reliable and more efficient results.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18577235 [PubMed - indexed for MEDLINE]

208: Am J Health Syst Pharm. 2008 Jul 1;65(13):1232-8.

Lutein and zeaxanthin for macular degeneration.

Zhao L, Sweet BV.

University of Michigan College of Pharmacy (UMCP), Ann Arbor, Michigan, USA.

PURPOSE: The effects of increasing lutein and zeaxanthin dosages in people with
age-related macular degeneration (AMD) are discussed. SUMMARY: AMD is a disorder 
of the macula, the area associated with the sharpest visual acuity. AMD is
classified as dry (nonneovascular) or wet (neovascular) and is associated with
several risk factors, the biggest being age. The pathogenesis of AMD is unknown. 
Like many chronic illnesses, prevention is a key factor for managing AMD. Lutein 
and zeaxanthin, natural xanthophylls not synthesized by the human body, have been
investigated for their use in promoting visual health. Lutein and zeaxanthin are 
dietary carotenoids that are components of a normal diet. The mechanism of
protection that they confer is unknown, but two mechanisms have been
hypothesized. Several studies have been conducted to assess the relationship
between plasma levels of lutein and zeaxanthin and the risk of developing AMD and
have yielded conflicting results. Increased dietary intake of or supplementation 
with lutein and zeaxanthin was found to result in increased plasma levels, which 
were positively and significantly associated with macular pigment optical
density. Limited data have suggested that supplementation may also improve visual
function. The optimal dose of lutein and zeaxanthin for the prevention or
treatment of AMD has not yet been defined. CONCLUSION: A definite association
between lutein and zeaxanthin supplementation and clinical benefit has yet to be 
shown; however, it may still be an appropriate cautionary measure for patients at
high risk for developing AMD.

PMID: 18574012 [PubMed - indexed for MEDLINE]

209: Surv Ophthalmol. 2008 Jul-Aug;53(4):359-67.

Cataract surgery and the development or progression of age-related macular
degeneration: a systematic review.

Bockelbrink A, Roll S, Ruether K, Rasch A, Greiner W, Willich SN.

Institute for Social Medicine, Epidemiology, and Health Economics,
Charité-University Medical Center, Berlin, Germany.
angelina.bockelbrink@charite.de

Age-related macular degeneration and cataract are the most frequent eye disorders
of elderly people worldwide. The aim of this systematic review was to evaluate
the effect of cataract surgery on the development and progression of age-related 
macular degeneration. Data were collected by means of a systematic literature
search in 28 databases and an additional update in Pubmed. Search results were
evaluated using pre-defined inclusion and exclusion criteria. All relevant
publications were rated in terms of scientific quality and analyzed regarding
their results. The literature search generated a total of 2,827 hits. Seven
publications on five observational studies and two non-randomized clinical trials
were eligible for analysis. The observational studies provided some evidence for 
an increased incidence of late age-related macular degeneration, respectively,
for a promoting influence of cataract surgery on the progression of early types
of age-related macular degeneration. The clinical trials did yield inconsistent
results. In conclusion, only a small number of published studies investigated the
development or progression of age-related macular degeneration following cataract
surgery. The scientific level of evidence of these articles was not high and
results were inconsistent, nevertheless a promoting influence of cataract surgery
on the progression of early age-related macular degeneration can be assumed.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18572053 [PubMed - indexed for MEDLINE]

210: J Cataract Refract Surg. 2008 Jul;34(7):1210-2.

Successful treatment of pseudophakic cystoid macular edema with intravitreal
bevacizumab.

Barone A, Prascina F, Russo V, Iaculli C, Primavera V, Querques G, Stella A,
Delle Noci N.

Department of Ophthalmology, Policlinico di Foggia, University di Foggia, Foggia,
Italy. antbarone@infinito.it

A 67-year-old woman developed refractory pseudophakic cystoid macular edema (CME)
after uneventful phacoemulsification. Three months after an intravitreal
injection of bevacizumab (1.25 mg), the CME was completely resolved, with
resultant improvement in visual acuity.

Publication Types: 
    Case Reports

PMID: 18571091 [PubMed - indexed for MEDLINE]

211: Ophthalmic Epidemiol. 2008 May-Jun;15(3):202-8.

Charles Bonnet syndrome in age-related macular degeneration: the nature and
frequency of images in subjects with end-stage disease.

Khan JC, Shahid H, Thurlby DA, Yates JR, Moore AT.

Department of Medical Genetics, University of Cambridge, Cambridge, United
Kingdom. jckhan@gmail.com

INTRODUCTION: The term Charles Bonnet syndrome (CBS) is used to describe visual
hallucinations resulting from ocular pathology. As part of a larger case-control 
study we assessed factors which may predispose to this phenomenon in Age-related 
macular degeneration (AMD). METHODS: Three-hundred and sixty cases of late AMD
underwent a detailed questionnaire about visual symptoms experienced. Potential
ocular and environmental risk factors were compared in two groups; those
experiencing symptoms of CBS (n = 97) and those not experiencing CBS symptoms (n 
= 263). RESULTS: Twenty-seven percent experienced CBS. Poor visual acuity was the
only factor associated with the development of these images in AMD with an odds
ratio of 3.50 (95% CI 1.64-7.48, p = 0.001) for those with best binocular visual 
acuity worse than 6/36. In those who experienced CBS, the images tended to be
straight ahead (84.5%), colored (72.2%), have moving parts (62.9%), and occur on 
average once per day (34%). The most common visual image was of people (19.6%)
followed by geometric patterns (15.8%). The majority (71.1%) felt the experience 
to be neither pleasant nor unpleasant. In 41% images were present throughout the 
course of their disease. There was no association between visual acuity and
complexity of images. CONCLUSION: The prevalence of CBS in late AMD is high, the 
main risk factor being poor better eye visual acuity. The most commonly
experienced hallucinations were of people. Although most patients were
unperturbed by the images, reassurance of their benign nature was welcomed.
Practitioners should be aware that resolution of symptoms over time does not
always occur.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18569816 [PubMed - indexed for MEDLINE]

212: Ophthalmic Epidemiol. 2008 May-Jun;15(3):191-201.

Reproducibility of gradings of retinal photographs in eyes with subfoveal
choroidal neovascularization and age-related macular degeneration in the macular 
photocoagulation study.

Jefferys JL, Alexander J, Hiner CJ, Javornik NB, Smith RE, Bressler NM, Hawkins
BS.

The Wilmer Eye Institute, The Johns Hopkins University School of Medicine,
Baltimore, Maryland, USA. jjeffrey@jhmi.edu

PURPOSE: To assess the reproducibility of the evaluation of color photographs and
fluorescein angiograms of the macula of each eye for patients enrolled in the
Macular Photocoagulation Study (MPS) trials of laser photocoagulation of
subfoveal choroidal neovascularization (CNV) secondary to age-related macular
degeneration. METHODS: A total of 65 pre-enrollment and 26 posttreatment sets of 
photographs were regraded. The two gradings were compared on selected items
judged to be of primary importance with respect to the role of the MPS Reading
Center. RESULTS: Agreement on eligibility of the neovascular lesion for an MPS
trial was 88% (kappa statistic = 0.59); agreement on the size of the lesion was
86% (kappa statistic = 0.80); agreement on whether the lesion was covered by
heavy treatment was 69% (kappa statistic = 0.35); and agreement on whether the
treatment was in compliance with the study protocol was 73% (kappa statistic =
0.06). CONCLUSIONS: Interpretation of photographs of eyes with CNV secondary to
age-related macular degeneration for eligibility and size of the lesion was
reproducible in the MPS. However, adequacy of laser photocoagulation treatment
could not be determined reliably from photographs.

Publication Types: 
    Evaluation Studies
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18569815 [PubMed - indexed for MEDLINE]

213: Ophthalmic Epidemiol. 2008 May-Jun;15(3):148-54.

LOC387715, smoking and their prognostic impact on visual functional status in
age-related macular degeneration-The Muenster Aging and Retina Study (MARS)
cohort.

Neuner B, Wellmann J, Dasch B, Dietzel M, Farwick A, Stoll M, Pauleikhoff D,
Hense HW.

Institute of Epidemiology and Social Medicine, Clinical Epidemiology Section,
University of Muenster, Muenster, Germany. neuner@uni-muenster.de

PURPOSE: To prospectively evaluate the impact of homozygosity in the A69S-SNP of 
the LOC387715-gene, smoking history, and their interaction on visual functional
status (v-FS) in age-related macular degeneration (AMD). METHODS: The Muenster
Aging and Retina Study (MARS) cohort (n = 656; 58.8% women, mean age 70.2 years) 
was followed over a mean of 2.5 years. AMD-status, genotype and smoking history
were assessed at baseline. V-FS [from 0 (low) to 100 (unimpaired) points in
general-, near- and far-vision], were AMD-status assessed at baseline and at
follow-up. Linear models with stepwise adjustments for covariates were used to
analyze decline of v-FS over time. RESULTS: In initial models, homozygosity for
the A69S-variant was negatively associated with all three dimensions of the v-FS.
After including smoking history, ever smoking was negatively associated with
declines in near and far vision (-4.82 and -5.12 points, respectively; each p <
0.05). In smokers homozygous for the A69S-variant the number of cigarettes smoked
per day (smoking intensity) was negatively associated with all three dimensions
of the v-FS (interaction term each p < 0.05). Time since smoking cessation in
former smokers protected against declines in near and far vision. These effects
were independent of the AMD-status at baseline. CONCLUSIONS: The interaction of
homozygosity for the A69S-variant and smoking intensity had a negative impact on 
general-, near-, and far visual functional status independent of AMD-status.
Quitting smoking seemed to have a time-dependent protective effect on near and
far vision.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18569809 [PubMed - indexed for MEDLINE]

214: Invest Ophthalmol Vis Sci. 2008 Nov;49(11):5048-54. Epub 2008 Jun 19.

Quantitative optical coherence tomography findings in various subtypes of
neovascular age-related macular degeneration.

Liakopoulos S, Ongchin S, Bansal A, Msutta S, Walsh AC, Updike PG, Sadda SR.

Doheny Image Reading Center, Doheny Eye Institute, Keck School of Medicine,
University of Southern California, Los Angeles, California 90033, USA.

PURPOSE: To compare the volume of various spaces visible on optical coherence
tomography (OCT) images in different angiographic lesion subtypes of neovascular 
age-related macular degeneration (AMD). METHODS: Sixty-six cases of previously
untreated, active subfoveal choroidal neovascularization (CNV) associated with
AMD were retrospectively collected. CNV lesions were classified as occult with no
classic CNV, minimally classic CNV, predominantly classic CNV, or CNV lesions
with associated retinal angiomatous proliferation (RAP). Corresponding OCT image 
sets were analyzed by trained graders using previously validated custom software 
that allows manual placement of boundaries on OCT B-scans. Spaces delineated by
these boundaries included the neurosensory retina, subretinal fluid, subretinal
tissue, and pigment epithelial detachments (PEDs). Volume measurements were
calculated by the software and compared among groups. RESULTS: Minimally and
predominantly classic CNV membranes demonstrated subretinal tissue on OCT in all 
cases and appeared to show a significantly greater volume of subretinal tissue
than did the occult membranes. Subretinal fluid was present in all the
predominantly classic cases. A PED was visible in all the occult CNV cases in our
study, demonstrating less retinal thickening and significantly greater PED
volumes than minimally and predominantly classic CNV lesions. Lesions associated 
with RAP showed the highest percentage of cystoid spaces. CONCLUSIONS: OCT and
angiography provide complementary information regarding CNV lesions. Quantitative
analysis of OCT images allows for an improved understanding of the anatomic
characteristics of angiographically defined CNV lesion subtypes.

Publication Types: 
    Comparative Study
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18566473 [PubMed - indexed for MEDLINE]

215: Invest Ophthalmol Vis Sci. 2009 Jan;50(1):101-6. Epub 2008 Jun 19.

Prospective study of incident age-related macular degeneration in relation to
vigorous physical activity during a 7-year follow-up.

Williams PT.

Donner Laboratory, Life Sciences Division, Ernest Orlando Lawrence Berkeley
National Laboratory, Berkeley, California 94720, USA. ptwilliams@lbl.gov

PURPOSE: To test whether the risk of age-related macular degeneration (AMD)
decreases with vigorous physical activity. METHODS: This was a prospective study 
of self-reported clinically diagnosed macular degeneration in male (n = 29,532)
and female (n = 12,176) runners followed prospectively for 7.7 years. Survival
analyses of incident AMD versus average running distance (kilometers per day),
cardiorespiratory fitness (10-km footrace performance), body mass index (BMI),
cigarette use, and diet at baseline. RESULTS: The 110 men and 42 women reporting 
incident AMD were older than those unaffected (mean +/- SE: 54.81 +/- 0.97 vs.
44.86 +/- 0.06 years), and the men were significantly more likely to have once
smoked cigarettes (50.6 vs. 41.2%, P = 0.04 when adjusted for age). Age- and
sex-adjusted AMD risk was greater in the men and women who consumed more meat
(3.17 +/- 0.20 vs. 2.55 +/- 0.02 servings/wk) and less fruit (9.41 +/- 0.70 vs.
10.92 +/- 0.05 pieces/wk). The men and women reporting incident AMD ran for
exercise significantly less than those who remained unaffected, when adjustment
was made for age and sex (4.57 +/- 0.30 vs. 5.34 +/- 0.02 km/d, P < or = 0.01).
When adjusted for age, sex, diet, and smoking history, the relative risk for AMD 
decreased 10% per km/d increment in running distance. Moreover, compared with the
men and women who averaged less than 2 km/d, those averaging 2 to 4 km/d had 19% 
lower adjusted risk, and those averaging > or = 4 km/d had 42% to 54% lower
adjusted AMD risk. CONCLUSIONS: Higher doses of vigorous exercise (running) are
associated with lower incident AMD risk independent of weight, cardiorespiratory 
fitness, and cigarette use. Limitations of the analyses include the select nature
of the sample and reliance on self-report of both running history and clinically 
diagnosed AMD.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, U.S. Gov't, Non-P.H.S.

PMID: 18566466 [PubMed - indexed for MEDLINE]

216: Invest Ophthalmol Vis Sci. 2009 Feb;50(2):560-6. Epub 2008 Jun 19.

Comparison of optical coherence tomography in diabetic macular edema, with and
without reading center manual grading from a clinical trials perspective.

Glassman AR, Beck RW, Browning DJ, Danis RP, Kollman C; Diabetic Retinopathy
Clinical Research Network Study Group.

Jaeb Center for Health Research, Tampa, Florida 33647, USA. drcrnetx3@jaeb.org

PURPOSE: To analyze the value of reading center error correction in automated
optical coherence tomography (OCT; Stratus; Carl Zeiss Meditec, Inc., Dublin, CA)
retinal thickness measurements in eyes with diabetic macular edema (DME).
METHODS: OCT scans (n=6522) obtained in seven Diabetic Retinopathy Clinical
Research Network (DRCR.net) studies were analyzed. The reading center evaluated
whether the automated center point measurement appeared correct, and when it did 
not, measured it manually with calipers. Center point standard deviation (SD) as 
a percentage of thickness, center point thickness, signal strength, and analysis 
confidence were evaluated for their association with an automated measurement
error (manual measurement needed and exceeded 12% of automated thickness). Curves
were constructed for each factor by plotting the error rate against the
proportion of scans sent to the reading center. The impact of measurement error
on interpretation of clinical trial results and statistical power was also
assessed. RESULTS: SD was the best predictor of an automated measurement error.
The other three variables did not augment the ability to predict an error using
SD alone. Based on SD, an error rate of 5% or less could be achieved by sending
only 33% of scans to the reading center (those with an SD >or= 5%). Correcting
automated errors had no appreciable effect on the interpretation of results from 
a completed randomized trial and had little impact on a trial's statistical
power. CONCLUSIONS: In DME clinical trials, the error involved with using
automated Stratus OCT center point measurements is sufficiently small that
results are not likely to be affected if scans are not routinely sent to a
reading center, provided adequate quality control measures are in place.

Publication Types: 
    Comparative Study
    Research Support, N.I.H., Extramural

PMID: 18566462 [PubMed - indexed for MEDLINE]

217: Invest Ophthalmol Vis Sci. 2008 Oct;49(10):4347-52. Epub 2008 Jun 19.

Intersession repeatability of visual acuity scores in age-related macular
degeneration.

Patel PJ, Chen FK, Rubin GS, Tufail A.

Moorfields Eye Hospital, London, United Kingdom.

PURPOSE: To describe the intersession repeatability of visual acuity measures
obtained with Early Treatment of Diabetic Retinopathy Study (ETDRS) charts in
patients with age-related macular degeneration. METHODS: Visual acuity was
measured in four sessions over 12 weeks using a standardized protocol with ETDRS 
charts in 107 nontreated eyes of 107 patients with age-related macular
degeneration enrolled in an ongoing clinical trial. RESULTS: Data from 90
patients were included in the analysis. The 95% coefficient of repeatability (CR)
was 12 ETDRS letters and ranged from 9 letters for 29 eyes with small to
intermediate drusen only to 17 letters for 25 eyes with late AMD (macular scars
or geographic atrophy). Ten (11%) eyes had a 5-letter reduction or more in visual
acuity at the week 1 visit compared with baseline. Excluding seven eyes with
visual acuity measurements potentially affected by measurement-related factors (a
change in testing distance between visits) the revised CR was 10 letters for the 
cohort (n = 83) and 11 letters for the late-AMD subgroup (n = 18). CONCLUSIONS:
Intersession ETDRS visual acuity measurements are subject to considerable
variability in patients with AMD. The variability may be due to both measurement-
and disease-related factors. The variable readings have implications for AMD
clinical trial design and for the assessment and treatment of patients with
neovascular AMD. Further work is needed to determine both the sources of
variability in visual acuity measurements and the optimal change criterion for
visual acuity measurements in this important group of patients.

Publication Types: 
    Randomized Controlled Trial

PMID: 18566455 [PubMed - indexed for MEDLINE]

218: J Immunol. 2008 Jul 1;181(1):712-20.

Altered function of factor I caused by amyloid beta: implication for pathogenesis
of age-related macular degeneration from Drusen.

Wang J, Ohno-Matsui K, Yoshida T, Kojima A, Shimada N, Nakahama K, Safranova O,
Iwata N, Saido TC, Mochizuki M, Morita I.

Department of Ophthalmology and Visual Science, Tokyo Medical and Dental
University, Tokyo, Japan.

The results of recent studies have implicated local inflammation and complement
activation as the processes involved in the pathogenesis of age-related macular
degeneration (AMD). We have demonstrated that amyloid beta (Abeta), which is
deposited in drusen, causes an imbalance in the angiogenesis-related factors in
retinal pigment epithelial cells. We have also shown that neprilysin
gene-disrupted mice accumulate Abeta, and develop several features of AMD. The
purpose of this study was to investigate the mechanisms involved in the
development of AMD that are triggered by Abeta. Our results showed that Abeta
binds to complement factor I which inhibits the ability of factor I to cleave C3b
to inactivated iC3b. Factor H and factor I are soluble complement-activation
inhibitors, and preincubation of factor I with Abeta in the presence of factor H 
abolished the ability of Abeta to cleave C3b, and also abolished the ability of
factor I to cleave FGR-AMC. In contrast, Abeta did not affect the function of
factor H even after binding. The production of iC3b was significantly decreased
when C3b and factor H were incubated with the eyes from neprilysin gene-disrupted
mice as compared with when C3b and factor H were incubated with eyes from
age-matched wild-type mice. These results suggest that Abeta activates the
complement system within drusen by blocking the function of factor I leading to a
low-grade, chronic inflammation in subretinal tissues. These findings link four
factors that have been suggested to be associated with AMD: inflammation,
complement activation, Abeta deposition, and drusen.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18566438 [PubMed - indexed for MEDLINE]

219: Ann Ophthalmol (Skokie). 2008 Spring;40(1):28-30.

Anecortave acetate for fibrotic lesions with presence of residual peripheral
activity in age-related macular degeneration.

Aggermann T, Haas P, Binder S.

Ludwig Boltzmann Institute for Retinology and Biomicroscopic Laser Surgery,
Vienna, Austria. tina@aggermann.at

We retrospectively examined the efficacy of a single juxtascleral anecortave
acetate depot injection for the treatment of fibrotic choroidal neovascular
lesions with presence of residual peripheral activity in age related macular
degeneration in 20 consecutive patients who rejected intravitreal treatment. As a
second line-therapy of classic and occult fibrotic lesions with active peripheral
zones, anecortave seems to be a vision conserving therapeutic option.

PMID: 18556978 [PubMed - indexed for MEDLINE]

220: Br J Ophthalmol. 2008 Aug;92(8):1046-50. Epub 2008 Jun 12.

Intravitreal triamcinolone acetonide combined with subthreshold grid laser
treatment for macular oedema in branch retinal vein occlusion: a pilot study.

Parodi MB, Iacono P, Ravalico G.

Eye Clinic, Azienda Ospedaliero-Universitaria di Trieste, Ospedale Maggiore,
Piazza Ospedale 1, Trieste, Italy. maubp@yahoo.it

BACKGROUND: To compare the effectiveness of subthreshold grid laser treatment
(SGLT) with infrared micropulse diode laser alone or in combination with
intravitreal triamcinolone injection (SGLT-IVTJ) for the treatment of macular
oedema (MO) secondary to branch retinal vein occlusion (BRVO). METHODS: Pilot
randomised clinical trial including 24 patients (24 eyes) who were randomised
either to the SGLT (13 eyes) or to SGLT-IVTJ (11 eyes). Complete ophthalmic
examinations, including Early Treatment of Diabetic Retinopathy Study visual
acuity, OCT and fluorescein angiography, were performed at the moment of the
study entry and at 3-month intervals, with a planned follow-up of 12 months. Main
outcome measures were the decrease in mean foveal thickness (MFT) on OCT, and the
proportion of eyes that gained at least 10 letters (approximately two or more
lines of visual acuity gain) at the 12-month examination. Secondary outcomes were
the decrease in mean total macular volume on OCT, and the timing of MO
resolution. RESULTS: The change in MFT from the initial values was statistically 
significant for the SGLT-IVTJ from the 3-month examination and for the SGLP from 
the 6-month examination (p<0.001). At the 12-month evaluation, 10 patients of the
SGLT-IVTJ group (91%) and eight of the SGLT group (62%) gained at least 10
letters (two lines) in visual acuity. The mean number of lines gained was 3.4 and
1.3 in the SGLT-IVTJ and in the SGLT group, respectively. CONCLUSIONS: The
combined SGLT-IVT treatment of MO secondary to BRVO allows a significant visual
acuity improvement, when compared with simple grid laser treatment.

Publication Types: 
    Randomized Controlled Trial

PMID: 18556425 [PubMed - indexed for MEDLINE]

221: Invest Ophthalmol Vis Sci. 2008 Oct;49(10):4568-72. Epub 2008 Jun 14.

Visual acuity is related to parafoveal retinal thickness in patients with
retinitis pigmentosa and macular cysts.

Sandberg MA, Brockhurst RJ, Gaudio AR, Berson EL.

The Berman-Gund Laboratory, Study of Retinal Degenerations, Harvard Medical
School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts 02114, USA.
masandberg@aol.com

PURPOSE: To quantify the prevalence and effect on visual acuity of macular cysts 
in a large cohort of patients with retinitis pigmentosa. METHODS: In 316 patients
with typical forms of retinitis pigmentosa, visual acuity was measured with Early
Treatment Diabetic Retinopathy Study (ETDRS) charts, macular cysts were detected 
with optical coherence tomography (OCT), and retinal thicknesses was quantified
by OCT. The FREQ, LOGISTIC, and GENMOD procedures of SAS (SAS Institute, Cary,
NC) were used to evaluate possible risk factors for cyst prevalence, and the
MIXED procedure was used to quantify the relationships of visual acuity to
retinal thickness measured at different locations within the macula. RESULTS:
Macular cysts were found in 28% of the patients, 40% of whom had cysts in only
one eye. Macular cysts were seen most often in patients with dominant disease and
not at all in patients with X-linked disease (P = 0.006). In eyes with macular
cysts, multiple regression analysis revealed that visual acuity was inversely and
independently related to retinal thickness at the foveal center (P = 0.038) and
within a parafoveal ring spanning an eccentricity of 5 degrees to 10 degrees from
the foveal center (P = 0.004). CONCLUSIONS: Macular cysts are a common occurrence
in retinitis pigmentosa, especially among patients with dominantly inherited
disease. Visual acuity is influenced by edema in the parafovea, as well as in the
fovea.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18552390 [PubMed - indexed for MEDLINE]

222: Am J Ophthalmol. 2008 Sep;146(3):447-454. Epub 2008 Jun 11.

The MacDQoL individualized measure of the impact of macular degeneration on
quality of life: reliability and responsiveness.

Mitchell J, Wolffsohn J, Woodcock A, Anderson SJ, Ffytche T, Rubinstein M, Amoaku
W, Bradley C.

Department of Psychology, Royal Holloway, University of London, Egham, Surrey,
United Kingdom. j.mitchell@rhul.ac.uk

PURPOSE: To investigate the MacDQoL test-retest reliability and sensitivity to
change in vision over a period of one year in a sample of patients with
age-related macular degeneration (AMD). DESIGN: A prospective, observational
study. METHOD: Patients with AMD from an ophthalmologist's list (n = 135)
completed the MacDQoL questionnaire by telephone interview and underwent a vision
assessment on two occasions, one year apart. RESULTS: Among participants whose
vision was stable over one year (n = 87), MacDQoL scores at baseline and
follow-up were highly correlated (r = 0.95; P < .0001). Twelve of the 22 scale
items had intraclass correlations of >.80; only two were correlated <.7. There
was no difference between baseline and follow-up scores (P = .85), indicating
excellent test-retest reliability. Poorer quality of life (QoL) at follow-up,
measured by the MacDQoL present QoL overview item, was associated with
deterioration in both the better eye and binocular distance visual acuity [VA] (r
= 0.29; P = .001, r = 0.21; P = .016, respectively; n = 135). There was a
positive correlation between deterioration in the MacDQoL average weighted impact
score and deterioration in both binocular near VA and reading speed (r = 0.20; P 
= .019, r = 0.18; P = .041, respectively; n = 135). CONCLUSION: The MacDQoL has
excellent test-retest reliability. Its sensitivity to change in vision status was
demonstrated in correlational analyses. The measure indicates that the negative
impact of AMD on QoL increases with increasing severity of visual impairment.

PMID: 18547542 [PubMed - indexed for MEDLINE]

223: Am J Ophthalmol. 2008 Aug;146(2):172-182. Epub 2008 Jun 10.

Comment in:
    Am J Ophthalmol. 2008 Aug;146(2):151-3.

Vision improvement in retinal degeneration patients by implantation of retina
together with retinal pigment epithelium.

Radtke ND, Aramant RB, Petry HM, Green PT, Pidwell DJ, Seiler MJ.

Retina Vitreous Resource Center, University of Louisville, Louisville, Kentucky, 
USA. nradtke@rvrc.com

PURPOSE: To demonstrate efficacy and safety of the implantation of neural retinal
progenitor cell layers (sheets) with its retinal pigment epithelium (RPE) in
retinitis pigmentosa (RP) and dry age-related macular degeneration (AMD) patients
with 20/200 or worse vision in the surgery eye. DESIGN: Interventional
nonrandomized clinical trial. METHODS: Ten patients (six RP, four AMD) received
retinal implants in one eye and were followed in a phase II trial conducted in a 
clinical practice setting. Early Treatment Diabetic Retinopathy Study (EDTRS) was
the primary outcome measure. All implant recipients and nine of 10 tissue donors 
were deoxyribonucleic acids typed. RESULTS: Seven patients (three RP, four AMD)
showed improved EDTRS visual acuity (VA) scores. Three of these patients (one RP,
two AMD) showed improvement in both eyes to the same extent. Vision in one RP
patient remained the same, while vision in two RP patients decreased. One RP
patient has maintained an improvement in vision from 20/800 to 20/200 ETDRS for
more than five years; at the six-year examination, it was still maintained at
20/320 while the nonsurgery eye had deteriorated to hand motion vision. This
patient also showed a 22.72% increase in light sensitivity at five years compared
to microperimetry results at two years; the other patients showed no improved
sensitivity. Although no match was found between donors and recipients, no
rejection of the implanted tissue was observed clinically. CONCLUSIONS: Seven
(70%) of 10 patients showed improved VA. This outcome provides clinical evidence 
of the safety and beneficial effect of retinal implants and corroborates results 
in animal models of retinal degeneration.

Publication Types: 
    Clinical Trial, Phase II
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 18547537 [PubMed - indexed for MEDLINE]

224: Curr Med Res Opin. 2008 Jul;24(7):2103-11. Epub 2008 Jun 10.

Burden of illness of bilateral neovascular age-related macular degeneration in
Spain.

Ruiz-Moreno JM, Coco RM, García-Arumí J, Xu X, Zlateva G.

University of Castilla La Mancha, Albacete, Spain. josemaria.ruiz@uclm.es

BACKGROUND: The burden of illness, including health resource utilization and
costs associated with bilateral neovascular age-related macular degeneration
(Nv-AMD), was assessed in Spain. PATIENTS AND METHODS: As part of an
international prospective, case-controlled study, 89 Spanish patients with
bilateral Nv-AMD were recruited by retina specialists and 96 Spanish control
subjects were recruited by general practitioners and ophthalmologists. Physicians
recorded clinical data and visual acuity (VA). In a subsequent telephone
interview, Nv-AMD patients and controls completed the National Eye Institute
Visual Function Questionnaire (NEI VFQ)-25, the EuroQol (EQ-5D), and the Hospital
Anxiety and Depression Scale (HADS) questionnaire. Annual vision-related and
non-vision-related medical costs and non-medical-related costs were calculated
from study-specific questions. RESULTS: The mean age was 76.2 years for Nv-AMD
patients and 61.9 years for control subjects. The adjusted mean (95% CI) NEI
VFQ-25 summary score was 51.9 (48.5; 55.4) for Nv-AMD patients and 87.7 (85.5;
89.9) for control subjects (p<0.05). The summary score of Nv-AMD patients
decreased significantly with VA declination. Mean direct vision-related medical
and non-medical-related costs were significantly greater for Nv-AMD patients than
the control subjects, whereas non-vision-related medical costs were similar
between groups. The total mean annual resource utilization cost was euro5733 for 
Nv-AMD patients compared to euro1070 for control subjects (p<0.0001).
CONCLUSIONS: Although the study design is subject to a number of limitations,
patients with Nv-AMD in Spain have worse quality of life outcomes, greater
depression, and higher healthcare costs as compared with similarly-aged
individuals who are not affected by this disease.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18547463 [PubMed - indexed for MEDLINE]

225: Acta Ophthalmol. 2008 Nov;86(7):800-5. Epub 2008 Jun 11.

Efficacy and safety of one intravitreal injection of bevacizumab in diabetic
macular oedema.

Fang X, Sakaguchi H, Gomi F, Oshima Y, Sawa M, Tsujikawa M, Ikuno Y, Kamei M,
Kusaka S, Tano Y.

Department of Ophthalmology, Osaka University Medical School, Osaka, Japan.

PURPOSE: To assess the efficacy, duration of effect and safety of one
intravitreal injection of bevacizumab in diabetic macular oedema (DMO). METHODS: 
Bevacizumab (1 mg/0.04 ml) was injected intravitreally into eyes with DMO (29
with and nine without previous treatments). Best corrected visual acuity (BCVA), 
intraocular pressure and central retinal thickness (CRT) were measured; slit-lamp
examination, macular biomicroscopy, optical coherence tomography and fluorescein 
angiography were performed before and at 2-4, 8 and 12 weeks post-injection. Best
corrected VA and CRT were analysed in both groups. RESULTS: In the non-pretreated
group, mean BCVA improved from 0.76 +/- 0.33 (baseline) to 0.57 +/- 0.30 and 0.54
+/- 0.27 at 2-4 weeks and 8 weeks post-injection, respectively (p = 0.02, p =
0.014, paired t-test). Mean CRT decreased from 632.4 +/- 196.0 microm (baseline) 
to 392.3 +/- 113.6 microm and 370.4 +/- 141.7 microm at the same time-points,
respectively (p = 0.01, p = 0.01). There was no difference in BCVA or CRT at 12
weeks. In the pretreated group, mean BCVA improved from 0.62 +/- 0.30 (baseline) 
to 0.53 +/- 0.33 at 2-4 weeks post-injection (p = 0.01), and mean CRT decreased
from 583.9 +/- 180.7 microm (baseline) to 404.1 +/- 197.9 microm at 2-4 weeks
post-injection (p < 0.001). Mean BCVA was unchanged at 8 weeks and 12 weeks
post-injection, although mean CRT remained lower at 8 weeks (p = 0.004). No
ocular or systemic side-effects developed during follow-up. CONCLUSIONS: One
intravitreal injection of bevacizumab for DMO seems to be effective and safe in
both eyes that have been treated previously and eyes that have not. The
therapeutic effect is temporary and repeat treatment may be needed.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18547274 [PubMed - indexed for MEDLINE]

226: Graefes Arch Clin Exp Ophthalmol. 2008 Sep;246(9):1241-7. Epub 2008 Jun 11.

Prognostic factors for visual outcome after intravitreal bevacizumab for macular 
edema due to branch retinal vein occlusion.

Chung EJ, Hong YT, Lee SC, Kwon OW, Koh HJ.

Department of Ophthalmology, NHIC Ilsan Hospital, Gyounggi-do, Korea.

PURPOSE: To evaluate the prognostic factors for visual outcome after intravitreal
bevacizumab injection to treat macular edema due to branch retinal vein occlusion
(BRVO). METHODS: Fifty eyes of 50 consecutive patients treated with intravitreal 
bevacizumab for macular edema due to BRVO with minimum follow-up of 3 months were
retrospectively reviewed. Patients were categorized into two groups according to 
the final visual acuity. Group 1 consisted of eyes with 5 or more ETDRS letters
gain, and group 2 consisted of eyes with less than 5 letters improvement or which
had worsened at last follow-up visit. Comparative clinical and fluorescein
angiographic characteristics were analyzed between the two groups. RESULTS: Of 50
eyes, 28 (56%) had improved vision after intravitreal bevacizumab injections and 
were categorized as group 1; 22 eyes (44%) were categorized as group 2. The
number of early VA gainers, who showed visual improvement at 1 month after
bevacizumab injection, was significantly higher in group 1 (P < 0.001, chi-square
test). The early gainers tend to maintain significantly better visual outcome
until last follow-up. The number of eyes with angiographically documented macular
ischemia was significantly higher in group 2 (P < 0.001). In group 2, the
decrease in central macular thickness was not accompanied by visual acuity
improvement. CONCLUSION: Preoperative presence of macular ischemia can be useful 
in predicting the outcome of visual acuity after intravitreal bevacizumab for
macular edema due to BRVO. The early gainers who favorably responded to the
initial intravitreal bevacizumab injection are most likely to benefit from the
bevacizumab treatment.

PMID: 18546006 [PubMed - indexed for MEDLINE]

227: Mol Ther. 2008 Aug;16(8):1444-9. Epub 2008 Jun 10.

Repeat administration of proteins to the eye with a single intraocular injection 
of an adenovirus vector.

McVey D, Hamilton MM, Hsu C, King CR, Brough DE, Wei LL.

Vector Sciences, GenVec, Inc., Gaithersburg, Maryland, USA.

Delivery of therapeutic proteins, such as antiangiogenic proteins, to the eye is 
a demonstrated method for the control of age-related macular degeneration (AMD). 
However, one of the key limitations is the requirement for frequent and repeated 
intraocular injections. In this article, we demonstrate that repeated protein
production in the eye can be stimulated from the cytomegalovirus (CMV) promoter
without repeat intraocular injections using a small molecule, all-trans retinoic 
acid (ATRA). ATRA by systemic delivery can stimulate protein production multiple 
times in the eye. Administration of ATRA resulted in stimulation of gene
expression to relevant levels that block abnormal blood vessel growth in an
experimental animal model for AMD. These data support the principles of this
technological discovery to therapeutic applications for chronic ocular diseases.

PMID: 18545220 [PubMed - indexed for MEDLINE]

228: Arch Ophthalmol. 2008 Jun;126(6):840-6.

Pulmonary disease and age-related macular degeneration: the Beaver Dam Eye Study.

Klein R, Knudtson MD, Klein BE.

Department of Ophthalmology and Visual Sciences, University of Wisconsin School
of Medicine and Public Health, Madison, WI 53726-2336, USA.
kleinr@epi.ophth.wisc.edu

OBJECTIVE: To examine the association of pulmonary symptoms, disease, and
function with the incidence of age-related macular degeneration (AMD). DESIGN:
Population-based cohort study of persons aged 43 to 86 years at baseline (N =
4926), of whom 3779 participated in 1 or more follow-up examinations. METHODS:
Stereoscopic photographs of the macula were graded to determine the presence of
AMD. Existence of emphysema, asthma, and respiratory symptoms was determined from
subjects' medical history questionnaires; the peak expiratory flow rate was
measured using a Mini-Wright Peak Flow Meter (Clement Clarke International,
Harlow, England). Discrete logistic hazard and logistic regression models were
used. MAIN OUTCOME MEASURES: Incidence and progression of AMD. RESULTS: While
controlling for age, sex, and other factors, a history of emphysema at baseline
was found to be associated with the 15-year cumulative incidence of increased
retinal pigment (odds ratio, 2.08; 95% confidence interval, 1.06-4.06), retinal
pigment epithelium depigmentation (2.40; 1.23-4.67), and exudative AMD (3.65;
1.24-10.73). Mild pulmonary symptoms were associated with the 5-year incidence of
exudative AMD (odds ratio, 3.83; 95% confidence interval, 1.39-10.58), and the
fourth (ie, highest) quartile of pulmonary expiratory flow rate showed a
protective effect for progression of AMD among women (0.36; 0.15-0.86).
CONCLUSION: Independent of smoking, a history of emphysema and respiratory
symptoms and function are modestly but inconsistently associated with the
incidence and progression of AMD.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18541850 [PubMed - indexed for MEDLINE]

229: Arch Ophthalmol. 2008 Jun;126(6):834-9.

Alcohol consumption and risk of aging macula disorder in a general population:
the Rotterdam Study.

Boekhoorn SS, Vingerling JR, Hofman A, de Jong PT.

Department of Epidemiology and Biostatistics, Erasmus Medical Center, Rotterdam, 
the Netherlands.

OBJECTIVE: To investigate the possible relationship between overall or specific
alcohol consumption and risk of aging macula disorder (AMD), a synonym for
age-related macular degeneration, in a general population. METHODS: Alcohol
consumption and risk of early or late incident AMD (iAMD) were examined among all
participants in the prospective population-based Rotterdam Study, with complete
data on alcohol consumption among 4229 subjects at risk of AMD. Aging macula
disorder was graded according to the International Classification and Grading
System for AMD by 2 trained professionals who were masked for all other
determinants. We used Cox proportional hazards regression models to estimate
hazard ratios and corresponding 95% confidence intervals. RESULTS: During a mean 
follow-up period of 8.0 years, 600 cases of iAMD were identified, of which 519
were early iAMD and 81 were late iAMD. After correction for age, sex, smoking,
complement factor H genotype status, and other potential confounders, we did not 
find an association between overall or specific alcohol consumption and
development of early iAMD or dry or wet late iAMD. CONCLUSION: Our findings
suggest that overall or specific alcohol consumption is not a risk factor for
AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18541849 [PubMed - indexed for MEDLINE]

230: Arch Ophthalmol. 2008 Jun;126(6):826-33.

Dietary omega-3 fatty acid and fish intake in the primary prevention of
age-related macular degeneration: a systematic review and meta-analysis.

Chong EW, Kreis AJ, Wong TY, Simpson JA, Guymer RH.

Centre for Eye Research Australia, University of Melbourne, Victoria, Australia.

OBJECTIVE: To systematically review the evidence on dietary omega-3 fatty acid
and fish intake in the primary prevention of age-related macular degeneration
(AMD). METHODS: Seven databases were systematically searched with no limits on
publication year or language using standardized criteria. Randomized controlled
trials and prospective cohort, case-control, and cross-sectional studies were
included. Of 2754 abstracts identified, 3 prospective cohort, 3 case-control, and
3 cross-sectional studies met the criteria. Measures of associations were pooled 
quantitatively using meta-analytic methods. RESULTS: Nine studies provided data
on a total sample of 88 974 people, including 3203 AMD cases. A high dietary
intake of omega-3 fatty acids was associated with a 38% reduction in the risk of 
late AMD (pooled odds ratio [OR], 0.62; 95% confidence interval [CI], 0.48-0.82).
Fish intake at least twice a week was associated with a reduced risk of both
early AMD (pooled OR, 0.76; 95% CI, 0.64-0.90) and late AMD (pooled OR, 0.67; 95%
CI, 0.53-0.85). CONCLUSIONS: Although this meta-analysis suggests that
consumption of fish and foods rich in omega-3 fatty acids may be associated with 
a lower risk of AMD, there is insufficient evidence from the current literature, 
with few prospective studies and no randomized clinical trials, to support their 
routine consumption for AMD prevention.

Publication Types: 
    Meta-Analysis
    Research Support, Non-U.S. Gov't
    Review

PMID: 18541848 [PubMed - indexed for MEDLINE]

231: Am J Clin Nutr. 2008 Jun;87(6):1837-43.

Prospective study of lutein/zeaxanthin intake and risk of age-related macular
degeneration.

Cho E, Hankinson SE, Rosner B, Willett WC, Colditz GA.

Department of Medicine, Channing Laboratory, Brigham and Women's Hospital and
Harvard Medical School, Boston, MA 02115, USA. eunyoung.cho@channing.harvard.edu

BACKGROUND: The association between lutein/zeaxanthin intake and age-related
macular degeneration (AMD) risk may differ by smoking status, vitamin C and E
intakes, and body fatness. OBJECTIVE: The objective was to evaluate the
association between lutein/zeaxanthin intake and AMD risk by smoking status,
intake of antioxidant vitamins, and body fatness. DESIGN: We conducted a
prospective follow-up study of 71 494 women and 41 564 men aged >or=50 y and had 
no diagnosis of AMD or cancer. Diet was assessed with a validated
semiquantitative food-frequency questionnaire. RESULTS: During up to 18 y of
follow-up, we documented 673 incident cases of early AMD and 442 incident cases
of neovascular AMD with a visual loss of 20/30 or worse due primarily to AMD.
Lutein/zeaxanthin intake was not associated with the risk of self-reported early 
AMD. There was a statistically nonsignificant and nonlinear inverse association
between lutein/zeaxanthin intake and neovascular AMD risk; the pooled
multivariate relative risks for increasing quintiles of intake were 1.00
(referent), 0.80, 0.84, 0.97, and 0.72 (95% CI: 0.53, 0.99) (P for trend = 0.14).
For early AMD, the association with lutein/zeaxanthin intake did not vary by
smoking status, intakes of vitamins C and E, or body mass index. For neovascular 
AMD, a nonlinear inverse association was found among never smokers. CONCLUSIONS: 
These data do not support a protective role of lutein/zeaxanthin intake on risk
of self-reported early AMD. The suggestion of inverse associations related to the
risk of neovascular AMD needs to be examined further.

Publication Types: 
    Multicenter Study
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18541575 [PubMed - indexed for MEDLINE]

232: J Coll Physicians Surg Pak. 2008 May;18(5):294-8.

Visual rehabilitation of patients with Stargardt's disease.

Shah M, Zaman M, Khan MT, Khan MD.

Department of Ophthalmology, Khyber Institute of Ophthalmic Medical Sciences,
Hayatabad Medical Complex, Peshawar, Pakistan. mufarriq1@hotmail.com

OBJECTIVE: To assess the role of low vision devices in visual rehabilitation of
patients with Stargardt's disease. STUDY DESIGN: Descriptive study. PLACE AND
DURATION OF STUDY: The Khyber Institute of Ophthalmic Medical Sciences, Hayatabad
Medical Complex, Peshawar, Pakistan, from June 2003 to June 2005. PATIENTS AND
METHODS: Patients diagnosed as having Stargardt's disease and confirmed by two
senior ophthalmologists clinically and after fluorescein fundus angiography and
Electro-Retinogram (ERG) when needed, were included in the study. Patients with
fundus pathologies other than Stargardt's disease were excluded. Each subject
underwent an ophthalmic examination. Visual acuity was tested with a logarithm of
the minimum angle of resolution chart; Feinbloom chart and Snellen type. Low
vision assessment was performed on all individuals. SPSS version 10 was used for 
analysis of the data regarding the severity of visual impairment, visual acuity
and devices used for aiding vision. Chi-square test was used for comparison of
proportions. RESULTS: Of this cohort of 64 patients, 72% were aged between 7 to
15 years and 28% were 16 to 32 years. Using WHO low vision criteria, the
percentage of visually impaired, severe visually impaired and blind (at the time 
of presentation) were 56.3%; 31.3% and 9.4% respectively. Among those patients,
3.1% had distance visual acuity of 6/18 or better in the better eye and 53% had
normal near visual acuity of 1M (0.8 print size). Telescopes were prescribed to
53% patients for enhancement of distance visual acuity to meet their needs.
CONCLUSION: Stargardt's patients respond well to magnification. Simple bifocal
glasses may be used in the early stages. Visual rehabilitation can help
Stargardt's patients to learn independence in their activities of daily living.

Publication Types: 
    Comparative Study

PMID: 18541085 [PubMed - indexed for MEDLINE]

233: BMC Med Genet. 2008 Jun 9;9:51.

The NEI/NCBI dbGAP database: genotypes and haplotypes that may specifically
predispose to risk of neovascular age-related macular degeneration.

Zhang H, Morrison MA, Dewan A, Adams S, Andreoli M, Huynh N, Regan M, Brown A,
Miller JW, Kim IK, Hoh J, Deangelis MM.

Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear
Infirmary, Boston, MA, USA. hong.zhang@yale.edu

BACKGROUND: To examine if the significantly associated SNPs derived from the
genome wide allelic association study on the AREDS cohort at the NEI (dbGAP)
specifically confer risk for neovascular age-related macular degeneration (AMD). 
We ascertained 134 unrelated patients with AMD who had one sibling with an AREDS 
classification 1 or less and was past the age at which the affected sibling was
diagnosed (268 subjects). Genotyping was performed by both direct sequencing and 
Sequenom iPLEX system technology. Single SNP analyses were conducted with
McNemar's Test (both 2 x 2 and 3 x 3 tests) and likelihood ratio tests (LRT).
Conditional logistic regression was used to determine significant gene-gene
interactions. LRT was used to determine the best fit for each genotypic model
tested (additive, dominant or recessive). RESULTS: Before release of individual
data, p-value information was obtained directly from the AREDS dbGAP website. Of 
the 35 variants with P < 10-6 examined, 23 significantly modified risk of
neovascular AMD. Many variants located in tandem on 1q32-q22 including those in
CFH, CFHR4, CFHR2, CFHR5, F13B, ASPM and ZBTB were significantly associated with 
AMD risk. Of these variants, single SNP analysis revealed that CFH rs572515 was
the most significantly associated with AMD risk (P < 10-6). Haplotype analysis
supported our findings of single SNP association, demonstrating that the most
significant haplotype, GATAGTTCTC, spanning CFH, CFHR4, and CFHR2 was associated 
with the greatest risk of developing neovascular AMD (P < 10-6). Other than
variants on 1q32-q22, only two SNPs, rs9288410 (MAP2) on 2q34-q35 and rs2014307
(PLEKHA1/HTRA1) on 10q26 were significantly associated with AMD status (P = .03
and P < 10-6 respectively). After controlling for smoking history, gender and
age, the most significant gene-gene interaction appears to be between rs10801575 
(CFH) and rs2014307 (PLEKHA1/HTRA1) (P < 10-11). The best genotypic fit for
rs10801575 and rs2014307 was an additive model based on LRT. After applying a
Bonferonni correction, no other significant interactions were identified between 
any other SNPs. CONCLUSION: This is the first replication study on the NEI dbGAP 
SNPs, demonstrating that alleles on 1q, 2q and 10q may predispose an individual
to AMD.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 18541031 [PubMed - indexed for MEDLINE]

234: Invest Ophthalmol Vis Sci. 2008 Nov;49(11):5041-7. Epub 2008 Jun 6.

A severity scale for diabetic macular edema developed from ETDRS data.

Gangnon RE, Davis MD, Hubbard LD, Aiello LM, Chew EY, Ferris FL 3rd, Fisher MR;
Early Treatment Diabetic Retinopathy Study Research Group.

Department of Population Health Sciences, University of Wisconsin, Madison,
Wisconsin 53711-1068, USA.

PURPOSE: To develop a severity scale for diabetic macular edema (DME) and to
assess relationships between severity and duration of DME and visual acuity (VA).
METHODS: From the Early Treatment Diabetic Retinopathy Study (ETDRS), mean
baseline VA scores were tabulated for 7422 eyes cross-classified by (1) location 
of retinal thickening (RT) and its area within 1 disc diameter of the macular
center, and (2) degree of RT at the center. Adjacent (row, column, and
off-diagonal) cells with the greatest similarity in baseline VA (mean and SD)
based on a Gaussian (normal) likelihood were merged. An initial eight-step scale 
was chosen using the Schwarz criterion (Bayesian information criterion; BIC) and 
was revised based on clinical judgment to nine steps. Relationships between
baseline VA and other photographic and fluorescein angiographic characteristics
were examined singly and in combination with the scale. RESULTS: Modeling
baseline VA as a function of the nine-step scale yielded an R(2) of 38.0%,
compared with 38.4% using the full cross-classification of these variables.
Addition of each of the other baseline characteristics changed the adjusted R(2) 
for the combination very little. Between scale levels 1A and 5B mean (SD) VA
decreased from 86.8 (5.8) letters to 59.8 (13.6) letters. In a model of change in
VA as a function of time spent at each DME severity level, VA loss increased
progressively from 1 letter per year at level 2 to 17 letters per year at level
5B. CONCLUSIONS: The scale facilitates documentation of the relationship of
severity and duration of DME with VA.

Publication Types: 
    Comparative Study
    Research Support, N.I.H., Extramural

PMID: 18539929 [PubMed - indexed for MEDLINE]

235: Am J Ophthalmol. 2008 Aug;146(2):218-227. Epub 2008 Jun 6.

Comment in:
    Am J Ophthalmol. 2009 Feb;147(2):375-6; author reply 376-7.

The role of abnormal vitreomacular adhesion in age-related macular degeneration: 
spectral optical coherence tomography and surgical results.

Mojana F, Cheng L, Bartsch DU, Silva GA, Kozak I, Nigam N, Freeman WR.

Jacobs Retina Center at the Shiley Eye Center, Department of Ophthalmology,
University of California San Diego, La Jolla, California, USA.

PURPOSE: To assess the incidence of vitreomacular adhesion and traction in
age-related macular degeneration (AMD), and to evaluate surgical treatment in a
subset of patients with choroidal neovascularization (CNV) nonresponsive to
anti-neovascular growth factor (anti-VEGF) treatment. DESIGN: Retrospective
observational case-control and interventional case series. METHODS: Spectral
optical coherence tomography, combined with simultaneous scanning laser
ophthalmoscope (Spectral OCT/SLO), was performed in 170 eyes of 94 elderly
patients, 61 with exudative AMD, 59 with nonexudative AMD, and 50 control eyes.
The presence of hyaloid adhesion to the posterior pole, and vitreomacular
traction (VMT) were determined. Five patients with VMT underwent surgical hyaloid
removal. Best-corrected visual acuity (BCVA) and retinal thickness were evaluated
as outcomes. RESULTS: Hyaloid adhesion was present in 17 eyes with exudative AMD 
(27.8%), 15 eyes with nonexudative AMD (25.4%), and eight control eyes (16%).
Significant difference was found among the groups (P = .002). Among the eyes with
hyaloid adhesion, VMT was shown in 10 eyes (59%) with exudative AMD, two eyes
(13%) with nonexudative AMD, and one control eye (12%). VMT was associated with
the severity of AMD (P = .0082). The area of hyaloid adhesion was significantly
smaller than and concentric to the area of CNV complex in eyes with exudative
AMD. Eyes with VMT that underwent surgery experienced a modest improvement of
BCVA and decrease of retinal thickness. CONCLUSIONS: Hyaloid adhesion to the
macula is associated with AMD, and frequently causes VMT in eyes with CNV.
Tractional forces may antagonize the effect of anti-VEGF treatment, and cause
pharmacological resistance in a subpopulation of patients. Future studies are
needed to define the role of vitreoretinal surgery in such cases. Spectral
OCT/SLO allows careful diagnosis and follow-up.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18538742 [PubMed - indexed for MEDLINE]

236: Ophthalmology. 2008 Oct;115(10):1742-9. Epub 2008 Jun 5.

Inflammation, complement factor h, and age-related macular degeneration: the
Multi-ethnic Study of Atherosclerosis.

Klein R, Knudtson MD, Klein BE, Wong TY, Cotch MF, Liu K, Cheng CY, Burke GL,
Saad MF, Jacobs DR Jr, Sharrett AR.

Department of Ophthalmology and Visual Sciences, University of Wisconsin School
of Medicine and Public Health, Madison, Wisconsin 53726-2397, USA.
kleinr@epi.ophth.wisc.edu

OBJECTIVE: To describe the relationship of systemic inflammatory disease,
complement factor H (CFH) Y402H (1277T-->C) genotype status and age-related
macular degeneration (AMD) prevalence in a multiethnic population of whites,
blacks, Hispanics, and Chinese. DESIGN: Population-based, cross-sectional study. 
PARTICIPANTS: We included 5887 persons aged 45 to 84 years with gradable AMD.
METHODS: Digital fundus photographs were used to measure AMD. Two years earlier, 
biomarkers of inflammation were measured and history of inflammatory disease and 
use of antiinflammatory agents obtained. MAIN OUTCOME MEASURE: Prevalence of AMD.
RESULTS: While controlling for age, gender, race/ethnicity, and study site, there
were no associations between systemic inflammatory factors and AMD severity.
Higher levels of high-sensitivity C-reactive protein (odds ratio [OR] per
standard deviation [SD] increase in natural log [ln] units, 2.34; 95% confidence 
interval [CI], 1.33-4.13) and interleukin-6 (OR per SD in ln, 2.06; 95% CI,
1.21-3.49) were associated with geographic atrophy but not other AMD end points. 
History of periodontal disease (OR, 1.68; 95% CI, 1.14-2.47) was related to
increased retinal pigment. A history of arthritis was associated with soft
distinct drusen (OR, 1.24; 95% CI, 1.06-1.46). A history of oral steroid use was 
related to large drusen (OR, 2.13; 95% CI, 1.14-3.97) and soft distinct drusen
(OR, 1.76; 95% CI, 1.00-3.10) and history of cyclooxygenase 2 inhibitor use were 
associated with large drusen (OR, 1.50; 95% CI, 1.10-2.04), soft indistinct
drusen (OR, 1.84; 95% CI, 1.09-3.10), and large drusen area (OR, 1.66; 95% CI,
1.02-2.71). Whites, blacks, and Hispanics with CFH Y402H CC variant genotype had 
the highest frequency of early AMD compared with those with wild TT genotype. The
frequency of CFH did explain some of the difference in AMD prevalence between
Chinese and Hispanics compared with whites, but did not explain the difference in
prevalence between whites and blacks. CONCLUSIONS: This study confirmed
associations of the Y402H CFH gene variant with AMD in nonwhite populations, but 
neither explained the lack of association between inflammatory factors and AMD in
the cohort nor the basis for the observed differences in AMD prevalence across
ethnic groups.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 18538409 [PubMed - indexed for MEDLINE]

237: Acta Ophthalmol. 2008 Aug;86(5):470-81. Epub 2008 Jun 28.

Comment in:
    Acta Ophthalmol. 2008 Aug;86(5):468-9.

Vitreomacular traction and exudative age-related macular degeneration.

Schulze S, Hoerle S, Mennel S, Kroll P.

Department of Ophthalmology, University Hospital Giessen and Marburg GmbH,
Philipps University Marburg, Marburg, Germany. schulzes@med.uni-marburg.de

Vitreomacular traction resulting from lacking, incomplete or anomalous posterior 
vitreous detachment is suspected to play a crucial role in the pathogenesis of
different forms of age-related macular degeneration (AMD) along with the known
mechanisms. It is probable that the fundamental pathomechanisms of AMD formation 
have already begun by the time tractional forces lead to a change for the worse. 
Vitreomacular traction alone is perhaps not able to induce AMD. It would seem
sensible to consider vitreous changes when diagnosing and treating AMD patients
because of the high coincidence of vitreomacular traction and choroidal
neovascularization (CNV) and the often successful treatment of other diseases of 
the vitreoretinal interface by vitrectomy. The concept of the pathogenesis of AMD
should therefore be extended to include the influence of the vitreous, especially
where therapeutic concepts such as pharmacological vitreolysis and vitreous
separation have been established as causative treatment of late forms of AMD.

Publication Types: 
    Review

PMID: 18537930 [PubMed - indexed for MEDLINE]

238: Retina. 2008 Jun;28(6):870-6.

A method of reporting macular edema after cataract surgery using optical
coherence tomography.

Kim SJ, Belair ML, Bressler NM, Dunn JP, Thorne JE, Kedhar SR, Jabs DA.

Department of Ophthalmology, Emory University School of Medicine, Atlanta, GA
30322, USA. Skim30@gmail.com

OBJECTIVE: To validate a method of reporting postcataract macular edema (ME)
using optical coherence tomography (OCT). METHODS:: Data were analyzed for 130
eyes followed prospectively for ME after uncomplicated cataract surgery. Each eye
underwent OCT within 4 weeks before surgery and at 1 month and 3 months after
surgery. ME was defined by observation of cystoid changes by OCT. RESULTS:
Incidence of ME was 14% (95% confidence interval, 8-20). Average increase in
baseline center point thickness (CPT) +/- SD at 1 month for eyes with and without
ME was 202 +/- 113 microm and 8 +/- 19 microm, respectively (P < 0.001), which
resulted in a 1-letter loss (-0.02 logMAR [logarithm of the minimum angle of
resolution]) and a 3-line gain (0.29 logMAR) in vision, respectively (P < 0.001).
Percent change in baseline CPT +/- SD for eyes with and without ME was 115 +/-
67% and 6 +/- 11%, respectively (P < 0.001). A > or =40% increase in baseline CPT
accurately determined 100% of eyes with ME and 99% of eyes without ME.
CONCLUSIONS: A > or =40% increase in baseline CPT, determined by OCT, offers a
valid and objective method of reporting clinically relevant postcataract ME.
Standardized reporting of postcataract ME would allow objective assessment and
comparison of treatment outcomes among clinical studies.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Validation Studies

PMID: 18536605 [PubMed - indexed for MEDLINE]

239: Retina. 2008 Jun;28(6):825-30.

Intravitreal triamcinolone for diabetic macular edema: comparison of 1, 2, and 4 
mg.

Hauser D, Bukelman A, Pokroy R, Katz H, Len A, Thein R, Parness-Yossifon R,
Pollack A.

Department of Ophthalmology, Kaplan Medical Center, Rehovot, affiliated with the 
Hebrew University-Hadassah Medical School, Jerusalem, Israel.

PURPOSE: To compare the efficacy and safety of different doses of intravitreal
triamcinolone (IVTA) in treating eyes with refractory diffuse diabetic macular
edema (DME) with cystic changes. METHODS: Forty-five eyes of 45 patients with
diffuse DME were randomized to receive 1, 2, or 4 mg IVTA. Patients were observed
for 6 months and changes in best-corrected visual acuity (VA) in Early Treatment 
Diabetic Retinopathy Study (ETDRS) scores, retinal thickness analyzer (RTA)
central macular thickness (CMT), intraocular pressure, and cataract progression
were compared among the three groups. RESULTS: Forty-two patients completed 6
months of follow-up and were included in the analysis. Following IVTA injection, 
the ETDRS score improved similarly, eight to nine letters, in all three groups at
4 weeks. The standardized CMT improved in all three groups at 4 weeks. This
improvement was maintained through 12 and 24 weeks in the 1 and 2 mg groups, but 
not in the 4 mg group, which was significantly worse than the 1 and 2 mg groups
at 12 and 24 weeks (P = 0.01, 0.03, 0.01, and 0.05). CONCLUSIONS: Regarding eyes 
with refractory diffuse DME with cystic changes, 4 mg IVTA does not appear to be 
more effective than 1 or 2 mg IVTA.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial

PMID: 18536598 [PubMed - indexed for MEDLINE]

240: Retina. 2008 Jun;28(6):789-93.

Combination treatment with reduced-fluence photodynamic therapy and intravitreal 
injection of triamcinolone for subfoveal choroidal neovascularization in macular 
degeneration.

Singh CN, Saperstein DA.

Department of Ophthalmology, University of Washington, Seattle, WA, USA.

PURPOSE: To evaluate combination treatment with reduced-fluence photodynamic
therapy (PDT) and intravitreal triamcinolone acetonide (IVT) injection for
choroidal neovascularization (CNV) in age-related macular degeneration (AMD).
METHODS: This is a retrospective consecutive case series of 23 previously
untreated eyes of 22 patients with subfoveal CNV secondary to AMD. Six eyes were 
treated with 50 J/cm; 8, with 40 J/cm; and 9, with 25 J/cm. PDT was immediately
followed by a 4-mg IVT injection. Patients were observed for 6 months at 6-week
intervals. RESULTS:: The 50 J/cm subset lost a mean of 2.2 lines of Snellen
visual acuity at the 6-month follow-up compared with a 1-line lost in the 40 J/cm
subset and a 0.9-line gain in the 25 J/cm subset. In the 50 J/cm subset, 60% lost
< or =3 lines of Snellen visual acuity, 33% gained > or =0 line, and 33% gained >
or =3 lines. In the 40 J/cm subset, 75% lost < or =3 lines of Snellen visual
acuity, 50% gained > or =0 line, and 25% gained > or =3 lines. In the 25 J/cm
subset, 89% lost < or =3 lines of Snellen visual acuity, 56% gained > or =0 line,
and 33% gained > or =3 lines. Fifty percent of the 50 J/cm subset, 50% of the 40 
J/cm subset, and 33% of the 25 J/cm subset required retreatment by 6 months.
CONCLUSION: Although the sample in this study was small, there was a
dose-response trend toward better visual outcomes and fewer treatments in the
group treated with IVT injection and reduced-fluence PDT. This study along with
other previously reported work suggests that studies using PDT in combination
treatment for CNV should consider adding a reduced-fluence PDT arm.

PMID: 18536593 [PubMed - indexed for MEDLINE]

241: Hum Mol Genet. 2008 Sep 1;17(17):2673-80. Epub 2008 Jun 4.

Rhesus monkeys and humans share common susceptibility genes for age-related
macular disease.

Francis PJ, Appukuttan B, Simmons E, Landauer N, Stoddard J, Hamon S, Ott J,
Ferguson B, Klein M, Stout JT, Neuringer M.

Casey Eye Institute, Oregon Health and Science University, Portland, OR 97239,
USA. francisp@ohsu.edu

Age-related macular degeneration (AMD), a complex multigenic disorder and the
most common cause of vision loss in the elderly, is associated with polymorphisms
in the LOC387715/ARMS2 and HTRA1 genes on 10q26. Like humans, macaque monkeys
possess a macula and develop age-related macular pathologies including drusen,
the phenotypic hallmark of AMD. We genotyped a cohort of 137 unrelated rhesus
macaques with and without macular drusen. As in humans, one variant within
LOC387715/ARMS2 and one in HTRA1 were significantly associated with affected
status. HTRA1 and the predicted LOC387715/ARMS2 gene were both transcribed in
rhesus and human retina and retinal pigment epithelium. Among several primate
species, orthologous exons for the human LOC387715/ARMS2 gene were present only
in Old World monkeys and apes. In functional analyses, the disease-associated
HTRA1 polymorphism resulted in a 2-fold increase in gene expression, supporting a
role in pathogenesis. These results demonstrate that two genes associated with
AMD in humans are also associated with macular disease in rhesus macaques and
that one of these genes is specific to higher primates. This is the first
evidence that humans and macaques share the same genetic susceptibility factors
for a common complex disease.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18535016 [PubMed - indexed for MEDLINE]

242: Am J Ophthalmol. 2008 Aug;146(2):285-291. Epub 2008 Jun 4.

Fluocinolone acetonide sustained drug delivery device for chronic central retinal
vein occlusion: 12-month results.

Ramchandran RS, Fekrat S, Stinnett SS, Jaffe GJ.

Department of Ophthalmology, Duke University Medical Center, Durham, North
Carolina, USA.

PURPOSE: To determine treatment outcomes of a long-acting intravitreal
fluocinolone acetonide sustained drug delivery implant in eyes with central
retinal vein occlusion (CRVO) and chronic refractory macular edema. DESIGN:
Prospective, noncomparative, interventional case series. METHODS: Fourteen eyes
of 14 patients with chronically persistent macular edema associated with CRVO
underwent intraocular implantation of a three-year fluocinolone acetonide
sustained drug delivery system. Best-corrected Early Treatment of Diabetic
Retinopathy visual acuity (VA), central foveal thickness determined by optical
coherence tomography, and intraocular pressure (IOP) were recorded after the
first 12 months after implant insertion. RESULTS: The median (range) vein
occlusion and macular edema duration were 12.5 months (range, seven to 49). No
eye experienced intraoperative complications. At baseline, median VA was 20/126, 
improved to 20/60 by two months, and was 20/80 by 12 months. A significant
proportion of eyes had gained lines of VA at 12 months compared with baseline (P 
= .002). At 12 months, the mean and median central retinal thickness decreased
from 622 and 600 microm before surgery, respectively, to 307 and 199 microm after
surgery, respectively (P = .008). By month 12, cataract had developed in all five
phakic patients, and 13 of 14 eyes required medical or surgical IOP-lowering
interventions. CONCLUSIONS: VA improved and macular edema decreased in a
significant proportion of implanted eyes with chronic, CRVO-associated macular
edema. Cataract formation and elevated IOP, the main side effects, were managed, 
respectively, with cataract extraction and medical or surgical IOP control, or
both. This system is a promising novel alternative to currently available
treatments for this challenging patient population.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18533125 [PubMed - indexed for MEDLINE]

243: J Biomech Eng. 2008 Jun;130(3):031010.

Temperature distribution during ICG-dye-enhanced laser photocoagulation of feeder
vessels in treatment of AMD-related choroidal neovascularization.

Zhu L, Banerjee RK, Salloum M, Bachmann A, Flower RW.

Department of Mechanical Engineering, University of Maryland, Baltimore County,
Baltimore, MD 21250, USA. zliang@umbc.edu

Laser photocoagulation of the feeder vessels of age-related macula
degeneration-related choroidal neovascularization (CNV) membranes is a compelling
treatment modality, one important reason being that the treatment site is removed
from the fovea in cases of sub- or juxtafoveal CNV. To enhance the energy
absorption in a target feeder vessel, an indocyanine green dye bolus is injected 
intravenously, and the 805 nm wavelength diode laser beam is applied when the dye
bolus transits the feeder vessel; this tends to reduce concomitant damage to
adjacent tissue. A 3D theoretical simulation, using the Pennes bioheat equation, 
was performed to study the temperature distribution in the choroidal feeder
vessel and its vicinity during laser photocoagulation. The results indicate that 
temperature elevation in the target feeder vessel increases by 20% in
dye-enhanced photocoagulation, compared to just photocoagulation alone. The dye
bolus not only increases the laser energy absorption in the feeder vessel but
also shifts the epicenter of maximum temperature away from the sensitive sensory 
retina and retinal pigment epithelial layers and toward the feeder vessel. Two
dominant factors in temperature elevation of the feeder vessel are location of
the feeder vessel and blood flow velocity through it. Feeder vessel temperature
elevation becomes smaller as distance between it and the choriocapillaris layer
increases. The cooling effect of blood flow through the feeder vessel can reduce 
the temperature elevation by up to 21% of the maximum that could be produced.
Calculations were also performed to examine the effect of the size of the laser
spot. To achieve the same temperature elevation in the feeder vessel when the
laser spot diameter is doubled, the laser power level has to be increased by only
60%. In addition, our results have suggested that more studies are needed to
measure the constants in the Arrhenius integral for assessing thermal damage in
various tissues.

Publication Types: 
    Research Support, U.S. Gov't, Non-P.H.S.

PMID: 18532859 [PubMed - indexed for MEDLINE]

244: J Vestib Res. 2007;17(4):183-93.

Balance training and visual rehabilitation of age-related macular degeneration
patients.

Radvay X, Duhoux S, Koenig-Supiot F, Vital-Durand F.

Inserm U846, Stem Cell and Brain Research Institute, F 69500 Bron, France.

Patients with Age-Related Macular Degeneration (AMD) experience a large scotoma
precluding central vision. In addition, 2/3 of these patients present visuomotor 
and balance deficits resulting in clumsiness and increased risk of falls. On the 
basis of previous work demonstrating that visual, vestibular and somatosensory
functions involved in balance control can be rehabilitated by training, we
attempted to improve these functions by balance training. We measured the impact 
of balance training on several visuomotor functions and reading speed. We
compared balance status of 54 AMD patients to 55 normal controls. Sixteen of
these patients and 14 controls subsequently received balance training sessions on
a postural platform (Multitest) stressing sensorimotor coordination by
selectively inhibiting or disturbing either, visual, vestibular or somatosensory 
input. Producing a conflict between two inputs reinforces the use of the third.
We assessed postural sway, pointing accuracy, reading performance and, for the
patients, the effect of low vision training and balance training on the shift
from several spontaneous Preferred Retinal Loci (PRLs) to one or more Trained
Retinal Loci (TRL). Even after a limited number of sessions of cross-modal
balance training, the results show a significant improvement for the vestibular
input and fixation stability. A decrease of visual dependency was observed only
in the control group. Apart from these improvements, pointing accuracy and
reading speed were not significantly improved compared to controls, leading to
the conclusion that more training sessions may be necessary to gain more
significant improvement of visuo-motor functions.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18525144 [PubMed - indexed for MEDLINE]

245: PLoS ONE. 2008 Jun 4;3(6):e2339.

The aged retinal pigment epithelium/choroid: a potential substratum for the
pathogenesis of age-related macular degeneration.

Chen H, Liu B, Lukas TJ, Neufeld AH.

Forsythe Laboratory for the Investigation of the Aging Retina, Department of
Ophthalmology, Northwestern University School of Medicine, Chicago, Illinois,
United States of America.

BACKGROUND: Although the statement that age is the greatest risk factor for
Age-related macular degeneration (AMD) is widely accepted, the cellular and
molecular explanations for that clinical statement are not generally known. A
major focus of AMD research is the retinal pigment epithelium (RPE)/choroid. The 
purpose of this study was to characterize the changes in the RPE/choroid with age
that may provide a background for the development of AMD. METHODOLOGY/PRINCIPAL
FINDINGS: We compared the transcriptional profiles, key protein levels and
histology of the RPE/choroid from young and old mice. Using three statistical
methods, microarray data demonstrated marked changes in the old mouse. There were
315 genes differentially expressed with age; most of these genes were related to 
immune responses and inflammatory activity. Canonical pathways having significant
numbers of upregulated genes in aged RPE/choroid included leukocyte
extravasation, complement cascades, natural killer cell signaling and IL-10
signaling. By contrast, the adjacent neural retina showed completely different
age-related changes. The levels of proteins that participate in leukocyte
extravasation and complement pathways were consistently increased in the normal, 
aged RPE/choroid. Furthermore, there was increased gene expression and protein
levels of leukocyte attracting signal, chemokine ligand 2 (Ccl2) in aged
RPE/choroid. In old animals, there was marked extravasation and accumulation of
leukocytes from the choroidal circulation onto Bruch's membrane and into the RPE.
CONCLUSIONS/SIGNIFICANCE: These phenotypic changes indicate that the RPE/choroid 
in the normal, old mouse has become an immunologically active tissue. There are
signals from the normal, aged RPE/choroid which recruit leukocytes from the
circulation and activate the complement cascade. These age-related changes that
occur in the RPE/choroid with age, to the extent that they occur in the human
retina, may provide the background for an error in regulation of immunological
activity to cause AMD to appear in an elderly individual.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18523633 [PubMed - indexed for MEDLINE]

246: Am J Geriatr Psychiatry. 2008 Jun;16(6):454-9.

Preventing late-life depression in age-related macular degeneration.

Rovner BW, Casten RJ.

Department of Psychiatry and Neurology, Jefferson Medical College, Jefferson
Medical College, Philadelphia, PA 19107, USA. barry.rovner@jefferson.edu

OBJECTIVE: To determine whether problem-solving treatment (PST) can prevent
depressive disorders in patients with age-related macular degeneration (AMD).
DESIGN: Two hundred six patients with AMD were randomly assigned to PST (n = 105)
or usual care (n = 101). PST therapists delivered six PST sessions over 8 weeks
in subjects' homes. MEASUREMENTS: Diagnostic and Statistical Manual of Mental
Disorders - Fourth Edition Diagnoses of Depressive Disorders, Hamilton Depression
Rating Scale scores, and rates of relinquishing valued activities were assessed
at 2 months for short-term effects and 6 months for maintenance effects. RESULTS:
The 2-month incidence rate of depressive disorders in PST-treated subjects was
significantly lower than controls (11.6% versus 23.2%, respectively; OR = 0.43;
95% CI [0.20, 0.95]). PST also reduced the odds of relinquishing a valued
activity (OR = 0.48; 95% CI [0.25, 0.96]); this effect mediated the relationship 
between treatment group and depression. By 6 months most earlier observed
benefits had diminished. Secondary analyses showed that a minimal level of
depressive symptoms were disabling and predicted incident depressive disorders.
CONCLUSION: PST prevented depressive disorders and loss of valued activities as a
short-term treatment but these benefits were not maintained over time. To sustain
PST's effect, an intervention that uses a problem-solving framework to enhance
rehabilitative skills may be necessary.

Publication Types: 
    Randomized Controlled Trial
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18515689 [PubMed - indexed for MEDLINE]

247: Invest Ophthalmol Vis Sci. 2008 Jun;49(6):2696-708.

Late outgrowth endothelial progenitor cells in patients with age-related macular 
degeneration.

Thill M, Strunnikova NV, Berna MJ, Gordiyenko N, Schmid K, Cousins SW, Thompson
DJ, Csaky KG.

National Eye Institute, National Institutes of Health, Bethesda, Maryland, USA.

PURPOSE: To evaluate the feasibility of isolating and expanding endothelial
progenitor cells (EPCs), in the form of late outgrowth endothelial progenitor
cells (OECs), from the peripheral blood of an aged population, particularly
patients affected by different forms of AMD. METHODS: Peripheral blood
mononuclear cells were collected from young control subjects (n = 18) and from
elderly subjects with non-AMD/low-risk dry AMD (n = 15), high-risk dry AMD (n =
6), or neovascular AMD (nvAMD; n = 32); cultured in established conditions; and
observed for appearance of OEC clusters and growth characteristics on expansion. 
Expression of VEGF receptor-2 (KDR) in OECs after expansion was determined by
Western blot. Plasma samples of study subjects were analyzed for CRP and VEGF
levels. RESULTS: OEC cultures were successfully generated from a similar number
of subjects in each group. After adjustment for all other variables, subjects
with high-risk dry AMD had a 5.6-fold higher number of OEC clusters per 20 mL
blood, and subjects with nvAMD had a 5.1-fold high number than did subjects with 
non-AMD/low-risk dry AMD (P < 0.05). High-risk dry AMD generated 63 times more
(NS) and nvAMD 32-times more (P < 0.05) OECs on expansion of clusters than did
non-AMD/low-risk dry AMD. Population doubling occurred significantly faster in
cultures from nvAMD eyes compared to non-AMD/low-risk dry AMD eyes. In addition, 
a significant correlation between the number of OEC clusters, expanded OECs and
levels of KDR was demonstrated. CONCLUSIONS: An OEC population was isolated and
expanded from the blood of elderly control and AMD-affected patients and
demonstrated significantly higher number of initial OEC clusters and expansion
potential of OECs in patients at risk for or already affected by nvAMD. OECs may 
be used for further phenotypic, genetic, and functional analyses in patients with
nvAMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18515596 [PubMed - indexed for MEDLINE]

248: Invest Ophthalmol Vis Sci. 2008 Jun;49(6):2661-7.

Imaging polarimetry in age-related macular degeneration.

Miura M, Yamanari M, Iwasaki T, Elsner AE, Makita S, Yatagai T, Yasuno Y.

Computational Optics and Ophthalmology Group, Tokyo Medical University, Tokyo,
Japan. m-miura@tokyo-med.ac.jp

PURPOSE: To evaluate the birefringence properties of eyes with age-related
macular degeneration (AMD). To compare the information from two
techniques--scanning laser polarimetry (GDx) and polarization-sensitive
spectral-domain optical coherence tomography (OCT)--and investigate how they
complement each other. METHODS: The authors prospectively examined the eyes of
two healthy subjects and 13 patients with exudative AMD. Using scanning laser
polarimetry, they computed phase-retardation maps, average reflectance images,
and depolarized light images. To obtain polarimetry information with improved
axial resolution, they developed a fiber-based, polarization-sensitive,
spectral-domain OCT system and measured the phase retardation associated with
birefringence in the same eyes. RESULTS: Both GDx and polarization-sensitive
spectral-domain optical coherence tomography detected abnormal birefringence at
the locus of exudative lesions. Polarization-sensitive, spectral-domain OCT
showed that in the old lesions with fibrosis, phase-retardation values were
significantly larger than in the new lesions (P = 0.020). Increased scattered
light and altered polarization scramble were associated with portions of the
lesions. CONCLUSIONS: GDx and polarization-sensitive spectral-domain OCT are
complementary in probing birefringence properties in exudative AMD. Polarimetry
findings in exudative AMD emphasized different features and were related to the
progression of the disease, potentially providing a noninvasive tool for
microstructure in exudative AMD.

Publication Types: 
    Comparative Study
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18515594 [PubMed - indexed for MEDLINE]

249: Invest Ophthalmol Vis Sci. 2008 Jun;49(6):2627-34.

Precision and reliability of retinal thickness measurements in foveal and
extrafoveal areas of healthy and diabetic eyes.

Tangelder GJ, Van der Heijde RG, Polak BC, Ringens PJ.

Department of Ophthalmology, VU University Medical Center, Amsterdam, The
Netherlands. g.tangelder@vumc.nl

PURPOSE: To determine the precision and reliability of retinal thickness
measurements with an optical coherence tomograph (Stratus OCT 3; Carl Zeiss
Meditec, Dublin, CA) and a retinal thickness analyzer (RTA; Talia Technology
Ltd., Neve-Ilan, Israel) in foveal, parafoveal, and perifoveal areas. METHODS:
Three measurements of all areas were performed within 1 hour on the same day with
each instrument in the eyes of healthy volunteers and diabetic patients. The
latter group was divided into eyes with and without macular edema. RESULTS:
Measurement precision, expressed as the 95% limits of agreement (LA 95%), was
significantly higher (i.e., a lower LA 95%, P < 0.01) for the OCT in comparison
to the RTA in virtually all areas of the retina. Moreover, measurement
reliability, expressed as the intraclass correlation coefficient, was high with
the OCT (>0.90) and moderate to low with the RTA (0.26-0.89). A direct influence 
of macular edema itself on measurement precision of para- and perifoveal areas
was found in the OCT measurements. CONCLUSIONS: The high measurement precision
and reliability of the OCT suggests that this instrument is currently the most
suitable technique for detection and follow-up of diabetic macular edema. When
macular edema is present, the OCT can reliably detect changes of at least 36
microm at the fovea, 55 microm in parafoveal areas below a thickness of 744
microm, and 42 microm in perifoveal areas below a thickness of 1011 microm.

Publication Types: 
    Comparative Study

PMID: 18515592 [PubMed - indexed for MEDLINE]

250: Invest Ophthalmol Vis Sci. 2008 Nov;49(11):5077-82. Epub 2008 May 30.

Age-related macular degeneration is associated with the HLA-Cw*0701 Genotype and 
the natural killer cell receptor AA haplotype.

Goverdhan SV, Khakoo SI, Gaston H, Chen X, Lotery AJ.

Division of Clinical Neurosciences, University of Southampton, Southampton
General Hospital, Southampton, United Kingdom.

PURPOSE: To determine the association of human leukocyte antigen (HLA) C and its 
cognate killer cell immunoglobulin-like receptor (KIR) ligands with age-related
macular degeneration (AMD). METHODS: HLA class I allele groups including the
HLA-C principal alleles were genotyped in a cohort of 104 AMD cases and 93
controls by using the PCR-SSP (sequence-specific primers) METHOD: This cohort was
then genotyped for 16 KIR genes by PCR-SSP. Frequencies of the tested HLA/KIR
alleles were then compared between patients with AMD and normal control subjects.
HLA-C1, -Cw*07, and -Cw*0701 genotypes and their combinations with KIR
genotypes/haplotypes were tested for association with AMD. Probabilities were
obtained with a two-tailed chi(2) test and Bonferroni correction applied for
multiple testing (P(c)). RESULTS: The HLA-Cw*0701 allele, in combination with the
inhibitory KIR AA haplotype was associated with AMD after logistic regression
analysis (P = 0.006, P(c) = 0.036, OR = 4.35, 95% CI = 1.41-13.44). CONCLUSIONS: 
The HLA-Cw*0701 allele and KIR haplotype AA are associated with AMD. This
genotype combination suggests that natural killer cells have a role in the
pathogenesis of AMD. Replication studies are needed to confirm these novel
HLA-KIR associations with AMD.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 18515573 [PubMed - indexed for MEDLINE]

251: Invest Ophthalmol Vis Sci. 2008 Oct;49(10):4290-6. Epub 2008 May 30.

Evaluation of time domain and spectral domain optical coherence tomography in the
measurement of diabetic macular edema.

Forooghian F, Cukras C, Meyerle CB, Chew EY, Wong WT.

Division of Epidemiology and Clinical Research, National Eye Institute, National 
Institutesof Health, Bethesda, Maryland 20892, USA.

PURPOSE: To evaluate macular thickness and volume measurements and their
intrasession repeatability in two optical coherence tomography (OCT) systems: the
Stratus OCT, a time domain system, and the Cirrus HD-OCT, a spectral domain
system (both by Carl Zeiss Meditec, Inc., Dublin, CA), in the context of diabetic
macular edema (DME). METHODS: Thirty-three eyes of 33 diabetic patients with
clinically significant macular edema (CSME) were scanned in a single session by a
single operator on both OCT systems. Macular thickness measurements of nine
standard macular subfields and total macular volume were obtained and analyzed.
Bland-Altman plots were constructed to assess agreement in macular measurements. 
Intraclass correlation coefficients (ICCs), coefficients of repeatability
(CR(W)), and coefficients of variation (CV(W)) were used to assess intrasession
repeatability. RESULTS: Macular thickness in nine retinal subfields and macular
volume were significantly higher in the Cirrus HD-OCT system compared with the
Stratus OCT system. Subfield thickness and total volume measurements,
respectively, were 30 to 55 microm and 3.2 mm(3) greater for the Cirrus HD-OCT
system compared with the Stratus OCT system. Both Stratus OCT and Cirrus HD-OCT
systems demonstrated high intrasession repeatability, with overlapping ranges for
CR(W), CV(W), and ICC. Repeatability measures (CR(W) and CV(W)) differed
significantly between systems in only one of nine subfields (outer temporal
subfield). CONCLUSIONS: Absolute measures of macular thickness and volume in
patients with DME differed significantly in magnitude between the Stratus OCT and
Cirrus HD-OCT systems. However, both OCT systems demonstrated high intrasessional
repeatability. Although the two systems may not be used interchangeably, they
appear equally reliable in generating macular measurements for clinical practice 
and research.

Publication Types: 
    Comparative Study
    Evaluation Studies
    Research Support, N.I.H., Intramural

PMID: 18515567 [PubMed - indexed for MEDLINE]

252: Am J Ophthalmol. 2008 Aug;146(2):183-92. Epub 2008 Jun 2.

Evaluation of autofluorescence imaging with the scanning laser ophthalmoscope and
the fundus camera in age-related geographic atrophy.

Schmitz-Valckenberg S, Fleckenstein M, Göbel AP, Sehmi K, Fitzke FW, Holz FG,
Tufail A.

Department of Ophthalmology, University of Bonn, Bonn, Germany.
steffen.schmitz-valckenberg@ukb.uni-bonn.de

PURPOSE: To compare fundus autofluorescence images (FAF) between a modified
fundus camera (mFC) and a confocal scanning laser ophthalmoscope (cSLO). DESIGN: 
Evaluation of diagnostic technology. METHODS: Thirty-two eyes of 16 patients with
age-related geographic atrophy (GA) treated in an institutional setting were
included. FAF images were obtained with both the cSLO (excitation, 488 nm;
emission, > 500 nm) and the mFC (excitation, approximately 500 to 610 nm;
emission, approximately 675 to 715 nm). Using established algorithms, images were
graded by two independent observers and agreements were evaluated. The main
outcome measures were image quality, quantification of total atrophy, and
classification of FAF patterns. RESULTS: In two eyes with advanced cataract (lens
grade 7 according to the Age-Related Eye Disease Study classification), FAF image
quality with both systems was not sufficient for any meaningful analysis. In the 
remaining 30 eyes, the mean differences of the interobserver agreements for
atrophy quantification were 0.16 mm2 (95% confidence interval [CI], 0.07 to 0.38)
for mFC and 0.15 mm2 (95% CI, -0.04 to 0.33) for cSLO images. Because of inferior
signal-to-noise ratios, FAF pattern classification was possible in a lower number
of mFC images (69%) compared with cSLO images (88%). CONCLUSIONS: This study
suggests that the agreements for atrophy quantification are similar with both
devices. The lesser visualization of FAF patterns with the mFC and thus inferior 
determination of disease markers may be the result of the nonconfocality and the 
use of single instead of mean images compared with the cSLO. These findings may
be important for the design of interventional trials as well as the routine use
of FAF imaging in age-related geographic atrophy.

Publication Types: 
    Comparative Study
    Evaluation Studies

PMID: 18514607 [PubMed - indexed for MEDLINE]

253: Health Technol Assess. 2008 Jun;12(27):iii-iv, ix-124.

A preliminary model-based assessment of the cost-utility of a screening programme
for early age-related macular degeneration.

Karnon J, Czoski-Murray C, Smith K, Brand C, Chakravarthy U, Davis S, Bansback N,
Beverley C, Bird A, Harding S, Chisholm I, Yang YC.

School of Health and Related Research, University of Sheffield, UK.

OBJECTIVES: To estimate the cost-effectiveness of screening for age-related
macular degeneration (AMD) by developing a decision analytic model that
incorporated and assessed all of the National Screening Committee criteria. A
further objective was to identify the major areas of uncertainty in the model,
and so inform future research priorities in this disease area. DATA SOURCES:
Major databases were searched in March 2004 and updated in January 2005. REVIEW
METHODS: Systematic literature reviews covered the epidemiology and natural
history of AMD, the screening and treatment effectiveness and health-related
quality of life relating to AMD. A hybrid cohort-individual sampling model was
implemented to describe the range of pathways between the incidence of
age-related maculopathy (ARM) and death via clinical presentation and treatment
at different stages of the disease. As significant shortfalls in the data
available from the literature were apparent, so a range of primary data sources
were also used to populate the model. To obtain estimates for the value of
parameters deemed to be within an expert's remit, data describing some parameters
were elicited from relevant experts. The data identified informed probability
distributions describing the uncertainty around the model parameters. To
incorporate joint parameter uncertainty (i.e. correlations between parameters),
the AMD natural history model was calibrated probabilistically. Randomly sampled 
sets of input parameters were assigned weights representing the accuracy of their
predictions of a set of observed model outputs. The analysis of the AMD screening
model estimated the costs, numbers of quality-adjusted life-years (QALYs) and
cases of blindness in a general population sample of 50-year-olds over the
remainder of their lifetime, for 16 alternative screening options (including no
screening). The reference case analysis incorporated current treatment options of
laser photocoagulation and photodynamic therapy. Sensitivity analyses describing 
six alternative sets of intervention strategies, based on horizon scanning of
potential future treatments for AMD, were also undertaken. RESULTS: There remains
significant uncertainty about whether any form of screening for AMD is
cost-effective. However, annual screening from age 60 years seems to provide the 
highest mean net benefits, but this is based on a cost-effectiveness estimate
that has very poor precision (high levels of uncertainty). The probabilistic
sensitivity analysis shows that the 95% credible interval for annual screening
from age 60 years ranges from this option dominating the previous option to an
incremental cost per QALY of over 0.5 million pounds sterling. Plotting a
cost-effectiveness acceptability frontier shows that although annual screening
from age 60 years has the highest net benefits at a value of QALY of 30,000
pounds sterling, the associated probability of this option being the most
cost-effective option is only around 20%. The sensitivity analyses around
potential future treatment options indicate that screening may become more
cost-effective with the new treatments. CONCLUSIONS: The conclusions focus on the
interpretation of the results from the perspective of defining the major areas of
uncertainty, which were defined as disease progression, rates of clinical
presentation, screening test and optician effectiveness, treatment effectiveness,
and costs of blindness. Future research may be best targeted at assessing how
routine data may be used to describe clinical presentation rates of ARM. Other
potential studies include a pilot study of the effectiveness of screening and
opticians' referral patterns for AMD and a costing study of blindness as a
continuum of association with deterioration in vision.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18513468 [PubMed - indexed for MEDLINE]

254: Nat Genet. 2008 Jul;40(7):892-6. Epub 2008 May 30.

Comment in:
    Nat Genet. 2008 Jul;40(7):820-1.

Age-related macular degeneration is associated with an unstable ARMS2 (LOC387715)
mRNA.

Fritsche LG, Loenhardt T, Janssen A, Fisher SA, Rivera A, Keilhauer CN, Weber BH.

Institute of Human Genetics, University of Regensburg, Franz-Josef-Strauss-Allee 
11, 93053 Regensburg, Germany.

Age-related macular degeneration (AMD) is a prevalent multifactorial disorder of 
the central retina. Genetic variants at two chromosomal loci, 1q31 and 10q26,
confer major disease risks, together accounting for more than 50% of AMD
pathology. Signals at 10q26 center over two nearby genes, ARMS2 (age-related
maculopathy susceptibility 2, also known as LOC387715) and HTRA1
(high-temperature requirement factor A1), suggesting two equally probable
candidates. Here we show that a deletion-insertion polymorphism in ARMS2
(NM_001099667.1:c.(*)372_815del443ins54) is strongly associated with AMD,
directly affecting the transcript by removing the polyadenylation signal and
inserting a 54-bp element known to mediate rapid mRNA turnover. As a consequence,
expression of ARMS2 in homozygous carriers of the indel variant is not
detectable. Confirming previous findings, we demonstrate a mitochondrial
association of the normal protein and further define its retinal localization to 
the ellipsoid region of the photoreceptors. Our data suggest that ARMS2 has a key
role in AMD, possibly through mitochondria-related pathways.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18511946 [PubMed - indexed for MEDLINE]

255: Graefes Arch Clin Exp Ophthalmol. 2008 Sep;246(9):1229-34. Epub 2008 May 29.

Foveal RPE autofluorescence as a prognostic factor for anti-VEGF therapy in
exudative AMD.

Heimes B, Lommatzsch A, Zeimer M, Gutfleisch M, Spital G, Bird AC, Pauleikhoff D.

Department of Ophthalmology, St. Franziskus Hospital, Hohenzollernring 74, 48145 
Münster, Germany. heimesb@web.de

BACKGROUND: Autofluorescence (AF) of the retinal pigment epithelium (RPE) are
thought to reflect metabolic activity of the RPE cells, which in turn is largely 
driven by photoreceptor outer segment renewal. In exudative AMD, choroidal new
vessels (CNV) may be confined to Bruch's membrane, or transgress the RPE, with
consequence loss of photoreceptor cells. It has been suggested that they may be
distinguished with autofluorescence imaging. The aim of our study was to analyze 
the prognostic value of RPE autofluorescence in relationship to the therapeutic
outcome of anti-VEGF (vascular endothelial growth factor) therapy in exudative
AMD. PATIENTS AND METHODS: AF images (Heidelberg Retina Angiograph) were obtained
from 95 eyes (95 patients, mean age 77.64 years, 39 male and 56 female) with
exudative macular lesions and associated drusen before therapy with intravitreal 
Bevacizumab (Avastin). Increased, normal, or decreased AF of a central area with 
diameters of 500 and 1,000 microm around the foveola were distinguished, and
compared with the outcome of central vision. As a measure of data reproducibility
(inter- and intraobserver variability), the kappa statistics (K > 0.6 "good", K >
0.8 "excellent") and exact agreement in % were calculated. RESULTS: Analysis of
AF showed a significant difference in outcome of visual acuity in eyes with
changes in AF of the central 500 and 1000 microm (Mann-Whitney test, p500 mum <
0.001, p1,000 microm = 0.02). Comparison of eyes with increased AF to the other
eyes also resulted a significant difference in visual acuity at follow-up (p
(incr) < 0.001); those with decreased AF had no significant difference to the
eyes with normal or increased AF (p (decr) = 0.1733). CONCLUSIONS: The RPE-AF of 
exudative AMD lesions varies greatly. The AF differences probably represent
different kinds of metabolism disorders in the RPE. Furthermore, they apparently 
have a great influence on the chances of anti- vascular endothelial growth factor
(VEGF) therapy success; in particular the development of visual acuity is less
favorable in eyes with initially increased central AF.

PMID: 18509668 [PubMed - indexed for MEDLINE]

256: Int J Mol Med. 2008 Jun;21(6):715-20.

Evaluation of the common variants of the ABCA4 gene in families with Stargardt
disease and autosomal recessive retinitis pigmentosa.

Shastry BS.

Department of Biological Sciences, Oakland University, Rochester, MI 48309, USA. 
shastry@oakland.edu.

Stargardt disease (STGD) is one of the most common autosomal recessive retinal
dystrophies with an estimated incidence of one in 10,000. It affects the central 
retina (macula). Retinitis pigmentosa (RP) comprises a large and exceptionally
heterogeneous group of hereditary disorders of the retina. It is caused by the
loss of photoreceptors. The condition is a degenerative disorder characterized by
retinal pigment deposits and has an estimated incidence of one in 4,000.
Although, to date, 45 known loci have been identified, none of them independently
account for a substantial portion of RP. Recently, the photoreceptor
cell-specific ATP-binding cassette transporter (ABCA4) gene was found to be
mutated in patients with STGD as well as autosomal recessive RP. In order to
further understand the contribution of this gene to the susceptibility to STGD
and RP, we analyzed three unrelated STGD families and one autosomal recessive RP 
family specifically for the more common variants (A1038V, G1961E, 2588G-->C,
R943Q or 2828G-->A) in the ABCA4 gene. Our analyses employing standard techniques
such as polymerase chain reaction, restriction fragment length polymorphism, and 
direct DNA sequencing of amplified products were able to identify one common
variant (R943Q) in all three STGD families but not in the RP family. All three
affected STGD individuals, however, were heterozygous for this variation, and
this alteration did not segregate with the disease and was also present in the
normal controls. Similar analysis of other common variants revealed no pathogenic
mutations in the STGD and RP families. It is likely that the variant identified
in this study represents a rare polymorphism (non-pathogenic). Although, at
present we cannot eliminate the possibility of this gene as a candidate gene,
future extensive studies on this as well as other candidate genes may uncover the
susceptibility gene for these recessive forms of the disorders in these families.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18506364 [PubMed - indexed for MEDLINE]

257: Ophthalmology. 2008 Sep;115(9):1474-9, 1479.e1-6. Epub 2008 May 27.

Risk factors for choroidal neovascularization and geographic atrophy in the
complications of age-related macular degeneration prevention trial.

Complications of Age-related Macular Degeneration Prevention Trial (CAPT)
Research Group.

Collaborators: Ying GS, Folk JC, Klein ML, Bressler SB, Browning DJ, Stoltz RA,
Grunwald JE, Alexander J, Liu C, Maguire MG, Park DW, Dugel PV, Thach AB,
Adhikari S, Alvarado C, Blaisdell J, Cavanagh J, Cornelius J, Marcos E, Tysiac K,
Jimenez N, Falcon A, Kosecki S, Marcos E, Slagle C, Tuttle C, Bohnen SE, Manor
BM, Martin J, Monday AC, Johnson RN, Ai E, McDonald HR, Rozenfeld I, Stolarczuk
M, Wood P, Curren K, Rozenfeld I, Teske B, Apushkin M, Linares S, DeBoer K,
Huggans S, Miller J, Uy J, Pavan PR, Billiris KK, Goldstein B, Iyer M, Menosky
MM, Mines J, Pautler SE, Millard SM, Sherouse S, West MD, Carlton S, Saxon W,
Sternberg P Jr, Aaberg T Sr, Hubbard B 3rd, Saperstein D, DuBois L, Ervin A,
Brower J, Brown J, Browne G, Burian G, Schmitz N, Waldron R, Gilman J, Myles BA, 
Anderson-Nelson S, Jampol LM, Weinberg DV, Muñana A, Rozenbajgier Z, Kaminski L, 
Koecher J, O'Donnell L, Swigost R, Volland L, Apushkin M, Habib A, Hulvey P,
Shankle J, Yuhr J, Orth D, Cohen J, MacCumber M, Merrill P, Figliulo C, Porcz L, 
Violetto CL, Drefcinski TN, Nenadov HP, Rago L, Doherty D, McVicker M, Nash D,
Folk JC, Boldt HC, Gehrs KM, Russell SR, Ivins R, Wallace SA, Hinz C, Harker M,
Heffron E, Karakas S, Barr CC, Bloom S, Kritchman B, Whittington G, Bowyer R,
Denning D, Goatley J, Nutting J, Swartz J, Temple E, Wilson W, Heier J, Frederick
AR Jr, Morley MG, Topping T, Hanner T, Doherty M, Davis HL, Beal L, Mahoney S, Ty
RA, Jones CM, Rapp E, Bressler SB, Schachat AP, Pieramici D, Bressler NM, Doll W,
Greenberg E, Jurao RA, Donohue DF, Frey M, Sheehan S, Porter T, Belt JE, Cain DR,
Falk R, Herring CM, McDonald JM, Capone A, Garretson BR, Hassan TS, Ruby AJ,
Kulak MM, Manatrey P, Osentoski T, Vandell L, Cumming K, Mitchell B, Zajechowski 
M, Bridges C, Siedlak P, Streasick P, Szydlowski L, McCannel CA, Buettner H, Pach
JM, Robertson DM, Ruszczyk MJ, Burrington J, LeBarron K, Stephan CA, Link T,
Rostvold JA, Grand G, Blinder K, Holekamp NM, Joseph DP, Meredith TA, Shah G,
Binning JA, Nobel GS, Wright CM, Boyd L, Gualdoni J, Light P, Soueidan N, Barts
B, Dahl J, Holle T, Raeber M, Rogers JM, Antoszyk AM, Browning DJ, Ellsmore T,
Helms JV, Lundy L, Stallings AH, Clark L, Efird S, Evans M, Jarrahi F, Mundy K,
Murphy H, O'Marah TL, Wike J, Woodland P, Davis L, McOwen M, Leff SR, Friedman E,
Green SN, Keyser B, Kushner M, Yarian DL, Hambrock C, Wagner L, Lucido M, Coffey 
D, Geddes M, Tantum T, Andersen F, Schlosser A, Singerman LJ, Miller D, Mittra R,
Novak M, Pendergast S, Stockfish JH, Zegarra H, Marella SD, Schura SA,
Smith-Brewer S, DuBois K, Hursky JL, Ilc M, Joyce SL, Tanner V, DuBois J,
Greanoff G, Lehnhardt DS, Davidorf FH, Chambers R, Chorich L, Taylor CS, Salerno 
J, Deringer MT, Milliron J, Perry J, Savage S, Dreyer RF, Ma C, Bartholomew P,
Crider HL, Kopfer MR, Larson JR, Armstrong C, DeShazer D, Hobbs S, Raunig W,
Reichenberger K, Schmidt S, Sitts D, Daniel HD, Johnson M, Logan RJ, Wohlsein HJ 
Jr, Klein ML, Wilson DJ, Nolte SK, Lindstrom PD, Pope S, Vahrenwald DR, Gaultney 
J, Redenbo E, Rice P, Steinkamp P, Wallace P, Grunwald JE, Berger JW, Brucker AJ,
Dunaief J, Fine SL, Ho A, Maguire AM, Tolentino M, Decker S, Hall E, Levin J,
McRay MN, Warley G, Boxley S, DuPont J, Geist C, Metelitsina T, Sheehan M, Devine
C, Elkins D, Nyberg W, Weeney L, Fish GE, Anand R, Spencer R, Arnwine J, Harris
J, Resmini N, Andrews M, Arceneaux S, McCarty B, Pierce D, Rollins R, Sanchez B, 
Aguado HA, Boleman B, Ellenich PB, King JG, Chandra SR, Altaweel M, Blodi B,
Gottlieb J, Ip M, Nork TM, Soderling ED, Walker W, Perry-Raymond J, Blatz M,
Buechner JM, Olson S, Pohlman A, Soderling B, Knutson G, Krolnik D, Peterson J,
Fine SL, Marilyn K.

CAPT Coordinating Center, University of Pennsylvania, Philadelphia, PA
19104-3309, USA.

OBJECTIVE: To determine risk factors for choroidal neovascularization (CNV) and
of geographic atrophy (GA) in eyes with large drusen. DESIGN: Cohort study within
a multicenter, randomized clinical trial of laser treatment for the prevention of
vision loss from advanced age-related macular degeneration. PARTICIPANTS: One
thousand fifty-two participants with 10 or more large drusen (>or=125 microm) and
visual acuity of 20/40 or better in each eye. METHODS: At baseline, participants 
provided a brief medical history. Trained readers evaluated baseline color
photographs for drusen characteristics and pigmentary abnormalities. One eye of
each participant was assigned to laser treatment and the contralateral eye was
assigned to observation. The Complications of Age-Related Macular Degeneration
Prevention Trial (CAPT) Reading Center readers identified CNV and endpoint GA
from color photographs and fluorescein angiograms obtained during follow-up
visits scheduled for 5 or 6 years. Estimates of relative risks (RRs) and 95%
confidence intervals (CIs) were obtained from survival analyses of observed and
treated eyes, considered separately and combined. MAIN OUTCOME MEASURES:
Development of CNV and of endpoint GA. RESULTS: Choroidal neovascularization
developed in 141 observed eyes and 141 treated eyes, including 57 patients
affected bilaterally. Statistically significant risk factors for CNV in the
multivariate model for all eyes were older age (RR, 2.81 [95% CI, 1.33-5.94] for 
>79 years vs. 50-59 years), cigarette smoking (RR, 1.98 [95% CI, 1.16-3.39] for
current vs. never), and focal hyperpigmentation (RR, 1.84 [95% CI, 1.22-2.76] for
>or=250 microm vs. none). Among eyes free of GA at baseline, endpoint GA
developed in 61 observed eyes and in 58 treated eyes, including 29 patients
affected bilaterally. Statistically significant risk factors for GA in the
multivariate model for all eyes were older age (RR, 6.39 [95% CI, 1.64-24.9] for 
>79 years vs. 50-59 years), greater retinal area covered by drusen (RR, 5.10 [95%
CI, 2.57-10.1] for >or=25% vs. <10%), retinal pigment epithelium (RPE)
depigmentation (RR, 2.64 [95% CI, 1.26-5.53), and focal hyperpigmentation (RR,
10.4 [95% CI, 4.51-24.0] for >or=250 microm vs. none). CONCLUSIONS: Among CAPT
participants, increased age and focal hyperpigmentation were risk factors for the
development of CNV and for GA. Cigarette smoking was significantly associated
with CNV only, whereas retinal area covered by drusen and RPE depigmentation were
associated significantly with GA only.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial
    Research Support, N.I.H., Extramural

PMID: 18502512 [PubMed - indexed for MEDLINE]

258: Acta Ophthalmol. 2008 Jun;86(4):401-3.

Apolipoprotein E genotype and risk for development of cataract and age-related
macular degeneration.

Utheim ØA, Ritland JS, Utheim TP, Espeseth T, Lydersen S, Rootwelt H, Semb SO,
Elsås T.

Eye Department, Ullevål University Hospital, Oslo, Norway. utyg@uus.no

PURPOSE: To study whether apolipoprotein E (APOE) genotypes are associated with
risk for developing cataract and age-related macular degeneration (AMD). METHODS:
A sample of 88 healthy adults (50-75 years) genotyped for polymorphisms of APOE
underwent an eye examination which included visual acuity (VA) testing, slit-lamp
cataract evaluation, optical coherence tomography (OCT) and fundus photography,
the last of which was analysed and graded for macular pathology at the Reading
Centre, Moorfields Eye Hospital, London. Two-by-two cross tables were analysed
using the Fisher-Boschloo unconditional full multinomial test. Two-sample t-tests
were used for comparing means of scale variables. RESULTS: Thirty-two
participants were diagnosed with cataract or had undergone cataract surgery in
one or both eyes, and 56 participants demonstrated no signs of cataract. We found
that APOE4 carriers were less likely to have cataract than non-APOE4 carriers (p 
= 0.039). No correlation between APOE genotypes and morphologic changes in the
macular region was revealed. However, APOE3 carriers disclosed significantly
higher average macular thickness in both eyes than non-APOE3 carriers (p =
0.012), and APOE3 carriers also had significantly better VA than non-APOE3
carriers (p = 0.041). CONCLUSIONS: We found no association between AMD and APOE
polymorphism in a population of 96 individuals aged 50-75 years. A weak negative 
association between APOE4 and cataract was uncovered in the same population.
Apolipoprotein E3 may be a protective factor against the loss of nerve fibres in 
the macular region.

PMID: 18498549 [PubMed - indexed for MEDLINE]

259: Ophthalmologica. 2008;222(3):199-204. Epub 2008 May 22.

Subretinal hemorrhages secondary to age-related macular degeneration:
psychological and vision-related functional perspectives.

Mozaffarieh M, Sacu S, Benesch T, Wedrich A.

Department of Ophthalmology, Medical University of Vienna, Vienna, Austria.

PURPOSE: To assess psychological, visual and functional aspects associated with
subretinal hemorrhages secondary to age-related macular degeneration (AMD).
METHOD: In this prospective, comparative, longitudinal study, 90 eyes of 90
patients with a subretinal hemorrhage, secondary to AMD, of at least 1 disk
diameter were treated with recombinant tissue plasminogen activator (rTPA) and
gas, and compared to 25 eyes of 25 controls. Outcome measures were: (1) visual
acuity, (2) self-reported vision-related quality of life (Visual Function 14-item
questionnaire) and (3)Hospital Anxiety and Depression (HAD) scores. Visual acuity
and questionnaire responses were recorded prior to as well as 2 weeks and 4
months after treatment. RESULTS: Improvements across objective visual acuity and 
vision-related functional measures, assessed at 2 weeks and 4 months, were
significantly higher in patients who had rTPA and gas injections than in controls
(p < 0.01). Patients were significantly more distressed at their 2-week follow-up
in comparison to controls (HAD scores p < 0.01). Comparisons to controls showed
no significant difference in psychological scores at the 4-month follow-up (p >
0.32). CONCLUSIONS: Patients with subretinal hemorrhages secondary to AMD are
psychologically distressed as a result of acute loss of vision. More attention
should be given to strategies that teach patients to cope with acute vision loss 
and thereby psychological disorder. (c) 2008 S. Karger AG, Basel

Publication Types: 
    Comparative Study

PMID: 18497530 [PubMed - indexed for MEDLINE]

260: PLoS ONE. 2008 May 21;3(5):e2199.

C2 and CFB genes in age-related maculopathy and joint action with CFH and
LOC387715 genes.

Jakobsdottir J, Conley YP, Weeks DE, Ferrell RE, Gorin MB.

Department of Biostatistics, Graduate School of Public Health, University of
Pittsburgh, Pittsburgh, Pennsylvania, United States of America.

BACKGROUND: Age-related maculopathy (ARM) is a common cause of visual impairment 
in the elderly populations of industrialized countries and significantly affects 
the quality of life of those suffering from the disease. Variants within two
genes, the complement factor H (CFH) and the poorly characterized LOC387715
(ARMS2), are widely recognized as ARM risk factors. CFH is important in
regulation of the alternative complement pathway suggesting this pathway is
involved in ARM pathogenesis. Two other complement pathway genes, the closely
linked complement component receptor (C2) and complement factor B (CFB), were
recently shown to harbor variants associated with ARM. METHODS/PRINCIPAL
FINDINGS: We investigated two SNPs in C2 and two in CFB in independent
case-control and family cohorts of white subjects and found rs547154, an intronic
SNP in C2, to be significantly associated with ARM in both our case-control
(P-value 0.00007) and family data (P-value 0.00001). Logistic regression analysis
suggested that accounting for the effect at this locus significantly (P-value
0.002) improves the fit of a genetic risk model of CFH and LOC387715 effects
only. Modeling with the generalized multifactor dimensionality reduction method
showed that adding C2 to the two-factor model of CFH and LOC387715 increases the 
sensitivity (from 63% to 73%). However, the balanced accuracy increases only from
71% to 72%, and the specificity decreases from 80% to 72%.
CONCLUSIONS/SIGNIFICANCE: C2/CFB significantly influences AMD susceptibility and 
although accounting for effects at this locus does not dramatically increase the 
overall accuracy of the genetic risk model, the improvement over the
CFH-LOC387715 model is statistically significant.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18493315 [PubMed - indexed for MEDLINE]

261: Invest Ophthalmol Vis Sci. 2008 Sep;49(9):4126-36. Epub 2008 May 16.

Evaluation of adenovirus-delivered human CD59 as a potential therapy for AMD in a
model of human membrane attack complex formation on murine RPE.

Ramo K, Cashman SM, Kumar-Singh R.

Department of Ophthalmology, Tufts University School of Medicine, Boston,
Massachusetts, USA.

PURPOSE: Complement-mediated damage to the retinal pigment epithelium (RPE),
Bruch membrane, and choroid has been associated with pathogenesis in age-related 
macular degeneration (AMD). The terminal step of complement activation involves
lysis of cells by the insertion of the membrane attack complex (MAC) in the
plasma membrane. The hypothesis that local overexpression of human CD59 (hCD59)
delivered by an adenovirus (Ad) vector to primary murine RPE cells in vitro, RPE 
in vivo, or cornea ex vivo protects those cells from human MAC deposition and
lysis was tested. METHODS: A humanized model of MAC deposition on murine cells
and murine ocular tissues including RPE and cornea was developed to permit
testing of human complement regulators in mice. A recombinant
adenovirus-expressing hCD59 was generated, and this virus was injected into the
subretinal space of adult mice. Subsequently, eyecups from these mice were
exposed to human serum, and the levels of MAC deposition on the RPE were
quantified. hCD59 was also expressed on murine cornea ex vivo and in murine
hepatocytes, and primary RPE cells in vitro and levels of human MAC deposition
and cell lysis were measured. RESULTS: Adenovirus-mediated delivery of hCD59 to
the RPE, cornea, or cells in culture protects those cells from human MAC
deposition and MAC-mediated damage and vesiculation. CONCLUSIONS: The humanized
model of MAC deposition on murine ocular tissues allows testing of human
complement regulators that may have potential in the treatment of AMD or other
diseases associated with complement activation.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18487376 [PubMed - indexed for MEDLINE]

262: Invest Ophthalmol Vis Sci. 2008 Sep;49(9):4137-44. Epub 2008 May 16.

High-resolution spectral domain-OCT imaging in geographic atrophy associated with
age-related macular degeneration.

Fleckenstein M, Charbel Issa P, Helb HM, Schmitz-Valckenberg S, Finger RP, Scholl
HP, Loeffler KU, Holz FG.

Department of Ophthalmology, University of Bonn, Bonn, Germany.

PURPOSE: To describe morphologic variations in outer retinal layers in eyes with 
atrophic age-related macular degeneration (AMD) using high-resolution,
spectral-domain optical coherence tomography (SD-OCT). METHODS: SD-OCT scans were
obtained with a combined confocal scanning laser ophthalmoscope (cSLO) and SD-OCT
for simultaneous tomographic and topographic in vivo imaging. A total of 81 eyes 
of 56 patients (mean age, 77.8 +/- 7.4 years) with geographic atrophy (GA) were
examined. Morphologic alterations were analyzed and classified in the
perilesional zone, at the junction between GA and nonatrophic retina, and in the 
atrophic area itself. RESULTS: In the perilesional zone, distinct morphologic
alterations included elevations of the outer retinal layers, thickening, and
spikes of the outer hyperreflective band as well as clumps at different
neurosensory retinal levels. At the junction, highly variable transitions of the 
outer retinal layers were present with different degrees of loss of the normal
hyperreflective bands. Within the actual GA, hyperreflective clumps at different 
retinal levels, segmented plaques of the outer band and elevations with variable 
reflectivity were visualized. CONCLUSIONS: SD-OCT imaging in eyes with GA
revealed a wide spectrum of morphologic alterations, both in the surrounding
retinal tissue and in the atrophic area. These alterations may reflect different 
disease stages or, alternatively, heterogeneity on a cellular and molecular
level. Longitudinal studies using in vivo SD-OCT imaging may allow evaluation of 
the relevance of these phenotypic changes as potential predictive markers for the
progression of disease (i.e., enlargement rates of GA over time) and may be used 
for monitoring of future therapeutic interventions.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18487363 [PubMed - indexed for MEDLINE]

263: Ophthalmology. 2008 Sep;115(9):1468-73, 1473.e1-2. Epub 2008 May 16.

Characteristics of choroidal neovascularization in the complications of
age-related macular degeneration prevention trial.

Maguire MG, Alexander J, Fine SL; Complications of Age-related Macular
Degeneration Prevention Trial (CAPT) Research Group.

Collaborators: Folk JC, Klein ML, Bressler SB, Browning DJ, Stoltz RA, Grunwald
JE, Alexander J, Liu C, Maguire MG, Park DW, Dugel PV, Thach AB, Adhikari S,
Alvarado C, Blaisdell J, Cavanagh J, Cornelius J, Marcos E, Tysiac K, Jimenez N, 
Falcon A, Kosecki S, Marcos E, Slagle C, Tuttle C, Bohnen SE, Manor BM, Martin J,
Monday AC, Johnson RN, Ai E, McDonald HR, Rozenfeld I, Stolarczuk M, Wood P,
Curren K, Rozenfeld I, Teske B, Apushkin M, Linares S, Huggans S, Miller J, Uy J,
Pavan PR, Billiris KK, Goldstein B, Iyer M, Menosky MM, Mines J, Pautler SE,
Millard SM, Sherouse S, West MD, Carlton S, Saxon W, Sternberg P Jr, Aaberg T Sr,
Hubbard B 3rd, Saperstein D, DuBois L, Ervin A, Brower J, Brown J, Browne G,
Burian G, Schmitz N, Waldron R, Gilman J, Myles BA, Anderson-Nelson S, Jampol LM,
Weinberg DV, Muñana A, Rozenbajgier Z, Kaminski L, Koecher J, O'Donnell L,
Swigost R, Volland L, Apushkin M, Habib A, Hulvey P, Shankle J, Yuhr J, Orth D,
Cohen J, MacCumber M, Merrill P, Figliulo C, Porcz L, Violetto CL, Drefcinski TN,
Nenadov HP, Rago L, Doherty D, McVicker M, Nash D, Folk JC, Boldt HC, Gehrs KM,
Russell SR, Ivins R, Wallace SA, Hinz C, Harker M, Heffron E, Karakas S, Barr CC,
Bloom S, Kritchman B, Whittington G, Bowyer R, Denning D, Goatley J, Nutting J,
Swartz J, Temple E, Wilson W, Heier J, Frederick AR Jr, Morley MG, Topping T,
Hanner T, Doherty M, Davis HL, Beal L, Mahoney S, Ty RA, Jones CM, Rapp E,
Bressler SB, Schachat AP, Pieramici D, Bressler NM, Doll W, Greenberg E, Jurao
RA, Donohue DF, Frey M, Sheehan S, Porter T, Belt JE, Cain DR, Falk R, Herring
CM, McDonald JM, Trese M, Capone A, Garretson BR, Hassan TS, Ruby AJ, Kulak MM,
Manatrey P, Osentoski T, Vandell L, Cumming K, Mitchell B, Zajechowski M, Bridges
C, Siedlak P, Streasick P, Szydlowski L, Buettner H, Pach JM, Robertson DM,
Ruszczyk MJ, Burrington J, LeBarron K, Stephan CA, Link T, Rostvold JA, Grand G, 
Blinder K, Holekamp NM, Joseph DP, Meredith TA, Shah G, Binning JA, Nobel GS,
Wright CM, Boyd L, Gualdoni J, Light P, Soueidan N, Barts B, Dahl J, Holle T,
Raeber M, Rogers JM, Antoszyk AN, Browning DJ, Ellsmore T, Helms JV, Lundy L,
Stallings AH, Clark L, Efird S, Evans M, Jarrahi F, Mundy K, Murphy H, O'Marah
TL, Wike J, Woodland P, Davis L, McOwen M, Leff SR, Friedman E, Green SN, Keyser 
B, Kushner M, Yarian DL, Hambrock C, Wagner L, Lucido M, Coffey D, Geddes M,
Tantum T, Andersen F, Schlosser A, Singerman LJ, Miller D, Mittra R, Novak M,
Pendergast S, Stockfish JH, Zegarra H, Marella SD, Schura SA, Smith-Brewer S,
DuBois K, Hursky JL, Ilc M, Joyce SL, Tanner V, DuBois J, Greanoff G, Lehnhardt
DS, Davidorf FH, Chambers R, Chorich L, Taylor CS, Salerno J, Deringer MT,
Milliron J, Perry J, Savage S, Dreyer RF, Ma C, Bartholomew P, Crider HL, Kopfer 
MR, Larson JR, Armstrong C, DeShazer D, Hobbs S, Raunig W, Reichenberger K,
Schmidt S, Sitts D, Daniel HD, Johnson M, Logan RJ, Wohlsein HJ Jr, Klein ML,
Wilson DJ, Nolte SK, Lindstrom PD, Pope S, Vahrenwald DR, Gaultney J, Redenbo E, 
Rice P, Steinkamp P, Wallace P, Grunwald JE, Berger JW, Brucker AJ, Dunaief J,
Fine SL, Ho A, Maguire AM, Tolentino M, Decker S, Hall E, Levin J, McRay MN,
Warley G, Boxley S, DuPont J, Geist C, Metelitsina T, Sheehan M, Devine C, Elkins
D, Nyberg W, Weeney L, Fish GE, Anand R, Spencer R, Arnwine J, Harris J, Resmini 
N, Andrews M, Arceneaux S, McCarty B, Pierce D, Rollins R, Sanchez B, Aguado HA, 
Boleman B, Ellenich PB, King JG, Chandra SR, Altaweel M, Blodi B, Gottlieb J, Ip 
M, Nork TM, Soderling ED, Walker W, Perry-Raymond J, Blatz M, Buechner JM, Olson 
S, Pohlman A, Soderling B, Knutson G, Krolnik D, Peterson J, Fine SL, Katz M.

Department of Ophthalmology, School of Medicine, University of Pennsylvania,
Philadelphia, Pennsylvania 19104-3309, USA.

OBJECTIVE: To describe the characteristics of incident choroidal
neovascularization (CNV) in observed and treated eyes in the Complications of
Age-related Macular Degeneration Prevention Trial (CAPT). DESIGN: Cross-sectional
descriptive study within a multicenter, randomized clinical trial. PARTICIPANTS: 
Patients who developed CNV during CAPT follow-up. METHODS: Inclusion criteria for
CAPT specified bilateral large drusen (>or=10 drusen at least 125 micro), visual 
acuity >or=20/40 in each eye, and age >or=50. Exclusion criteria included CNV and
geographic atrophy >1 Macular Photocoagulation Study (MPS) disc area or within
500 micro of the foveal center. One eye of each person was selected randomly for 
low-intensity laser treatment and the contralateral eye was observed. Fluorescein
angiography was performed at baseline, annually for >or=5 years, and whenever
there were symptoms of CNV. Trained readers at the CAPT Photograph Reading Center
assessed color stereo photographs and angiogram negatives to identify CNV. MAIN
OUTCOME MEASURES: Choroidal neovascularization was classified by type
(predominantly classic CNV, minimally classic CNV, occult only CNV, or scar),
location, and area. Visual acuity was measured by certified examiners. Symmetry
of characteristics between eyes of bilaterally affected patients was examined.
RESULTS: Choroidal neovascularization developed in 282 eyes of 225 patients. At
the time of detection, 192 (68%) of the lesions were occult only, 153 (54%) were 
subfoveal, and 157 (56%) were <or=2 MPS disc areas. Visual acuity was >or=20/40
in 123 (69%) of 179 eyes with visual acuity measured at the time of detection.
Choroidal neovascularization developed in both eyes in 57 patients (25%) during
CAPT follow-up. Lesions in eyes of bilaterally affected patients were no more
similar to each other than affected eyes in 2 different patients. CONCLUSIONS:
When patients are monitored closely, many CNV lesions can be detected outside of 
the fovea and when they are relatively small. Early detection may lead to
improved long-term visual acuity.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial
    Research Support, N.I.H., Extramural

PMID: 18486222 [PubMed - indexed for MEDLINE]

264: Ophthalmology. 2008 Sep;115(9):1480-8, 1488.e1-2. Epub 2008 May 16.

Low luminance visual dysfunction as a predictor of subsequent visual acuity loss 
from geographic atrophy in age-related macular degeneration.

Sunness JS, Rubin GS, Broman A, Applegate CA, Bressler NM, Hawkins BS.

The Richard E Hoover Rehabilitation Services for Low Vision and Blindness,
Greater Baltimore Medical Center, Baltimore, Maryland 21204, USA.
jsunness@gbmc.org

OBJECTIVE: To show that low luminance visual dysfunction is predictive of
subsequent visual acuity (VA) loss in eyes with geographic atrophy (GA) resulting
from age-related macular degeneration (AMD). DESIGN: Cohort study examining the
prospective natural history study of GA from 1992 through 2000 at the Wilmer Eye 
Institute. PARTICIPANTS: Ninety-one participants with GA resulting from AMD
without choroidal neovascularization in at least 1 eye who completed a 2-year
study examination. METHODS: Annual examinations included measurement of
best-corrected VA, low luminance VA, Pelli-Robson contrast sensitivity, reading
speed, examination, and fundus photography. The total GA area was quantified, as 
was the GA within a 10.2-mm(2) circle centered on the fovea. MAIN OUTCOME
MEASURES: Visual acuity loss at 2 years and risk factors for visual loss.
RESULTS: Participants with baseline VA of 20/50 or more had a 40% 2-year rate of 
VA loss of 3 lines or more, compared with 13% for the participants with worse
baseline acuities. The baseline low-luminance deficit (LLD) in VA was a strong
predictor of subsequent VA loss for all levels of baseline VA. Within the good
baseline VA group, the relative risk (RR) of 3-line loss for the worse LLD group 
compared with the better LLD group was 2.88 (95% confidence interval [CI],
1.13-7.35). The LLD is a stable and reproducible measure. Other significant
visual function predictors of subsequent VA loss in eyes with good baseline VA
included foveal dark-adapted sensitivity (RR, 4.20; 95% CI, 1.39-12.71) and
reduced reading rate (RR, 2.43; 95% CI, 1.11-5.31). The rate of VA loss within
the good acuity group was higher when the GA included 25% to 75% of the central
10.2 mm(2) than in eyes with GA including less than 25% or more than 75% of the
central 10.2 mm(2). The following were not significant predictors of subsequent
VA loss among these participants: age, gender, fellow eye diagnosis, fellow eye
VA, baseline GA area, and GA enlargement rate. CONCLUSIONS: Visual function
measures can predict the risk of future VA loss in subjects with GA and good
baseline VA. They may allow identification of the highest risk group for VA loss,
enabling more efficient design of clinical trials. They also may be appropriate
surrogate measures of foveal health in short-term treatment trials.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 18486216 [PubMed - indexed for MEDLINE]

265: Drugs. 2008;68(8):1029-36.

Neovascular age-related macular degeneration: potential therapies.

Chappelow AV, Kaiser PK.

Cole Eye Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.

Age-related macular degeneration (AMD) affects an estimated 14 million people
worldwide, and is the leading cause of severe, irreversible vision loss in
individuals over the age of 50 years in Western societies. Choroidal
neovascularization (CNV), the hallmark of 'wet', 'exudative' or 'neovascular'
AMD, is responsible for approximately 90% of cases of severe vision loss due to
AMD. Vascular endothelial growth factor (VEGF) has been shown to play a key role 
in the regulation of CNV and vascular permeability. Ranibizumab, the current gold
standard in the US for the treatment of neovascular AMD, exerts its effect
through binding and inhibition of all isoforms of VEGF. Randomized controlled
clinical trials have established ranibizumab as the first US FDA-approved therapy
for neovascular AMD to result in improvement in visual acuity. Despite impressive
outcomes, treatment with ranibizumab requires sustained treatment regimens and
frequent intravitreal injections. In this review, we discuss promising emerging
therapies for neovascular AMD that aim to improve outcomes, safety and treatment 
burden through novel mechanisms of action. Currently in phase III clinical
trials, VEGF Trap is a receptor decoy that targets VEGF with higher affinity than
ranibizumab and other currently available anti-VEGF agents. Another promising
therapeutic strategy is the blockade of VEGF effects by inhibition of the
tyrosine kinase cascade downstream from the VEGF receptor; such therapies
currently in development include vatalanib, TG100801, pazopanib, AG013958 and
AL39324. Small interfering RNA technology-based therapies have been designed to
downregulate the production of VEGF (bevasiranib) or VEGF receptors (AGN211745)
by degradation of specific messenger RNA. Other potential therapies include
pigment epithelium-derived factor-based therapies, nicotinic acetylcholine
receptor antagonists, integrin antagonists and sirolimus.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18484796 [PubMed - indexed for MEDLINE]

266: Mol Vis. 2008 Apr 25;14:782-806.

Extreme retinal remodeling triggered by light damage: implications for age
related macular degeneration.

Marc RE, Jones BW, Watt CB, Vazquez-Chona F, Vaughan DK, Organisciak DT.

Ophthalmology, University of Utah, John A. Moran Eye Center, Salt Lake City, UT
84132, USA. robert.marc@hsc.utah.edu

PURPOSE: Our objective was to comprehensively assess the nature and chronology of
neural remodeling in retinal degenerations triggered by light-induced retinal
damage (LIRD) in adult albino rodents. Our primary hypothesis is that all
complete photoreceptor degenerations devolve to extensive remodeling. An
hypothesis emergent from data analysis is that the LIRD model closely mimics
late-stage atrophic age relared macular degeneration (AMD). METHODS:
Sprague-Dawley (SD) rats received intense light exposures of varied durations and
survival times ranging from 0 to 240 days. Remodeling was visualized by
computational molecular phenotyping (CMP) of a small molecule library:
4-aminobutyrate (gamma), arginine (R), aspartate (D), glutamate (E), glutamine
(Q), glutathione (J), glycine (G), and taurine (tau). This library was augmented 
by probes for key proteins such as rod opsin, cone opsin and cellular retinal
binding protein (CRALBP). Quantitative CMP was used to profile 160 eyes from 86
animals in over 6,000 sections. RESULTS: The onset of remodeling in LIRD retinas 
is rapid, with immediate signs of metabolic stress in photoreceptors, the retinal
pigmented epithelium (RPE), the choriocapillaris, and Müller cells. In
particular, anomalous elevated aspartate levels appear to be an early stress
marker in photoreceptors. After the stress phase, LIRD progresses to focal
photoreceptor degeneration within 14 days and extensive remodeling by 60 days.
RPE and choriocapillaris losses parallel Müller cell distal seal formation, with 
progressive neuronal migration, microneuroma evolution, fluid channel formation, 
and slow neuronal death. The remaining retina in advanced light damage can be
classified as survivor, light damage (LD), or decimated zones where massive
Müller cell and neuronal emigration into the choroid leaves a retina depleted of 
neurons and Müller cells. These zones and their transitions closely resemble
human geographic atrophy. Across these zones, Müller cells manifest extreme
changes in the definitive Müller cell tauQE signature, as well as CRALBP and
arginine signals. CONCLUSIONS: LIRD retinas manifest remodeling patterns of
genetic retinal degeneration models, but involve no developmental complexities,
and are ultimately more aggressive, devastating the remaining neural retina. The 
decimation of the neural retina via cell emigration through the perforated
retina-choroid interface is a serious denouement. If focal remodeling in LIRD
accurately profiles late stage atrophic age-related macular degenerations, it
augurs poorly for simple molecular interventions. Indeed, the LIRD profile in the
SD rat manifests more similarities to advanced human atrophic AMD than most
genetically or immunologically induced murine models of AMD.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18483561 [PubMed - indexed for MEDLINE]

267: Ophthalmologica. 2008;222(4):240-4. Epub 2008 May 10.

Fundus autofluorescence, optical coherence tomography and visual acuity in
adult-onset foveomacular dystrophy.

Furino C, Boscia F, Cardascia N, Sborgia L, Sborgia C.

Department of Ophthalmology and Otolaryngology, University of Bari, Bari, Italy. 
caf.furino@libero.it

AIM: We investigated fundus autofluorescence (FA) patterns and tomographic
retinal changes by means of optical coherence tomography (OCT 3) in adult-onset
foveomacular vitelliform dystrophy (AOFVD) and their possible correlation with
best-corrected visual acuity (BCVA). METHODS: Eighteen eyes of 15 consecutive
patients (mean age: 73.73 +/- 9.5 years) presented to our observation with a
diagnosis of AOFVD underwent BCVA measurement, evaluation of FA distribution by
means of a confocal laser scanning ophthalmoscope and OCT 3 tomography. RESULTS: 
The mean BCVA was 20/40 (range: 20/20-20/100). The FA pattern was patchy in 9
eyes (50%), ring-like in 5 (27.7%), focal in 3 (16.6%) and linear in 1 (5.5%). No
correlation between FA patterns and BCVA was found. OCT 3 showed accumulation of 
highly reflective material between the neurosensory retina and retinal pigment
epithelium (RPE) in 12 eyes (66.6%) with an evident overlying photoreceptor layer
(PRL). In 5 eyes the highly reflective material was built up between the
neurosensory retina and RPE without evidence of PRL (27.7%). Only in 1 eye was
the subretinal accumulation site not well defined (5.5%). The mean thickness of
the deposit was 135.52 +/- 47.53 microm, while the residual neurosensory retina
thickness was 103.94 +/- 24.21 microm. The relationship between BCVA and the
thickness of the neurosensory retina over the lesion was not significant (p =
0.016, r = 0.33), while the correlation between BCVA and the material deposit
thickness (p = 0.017, r = 0.12) was significant. CONCLUSIONS: In AOFVD, FA
presented different patterns, while OCT usually shows a well-defined material
accumulation with a generally reduced neurosensory thickness between PRL and RPE.
FA imaging and OCT are useful and safe for the diagnosis and follow-up of AOFVD. 
(c) 2008 S. Karger AG, Basel.

PMID: 18477856 [PubMed - indexed for MEDLINE]

268: Arch Ophthalmol. 2008 May;126(5):670-8.

Reduction of endogenous angiogenesis inhibitors in Bruch's membrane of the
submacular region in eyes with age-related macular degeneration.

Bhutto IA, Uno K, Merges C, Zhang L, McLeod DS, Lutty GA.

Wilmer Ophthalmological Institute, Johns Hopkins University School of Medicine,
Baltimore, MD 21287-9115, USA.

OBJECTIVES: To determine the relative levels of 3 potent inhibitors of
angiogenesis (endostatin, pigment epithelium-derived factor, and thrombospondin
1) in the retinal pigment epithelium-Bruch's membrane-choriocapillaris complex in
the submacular region in aged control eyes and eyes with age-related macular
degeneration (AMD). METHODS: Immunohistochemical analysis with antibodies against
endostatin, pigment epithelium-derived factor, and thrombospondin 1 was performed
on the macular region of aged control donor eyes (n = 8; mean age, 79.8 years)
and eyes with AMD (n = 12; mean age, 83.9 years). Three independent masked
observers scored the reaction product (scored from 0-7). Mean scores from the
control eyes and the eyes with AMD were analyzed using 1-way analysis of variance
and unpaired t test. RESULTS: In control eyes, strong immunoreactivity of all 3
inhibitors was observed in the retinal pigment epithelium-Bruch's
membrane-choriocapillaris complex. Immunoreactivity for endostatin, pigment
epithelium-derived factor, and thrombospondin 1 in Bruch's membrane was
significantly lower in eyes with AMD compared with aged control eyes (analysis of
variance, P = .003, P = .009, and P < .001, respectively). In the
choriocapillaris, a significant reduction was observed in endostatin (analysis of
variance, P = .02) and thrombospondin 1 (analysis of variance, P = .005) in eyes 
with AMD. CONCLUSIONS: These findings suggest that endogenous angiogenesis
inhibitors in the retinal pigment epithelium-Bruch's membrane-choriocapillaris
complex may provide a biochemical barrier for choroidal neovascular invasion.
CLINICAL RELEVANCE: Decreased levels of angiogenic inhibitors at the retinal
pigment epithelium-Bruch's membrane-choriocapillaris complex in eyes with AMD
make Bruch's membrane vulnerable to choroidal neovascularization.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18474778 [PubMed - indexed for MEDLINE]

269: Ophthalmologica. 2008;222(4):249-53. Epub 2008 May 9.

Relationship between diabetic macular edema and peripheral Th1/Th2 balance.

Itoi K, Nakamura K, Oku H, Ishizaki E, Sugiyama T, Ueki M, Maeno T, Sato B, Ikeda
T.

Department of Ophthalmology, Osaka Medical College, Osaka, Japan.

PURPOSE: To determine whether inflammatory reactions are involved in the
pathogenesis of diabetic macular edema, we examined the relationship between
diabetic macular edema and the ratio of T helper 1 (Th1) to T helper 2 (Th2)
cells. METHODS: Thirty-nine diabetic patients with diabetic retinopathy were
evaluated at our hospital between February 2004 and February 2005. Blood samples 
were collected from each patient, and the ratio of CD4+ Th1 to Th2 cells
(Th1/Th2) was determined by flow cytometry after fluorescent antibody staining
for intracellular cytokines. Logistic regression analysis was used to determine
the association of macular edema with age, gender, HbA(1c) level, interval after 
retinal photocoagulation and Th1/Th2 ratios. Differences in these parameters were
also compared between patients with and without macular edema. RESULTS: Logistic 
regression analysis showed that the Th1/Th2 ratios were significantly associated 
with macular edema (odds ratio = 0.838; p = 0.02), while other variables were
not. The Th1/Th2 ratio was significantly lower in the patients with diabetic
macular edema than in those without (p = 0.02; t test). Higher Th1/Th2 ratios
tended to be associated with better visual acuity. CONCLUSIONS: Shifts in the
balance of Th1/Th2 towards a predominance of Th2 may represent an exacerbating
factor for diabetic macular edema, although a causal relationship has still not
been definitively determined. (c) 2008 S. Karger AG, Basel.

PMID: 18467850 [PubMed - indexed for MEDLINE]

270: Eur J Ophthalmol. 2008 May-Jun;18(3):469-72.

Incomplete posterior hyaloid detachment after intravitreal pegaptanib injection
in diabetic macular edema.

Montero JA, Ruiz-Moreno JM, De La Vega C.

Pio del Rio Hortega University Hospital, Ophthalmology Unit, Valladolid; and
Alicante Institute of Ophthalmology, VISSUM, Retina Unit, Alicante - Spain.
javmonmor@hotmail.com

PURPOSE: Posterior hyaloid adherences play a role in the pathogenesis of diabetic
macular edema (DME). Intravitreal antivascular endothelial growth factor (VEGF)
drugs are presently being used to treat DME. The authors report one case of
incomplete posterior hyaloid detachment (PHD) following intravitreal pegaptanib
to treat DME. This case shows a combined mechanism of DME resolution by anti VEGF
and PHD. METHODS: Prospective, interventional, single case report. One male
patient with bilateral DME was treated by intravitreal pegaptanib in his right
eye every 6 weeks for 6 months (five injections) and followed for 42 months.
RESULTS: Central macular thickness decreased from 511 to 376 microm at month 4 in
the treated eye and remained within 10% of this value during follow-up. The
posterior hyaloid became taut and partially detached after the third injection
and was almost completely detached 1 year later. Visual acuity remained unchanged
in both eyes during follow-up. CONCLUSIONS: PHD may play an important role in
cases where macular thickness is successfully reduced or better acuity is
achieved after intravitreal injections.

Publication Types: 
    Case Reports

PMID: 18465737 [PubMed - indexed for MEDLINE]

271: Eur J Ophthalmol. 2008 May-Jun;18(3):429-34.

Intravitreal triamcinolone for the treatment of refractory macular edema in
idiopathic intermediate or posterior uveitis.

Hogewind BF, Zijlstra C, Klevering BJ, Hoyng CB.

UMC St Radboud, Department of Ophthalmology, Nijmegen - The Netherlands.
b.hogewind@ohk.umcn.nl

PURPOSE: Cystoid macular edema (CME) is the most significant cause of visual loss
associated with idiopathic uveitis. The authors report on the use of intravitreal
triamcinolone acetonide (IVTA) in a group of patients with macular edema due to
idiopathic intermediate and posterior uveitis. METHODS: Retrospective,
noncomparative, interventional case series. Thirty-three eyes were included with 
uveitic CME that was refractory to topical steroids, oral prednisone, or a
combination thereof. Previous steroid treatment did not result in elevated
intraocular pressure (IOP). The eyes received an intravitreal injection with 10
mg triamcinolone acetonide, after best-corrected visual acuity (BCVA) and
fluorescein angiography (FA) were assessed. Ophthalmologic examination including 
FA was regularly performed during a 1-year follow-up period. RESULTS: Within 12
weeks after injection of IVTA, 50% of the eyes responded with an improvement in
vision of more than two lines and 30% of the eyes reached an IOP of > or = 21
mmHg (p<0.01). All eyes with an elevated IOP responded well on topical
antiglaucoma medication. After 12 months follow-up 40% of the eyes responded with
an improvement in vision of more than two lines and 28% of the affected eyes
underwent phacoemulsification during the follow-up. No other complications
occurred within a year after the treatment. CONCLUSIONS: In macular edema due to 
idiopathic intermediate or posterior uveitis IVTA improves the visual acuity
within the first 3 months. However, thereafter the visual acuity decreases again.
Cataract and elevated IOP are common side effects.

PMID: 18465727 [PubMed - indexed for MEDLINE]

272: Eur J Ophthalmol. 2008 May-Jun;18(3):384-91.

Endothelial function, intima-media thickness, and ankle-brachial index in
patients with cataract and age-related macular degeneration.

Zaliuniene D, Jasinskas V, Jurkevicius R, Gustiene O, Zaliunas R.

Department of Ophthalmology, Kaunas University of Medicine, Kaunas - Lithuania.
r.zaliunas@gmail.com

PURPOSE: To evaluate the association between cardiovascular risk factors,
including endothelial dysfunction, increased intima-media thickness (IMT) of the 
carotid arteries, ankle-brachial index (ABI), and age-related macular
degeneration (AMD), and cataract. METHODS: Forty-seven patients with AMD and
cataract, 35 with cataract only, and 49 with AMD were included. Carotid
ultrasound, ischemia-induced brachial artery reactivity test, and ABI in
conjunction with investigation of conventional cardiovascular risk factors were
performed. RESULTS: Increased levels (more than 1.23 mg/L) of high-sensitivity
C-reactive protein (hsCRP) and IMT (more than 0.97 mm) increased prevalence odds 
for AMD and cataract 3.1 and 3.9 times, respectively. CONCLUSIONS: Elevated hsCRP
or increased IMT of the carotid arteries are associated with comorbid cataract
and AMD, whereas there were no reliable differences between groups in respect to 
endothelial function and ABI.

PMID: 18465721 [PubMed - indexed for MEDLINE]

273: Retina. 2008 May;28(5):735-40.

ISIS-DME: a prospective, randomized, dose-escalation intravitreal steroid
injection study for refractory diabetic macular edema.

Kim JE, Pollack JS, Miller DG, Mittra RA, Spaide RF; Isis Study Group.

Medical College of Wisconsin, Milwaukee, USA.

PURPOSE:: To determine safety and efficacy of intravitreal triamcinolone
acetonide (IVTA) for refractory clinically significant diabetic macular edema
(DME). DESIGN:: Prospective, randomized, dose-escalation pilot study comparing
single injection of 2 mg versus 4 mg doses of IVTA. METHODS:: Inclusion criteria 
included clinically significant DME persisting >/=3 months after maximal laser
treatment and visual acuity </=20/40. Best-corrected ETDRS vision, intraocular
pressure, presence of DME, and fluorescein angiography (FA) were evaluated at 3
months and 6 months after injection. RESULTS:: Mean change in visual acuity at 3 
months compared to baseline was 7.1 letters (P = 0.01) in the 2 mg group and 12.5
letters in the 4 mg group (P < 0.0001). However, there was not a significant
difference in visual improvement between the 2 mg and 4 mg dose groups (P =
0.11). Vision improved >15 letters at 3 months in 23% (3/13) of 2 mg group and in
33% (5/15) of 4 mg group (P = 0.69), and 0% (0/11) and 21% (3/14) at 6 months,
respectively (P = 0.23). Visual improvement was more likely in cystoid-type DME
than diffuse DME. Intraocular pressure rise of >/=10 mmHg occurred in 19% (3/16) 
of 2 mg group and 41% (7/17) of 4 mg group. CONCLUSIONS:: Both doses of IVTA were
well tolerated and had significant positive effects on refractory DME for short
term. There were consistent trends throughout the study that suggest that a 4 mg 
IVTA may be more effective than a 2 mg dose. The benefit of IVTA was greater for 
cystoid-type DME.

Publication Types: 
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18463518 [PubMed - indexed for MEDLINE]

274: Retina. 2008 May;28(5):682-8.

Erratum in:
    Retina. 2008 Oct; 28(8):1178.

Changes in retinal sensitivity in patients with neovascular age-related macular
degeneration after systemic bevacizumab (avastin) therapy.

Prager F, Michels S, Simader C, Geitzenauer W, Schmidt-Erfurth U.

Department of Ophthalmology and Optometry, Medical University of Vienna, Vienna, 
Austria.

OBJECTIVE: To evaluate changes in central retinal sensitivity in patients with
neovascular age-related macular degeneration after systemic bevacizumab (Avastin;
Genentech, Inc., South San Francisco, CA) therapy. METHODS: For all eyes, the
central 12 x 12 degrees visual field was recorded using the MP 1 Microperimeter
(Nidek, Gamagori, Japan) at baseline and 1 week, 1 month, 3 months, and 6 months 
after initial treatment. Patients received systemic anti-vascular endothelial
growth factor (VEGF) therapy with three initial bevacizumab infusions at 2-week
intervals. Retreatment during follow-up was performed only in cases of choroidal 
neovascularization recurrence. Seven patients (12 eyes) received bevacizumab
infusions at a dose of 5 mg/kg, and 7 patients (9 eyes), at a dose of 2.5 mg/kg. 
RESULTS: Of 41 stimulation points, a mean absolute scotoma of 15 missed
stimulation points was measured at baseline, which decreased to 10 missed
stimulation points at month 3 (-5; P = 0.005) and to 11 stimulation points at
month 6 (-4; P = 0.106). The mean absolute scotoma size (in % of total tested
area) decreased from 33% to 22% (-11%; P = 0.011) at month 3 and to 23% (-10%, P 
= 0.123) at month 6. Mean differential light threshold increased significantly
throughout the observation period from 3.8 dB at baseline to 5.5 dB (+1.7 dB; P =
0.012) at month 6. CONCLUSIONS: Systemic bevacizumab therapy induced a
significant increase in mean retinal sensitivity at month 6 of follow-up and a
significant decrease of mean absolute scotoma size at month 3. The MP 1
Microperimeter proved to be a valuable tool in the evaluation of functional
benefits and retinal safety of anti-VEGF therapy with systemic bevacizumab.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18463510 [PubMed - indexed for MEDLINE]

275: Retina. 2008 May;28(5):675-81.

Intravitreal injection of bevacizumab combined with verteporfin photodynamic
therapy for choroidal neovascularization in age-related macular degeneration.

Smith BT, Dhalla MS, Shah GK, Blinder KJ, Ryan EH Jr, Mittra RA.

Barnes Retina Institute, St. Louis, Missouri, USA.

PURPOSE: To report the outcome for eyes treated with intravitreal injection of
bevacizumab combined with verteporfin photodynamic therapy (PDT) for choroidal
neovascularization (CNV) in age-related macular degeneration (AMD). STUDY DESIGN 
AND PARTICIPANTS: Interventional, consecutive, retrospective case series
including 40 eyes of 40 patients with newly diagnosed juxtafoveal or subfoveal
CNV secondary to AMD. METHODS: The charts of patients treated with a 1.25-mg
intravitreal injection of bevacizumab followed by PDT within a 2-week period were
reviewed. Main outcome measures were visual acuity stabilization (defined as no
change or a gain in visual acuity) and need for retreatment. RESULTS:
Thirty-three (83%) of 40 eyes had stabilization of visual acuity. Mean
improvement in visual acuity was 1.73 lines. Twenty-six eyes (65%) required only 
a single intravitreal injection of bevacizumab combined with PDT. Of the 23 eyes 
with 12 months of follow-up, 17 (74%) had stabilization of visual acuity, while 9
(40%) had improvement in visual acuity (mean, 1.22 Snellen lines). Eleven eyes
(48%) required only a single combined treatment for CNV resolution at the
12-month follow-up. Fifteen (88%) of 17 eyes with only 6 months of follow-up
required only a single combined treatment. There were no complications such as
endophthalmitis, uveitis, or ocular hypertension. CONCLUSION: These findings
suggest that eyes treated with both intravitreal injection of bevacizumab and PDT
require none to a minimal number of re-treatments to have stabilization of
vision, even at 12 months of follow-up. Further investigation with large
controlled trials is warranted to outline the appropriate treatment paradigm for 
combination therapy.

PMID: 18463509 [PubMed - indexed for MEDLINE]

276: Health Technol Assess. 2008 May;12(16):iii-iv, ix-201.

Ranibizumab and pegaptanib for the treatment of age-related macular degeneration:
a systematic review and economic evaluation.

Colquitt JL, Jones J, Tan SC, Takeda A, Clegg AJ, Price A.

Southampton Health Technology Assessments Centre, Wessex Institute for Health
Research and Development, University of Southampton, UK.

OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of
ranibizumab and pegaptanib for subfoveal choroidal neovascularisation (CNV)
associated with wet age-related macular degeneration (AMD). DATA SOURCES:
Electronic databases were searched from inception to September 2006. Experts in
the field were consulted and manufacturers' submissions were examined. REVIEW
METHODS: The quality of included studies was assessed using standard methods and 
the clinical effectiveness data were synthesised through a narrative review with 
full tabulation of results. A model was developed to estimate the
cost-effectiveness of ranibizumab and of pegaptanib (separately), compared with
current practice or best supportive care, from the perspective of the NHS and
Personal Social Services. Two time horizons were adopted for each model. The
first adopted time horizons determined by the available trial data. The second
analysis extrapolated effects of treatment beyond the clinical trials, adopting a
time horizon of 10 years. RESULTS: The combined analysis of two randomised
controlled trials (RCTs) of pegaptanib [0.3 mg (licensed dose), 1.0 mg and 3.0
mg] versus sham injection in patients with all lesion types was reported by three
publications (the VISION study). Three published RCTs of ranibizumab were
identified (MARINA, ANCHOR, FOCUS), and an additional unpublished RCT was
provided by the manufacturer (PIER). Significantly more patients lost less than
15 letters of visual acuity at 12 months when taking pegaptanib (0.3 mg: 70% of
patients; 1.0 mg: 71% of patients; 3.0 mg: 65% of patients) or ranibizumab (0.3
mg: 94.3-94.5%; 0.5 mg: 94.6-96.4%) than sham injection patients (55% versus
pegaptanib and 62.2% versus ranibizumab) or, in the case of ranibizumab,
photodynamic therapy (PDT) (64.3%). The proportion of patients gaining 15 letters
or more (a clinically important outcome having a significant impact on quality of
life) was statistically significantly greater in the pegaptanib group for doses
of 0.3 and 1.0 mg but not for 3.0 mg, and for all ranibizumab groups compared to 
the sham injection groups or PDT. This was also statistically significant for
patients receiving 0.5 mg ranibizumab plus PDT compared with PDT plus sham
injection. Pegaptanib patients lost statistically significantly fewer letters
after 12 months of treatment than the sham group [mean letters lost: 7.5 (0.3
mg), 6.5 (1.0 mg) or 10 (3.0 mg) vs 14.5 (sham)]. In the MARINA and ANCHOR
trials, ranibizumab patients gained letters of visual acuity at 12 months whereas
patients with sham injection or PDT lost about 10 letters (p<0.001) and in the
PIER study, ranibizumab patients lost significantly fewer than the sham injection
group. Significantly fewer patients receiving pegaptanib or ranibizumab
deteriorated to legal blindness compared with the control groups. Adverse events 
were common for both pegaptanib andranibizumab but most were mild to moderate.
Drug costs for 1 year of treatment were estimated as 4626 pounds for pegaptanib
and 9134 pounds for ranibizumab. Non-drug costs accounted for an additional 2614 
pounds for pegaptanib and 3120 pounds for ranibizumab. Further costs are
associated with the management of injection-related adverse events, from 1200
pounds to 2100 pounds. For pegaptanib compared with usual care, the incremental
cost-effectiveness ratio (ICER) ranged from 163,603 pounds for the 2-year model
to 30,986 pounds for the 10-year model. Similarly, the ICERs for ranibizumab for 
patients with minimally classic and occult no classic lesions, compared with
usual care, ranged from 152,464 pounds for the 2-year model to 25,098 pounds for 
the 10-year model. CONCLUSIONS: Patients with AMD of any lesion type benefit from
treatment with pegaptanib or ranibizumab on measures of visual acuity when
compared with sham injection and/or PDT. Patients who continued treatment with
either drug appeared to maintain benefits after 2 years of follow-up. When
comparing pegaptanib and ranibizumab, the evidence was less clear due to the lack
of direct comparison through head-to-head trials and the lack of opportunity for 
indirect statistical comparison due to heterogeneity. The cost-effectiveness
analysis showed that the two drugs offered additional benefit over the
comparators of usual care and PDT but at increased cost. Future research should
encompass trials to compare pegaptanib with ranibizumab and bevacizumab, and to
investigate the role of verteporfin PDT in combination with these drugs. Studies 
are also needed to assess adverse events outside the proposed RCTs, to consider
the optimal dosing regimes of these drugs and the benefits of re-treatment after 
initial treatment, and to review costing in more detail. Health state utilities
and their relationship with visual acuity and contrast sensitivity, the
relationship between duration of vision loss and the quality of life and
functional impact of vision loss, behavioural studies of those genetically at
risk are other topics requiring further research.

Publication Types: 
    Review

PMID: 18462575 [PubMed - indexed for MEDLINE]

277: PLoS ONE. 2008 May 7;3(5):e2091.

Mitochondrial DNA polymorphism A4917G is independently associated with
age-related macular degeneration.

Canter JA, Olson LM, Spencer K, Schnetz-Boutaud N, Anderson B, Hauser MA, Schmidt
S, Postel EA, Agarwal A, Pericak-Vance MA, Sternberg P Jr, Haines JL.

Center for Human Genetics Research, Department of Molecular Physiology and
Biophysics, Vanderbilt University Medical Center, Nashville, Tennessee, United
States of America. jeff.canter@vanderbilt.edu

The objective of this study was to determine if MTND2*LHON4917G (4917G), a
specific non-synonymous polymorphism in the mitochondrial genome previously
associated with neurodegenerative phenotypes, is associated with increased risk
for age-related macular degeneration (AMD). A preliminary study of 393
individuals (293 cases and 100 controls) ascertained at Vanderbilt revealed an
increased occurrence of 4917G in cases compared to controls (15.4% vs.9.0%, p =
0.11). Since there was a significant age difference between cases and controls in
this initial analysis, we extended the study by selecting Caucasian pairs matched
at the exact age at examination. From the 1547 individuals in the Vanderbilt/Duke
AMD population association study (including 157 in the preliminary study), we
were able to match 560 (280 cases and 280 unaffected) on exact age at
examination. This study population was genotyped for 4917G plus specific
AMD-associated nuclear genome polymorphisms in CFH, LOC387715 and ApoE. Following
adjustment for the listed nuclear genome polymorphisms, 4917G independently
predicts the presence of AMD (OR = 2.16, 95%CI 1.20-3.91, p = 0.01). In
conclusion, a specific mitochondrial polymorphism previously implicated in other 
neurodegenerative phenotypes (4917G) appears to convey risk for AMD independent
of recently discovered nuclear DNA polymorphisms.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 18461138 [PubMed - indexed for MEDLINE]

278: Br J Ophthalmol. 2008 Jul;92(7):916-21. Epub 2008 May 6.

Use of ocular hypotensive prostaglandin analogues in patients with uveitis: does 
their use increase anterior uveitis and cystoid macular oedema?

Chang JH, McCluskey P, Missotten T, Ferrante P, Jalaludin B, Lightman S.

Department of Clinical Ophthalmology, Institute of Ophthalmology, Moorfields Eye 
Hospital, City Road, London, UK.

AIM: A retrospective comparative case series was studied to determine whether the
use of prostaglandin (PG) analogues to treat raised intraocular pressure (IOP) in
patients with uveitis resulted in an increase in the frequency of anterior
uveitis or cystoid macular oedema (CMO). METHODS: 163 eyes of 84 consecutive
patients with uveitis and raised IOP treated with a PG analogue at two tertiary
referral uveitis clinics were identified over a 3-month period. Control eyes were
selected as those uveitic eyes of the same patients, which were treated with
topical IOP-lowering agent(s) other than a PG analogue. Pretreatment IOP was
compared with the mean IOP during PG analogue treatment. The frequency of
anterior uveitis and CMO during PG analogue treatment was compared with the
frequency of these complications in the control eyes during non-PG IOP-lowering
treatment. RESULTS: Significant IOP reductions were observed during PG analogue
treatment. There was no significant difference in the frequency of anterior
uveitis in those eyes treated with PG analogues and those treated with non-PG
agents (p = 0.87, Fisher exact test). None of the 69 uveitic eyes without a
previous history of CMO developed this complication. There was no increase in the
frequency of visually significant CMO during PG treatment compared with that
during non-PG treatment (p = 0.19, Fisher exact test). CONCLUSION: This study
demonstrates that PG analogues are potent topical medications for lowering raised
IOP in patients with uveitis and are not associated with increased risk of CMO or
anterior uveitis.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 18460537 [PubMed - indexed for MEDLINE]

279: Am J Ophthalmol. 2008 Jul;146(1):91-5. Epub 2008 May 2.

Treatment of neovascular age-related macular degeneration with intravitreal
bevacizumab: efficacy of three consecutive monthly injections.

Melamud A, Stinnett S, Fekrat S.

Duke University Eye Center, Erwin Road, Durham, NC 27710, USA.

PURPOSE: To report the efficacy of treatment of neovascular age-related macular
degeneration (AMD) with intravitreal bevacizumab (Avastin; Genentech, Inc, South 
San Francisco, California, USA) when administered in a series of three monthly
injections followed by a period of observation. DESIGN: Retrospective case
series. METHODS: Retrospective review of consecutive eyes with all choroidal
neovascular lesion subtypes resulting from neovascular AMD treated with
intravitreal bevacizumab. Treatment consisted of a pars plana injection of 1.25
mg Avastin (0.05 ml bevacizumab at a concentration of 25 mg/ml). Evaluation
consisted of a complete ophthalmologic examination, including best-corrected
visual acuity (VA) measurement, ophthalmoscopy, and optical coherence tomography.
Eyes received a series of three monthly injections followed by a three-month
period of observation. RESULTS: A total of 36 patients (37 eyes) received a
series of three consecutive monthly intravitreal injections of bevacizumab.
Twenty (54%) of 37 eyes had no previous treatments for neovascular AMD in the eye
that received bevacizumab. Seventeen (46%) of 37 eyes had received some previous 
treatment before initiation of bevacizumab therapy. Intravitreal Avastin therapy 
produced an improvement in foveal thickness over time in eyes with neovascular
AMD. This improvement was sustained during the series of three monthly
injections. All eyes experienced worsening after three months without treatment. 
No statistically significant effect on VA was demonstrated in this series.
CONCLUSION: Intravitreal bevacizumab therapy produced an improvement in foveal
thickness over time in eyes with neovascular AMD when one injection was given
each month for three consecutive months. All eyes experienced increased foveal
thickening during the subsequent three months without treatment.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18455144 [PubMed - indexed for MEDLINE]

280: Klin Monatsbl Augenheilkd. 2008 May;225(5):497-9.

Intravitreal triamcinolone injection for unresponsive cystoid macular oedema in
probable Behçet's disease as an additional therapy.

Oueghlani E, Pavésio CE.

Moorfields Eye Hospital, London, UK. oueghla_eve@hotmail.com

BACKGROUND: We present the description of a successful outcome of intravitreal
triamcinolone injection (IVTA) in a patient with cystoid macular oedema (CME) and
severe retinal vasculitis suggestive of ocular Behçet's disease. HISTORY AND
SIGNS: A healthy 32 year-old Caucasian man presented initially with right retinal
vasculitis with preserved vision. Despite initial systemic treatment with high
dose steroids, he developed CME with a reduction in vision. THERAPY AND OUTCOME: 
IVTA injection was carried out, and resulted in a good anatomic and functional
response. The same picture developed in his left eye 2 months later and a similar
response occurred following IVTA. Six months after the initial episode and
despite treatment with cyclosporine and azathioprine, CME reoccurred in his RE
inducing a decrease of his VA from 6/5 to 6/24. IVTA injection was repeated and a
week later his VA increased to 6/6. At this stage patient was referred for
initiation of therapy with infliximab. CONCLUSION: IVTA injection appears to be
very helpful for the resolution of acute CME and for visual recovery, but we
would like to emphasise that even though this approach seems to be helpful in an 
acute situation, the effect is short-lived and proper immunosuppression is needed
for long-term control of the disease and its complications.

PMID: 18454410 [PubMed - indexed for MEDLINE]

281: Klin Monatsbl Augenheilkd. 2008 May;225(5):491-4.

Retinal dysfunction in combined methylmalonic aciduria and homocystinuria (Cblc) 
disease: a spectrum of disorders.

Gaillard MC, Matthieu JM, Borruat FX.

Hôpital Ophtalmique Jules Gonin, Lausanne, Switzerland.

BACKGROUND: Cobalamin C methylmalonic aciduria with homocystinuria (cblC disease)
is a rare hereditary inborn error of cobalamin metabolism, characterised by
neurological, haematological and ophthalmological abnormalities. PATIENTS AND
METHODS: Three consecutive patients with Cblc disease were examined.
Investigations included slit lamp and fundus examination and full-field ERG.
RESULTS: A maculopathy associated with both photopic and scotopic abnormal ERG
was present in two cases and a salt and pepper retinopathy with abnormal photopic
ERG was detected in the third patient. CONCLUSIONS: Despite early treatment and
regular metabolic controls, all our patients exhibited both retinal and ERG
abnormalities. There was no correlation between funduscopic appearance and the
type of photoreceptor dysfunction. A literature review disclosed a retinopathy in
29 / 70 cases with cblC disease, with an abnormal ERG in 8 of the 12 tested
cases, most with retinopathy. Retinal dysfunction in cblC disease may be more
frequent than previously thought, and can involve cones only or both rods and
cones. We recommend a formal ocular examination with full-field ERG in patients
with Cblc disease.

Publication Types: 
    Case Reports

PMID: 18454408 [PubMed - indexed for MEDLINE]

282: Klin Monatsbl Augenheilkd. 2008 May;225(5):488-90.

Spectral optical coherence tomography findings in adult-onset foveomacular
vitelliform dystrophy.

Petropoulos IK, Desmangles PM, Matter MA.

Centre Ophtalmologique de la Terrassière, Geneva, Switzerland.
ipetropoulos@cot-ge.ch

BACKGROUND: Adult-onset foveomacular vitelliform dystrophy (AOFVD) is typically
bilateral and symmetrical. We present the spectral optical coherence tomography
(OCT) findings in two patients with unilateral AOFVD. PATIENTS AND METHODS: Case 
1 represents a 76-year-old man followed angiographically over the last 6 years
for a macular lesion in his right eye. Visual acuity in the right eye has
decreased from 1.0 to 0.6. In case 2, a 69-year-old man presented with blurred
vision in his right eye. Visual acuity was 0.7 in the right eye and 1.0 in the
left eye. In both patients, spectral OCT (Copernicus SOCT System) was performed. 
RESULTS: In case 1, fluorescein angiography showed a juxtafoveal hyperfluorescent
lesion 2 / 3 of disc area in size, without late leakage. OCT showed a cystic oval
lesion with thick walls, located between the retinal pigment epithelium (RPE) and
photoreceptor layers. In case 2, OCT showed a hyperreflective round lesion also
located between the RPE and photoreceptor layers, elevating the overlying inner
retina. CONCLUSIONS: Spectral OCT enables enhanced visualization of the retinal
layers and provides useful information regarding the diagnosis and the exact
location of AOFVD.

Publication Types: 
    Case Reports

PMID: 18454407 [PubMed - indexed for MEDLINE]

283: Klin Monatsbl Augenheilkd. 2008 May;225(5):465-8.

Early detection of Best's disease in childhood due to ineffective orthoptic
treatment.

Jaggi GP, Wirthlin J, Eggmann A, Killer HE, Forrer A.

Department of Ophthalmology Kantonsspital Aarau, Aarau, Switzerland.
gregor.jaggi@gmx.ch

BACKGROUND: A meticulous fundoscopy is an essential examination before
administering an orthoptic occlusion therapy (patching), even in cases with a
"clear indication" for patching. In this case of an 8-year-old hyperopic boy the 
subsequent fundoscopy revealed a bilateral maculopathy that explained the
stagnation of the increase of the monocular visual acuity (VA) in spite of a
correctly applied patching. HISTORY AND SIGNS: The patient was a boy (8 years
old) with a history of ineffective orthoptic treatment for 15 months due to
hyperopia. Complete ophthalmological examination, optical coherence tomography
(Cirrus HD-OCT, Zeiss, Germany) and electro-oculography (EOG) were performed. No 
"everyday" symptoms were found. Best corrected VA (hyperopic) on the right was 10
/ 20, on the left 8 / 20. Binocular VA was 20 / 20. 15 out of 15 Ishihara plates 
were identified on both sides. Orthophoria has been seen. Perimetry revealed
bilateral nasal-parafoveal microscotoma. Fundoscopy showed a confined and
slightly prominent yellow spot on the temporal side of the fovea. OCT revealed a 
subfoveal accumulation of solid material in the RPE in both eyes. EOG showed
normal findings in our case. THERAPY AND OUTCOME: There was no further
deterioration of VA in a follow-up time of 12 months. CONCLUSIONS: Ineffective
orthoptic treatment (patching) in amblyopic children should prompt the
ophthalmologist to a meticulous fundoscopy, even if done so before patching,
which is highly recommended. This young patient had no "everyday" visual
symptoms. Because mainly the temporal fovea on both sides was affected, he showed
normal binocular VA inspite of bilateral VA reduction. The authors think that
this effect is due to biretinal summation (retinal filling in).

Publication Types: 
    Case Reports

PMID: 18454400 [PubMed - indexed for MEDLINE]

284: Klin Monatsbl Augenheilkd. 2008 May;225(5):462-4.

Mitochondrial DNA (mtDNA) A 3243G mutation associated with an annular perimacular
retinal atrophy.

Adjadj E, Mansouri K, Borruat FX.

Hôpital Ophtalmique Jules Gonin, Lausanne, Switzerland.

BACKGROUND: A point mutation at the locus 3243 of the mitonchondrial DNA (mtDNA) 
is associated with either the MIDD syndrome (maternally inherited diabetes,
deafness), the MELAS syndrome (myopathy, encephalitis, lactic acidosis, stroke)
or cardiac, digestive, endocrine or exocrine dysfunctions. We report a peculiar
maculopathy in two patients with an mtDNA 3243 mutation. HISTORY AND SIGNS: Case 
1: A visually asymptomatic 40-year-old woman was examined for screening of
diabetic retinopathy. Visual acuity was 10 / 10 in both eyes. Case 2: A
54-year-old woman with deafness and diabetes complained of visual loss. Visual
acuity was 6 / 10 for the right eye and 0.5 / 10 for the left eye. Both patients 
exhibited a chorioretinal areolar atrophy. Case 1 was followed over 15 years and 
exhibited a slow progression of the maculopathy with moderate loss of visual
acuity to 6 / 10 in both eyes, but marked handicap from the annular scotoma.
THERAPY AND OUTCOME: None. CONCLUSION: Both patients presented a perimacular
annular retinal atrophy. Patients harbouring mtDNA 3243 mutation should be
examined for the presence of a maculopathy, even if they are asymptomatic.
Conversely, the finding of such a geographic maculopathy should suggest the
possibility of a point mutation at the locus 3243 of the mitochondrial DNA,
especially in the presences of diabetes mellitus and/or deafness.

Publication Types: 
    Case Reports
    Review

PMID: 18454399 [PubMed - indexed for MEDLINE]

285: Klin Monatsbl Augenheilkd. 2008 May;225(5):408-12.

Pattern of macular thickness changes measured by ocular coherence tomography in
patients with multiple sclerosis.

Gugleta K, Mehling M, Kochkorov A, Grieshaber M, Katamay R, Flammer J, Orgül S,
Kappos L.

Outpatient Neurology Clinic, University Hospital Basel, Basel, Switzerland.

BACKGROUND: An analysis of the pattern of retinal thickness changes in macula in 
patients with multiple sclerosis (MS) was performed. PATIENTS AND METHODS: In
fifteen patients with MS retinal thickness measurements in the central (fovea
plus inner macular ring) and peripheral (outer ring) macula obtained by ocular
coherence tomography (OCT-3 device) were compared to those of 15 age-matched
healthy controls. RESULTS: Eyes of MS patients had on the average a thinner
macula (241.8 +/- 20.6 micrometers) than control eyes (252.0 +/- 16.4, p value
0.038). Significant segmental differences occurred in the central macula (p =
0.013). Eight eyes with a positive history of optic neuritis (ON) had on average 
a thinner macula (226.8 +/- 14.0) than eyes of MS patients without a history of
ON (non-ON eyes: 247.3 +/- 20.1, p value 0.01). The only measure significantly
different between non-ON and control eyes was the ratio between the central and
peripheral macular thickness (p = 0.017). Average macular thickness in non-ON
eyes, unlike control eyes (r = - 0.63, p = 0.0002), did not correlate with age (r
= 0.01, p = 0.97), however, it did show a borderline correlation with disease
duration (r = - 0.41, p = 0.056). CONCLUSIONS: Preferential thinning in the
central relative to the peripheral macular region is present in eyes of patients 
with MS. The macular thickness pattern is likely due to the histological
distribution of nerve fibre layer and retinal ganglion cell in the macular area
and seems to be particularly informative of neurodegeneration in the eyes of MS
patients without a history of optic neuritis.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 18454382 [PubMed - indexed for MEDLINE]

286: Klin Monatsbl Augenheilkd. 2008 May;225(5):397-400.

Treatment of central retinal vein occlusion-related macular edema with
intravitreal bevacizumab (Avastin): preliminary results.

Pournaras JA, Nguyen C, Vaudaux JD, Konstantinidis L, Ambresin A, Wolfensberger
T.

Jules Gonin Eye Hospital, University of Lausanne, Lausanne, Switzerland.

PURPOSE: To assess the safety and efficacy of treatment of macular edema
secondary to central retinal vein occlusion (CRVO) with intravitreal bevacizumab.
PATIENTS AND METHOD: The ongoing prospective study included 8 consecutive
patients (8 eyes) with macular edema secondary to CRVO (6 non ischemic and 2
ischemic), treated with intravitreal injection of 1.25 mg (0.05 mL) of
bevacizumab. Main outcome was best corrected visual acuity (BCVA) and central
foveal thickness (CFT) measured by optical coherence tomography monthly during
one year. Retreatment criteria include decrease of BCVA, persistence of macular
edema on angiograms and increase of CFT. RESULTS: Mean age of the eight patients 
was 68 years (range: 50-82 years). Mean duration of symptoms before injection was
98 days (range: 3-289). Mean follow-up was 3.25 months. At baseline, mean BCVA
was 0.84 logMar and mean baseline CFT was 771 microm. Mean BCVA was 0.36 and mean
CFT thickness was 275 microm (n = 8) at month 1, 0.41 and 411 microm at month 2
(n = 7), 0.3 and 344 microm at month 3 (n = 6), 0.3 and 397 microm at month 4 (n 
= 5), respectively. In 75 % of patients, a single injection was not sufficient,
and retreatment needed. No serious adverse events were observed. CONCLUSIONS:
Treatment of macular edema secondary to CRVO with intravitreal bevacizumab
injection of 1.25 mg was well tolerated and associated with marked macular
thickness reduction and BCVA improvement in all patients. A trend towards
reduction of foveal thickness and improvement of visual acuity was observed in
both acute and chronic CRVO.

Publication Types: 
    Clinical Trial

PMID: 18454380 [PubMed - indexed for MEDLINE]

287: Klin Monatsbl Augenheilkd. 2008 May;225(5):376-9.

The potential effect of population development, smoking and antioxidant
supplementation on the future epidemiology of age-related macular degeneration in
Switzerland.

Bauer P, Barthelmes D, Kurz M, Fleischhauer JC, Sutter FK.

Department of Ophthalmology, University Hospital Zurich, Zurich, Switzerland.

BACKGROUND: Due to the predicted age shift of the population an increase in the
number of patients with late AMD is expected. At present smoking represents the
only modifiable risk factor. Supplementation of antioxidants in patients at risk 
is the sole effective pharmacological prevention. The aim of this study is to
estimate the future epidemiological development of late AMD in Switzerland and to
quantify the potential effects of smoking and antioxidants supplementation.
METHODS: The modelling of the future development of late AMD cases in Switzerland
was based on a meta-analysis of the published data on AMD-prevalence and on
published Swiss population development scenarios until 2050. Three different
scenarios were compared: low, mean and high. The late AMD cases caused by smoking
were calculated using the "population attributable fraction" formula and data on 
the current smoking habits of the Swiss population. The number of potentially
preventable cases was estimated using the data of the Age-Related Eye Disease
Study (AREDS). RESULTS: According to the mean population development scenario,
late AMD cases in Switzerland will rise from 37 200 cases in 2005 to 52 500 cases
in 2020 and to 93 200 cases in 2050. Using the "low" and the "high" scenarios the
late AMD cases may range from 49 500 to 56 000 in 2020 and from 73 700 to 118 400
in 2050, respectively. Smoking is responsible for approximately 7 % of all late
AMD cases, i. e., 2600 cases in 2005, 3800 cases in 2020, 6600 cases in 2050
("mean scenario"). With future antioxidant supplementation to all patients at
risk another 3100 cases would be preventable until 2020 and possibly 23 500 cases
until 2050. CONCLUSION: Due to age shift in the population a 2.5-fold increase in
late AMD cases until 2050 is expected, representing a socioeconomic challenge.
Cessation of smoking and supplementation of antioxidants to all patients at risk 
has the potential to reduce this number. Unfortunately, public awareness is low. 
These data may support health-care providers and public opinion leaders when
developing public education and prevention strategies.

PMID: 18454376 [PubMed - indexed for MEDLINE]

288: Invest Ophthalmol Vis Sci. 2008 Sep;49(9):3864-9. Epub 2008 Apr 30.

Oral supplementation of lutein/zeaxanthin and omega-3 long chain polyunsaturated 
fatty acids in persons aged 60 years or older, with or without AMD.

Huang LL, Coleman HR, Kim J, de Monasterio F, Wong WT, Schleicher RL, Ferris FL
3rd, Chew EY.

Clinical Trials Branch, Division of Epidemiology and Clinical Research, National 
Eye Institute, National Institutes of Health, Bethesda, Maryland, USA.

PURPOSE: Increased dietary intake of lutein/zeaxanthin and omega-long-chain
polyunsaturated fatty acids (omega-3 LCPUFA) was found to be associated with
reduced risk of advanced age-related macular degeneration (AMD). The purpose of
the study was to examine the effect of oral supplementation of omega-3 LCPUFA on 
changes in serum levels of lutein/zeaxanthin during supplementation in persons 60
years of age and older, with or without AMD. METHODS: Forty participants with AMD
of various degrees of severity received lutein (10 mg) and zeaxanthin (2 mg)
daily and were equally randomized to receive omega-3 LCPUFA (350 mg
docosahexaenoic acid [DHA] and 650 mg eicosapentaenoic acid [EPA]) or placebo for
6 months. Serum levels of lutein, zeaxanthin, and omega-3 LCPUFAs and macular
pigment optical densities were measured at baseline, 1 week, and 1, 3, 6, and 9
months. RESULTS: By month 6, the median serum levels of lutein/zeaxanthin
increased by two- to threefold compared with baseline. Increases in serum levels 
of lutein/zeaxanthin did not differ by omega-3 LCPUFA treatment (P > 0.5). After 
1 month, in the omega-3 LCPUFA-treated group, the median levels of DHA and EPA
increased and the placebo group had no changes. At month 6, participants with AMD
had a lower increase in serum lutein concentration than did those without AMD (P 
< 0.05). CONCLUSIONS: The addition of omega-3 LCPUFA to oral supplementation of
lutein/zeaxanthin did not change the serum levels of lutein and zeaxanthin. A
long-term large clinical trial is necessary to investigate the benefits and
adverse effects of these factors for the treatment of AMD.

Publication Types: 
    Research Support, N.I.H., Intramural
    Research Support, Non-U.S. Gov't

PMID: 18450596 [PubMed - indexed for MEDLINE]

289: Can J Ophthalmol. 2008 Jun;43(3):295-301.

Ocular blood flow in diabetes and age-related macular degeneration.

Pemp B, Schmetterer L.

Department of Clinical Pharmacology, Medical University of Vienna, Währinger
Gürtel 18-20, Vienna, Austria.

The 2 leading causes of blindness in adults in the industrialized nations,
diabetic retinopathy and age-related macular degeneration, have been investigated
thoroughly with respect to their pathogenesis. In recent years, it has been
discovered that dysfunctional ocular microcirculation appears to play a part in
the development of both diseases. In diabetic retinopathy, it has been shown that
the disease is associated with early retinal vascular dysregulation. In the later
states of the disease, retinal tissue hypoxia is a major trigger of
sight-threatening neovascularization. In age-related macular degeneration, there 
is increasing evidence that reduced blood flow in the choroid is associated with 
the development and progression of the disease. Knowledge of the
pathophysiological vascular states underlying these diseases is essential for the
assessment and development of future therapies.

Publication Types: 
    Review

PMID: 18443612 [PubMed - indexed for MEDLINE]

290: Br J Ophthalmol. 2008 May;92(5):630-4.

Age-related maculopathy and sunlight exposure evaluated by objective measurement.

Hirakawa M, Tanaka M, Tanaka Y, Okubo A, Koriyama C, Tsuji M, Akiba S, Miyamoto
K, Hillebrand G, Yamashita T, Sakamoto T.

Department of Ophthalmology, Kagoshima University Graduate School of Medical and 
Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.

AIM: To study the relationship between age-related maculopathy (ARM) and exposure
to sunlight using an objective method. METHODS: In a case-control study of
Japanese men aged > or = 50 years (67 controls without ophthalmic disease and 148
with ARM), those with ARM were separated into groups of early (n = 75) and late
(n = 73) ARM. Facial wrinkle length and area of hyperpigmentation, which are
considered to be associated with exposure to sun, were measured using imaging
with computer-based image analysis. Skin tone was also measured on the upper
inner arm, which is not exposed to sun. Early and late ARM association with skin 
measurements was then evaluated. RESULTS: Significantly more facial wrinkling (p 
= 0.047, odds ratio 3.8; 95% CI 1.01 to 13.97) and less facial hyperpigmentation 
(p = 0.035, odds ratio 0.3; 95% CI 0.08 to 0.92) was present in late ARM cases.
The relationship between skin tone and ARM risk was not statistically
significant. CONCLUSIONS: This objective method showed that lifetime exposure to 
sunlight is an important factor in the progression of late ARM. An individual's
reaction to sunlight exposure may have a role in ARM progression in addition to
total lifetime exposure to sunlight.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18441173 [PubMed - indexed for MEDLINE]

291: Ophthalmology. 2008 Oct;115(10):1735-41. Epub 2008 Apr 25.

Prevalence of age-related macular degeneration in a Malay population: the
Singapore Malay Eye Study.

Kawasaki R, Wang JJ, Aung T, Tan DT, Mitchell P, Sandar M, Saw SM, Wong TY;
Singapore Malay Eye Study Group.

Centre for Eye Research Australia, University of Melbourne, Melbourne, Australia.

OBJECTIVE: To describe the prevalence of age-related macular degeneration (AMD)
in an Asian Malay population. DESIGN: Population-based cross-sectional study.
PARTICIPANTS: An age-stratified random sample of Malay persons aged 40 to 80
years living in Singapore. METHODS: Participants were invited to a central clinic
for a comprehensive examination. MAIN OUTCOME MEASURES: Early and late AMD signs 
were graded from retinal photographs following the Wisconsin grading system.
RESULTS: Of 3280 participants who participated (78.7% response rate), 3265 had
photographs of sufficient quality for grading of AMD signs. Early and late AMD
were present in 160 (4.9%) and 23 (0.70%) participants, respectively. After age
standardization, the prevalence of early AMD in Malay persons aged 40 to 80 years
was estimated to be 3.5% (95% confidence interval [CI], 2.9%-4.1%) and that of
late AMD was 0.34% (95% CI, 0.20%-0.49%). Early AMD was more prevalent in men
than in women (6.1% vs. 3.8%); this was significant despite adjusting for age and
smoking (odds ratio [OR], 1.56; 95% CI, 1.11-2.20). Late AMD also was more
prevalent in men than in women (1.0% vs. 0.4%), although this was not
statistically significant after adjusting for age and smoking (OR, 1.39; 95% CI, 
0.52-3.68). The prevalence of early and late AMD was similar to that reported in 
the Blue Mountains Eye Study among white persons. CONCLUSIONS: The prevalence of 
AMD in Asian Malay people is similar to that in white persons from the Blue
Mountains Eye Study. Early AMD signs were more frequent in men compared with
women, an association that was not fully explained by the higher smoking rates in
men.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18439679 [PubMed - indexed for MEDLINE]

292: Am J Ophthalmol. 2008 Jul;146(1):96-101. Epub 2008 Apr 24.

Development of typical age-related macular degeneration and polypoidal choroidal 
vasculopathy in fellow eyes of Japanese patients with exudative age-related
macular degeneration.

Ueta T, Iriyama A, Francis J, Takahashi H, Adachi T, Obata R, Inoue Y, Tamaki Y, 
Yanagi Y.

Department of Ophthalmology, University of Tokyo School of Medicine, 7-3-1 Hongo,
Bunkyo-ku, Tokyo, Japan.

PURPOSE: To investigate the development of typical age-related macular
degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) in fellow eyes of 
Japanese patients with exudative AMD. DESIGN: Retrospective observational
consecutive case series. METHODS: Two hundred and sixteen Japanese patients were 
enrolled in this study from the outpatient clinic of the University of Tokyo
Hospital. Ninety-one patients had typical AMD and one hundred and twenty-five
patients had PCV. The average follow-up period was 33.6 and 25.1 months for
typical AMD and PCV patients. RESULTS: The cumulative incidence of involvement in
fellow eyes with overall exudative AMD, including both typical AMD and PCV, was
3.4% in one year, 9.3% in three years, and 11.3% in five years. It was 3.6%,
7.3%, and 11.2% in typical AMD, and 3.2%, 11.1%, and 11.1% in PCV in one, three, 
and five years, respectively. Before the development of exudative AMD, patients
with typical AMD had a variety of funduscopic findings including retinal pigment 
epithelium (RPE) atrophy, drusen, drusenoid pigment epithelial detachments (PED),
and normal macula. PCV patients, on the other hand, had funduscopic findings of
RPE atrophy. Inner choroidal vascular abnormality of vascular network and
polypoidal formation was observed in several eyes before the clinical
manifestation of exudative changes. CONCLUSIONS: Typical AMD and PCV had similar 
probabilities of involving the fellow eye in unilaterally affected Japanese
patients. RPE atrophy was a prevailing finding in fellow eyes of patients who
developed PCV. In PCV, choroidal vascular network and polypoidal formation
gradually grow before exudative changes.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18439567 [PubMed - indexed for MEDLINE]

293: Am J Ophthalmol. 2008 Jul;146(1):135-142. Epub 2008 Apr 24.

Correlation of visual function impairment and optical coherence tomography
findings in patients with adult-onset foveomacular vitelliform macular dystrophy.

Querques G, Bux AV, Prato R, Iaculli C, Souied EH, Delle Noci N.

Department of Ophthalmology, Ospedali Riuniti, University of Foggia, Viale Pinto 
1, Foggia, Italy. giuseppe.querques@hotmail.it

PURPOSE: To investigate the relationship between morphologic and functional
abnormalities in patients affected with adult-onset foveomacular vitelliform
macular dystrophy (AFVD). DESIGN: Prospective, noncomparative observational
study. METHODS: A complete ophthalmologic examination, including best-corrected
visual acuity (BCVA), fundus examination, fundus-related perimetry, and optical
coherence tomography (OCT), was performed in 20 consecutive AFVD patients. The
stage of the disease and the thickness of the neuroepithelium at the foveola
(neurosensory retina) were compared with the BCVA as well as with the type of
scotoma, the average retinal sensitivity, and the location and stability of
fixation. RESULTS: Thirty-five eyes of 20 consecutive patients (10 men and 10
women; mean age, 58.2 years) were graded as follows: 10 had vitelliform stage
(stage 1), nine had pseudohypopyon stage (stage 2), 10 had vitelliruptive (stage 
3), and six had atrophic stage (stage 4) disease. Reduced thickness of the
neuroepithelium at the foveola and BCVA were statistically correlated to an
advanced stage of the disease (P = .001 and P = .0062, respectively). Moreover,
worse BCVA was correlated statistically to reduced thickness of the
neuroepithelium at the foveola (r = 0.14; P = .02). Reduced thickness of the
neuroepithelium at the foveola was correlated statistically to the development of
absolute scotoma (P = .03), eccentric fixation (P = .01), and unstable fixation
(P = .03). CONCLUSIONS: OCT and fundus-related perimetry allow a correlation to
be defined between foveal thickness and visual function and are useful tools to
define better the degree of anatomic and functional impairment in AFVD patients.

PMID: 18439561 [PubMed - indexed for MEDLINE]

294: Ophthalmic Res. 2008;40(5):235-40. Epub 2008 Apr 25.

Optical coherence tomography fast versus regular macular thickness mapping in
diabetic retinopathy.

Ceklic L, Maár N, Neubauer AS.

Department of Ophthalmology, Clinical Center of Eastern Sarajevo, RS-Bosnia and
Herzegovina University of Sarajevo, Sarajevo, RS-Bosnia.

OBJECTIVE: The purpose of the study was to investigate if absolute values and
reproducibility of thickness maps obtained from 2 optical coherence tomography
(OCT) scanning protocols, regular high-resolution and fast low-density mode,
differ in patients with diabetic macular edema. METHODS: A total of 26
consecutive patients undergoing fluorescein angiography and Stratus OCT scanning 
for the evaluation of diabetic macular edema at the Departments of Ophthalmology 
in Munich and Vienna were included. RESULTS: Retinal thickness of the central
field of the thickness map measured by fast retinal thickness protocol was 287
+/- 97 and 290 +/- 113 microm by the regular protocol. This difference as well as
that for all other fields was not statistically significant. Three times repeated
measurements applying both OCT scanning modes in 10 patients yielded very good
intrasession correlation coefficients between 0.70 and 0.99, with corresponding
intrasession standard deviations ranging between 6 and 16 mum. The fast mode
yielded slightly less reproducible values than the regular mode. Visual acuity
did not influence the results. CONCLUSION: In practice both scanning modes can be
interchanged and absolute values can be compared directly. Best reproducibility
is obtained with higher sampling density even in patients with reduced visual
acuity due to diabetic macular edema. Copyright 2008 S. Karger AG, Basel.

PMID: 18437033 [PubMed - indexed for MEDLINE]

295: Invest Ophthalmol Vis Sci. 2008 May;49(5):2127-33.

Effect of posterior sub-tenon administration of triamcinolone acetonide on
leukocyte dynamics in rat retinal microcirculation after panretinal
photocoagulation.

Mizuno D, Matsubara A, Ogura Y.

Department of Ophthalmology and Visual Science, Nagoya City University Graduate
School of Medical Sciences, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Japan.

PURPOSE: Macular edema is one of the serious side effects associated with
panretinal photocoagulation (PRP). The inhibitory effect of triamcinolone
acetonide (TA) on leukocyte-endothelial cell interactions in vivo after PRP was
evaluated. METHODS: Argon laser photocoagulation was performed in one half of the
retinas in male Brown Norway rats. Experimental rats were injected with 2 mg TA
(50-microL volume) in the posterior sub-Tenon space, and the vehicle-treated rats
were injected with the same amount of saline (50 microL) immediately after PRP.
Untreated rats were used as the control. Leukocyte dynamics in retinal
microcirculation and retinal vessel diameters were evaluated 1 day after laser
photocoagulation with the use of acridine orange digital fluorography. Retinal
thickness was evaluated with optical coherence tomography. RESULTS: The number of
rolling leukocytes and accumulating leukocytes in the retina decreased by 66% in 
the TA-treated rats (P < 0.01) and by 24% (P < 0.05), respectively, compared with
the number in the vehicle-treated rats. Retinal thickness in the vehicle-treated 
rats was significantly thicker than that in control rats 1 day after laser
photocoagulation (P < 0.01). Retinal thickness in the TA-treated rats was
significantly suppressed compared with that in the vehicle-treated rats (P <
0.05). CONCLUSIONS: Sub-Tenon administration of TA significantly suppressed
leukocyte dynamics in rat retinal microcirculation and decreased retinal edema
after laser photocoagulation. The results suggest that the suppression of
leukocyte-endothelial cell interactions in retinal microcirculation may be one
mechanism responsible for the therapeutic effect of sub-Tenon TA on postlaser
retinal edema.

PMID: 18436845 [PubMed - indexed for MEDLINE]

296: Invest Ophthalmol Vis Sci. 2008 May;49(5):2046-52.

Increased-resolution OCT thickness mapping of the human macula: a statistically
based registration.

Bernardes R, Santos T, Cunha-Vaz J.

Centro de Novas Tecnologias para a Medicina da Associação para a Investigação
Biomédica e Inovação em Luz e Imagem, Azinhaga Sta Comba, Celas, Coimbra,
Portugal. rcb@aibili.pt

PURPOSE: To describe the development of a technique that enhances spatial
resolution of retinal thickness maps of the Stratus OCT (Carl Zeiss Meditec,
Inc., Dublin, CA). A retinal thickness atlas (RT-atlas) template was calculated, 
and a macular coordinate system was established, to pursue this objective.
METHODS: The RT-atlas was developed from principal component analysis of retinal 
thickness analyzer (RTA) maps acquired from healthy volunteers. The Stratus OCT
radial thickness measurements were registered on the RT-atlas, from which an
improved macular thickness map was calculated. Thereafter, Stratus OCT circular
scans were registered on the previously calculated map to enhance spatial
resolution. RESULTS: The developed technique was applied to Stratus OCT thickness
data from healthy volunteers and from patients with diabetic retinopathy (DR) or 
age-related macular degeneration (AMD). Results showed that for normal, or close 
to normal, macular thickness maps from healthy volunteers and patients with DR,
this technique can be an important aid in determining retinal thickness. Efforts 
are under way to improve the registration of retinal thickness data in patients
with AMD. CONCLUSIONS: The developed technique enhances the evaluation of data
acquired by the Stratus OCT, helping the detection of early retinal thickness
abnormalities. Moreover, a normative database of retinal thickness measurements
gained from this technique, as referenced to the macular coordinate system, can
be created without errors induced by missed fixation and eye tilt.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18436839 [PubMed - indexed for MEDLINE]

297: Invest Ophthalmol Vis Sci. 2008 May;49(5):1983-90.

Measurement of factor H variants in plasma using variant-specific monoclonal
antibodies: application to assessing risk of age-related macular degeneration.

Hakobyan S, Harris CL, Tortajada A, Goicochea de Jorge E, García-Layana A,
Fernández-Robredo P, Rodríguez de Córdoba S, Morgan BP.

Department of Medical Biochemistry and Immunology, School of Medicine, Cardiff
University, Heath Park Way, Cardiff, United Kingdom.

PURPOSE: The Y402H polymorphism in the complement regulator factor H (fH) is
strongly associated with age-related macular degeneration (AMD) across diverse
populations. Persons homozygous for histidine at this position have up to 12-fold
greater risk for AMD than those homozygous for tyrosine. Knowledge of fH-Y402H
status is, therefore, valuable in predicting risk and focusing preventive
measures in the elderly. This knowledge requires genetic analysis, which is
unavailable in most laboratories and which provides no information about the
levels of fH protein, a putative linked determinant of disease risk. METHODS: The
authors describe novel monoclonal antibodies that distinguish the two fH allelic 
variants in plasma. ELISA with these antibodies not only reliably identifies the 
fH-Y402H status, confirmed by genotyping, but also quantifies the concentration
of total fH and the fH-Y402 and fH-H402 variants. RESULTS: In young adult control
subjects, mean fH concentration was 233 mg/L. In elderly control subjects, mean
fH concentration was 269 mg/L, whereas in a matching AMD cohort, mean fH
concentration was 288 mg/L. Total fH concentration was similar in each subgroup
of young and elderly control subjects; however, in the AMD group, fH
concentration was significantly higher in the heterozygous subgroup. Measurement 
of the two variants in this subgroup showed that both were elevated to a similar 
degree. CONCLUSIONS: The novel monoclonal antibody MBI-7 was used to develop a
robust assay for measurement of fH and the variants in plasma. The simplicity of 
the assay means that it may be used by any clinical laboratory to identify
polymorphic status and to quantify plasma levels in persons at risk for AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Validation Studies

PMID: 18436830 [PubMed - indexed for MEDLINE]

298: Invest Ophthalmol Vis Sci. 2008 May;49(5):1771-6.

Variants in the 10q26 gene cluster (LOC387715 and HTRA1) exhibit enhanced risk of
age-related macular degeneration along with CFH in Indian patients.

Kaur I, Katta S, Hussain A, Hussain N, Mathai A, Narayanan R, Hussain A, Reddy
RK, Majji AB, Das T, Chakrabarti S.

Kallam Anji Reddy Molecular Genetics Laboratory, L.V. Prasad Eye Institute, Road 
No. 2, Banjara Hills, Hyderabad, India.

PURPOSE: Single nucleotide polymorphisms (SNPs) in the LOC387715 (rs10490924),
HTRA1 (rs11200638), and CFH (rs1061170) genes have been implicated in age-related
macular degeneration (AMD). The present study was undertaken to determine the
involvement of the LOC387715 and HTRA1 in an AMD cohort from India. METHODS: The 
coding region of LOC387715 (exon 1) and the promoter of HTRA1 were screened by
resequencing in AMD cases and normal controls. Odds ratios were calculated to
assess the risk of individual genotypes. Linkage disequilibrium (LD) and
haplotype frequencies were estimated with Haploview software. Population
attributable risk (PAR %) for the associated SNPs and their combined effects were
calculated. RESULTS: Resequencing revealed seven different SNPs in these genes,
of which significant associations were noted with the risk alleles of rs10490924 
(T allele; P = 5.34 x 10(-12)) in LOC387715, and rs11200638 (A allele; P = 4.32 x
10(-12)) and rs2672598 (C allele; P = 3.39 x 10(-11)) in HTRA1 among the cases.
Correspondingly, the homozygous risk genotypes TT, AA, and CC in these SNPs
exhibited higher disease odds and PAR %. rs10490924 and rs11200638 were in tight 
LD (D', 0.90; 95% CI, 0.84-0.93). G-C-T-A-C was the risk haplotype (P = 8.04 x
10(-15)), whereas the G-C-G-G-T haplotype was protective (P = 2.01 x 10(-4)). The
combined effect of the CFH (CC) and LOC387715 (TT) risk genotypes exhibited a PAR
of 93.7% (OR, 73.89; 95% CI, 8.69-628.13). CONCLUSIONS: The present data provided
an independent validation of the association of LOC387715 and HTRA1 SNPs, along
with their risk estimates among Indian patients with AMD. These associations
underscore their significant involvement in AMD susceptibility, which may be
useful for predictive testing.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18436811 [PubMed - indexed for MEDLINE]

299: Optometry. 2008 May;79(5):266-72.

Macular pigment: new clinical methods of detection and the role of carotenoids in
age-related macular degeneration.

Leung IY.

Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland, USA.
ileung@schepens.harvard.edu

Age-related macular degeneration (AMD) is the leading cause of irreversible
blindness in people over the age of 65. The Age-Related Eye Disease Study (AREDS)
suggests antioxidants may delay the advance of age-related macular degeneration. 
The macular pigments zeaxanthin and lutein may serve as antioxidants as well as
blue filter to protect the retina. In this review, the general characteristics of
macular pigment are described. The nutritional value of zeaxanthin/lutein and
methods to assess macular pigment are discussed. Several emerging instruments to 
assess macular pigment, including heterochromatic flickering photometer, motion
detection photometer, fundus reflectance spectroscope, Raman spectrometer, and
autofluorescence spectrometry, are introduced and reviewed. Optometrists should
be aware that they may play a role to assess and monitor the risk of AMD. There
is an opportunity to incorporate measurement of macular pigment in optometric
practice.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18436167 [PubMed - indexed for MEDLINE]

300: Ophthalmic Epidemiol. 2008 Mar-Apr;15(2):105-13.

Assessing participation in daily living and the effectiveness of rehabiliation in
age related macular degeneration patients using the impact of vision impairment
scale.

Lamoureux EL, Pallant JF, Pesudovs K, Tennant A, Rees G, O'Connor PM, Keeffe JE.

Centre for Eye Research Australia-The University of Melbourne, Victoria, 3002,
Australia. ecosse@unimelb.edu.au

PURPOSE: To assess if the Impact of Vision Impairment (IVI) is a valid instrument
to measure participation in daily activities and rehabilitation in patients with 
age-related macular degeneration (AMD) and varying levels of visual impairment.
METHODS: Participants, recruited from a public eye hospital and low vision
centers, completed the IVI questionnaire. The IVI and its three subscales were
assessed for fit to the Rasch model. Unidimensionality, item fit, response
category performance, and targeting of items to patients were assessed.
Confirmatory factor analysis (CFA) was used to assess the three-factor model of
the IVI in this sample of AMD patients. RESULTS: 219 patients (mean +/- SD age = 
83.5 +/- 7.4 yr) were recruited. Of these, 22%, 55% and 23% had mild (<
6/12-6/18), moderate (< 6/18-6/60) and severe (< 6/60) vision loss, respectively.
The IVI total and three subscales displayed discrete thresholds indicating that
the respondents understood the response categories. The IVI items fitted the
scale and unidimensionality was established. Person separation reliability for
the IVI score was substantial (0.94) indicating that the scale can discriminate
between several groups of AMD patients. The IVI items were significantly targeted
to the AMD patients with the means of the two distributions shown to be very
close (0.0 and 0.1, respectively). Substantial targeting was also evident for the
subscales. Poorer visual acuity was significantly associated (ANOVA; F (2, 216) =
23.4; p < 0.001) with greater restriction of participation suggesting that the
IVI has substantial construct validity. CFA supported the IVI three-factor model 
which includes items from the "emotional well-being, "reading and accessing
information" and "mobility and independence" subscales. CONCLUSIONS: Clinicians
and researchers can reliably use the IVI to assess the impact on daily life and
the effectiveness of clinical trials and rehabilitation interventions in patients
with AMD across a range of vision loss.

Publication Types: 
    Comparative Study

PMID: 18432494 [PubMed - indexed for MEDLINE]

301: Ophthalmic Epidemiol. 2008 Mar-Apr;15(2):84-91.

Economic evaluation of blind rehabilitation for veterans with macular diseases in
the Department of Veterans Affairs.

Stroupe KT, Stelmack JA, Tang XC, Reda DJ, Moran D, Rinne S, Mancil R, Wei Y,
Cummings R, Mancil G, Ellis N, Massof RW.

Veterans Affairs Cooperative Studies Program Coordinating Center, Edward Hines
Jr. Veterans Affairs Hospital, Hines, Illinois 60141, USA. Kevin.Stroupe@va.gov

PURPOSE: The Department of Veterans Affairs (VA) Low Vision Intervention Trial
(LOVIT) developed an outpatient low-vision programme for patients with macular
diseases providing low-vision rehabilitation comparable to VA inpatient blind
rehabilitation centres (BRCs). This programme targets veterans who do not need or
chose not to participate in a comprehensive inpatient blind rehabilitation
programme. We examined costs and consequences using veterans in LOVIT and
comparable veterans in an inpatient BRC. METHODS: We compared costs and
consequences between treatment patients who participated in LOVIT, a two-site
randomized clinical trial, and a sample of comparable patients who received
treatment at a VA inpatient BRC. We measured consequences as the change in
functional visual ability from baseline to follow-up (LOVIT: 4 months after
randomization; BRC: 3 months after discharge) using the VA Low Vision Visual
Functioning Questionnaire (VA LV VFQ-48). RESULTS: There were 55 LOVIT and 121
BRC patients for our analyses. Average costs were $38,627.3 higher for BRC
patients ($5,054.4 +/- $404.7 SD for LOVIT vs. $43,681.7 +/- $8,853.6 SD for BRC,
p < 0.0001). Thus, the BRC cost $38,627.3 per patient more than the LOVIT
programme (95% CI: $17,414 to $273,482). There was a greater improvement in
overall visual ability, mobility, and visual motor skill scores for BRC patients;
however, there was no significant difference in improvement in reading ability or
visual information processing scores. CONCLUSIONS: As VA increases outpatient
blind rehabilitation services, LOVIT provides a model for expanding outpatient
low-vision rehabilitation services for veterans at substantially lower costs than
current inpatient BRC services.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial
    Research Support, U.S. Gov't, Non-P.H.S.

PMID: 18432491 [PubMed - indexed for MEDLINE]

302: Ophthalmic Epidemiol. 2008 Mar-Apr;15(2):76-83.

An introduction to decision analysis in the economic evaluation of the prevention
and treatment of vision-related diseases.

Kymes SM.

Department of Ophthalmology and Visual Sciences, Washington University School of 
Medicine, St. Louis, Missouri 63110-1093, USA. kymes@vrcc.wustl.edu

Economic evaluation in the form of reports of cost-effectiveness of the treatment
and prevention of disease has only recently found widespread application in the
visual sciences. While economic evaluation takes a number of forms:
cost-minimization analysis, cost-benefit analysis, and cost-effectiveness
analysis--it is the latter that is seen most often in the evaluation of
vision-related health programs. Cost-effectiveness analysis is in particular seen
most commonly in its very particular form of cost-utility analysis. Decision
analysis is the analytic method most commonly used to perform cost-effectiveness 
analysis. In decision analysis, the expected cost and effectiveness of a health
program are estimated in a rigorous fashion. In this report, we take the reader
through the process of decision analysis including building the tree; populating 
the model with parameters for risk, cost and benefit; estimating expected cost
and benefit; and deterministic and probabilistic sensitivity analysis. Examples
employed include prominent studies of the cost-effectiveness of photodynamic
therapy for treatment of neovascular macular degeneration and the treatment
ocular hypertension to prevent glaucoma.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18432490 [PubMed - indexed for MEDLINE]

303: Trans Am Ophthalmol Soc. 2007;105:160-9; discussion 169-71.

The goal of value-based medicine analyses: comparability. The case for
neovascular macular degeneration.

Brown GC, Brown MM, Brown HC, Kindermann S, Sharma S.

Center for Value-Based Medicine, Flourtown, Pennsylvania, USA.

PURPOSE: To evaluate the comparability of articles in the peer-reviewed
literature assessing the (1) patient value and (2) cost-utility
(cost-effectiveness) associated with interventions for neovascular age-related
macular degeneration (ARMD). METHODS: A search was performed in the National
Library of Medicine database of 16 million peer-reviewed articles using the key
words cost-utility, cost-effectiveness, value, verteporfin, pegaptanib, laser
photocoagulation, ranibizumab, and therapy. All articles that used an outcome of 
quality-adjusted life-years (QALYs) were studied in regard to (1) percent
improvement in quality of life, (2) utility methodology, (3) utility respondents,
(4) types of costs included (eg, direct healthcare, direct nonhealthcare,
indirect), (5) cost bases (eg, Medicare, National Health Service in the United
Kingdom), and (6) study cost perspective (eg, government, societal, third-party
insurer). To qualify as a value-based medicine analysis, the patient value had to
be measured using the outcome of the QALYs conferred by respective interventions.
As with value-based medicine analyses, patient-based time tradeoff utility
analysis had to be utilized, patient utility respondents were necessary, and
direct medical costs were used. RESULTS: Among 21 cost-utility analyses performed
on interventions for neovascular macular degeneration, 15 (71%) met value-based
medicine criteria. The 6 others (29%) were not comparable owing to (1) varying
utility methodology, (2) varying utility respondents, (3) differing costs
utilized, (4) differing cost bases, and (5) varying study perspectives. Among
value-based medicine studies, laser photocoagulation confers a 4.4% value gain
(improvement in quality of life) for the treatment of classic subfoveal choroidal
neovascularization. Intravitreal pegaptanib confers a 5.9% value gain
(improvement in quality of life) for classic, minimally classic, and occult
subfoveal choroidal neovascularization, and photodynamic therapy with verteporfin
confers a 7.8% to 10.7% value gain for the treatment of classic subfoveal
choroidal neovascularization. Intravitreal ranibizumab therapy confers greater
than a 15% value gain for the treatment of subfoveal occult and minimally classic
subfoveal choroidal neovascularization. CONCLUSIONS: The majority of cost-utility
studies performed on interventions for neovascular macular degeneration are
value-based medicine studies and thus are comparable. Value-based analyses of
neovascular ARMD monotherapies demonstrate the power of value-based medicine to
improve quality of care and concurrently maximize the efficacy of healthcare
resource use in public policy. The comparability of value-based medicine
cost-utility analyses has important implications for overall practice standards
and public policy. The adoption of value-based medicine standards can greatly
facilitate the goal of higher-quality care and maximize the best use of
healthcare funds.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18427606 [PubMed - indexed for MEDLINE]

304: Trans Am Ophthalmol Soc. 2007;105:92-7; discussion 97-8.

Human HtrA1 in the archived eyes with age-related macular degeneration.

Chan CC, Shen D, Zhou M, Ross RJ, Ding X, Zhang K, Green WR, Tuo J.

Immunopathology Section, Laboratory of Immunology, National Eye Institute,
National Institutes of Health, Bethesda, Maryland, USA.

PURPOSE: HtrA1 belongs to the high temperature requirement factor A family of
serine proteases, which are involved in protein quality control and cell fate. A 
single-nucleotide polymorphism (SNP), rs11200638, in the promoter of HtrA1 at
chromosome 10q26 is reported as a likely causal variant for age-related macular
degeneration (AMD). The SNP is located in the regulatory region and increases
production of HtrA1 protein. This study investigates HtrA1 expression and SNP
genotypes in archived ocular slides with AMD. METHODS: Macular, nonretinal, and
peripheral retinal cells were microdissected from archived slides from 57 eyes
with AMD and 16 age-matched, non-AMD controls. HtrA1 rs11200638 SNP genotyping
was performed using polymerase chain reaction (PCR) and restriction fragment
length polymorphism analysis. HtrA1 transcripts were measured using real-time
reverse transcriptase-PCR. HtrA1 protein expression was evaluated using
avidin-biotin complex immunohistochemistry. RESULTS: HtrA1 (G/A) SNP was
successfully genotyped in 52 AMD cases and 13 non-AMD subjects. The frequencies
of the risk allele (A) were 55 of 104 (52.9%) and 8 of 26 (30.8%) in AMD and
control groups, respectively. HtrA1 mRNA was detected in normal peripheral and
macular retinas, higher in the periphery than maculae. HtrA1 mRNA was much higher
in the macula and a lot lower in the periphery of the AMD eyes as compared to
control eyes. HtrA1 protein was expressed in normal retinal vascular endothelia
and retinal pigment epithelia. Intense immunoreaction against HtrA1 was found in 
AMD lesions, slightly more in wet than dry AMD lesions. CONCLUSION: This study
successfully analyzes HtrA1 SNP and transcript expression in microdissected cells
from archived paraffin fixed slides. Up-regulation of HtrA1 is detected in the
macular lesions of AMD eyes. The data further suggest that rs11200638 in HtrA1
promoter is associated with AMD development.

Publication Types: 
    Research Support, N.I.H., Intramural

PMID: 18427598 [PubMed - indexed for MEDLINE]

305: Cochrane Database Syst Rev. 2008 Apr 16;(2):CD005139.

Antiangiogenic therapy with anti-vascular endothelial growth factor modalities
for neovascular age-related macular degeneration.

Vedula SS, Krzystolik MG.

BACKGROUND: Age-related macular degeneration (AMD) is a common cause of severe
vision loss in people 55 years and older. OBJECTIVES: The objective of this
review was to investigate the effects of anti-VEGF (vascular endothelial growth
factor) modalities for treating neovascular AMD. SEARCH STRATEGY: We searched
CENTRAL, MEDLINE, EMBASE and LILACS. We handsearched ARVO abstracts for 2006,
2007 for ongoing trials. SELECTION CRITERIA: We included randomized controlled
trials (RCTs). DATA COLLECTION AND ANALYSIS: Two review authors independently
extracted data. We contacted trial authors for additional data. We summarized
outcomes as relative risks (RR), number needed to treat (NNT) and weighted mean
differences. MAIN RESULTS: We included five RCTs of good methodological quality. 
All five trials were conducted by pharmaceutical companies. An intention-to-treat
analysis using the last observation carried forward method was done in most
trials.Two trials compared pegaptanib versus sham. One trial compared ranibizumab
versus sham, another compared ranibizumab/sham verteporfin PDT versus verteporfin
PDT/sham ranibizumab, and the final trial compared ranibizumab plus verteporfin
PDT versus verteporfin PDT alone.Fewer patients treated with pegaptanib lost 15
or more letters of visual acuity at one year follow-up compared to sham (pooled
relative risk (RR) 0.71; 95% confidence interval (CI) 0.61 to 0.84). The NNT was 
6.67 (95% CI 4.35 to 14.28) for 0.3 mg pegaptanib, 6.25 (95% CI 4.17 to 12.5) for
1 mg pegaptanib and 14.28 (95% CI 6.67 to 100) for 3 mg pegaptanib. In a trial of
ranibizumab versus sham, RR for loss of 15 or more letters visual acuity at one
year was 0.14 (95% CI 0.1 to 0.22) in favour of ranibizumab. The NNT was 3.13
(95% CI 2.56 to 3.84) for 0.3 mg ranibizumab and 3.13 (95% CI 2.56 to 3.84) for
0.5 mg ranibizumab. In a trial of ranibizumab versus verteporfin PDT, RR for loss
of 15 or more letters at one year was 0.13 (95% CI 0.07 to 0.23) favouring
ranibizumab. The NNT was 3.33 (95% CI 2.56 to 4.76) for 0.3 mg ranibizumab and
3.12 (95% CI 2.43 to 4.17) for 0.5 mg ranibizumab. In another trial of combined
ranibizumab plus verteporfin PDT versus verteporfin PDT, RR for loss of 15 or
more letters at one year favoured combined therapy (RR 0.3 (95% CI 0.15 to 0.60).
The NNT was 4.35 (95% CI 2.78 to 11.11).Pooled RR for gain of 15 or more letters 
visual acuity at one year was 5.81 (95% CI 3.29 to 10.26) for ranibizumab versus 
sham, 6.79 (95% CI 3.41 to 13.54) for ranibizumab/sham verteporfin PDT versus
verteporfin PDT/sham ranibizumab, and 4.44 (95% CI 1.40 to 14.08) for ranibizumab
plus verteporfin PDT versus verteporfin PDT.Frequency of endophthalmitis in
included studies was between 0.7% to 4.7% with ranibizumab and 1.3% with
pegaptanib. Improvement in vision-specific quality of life was reported for both 
treatments. AUTHORS' CONCLUSIONS: Pegaptanib and ranibizumab reduce the risk of
visual acuity loss in patients with neovascular AMD. Ranibizumab causes gains in 
visual acuity in many eyes. Quality of life and cost will be important for
treatment decisions. Other agents blocking VEGF are being tested in ongoing
trials.

Publication Types: 
    Meta-Analysis
    Review

PMID: 18425911 [PubMed - indexed for MEDLINE]

306: Graefes Arch Clin Exp Ophthalmol. 2008 Jul;246(7):967-74. Epub 2008 Apr 19.

Arteriovenous crossing sheathotomy versus intravitreal triamcinolone acetonide
injection for treatment of macular edema associated with branch retinal vein
occlusion.

Chung EJ, Lee H, Koh HJ.

Department of Ophthalmology, NHIC Ilsan Hospital, Gyounggi-do, Korea.

PURPOSE: To compare the functional and anatomical outcomes of arteriovenous (AV) 
sheathotomy and intravitreal triamcinolone acetonide (IVTA) injection in the
treatment of macular edema associated with branch retinal vein occlusion (BRVO). 
METHODS: Forty eyes of 40 patients with macular edema secondary to BRVO were
randomized into two treatment groups. A total of 20 patients received AV
sheathotomy (sheathotomy group), and the second group of 20 patients was treated 
with IVTA (IVTA group). Early Treatment Diabetic Retinopathy Study (ETDRS) visual
acuity (VA) score, total macular volume measured, and foveal thickness by 3rd
generation optical coherence tomography (OCT3) were evaluated as main outcome
measurements. RESULTS: The average changes in ETDRS scores, total macular
volumes, and foveal thicknesses compared to baseline values, were significant 3
months and 6 months after treatment in both groups (P < 0.05, paired t-test), but
only the IVTA group showed significant improvements 1 month after treatment. The 
between-group differences in average ETDRS score, total macular volume, and
foveal thickness changes were significantly better at 1 month after treatment in 
the ITVA group (P = 0.026, P < 0.001, P = 0.001, respectively, Student's t-test),
at which time IVTA patients had better vision and anatomical outcomes than did
those in the sheathotomy group. CONCLUSIONS: After either AV sheathotomy or IVTA 
treatment, patients with macular edema secondary to BRVO showed similar
functional and anatomical outcomes 6 months later. When the cost and the risks of
vitreoretinal surgery are considered, IVTA treatment may be a better treatment
option, as the drug yields better short-term outcomes.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial

PMID: 18425522 [PubMed - indexed for MEDLINE]

307: Eye. 2008 Jun;22(6):751-60. Epub 2008 Apr 18.

Antioxidant supplements to prevent or slow down the progression of AMD: a
systematic review and meta-analysis.

Evans J.

International Centre for Eye Health, London School of Hygiene and Tropical
Medicine (LSHTM), London, UK. jennifer.evans@Ishtm.ac.uk

INTRODUCTION: The aim of this review was to examine the evidence as to whether
antioxidant vitamin or mineral supplements prevent the development of AMD or slow
down its progression. METHODS: Randomised trials comparing antioxidant vitamin
and/or mineral supplement to control were identified by systematic electronic
searches (updated August 2007) and contact with investigators. Data were pooled
after investigating clinical and statistical heterogeneity. RESULTS: There was no
evidence that antioxidant (vitamin E or beta-carotene) supplementation prevented 
AMD. A total of 23 099 people were randomised in three trials with treatment
duration of 4-12 years; pooled risk ratio=1.03 (95% CI, 0.74-1.43). There was
evidence that antioxidant (beta-carotene, vitamin C, and vitamin E) and zinc
supplementation slowed down the progression to advanced AMD and visual acuity
loss in people with signs of the disease (adjusted odds ratio=0.68, 95% CI,
0.53-0.87 and 0.77, 95% CI, 0.62-0.96, respectively). The majority of people were
randomised in one trial (AREDS, 3640 people randomised). There were seven other
small trials (total randomised 525). CONCLUSIONS: Current evidence does not
support the use of antioxidant vitamin supplements to prevent AMD. People with
AMD, or early signs of the disease, may experience some benefit from taking
supplements as used in the AREDS trial. Potential harms of high-dose antioxidant 
supplementation must be considered. These may include an increased risk of lung
cancer in smokers (beta-carotene), heart failure in people with vascular disease 
or diabetes (vitamin E) and hospitalisation for genitourinary conditions (zinc).

Publication Types: 
    Meta-Analysis
    Review

PMID: 18425071 [PubMed - indexed for MEDLINE]

308: Ophthalmology. 2008 Jun;115(6):1019-25.

CFH and LOC387715/ARMS2 genotypes and treatment with antioxidants and zinc for
age-related macular degeneration.

Klein ML, Francis PJ, Rosner B, Reynolds R, Hamon SC, Schultz DW, Ott J, Seddon
JM.

Macular Degeneration Center, Casey Eye Institute, Oregon Health & Science
University, Portland, Oregon, USA.

OBJECTIVE: To determine if CFH and LOC387715/ARMS2 genotypes influence treatment 
response to AREDS-type nutritional supplementation with antioxidants and zinc.
DESIGN: Retrospective analysis of participants in a randomized, controlled
clinical trial, the Age-Related Eye Disease Study (AREDS). PARTICIPANTS AND/OR
CONTROLS: Eight hundred seventy-six AREDS study participants who were considered 
at high risk for developing advanced age-related macular degeneration (AMD).
METHODS: Using DNA extracted from venous blood of 876 white participants in AREDS
categories 3 and 4, that is, those considered to be at high risk for progression 
to advanced AMD, the authors genotyped for the single nucleotide polymorphisms in
the CFH (Y402H, rs1061170) and LOC387715/ARMS2 (A69S, rs10490924) genes. The
authors performed adjusted unconditional logistic regression analysis and
assessed interactions of these genotypes to determine the relationship between
CFH and LOC387715/ARMS2 genotype and treatment with antioxidants plus zinc. MAIN 
OUTCOME MEASURES: Interaction between genetic variants and treatment response as 
determined by progression from high-risk to advanced AMD. RESULTS: Progression
occurred in 264 of 876 patients from AREDS category 3 (intermediate AMD) to
category 4 or 5 (unilateral or bilateral advanced AMD, respectively), or from
category 4 to category 5. A treatment interaction was observed between the CFH
Y402H genotype and supplementation with antioxidants plus zinc (CC; P = 0.03). An
interaction (P = 0.004) was observed in the AREDS treatment groups taking zinc
when compared with the groups taking no zinc, but not in groups taking
antioxidants compared with those taking no antioxidants (P = 0.59). There were no
significant treatment interactions observed with LOC387715/ARMS2. CONCLUSIONS:
The findings of this study indicate that an individual's response to AREDS
supplements may be related to CFH genotype. This could have clinical relevance by
predicting treatment outcome and potentially preventing unwanted side effects in 
those who may not benefit. Corroboration of these analyses is needed before
considering modification of current management. This is among the first
pharmacogenetic studies to suggest interaction between genotype and treatment.

Publication Types: 
    Randomized Controlled Trial
    Research Support, N.I.H., Extramural

PMID: 18423869 [PubMed - indexed for MEDLINE]

309: Ophthalmic Res. 2008;40(3-4):203-7. Epub 2008 Apr 18.

PlGF-1 and VEGFR-1 pathway regulation of the external epithelial hemato-ocular
barrier. A model for retinal edema.

Miyamoto N, de Kozak Y, Normand N, Courtois Y, Jeanny JC, Benezra D, Behar-Cohen 
F.

INSERM, UMRS 872, Equipe 17, Centre de Recherche des Cordeliers, Paris, France.

VEGF is considered as an important factor in the pathogenesis of macular edema.
VEGF induces the rupture of the blood retinal barrier and may also influence the 
retinal pigment epithelial (RPE) outer retinal barrier. The aim of this work was 
to analyze the influence of the VEGF receptor pathways in the modulation of the
RPE barrier breakdown in vitro and in vivo. The ARPE19 human junctions in culture
are modulated by VEGF through VEGFR-1 but not through VEGFR-2. PlGF-1, that is a 
pure agonist of VEGFR-1, is produced in ARPE-19 cells under hypoxic conditions
and mimics VEGF effects on the external retinal barrier as measured by TER and
inulin flux. In vivo, the intravitreous injection of PlGF-1 induces a rupture of 
the external retinal barrier together with a retinal edema. This effect is
reversible within 4 days. VEGF-E, that is a pure agonist of VEGFR-2, does not
induce any acute effect on the RPE barrier. These results demonstrate that PlGF-1
can reproduce alterations of the RPE barrier occurring during diabetic
retinopathy. 2008 S. Karger AG, Basel.

Publication Types: 
    Comparative Study

PMID: 18421240 [PubMed - indexed for MEDLINE]

310: Ophthalmic Res. 2008;40(3-4):124-8. Epub 2008 Apr 18.

Ccl2/Cx3cr1-deficient mice: an animal model for age-related macular degeneration.

Chan CC, Ross RJ, Shen D, Ding X, Majumdar Z, Bojanowski CM, Zhou M, Salem N Jr, 
Bonner R, Tuo J.

Section of Immunopathology, Laboratory of Immunology, National Eye Institute,
Bethesda, MD 20892-1857, USA. chanc@nei.nih.gov

BACKGROUND/AIMS: Senescent Ccl2-/- mice develop cardinal features of human
age-related macular degeneration (AMD). Loss-of-function single-nucleotide
polymorphisms within CX3CR1 are associated with AMD. METHODS: We generated
Ccl2-/-/Cx3cr1-/- [double-knockout (DKO)] mice and evaluated the eyes using
fundoscopy routine histology, immunochemistry, biochemistry and proteomics.
RESULTS: At 6 weeks old, all DKO mice developed AMD-like retinal lesions such as 
abnormal retinal pigment epithelium cells, drusen, photoreceptor atrophy and
choroidal neovascularization, which progressed with age and reversed with high
omega-3 long-chain polyunsaturated fatty acid diet.
N-retinylidene-N-retinylethanolamine (A2E), a major lipofuscin fluorophore,
illustrated by an emission peak at approximately 600 nm, was significantly higher
in DKO retinal pigment epithelium. Decreased ERp29 was found in the retina of DKO
mice. CONCLUSION: A broad spectrum of AMD pathologies with early onset and high
penetrance in these mice implicate certain chemokines, A2E and endoplasmic
reticulum proteins in AMD pathogenesis. 2008 S. Karger AG, Basel.

Publication Types: 
    Comparative Study

PMID: 18421225 [PubMed - indexed for MEDLINE]

311: Ophthalmic Res. 2008;40(3-4):120-3. Epub 2008 Apr 18.

Lack of alphavbeta5 integrin receptor or its ligand MFG-E8: distinct effects on
retinal function.

Nandrot EF, Finnemann SC.

Department of Ophthalmology, Dyson Vision Research Institute, New York, NY 10065,
USA.

BACKGROUND/AIMS: Diurnal phagocytosis of spent photoreceptor outer segment
fragments by the retinal pigment epithelium (RPE) is critical for vision. We
recently identified an important role for alphavbeta5 integrin receptors and
their ligand Milk fat globule-EGF factor 8 (MFG-E8) in RPE phagocytosis. METHODS:
We compared RPE phagocytosis and retinal function between mice deficient in
alphavbeta5 integrin receptors and mice deficient in the secreted integrin ligand
MFG-E8. RESULTS: Both beta5-/- and MFG-E8-/- mice exhibit the same phagocytic
defect: RPE cells retain basal uptake activity but completely lack the burst of
phagocytic activity as well as the rhythmic activation of Mer tyrosine kinase
that follow circadian photoreceptor shedding in wild-type RPE. Strikingly,
electroretinogram photoresponses decline with age only in beta5 -/- but not in
MFG-E8-/- retina. CONCLUSION: These results identify a critical role of
alphavbeta5 integrin receptors and their ligand MFG-E8 in synchronizing retinal
phagocytosis. Additionally, we show that lack of alphavbeta5 receptors and MFG-E8
ligand have distinct consequences for retinal function. These intriguing results 
suggest that loss of phagocytic rhythm is not solely responsible for the
age-related blindness of beta5-/- mice. 2008 S. Karger AG, Basel.

Publication Types: 
    Comparative Study
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18421224 [PubMed - indexed for MEDLINE]

312: Invest Ophthalmol Vis Sci. 2008 Aug;49(8):3312-7. Epub 2008 Apr 17.

Multiple gene polymorphisms in the complement factor h gene are associated with
exudative age-related macular degeneration in chinese.

Ng TK, Chen LJ, Liu DT, Tam PO, Chan WM, Liu K, Hu YJ, Chong KK, Lau CS, Chiang
SW, Lam DS, Pang CP.

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong
Kong, Hong Kong, China.

PURPOSE: Variants in the complement factor H (CFH) gene have been shown to be
strongly associated with age-related macular degeneration (AMD). In this study,
sequence alterations in CFH were investigated in 163 Chinese patients with
exudative AMD and 155 unrelated Chinese control subjects. METHODS: All the 22 CFH
exons, intron-exon boundaries, and promoter sequences were screened by polymerase
chain reaction and DNA sequencing. RESULTS: Fifty-eight sequence changes, 42 of
them novel, were identified. Six SNPs with an allele frequency >30% were
significantly associated with exudative AMD. SNP rs3753396 was novel; the rest
had been reported: rs3753394, rs551397, rs800292, rs2274700, and rs1329428. Two
haplotype blocks were constructed. The TG haplotype for rs551397 and rs800292 was
the major haplotype that conferred a significantly increased susceptibility to
exudative AMD (P(corr) = 0.0001, OR = 1.91, 95% CI = 1.36-2.68). CONCLUSIONS: The
findings support prior evidence that the CFH gene is one of the AMD-associated
genes. There is a different distribution pattern of CFH variants in the Chinese
compared with other populations. Individual SNP and haplotype analyses revealed
that the ancient alleles at the 5' end of CFH contribute to an increased
susceptibility to exudative AMD.

PMID: 18421087 [PubMed - indexed for MEDLINE]

313: Invest Ophthalmol Vis Sci. 2008 Aug;49(8):3269-82. Epub 2008 Apr 17.

Brightness, contrast, and color balance of digital versus film retinal images in 
the age-related eye disease study 2.

Hubbard LD, Danis RP, Neider MW, Thayer DW, Wabers HD, White JK, Pugliese AJ,
Pugliese MF; Age-Related Eye Disease 2 Research Group.

Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison,
Madison, Wisconsin 53711-1068, USA. hubbard@rc.ophth.wisc.edu

PURPOSE: To analyze brightness, contrast, and color balance of digital versus
film retinal images in a multicenter clinical trial, to propose a model image
from exemplars, and to optimize both image types for evaluation of age-related
macular degeneration (AMD). METHODS: The Age-Related Eye Disease Study 2 (AREDS2)
is enrolling subjects from 90 clinics, with three quarters of them using digital 
and one quarter using film cameras. Image brightness (B), contrast (C), and color
balance (CB) were measured with three-color luminance histograms. First, the
exemplars (film and digital) from expert groups were analyzed, and an
AMD-oriented model was constructed. Second, the impact of B/C/CB on the
appearance of typical AMD abnormalities was analyzed. Third, B/C/CB in AREDS2
images were compared between film (156 eyes) and digital (605 eyes), and against 
the model. Fourth, suboptimal images were enhanced by adjusting B/C/CB to bring
them into accord with model parameters. RESULTS: Exemplar images had similar
brightness, contrast, and color balance, supporting an image model. Varying a
specimen image through a wide range of B/C/CB revealed greatest contrast of
drusen and pigment abnormalities against normal retinal pigment epithelium with
the model parameters. AREDS2 digital images were more variable than film, with
lower correspondence to our model. Ten percent of digital were too dim and 19%
too bright (oversaturated), versus 1% and 4% of film, respectively. On average,
digital had lower green channel contrast (giving less retinal detail) than film. 
Overly red color balance (weaker green) was observed in 23% of digital versus 8% 
of film. About half of digital (but fewer film) images required enhancement
before AMD grading. After optimization of both image types, AREDS2 image quality 
was judged as good as that in AREDS (all film). CONCLUSIONS: A histogram-based
model, derived from exemplars, provides a pragmatic guide for image analysis and 
enhancement. In AREDS2, the best digital images matched the best film. Overall,
however, digital provided lower contrast of retinal detail. Digital images taken 
with higher G-to-R ratio showed better brightness and contrast management.
Optimization of images in the multicenter study helps standardize documentation
of AMD (ClinicalTrials.gov NCT00345176).

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Research Support, N.I.H., Extramural

PMID: 18421079 [PubMed - indexed for MEDLINE]

314: Br J Ophthalmol. 2008 Jun;92(6):795-9. Epub 2008 Apr 17.

Intravitreal triamcinolone versus laser photocoagulation for persistent diabetic 
macular oedema.

Ockrim ZK, Sivaprasad S, Falk S, Roghani S, Bunce C, Gregor Z, Hykin P.

Royal Alexander Hospital, Corsebar Road, Paisley PA2 9PN, UK.
zoe_ockrim@hotmail.com

AIM: To determine if repeated intravitreal triamcinolone improves best corrected 
visual acuity at 1 year compared with conventional laser therapy for persistent
diabetic macular oedema. METHODS: 88 eyes with persistent clinically significant 
macular oedema, after at least one prior laser photocoagulation, were included in
this prospective randomised controlled trial. 43 patients were randomised to 4 mg
of intravitreal triamcinolone (TA) and 45 to laser photocoagulation. The primary 
endpoint was the proportion of patients who improved by 15 Early Treatment of
Diabetic Retinopathy Study (ETDRS) letters at 12 months in TA versus laser
groups. Secondary endpoints were the change in mean best corrected visual acuity,
difference in macular thickness and macular volume and adverse event reporting in
particular elevated intraocular pressure at 12 months. RESULTS: Improvement in > 
or =15 ETDRS letters occurred in two of 42 patients in the TA group (4.8%) and in
five of 41 (12.2%) patients in the laser group (p = 0.265). At baseline, the mean
ETDRS scores at baseline were 54.4 letters in the TA group and 53.0 letters in
the laser group. At 12 months, these were 54.5 and 54.6, respectively. Optical
coherence tomography showed a reduction in central macular thickness of 82.0
microm with TA and 62.3 microm with laser at 12 months. There was one case of
sterile endophthalmitis. 22 out of 43 patients in the triamcinolone group
required ocular antihypertensives. CONCLUSION: This study did not show a benefit 
from intravitreal triamcinolone over conventional laser therapy for patients with
chronic diabetic macular oedema.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18420749 [PubMed - indexed for MEDLINE]

315: Graefes Arch Clin Exp Ophthalmol. 2008 Jun;246(6):803-10. Epub 2008 Apr 15.

Are low inflammatory reactions involved in exudative age-related macular
degeneration? Morphological and immunhistochemical analysis of AMD associated
with basal deposits.

Lommatzsch A, Hermans P, Müller KD, Bornfeld N, Bird AC, Pauleikhoff D.

Department of Ophthalmology and Ophtha-Lab, St. Franziskus Hospital Münster,
Münster, Germany. Albrecht.Lommatzsch@web.de

PURPOSE: Basal laminar and linear deposits (BLD) are associated with the
development of choroidal neovascularization (CNV). Therefore, analysis of BLD
composition may provide further information concerning the pathogenesis of BLD
and CNV in age-related macular degeneration (AMD). METHODS: BLD in 25 specimens
of surgically removed CNV were examined, using histochemical and
immunohistochemical methods, for extracellular matrix proteins and their
modulating enzymes, and for cell markers and proteins involved in inflammatory
processes. In addition, ultrastructural electron microscopic analysis (EM) was
performed. RESULTS: The chemical and structural composition of all the BLD was
similar. Only the inner aspect of the BLD contained laminin and collagen IV,
which corresponded to a new RPE basal lamina upon EM analysis. The extracellular 
matrix protein predominantly found in all layers of BLD was vitronectin, which
was seen as a homogeneous material within the BLD upon EM analysis. The
metalloproteinases MMP-2 and MMP-9 could only be detected in the inner aspect,
while MMP-7 and TIMP-3 were observed predominantly in the outer aspect of BLD. In
this area, staining for phospholipids and less intensely for neutral lipids was
also visible. The labelling of complement complexes C3 and C5b-9 was intensely
positive, and vascular endothelial growth factor (VEGF) was detected in all BLDs.
CONCLUSIONS: Diffuse deposits such as BLD appear consistently with the
development of CNV in AMD. They consist of extracellular matrix components and
predominantly vitronectin. However, activated complement and VEGF could also be
detected. The results of the current study may support the hypothesis that
inflammatory processes are involved in the pathogenesis of BLD and CNV in AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18414889 [PubMed - indexed for MEDLINE]

316: Br J Community Nurs. 2008 Feb;13(2):68-75.

Age related macular degeneration: visual impairment with advancing age.

Redmond N, While A.

Florence Nightingale School of Nursing and Midwifery, King's College London.
alison.while@kcl.ac.uk

This article sets out a comprehensive outline of age related macular degeneration
including the underlying disease mechanisms. Current treatment options are
described together with recommendations for preventive care and support for those
with visual impairment.

PMID: 18414241 [PubMed - indexed for MEDLINE]

317: Arch Ophthalmol. 2008 Apr;126(4):519-24.

Menopausal and reproductive factors and risk of age-related macular degeneration.

Feskanich D, Cho E, Schaumberg DA, Colditz GA, Hankinson SE.

Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and
Harvard Medical School, Boston, Massachusetts 02115, USA.
diane.feskanich@channing.harvard.edu

OBJECTIVE: To investigate whether estrogen exposures are associated with lower
risks of age-related macular degeneration (AMD). METHODS: Postmenopausal hormone 
(PMH) use, past use of oral contraceptives (OCs), ages at menarche and menopause,
and parity were assessed among 74,996 postmenopausal women. Over 22 years, cases 
of early (n = 554) and neovascular (n = 334) AMD with a visual acuity of 20/30 or
worse were identified. Cox models were used to calculate the relative risk for
each exposure, adjusted for smoking and other factors. RESULTS: Current PMH users
had a notable 48% lower risk of neovascular AMD compared with those who had never
used PMH, although risk did not decline linearly with longer durations of use.
Risk was lowest for PMH users who had used OCs in the past (P value for
interaction, .03). In contrast, risk of early AMD was a notable 34% higher among 
current PMH users and OC use was unassociated with risk. The only remarkable
finding for the endogenous estrogenic factors was a 26% lower risk of early AMD
for parous women. CONCLUSIONS: Although PMH and OC use were associated with a
lower risk of neovascular AMD, no benefit was observed for early AMD. Factors
influencing lifetime exposure to estrogens were not consistently associated with 
the disease.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 18413522 [PubMed - indexed for MEDLINE]

318: Clin Experiment Ophthalmol. 2008 Apr;36(3):252-6.

Retinal pigment epithelial tears after intravitreal bevacizumab injection for
exudative age-related macular degeneration.

Garg S, Brod R, Kim D, Lane RG, Maguire J, Fischer D.

The Retina Service of Wills Eye Institute, Thomas Jefferson University,
Philadelphia, PA, USA.

PURPOSE: To determine the incidence of and the risk factors for the development
of retinal pigment epithelial (RPE) tears after intravitreal bevacizumab
(Avastin) injection for the treatment of exudative age-related macular
degeneration (AMD). METHODS: A retrospective, multicentre, consecutive
interventional case series of all patients with subfoveal exudative AMD treated
with intravitreal bevacizumab between August 2005 and April 2007. The main
outcome measures were pre- and post-RPE tear visual acuity and choroidal
neovascular membrane lesion types, incidence of tears and time from first
injection until development of the tear. RESULTS: A total of 920 eyes with
exudative AMD were treated with intravitreal bevacizumab. Fifteen eyes from 15
patients developed a RPE tear for an incidence of 1.6%. The average patient age
was 79 years. Fourteen of the fifteen eyes (93%) had an occult subfoveal
choroidal neovascular membrane. Forty-seven per cent (7/15) of the RPE tears
occurred within the first 6 weeks of treatment, and all tears occurred within the
first 18 weeks of treatment initiation. The mean pre-injection visual acuity was 
20/100 with a mean post-tear visual acuity of 20/200. In all 10 eyes in which the
tear involved the fovea, the final visual acuity was poor. Six of the 15 eyes
continued with bevacizumab/ranibizumab (Lucentis) injections after tear
development, and four of these six eyes continued to have visual improvement.
CONCLUSION: RPE tears occur after intravitreal bevacizumab injections for
exudative AMD in approximately 1.6% of eyes and can cause severe vision loss.
Maintenance of therapy may help preserve vision after RPE tear development.

Publication Types: 
    Multicenter Study

PMID: 18412594 [PubMed - indexed for MEDLINE]

319: Curr Opin Ophthalmol. 2008 May;19(3):202-7.

The comparative effectiveness and cost-effectiveness of vitreoretinal
interventions.

Brown MM, Brown GC, Brown HC, Irwin B, Brown KS.

Center for Value-Based Medicine, Flourtown, USA. mbrown@valuebasedmedicine.com

PURPOSE OF REVIEW: The comparative effectiveness of medical interventions has
recently been emphasized in the literature, typically for interventions in a
similar class. Value-based medicine, the practice of medicine based on the value 
(improvement in quality of life and/or length of life) conferred by medical
interventions, allows a measure of comparative effectiveness of interventions
across all of health care, no matter how disparate. This report discusses recent 
comparative effectiveness studies in the vitreoretinal literature. RECENT
FINDINGS: Vitreoretinal interventions have good to excellent comparative
effectiveness compared with commonly utilized interventions across health care,
such as treatment for osteoporosis and hyperlipidemia. They also tend to be
cost-effective when an upper limit of $100 000/quality-adjusted life-year is
utilized. SUMMARY: Value can be measured using either or both of two outcomes -
the quality-adjusted life-year gain and/or the percentage improvement in value - 
both of which allow for an evaluation of comparative effectiveness, which can be 
compared on the same scale for every intervention. This value can also be
integrated with costs using the outcome of dollars expended per quality-adjusted 
life-year ($/quality-adjusted life-year, or the cost-utility ratio), which allows
a comparison of cost-effectiveness across all interventions. The majority of
vitreoretinal interventions confer considerable value and are cost-effective.

Publication Types: 
    Review

PMID: 18408494 [PubMed - indexed for MEDLINE]

320: Curr Opin Ophthalmol. 2008 May;19(3):195-201.

The cost of vision for vitreoretinal interventions.

Smiddy WE.

The Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami
Miller School of Medicine, Miami, Florida, USA. wsmiddy@med.miami.edu

PURPOSE OF REVIEW: This article reviews the current status of treatments for
age-related macular degeneration from a cost-effectiveness perspective. RECENT
FINDINGS: Treatments are now available to a broad range of patients with
age-related macular degeneration, but they are pharmaceutical based and require
repeated evaluation and treatment. The resulting unprecedented levels of cost
make cost-effectiveness considerations more prescient. Newer methods to evaluate 
cost-effectiveness and treatment outcomes have included utility and value-based
analyses. These have attempted to utilize accurate, objective parameters, but are
calibrated by subjective patient assessments and are limited by certain
methodological assumptions. Treatment methods to improve outcomes are
increasingly being considered within the context of cost-effectiveness. SUMMARY: 
Although improved understanding of basic, cellular processes has led to markedly 
improved treatment options for age-related macular degeneration within the past
decade, the high costs and wide applicability threaten the balance and viability 
of the payor system. Accurate means of assessing cost-effectiveness are critical 
to defining clinical applications.

Publication Types: 
    Review

PMID: 18408493 [PubMed - indexed for MEDLINE]

321: Curr Opin Ophthalmol. 2008 May;19(3):185-9.

Update on treatments for diabetic macular edema.

Fraser-Bell S, Kaines A, Hykin PG.

Medical Retinal Service, Moorfields Hospital, London, UK bDepartment of
Ophthalmology, University of Sydney, NSW, Australia.

PURPOSE OF REVIEW: Due to modest outcomes with macular laser, other treatment
modalities for diabetic macular edema have been evaluated. Intravitreal
triamcinolone acetonide, pars plana vitrectomy, oral protein kinase C inhibitors 
and, from more recently, anti-vascular endothelial growth factor therapy are
reviewed. RECENT FINDINGS: Intravitreal triamcinolone acetonide may be more
effective than laser. Intravitreal triamcinolone acetonide followed by laser may 
be more effective than intravitreal triamcinolone acetonide alone. Ruboxistaurin,
a selective protein kinase C betainhibitor, reduced retinal vascular leakage in
patients with diabetic macular edema and reduced the rate of sustained moderate
visual loss in those with moderately severe to very severe non proliferative
diabetic retinopathy. Several anti-vascular endothelial growth factor agents are 
under evaluation. Intravitreal pegaptanib sodium (0.3 mg) improved vision and
reduced central retinal thickness compared to sham. Data on the other
anti-vascular endothelial growth factor agents is limited, but there are
promising results, with ranibizumab (0.5 mg) and bevacizumab reducing foveal
thickness and improving visual acuity in some patients with diabetic macular
edema. SUMMARY: There remains no proven intervention that consistently prevents
or reverses visual loss from diabetic macular edema in all patients. A variety of
promising new medical and surgical therapies are under investigation, but further
research is required to determine their role alone or in combination.

Publication Types: 
    Review

PMID: 18408491 [PubMed - indexed for MEDLINE]

322: Invest Ophthalmol Vis Sci. 2008 Jul;49(7):3121-5. Epub 2008 Apr 11.

Focal macular electroretinograms in eyes with wet-type age-related macular
degeneration.

Nishihara H, Kondo M, Ishikawa K, Sugita T, Piao CH, Nakamura Y, Terasaki H.

Department of Ophthalmology, Nagoya University Graduate School of Medicine,
Nagoya, Japan.

PURPOSE: To study the properties of the focal macular electroretinograms (fmERGs)
in eyes with untreated wet-type age-related macular degeneration (AMD). METHODS: 
fmERGs were recorded from 157 eyes of 157 consecutive patients with untreated
wet-type AMD (113 men, 44 women; age, 71.3 +/- 8.0 years). The fmERGs were
recorded under direct fundus observation using a modified infrared fundus camera 
and a 15 degrees stimulus spot. Amplitudes and implicit times of the fmERGs
recorded from the AMD patients were compared with those from 21 age-similar
healthy controls. RESULTS: The amplitudes of fmERGs in the AMD patients were
significantly smaller (P < 0.001) and the implicit times were significantly
longer (P < 0.001) than the corresponding values in the control eyes. There was a
significant correlation between amplitude and implicit time of the fmERG and
visual acuity (logMAR), but the degree of correlation was weak. The difference in
the b/a amplitude ratio between the AMD patients and healthy controls was not
significant. CONCLUSIONS: The significant reduction in amplitude and the severe
delay in implicit times of a- and b-waves of the fmERGs indicated significant
functional alterations in the inner and the outer retinal layers of the macular
area of eyes with wet-type AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18408182 [PubMed - indexed for MEDLINE]

323: Invest Ophthalmol Vis Sci. 2008 Jul;49(7):3115-20. Epub 2008 Apr 11.

Quantitative subanalysis of optical coherence tomography after treatment with
ranibizumab for neovascular age-related macular degeneration.

Keane PA, Liakopoulos S, Ongchin SC, Heussen FM, Msutta S, Chang KT, Walsh AC,
Sadda SR.

Doheny Image Reading Center, Doheny Eye Institute, Keck School of Medicine of the
University of Southern California, Los Angeles, California 90033, USA.

PURPOSE: To investigate the effects of ranibizumab on retinal morphology in
patients with neovascular age-related macular degeneration (AMD) using optical
coherence tomography (OCT) quantitative subanalysis. METHODS: Data from 95
patients receiving intravitreal ranibizumab for neovascular AMD were collected.
StratusOCT images were analyzed using custom software that allows precise
positioning of prespecified boundaries on every B-scan. Changes in
thickness/volume of the retina, subretinal fluid (SRF), subretinal tissue (SRT), 
and pigment epithelial detachments (PEDs) at week 1 and at months 1, 3, 6, and 9 
after treatment were calculated. RESULTS: Total retinal volume reached its nadir 
at month 1, with an average reduction of 0.43 mm(3) (P < 0.001). By month 9, this
initial change had been reduced to a mean reduction of 0.32 mm(3) (P = 0.0011).
Total SRF volume reached its lowest level by month 1, with an average reduction
of 0.24 mm(3) (P < 0.001). This reduction lessened subsequently, to 0.18 mm(3),
by month 9. There was an average 0.3-mm(3) decrease in total PED volume by month 
1 (P < 0.001), and this later declined further, to 0.45 mm(3), by month 9 (P =
0.0014). Total SRT volume was reduced by an average of 0.07 mm(3) at month 1 (P =
0.0159) and subsequently remained constant. CONCLUSIONS: Although neurosensory
retinal edema and SRF showed an early reduction to nadir after the initiation of 
ranibizumab therapy, the effect on the retina was attenuated over time,
suggesting possible tachyphylaxis. PED volume showed a slower but progressive
reduction. Manual quantitative OCT subanalysis may allow a more precise
understanding of anatomic outcomes and their correlation with visual acuity.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 18408176 [PubMed - indexed for MEDLINE]

324: Clin Drug Investig. 2008;28(5):327-32.

Retrospective analysis of rosiglitazone and macular oedema in patients with type 
2 diabetes mellitus.

Tatti P, Arrigoni F, Longobardi A, Costanza F, Di Blasi P, Merante D.

Diabetes Center, Marino Hospital, Rome, Italy. tatti0@tin.it

BACKGROUND: Macular oedema tends to be a more rapid complication of diabetic
retinopathy and represents the major cause of blindness. Among subjects with type
2 diabetes mellitus, it can be found in 15% of those who use insulin and 4% of
those who do not. Use of thiazolidinediones (glitazones) has recently been
associated with some cases of macular oedema. METHODS: We recalled 102 diabetic
subjects treated with rosiglitazone to our diabetes centre in order to evaluate a
possible association of this drug with macular oedema. Of these 102 subjects, we 
evaluated all 76 who provided written informed consent to participate in the
analysis. All of these underwent a battery of four diagnostic tests: (1) visual
acuity, (2) Amsler visual field test, (3) Ishihara colour recognition test, and
(4) retinal fundus photography. All retinal photographs were examined by two
experienced ophthalmologists. RESULTS: The most noticeable result was that most
subjects (80%) had satisfactory visual acuity. The Ishihara test chart showed
that three subjects were colour blind, but this abnormality was already known. On
the Amsler test, one subject had a positive result consisting of visual
distortion of a series of straight lines. In the retinal photos, two expert
ophthalmologists independently identified one case of 'paramacular oedema' in a
subject with diabetes of long duration with a proliferative retinopathy. The
patient developed bilateral macular oedema during treatment with rosiglitazone 8 
mg/day. The patient had been diagnosed with diabetes at the age of 45 years and
after a period of 6 years taking oral antihyperglycaemic agents had been switched
to insulin, up to four injections per day (total 60-70 IU/day), for the next 15
years. In 2000 a routine examination demonstrated the presence of sustained
hypertension and the patient was started on an ACE inhibitor. A computerized test
for autonomic neuropathy demonstrated abnormal deep breathing and
lying-to-standing responses. Treatment with rosiglitazone was interrupted and the
subject underwent a series of retinal photocoagulations for proliferative
retinopathy. Two months after rosiglitazone therapy had been discontinued, the
visual acuity of the patient reversed to baseline values. CONCLUSION: The study
shows that rosiglitazone was not linked to formation of macular oedema, with the 
exception of one case of bilateral and clinically reversible paramacular oedema, 
where rosiglitazone was given in co-administration with a long-term insulin
treatment regimen in a subject with pre-existing diabetic retinopathy. This
patient had a long duration of diabetes and had also been hypertensive since
2000.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18407718 [PubMed - indexed for MEDLINE]

325: Comput Biol Med. 2008 May;38(5):611-9. Epub 2008 Apr 9.

Automatic segmentation of age-related macular degeneration in retinal fundus
images.

Köse C, Sevik U, Gençalioğlu O.

Department of Computer Engineering, Faculty of Engineering, Karadeniz Technical
University, 61080 Trabzon, Turkey. ckose@ktu.edu.tr <ckose@ktu.edu.tr>

Every year an increasing number of people are affected by age-related macular
degeneration (ARMD). Consequently, vast amount of information is accumulated in
medical databases and manual classification of this information is becoming more 
and more difficult. Therefore, there is an increasing interest in developing
automated evaluation methods to follow up the diseases. In this paper, we have
presented an automatic method for segmenting the ARMD in retinal fundus images.
Previously used direct segmentation techniques, generating unsatisfactory results
in some cases, are more complex and costly than our inverse method. This is
because of the fact that the texture of unhealthy areas of macula is quite
irregular and varies from eye to eye. Therefore, a simple inverse segmentation
method is proposed to exploit the homogeneity of healthy areas of the macula
rather than unhealthy areas. This method first extracts healthy areas of the
macula by employing a simple region growing method. Then, blood vessels are also 
extracted and classified as healthy regions. In order to produce the final
segmented image, the inverse image of the segmented image is generated as
unhealthy region of the macula. The performance of the method is examined on
various qualities of retinal fundus images. The segmentation method without any
user involvement provides over 90% segmentation accuracy. Segmented images with
reference invariants are also compared with consecutive images of the same
patient to follow up the changes in the disease.

PMID: 18402931 [PubMed - indexed for MEDLINE]

326: Am J Ophthalmol. 2008 Jun;145(6):1052-1057. Epub 2008 Apr 9.

Photodynamic therapy for predominantly hemorrhagic lesions in neovascular
age-related macular degeneration.

Ahmad S, Bearelly S, Stinnett SS, Cooney MJ, Fekrat S.

Department of Ophthalmology, Duke University Medical Center, Erwin Road, Durham, 
NC 27710, USA.

PURPOSE: To evaluate the response of eyes treated with photodynamic therapy (PDT)
for predominantly hemorrhagic lesions in neovascular age-related macular
degeneration (NVAMD). DESIGN: Consecutive, interventional case series. METHODS: A
retrospective review was conducted of eyes with NVAMD that were treated with PDT 
for predominantly hemorrhagic subfoveal lesions. Baseline data recorded were
patient age, use of aspirin or warfarin, history of previous PDT treatment,
visual acuity (VA), extent of subretinal hemorrhage (SRH), and central foveal
thickness (CFT) and total macular volume (TMV) measured by optical coherence
tomography (OCT). Follow-up VA, SRH status, and complications were recorded.
RESULTS: Twenty-one eyes of 21 patients were identified with a mean posttreatment
follow-up of 9.4 months. Mean pretreatment VA was 20/210, and mean SRH size was
16 disk areas. The SRH resolved in 18 eyes (86%) after a mean of six months, with
a mean VA of 20/210. Mean VA for all eyes at most recent follow-up was 20/250.
Thirteen (62%) of 21 eyes exhibited stable or improved VA at the most recent
follow-up. VA one year after PDT inversely correlated with patient age (P = .045)
and initial SRH size (P = .04) and positively correlated with pretreatment VA (P 
= .01). Previous PDT treatment, use of aspirin or warfarin, and OCT data did not 
significantly correlate with VA or SRH resolution. CONCLUSIONS: PDT may be an
effective treatment for minimizing visual loss in eyes with NVAMD and
predominantly hemorrhagic lesions. Further study is warranted to detail the
risk-benefit ratio and compare PDT with other treatment modalities.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18400198 [PubMed - indexed for MEDLINE]

327: Retina. 2008 Apr;28(4):615-21.

Large-spot subthreshold infrared laser to treat diabetic macular edema.

Squirrell DM, Stewart AW, Joondeph BC, Danesh-Meyer HV, McGhee CN, Donaldson ML.

Department of Ophthalmology, Royal Hallamshire Hospital, Sheffield, United
Kingdom. David.Squirrell@sth.nhs.uk

PURPOSE: To evaluate the efficacy of a large-spot subthreshold infrared laser
protocol to treat diabetic maculopathy. METHODS: In a prospective, fellow eye,
controlled case series, all patients had clinically significant diabetic macular 
edema (DME) treated with a single application of subthreshold infrared (810 nm)
laser. If bilateral disease was present, the fellow eye was treated with
conventional macular laser. The study was to include 20 patients. Visual acuity
and central macular thickness (CMT) measured by optical coherence tomography
(OCT) were assessed in the study and fellow eyes at baseline and 6 months, and
any changes were compared. RESULTS: The 11th patient developed a choroidal
infarct with subsequent profound loss of vision immediately after treatment. The 
study was terminated prematurely at this point. For the remaining 10 patients,
there was a trend toward improvement in visual acuity in the study eye compared
with the fellow eye at the 6-month follow-up (median change: +1.5 letters for
study eye vs -6.5 letters for fellow eye; P = 0.08). There was also significant
improvement in OCT-measured CMT in the study eye (mean decrease, 117 microm)
compared with deterioration in OCT-measured CMT in the fellow eye (mean increase,
24 microm; P = 0.02). CONCLUSION: This subthreshold infrared laser protocol led
to improvement in OCT-measured CMT and stabilization of vision in most subjects. 
The current protocol is however unpredictable and should not be used in the
treatment of DME without further modification.

Publication Types: 
    Case Reports
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 18398365 [PubMed - indexed for MEDLINE]

328: Retina. 2008 Apr;28(4):538-44.

Discrepancy between fluorescein angiography and optical coherence tomography in
detection of macular disease.

Kozak I, Morrison VL, Clark TM, Bartsch DU, Lee BR, Falkenstein I, Tammewar AM,
Mojana F, Freeman WR.

Jacobs Retina Center at Shiley Eye Center, University of California at San Diego,
La Jolla, California 92037, USA.

PURPOSE: To compare high-resolution optical coherence tomography (OCT) and
fluorescein angiography (FA) in detection of macular edema (ME) of various
etiologies. METHODS: In a retrospective study over a 12-month period at one
retina center, data for consecutive eyes that had undergone simultaneous
conventional FA (HRA; Heidelberg Engineering, Vista, CA) and StratusOCT (Carl
Zeiss Meditec, Dublin, CA) to rule out ME were reviewed. A subset of patients
underwent additional examination with extremely high-resolution
(6-microm)/ultrahigh-speed spectral OCT/scanning laser ophthalmoscopy (OTI, Inc.,
Toronto, Ontario, Canada). RESULTS: Of 1,272 eyes, 1,208 (94.97%) had the finding
of ME or subretinal fluid confirmed by both techniques. There were 49 eyes
(3.86%) for which FA showed dye leakage in the macular area and OCT showed normal
foveal contour. Of 10 eyes in this group that underwent imaging with
ultrahigh-speed spectral OCT/scanning laser ophthalmoscopy, 8 had subtle diffuse 
lucencies in the retina. For 15 eyes (1.17%), OCT showed intraretinal and
subretinal fluid, which was missed by FA. CONCLUSIONS: Both FA and
high-resolution OCT are highly sensitive techniques and correlate well in
detection of ME. However, there is a small chance that when performed alone they 
might miss existing subtle ME.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 18398354 [PubMed - indexed for MEDLINE]

329: Physiol Rev. 2008 Apr;88(2):639-72.

Molecular physiology of bestrophins: multifunctional membrane proteins linked to 
best disease and other retinopathies.

Hartzell HC, Qu Z, Yu K, Xiao Q, Chien LT.

Department of Cell Biology, Center for Neurodegenerative Disease, Emory
University School of Medicine, Atlanta, Georgia 30322, USA. hartzell@emory.edu

This article reviews the current state of knowledge about the bestrophins, a
newly identified family of proteins that can function both as Cl(-) channels and 
as regulators of voltage-gated Ca(2+) channels. The founding member, human
bestrophin-1 (hBest1), was identified as the gene responsible for a dominantly
inherited, juvenile-onset form of macular degeneration called Best vitelliform
macular dystrophy. Mutations in hBest1 have also been associated with a small
fraction of adult-onset macular dystrophies. It is proposed that dysfunction of
bestrophin results in abnormal fluid and ion transport by the retinal pigment
epithelium, resulting in a weakened interface between the retinal pigment
epithelium and photoreceptors. There is compelling evidence that bestrophins are 
Cl(-) channels, but bestrophins remain enigmatic because it is not clear that the
Cl(-) channel function can explain Best disease. In addition to functioning as a 
Cl(-) channel, hBest1 also is able to regulate voltage-gated Ca(2+) channels.
Some bestrophins are activated by increases in intracellular Ca(2+)
concentration, but whether bestrophins are the molecular counterpart of
Ca(2+)-activated Cl(-) channels remains in doubt. Bestrophins are also regulated 
by cell volume and may be a member of the volume-regulated anion channel family.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Review

PMID: 18391176 [PubMed - indexed for MEDLINE]

330: Invest Ophthalmol Vis Sci. 2008 Jul;49(7):3126-33. Epub 2008 Apr 4.

Prevalence and associated risk factors of age-related macular degeneration in an 
elderly Chinese population in Taiwan: the Shihpai Eye Study.

Chen SJ, Cheng CY, Peng KL, Li AF, Hsu WM, Liu JH, Chou P.

Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, Taiwan.

PURPOSE: To assess the prevalence and associated risk factors of age-related
macular degeneration (AMD) in an elderly Chinese population in Taiwan. METHODS:
The Shihpai Eye Study was a survey of vision and ocular disease in an elderly
Chinese population 65 years of age or older residing in Shihpai, Taipei, Taiwan. 
Of 2045 elderly residents randomly sampled from the household registration
databank, 1361 (66.6%) underwent a detailed ophthalmic examination that included 
fundus color slides by fundus camera after pupil dilatation. Photographs were
graded according to the Wisconsin Age-Related Maculopathy Grading System.
RESULTS: Fundus photographs were available for 1105 (54.0% in the eligible, 81.2%
in the ocular examined) participants. The 47 (4.3%) participants who had
ungradable fundus images were older and had more lens opacity. Of the 1058
gradable photographs, the prevalence of early AMD was 9.2% (95% confidence
interval [CI], 7.8-10.8); of late AMD, 1.9% (95% CI, 1.3-2.7); of soft drusen,
42.2% (95% CI, 39.7-44.8); of soft indistinct drusen, 4.1% (95% CI, 3.1-5.2); and
of any pigmentary change, 8.6% (95% CI, 7.2-10.2). Age was the most significant
factor associated with both early and late AMD. The prevalence of early AMD rose 
from 5.0% in the 65- to 69-year age group to 24.4% in those 80 years of age and
older; and for late AMD, from 1.0% to 9.0%. Those who currently drank alcohol had
a lower rate of early AMD than did the nondrinker (adjusted odd ratio 0.32, 95%
CI: 0.11-0.93, P = 0.037). CONCLUSIONS: AMD is a common eye disease in the
elderly Chinese people in Taiwan. The adjusted prevalence rate of exudative AMD
is comparable to that in the Chinese people in the Multiethnic Study of
Atherosclerosis (MESA) in the United States but is higher than in the Chinese
people in the Beijing study in China. Further studies are needed to clarify the
incidence and associated risk factors.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18390643 [PubMed - indexed for MEDLINE]

331: Invest Ophthalmol Vis Sci. 2008 Jul;49(7):3253-8. Epub 2008 Apr 4.

Increased role of peripheral vision in self-induced motion in patients with
age-related macular degeneration.

Tarita-Nistor L, González EG, Markowitz SN, Lillakas L, Steinbach MJ.

Vision Science Research Program, Toronto Western Hospital, Toronto, Ontario,
Canada.

PURPOSE: The contribution of peripheral vision in inducing self-motion (vection) 
was investigated in people with bilateral age-related macular degeneration (AMD).
METHODS: Eleven patients with bilateral AMD and dense central scotomas with no
islands of functional central retina and 12 age-matched control subjects were
exposed to random-dot patterns projected on a large screen. The dots either moved
from left to right, inducing linear vection, or rotated about the roll axis,
inducing roll vection. Latency, total vection time, and objective and subjective 
measures of tilt were recorded. RESULTS: The patients with AMD experienced
shorter latencies than did the age-matched control participants, but the total
vection time in both conditions and tilt during roll vection were the same in
both groups. There was a positive correlation between objective tilt and
subjective measures of tilt in the AMD, but not in the age-matched control group.
There was a negative relationship between absolute scotoma size and latency.
CONCLUSIONS: Two main conclusions were drawn. First, the role of peripheral
vision in inducing vection is enhanced in people with bilateral central vision
loss. Second, people with bilateral AMD adapt successfully to a moving
environment (they do not experience vection longer, nor do they tilt more) and
are more aware of their postural position than are age-matched control subjects.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18390642 [PubMed - indexed for MEDLINE]

332: Invest Ophthalmol Vis Sci. 2008 Jul;49(7):2790-8. Epub 2008 Apr 4.

AMD-like lesions in the rat retina: a latent consequence of perinatal hemorrhage.

Pow DV, Diaz CM.

Department of Anatomy, University of Newcastle, NSW, Australia.
david@powfamily.com

PURPOSE: Hemorrhaging is a commonplace event in the human retina around the time 
of birth. This study was conducted to examine the potential long-term sequelae of
hemorrhaging in the eyes of rats that exhibited transient spontaneous
microhemorrhages a few days after birth. METHODS: Retinas of Dark Agouti rats
aged from day of birth to 2 years old were analyzed histologically,
histochemically, and by immunocytochemistry. Fetal human retinas were also
examined anatomically and histochemically for evidence of hemorrhages. RESULTS:
Dark Agouti rats from our colony consistently exhibited spontaneous focal
hemorrhages at the vitread surface of the retina between postnatal days 3 and 6. 
Erythrocytes were subsequently cleared by macrophages, which accumulated
hemosiderin. These macrophages remained in focal patches in the inner retina for 
the duration of the study. For at least 6 months after the initial transient
hemorrhages, the retinas exhibited no overt histologic damage. At approximately 8
to 9 months, photoreceptor degenerative changes were apparent in spatial register
with the patches of macrophages in the inner retina. Additional events such as
breakdown of Bruch's membrane, glial remodeling, neovascularization, ingress of
RPE cells into the retina and accumulation of drusen-like autofluorescent
structures were also observed in topographic register with macrophage-laden
patches in aged animals. CONCLUSIONS: Microhemorrhages in the retina may initiate
the formation of focal lesions, months or years after the initial insult. The
lesions exhibit key features of AMD. These animals may represent a useful model
for studying the potential basis of the pathogenesis of AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18390639 [PubMed - indexed for MEDLINE]

333: Invest Ophthalmol Vis Sci. 2008 Oct;49(10):4545-52. Epub 2008 Apr 4.

In vivo three-dimensional imaging of neovascular age-related macular degeneration
using optical frequency domain imaging at 1050 nm.

de Bruin DM, Burnes DL, Loewenstein J, Chen Y, Chang S, Chen TC, Esmaili DD, de
Boer JF.

Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard
Medical School, Boston, Massachusetts, USA.

PURPOSE: To assess the application of optical frequency domain imaging (OFDI) at 
1050 nm for the detection of choroidal neovascularization (CNV) in age-related
macular degeneration (AMD) and its response to treatment. Three patients
presenting with blurred vision and exudative AMD were imaged before and after
anti-VEGF treatment with ranibizumab. METHODS: The patients were imaged with
OFDI, a swept-source-based, high-speed optical coherence tomography (OCT) system 
developed at the Wellman Center for Photomedicine. A center wavelength of 1050 nm
was used that has been demonstrated to provide better imaging of the deeper
structures of the retina below the RPE, such as the choroidal vasculature.
Three-dimensional data sets were acquired in 2 to 4 seconds. RESULTS: En face
images were compiled from cross-sectional OFDI data and correlated with color
fundus photography (CF) and fluorescein angiograms (FAs). Cross-sectional images 
were coregistered with CF and FA to obtain depth-resolved information about CNV, 
CNV volume, retinal thickness, subretinal fluid volume and height of neurosensory
detachment before and after treatment with ranibizumab. A band of reduced
reflectivity below the RPE was identified in all three subjects that corresponded
to areas of confirmed and suspected occult CNV on FA. After treatment, this band 
was reduced in volume in all patients. CONCLUSIONS: High-speed 3-D OFDI at 1050
nm is a promising technology for imaging the retina and choroid in neovascular
AMD. The developed system at 1050 nm provides good contrast for occult (type 1)
CNV and may have advantages compared with time domain and current state of the
art spectral domain OCT systems (SD-OCT) at 850 nm.

Publication Types: 
    Case Reports
    Clinical Trial
    Research Support, N.I.H., Extramural
    Research Support, U.S. Gov't, Non-P.H.S.

PMID: 18390638 [PubMed - indexed for MEDLINE]

334: Eye. 2008 Jun;22(6):761-7. Epub 2008 Apr 4.

The evolving role of vascular endothelial growth factor inhibitors in the
treatment of neovascular age-related macular degeneration.

Dadgostar H, Waheed N.

Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.

Age-related macular degeneration (AMD) is the leading cause of blindness among
the ageing population. The introduction of molecular inhibitors of vascular
endothelial growth factor (VEGF), such as pegaptanib, ranibizumab, and
bevacizumab, as treatments for exudative AMD has provided new hope for affected
patients and has transformed the practices of retina specialists. Phase III
clinical trials have demonstrated the efficacy and safety of monthly ranibizumab 
for the preservation as well as improvement of visual acuity in patients with
exudative AMD. Ongoing trials are evaluating the effectiveness of different
dosing regimens, monitoring strategies, and combination therapies to determine
the optimal niche for this new class of drugs in AMD management. Based on
emerging evidence, most clinicians are now adopting a variable VEGF inhibitor
dosing strategy guided by serial diagnostic re-evaluation by optical coherence
tomography. Some are also finding benefit through the addition of photodynamic
therapy and steroids to the treatment regimen. The results of current and
upcoming trials systematically addressing these issues are expected to establish 
new guidelines for the management of AMD. Indeed, a new paradigm may emerge
wherein numerous modular therapeutic modalities are administered in customized
combinations based on specific clinical and diagnostic findings.

Publication Types: 
    Review

PMID: 18388961 [PubMed - indexed for MEDLINE]

335: Graefes Arch Clin Exp Ophthalmol. 2008 Aug;246(8):1189-93. Epub 2008 Apr 2.

Bevacizumab in the treatment of idiopathic macular telangiectasia.

Gamulescu MA, Walter A, Sachs H, Helbig H.

University Eye Clinic, Franz-Joseph-Strauss Allee 11, 93053, Regensburg, Germany.
gamulescu@eye-regensburg.de

BACKGROUND: To describe functional and morphological long-term follow-up results 
in patients with idiopathic macular telangiectasia (IMT) treated with
intravitreal bevacizumab. METHODS: Retrospective case series of three consecutive
male patients with IMT who were treated with intravitreal bevacizumab injections.
Best corrected visual acuity (BCVA) as well as fluorescein angiography (FA) and
optical coherence tomography (OCT) were monitored over the period of up to 12
months. RESULTS: Single intravitreal bevacizumab injection resulted in a marked
increase in BCVA from 20/50 to 20/20 in the patient with type 1 (aneurysmal) IMT 
during the first 4 weeks. Late-phase leakage on FA and cystoid macular oedema on 
OCT decreased significantly. This was sustained over the whole follow-up period
of 12 months. In contrast, in the two patients with type 2 (perifoveal) IMT,
leakage on FA decreased likewise, but this was not accompanied by an increase in 
BCVA despite triple injections. Small cystic changes seen on OCT remained
unchanged. CONCLUSION: Patients with type 1 IMT with pronounced macular oedema on
OCT may benefit from intravitreal bevacizumab injections, showing functional as
well as morphological improvement, while patients with type 2 IMT with minimal
cystic changes on OCT do not show functional improvement despite repeated
injections.

Publication Types: 
    Case Reports

PMID: 18386039 [PubMed - indexed for MEDLINE]

336: Invest Ophthalmol Vis Sci. 2008 Apr;49(4):1728-35.

An FMRI study of saccadic and smooth-pursuit eye movement control in patients
with age-related macular degeneration.

Little DM, Thulborn KR, Szlyk JP.

Department of Neurology and Rehabilitation, University of Illinois at Chicago
College of Medicine, Chicago, Illinois 60612, USA. little@uic.edu

PURPOSE: To compare the cortical networks that underlie oculomotor function in
patients with age-related macular degeneration (AMD) with those in normally
sighted control subjects, using functional magnetic resonance imaging (fMRI).
METHODS: Six patients with bilateral geographic retinal atrophy due to AMD (age
range, 55-83 years) were recruited for the study. The visual acuities of the
patients ranged from 20/76 (0.58 logMAR) to 20/360 (1.26 logMAR). An additional
six younger (age range, 22-31 years) and six older (age range, 54-78 years)
normally sighted individuals were recruited as control subjects. fMRI data were
acquired on a 3.0-Tesla, scanner while subjects performed visually guided saccade
(VGS) and smooth-pursuit (SmP) tasks. RESULTS: Contrasts between VGS and fixation
on a stationary target identified a network of activation that included the
frontal eye fields (FEFs), supplementary eye fields (SMA/SEFs), prefrontal cortex
(PFC), intraparietal sulci (IPS), and the areas of the visual cortex (MT/V5,
V2/V3, and V1) in control subjects and patients. A similar network was identified
for comparisons between SmP and periods of fixation. Marked variability was
observed in the performance of both tasks across all patients. For both tasks,
the patients generally showed increased PFC and IPS activation, with decreased
activation in visual cortex compared with the control subjects. The patients
showed significantly increased activation of the FEFs and SMA/SEFs in the SmP
task, compared with the control subjects. CONCLUSIONS: These data suggest that
performance of both eye movement tasks required greater involvement of the
cortical regions generally implicated in attention and effort in patients with
AMD.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, Non-P.H.S.

PMID: 18385097 [PubMed - indexed for MEDLINE]

337: Invest Ophthalmol Vis Sci. 2008 Apr;49(4):1652-9.

Toll-like receptor polymorphisms and age-related macular degeneration.

Edwards AO, Chen D, Fridley BL, James KM, Wu Y, Abecasis G, Swaroop A, Othman M, 
Branham K, Iyengar SK, Sivakumaran TA, Klein R, Klein BE, Tosakulwong N.

Department of Ophthalmology, Mayor Clinic, Rochester, MN 55905, USA.
edwardslab@mayo.edu

PURPOSE: Evidence from genetic-association studies in conjunction with the
demonstration of complement deposition in the retina and choroid implicates
noncellular pathways of innate immunity in the pathogenesis of age-related
macular degeneration (AMD). The purpose of this study was to determine whether
common variation in the 10 human toll-like receptors (TLRs) alters the risk of
AMD. METHODS: Sixty-eight SNPs were iteratively genotyped across the TLR genes in
a cohort of 577 subjects, with and without AMD. Two additional cohorts were used 
for replication studies. Standard genetic-association methods were used to
analyze the results for association with disease and interaction with other loci.
RESULTS: Coding SNPs in TLR3 (rs3775291) and TLR7 (rs179008) showed association
with AMD in one group (P = 0.01 and P = 0.02, respectively) before correction for
multiple testing. For both SNPs, the association with AMD arose due to an excess 
of heterozygotes compared with homozygotes for the major allele. The two coding
SNPs were not associated with AMD in another case-control cohort or an
extended-family cohort. Although an intronic SNP in TLR4 was associated
marginally with AMD (P = 0.03), it was not possible to replicate a previous
association with the rare coding SNP D299G in this gene (P = 0.6). CONCLUSIONS:
Although borderline support for association between polymorphisms in TLR genes
and AMD was reported for some cohorts, these initial observations of coding SNPs 
in TLR3, TLR4, and TLR7 were not replicated. TLR variants are unlikely to have a 
major impact on overall AMD risk, and the common variants studied were not
associated with AMD.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18385087 [PubMed - indexed for MEDLINE]

338: Invest Ophthalmol Vis Sci. 2008 Apr;49(4):1345-9.

Associations of plasma-soluble fas ligand with aging and age-related macular
degeneration.

Jiang S, Moriarty-Craige SE, Li C, Lynn MJ, Cai J, Jones DP, Sternberg P.

Department of Medicine, Emory University School of Medicine, Emory University,
Atlanta, Georgia, USA.

PURPOSE: To evaluate the associations between plasma-soluble Fas ligand (sFasL)
and age-related macular degeneration (AMD). METHODS: Plasma samples were obtained
from 230 individuals (age range, 45-85), with or without AMD. The concentrations 
of sFasL were determined by an enzyme-linked immunosorbent assay (ELISA). The
measured sFasL levels were transformed into cubic roots and were fitted into
linear regression models against AMD status, with adjustment for age and sex.
RESULTS: Plasma sFasL increased with age and AMD. There was a linear correlation 
between age and the cubic roots of sFasL. The plasma sFasL concentrations in
non-AMD subjects ranged from 0 to 1.63 ng/mL (median, 0.69 ng/mL), whereas in
patients with AMD, sFasL ranged from 0 to 2.43 ng/mL (median, 0.18 ng/mL).
Between the ages of 61 and 84, the subjects with AMD had significantly higher
sFasL than did the non-AMD subjects. There was a sexual dimorphism of the plasma 
sFasL levels. In non-AMD subjects, sFasL was lower in the females. In patients
with AMD, sFasL was higher in the females. CONCLUSIONS: An elevation of plasma
sFasL with aging may play a role in the development of AMD and is a potential
peripheral marker for monitoring disease progression.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18385048 [PubMed - indexed for MEDLINE]

339: J Opt Soc Am A Opt Image Sci Vis. 2008 Apr;25(4):947-57.

Resonance Raman imaging of macular pigment distributions in the human retina.

Sharifzadeh M, Zhao DY, Bernstein PS, Gellermann W.

Department of Physics, University of Utah, Salt Lake City, Utah 84112, USA.

We describe resonance Raman imaging (RRI) of macular pigment (MP) distributions
in the living human eye. MP consists of the antioxidant carotenoid compounds
lutein and zeaxanthin, is typically present in high concentrations in the healthy
human macula relative to the peripheral retina, and is thought to protect this
important central region from age-related macular degeneration. We demonstrate
that RRI is capable of quantifying and imaging the spatially strongly varying MP 
distribution in the human retina. Using laser excitation of the MP molecules at
488nm, and sequential camera detection of light emitted back from the retina at
the MP's strongest Raman peak position and at an off-peak position, RRI maps of
MP are obtained at a resolution below 50microm within a fraction of a second per 
exposure. RRI imaging can be carried out with undilated pupils and provides a
highly molecule-specific diagnostic imaging approach for MP distributions in
human subjects.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18382494 [PubMed - indexed for MEDLINE]

340: Ocul Immunol Inflamm. 2008 Jan-Feb;16(1):67-71.

Treatment of cystoid macular edema due to acute posterior multifocal placoid
pigment epitheliopathy.

Yenerel NM, Gorgun E, Dinc UA, Oncel M.

Yeditepe University Eye Hospital, Istanbul, Turkey. meldayen@hotmail.com

PURPOSE: To report a case of unilateral late-presenting acute posterior
multifocal placoid pigment epitheliopathy (APMPPE) with CME evaluated before and 
after administration of IVTA. METHOD: A 29-year-old male diagnosed as APMPPE with
CME was treated with IVTA. RESULTS: Fundus examination revealed CME and sequelae 
APMPPE lesions without involvement of posterior pole. FA and OCT findings were
consistent with CME. After IVTA (4 mg/0.1 mL) administration; BCVA increased from
20/28 to 20/20, mean retinal thickness decreased in OCT, and mean sensitivity in 
microperimetry increased from 15.7 to 17.2 dB. CONCLUSION: In this case report,
IVTA improved macular anatomy, visual acuity, and macular sensitivity.

Publication Types: 
    Case Reports

PMID: 18379948 [PubMed - indexed for MEDLINE]

341: Invest Ophthalmol Vis Sci. 2008 Jul;49(7):3095-9. Epub 2008 Mar 31.

Morphologic changes in patients with geographic atrophy assessed with a novel
spectral OCT-SLO combination.

Wolf-Schnurrbusch UE, Enzmann V, Brinkmann CK, Wolf S.

Klinik und Poliklinik für Augenheilkunde, Inselspital, University of Bern, Bern, 
Switzerland.

PURPOSE: To investigate the appearance of geographic atrophy in high-resolution
optical coherence tomography (OCT) images, the fundus autofluorescence (FAF)
pattern, and infrared images simultaneously recorded with a novel combined
OCT-scanning laser ophthalmology (SLO) system. METHODS: Patients aged over 50
years with geographic atrophy secondary to dry age-related macular degeneration
(ARMD) were assessed in a prospective cross-sectional study by means of
simultaneous spectral OCT-SLO (Spectralis HRA+OCT; Heidelberg Engineering,
Heidelberg, Germany). The integrity of the retinal layers was analyzed in the
apparently normal areas, the junctional zone between the normal retina and the
geographic atrophy, and the atrophic area. The presence and integrity of the
external limiting membrane, the photoreceptor inner segments, the outer segments,
and the retinal pigment epithelium were assessed. RESULTS: Fifty-two eyes of 52
patients (28 women, 24 men) aged 51 to 92 years were examined. Retinal layer
alterations were documented, not only in atrophic zones, but also in junctional
zones surrounding the geographic atrophy. Disintegration of the retinal layers
began in the RPE and adjacent retinal layers, such as the photoreceptor inner and
outer segments and external limiting membrane. CONCLUSIONS: Novel imaging
modalities will provide further valuable insight into ARMD pathogenesis. The key 
to understanding the morphologic change lies in in vivo depiction of retinal
layers by spectral OCT technology in combination with other imaging modalities
such as FAF.

PMID: 18378583 [PubMed - indexed for MEDLINE]

342: Invest Ophthalmol Vis Sci. 2008 Jul;49(7):3100-6. Epub 2008 Mar 31.

Coagulation gene predictors of photodynamic therapy for occult choroidal
neovascularization in age-related macular degeneration.

Parmeggiani F, Costagliola C, Gemmati D, D'Angelo S, Perri P, Campa C, Catozzi L,
Federici F, Sebastiani A, Incorvaia C.

Department of Ophthalmology, University of Ferrara, Ferrara, Italy.
francesco.parmeggiani@unife.it

PURPOSE: To determine whether different coagulation-balance genetic polymorphisms
explain the variable clinical outcomes of photodynamic therapy with verteporfin
(PDT-V) in Caucasian patients with occult subfoveal choroidal neovascularization 
(CNV) due to age-related macular degeneration (AMD). METHODS: The clinical
records of consecutive patients with AMD-related occult CNV, treated with PDT-V
for evidence of disease progression, were retrospectively examined. Eighty-four
eligible subjects were subdivided into responders and nonresponders based on CNV 
responsiveness to the first PDT-V over a 3-month period. Six gene polymorphisms
(i.e., factor V G1691A, prothrombin G20210A, factor XIII-A G185T,
methylenetetrahydrofolate reductase C677T, methionine synthase A2756G, and
methionine synthase reductase A66G) were genotyped in each patient. Logistic
regression analyses were performed to explore the predictive role of phenotypic
and genotypic variables for PDT-V effectiveness. RESULTS: Regression models
documented that PDT-V nonresponders were more frequently patients with the
hyperfibrinolytic G185T mutation of factor XIII-A (odds ratio [OR], 0.28; 95%
confidence interval [CI], 0.11-0.73; P < 0.01). Univariate logistic regression
was indicative of an overrepresentation of PDT-V responders among the combined
carriers of thrombophilic factor V 1691A and prothrombin 20210A alleles (OR =
3.8; 95% CI: 0.94-15.6; P = 0.07). All the other predictors considered did not
significantly influence the short-term CNV responsiveness to PDT-V. CONCLUSIONS: 
These data provide evidence of the presence of a pharmacogenetic relationship
between peculiar coagulation-balance genetic backgrounds and different levels of 
PDT-V effectiveness in patients with AMD with occult CNV.

PMID: 18378576 [PubMed - indexed for MEDLINE]

343: Am J Ophthalmol. 2008 Jun;145(6):1045-1051. Epub 2008 Apr 18.

Vascular endothelial growth factor gene polymorphisms in age-related macular
degeneration.

Lin JM, Wan L, Tsai YY, Lin HJ, Tsai Y, Lee CC, Tsai CH, Tseng SH, Tsai FJ.

Department of Ophthalmology, China Medical University Hospital, No. 2 Yuh Der
Road, Taichung, Taiwan.

PURPOSE: To investigate vascular endothelial growth factor (VEGF) gene
polymorphisms in unrelated Taiwan Chinese patients with late age-related macular 
degeneration (AMD) and controls. DESIGN: Retrospective case-control study.
METHODS: We enrolled 190 late AMD patients and 180 age-matched and gender-matched
controls. Late AMD was classified as either dry (atrophic; grade 4) or wet
(neovascular; grade 5) according to the International Age-Related Maculopathy
Epidemiologic Study. Genomic deoxyribonucleic acid was prepared from peripheral
blood obtained from all subjects. Polymerase chain reactions were used to analyze
five candidate single-nucleotide polymorphisms (SNPs) in VEGF gene: +405C/G
(rs2010963), -460 T/C (rs833061), +674 C/T (rs1413711), +936C/T (rs3025039), and 
-2578C/A (rs699947). RESULTS: Of the 190 late AMD patients, dry AMD was diagnosed
in 104 and wet AMD in 86. Among the five candidate SNPs studied, only the +936
C/T was significantly associated with wet AMD (T allele: 30% in wet AMD vs 14% in
controls; P = 1.45 x 10(-5); odds ratio, 2.61; 95% confidence interval, 1.68 to
4.07). No single haplotype was significantly associated with either late AMD or
controls. Based on genotypes at both VEGF +936 C/T and the complement factor H
(CFH) Y402H (rs1061170), the association of VEGF +936 C/T to AMD was significant 
when analyzed conditional on the presence of the CFH C risk allele and vice versa
(P < .0001). The VEGF +936 C/T was in strong linkage disequilibrium with CFH
Y402H (D' = 0.99). CONCLUSIONS: Both VEGF +936 C/T and CFH Y402H polymorphisms
are dependently associated with wet AMD in the Taiwan Chinese population.

PMID: 18378209 [PubMed - indexed for MEDLINE]

344: Am J Med. 2008 Apr;121(4):279-81.

Age-related macular degeneration: an update on treatment.

Gohel PS, Mandava N, Olson JL, Durairaj VD.

University of Colorado School of Medicine, Department of Ophthalmology, Denver,
CO, USA.

Age-related macular degeneration is a chronic disease leading to progressive
central vision loss. It is the leading cause of irreversible blindness in the
United States, most commonly affecting white Caucasians aged more than 55 years. 
Typical symptoms include decreased central vision, central scotoma, and
metamorphopsia. Patients with acute loss of vision should be promptly referred to
an ophthalmologist. New antiangiogenic therapies have significantly improved
visual prognosis in these patients.

Publication Types: 
    Case Reports

PMID: 18374683 [PubMed - indexed for MEDLINE]

345: Med Health R I. 2008 Feb;91(2):51-3, 56.

The quest to conquer age-related macular degeneration.

Bryan RG.

Warren Alpert Medical School, Brown University, Providence, RI, USA.
rgbryan@alumni.duke.edu

AMD causes irreversible blindness in the elderly. For years, treatment has been
non-existent or ineffective. With the advent of anti-VEGF agents,
ophthalmologists can stabilize and even improve visual function in these
patients. To accomplish this, however, requires frequent intraocular injections
and follow-up, costly in time and money to the patient and the health-care
system. In the near future, it is likely that newer strategies and newer drugs
will make the treatment of AMD easier, more effective, and more affordable.

Publication Types: 
    Review

PMID: 18372860 [PubMed - indexed for MEDLINE]

346: Jpn J Ophthalmol. 2008 Jan-Feb;52(1):52-6. Epub 2008 Mar 28.

Intravitreal bevacizumab for subfoveal choroidal neovascularization secondary to 
age-related macular degeneration in an Indian population.

Azad RV, Khan MA, Chanana B, Azad S.

Vitreo-Retina Services, Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All
India Institute of Medical Sciences, New Delhi, India.

PURPOSE: To investigate the 6-month safety profile and clinical outcomes of
intravitreal bevacizumab for treating subfoveal choroidal neovascularization
(CNV) in age-related macular degeneration (AMD). METHODS: We performed a
prospective nonrandomized interventional study of 40 consecutive patients (40
eyes) with subfoveal CNV due to AMD. Patients underwent standard ophthalmic
examination, optical coherence tomography, and fundus fluorescein angiography.
All patients were administered one or more intravitreal injections of bevacizumab
(1.25 mg) as primary therapy. Outcomes were also analyzed in subgroups based on
lesion type (classic or occult) and lesion size (< or =3000 microm or >3000
microm). RESULTS: At the 6 months' follow-up, mean best-corrected visual acuity
(BCVA) improved from 20/160 to 20/100 (P = 0.014), and the mean contrast
sensitivity improved from 0.38 to 0.62 (P = 0.001). The mean greatest linear
diameter and mean central macular thickness significantly decreased from 3.79 mm 
to 2.4 mm (P = 0.0001) and from 438.5 microm to 363 microm (P = 0.0001),
respectively. Visual acuity gain of 15 letters or more was seen in 20% of
patients, and the gain was more in the small-lesion subgroup (31.5%) than in the 
large-lesion subgroup (9.5%). No significant adverse effects were observed.
CONCLUSION: Intravitreal bevacizumab is a safe and effective modality for
treatment of CNV secondary to AMD. A significant improvement in BCVA with
intravitreal bevacizumab was observed for all lesion types.

PMID: 18369701 [PubMed - indexed for MEDLINE]

347: Diabetes Res Clin Pract. 2008 Jun;80(3):e8-10. Epub 2008 Mar 26.

Lanreotide Autogel for persistent diabetic macular edema.

Hernaez-Ortega MC, Soto-Pedre E, Piniés JA.

European Innovative Biomedicine Institute (EIBI), Cantabria, Spain.
concha.hernaez@eibi.es

Diffuse diabetic macular edema is usually refractory to conventional treatment.
We investigated the effectiveness of a new prolonged lanreotide formulation in
patients with bad-controlled diabetes and persistent cystoid macular edema. Our
findings suggest that monthly subcutaneous injections of lanreotide Autogel
offered an effective treatment alternative in these patients.

Publication Types: 
    Case Reports

PMID: 18367285 [PubMed - indexed for MEDLINE]

348: BMC Ophthalmol. 2008 Mar 17;8:5.

Intravitreal vs. subtenon triamcinolone acetonide for the treatment of diabetic
cystoid macular edema.

Cellini M, Pazzaglia A, Zamparini E, Leonetti P, Campos EC.

Department of Surgery and Transplant A, Valsalva, Ophthalmology Service (Chief:
Prof, E,C, Campos), University of Bologna, Italy. mauro.cellini@unibo.it

BACKGROUND: To assess the efficacy of the intravitreal (IVT) injection of
Triamcinolone Acetonide (TA) as compared to posterior subtenon (SBT) capsule
injection for the treatment of cystoid diabetic macular edema. METHODS: Fourteen 
patients with type II diabetes mellitus and on insulin treatment, presenting
diffuse cystoid macular edema were recruited. Before TA injection all focal lakes
were treated by laser photocoagulation. In the same patients one eye was assigned
to 4 mg IVT injection of TA and the fellow eye was then treated with 40 mg SBT
injection of TA. Before and one, three and six months after treatment we measured
visual acuity with ETDRS chart as well as thickness of the macula with optical
coherence tomography (OCT) and intraocular pressure (IOP). RESULTS: The eyes
treated with an IVT injection displayed significant improvement in visual acuity,
both after one (0.491 +/- 0.070; p < 0.001) and three months (0.500 +/- 0.089; p 
< 0.001) of treatment. Significant improvement was displayed also in eyes treated
with an SBT injection, again after one (0.455 +/- 0.069; p < 0.001) and three
months (0.427 +/- 0.065; p < 0.001). The difference between an IVT injection
(0.809 +/- 0.083) and SBT injection (0.460 +/- 0.072) becomes significant six
months after the treatment (p < 0.001).Macular thickness of the eyes treated with
IVT injection was significantly reduced both after one (222.7 +/- 13.4 microm; p 
< 0.001) and after three months (228.1 +/- 10.6 microm; p < 0.001) of treatment. 
The eyes treated with SBT injection displayed significant improvement after one
(220.1 +/- 15.1 microm; p < 0.001) and after three months (231.3 +/- 10.9 microm;
p < 0.001). The difference between the eyes treated with IVT injection (385.2 +/-
11.3 microm) and those treated with SBT injection (235.4 +/- 8.7 microm) becomes 
significant six months after the treatment (p < 0.001).Intraocular pressure of
the eyes treated with IVT injection significantly increased after one month (17.7
+/- 1.1 mm/Hg; p < 0.020), three (18.2 +/- 1.2 mm/Hg; p < 0.003) and six month
(18.1 +/- 1.3 mm/Hg; p < 0.007) when compared to baseline value (16.1 +/- 1.402
mm/Hg). In the SBT injection eyes we didn't display a significant increase of
intraocular pressure after one (16.4 +/- 1.2 mm/Hg; p < 0.450), three (16.3 +/-
1.1 mm/Hg; p < 0.630) and six months (16.2 +/- 1.1 mm/Hg; p < 0.720) when
compared to baseline value (16.2 +/- 1.3 mm/Hg). CONCLUSION: The parabulbar
subtenon approach can be considered a valid alternative to the intravitreal
injection. TRIAL REGISTRATION: Current Controlled Trials ISRCTN67086909.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 18366650 [PubMed - indexed for MEDLINE]

349: Qual Life Res. 2008 May;17(4):559-74.

Quality of life in age-related macular degeneration: a review of available
vision-specific psychometric tools.

Finger RP, Fleckenstein M, Holz FG, Scholl HP.

Department of Ophthalmology, University of Bonn, Bonn, Germany.

PURPOSE: Age-related macular degeneration (AMD) has a considerable impact on
older adults' independence and autonomy. Recently, patient reported outcomes
(PROs) such as QoL have been met with increasing interest by the scientific
community, healthcare payers and planners. Against this background, the multitude
of psychometric tools used to measure QoL in AMD was reviewed. METHODS: A search 
of the literature from 1990 onwards yielded 355 results, out of which 58
publications were included in the review. Data regarding design, validation and
extent of utilization were obtained where available. RESULTS: The National Eye
Institute-Visual Function Questionnaire (NEI VFQ-25-item) was found to be the
most often used (29% of studies) and best validated psychometric tool, followed
by the Visual Function Questionnaire (VF-14; 17%), and the Impact of Vision
Impairment Profile (IVI; 9%). Most tools that were identified have been validated
for the use in AMD patients. CONCLUSION: Psychometric tools specifically designed
to measure vision-related quality of life are well equipped and validated to
measure QoL in AMD. More recent developments such as the Macular
Disease-dependent Quality of Life (MacDQoL) questionnaire might be able to depict
dimensions of vision-related QoL in greater depth. Future studies should
endeavour to use a suggested standard when gathering data on vision related QoL, 
allowing for international comparisons.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18365767 [PubMed - indexed for MEDLINE]

350: J Am Geriatr Soc. 2008 May;56(5):800-7. Epub 2008 Mar 20.

Older women with age-related macular degeneration have a greater risk of falls: a
physiological profile assessment study.

Szabo SM, Janssen PA, Khan K, Potter MJ, Lord SR.

Department of Health Care and Epidemiology, University of British Columbia,
Vancouver, Canada. shelaghs@telus.net

OBJECTIVES: To determine whether older women with exudative age-related macular
degeneration (AMD) are at greater risk of falls. DESIGN: Cross-sectional study.
SETTING: A hospital-based ophthalmology clinic in Vancouver, Canada.
PARTICIPANTS: One hundred fifteen older (aged > or = 70) community-dwelling women
with exudative AMD (AMD cohort) and two control groups: 54 community-dwelling
women without exudative AMD drawn from the same community (non-AMD cohort) and
341 community-dwelling Australian women (Australian normative cohort).
MEASUREMENTS: Participants were assessed for falls risk using the short-form
Physiological Profile Assessment (PPA), which provides a fall risk index score
and subcomponent measures of vision, proprioception, strength, reaction time, and
postural sway. RESULTS: The mean fall risk index score in the AMD cohort (3.20)
was significantly greater than that of the non-AMD cohort (1.21; P<.001), and
fall risk scores increased with age to a greater extent in the AMD cohort. The
higher fall risk scores in the AMD cohort resulted from significantly worse
performance on each PPA test, not just the test of vision. The AMD cohort also
performed worse than the Australian normative cohort in tests of vision, reaction
time, and postural sway. CONCLUSION: Older women with AMD have impaired balance, 
slow visual reaction times, and poor vision, which in combination result in a
significantly greater risk of falls than population norms. These deficits are
clearly indicated in the physiological falls profile for the group. Strategies to
enhance balance may be particularly beneficial to prevent falls in this group.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18363677 [PubMed - indexed for MEDLINE]

351: Mol Ther. 2008 Apr;16(4):791-9. Epub 2008 Feb 5.

Ranibizumab for macular edema due to retinal vein occlusions: implication of VEGF
as a critical stimulator.

Campochiaro PA, Hafiz G, Shah SM, Nguyen QD, Ying H, Do DV, Quinlan E,
Zimmer-Galler I, Haller JA, Solomon SD, Sung JU, Hadi Y, Janjua KA, Jawed N, Choy
DF, Arron JR.

Department of Ophthalmology, Johns Hopkins University School of Medicine,
Baltimore, Maryland 21287-9277, USA. pcampo@jhmi.edu

Macular edema is a major cause of vision loss in patients with central retinal
vein occlusion (CRVO) or branch retinal vein occlusion (BRVO). It is not clear
how much of the edema is due to hydrodynamic changes from the obstruction and how
much is due to chemical mediators. Patients with macular edema due to CRVO (n =
20) or BRVO (n = 20) were randomized to receive three monthly injections of 0.3
or 0.5 mg of ranibizumab. At the primary endpoint, month 3, the median
improvement in letters read at 4 m was 17 in the 0.3-mg group and 14 in the
0.5-mg group for CRVO, and 10 and 18, respectively for the BRVO group. Optical
coherence tomography (OCT) showed that compared to injections of 0.3 mg,
injections of 0.5 mg of ranibizumab tended to cause more rapid reductions of
central retinal thickening that lasted longer between injections, but in 3
months, excess central retinal thickening which is a quantitative assessment of
the macular edema, was reduced by approximately 90% in all four treatment groups.
There was no correlation between the amount of improvement and duration of
disease or patient age at baseline, but there was some correlation between the
aqueous vascular endothelial growth factor (VEGF) level at baseline and amount of
improvement. These data indicate that excess production of VEGF in the retinas of
patients with CRVO or BRVO is a major contributor to macular edema and suggest
that additional studies investigating the efficacy of intraocular injections of
ranibizumab are needed.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18362932 [PubMed - indexed for MEDLINE]

352: Invest Ophthalmol Vis Sci. 2008 Jul;49(7):3090-4. Epub 2008 Mar 24.

Genotype-phenotype correlations for exudative age-related macular degeneration
associated with homozygous HTRA1 and CFH genotypes.

Leveziel N, Zerbib J, Richard F, Querques G, Morineau G, Fremeaux-Bacchi V,
Coscas G, Soubrane G, Benlian P, Souied EH.

Faculte de Medecine Henri Mondor, Creteil University Eye Clinic, Creteil, France.

PURPOSE: Major genetic factors for age-related macular degeneration (AMD) have
recently been identified as susceptibility risk factors, including polymorphisms 
of HTRA1 and CFH genes. The purpose was to analyze the angiographic features of
patients harboring homozygous genotypes for HTRA1 and CFH genes in a French
exudative AMD population. METHODS: Two hundred patients affected with exudative
AMD were genotyped for the polymorphisms rs11200638 of the HTRA1 gene and
rs10611710 of the CFH gene. Four homozygous groups were extracted from the entire
cohort: double homozygous for wild-type alleles of both genes (group 1),
homozygous for the polymorphism of the HTRA1 gene only (group 2), homozygous for 
the polymorphism of the CFH gene only (group 3), and double homozygous carriers
for both polymorphisms (group 4). Choroidal neovascularization (CNV) was graded
as classic and predominantly classic (PC), occult, minimally classic (MC), or
retinal angiomatosis proliferation (RAP). RESULTS: Group 1 (n = 9) presented
44.4% classic and PC, 33.3% occult, 11.1% MC, and 11.1% RAP. Group 2 (n = 12)
presented 50.0% classic and PC, 33.3% occult, no MC CNV and 16.7% RAP. Group 3 (n
= 28) presented 10.7% classic and PC, 67.9% occult, 14.3% MC, and 7.1% RAP. Group
4 (n = 17) presented 29.4% classic and PC, 52.9% occult, 11.8% MC, and 5.9% RAP. 
Occult CNV or MC CNV was more frequently observed in group 3 than in group 2
(82.1% vs 33.3%; P < 0.02). Classic and PC CNV were more frequently observed in
group 2 than in group 3 (50% vs. 10.7%; P < 0.03). CONCLUSIONS: This attempt at a
genotypic-angiographic correlation in an exudative AMD sample suggests an
association between occult or MC CNV and the CFH polymorphism and between classic
and PC CNV and the HTRA1 polymorphism.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 18362109 [PubMed - indexed for MEDLINE]

353: Am J Epidemiol. 2008 May 15;167(10):1217-25. Epub 2008 Mar 20.

Estrogen receptor alpha and matrix metalloproteinase 2 polymorphisms and
age-related maculopathy in older women.

Seitzman RL, Mahajan VB, Mangione C, Cauley JA, Ensrud KE, Stone KL, Cummings SR,
Hochberg MC, Hillier TA, Sinsheimer JS, Yu F, Coleman AL; Study of Osteoporotic
Fractures Research Group.

Department of Ophthalmology, David Geffen School of Medicine, University of
California, Los Angeles, Los Angeles, CA 92122, USA. seitzman@ucla.edu

In this study, the authors sought to determine whether single nucleotide
polymorphisms in the estrogen receptor alpha (ESR1) and matrix metalloproteinase 
2 (MMP2) genes are associated with age-related maculopathy (ARM) in older women. 
Subjects comprised a random sample of Caucasian women aged > or =74 years
participating in the Study of Osteoporotic Fractures year 10 follow-up (n = 906) 
in 1997-1998. Fundus photographs were graded for ARM using a modification of the 
Wisconsin Age-Related Maculopathy Grading System. The prevalences of early ARM
and late ARM were 46% and 4%, respectively. The MMP2 rs2287074 single nucleotide 
polymorphism (G-->A) was associated with ARM. The A allele was present in 47%,
43%, and 30% of subjects with no, early, and late ARM, respectively (p = 0.01),
and was associated with lower odds of any ARM (for AG vs. GG, odds ratio = 0.80, 
95% confidence interval: 0.65, 0.99; for AA vs. GG, odds ratio = 0.64, 95%
confidence interval: 0.42, 0.98). An interaction with use of postmenopausal
hormone therapy was significant (p = 0.02). The MMP2 rs2287074 A allele may be
associated with a lower likelihood of ARM in older Caucasian women, particularly 
those who have never used hormone therapy. The role of MMP2 rs2287074 in ARM
should be further elucidated.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18359774 [PubMed - indexed for MEDLINE]

354: Prilozi. 2007 Dec;28(2):149-60.

Association of dyslipidaemia with macular oedema and hard exudates in diabetic
maculopathy.

Golubovic-Arsovska M.

Eye Diseases Clinic, Clinical Centre, Medical Faculty, Ss. Cyril and Methodius
University, Skopje, Macedonia. golubovicarsovska@yahoo.com

Diabetic retinal changes, diabetic maculopathy and prolixferative retinopathy are
major causes of loss of vision worldwide in people of working age. In addition to
oedema in the area of the macula lutea, diabetic maculopathy is often
characterized by white changes termed hard exudates. It has been observed that
the appearance of hard exudates is consistent with the appearance of
dyslipidaemia, which is typical for diabetic patients. The aim of this paper was 
to underline the role of elevated serum lipids in the onset of macular oedema and
hard exudates. MATERIAL AND METHODS: The examined group comprised 38 patients
with diabetes mellitus type 2 who had medioretinal changes of the eye fundus as
well as changes in the macular area manifested by retinal oedema and the presence
of hard exudates. The control group consisted of type 2 diabetic patients without
changes associated with diabetic maculopathy. RESULTS: The examined group of
diabetic patients that manifested diabetic maculopathy had significantly higher
values of total lipids (9.49 +/- 2.02 g/L vs. 8.06 +/- 0.84 g/L), triglycerol
(2.02 +/- 1.23 mmol/l vs. 1.24 +/- 0.37 mmol/l), total cholesterol (6.03 +/- 1.13
mmol/l vs. 5.21 +/- 0.62 mmol/l) and cholesterol ester (4.02 +/- 0.72 mmol/l vs. 
3.48 +/- 0.46 mmol/l) as compared to the control group. Although values of HDL
(1.39 +/- 1.01 mmol/l) and LDL (3.69 +/- 1.0 mmol/l) cholesterol were higher in
the examined group than in the control one, there were no statistically
significant differences (1.39 +/- 1.01 mmol/l vs. 1.30 +/- 0.33 mmol/l) and (3.69
+/- 1.0 mmol/l vs. 3.60 +/- 0.72 mmol/l) respectively. The analysis of the
severity of hard exudates and oedema in relation to lipid fractions in the
examined group showed that total lipids, total cholesterol and cholesterol were
significantly higher than in the subjects where exudates were less severe.
CONCLUSION: Hyperlipidaemia is a risk factor for the development of hard exudates
in diabetic maculopathy.

PMID: 18356786 [PubMed - indexed for MEDLINE]

355: Br J Ophthalmol. 2008 Jun;92(6):757-61. Epub 2008 Mar 20.

A prospective randomised study on low-dose transpupillary thermotherapy versus
photodynamic therapy for neovascular age-related macular degeneration.

Odergren A, Algvere PV, Seregard S, Kvanta A.

Vitreoretinal Department, Karolinska Institutet, St. Eriks Eye Hospital,
Polhemsgatan 50, SE-11282 Stockholm, Sweden. anne.odergren@sankterik.se

AIM: To compare the efficacy of low-dose transpupillary thermotherapy (TTT) and
verteporfin photodynamic therapy (PDT) in patients with occult neovascular
age-related macular degeneration (AMD). METHODS: Patients were randomised to
receive either low-dose TTT (136 mW/mm) (and sham PDT) (n = 52) or PDT (and sham 
TTT) (n = 46) with retreatment if leakage was documented by fluorescein
angiography. At baseline and at every follow-up, best corrected visual acuity
(BCVA) was measured with the Early Treatment Diabetic Retinopathy Study (ETDRS)
chart, lesion size on fluorescein angiography and foveal thickness with optical
coherence tomography. The primary outcome measure was the proportion of patients 
who lost <15 letters at 12 months' follow-up. Secondary outcome measures included
the proportion of patients who gained >/=0 letters, the change in mean lesion
size and the change in foveal thickness at 12 months' follow-up. RESULTS: The
percent of patients losing fewer than 15 letters at 12 months was 75.0% in the
TTT group and 73.9% in the PDT group (p>0.05). The percent of patients with
preserved or improved BCVA was 36.5% in the TTT group versus 23.9% in the PDT
group (p>0.05). The mean decrease in foveal thickness was 15% for TTT and 24%
(p>0.05) for PDT-treated patients, and the mean increase in total lesion area was
-0.7% and -1.1% (p>0.05), respectively. CONCLUSION: In this prospective,
randomised trial low-dose TTT and PDT appeared to be equally efficient at
stabilising visual acuity in patients with occult neovascular AMD. Low-dose TTT
may be considered as an alternative to PDT in this set of patients and also as an
adjuvant to pharmacotherapy.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial

PMID: 18356266 [PubMed - indexed for MEDLINE]

356: Br J Ophthalmol. 2008 May;92(5):667-8. Epub 2008 Mar 20.

Predicted biological activity of intravitreal VEGF Trap.

Stewart MW, Rosenfeld PJ.

Mayo Clinic College of Medicine, Jacksonville, Florida, USA.
stewart.michael@mayo.edu

AIM: To compare the intravitreal binding activity of VEGF Trap with that of
ranibizumab against vascular endothelial growth factor (VEGF) using a
time-dependent and dose-dependent mathematical model. METHODS: Intravitreal
half-lives and relative equimolar VEGF-binding activities of VEGF Trap and
ranibizumab were incorporated into a first-order decay model. Time-dependent VEGF
Trap activities (relative to ranibizumab) for different initial doses (0.5, 1.15,
2 and 4 mg) were calculated and plotted. RESULTS: Seventy-nine days after a
single VEGF Trap (1.15 mg) injection, the intravitreal VEGF-binding activity
would be comparable to ranibizumab at 30 days. After injection of 0.5, 2 and 4 mg
VEGF Trap, the intravitreal VEGF-binding activities (comparable to ranibizumab at
30 days) would occur at 73, 83 and 87 days, respectively CONCLUSION: On the basis
of this mathematical model, VEGF Trap maintains significant intravitreal
VEGF-binding activity for 10-12 weeks after a single injection.

Publication Types: 
    Comparative Study

PMID: 18356264 [PubMed - indexed for MEDLINE]

357: Exp Eye Res. 2008 May;86(5):856-9. Epub 2008 Jan 31.

Immunohistochemical analysis of aldehyde-modified proteins in drusen in
cynomolgus monkeys (Macaca fascicularis).

Kaidzu S, Tanito M, Ohira A, Umeda S, Suzuki M, Yoshikawa Y, Iwata T.

Department of Ophthalmology, Shimane University Faculty of Medicine, 89-1 Enya,
Izumo, Shimane 693-8501, Japan.

Protein modifications resulting from reactive aldehydes are thought to be
involved in the pathogenesis of various degenerative diseases. Aged cynomolgus
monkey (Macaca fascicularis) spontaneously develop drusen in the macula,
consistent with the phenotype observed in early-stage age-related macular
degeneration (AMD), indicating that this animal is an optimum model for AMD. In
retinal sections from three monkeys with macular degeneration, regardless of
their size, drusen were consistently positive with immunohistochemical labeling
against protein modifications by 4-hydroxynonenal and 4-hydroxyhexenal, end
products of non-enzymatic oxidation of n-6 and n-3 polyunsaturated fatty acids,
respectively. Positive labeling for both modifications was observed in the
ganglion cell layer, the inner nuclear layer, the outer nuclear layer, and the
retinal pigment epithelium. However, no consistent differences in location or
intensity of the labeling were observed between monkeys with normal macula and
macular degeneration. The results suggest a possible association between drusen
formation and protein modifications by aldehydes in the pathogenesis of AMD.

PMID: 18355809 [PubMed - indexed for MEDLINE]

358: Prescrire Int. 2008 Feb;17(93):3-6.

Ranibizumab: new drug. Macular degeneration: second-line use due to risks.

[No authors listed]

(1) Due to a lack of any better alternatives, photodynamic therapy is the
standard treatment for subfoveal lesions due to neovascular age-related macular
degeneration (AMD). It consists of intravenous injection of a photosensitizer,
verteporfin, followed by local red laser activation. This treatment, sometimes
repeated every 3 months, stabilises the loss of visual acuity for 2 years in
about 50% of patients. Adverse effects are generally acceptable. (2) Ranibizumab 
is an antibody fragment targeting vascular endothelial growth factor (VEGF). VEGF
is implicated in the neovascularisation involved in age-related macular
degeneration. Ranibizumab is injected into the vitreous in the same way as
pegaptanib, the first VEGF antagonist to be approved for an ocular indication.
(3) Clinical evaluation of ranibizumab includes 2 placebo-controlled trials (900 
patients in total), a trial versus verteporfin (423 patients), and a trial
testing ranibizumab in combination with verteporfin (162 patients). More than 90%
of patients treated with ranibizumab in these two trials had no tangible loss of 
vision for one to two years, compared to about 68% of patients treated with
verteporfin (statistically significant difference). These trials did not attempt 
to determine the optimal interval between intravitreal injections. (4) No trials 
have directly compared ranibizumab with pegaptanib; indirect comparisons suggest 
that ranibizumab is better than pegaptanib. (5) Intravitreal injection of
ranibizumab can have local adverse effects, similar to pegaptanib. These include 
inflammatory reactions, infections, and elevated intraocular pressure. Arterial
thromboses at distant sites, in particular strokes, have been reported with
ranibizumab, at a higher frequency with 0.5 mg per infection (about 1%) than with
0.3 mg per injection. (6) When visual acuity continues to deteriorate in patients
with age-related macular degeneration despite treatment with verteporfin,
ranibizumab provides an effective alternative for patients with no particular
risk factors for stroke.

PMID: 18354841 [PubMed - indexed for MEDLINE]

359: Surv Ophthalmol. 2008 Mar-Apr;53(2):139-49.

Intravitreal steroids for macular edema: the past, the present, and the future.

Cunningham MA, Edelman JL, Kaushal S.

Department of Ophthalmology, University of Florida College of Medicine,
Gainesville, Florida 32610-0284, USA.

Macular edema, a condition usually associated with an underlying disease process,
is a common cause of severe visual loss. There have been a variety of approaches 
to the treatment of macular edema; within the past few years, however,
intravitreal corticosteroid treatments have emerged as an increasingly used
treatment option for patients with macular edema. Intravitreal delivery allows
the steroid to bypass the blood-retinal barrier, leading to a more concentrated
dose of steroid for a prolonged period of time. Corticosteroids have likely been 
successful in the treatment of various forms of macular edema, due to their known
anti-angiogenic, anti-edematous, anti-inflammatory, anti-apoptotic, and
anti-proliferative effects. Intravitreal triamcinolone acetonide has been
repeatedly successful in reducing macular edema and improving visual acuity,
although the duration of action is typically short-term. Due to the recurrent and
chronic nature of macular edema, biodegradable implants may be the future of
intravitreal steroids. Intravitreal corticosteroids are not without risks.
Steroid-related side effects include cataract formation and elevated intraocular 
pressure. Injection-related side effects include retinal detachment, vitreous
hemorrhage, bacterial endophthalmitis, and sterile endophthalmitis. This article 
reviews the evolving role of intravitreal corticosteroids in the treatment of
macular edema secondary to uveitis, diabetes, and retinal vascular disorders.

Publication Types: 
    Review

PMID: 18348879 [PubMed - indexed for MEDLINE]

360: Can J Ophthalmol. 2008 Apr;43(2):180-7.

Age-related macular degeneration and low-vision rehabilitation: a systematic
review.

Hooper P, Jutai JW, Strong G, Russell-Minda E.

Ivey Eye Institute, The University of Western Ontario, London, ON, Canada.

BACKGROUND: Because of the prevalence and devastating consequences of age-related
macular degeneration (AMD), a systematic review devoted to low-vision
rehabilitation and AMD seems timely and appropriate. METHODS: Several electronic 
databases were searched for studies from 1980 to 2006 involving individuals with 
low vision or visual impairment and rehabilitation interventions. Studies were
assessed for quality and level of evidence. RESULTS: The findings indicate that
standard low-vision rehabilitation programs, conventional in-clinic assessments, 
and optical devices are effective ways of managing and living with vision loss.
Areas of unmet need include determining which types of orientation and mobility
programs and devices are most effective and developing methods of matching
assistive technologies with the individual's visual and environmental
requirements. INTERPRETATION: Additional randomized controlled trials with
similar intervention comparisons and outcome measures are needed to form stronger
conclusions for the most effective low-vision rehabilitation interventions for
individuals with AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18347620 [PubMed - indexed for MEDLINE]

361: Photochem Photobiol. 2008 May-Jun;84(3):639-44. Epub 2008 Mar 8.

Role of ocular melanin in ophthalmic physiology and pathology.

Hu DN, Simon JD, Sarna T.

Tissue Culture Center, Department of Pathology, The New York Eye and Ear
Infirmary and New York Medical College, New York, NY, USA. hu2095@yahoo.com

The mammalian eye consists of several layers of pigmented tissues that contain
melanin. The eye is a unique organ for pigment cell research because one can
isolate and compare melanosomes from different tissues and embryonic origins.
Retinal, iris and ciliary pigment epithelial cells are derived from the neural
ectoderm, more specifically from the extremity of the embryonic optical cup,
which is also the origin of the retina. In contrast, the pigment-generating cells
in the choroid and in the stroma of the iris and ciliary body, uveal melanocytes,
are developed from the neural crest, the same origin as the melanocytes in skin
and hair. This review examines the potential functions of ocular melanin in the
human eye. Following a discussion of the role of melanins in the pigment
epithelium and uveal melanocytes, three specific topics are explored in
detail-photo-screening protective effects, biophysical and biochemical protective
effects, and the biologic and photobiologic effects of the two main classes of
melanins (generally found as mixtures in ocular melanosomes)--eumelanin and
pheomelanin.

Publication Types: 
    Review

PMID: 18346089 [PubMed - indexed for MEDLINE]

362: Invest Ophthalmol Vis Sci. 2008 Jul;49(7):2848-55. Epub 2008 Mar 14.

Mitochondrial proteomics of the retinal pigment epithelium at progressive stages 
of age-related macular degeneration.

Nordgaard CL, Karunadharma PP, Feng X, Olsen TW, Ferrington DA.

Department of Ophthalmology, University of Minnesota, Minneapolis, Minnesota,
USA.

PURPOSE: Age-related macular degeneration (AMD) is the leading cause of vision
loss in individuals over the age of 65. Histopathological changes become evident 
in the retinal pigment epithelium (RPE), a monolayer that provides metabolic
support for the overlying photoreceptors, even at the earliest stages of AMD that
precede vision loss. In a previous global RPE proteome analysis, changes were
identified in the content of several mitochondrial proteins associated with AMD. 
In this study, the subproteome of mitochondria isolated from human donor RPE
graded with the Minnesota Grading System (MGS) was analyzed. METHODS: Human donor
eye bank eyes were categorized into one of four progressive stages (MGS 1-4)
based on the clinical features of AMD. After dissection of the RPE, mitochondrial
proteins were isolated and separated by two-dimensional gel electrophoresis based
on their charge and mass. Protein spot densities were compared between the four
MGS stages. Peptides from spots that changed significantly with MGS stage were
extracted and analyzed by using mass spectrometry to identify the protein.
RESULTS: Western blot analyses verified that mitochondria were consistently
enriched between MGS stages. The densities of eight spots increased or decreased 
significantly as a function of MGS stage. These spots were identified as the
alpha-, beta-, and delta-ATP synthase subunits, subunit VIb of the cytochrome c
oxidase complex, mitofilin, mtHsp70, and the mitochondrial translation factor Tu.
CONCLUSIONS: The results are consistent with the hypothesis that mitochondrial
dysfunction is associated with AMD and further suggest specific
pathophysiological mechanisms involving altered mitochondrial translation, import
of nuclear-encoded proteins, and ATP synthase activity.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18344451 [PubMed - indexed for MEDLINE]

363: Stat Med. 2008 Sep 10;27(20):4094-106.

Multi-rule quality control for the age-related eye disease study.

Caudill SP, Schleicher RL, Pirkle JL.

Division of Laboratory Sciences, National Center for Environmental Health,
Centers for Disease Control & Prevention, Public Health Service, U.S. Department 
of Health and Human Services, Atlanta, GA 30333, USA. spc1@cdc.gov

The Age-Related Eye Disease Study (AREDS), sponsored by the National Eye
Institute, was designed to study the natural history and risk factors of
age-related macular degeneration (AMD) and cataract, and to evaluate the effect
of high doses of antioxidants and zinc on eye disease progression. AMD and
cataract are leading causes of visual impairment and blindness in the U.S., with 
frequency of both diseases increasing dramatically after age 65. Participants
were randomly chosen to receive antioxidant or placebo tablets. Blood was drawn
annually from a subset of patients, and serum concentrations of 17 different
nutritional indicators were measured. Because of the complexity of the analytical
methods, and possibility of instrument error due to failure of any one of many
component parts, several different instruments were used for most analytes. In
addition, to assure that the measurement systems were performing adequately
across a wide range of concentrations, multiple control pools were monitored with
analyte concentrations at low, medium, and high concentrations. We report here
the multi-rule quality control system (MRQCS) used during the later part of the
trial (AREDS Phase III). This system was designed to monitor systematic error and
random within- and among-run error for analytical runs using 1-3 different
quality control pools per run and 1-2 measurements of each pool per run. We
demonstrate the features of the MRQCS using quality control (QC) data associated 
with vitamin C measurements. We also provide operating characteristics to
demonstrate how the MRQCS responds to increases in systematic and/or random
error.

Publication Types: 
    Randomized Controlled Trial

PMID: 18344178 [PubMed - indexed for MEDLINE]

364: Genes Immun. 2008 Apr;9(3):231-9. Epub 2008 Mar 13.

Complement factor H polymorphisms, renal phenotypes and age-related macular
degeneration: the Blue Mountains Eye Study.

Xing C, Sivakumaran TA, Wang JJ, Rochtchina E, Joshi T, Smith W, Mitchell P,
Iyengar SK.

Department of Epidemiology and Biostatistics, Case Western Reserve University,
Cleveland, OH 44106, USA.

Complement factor H (CFH) is a key regulator of the alternative pathway of
complement and its mutations have been associated with membranoproliferative
glomerulonephritis type II, atypical hemolytic uremic syndrome and age-related
macular degeneration (AMD), suggesting that alternative pathway dysregulation is 
a common pathogenetic feature of these ocular and renal conditions. In this study
we tested the hypothesis that common CFH variants have a global role in renal
function in the Australian population-based Blue Mountains Eye Study (BMES). We
replicated the association of I62V with estimated glomerular filtration rate
(GFR; P=0.017) and creatinine clearance (CRCL; P=0.015). The minor allele of I62V
(G) was deleterious: adding one copy of the G allele decreased GFR/CRCL by
approximately 0.98 ml min(-1) per 1.73 m(2) (95% confidence interval (CI): 0.97, 
0.99). We also replicated the association of Y402H with AMD and provided an
unbiased estimate of population attributable risk (PAR). The minor allele of
Y402H (C) was deleterious: the odds ratio estimate of CC genotype compared to TT 
was 1.87 (95% CI: 1.44, 2.45). The PAR of the C allele was estimated as 0.22 (95%
CI: 0.15, 0.28). In summary, in the BMES population we confirmed the association 
between I62V and renal function, as measured by the estimated GFR, plus the
association of Y402H with both early- and late-stage AMD.

Publication Types: 
    Comparative Study
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18340363 [PubMed - indexed for MEDLINE]

365: Mol Immunol. 2008 May;45(10):2897-904. Epub 2008 Mar 12.

Genetic deficiency of complement factor H in a patient with age-related macular
degeneration and membranoproliferative glomerulonephritis.

Montes T, Goicoechea de Jorge E, Ramos R, Gomà M, Pujol O, Sánchez-Corral P,
Rodríguez de Córdoba S.

Centro de Investigaciones Biológicas and Centro de Investigación Biomédica en
Enfermedades Raras, Ramiro de Maeztu 9, Madrid, Spain.

Age-related macular degeneration (AMD) and membranoproliferative
glomerulonephritis type II (MPGN2) are dense deposit diseases that share a
genetic association with complement genes and have complement proteins as
important components of the dense deposits. Here, we present the case of a
64-year-old smoker male who developed both AMD and MPGN2 in his late 50s. The
patient presented persistent low plasma levels of C3, factor H levels in the
lower part of the normal range and C3NeF traces. Genetic analyses of the CFH,
CFB, C3, CFHR1-CFHR3 and LOC387715/HTRA1 genes revealed that the patient was
heterozygote for a novel missense mutation in exon 9 of CFH (c.1292 G>A) that
results in a Cys431Tyr substitution in SCR7 of the factor H protein. In addition,
he was homozygote for the His402 CFH allele, heterozygote for the Ser69 LOC387715
allele, homozygote for the Arg32 (BFS) CFB allele, heterozygote for the Gly102
(C3F) C3 allele and carried no deletion of the CFHR1/CFHR3 genes. Proteomic and
functional analyses indicate absence in plasma of the factor H allele carrying
the Cys431Tyr mutation. As a whole, these data recapitulate a prototypical
complement genetic profile, including a partial factor H deficiency and the
presence of major risk factors for AMD and MPGN2, which support the hypothesis
that these dense deposit diseases have a common pathogenic mechanism involving
dysregulation of the alternative pathway of complement activation.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 18336910 [PubMed - indexed for MEDLINE]

366: Mol Vis. 2008 Feb 4;14:262-7.

Molecular analysis of ABCA4 and CRB1 genes in a Spanish family segregating both
Stargardt disease and autosomal recessive retinitis pigmentosa.

Riveiro-Alvarez R, Vallespin E, Wilke R, Garcia-Sandoval B, Cantalapiedra D,
Aguirre-Lamban J, Avila-Fernandez A, Gimenez A, Trujillo-Tiebas MJ, Ayuso C.

Genetics Department, Fundacion Jimenez Diaz-CIBERER, Madrid, Spain.
rriveiro@fjd.es

PURPOSE: Stargardt disease (STGD), characterized by central visual impairment, is
the most common juvenile macular dystrophy. All recessively inherited cases are
thought to be due to mutations in the ABCA4 gene. Early-onset autosomal recessive
retinitis pigmentosa (arRP) is a severe retinal degeneration that presents before
the patient is ten years old. It has been associated with mutations in different 
genes, including CRB1. The aim of this study was to determine the genetic causes 
for two different retinal dystrophies, STGD and early-onset arRP, both
segregating in one Spanish family. METHODS: Mutational analyses were performed
using the ABCR400 and Leber congenital amaurosis (LCA) genotyping microarrays.
Additional scanning for mutations was conducted by denaturing high performance
liquid chromatography (dHPLC); results were confirmed by direct sequencing.
RESULTS: A patient, who exhibited a STGD phenotype, was found to be homozygous
for the p.Asn1805Asp (c.5413A>G) mutation in ABCA4. However, his affected sister,
who had the arRP phenotype, was found to be heterozygous for this allele; no
other sequence change could be found in ABCA4. Analysis using the LCA chip
revealed the p.Cys948Tyr mutation in CRB1 in heterozygous state. A second
mutation (p.Trp822ter) was found in the CRB1 gene in the affected female by
denaturing high performance liquid chromatography (dHPLC) and direct sequencing. 
CONCLUSIONS: Two distinct retinal dystrophies with mutations affecting two
different genes cosegregated in this family. The presence of two different
phenotypes associated with mutations in two distinct genes in one single family
must be considered especially when dealing with retinal dystrophies which bear
high carrier frequencies in general population.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 18334942 [PubMed - indexed for MEDLINE]

367: Br Med Bull. 2008;85:127-49.

Age-related macular degeneration: diagnosis and management.

Cook HL, Patel PJ, Tufail A.

Moorfields Eye Hospital, City Road, London EC1V 2PD, UK.
adnan.tufail@moorfields.nhs.uk

BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of blind
registration in Western Europe and the third leading cause of blindness
worldwide. METHODS: The management of AMD is discussed with a review of current
and new treatments. RESULTS: Although there is no treatment for advanced dry AMD 
(geographic atrophy), there have been considerable advances in the management of 
neovascular AMD (nAMD). Established therapies for nAMD include laser
photocoagulation and photodynamic therapy (PDT), but these have largely been
superseded by agents which block the action of vascular endothelial growth factor
(anti-VEGF agents). Current preventative strategies involve cessation of smoking 
and use of specific nutritional supplements to reduce the risk of developing
nAMD. CONCLUSIONS: There have been exciting advances in the treatment of nAMD and
increased understanding of the genetics and pathogenic mechanisms involved will
hopefully lead to the development of new therapies in the future.

Publication Types: 
    Review

PMID: 18334518 [PubMed - indexed for MEDLINE]

368: Arch Ophthalmol. 2008 Mar;126(3):320-8.

Macular dystrophy associated with the A3243G mitochondrial DNA mutation. Distinct
retinal and associated features, disease variability, and characterization of
asymptomatic family members.

Michaelides M, Jenkins SA, Bamiou DE, Sweeney MG, Davis MB, Luxon L, Bird AC,
Rath PP.

Moorfields Eye Hospital, London, England. michel.michaelides@ucl.ac.uk

OBJECTIVES: To determine (1) detailed retinal and audiological features of
probands harboring the A3243G mitochondrial DNA mutation (m.3243A>G) and their
asymptomatic maternal relatives, (2) intrafamilial and interfamilial phenotypic
variability, and (3) the presence of other systemic features. METHODS: Seven
probands harboring the A3243G mitochondrial DNA mutation and 36 asymptomatic
maternal relatives were ascertained. Participants underwent ophthalmologic
examination, fundus photography, autofluorescence imaging, and audiological
evaluation and completed a questionnaire. Blood samples were taken to test for
diabetes, determine renal function, and screen relatives for the A3243G mutation.
RESULTS: The A3243G mutation was associated with both intrafamilial and
interfamilial variable expressivity regarding retinal appearance, hearing loss,
diabetes, and other systemic features. The most common macular appearance in
maternal relatives (one-third of those positive for the mutation) was mild
abnormalities of the retinal pigment epithelium (more clearly identified using
autofluorescence), which may therefore be a useful clinical indicator suggesting 
positive mutation status. Four probands and 13 mutation-positive relatives were
found to have evidence of significant bilateral, cochlear, symmetrical
age-adjusted hearing loss, predominantly affecting high frequencies. CONCLUSIONS:
Hearing loss and macular disturbance were the most frequent findings in
mutation-positive participants, with 95% of mutation-positive relatives having
hearing loss. Diabetes was the least frequent finding. Patients with progressive 
hearing loss may merit ophthalmologic assessment to detect retinal abnormalities 
consistent with the A3243G mutation. Conversely, patients with macular features
in keeping with the A3243G mutation should have audiological testing, even in the
absence of diabetes or a positive family history.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18332310 [PubMed - indexed for MEDLINE]

369: Drugs Aging. 2008;25(3):255-68.

Association between visual acuity and medical and non-medical costs in patients
with wet age-related macular degeneration in France, Germany and Italy.

Bandello F, Augustin A, Sahel JA, Benhaddi H, Negrini C, Hieke K, Berdeaux GH;
MICMAC (MICro-economics of MACular degeneration) Study Group.

Collaborators: Sahel J, Chaine G, Weber M, Quentel G, Cohen SY, Mauget-Faysse M, 
Brasseur G, Nicole C, Korobelnik JF, Benchaboune M, Charlin JF, Augustin,
Weinhold, Kaut, Hyppa, Jurgeit, Incorvaia C, Bandello F, Menchini U, Boscia F,
Malerba, Setaccioli, Varano M, Schiano.

University of Udine, Udine, Italy.

INTRODUCTION: Exudative ('wet') age-related macular degeneration (ARMD) is the
major cause of blindness in Western developed countries. Treatments aimed at
preserving vision are already available and new compounds are under development. 
Micro-economics information will be pivotal to justifying forthcoming investment.
OBJECTIVE: This study sought to investigate the costs of exudative ARMD in
patients who were actively treated at ophthalmology referral centres in three
European countries: France, Germany and Italy. METHOD: This cross-sectional
observational study was conducted in France, Germany and Italy in 2004. The
following data were collected: ARMD description, visual acuity (VA), and the
medical and non-medical resources used for ARMD in the preceding year. The
economic perspective was that of society. ANOVA for cost variables estimated the 
impact of ARMD per eye, adjusted for sex and age. Both hospital and ambulatory
eye centres were included. Patients with exudative ARMD were stratified into four
levels of severity using VA thresholds of 20/200 for the worst eye (WE) and 20/40
for the best eye (BE). The main outcome measure was medical and non-medical
costs. RESULTS: 360 patients were included (females 60%; mean age 77 years; mean 
interval since diagnosis 2.3 years). The two groups with the greatest difference 
in severity of VA loss consisted of BE >or= 20/40, WE >or= 20/200 (27.2% of
patients) and BE <20/40, WE <20/200 (25.5% of patients). Total cost was
two-thirds medical and one-third non-medical. Total costs increased with ARMD
severity and were 1.1-2 times greater for severe disease compared with less
severe disease. Average medical costs (2004 values) in France were euro 3714,
compared with euro 1810 in Germany and euro 2020 in Italy, and showed slight
increases with ARMD severity. Non-medical costs were significantly higher for
patients with severe disease and highest in Germany. CONCLUSION: The impact of
ARMD on costs was considerable and a positive correlation was found between total
costs and ARMD severity. Differences among countries were partly explained by
differences in customary care delivery.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18331076 [PubMed - indexed for MEDLINE]

370: Am J Ophthalmol. 2008 May;145(5):854-61. Epub 2008 Mar 6.

Comment in:
    Am J Ophthalmol. 2008 Dec;146(6):974; author reply 974-5.

Comparative therapy evaluation of intravitreal bevacizumab and triamcinolone
acetonide on persistent diffuse diabetic macular edema.

Shimura M, Nakazawa T, Yasuda K, Shiono T, Iida T, Sakamoto T, Nishida K.

Department of Ophthalmology, NTT East Japan Tohoku Hospital, Sendai, Miyagi,
Japan. masahiko@v101.vaio.ne.jp

PURPOSE: To compare the effect of an intravitreal injection of bevacizumab, an
anti-vascular endothelial growth factor (VEGF) antibody, with that of
triamcinolone acetonide, a corticosteroid for reduction of diabetic macular edema
(DME). DESIGN: Prospective, comparative interventional case series. METHODS:
Twenty-eight eyes of 14 patients with bilateral DME participated in this study.
In each patient, one eye received an intravitreal injection of 4 mg triamcinolone
acetonide and the other eye received 1.25 mg bevacizumab. The clinical course of 
best-corrected visual acuity (VA) with a logarithm of the minimum angle of
resolution chart and averaged foveal thickness using optical coherence tomography
was monitored for up to 24 weeks after the injection. RESULTS: Before the
injection, foveal thickness and VA were 522.3 +/- 91.3 microm and 0.64 +/- 0.28
microm in the triamcinolone-injected eye, and 527.6 +/- 78.8 microm and 0.61 +/- 
0.18 microm in the bevacizumab-injected eye, respectively; there was no
significant difference between the eyes. One week after the injection, both eyes 
showed significant regression of macular edema. The triamcinolone-injected eye
(342.6 +/- 85.5 microm and 0.33 +/- 0.21 microm) showed significantly better
results than the bevacizumab-injected eye (397.6 +/- 103.0 microm and 0.37 +/-
0.17 microm). However, both eyes showed the recurrence of macular edema with
time, even at 24 weeks. Triamcinolone (410.4 +/- 82.4 microm and 0.47 +/- 0.25
microm) kept better results than bevacizumab (501.6 +/- 92.5 microm and 0.61 +/- 
0.17 microm). CONCLUSIONS: With the generally used concentration, intravitreal
injection of triamcinolone acetonide showed better results in reducing DME and in
the improvement of VA than that of bevacizumab, suggesting that the pathogenesis 
of DME is not only attributable to VEGF-dependency, but is also attributable to
other mechanisms suppressed by corticosteroid.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 18328456 [PubMed - indexed for MEDLINE]

371: Retina. 2008 Mar;28(3):498-503.

Angiographic evidence for revascularization of an rpe-choroid graft in patients
with age-related macular degeneration.

Maaijwee K, Van Den Biesen PR, Missotten T, Van Meurs JC.

The Rotterdam Eye Hospital, Erasmus University, Rotterdam, The Netherlands.
kmaaijwee@hotmail.com

PURPOSE: To study graft perfusion using fluorescein angiography (FA) and
indocyanine green angiography (ICG) after the translocation of an autologous
retinal pigment epithelium (RPE)-choroid graft in patients with exudative
age-related macular degeneration (AMD). METHODS: Retrospective observational case
series of 31 patients with AMD who had FA and/or ICG performed after an
RPE-choroid graft translocation. The FAs (n = 25) and ICGs (n = 23) were assessed
by an independent masked reader for the presence of early fluorescence of the
graft in FA, and for perfusion of the choroidal vessels of the graft and
recipient bed in ICG. RESULTS: Early fluorescence of the graft was present in 23 
of the 25 FAs. Perfusion of the graft vasculature was observed in 12 of the 23
ICGs. The two grafts that lacked early fluorescence in FA also had no signs of
choroidal perfusion of the graft and the recipient bed with ICG. CONCLUSION:
Revascularization of the RPE-choroid graft was observed in all but 2 of the 31
patients either by early fluorescence of the graft by FA or by identification of 
perfused choroidal graft vessels with ICG from 1 week up to 3 years after
surgery. For assessment of revascularization of the graft evaluation of the early
phase of the FA is recommended.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18327145 [PubMed - indexed for MEDLINE]

372: Retina. 2008 Mar;28(3):477-84.

Induction of retinochoroidal venous anastomosis in central retinal vein occlusion
with macular edema via a full-thickness retinochoroidal incision.

Kang JH, Kim JH, Kim JI, Kang SW.

Department of Ophthalmology, Samsung Medical Center, Sungkyunkwan University
School of Medicine, Seoul, Republic of Korea.

PURPOSE: To report the induction of retinochoroidal venous anastomosis (RCVA) in 
the treatment of nonischemic central retinal vein occlusion (CRVO) with macular
edema via a full-thickness retinochoroidal incision. METHODS: In nine eyes with
nonischemic CRVO and intractable macular edema, one or two full-thickness
incisions transacting a major retinal branch vein to the level of inner sclera
were made in conjunction with vitrectomy. Fluorescein angiography was conducted
to evaluate the formation of functional RCVA. Best-corrected visual acuity (BCVA)
and central macular thickness (CMT) were compared before and after the surgery.
RESULTS: The mean follow-up period +/- SD was 12.0 +/- 5.1 months. All nine eyes 
developed functional RCVA after the surgery. The mean BCVA +/- SD improved from
0.75 +/- 0.30 logMAR (logarithm of the minimal angle of resolution) to 0.55 +/-
0.26 logMAR (P = 0.018), and the mean CMT +/- SD was reduced from 686 +/- 265
microm to 251 +/- 150 microm (P = 0.011). Additional surgery was performed on one
eye due to persistent vitreous hemorrhage. CONCLUSION: Full-thickness
retinochoroidal incision appears to raise the rate of successful RCVA formation
and may improve the outcome of CRVO with macular edema.

PMID: 18327142 [PubMed - indexed for MEDLINE]

373: Retina. 2008 Mar;28(3):465-72.

Efficacy of intravitreal triamcinolone for the treatment of macular edema
secondary to branch retinal vein occlusion in eyes with or without grid laser
photocoagulation.

Cakir M, Dogan M, Bayraktar Z, Bayraktar S, Acar N, Altan T, Kapran Z, Yilmaz OF.

Beyoglu Eye Research and Education Hospital, Istanbul, Turkey.
drmcakir@hotmail.com

PURPOSE: To evaluate the efficacy of primary and secondary (following grid laser 
photocoagulation) intravitreal triamcinolone acetonide (IVTA) injection for the
treatment of macular edema associated with branch retinal vein occlusion (BRVO). 
METHODS: Eyes with macular edema secondary to BRVO and best-corrected visual
acuity (BCVA) worse than 20/40 were included. Eyes eligible for Branch Retinal
Vein Occlusion Study (BVOS) guidelines received grid laser treatment first. Those
that were not improved at least two lines following grid laser or that did not
meet those guidelines received 4 mg IVTA injection. The efficacy of IVTA
treatment was assessed by analyzing the change in BCVA and reduction in central
macular thickness (CMT) measured by optical coherence tomography. Intraocular
pressure (IOP) spikes and other complications were recorded. RESULTS: The data
from 37 eyes were included; in 12 of them IVTA injection was given after grid
laser while 25 of them received IVTA as a primary treatment. Mean follow-up was
9.6 +/- 4.5 months. BCVA was 0.06 +/- 0.30 and 0.17 +/- 0.50 in the primary and
secondary IVTA injection groups, respectively. In the primary injection group,
there was a statistically significant gain in BCVA throughout the follow-up (P < 
0.05), while a small increase in BCVA was noted only at the third month visit in 
the secondary IVTA injection group (P = 0.04). Average CMT were 434.8 +/-
122.1microm and 389.0 +/- 171.9 microm before IVTA injection in the two groups,
respectively. In the primary IVTA injection group, CMT decreased at 1 month
following IVTA injection and remained statistically significant until the sixth
month visit (P < 0.05). In the secondary IVTA injection group, a slight reduction
in CMT was noted only in the first month visit (P = 0.02). Pre-IVTA BCVA was
found to be the single statistically significant predictor of BCVA gain following
IVTA injection. In 8 patients (21.6%), the IOP increased above 25 mmHg
postoperatively, and was successfully managed by medical treatment.
Endophthalmitis did not develop in any of the patients. CONCLUSION: IVTA
injection produced a significant reduction of macular edema in eyes with BRVO
either with or without prior grid laser treatment. Reduction of CMT increased the
BCVA in most of the eyes receiving IVTA primarily, while only a slight
improvement of BCVA was found in eyes with prior grid laser. The IVTA effect was 
transient. Larger studies are necessary to find the best approach (either grid
laser or IVTA) to patients with macular edema associated with BRVO.

Publication Types: 
    Comparative Study

PMID: 18327140 [PubMed - indexed for MEDLINE]

374: Retina. 2008 Mar;28(3):420-6.

Surgical and anatomical outcomes of pars plana vitrectomy for diffuse
nontractional diabetic macular edema.

Figueroa MS, Contreras I, Noval S.

Department of Ophthalmology, Ramón y Cajal Hospital, Madrid, Spain.

PURPOSE: To prospectively determine the efficacy of vitrectomy combined with
intravitreal triamcinolone acetonide (IVTA) injection, internal limiting membrane
(ILM) peeling, or both in treating diffuse nontractional diabetic macular edema
(ME). METHODS: Patients with diffuse ME of <6 months who had no evidence of
macular traction or macular ischemia were included in the study. Patients
previously diagnosed with glaucoma underwent vitrectomy with ILM peeling. All
other patients were randomly assigned to vitrectomy or vitrectomy with ILM
peeling followed by IVTA injection. RESULTS: Forty-two eyes of 38 patients were
included in the study. Mean follow-up was 12 months. A statistically significant 
reduction in macular thickness was found at 1 month to 6 months, disappearing at 
12 months. No differences in visual acuity between treatment groups were found
during follow-up. Visual acuity improved in 5 (12%) of 42 eyes, remained
unchanged in 32 (76%) of 42 eyes, and worsened in 5 (12%) of 42 eyes.
Complications included increase in intraocular pressure in 8 (26%) of 31 eyes,
mild vitreous hemorrhage in 6 (14%) of 42 eyes, central retinal pigment
epithelium changes in 5 (12%) of 42 eyes, and cataract progression in 11 (38%) of
29 phakic eyes. CONCLUSION: In diffuse diabetic ME with no retinal traction,
vitrectomy with either ILM peeling or IVTA injection at the end of surgery
produces a short-term improvement in retinal thickness but no long-term
anatomical or functional improvements.

Publication Types: 
    Randomized Controlled Trial

PMID: 18327133 [PubMed - indexed for MEDLINE]

375: Retina. 2008 Mar;28(3):410-9.

Pars plana vitrectomy with internal limiting membrane peeling for diabetic
macular edema.

Hartley KL, Smiddy WE, Flynn HW Jr, Murray TG.

Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami,
Miller School of Medicine, Florida, USA.

PURPOSE: To evaluate anatomic and visual acuity (VA) results of pars plana
vitrectomy (PPV) with internal limiting membrane (ILM) peeling for diffuse
diabetic macular edema (DME), and to review the literature on the topic. METHODS:
Retrospective noncomparative case series of patients who underwent PPV with ILM
peeling for diffuse DME between January 1, 2000, and December 1, 2005, performed 
by three surgeons at Bascom Palmer Eye Institute. Main outcome measures included 
pre- and postoperative optical coherence tomography (OCT) and visual acuity. Mean
follow-up period was 8 months (range, 43 days-2 years). RESULTS: Twenty-four eyes
of 23 patients meeting the criteria were evaluated. Duration of DME ranged from 1
to 93 months. Mean preoperative logMAR vision was 0.782 (range, 0.30-1.82). Mean 
logMAR visual acuity at final follow-up was 0.771 (range, 0.10-2.00). At last
follow-up, 25% of eyes had > or =2 line increase in VA from baseline, 54% of eyes
had no improvement in VA, and 21% of eyes had > or =2 line decrease in VA. Of 9
eyes with pre- and postoperative OCT, there was an overall reduction in central
macular thickness of 141 microm at postoperative month 3 and 120 microm at last
follow-up. Postoperative complications included progression of cataract in 6
(60%) of 10 phakic eyes, postoperative intraocular pressure > or =30 mmHg in 6
(24%) eyes, and postoperative vitreous hemorrhage in 2 (8%) eyes. CONCLUSIONS:
Pars plana vitrectomy with ILM peeling was associated with a reduction in DME
when measured by OCT in the majority of eyes, but visual acuity outcomes showed
minimal improvement compared to baseline. These results suggest the efficacy of
PPV with ILM peeling for eyes with DME has not been well established and should
be reserved for therapy with selected cases.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18327132 [PubMed - indexed for MEDLINE]

376: Invest Ophthalmol Vis Sci. 2008 Mar;49(3):1200-9.

Prevalence and morphology of druse types in the macula and periphery of eyes with
age-related maculopathy.

Rudolf M, Clark ME, Chimento MF, Li CM, Medeiros NE, Curcio CA.

Department of Ophthalmology, University of Alabama at Birmingham, Callahan Eye
Foundation Hospital, Birmingham, Alabama 35294-0009, USA. mirudolf@aol.com

PURPOSE: Macular drusen are hallmarks of age-related maculopathy (ARM), but these
focal extracellular lesions also appear with age in the peripheral retina. The
present study was conducted to determine regional differences in morphology that 
contribute to the higher vulnerability of the macula to advanced disease.
METHODS: Drusen from the macula (n = 133) and periphery (n = 282) were isolated
and concentrated from nine ARM-affected eyes. A semiquantitative light
microscopic evaluation of 1-mum-thick sections included 12 parameters. RESULTS:
Significant differences were found between the macula and periphery in ease of
isolation, distribution of druse type, composition qualities, and substructures. 
On harvesting, macular drusen were friable, with liquefied or crystallized
contents. Peripheral drusen were resilient and never crystallized. On
examination, soft drusen appeared in the macula only, had homogeneous content
without significant substructures, and had abundant basal laminar deposits
(BlamD). Several substructures, previously postulated as signatures of druse
biogenesis, were found primarily in hard drusen. Specific to hard drusen, which
appeared everywhere, were central subregions and reduced RPE coverage. Macular
hard drusen with a rich substructure profile differed from primarily homogeneous 
peripheral hard drusen. Compound drusen, found in the periphery only, exhibited a
composition profile that was not intermediate between hard and soft. CONCLUSIONS:
The data confirm regional differences in druse morphology, composition, and
physical properties, most likely based on different formative mechanisms that may
contribute to macular susceptibility for ARM progression. Two other reasons that 
only the macula is at high risk despite having relatively few drusen are the
exclusive presence of soft drusen and the abundant BlamD in this region.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18326750 [PubMed - indexed for MEDLINE]

377: Invest Ophthalmol Vis Sci. 2008 Mar;49(3):1191-9.

Evidence of widespread retinal dysfunction in patients with stargardt disease and
morphologically unaffected carrier relatives.

Maia-Lopes S, Silva ED, Silva MF, Reis A, Faria P, Castelo-Branco M.

Visual Neuroscience Laboratory, Centre for Ophthalmology, IBILI (Institute for
Biomedical Research on Light and Image), Faculty of Medicine, Coimbra, Portugal.

PURPOSE: To characterize contrast sensitivity (CS) across the visual field for
two achromatic spatial-temporal frequencies in 21 families with Stargardt disease
(STGD) and to correlate psychophysical impairment with patterns of change in
multifocal electroretinography (mfERG). METHODS: Twenty-seven eyes from patients 
with STGD, 16 eyes from asymptomatic relatives, and 44 age-matched control eyes
were included. Chromatic CS function was assessed by comparing protan, deutan,
and tritan (Cambridge Color Test; Cambridge Research Systems Ltd., Rochester, UK)
and anomaloscope measures (IF-2; Roland Consult, Wiesbaden, Germany). Achromatic 
CS measures were obtained with custom-made software in nine locations by using
randomly interleaved staircases. The first task-low spatial frequency
(LSF)-matched the known frequency-doubling method that is believed to activate
the magnocellular pathway preferentially. The second included an intermediate
spatial frequency (ISF, 3.5 cyc/deg). mfERGs (RETIscan; Roland Consult) were also
obtained. Relatives were screened for ABCA4 mutations by ABCR400 microarray and
direct sequencing. RESULTS: Central impairment of achromatic and chromatic CS
(along the three isolation axes) was observed in STGD. LSF and ISF tasks revealed
significant and widespread dysfunction in patients and their morphologically
unaffected relatives, 80% of whom were found to be ABCA4 mutation carriers.
Significant reduction of P1 amplitudes was also observed in both groups.
CONCLUSIONS: CS function is impaired in patients with STGD at distinct
spatial-temporal frequencies, which, in addition to the color vision deficits,
suggests dual impairment of the magno- parvocellular pathways. STGD
morphologically unaffected carriers may show patterns of psychophysical
dysfunction that are mirrored by abnormal mfERG responses.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18326749 [PubMed - indexed for MEDLINE]

378: Invest Ophthalmol Vis Sci. 2008 Mar;49(3):1101-5.

Elastin gene polymorphisms in neovascular age-related macular degeneration and
polypoidal choroidal vasculopathy.

Kondo N, Honda S, Ishibashi K, Tsukahara Y, Negi A.

Department of Organ Therapeutics, Division of Ophthalmology, Kobe University
Graduate School of Medicine, Kobe, Japan.

PURPOSE: To study and reveal genetic variation in the elastin gene (ELN) that may
be associated with neovascular age-related macular degeneration (AMD) and/or
polypoidal choroidal vasculopathy (PCV). Eyes with neovascular AMD and PCV
exhibit substantially different structural alterations of the elastic layer in
the Bruch's membrane. The hypothesis for the present study was that ELN
polymorphisms may play a role in the development of neovascular AMD and PCV and
that genetic differences in ELN between these two phenotypes may be a reason for 
the histopathologic differences. To test these hypotheses, ELN was screened for
genetic variation in a Japanese case-control dataset. METHODS: Two hundred
eighty-five subjects were enrolled: 78 with neovascular AMD, 103 with PCV, and
104 control. We genotyped five tagged single nucleotide polymorphisms (SNPs) in
ELN, and allele, genotype, and haplotype frequency distributions among
neovascular AMD, PCV, and control subjects were compared by chi(2) tests.
RESULTS: A common ELN variant was significantly associated with susceptibility to
PCV. The age- and sex-adjusted odds ratio was 7.56 for individuals homozygous for
the risk allele compared with those carrying no more than one copy of the risk
allele. Significantly different distributions were found in allele and haplotype 
frequencies between neovascular AMD and PCV in this region, but no particular ELN
SNPs or haplotypes were significantly associated with neovascular AMD.
CONCLUSIONS: The findings implicate ELN as a susceptibility gene for PCV, and
suggest that a different pathogenic process may be involved in the phenotypic
expression of neovascular AMD and PCV.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18326737 [PubMed - indexed for MEDLINE]

379: Invest Ophthalmol Vis Sci. 2008 Mar;49(3):1084-8.

Repeatability of stratus optical coherence tomography measures in neovascular
age-related macular degeneration.

Patel PJ, Chen FK, Ikeji F, Xing W, Bunce C, Da Cruz L, Tufail A.

Moorfields Eye Hospital, London, United Kingdom.

PURPOSE: To determine the repeatability of Stratus optical coherence tomography
(OCT) measures of retinal thickness and volume in patients with neovascular
age-related macular degeneration (nAMD) METHOD: Fifty-one eyes of 51 consecutive 
patients with nAMD underwent an OCT imaging session in which two fast macular
thickness map (FMTM) protocol scans sets were acquired by a single experienced
operator certified for clinical trials work. Coefficients of repeatability for
each of nine Early Treatment of Diabetic Retinopathy Study (ETDRS)-like regions, 
foveolar center-point retinal thickness (CPT) and total macular volume (TMV),
were calculated. Scans were analyzed retrospectively for errors in retinal
boundary placement by two observers, with revised coefficients of repeatability
calculated after excluding any scan sets with significant segmentation error.
RESULTS: The coefficient of repeatability for the central 1-mm macular subfield
was 67 mum (23%) and was less than 75 mum for all macular subfields. There was
much larger variability in the center-point thickness measure, with a coefficient
of repeatability of 88 mum (32%) for the automated center-point thickness (ACPT).
After excluding nine scan set pairs with significant segmentation error, the
coefficient of repeatability for the central 1-mm macular subfield was reduced to
50 mum (19%). CONCLUSIONS: OCT-derived retinal thickness measurements are subject
to considerable measurement variability in patients with nAMD. Changes in central
macular thickness of more than 50 mum may better reflect true clinical change in 
scan sets without significant segmentation error and may be used to guide the
retreatment of patients with nAMD in clinical trials and clinical practice.

PMID: 18326734 [PubMed - indexed for MEDLINE]

380: Invest Ophthalmol Vis Sci. 2008 Mar;49(3):1079-83.

Phacoemulsification does not induce neovascular age-related macular degeneration.

Baatz H, Darawsha R, Ackermann H, Scharioth GB, de Ortueta D, Pavlidis M,
Hattenbach LO.

Recklinghausen Eye Centre, Recklinghausen, Germany. holger.baatz@augenzentrum.org

PURPOSE: To investigate whether cataract surgery by phacoemulsification induces
progression of early age-related macular degeneration (AMD) to neovascular AMD.
METHODS: Retrospective case-control study. Included were consecutive patients who
had undergone phacoemulsification from January 2000 to February 2006 at the
Recklinghausen Eye Centre, who had a preexisting diagnosis of early AMD and who
were followed up for at least 1 year after surgery (n = 1152 eyes of 696
patients). The control group comprised phakic patients diagnosed with early AMD
from January 2000 to February 2006, who did not undergo eye surgery and were
followed up for at least 1 year (n = 334 eyes of 202 patients). RESULTS: At
baseline, control eyes had significantly better visual acuity than those of
patients who were going to have cataract surgery (0.30/0.35 +/- 0.34 vs.
0.40/0.49 +/- 0.34, respectively; median/mean +/- SD; P < 0.001, Mann-Whitney
rank sum test). After 1 year, visual acuity in the control group was worse than
in surgical eyes (0.30/0.39 +/- 0.38 vs. 0.20/0.26 +/- 0.30, respectively;
median/mean +/- SD; P < 0.001, Mann-Whitney rank sum test). In the cataract
surgery group, neovascular AMD developed in 28 (2.43%) of 1152 eyes in the first 
postoperative year. In the control group, it developed in 6 (1.74%) of 344 eyes
within 1 year. There was no significant difference between the groups in the
incidence of neovascular AMD (P = 0.57, odds ratio 1.30, 95% CI 0.52-3.24,
logistic regression analysis, adjusted for age and baseline visual acuity).
CONCLUSIONS: The results indicate that cataract surgery in eyes with early AMD is
not a causative factor in neovascular AMD.

PMID: 18326733 [PubMed - indexed for MEDLINE]

381: Invest Ophthalmol Vis Sci. 2008 Jun;49(6):2728-36. Epub 2008 Mar 7.

Ceruloplasmin/hephaestin knockout mice model morphologic and molecular features
of AMD.

Hadziahmetovic M, Dentchev T, Song Y, Haddad N, He X, Hahn P, Pratico D, Wen R,
Harris ZL, Lambris JD, Beard J, Dunaief JL.

FM Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of 
Pennsylvania, Philadelphia, Pennsylvania, USA.

PURPOSE: Iron is an essential element in human metabolism but also is a potent
generator of oxidative damage with levels that increase with age. Several studies
suggest that iron accumulation may be a factor in age-related macular
degeneration (AMD). In prior studies, both iron overload and features of AMD were
identified in mice deficient in the ferroxidase ceruloplasmin (Cp) and its
homologue hephaestin (Heph) (double knockout, DKO). In this study, the location
and timing of iron accumulation, the rate and reproducibility of retinal
degeneration, and the roles of oxidative stress and complement activation were
determined. METHODS: Morphologic analysis and histochemical iron detection by
Perls' staining was performed on retina sections from DKO and control mice.
Immunofluorescence and immunohistochemistry were performed with antibodies
detecting activated complement factor C3, transferrin receptor, L-ferritin, and
macrophages. Tissue iron levels were measured by atomic absorption
spectrophotometry. Isoprostane F2alpha-VI, a specific marker of oxidative stress,
was quantified in the tissue by gas chromatography/mass spectrometry. RESULTS:
DKOs exhibited highly reproducible age-dependent iron overload, which plateaued
at 6 months of age, with subsequent progressive retinal degeneration continuing
to at least 12 months. The degeneration shared some features of AMD, including
RPE hypertrophy and hyperplasia, photoreceptor degeneration, subretinal
neovascularization, RPE lipofuscin accumulation, oxidative stress, and complement
activation. CONCLUSIONS: DKOs have age-dependent iron accumulation followed by
retinal degeneration modeling some of the morphologic and molecular features of
AMD. Therefore, these mice are a good platform on which to test therapeutic
agents for AMD, such as antioxidants, iron chelators, and antiangiogenic agents.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18326691 [PubMed - indexed for MEDLINE]

382: Am J Clin Nutr. 2008 Mar;87(3):712-22.

Diet and risk factors for age-related maculopathy.

O'Connell ED, Nolan JM, Stack J, Greenberg D, Kyle J, Maddock L, Beatty S.

Macular Pigment Research Group, Department of Chemical and Life Sciences,
Waterford Institute of Technology, Waterford, Ireland.
dreamonnoconnell@iolfree.ie

BACKGROUND: Evidence continues to accumulate that oxidative stress is
etiologically important in the pathogenesis of age-related maculopathy (ARM) and 
that appropriate antioxidants of dietary origin may protect against this
condition. OBJECTIVE: Risk factors for ARM may be classed as established or
putative. We report a study designed to investigate whether such risk factors are
associated with a dietary lack of antioxidants relevant to retinal health.
DESIGN: Dietary, anthropometric, and sociodemographic details relating to 828
healthy Irish subjects aged 20-60 y were recorded in a cross-sectional fashion
and analyzed for associations between risk factors for ARM and dietary intake of 
relevant nutrients. RESULTS: Of the established risk factors for ARM, increasing 
age was associated with a relative lack of dietary zeaxanthin (P < 0.05) and
tobacco use with a relative lack of dietary vitamin C (P < 0.05). Of the putative
risk factors for ARM, alcohol consumption was associated with a relative lack of 
dietary alpha-linoleic acid (P < 0.05), and female sex was associated with a
relative lack of dietary zinc (P < 0.05). CONCLUSIONS: We showed that several
variables related to risk for ARM are associated with a relative dietary lack of 
key nutrients. Our finding that age, the most important and universal risk factor
for ARM, is associated with a relative lack of dietary zeaxanthin, is an
important finding that warrants further investigation.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18326611 [PubMed - indexed for MEDLINE]

383: Hum Mol Genet. 2008 Jun 15;17(12):1821-4. Epub 2008 Mar 6.

C3 R102G polymorphism increases risk of age-related macular degeneration.

Spencer KL, Olson LM, Anderson BM, Schnetz-Boutaud N, Scott WK, Gallins P,
Agarwal A, Postel EA, Pericak-Vance MA, Haines JL.

Center for Human Genetics Research, Vanderbilt University, Nashville, TN 37232,
USA. kylee.spencer@vanderbilt.edu

Inflammation has long been suspected to play a role in the pathogenesis of
age-related macular degeneration (AMD). Association of variants in the complement
factor H (CFH) and complement factor B (CFB) genes has targeted the search for
additional loci to the alternative complement cascade, of which C3 is a major
component. Two non-synonymous coding polymorphisms within C3, R102G and L314P,
have previously been strongly associated with increased risk. These variants are 
in strong linkage disequilibrium (LD), making the contribution of this locus to
AMD even more difficult to ascertain. We sought to determine whether the C3
association resulted primarily from only one of these two variants or from a
combined effect of both in 223 families and an independent dataset of 701 cases
and 286 unrelated controls. The C3 polymorphisms were in strong LD (r(2) = 0.85),
and both were associated in the family-based and case-control datasets (R102G
genoPDT P = 0.02, case-control genotypic P = 0.004; L314P genoPDT P = 0.001,
case-control genotypic P = 0.04). In conditional analyses in the case-control
dataset, R102G remained associated with disease in the L314P risk allele carriers
(P = 0.01), but there was no effect of L314P in the R102G risk allele carriers (P
= 0.2). After adjusting for age, smoking, CFH Y402H, LOC387715 A69S, and CFB
R32Q, the effect of R102G remained strong [P = 0.015, odds ratio = 1.55, 95%
confidence interval 1.09 to 2.21, adjusted PAR(population attributable risk) =
0.17]. Therefore, while the strong LD between R102G and L314P makes it difficult 
to disentangle their individual effects on disease risk, the R102G polymorphism
acting alone provides the best model for disease in our data.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 18325906 [PubMed - indexed for MEDLINE]

384: Korean J Ophthalmol. 2008 Mar;22(1):1-5.

Long-term visual outcome of arteriovenous adventitial sheathotomy on branch
retinal vein occlusion induced macular edema.

Oh IK, Kim S, Oh J, Huh K.

Department of Ophthalmology, College of Medicine, Korea University, Seoul, Korea.

PURPOSE: To evaluate long-term visual outcome of arteriovenous adventitial
sheathotomy in BRVO-induced macular edema. METHODS: The visual outcomes of 8
patients following vitrectomy with arteriovenous adventitial sheathotomy for
BVO-induced macular edema (surgery group) were retrospectively evaluated. The
three-year post-operative visual acuity of the surgery group was compared with
that of the conservatively managed controls. RESULTS: All patients were followed 
for a minimum of 36 months. Mean BCVA (logMAR) in the surgery group changed from 
1.10+/-0.34 to 1.19+/-0.70 and to 0.80+/-0.36 at 12 and 36 months, respectively
(p=0.959 at 12 months, p=0.018 at 36 months). In the control group, visual acuity
improved from 1.15+/-0.43 to 0.43+/-0.44 and to 0.43+/-0.39 at 12 and 36 months, 
respectively (p=0.015 at 12 months, at p=0.003 at 36 months). A strong trend
toward better visual acuity at 12 months and final examination was observed for
controls. (surgery vs. control group, p=0.052 at 12 months, p=0.066 at 36
months). CONCLUSIONS: Considering the favorable natural course of BVO and the
unproven effect of reperfusion on macular edema, surgical efficacy of
arteriovenous adventitial sheathotomy requires further evaluation.

PMID: 18323698 [PubMed - indexed for MEDLINE]

385: Am J Ophthalmol. 2008 May;145(5):841-6. Epub 2008 Mar 5.

Smoking as a risk factor for cystoid macular edema complicating intermediate
uveitis.

Thorne JE, Daniel E, Jabs DA, Kedhar SR, Peters GB, Dunn JP.

Department of Ophthalmology, the Johns Hopkins University School of Medicine,
Baltimore, Maryland 21205, USA. jthorne@jhmi.edu

PURPOSE: To describe risk factors for the presence of cystoid macular edema (CME)
among patients presenting with intermediate uveitis. DESIGN: Cross-sectional
study. METHODS: SETTINGS: Single-center, academic practice. STUDY POPULATION: Two
hundred and eight patients with intermediate uveitis evaluated from July 1, 1984 
through September 30, 2006. PROCEDURES: Clinical and demographic data were
entered retrospectively into a database and analyzed. OUTCOME MEASURES: Presence 
of CME at presentation to our clinic; risk factors for presenting with CME.
RESULTS: Of the 208 patients, 74% had bilateral intermediate uveitis, yielding
363 affected eyes. Eighty-nine patients (43%) had CME in at least one eye at the 
time of presentation to our clinic. After controlling for potentially confounding
variables including demographics, duration of disease, active intraocular
inflammation, history of diabetes mellitus or hypertension, and presence of
epiretinal membrane, actively smoking at presentation was associated with a
four-fold increased risk of CME at presentation vs never smoking (odds ratio
(OR), 3.90; 95% confidence interval (CI), 1.43, 10.66; P = .008). Former smoking 
also appeared to increase the risk of CME at presentation in the multivariate
analysis, but the result was of borderline statistical significance (OR, 1.97;
95% CI, 0.99, 3.94; P = .055). After adjusting for confounding, there was a 4%
increased risk of CME at presentation for each cigarette smoked per day (OR,
1.04; 95% CI, 1.01, 1.7; P = .005). CONCLUSIONS: CME was a common structural
ocular complication observed in our cohort. Current smoking was associated with a
dose-dependent increased risk of having CME at the time of presentation to our
clinic.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 18321467 [PubMed - indexed for MEDLINE]

386: Am J Ophthalmol. 2008 May;145(5):862-74. Epub 2008 Mar 5.

Ranibizumab combined with verteporfin photodynamic therapy in neovascular
age-related macular degeneration (FOCUS): year 2 results.

Antoszyk AN, Tuomi L, Chung CY, Singh A; FOCUS Study Group.

Charlotte Eye, Ear, Nose and Throat Associates, Charlotte, North Carolina 28210, 
USA. ana@ceenta.com

PURPOSE: To assess the efficacy and adverse-events profile of combined treatment 
with ranibizumab and verteporfin photodynamic therapy (PDT) in patients with
predominantly classic choroidal neovascularization (CNV) secondary to neovascular
age-related macular degeneration. DESIGN: Two-year, multicenter, randomized,
single-masked, controlled study. METHODS: Patients received monthly intravitreal 
injections of ranibizumab 0.5 mg (n = 106) or sham injections (n = 56). All
patients received PDT on day zero, then quarterly as needed. Efficacy assessment 
included changes in visual acuity (VA) and lesion characteristics and PDT
frequency. Adverse events were summarized by incidence and severity. RESULTS: At 
month 24, 88% of ranibizumab + PDT patients had lost <15 letters from baseline VA
(vs 75% for PDT alone), 25% had gained >or=15 letters (vs 7% for PDT alone), and 
the two treatment arms differed by 12.4 letters in mean VA change (P < .05 for
all between-group differences). The VA benefit of adding ranibizumab to PDT in
year one persisted through year two. On average, ranibizumab + PDT patients
exhibited less lesion growth and greater reduction of CNV leakage and subretinal 
fluid accumulation, and required fewer PDT retreatments, than PDT-alone patients 
(mean = 0.4 vs 3.0 PDT retreatments). Endophthalmitis and serious intraocular
inflammation occurred, respectively, in 2.9% and 12.4% of ranibizumab + PDT
patients and 0% of PDT-alone patients. Incidences of serious nonocular adverse
events were similar in the two treatment groups. CONCLUSIONS: Through two years, 
ranibizumab + PDT was more effective than PDT alone and had a low rate of
associated adverse events.

Publication Types: 
    Clinical Trial, Phase I
    Clinical Trial, Phase II
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18321465 [PubMed - indexed for MEDLINE]

387: Eur J Ophthalmol. 2008 Mar-Apr;18(2):297-300.

Single-session photodynamic therapy combined with intravitreal bevacizumab for
neovascular age-related macular degeneration.

Ahmadieh H, Taei R, Soheilian M, Riazi-Esfahani M, Ahadi H.

Ophthalmic Research Center of Shaheed Beheshti Medical University, Labbafinejad
Medical Center, Tehran, Iran. hahmadieh@hotmail.com

PURPOSE: To evaluate the efficacy of combined single-session photodynamic therapy
(PDT) and intravitreal bevacizumab (IVB) for treatment of neovascular age-related
macular degeneration (AMD). METHODS: In a prospective interventional case series,
patients with subfoveal choroidal neovascularization (CNV) underwent PDT followed
by 1.25 mg IVB injection. Best-corrected visual acuity (BCVA) and optical
coherence tomography (OCT) measurements were repeated at 6-week intervals and
fluorescein angiography was performed after 12 weeks and when considered
necessary thereafter. Repeat injections of IVB were performed based on
fluorescein angiographic evidence of CNV leakage. RESULTS: Fourteen eyes were
included in this study. Mean follow-up was 52.4+/-15.2 weeks (range: 26-74
weeks). Initially, mean BCVA was 0.80+/-0.42 logMAR and mean central macular
thickness (CMT) was 308+/88 microm. At week 12, BCVA improved to 0.62+/-0.47
logMAR (p=0.006) and CMT reduced to 186+/-53 microm (p=0.003). Corresponding
results were 0.53+/-0.52 logMAR (p=0.02) and 193+/-78 microm (p=0.002) after 24
weeks. A second IVB injection was performed in 13 eyes with a mean interval of
16.3+/-5.9 weeks. CONCLUSIONS: Combination therapy with single-session PDT and
IVB can improve vision and reduce CMT in neovascular AMD. Repeat IVB injections
may maintain the visual gain from the initial combination therapy.

PMID: 18320527 [PubMed - indexed for MEDLINE]

388: Eur J Ophthalmol. 2008 Mar-Apr;18(2):226-32.

Association of plasma homocysteine and macular edema in type 2 diabetes mellitus.

Aydin E, Demir HD, Ozyurt H, Etikan I.

Department of Ophthalmology, Gaziosmanpasa University Faculty of Medicine, Tokat,
Turkey. erdincaydin@yahoo.com

PURPOSE: The aim of this study was to assess the association of macular edema
(ME) with plasma homocysteine, vitamin B6, vitamin B12, and folic acid levels in 
patients with Type 2 diabetes. METHODS: Sixty-five diabetic subjects with no
retinopathy and nonproliferative diabetic retinopathy (NPDR) (no DR, without ME, 
with ME: 16, 25, 24, respectively), 28 with proliferative diabetic retinopathy
(PDR) (with and without ME: 14, 14, respectively), and 19 healthy subjects as
control were recruited in this cross-sectional study. Plasma homocysteine,
vitamin B12, vitamin B6, and folate levels were determined after 8-hour of
fasting for all subjects. The levels of serum homocysteine and vitamin B6 were
measured using high performance liquid chromatography (HPLC) with fluorescence
detection, and the levels of serum vitamin B12 and folic acid were measured by
electrochemiluminescence immunoassay. RESULTS: When diabetic groups with ME were 
compared with diabetic groups without ME for homocysteine, vitamin B12, vitamin
B6, and folic acid, the only significant difference was detected in homocysteine 
levels (p=0.001). There was no significant difference between NPDR with ME group 
compared with NPDR without ME group and no DR group for plasma homocysteine,
vitamin B12, vitamin B6, and folic acid (p=0.200, p=0.660; p=0.999, p=0.678;
p=1.0, p=0.248; p=1.0, p=0.982, respectively). On the other hand, when PDR with
ME group was compared with PDR without ME group, there was only significant
difference in homocysteine levels (p=0.023). CONCLUSIONS: Mild to moderate
elevation of homocysteine may explain the role of vascular dysregulation and
endothelial dysfunction in patients with DR. The present study suggests
hyperhomocysteinemia may be one of the crucial risk factors for development of
ME.

PMID: 18320515 [PubMed - indexed for MEDLINE]

389: Eur J Nutr. 2008 Mar;47(2):99-103. Epub 2008 Mar 4.

Zeaxanthin is bioavailable from genetically modified zeaxanthin-rich potatoes.

Bub A, Möseneder J, Wenzel G, Rechkemmer G, Briviba K.

Federal Research Centre for Nutrition and Food, Institute of Nutritional
Physiology, Haid-und-Neu-Str. 9, 76131 Karlsruhe, Germany. achim.bub@bfel.de

The carotenoid zeaxanthin accumulates in the human macula lutea and protects
retinal cells from blue light damage. However, zeaxanthin intake from food
sources is low. Increasing zeaxanthin in common foods such as potatoes by
traditional plant breeding or by genetic engineering could contribute to an
increased intake of this carotenoid and, consequently, to a decreased risk of
age-related macular degeneration. Our aim was to investigate whether zeaxanthin
from genetically modified zeaxanthin-rich potatoes is bioavailable in humans.
Three men participated in this randomized, controlled double-blinded, crossover
pilot study. All subjects consumed 1,100 g of mashed potatoes, either genetically
modified (Solanum tuberosum L. var. Baltica GM47/18; 3 mg zeaxanthin) or
wild-type control potatoes (Solanum tuberosum L. var. Baltica; 0.14 mg
zeaxanthin). A second treatment was followed after a 7-day wash-out period. The
concentration of zeaxanthin was significantly increased in chylomicrons after
consumption of genetically modified potatoes and 0.27 mg of the 3 mg zeaxanthin
dose could be detected in chylomicrons. Consumption of control potatoes had no
effect on concentrations of zeaxanthin in chylomicrons. After normalization of
chylomicron zeaxanthin for plasma triacylglycerol, the time course of zeaxanthin 
concentrations peaked at 7 h after consumption of genetically modified potatoes. 
There were no significant differences in the concentrations of other major potato
carotenoids such as lutein and beta-carotene in chylomicrons after consumption of
genetically modified and wild type control potatoes. Thus, consumption of
zeaxanthin-rich potatoes significantly increases chylomicron zeaxanthin
concentrations suggesting that potentially such potatoes could be used as an
important dietary source of zeaxanthin.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18320254 [PubMed - indexed for MEDLINE]

390: Invest Ophthalmol Vis Sci. 2008 Jun;49(6):2357-65. Epub 2008 Mar 3.

HTRA1 variants in exudative age-related macular degeneration and interactions
with smoking and CFH.

Tam PO, Ng TK, Liu DT, Chan WM, Chiang SW, Chen LJ, DeWan A, Hoh J, Lam DS, Pang 
CP.

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong
Kong, Hong Kong, China.

PURPOSE: Mapping the genes for age-related macular degeneration (AMD) had not
been successful until recent genome-wide association studies revealed Tyr402His
in CFH and rs11200638 in HTRA1 as AMD-related genetic variants. This study was
conducted to identify other critical factors in HTRA1 that are associated with
exudative AMD. METHODS: The promoter, splice regions, and coding exons of HTRA1
were sequenced in 163 patients with exudative AMD and 183 sex- and age-matched
control subjects. Also documented were the CFH genotype and smoking status.
RESULTS: Four significant SNPs were found in the promoter and the first exon of
HTRA1: rs11200638 (-625G>A), rs2672598 (-487T>C), rs1049331 (102C>T, Ala34Ala),
and rs2293870 (108G>T, Gly36Gly) with respective P = 1.7 x 10(-14), 3.0 x
10(-10), 3.7 x 10(-12), and 3.7 x 10(-12). Among them, rs11200638 is the most
significant associated SNP with a high odds ratio (OR) of 7.6 (95% CI:
3.94-14.51). One risk haplotype block across the promoter and exon 1, ACCTT,
significantly predisposes to AMD (P = 6.68 x 10(-14)). In both models,
significant independent additive effects were identified with smoking and
rs800292 (184G>A, Val62Ile) of CFH. Smoking and rs11200638 (HTRA1) combined
caused a 15.7-fold increased risk, whereas combined rs800292 and rs11200638
caused a 23.3-fold increased risk. An extremely high population attributable risk
(PAR) of 78% was also found. CONCLUSIONS: A high impact of the additive effect of
CFH and HTRA1 in the development of exudative AMD was shown. The HTRA1-smoking
additive effect found in this study further suggests the importance of this
environmental risk factor in AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18316707 [PubMed - indexed for MEDLINE]

391: Invest Ophthalmol Vis Sci. 2008 May;49(5):1745-52. Epub 2008 Mar 3.

Comparison of time-domain OCT and fundus photographic assessments of retinal
thickening in eyes with diabetic macular edema.

Davis MD, Bressler SB, Aiello LP, Bressler NM, Browning DJ, Flaxel CJ, Fong DS,
Foster WJ, Glassman AR, Hartnett ME, Kollman C, Li HK, Qin H, Scott IU; Diabetic 
Retinopathy Clinical Research Network Study Group.

Department of Ophthalmology and Visual Sciences, University of Wisconsin,
Madison, WI, USA.

PURPOSE: To explore the correlation between optical coherence tomography (OCT)
and stereoscopic fundus photographs (FP) for the assessment of retinal thickening
(RT) in diabetic macular edema (DME) within a clinical trial. METHODS: OCT, FP,
and best corrected visual acuity (VA) measurements were obtained in both eyes of 
263 participants in a trial comparing two photocoagulation techniques for DME.
Correlation coefficients (r) were calculated comparing RT measured by OCT, RT
estimated from FP, and VA. Principal variables were central subfield retinal
thickness (CSRT) obtained from the OCT fast macular map and DME severity assessed
by a reading center using a seven-step photographic scale combining the area of
thickened retina within 1 disc diameter of the foveal center and thickening at
the center. RESULTS: Medians (quartiles) for retinal thickness within the center 
subfield by OCT at baseline increased from 236 (214, 264) microm in the lowest
level of the photographic scale to 517 (455, 598) microm in the highest level (r 
= 0.67). However, CSRT interquartile ranges were broad and overlapping between FP
scale levels, and there were many outliers. Correlations between either modality 
and VA were weaker (r = 0.57 for CSRT, and r = 0.47 for the FP scale). OCT
appeared to be more reproducible and more sensitive to change in RT between
baseline and 1 year than was FP. CONCLUSIONS: There was a moderate correlation
between OCT and FP assessments of RT in patients with DME and slightly less
correlation of either measure with VA. OCT and FP provide complementary
information but neither is a reliable surrogate for VA.

Publication Types: 
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, N.I.H., Extramural

PMID: 18316700 [PubMed - indexed for MEDLINE]

392: J Med Chem. 2008 Mar 27;51(6):1546-59. Epub 2008 Feb 27.

Development of prodrug
4-chloro-3-(5-methyl-3-{[4-(2-pyrrolidin-1-ylethoxy)phenyl]amino}-1,2,4-benzotria
zin-7-yl)phenyl benzoate (TG100801): a topically administered therapeutic
candidate in clinical trials for the treatment of age-related macular
degeneration.

Palanki MS, Akiyama H, Campochiaro P, Cao J, Chow CP, Dellamary L, Doukas J, Fine
R, Gritzen C, Hood JD, Hu S, Kachi S, Kang X, Klebansky B, Kousba A, Lohse D, Mak
CC, Martin M, McPherson A, Pathak VP, Renick J, Soll R, Umeda N, Yee S, Yokoi K, 
Zeng B, Zhu H, Noronha G.

TargeGen Inc., 9890 Judicial Drive, San Diego, CA 92121, USA.
Palanki@targegen.com

Age-related macular degeneration (AMD) is one of the leading causes of loss of
vision in the industrialized world. Attenuating the VEGF signal in the eye to
treat AMD has been validated clinically. A large body of evidence suggests that
inhibitors targeting the VEGFr pathway may be effective for the treatment of AMD.
Recent studies using Src/YES knockout mice suggest that along with VEGF, Src and 
YES play a crucial role in vascular leak and might be useful in treating edema
associated with AMD. Therefore, we have developed several potent benzotriazine
inhibitors designed to target VEGFr2, Src, and YES. One of the most potent
compounds is
4-chloro-3-{5-methyl-3-[4-(2-pyrrolidin-1-yl-ethoxy)phenylamino]benzo[1,2,4]triaz
in-7-yl}phenol ( 5), a dual inhibitor of both VEGFr2 and the Src family (Src and 
YES) kinases. Several ester analogues of 5 were prepared as prodrugs to improve
the concentration of 5 at the back of the eye after topical administration. The
thermal stability of these esters was studied, and it was found that benzoyl and 
substituted benzoyl esters of 5 showed good thermal stability. The hydrolysis
rates of these prodrugs were studied to analyze their ability to undergo
conversion to 5 in vivo so that appropriate concentrations of 5 are available in 
the back-of-the-eye tissues. From these studies, we identified
4-chloro-3-(5-methyl-3-{[4-(2-pyrrolidin-1-ylethoxy)phenyl]amino}-1,2,4-benzotria
zin-7-yl)phenyl benzoate ( 12), a topically administered prodrug delivered as an 
eye drop that is readily converted to the active compound 5 in the eye. This
topically delivered compound exhibited excellent ocular pharmacokinetics and poor
systemic circulation and showed good efficacy in the laser induced choroidal
neovascularization model. On the basis of its superior profile, compound 12 was
advanced. It is currently in a clinical trial as a first in class, VEGFr2
targeting, topically applied compound for the treatment of AMD.

PMID: 18311895 [PubMed - indexed for MEDLINE]

393: Br J Ophthalmol. 2008 Apr;92(4):537-40. Epub 2008 Feb 29.

Comment in:
    Br J Ophthalmol. 2008 Apr;92(4):448-50.

Interleukin-8 promoter polymorphism -251A/T is a risk factor for age-related
macular degeneration.

Goverdhan SV, Ennis S, Hannan SR, Madhusudhana KC, Cree AJ, Luff AJ, Lotery AJ.

Clinical Neurosciences Division, Mailpoint 806, Southampton General Hospital,
Southampton SO16 6YD, UK.

BACKGROUND/AIMS: To determine whether four expression-related cytokine
polymorphisms are associated with age-related macular degeneration (AMD).
METHODS: DNA from 478 cases with AMD and 555 normal controls was genotyped for
the pro-inflammatory IL1beta -511C/T, IL6 -174C/G, IL8 -251A/T and
anti-inflammatory IL10 -1082G/A cytokine polymorphisms using the 5' nuclease
TaqMan(R) assay for allelic discrimination. Associations with AMD were analysed
using allelic frequencies. RESULTS: The -251A allele of the IL8 promoter gene
polymorphism was more prevalent in AMD patients than controls (p = 0.037, OR =
1.21, 95% CI = 1.01 to 1.44). Adjusting for age, sex, body mass index (BMI),
current smoking and past smoking status did not alter the AMD association
significantly (corrected p value = 0.043, OR = 1.23, 95% CI = 1.0 to 1.50).
CONCLUSION: The pro-inflammatory homozygous IL8 -251AA genotype is an important
risk factor for AMD. This may have implications for future therapy with
biological agents that could target this cytokine.

Publication Types: 
    Research Support, N.I.H., Intramural
    Research Support, Non-U.S. Gov't

PMID: 18310311 [PubMed - indexed for MEDLINE]

394: Br J Ophthalmol. 2008 Apr;92(4):509-12. Epub 2008 Feb 29.

Comment in:
    Br J Ophthalmol. 2008 Nov;92(11):1564.

Age-related macular degeneration and mortality from cardiovascular disease or
stroke.

Tan JS, Wang JJ, Liew G, Rochtchina E, Mitchell P.

Centre for Vision Research, Department of Ophthalmology, University of Sydney,
Westmead Hospital, Hawkesbury Rd, Westmead, NSW Australia.

BACKGROUND/AIMS: Age-related macular degeneration (AMD) and vascular disease
share similar risk factors. Recent data suggest AMD may independently predict
stroke or coronary heart disease. We prospectively assessed the relationship
between AMD and risk of stroke- or cardiovascular-related death in an Australian 
population. METHODS: Of 3654 baseline participants (1992-4) aged 49+ years, 2335 
were re-examined after 5 years and 1952 after 10 years. Retinal photographs were 
graded using the Wisconsin System. History and physical examination provided data
on possible risk factors. Deaths and cause of death were confirmed by data
linkage with the Australian National Death Index. Risk ratios (RR) were estimated
in Cox models. RESULTS: Among persons aged <75 years at baseline, early AMD
predicted a doubling of cardiovascular mortality (RR, 2.32; 95% confidence
interval (CI), 1.03 to 5.19), over the next decade, after controlling for
traditional cardiovascular risk factors. Late AMD predicted fivefold higher
cardiovascular mortality (RR, 5.57; 95% CI, 1.35 to 22.99) and 10-fold higher
stroke mortality (RR, 10.21; 95% CI, 2.39 to 43.60) after adjusting for age and
sex only. These associations were not present when persons older than 75 were
included. CONCLUSION: AMD predicted stroke and cardiovascular events over the
long term in persons aged 49-75 years. This may have potential implications for
new intravitreal anti-VEGF AMD therapies.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18310310 [PubMed - indexed for MEDLINE]

395: Exp Eye Res. 2008 Apr;86(4):675-83. Epub 2008 Jan 25.

Immunological protein expression profile in Ccl2/Cx3cr1 deficient mice with
lesions similar to age-related macular degeneration.

Ross RJ, Zhou M, Shen D, Fariss RN, Ding X, Bojanowski CM, Tuo J, Chan CC.

Section of Immunopathology, Laboratory of Immunology, National Eye Institute,
Bethesda, MD 20892, USA.

Age-related macular degeneration (AMD) is the leading cause of blindness in the
United States. Ccl2 knock-out (KO) mice sporadically develop the cardinal
features of AMD in their senescent stage. Humans bearing a loss of function
variant or single nucleotide polymorphism (SNP) in CX3CR1 are at increased risk
of developing AMD. We recently developed Ccl2(-/-)/Cx3cr1(-/-) mice, which
consistently develop retinal degeneration with many AMD features. Since there is 
strong evidence for an immunological role in AMD pathogenesis, we examined ocular
immune protein expression levels in Ccl2(-/-)/Cx3cr1(-/-), Ccl2(-/-),
Cx3cr1(-/-), and age-matched wild-type (WT) mice. Immunohistochemistry revealed
increased complement C3d in Bruch's membrane, retinal pigment epithelium (RPE),
choroidal capillaries, and particularly drusen of the Ccl2(-/-)/Cx3cr1(-/-) mice 
relative to the WT controls. No change was detected in single KO mice. Real-time 
RT-PCR revealed a 2.5-fold increase in C3 expression in the
Ccl2(-/-)/Cx3cr1(-/-). While the retinas of four month old WT and Ccl2(-/-)
showed minimal immunoreactivity for markers of macrophages and microglia,
infiltrates of these mononuclear phagocytic cells were detected in the
Ccl2(-/-)/Cx3cr1(-/-)retinal lesions and a few foci in the Cx3cr1(-/-) retina.
The Ccl2(-/-)/Cx3cr1(-/-) had reduced toll-like receptor 4 (TLR4) expression in
the RPE. Following LPS injection, the Ccl2(-/-)/Cx3cr1(-/-) had significantly
reduced endotoxin-induced uveitis scores and showed a diminished increase in Tlr4
mRNA expression. No changes in TLR4 expression were detected in either single KO.
Autoantibodies against the retina and photoreceptors were also detected in the
Ccl2(-/-)/Cx3cr1(-/-) serum. Real-time RT-PCR revealed significant increases in
Ccl5 transcript in the Ccl2(-/-)/Cx3cr1(-/-) relative to the WT. These results
suggest that innate immunity and possibly adaptive immunity play an important
role in Ccl2(-/-)/Cx3cr1(-/-) retinal degeneration. Moreover, since human AMD
patients show similar immunopathological profiles, these results support the
Ccl2(-/-)/Cx3cr1(-/-) as a suitable model for human AMD.

PMID: 18308304 [PubMed - indexed for MEDLINE]

396: Ophthalmologica. 2008;222(2):117-22. Epub 2008 Feb 22.

Transpupillary thermotherapy in chinese patients with choroidal
neovascularization secondary to age-related macular degeneration: emphasis on the
influence of power setting.

Kuo HK, Kao MT, Chen YJ, Chen CH, Wu PC, Kao ML.

Department of Ophthalmology, Chang-Gung Memorial Hospital, Kaohsiung Medical
Center, Kaohsiung, Taiwan. d2767@cgmh.org.tw

PURPOSE: To perform a safety and efficacy study of transpupillary thermotherapy
(TTT) in Chinese patients with choroidal neovascularization (CNV) secondary to
age-related macular degeneration (ARMD). METHODS: In a prospective study,
patients with subfoveal or juxtafoveal CNV secondary to ARMD underwent TTT with
fixed treatment and follow-up protocols. From August 2002 to December 2004, 26
patients (27 eyes) completed > or =6 months of follow-up and were included in
this report. RESULTS: Fourteen eyes (52%) had improved or stable visual acuity
(loss of <3 lines) and 13 eyes (48%) had vision loss of > or =3 lines. The serial
mean visual acuity initially decreased during follow-up, then stabilized by 6
months. In the subgroup of occult or minimally classic CNV (20 eyes), 13 eyes
(65%) had improved or stable vision. The major complication of TTT included
laser-related retinal pigment epithelium (RPE) atrophy in 10 eyes (37%). Six eyes
had mild RPE atrophy, 4 eyes had severe RPE-choroid atrophy (macular burn).
Analysis of possible risk factors for macular burn showed that 3 eyes had to have
the power amplified due to nuclear sclerosis, and 1 pseudophakic eye had regular 
power. CONCLUSIONS: TTT in Chinese ARMD patients with occult or minimally classic
CNV, according to our protocol, prevented severe vision loss in the majority of
patients, but power amplification due to medium lens opacity induced RPE atrophy 
or burn in some patients. Copyright 2008 S. Karger AG, Basel.

PMID: 18303233 [PubMed - indexed for MEDLINE]

397: Br J Ophthalmol. 2008 Mar;92(3):361-4.

Relationships between clinical measures of visual function, fluorescein
angiographic and optical coherence tomography features in patients with subfoveal
choroidal neovascularisation.

Moutray T, Alarbi M, Mahon G, Stevenson M, Chakravarthy U.

Directorate of Ophthalmology, Head and Skeletal Division, Royal Victoria
Hospital, Belfast, Northern Ireland.

AIMS: To examine the relationships between measures of vision, optical coherence 
tomography (OCT) and fundus fluorescein angiography (FFA) characteristics in
patients with exudative age-related macular degeneration (AMD). STUDY DESIGN:
Retrospective case note review. Inclusion criteria were: confirmed diagnosis of
new exudative AMD; recorded visual function using best corrected distance visual 
acuity (DVA), near visual acuity (NVA) and contrast sensitivity; corresponding
FFA and OCT. FFA parameters included greatest linear diameter of lesion (GLD),
area of choroidal neovascularisation (CNV) and area of leakage. OCT parameters
included maximum retinal thickness (Ret(max)), central foveal thickness, maximum 
thickness of the CNV (CNV(max)), and the distances from the foveal depression to 
Ret(max) and CNV(max). RESULTS: 74 patients were included in this study.
Correlations were highly statistically significant for both NVA and contrast
sensitivity with GLD, CNV area and leakage (p<0.01 for all combinations). With
DVA, modest statistically significant correlations were seen with CNV area and
GLD (p<0.05). There was a statistically significant correlation between CNV
leakage and the distance of CNV(max) to the fovea (p<0.05). The relationships
between the measures of vision and OCT parameters were weak and did not reach
significance. Regression analysis showed that the combination of Ret(max), GLD,
and CNV(max) to fovea had the highest coefficient (r2 = 0.27). CONCLUSION: OCT
measurements by themselves are not robust markers for visual function.

PMID: 18303157 [PubMed - indexed for MEDLINE]

398: Br J Ophthalmol. 2008 Mar;92(3):356-60.

Intravitreal bevacizumab (Avastin) therapy versus photodynamic therapy plus
intravitreal triamcinolone for neovascular age-related macular degeneration:
6-month results of a prospective, randomised, controlled clinical study.

Weigert G, Michels S, Sacu S, Varga A, Prager F, Geitzenauer W, Schmidt-Erfurth
U.

Department of Ophthalmology, Medical University of Vienna, Vienna, Austria.

AIMS: To compare functional and anatomical outcomes of intravitreal bevacizumab
(Avastin) and verteporfin (photodynamic) therapy (PDT) combined with intravitreal
triamcinolone (IVTA) in patients with neovascular age-related macular
degeneration (AMD). METHODS: Twenty-eight patients with neovascular AMD were
enrolled in a prospective, randomised, controlled clinical trial. All patients
randomly assigned to 1 mg intravitreal bevacizumab (0.04 ml) received three
initial treatments at 4-week intervals. In further follow-up retreatment was
based on optical coherence tomography (OCT). Patients randomly assigned to
standard PDT received a same-day intravitreal injection of 4 mg triamcinolone
(Kenalog). Retreatment was based on fluorescein angiography at 3-month intervals.
Functional and anatomical results were evaluated using the Early Treatment
Diabetic Retinopathy Study protocol vision charts, fluorescein angiography and
OCT. RESULTS: In the bevacizumab-treated group mean visual acuity (VA) improved
to a 2.2 line gain at 6 months follow-up. Eyes treated in the PDT plus IVTA group
had a stable mean VA at month 6 compared with baseline. There was a statistically
significant difference (p = 0.03, analysis of variance (ANOVA)) between both
groups as early as one day after initial treatment. The reduction in central
retinal thickness (CRT) showed no significant difference between both groups (p =
0.3, ANOVA). Mean CRT was reduced from 357 microm at baseline to 239 microm at
month 6 in bevacizumab-treated patients and from 326 microm to 222 microm,
respectively, in PDT plus IVTA-treated patients. No significant local or systemic
safety concerns were detected up to month 6. CONCLUSION: Intravitreal bevacizumab
showed promising 6-month results in patients with neovascular AMD. Functional
outcomes appear not only to be dependent on a reduction in CRT but also on the
treatment modality used.

Publication Types: 
    Randomized Controlled Trial

PMID: 18303156 [PubMed - indexed for MEDLINE]

399: Retina. 2008 Feb;28(2):289-97.

12-month retrospective study and review of photodynamic therapy with verteporfin 
for subfoveal choroidal neovascularization in age-related macular degeneration.

Incorvaia C, Campa C, Parmeggiani F, Menzione M, D'Angelo S, Della Corte M,
Rinaldi M, Romano M, Dell'omo R, Costagliola C.

Department of Ophthalmology, University of Ferrara, Ferrara, Italy.

PURPOSE: To evaluate the 12-month visual outcome of photodynamic therapy with
verteporfin (PDT-V) for patients with subfoveal choroidal neovascularization
(CNV) secondary to age-related macular degeneration and to verify the predictive 
role of visual and angiographic factors. METHODS: This retrospective,
interventional, consecutive case series study included subjects with different
forms of subfoveal CNV. All patients received PDT-V according to Treatment of
Age-Related Macular Degeneration With Photodynamic Therapy/Visudyne in
Photodynamic Therapy guidelines. A review of medical and angiographic records was
performed. RESULTS: Two hundred sixteen patients were divided into 4 study
groups: group I, 60 eyes with classic CNV; group II, 56 eyes with predominantly
classic CNV; group III, 42 eyes with minimally classic CNV; and group IV, 58 eyes
with occult CNV. In groups I and II, best-corrected visual acuity (BCVA) was
moderately decreased, without reaching a statistically noticeable level during
the entire follow-up; lesion size reduction only reached significance in group I.
Groups III and IV showed evident worsening of BCVA (P < 0.05), despite
concomitant reduction in CNV size (statistically remarkable only for occult CNV).
All study groups exhibited a significant correlation between higher baseline BCVA
and better final visual outcome. In groups II and IV, smaller baseline CNV sizes 
also favorably influenced final BCVA. CONCLUSIONS: Standardized PDT-V minimizes
deterioration of central vision only in patients with classic and predominantly
classic CNV. Irrespective of the CNV type, better BCVA at presentation represents
a good predictive sign. In predominantly classic and occult lesions, minor
initial CNV dimension is also a positive prognostic element.

PMID: 18301052 [PubMed - indexed for MEDLINE]

400: Retina. 2008 Feb;28(2):309-13.

HTRA1 polymorphism in dry and wet age-related macular degeneration.

Lin JM, Wan L, Tsai YY, Lin HJ, Tsai Y, Lee CC, Tsai CH, Tsai FJ, Tseng SH.

Department of Ophthalmology, China Medical University Hospital, Taichung, Taiwan.

PURPOSE: To investigate HTRA1 polymorphisms in unrelated Taiwan Chinese patients 
with age-related macular degeneration (AMD) and control subjects without AMD.
METHODS: A total of 95 unrelated Taiwan Chinese patients with AMD and 90 age- and
sex-matched control subjects were enrolled in the study. Genomic DNA was prepared
from peripheral blood obtained from all patients with AMD and control subjects.
Polymerase chain reactions were used to analyze two HTRA1 single-nucleotide
polymorphisms (rs11200638 [G/A] and rs10490924 [G/T]). RESULTS: Of the 95
participants with AMD, dry AMD was diagnosed in 52 patients and wet AMD in 43
patients. Both rs11200638 (G/A) and rs10490924 (G/T) were significantly
associated with all AMD (rs11200638: P = 6.7 x 10(-7) for an additive
allele-dosage model, OR(het) = 1.97 [0.81, 4.81], OR(hom) = 8.59 [3.28, 22.49], A
allele: 73% in all AMD versus 47% in controls; rs10490924: P = 9.2 x 10(-6),
OR(het) = 1.86 [0.79, 4.35], OR(hom) = 5.08 [2.21, 11.70], T allele: 73% in all
AMD versus 50% in controls). In terms of significance of association, rs11200638 
was the most significantly associated variant. Subtype analysis including dry and
wet AMD also revealed similar results. Haplotype analysis demonstrated that AT
was significantly associated with wet and all AMD (P = 0.011 and 0.004,
respectively), whereas GG was significantly associated with the control group
when compared with all AMD (P = 0.035). CONCLUSIONS: The study demonstrated that 
both single-nucleotide polymorphisms were significantly associated with dry and
wet AMD and rs11200638 was the most significantly associated variant in a Taiwan 
Chinese population.

Publication Types: 
    Comparative Study

PMID: 18301036 [PubMed - indexed for MEDLINE]

401: Retina. 2008 Feb;28(2):298-308.

Correlation of pathologic features in spectral domain optical coherence
tomography with conventional retinal studies.

Stopa M, Bower BA, Davies E, Izatt JA, Toth CA.

Department of Ophthalmology, Duke University Medical Center, Durham, NC 27710,
USA.

PURPOSE: To delineate pathologic changes in retinal cross sections obtained with 
spectral (Fourier) domain optical coherence tomography (SDOCT), so that the
findings are maintained when collapsed into a two-dimensional fundus image for
comparison with conventional retinal studies. METHODS: SDOCT of the posterior
pole of 12 eyes (5 with neovascular age-related macular degeneration [AMD]; 7
with nonneovascular AMD) produced three-dimensional stacks of scans. Location of 
pathologic features was delineated with color markings in each scan before the
stack was collapsed along the depth axis. This en face image contained retinal
vessel shadowing and preserved color markings of delineated pathologic features
relative to the vessel pattern and was superimposed onto conventional studies.
RESULTS: For patients with neovascular AMD, location and extent of choroidal
neovascularization, macular edema, and subretinal fluid were visible on the
two-dimensional summed images and, in some cases, involved sites not suspected
with conventional imaging. For patients with nonneovascular AMD, the location of 
drusen and geographic atrophy were correlated with autofluorescence images. For
one eye with drusen and three eyes with neovascular AMD, presence or extent of
subretinal fluid identified by SDOCT was not visible using other imaging methods.
CONCLUSIONS: In this pilot AMD study, pathologic features within SDOCT scans were
transferred into two-dimensional en face projections, enabling researchers to
correlate lateral extent of pathologic features from SDOCT with conventional
studies. This integration of SDOCT with other retinal studies is promising and
will be useful to study the relationship between local OCT morphology and other
parameters of retinal disease or function.

Publication Types: 
    Case Reports
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18301035 [PubMed - indexed for MEDLINE]

402: Retina. 2008 Feb;28(2):263-73.

Early macular morphological changes following plaque radiotherapy for uveal
melanoma.

Horgan N, Shields CL, Mashayekhi A, Teixeira LF, Materin MA, Shields JA.

Ocular Oncology Service, Wills Eye Institute, Thomas Jefferson University,
Philadelphia, PA 19107, USA.

PURPOSE: To evaluate the time of onset and risk factors for the development of
macular edema following plaque radiotherapy for uveal melanoma, using optical
coherence tomography (OCT). METHODS: This observational case series included 135 
consecutive patients with uveal melanoma treated with Iodine(125) plaque
radiotherapy and adjunctive transpupillary thermotherapy (TTT) laser. Patients
were evaluated at baseline and 6-month intervals following treatment using
ophthalmoscopy, B-scan ultrasonography, fundus photography, and OCT. RESULTS:
Median follow-up was 24 months. The mean time to onset of macular edema by OCT
was 12 months. Median best-corrected logMAR visual acuity at the time of onset of
OCT-evident macular edema was 0.3 (equivalent to 20/40 Snellen). The development 
of OCT-evident macular edema was significantly associated with maximum tumor
thickness (P = 0.0016), largest tumor base (P < 0.0001), radiation dose, and
dose-rate to the tumor base (P = 0.0315 and P = 0.0204, respectively). Neither
radiation dose to the foveola nor treatment with adjunctive TTT laser was
significantly associated with the development of macular edema. CONCLUSIONS: OCT 
is useful in the early detection of radiation-induced macular edema, before
clinical signs of radiation maculopathy develop and before substantial visual
loss occurs. The development of macular edema is significantly associated with
larger initial tumor size.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18301032 [PubMed - indexed for MEDLINE]

403: Retina. 2008 Feb;28(2):220-5.

Visual acuity and multifocal electroretinographic changes after arteriovenous
crossing sheathotomy for macular edema associated with branch retinal vein
occlusion.

Chung EJ, Freeman WR, Koh HJ.

The Institute of Vision Research, Department of Ophthalmology, Yonsei University 
College of Medicine, Sodaemun-Gu, Seoul, Korea.

PURPOSE: To evaluate the influence of arteriovenous (AV) sheathotomy on retinal
function with central multifocal electroretinography (mfERG) in eyes with macular
edema secondary to branch retinal vein occlusion (BRVO). METHODS: Fifteen
patients (15 eyes) who underwent AV sheathotomy for macular edema secondary to
BRVO were included in the study. Best-corrected visual acuity and mfERG responses
from the most central seven hexagons were analyzed before and 6 months after the 
operation. RESULTS: The mean preoperative Early Treatment Diabetic Retinopathy
Study (ETDRS) score +/- SD was 34.1 +/- 12.7 letters (Snellen equivalent, 20/50) 
and significantly improved up to 40.5 +/- 10.9 letters (Snellen equivalent,
20/40) at 6 months after AV sheathotomy (P = 0.027, Wilcoxon signed rank test).
The mean preoperative P1 amplitude +/- SD of the most central 7 hexagons was
39.30 +/- 10.86 nV/deg(2) for the affected eye versus 47.72 +/- 6.67 nV/deg(2)
for the normal fellow (control) eye (P = 0.013, Mann-Whitney U test) and
significantly increased up to 50.71 +/- 15.58 nV/deg at 6 months after the
operation (P = 0.014, Wilcoxon signed rank test). Significant correlations
between preoperative and postoperative ETDRS score and preoperative P1 amplitude 
were present (r = 0.929, P < 0.001; r = 0.768, P = 0.001; respectively [Spearman 
correlation]). CONCLUSIONS: AV sheathotomy improved macular function and
anatomical outcome as measured by ETDRS score and mfERG responses in patients
with macular edema due to BRVO.

PMID: 18301026 [PubMed - indexed for MEDLINE]

404: Retina. 2008 Feb;28(2):212-9.

Comparison of two doses of intravitreal bevacizumab (Avastin) for treatment of
macular edema secondary to branch retinal vein occlusion: results from the
Pan-American Collaborative Retina Study Group at 6 months of follow-up.

Wu L, Arevalo JF, Roca JA, Maia M, Berrocal MH, Rodriguez FJ, Evans T, Costa RA, 
Cardillo J; Pan-American Collaborative Retina Study Group (PACORES).

Collaborators: Cardillo J, Wu L, Evans T, Arevalo JF, Sanchez JG, Garcia-Amaris
RA, Farah M, Maia M, Aggio FB, Quiroz-Mercado H, Fromow-Guerra J, Morales-Canton 
V, Guerrero-Naranjo J, Rodriguez FJ, Infante R, Flores S, Medina D, Figueroa G,
Berrocal MH, Cruz-Villegas V, Graue-Wiechers F, Lozano-Rechy D, Robledo V, Roca
JA, Reategui G, Saravia MJ, Martinez-Cartier M, Avila M, Costa RA, Cardillo J.

Instituto de Cirugia Ocular, San José, Costa Rica. LW65@cornell.edu

PURPOSE: To report the 6-month anatomical and visual outcomes after injecting two
different doses of intravitreal bevacizumab in patients with macular edema
secondary to branch retinal vein occlusion (BRVO). METHODS: An interventional,
retrospective multicenter study of 45 eyes that were treated with at least one
intravitreal injection (24 eyes, 1.25 mg; 21 eyes, 2.5 mg) of bevacizumab is
reported. The main outcome measures were the central 1-mm macular thickness (CMT)
and the change in ETDRS lines of best-corrected visual acuity (BCVA) at 6 months.
RESULTS: Forty-five eyes were injected on average 26.1 months (range, 3-86
months) after the diagnosis. The average follow-up was 35.2 weeks (range, 24-52
weeks). All patients completed at least 6 months of follow-up. In the 1.25-mg
dose group, at 1 month, there was an average gain of 4.5 lines of BCVA; at 3
months, 5.1 lines of BCVA; and at 6 months, 5.1 lines of BCVA (P < 0.005). In the
2.5-mg dose group, at 1 month, there was an average gain of 2.3 lines of BCVA; at
3 months, 3.8 lines of BCVA; and at 6 months, 4.8 lines of BCVA (P = 0.05). In
the 1.25-mg dose group, the mean CMT +/- SD decreased from 461 +/- 211 microm at 
baseline to 321 +/- 152 microm at 1 month, 273 +/- 99 microm at 3 months, and 277
+/- 114 microm at 6 months (P = 0.0002). In the 2.5-mg group, the mean CMT +/- SD
decreased from 385 +/- 168 microm at baseline to 279 +/- 111 microm at 1 month,
249 +/- 97 microm at 3 months, and 240 +/- 93 microm at 6 months (P = 0.011).
CONCLUSION: There were no statistically significant differences between the two
dose groups with regard to the number of injections and anatomical and functional
outcomes. Intravitreal injection of bevacizumab at doses up to 2.5 mg appears to 
be effective in improving BCVA and reducing CMT in BRVO in the short term.
Multiple injections are needed in a large number of eyes for continued control of
macular edema and preservation of visual acuity in the short term. Longer studies
are needed to determine what role if any intravitreal injection of bevacizumab
may play in the long-term treatment of this condition.

Publication Types: 
    Comparative Study
    Multicenter Study

PMID: 18301025 [PubMed - indexed for MEDLINE]

405: Ophthalmic Epidemiol. 2008 Jan-Feb;15(1):56-61.

The relationship between birthweight and early age-related maculopathy: the
atherosclerosis risk in communities study.

Liew G, Wang JJ, Klein R, Duncan BB, Brancati F, Yeh HC, Wong TY.

Centre for Vision Research, University of Sydney, Department of Ophthalmology,
Westmead Hospital, The Westmead Millennium Institute, Australia.

PURPOSE: Birthweight is a marker of fetal growth, and has been linked to future
risk of chronic diseases in adults. We examined the association between
birthweight and age-related maculopathy (ARM). METHODS: We studied 9730 adults
from the population-based Atherosclerosis Risk in Communities study, of whom 4744
reported their exact birthweight and an additional 4986 provided categorical
birthweight data (low, medium or high). We graded retinal photographs for
presence of ARM using a modification of the Wisconsin ARM Grading System.
RESULTS: Early ARM was present in 479 (4.9%) adults. Among persons with exact
birthweight data, there was no association between birthweight and early ARM (OR 
1.1, 95% CI 0.9-1.3, for each kg increase in birthweight). However, in Whites,
greater birthweight was associated with an increased risk of early ARM (OR 1.2,
95% CI 1.0-1.4, for each kilogram increase in birthweight), after adjustment for 
age, sex, smoking, blood pressure and education level. In analyses including
additional participants who provided categorical birthweight data, the pattern of
associations were similar but not statistically significant. We did not have
sufficient numbers to examine associations for late ARM (n = 12) or in
African-Americans separately. CONCLUSIONS: We found no association between
birthweight and risk of early ARM in the whole population. Among the white
participants, higher birthweight was associated with a slight increased risk of
early ARM. These findings, if confirmed in other studies, suggest that fetal
growth may be important in ARM development in white persons.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18300090 [PubMed - indexed for MEDLINE]

406: Semin Immunopathol. 2008 Apr;30(2):97-110. Epub 2008 Feb 26.

Immunopathological aspects of age-related macular degeneration.

Patel M, Chan CC.

Section of Immunopathology, Laboratory of Immunology, National Eye Institute,
National Institutes of Health, 10 Center Drive, 10/10N103, NIH/NEI, Bethesda, MD 
20892-1857, USA.

Age-related macular degeneration (AMD) represents a leading cause of blindness
worldwide. While the clinical and histopathological aspects of AMD are well
characterized, its etiology and pathogenesis remain unclear. Recent findings
suggest a role for immunologic processes in AMD pathogenesis, including the
age-related generation of extracellular deposits inside the Brusch membrane and
beneath the retinal pigment epithelium, recruitment of macrophages for clearance 
of these deposits, complement activation, recruitment of tissue-destructive
macrophages, microglial activation and accumulation, and proinflammatory effects 
of chronic inflammation by Chlamydia pneumoniae. This review discusses the
evidence for the role of inflammation in human AMD and in animal models of AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18299834 [PubMed - indexed for MEDLINE]

407: Arch Iran Med. 2008 Mar;11(2):143-7.

The impact of macular laser photocoagulation on contrast sensitivity function in 
patients with clinically significant macular edema.

Farahvash MS, Mahmoudi AH, Farahvash MM, Tabatabaee A, Riazi M, Mohammadzadeh S, 
Faghihi H, Nilli-Ahmadabadi M, Mirshahi A, Karkhaneh R, Aalami-Harandi Z,
Javadian A, Abdolahi A, Lashey A.

Department of Ophthalmology, Tehran University of Medical Sciences, Tehran, Iran.
Farahva@yahoo.com

BACKGROUND: Contrast sensitivity is an important aspect of visual function and is
even more important for ordinary daily tasks than visual acuity. Contrast
sensitivity function may be deteriorated to a significant level in diabetic
retinopathy, especially in diabetic macular edema. The objective of this study
was to determine the impact of macular laser photocoagulation-as the standard
treatment of clinically significant macular edema-on contrast sensitivity
function. METHODS: In a prospective noncomparative interventional case series, 17
patients with clinically significant bilateral macular edema and no history of
prior macular laser photocoagulation were enrolled. Baseline visual acuity,
contrast sensitivity function, and fluorescein angiography were obtained and
reassessed three months after macular laser photocoagulation. RESULTS: Clinically
significant macular edema resolved in 22 (65%) of 34 eyes, three months after
their first session of macular laser photocoagulation. The mean pretreatment
visual acuity was 24.5/40 (0.21 logMAR) +/-10.3/40. Three months after macular
photocoagulation, visual acuity remained stable in 19 eyes, decreased in 12 eyes,
and increased in three eyes. The mean post-treatment visual acuity was 24/40
(0.24 logMAR) +/-10.8/40. There was a statistically significant (P = 0.02)
decrease in visual acuity following laser therapy. In subgroup analysis, this
decrease in visual acuity was only observed in those with unresolved clinically
significant macular edema. The mean contrast sensitivity threshold increased in
all spatial frequencies by three months after macular photocoagulation. The
maximum rise was observed in the frequency of 6.4 cycles per degree in the mid
range of frequencies, with a pretreatment mean of 9.41 dB and a post-treatment
mean of 11.50 dB (P<0.05). CONCLUSION: Contrast sensitivity function improved
after macular laser photocoagulation in clinically significant macular edema
patients.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18298289 [PubMed - indexed for MEDLINE]

408: Invest Ophthalmol Vis Sci. 2008 Jun;49(6):2721-7. Epub 2008 Feb 22.

Morphometric analysis of lipoprotein-like particle accumulation in aging human
macular Bruch's membrane.

Huang JD, Curcio CA, Johnson M.

Department of Biomedical Engineering, Northwestern University, Evanston, Illinois
60208-3107, USA.

PURPOSE: To determine the size and regional distribution of lipoprotein-like
particles (LLPs) that accumulate with age in Bruch's membrane (BrM). METHODS: The
quick-freeze/deep-etch method was used to prepare specimens of human BrM (age
range, 27-78) for electron microscopic examination. Stereologic methods were used
to analyze the resultant micrographs and determine the age-related changes of the
LLP volume fraction and diameter distribution in various locations in BrM.
RESULTS: The volume fraction occupied by LLPs was found to increase monotonically
with age in both the inner collagenous layer (ICL) and elastic layer (EL), but
not in the outer collagenous layer (OCL). The mass of total LLP-associated lipids
in BrM also increased with age. There was no significant increase in LLP size
with age, but there was a modest increase in size with increased volume fraction 
of LLPs in BrM. CONCLUSIONS: The pattern of accumulation of particles was
consistent with a retinal pigment epithelium (RPE) source for the LLPs, which
explains why once the EL and ICL were filled with particles, LLPs continued to
accumulate near the RPE, but no further accumulation was found in the OCL. The
quantity of LLP-associated lipids found in BrM accounts for a large portion of
the accumulated lipids measured in this tissue.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18296655 [PubMed - indexed for MEDLINE]

409: Matrix Biol. 2008 Jun;27(5):381-92. Epub 2008 Feb 5.

Comment in:
    Matrix Biol. 2008 Jun;27(5):379-80.

Molecular dissection of TIMP3 mutation S156C associated with Sorsby fundus
dystrophy.

Fogarasi M, Janssen A, Weber BH, Stöhr H.

Institute of Human Genetics, University of Regensburg, Franz-Josef-Strauss-Allee 
11, D-93053 Regensburg, Germany.

Sorsby fundus dystrophy (SFD) is an autosomal dominant macular degeneration of
late onset. A key feature of the disease is the thickening of Bruch's membrane,
an ECM structure located between the RPE and the choroid. SFD is caused by
mutations in the gene encoding the ECM-associated tissue inhibitor of
metalloproteases-3 (TIMP3). We have recently generated two Timp3 gene-targeted
mouse lines, one deficient for the murine gene (Timp3-/-) and one carrying an
SFD-related S156C mutation. Based on extracts and cell cultures derived from
tissues of these animals we now evaluated TIMP3 functionality and its
contribution to SFD. We show that the activity levels of TIMP3 target proteases
including TACE, ADAMTS4/5 and aggrecan-cleaving MMPs are similar in Timp3S156/+
and Timp3S156C/S156C mice when compared to controls. In Timp3-/- mice, a
significant enhancement of enzyme activity was observed for TACE but not for
ADAMTS4/5 and MMPs indicating a compensatory effect of other inhibitors
regulating the latter two groups of proteases. Fibrin bead assays show that
angiogenesis in Timp3S156/+ and Timp3S156C/S156C mice is not altered whereas
increased formation of capillary tubes was observed in Timp3-/- animals over
controls. Rescue experiments using recombinant proteins demonstrate that the
inhibitory activities of TIMP3 towards TACE and aggrecan-cleaving MMPs as well as
the anti-angiogenic properties of TIMP3 are not impaired by SFD mutation S156C.
We finally demonstrate that wild-type and S156C-TIMP3 proteins block the binding 
of VEGF to its receptor VEGFR2 to a similar extent. Taken together, this study
shows that S156C-TIMP3 retains its known functional properties suggesting that
causes other than an imbalance in protease or angiogenic activities represent the
primary molecular defect underlying SFD.

PMID: 18295466 [PubMed - indexed for MEDLINE]

410: Genet Test. 2007 Winter;11(4):421-6.

Mutation analysis of oxisterol-binding-protein gene in patients with age-related 
macular degeneration.

Torrini M, Marchese C, Vanzetti M, Marini V, Origone P, Garré C, Mareni C.

Department of Internal Medicine, University of Genova, Genova, Italy.

Allelic variants of several genes are increasingly recognized as susceptibility
factors in age-related macular degeneration (AMD). Because of its metabolic
characteristics the macula is sensitive to oxidative damage, and supplementation 
with antioxidants has been shown to be effective in slowing the progression of
disease in AMD patients. The oxisterol-binding-protein (OSBP2) gene is expressed 
mainly in the retinal pigmented epithelium underlying the macular region. Its
product specifically binds and transports oxisterols, the cytotoxic effects of
which may be involved in macular damage. The aim of this study was to search for 
allelic variants of OSBP2 gene, as well as to evaluate several risk factors in 24
patients with AMD; 17 with nonexudative (NE) and 7 with neovascular (NV) form.
Total cholesterol was elevated in 66% of the patients, high-density lipoprotein
(HDL) cholesterol was reduced in 12%; vitamin A or vitamin E deficiency was not
observed. OSBP2 gene analysis was performed in AMD patients and in 110 control
subjects by single-stranded conformational polymorphism (SSCP) analysis followed 
by direct sequencing. Six allelic variants were detected: 2 nonpolymorphic unique
exonic variants in 2 AMD subjects and 4 polymorphic variants (2 exonic and 2
intronic). These data indicate a possible role of OSBP2 gene in the pathogenesis 
of oxidative damage to the macula induced by oxysterols in AMD patients.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18294060 [PubMed - indexed for MEDLINE]

411: J Nutr Elder. 2007;26(3-4):139-57.

Lutein and age-related ocular disorders in the older adult: a review.

Renzi LM, Johnson EJ.

Vision Science Laboratory, University of Georgia, Athens 30602, USA.

Lutein, a carotenoid found in dark green, leafy vegetables, has been implicated
as being protective against the acquired ocular diseases, such as cataracts and
age-related macular degeneration. In the eye, lutein may act as an antioxidant
and as a blue light filter to protect the underlying tissues from phototoxic
damage. Average intakes of lutein in the U.S. are below levels associated with
eye disease prevention. Therefore, increased intakes of food sources rich in
lutein may be warranted. Age-related factors, such as increased inflammation and 
body fat, are also related to increased risk of age-related eye disease. The
mechanism by which these factors are related to risk may be partially due to
adverse effects on lutein status.

Publication Types: 
    Research Support, U.S. Gov't, Non-P.H.S.
    Review

PMID: 18285296 [PubMed - indexed for MEDLINE]

412: Arch Ophthalmol. 2008 Feb;126(2):241-5.

Racial differences in the prevalence of age-related macular degeneration: the
Salisbury Eye Evaluation (SEE) Project.

Bressler SB, Muñoz B, Solomon SD, West SK; Salisbury Eye Evaluation (SEE) Study
Team.

The Wilmer Eye Institute, Johns Hopkins Hospital, 600 N Wolfe St, Baltimore, MD
21287-9228, USA. khansbe@jhmi.edu

OBJECTIVE: To determine differences in the prevalence of age-related macular
degeneration (AMD) and its fundus manifestations in a population-based sample of 
older black and white Americans. DESIGN: Cross-sectional population-based study
of 2520 participants of whom 1854 are white and 666 are black. Mean age was 73.5 
years. Stereoscopic color fundus photographs were graded for presence, severity, 
and location of drusen, retinal pigment epithelium abnormalities, and choroidal
neovascularization or disciform scarring. RESULTS: Drusen at least 64 microm in
size were identified in 56% of black and white individuals within 3000 microm of 
the foveal center, but drusen larger than 125 microm were more common among white
participants (16% white vs 11% black individuals). Drusen at least 250 microm in 
size, confluent drusen, or a larger area (> 10%) occupied by drusen were each
more common among white participants. White individuals were 3 times more likely 
to have focal hyperpigmentation than black individuals. Racial differences were
most pronounced for features within the central 1500-microm macular zone.
Neovascular AMD was present in 1.7% of white participants and 1.1% of black
participants (age-adjusted, P = .38), whereas geographic atrophy was more common 
in white than black individuals (1.8% vs 0.3%; age-adjusted, P = .02).
CONCLUSIONS: White persons are generally more likely than black persons to have
medium or large drusen, focal pigment abnormalities, and advanced AMD. Racial
differences were prominent for nonneovascular AMD features only when present in
the central zone. These data suggest that black individuals may have a mechanism 
for protection in the central zone against these critical fundus features, which 
themselves convey high risk of progression to advanced AMD.

Publication Types: 
    Comparative Study
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18268216 [PubMed - indexed for MEDLINE]

413: Arch Ophthalmol. 2008 Feb;126(2):200-5.

Short-term safety and efficacy of intravitreal triamcinolone acetonide for
uveitic macular edema in children.

Sallam A, Comer RM, Chang JH, Grigg JR, Andrews R, McCluskey PJ, Lightman S.

Department of Clinical Ophthalmology, Institute of Ophthalmology, Moorfields Eye 
Hospital, City Road, London EC1V 2PD, England.

OBJECTIVES: To evaluate the short-term safety and efficacy of intravitreal (IV)
triamcinolone acetonide (TA) for treating pediatric cystoid macular edema (CME)
secondary to noninfectious uveitis. METHODS: A retrospective noncomparative
interventional case series. The medical records of 15 consecutive children (16
eyes) with uveitic CME treated with IVTA (2 or 4 mg) were reviewed. Data
collected included details of uveitis, CME, visual acuity, intraocular pressure, 
and cataract development. The median follow-up time was 16 months (range, 9-36
months). RESULTS: Resolution of CME was achieved in all of the treated eyes. The 
median time taken for CME to resolve was 3 weeks (range, 1-24 weeks). The mean
improvement of visual acuity after IVTA was 0.6 logarithm of the minimum angle of
resolution. Following initial response to IVTA, CME relapsed in 5 eyes (31%)
after a median time of 7 months (range, 3-13 months). The most common adverse
effect was increased intraocular pressure, with an increase of more than 15 mm Hg
in 5 eyes (31%). Steroid-induced cataract was observed in 6 of 11 phakic eyes
(55%). CONCLUSIONS: We found that IVTA is efficacious in the treatment of uveitic
CME in children and results in CME resolution and visual acuity improvement. As
in adults, treatment in children may be associated with elevated intraocular
pressure and cataract.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18268210 [PubMed - indexed for MEDLINE]

414: Ophthalmology. 2008 Apr;115(4):700-707.e1. Epub 2008 Feb 11.

Prevalence of age-related maculopathy and age-related macular degeneration among 
the inuit in Greenland. The Greenland Inuit Eye Study.

Andersen MV, Rosenberg T, la Cour M, Kiilgaard JF, Prause JU, Alsbirk PH,
Borch-Johnsen K, Peto T, Carstensen B, Bird AC.

Department of Ophthalmology, Rigshospitalet, University Hospital of Copenhagen
and Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.

PURPOSE: To examine the age- and gender-specific prevalence and describe the
common phenotype of early age-related maculopathy (ARM) and late-stage
age-related macular degeneration (AMD) among the Inuit in Greenland. DESIGN:
Population-based cross-sectional study. PARTICIPANTS: All > or =60-year-olds born
in Greenland and living in the communities of Nuuk and Sisimiut, Greenland.
METHODS: The presence and form of early (ARM) and late age-related macular
disease (AMD) were determined by grading color fundus photographs using the
international classification and grading system for ARM and AMD. MAIN OUTCOME
MEASURES: Prevalences of ARM and AMD were assessed by masked grading of fundus
photographs. RESULTS: Overall, 695 persons were included in the study (response
rate, 74.8%). Prevalence of any ARM was 52.3%. Age-related maculopathy was
present in the worse eye in 50.0%, 58.8%, and 44.7% of age groups 60 to 69, 70 to
79, and > or =80, respectively. Prevalence of any AMD was 9.5%. Any AMD was
present in the worse eye in 3.9%, 14.6%, and 43.2% of age groups 60 to 69, 70 to 
79, and > or =80. Prevalences of pure geographic atrophy (GA) in one or both
eyes, exudative degeneration in one or both eyes, and GA in one eye and exudative
degeneration in the other eye were 2.3%, 6.1%, and 1.1%, respectively.
CONCLUSIONS: The prevalence of ARM is higher than in most other populations
studied, and the prevalence of AMD in the oldest age group is higher than in most
other populations studied. The prevalence of exudative degeneration is higher
than the prevalence of GA, in contrast to findings in some of the Nordic
countries-particularly Iceland-and earlier observations in Greenland.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18267341 [PubMed - indexed for MEDLINE]

415: Invest Ophthalmol Vis Sci. 2008 May;49(5):1763-70. Epub 2008 Feb 8.

Functional and structural implications of the complement factor H Y402H
polymorphism associated with age-related macular degeneration.

Ormsby RJ, Ranganathan S, Tong JC, Griggs KM, Dimasi DP, Hewitt AW, Burdon KP,
Craig JE, Hoh J, Gordon DL.

Department of Microbiology and Infectious Diseases, Flinders Medical Centre and
Flinders University of South Australia, Bedford Park, SA 5042, Australia.
rebecca.ormsby@flinders.edu.au

PURPOSE: A Tyr-to-His (Y402H) sequence variant in the factor H (FH) and factor
H-like protein (FHL-1) gene is strongly associated with an increased
susceptibility for age-related macular degeneration (AMD). The purpose of this
study was to understand how the Y402H variant in FH/FHL-1 contributes to the
pathogenesis of AMD and, in particular, whether interactions mediated by
FH/FHL-1, including binding to C-reactive protein (CRP), group A streptococcal M 
protein (GAS M6), heparin, and retinal pigment epithelial cells (RPE), are
affected. METHODS: FH was purified from sera of patients homozygous for FH(Y402) 
or (H402), and recombinant FH fragments representing FHL-1 were generated.
Proteins were analyzed for binding to CRP, GAS M6, heparin, and RPE cells.
RESULTS: Binding of the FH and FH1 to seven polymorphic variants to CRP and M
protein was reduced. The variant did not influence the interaction of FH with
heparin but did reduce binding of FHL-1. Binding of the FH and FHL-1 polymorphic 
variant to RPE cells was not affected. CONCLUSIONS: The FH Y402H polymorphism
associated with AMD causes a reduction in binding of FH and FHL-1 to CRP and M
protein. Both variants show comparable binding to RPE cells, indicating that AMD 
is unlikely to manifest as a result of impaired host cell-surface recognition.
The decreased interaction between FH and CRP, which is essential for the
anti-inflammatory function of CRP, provides a possible pathophysiological
explanation for the association of the Y402H variant with AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18263814 [PubMed - indexed for MEDLINE]

416: Invest Ophthalmol Vis Sci. 2008 Jun;49(6):2395-402. Epub 2008 Feb 8.

Racial differences and other risk factors for incidence and progression of
age-related macular degeneration: Salisbury Eye Evaluation (SEE) Project.

Chang MA, Bressler SB, Munoz B, West SK.

Retina Division and Dana Center for Preventative Ophthalmology, Wilmer Eye
Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland
21287, USA. mchang19@jhmi.edu

PURPOSE: To evaluate risk factors for the incidence and progression of
age-related macular degeneration (AMD) in a racially heterogeneous, geriatric
population. METHODS: Subjects (n = 2240) aged 65 to 84 years underwent 2
examinations separated by 2 years, of which 1937 subjects (85%) were included in 
this report. Fundus photographs were performed at each examination and were
graded by trained readers. Multivariate logistic regression models adjusted for
age, sex, race, and clustering between eyes were used to evaluate risk factors
for AMD incidence and progression. RESULTS: Smoking was a strong, dose-dependent,
risk factor for progression from medium size drusen to large drusen or pigmentary
abnormalities within the central 1500-microm macular zone. Smoking was also a
strong risk factor for development of incident focal pigmentation within 3000
microm of the foveal center. White participants were significantly more likely
than blacks to develop large drusen and focal pigmentation and to progress from
medium- to large-sized drusen or pigment abnormalities within the central 1500
microm macular zone. However, whites did not have an increased risk of
progression from large drusen or pigment abnormalities within the central
1500-microm perimacular zone to foveal GA or CNV when compared with blacks.
CONCLUSIONS: Smoking and race are important risk factors for progression from
medium to large drusen or to pigment abnormalities within the central 1500-microm
macular zone. Limitations in the power of this study preclude assessment of the
roles of smoking and race on the ultimate progression to foveal GA or CNV once
central large drusen or pigment abnormalities are present.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18263809 [PubMed - indexed for MEDLINE]

417: Med Decis Making. 2008 Jan-Feb;28(1):33-43.

Identifying research priorities: the value of information associated with repeat 
screening for age-related macular degeneration.

Bojke L, Claxton K, Sculpher MJ, Palmer S.

Centre for Health Economics, University of York, York, United Kingdom.
kpc1@york.ac.uk

The authors report an analysis that was developed as part of a pilot study
examining the use of decision analysis and value-of-information methods to inform
research prioritization decisions for the UK health care system. This analysis
was conducted to inform decision makers whether additional research on screening 
for age-related macular degeneration (AMD) would be worthwhile and to demonstrate
the benefits and feasibility of using such analytic methods to inform policy
decision within the time-lines demanded by existing procedures. A probabilistic
decision model was developed to establish the cost-effectiveness of a policy of
repeat screening for AMD using the Amsler grid followed by treatment with
photodynamic therapy (PDT) compared with 2 alternatives: PDT without screening
(self-referral) and no screening or treatment. Screening for AMD appears to be
cost-effective on the basis of existing evidence; however, the decision to
implement a policy of screening is somewhat uncertain, with a probability that
screening is cost-effective of 0.87 and 0.72 for the 20/40 and 20/80 models,
respectively, at a threshold of 30,000 pounds per quality-adjusted life-year. The
expected value of perfect information (EVPI) associated with this decision is
substantial (6.9 million pounds for the 20/40 model and 14.5 million pounds for
the 20/80 model), with a sizeable EVPI associated with the effect of PDT on
quality of life. The analysis demonstrates that EVPI analysis can be implemented 
in a timely fashion to inform the type of research prioritization decisions faced
by any health care system. This case study also illustrates the need to account
for any structural uncertainties appropriately.

PMID: 18263560 [PubMed - indexed for MEDLINE]

418: Ophthalmic Surg Lasers Imaging. 2008 Jan-Feb;39(1):69-72.

Optical coherence tomography findings in autosomal dominant macular dystrophy.

Schadlu R, Shah GK, Prasad AG.

Department of Ophthalmology and Visual Sciences, Washington University School of 
Medicine, St. Louis, MO, USA.

The authors report a case of autosomal dominant cystoid macular dystrophy in
which optical coherence tomography outlined the pathology and assisted in
determining the etiology of the patient's macular edema.

Publication Types: 
    Case Reports

PMID: 18254357 [PubMed - indexed for MEDLINE]

419: Ophthalmic Surg Lasers Imaging. 2008 Jan-Feb;39(1):63-4.

Resolution of tractional macular edema following spontaneous detachment of
residual vitreous cortex in a vitrectomized eye.

Maguluri S, Recchia FM.

Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville,
Tennessee 37232, USA.

A 15-year-old boy underwent pars plana vitrectomy and lensectomy following blunt 
closed-globe injury. Postoperatively, he had visual distortion and a decline in
visual acuity attributable to tractional macular edema caused by clinically
apparent residual vitreous cortex. One month later, macular edema resolved and
visual acuity improved following spontaneous vitreous separation. This case
illustrates what has been termed the posterior bursa macularis and emphasizes its
pathoetiologic role in vitreomacular disease.

Publication Types: 
    Case Reports

PMID: 18254355 [PubMed - indexed for MEDLINE]

420: Ophthalmic Surg Lasers Imaging. 2008 Jan-Feb;39(1):12-6.

The temporal sequence of combined intravitreal triamcinolone acetonide and
photodynamic therapy for exudative age-related macular degeneration.

Roth DB, Kulkarni KM, Feuer WJ.

Retina Vitreous Center, Department of Ophthalmology, Robert Wood Johnson Medical 
School, University of Medicine & Dentistry of New Jersey, New Brunswick
08901-1977, USA.

BACKGROUND AND OBJECTIVE: To compare visual acuity results in patients with
exudative age-related macular degeneration treated with two different temporal
sequences of combination intravitreal triamcinolone acetonide and photodynamic
therapy with verteporfin. PATIENTS AND METHODS: A retrospective, comparative,
interventional case series was used. Thirty-one eyes received intravitreal
triamcinolone acetonide 1 week prior to photodynamic therapy, and 30 eyes
received intravitreal triamcinolone acetonide followed by photodynamic therapy
the same day. RESULTS: There was no significant difference in visual acuity
between the groups at baseline (P = .084), 6 to 12 weeks of follow-up (P = .085),
or 1 year of follow-up (P= .093). When visual acuity outcomes were adjusted for
baseline visual acuity, spot size, lesion type, age, and gender, there was no
significant difference in visual acuity at 6 to 12 weeks (P = .44) or 1 year (P= 
.28). CONCLUSIONS: There appears to be no significant difference in visual
outcomes in eyes with exudative age-related macular degeneration treated with
intravitreal triamcinolone acetonide 1 week prior to photodynamic therapy or
those treated with intravitreal triamcinolone acetonide on the same day as
photodynamic therapy.

Publication Types: 
    Comparative Study

PMID: 18254345 [PubMed - indexed for MEDLINE]

421: Cochrane Database Syst Rev. 2008 Jan 23;(1):CD005656.

Intravitreal steroids for macular edema in diabetes.

Grover D, Li TJ, Chong CC.

Strong Memorial Hospital, Department of Ophthalmology, Box 659, 601 Elmwood
Avenue, Rochester, NY 14642, USA. dagrover@frontiernet.net

BACKGROUND: Macular edema is secondary to leakage from diseased retinal
capillaries and is an important cause of poor central visual acuity in patients
with diabetic retinopathy. OBJECTIVES: This review evaluated the effectiveness
and safety of intraocular steroids in treating diabetic macular edema (DME).
SEARCH STRATEGY: We searched CENTRAL, MEDLINE, EMBASE in June 2007, reference
lists, Science Citation Index and conference proceedings. SELECTION CRITERIA: We 
included randomized clinical trials (RCTs) evaluating any form of intravitreal
steroids for treating DME. DATA COLLECTION AND ANALYSIS: Two authors
independently assessed eligibility, methodological quality and extracted data. We
performed meta-analyses when appropriate. MAIN RESULTS: Seven studies, involving 
632 DME eyes were included. Four examined the effectiveness of intravitreal
triamcinolone acetate injection (IVTA), three examined intravitreal steroids
implantation (fluocinolone acetonide implant (FAI) or dexamethasone drug delivery
system (DDS)). Two trials were at low risk of bias, one was at median risk of
bias, two were at high risk of bias and the remaining two were at unclear risk of
bias.The preponderance of data suggest a beneficial effect from IVTA. Comparing
IVTA with controls, the mean difference in visual acuity was -0.15 LogMAR (95% CI
-0.21 to -0.09) at 3 months (based on three trials), -0.23 LogMAR (95% CI -0.33
to -0.13) at 6 months (two trials), -0.29 LogMAR (95% CI -0.47 to -0.11) at 9
months (one trial), and -0.11 LogMAR (95% CI -0.20 to -0.03) at 24 months (one
trial), all in favor of IVTA. The relative risk (RR) for one or more lines
improvement in visual acuity was 2.85 (95% CI 1.59 to 5.10) at 3 months (two
trials), 1.25 (95% CI 0.66 to 2.38) at 6 months (one trial), and 2.17 (95% CI
1.15 to 4.11) at 24 months (one trial), all in favor of IVTA. We did not find
evidence for three or more lines improvement in visual acuity. The mean
difference in retinal thickness was -131.97 um (95% CI -169.08 to -94.86) at 3
months (two trials), -135.00 um (95% CI -194.50 to -75.50) at 6 months (one
trial), -133.00 um (95% CI -199.86 to -66.14) at 9 months (one trial), and -59.00
um (95% CI -103.50 to -14.50) at 24 months (one trial), all in favor of IVTA. The
RR for at least one grade macular edema resolution was 5.15 (95% CI 2.23 to
11.88) at 3 months in favor of IVTA (one trial).Two trials reported improved
clinical outcome when FAI was compared to standard of care. Beneficial effect was
also observed in one dexamethasone DDS trial.Increased intraocular pressure and
cataract formation were side effects requiring monitoring and management.
AUTHORS' CONCLUSIONS: RCTs included in this review suggest that steroids placed
inside the eye by either intravitreal injection or surgical implantation may
improve visual outcomes in eyes with persistent or refractory DME. Since the
studies in our report focused on chronic or refractory DME, the question arises
whether intravitreal steroids therapy could be of value in other stages of DME,
especially the earlier stages either as standalone therapy or in combination with
other therapies, such as laser photocoagulation.

Publication Types: 
    Meta-Analysis
    Review

PMID: 18254088 [PubMed - indexed for MEDLINE]

422: Cochrane Database Syst Rev. 2008 Jan 23;(1):CD000253.

Update of:
    Cochrane Database Syst Rev. 2000;(2):CD000253.

Antioxidant vitamin and mineral supplements for preventing age-related macular
degeneration.

Evans JR, Henshaw K.

London School of Hygiene & Tropical Medicine, International Centre for Eye
Health, Keppel Street, London, UK WC1E 7HT. jennifer.evans@lshtm.ac.uk

BACKGROUND: Some observational studies have suggested that people who eat a diet 
rich in antioxidant vitamins (carotenoids, vitamins C and E) or minerals
(selenium and zinc) may be less likely to develop age-related macular
degeneration (AMD). OBJECTIVES: The aim of this review was to examine the
evidence as to whether or not taking vitamin or mineral supplements prevents the 
development of AMD. SEARCH STRATEGY: We searched the Cochrane Central Register of
Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group
Trials Register) in The Cochrane Library (2007, Issue 3), MEDLINE (1966 to August
2007), SIGLE (1980 to 2005/03), EMBASE (1980 to August 2007), National Research
Register (2007, Issue 3), AMED (1985 to January 2006) and PubMed (on 24 January
2006 covering last 60 days), reference lists of identified reports and the
Science Citation Index. We contacted investigators and experts in the field for
details of unpublished studies. SELECTION CRITERIA: We included all randomised
trials comparing an antioxidant vitamin and/or mineral supplement (alone or in
combination) to control. We included only studies where supplementation had been 
given for at least one year. DATA COLLECTION AND ANALYSIS: Both review authors
independently extracted data and assessed trial quality. Data were pooled using a
fixed-effect model. MAIN RESULTS: Three randomised controlled trials were
included in this review (23,099 people randomised). These trials investigated
alpha-tocopherol and beta-carotene supplements. There was no evidence that
antioxidant vitamin supplementation prevented or delayed the onset of AMD. The
pooled risk ratio for any age-related maculopathy (ARM) was 1.04 (95% CI 0.92 to 
1.18), for AMD (late ARM) was 1.03 (95% CI 0.74 to 1.43). Similar results were
seen when the analyses were restricted to beta-carotene and alpha-tocopherol.
AUTHORS' CONCLUSIONS: There is no evidence to date that the general population
should take antioxidant vitamin and mineral supplements to prevent or delay the
onset of AMD. There are several large ongoing trials. People with AMD should see 
the related Cochrane review "Antioxidant vitamin and mineral supplements for
slowing the progression of age-related macular degeneration" written by the same 
author.

Publication Types: 
    Meta-Analysis
    Review

PMID: 18253971 [PubMed - indexed for MEDLINE]

423: Vision Res. 2008 Feb;48(3):494-500.

Familial aggregation of age-related macular degeneration in the Utah population.

Luo L, Harmon J, Yang X, Chen H, Patel S, Mineau G, Yang Z, Constantine R,
Buehler J, Kaminoh Y, Ma X, Wong TY, Zhang M, Zhang K.

Department of Ophthalmology and Visual Sciences, Moran Eye Center, University of 
Utah School of Medicine, Salt Lake City, UT 84132, USA.

We examined familial aggregation and risk of age-related macular degeneration in 
the Utah population using a population-based case-control study. Over one million
unique patient records were searched within the University of Utah Health
Sciences Center and the Utah Population Database (UPDB), identifying 4764
patients with AMD. Specialized kinship analysis software was used to test for
familial aggregation of disease, estimate the magnitude of familial risks, and
identify families at high risk for disease. The population-attributable risk
(PAR) for AMD was calculated to be 0.34. Recurrence risks in relatives indicate
increased relative risks in siblings (2.95), first cousins (1.29), second cousins
(1.13), and parents (5.66) of affected cases. There were 16 extended large
families with AMD identified for potential use in genetic studies. Each family
had five or more living affected members. The familial aggregation of AMD shown
in this study exemplifies the merit of the UPDB and supports recent research
demonstrating significant genetic contribution to disease development and
progression.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18252239 [PubMed - indexed for MEDLINE]

424: Am J Hum Genet. 2008 Feb;82(2):516-23.

Basal laminar drusen caused by compound heterozygous variants in the CFH gene.

Boon CJ, Klevering BJ, Hoyng CB, Zonneveld-Vrieling MN, Nabuurs SB, Blokland E,
Cremers FP, den Hollander AI.

Department of Ophthalmology, Radboud University Nijmegen Medical Centre, 6525 GA 
Nijmegen, The Netherlands.

Age-related macular degeneration (AMD) is a multifactorial disease that is
strongly associated with the Tyr402His variant in the complement factor H (CFH)
gene. Drusen are hallmark lesions of AMD and consist of focal-inflammatory and/or
immune-mediated depositions of extracellular material at the interface of the
retinal pigment epithelium (RPE) and the Bruch membrane. We evaluated the role of
CFH in 30 probands with early-onset drusen and identified heterozygous nonsense, 
missense, and splice variants in five families. The affected individuals all
carried the Tyr402His AMD risk variant on the other allele. This supports an
autosomal-recessive disease model in which individuals who carry a CFH mutation
on one allele and the Tyr402His variant on the other allele develop drusen. Our
findings strongly suggest that monogenic inheritance of CFH variants can result
in basal laminar drusen in young adults, and this can progress to maculopathy and
severe vision loss later in life.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 18252232 [PubMed - indexed for MEDLINE]

425: Cereb Cortex. 2008 Nov;18(11):2483-93. Epub 2008 Feb 3.

V1 projection zone signals in human macular degeneration depend on task, not
stimulus.

Masuda Y, Dumoulin SO, Nakadomari S, Wandell BA.

Psychology, Stanford University, Stanford, CA 94305, USA. massuuu@gmail.com

We used functional magnetic resonance imaging to assess abnormal cortical signals
in humans with juvenile macular degeneration (JMD). These signals have been
interpreted as indicating large-scale cortical reorganization. Subjects viewed a 
stimulus passively or performed a task; the task was either related or unrelated 
to the stimulus. During passive viewing, or while performing tasks unrelated to
the stimulus, there were large unresponsive V1 regions. These regions included
the foveal projection zone, and we refer to them as the lesion projection zone
(LPZ). In 3 JMD subjects, we observed highly significant responses in the LPZ
while they performed stimulus-related judgments. In control subjects, where we
presented the stimulus only within the peripheral visual field, there was no V1
response in the foveal projection zone in any condition. The difference between
JMD and control responses can be explained by hypotheses that have very different
implications for V1 reorganization. In controls retinal afferents carry signals
indicating the presence of a uniform (zero-contrast) region of the visual field. 
Deletion of retinal input may 1) spur the formation of new cortical pathways that
carry task-dependent signals (reorganization), or 2) unmask preexisting
task-dependent cortical signals that ordinarily are suppressed by the deleted
signals (no reorganization).

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18250083 [PubMed - indexed for MEDLINE]

426: Am J Ophthalmol. 2008 Apr;145(4):707-715. Epub 2008 Feb 1.

Alcohol consumption and the risk of age-related macular degeneration: a
systematic review and meta-analysis.

Chong EW, Kreis AJ, Wong TY, Simpson JA, Guymer RH.

Centre for Eye Research Australia, The University of Melbourne, Victoria,
Australia.

PURPOSE: To review systematically the evidence currently available on alcohol
consumption and the risk of age-related macular degeneration (AMD). DESIGN:
Systematic review and meta-analysis of observational studies. METHODS: Seven
databases were searched systematically with no limits on the year or language of 
publication for prospective cohort studies. References identified from pertinent 
reviews and articles also were retrieved. Two reviewers independently searched
the above databases and selected the studies using prespecified standardized
criteria. These criteria included appropriate adjustment for age and smoking in
the analysis. Of the 441 studies identified initially, five cohort studies met
the selection criteria. Data extraction and study quality evaluation were
performed independently by two reviewers and results were pooled quantitatively
using meta-analytic methods. RESULTS: The five cohort studies included 136,946
people, among whom AMD developed in 1923 (1,513 early and 410 late). Pooled
results showed that heavy alcohol consumption was associated with an increased
risk of early AMD (pooled odds ratio, 1.47; 95% confidence interval, 1.10 to
1.95), whereas the association between heavy alcohol consumption and risk of late
AMD was inconclusive. There were insufficient data to evaluate a dose-response
association between alcohol consumption and AMD or the association between
moderate alcohol consumption and AMD. CONCLUSIONS: Heavy alcohol consumption
(more than three standard drinks per day) is associated with an increased risk of
early AMD. Although this association seems to be independent of smoking, residual
confounding effects from smoking cannot be excluded completely.

Publication Types: 
    Meta-Analysis
    Research Support, Non-U.S. Gov't
    Review

PMID: 18242575 [PubMed - indexed for MEDLINE]

427: Mayo Clin Proc. 2008 Feb;83(2):231-4.

Ranibizumab combined with low-dose sorafenib for exudative age-related macular
degeneration.

Diago T, Pulido JS, Molina JR, Collett LC, Link TP, Ryan EH Jr.

Department of Ophthalmology, Mayo Clinic, 200 First St SW, Rochester, MN 55905,
USA.

Angiogenesis is a common factor in the pathogenesis of cancer and in exudative
age-related macular degeneration (AMD). Therefore, angiogenesis inhibition has
been developed as a therapeutic strategy. We report 2 cases of recurrent
exudative AMD in which oral sorafenib, a tyrosine kinase inhibitor approved for
cancer, was added to intravitreal ranibizumab, an antibody to vascular
endothelial growth factor. These 2 patients were followed up by determination of 
visual acuity, fluorescein angiography, fundoscopy, and optical coherence
tomography. The visual acuity of 1 patient improved from 20/70 to 20/60 while he 
was receiving sorafenib therapy; that of the other did not. Marked improvement
was noted in both patients on optical coherence tomography. Additionally, both
patients appeared to receive some benefit when low-dose oral sorafenib was used
as monotherapy after its initial addition to ranibizumab therapy. Randomized
trials of adding sorafenib to standard therapy for patients with neovascular AMD 
should be considered.

Publication Types: 
    Case Reports

PMID: 18241635 [PubMed - indexed for MEDLINE]

428: Clin Hemorheol Microcirc. 2008;38(3):209-16.

Correlations in some pathogenetic factors and values of hemorheological
parameters in age-related macular degeneration.

Michalska-Malecka K, Slowinska L, Dorecka M, Romaniuk W.

The Department and Clinical Ward of Ophthalmology of the Silesian Medical
University, St. Barbara's Hospital in Sosnowiec, Plac Medykow 1, 41-200
Sosnowiec, Poland. Kasia@marat.com.pl

The aim of this study was to correlate some pathogenetic factor with the
hemorheological parameters in ills with age-related macular degeneration. The
studies were performed on 52 patients suffering from AMD. The control group
consisted of 42 healthy persons. Blood samples were taken from patients
immediately after ophthalmological examination from antecubital vein and
anticoagulated with K3EDTA. The symptoms of macular degeneration were drusen;
changes in retinal pigmentation, areolar atrophy, neovascularization. Blood
viscosity measurements were performed with use of cone-plate Brookfield
viscometer at sheer rate 150 s(-1) and plasma viscosity with capillary
Ubbelohde's viscometer. Fibrinogen concentration has been measured according to
Clauss method, and level of triglycerides was measured using coupled enzymatic
reactions. Haematocrit level was measured with the help of micromethod. The
viscosity of whole blood, corrected viscosity and plasma viscosity were
respectively 6.9%, 14.6% and 15.7% higher in the patient group than in the
control group, while fibrinogen-plasma factor was 16% higher. Aggregation
amplitude and time t(1/2) were 89.3% and 28.6% lower in AMD group. Erythrocyte
deformability was 18% lower. The aggregation index was 7.6% higher in the AMD
group then in the control group. Summing up in people suffering from AMD
rheological disturbances is observed increased blood and plasma viscosity.

Publication Types: 
    Historical Article

PMID: 18239263 [PubMed - indexed for MEDLINE]

429: Invest Ophthalmol Vis Sci. 2008 Feb;49(2):758-61.

Influence of intraoperative course on visual outcome after an RPE-choroid
translocation.

Maaijwee K, Missotten T, Mulder P, van Meurs JC.

Department of Vitreoretinal Surgery, Rotterdam Eye Hospital, Rotterdam, The
Netherlands. kmaaijwee@hotmail.com

PURPOSE: In a previous study, preoperative variables were correlated with
postoperative visual outcome after the translocation of a free RPE-choroid graft.
The present study was conducted to investigate whether the intraoperative course 
was an independent factor influencing visual outcome in these patients. METHODS: 
This was a prospective interventional case series of 48 patients with exudative
AMD treated with an RPE-choroid translocation. Preoperative and postoperative
evaluation included ETDRS visual acuity (VA) and fixation testing by a masked
examiner. Four critical surgical steps were evaluated, and the intraoperative
course was graded from 0 (uncomplicated surgery) to 5 (most complicated surgery).
The relationship between intraoperative course adjusted for preoperative
delay/lesion composition and visual outcome at 3 months and 1 year after surgery 
was analyzed with multivariate analysis. RESULTS: The mean VA (logMAR) improved
slightly from 0.99 before surgery to 1.00, 0.94, 0.89, and 0.91 after 3, 6, 9,
and 12 months, respectively. Foveal fixation on the graft was present in 34 (71%)
of the eyes at 1 year after surgery. The intraoperative course was statistically 
significantly associated with the DeltaVA (logMAR) at 3 months (P = 0.037) and at
1 year after surgery (P = 0.020) and if measured as gain or loss of > or =2
ETDRS-lines (odds ratio [OR] 1.8, 95% confidence interval [CI] 1.7 to 2.8, P =
0.027) and > or =3 ETDRS lines (OR, 2.2, 95% CI 1.9-3.5, P = 0.003); better
surgery was associated with visual gain whereas eventful surgery was associated
with visual loss. CONCLUSIONS: The intraoperative course adjusted for
preoperative variables had a statistically significant influence on postoperative
visual outcomes in patients treated with a free RPE-choroid translocation.
Refining the surgery could improve results.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18235025 [PubMed - indexed for MEDLINE]

430: Invest Ophthalmol Vis Sci. 2008 Feb;49(2):693-8.

Interleukin gene polymorphisms in age-related macular degeneration.

Tsai YY, Lin JM, Wan L, Lin HJ, Tsai Y, Lee CC, Tsai CH, Tsai FJ, Tseng SH.

Department of Ophthalmology, China Medical University Hospital, Taichung, Taiwan.

PURPOSE: To investigate polymorphisms in a candidate gene of interleukin (IL) in 
unrelated Taiwan Chinese patients with late age-related macular degeneration
(AMD) and control subjects without AMD. METHODS: In this retrospective,
case-control study, 312 unrelated Taiwan Chinese patients with late AMD and 180
age- and sex-matched control subjects were enrolled. Late AMD was classified as
either atrophic (dry) or neovascular (wet) according to the International ARM
Epidemiologic Study. Genomic DNA was prepared from peripheral blood obtained from
all patients with AMD and control subjects. Polymerase chain reactions were used 
to analyze 14 single-nucleotide polymorphisms (SNPs) in candidate genes of 5 ILs:
IL-1beta(2q14): -511 T/C; IL-6 (7p21): -572 C/G and -596 G/A; IL-8 (4q13-q21):
-251 A/T, +781 C/T, +1633 T/C, and +2767 A/T; IL-10 (1q31-q32): -592 A/C, -819
C/T, and -1082 G/A; and IL-18 (11q22.2-q22.3): +105 A/C, -137 C/G, -607 A/C, and 
-656 T/G. RESULTS: In the 312 patients with late AMD, dry AMD was diagnosed in
136 and wet AMD in 176. Among the 14 SNPs in the 5 IL genes studied, only the
IL-8 +781 C/T SNP was significantly associated with wet AMD (T allele: 46% in wet
AMD versus 28% in the control subjects, P = 1.03 x 10(-6), OR = 2.16, 95% CI =
1.58-2.94). The association analysis based on genotypes at both IL-8 +781 C/T and
the CFH Y402H demonstrated that the IL-8 +781 C/T to AMD was not significant when
analyzed conditional on the presence of the CFH Y402H C risk allele and vice
versa. The IL-8 +781 C/T was in low linkage disequilibrium with CFH Y402H (D' =
0.02). CONCLUSIONS: The data suggest that Taiwan Chinese carriers of the IL-8
+781 T allele, independent of the CFH Y402H polymorphism, are at increased risk
of developing wet AMD.

PMID: 18235016 [PubMed - indexed for MEDLINE]

431: Am J Ophthalmol. 2008 Apr;145(4):716-721. Epub 2008 Jan 28.

Pigment epithelium-derived factor gene Met72Thr polymorphism is associated with
increased risk of wet age-related macular degeneration.

Lin JM, Wan L, Tsai YY, Lin HJ, Tsai Y, Lee CC, Tsai CH, Tseng SH, Tsai FJ.

Department of Ophthalmology, China Medical University Hospital, Taichung, Taiwan.

PURPOSE: To investigate the Met72Thr (T/C) polymorphism (rs1136287) of pigment
epithelium-derived factor (PEDF) gene exon 3 in unrelated Taiwan Chinese patients
with late age-related macular degeneration (AMD) and control subjects without
AMD. DESIGN: Retrospective case-control study. METHODS: We enrolled 190 unrelated
Taiwan Chinese patients with late AMD and 90 age- and gender-matched control
subjects. Grading of late AMD was classified based on a standardized set of
diagnostic criteria established by the International Age-Related Maculopathy
Epidemiologic Study. Late AMD was classified as either atrophic (dry, grade 4) or
neovascular (wet, grade 5). Atrophic AMD refers to dry late-stage AMD without
neovascularization, and wet AMD refers to neovascular AMD. Genomic
deoxyribonucleic acid was prepared from peripheral blood obtained from all AMD
patients and control subjects. Polymerase chain reaction analysis was used to
analyze this polymorphism. RESULTS: Of the 190 participants with late AMD,
atrophic AMD was diagnosed in 104 patients and wet AMD was diagnosed in 86
patients. The genotype distribution of the Met72Thr (T/C) variant of PEDF was TT 
(homozygous T), TC (heterozygous), and CC (homozygous C). The T allele was found 
significantly more frequently in wet AMD patients than in controls (50% vs 31%; P
=.0005). The allele frequencies in atrophic AMD (30%) and controls (31%) did not 
differ significantly (all P = .87). The homozygous T genotype was more prevalent 
in wet AMD than in controls (26/86 [30%] vs nine/90 [10%]; odds ratio, 3.9; all P
= .0015). The homozygous T genotype in atrophic AMD patients (8%) and controls
(10%) did not differ significantly (all P = .75). CONCLUSIONS: Our data suggest
that the PEDF Met72Thr T allele may be a risk factor for wet AMD in the Taiwan
Chinese population. PEDF may play a role in the pathogenesis of wet AMD.

PMID: 18226801 [PubMed - indexed for MEDLINE]

432: Am J Ophthalmol. 2008 Apr;145(4):700-6. Epub 2008 Jan 28.

Clinically significant macular edema and survival in type 1 and type 2 diabetes.

Hirai FE, Knudtson MD, Klein BE, Klein R.

Department of Ophthalmology and Visual Sciences, University of Wisconsin,
Madison, Madison, Wisconsin 53726, USA.

PURPOSE: To investigate the association of clinically significant macular edema
(CSME) and long-term survival in individuals with type 1 and type 2 diabetes.
DESIGN: Population-based cohort study. METHODS: The Wisconsin Epidemiologic Study
of Diabetic Retinopathy (WESDR) is an ongoing prospective population-based cohort
study initiated from August 21, 1980 through July 30, 1982 of individuals with
diabetes diagnosed at either younger than 30 years of age (younger-onset group; n
= 996) or 30 years of age or older (older-onset group; n = 1,370). Stereoscopic
color retinal photographs were graded for retinopathy using the modified Airlie
House classification scheme. CSME was defined by the Early Treatment Diabetic
Retinopathy Study criteria. RESULTS: Prevalence of CSME was 5.9% and 7.5% for the
younger- and older-onset groups, respectively. After 20 years of follow-up, 276
younger-onset and 1,197 older-onset persons died. When adjusting for age and
gender, CSME was not significantly associated with all-cause mortality (hazard
ratio [HR], 1.41; 95% confidence interval [CI], 0.96 to 2.07; P = .08) or
ischemic heart disease mortality (HR, 1.14; 95% CI, 0.61 to 2.12; P = .68) in the
younger-onset group. In the older-onset group, there was increased all-cause and 
ischemic heart disease mortality when CSME was present (HR, 1.55; 95% CI, 1.25 to
1.92; P < .01; and HR, 1.56; 95% CI, 1.15 to 2.13; P < .01, respectively), when
adjusting for age and gender. After controlling for other risk factors, the
association remained significant for ischemic heart disease (HR, 1.58; 95% CI,
1.07 to 2.35; P = .02) among those taking insulin. CSME was not significantly
associated with stroke mortality in either group. CONCLUSIONS: CSME seems to be a
risk indicator for decreased survival in persons with older-onset diabetes
mellitus. The presence of CSME may identify individuals who should be receiving
care for detection and treatment of cardiovascular disease.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 18226797 [PubMed - indexed for MEDLINE]

433: Free Radic Biol Med. 2008 Apr 1;44(7):1348-61. Epub 2008 Jan 28.

Prematurely senescent ARPE-19 cells display features of age-related macular
degeneration.

Glotin AL, Debacq-Chainiaux F, Brossas JY, Faussat AM, Tréton J, Zubielewicz A,
Toussaint O, Mascarelli F.

Centre de Recherche des Cordeliers, Université Pierre et Marie Curie-Paris 6, UMR
S 872, Paris F-75006, France.

The etiology of age-related macular degeneration (AMD), the leading cause of
blindness in the developed world, remains poorly understood, but may be related
to cumulative oxidative stress. The prime target of the disease is the retinal
pigmented epithelium (RPE). To study the molecular mechanisms underlying RPE
degeneration, we investigated whether repetitive oxidative stress induced
premature senescence in RPE cells from the human ARPE-19 cell line. After
exposure to 8 mM tert-butylhydroperoxide (tert-BHP) for 1 h daily for 5 days, the
cells showed four well-known senescence biomarkers: hypertrophy,
senescence-associated beta-galactosidase activity, growth arrest, and cell cycle 
arrest in G1. A specific low-density array followed by qRT-PCR validation allowed
us to identify 36 senescence-associated genes differentially expressed in the
prematurely senescent cells. Functional analysis demonstrated that premature
senescence induced amyloid beta secretion, resistance to acute stress by tert-BHP
and amyloid beta, and defects in adhesion and transepithelial permeability.
Coculture assays with choroidal endothelial cells showed the proangiogenic
properties of the senescent RPE cells. These results demonstrate that chronic
oxidative stress induces premature senescence in RPE cells that modifies the
transcriptome and substantially alters cell processes involved in the
pathophysiology of AMD. Oxidative stress-induced premature senescence may
represent an in vitro model for screening therapeutics against AMD and other
retinal degeneration disorders.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18226607 [PubMed - indexed for MEDLINE]

434: Nat Med. 2008 Feb;14(2):194-8. Epub 2008 Jan 27.

Oxidative damage-induced inflammation initiates age-related macular degeneration.

Hollyfield JG, Bonilha VL, Rayborn ME, Yang X, Shadrach KG, Lu L, Ufret RL,
Salomon RG, Perez VL.

Cole Eye Institute (i31), Department of Ophthalmology, Cleveland Clinic Lerner
College of Medicine, Cleveland, Ohio 44195, USA.

Oxidative damage and inflammation are postulated to be involved in age-related
macular degeneration (AMD). However, the molecular signal(s) linking oxidation to
inflammation in this late-onset disease is unknown. Here we describe AMD-like
lesions in mice after immunization with mouse serum albumin adducted with
carboxyethylpyrrole, a unique oxidation fragment of docosahexaenoic acid that has
previously been found adducting proteins in drusen from AMD donor eye tissues and
in plasma samples from individuals with AMD. Immunized mice develop antibodies to
this hapten, fix complement component-3 in Bruch's membrane, accumulate drusen
below the retinal pigment epithelium during aging, and develop lesions in the
retinal pigment epithelium mimicking geographic atrophy, the blinding end-stage
condition characteristic of the dry form of AMD. We hypothesize that these mice
are sensitized to the generation of carboxyethylpyrrole adducts in the outer
retina, where docosahexaenoic acid is abundant and conditions for oxidative
damage are permissive. This new model provides a platform for dissecting the
molecular pathology of oxidative damage in the outer retina and the immune
response contributing to AMD.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18223656 [PubMed - indexed for MEDLINE]

435: Invest Ophthalmol Vis Sci. 2008 May;49(5):2071-6. Epub 2008 Jan 25.

Association between complement factor H gene polymorphisms and neovascular
age-related macular degeneration in Koreans.

Kim NR, Kang JH, Kwon OW, Lee SJ, Oh JH, Chin HS.

Department of Ophthalmology, Inha University Hospital, 7-206 Shinheung-Dong,
Jung-Gu, Incheon, Korea.

PURPOSE: This study was undertaken to investigate the association between the
complement factor H (CFH) gene and exudative age-related macular degeneration
(AMD) in Korean patients. METHODS: Genomic DNA was isolated from the peripheral
leukocytes of patients with exudative AMD (n = 114) and control subjects (n =
187). The sole criterion for exudative AMD was the presence of choroidal
neovascularization. Four single-nucleotide polymorphisms (SNPs: -275C>T, I62V,
Y402H, and IVS15) located in promoter, exon 2, exon 9, and intron 15 of the CFH
gene were genotyped by PCR-based direct sequencing. RESULTS: The frequency of the
C allele of Y402H (AMD, 10.5%; control, 6.5%) was found to be lower in Koreans
than in Caucasians. In the present study, the difference between the frequencies 
of Y402H in cases and control subjects did not reach statistical significance (P 
= 0.071). However, the frequencies of the major alleles of three SNPs (-275C>T,
I62V, and IVS15) were significantly different in patients and control subjects,
and these SNPs were found to be separately associated with an elevated risk of
exudative AMD. Seven haplotypes were identified in Koreans. Haplotype analysis
showed that two haplotypes (TGTG, CGTG) conferred significantly higher risks of
exudative AMD (P = 0.013, 0.035), and one haplotype (CATA) was significantly
protective (P < 0.001). CONCLUSIONS: In Korean subjects, CFH polymorphism appears
to be a considerable hereditary contributor to exudative AMD. Y402H polymorphism 
which has been suggested to be a major risk factor of AMD in Caucasians was found
to be only marginally associated with exudative AMD with low frequency, whereas
three adjacent SNPs in the CFH gene were significantly associated with AMD in
Koreans.

PMID: 18223247 [PubMed - indexed for MEDLINE]

436: Invest Ophthalmol Vis Sci. 2008 May;49(5):2077-81. Epub 2008 Jan 25.

Foveal cone-photoreceptor integrity in aging macula disorder.

Kanis MJ, Wisse RP, Berendschot TT, van de Kraats J, van Norren D.

Department of Ophthalmology, University Medical Center Utrecht, Utrecht, The
Netherlands. m.j.kanis@umcutrecht.nl

PURPOSE: To establish the relation between AMD stage and a quantitative measure
for the integrity of foveal cone photoreceptors related to the optical
Stiles-Crawford effect. METHODS: Fifty-six AMD eyes and 57 control eyes were
included in the final analysis. AMD was graded in accordance with the
International Classification System into five mutually exclusive stages. Stages 0
to 1 were labeled no AMD, stages 2 to 3 were labeled early AMD, and stage 4 was
labeled late AMD. Fundus reflectometry, together with a model-fit procedure,
provided information on directional cone reflectance (Rd), a quantitative measure
for the integrity of foveal cone photoreceptors. Optical densities of macular
pigment (MPOD) and melanin (MOD) were also obtained. A general linear model
analysis was used to compare Rd, MPOD, and MOD among the AMD stages. RESULTS:
Mean Rd was lower in early AMD (0.92%, P < 0.001) and late AMD (0.86%, P < 0.001)
compared with mean Rd in the no-AMD stage (1.76%). Mean MPOD was not different in
early AMD (0.53, P = 0.05), but it was lower in late AMD (0.19, P < 0.001)
compared with mean MPOD in the no-AMD stage (0.42). Mean MOD was lower in early
(1.09, P = 0.001) and late (1.01, P = 0.004) AMD compared with mean MOD in the
no-AMD stage (1.23). CONCLUSIONS: Foveal cones show signs of misalignment and/or 
outer segment deterioration in early AMD. Melanin rather than macular pigment may
play a protective role against AMD, although loss of these ocular pigments can
also be caused by AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18223244 [PubMed - indexed for MEDLINE]

437: Am J Ophthalmol. 2008 Feb;145(2):308-16.

Cardiovascular risk factors and age-related macular degeneration: the Los Angeles
Latino Eye Study.

Fraser-Bell S, Wu J, Klein R, Azen SP, Hooper C, Foong AW, Varma R.

Department of Preventive Medicine, Keck School of Medicine, University of
Southern California, Los Angeles, CA, USA.

PURPOSE: To assess the association of cardiovascular risk factors and ocular
perfusion pressure with early and advanced age-related macular degeneration (AMD)
in Latinos. DESIGN: Population-based, cross-sectional study. METHODS: Data were
collected from a population-based sample of self-identified adult Latinos using
standardized protocols for assessing blood pressure and intraocular pressure
(IOP) measurement and stereoscopic macular photography. Hypertension was defined 
as either a history of hypertension or systolic blood pressure (SBP) > 140 mm Hg 
+/- diastolic blood pressure (DBP) > or = 85 mm Hg. Ocular perfusion pressure
(OPP) was defined as the difference between mean arterial blood pressure and IOP.
AMD was diagnosed from photographic grading by masked trained graders. Logistic
regression was used to assess associations. RESULTS: Gradable retinal photographs
were available in 5,875 participants. After adjusting for age, gender, and
cigarette smoking, higher DBP and uncontrolled diastolic hypertension were
associated with exudative AMD (odds ratio [OR], 1.8; 95% confidence interval
[CI], 1.1 to 2.8; and OR, 3.3; CI, 1.2 to 9.3, respectively). Higher OPP was
associated with a decreased risk of geographic atrophy (GA) (OR, 0.4 per 10 mm
Hg; CI, 0.3 to 0.5). Low pulse pressure was associated with a lower risk of
exudative AMD (OR, 0.2; CI, 0.1 to 0.6). Obesity was associated with increased
retinal pigment (OR, 1.6; CI, 1.0 to 2.3). CONCLUSIONS: These data suggest that
in Latinos cardiovascular risk factors may play a role in advanced AMD. Given
that Latinos have a high prevalence of cardiovascular risk factors, an
intervention aimed at reducing these risk factors may also have a beneficial
impact on the risk of having early and advanced AMD.

PMID: 18222193 [PubMed - indexed for MEDLINE]

438: Am J Ophthalmol. 2008 Feb;145(2):239-248.

Randomized, double-masked, sham-controlled trial of ranibizumab for neovascular
age-related macular degeneration: PIER Study year 1.

Regillo CD, Brown DM, Abraham P, Yue H, Ianchulev T, Schneider S, Shams N.

Retina Service, Wills Eye Institute, 840 Walnut Street, Philadelphia, PA 19107,
USA. cregillo@aol.com

PURPOSE: To evaluate the efficacy and safety of ranibizumab administered monthly 
for three months and then quarterly in patients with subfoveal choroidal
neovascularization (CNV) secondary to age-related macular degeneration (AMD).
DESIGN: Phase IIIb, multicenter, randomized, double-masked, sham
injection-controlled trial in patients with predominantly or minimally classic or
occult with no classic CNV lesions. METHODS: Patients were randomized 1:1:1 to
0.3 mg ranibizumab (n = 60), 0.5 mg ranibizumab (n = 61), or sham (n = 63)
treatment groups. The primary efficacy endpoint was mean change from baseline
visual acuity (VA) at month 12. RESULTS: Mean changes from baseline VA at 12
months were -16.3, -1.6, and -0.2 letters for the sham, 0.3 mg, and 0.5 mg
groups, respectively (P < or = .0001, each ranibizumab dose vs sham). Ranibizumab
arrested CNV growth and reduced leakage from CNV. However, the treatment effect
declined in the ranibizumab groups during quarterly dosing (e.g., at three months
the mean changes from baseline VA had been gains of 2.9 and 4.3 letters for the
0.3 mg and 0.5 mg doses, respectively). Results of subgroups analyses of mean
change from baseline VA at 12 months by baseline age, VA, and lesion
characteristics were consistent with the overall results. Few serious ocular or
nonocular adverse events occurred in any group. CONCLUSIONS: Ranibizumab
administered monthly for three months and then quarterly provided significant VA 
benefit to patients with AMD-related subfoveal CNV and was well tolerated. The
incidence of serious ocular or nonocular adverse events was low.

Publication Types: 
    Clinical Trial, Phase III
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18222192 [PubMed - indexed for MEDLINE]

439: Ophthalmology. 2008 Aug;115(8):1376-81, 1381.e1-2. Epub 2008 Jan 25.

Prevalence and risk factors for age-related macular degeneration in an adult
Japanese population: the Funagata study.

Kawasaki R, Wang JJ, Ji GJ, Taylor B, Oizumi T, Daimon M, Kato T, Kawata S,
Kayama T, Tano Y, Mitchell P, Yamashita H, Wong TY.

Yamagata University Faculty of Medicine, Yamagata, Japan.
ryok@med.id.yamagata-u.ac.jp

OBJECTIVE: To describe the prevalence and risk factors for age-related macular
degeneration (AMD) in a Japanese population and to compare these with data from a
white population. DESIGN: Population-based cross-sectional epidemiologic study.
PARTICIPANTS: A population-based sample of Japanese persons 35 years or older
from Funagata, Japan. METHODS: The Funagata study is a population-based study of 
1758 (43% of eligible) Japanese persons 35 years or older from Funagata, Japan.
In 2000 to 2002, 1625 (92.4%) participants had a nonmydriatic fundus photograph
of one eye with sufficient quality for grading of AMD lesions, using the
Wisconsin protocol. Age-standardized prevalence rates compared with the Blue
Mountains Eye Study (BMES) population, odds ratios (ORs), and 95% confidence
intervals (CIs) were calculated. Risk factors were assessed by logistic
regression. MAIN OUTCOME MEASURES: Early and late AMD. RESULTS: Of 1625
participants, early AMD and late AMD were present in 3.5% and 0.5%, respectively.
Age-standardized early AMD prevalence in right eyes was 4.1%, similar to the
corresponding prevalence of 4.4% in the BMES. For men, age-standardized
prevalences of late AMD in right eyes were 1.1% and 1.2% in the BMES; for women, 
the corresponding prevalences were 0.3% and 2.1%, respectively. Increasing age
(per 10 years; gender-adjusted OR, 2.27; 95% CI, 1.10-4.67) and current cigarette
smoking (age- and gender-adjusted OR, 5.03; 95% CI, 1.00-25.47) were associated
with late AMD. CONCLUSIONS: In this Japanese population, prevalence of early AMD 
was similar to that for whites in the BMES. Although the late AMD prevalence was 
lower in Japanese women, in Japanese men it was similar to that in whites. This
could have resulted from the substantially high proportion of Japanese men who
are smokers. Cigarette smoking and increasing age were the 2 principal factors
found associated with late AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18222000 [PubMed - indexed for MEDLINE]

440: Curr Diabetes Rev. 2006 Feb;2(1):99-112.

Intravitreal triamcinolone for the treatment of diabetic macular edema.

Gómez-Ulla F, Marticorena J, Alfaro DV 3rd, Fernández M, Méndez ER, Rothen M.

Ophthalmology Service, Complejo Hospitalario Universitario de Santiago de
Compostela, Spain. ciulla@usc.es

Diabetic macular edema is one of the leading causes of visual loss in first world
countries and the first cause in diabetic retinopathy. The Early Treatment
Diabetic Retinopathy Study showed a significant benefit in using focal laser
photocoagulation for the treatment of macular edema, more specifically defined as
clinically significant macular edema. Nevertheless, progressive visual loss is
found in the 26% of patients with diabetic macular edema treated with
photocoagulation. The failure of laser treatment and the destructive nature of
the therapy has forced researchers to pursue new alternatives including
vitrectomy with or without internal limiting membrane peels, the use of
proteinkinase C inhibitors, intravitreal injections of antibodies that inhibit
the vascular endothelial growth factor, somatostatin analog, or the intravitreal 
injection with corticosteroids. Triamcinolone acetonide is glucocoticosteroid
with antiangiogenic and antiedematous properties. Publications evaluating the
safety and efficacy of intravitreal injection of triamcinolone in the treatment
of diabetic macular edema show varying outcomes with respect to the increases of 
visual acuity and decreases in foveal thickness. Despite this, intravitreal
triamcinolone is a treatment that has evolved quickly and is considered
increasingly useful.

Publication Types: 
    Review

PMID: 18220620 [PubMed - indexed for MEDLINE]

441: Expert Opin Pharmacother. 2008 Feb;9(3):499-508.

Pegaptanib sodium for the treatment of age-related macular degeneration.

Apte RS.

Department of Ophthalmology & Visual Sciences, Barnes Retina Institute, St Louis 
School of Medicine, Washington University, 660 S. Euclid Avenue, PO Box 8096, St 
Louis, MO 63110, USA. Apte@vision.wustl.edu

BACKGROUND: Pegaptanib sodium, the first aptamer therapeutic approved for use and
the first antiangiogenic agent used to treat ocular neovascular disease, acts by 
inhibiting the 165 isoform of vascular endothelial growth factor believed
primarily responsible for pathologic ocular neovascularization and vascular
permeability. OBJECTIVE: To briefly present the pharmacology, clinical efficacy
and safety, and role of pegaptanib in treating ocular neovascular diseases.
METHODS: A systematic literature review and synopsis. RESULTS/CONCLUSION: After
more than 10 years in development, clinical trials have shown pegaptanib efficacy
in treating choroidal neovascularization of age-related macular degeneration. Its
excellent ocular and systemic safety profiles have been confirmed in up to 3
years of experience. Early phase, well-controlled studies also suggest
therapeutic benefit in diabetic retinopathy and retinal vein occlusion.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18220500 [PubMed - indexed for MEDLINE]

442: J Am Soc Nephrol. 2008 Apr;19(4):806-11. Epub 2008 Jan 23.

CKD increases the risk of age-related macular degeneration.

Liew G, Mitchell P, Wong TY, Iyengar SK, Wang JJ.

Centre for Vision Research, Department of Ophthalmology, University of Sydney,
Westmead Hospital, Hawkesbury Road, Westmead, NSW Australia.

Age-related macular degeneration is the leading cause of irreversible blindness
in the United States and often coexists with chronic kidney disease. Both
conditions share common genetic and environmental risk factors. A total of 1183
participants aged 54+ were examined in the population-based, prospective cohort
Blue Mountains Eye Study (Australia) to determine if chronic kidney disease
increases the risk of age-related macular degeneration. Moderate chronic kidney
disease (estimated glomerular filtration rate < 60 ml/min per 1.73 m(2) based on 
the Cockcroft-Gault equation) was present in 24% of the population (286 of 1183).
The 5-yr incidence of early age-related macular degeneration was 3.9% in
participants with no/mild chronic kidney disease (35 of 897) and 17.5% in those
with moderate chronic kidney disease (50 of 286). After adjusting for age, sex,
cigarette smoking, hypertension, complement factor H polymorphism, and other risk
factors, persons with moderate chronic kidney disease were 3 times more likely to
develop early age-related macular degeneration than persons with no/mild chronic 
kidney disease (odds ratio = 3.2; 95% confidence interval, 1.8 to 5.7, P <
0.0001). Each SD (14.8 ml/min per 1.73 m(2)) decrease in Cockcroft-Gault
estimated glomerular filtration rate was associated with a doubling of the
adjusted risk for early age-related macular degeneration (odds ratio = 2.0; 95%
confidence interval, 1.5 to 2.8, P < 0.0001). In conclusion, persons with chronic
kidney disease have a higher risk of early age-related macular degeneration,
suggesting the possibility of shared pathophysiologic mechanisms between the two 
conditions.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18216312 [PubMed - indexed for MEDLINE]

443: Semin Ophthalmol. 2008 Jan-Feb;23(1):59-65.

Stargardt's disease and the ABCR gene.

Westerfeld C, Mukai S.

Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114,
USA. corey_westerfeld@meei.harvard.edu

Stargardt's disease is an autosomal recessive form of juvenile macular
degeneration. The clinical presentation, relevant ancillary tests, and classic
histologic features will be reviewed. The role of genetic mutations in the
pathophysiology of Stargardt's disease will also be explored. Stargardt's disease
is caused by mutations in the ABCR (ABCA4) gene on chromosome 1. Mutations in
this gene have also been attributed to some cases of cone-rod dystrophy,
retinitis pigmentosa, and age-related macular degeneration. The genetic and
molecular pathways that produce Stargardt's disease will be discussed. Future
diagnostic and therapeutic objectives for this visually disabling condition will 
also be presented.

Publication Types: 
    Review

PMID: 18214793 [PubMed - indexed for MEDLINE]

444: Br J Ophthalmol. 2008 Apr;92(4):518-22. Epub 2008 Jan 22.

Intravitreal Avastin for macular oedema secondary to retinal vein occlusion: a
prospective study.

Kriechbaum K, Michels S, Prager F, Georgopoulos M, Funk M, Geitzenauer W,
Schmidt-Erfurth U.

University Eye Hospital Zürich, Frauenklinikstrasse 24, CH-8091 Zurich,
Switzerland.

OBJECTIVE: To evaluate efficacy and safety of intravitreal bevacizumab (Avastin) 
in eyes with macular oedema secondary to central retinal vein occlusion (CRVO) or
branch retinal vein occlusion (BRVO). METHODS: Twenty-eight consecutive patients 
(28 patients, 29 eyes, 8 CRVO, 21 BRVO) were enrolled in the study. Three
intravitreal injections of 1 mg bevacizumab (0.04 ml) were administered at 4-week
intervals; further retreatment was based on optical coherence tomography (OCT)
findings. Follow-up examinations were done at days 1, 7 and 28 and at monthly
intervals thereafter. RESULTS: Mean baseline central retinal thickness (CRT) in
OCT was 558 microm (range 353-928 microm) and mean BCVA was 20/100. One day after
the first injection, CRT significantly decreased to 401 microm (p<0.01). Three
injections reduced macular oedema to 328 microm CRT (p<0.01) and improved BCVA to
20/50 (p<0.01). At 6 months, CRT was 382 microm (p<0.01), and BCVA was stable at 
20/50(-2) (p<0.01), FA showed no evidence of increased avascular zones.
CONCLUSION: Intravitreal injections of bevacizumab appear to be a safe and
effective therapy in the treatment of macular oedema secondary to retinal vein
occlusion.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 18211942 [PubMed - indexed for MEDLINE]

445: Br J Ophthalmol. 2008 Mar;92(3):351-5. Epub 2008 Jan 22.

Intravitreal bevacizumab for the treatment of macular oedema secondary to branch 
retinal vein occlusion.

Kreutzer TC, Alge CS, Wolf AH, Kook D, Burger J, Strauss R, Kunze C, Haritoglou
C, Kampik A, Priglinger S.

Department of Ophthalmology, Ludwig-Maximilians-University, Munich, Mathildenstr 
8, 80336 Munich, Germany.

PURPOSE: To evaluate the effect of intravitreal bevacizumab (Avastin) injections 
on visual acuity (VA) and foveal retinal thickness in patients with macular
oedema secondary to branch retinal vein occlusion. METHODS: A prospective,
non-comparative, consecutive, interventional case series of 34 patients. Patients
received repeated intravitreal injections of 1.25 mg bevacizumab. Main outcome
measures were VA (Snellen charts and ETDRS) and retinal thickness (optical
coherence tomography measurements) in a follow-up period of 6 months. RESULTS:
Patients presented at a mean age of 69 years (range 44-86). Mean duration of
symptoms was 40 weeks (range 1-300). Mean (SD) VA at baseline was 0.79 (0.39)
logMAR, improving to 0.51 (0.34) logMAR at 6 months (p = 0.009). Mean number of
letters on the ETDRS chart at baseline was 45.3 (19.0), improving to 60.6 (19.9) 
at 6 months (p = 0.003). Mean (SD) retinal thickness at baseline was 474 (120)
microm, declining to 316 (41) microm at 6 months. CONCLUSION: Intravitreal
injection of 1.25 mg bevacizumb appears to be an effective treatment option for
branch retinal vein occlusion.

Publication Types: 
    Clinical Trial

PMID: 18211925 [PubMed - indexed for MEDLINE]

446: Br J Ophthalmol. 2008 Apr;92(4):513-7. Epub 2008 Jan 22.

Genotype-phenotype correlation of age-related macular degeneration: influence of 
complement factor H polymorphism.

Droz I, Mantel I, Ambresin A, Faouzi M, Schorderet DF, Munier FL.

University Eye Hospital Jules Gonin, 15, Av. de France - Case postale 133, CH -
1000 Lausanne 7, Switzerland.

BACKGROUND/AIMS: Complement factor H (CFH) Y402H polymorphism shows a strong
association with age-related macular degeneration (AMD). Although the phenotypic 
concordance of AMD has been shown in sibling/twin studies, little is known about 
the genotype-phenotype association. In this study, we investigated whether CFH
Y402H is associated with early phenotypic features. METHODS: Statistical analysis
was performed on 420 patients with AMD with complete clinical and genetic data
(graded colour fundus photographs, according to the International Classification 
and Grading System for AMD and successful testing for CFH Y402H). RESULTS: In
this Swiss population, an OR of 2.95 was confirmed for AMD in the presence of at 
least one risk C allele and OR of 9.05 for the CC homozygotes, corrected for age 
and sex. No difference was found between the AMD stages. Patients homozygous for 
the risk allele showed significant association with peripheral drusen (p = 0.028)
and for central drusen location (p = 0.049). No trend was found for other drusen 
criteria (size, total surface, location nasal to disc) and for pigmentary
changes. CONCLUSIONS: The CFH Y402H polymorphism showed a genotype-phenotype
association for some drusen features. Additional genetic factors are likely to
influence drusen phenotype.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18211923 [PubMed - indexed for MEDLINE]

447: In Vivo. 2007 Nov-Dec;21(6):1049-52.

Photodynamic therapy versus thermal laser photocoagulation for the treatment of
recurrent choroidal neovascularization due to AMD.

Kallitsis A, Moschos MM, Ladas ID.

First Department of Ophthalmology, Medical School of Athens University, Athens,
Greece.

The aim of this study was to compare the effectiveness of thermal laser
photocoagulation (TLP) to that of photodynamic therapy (PDT) for the treatment of
recurrent choroidal neovascularization (CNV) in patients with age-related macular
degeneration (AMD). PATIENTS AND METHODS: We prospectively studied 38 patients
(40 eyes) with AMD presented with recurrent CNV after TLP. The study eyes were
assigned to one of the two groups according to their treatment (repetition of TLP
or PDT). PDT was performed according to the standard protocol. The follow-up time
ranged from 9 months to 9 years. RESULTS: The mean best-corrected visual acuity
(VA) was statistically significantly lower compared to that of the baseline in
both groups of the study. There were no statistically significant differences
between the two groups with regard to the stabilization, improvement or decline
of the best-corrected VA. CONCLUSION: According to our results TLP and PDT are
equally ineffective for the treatment of recurrent CNV in patients with AMD.

PMID: 18210754 [PubMed - indexed for MEDLINE]

448: Clinics. 2007 Dec;62(6):721-4.

Consistency of ocular coherence tomography fast macular thickness mapping in
diabetic diffuse macular edema.

Saraiva FP, Costa PG, Inomata DL, Melo CS, Helal Júnior J, Nakashima Y.

Departament of Ophthalmology, Hospital das Clínicas, Faculdade de Medicina,
Universidade de São Paulo, São Paulo, SP, Brazil. fabiopetersen@yahoo.com.br

OBJECTIVES: To investigate optical coherence tomography consistency on foveal
thickness, foveal volume, and macular volume measurements in patients with and
without diffuse diabetic macular edema. INTRODUCTION: Optical coherence
tomography represents an objective technique that provides cross-sectional
tomographs of retinal structure in vivo. However, it is expected that poor
fixation ability, as seen in diabetic macular edema, could alter its results.
Several authors have discussed the reproducibility of optical coherence
tomography, but only a few have addressed the topic with respect to diabetic
maculopathy. METHODS: The study recruited diabetic patients without clinically
evident retinopathy (control group) and with diffuse macular edema (case group). 
Only one eye of each patient was evaluated. Five consecutive fast macular scans
were taken using Ocular Coherence Tomography 3; the 6 mm macular map was chosen. 
The consistency in measurements of foveal thickness, foveal volume, and total
macular volume for both groups was evaluated using the Pearson's coefficient of
variation. The T-test for independent samples was used in order to compare
measurements of both groups. RESULTS: Each group consisted of 20 patients. All
measurements had a coefficient of variation less than 10%. The most consistent
parameter for both groups was the total macular volume. DISCUSSION: Consistency
in measurement is a mainstay of any test. A test is unreliable if its
measurements can not be correctly repeated. We found a good index of consistency,
even considering patients with an unstable gaze. CONCLUSIONS: Optical coherence
tomography is a consistent method for diabetic subjects with diffuse macular
edema.

PMID: 18209914 [PubMed - indexed for MEDLINE]

449: Vision Res. 2008 Feb;48(5):685-9. Epub 2008 Jan 22.

Further mapping of 10q26 supports strong association of HTRA1 polymorphisms with 
age-related macular degeneration.

Gibbs D, Yang Z, Constantine R, Ma X, Camp NJ, Yang X, Chen H, Jorgenson A, Hau
V, Dewan A, Zeng J, Harmon J, Buehler J, Brand JM, Hoh J, Cameron DJ, Dixit M,
Tong Z, Zhang K.

Department of Ophthalmology and Visual Science, Moran Eye Center, Building 533,
Room 3160A, 15 North 2030 East, Salt Lake City, UT 84132, USA.

Age-related macular degeneration (AMD) is a complex disorder with genetic and
environmental influences. The genetic influences affecting AMD are not well
understood and few genes have been consistently implicated and replicated for
this disease. A polymorphism (rs11200638) in a transcription factor binding site 
of the HTRA1 gene has been described, in previous reports, as being most
significantly associated with AMD. In this paper, we investigate haplotype
association and individual polymorphic association by genotyping additional
variants in the AMD risk-associated region of chromosome 10q26. We demonstrate
that rs11200638 in the promoter region and rs2293870 in exon 1 of HTRA1, are
among the most significantly associated variants for advanced forms of AMD.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18207215 [PubMed - indexed for MEDLINE]

450: Vision Res. 2008 Feb;48(5):690-4.

Association of HTRA1 polymorphism and bilaterality in advanced age-related
macular degeneration.

Chen H, Yang Z, Gibbs D, Yang X, Hau V, Zhao P, Ma X, Zeng J, Luo L, Pearson E,
Constantine R, Kaminoh Y, Harmon J, Tong Z, Stratton CA, Cameron DJ, Tang S,
Zhang K.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen
University, Guangzhou, China.

Single nucleotide polymorphism (SNP), rs11200638, in the promoter of HTRA1 has
recently been shown to increase the risk for AMD. In order to investigate the
association of this HTRA1 polymorphism and the bilaterality of AMD, we genotyped 
rs11200638 in control, unilateral, and bilateral advanced AMD patients. The A
allele for SNP rs11200638 in HTRA1, was significantly more prevalent in bilateral
wet AMD and GA patients than in unilateral groups (p=.02 and p=.03,
respectively). The homozygote odds ratios of bilateral wet AMD and GA are
significantly greater than those seen in unilateral groups (twofold and threefold
increase, respectively). This finding is consistent with the role of HTRA1 in AMD
pathogenesis and will help aid in the clinical management and prognosis of AMD
patients.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18206206 [PubMed - indexed for MEDLINE]

451: Hum Mol Genet. 2008 May 1;17(9):1299-305. Epub 2008 Jan 18.

Gene-environment interaction in progression of AMD: the CFH gene, smoking and
exposure to chronic infection.

Baird PN, Robman LD, Richardson AJ, Dimitrov PN, Tikellis G, McCarty CA, Guymer
RH.

Centre for Eye Research Australia, University of Melbourne, 32 Gisborne Street,
East Melbourne, VIC 3002, Australia. pnb@unimelb.edu.au

A number of risk factors including the complement factor H (CFH) gene, smoking
and Chlamydia pneumoniae have been associated with age-related macular
degeneration (AMD). However, the mechanisms underlying how these risk factors
might be involved in disease progression and disease aetiology is poorly
understood. A cohort series of 233 individuals followed for AMD progression over 
a mean period of 7 years underwent a full eye examination, blood was taken for
DNA and antibody titre and individuals completed a standard medical and general
questionnaire. Y402H variants of the CFH gene were assessed with disease
progression as well as examination of interaction between Y402H variants and
smoking and Y402H variants and the pathogen C. pneumoniae. The CC risk genotype
of Y402H was significantly associated with increased AMD progression [odds ratio 
(OR) 2.43, 95% confidence interval (95% CI) 1.07-5.49] as was smoking (OR 2.28,
95% CI 1.26-4.12). However, the risk of progression was greatly increased to
almost 12-fold (OR 11.8, 95% CI 2.1-65.8) when, in addition to having the C risk 
allele, subjects also presented with the upper tertile of antibodies to the
bacterial pathogen C. pneumoniae compared with those with the T allele of Y402H
and the lowest antibody tertile. This demonstrates for the first time the
existence of a gene environment-interaction between pathogenic load of C.
pneumoniae and the CFH gene in the aetiology of AMD.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 18203751 [PubMed - indexed for MEDLINE]

452: Eur J Ophthalmol. 2008 Jan-Feb;18(1):138-41.

Intravitreal pegaptanib sodium for Irvine-Gass syndrome.

Querques G, Iaculli C, Delle Noci N.

Department of Ophthalmology, Policlinico Riuniti di Foggia, University of Foggia,
Foggia, Italy. giuseppe.querques@hotmail.it

PURPOSE: To report the novel use of intravitreal pegaptanib sodium for the
treatment of refractory cystoid macular edema (CME) following cataract
extraction. METHODS: A 72-year-old man presented with decreased visual acuity in 
his right eye 8 months after uncomplicated phacoemulsification cataract
extraction and intraocular lens implantation. His bestcorrected visual acuity
(BCVA) was 20/125 in the affected eye, and fundus examination revealed CME
despite 6 months of oral and topical indomethacin therapy. Fluorescein
angiography (FA) showed leakage in the central region with no signs of
neovascularization, and optical coherence tomography (OCT) confirmed the
diagnosis with thickening of the fovea. Because of his history of glaucoma, the
patient chose to be treated with intravitreal pegaptanib sodium 0.3 mg. RESULTS: 
At the 1-week follow-up, BCVA was 20/25, and the FA and OCT revealed almost total
resolution of the CME with no adverse sequelae. Six months postinjection, the
patient's BCVA remained 20/25 with no recurrence of CME. Perimetry revealed a
stable fixation within 4 degrees with slight reduction of sensitivity.
CONCLUSIONS: Vascular endothelial growth factor inhibition with intravitreal
pegaptanib sodium appears to be of benefit in the treatment of chronic refractory
CME with improvement of visual acuity. Studies evaluating pegaptanib''s use in
this setting with long-term follow-up are warranted to confirm its efficacy and
safety.

Publication Types: 
    Case Reports

PMID: 18203101 [PubMed - indexed for MEDLINE]

453: Eur J Ophthalmol. 2008 Jan-Feb;18(1):99-103.

Octreotide acetate in dominant cystoid macular dystrophy.

Hogewind BF, Pieters G, Hoyng CB.

University Medical Centre St Radboud, Nijmegen, Gelderland, The Netherlands.
b.hogewind@ohk.umcn.nl

PURPOSE: Dominant cystoid macular degeneration (DCMD) is an autosomal dominant
trait of cystoid macular edema with poor visual prognosis. Until now, no
efficient treatments for DCMD have been reported. The authors evaluated a
somatostatin-analogue (octreotide acetate) as treatment for DCMD. METHODS: The
authors treated four patients with early DCMD by intramuscular longacting
octreotide acetate, 20 mg every 4 weeks for 1 year. In addition to general
ophthalmologic examination the authors performed fluorescein angiography (FA)
before and after treatment. RESULTS: Seven out of eight eyes showed improvement
on FA and stabilization of visual acuity. CONCLUSIONS: Somatostatin-analogues may
reduce cystoid edema in DCMD and may thus prevent disease-related visual loss.

PMID: 18203093 [PubMed - indexed for MEDLINE]

454: J Ocul Pharmacol Ther. 2008 Feb;24(1):15-24.

Intravitreal bevacizumab and triamcinolone acetonide combination therapy for
exudative neovascular age-related macular degeneration: short-term optical
coherence tomography results.

Colucciello M.

Retina Department, South Jersey Eye Physicians, Moorestown, NJ 08057, USA.
michael@macula.us

PURPOSE: The aim of this study to describe the short-term anatomical results
after an intravitreal injection of bevacizumab and triamcinolone acetonide in
patients with foveal edema and/or subfoveal fluid associated with
neovascularization (NV) due to age-related macular degeneration (AMD). METHODS: A
retrospective, noncomparative case series was conducted in patients with foveal
edema and/or subfoveal fluid associated with NV due to AMD during a 3-month
period. Patients were treated with intravitreal injections of bevacizumab (1.25
mg/0.05 mL) and followed immediately with triamcinolone acetonide (2 mg/ 0.05 mL)
in separate syringes. Ophthalmoscopic examination with optical coherence
tomography analysis of foveal edema and subfoveal fluid volume was performed at
baseline and follow-up visits. RESULTS: There were 30 consecutive eyes of 27
patients who received a short-term follow-up between 1 and 8 weeks after
injection. Foveal thickness and subfoveal fluid volume were each statistically
significantly reduced in the short term (paired Student t test; P < 0.01). No
complications of intraocular pressure greater than 30 mmHg, endophthalmitis,
retinal detachment, or vitreous hemorrhage developed. CONCLUSIONS: Reduction of
foveal edema and subfoveal fluid in patients with NV due to AMD suggests that
combination treatment with intravitreal bevacizumab and triamcinolone merits
further investigation.

PMID: 18201136 [PubMed - indexed for MEDLINE]

455: Arch Ophthalmol. 2008 Jan;126(1):115-21.

Further observations on the association between smoking and the long-term
incidence and progression of age-related macular degeneration: the Beaver Dam Eye
Study.

Klein R, Knudtson MD, Cruickshanks KJ, Klein BE.

Department of Ophthalmology and Visual Sciences, University of Wisconsin, 417
WARF, Madison, WI 53726-2336, USA. kleinr@epi.ophth.wisc.edu

OBJECTIVE: To examine the association between smoking and the 15-year cumulative 
incidence of age-related macular degeneration (AMD). METHODS: Population-based
longitudinal cohort study of people in Beaver Dam, Wisconsin, who were aged 43 to
84 years (N = 4926) in 1987-1988. Participants were examined in 1988-1990 and
were reexamined at 5-year intervals during a 15-year period. Age-related macular 
degeneration status was determined by grading stereoscopic color fundus
photographs. RESULTS: Controlling for age, sex, and baseline AMD severity, people
who were current smokers at baseline, compared with those who never smoked, were 
at increased risk of incident early AMD (odds ratio, 1.47; 95% confidence
interval, 1.08-1.99; P = .01) and for progression of AMD (odds ratio, 1.43; 95%
confidence interval, 1.05-1.94; P = .02) during a 15-year follow-up. There were
few associations of specific characteristics of smoking (eg, intensity,
pack-years smoked, duration, and age at initiation and quitting) with AMD
outcomes. CONCLUSIONS: Smoking appears to be related to the long-term incidence
and progression of AMD. This has important health care implications because early
AMD increases the risk of developing late AMD and smoking behavior is modifiable.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18195228 [PubMed - indexed for MEDLINE]

456: Arch Ophthalmol. 2008 Jan;126(1):45-50.

Results and repeatability of retinal thickness measurements from certification
submissions.

Danis RP, Fisher MR, Lambert E, Goulding A, Wu D, Lee LY.

Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison,
Madison, WI 53711, USA. rdanis@rc.ophth.wisc.edu

OBJECTIVES: To present the results for subgroups defined by center point (CP)
measurement and to assess the repeatability of the Fast Retinal Thickness Map
analysis results from the Stratus OCT3 machine. METHODS: Two hundred eighty-one
replicate OCT3 scans from 134 operators' certification submissions to a reading
center were analyzed, including scans from eyes that were reported to be normal
and eyes with exudative age-related macular degeneration and with macular edema
due to diabetic retinopathy or retinal vascular occlusion. RESULTS: The mean (SD)
of the CP was 284 (150) microm and the center subfield (CC) was 301 (130) microm.
The CP coefficient of repeatability (CR) was 49 microm and the CC CR was 27
microm. The CR increased by increasing retinal thickness for the CP and the CC
within arbitrarily defined subgroups. For the 87 eyes with a session 1 CP of 175 
microm or less, the CP CR was 17 microm and the CC CR was 10 microm. CONCLUSIONS:
Among experienced operators, given the same operator, machine, and eye at the
same sitting, OCT3 retinal thickness maps appear to have a CR that is likely to
be less than the clinically important difference.

PMID: 18195217 [PubMed - indexed for MEDLINE]

457: Graefes Arch Clin Exp Ophthalmol. 2008 Mar;246(3):457-8. Epub 2008 Jan 12.

Intravitreal triamcinolone for macular edema in Lyme disease.

Reibaldi M, Faro S, Motta L, Longo A.

Eye Clinic, University of Catania, via Santa Sofia 78, Catania, Italy.

BACKGROUND: To describe the outcome in a patient with macular edema caused by
Lyme disease treated with injection of 4 mg intravitreal triamcinolone. METHODS: 
The patient, 2 years after systemic Lyme disease treated with doxycycline for 4
weeks, developed macular edema with serous retinal detachment in one eye (visual 
acuity: 0.6). After unsuccessful therapy with intravenous ceftriaxone,
indomethacin and acetazolamide, 4 mg intravitreal triamcinolone (IVTA) was
injected via the pars plana. RESULTS: Visual acuity improved to 1.0 and macular
thickness recovered over 1 month. No changes were found in intraocular pressure. 
No recurrence of macular edema was seen after 2 years. CONCLUSIONS: IVTA can
restore visual acuity and reduce macular thickness in macular edema caused by
Lyme disease. However, since borreliosis is a systemic disease, previous systemic
antibiotic treatment is recommended.

Publication Types: 
    Case Reports

PMID: 18193264 [PubMed - indexed for MEDLINE]

458: Vision Res. 2008 Feb;48(4):577-88. Epub 2008 Jan 14.

Relationship between visual span and reading performance in age-related macular
degeneration.

Cheong AM, Legge GE, Lawrence MG, Cheung SH, Ruff MA.

Minnesota Laboratory for Low Vision Research, University of Minnesota, Department
of Psychology, 75 East River Road, N218 Elliott Hall, Minneapolis, MN 55455, USA.
cheon015@umn.edu

PURPOSE: Visual-span profiles are plots of letter-recognition accuracy as a
function of letter position left and right of the point of fixation. Legge,
Mansfield, and Chung [Legge, G. E., Mansfield, J. S., & Chung, S. T. L. (2001).
Psychophysics of reading-XX. Linking letter recognition to reading speed in
central and peripheral vision. Vision Research, 41(6), 725-743] proposed that
reduced size of the visual span is a spatial factor limiting reading speed in
patients with age-related macular degeneration (AMD). We have recently shown that
a temporal property of letter recognition--the exposure time required for a high 
level of accuracy--is also a factor limiting reading speed in AMD [Cheong, A. M. 
Y., Legge, G. E., Lawrence, M. G., Cheung, S. H., & Ruff, M. (2007). Relationship
between slow visual processing and reading speed in people with macular
degeneration. Vision Research, 47, 2943-2965]. We measured the visual-span
profiles of AMD subjects and assessed the relationship of the spatial and
temporal properties of these profiles to reading speed. METHODS: Thirteen AMD
subjects and 11 age-matched normals were tested. Visual-span profiles were
measured by using the trigram letter-recognition method described by Legge et al.
(2001). Each individual's temporal threshold for letter recognition (80% accuracy
criterion) was used as the exposure time for measuring the visual-span profile.
Size of the visual span was computed as the area under the profile in bits of
information transmitted. The information transfer rate in bits per second was
defined as the visual-span size in bits divided by the exposure time in sec.
RESULTS: AMD visual-span sizes were substantially smaller (median of 23.9 bits)
than normal visual-span sizes in central vision (median of 40.8 bits, p<.01). For
the nine AMD subjects with eccentric fixation, the visual-span sizes (median of
20.6 bits) were also significantly smaller than visual spans of normal controls
at 10 degrees below fixation in peripheral vision (median of 29.0 bits, p=.01).
Information transfer rate for the AMD subjects (median of 29.5 bits/s) was
significantly slower than that for the age-matched normals at both central and
peripheral vision (median of 411.7 and 290.5 bits/s respectively, ps<.01).
Information transfer rates were more strongly correlated with reading speed than 
the size of the visual span, and explained 36% of the variance in AMD reading
speed. CONCLUSION: Both visual-span size and information transfer rate were
significantly impaired in the AMD subjects compared with age-matched normals.
Information transfer rate, representing the combined effects of a reduced visual 
span and slower temporal processing of letters, was a better predictor of reading
speed in AMD subjects than was the size of the visual span.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 18191983 [PubMed - indexed for MEDLINE]

459: Surv Ophthalmol. 2008 Jan-Feb;53(1):68-81.

Transport and retinal capture of lutein and zeaxanthin with reference to
age-related macular degeneration.

Loane E, Nolan JM, O'Donovan O, Bhosale P, Bernstein PS, Beatty S.

Macular Pigment Research Group, Waterford Institute of Technology, Waterford,
Ireland.

Age-related macular degeneration (AMD) is the most common cause of irreversible
blindness in the elderly population in the western world. The etiology and
pathogenesis of this disease remain unclear. However, there is an increasing body
of evidence supporting the hypothesis that the macular pigment carotenoids,
lutein and zeaxanthin, play an important role in protection against AMD, by
filtering out blue light at a pre-receptoral level, or by quenching free
radicals. Lutein and zeaxanthin are dietary xanthophyll carotenoids, which are
delivered to the retina via plasma lipoproteins. The biological mechanisms
governing retinal capture and accumulation of lutein and zeaxanthin, to the
exclusion of other carotenoids, are still poorly understood. Although these
mechanisms remain unclear, it is possible that selective capture of these
carotenoids is related to lipoprotein, or apolipoprotein, function and profile.
Xanthophyll-binding proteins appear to play an important role in the retinal
capture of the xanthophyll carotenoids. The Pi isoform of GSTP1 has been isolated
as a specific binding protein for zeaxanthin. The binding protein responsible for
retinal uptake of lutein remains elusive. This article reviews the literature
germane to the mechanisms involved in the capture, accumulation and stabilization
of lutein and zeaxanthin by the retina, and the processes involved in their
transport in serum.

Publication Types: 
    Review

PMID: 18191658 [PubMed - indexed for MEDLINE]

460: Doc Ophthalmol. 2008 Mar;116(2):147-52. Epub 2008 Jan 10.

Intraocular bevacizumab for macular edema due to CRVO. A multifocal-ERG and OCT
study.

Moschos MM, Moschos M.

Department of Ophthalmology, University of Athens, 144, Kountouriotou Str, 185 35
Piraeus, Athens, Greece. moschosmarilita@yahoo.fr

PURPOSE: To evaluate by multifocal electroretinography (MFERG) and optical
coherence tomography (OCT) the effectiveness of intravitreal use of bevacizumab
(Avastin) in the treatment of macular edema due to central retinal vein occlusion
(CRVO). METHODS: A total of 10 eyes of 10 patients (six males and four females)
with macular edema due to CRVO were studied before and after intravitreal use of 
bevacizumab with MFERG and OCT. The post treatment follow-up was 3 months.
Examination included measurement of best-corrected visual acuity (BCVA) for
distance, measurement of intraocular pressure (IOP), fluorescein angiography,
foveal-retinal thickness measurement by OCT, and MFERG recordings before
treatment and 1 and 3 months after treatment. RESULTS: Before treatment, OCT
shows an increase of the retinal thickness of the fovea. About 1 and 3 months
after treatment the foveal thickness decreased to a significant level. The
electrical responses in the fovea and parafovea of the MFERG recording depicted a
significant improvement at 1 and 3 months after the injection. No patient
manifested IOP increase. CONCLUSION: The intravitreal use of bevacizumab may
provide anatomical and functional amelioration of the macula in patients with
macular edema due to CRVO. However, further study is needed in order to assess
the treatment's long-term efficacy.

PMID: 18189152 [PubMed - indexed for MEDLINE]

461: Eye. 2008 Jun;22(6):742-50. Epub 2008 Jan 11.

Looking beyond Lucentis on the management of macular degeneration.

Fletcher EC, Chong NV.

Oxford Eye Hospital, Oxford, UK.

PURPOSE: Age-related macular degeneration (AMD) is the leading cause of blindness
in the developed world. In the past decade, AMD research has improved our
understanding of the pathogenesis of the condition. There is no doubt that
anti-VEGF therapies will play a major role in the reduction of blindness, but it 
needs close monitoring and frequent treatments. In this review we summarise the
key pathophysiology of the condition and some of the new treatment strategies
under development. METHODS: Literature review. RESULTS: Oxidative stress,
inflammation, hypoxia, and angiogenesis are key pathophysiological processes in
AMD, this diversity has provided a variety of possible areas amenable to
modification to enhance the treatment options for AMD.

Publication Types: 
    Review

PMID: 18188178 [PubMed - indexed for MEDLINE]

462: Retina. 2008 Jan;28(1):125-33.

Fixation characteristics of patients with macular degeneration recorded with the 
mp-1 microperimeter.

Tarita-Nistor L, González EG, Markowitz SN, Steinbach MJ.

Vision Science Research Program, Toronto Western Hospital, Toronto, Canada.

PURPOSE: The authors examined the fixation stability patterns of people with
age-related macular degeneration (AMD) using the MP-1 microperimeter and describe
a method to bypass some calibration artifacts that can influence the fixation
results. METHOD: The preferred retinal locus (PRL) and fixation patterns of 37
eyes with AMD and the fovea's location relative to the middle of the optic disc
of 10 experienced controls were measured. For the patients, fixation
characteristics such as the former fovea's location, PRL distance, and fixation
stability were analyzed. RESULTS: For the controls, the mean foveal distance
temporal to the middle of the optic disc was 15.5 deg +/- 0.86 deg horizontally
and -1.33 deg +/- 0.71 deg vertically. Thirty-one out of 37 PRLs occurred in the 
upper and right quadrants of the retina. There were significant positive
correlations between fixation stability and PRL distance from the former fovea.
Time since diagnosis and acuity also showed positive correlations with fixation
stability and PRL distance from the fovea. CONCLUSIONS: The authors recommend
that fixation stability recorded with the MP-1 be analyzed based on the raw data.
Most of the fixation parameters obtained agree with those reported in the
literature, if proper calibration is used.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18185148 [PubMed - indexed for MEDLINE]

463: Retina. 2008 Jan;28(1):103-10.

Prevalence of cystoid macular edema and stability in oct retinal thickness in
eyes with retinitis pigmentosa during a 48-week lutein trial.

Adackapara CA, Sunness JS, Dibernardo CW, Melia BM, Dagnelie G.

Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore,
Maryland, USA.

PURPOSE: To describe, in a group of patients with moderately advanced retinitis
pigmentosa (RP), the prevalence of cystoid macular edema (CME), the variation in 
foveal thickness over a 48-week period, the correlation of visual acuity (VA)
with retinal thickness, and the lack of response of CME to lutein administration.
METHODS: Optical coherence tomography (OCT) imaging of the macula and clinical
examination were evaluated for 77 eyes of 39 patients with RP over 11 months,
with a scan done every 6 weeks. RESULTS: The prevalence of CME, defined by cysts 
visible on OCT, was 49%. Bilateral CME was present in 44% of patients (17 of 39),
and an additional two patients had unilateral CME. Central retinal thickness
varied little over the 48 weeks. Sixty-six percent of the eyes with CME had VA of
20/40 or better. The eyes with CME with VA worse than 20/40 had either greater
degrees of thickening or in fact had lower thickness measures. For the eyes
without CME, the eyes with VA worse than 20/40 tended to have lower retinal
thickness than the eyes with VA of 20/40 or better. VA was highly concordant
between eyes, and did not differ significantly between the groups with and
without CME. Lutein did not show a statistically significant effect on retinal
thickness in the patients with or without CME, nor was such an effect observed in
subgroups of patients with vision better or worse than 20/40. CONCLUSION: The
prevalence rate of CME is higher than in previous reports, perhaps because the
patients had some preserved macular vision and because of the use of a definition
based on OCT findings. Retinal thickness remains fairly stable over time, both in
eyes with CME and in eyes without CME.

Publication Types: 
    Clinical Trial, Phase I
    Clinical Trial, Phase II
    Randomized Controlled Trial
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18185146 [PubMed - indexed for MEDLINE]

464: Retina. 2008 Jan;28(1):41-5.

Intravitreal bevacizumab (avastin) as a treatment for refractory macular edema in
patients with uveitis: a pilot study.

Mackensen F, Heinz C, Becker MD, Heiligenhaus A.

Interdisciplinary Uveitis Center, Department of Ophthalmology, University of
Heidelberg, Germany. friederike.mackensen@uveitiszentrum.de

PURPOSE:: Bevacizumab is a monoclonal antibody to vascular endothelial growth
factor (VEGF) which has been successfully used for the treatment of age-related
macular degeneration with choroidal neovascularization. As VEGF is involved in
the pathomechanisms of inflammation and endothelial dysfunction the authors used 
bevacizumab as a last resort treatment in patients with persistent uveitic
cystoid macular edema (CME). PATIENTS AND METHODS:: Persistent uveitic CME was
defined by optical coherence tomography (OCT) measurements >250 mum despite
previous treatments. The authors reviewed patients with persistent CME who
subsequently had been treated with intravitreous bevacizumab 1.25 or 2.5 mg.
Improvement was judged by visual acuity (VA) gain >/=2 lines and thickness
reduction in OCT. RESULTS:: Eleven eyes of 10 patients were injected since
February 2006. Median follow-up was 70 days. Reduction in central retinal
thickness could be seen as early as 2 weeks with a mean foveal thickness
reduction of 127.2 mum at 4 weeks. Concurrent improvement in VA was seen in 4 of 
10 patients, and was unchanged in the others. Four patients received two
injections and five patients received three injections. Except for progression of
cataract in one eye no ocular or systemic adverse events were recorded.
CONCLUSIONS:: Intravitreal bevacizumab seems to be an effective and safe
treatment in the management of refractory inflammatory CME. The effect is
transient, and reinjections may be necessary, although the time until reinjection
is needed differs individually.

Publication Types: 
    Clinical Trial

PMID: 18185136 [PubMed - indexed for MEDLINE]

465: Retina. 2008 Jan;28(1):36-40.

Agreement between clinician and reading center gradings of diabetic retinopathy
severity level at baseline in a phase 2 study of intravitreal bevacizumab for
diabetic macular edema.

Scott IU, Bressler NM, Bressler SB, Browning DJ, Chan CK, Danis RP, Davis MD,
Kollman C, Qin H; Diabetic Retinopathy Clinical Research Network Study Group.

Pennsylvania State University College of Medicine, Hershey, PA, USA.

PURPOSE: To evaluate agreement in diabetic retinopathy severity classification by
retina specialists performing ophthalmoscopy versus reading center (RC) grading
of seven-field stereoscopic fundus photographs in a phase 2 clinical trial of
intravitreal bevacizumab for center-involved diabetic macular edema. METHODS:
Clinicians' grading scale used four levels: microaneurysms only, mild/moderate
nonproliferative diabetic retinopathy (NPDR), severe NPDR, and proliferative
diabetic retinopathy (PDR) or prior panretinal photocoagulation (PRP) or both.
The RC scale used eight levels: microaneurysms only, mild NPDR, moderate NPDR,
moderately severe NPDR, severe NPDR, mild PDR, moderate PDR, and high-risk PDR.
Percent agreement and kappa statistic were defined by collapsing RC categories to
match those used by clinicians. RESULTS: There was agreement in 89/118 eyes (75%)
with kappa = 0.55 (95% confidence interval [0.41, 0.68]). In six eyes,
disagreements were of potential substantial clinical importance: five eyes with
subtle retinal neovascularization and one with a small preretinal hemorrhage
identified only in photographs. CONCLUSIONS: Clinician grading of retinopathy
severity had moderate agreement with RC grading and might be useful for placing
eyes into broad baseline categories.

Publication Types: 
    Clinical Trial, Phase II
    Multicenter Study
    Randomized Controlled Trial
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18185135 [PubMed - indexed for MEDLINE]

466: J Am Geriatr Soc. 2008 Mar;56(3):478-83. Epub 2008 Jan 4.

Health-protective and adverse effects of the apolipoprotein E epsilon2 allele in 
older men.

Kulminski AM, Ukraintseva SV, Arbeev KG, Manton KG, Oshima J, Martin GM,
Il'yasova D, Yashin AI.

Center for Population Health and Aging, Duke University, Trent Hall, Room 002,
Trent Drive, Box 90408, Durham, NC 27708, USA. Alexander.Kulminski@duke.edu

OBJECTIVES: To reexamine a health-protective role of the common apolipoprotein E 
(APOE) polymorphism focusing on connections between the APOE epsilon2-containing 
genotypes and impairments in instrumental activities of daily living (IADLs) in
older (> or = 65) men and women and to examine how diagnosed coronary heart
disease (CHD), Alzheimer's disease, colorectal cancer, macular degeneration, and 
atherosclerosis may mediate these connections. DESIGN: Retrospective
cross-sectional study. SETTING: The unique disability-focused data from a genetic
subsample of the 1999 National Long Term Care Survey linked with Medicare service
use files. PARTICIPANTS: One thousand seven hundred thirty-three genotyped
individuals interviewed regarding IADL disabilities. MEASUREMENTS: Indicators of 
IADL impairments, five geriatric disorders, and epsilon2-containing genotypes.
RESULTS: The epsilon2/3 genotype is a major contributor to adverse associations
between the epsilon2 allele and IADL disability in men (odds ratio (OR)=3.09, 95%
confidence interval (CI)=1.53-6.26), although it provides significant protective 
effects for CHD (OR=0.55, 95% CI=0.33-0.92), whereas CHD is adversely associated 
with IADL disability (OR=2.18, 95% CI=1.28-3.72). Adjustment for five diseases
does not significantly alter the adverse association between epsilon2-containing 
genotypes and disability. Protective effects of the epsilon2/3 genotype for CHD
(OR=0.52, 95% CI=0.27-0.99) and deleterious effects for IADLs (OR=3.50, 95%
CI=1.71-7.14) for men hold in multivariate models with both these factors
included. No significant associations between the epsilon2-containing genotypes
and IADL are found in women. CONCLUSION: The epsilon2 allele can play a dual role
in men, protecting them against some health disorders, while promoting others.
Strong adverse relationships with disability suggest that epsilon2-containing
genotypes can be unfavorable factors for the health and well-being of aging men.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 18179501 [PubMed - indexed for MEDLINE]

467: Invest Ophthalmol Vis Sci. 2008 Jan;49(1):364-71.

Comprehensive analysis of the candidate genes CCL2, CCR2, and TLR4 in age-related
macular degeneration.

Despriet DD, Bergen AA, Merriam JE, Zernant J, Barile GR, Smith RT, Barbazetto
IA, van Soest S, Bakker A, de Jong PT, Allikmets R, Klaver CC.

Department of Clinical and Molecular Ophthalmogenetics, Netherlands Institute for
Neuroscience, Royal Netherlands Academy of Arts and Sciences (KNAW), Amsterdam,
The Netherlands.

PURPOSE: To determine whether variants in the candidate genes TLR4, CCL2, and
CCR2 are associated with age-related macular degeneration (AMD). METHODS: This
study was performed in two independent Caucasian populations that included 357
cases and 173 controls from the Netherlands and 368 cases and 368 controls from
the United States. Exon 4 of the TLR4 gene and the promoter, all exons, and
flanking intronic regions of the CCL2 and CCR2 genes were analyzed in the Dutch
study and common variants were validated in the U.S. study. Quantitative (q)PCR
reactions were performed to evaluate expression of these genes in laser-dissected
retinal pigment epithelium from 13 donor AMD and 13 control eyes. RESULTS:
Analysis of single nucleotide polymorphisms (SNPs) in the TLR4 gene did not show 
a significant association between D299G or T399I and AMD, nor did haplotypes
containing these variants. Univariate analyses of the SNPs in CCL2 and CCR2 did
not demonstrate an association with AMD. For CCR2, haplotype frequencies were not
significantly different between cases and controls. For CCL2, one haplotype
containing the minor allele of C35C was significantly associated with AMD (P =
0.03), but this did not sustain after adjustment for multiple testing (q = 0.30).
Expression analysis did not demonstrate altered RNA expression of CCL2 and CCR2
in the retinal pigment epithelium from AMD eyes (for CCL2 P = 0.62; for CCR2 P = 
0.97). CONCLUSIONS: No evidence was found of an association between TLR4, CCR2,
and CCL2 and AMD, which implies that the common genetic variation in these genes 
does not play a significant role in the etiology of AMD.

Publication Types: 
    Multicenter Study
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18172114 [PubMed - indexed for MEDLINE]

468: Invest Ophthalmol Vis Sci. 2008 Jan;49(1):358-63.

Foveolar choroidal circulation and choroidal neovascularization in age-related
macular degeneration.

Metelitsina TI, Grunwald JE, DuPont JC, Ying GS, Brucker AJ, Dunaief JL.

Department of Ophthalmology, Scheie Eye Institute, School of Medicine, University
of Pennsylvania, 51 North 39th Street, Philadelphia, PA 19104, USA.

PURPOSE: To investigate in a longitudinal study whether foveolar choroidal blood 
flow changes are associated with the development of choroidal neovascularization 
(CNV) in AMD. METHODS: Relative foveolar choroidal blood velocity (ChBVel),
volume (ChBVol), and flow (ChBFlow) were assessed in 135 patients with AMD, at
baseline and then annually with laser Doppler flowmetry. All study eyes had
visual acuity of 20/40 or better and no CNV at the time of enrollment. Comparison
of foveolar choroidal circulatory measurements at baseline and their change
before the development of CNV was made between eyes that had CNV and those that
did not. RESULTS: CNV developed in 28 eyes during the study. Baseline average
foveolar ChBVol and ChBFlow in these eyes were 24% (P < 0.0001) and 20% (P =
0.0007) lower than that observed in the 165 eyes in which CNV did not develop. In
the eyes with CNV, foveolar ChBVol and ChBFlow decreased by 9.6% and 11.5% before
the formation of CNV, whereas in the eyes that did not, they increased by 6.7% (P
= 0.006) and 2.8% (P = 0.004), respectively. Eyes with lower baseline foveolar
ChBFlow were more likely (risk ratio = 3.47, 95% CI: 1.24-8.70) to show visual
loss of three or more lines than were eyes with a higher baseline ChBFlow (P =
0.005). CONCLUSIONS: The development of CNV and visual loss are associated with
lower choroidal circulatory parameters at baseline. In addition, the results
suggest that decreases in the foveolar choroidal circulation precede the
development of CNV in AMD and may play some role in its development.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18172113 [PubMed - indexed for MEDLINE]

469: Invest Ophthalmol Vis Sci. 2008 Jan;49(1):55-65.

Measuring rod and cone dynamics in age-related maculopathy.

Dimitrov PN, Guymer RH, Zele AJ, Anderson AJ, Vingrys AJ.

Centre for Eye Research Australia, Department of Ophthalmology, The University of
Melbourne, East Melbourne, Victoria, Australia.

PURPOSE: A cathode-ray-tube (CRT) monitor-based technique was used to isolate
clinically significant components of dark adaptation. The utility of the
technique in identifying adaptation abnormalities in eyes with age-related
maculopathy (ARM) is described. METHODS: A CRT dark adaptometer was developed to 
assess cone and rod recovery after photopigment bleach. The following measures
were obtained: cone recovery rate (R(c); in decades per minute) and absolute
threshold (Tf(c); log candelas per square meter), rod recovery rate (R(r);
decades per minute), and rod-cone transition (rod-cone break [RCB], in minutes). 
These components were isolated by appropriately selecting stimulus size, stimulus
location, pigment bleach, and test duration and by coupling the CRT with
judiciously selected neutral-density (ND) filters. The protocol was developed by 
using 5 young observers and was tested on 27 subjects with ARM in the study eye
and 22 age-matched control subjects. RESULTS: The parameters necessary for
effective isolation of cone and early phase rod dark adaptation were a 2.6 ND
filter (for a standard CRT monitor, 0.08-80 cd . m(-2) luminance output); a 4
degrees foveated, 200-ms, achromatic spot; approximately 30% pigment bleaching;
and a 30-minute test duration. These settings returned obvious rod and cone
recovery curves in control and ARM eyes that were compatible with conventional
test methods and identified 93% of participants with ARM as having delayed
dynamics in at least one of the parameters. Cone recovery dynamics were
significantly slower in the ARM group when compared with age-matched control
subjects (R(c), 0.99 +/- 0.35 vs. 2.63 +/- 0.61 decades . min(-1), P < 0.0001).
Three of the 27 eyes with ARM did not achieve RCB during the allowed duration (30
minutes). The remaining eyes with ARM (n = 24) exhibited a significant delay in
rod recovery (R(r)(,) ARM, 0.16 +/- 0.03 vs. controls, 0.22 +/- 0.02 decades .
min(-1), P < 0.0001) and the average time to RCB (+/-SD) in the ARM group was
significantly longer than in the control subjects (19.12 +/- 5.17 minutes vs.
10.40 +/- 2.49 minutes, P < 0.0001). CONCLUSIONS: The CRT dark-adaptation
technique described in this article is an effective test for identifying
abnormalities in cone and rod recovery. Slowed cone and rod recovery and a
delayed RCB were evident in the eyes with ARM. The test method is potentially
useful for clinical intervention trials in which ARM progression is monitored.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18172075 [PubMed - indexed for MEDLINE]

470: Ophthalmology. 2008 Jan;115(1):147-57.

Macular carotenoid levels of normal subjects and age-related maculopathy patients
in a Japanese population.

Obana A, Hiramitsu T, Gohto Y, Ohira A, Mizuno S, Hirano T, Bernstein PS, Fujii
H, Iseki K, Tanito M, Hotta Y.

Department of Ophthalmology, Seirei Hamamatsu General Hospital, Hamamatsu, Japan.

PURPOSE: Macular carotenoid pigments composed of lutein and zeaxanthin are
thought to affect the development of age-related maculopathy (ARM). Macular
carotenoid levels were measured in normal Japanese subjects and Japanese patients
with ARM. DESIGN: Observational case-control series. PARTICIPANTS: One hundred
normal eyes of 100 normal subjects and 187 eyes of 97 patients with ARM; all were
Japanese. The definitions of early ARM and late ARM (exudative age-related
macular degeneration [AMD] and dry AMD) were used according to an accepted
international classification system. METHODS: Macular carotenoid levels were
measured using resonance Raman spectroscopy. MAIN OUTCOME MEASURE: Raman signal
intensity generated from carbon-carbon double bond vibrations of lutein and
zeaxanthin. RESULTS: The mean (+/-standard deviation [SD]) macular carotenoid
level in normal subjects was 1471+/-540 Raman counts. The macular carotenoid
levels in normal subjects declined with age. The mean macular carotenoid level
was 620+/-204 (+/-SD) in eyes with early ARM and 427+/-283 (+/-SD) in eyes with
late ARM (equal to AMD). The macular carotenoid levels of early ARM and AMD were 
significantly lower than those in normal subjects older than 60 years (1100+/-340
[+/-SD]). No difference was revealed in carotenoid levels by the severity for
ARM, type of AMD (exudative, atrophic, and disciform scar), or types of choroidal
neovascularization (classic, minimally classic, occult, polypoidal choroidal
vasculopathy), although small numbers in some groups weakened statistical power. 
Macular carotenoid levels were affected by the severity of macular disease in the
opposing eye. The average for normal eyes where AMD was found in the opposite eye
was significantly lower than that of normal eyes in the absence of AMD in the
opposite eye (i.e., healthy volunteers older than 60 years). CONCLUSIONS: Macular
carotenoids decreased even in older healthy individuals. The ARM patients showed 
lower macular carotenoid levels than healthy people. Low macular carotenoid
levels may be one of the risk factors of progression in ARM.

PMID: 18166409 [PubMed - indexed for MEDLINE]

471: Ophthalmology. 2008 Jan;115(1):134-40.

Randomized multicenter trial of more intense and standard early verteporfin
treatment of neovascular age-related macular degeneration.

Schmidt-Erfurth U, Sacu S; Early Retreatment Study Group.

Department of Ophthalmology, Medical University of Vienna, Vienna, Austria.

PURPOSE: To compare efficacy and safety of a more intense regimen versus a
standard one for retreatment of neovascular age-related macular degeneration
(AMD) during the early period of verteporfin therapy (VT). DESIGN: Prospective,
randomized, multicenter clinical trial. PARTICIPANTS: Two hundred three patients 
with predominantly classic choroidal neovascularization (CNV) secondary to AMD.
METHODS: During the first 6 months of VT, patients underwent retreatment every 2 
(group A) or 3 (group B) months. After 6 months, both groups underwent
retreatment every 3 months for as long as CNV activity was documented. MAIN
OUTCOME MEASURES: Best-corrected visual acuity (BCVA) measured every 6 months,
mean number of treatments per patient during 24 months' follow-up, proportions of
patients in each group losing at least 3 lines of vision or gaining at least 1
line, greatest linear dimension (GLD) of the lesion as documented by fluorescein 
angiography every 6 months, and relationship between initial lesion size and
BCVA. RESULTS: At all follow-up times, mean BCVAs were similar for groups A and
B. Mean numbers of photodynamic therapy treatments were similar for both groups
(4.07 vs. 4.36; P = 0.451, paired t test). A lower proportion (51.9% vs. 56.7%)
of patients in group A had lost at least 3 lines of vision at 24 months. Groups A
and B had similar increases in mean lesion size from baseline to 24 months
(2104-3056 microm and 2179-3020 microm). At 24 months, patients in group A with a
baseline lesion GLD of < or =2000 microm had significantly less mean loss of
vision than patients in group A with a GLD of >2000 microm (P = 0.032);
differences also were significant for group A with GLD of < or =2000 microm
versus group B with GLD of < or =2000 microm (P = 0.041) or GLD of >2000 microm
(P = 0.045); and mean vision losses from baseline were 8, 17, 15, and 14 letters,
respectively. CONCLUSIONS: Overall outcomes regarding visual benefit, lesion
anatomic features, and number of retreatments after 6 months were similar for
patients receiving more intense or standard early therapy. An unplanned
retrospective analysis showed that there was significantly less vision loss when 
the more intense regimen was used to treat smaller lesions.

Publication Types: 
    Clinical Trial, Phase III
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18166408 [PubMed - indexed for MEDLINE]

472: J Cataract Refract Surg. 2008 Jan;34(1):87-94.

Mirror telescopic intraocular lens for age-related macular degeneration: design
and preliminary clinical results of the Lipshitz macular implant.

Agarwal A, Lipshitz I, Jacob S, Lamba M, Tiwari R, Kumar DA, Agarwal A.

Dr. Agarwal's Eye Hospital and Eye Research Centre, Chennai, India.
dragarwal@vsnl.com

PURPOSE: To conduct a pilot study evaluating the visual and surgical outcomes of 
an intraocular mirror telescopic intraocular lens, the Lipshitz macular implant
(LMI) (Optolight Vision Technology), for age-related macular degeneration (ARMD) 
and other macular pathology. SETTING: Dr. Agarwal's Eye Hospital and Eye Research
Centre, Chennai, India. METHODS: The LMI was implanted in patients with bilateral
macular pathology and visual acuity worse than 20/200 in whom vision improved
with a x2.5 external telescope preoperatively. The LMI was implanted after
conventional phacoemulsification or microphakonit. The minimum follow-up was 6
months. RESULTS: Six eyes of 6 patients had surgery in the worse eye. Four eyes
had ARMD, and 1 eye each had myopic macular degeneration or macular dystrophy.
There were no intraoperative complications. The mean gain in distance acuity was 
3.66 lines +/- 1.88 (SD), and the mean increase in the Early Treatment Diabetic
Retinopathy Study score for near acuity was 50.83 +/- 9.15 logMAR. The best
corrected distance acuity and near acuity improved significantly (both P = .014).
The mean change in endothelial count was -5.79% +/- -4.07%. The mean
postoperative corneal endothelial-LMI distance was 3.15 +/- 0.31 mm. A good
central fundus view was possible around the mirrors in all eyes. Fundus
fluorescein angiography showed good visibility of the retina up to the
midperiphery. The mean score on a quality-of-life questionnaire was 11.16 +/-
1.72 (SD) preoperatively and 4.50 +/- 0.83 postoperatively, a statistically
significant improvement (P = .014). CONCLUSIONS: The LMI may be an effective
solution for optical rehabilitation of patients with ARMD or other macular
pathology by increasing the central image on the retina while preserving
peripheral vision. The surgery and visual recovery were quick, and the
improvement in quality of life was significant.

Publication Types: 
    Clinical Trial

PMID: 18165087 [PubMed - indexed for MEDLINE]

473: J Cataract Refract Surg. 2008 Jan;34(1):70-5.

Efficacy of intravitreal bevacizumab in treating postoperative pseudophakic
cystoid macular edema.

Spitzer MS, Ziemssen F, Yoeruek E, Petermeier K, Aisenbrey S, Szurman P.

University Eye Clinic Tuebingen, Centre of Ophthalmology, Eberhard-Karls
University, Tuebingen, Germany.

PURPOSE: To describe the efficacy of intravitreal bevacizumab (Avastin) in
patients with cystoid macular edema (CME) after cataract surgery (Irvine-Gass
syndrome). METHODS: This retrospective case series comprised 16 eyes of 16
patients with CME after cataract surgery refractory to current standard treatment
who received an injection of 1.25 mg intravitreal Avastin. The main outcome
measures were visual acuity, retinal thickness on optical coherence tomography
(OCT), and complications related to treatment. RESULTS: The median duration of
CME before treatment with intravitreal Avastin was 14 weeks (range 3 to 84
weeks). Although the mean retinal thickness decreased slightly after intravitreal
Avastin, the mean visual acuity remained unchanged. Visual acuity improved by 2
Early Treatment Diabetic Retinopathy Study lines in 1 patient, remained unchanged
in 12 patients, and decreased by 2 lines in 2 patients. Repeated Avastin
injections did not result in a better outcome. Other than mild ocular irritation,
there were no adverse effects of the intravitreal injections. CONCLUSIONS:
Intravitreal injection of Avastin, although safe, did not result in improved
visual function in patients with postoperative CME. In contrast to findings in a 
previous case report, the beneficial effect of vascular endothelial growth factor
inhibition in Irvine-Gass syndrome was not observed.

Publication Types: 
    Clinical Trial

PMID: 18165084 [PubMed - indexed for MEDLINE]

474: J Cataract Refract Surg. 2008 Jan;34(1):64-9.

Effect of prophylactic nonsteroidal antiinflammatory drugs on cystoid macular
edema assessed using optical coherence tomography quantification of total macular
volume after cataract surgery.

Almeida DR, Johnson D, Hollands H, Smallman D, Baxter S, Eng KT, Kratky V, ten
Hove MW, Sharma S, El-Defrawy S.

Department of Ophthalmology, Queen's University, Hotel Dieu Hospital, Kingston,
Ontario, Canada.

PURPOSE: To evaluate the efficacy of prophylactic administration of the topical
nonsteroidal antiinflammatory drug (NSAID) ketorolac tromethamine 0.5% on acute
(within 4 weeks of surgery) cystoid macular edema (CME) and total macular volume 
(TMV) in patients having phacoemulsification cataract surgery. SETTING:
Department of Ophthalmology, Queen's University, Hotel Dieu Hospital, Kingston,
Ontario, Canada. METHODS: This open-label nonmasked randomized (random number
assignment) study comprised 106 eyes of 98 patients. Exclusion criteria included 
hypersensitivity to the NSAID drug class, aspirin/NSAID-induced asthma, and
pregnancy in the third trimester. Ketorolac tromethamine 0.5% was administered
starting 2 days before surgery and for 29 days after surgery for a total of 31
days. The outcome measure was macular swelling, which was quantified by the
optical coherence tomography. RESULTS: At 1 month, there was a statistically
significant difference in TMV between the control group (0.4420 mm3) and the
ketorolac group (0.2392 mm3), with the ketorolac group having 45.8% less macular 
swelling (P = .009). Multiple linear regression with backward selection indicated
a 44.3% (P = .013) and 46.1% (P = .030) reduction in macular swelling in the
ketorolac group at 1 week and 1 month, respectively. CONCLUSION: Used
prophylactically after cataract surgery, ketorolac 0.5% was efficacious in
decreasing postoperative macular edema.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18165083 [PubMed - indexed for MEDLINE]

475: J Cataract Refract Surg. 2008 Jan;34(1):57-63.

Reducing angiographic cystoid macular edema and blood-aqueous barrier disruption 
after small-incision phacoemulsification and foldable intraocular lens
implantation: multicenter prospective randomized comparison of topical diclofenac
0.1% and betamethasone 0.1%.

Asano S, Miyake K, Ota I, Sugita G, Kimura W, Sakka Y, Yabe N.

Shohzankai Medical Foundation, Miyake Eye Hospital, Kita-ku, Nagoya, Japan.

PURPOSE: To compare the effectiveness of a topical nonsteroidal drug (diclofenac 
0.1%) and a topical steroidal drug (betamethasone 0.1%) in preventing cystoid
macular edema (CME) and blood-aqueous barrier (BAB) disruption after
small-incision cataract surgery and foldable intraocular lens (IOL) implantation.
SETTINGS: Shohzankai Medical Foundation Miyake Eye Hospital, Tokyo, Japan.
METHODS: This multicenter interventional double-masked randomized study comprised
142 patients having phacoemulsification and foldable IOL implantation.
Seventy-one patients were randomized to receive diclofenac eyedrops and 71,
betamethasone eyedrops for 8 weeks postoperatively. The incidence and severity of
CME were evaluated by fluorescein angiography. Blood-aqueous barrier disruption
was determined by laser flare-cell photometry. RESULTS: Of the patients, 63 were 
men and 79 were women. Five weeks after surgery, the incidence of fluorescein
angiographic CME was lower in the diclofenac group (18.8%) than in the
betamethasone group (58.0%) (P<.001). At 1 and 2 weeks, the amount of anterior
chamber flare was statistically significantly less in the diclofenac group than
in the betamethasone group (P<.05). At 8 weeks, intraocular pressure was
statistically significantly higher in the betamethasone group (P = .0003).
CONCLUSIONS: Diclofenac was more effective than betamethasone in preventing
angiographic CME and BAB disruption after small-incision cataract surgery. Thus, 
nonsteroidal antiinflammatory agents should be considered for routine treatment
of eyes having cataract surgery.

Publication Types: 
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial

PMID: 18165082 [PubMed - indexed for MEDLINE]

476: Ophthalmology. 2008 Jul;115(7):1209-1215.e7. Epub 2007 Dec 27.

Alleles in the HtrA serine peptidase 1 gene alter the risk of neovascular
age-related macular degeneration.

Deangelis MM, Ji F, Adams S, Morrison MA, Harring AJ, Sweeney MO, Capone A Jr,
Miller JW, Dryja TP, Ott J, Kim IK.

Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear
Infirmary, Boston, Massachusetts 02114, USA. margaret_deangelis@hms.harvard.edu

OBJECTIVE: To examine if the genes encoding the pleckstrin homology
domain-containing protein gene (PLEKHA1), hypothetical LOC387715/ARMS2 gene, and 
HtrA serine peptidase 1 gene (HTRA1) located on the long arm of chromosome 10
(10q26 region) confer risk for neovascular age-related macular degeneration (AMD)
in an independent or interactive manner when controlling for complement factor H 
gene (CFH) genotype and smoking exposure. DESIGN: Retrospective matched-pair
case-control study. PARTICIPANTS: Hospital clinic-based sample of 134 unrelated
patients with neovascular AMD who have a sibling with normal maculae (268
subjects). METHODS: Disease status was ascertained by at least 2 investigators by
review of fundus photographs and/or fluorescein angiography according to the
Age-Related Eye Disease Study grading scale. If necessary, a home retinal
examination was performed (n = 6). A combination of direct sequencing and
analysis of 8 highly polymorphic microsatellite markers was used to genotype 33
megabases of the 10q26 region on leukocyte DNA. Smoking history was obtained via 
a standardized questionnaire and measured in pack-years. The family-based
association test, haplotype analysis, multiple conditional logistic regression,
and linkage analysis were used to determine significant associations. MAIN
OUTCOME MEASURE: Neovascular AMD status. RESULTS: Of the 23 variants we
identified in the 10q26 region, 6 were significant. Four of the 6 were novel and 
included 2 genotypes that reduced risk of AMD. Many single-nucleotide
polymorphisms (SNPs), including the previously reported variants rs10490924
(hypothetical LOC387715/ARMS2) and rs11200638 (HTRA1), defined 2 significant
haplotypes associated with increased risk of neovascular AMD. The coding HTRA1
SNP rs2293870, not part of the significant haplotypes containing rs10490924 and
rs11200638, showed as strong an association with increased susceptibility to
neovascular AMD. Linkage analysis supported our findings of SNP association
(P<10(-15)). No significant interactions were found between any of the SNPs in
the 10q26 and smoking or between these SNPs and CFH genotype. CONCLUSIONS:
Independent of CFH genotype or smoking history, an individual's risk of AMD could
be increased or decreased, depending on their genotype or haplotype in the 10q26 
region.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18164066 [PubMed - indexed for MEDLINE]

477: Curr Opin Ophthalmol. 2007 Nov;18(6):487-92.

Inflammatory cystoid macular edema.

Rothova A.

Department of Ophthalmology, University Medical Center, Utrecht, The Netherlands.
a.rothova@umcutrecht.nl

PURPOSE OF REVIEW: The aim of this article is to update our current understanding
and management of inflammatory cystoid macular edema. RECENT FINDINGS: Cystoid
macular edema is a common cause of visual loss in uveitis, which occurs
predominantly in older patients with chronic uveitis forms and might be heralded 
by subclinical changes on optic coherence tomography. Cystoid macular edema is
emerging as a major cause of visual loss in HIV-infected patients with immune
recovery uveitis. Elevated levels of proinflammatory cytokines and vascular
endothelial growth factor were found in all types of cystoid macular edema.
Treatment with anti-inflammatory and anti-vascular endothelial growth factor
drugs is widely applied for all forms of cystoid macular edema and usually has a 
beneficial, but temporary effect. So far, there are no clear guidelines for the
treatment of subclinical cystoid macular edema in uveitis. The effect of
vitrectomy in inflammatory cystoid macular edema is not yet clear and might
become more important in the future. Recent advances in management include
intravitreal drug delivery systems of cystoid macular edema-modifying drugs.
SUMMARY: This review summarizes current thoughts on inflammatory cystoid macular 
edema focusing on the new, clinically relevant findings. Upcoming data on aqueous
constituents in cystoid macular edema and imaging with the new generation of
optic coherence tomography offer the hope that a better treatment strategy will
soon be established.

Publication Types: 
    Review

PMID: 18163001 [PubMed - indexed for MEDLINE]

478: Acta Ophthalmol. 2008 Aug;86(5):482-9. Epub 2007 Dec 14.

A prospective study on intravitreal bevacizumab (Avastin) for neovascular
age-related macular degeneration of different durations.

Algvere PV, Steén B, Seregard S, Kvanta A.

Karolinska Institute, St Erik's Eye Hospital, Stockholm, Sweden.
peep.algvere@sankterik.se

PURPOSE: Choroidal neovascularization (CNV) accounts for 85-90% of severe visual 
impairment in age-related macular degeneration (AMD). Vascular endothelial growth
factor (VEGF) is a major factor mediating angiogenesis, and VEGF inhibitors have 
become a new treatment modality. In this prospective study, we used bevacizumab
(Avastin), a recombinant monoclonal antibody to VEGF, to treat neovascular AMD.
METHODS: The case material comprised 36 subjects (26 females, 10 males) aged
65-88 years with subfoveal neovascular AMD with all subtypes of CNV. There were
two categories of patients: category I, long-standing CNV (12 months or more),
preoperative visual acuity (VA) 0.16 (mean); category II, CNV (duration < 12
months), preoperative VA 0.25 (mean). Evaluation protocol included the Early
Treatment Diabetic Retinopathy Study (ETDRS) VA, clinical ophthalmological
examination, fluorescein angiography and optical coherence tomography (OCT).
Intravitreal injections of bevacizumab (Avastin) (IVB), 1.25 mg (0.05 ml), were
given under an operating microscope and aseptic conditions in a theatre for
surgery with intervals of 4 or 6 weeks during the first 3 months and subsequently
according to clinical assessment. The follow-up was 6 months in all cases.
RESULTS: At 6 months, mean VA had improved by 4.6 ETDRS letters in the entire
case material (P = 0.001), by 3.9 letters in category I (duration 12 months or
more) and by 6.0 letters in category II (duration < 12 months). A total of 148
IVB (mean 4.1 injections/eye) were delivered during 6 months, the first 3 months 
comprising 3.1 IVB (mean) and the last 3 months 1.0 IVB (mean). No eyes suffered 
visual decline of 15 ETDRS letters. Fluorescein angiograms displayed
stabilization or regression of CNV activity; OCT showed resorption of
intraretinal oedema and subretinal fluid. No severe complications occurred but
recurrence was common, and repeated IVBs were necessary in most cases during the 
6-month period. CONCLUSION: When addressing the issue of frequency of IBV, we
observed that 6-week intervals were sufficient because VA and CNV lesions
generally stabilized at 4 weeks. The gain in VA was promising in eyes with < 12
months CNV duration. Even in eyes with a longer CNV duration, a slight visual
improvement was observed when retinal oedema resorbed, although subretinal
fibrosis and general cellular damage certainly limited recovery.

PMID: 18162062 [PubMed - indexed for MEDLINE]

479: PLoS Med. 2007 Dec;4(12):e355.

Neovascular age-related macular degeneration risk based on CFH, LOC387715/HTRA1, 
and smoking.

Hughes AE, Orr N, Patterson C, Esfandiary H, Hogg R, McConnell V, Silvestri G,
Chakravarthy U.

Department of Medical Genetics, Queen's University Belfast, Belfast, United
Kingdom. A.Hughes@qub.ac.uk

BACKGROUND: Age-related macular degeneration (AMD) is the major cause of
blindness in the elderly. Those with the neovascular end-stage of disease have
irreversible loss of central vision. AMD is a complex disorder in which genetic
and environmental factors play a role. Polymorphisms in the complement factor H
(CFH) gene, LOC387715, and the HTRA1 promoter are strongly associated with AMD.
Smoking also contributes to the etiology. We aimed to provide a model of disease 
risk based on these factors. METHODS AND FINDINGS: We genotyped polymorphisms in 
CFH and LOC387715/HTRA1 in a case-control study of 401 patients with neovascular 
AMD and 266 controls without signs of disease, and used the data to produce
genetic risk scores for the European-descent population based on haplotypes at
these loci and smoking history. CFH and LOC387715/HTRA1 haplotypes and smoking
status exerted large effects on AMD susceptibility, enabling risk scores to be
generated with appropriate weighting of these three factors. Five common
haplotypes of CFH conferred a range of odds ratios (ORs) per copy from 1 to 4.17.
Most of the effect of LOC387715/HTRA1 was mediated through one detrimental
haplotype (carriage of one copy: OR 2.83; 95% confidence interval [CI]
1.91-4.20), with homozygotes being at particularly high risk (OR 32.83; 95% CI
12.53-86.07). Patients with neovascular macular degeneration had considerably
higher scores than those without disease, and risk of blinding AMD rose to 15.5% 
in the tenth of the population with highest predicted risk. CONCLUSIONS: An
individual's risk of developing AMD in old age can be predicted by combining
haplotype data with smoking status. Until there is effective treatment for AMD,
encouragement to avoid smoking in those at high genetic risk may be the best
option. We estimate that total absence of smoking would have reduced the
prevalence of severe AMD by 33%. Unless smoking habits change or preventative
treatment becomes available, the prevalence of AMD will rise as a consequence of 
the increasing longevity of the population.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18162041 [PubMed - indexed for MEDLINE]

480: Ophthalmic Genet. 2007 Dec;28(4):203-7.

LOC387715/HTRA1 and complement factor H variants in patients with age-related
macular degeneration seen at the mayo clinic.

Pulido JS, Peterson LM, Mutapcic L, Bryant S, Highsmith WE.

Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota, USA.

PURPOSE: To confirm association of the complement factor H allelic variant (CFH
Y402H) and the LOC387715/HTRA1 (LOC387715 A69S) risk alleles with age-related
macular degeneration (AMD). STUDY POPULATION: Study of 89 Caucasian patients with
neovascular (exudative) AMD and 232 Caucasian controls. METHODS: The Y402H
variant of CFH gene and A69S variant of LOC387715/HTRA1 gene locus were examined.
RESULTS: For CFH, the odds ratio for the homozygous variant was 4.97 (CI 2.52 to 
9.79). For LOC387715/HTRA1 the odds ratio for the homozygous risk variant was
7.75 (CI 3.46 to 17.35). The odds ratio for heterozygous carriers was 3.35 (CI
1.91 to 5.90).

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18161619 [PubMed - indexed for MEDLINE]

481: Ophthalmic Epidemiol. 2007 Nov-Dec;14(6):408-14.

Australian prospective study of cataract surgery and age-related macular
degeneration: rationale and methodology.

Cugati S, de Loryn T, Pham T, Arnold J, Mitchell P, Wang JJ.

Centre for Vision Research, Department of Ophthalmology and the Westmead
Millennium Institute, University of Sydney, Sydney, Australia.

BACKGROUND: Cataract surgery is the most frequently performed ophthalmic
procedure worldwide. While benefits gained from cataract surgery outweigh
surgical risks, there have been concerns that older persons may have an increased
risk of developing age-related macular degeneration (AMD) after cataract surgery.
OBJECTIVE: The Australian Prospective Study of Cataract Surgery and Age-Related
Macular Degeneration Study aims to assess the risk of AMD in a large cohort of
older patients following cataract surgery. The current report describes the study
rationale, design and methodology. DESIGN: Longitudinal study. PARTICIPANTS:
Approximately 2000 cataract surgical patients aged 65 years or older are being
recruited from both public and private sources in western Sydney, Australia.
METHODS: At study visits, participants are interviewed using standardized
questionnaires to obtain information on demographic, medical, and ocular
conditions and AMD risk factors, together with data on general health and
vision-related quality of life. Eye examinations include visual acuity,
intraocular pressure, keratometry and A-scan measurements, plus lens and retinal 
photography, following pupil dilatation. Retinal photographs taken before
cataract surgery, and at 1, 6, 12, and 24 months after surgery are graded for
early and late AMD lesions, using the Wisconsin age-related maculopathy grading
system. The 1-month post-operative retinal photographs supplement the baseline
macular assessment for cases in which cataract occludes a clear view of the
macula pre-operatively. It is intended that study participants will be followed
for up to five years post-operatively to clarify the question of whether aphakic 
or pseudophakic, compared to phakic eyes, have a greater risk of developing AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18161615 [PubMed - indexed for MEDLINE]

482: Ophthalmic Epidemiol. 2007 Nov-Dec;14(6):399-407.

The epidemiology of age-related eye diseases in Mainland China.

Zhou Q, Friedman DS, Lu H, Duan X, Liang Y, Yang X, Wang F, Wang N.

Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital University of
Medical Sciences, China.

While many papers have been published regarding age-related eye diseases in
Mainland China in the past two decades, the variable quality of those reports
limit the conclusions that can be drawn. Many of these studies assessed blindness
and low vision rates, and these estimates are likely accurate. However, due to
lack of standardization of techniques for assessing cataract, glaucoma,
age-related macular degeneration, and diabetic retinopathy, estimates of the
burden of these diseases on the population are less reliable. Owing to the rapid 
economic development of China in the last decade, resources to address eyecare
problems are more likely to be available. Therefore, an accurate assessment of
the burden of various eye diseases is needed in order to improve blindness
prevention planning and program development.

Publication Types: 
    Review

PMID: 18161614 [PubMed - indexed for MEDLINE]

483: Ophthalmic Epidemiol. 2007 Nov-Dec;14(6):367-74.

Use of lipid-lowering agents for the prevention of age-related macular
degeneration: a meta-analysis of observational studies.

Chuo JY, Wiens M, Etminan M, Maberley DA.

Department of Ophthalmology and Visual Sciences, Faculty of Medicine, University 
of British Columbia, Vancouver, British Columbia, Canada. chuo@interchange@ubc.ca

PURPOSE: To examine the effect of lipid-lowering agents in the development of
age-related macular degeneration (AMD) through the techniques of meta-analysis.
METHODS: Case-control and cohort studies presenting relative risks and 95%
confidence intervals were identified through a literature review. Inclusion was
limited to studies where both the exposure of interest (lipid-lowering agents)
and outcome (AMD) were explicitly defined. Pooled estimates were computed using
the random effects model. To quantify heterogeneity we calculated the proportion 
of total variance of between study variance using the Ri statistic. The Q
statistic for heterogeneity was also calculated. RESULTS: Eight studies were
identified. The pooled relative risk (RR) for all studies was 0.74 (95% CI,
0.55-1.00). When only those studies examining the use of statins were pooled
(n=7), the RR was 0.70 (95% CI, 0.48-1.03). Using the Ri statistic, the
heterogeneity between studies was found to be 0.85 for all studies and 0.89 for
studies examining statins. CONCLUSION: Lipid-lowering agents, including statins, 
do not appear to lower the risk of developing AMD, although clinically
significant effects cannot be excluded. The use of these agents in the prevention
of AMD cannot be recommended until well designed prospective studies with long
follow up have demonstrated a benefit.

Publication Types: 
    Meta-Analysis
    Review

PMID: 18161610 [PubMed - indexed for MEDLINE]

484: Home Healthc Nurse. 2008 Jan;26(1):8-14; quiz 15-6.

My father's experience with macular degeneration: implications for the home
healthcare nurse.

Schexnaydre M, Carruth AK.

Southeastern Louisiana University, Hammond, Louisiana, USA.
maryleeschex@yahoo.com

Macular degeneration has become a problem of substantial proportions for older
adults. This article can help the home health nurse gain a greater understanding 
of macular degeneration and therefore be more effective in the home setting. The 
addition of vision rehabilitation also can prolong older adults' independent
years and enhance their satisfaction with life. Using Parse's human-becoming
theory as a theoretical framework, the home health nurse can coparticipate in the
older adult's experience of living and thus enhance the probability that the last
years will be a rewarding time of life.

Publication Types: 
    Review

PMID: 18158486 [PubMed - indexed for MEDLINE]

485: Arq Bras Oftalmol. 2007 Sep-Oct;70(5):858-61.

Macular edema associated with gyrate atrophy managed with intravitreal
triamcinolone: a case report.

Vasconcelos-Santos DV, Magalhães EP, Nehemy MB.

Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil. dvitor@ufmg.br

PURPOSE: To describe the use of 4 mg intravitreal triamcinolone acetonide (IVTA) 
for gyrate atrophy-related macular edema (ME) and to report anatomic and
functional outcomes, during a nine-month period. CASE REPORT: A 27-year-old
female complained of decreased vision since diagnosis of gyrate athrophy (GA),
six years before admission. At presentation visual acuity was 20/100 in OD and
20/80 in OS. Ophthalmological examination disclosed significant cataract in OD,
pseudophakia in OS and typical GA findings. Fluorescein angiography (FA)
disclosed ME that was confirmed by optical coherence tomography (OCT), which also
showed subfoveal fluid. OS was treated with a 4-mg IVTA injection. One month
later, vision improved to 20/50+1 and foveal thickness decreased, with less
leakage in FA. This picture was maintained up to six months, when there was
recurrence of ME to a level similar to the baseline. At nine months, visual
acuity dropped to 20/80, and ME was maintained, with remodeling in macular
profile. CONCLUSION:There is a transient therapeutic effect with 4-mg IVTA
injection for GA-related ME. After drug clearance, edema recurs, with return of
visual acuity to pretreatment level.

Publication Types: 
    Case Reports

PMID: 18157315 [PubMed - indexed for MEDLINE]

486: Arq Bras Oftalmol. 2007 Sep-Oct;70(5):771-6.

Comparison of the original Amsler grid with the preferential hyperacuity
perimeter for detecting choroidal neovascularization in age-related macular
degeneration.

Isaac DL, Avila MP, Cialdini AP.

Setor de Retina e Vítreo, Centro de Referência em Oftalmologia, Universidade
Federal de Goiás, Goiânia, GO, Brazil. cruvinelisaac@hotmail.com

PURPOSE: To compare the preferential hyperacuity perimeter (Preview PHP; Carl
Zeiss Meditec, Dublin, CA) with the original Amsler grid in the detection of
choroidal neovascularization (CNV) in patients with age-related macular
degeneration (AMD). METHODS: Patients were classified into groups, based on the
severity of the age-related macular degeneration and underwent preferential
hyperacuity perimeter and Amsler grid testing. High sensitivity and or high
specificity of a method were defined as the observation of at least 80% of each
one the parameters. RESULTS: Sixty-five patients (65 eyes) were analyzed
statistically. The sensitivity of detection of choroidal neovascularization was
70% by the Amsler grid and 90% by the preferential hyperacuity perimeter and the 
specificity of the Amsler grid was 85.5% and that of the preferential hyperacuity
perimeter 81.8%. CONCLUSIONS: The preferential hyperacuity perimeter has greater 
sensitivity than the Amsler grid in the detection of choroidal neovascularization
among patients over 50 years of age and is a promising method for monitoring
patients with age-related macular degeneration. Although the original Amsler grid
is less sensitive, it is a portable method, not expensive, accessible and
presents reasonable sensitivity and high specificity in the diagnosis of
choroidal neovascularization. Its use can be recommended for self-monitoring in
patients with age-related macular degeneration as an alternative to preferential 
hyperacuity perimeter and when this method is not available.

Publication Types: 
    Comparative Study

PMID: 18157300 [PubMed - indexed for MEDLINE]

487: Br J Ophthalmol. 2008 Jan;92(1):74-5.

Combined Pegaptanib sodium (Macugen) and photodynamic therapy in predominantly
classic juxtafoveal choroidal neovascularisation in age related macular
degeneration.

Calvo-González C, Reche-Frutos J, Donate-López J, García-Feijoó J, Leila M,
Fernández-Pérez C, Garcia-Sánchez J.

Hospital Universitario Clínico San Carlos, Madrid, Spain. calvo_glez@yahoo.es

AIMS: This prospective, open label, non-comparative, observational case series
evaluates 6-month results of Pegaptanib Sodium (Macugen) and Photodynamic Therapy
(PDT) in predominantly classic juxtafoveal choroidal neovascularisation (CNV) in 
age-related macular degeneration (AMD) in seven eyes of seven patients. RESULTS: 
Best corrected visual acuity (BCVA) diminished with a mean of five letters.
Initial area of CNV increased significantly from 1.4 mm2 to 2.7 mm2. There was a 
significant increase in the greatest linear dimension (GLD) from 1280.3 microm to
2065.7 microm at the 24-week follow-up. CONCLUSION: Predominantly classic
juxtafoveal CNVs are highly aggressive lesions that demonstrate poor response
despite combined therapy using PDT and Macugen.

Publication Types: 
    Clinical Trial

PMID: 18156376 [PubMed - indexed for MEDLINE]

488: Semin Ophthalmol. 2007 Oct-Dec;22(4):229-40.

Review of genetics in age related macular degeneration.

Montezuma SR, Sobrin L, Seddon JM.

Massachusetts Eye and Ear Infirmary and the Department of Ophthalmology, Harvard 
Medical School, 243 Charles Street, Boston, MA 02114, USA.

Age-related macular degeneration (AMD) is a degenerative disease of the retina
and the leading cause of blindness in industrialized countries. AMD is a complex 
disease caused by the combination of genetic predisposition and environmental
factors. The prevalence of AMD increases with age. The adverse effect of smoking 
is well established. Genetic predisposition has been demonstrated by familial
aggregation studies and twin studies. Using genome linkage scan and association
studies, multiple potentially causative genes have been identified. The
chromosomes most commonly implicated are 1q25-31 and 10q26. In particular,
variants in the gene for the complement factor H (CFH) and the genes
PLEKHA1/LOC387715/HTRA1, Factor B (BF) and complement component 2 (C2) have been 
implicated as major risk or protective factors for the development of AMD. There 
have been some advances in the treatment of this condition; however, a complete
cure remains remote but hopeful. Understanding the causative environmental and
genetic interactions will facilitate the development of future preventive methods
and treatments.

Publication Types: 
    Review

PMID: 18097986 [PubMed - indexed for MEDLINE]

489: Electromagn Biol Med. 2007;26(4):293-8.

Effects of endogenous cyclotronic ionic resonance (ICR) on macular diabetic
edema: preliminary results.

D'Andrea P, Maurizio L.

D'Andrea Clinic, Pescara, Italy. crs767fr@yahoo.com

The intent in this research was to verify the effects of the application of low
frequency magnetic fields to cases of macular diabetic edema. We treated six
patients afflicted by non-proliferating diabetic retinopathy with macular oedema.
Quantitative clinical appraisals of the retinal thickness were obtained for the
Optical Coherence Tomography (OCT I). None of the cases affected by non-cystoid
macular oedema (non-CMO), or with a relevant ischemic component, evidenced by
retinal fluorangiography, had further worsening in their clinical course during
the treatment. Only one of the patients, who underwent a long treatment period
with ICR demonstrated a significant reduction of the macular edema, with no need 
of other invasive therapeutic procedures (intravitreous injection of
triamcinolone and/or laser therapy).

Publication Types: 
    Case Reports

PMID: 18097816 [PubMed - indexed for MEDLINE]

490: Ophthalmologica. 2008;222(1):32-6. Epub 2007 Dec 19.

The status of diabetic retinopathy and diabetic macular edema in patients with
type 2 diabetes: a survey from Beixinjing District of Shanghai city in China.

Wang N, Xu X, Zou H, Zhu J, Wang W, Ho PC.

Department of Ophthalmology, Shanghai Jiaotong University Affiliated First
People's Hospital, Shanghai, China.

Diabetic macular edema (DME) is the major cause of vision loss in patients with
diabetic retinopathy (DR). The purpose of this study was to assess the prevalence
of DR and DME in a community in China and to analyze the characteristics of their
optical coherence tomography (OCT) images. This study was an incidence survey
based on data from 108,132 residents living in the Beixinjing District, Shanghai,
China. Patients with DME came from the local health network. OCT was performed in
151 eyes of 100 type 2 diabetes patients with DR and 102 eyes of normal control
subjects. Totally 795 cases were examined, and 215 of them were diagnosed to have
DR. The average thickness of the macular fovea was 195.56 microm in 151 eyes from
100 random samples. Forty-six eyes had macular thickening. The statistical
analysis showed that there was a positive correlation between the thickness of
the macular fovea and -log of best-corrected visual acuity (r = 0.2869, p =
0.0004) as well as the severity of DR (p = 0.0003). However, there was no
statistical significance between DME and posterior vitreous detachment. The
images of OCT in DME included 3 types. Best-corrected visual acuity moderately
correlated with retinal thickness. The macular thickness correlated with the
severity of DR but not with posterior vitreous detachment. (c) 2007 S. Karger AG,
Basel.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18097178 [PubMed - indexed for MEDLINE]

491: Ophthalmology. 2008 Jun;115(6):1032-1038.e4. Epub 2007 Dec 21.

Vitamin usage patterns in the prevention of advanced age-related macular
degeneration.

Charkoudian LD, Gower EW, Solomon SD, Schachat AP, Bressler NM, Bressler SB.

Scheie Eye Institute, University of Pennsylvania School of Medicine,
Philadelphia, Pennsylvania, USA.

OBJECTIVE: To describe micronutrient usage patterns among patients at a tertiary 
ophthalmic center. DESIGN: Cross-sectional clinical case series. PARTICIPANTS:
Three hundred thirty-two adult patients with a diagnosis of age-related macular
degeneration (AMD). METHODS: Participants were surveyed about micronutrient usage
patterns. The treating ophthalmologist recorded AMD severity using the
Age-Related Eye Disease Study (AREDS) classification system. MAIN OUTCOME
MEASURES: Responses to study questionnaire and level of AMD severity. RESULTS:
Among 332 participants, 309 (93%) were using supplements, among which 174 (52%)
supplemented with an AREDS-like formulation. Of these 174, 140 (80%) were
considered AREDS supplement candidates based on study guidelines. Applying AREDS 
supplementation guidelines to the full cohort, 228 (69%) were candidates for
supplementation. Only 140 (61%) of these individuals were confirmed to be using
the correct formulation and dosage; an additional 13 (6%) used the AREDS
formulation but were not using the recommended dosage. CONCLUSIONS: Among
patients receiving care for AMD at a tertiary retinal center, more than one third
of those deemed candidates for AREDS-type supplements were not using them or were
using an incorrect dose. Furthermore, nearly one fifth of participants who were
using high-dose supplements did not have a level of AMD anticipated to benefit
from usage. Increased patient education is needed regarding the recommendations
of AREDS.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18096234 [PubMed - indexed for MEDLINE]

492: Exp Eye Res. 2008 Feb;86(2):296-304. Epub 2007 Nov 12.

Analysis of visual pigment by fundus autofluorescence.

Theelen T, Berendschot TT, Boon CJ, Hoyng CB, Klevering BJ.

Department of Ophthalmology, Radboud University Nijmegen Medical Centre, Philips 
van Leydenlaan 15, Nijmegen, The Netherlands. t.theelen@ohk.umcn.nl

This study investigated changes of short-wavelength fundus autofluorescence
(SW-AF) by retinal bleaching effects. All measurements were performed with the
Heidelberg Retina Angiograph 2 (HRA 2). Initially, experimental imaging was done 
on a healthy eye after dark adaptation. Photopigment was bleached within the
central 30 degrees of the fundus by HRA 2 excitation light. Then SW-AF imaging of
this region was performed, and SW-AF of the surrounding, unbleached 25 degrees
fundus region was subsequently studied by a wide-field lens. Next, another 30
degrees SW-AF image of the posterior pole was obtained after complete dark
adaptation. Then an extra SW-AF examination was performed with 15 degrees
temporal eccentricity, overlapping the original examination area. Finally, a
successive image series was carried out on the dark-adapted eye to test for
bleaching kinetics. The second and third experiments were also performed on eyes 
with macular dystrophies. Distinct regions of increased SW-AF were observed after
strong illumination with the blue excitation light in all eyes studied. During
light adaptation mean gray levels showed a saturation plateau after an initial
steep increase. The resulting gray-value maps showed significant differences of
pixel intensities between bleached and unbleached parts of the fundus.
Two-dimensional density difference maps allowed analysis of visual pigment
distribution and density in both healthy eyes and eyes with macular dystrophies. 
Our observations highlight the viability of objective, non-invasive evaluation of
visual pigment in the healthy and diseased human retina by means of confocal
fundus autofluorescence.

PMID: 18096158 [PubMed - indexed for MEDLINE]

493: Pharmacoeconomics. 2008;26(1):57-73.

Economic burden of bilateral neovascular age-related macular degeneration:
multi-country observational study.

Cruess AF, Zlateva G, Xu X, Soubrane G, Pauleikhoff D, Lotery A, Mones J, Buggage
R, Schaefer C, Knight T, Goss TF.

Department of Ophthalmology and Visual Sciences, Dalhousie University, Halifax,
Nova Scotia, Canada. cruess@dal.ca <cruess@dal.ca>

BACKGROUND: There is limited previous research examining the healthcare costs of 
neovascular age-related macular degeneration (NV-AMD), which constrains our
understanding of the economic impact of this condition. With aging populations,
this leading cause of rapid vision loss in Western countries is expected to
become a pressing health predicament, requiring decision makers to evaluate
alternative treatment strategies for AMD. OBJECTIVE: To document the economic
burden of bilateral NV-AMD, the late stage of AMD, in elderly patients, from a
societal perspective. STUDY DESIGN, SETTING AND PARTICIPANTS: A cross-sectional, 
observational study surveyed 401 patients with bilateral NV-AMD and 471 non-AMD
subjects in Canada, France, Germany, Spain and the UK. Physicians' records and
subjects' standardized telephone interviews were used to record medical resource 
utilization, assistance with daily living and social benefits. Annual bilateral
NV-AMD-related socioeconomic costs were calculated in euro, year 2005 values.
MAIN OUTCOME MEASURES: Societal costs including direct vision-related medical
costs (e.g. treatment of AMD and vision-related equipment), direct
non-vision-related medical costs (e.g. medications) and direct
non-medical-related costs (e.g. home healthcare and social services) were the
main outcome measures. RESULTS: The demographic profile of NV-AMD patients was
similar across countries; however, co-morbid condition profiles varied. NV-AMD
patients reported substantial health-related problems and associated health
resource utilization (HRU). In the previous 12 months, 12-22% of patients fell,
and half of these patients required medical treatments. More than 20% (range
21-59%) of patients were prescribed vision-enhancing equipment. More than half of
the patients (54-81%) were living with a spouse or family member and 19-41%
reported receiving assistance for activities of daily living.The average annual
societal cost per bilateral NV-AMD patient treated was estimated to be euro 7879 
in Canada, euro 7349 in France, euro 12 445 in Germany, euro 5732 in Spain and
euro 5300 in the UK, and direct vision-related medical costs accounted for 23-63%
of the total cost. Half of the patients were diagnosed with bilateral NV-AMD for 
<1 year, with an average length of 5 months; there were no statistically
significant differences in total annual costs per patient between these patients 
and those who were diagnosed with bilateral disease for > or =1 year. Estimated
annual societal costs of bilateral NV-AMD patients in these countries ranged from
euro 268 to euro 1311 million. Estimated annual societal costs of all NV-AMD
patients in these countries ranged from euro 671 to euro 3278 million.
CONCLUSIONS: Bilateral NV-AMD imposes significant functional impairment on
patients, leading to increased HRU and a high societal cost burden. Differences
in national healthcare systems and NV-AMD treatment patterns were reflected in
the wide variation of NV-AMD costs across the five surveyed countries. Even
though the prevalence rates and per-patient costs varied by country, the societal
costs of NV-AMD patients were substantial in each country. Earlier intervention
with effective therapies is expected to reduce disease burden and disability
associated with NV-AMD and, thus, decrease the overall societal cost.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18088159 [PubMed - indexed for MEDLINE]

494: Curr Eye Res. 2007 Dec;32(12):1073-82.

Preservation of retinoid influx into eye tissues of ABCR-deficient mice.

Qtaishat NM, Pepperberg DR.

Lions of Illinois Eye Research Institute, Department of Ophthalmology and Visual 
Sciences, University of Illinois at Chicago, College of Medicine, Chicago 60612, 
USA.

Using an in vivo radiolabeling technique, we investigated the movement of
retinoid into the retinal pigment epithelium (RPE) of the abcr-/- mouse, which
lacks the photoreceptor ABCR protein and is a model for Stargardt disease. Eye
tissues and serum obtained from dark-adapted, 5- to 8-month-old abcr-/- and
control mice following the intraperitoneal injection of all-trans ((3)H)retinol
were analyzed to determine the inferred influx of retinoid from the serum into
the RPE. At 4.5 hr post-injection, the inferred all-trans retinol influx in
abcr-/- mice, which possess the leucine 450 variant of RPE65 protein, was 0.011
+/- 0.004 nmol (n = 3). This value did not differ significantly from that
determined in age-matched controls possessing the methionine 450 variant of RPE65
(0.015 +/- 0.003 nmol; n = 3) or from 3-month-old wildtype mice that possess the 
leucine 450 RPE65 variant (0.020 +/- 0.007; n = 4). Thus, the absence of ABCR
does not significantly compromise the passage of retinoid from the serum into the
RPE under dark-adapted conditions.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18085472 [PubMed - indexed for MEDLINE]

495: Hum Mol Genet. 2008 Apr 1;17(7):971-7. Epub 2007 Dec 15.

Deletion of CFHR3 and CFHR1 genes in age-related macular degeneration.

Spencer KL, Hauser MA, Olson LM, Schmidt S, Scott WK, Gallins P, Agarwal A,
Postel EA, Pericak-Vance MA, Haines JL.

Center for Human Genetics Research, Vanderbilt University Medical Center,
Nashville, TN 37232, USA.

Age-related macular degeneration (AMD) impairs vision for approximately 7.5
million Americans. Both susceptibility variants and protective haplotypes in the 
complement factor H (CFH) gene modulate risk for AMD. Recently, deletion of the
'CFH-related' genes CFHR1 and CFHR3 was found to be segregating with a particular
CFH haplotype, which reduced the risk of AMD. We tested the deletion for
association in a Caucasian population of 780 cases and 265 controls and examined 
its effect in the context of known AMD risk factors. The deletion did not
segregate perfectly with any one SNP, as previously suggested. CFH haplotype P2
was the most frequent haplotype in deletion homozygotes (47%), and the majority
(14/16) of these individuals were homozygous for the non-risk allele of Y402H.
Overall, deletion homozygosity was significantly more frequent in controls than
cases (2.6% controls, 0.8% cases, P = 0.025, OR = 0.29, 95% CI = 0.10-0.86).
After controlling for age, Y402H, smoking and LOC387715 A69S, the protective
effect of the deletion was no longer statistically significant (P = 0.27).
However, using a CFH haplotype that all deletion homozygotes share as a surrogate
for the deletion, this marker remained modestly associated with AMD after
adjustment for known risk factors (OR = 0.63, 95% CI 0.39-1.04, P = 0.07).
Therefore, deletion of CFHR1 and CFHR3 may account for a small portion of the
protection from AMD associated with particular haplotypes in CFH. The presence of
protective haplotypes in CFH that do not carry the deletion, suggests that other 
protective variants in this region have yet to be discovered.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 18084039 [PubMed - indexed for MEDLINE]

496: Clin Exp Immunol. 2008 Jan;151(1):1-13.

Translational mini-review series on complement factor H: genetics and disease
associations of human complement factor H.

de Córdoba SR, de Jorge EG.

Centro de Investigaciones Biológicas and Centro de Investigación Biomédica en Red
de Enfermedades Raras, Madrid, Spain. SRdeCordoba@cib.csic.es

Factor H is an abundant plasma glycoprotein that plays a critical role in the
regulation of the complement system in plasma and in the protection of host cells
and tissues from damage by complement activation. Several recent studies have
described the association of genetic variations of the complement factor H gene
(CFH) with atypical haemolytic uraemic syndrome (aHUS), age-related macular
degeneration (AMD) and membranoproliferative glomerulonephritis (MPGN). This
review summarizes our current knowledge of CFH genetics and examines the CFH
genotype-phenotype correlations that are helping to understand the molecular
basis underlying these renal and ocular pathologies.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18081690 [PubMed - indexed for MEDLINE]

497: Mol Vis. 2007 Nov 26;13:2153-9.

PLEKHA1-LOC387715-HTRA1 polymorphisms and exudative age-related macular
degeneration in the French population.

Leveziel N, Souied EH, Richard F, Barbu V, Zourdani A, Morineau G, Zerbib J,
Coscas G, Soubrane G, Benlian P.

Creteil University Eye Clinic, Faculte de Medecine Henri Mondor, Creteil, France.

PURPOSE: Identification of genetic factors for age-related macular degeneration
(AMD) is of crucial importance in this common cause of blindness. Exudative AMD
is rapidly progressive and usually associated with severe prognosis. Our purpose 
was to investigate this association on locus 10q26 in a case-control study
including French patients specifically affected with exudative AMD. METHODS:
Polymorphisms rs4146894:G>A of Pleckstrin Homology Domain-containing Protein
Family A member 1 (PLEKHA1) gene, rs10490924:G>T at LOC387715, and rs11200638:G>A
of HTRA1 (HTRA serine peptidase 1) gene were analyzed in AMD cases (n=118,
age=72.3+/-3.8 years old) and healthy controls (n=116, age=72.0+/-3.8 years old).
RESULTS: PLEKHA1 polymorphism was associated with AMD. The A allele frequency was
0.67 in cases versus 0.41 in controls, (p=0.0001). After age and sex adjustment, 
the odds ratio for risk of AMD was 9.1 (4.0-20.9, 95% CI, p=0.0001) for the AA
genotype and 2.6 (1.3-5.5, 95% CI, p=0.04) for the AG genotype, conditional on
HTRA1. Association was even stronger and independent with HTRA1. The A allele
frequency was 0.51 in cases versus 0.22 in controls, (p=0.0001). The odds ratio
was 15.5 (5.5-43.9, 95% CI, p=0.0001) for the AA genotype and 3.4 (1.9-6.1, 95%
CI, p=0.0001) for the AG genotype. No further information was obtained from
LOC387715 due to virtually complete linkage disequilibrium with HTRA1
polymorphism in cases (D'=1.0) and controls (D'=0.98). Although a role for
PLEKHA1 could not be totally excluded, there was a four times higher AMD risk was
associated with haplotype "A-T-A" involving "PLEKHA1-LOC387715-HTRA1" risk
alleles. CONCLUSIONS: Compared to PLEKHA1, HTRA1/LOC387715 genetic variations
were independently and strongly associated with exudative AMD in the French
population. Chromosome-10 genetic variants appear as potentially useful risk
markers for early detection of AMD.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 18079691 [PubMed - indexed for MEDLINE]

498: Mol Vis. 2007 Nov 26;13:2148-52.

A tag-single nucleotide polymorphisms approach to the vascular endothelial growth
factor-A gene in age-related macular degeneration.

Richardson AJ, Islam FM, Guymer RH, Cain M, Baird PN.

Centre for Eye Research Australia, University of Melbourne, Australia.
andreajr@unimelb.edu.au

PURPOSE: Age-related macular degeneration (AMD) is the leading cause of poor
vision in the developed world, and its pathogenesis remains unknown. The most
devastating form of end stage disease is neovascular or wet AMD, where there is
abnormal growth of new blood vessels under the retina. Vascular endothelial
growth factor (VEGF) is thought to be a major player in the stimulus of this
abnormal growth of blood vessels. We undertook a case-control association study
to investigate the VEGF-A gene, a known angiogenic gene that has previously been 
associated with AMD. METHODS: We recruited 577 individuals with AMD (early,
atrophic, and neovascular AMD) and 173 ethnically matched controls for our study.
We employed a tag-single nucleotide polymorphisms (tSNP) approach to investigate 
this gene using a series of seven tSNPs that encompassed the coding region of the
VEGF gene as well as its promoter. Alleles were determined by a MALDI-TOF based
approach followed by statistical analysis. RESULTS: One SNP (rs3024997) showed
evidence of departure from Hardy-Weinberg equilibrium in only the AMD cases.
Therefore, it was retained for further analysis. All other SNPs in our study
showed no departure from Hardy-Weinberg equilibrium. No association was found
between any of the VEGF tSNPs analyzed in our study and AMD nor any of its
sub-types. CONCLUSIONS: Using a tSNP approach, we found no evidence of an
association of these SNPs within the VEGF-A gene being associated with either AMD
or any of its subtypes in our population.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18079689 [PubMed - indexed for MEDLINE]

499: Aust Fam Physician. 2007 Dec;36(12):1026-8.

Age related macular degeneration--should your patients be taking additional
supplements?

Jones AA.

City Eye Centre, Brisbane, Queensland. draajones@hotmail.com

BACKGROUND: The use of over-the-counter complementary medicines and supplements
is growing. Patients with age related macular degeneration (AMD) are likely to
have heard of, or are possibly already taking, additional supplements that may
increase their chances of retaining useful eyesight. OBJECTIVE: This article
looks specifically at evidence regarding the effects of over-the-counter oral
supplements such as antioxidants and omega-3 fatty acids on AMD. DISCUSSION: Diet
manipulation and supplementation has a role to play in modifying the risk of
disease progression in AMD patients. A combination of vitamins C and E, beta
carotene, zinc oxide and cupric oxide has been shown to reduce the rate of visual
loss in dry AMD. However, commercially available preparations do not always
recommend the correct intake that would match levels found in clinical trials.
Other carotenoids such as lutein and zeaxanthin may also be beneficial, intake of
these can be increased by altering diet alone. Other useful dietary changes
include reducing both animal and vegetable fats and increasing the consumption of
fish and nuts.

Publication Types: 
    Review

PMID: 18075628 [PubMed - indexed for MEDLINE]

500: Graefes Arch Clin Exp Ophthalmol. 2008 May;246(5):653-9. Epub 2007 Dec 11.

Time-dependent effects on contrast sensitivity, near and distance acuity:
difference in functional parameters? (Prospective, randomized pilot trial of
photodynamic therapy versus full macular translocation).

Ziemssen F, Lüke M, Bartz-Schmidt KU, Gelisken F.

Department for Ophthalmology, University Eye Hospital, Eberhard-Karls University,
Schleichstr. 12-16, 72076 Tuebingen, Germany. focke.ziemssen@med.uni-tuebingen.de

PURPOSE: To report the change of contrast sensitivity (CS) after photodynamic
therapy (PDT) vs full macular translocation (FMT) for neovascular age-related
macular degeneration (AMD), and to relate this to other measures of visual
function (distance and near acuity). METHODS: Fifty patients (50 eyes) with
predominantly classic subfoveal choroidal neovascularisation (CNV) secondary to
AMD were randomized to PDT or FMT. CS was measured with Pelli-Robson charts.
Acuity scores of near visual function (NVS) were calculated after testing with
visual acuity cards of the Swiss National Association of and for the Blind
(SNAB). Best corrected distance visual acuity (DVA) was determined according to a
standardized protocol with EDTRS charts. Primary end point was the change of CS
at 12-month examination from baseline. The interaction of the CS with NVS and DVA
was analysed. RESULTS: Mean CS showed a decrease in both treatment groups (FMT:
-2 letters, PDT: -3 letters, p=0.969) at 12-month examination from baseline.
While mean NVS improved by seven letters in the FMT group, a decrease of more
than ten letters was seen in the PDT group (p<0.05). We found no agreement
between CS and high-contrast acuity (NVS, DVA). In FMT patients, the parameters
at baseline (CS, NVS, DVA) correlated poorly with the corresponding 12-month
results, therefore providing no informative basis to predict the later functional
development. In contrast, PDT patients showed strong baseline-to-outcome
coherence with baseline measures also associated with better final values.
CONCLUSIONS: Although FMT can initiate recovery of near and distance acuity over 
the period of 1 year in selected patients with classic CNV, CS did not differ
between FMT and PDT. We found no close connection of CS with DVA or NVS,
especially after FMT. Knowledge about the unequal variation of visual parameters 
can provide more comprehensive information when advising patients on different
therapeutic options. That also applies in particular to vascular endothelial
growth factor inhibitors, which seem to promise an even higher extent of gain in 
CS and to reach the peak of recovery at an earlier time.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial

PMID: 18071731 [PubMed - indexed for MEDLINE]

501: Geriatr Nurs. 2007 Nov-Dec;28(6):387-92.

Macular degeneration: types, causes, and possible interventions.

Feret A, Steinweg S, Griffin HC, Glover S.

Department of Curriculum and Instruction, East Carolina University, Greenville,
North Carolina, USA.

Macular degeneration is the most common cause of blindness in individuals over 50
years of age. The condition is frequently classified into the categories of
early, intermediate, and advanced stages. Current interventions concerning
macular degeneration include a healthy lifestyle, diet, medical intervention,
surgery, and environmental assistance. Future strategies for individuals with
macular degeneration will possibly stress gene therapy, retinal transplantation, 
artificial vision, retinal prosthesis, and neuroprotection.

Publication Types: 
    Review

PMID: 18068822 [PubMed - indexed for MEDLINE]

502: Ophthalmology. 2008 Mar;115(3):520-4. Epub 2007 Dec 11.

Peripheral reticular pigmentary change is associated with complement factor H
polymorphism (Y402H) in age-related macular degeneration.

Shuler RK Jr, Schmidt S, Gallins P, Hauser MA, Scott WK, Caldwell J, Agarwal A,
Haines JL, Pericak-Vance MA, Postel EA.

Duke University Eye Center, Durham, North Carolina 27710, USA.

OBJECTIVE: To examine phenotypes of age-related macular degeneration (AMD)
patients with the complement factor H (CFH) variant (Y402H, C allele at
rs1061170). DESIGN: Clinic-based case series study. PARTICIPANTS: The data set
contained a total of 956 unrelated cases of AMD. METHODS: Age-related macular
degeneration phenotypes of 796 carriers of the CFH Y402H variant were compared
with the AMD phenotypes of 160 noncarriers. MAIN OUTCOME MEASURES: Presence or
absence of 34 phenotypic features. RESULTS: Of the 34 features analyzed, only
peripheral reticular pigmentary change (PRPC) was associated with this CFH
variant (P = 0.0006). The proportion of AMD cases with PRPC correlated with the
number of CFH risk C alleles in a dose-response fashion. CONCLUSIONS: The CFH
Y402H polymorphism is associated with PRPC, suggesting that AMD changes are not
limited to the macula. Current AMD grading methods assess only the macula and
should consider incorporating peripheral retinal changes. Phenotypes that suggest
a high-risk genotype may prove valuable for diagnostic, therapeutic, and research
purposes.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18067970 [PubMed - indexed for MEDLINE]

503: Ophthalmology. 2008 Mar;115(3):533-539.e2. Epub 2007 Dec 11.

The relationship of macular thickness to clinically graded diabetic retinopathy
severity in eyes without clinically detected diabetic macular edema.

Browning DJ, Fraser CM, Clark S.

Charlotte Eye, Ear, Nose, and Throat Associates, PA, Charlotte, North Carolina,
USA. djbrowning@carolina.rr.com

PURPOSE: To examine the relationship of optical coherence tomography (OCT)
measured macular thickness to retinopathy severity in patients with diabetes and 
no clinically detectable macular edema. DESIGN: Retrospective observational case 
series. PARTICIPANTS: Three hundred eighty-three eyes of 383 patients of a
private retina practice; including 100 normal eyes of patients without diabetes, 
100 eyes of diabetics without retinopathy, 100 eyes of diabetics with mild to
moderate retinopathy, 35 eyes of diabetics with severe nonproliferative or
proliferative retinopathy, and 48 eyes of diabetics with regressed proliferative 
retinopathy. METHODS: Review of clinical charts and optical coherence tomography 
measurements. MAIN OUTCOME MEASURES: Central subfield mean thickness (CSMT),
inner and outer zone measurements, and total macular volume. RESULTS: Central
subfield mean thicknesses (mean +/- standard deviation) were 208+/-22, 198+/-25, 
204+/-26, 224+/-38, and 205+/-27 microm for normals, eyes of diabetics without
retinopathy, eyes with mild to moderate nonproliferative retinopathy, eyes with
severe nonproliferative to proliferative retinopathy, and eyes with regressed
proliferative retinopathy, respectively. For all groups, mean CSMT was larger in 
males than in females. Statistically significant differences by gender were
observed for normals, diabetics without retinopathy, and diabetics with mild to
moderate nonproliferative retinopathy (mean differences, 12, 14, and 18 microm,
respectively; Ps = 0.0057, 0.0057, and 0.0002). For increasing retinopathy
severity, the probability of macular thickening detected by OCT but not detected 
by clinical examination increased. Fifteen percent of eyes with severe
nonproliferative or proliferative retinopathy and no clinically detected edema
had OCT-measured macular thickening. CONCLUSIONS: Because OCT measurements are
gender dependent, gender balance or statistical adjustment for gender imbalances 
of compared groups in OCT studies of diabetic macular edema is important. As
retinopathy severity increases, the probability of subclinical edema rises.
Except for an individual baseline measurement possibly useful for longitudinal
comparison, the data suggest that there is little reason routinely to obtain OCT 
in eyes with diabetes and no retinopathy or mild to moderate diabetic retinopathy
when clinical examination fails to show macular edema.

PMID: 18067962 [PubMed - indexed for MEDLINE]

504: Am J Ophthalmol. 2008 Feb;145(2):249-256. Epub 2007 Dec 11.

Comment in:
    Am J Ophthalmol. 2008 May;145(5):937; author reply 938.

Intravitreal bevacizumab for treatment of neovascular age-related macular
degeneration: a one-year prospective study.

Bashshur ZF, Haddad ZA, Schakal A, Jaafar RF, Saab M, Noureddin BN.

Department of Ophthalmology, American University of Beirut-Medical Center,
Beirut, Lebanon. zb00@aub.edu.lb

PURPOSE: To investigate the efficacy of intravitreal bevacizumab for treatment of
neovascular age-related macular degeneration (AMD). DESIGN: Prospective,
open-label, nonrandomized clinical study. METHODS: Sixty patients (60 eyes) with 
subfoveal choroidal neovascular membrane (CNV) attributable to AMD participated
in this study at the American University of Beirut and Hotel Dieu de France
Retina Clinics. All lesion types were included except for retinal angiomatous
proliferation. In the initial treatment phase, intravitreal bevacizumab (2.5
mg/0.1 ml) was given at baseline, and then two additional monthly injections were
given if the macula was not dry on optical coherence tomography. The criteria for
re-injection after the induction phase were presence of new fluid in the macula, 
increased central retinal thickness (CRT) at least 100 microm, loss of at least
five letters of vision with increased fluid in the macula, new classic CNV or new
macular hemorrhages. Main outcome measure was the proportion of eyes losing <15
letters of vision after 12 months. RESULTS: Fifty-one patients (51 eyes)
completed the 12 months. Mean visual acuity improved from 45.7 letters at
baseline to 53.1 letters at 12 months (P = .004), and 47 eyes (92.2%) lost <15
letters. Mean CRT decreased from 327.4 microm at baseline to 227.8 microm at 12
months (P < .001). A mean of 3.4 injections were given over the course of the
study, and no ocular or systemic side-effects were noted. CONCLUSION: Eyes with
neovascular AMD treated with intravitreal bevacizumab over 12 months had
significant anatomical and functional improvement. Further studies need to
confirm the long-term efficacy of this treatment.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 18067876 [PubMed - indexed for MEDLINE]

505: Am J Ophthalmol. 2008 Feb;145(2):303-307. Epub 2007 Dec 3.

Phenotype analysis of patients with the risk variant LOC387715 (A69S) in
age-related macular degeneration.

Shuler RK Jr, Schmidt S, Gallins P, Hauser MA, Scott WK, Caldwell J, Agarwal A,
Haines JL, Pericak-Vance MA, Postel EA.

Duke University Eye Center, Durham, NC 27710, USA.

PURPOSE: To examine phenotypes of age-related macular degeneration (AMD) patients
with the LOC387715 variant (T allele at rs10490924, A69S). DESIGN: Retrospective,
observational case series. METHODS: This clinic-based case series data set
contained 775 unrelated cases of AMD. AMD phenotypes of three groups, determined 
by the number of LOC387715 risk alleles, were compared regarding the presence or 
absence of 16 phenotypic features. RESULTS: The number of AMD cases in each group
was 164 cases (two risk alleles), 330 cases (one risk allele), and 281 cases
(zero risk allele). The mean age at examination for homozygous carriers of the
LOC387715 risk allele was significantly lower (73.9 years) than the age for
carriers of one (76.4 years) or no (77.1 years) risk allele (P = .0003). Of the
16 features analyzed, only AMD grade (P = .00002) was significantly associated
with the LOC387715 variant. As the number of LOC387715 risk alleles increased,
the proportion of grade 5 AMD cases increased in a dose-response fashion.
CONCLUSIONS: The LOC387715 variant appears to be an independent risk factor for
grade 5 (neovascular) AMD. This variant may also be associated with an earlier
onset of AMD. Phenotypes that suggest a high-risk genotype may prove valuable for
diagnostic, therapeutic, and research purposes.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 18061132 [PubMed - indexed for MEDLINE]

506: Hong Kong Med J. 2007 Dec;13(6):460-70.

Comment in:
    Hong Kong Med J. 2008 Feb;14(1):81.

An update of treatment options for neovascular age-related macular degeneration.

Iu LP, Kwok AK.

Department of Ophthalmology, Hong Kong Sanatorium and Hospital, Hong Kong.

OBJECTIVES: To review the role of conventional and new treatment modalities in
the management of neovascular age-related macular degeneration. DATA SOURCES AND 
EXTRACTION: Literature search of Medline till March 2007, using the key
words/terms 'treatment' and 'age-related macular degeneration' to retrieve
relevant original papers and review articles. DATA SYNTHESIS: Age-related macular
degeneration is the leading cause of irreversible visual loss in the elderly in
developed countries. Neovascular age-related macular degeneration has a
relentless course and the consequent visual loss is debilitating. Successful
treatment has always been a challenge due to poor understanding of its
pathogenesis. Laser photocoagulation and photodynamic therapy with verteporfin
are the standard conventional treatments. However, these approaches do not
prevent disease recurrence and repeated treatments are required. Recent advances 
in understanding the molecular pathway for the angiogenesis of neovascular
age-related macular degeneration enables exploration of new treatment approaches.
Antiangiogenic therapy with anti-vascular endothelial growth factor agents, such 
as pegaptanib and ranibizumab, have recently been approved for clinical practice.
Other antiangiogenic agents include bevacizumab, triamcinolone, and anecortave
are also being evaluated in clinical trials. Additional treatment modalities
include transpupillary thermotherapy and surgical intervention. CONCLUSIONS:
Regarding patients with neovascular age-related macular degeneration, increased
understanding in its pathogenesis coupled with rapid development in instrumental 
technology and new/emerging medications greatly expands available treatment
options. Despite these various therapeutic options, current treatment is mainly
directed at achieving visual stabilisation. Restoration of vision with newer
agents is limited and not possible in every patient. Thus, early recognition and 
treatment to arrest the progression of neovascular age-related macular
degeneration is the preferred means of attaining the best visual outcome.

Publication Types: 
    Review

PMID: 18057435 [PubMed - indexed for MEDLINE]

507: Invest Ophthalmol Vis Sci. 2007 Dec;48(12):5815-22.

Eccentric fixation in Stargardt's disease assessed by Tübingen perimetry.

Messias A, Reinhard J, Velasco e Cruz AA, Dietz K, MacKeben M,
Trauzettel-Klosinski S.

Centre for Ophthalmology, University of Tübingen, Tübingen, Germany.

PURPOSE: To measure eccentric fixation characteristics in visual fields of
patients with Stargardt's disease. METHODS: The positions of fixation loci (FL)
in the visual field were determined by Tübingen perimetry (TP), using the
position of the blind spots in 173 patients. Altogether, 669 visual fields were
measured at baseline and during follow-up. Twenty patients were also examined by 
scanning laser ophthalmoscope (SLO). RESULTS: Ninety-five of 173 patients showed 
a ring scotoma with central fixation in at least one test, which could persist
for up to 18.8 years. The median age for a 50% chance of the development of
eccentric fixation was 23.6 years. One hundred four patients (203 eyes) used
eccentric fixation in at least one eye; in 154 eyes, the FL was placed below the 
scotoma and in 33 eyes to the left of it, in 11 to the right of it, and in 5
above it. Once the FL was chosen, it remained within the same visual field area
at subsequent tests, varying on average by 1.76 degrees. Compared with SLO
results, the mean distance between FL and PRL was 1.90 degrees. CONCLUSIONS: It
is possible to determine the position of the FL by perimetry with sufficient
accuracy if the blind spot is well delimited. Stargardt patients can keep central
fixation for different time intervals before changing to an eccentric FL. Most of
them show an FL below the central scotoma, which is considered favorable for
horizontal reading.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18055836 [PubMed - indexed for MEDLINE]

508: Invest Ophthalmol Vis Sci. 2007 Dec;48(12):5647-52.

The effect of topical diclofenac on choroidal blood flow in early postoperative
pseudophakias with regard to cystoid macular edema formation.

Miyake K, Nishimura K, Harino S, Ota I, Asano S, Kondo N, Miyake S.

Shohzankai Medical Foundation, Miyake Eye Hospital, Kita-ku, Nagoya, Japan.
miyake@spice.or.jp

PURPOSE: To study the chronological change in choroidal blood flow (ChBFlow),
disruption of the blood-aqueous barrier, and incidence of cystoid macular edema
(CME) in early postoperative pseudophakic eyes, as well as the effect of
nonsteroidal anti-inflammatory drug (NSAID) eye drops on these phenomena.
METHODS: Fifty patients who underwent phacoemulsification and foldable
intraocular lens (IOL) implantation were randomized to receive either topical
diclofenac or fluorometholone for 5 postoperative weeks. An additional 20
subjects, with long-standing pseudophakia served as the control. The
blood-aqueous barrier was examined by laser flarimetry and choroidal blood
velocity (ChBVel), volume (ChBVol), and ChBFlow by laser Doppler flowmetry (LDF) 
at 2 days and 1, 2, and 5 weeks after surgery. The incidence and severity of CME 
were evaluated by fluorescein angiography at 2 and 5 weeks after surgery.
RESULTS: Compared with patients taking diclofenac, those receiving
fluorometholone showed significantly reduced ChBVol at 2 weeks (0.38 +/- 0.08 vs.
0.32 +/- 0.07, P = 0.022) and ChBFlow at 1 (11.01 +/- 1.74 vs. 9.35 +/- 1.51, P =
0.003) and 2 (11.15 +/- 1.43 vs. 8.47 +/- 1.27, P = 0.000) weeks after surgery,
as well as a significantly elevated amount of anterior flare at 1 (8.9 +/- 2.2
vs. 24.4 +/- 18.9, P = 0.001) and 2 (9.2 +/- 3.5 vs. 16.7 +/- 12.3, P = 0.025)
weeks after surgery. The ChBVol and ChBFlow in the fluorometholone group,
however, returned to normal and was not different from the diclofenac group at 5 
weeks after surgery. The incidence of fluorescein angiographic CME trended to be 
higher (P = 0.08) at 2 weeks and was significantly higher (P = 0.001) at 5 weeks 
after surgery in eyes with fluoromethalone than with diclofenac. CONCLUSIONS:
Reduction of ChBFlow, disruption of the blood-aqueous barrier, and incidence of
CME in early postsurgical pseudophakic eyes were more effectively prevented
chronologically in eyes treated with diclofenac than in those treated with
fluorometholone.

Publication Types: 
    Randomized Controlled Trial

PMID: 18055815 [PubMed - indexed for MEDLINE]

509: Invest Ophthalmol Vis Sci. 2007 Dec;48(12):5464-72.

Circulating hematopoietic stem cells in patients with neovascular age-related
macular degeneration.

Yodoi Y, Sasahara M, Kameda T, Yoshimura N, Otani A.

Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School
of Medicine, Sakyo-ku, Kyoto, Japan.

PURPOSE: Circulating hematopoietic stem cells (HSCs) appear to have roles in the 
formation of choroidal neovascularization (CNV) in age-related macular
degeneration (AMD). This study was conducted to investigate whether the number or
function of HSCs plays a role in neovascular AMD. METHODS: Eighty-one patients
with neovascular AMD who underwent comprehensive fundus examinations every 3
months were included. The number of CD34(+) HSCs isolated from peripheral blood
was counted by flow cytometry. Serum cytokine levels were assessed by
enzyme-linked immunosorbent assay. To examine the function of circulating HSCs,
mononuclear cells were cultured and then colony forming unit (CFU-EC) and
migration were measured. RESULTS: The number of circulating CD34(+) HSCs was
significantly increased in the patients with active CNV without major systemic
diseases (stable: 3.8 +/- 0.3 cells/microL, active: 5.5 +/- 0.7 cells/microL,
stable versus active: P < 0.05). The number of HSCs correlated positively with
the erythropoietin serum level (r = 0.47, P = 0.002). Although there was no
significant difference in the CFU-EC between the patients with CNV and the
control subjects, a significant decrease of CFU-EC was observed in the patients
with bilateral or larger CNV. CONCLUSIONS: The findings suggest that CD34(+) HSCs
may be recruited from bone marrow through a signal from active CNV. Furthermore, 
HSCs may play a role in the severity of CNV.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18055794 [PubMed - indexed for MEDLINE]

510: Am J Ophthalmol. 2008 Feb;145(2):289-296. Epub 2007 Dec 11.

Optical coherence tomography features during the evolution of serous retinal
detachment in patients with diabetic macular edema.

Gaucher D, Sebah C, Erginay A, Haouchine B, Tadayoni R, Gaudric A, Massin P.

Department of Ophthalmology, Assistance Publique des Hôpitaux de Paris, Hôpital
Lariboisière, 2 rue Ambroise Paré, Paris cedex 10, France.
david.gaucher@lrb.aphp.fr

PURPOSE: To characterize the evolution of serous retinal detachment (SRD)
combined with diabetic macular edema (DME) using optical coherence tomography
(OCT). DESIGN: Observational retrospective case series. METHODS: In our
institution, 64 eyes of 40 diabetic patients who had SRD combined with DME were
studied. All patients had fluorescein angiography and several OCT3 examinations
during follow-up. Foveolar neuroretinal thickness (NRT) and SRD height were
measured. The evolution of OCT macular profiles was qualitatively assessed.
RESULTS: Mean follow-up was 11.8 months. DME was focal in 10 eyes (15.6%),
diffuse in 17 (26.6%) and both diffuse and focal in 37 (57.8%). Mean initial
decimal visual acuity (VA), NRT, and SRD height (+/- standard deviation) were
0.35 +/- 0.21, 346.88 +/- 138.61 and 199.48 +/- 139.8 microm, respectively. SRD
height did not correlate with VA (P = .23) or NRT (P = .31). In 13 eyes (20.3%), 
NRT above the SRD was normal. In the 19 eyes where DME improved during follow-up,
SRD disappeared before the maximal reduction of retinal thickness in seven eyes
(36.8%) and after or simultaneously with this reduction, in 12 eyes (63.2%).
Among the 45 eyes where DME worsened during follow-up, SRD disappeared from 15
eyes (33.3%). CONCLUSION: In this series, SRD height did not correlate with
retinal thickening. The latter may appear before central neuroretinal thickening 
and disappear before or after its regression. Consequently, SRD does not seem to 
be related either to the severity of DME or to its resorption.

PMID: 18054885 [PubMed - indexed for MEDLINE]

511: Ophthalmology. 2007 Dec;114(12):2183-9.

Triamcinolone acetonide as adjunctive treatment to verteporfin in neovascular
age-related macular degeneration: a prospective randomized trial.

Chaudhary V, Mao A, Hooper PL, Sheidow TG.

Ivey Eye Institute, University of Western Ontario, London, Canada.
vchaudha@uwo.ca

PURPOSE: To examine the use of intravitreal triamcinolone acetonide (IVTA) as
adjunctive therapy to photodynamic therapy (PDT) in the treatment of occult and
minimally classic choroidal neovascularization (CNV) secondary to age-related
macular degeneration (AMD). DESIGN: Single-center prospective randomized pilot
clinical trial. PARTICIPANTS: Thirty eyes of 30 patients with occult or minimally
classic CNV secondary to AMD. METHODS: Patients were randomized prospectively to 
receive either PDT alone or combined PDT plus IVTA treatment for CNV secondary to
AMD. Standard verteporfin PDT was performed in all patients. In the PDT plus IVTA
group, a 12-mg intravitreal injection of triamcinolone acetonide was given 30
minutes after PDT. Active lesions were retreated every 3 months for 1 year. MAIN 
OUTCOME MEASURES: Change in visual acuity and retreatment rate. RESULTS: Mean
visual acuity remained stable in the PDT plus IVTA group (-1.9 Early Treatment
Diabetic Retinopathy Study [ETDRS] letters; P = 0.58), but declined significantly
in the PDT alone group (-13.3 ETDRS letters; P = 0.02). The treatment rate was
1.13 in the PDT plus IVTA group and 3.6 in the PDT alone group (P<0.0001). Mean
contrast sensitivity increased by 3.6 letters (P = 0.09) in the PDT plus IVTA
group and decreased by -1.84 letters (P = 0.07) in the PDT alone group. Cataract 
progression was noted in 4 of 7 phakic eyes in the PDT plus IVTA group. Six
patients (40%) in the combined PDT plus IVTA group required topical glaucoma
therapy for control of elevated intraocular pressure. CONCLUSIONS: This pilot
study demonstrated effective stabilization of visual acuity and reduced treatment
frequency at 12 months with combination PDT plus IVTA therapy versus PDT alone.
Larger randomized trials are ongoing to determine the efficacy and risks of PDT
with IVTA.

Publication Types: 
    Randomized Controlled Trial

PMID: 18054638 [PubMed - indexed for MEDLINE]

512: Ophthalmology. 2007 Dec;114(12):2174-8.

Annual rates of arterial thromboembolic events in medicare neovascular
age-related macular degeneration patients.

Alexander SL, Linde-Zwirble WT, Werther W, Depperschmidt EE, Wilson LJ, Palanki
R, Saroj N, Butterworth SL, Ianchulev T.

Genentech, Inc., South San Francisco, California, USA.

PURPOSE: Smoking, age, and nutrition have been associated with the development of
neovascular age-related macular degeneration (AMD) and can increase the risk of
arterial thromboembolic events (ATEs). This study assesses annual rates of ATEs
in new-onset neovascular AMD patients compared with matched controls. DESIGN:
Retrospective study. PARTICIPANTS: New-onset neovascular AMD patients and age-,
race-, gender-, and database length-matched controls from the 5% Medicare
database. METHODS: We conducted a retrospective analysis of the 5% Medicare
database from 2001 to 2003. New-onset neovascular AMD patients were included if
they were > or =65 years old, had 2 diagnoses of neovascular AMD, and had at
least 1 year of data before the first diagnosis of AMD within the dataset. A
control group was constructed in a 3:1 ratio from those without a diagnosis of a 
major eye disorder and matched by age, race, gender, and length of data. Annual
prevalence rates were determined for myocardial infarctions (MIs) and ischemic
cerebral vascular accidents (CVAs). MAIN OUTCOME MEASURES: Rates of MIs and
ischemic CVAs in new-onset neovascular AMD patients and matched controls from
2001 to 2003. RESULTS: There were 15771 new-onset neovascular AMD patients
identified and matched with 46 408 controls. Average age was 80.5 years, with 64%
> or =80; 65% were female; and 95.9% were white. Inpatient MI rates for
neovascular AMD patients and controls were 2.2% and 2.2%, respectively (P =
0.74). Inpatient ischemic CVA rates for neovascular AMD patients and controls
were 3.5% and 3.6%, respectively (P = 0.59). Myocardial infarction rates and
ischemic CVA rates for both groups increased with age. Subgroups of patients with
comorbidities known to be risk factors for ATEs (i.e., hypertension,
hyperlipidemia, diabetes, and arrhythmias) had a higher rate of events. Patients 
with previous ATEs were also at a higher risk of subsequent events, at 7.4% for
inpatient MI and 35.1% for inpatient ischemic stroke. CONCLUSION: Despite the
shared risk factors associated with neovascular AMD and ATEs, Medicare
beneficiaries with neovascular AMD had a rate of ATEs similar to that of matched 
controls. Rates of ATEs increased in patients with comorbidities and for patients
with previous events.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18054636 [PubMed - indexed for MEDLINE]

513: Ophthalmology. 2007 Dec;114(12):2168-73.

Association of complement factor H and LOC387715 genotypes with response of
exudative age-related macular degeneration to intravitreal bevacizumab.

Brantley MA Jr, Fang AM, King JM, Tewari A, Kymes SM, Shiels A.

Department of Ophthalmology and Visual Sciences, Washington University School of 
Medicine, St. Louis, Missouri 63110, USA. Brantley@vision.wustl.edu

PURPOSE: To investigate whether there is an association between complement factor
H (CFH) or LOC387715 genotypes with response to treatment with intravitreal
bevacizumab for exudative age-related macular degeneration (AMD). DESIGN:
Retrospective cohort study. PARTICIPANTS: The study cohort consisted of 86
patients being treated for neovascular AMD with bevacizumab alone. METHODS:
Genotype determination for the CFH Y402H and LOC387715 A69S polymorphisms was
performed by allele-specific digestion of polymerase chain reaction products. All
patients were treated with 1.25 mg intravitreal bevacizumab at 6-week intervals
until choroidal neovascularization was no longer active. MAIN OUTCOME MEASURES:
CFH Y402H and LOC387715 A69S polymorphisms. Choroidal neovascular lesion
characteristics were ascertained by fluorescein angiography. Snellen visual
acuity (VA) was measured before and after treatment. RESULTS: For the CFH Y402H
polymorphism, patients with the CFH TT genotype had the largest choroidal
neovascular lesions (P = 0.02). With treatment, VA improved from 20/248 to 20/166
for the CFH TT genotype and from 20/206 to 20/170 for the TC genotype, but fell
from 20/206 to 20/341 for the CFH CC genotype (P = 0.016). Only 10.5% of patients
with the CFH CC genotype demonstrated improved VA with treatment, compared with
53.7% of CFH TT and TC genotypes (P = 0.004). For the LOC387715 A69S variant,
patients with the TT genotype had the largest choroidal neovascular lesions (P = 
0.012). There was no significant difference in response to bevacizumab treatment 
according to LOC387715 genotype. CONCLUSIONS: The AMD-associated CFH Y402H and
LOC387715 A69S variants were associated with differences in choroidal neovascular
lesion size in this study. Patients with the CFH CC genotype fared significantly 
worse with intravitreal bevacizumab than did those with the CFH TC and TT
genotypes, suggesting a potential pharmacogenetic relationship. Prospective
studies to confirm or refute this observation should be considered.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18054635 [PubMed - indexed for MEDLINE]

514: Optometry. 2007 Dec;78(12):664-73.

Exam room, chair side evaluation of retinal edema: improving accuracy and
precision for identification of subclinical diabetic macular edema.

Richer S.

Veterans Administration Medical Center, Eye Clinic 112e, North Chicago, Illinois 
60064, USA. Stuart.Richer1@med.va.gov

BACKGROUND: Early detection of diabetic macular edema (DME) is important for
improving patient outcomes. Currently, the gold standards are slit lamp stereo
biomicroscopy examination and fluorescein angiography (FA). Detecting DME with a 
slit lamp is subjective and can be difficult in the early stages of the disease. 
FA is invasive and involves discomfort and risk to the patient. A new diagnostic 
test, the Heidelberg Retina Tomograph (HRT) Retina Module (Heidelberg
Engineering, Heidelberg, Germany), is noninvasive, objective, and sensitive to
early changes in the retina. It is purported to locate and quantify retinal edema
such as DME, independent of retina thickening. Presented are a series of case
reports comparing retinal photography, FA, HRT, and ocular coherence tomography
(Stratus OCT; Carl Zeiss Meditec, Jena, Germany) results on patients with DME.
The purpose is to determine the clinical utility of the HRT for discerning DME
compared with clinical stereo biomicroscopy impression and FA. CASE REPORTS: In
this representative case series, the author's first stereo biomicroscopy
impression, macular photographs, retinal fluorescein angiographs, Stratus OCT
images, and HRT Retina Module images from 5 type 2 diabetic patients (3 insulin
and 2 non-insulin dependent) with retinopathy are presented. All patients are
men, with a mean age of 56.4 (range, 51 to 62). Subjects had diabetes mellitus
type 2 for an average of 14.4 years (range, 10 to 22) and were experiencing
fluctuations or loss in vision. In all cases, DME was clearly identifiable on FA 
although sometimes questionable by stereo biomicroscopy. Nonstereo retinal photos
and OCT examinations were inconclusive or unremarkable in 4 of 5 cases. The HRT
Edema surrogate "e" index and map results showed areas of DME that were very
similar to those of the FA images. CONCLUSIONS: In this case series, the HRT
Retina Module provided useful clinical information on DME patients including the 
quantification and extent of both subclinical and clinically significant DME.
Although more rigorous study is warranted, such immediate feedback from a
noninvasive, safe, diagnostic tool is invaluable in clinical practice,
particularly with the advent of prophylactic nutritional genistein-based
multivitamin supplements such as Bausch & Lomb Ocuvite DF (Rochester, New York).

Publication Types: 
    Case Reports
    Comparative Study
    Research Support, U.S. Gov't, Non-P.H.S.

PMID: 18054137 [PubMed - indexed for MEDLINE]

515: J Cataract Refract Surg. 2007 Dec;33(12):2098-105.

Comment in:
    J Cataract Refract Surg. 2008 Jun;34(6):880; author reply 880-1.

Primary intravitreal bevacizumab for the management of pseudophakic cystoid
macular edema: pilot study of the Pan-American Collaborative Retina Study Group.

Arevalo JF, Garcia-Amaris RA, Roca JA, Sanchez JG, Wu L, Berrocal MH, Maia M;
Pan-American Collaborative Retina Study Group.

Retina and Vitreous Service, Clinica Oftalmológica Centro Caracas, Caracas,
Venezuela. arevalojf@movistar.net.ve

PURPOSE: To determine the feasibility, safety, and clinical effect of primary
intravitreal bevacizumab (Avastin) in patients with cystoid macular edema (CME)
after cataract surgery. SETTING: Five institutions in Venezuela, Costa Rica,
Puerto Rico, Peru, and Brazil. METHODS: Twenty-eight eyes of 25 patients treated 
with at least 1 intravitreal injection of 1.25 mg or 2.50 mg of Avastin
participated in this interventional retrospective multicenter study at 5
institutions from 5 countries. Baseline and follow-up visits included Early
Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing, optical
coherence tomography (OCT) imaging, and ophthalmoscopic examination. RESULTS: The
mean follow-up was 32 weeks (range 24 to 52 weeks). Twenty eyes (71.4%) had
improved best corrected visual acuity (BCVA) (> or =2 ETDRS lines), and no eye
had worse visual acuity (> or =2 ETDRS lines). The BCVA remained stable in 8 eyes
(28.6%). The mean baseline BCVA was 20/160 (logMAR = 0.92) and the mean final
BCVA, 20/63 (logMAR = 0.50); the difference was statistically significant
(P<.0001). The mean central macular thickness at baseline (466.3 microm; range
208 to 784 microm) decreased significantly (264.5 microm; range 176 to 513
microm) by the end of follow-up (P<.0001). Eight eyes (28.6%) required a second
injection and 4 (14.3%), a third injection. The mean interval between injections 
was 13 weeks (range 5 to 26 weeks). No ocular or systemic adverse events were
observed. CONCLUSIONS: Short-term results suggest that primary intravitreal
Avastin is well tolerated in patients with pseudophakic CME. Treated eyes had a
significant improvement in BCVA and decrease in macular thickness by OCT.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 18053911 [PubMed - indexed for MEDLINE]

516: Med Image Comput Comput Assist Interv Int Conf Med Image Comput Comput
Assist Interv. 2007;10(Pt 1):244-51.

Use of varying constraints in optimal 3-D graph search for segmentation of
macular optical coherence tomography images.

Haeker M, Abràmoff MD, Wu X, Kardon R, Sonka M.

Department of Electrical & Computer Engineering, The University of Iowa, Iowa
City, IA 52242, USA. mona-haeker@uiowa.edu

An optimal 3-D graph search approach designed for simultaneous multiple surface
detection is extended to allow for varying smoothness and surface interaction
constraints instead of the traditionally used constant constraints. We apply the 
method to the intraretinal layer segmentation of 24 3-D optical coherence
tomography (OCT) images, learning the constraints from examples in a
leave-one-subject-out fashion. Introducing the varying constraints decreased the 
mean unsigned border positioning errors (mean error of 7.3 +/- 3.7 microm using
varying constraints compared to 8.3 +/- 4.9 microm using constant constraints and
8.2 +/- 3.5 microm for the inter-observer variability).

Publication Types: 
    Evaluation Studies

PMID: 18051065 [PubMed - indexed for MEDLINE]

517: J Microbiol Biotechnol. 2007 Jun;17(6):1024-30.

Human apolipoprotein E2 transgenic mice show lipid accumulation in retinal
pigment epithelium and altered expression of VEGF and bFGF in the eyes.

Lee SJ, Kim JH, Kim JH, Chung MJ, Wen Q, Chung H, Kim KW, Yu YS.

Division of Food Bioscience and Technology, College of Life Sciences and
Biotechnology, Institute of Biomedical Science and Safety, Korea University,
Seoul 136-713, Korea.

We investigated the human apolipoprotein E2 (apoE2) transgenic mouse as an animal
model system for age-related macular degeneration (AMD). Transgenic mice
expressing human apoE2 and C57BL/6J mice were fed normal chow or a high-fat diet 
for 4 weeks. Eyes were collected from the mice and lipid deposits in retinal
pigment epithelium (RPE) were assessed using electron microscopy. The expressions
of apoE, vascular endothelial growth factor (VEGF), basic fibroblast growth
factor (bFGF), and pigment-epithelium derived factor (PEDF), which are molecular 
markers for angiogenesis, were assessed with immunohistochemistry. Eyes from
apoE2 mice, regardless of diet, contained lipid accumulation in RPE under
electron microscopy, whereas control C57BL/6J eyes did not. Lipid accumulation
was found predominantly in the RPE and the Bruch's membrane and increased in the 
eyes of apoE2 mice after one month of a high-fat diet (8 +/- 2 per 50 microm2 for
normal chow and 11 +/- 2 per 50 microm2, p < 0.05). ApoE expression was similar
in the apoE2 and control mice; however, VEGF and bFGF were overexpressed in the
retinal pigment epithelium of apoE2 eyes compared with control eyes, and PEDF
expression was slightly decreased. These expression patterns of VEGF, bFGF, and
PEDF suggest angiogenesis is progressing in apoE2 eyes. In conclusion, the eyes
of apoE2 mice develop typical lipid accumulations, a common characteristic of
AMD, making them a suitable animal model for AMD. The expression profile of VEGF 
and bFGF on the retinal pigment epithelium suggests that apoE2 may induce
neovascularization by altering angiogenic cytokines.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18050922 [PubMed - indexed for MEDLINE]

518: Ophthalmic Surg Lasers Imaging. 2007 Nov-Dec;38(6):511-3.

Optical coherence tomography demonstration of Best's vitelliform macular
dystrophy in a child.

Al-Kahtani E, Nowilaty SR.

Department of Ophthalmology, King Khaled Eye Specialist Hospital, Riyadh, Kingdom
of Saudi Arabia.

Considering the importance of optical coherence tomography in clinical decision
making, the veracity of these images is critical. The authors describe a
5-year-old girl with Best's vitelliform macular dystrophy of different stages of 
development in both eyes in which the optical coherence tomography appearance
correlated well with both the staves of the disease and the visual function.

Publication Types: 
    Case Reports

PMID: 18050818 [PubMed - indexed for MEDLINE]

519: Ophthalmic Surg Lasers Imaging. 2007 Nov-Dec;38(6):478-83.

Can optical coherence tomography predict the outcome of laser photocoagulation
for diabetic macular edema?

Estabrook EJ, Madhusudhana KC, Hannan SR, Newsom RS.

University of Southampton, Southampton, United Kingdom.

BACKGROUND AND OBJECTIVE: To assess the outcome of laser photocoagulation in
patients with diabetic macular edema. PATIENTS AND METHODS: Forty-seven patients 
(51 eyes) with clinically significant macular edema (CSME) undergoing grid laser 
photocoagulation were included. Clinical examination and optical coherence
tomography (OCT) were performed at baseline and 3 to 4 months after treatment.
The central foveal thickness, mean inner macular thickness (average retinal
thickness in fovea and inner macular circle), and mean macular thickness were
calculated. Based on the greatest OCT thickness at baseline, patients were
grouped according to mild (< 300 microm; Group 1), moderate (300 to 399 microm;
Group 2), and severe (> or = 400 microm; Group 3) macular edema. RESULTS: Group 2
showed significant reductions in central foveal thickness (23 microm, P = .02),
mean inner macular thickness (18 microm, P = .02), and mean macular thickness (9 
microm, P = .04) with slight improvement in visual acuity. Groups 1 and 3 did not
show any significant change in macular thickness values and there was a
statistically insignificant worsening of visual acuity in these groups.
CONCLUSIONS: Patients with moderate macular thickening of 300 to 400 microm
benefit most from laser treatment. OCT may help in choosing the appropriate
treatment for CSME based on the degree of macular thickening. Long-term studies
are warranted to confirm these findings.

PMID: 18050810 [PubMed - indexed for MEDLINE]

520: Eur J Ophthalmol. 2007 Nov-Dec;17(6):1000-3.

Phenotypic intrafamilial variability associated with S212G mutation in the
RDS/peripherin gene.

Passerini I, Sodi A, Giambene B, Menchini U, Torricelli F.

Department of Genetic Diagnosis, Careggi University Hospital, Firenze, Italy.
ilariapasserini@libero.it

PURPOSE: To describe an Italian family in which two separate phenotypes
(retinitis pigmentosa and adult onset vitelliform macular dystrophy) are
associated with an identical mutation (S212G) in the peripherin/RDS gene. This
mutation has already been reported in patients with retinitis pigmentosa, but it 
has never been previously detected in association with adult onset vitelliform
macular dystrophy. METHODS: A 38-year-old woman complained of bilateral mild
metamorphopsias and on ophthalmologic examination she showed the clinical
phenotype of adult onset vitelliform macular dystrophy. Her 62-year-old mother
was clinically diagnosed with a retinitis pigmentosa, with a severe clinical
course. RESULTS: In both patients, molecular genetic analysis revealed a 874A-->G
transition in the exon 2 of the RDS gene leading to the amino acid change of
S212G. CONCLUSIONS: Peripherin/RDS S212G mutation may have damaging effects on
the formation and stability of the photoreceptors' disk structure and may be
associated with different clinical phenotypes, even in the same family.
Intrafamilial phenotypic variability has been reported for other RDS mutations;
this supports the possible influence of modifier genes or environmental factors
in the clinical expression of RDS gene variants. Moreover, it suggests that in
patients with retinal degeneration and peripherin/RDS mutation, caution should be
taken both in using molecular genetic results to predict the clinical course of
the disease and in offering genetic counseling.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 18050133 [PubMed - indexed for MEDLINE]

521: Eur J Ophthalmol. 2007 Nov-Dec;17(6):996-9.

Intravitreal ranibizumab in a patient with choroidal neovascularization secondary
to multiple evanescent white dot syndrome.

Rouvas AA, Ladas ID, Papakostas TD, Moschos MM, Vergados I.

2nd Department of Ophthalmology, Medical School of Athens University, Athens,
Greece.

PURPOSE: To report the effect of a single intravitreal injection of ranibizumab
in a patient with choroidal neovascularization (CNV) secondary to multiple
evanescent white dot syndrome (MEWDS). METHODS: A 65-year-old woman with visual
acuity (VA) 20/40, mild vitreous inflammation, optic disc edema, and white deep
retinal round lesions in the right eye underwent fluorescein angiography,
indocyanine green angiography, and optical coherence tomography. The diagnosis of
MEWDS with peripapillary CNV was made and a single injection of ranibizumab (0.5 
mg) was administered. RESULTS: At the 6-month follow-up visit, the VA in the
right eye was 20/20, the CNV completely regressed, and the MEWDS findings
disappeared. CONCLUSIONS: Intravitreal ranibizumab appears to be a safe and
effective treatment option in cases of CNV secondary to MEWDS, resulting in fast 
resolution of the macular edema and regression of the CNV. On the other hand, it 
is unclear whether the administration of ranibizumab contributed to a prompt
regression of MEWDS.

Publication Types: 
    Case Reports

PMID: 18050132 [PubMed - indexed for MEDLINE]

522: Eur J Ophthalmol. 2007 Nov-Dec;17(6):987-91.

Systemic bevacizumab for retinal angiomatous proliferation associated with
retinal pigment epithelial detachment.

Abi-Ayad N, Mauget-Faysse M, Amara-Allieu S, Ardisson P.

Department of Ophthalmology, Croix-Rousse Hospital, Lyon, France.

PURPOSE: To report the off-label use of systemic bevacizumab in a patient with
stage 3 retinal angiomatous proliferation (RAP) associated with a vascularized
pigmented epithelium detachment (PED). METHODS: Interventional case report.
RESULTS: The patient was treated with systemic bevacizumab after obtaining fully 
informed consent. At 3 months post-treatment, the authors observed an improvement
of one line (seven letters) in visual acuity and total regression of the PED on
ocular coherence tomography. No adverse effects were observed. CONCLUSIONS:
Systemic bevacizumab therapy appears to be safe and effective in the treatment of
RAP associated with PED during this short follow-up period of 3 months. The
authors recommend a large trial with long-term follow-up to confirm the promising
results and evaluate the occurrence of adverse effects associated with systemic
bevacizumab.

Publication Types: 
    Case Reports

PMID: 18050130 [PubMed - indexed for MEDLINE]

523: Eur J Ophthalmol. 2007 Nov-Dec;17(6):983-6.

Intravitreal bevacizumab for adult-onset vitelliform dystrophy: a case report.

Montero JA, Ruiz-Moreno JM, De La Vega C.

Pio del Rio Hortega University Hospital, Ophthalmology Unit, Valladolid, Spain.
javmonmor@hotmail.com

PURPOSE: Adult-onset foveomacular vitelliform dystrophy (AFVD) is often
misdiagnosed as occult choroidal neovascularization (CNV) secondary to
age-related macular degeneration (AMD). The authors report the anatomic and
functional outcome of intravitreal bevacizumab in a case of AFVD associated with 
a suspected occult CNV. METHODS: Prospective, interventional, single case report.
One female patient with decreased visual acuity (VA) and metamorphopsia secondary
to AFVD received one single intravitreal injection of bevacizumab 1.25 mg.
RESULTS: The patient reported unchanged VA and decreased metamorphopsia 6 weeks
after the injection. Fluorescein angiography (FA) and optical coherence
tomography (OCT) showed progressive decrease of subretinal fluid until complete
disappearance. VA, OCT, and FA remained unchanged during 10 months follow-up.
CONCLUSIONS: Intravitreal bevacizumab showed a morphologic improvement and stable
VA in a patient with AFVD. Further case series are required to confirm this
observation.

Publication Types: 
    Case Reports

PMID: 18050129 [PubMed - indexed for MEDLINE]

524: Eur J Ophthalmol. 2007 Nov-Dec;17(6):943-9.

The effect of complement factor H Y402H polymorphism on the outcome of
photodynamic therapy in age-related macular degeneration.

Seitsonen SP, Jarvela IE, Meri S, Tommila PV, Ranta PH, Immonen IJ.

Department of Ophthalmology, Helsinki University Central Hospital, Helsinki,
Finland. sanna.seitsonen@hus.fi

PURPOSE: Photodynamic therapy (PDT) has been widely used in the treatment of
age-related macular degeneration (AMD). The complement cascade has an important
role in the tissue reactions occurring after PDT. The Y402H polymorphism of the
complement factor H (CFH) gene has been identified as a risk factor for AMD.
Since CFH is central in the regulation of the complement system the authors
wanted to analyze whether the CFH Y402H polymorphism modifies the PDT outcome in 
AMD. METHODS: A total of 88 patients having been treated with PDT and without
further scheduled PDT sessions were analyzed. Depending on the situation at their
final PDT session the patients were classified retrospectively as PDT-responders 
or PDT-nonresponders. All patients were genotyped for the CFH Y402H polymorphism.
RESULTS: The proportion of PDT-responders was 18/26 (69.2%) in patients
homozygous for the CFH Y402H risk allele, 34/50 (68.0%) in heterozygous, and 7/12
(58.3%) in patients with the normal genotype (p=0.520). The median number of PDT 
treatments of the PDT-responders was three for all the genotypes. CONCLUSIONS:
The dysfunction of the CFH related to the risk of AMD and caused by the Y402H
polymorphism does not modify the outcome of PDT. Genotyping for CFH Y402H cannot 
be used to select patients for this treatment.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18050121 [PubMed - indexed for MEDLINE]

525: Eur J Ophthalmol. 2007 Nov-Dec;17(6):919-27.

Pre- and postoperative C-reactive protein levels in patients with cataract and
age-related macular degeneration.

Zaliuniene D, Paunksnis A, Gustiene O, Brazdzionyte J, Zaliunas R.

Department of Ophthalmology, Kaunas University of Medicine, Kaunas, Lithuania.
r.zaliunas@takas.lt

PURPOSE: To assess whether patients with early or intermediate forms of
age-related macular degeneration (AMD) benefit from cataract surgery in terms of 
visual acuity and contrast sensitivity, and to determine the levels of high
sensitivity C-reactive protein (hsCRP) as a systemic marker of inflammation
before and after cataract surgery in patients with AMD. METHODS: Three groups of 
patients (n=132) were studied at baseline and 8-12 weeks later: 1) a study group 
of patients with AMD who underwent cataract surgery (n=47), 2) a control group of
patients without ocular comorbidities who underwent cataract surgery (n=36), and 
3) a second control group with AMD and no surgery (n=49). Visual acuity (VA) was 
obtained by letter charts and expressed as decimal notations +/- SD. Contrast
sensitivity was measured employing a Ginsburg Box, VSCR-CST-6500. The hsCRP was
measured by means of particle enhanced immunonephelometry on a BN Systems.
RESULTS: Postoperatively in both groups of the operated patients an improvement
of VA (0.23+/-0.17 vs 0.64+/-0.25 and 0.23+/-0.18 vs 0.83+/-0.17, respectively,
p<0.0001) and contrast sensitivity (at different spatial frequencies, from 1.5 to
18 cycles/degree, p<0.05) was determined. At baseline, the hsCRP level in Group 1
patients was higher than the level in controls (2.67+/-2.36 vs 1.67+/-1.36,
p<0.01, or 1.12+/-0.99 mg/L, p<0.0001, respectively). After 8-12 weeks, the hsCRB
level only in Group 1 significantly increased (2.67+/-2.36 vs 3.74+/-3.54 mg/L,
p<0.05), whereas in the controls it did not change. CONCLUSIONS: Patients with
AMD benefit from cataract surgery, both in terms of VA and contrast sensitivity. 
The level of hsCRP is significantly higher in patients with AMD and moderate
cataract than in patients with one of these eye disorders. The hsCRP only
increases after cataract surgery in patients with AMD.

PMID: 18050118 [PubMed - indexed for MEDLINE]

526: Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19273-8. Epub 2007 Nov 28.

The all-trans-retinal dimer series of lipofuscin pigments in retinal pigment
epithelial cells in a recessive Stargardt disease model.

Kim SR, Jang YP, Jockusch S, Fishkin NE, Turro NJ, Sparrow JR.

Department of Ophthalmology, Columbia University, New York, NY 10032, USA.

The bis-retinoid pigments that accumulate in retinal pigment epithelial cells as 
lipofuscin are associated with inherited and age-related retinal disease. In
addition to A2E and related cis isomers, we previously showed that condensation
of two molecules of all-trans-retinal leads to the formation of a protonated
Schiff base conjugate, all-trans-retinal dimer-phosphatidylethanolamine. Here we 
report the characterization of the related pigments, all-trans-retinal
dimer-ethanolamine and unconjugated all-trans-retinal dimer, in human and mouse
retinal pigment epithelium. In eyecups of Abcr(-/-) mice, a model of recessive
Stargardt macular degeneration, all-trans-retinal dimer-phosphatidylethanolamine 
was increased relative to wild type and was more abundant than A2E. Total pigment
of the all-trans-retinal dimer series (sum of all-trans-retinal
dimer-phosphatidylethanolamine, all-trans-retinal dimer-ethanolamine, and
all-trans-retinal dimer) increased with age in Abcr(-/-) mice and was modulated
by amino acid variants in Rpe65. In in vitro assays, enzyme-mediated hydrolysis
of all-trans-retinal dimer-phosphatidylethanolamine generated all-trans-retinal
dimer-ethanolamine, and protonation/deprotonation of the Schiff base nitrogen of 
all-trans-retinal dimer-ethanolamine was pH-dependent. Unconjugated
all-trans-retinal dimer was a more efficient generator of singlet oxygen than
A2E, and the all-trans-retinal dimer series was more reactive with singlet oxygen
than was A2E. By analyzing chromatographic properties and UV-visible spectra
together with mass spectrometry, mono- and bis-oxygenated all-trans-retinal dimer
photoproducts were detected in Abcr(-/-) mice. The latter findings are
significant to an understanding of the adverse effects of retinal pigment
epithelial cell lipofuscin.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18048333 [PubMed - indexed for MEDLINE]

527: Clin Interv Aging. 2006;1(1):11-31.

Dietary approaches that delay age-related diseases.

Everitt AV, Hilmer SN, Brand-Miller JC, Jamieson HA, Truswell AS, Sharma AP,
Mason RS, Morris BJ, Le Couteur DG.

Centre for Education and Research on Ageing and Anzac Research Institute,
University of Sydney, Concord Repatriation General Hospital, Concord, NSW,
Australia. arthureveritt@yahoo.com.au

Reducing food intake in lower animals such as the rat decreases body weight,
retards many aging processes, delays the onset of most diseases of old age, and
prolongs life. A number of clinical trials of food restriction in healthy adult
human subjects running over 2-15 years show significant reductions in body
weight, blood cholesterol, blood glucose, and blood pressure, which are risk
factors for the development of cardiovascular disease and diabetes. Lifestyle
interventions that lower energy balance by reducing body weight such as physical 
exercise can also delay the development of diabetes and cardiovascular disease.
In general, clinical trials are suggesting that diets high in calories or fat
along with overweight are associated with increased risk for cardiovascular
disease, type 2 diabetes, some cancers, and dementia. There is a growing
literature indicating that specific dietary constituents are able to influence
the development of age-related diseases, including certain fats (trans fatty
acids, saturated, and polyunsaturated fats) and cholesterol for cardiovascular
disease, glycemic index and fiber for diabetes, fruits and vegetables for
cardiovascular disease, and calcium and vitamin D for osteoporosis and bone
fracture. In addition, there are dietary compounds from different functional
foods, herbs, and neutraceuticals such as ginseng, nuts, grains, and polyphenols 
that may affect the development of age-related diseases. Long-term prospective
clinical trials will be needed to confirm these diet-disease relationships. On
the basis of current research, the best diet to delay age-related disease onset
is one low in calories and saturated fat and high in wholegrain cereals, legumes,
fruits and vegetables, and which maintains a lean body weight. Such a diet should
become a key component of healthy aging, delaying age-related diseases and
perhaps intervening in the aging process itself. Furthermore, there are studies
suggesting that nutrition in childhood and even in the fetus may influence the
later development of aging diseases and lifespan.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18047254 [PubMed - indexed for MEDLINE]

528: Clin Interv Aging. 2006;1(4):451-66.

Ranibizumab in neovascular age-related macular degeneration.

Kenneth TE, Kertes PJ.

Hotel Dieu Hospital, Kingston, Canada.

Neovascular age-related macular degeneration (AMD) is a visually devastating
condition resulting from choroidal neovascularization and secondary photoreceptor
loss. Ranibizumab and bevacizumab are medications that target vascular
endothelial growth factor (VEGF). While other therapies have demonstrated some
ability to reduce the risk of losing vision from neovascular AMD, most patients
continue to lose some degree of central visual acuity. There is growing evidence 
that intravitreal administration of ranibizumab and bevacizumab is effective in
significantly improving the visual acuity in patients with neovascular
age-related macular degeneration.

Publication Types: 
    Review

PMID: 18046922 [PubMed - indexed for MEDLINE]

529: Clin Interv Aging. 2006;1(3):237-46.

Anecortave acetate in the treatment of age-related macular degeneration.

Augustin A.

Department of Ophthalmology, Moltkestrasse 90, 76 133 Karlsruhe, Germany.
106020.560@compuserve.com

RETAANE 15mg (anecortave acetate suspension) is under investigation to treat
exudative age-related macular degeneration (AMD), the single largest cause of
blindness in the Western world, affecting over 15 million people in the USA.
RETAANE suspension is a unique synthetic cortisene and has antiangiogenic
properties that were established in multiple experimental models of angiogenesis.
The molecule acts at multiple sites of the angiogenic cascade. Clinical trials in
patients with exudative AMD have demonstrated the excellent safety record of both
the drug anecortave acetate and the posterior juxtascleral depot (PJD)
administration procedure. A pivotal study comparing RETAANE suspension with
placebo showed a significantly higher chance of maintaining vision in the
treatment (73%) as compared with placebo (47%). Another study compared RETAANE
suspension with Visudyne photodynamic therapy, revealing no statistically
significant differences between the two treatments over 24 months. AMD is a
multi-faceted disease and therefore a molecule such as RETAANE suspension with a 
unique mechanism of action, demonstrated clinical efficacy, and retreatment every
six months is an important potential treatment option which should be further
investigated both as a monotherapy or in combination with other treatment
strategies.

Publication Types: 
    Review

PMID: 18046876 [PubMed - indexed for MEDLINE]

530: Retina. 2007 Nov-Dec;27(9):1292-9.

Comparison of comorbid conditions between neovascular age-related macular
degeneration patients and a control cohort in the medicare population.

Zlateva GP, Javitt JC, Shah SN, Zhou Z, Murphy JG.

Pfizer Inc., New York, New York, USA.

PURPOSE: To determine whether comorbidities are more prevalent among individuals 
with neovascular age-related macular degeneration (NV-AMD) than individuals
without AMD. METHODS: This 2-year, retrospective, case-control study included
Medicare beneficiaries (standard 5% analytic sample) continuously enrolled from
January 1, 2003, to December 31, 2004, excluding those in managed care plans. The
NV-AMD cohort included individuals >or=65 at baseline with a diagnosis of NV-AMD 
in 2003 and 2004. Age-, gender-, and race-matched controls were selected from
those with no AMD. Comparisons were made for 13 general categories of
non-eye-related diseases and 18 specific comorbidities based on ICD-9-CM codes.
Two-year prevalence was calculated by condition and cohort; odds ratios and 99%
confidence intervals were calculated (logistic regression). RESULTS: Analyses
included 26,057 subjects and an equal number of controls. Nearly all subjects had
at least one comorbidity, and >80% in each cohort had five or more comorbidities 
across general disease categories. Prevalence of 7/13 general disease categories 
exceeded 50% in both cohorts; rates for 12/13 categories were significantly
higher in those with NV-AMD (P < 0.001). Prevalence of 13/14 non-eye-related and 
4/4 eye-related specific comorbidities was significantly higher among NV-AMD
subjects (P < 0.05). A more than 20% greater odds for NV-AMD subjects was noted
for hypertension, hypercholesterolemia, emphysema, chronic obstructive pulmonary 
disease, atherosclerosis, arthritis, coronary heart disease, cataract, glaucoma, 
and myopia. CONCLUSION: Patients with NV-AMD are significantly more likely to
have comorbidities, many of which could be life-threatening.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 18046240 [PubMed - indexed for MEDLINE]

531: Retina. 2007 Nov-Dec;27(9):1205-13.

Prospective, randomized clinical trial of intravitreal triamcinolone treatment of
neovascular age-related macular degeneration: one-year results.

Lee J, Freeman WR, Azen SP, Chung EJ, Koh HJ.

Department of Ophthalmology, Ilsan Paik Hospital, College of Medicine, Inje
University, Gyeonggido, Korea.

PURPOSE: To investigate the effect of intravitreal injection of high-dose (20-25 
mg) triamcinolone acetonide on minimally classic or occult choroidal
neovascularization (CNV) secondary to age-related macular degeneration (AMD).
METHODS: A prospective, double-masked, placebo-controlled, randomized clinical
trial included 39 eyes with minimally classic or occult CNV secondary to AMD. The
treatment group (21 eyes) received intravitreal injection (20-25 mg) of
triamcinolone acetonide and the control group (18 eyes) received intravitreal
injection (500 mug) of dexamethasone at 6-month intervals. Best-corrected ETDRS
(Early Treatment Diabetic Retinopathy Study) score, contrast sensitivity score,
and central macular volume were measured at 1 month, 3 months, 6 months, and 12
months. RESULTS: Mean baseline best-corrected visual acuity (BCVA [logarithm of
the minimal angle of resolution]) was 0.64 (Snellen equivalent, 20/80) in each
group. At 1 month, 3 months, and 6 months after the injection, neither group had 
a significant change in BCVA. At 12 months, mean BCVA +/- SD significantly
decreased to 1.06 +/- 0.34 (Snellen equivalent, 20/200) in the treatment group
(paired t-test, P < 0.001), whereas it was 0.78 +/- 0.52 (Snellen equivalent,
20/125) in the control group (P = 0.23). The difference was marginally
significant (P = 0.06, Student's t-test). All phakic eyes in the treatment group 
developed marked cataract progression. CONCLUSIONS: Intravitreal injection of
high-dose triamcinolone had no beneficial effect on eyes with minimally classic
or occult CNV secondary to AMD and was associated with outcomes similar to those 
associated with intravitreal injection of dexamethasone, which was used as
placebo.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial

PMID: 18046226 [PubMed - indexed for MEDLINE]

532: Retina. 2007 Nov-Dec;27(9):1187-95.

Intravitreal bevacizumab (avastin) injection alone or combined with triamcinolone
versus macular photocoagulation as primary treatment of diabetic macular edema.

Soheilian M, Ramezani A, Bijanzadeh B, Yaseri M, Ahmadieh H, Dehghan MH, Azarmina
M, Moradian S, Tabatabaei H, Peyman GA.

Ophthalmology Department and Ophthalmic Research Center, Labbafinejad Medical
Center, Shaheed Beheshti Medical University, Tehran, Iran.
masoud_soheilian@yahoo.com

PURPOSE: To report the efficacy of a single intravitreal bevacizumab injection
alone or in combination with intravitreal triamcinolone acetonide versus macular 
laser photocoagulation (MPC) as primary treatment of diabetic macular edema
(DME). METHODS: In this randomized, three-arm clinical trial, 103 eyes of 97
patients with clinically significant DME and no previous treatment were enrolled.
The eyes were randomly assigned to one of three study arms: the intravitreal
bevacizumab (IVB) group, patients who received 1.25 mg of intravitreal
bevacizumab (37 eyes); the IVB/IVT group, patients who received 1.25 mg of
intravitreal bevacizumab and 2 mg of intravitreal triamcinolone (33 eyes); and
the MPC group, patients who underwent focal or modified grid laser (33 eyes).
Primary outcome measure was change in visual acuity. RESULTS: Visual acuity
changes +/- SD at 12 weeks were -0.22 +/- 0.23, -0.13 +/- 0.31, and + 0.08 +/-
0.31 logarithm of the minimal angle of resolution in the IVB, IVB/IVT, and MPC
groups, respectively. The marginal regression model based on generalized
estimating equation analysis demonstrated that the visual acuity changes in the
groups were statistically significant at both 6 weeks (P < 0.0001) and 12 weeks
(P = 0.024). The significant treatment effect was demonstrated at both 6 weeks
and 12 weeks in the IVB group and only at 6 weeks in the IVB/IVT group.
Significant central macular thickness (CMT) reduction was observed in eyes in the
IVB and IVB/IVT groups only up to 6 weeks; however, CMT changes were not
significant in the groups. CONCLUSION: Up to 12 weeks, intravitreal bevacizumab
treatment of patients with DME yielded better visual outcome than laser
photocoagulation, although it was not associated with a significant decrease in
CMT. No further beneficial effect of intravitreal triamcinolone could be
demonstrated. Further clinical trials with longer follow-up are required to
evaluate the long-term visual outcomes and complication profiles after primary
treatment with such medications.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18046223 [PubMed - indexed for MEDLINE]

533: Am J Ophthalmol. 2008 Feb;145(2):273-280. Epub 2007 Nov 28.

Foveal photoreceptor layer in eyes with persistent cystoid macular edema
associated with branch retinal vein occlusion.

Ota M, Tsujikawa A, Murakami T, Yamaike N, Sakamoto A, Kotera Y, Miyamoto K, Kita
M, Yoshimura N.

Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School
of Medicine, Sakyo-ku, Kyoto, Japan.

PURPOSE: To study the correlation of visual acuity and the foveal photoreceptor
layer in eyes with persistent cystoid macular edema associated with branch
retinal vein occlusion (BRVO). DESIGN: Retrospective chart review. METHODS: We
studied retrospectively the medical records of 42 eyes of 42 patients with
persistent cystoid macular edema secondary to BRVO, eyes in which the foveal
thickness was greater than 250 microm at final examination. On the vertical image
obtained by optical coherence tomography at the final examination, we measured
thickness of the foveal photoreceptor layer that was beneath the foveal cystoid
spaces. We also assessed status of the junction between inner and outer segments 
of the photoreceptors (IS/OS) in the fovea. RESULTS: The photoreceptor layer
beneath the foveal cystoid spaces was detected as a distinct layer with thickness
varying between 33 microm and 124 microm (mean, 71.1 +/- 26.8 microm). Final
visual acuity showed no correlation with total foveal thickness (r = 0.336, P =
.092). However, it did show a close correlation with thickness of the foveal
photoreceptor layer (r = -0.571, P < .0001). Of the 42 eyes, 15 showed a
continuous IS/OS line in the fovea. Visual acuity in these eyes with a continuous
IS/OS line in the fovea was significantly better than that in eyes with a
discontinuous or interrupted IS/OS line (P < .0001). CONCLUSIONS: Both the
thickness and the integrity of the foveal photoreceptor layer are associated with
visual function in eyes with persistent cystoid macular edema associated with
BRVO.

PMID: 18045566 [PubMed - indexed for MEDLINE]

534: PLoS ONE. 2007 Nov 28;2(11):e1197.

Haplotypes in the complement factor H (CFH) gene: associations with drusen and
advanced age-related macular degeneration.

Francis PJ, Schultz DW, Hamon S, Ott J, Weleber RG, Klein ML.

Macular Degeneration Center, Casey Eye Institute, Oregon Health & Science
University, Portland, Oregon, United States of America. francisp@ohsu.edu

BACKGROUND: Age-related macular degeneration (AMD), the leading cause of
blindness in the Western world, is a complex disease that affects people over 50 
years old. The complement factor H (CFH) gene has been repeatedly shown to be a
major factor in determining susceptibility to the advanced form of the condition.
We aimed to better understand the functional role of this gene in the AMD disease
process and assess whether it is associated with earlier forms of the disease.
METHODOLOGY/PRINCIPAL FINDINGS: WE genotyped SNPS at the cfh gene locus in three 
independent populations with AMD: (a) extended families where at least 3 family
members had AMD; (b) sporadic cases of advanced AMD and (c) cases from the
Age-Related Eye Disease Study (AREDS). We investigated polymorphisms and
haplotypes in and around the CFH gene to assess their role in AMD. CFH is
associated with early/intermediate and advanced AMD in both familial and sporadic
cases. In our populations, the CFH SNP, rs2274700, is most strongly associated
with AMD and when incorporated into a haplotype with the Y402H SNP and rs1061147,
the strongest association is observed (p<10(-9)). CONCLUSIONS/SIGNIFICANCE: Our
results, reproduced in three populations that represent the spectrum of AMD
cases, provide evidence that the CFH gene is associated with drusen as well as
with advanced AMD. We also identified novel susceptibility and protective
haplotypes in the AMD populations.

Publication Types: 
    Multicenter Study
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18043728 [PubMed - indexed for MEDLINE]

535: Cornea. 2007 Dec;26(10):1159-64.

Impaired corneal wound healing associated with ketorolac 0.5% after uncomplicated
extracapsular cataract extraction.

Arey ML, Sullivan BR, Reinert CG, McCulley JP.

Department of Ophthalmology, University of Texas Southwestern Medical Center,
Dallas, TX 75390-9057, USA.

PURPOSE: To describe an apparent association between the use of ketorolac 0.5%
(Acular; Allergan) for cystoid macular edema (CME) prophylaxis and impaired
corneal wound healing in patients undergoing extracapsular cataract extraction
(ECCE) with intraocular lens (IOL) implantation. METHODS: A retrospective case
series reviewing 7 eyes of 7 patients who underwent uncomplicated ECCE with IOL
implantation and were treated postoperatively with ketorolac 0.5% 4 times daily
as a prophylactic measure against CME. RESULTS: Patients were treated with
ketorolac 0.5% 4 times a day for an average of 30 days (range, 20-44 days) after 
uncomplicated ECCE with IOL implantation. Two eyes developed postoperative
endophthalmitis necessitating vitreous tap with intravitreal antibiotic
injection; 1 eye went on to require pars plana vitrectomy with corneal wound
resuturing. One eye developed corneal wound dehiscence that required wound
resuturing in the operating room. One eye developed an inadvertent filtering bleb
despite the lack of postoperative suture lysis. Three others were followed up
closely postoperatively with slit-lamp evidence of impaired wound healing,
manifested by wound avascularity and/or wound gape, and did not require surgical 
intervention. CONCLUSIONS: The use of nonsteroidal anti-inflammatory agents for
prophylaxis of CME after cataract surgery is an evolving trend. This
retrospective case series showed a possible link between the use of ketorolac
0.5% and impaired corneal wound healing, and caution is urged in the liberal use 
of this agent postoperatively after ECCE.

Publication Types: 
    Case Reports

PMID: 18043168 [PubMed - indexed for MEDLINE]

536: Curr Opin Mol Ther. 2007 Dec;9(6):592-602.

Ranibizumab, a mAb against VEGF-A for the potential treatment of age-related
macular degeneration and other ocular complications.

Lantry LE.

Bracco Research USA, NJ 08540, USA. laura.lantry@bru.bracco.com

Genentech Inc and Novartis Ophthalmics AG have developed and launched the
humanized anti-VEGF antibody fragment ranibizumab, a 48-kDa humanized antibody
fragment that inhibits all forms of biologically active VEGF-A, for the treatment
ofage-related macular degeneration by intravitreal administration. Phase I to III
clinical trials to confirm the role of ranibizumab in the treatment of choroidal 
neovascularization (phase II and III), diabetic macular edema (phase II and III),
retinal venous occlusion (phase II and III), telangiectasia (phase I and II),
central serous chorioretinopathy (phase I), polypoidal choroidal vasculopathy
(phase I/II), conjunctival neoplasms (phase I) and von Hippel-Lindau syndrome
(phase I) are ongoing.

Publication Types: 
    Review

PMID: 18041670 [PubMed - indexed for MEDLINE]

537: J Med Assoc Thai. 2007 Oct;90(10):2090-6.

Photodynamic therapy for AMD and non-AMD patients: one-year results in Thais.

Ratanasukon M, Visaetsilpanonta S, Hanutsaha P, Patikulsila D.

Department of Ophthalmology, Faculty of Medicine, Prince of Songkla University,
Songkhla, Thailand. mratanasukon@yahoo.com

OBJECTIVE: To evaluate the effect of photodynamic therapy (PDT) with verteporfin 
for age-related macular degeneration (AMD) and non-AMD in Thais, and compare with
the Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP)
and Verteporfin in Photodynamic Therapy (VIP) study. MATERIAL AND METHOD: The
authors prospectively evaluated all data of 51 eyes of 51 patients who had
undergone PDT and accomplished a 1-year follow up. The assessments were divided
into two categories: group 1 included three subsets of AMD, and group 2 was
non-AMD. The first group classified into three subgroups: group 1A: AMD with
subfoveal choroidal neovascularization (CNV) and TAP/VIP compatible with
recommendation guidelines characteristics, group 1B: AMD with subfoveal CNV and
TAP/VIP incompatible, and group 1C: AMD with non-subfoveal CNV. The measurement
outcomes comprised of the baseline characteristics, change in visual acuity, and 
number of treatments. RESULTS: Thirty-eight eyes had CNV-related AMD and 13 eyes 
were non-AMD. At the 12-month examination, the mean visual acuity change in group
1A, 1B, 1C had increased 0.19 (p = 0.077), 0.14 (p = 0.076), and 0.24 (p =
0.003), respectively. The number of treatments was 1.8 in group 1A, 2.3 in group 
1B, and 1.5 in group 1C. CONCLUSION: PDT is beneficial to Thai patients with AMD 
at first year even if they were not compatible with TAP/VIP criteria.

PMID: 18041428 [PubMed - indexed for MEDLINE]

538: Retina. 2007 Oct;27(8):1112-8.

Rebound of cystoid macular edema with continued use of acetazolamide in patients 
with retinitis pigmentosa.

Apushkin MA, Fishman GA, Grover S, Janowicz MJ.

Department of Ophthalmology and Visual Sciences, University of Illinois at
Chicago, Chicago, Illinois 60612, USA.

PURPOSE: To demonstrate the presence of a rebound effect with the use of
acetazolamide for the treatment of cystoid macular edema (CME) in patients with
retinitis pigmentosa (RP). METHODS: Six patients with RP and cystic-appearing
lesions in the macula demonstrated by fluorescein angiography and/or optical
coherence tomography (OCT) were treated with an oral form of carbonic anhydrase
inhibitor (acetazolamide [500 mg]) as a single daily dose. RESULTS: All patients,
treated with acetazolamide for a period of 3 weeks to 5 weeks, had initial
improvement of macular edema demonstrated by OCT. However, extended use of
acetazolamide, for at least 8 weeks to 12 weeks, resulted in recurrence (rebound)
of CME in 3 of the 6 patients. CONCLUSIONS: Results from our study suggest that
rebound of CME with the continued use of acetazolamide observed by OCT may occur 
more frequently than previously appreciated.

Publication Types: 
    Case Reports
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18040255 [PubMed - indexed for MEDLINE]

539: Retina. 2007 Oct;27(8):1044-7.

Comment in:
    Retina. 2008 Apr;28(4):667; author reply 667-8.

Changes of intraocular pressure after intravitreal injection of bevacizumab
(avastin).

Falkenstein IA, Cheng L, Freeman WR.

Joan and Irwin Jacobs Retina Center, Department of Ophthalmology, Shiley Eye
Center, University of California, La Jolla, CA 92037, USA.

PURPOSE: To determine changes and need to monitor intraocular pressure (IOP)
following intravitreal injection of bevacizumab (Avastin). METHODS: Seventy
patients (122 injections) underwent an intravitreal injection of Avastin for
exudative age-related macular degeneration treatment. Forty-one eyes (59%) had
single injection, 29 eyes (41%) had repeated injections. IOP was measured before 
and after Avastin injection at 3, 10, and 15 minutes. Twenty-nine eyes were
evaluated for baseline IOP changes after multiple injections. Statistical
analysis was performed. RESULTS: Baseline mean IOP was 15.17 +/- 3.42 mm Hg, with
range from 08 mm Hg to 23 mm Hg. Postinjection 3 minutes the IOP had risen to a
mean of 36.27 +/- 5.1 mm Hg and fell spontaneously to a mean of 24.56 +/- 5.9 mm 
Hg at 10 minutes. Ten eyes (14%) needed 15 minutes to drop below 30 mm Hg. All
eyes were below 30 mm Hg at 15 minutes. No significant change between multiple
baseline IOP measurements was detected. CONCLUSION: Avastin injections caused a
predictable probably volume-related rise in IOP which never occluded the central 
retinal artery and which spontaneously fell to below 30 mm Hg in all eyes within 
15 minutes. This strong safety profile provides guidelines on monitoring IOP
after Avastin injections. There was no IOP change after multiple injections.

PMID: 18040242 [PubMed - indexed for MEDLINE]

540: Retina. 2007 Oct;27(8):1031-7.

Role of posterior vitreous detachment induced by intravitreal tissue plasminogen 
activator in macular edema with central retinal vein occlusion.

Murakami T, Takagi H, Ohashi H, Kita M, Nishiwaki H, Miyamoto K, Watanabe D,
Sakamoto A, Yamaike N, Yoshimura N.

Department of Ophthalmology and Visual Sciences, Graduate School of Medicine,
Kyoto University, Japan.

PURPOSE: To evaluate the effects of posterior vitreous detachment (PVD) in
macular edema associated with central retinal vein occlusion (CRVO) treated with 
intravitreal tissue plasminogen activator (tPA). METHODS: The authors conducted a
retrospective study of 36 eyes of 36 patients with macular edema by CRVO treated 
with intravitreal tPA. In 16 of 21 eyes without pretreatment PVD, PVD developed
after the treatment. Multiple linear regression analysis was used to evaluate the
correlation between logarithm of the minimum angle of resolution (logMAR) visual 
acuity (VA) changes and several variables. RESULTS: The VA and macular thickness 
significantly improved after treatment. The pretreatment logMAR VA (R = 0.646; P 
< 0.0001), PVD development after tPA (R = -0.303; P = 0.025), and age (R = 0.255;
P = 0.050) correlated with the logMAR VA at final visit. The greater improvement 
in logMAR VA was correlated only with PVD development (R = 0.467; P = 0.0041).
Macular thickness in the eyes with PVD development was significantly less than
without PVD development at the 6-month visit and the end of follow-up.
CONCLUSION: The findings suggest that PVD development after intravitreal tPA may 
partly contribute to the resolution of macular edema and a better VA outcome.

PMID: 18040240 [PubMed - indexed for MEDLINE]

541: Retina. 2007 Oct;27(8):1020-5.

Effect of oral pentoxifylline on cystoid macular edema associated with central
retinal vein occlusion.

Park CH, Scott AW, Fekrat S.

Retina Service, Wills Eye Hospital, Philadelphia, Pennsylvania, USA.

PURPOSE: To determine whether oral pentoxifylline, a xanthine-derived
hemorheologic agent, decreases cystoid macular edema (CME) and improves visual
acuity in eyes with a perfused central retinal vein occlusion (CRVO). METHODS:
Retrospective chart review of consecutive patients on pentoxifylline (400 mg po
TID) for CRVO was performed. Inclusion criteria included CME, pentoxifylline use 
for at least 1 month, and a follow-up period of at least 4 months. Exclusion
criteria included nonperfused or indeterminate CRVO, the presence of
neovascularization, and previous or concurrent laser therapy or any other
treatment for CRVO. Statistical analysis of collected data was performed.
RESULTS: Eleven patients were identified. All patients had a perfused CRVO. The
mean best-corrected Early Treatment Diabetic Retinopathy Study visual acuity was 
60 letters (Snellen equivalent 20/128) before the initiation of oral
pentoxifylline. The mean time from onset of CRVO to start of pentoxifylline
therapy was 5 months (range, 1-12 months). The mean duration of pentoxifylline
use was 5.3 months (range, 2.5-10.2 months). The mean follow-up period was 8
months (range, 2.7-16.5 months). Cystoid macular edema had improved in 64% (7/11)
of eyes at last follow-up as measured by biomicroscopy and optical coherence
tomography. The visual acuity was not significantly changed at 62 letters (20/128
+2) (Student t-test, P = 0.7) at last follow-up. There were no significant side
effects from pentoxifylline. One patient had mild gastrointestinal disturbance.
CONCLUSION: Pentoxifylline has a favorable adverse effect profile, and can reduce
CME in eyes with CRVO. Visual acuity does not appear to change significantly. A
larger, randomized, multiarmed clinical trial evaluating the effects of
pentoxifylline as an adjunctive treatment modality may be of benefit since even a
small positive effect in altering the natural history of CME related to CRVO may 
be of value for these patients.

Publication Types: 
    Case Reports

PMID: 18040238 [PubMed - indexed for MEDLINE]

542: Retina. 2007 Oct;27(8):997-1003.

Iron toxicity as a potential factor in AMD.

Wong RW, Richa DC, Hahn P, Green WR, Dunaief JL.

F. M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University 
of Pennsylvania, Philadelphia, USA.

While it has been known for years that iron overload is associated with retinal
degeneration in the context of ocular siderosis, intraocular hemorrhage, and the 
hereditary diseases aceruloplasminemia and pantothenate kinase associated
neurodegeneration, recent evidence suggests that age-related macular degeneration
(AMD) may also be exacerbated by retinal iron overload. In the retina, iron is
necessary for normal cellular function. Iron overload, however, can cause retinal
toxicity through the generation of oxygen free radicals. Histopathology of eyes
with macular degeneration has shown elevated levels of iron in the retinal
pigment epithelium, Bruch membrane, and within drusen, some of which was
chelatable in vitro with deferoxamine. In this review, the authors summarize the 
evidence that iron overload may contribute to AMD pathogenesis. It is hoped that 
continued investigation of the role of iron and iron associated proteins in the
retina will uncover clues to AMD pathogenesis and lead to new preventative or
therapeutic options.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Review

PMID: 18040235 [PubMed - indexed for MEDLINE]

543: Acta Ophthalmol. 2008 Jun;86(4):377-84. Epub 2007 Nov 26.

Visual prognosis and vitreous cytokine levels after arteriovenous sheathotomy in 
branch retinal vein occlusion associated with macular oedema.

Shimura M, Nakazawa T, Yasuda K, Kunikata H, Shiono T, Nishida K.

Department of Ophthalmology, NTT East Japan Tohoku Hospital, Sendai, Japan.
masahiko@oph.med.tohoku.ac.jp

PURPOSE: To investigate the relationship between vitreous levels of cytokines,
including interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF), and
visual prognosis after pars plana vitrectomy (PPV) with arteriovenous sheathotomy
in patients with branch retinal vein occlusion (BRVO) associated with macular
oedema. METHODS: We studied 60 patients with logMAR visual acuity (VA) scores of 
< 0.3 and visual impairment secondary to BRVO-associated macular oedema. All
patients underwent PPV with arteriovenous sheathotomy. At the time of PPV,
vitreous samples were collected from the operated eye and vitreous levels of VEGF
and IL-6 were measured. Best corrected VA (BCVA) (using a logMAR chart) and
foveal thickness (FT) (using optical coherence tomography) were monitored for up 
to 6 months after PPV. RESULTS: Both BCVA and FT significantly improved after
PPV. According to multiple regression analysis, both the improvement in BCVA and 
decrease in FT were closely related to the vitreous level of IL-6 but not to that
of VEGF. The vitreous level of VEGF was strongly correlated with duration of
BRVO. CONCLUSIONS: Both improvement in BCVA and decrease in FT were observed
after PPV in BRVO patients with macular oedema. Interestingly, these visual
prognoses strongly correlate with the vitreous level of IL-6, whereas the
duration of BRVO strongly correlates with the vitreous level of VEGF.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 18039346 [PubMed - indexed for MEDLINE]

544: Am J Ophthalmol. 2007 Dec;144(6):970-972.

Verteporfin therapy of subfoveal occult choroidal neovascularization in AMD using
delayed light application: one-year results of the VALIO Study.

Rosenfeld PJ, Boyer DS, Bressler NM, Fish G, Grizzard WS, Hao Y, Hnik P, Hudson
HL, Singerman L, Slakter JS; VALIO Study Group.

Bascom Palmer Eye Institute, Miami, FL, USA. prosenfeld@med.miami.edu

PURPOSE: To compare photodynamic therapy (PDT) with verteporfin (Visudyne;
Novartis Pharma AG, Basel, Switzerland) using either standard or delayed light
application. DESIGN: Phase II, multicenter, masked, randomized clinical trial.
METHODS: Sixty patients with occult with no classic choroidal neovascularization 
(CNV) resulting from age-related macular degeneration were assigned randomly
(1:1) to verteporfin infusion followed by light application either at 15 minutes 
(standard light) or 30 minutes (delayed light) after the start of the infusion.
The assigned treatment was repeated every three months if fluorescein leakage was
detected. RESULTS: At month 12, patients lost a mean of 15.7 letters and 11.4
letters from baseline in the standard and delayed light groups, respectively (P =
.38). Twelve (52%) of 23 patients in the standard light group and 11 (42%) of 26 
in the delayed light group lost at least 15 letters of visual acuity (P = .57).
CONCLUSIONS: There were no statistically significant differences between
verteporfin therapy using the delayed light regimen of 30 minutes or the standard
light regimen of 15 minutes in eyes with occult with no classic CNV.

Publication Types: 
    Clinical Trial, Phase II
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18036873 [PubMed - indexed for MEDLINE]

545: Exp Eye Res. 2008 Jan;86(1):150-6. Epub 2007 Oct 25.

Semenogelins in the human retina: Differences in distribution and content between
AMD and normal donor tissues.

Bonilha VL, Rayborn ME, Shadrach KG, Li Y, Lundwall A, Malm J, Hollyfield JG.

Department of Ophthalmology, The Cole Eye Institute, Cleveland Clinic Lerner
College of Medicine, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
bonilhav@ccf.org

The two cellular targets of interest in age-related macular degeneration (AMD)
are the photoreceptors and the RPE. However, the mechanisms involved in AMD
pathology are not yet fully understood. In the present report, we extend our
previous studies on semenogelin proteins (Sgs) in normal human retina and compare
these with the distribution in retinas from AMD donor eyes. Semenogelins I (SgI) 
and II (SgII) are the major structural protein components of semen coagulum, but 
have been recently found in non-genital tissues as well. Cryo and paraffin
sections of human retina were processed for both immunofluorescence and DAB
reaction with a specific antibody. The presence of SgI was analyzed in retina and
RPE total lysates and SgI was detected by western blot in human retina and RPE.
The intensity of immunoreactivity was significantly reduced in the AMD eyes. SgI 
is expressed in the normal human retina and in the retina of AMD donor eyes,
where localization was detected in the photoreceptors and in a few ganglion
cells. We find the distribution of SgI in the AMD retinas substantially lower
than observed in normal retina. SgI localization to photoreceptors and the RPE
suggests a possible function related to the ability of these cells to sequester
zinc.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18036592 [PubMed - indexed for MEDLINE]

546: Clin Ther. 2007 Sep;29(9):2096-106; discussion 2094-5.

Cost-effectiveness of pegaptanib compared to photodynamic therapy with
verteporfin and to standard care in the treatment of subfoveal wet age-related
macular degeneration in Canada.

Earnshaw SR, Moride Y, Rochon S.

RTI Health Solutions, Research Triangle Park, North Carolina, USA.

BACKGROUND: Age-related macular degeneration (AMD) is characterized by loss of
central vision and is the leading cause of blindness among persons over the age
of 50 years in Canada. The wet form of AMD has 3 subtypes-occult, minimally
classic, and predominantly classic. Photodynamic therapy (PDT) with verteporfin
is indicated only for the category of predominantly classic wet AMD. Currently,
there are no treatments available for the other AMD subtypes. Pegaptanib sodium
was the first pharmacologic therapy approved in Canada for the treatment of
subfoveal wet AMD regardless of subtype. OBJECTIVE: The aim of this study was to 
examine the cost-effectiveness of pegaptanib versus PDT with verteporfin and
versus standard care for the treatment of subfoveal wet AMD in patients aged 65
years in Canada. METHODS: A Markov model based on visual acuity in the
better-seeing eye was developed. Clinical efficacy was taken from the clinical
trials. Costs of treatment, comorbidities (eg, depression, fractures, need for
assisted living), vision rehabilitation, visual aids, and adverse events were
considered. Costs, utilities, and mortality were estimated from data from the
available published literature. Costs were reported in 2004 Canadian dollars, and
costs and outcomes were discounted at 3% per annum. Lifetime costs,
quality-adjusted life-years (QALYs), and vision years gained (VYGs) were
estimated. Sensitivity analyses were performed to determine model robustness.
RESULTS: Patients who received pegaptanib experienced more QALYs gained (4.17)
and VYGs (3.83) compared with patients who received PDT (3.87 and 3.01,
respectively) or standard care (3.96 and 3.26). Mean total costs per patient were
greater in patients who received pegaptanib compared to those who received PDT or
standard care ($20,016 vs $15,345 or $7669, respectively). The incremental cost
per QALY in patients receiving pegaptanib compared to those receiving PDT was
$49,052 and $59,039 for patients receiving pegaptanib versus standard care. The
incremental cost per VYG was $20,401 and $21,559 with pegaptanib versus PDT and
standard care, respectively. Sensitivity analyses found that the model was
relatively robust to changes in various model parameters. CONCLUSION: The results
of this analysis suggest that in Canada, pegaptanib is a cost-effective treatment
for subfoveal wet AMD in elderly patients, regardless of lesion subtype, compared
to PDT with verteporfin and to standard care.

Publication Types: 
    Comparative Study

PMID: 18035208 [PubMed - indexed for MEDLINE]

547: Clin Ther. 2007 Sep;29(9):1850-61.

Ranibizumab for the treatment of neovascular age-related macular degeneration: a 
review.

Kourlas H, Abrams P.

Department of Pharmacy Practice, Arnold and Marie Schwartz College of Pharmacy
and Health Sciences, Long Island University, Brooklyn, New York 11201, USA.
Helen.Kourlas@liu.edu

BACKGROUND: Choroidal neovascular (wet) age-related macular degeneration (ARMD)
is becoming more prevalent worldwide as life expectancy continues to increase.
Ranibizumab for intravitreal injection is an inhibitor of human vascular
endothelial growth factor A approved by the US Food and Drug Administration for
the treatment of ARMD in June 2006. The actions of ranibizumab result in reduced 
cell proliferation, reduced formation of new blood vessels, and minimization of
vascular leakage. OBJECTIVE: This paper reviews the pharmacologic and
pharmacokinetic properties, clinical efficacy, and safety profile of ranibizumab,
and pharmacoeconomic considerations associated with its use. METHODS: MEDLINE
(1966-December 2006) and International Pharmaceutical Abstracts (1970-December
2007) were searched for original research studies (Phase I, II, III, and IIIb),
abstracts, and review articles concerning ranibizumab. The search terms were
choroidal neovascularization, macular degeneration, Lucentis, ranibizumab,
retinal degeneration, and vascular endothelial growth factor. Preference was
given to Phase IlfllI studies. Selected information from the manufacturer of
ranibizumab was also included. RESULTS: The efficacy of ranibizumab has been
studied in 3 large clinical trials having the same primary efficacy end point,
the proportion of patients losing <15 letters from baseline at 12 months (Early
Treatment of Diabetic Retinopathy Study chart). A multicenter, Phase III,
randomized, double-blind, sham-controlled, 24-month clinical trial evaluated
ranibizumab 0.3 and 0.5 mg in 716 patients with minimally classic or occult
choroidal neovascularization (CNV) associated with ARMD. The results for the
primary efficacy end point were 94.5% and 94.6% in the ranibizumab 0.3- and
0.5-mg groups, respectively, compared with 62.2% in the sham-injection group (P <
0.001, both ranibizumab groups vs sham injection); at 24 months, the
corresponding proportions were 92.0%, 90.0%, and 52.9% (P < 0.001, both
ranibizumab groups vs sham injection). A 2-year, Phase I/II, single-masked
(masked patient and visual acuity examiner, unmasked investigator), multicenter
trial evaluated the tolerability and efficacy of the combination of ranibizumab
0.5 mg and verteporfin photodynamic therapy (PDT) compared with verteporfin PDT
alone in 162 patients with predominantly classic CNV. For the primary efficacy
end point, the results were 90.5% for ranibizumab + PDT and 67.9% for PDT alone
(P < 0.001). Receipt of ranibizumab + PDT was also associated with improved
visual acuity, with 23.8% of patients gaining >15 letters from baseline, compared
with 5.4% of those who received PDT alone (P = 0.003). Finally, an international 
Phase III, double-blind, active-controlled study compared ranibizumab 0.3 and 0.5
mg with verteporfin PDT in 423 patients with predominantly classic lesions
associated with CNV secondary to ARMD. For the primary efficacy end point, the
results were 35.7% for ranibizumab 0.3 mg, 40.3% for ranibizumab 0.5 mg, and 5.6%
for verteporfin PDT (P < 0.001). Serious adverse ocular events, which occurred in
association with < 0.1% of intravitreal injections in these trials, included
retinal detachment and endophthalmitis. Less serious adverse ocular reactions
occurring in < 2% of patients included intraocular inflammation and increased
intraocular pressure. CONCLUSION: The findings of these 3 large clinical trials
suggest that ranibizumab was effective and well tolerated in patient.

Publication Types: 
    Comparative Study
    Review

PMID: 18035187 [PubMed - indexed for MEDLINE]

548: Surv Ophthalmol. 2007 Nov-Dec;52(6):655-71.

Use of fundus imaging in quantification of age-related macular change.

Bartlett H, Eperjesi F.

Ophthalmic Research Group, School of Life and Health Sciences, Aston University, 
Birmingham, United Kingdom.

This review will discuss the use of manual grading scales, digital photography,
and automated image analysis in the quantification of fundus changes caused by
age-related macular disease. Digital imaging permits processing of images for
enhancement, comparison, and feature quantification, and these techniques have
been investigated for automated drusen analysis. The accuracy of automated
analysis systems has been enhanced by the incorporation of interactive elements, 
such that the user is able to adjust the sensitivity of the system, or manually
add and remove pixels. These methods capitalize on both computer and human image 
feature recognition and the advantage of computer-based methodologies for
quantification. The histogram-based adaptive local thresholding system is able to
extract useful information from the image without being affected by the presence 
of other structures. More recent developments involve compensation for fundus
background reflectance, which has most recently been combined with the Otsu
method of global thresholding. This method is reported to provide results
comparable with manual stereo viewing. Developments in this area are likely to
encourage wider use of automated techniques. This will make the grading of
photographs easier and cheaper for clinicians and researchers.

Publication Types: 
    Review

PMID: 18029272 [PubMed - indexed for MEDLINE]

549: Acta Ophthalmol. 2008 Jun;86(4):372-6. Epub 2007 Nov 17.

Complications in patients after intravitreal injection of bevacizumab.

Shima C, Sakaguchi H, Gomi F, Kamei M, Ikuno Y, Oshima Y, Sawa M, Tsujikawa M,
Kusaka S, Tano Y.

Department of Ophthalmology, Osaka University Medical School, Suita, Japan.

PURPOSE: To report complications in patients after intravitreal injection of
bevacizumab to treat ocular diseases associated with vascular endothelial growth 
factor. METHODS: We retrospectively reviewed the systemic and ocular
complications that developed within 2 months of each intravitreal injection of
bevacizumab in 707 patients (1300 injections) with intraocular neovascularization
or macular oedema. RESULTS: Nine ocular (1.27%) and eight systemic (1.13%)
complications occurred in 707 patients. The ocular complications included corneal
abrasion (n = 2), chemosis (n = 2), lens injury (n = 1), ocular inflammation (n =
2), retinal pigment epithelial tear (n = 1) and acute vision loss (n = 1). The
systemic complications included cerebral infarction (n = 1), elevation of
systolic blood pressure (n = 2), facial skin redness (n = 1), itchy diffuse rash 
(n = 1) and menstrual irregularities (n = 3). CONCLUSION: Intravitreal injection 
of bevacizumab may cause systemic or ocular complications. Caution is advised
when considering intravitreal injection of this drug.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 18028234 [PubMed - indexed for MEDLINE]

550: Can J Ophthalmol. 2007 Dec;42(6):836-43.

Burden of illness of neovascular age-related macular degeneration in Canada.

Cruess A, Zlateva G, Xu X, Rochon S.

Department of Ophthalmology and Visual Sciences, Dalhousie University, Halifax,
NS.

BACKGROUND: Age-related macular degeneration (AMD) is a retinal disease affecting
more than 2 million Canadians over the age of 50. The neovascular form of AMD is 
responsible for 90% of severe vision loss associated with the disease. This study
was conducted to assess the burden of neovascular AMD in the Canadian population.
METHODS: A cross-sectional, observational study was conducted of self-reported
functional health, well-being, and disease burden among elderly subjects in
Canada with (n = 67) and without (n = 99) neovascular AMD. Subjects completed
telephone surveys of the National Eye Institute Visual Function Questionnaire
(NEI-VFQ-25), the EuroQol questionnaire (EQ-5D), and the Hospital Anxiety and
Depression Scale (HADS). Subjects also reported their history of falls and
fractures and annual health care resource utilization. RESULTS: Subjects with
neovascular AMD reported significantly worse vision-related functioning and
overall well-being than controls (adjusted mean scores on the NEI-VFQ-25: 48.0
vs. 87.5; p < 0.0001) and significantly more depression symptoms than controls
(HADS depression: 5.8 vs. 4.3; p = 0.037). Subjects with neovascular AMD also
reported more than twice the need for assistance with daily activities compared
with controls (19.4% vs. 9.1%; p = 0.013) and a nearly 3 times higher fall rate
than the control group (22.4% vs. 8.1%; p = 0.014). The annual neovascular AMD
cost per patient was Can dollars 11,334, which is over 8 times that of elderly
subjects without neovascular AMD (Can dollars 1,412). Over half of the
neovascular AMD costs were direct medical costs. INTERPRETATION: Neovascular AMD 
is associated with significant limitation in functional abilities and quality of 
life, resulting in increased health care resource utilization and high patient
support costs. These findings emphasize the need for new treatments for
neovascular AMD that will prevent vision loss and progression to blindness in
order to lessen the ensuing economic burden.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 18026200 [PubMed - indexed for MEDLINE]

551: Ophthalmic Res. 2008;40(1):26-31. Epub 2007 Nov 20.

Posterior subtenon triamcinolone, intravitreal triamcinolone and grid laser
photocoagulation for the treatment of macular edema in branch retinal vein
occlusion.

Ozdek S, Deren YT, Gurelik G, Hasanreisoglu B.

Department of Ophthalmology, School of Medicine, Gazi University, Ankara, Turkey.
sozdek@gazi.edu.tr

PURPOSE: To evaluate the efficacy of posterior subtenon triamcinolone (PSTT),
intravitreal triamcinolone (IVT) injections and grid laser photocoagulation (GLP)
in eyes with macular edema secondary to branch retinal vein occlusion (BRVO).
MATERIAL AND METHODS: Patients with macular edema due to BRVO treated with PSTT, 
IVT injections or GLP were evaluated retrospectively. Complete ophthalmic
examination with fluorescein angiography and optic coherence tomography were
noted before and in the 1st, 3rd, and 6th months of the treatment. The visual and
anatomical responses were evaluated and compared between the groups using paired 
t test and one-way ANOVA test. RESULTS: There were 20, 35 and 24 eyes in the
PSTT, IVT and GLP groups. In the PSTT group, the mean visual acuity (VA) and
central foveal thickness (CFT) were 0.23 +/- 0.23 and 413.2 +/- 143.5 microm
before treatment and 0.23 +/- 0.18 and 358.7 +/- 109.2 microm at the 3rd month,
respectively (p = 0.504 and p = 0.031). The mean VA increased from 0.14 +/- 0.15 
to 0.33 +/- 0.26 and the mean CFT decreased from 518.2 +/- 145 to 292.9 +/- 121
microm in IVT group at the 3rd month (p = 0.001). The mean VA increased from 0.29
+/- 0.25 to 0.47 +/- 0.32 (p = 0.001); CFT decreased from 397.3 +/- 105.9 to
307.1 +/- 88.4 microm (p = 0.005) in the GLP group. VA and CFT changes were
significantly different between the groups at the 3rd month (p = 0.031). VA
increase was significantly greater in the IVT group than in the PSTT group.
Decrease in CFT was the highest in the IVT group (Tukey, p = 0.001). CONCLUSIONS:
IVT and GLP seemed to be more effective than PSTT for the treatment of
BRVO-associated macular edema. Possible complications of IVT and GLP must be
weighted with the advantages of each treatment modality for each patient.

Publication Types: 
    Comparative Study
    Evaluation Studies

PMID: 18025838 [PubMed - indexed for MEDLINE]

552: Ann Ophthalmol (Skokie). 2007 Dec;39(4):307-12.

Two-year results of intravitreal triamcinolone acetonide injection for the
treatment of macular edema due to central retinal vein occlusion.

Batioglu F, Ozmert E, Akmese E.

Department of Ophthalmology, Faculty of Medicine, Ankara University, Ankara,
Turkey. fbatioglu@gmail.com

We investigated intravitreal triamcinolone acetonide injection for the treatment 
of macular edema due to central retinal vein occlusion in 20 patients. Mean
central macular thickness at 3 days, 1, 3, 6, 12, 18, and 24 months
postoperatively was different than baseline. Visual acuity did not change.
Intravitreal triamcinolone injection significantly improves short-term anatomy,
but recurrences and steroid-related complications were noted in the longer term.

PMID: 18025651 [PubMed - indexed for MEDLINE]

553: Ann Ophthalmol (Skokie). 2007 Sep;39(3):222-7.

Vitreous surgery for diabetic macular edema--its prognosis and correlation
between preoperative systemic and ocular conditions and visual outcome.

Hatano N, Mizota A, Tanaka M.

Department of Ophthalmology, Juntendo University Urayasu Hospital, 2-1-1 Tomioka,
Urayasu, 279-0021, Japan.

The effectiveness of vitreous surgery for diabetic macular edema (DME), and the
correlation between the preoperative systemic and ocular conditions and the
visual outcome following vitrectomy were studied. Visual acuity improved in about
50% of the eyes. Both visual acuity and foveal thickness recovered 12 months
after surgery and the improvement of visual acuity occurred later than the
recovery of foveal thickness. The preoperative systemic condition does not affect
the improvement of visual acuity, and thus it is not necessary to wait for good
diabetic control if surgery is indicated.

PMID: 18025629 [PubMed - indexed for MEDLINE]

554: J Ocul Pharmacol Ther. 2007 Dec;23(6):599-600.

Intravitreal bevacizumab combined with cataract surgery for treatment of
exudative macular degeneration.

Jonas JB, Spandau UH, Schlichtenbrede F, Libondi T, Vossmerbaeumer U, von Baltz
S.

Department of Ophthalmology, Medical Faculty Mannheim of the
Ruprecht-Karls-University, Mannheim, Germany.
Jost.Jonas@augen.ma.uni-heidelberg.de

PURPOSE: The aim of this study was to report on the combination of an
intravitreal injection of bevacizumab and cataract surgery in patients with
exudative age-related macular degeneration (AMD). METHODS: The interventional
case series study included 11 patients (11 eyes) who received an intravitreal
injection of 1.5 mg bevacizumab as treatment of exudative AMD (n = 10) or
exudative myopic macular degeneration (n = 1), combined with a routine
phacoemulsification and posterior chamber lens implantation for treatment of
cataract. RESULTS: Intraoperatively and during the follow-up of 150 +/- 77.5
days, there were no complications related to the intravitreal application of
bevacizumab combined with cataract surgery, such as wound dehiscence and leakage,
delayed wound healing, corneal edema, dislocation of the pseudophakos, rupture of
the posterior lens capsule, or rhegmatogenous retinal detachment. CONCLUSIONS:
The results of this pilot study suggest that from a safety point of view,
intravitreal injections of bevacizumab may be combined with routine cataract
surgery.

PMID: 18020962 [PubMed - indexed for MEDLINE]

555: Bull Exp Biol Med. 2007 Jan;143(1):64-7.

Sorsby fundus dystrophy-related mutation in tissue inhibitor of
metalloproteinases-3 impairs regulation of its expression in mouse fibroblasts.

Sukhikh GT, Soboleva GM.

Research Center of Obstetrics, Gynecology, and Perinatology, Russian Academy of
Medical Sciences, Moscow.

Mutations in the C-terminal domain of tissue inhibitor of metalloproteinases-3
(TIMP-3) are linked with Sorsby fundus dystrophy (autosomal dominant retinal
dystrophy). Experiments on timp-3 gene knock-out and knock-in mice, carriers of
dystrophy-linked Timp-3S156C mutation, showed that expression of mutant
Timp-3S156C, in contrast to the normal one, is not regulated by
phorbol-myristate-12-acetate and is retained at a high level in a medium without 
FCS. The mutant protein is not transported into the nucleus, while fibroblasts
expressing it survive without FCS and other growth factors. It is hypothesized
that normal Timp-3 is involved in the regulation of expression of its own timp-3 
gene and, probably, other genes associated with growth and proliferation. The
absence of this characteristic in mutant Timp-3S156C is presumably responsible
for its accumulation in the extracellular matrix.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18019015 [PubMed - indexed for MEDLINE]

556: Aviat Space Environ Med. 2007 Nov;78(11):1064-7.

Maculopathy associated with Dengue fever in a military pilot.

Nah G, Tan M, Teoh S, Chong CH.

Singapore Armed Forces Medical Corps.

Dengue fever is the most prevalent vector-borne flavivirus infection in humans.
Its ocular manifestations have only recently been reported with increasing
frequency. We present a case of an air force rotary wing pilot who presented with
dengue-related maculopathy and decrement in visual function. The pilot ultimately
recovered full visual function and was returned to full unrestricted flying
duties with the proviso of regular ophthalmic monitoring. Dengue-related
maculopathy may present with retinal edema, blot hemorrhages, and vasculitis.
Less common features include exudative retinal detachment, cotton wool spots, and
anterior uveitis. It is generally self-resolving with good prognosis. Treatment
is controversial, but a course of corticosteroids has been tried in view of a
postulated underlying immune-mediated pathology. It is recommended that aviators 
who have recovered from dengue fever undergo a clinical ophthalmological
examination before return to flying duties.

Publication Types: 
    Case Reports

PMID: 18018440 [PubMed - indexed for MEDLINE]

557: Bull Soc Belge Ophtalmol. 2007;(305):23-6.

Peripheral exudative and hemorrhagic chorio-retinopathy...the peripheral form of 
age-related macular degeneration? Report on 2 cases.

Collaer N, James C.

Tobay Hospital, Department of Ophthalmology, Torquay, UK.
nanny_collaer@hotmail.com

Report of two patients presenting with peripheral exudative hemorrhagic
chorioretinopathy, an underrecognized, possible sight-threatening condition.
Thorough examination of the peripheral fundus remains the key factor in
recognizing this disease. The greatest immediate risk for the patient is an
incorrect diagnosis of suspected choroidal melanoma.

Publication Types: 
    Case Reports

PMID: 18018423 [PubMed - indexed for MEDLINE]

558: Doc Ophthalmol. 2008 Mar;116(2):91-5. Epub 2007 Nov 16.

Annular fundus autofluorescence abnormality in a case of macular dystrophy.

Poloschek CM, Hansen LL, Bach M.

Department of Ophthalmology, University of Freiburg, Killianstr. 5, 79106
Freiburg, Germany. charlotte.poloschek@uniklinik-freiburg.de

PURPOSE: To present a case of macular dystrophy with early changes in fundus
autofluorescence. METHODS: A 20-year-old woman with a recent loss of visual
acuity and onset of photophobia was examined. Color vision and visual field
testing, fluorescein angiography, full-field and multifocal electroretinograms as
well as fundus autofluorescence were performed. RESULTS: Best-corrected visual
acuity was 20/100 (right eye) and 20/60 (left eye). There was a red-green color
vision defect and a relative central scotoma in both eyes. Ophthalmoscopy and
fluorescein angiography were essentially normal, the presence of a dark choroid
was debatable. Full-field ERG responses were normal, but the multifocal ERG
showed severely reduced responses in the macular region. Both eyes showed a
slight circular parafoveolar increase of fundus autofluorescence. CONCLUSION:
Besides multifocal ERG, fundus autofluorescence aids to objectively assess the
manifestation of macular dystrophies but does not discern between different types
in early stages.

Publication Types: 
    Case Reports

PMID: 18008096 [PubMed - indexed for MEDLINE]

559: Acta Ophthalmol. 2008 May;86(3):284-91. Epub 2007 Nov 13.

The predictive value of optical coherence tomography after grid laser
photocoagulation for diffuse diabetic macular oedema.

Soliman W, Sander B, Soliman KA, Yehya S, Rahamn MS, Larsen M.

Department of Ophthalmology, Glostrup Hospital, University of Copenhagen,
Copenhagen, Denmark. waelsoliman73@yahoo.com

PURPOSE: To assess the predictive value of optical coherence tomography (OCT)
mapping of retinal thickness and intraretinal morphological changes after macular
grid for diffuse diabetic macular oedema (DMO). METHODS: We carried out a
prospective, non-controlled, case series study, in which 28 consecutive eyes with
previously untreated diffuse DMO underwent fundus photography and OCT at baseline
and at 1, 3 and 6 months after treatment. RESULTS: Macular photocoagulation was
followed by a significant reduction in retinal thickness in the foveal centre (- 
80 microm) and in the foveal subfield (- 65 microm) from baseline to 6 months (p 
< 0.01). The bulk of the reduction in retinal thickness and macular volume was
manifest after 1 month. No significant change in retinal thickness occurred from 
1 to 3 months or from 1 to 6 months in any macular subfield (p > 0.05). The
relative decrease in retinal thickness at 6 months was highest in the foveal
centre (- 22%), followed by the foveal region (- 18%), the inner parafoveal
region (- 8%), and the outer parafoveal region (- 2%). Thus, the effect of
photocoagulation on retinal thickness decreased with increasing eccentricity (p <
0.025). Overall, there was no statistically significant change in best corrected 
visual acuity (BCVA) between baseline and follow-up (p < 0.05), but changes in
foveal subfield thickness and changes in VA were highly correlated (r = 0.66, p <
0.0001). Visual outcome (final BCVA) and final foveal subfield thickness at 6
months were correlated with the pattern of intraretinal morphological changes at 
baseline (Spearman's correlation coefficient r = - 0.41, p = 0.03 and r = 0.45, p
= 0.02, respectively). In addition, visual outcome (final BCVA) and final foveal 
subfield thickness at 6 months were correlated with baseline foveal thickness
(Spearman's correlation coefficient (r = - 0.37, p = 0.05 and r = 0.5, p = 0.01, 
respectively). CONCLUSIONS: It seems that the 1-month time-point after macular
laser treatment is a critical point for establishing the outcome of this modality
of management of DMO. Baseline OCT mapping of intraretinal fluid accumulation
patterns and foveal thickness can help to predict the final visual outcome and
final foveal thickness, but not the absolute change in either of these parameters
after macular laser therapy.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18005220 [PubMed - indexed for MEDLINE]

560: Pharmacogenet Genomics. 2007 Dec;17(12):1039-46.

Predictive role of coagulation-balance gene polymorphisms in the efficacy of
photodynamic therapy with verteporfin for classic choroidal neovascularization
secondary to age-related macular degeneration.

Parmeggiani F, Costagliola C, Gemmati D, D'Angelo S, Perri P, Scapoli GL, Catozzi
L, Federici F, Sebastiani A, Incorvaia C.

Department of Ophthalmology, Center Study for Hemostasis and Thrombosis,
University of Ferrara, Ferrara, Italy. francesco.parmeggiani@unife.it

OBJECTIVES: Age-related macular degeneration (AMD) represents the leading cause
of blindness in Western populations. The majority of severe vision loss occurs in
the exudative form of AMD, characterized by the development of choroidal
neovascularization (CNV) beneath the fovea. Photodynamic therapy with verteporfin
(PDT-V) represents one of the most largely employed modality that maybe achieves 
the subfoveal CNV inactivation in AMD patients. Although several ocular factors
have been hitherto investigated as predictors, these researches have weakly
contributed to PDT-V optimization. As PDT-V benefit is determined by CNV
photothrombosis, we have retrospectively studied several coagulation-balance gene
polymorphisms as predictors of PDT-V efficacy. METHODS: Ninety Caucasian patients
with neovascular AMD were subdivided in responder and nonresponder, on the basis 
of CNV responsiveness to PDT-V application. Six gene polymorphisms, that is
factor V G1691A, prothrombin G20210A, factor XIII-A G185T,
methylenetetrahydrofolate reductase C677T, methionine synthase A2756G, and
methionine synthase reductase A66G, were genotyped in the entire cohort. RESULTS:
Logistic regression models showed that PDT-V responders were more prevalent
within patients with prothrombin G20210A mutation [odds ratio (OR)=5.6, 95%
confidence interval (CI) (1.2, 27.2), P=0.03], and within
methylenetetrahydrofolate reductase 677T carriers [OR=6.9, 95% CI (2.7, 18.1),
P<0.001]. Conversely, PDT-V nonresponders were overrepresented in carriers for
factor XIII-A 185T [OR=0.13, 95% CI (0.05, 0.36), P<0.001]. CONCLUSION: These
results provide evidences for the presence of pharmacogenetic relationship
between peculiar coagulation-balance gene polymorphisms and different levels of
PDT-V effectiveness in patients with AMD-related CNV.

PMID: 18004208 [PubMed - indexed for MEDLINE]

561: Conf Proc IEEE Eng Med Biol Soc. 2007;2007:4965-8.

A hybrid segmentation approach for geographic atrophy in fundus auto-fluorescence
images for diagnosis of age-related macular degeneration.

Lee N, Laine AF, Smith RT.

Heffner Biomedical Imaging Lab, Department of Biomedical Engineering, Columbia
University, CO 80305, USA. nl2168@columbia.edu

Fundus auto-fluorescence (FAF) images with hypo-fluorescence indicate geographic 
atrophy (GA) of the retinal pigment epithelium (RPE) in age-related macular
degeneration (AMD). Manual quantification of GA is time consuming and prone to
inter- and intra-observer variability. Automatic quantification is important for 
determining disease progression and facilitating clinical diagnosis of AMD. In
this paper we describe a hybrid segmentation method for GA quantification by
identifying hypo-fluorescent GA regions from other interfering retinal vessel
structures. First, we employ background illumination correction exploiting a
non-linear adaptive smoothing operator. Then, we use the level set framework to
perform segmentation of hypo-fluorescent areas. Finally, we present an energy
function combining morphological scale-space analysis with a geometric
model-based approach to perform segmentation refinement of false positive hypo-
fluorescent areas due to interfering retinal structures. The clinically apparent 
areas of hypo-fluorescence were drawn by an expert grader and compared on a pixel
by pixel basis to our segmentation results. The mean sensitivity and specificity 
of the ROC analysis were 0.89 and 0.98%.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18003121 [PubMed - indexed for MEDLINE]

562: J Ocul Pharmacol Ther. 2007 Dec;23(6):585-90.

Cystoid and diabetic macular edema treated with nepafenac 0.1%.

Hariprasad SM, Callanan D, Gainey S, He YG, Warren K.

Department of Ophthalmology and Visual Science, University of Chicago, Chicago,
IL 60637, USA. retina@uchicago.edu

Cystoid macular edema (CME), a common complication following cataract surgery, is
routinely medically treated with topical nonsteroidal anti-inflammatory drugs
(NSAIDs), alone or in combination with steroids. In this paper, we describe 6
patients with CME and 1 patient with diabetic macular edema (DME), all of whom
were treated with nepafenac 0.1%, a novel prodrug NSAID. Three (3) patients with 
acute CME following cataract surgery were treated for 3-4 weeks with nepafenac
0.1%, with or without concomitant steroids. Both retinal thickness and visual
acuity improved in all 3 cases. The 3 patients with chronic CME, each of whom had
been previously treated with steroids with or without concomitant NSAID therapy, 
were started on nepafenac 0.1% three times daily. Retinal thickness and visual
acuity improved in each case, except for 1 patient with 20/25 pretreatment visual
acuity. The mean improvement in visual acuity of all 6 CME patients was 2.5 lines
and the mean decrease in retinal thickness was 282.8 microm. The patient with DME
also showed improvement in retinal thickness and visual acuity after 6 months of 
treatment with nepafenac. These clinical data strongly suggest that nepafenac
0.1% is a promising drug for the treatment of posterior segment inflammation,
including CME, and warrants further investigation.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 18001248 [PubMed - indexed for MEDLINE]

563: J Ocul Pharmacol Ther. 2007 Dec;23(6):577-84.

Relationship between blood-aqueous barrier disruption and ischemic macular edema 
in patients with branch or central retinal vein occlusion: effects of sub-tenon
triamcinolone acetonide injection.

Asano S, Miyake K, Miyake S, Ota I.

Shohzankai Medical Foundation, Miyake Eye Hospital, Nagoya, Japan.

PURPOSE: The aim of this study was to study the effects of the sub-Tenon
triamcinolone acetonide (STA) injection on ischemic cystoid macular edema (CME)
or macular edema (ME) and blood-aqueous barrier (BAB) disruption associated with 
branch or central retinal vein occlusion (BRVO or CRVO). METHODS: Prior to, and
1, 2, 3, and 4 months after, STA injection, central retinal thickness was
measured by using optical coherence tomography and the amount of aqueous flare by
using laser flare metry. RESULTS: In the BRVO group treated by STA, the amount of
flare was significantly less at 1, 2, and 3 months after injection than in the
untreated BRVO group (P < 0.05). In the CRVO group treated by STA, the amount was
significantly less at 1 month after injection than in the untreated CRVO group (P
< 0.05). In the BRVO group with STA treatment, central retinal thickness was
significantly less at 1 and 2 months after the treatment than in the untreated
BRVO group (P < 0.05). In the CRVO group with STA treatment, the thickness was
significantly less at 1 month after treatment than in the untreated CRVO group (P
< 0.05). A correlation test revealed the amount of aqueous flare and the central 
retinal thickness to be well correlated (P < 0.01). CONCLUSIONS: The effects of
STA and its time course on CME or ME correlated well with those on BAB
disruption. Since there is the close correlation between the BAB and
blood-retinal barrier function, the effects of medical treatment on ME associated
with BRVO or CRVO can be evaluated by means of the BAB function.

Publication Types: 
    Randomized Controlled Trial

PMID: 18001246 [PubMed - indexed for MEDLINE]

564: J Ocul Pharmacol Ther. 2007 Dec;23(6):567-70.

Cystoid macular edema in a pseudophakic patient after switching from latanoprost 
to BAK-free travoprost.

Esquenazi S.

Department of Ophthalmology, LSU Eye and Neuroscience Center of Excellence, New
Orleans, LA 70112, USA. sesque@lsuhsc.edu

PURPOSE: The aim of this study was to report a case of cystoid macular edema
(CME) in a pseudophakic patient after switching from latanoprost to BAK-free
travoprost. METHODS: This study is presented as an interventional case report.
RESULTS: Clinical examination showed the development of CME, proven by ocular
coherence tomography, after institution of BAK-free travoprost in a patient that 
was previously treated with Latanoprost. Ocular signs and symptoms responded to
stopping travoprost and treatment with topical prednisolone and non-steroidal
anti-inflammatory medicines. The intraocular pressure was successfully controlled
with brimonidine tartrate 0.15%. CONCLUSIONS: CME is a known adverse effect of
all prostaglandin analogs. However, our patient developed this complication after
being switched from latanoprost to BAK-free travoprost. This may be due to
exacerbation of a previously undiagnosed CME or to the ionic-buffered
preservative system (sofZia) alone or in combination with travoprost unique to
this product. It is prudent to exercise caution in the use of prostaglandin
analogs and prostamides especially in high-risk eyes.

Publication Types: 
    Case Reports

PMID: 18001244 [PubMed - indexed for MEDLINE]

565: J Cancer Res Ther. 2007 Jan-Mar;3(1):12-6.

Age related macular degeneration: a study of patients managed with radiotherapy.

Munshi A, Sarin R, Dudhani A, Dinshaw KA.

Department of Radiation Oncology, Tata Memorial Hospital, Mumbai, India.
anusheel8@ hotmail.com

INTRODUCTION: Age-related macular degeneration (ARMD) is the leading cause of
blindness in the west. Radiotherapy affects the evolution of exudative macular
degeneration directly by its effect on the endothelium and inflammation
modulation. We conducted a retrospective study to evaluate the improvement in
visual acuity and healing of sub retinal neovascular membrane (SRNV) following
fractionated radiotherapy. MATERIALS AND METHODS: 47 patients (58 eyes) of ARMD
were retrospectively analyzed. One of the following radiotherapy fractionation
schedules was employed in all the patients in this study. a) 15 Gy/5 fractions/1 
week (five patients) b) 20 Gy/5 fractions/1 week (19 patients) c) 22.5 Gy/5
fractions/1 week (21 patients) d) 25 Gy/5 fractions/1 week (two patients). VA and
funduscopy was taken at each follow-up for objective improvement and to assess
the healing of SRNV. RESULTS: The median follow-up was 7.23 months. The mean
improvement in the VA in the entire group was of 0.44 line. (Median 1, SD 1.04). 
Overall 75% of the eyes showed either steady vision or an improvement in
subjective vision analysis. The deterioration free survival was significantly
better in the group that had a relatively short duration of symptoms (P = 0.01). 
Scarring at presentation was a significant adverse factor for improvement in
vision after radiotherapy (P = 0.001). CONCLUSIONS: In patients of ARMD treated
with radiotherapy, the initial duration of symptoms and scarring of eyes at
presentation were significant prognostic variables for improvement in VA after
radiotherapy.

PMID: 17998713 [PubMed - indexed for MEDLINE]

566: Arch Ophthalmol. 2007 Nov;125(11):1460-9.

Improved vision-related function after ranibizumab treatment of neovascular
age-related macular degeneration: results of a randomized clinical trial.

Chang TS, Bressler NM, Fine JT, Dolan CM, Ward J, Klesert TR; MARINA Study Group.

Retina Institute of California, 800 S Fairmount Ave, Ste 312, Pasadena, CA 91105,
USA. tomschang@hotmail.com

OBJECTIVE: To examine the effects of ranibizumab on patient-reported visual
function using the National Eye Institute Visual Function Questionnaire 25 (NEI
VFQ-25) in patients with neovascular age-related macular degeneration (AMD).
DESIGN: In MARINA, a randomized, double-masked clinical trial, 716 patients with 
AMD with recent disease progression and minimally classic or occult with no
classic lesion component were randomized 1:1:1 to monthly intravitreal
ranibizumab (0.3 or 0.5 mg) or sham injections. The NEI VFQ-25 was administered
at 0, 1, 2, 3, 6, 9, 12, 18, and 24 months. Main Outcome Measure Mean change from
baseline in NEI VFQ-25 scores at 12 and 24 months. RESULTS: At 12 months,
ranibizumab-treated patients (0.3 mg [n = 238] and 0.5 mg [n = 240]) had mean
improvements in NEI VFQ-25 composite scores of +5.2 (95% confidence interval
[CI], 3.5 to 6.9) and +5.6 (95% CI, 3.9 to 7.4), respectively; sham-injected
patients (n = 238) had a mean decline of -2.8 (95% CI, -4.6 to -1.1; P < .001 vs 
each dose). Ranibizumab-treated patients were more likely to improve in near
activities, distance activities, and vision-specific dependency through 24
months. CONCLUSIONS: In MARINA, ranibizumab-treated patients were more likely
than sham-treated patients to report visual function improvements at 12 and 24
months. APPLICATION TO CLINICAL PRACTICE: Treatment of neovascular AMD with
ranibizumab can improve patient-reported visual function in a meaningful way
compared with sham treatments. TRIAL REGISTRATION: clinicaltrials.gov Identifier:
NCT00056836.

Publication Types: 
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17998507 [PubMed - indexed for MEDLINE]

567: Clin Experiment Ophthalmol. 2007 Nov;35(8):781-3.

Abnormalities of visual-evoked potentials and pupillary light reflexes in a
family with autosomal dominant occult macular dystrophy.

Okuno T, Oku H, Kondo M, Miyake Y, Sugasawa J, Utsumi T, Ikeda T.

Occult macular dystrophy (OMD) is an unusual inherited or sporadic macular
dystrophy characterized by an essentially normal appearing ocular fundus and
normal ocular circulation determined by fluorescein angiography but with a
progressive decrease of visual acuity. We present a family with OMD who have a
delay in the implicit times of both the visual-evoked potentials and the
pupillary light reflexes. Because these delays are usually indicative of optic
nerve disorders, deciding on a diagnosis between OMD and optic nerve disorder
should be done carefully. We are not aware of any studies that have reported
these findings in patients with OMD.

Publication Types: 
    Case Reports
    Letter

PMID: 17997791 [PubMed - indexed for MEDLINE]

568: Clin Experiment Ophthalmol. 2007 Nov;35(8):777-9.

Retinal astrocytic hamartoma and Stargardt's disease: unusual association in a
patient with ABCR mutation without phacomatosis.

Bini A, Sodi A, Passerini I, Menchini U, Torricelli F.

We report the unusual association of a retinal astrocytic hamartoma and
Stargardt's disease in a patient with ABCR mutation. A healthy 24-year-old man
exhibited the typical fundus appearance of Stargardt's disease in both eyes,
associated with a white, well-circumscribed, elevated lesion in the
inferotemporal area of the right eye. Molecular genetic examination of the ABCR
gene detected three heterozygous missense mutations, described in the literature 
in association with Stargardt's disease. Optical coherence tomography,
fluorangiography, electroretinography and B scan ultrasonography were performed. 
The clinical findings were consistent with the diagnosis of retinal astrocytic
hamartoma. The connection between Stargardt's disease and this tumour has never
been previously reported. The astrocytic hamartoma of our patient showed unusual 
clinical features. This association is probably incidental.

Publication Types: 
    Case Reports
    Letter
    Research Support, Non-U.S. Gov't

PMID: 17997789 [PubMed - indexed for MEDLINE]

569: Clin Experiment Ophthalmol. 2007 Nov;35(8):719-23.

Tomographic assessment of therapeutic response to uveitic macular oedema.

Sivaprasad S, Ikeji F, Xing W, Lightman S.

Moorfields Eye Hospital, London, UK.

PURPOSE: To evaluate the therapeutic effects on the different morphological
patterns of uveitic macular oedema and central macular thickness using optical
coherence tomography (OCT). METHODS: Retrospective observational case series.
Fifty consecutive patients with a clinical diagnosis of new or recurrent macular 
oedema due to uveitis were examined with serial OCTs for 1 year. The correlation 
between different patterns of macular oedema (diffuse macular oedema, inner
cystoid oedema, outer cystoid oedema, oedema involving both inner and outer
layers of retina and serous retinal detachment) and change in logMAR visual
acuity and the recorded variables including age, gender, systemic disease
associated with uveitis, location and duration of uveitis, and duration of
macular oedema were examined. Response to treatment was measured as change in
logMAR visual acuity and evolution of patterns of macular oedema. RESULTS:
Diffuse macular oedema, external cystoid and serous retinal detachment responded 
well to treatment. Cysts in the inner retinal layers were more resistant to
treatment. The cysts in the outer layers disappeared faster than cysts in the
inner layers in patients with cysts in both layers at baseline. Multivariate
analysis showed that cystoid macular oedema (all types) (P = 0.03) and inner
cystoid oedema (P = 0.031) were the variables significantly associated with final
visual acuity. CONCLUSION: Assessment of patterns of uveitic macular oedema by
OCT gives useful information on the prognosis. Inner retinal cystoid oedema is
more resistant to treatment than any other patterns of oedema.

PMID: 17997774 [PubMed - indexed for MEDLINE]

570: Clin Experiment Ophthalmol. 2007 Nov;35(8):713-8.

Intravitreal and posterior subtenon triamcinolone acetonide in idiopathic
bilateral uveitic macular oedema.

Choudhry S, Ghosh S.

ICARE Eye Hospital and Postgraduate Institute, Glaucoma Research Centre, Noida,
Uttar Pradesh, India.

PURPOSE: To study the efficacy of intravitreal triamcinolone acetonide (IVTA)
versus posterior subtenon triamcinolone acetonide (PSTA) in bilateral macular
oedema secondary to idiopathic intermediate uveitis. METHODS: In a prospective,
interventional case series, 10 patients (20 eyes) with bilateral uveitic macular 
oedema were included. Patients underwent fundus fluorescein angiography, record
of visual acuity and intraocular pressure (IOP). Patients received IVTA 4 mg/0.1 
mL in one eye and PSTA 20 mg/0.5 mL in the fellow eye at an interval of > or =4
weeks. The outcome measures were record of IOP, best corrected visual acuity and 
angiographic resolution of cystoid macular oedema at 3 and 6 months. RESULTS: The
mean pre-intervention IOP at baseline between the IVTA and the PSTA group was
comparable. At 1 week, the mean IOP recorded was greater in the eyes that
received IVTA than those that received PSTA (P < 0.001). However, at 1- and
3-month follow up, the mean IOP between the two groups was similar. Best
corrected visual acuity of > or =6/12 achieved at 3 and 6 months in the IVTA and 
PSTA group was comparable (77.8% vs. 44.4% [P = 0.14] and 88.9% vs. 77.8% [P =
0.53]). There was also no significant difference in angiographic resolution of
cystoid macular oedema at 3 (P = 0.32) and 6 months (P = 0.53) between the two
groups. Recurrence of macular oedema was seen in one and two eyes that received
IVTA and PSTA, respectively, at 6 months. CONCLUSION: Triamcinolone acetonide
injection, whether administered intravitreally or via posterior subtenon route,
is an effective treatment option in achieving complete anatomic and functional
improvement in cases treated for macular oedema secondary to idiopathic
intermediate uveitis.

PMID: 17997773 [PubMed - indexed for MEDLINE]

571: Ophthalmology. 2008 Jul;115(7):1203-8. Epub 2007 Nov 12.

Supplements and age-related eye conditions the beaver dam eye study.

Klein BE, Knudtson MD, Lee KE, Reinke JO, Danforth LG, Wealti AM, Moore E, Klein 
R.

Department of Ophthalmology and Visual Sciences, University of Wisconsin School
of Medicine and Public Health, Madison, Wisconsin 53726, USA.
kleinb@epi.ophth.wisc.edu

OBJECTIVE: To investigate the association of use of vitamin, mineral, and
nonvitamin nonmineral supplements with common age-related eye diseases. DESIGN:
Population-based prospective study with incidence data. PARTICIPANTS: Subjects
were participants in the Beaver Dam Eye Study who contributed data in 1988 to
1990 (n = 4926), 1993 to 1995 (n = 3722), 1998 to 2000 (n = 2962), and 2003 to
2005 (n = 2375). METHODS: Use of all medications and supplements were collected
from study participants at each of 4 examinations. Intraocular pressure (IOP)
measurement and fundus and lens photography were done at each visit. Visual field
data are available only from baseline. Photographs of the lenses, retina, and
discs were graded using standard protocols by trained graders. MAIN OUTCOME
MEASURES: Incidence of age-related cataracts, macular degeneration (AMD), and
high IOP for one set of analyses and incidence of supplement use for the second
set of analyses. RESULTS: There was little evidence of any significant
associations between supplement use and incident ocular outcomes except for a
small protective effect for cortical cataracts by vitamins A and D, zinc, and
multivitamins and increased odds of late AMD. Late AMD was associated with
incident use of vitamins A, C, and E and zinc. CONCLUSIONS: Age-related macular
degeneration seems to precede use of vitamins A, C, and E and zinc. This may
reflect advice by family, friends, and health care providers about the benefits
of Age-Related Eye Disease Study-like supplements.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17997484 [PubMed - indexed for MEDLINE]

572: Am J Ophthalmol. 2008 Jan;145(1):149-154. Epub 2007 Nov 12.

The predictive value of patient and eye characteristics on the course of
subclinical diabetic macular edema.

Browning DJ, Fraser CM.

Charlotte Eye, Ear, Nose, and Throat Associates, Charlotte, North Carolina, USA. 
djbrowning@carolina.rr.com

PURPOSE: To define the course of subclinical diabetic macular edema (DME) and
identify any predictors of progression to clinically significant DME. DESIGN:
Retrospective, observational case series. METHOD: Setting: Private retina
practice. Patient population: One hundred and fifty-three eyes of 153 patients
with diabetic retinopathy and subclinical DME. Observation procedures: Clinical
charts review and longitudinal optical coherence tomography (OCT) measurements.
Main outcome measures: Change in OCT values and time to eventual treatment for
clinically significant DME. RESULTS: Over a median follow-up of 14 months
(interquartile range, seven to 25 months), 48 of 153 eyes (31.4%) progressed to
clinically significant DME. The numbers (%) of eyes showing decreased, unchanged,
and increased central subfield mean thickness were 16 (10.5%), 117 (76.5%), and
20 (13.1%), respectively. None of the patients or eye variables typically
assessed in clinical practice was predictive of progression from subclinical DME 
to clinically significant DME. CONCLUSIONS: Progression from subclinical DME to
clinically significant DME may be detected by serial clinical and OCT assessment.
Subclinical DME does not inexorably progress over time scales of one to two
years, and a substantial fraction of eyes spontaneously improve. Follow-up
intervals of four to six months allowed detection of progression to clinically
significant DME. In this sample of patients, OCT did not help in predicting which
eyes with subclinical DME would progress to clinically significant DME.

PMID: 17997393 [PubMed - indexed for MEDLINE]

573: Acta Ophthalmol. 2008 Jun;86(4):390-4. Epub 2007 Nov 7.

Complement factor H Y402H polymorphism and characteristics of exudative
age-related macular degeneration lesions.

Seitsonen S, Järvelä I, Meri S, Tommila P, Ranta P, Immonen I.

Department of Ophthalmology, Helsinki University Central Hospital, Helsinki,
Finland. sanna.seitsonen@hus.fi

PURPOSE: The Y402H polymorphism of the complement factor H (CFH) gene is
associated with age-related macular degeneration (AMD) in many populations. The
reported genotype-phenotype correlations in the CFH Y402H polymorphism have not
been pronounced and no studies on the effect of the polymorphism on the subgroups
within wet AMD have been performed. In this study, we wanted to evaluate whether 
the CFH Y402H polymorphism has an effect on clinical variables in recent
exudative AMD lesions. METHODS: The study included 172 patients with exudative
AMD. The size of AMD lesions and the presence and area of other AMD lesion
variables were recorded in fluorescein angiography (FA) and analysed in relation 
to the Y402H genotypes. RESULTS: The median lesion size (classic + occult
choroidal neovascularization [CNV] + serous pigment epithelium detachment [PED] +
haemorrhage, if present) was 8.15 mm(2) in patients homozygous for the CFH risk
allele (CC), 7.50 mm(2) in heterozygous patients (CT), and 7.05 mm(2) in those
with the normal genotype (TT) (p = 0.599). Areas of classic and occult CNV,
combined, without serous PED or haemorrhage were 6.37 mm(2), 5.00 mm(2) and 5.18 
mm(2), respectively (p = 0.407). There was a trend for CC patients to have more
frequently minimally classic and less frequently predominantly classic lesion
composition than CT or TT subjects. CONCLUSIONS: We detected no clear impact of
the CFH Y402H polymorphism on recent exudative AMD lesion characteristics.
Although the complement cascade is implicated in CNV formation and scarring
processes in the retina, the Y402H polymorphism appears relatively neutral in
these functions.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17995985 [PubMed - indexed for MEDLINE]

574: Ophthalmic Epidemiol. 2007 Sep-Oct;14(5):288-98.

Intake of zinc and antioxidant micronutrients and early age-related maculopathy
lesions.

Morris MS, Jacques PF, Chylack LT, Hankinson SE, Willett WC, Hubbard LD, Taylor
A.

Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on
Aging at Tufts University, Boston, Massachusetts 02111, USA.
martha.morris@tufts.edu

BACKGROUND: Macular degeneration, the end stage of age-related maculopathy (ARM),
is the leading cause of legal blindness worldwide, and few modifiable risk
factors are known. The high concentration of carotenoids in the macula, plus
evidence linking oxidative stress to ARM and carotenoids to antioxidation,
generated the hypothesis that higher antioxidant intakes can prevent ARM. Results
of observational and intervention studies have been inconsistent. OBJECTIVE: To
evaluate associations between intakes of zinc and antioxidant micronutrients and 
early ARM. METHODS: Between 1993 and 1995, ARM was assessed in 398 Boston-area
women aged 53-74 y using the Wisconsin Age-related Maculopathy System of grading 
retinal fundus photographs. The women were a subset of the Nurses' Health Study
cohort. Micronutrient intake was assessed by semi-quantitative food frequency
questionnaires administered four times between 1980 and the baseline eye
examinations. RESULTS: After multivariate adjustment for potential confounders,
1980 energy-adjusted intakes of alpha-carotene, beta-carotene, lycopene, total
retinol, total vitamin A, and total vitamin E were significantly inversely
related to the prevalence of pigmentary abnormalities (PA). Furthermore,
increasing frequency of consuming foods high in alpha-or beta-carotene was
associated with lower odds of PA; compared to women consuming these foods < 5
times/wk, odds ratios (95% CI) were 0.7 (0.3-1.6) for 5-6 times/wk, 0.6 (0.2-1.3)
for 7-9.5 times/wk, and 0.3 (0.1-0.7)for > or =10 times/wk. Lutein/zeaxanthin
intakes and more recent intakes of most carotenoids were unrelated to PA, and
intakes of zinc and antioxidant micronutrients were unrelated to having large or 
intermediate drusen alone.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, Non-P.H.S.

PMID: 17994438 [PubMed - indexed for MEDLINE]

575: J Bioenerg Biomembr. 2007 Dec;39(5-6):507-17.

ATP-binding cassette transporter ABCA4: molecular properties and role in vision
and macular degeneration.

Molday RS.

Department of Biochemistry & Molecular Biology, Centre for Macular Research,
University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, V6T
1Z3, Canada. molday@interchange.ubc.ca

ABCA4, also known as ABCR or the rim protein, is a member of the ABCA subfamily
of ATP binding cassette (ABC) transporters expressed in vertebrate rod and cone
photoreceptor cells and localized to outer segment disk membranes. ABCA4 is
organized in two tandem halves, each consisting of a transmembrane segment
followed successively by a large exocytoplasmic domain, a multispanning membrane 
domain, and a nucleotide-binding domain. Over 400 mutations in ABCA4 have been
linked to Stargardt macular degeneration and related retinal degenerative
diseases that cause severe vision loss in affected individuals. Direct binding
studies and ATPase activation measurements have identified
N-retinylidene-phosphatidylethanolamine, a product generated from the
photobleaching of rhodopsin, as the substrate for ABCA4. Mice deficient in ABCA4 
accumulate phosphatidylethanolamine, all-trans retinal, and
N-retinylidene-phosphatidylethanolamine in photoreceptors and the diretinal
pyridinium compound A2E in retinal pigment epithelial cells. On the basis of
these studies, ABCA4 is proposed to actively transport or flip
N-retinylidene-phosphatidylethanolamine from the lumen to the cytoplasmic side of
disc membranes following the photobleaching of rhodopsin. This transport activity
insures that retinoids do not accumulate in disc membranes. Disease-linked
mutations in ABCA4 that result in diminished transport activity lead to an
accumulation of all-trans retinal and N-retinylidene-PE in disc membranes which
react to produce A2E precursors. A2E progressively accumulates as lipofuscin
deposits in retinal pigment epithelial cells as a result of phagocytosis of outer
segment discs. A2E and photo-oxidation products cause RPE cell death and
consequently photoreceptor degeneration resulting in a loss in vision in
individuals with Stargardt macular degeneration and other retinal degenerative
diseases associated with mutations in ABCA4.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17994272 [PubMed - indexed for MEDLINE]

576: Int J Artif Organs. 2007 Oct;30(10):923-9.

Comment on:
    Int J Artif Organs. 2008 May;31(5):456-7.

Rheopheresis in vascular diseases.

Ferrannini M, Vischini G, Staffolani E, Scaccia F, Miani N, Parravano MC, Louis
MM, Splendiani G, Di Daniele N.

Nephrology and Dialysis Unit, Tor Vergata University, Rome, Italy.
m.ferrannini@inwind.it

BACKGROUND: Endothelial dysfunction is a common condition in many microvascular
diseases, such as Age-related Macular Degeneration (AMD) and Peripheral Arterial 
Occlusive Disease (PAOD). Rheopheresis therapy improves ematic viscosity, shear
stress and endothelial function while decreasing fibrinogen, LDL-cholesterol and 
alpha-2-macroglobulin levels. Objective: To evaluate the therapeutic efficacy of 
rheopheresis in patients with microcirculatory diseases. MATERIALS AND METHODS:
Eight patients (7 male and 1 female) were treated with rheopheresis: 3 males were
affected by AMD, 4 male and 1 female by uremia and PAOD. We used Membrane
Differential Filtration (MDF) with an ethinylvinyl alcohol copolymer membrane as 
plasmafiltrator. Patients with AMD were treated once a week for ten weeks.
Patients affected with PAOD were treated twice weekly for 3 weeks and then were
placed on a once-a-week program. RESULTS: In all treated patients with AMD,
visual acuity improved. In all patients affected with PAOD, we observed a
complete resolution of pain; 3 out of 5 had a complete remission of ulcers. There
was partial reduction of ulcers in the other patients and no adverse effects were
observed. CONCLUSION: Rheopheresis is a safe, effective form of hemorheotherapy.

Publication Types: 
    Clinical Trial
    Comment

PMID: 17992654 [PubMed - indexed for MEDLINE]

577: Endocrine. 2007 Aug;32(1):107-16. Epub 2007 Sep 27.

How the diabetic eye loses vision.

Davidson JA, Ciulla TA, McGill JB, Kles KA, Anderson PW.

Division of Endocrinology, University of Texas, Southwestern Medical School,
Dallas, Texas 75230, USA. jdavidson@medicalcitydallas.com

The objective is to review the most common causes of vision loss in patients with
diabetes with the goal of better managing patients with diabetic eye disease. In 
this review, the causes of vision loss, and the clinical evaluation and
management of diabetic retinopathy (DR) and diabetic macular edema (DME) are
outlined. Patients with diabetes mellitus have an increased risk of vision loss
and blindness. In patients with diabetes, the primary mechanism responsible for
vision loss is centrally involved DME or clinically significant macular edema
(CSME), defined as vascular leakage resulting in fluid accumulation that affects 
the center of the macula. DR and DME are thought to result from the effects of
excessive blood glucose on the vessels that produces microvascular damage. The
progression of DR can be slowed by intensive glycemic and blood pressure control.
Severe visual loss from proliferative DR and moderate visual loss from DME can be
reduced by laser photocoagulation. DR and DME are diagnosed on dilated retinal
examination and confirmed with diagnostic testing. Many experts and associations 
recommend that patients with diabetes have an yearly, thorough, dilated eye exam.
This manuscript describes the case history of a patient with diabetes and vision 
loss.

Publication Types: 
    Case Reports
    Review

PMID: 17992608 [PubMed - indexed for MEDLINE]

578: Lancet. 2007 Nov 17;370(9600):1687-97. Epub 2007 Nov 7.

Comment in:
    Lancet. 2007 Nov 17;370(9600):1667-8.    Lancet. 2008 Mar 1;371(9614):721-2; author reply 722.    Lancet. 2008 Mar 1;371(9614):721; author reply 722.    Lancet. 2008 Mar 1;371(9614):722; author reply 722.

Effect of fenofibrate on the need for laser treatment for diabetic retinopathy
(FIELD study): a randomised controlled trial.

Keech AC, Mitchell P, Summanen PA, O'Day J, Davis TM, Moffitt MS, Taskinen MR,
Simes RJ, Tse D, Williamson E, Merrifield A, Laatikainen LT, d'Emden MC, Crimet
DC, O'Connell RL, Colman PG; FIELD study investigators.

NHMRC Clinical Trials Centre, University of Sydney, NSW, Australia.
tony@ctc.usyd.edu.au

BACKGROUND: Laser treatment for diabetic retinopathy is often associated with
visual field reduction and other ocular side-effects. Our aim was to assess
whether long-term lipid-lowering therapy with fenofibrate could reduce the
progression of retinopathy and the need for laser treatment in patients with type
2 diabetes mellitus. METHODS: The Fenofibrate Intervention and Event Lowering in 
Diabetes (FIELD) study was a multinational randomised trial of 9795 patients aged
50-75 years with type 2 diabetes mellitus. Eligible patients were randomly
assigned to receive fenofibrate 200 mg/day (n=4895) or matching placebo (n=4900).
At each clinic visit, information concerning laser treatment for diabetic
retinopathy-a prespecified tertiary endpoint of the main study-was gathered.
Adjudication by ophthalmologists masked to treatment allocation defined instances
of laser treatment for macular oedema, proliferative retinopathy, or other eye
conditions. In a substudy of 1012 patients, standardised retinal photography was 
done and photographs graded with Early Treatment Diabetic Retinopathy Study
(ETDRS) criteria to determine the cumulative incidence of diabetic retinopathy
and its component lesions. Analyses were by intention to treat. This study is
registered as an International Standard Randomised Controlled Trial, number
ISRCTN64783481. FINDINGS: Laser treatment was needed more frequently in
participants with poorer glycaemic or blood pressure control than in those with
good control of these factors, and in those with a greater burden of clinical
microvascular disease, but the need for such treatment was not affected by plasma
lipid concentrations. The requirement for first laser treatment for all
retinopathy was significantly lower in the fenofibrate group than in the placebo 
group (164 [3.4%] patients on fenofibrate vs 238 [4.9%] on placebo; hazard ratio 
[HR] 0.69, 95% CI 0.56-0.84; p=0.0002; absolute risk reduction 1.5% [0.7-2.3]).
In the ophthalmology substudy, the primary endpoint of 2-step progression of
retinopathy grade did not differ significantly between the two groups overall (46
[9.6%] patients on fenofibrate vs 57 [12.3%] on placebo; p=0.19) or in the subset
of patients without pre-existing retinopathy (43 [11.4%] vs 43 [11.7%]; p=0.87). 
By contrast, in patients with pre-existing retinopathy, significantly fewer
patients on fenofibrate had a 2-step progression than did those on placebo (three
[3.1%] patients vs 14 [14.6%]; p=0.004). An exploratory composite endpoint of
2-step progression of retinopathy grade, macular oedema, or laser treatments was 
significantly lower in the fenofibrate group than in the placebo group (HR 0.66, 
95% CI 0.47-0.94; p=0.022). INTERPRETATION: Treatment with fenofibrate in
individuals with type 2 diabetes mellitus reduces the need for laser treatment
for diabetic retinopathy, although the mechanism of this effect does not seem to 
be related to plasma concentrations of lipids.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17988728 [PubMed - indexed for MEDLINE]

579: Ophthalmology. 2008 Jun;115(6):1026-31. Epub 2007 Nov 5.

Retinal precursors and the development of geographic atrophy in age-related
macular degeneration.

Klein ML, Ferris FL 3rd, Armstrong J, Hwang TS, Chew EY, Bressler SB, Chandra SR;
AREDS Research Group.

Devers Eye Institute, Legacy Good Samaritan Hospital and Medical Center,
Portland, Oregon, USA.

PURPOSE: To determine specific retinal precursor lesions and sequence of events
preceding the onset of geographic atrophy (GA) in eyes with age-related macular
degeneration (AMD). DESIGN: Retrospective review. PARTICIPANTS: All participants 
in the Age-Related Eye Disease Study (AREDS) at 2 clinical centers (Devers Eye
Institute, Portland, Oregon, and University of Wisconsin, Madison, Wisconsin) in 
whom GA initially appeared in at least one eye a minimum of 4 years after the
baseline study visit. METHODS: All stereoscopic fundus photographs taken before
the appearance of GA in the involved (study) eye were reviewed. Fundus features
at the site of future GA were graded and recorded. Three graders reviewed
photographs, with independent grading and adjudication by mutual agreement.
Features graded included drusen (classified by size and confluence), focal
hyperpigmentation, hypopigmentation, and refractile deposits. The time between
first appearance of these features and initial appearance of GA was recorded.
MAIN OUTCOME MEASURE: Appearance of GA. RESULTS: Of all AREDS participants at the
2 sites, 95 eyes of 77 developed GA at least 4 years after entrance into the
study. Average time from baseline to initial appearance of GA was 6.6 years
(range, 4-11). Drusen were found in 100% of eyes at the site of later developing 
GA, drusen >125 mum in diameter in 96% of eyes, confluent drusen in 94%,
hyperpigmentation in 96%, drusen > 250 mum in 83%, hypopigmentation in 82%, and
refractile deposits in 23%. Time from lesion appearance to onset of GA varied by 
lesion type, ranging from 5.9 years for drusen confluence to 2.5 years for
hypopigmentation or refractile deposits. Lesions generally followed a uniform
sequence of appearance. CONCLUSIONS: By focusing on the location of initial GA
appearance and then retrospectively analyzing prior photographs, we were able to 
identify specific precursor lesions and the most common sequence of events
leading to GA formation in eyes with AMD. The progression was usually
characterized by large drusen formation and development of hyperpigmentation,
followed by regression of drusen, appearance of hypopigmentation, and ultimately 
development of GA, sometimes preceded by the appearance of refractile deposits.

Publication Types: 
    Multicenter Study
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17981333 [PubMed - indexed for MEDLINE]

580: Adv Immunol. 2007;96:141-77.

Inherited complement regulatory protein deficiency predisposes to human disease
in acute injury and chronic inflammatory statesthe examples of vascular damage in
atypical hemolytic uremic syndrome and debris accumulation in age-related macular
degeneration.

Richards A, Kavanagh D, Atkinson JP.

Washington University School of Medicine, St. Louis, Missouri, USA.

In this chapter, we examine the role of complement regulatory activity in
atypical hemolytic uremic syndrome (aHUS) and age-related macular degeneration
(AMD). These diseases are representative of two distinct types of
complement-mediated injury, one being acute and self-limited, the other
reflecting accumulation of chronic damage. Neither condition was previously
thought to have a pathologic relationship to the immune system. However,
alterations in complement regulatory protein genes have now been identified as
major predisposing factors for the development of both diseases. In aHUS,
heterozygous mutations leading to haploinsufficiency and function-altering
polymorphisms in complement regulators have been identified, while in AMD,
polymorphic haplotypes in complement genes are associated with development of
disease. The basic premise is that a loss of function in a plasma or membrane
inhibitor of the alternative complement pathway allows for excessive activation
of complement on the endothelium of the kidney in aHUS and on retinal debris in
AMD. These associations have much to teach us about the host's innate immune
response to acute injury and to chronic debris deposition. We all experience
cellular injury and, if we live long enough, will deposit debris in blood vessel 
walls (atherosclerosis leading to heart attacks and strokes), the brain (amyloid 
proteins leading to Alzheimer's disease), and retina (lipofuscin pigments leading
to AMD). These are three common causes of morbidity and mortality in the
developed world. The clinical, genetic, and immunopathologic understandings
derived from the two examples of aHUS and AMD may illustrate what to anticipate
in related conditions. They highlight how a powerful recognition and effector
system, the alternative complement pathway, reacts to altered self. A response to
acute injury or chronic debris accumulation must be appropriately balanced. In
either case, too much activation or too little regulation promotes undesirable
tissue damage and human disease.

Publication Types: 
    Review

PMID: 17981206 [PubMed - indexed for MEDLINE]

581: Expert Opin Emerg Drugs. 2007 Nov;12(4):591-603.

Emerging pharmacotherapies for diabetic macular edema.

Furlani BA, Meyer CH, Rodrigues EB, Maia M, Farah ME, Penha FM, Holz FG.

Federal University of Sao Paulo, Vision Institute, Department of Ophthalmology,
Sao Paulo, Brazil.

Diabetic macular edema (DME) is the most frequent cause of severe vision
impairment in patients with non-proliferative diabetic retinopathy. Even though
patients should achieve optimal glycemic control, normalization of blood pressure
and serum lipids, as well as improvement of cardiac and renal status, these
measures alone will not prevent every patient from developing visual loss caused 
by DME. The goal of local treatment for DME is vision improvement, usually
achieved after reducing leakage on fluorescein angiography (FA) and retinal
thickness on optical coherence tomography (OCT). Laser photocoagulation is still 
the standard treatment for clinically significant DME. However, laser
photocoagulation rarely provides major visual improvement, especially in patients
with diffuse DME. Thus, a therapeutic intervention that restores visual acuity
impaired by DME more often remains a significant unmet medical need. This review 
aims to present the most important emerging drug technologies for therapy of DME 
at present, including corticosteroids, vascular endothelial growth factor
inhibitors, protein kinase C inhibitors, small interfering RNA,
hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitors and non-hormonal
anti-inflammatory agents. Recent progress in this field suggests that local
management of DME may change rapidly in the near future. Novel emerging drugs
should enable better anatomical and functional outcomes for therapy of this
sight-threatening disease.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17979601 [PubMed - indexed for MEDLINE]

582: Ophthalmology. 2008 Jun;115(6):1039-1045.e5. Epub 2007 Nov 5.

Comment in:
    Ophthalmology. 2008 Nov;115(11):2099; author reply 2100.

A value-based medicine analysis of ranibizumab for the treatment of subfoveal
neovascular macular degeneration.

Brown MM, Brown GC, Brown HC, Peet J.

Center for Value-Based Medicine, Flourtown, Pennsylvania 19031, USA.
valuebasedmedicine.com

OBJECTIVE: To assess the conferred value and average cost-utility
(cost-effectiveness) for intravitreal ranibizumab used to treat occult/minimally 
classic subfoveal choroidal neovascularization associated with age-related
macular degeneration (AMD). DESIGN: Value-based medicine cost-utility analysis.
PARTICIPANTS: MARINA (Minimally Classic/Occult Trial of the Anti-Vascular
Endothelial Growth Factor Antibody Ranibizumab in the Treatment of Neovascular
AMD) Study patients utilizing published primary data. METHODS: Reference case,
third-party insurer perspective, cost-utility analysis using 2006 United States
dollars. MAIN OUTCOME MEASURES: Conferred value in the forms of (1)
quality-adjusted life-years (QALYs) and (2) percent improvement in health-related
quality of life. Cost-utility is expressed in terms of dollars expended per QALY 
gained. All outcomes are discounted at a 3% annual rate, as recommended by the
Panel on Cost-effectiveness in Health and Medicine. Data are presented for the
second-eye model, first-eye model, and combined model. RESULTS: Twenty-two
intravitreal injections of 0.5 mg of ranibizumab administered over a 2-year
period confer 1.039 QALYs, or a 15.8% improvement in quality of life for the
12-year period of the second-eye model reference case of occult/minimally classic
age-related subfoveal choroidal neovascularization. The reference case treatment 
cost is $52652, and the cost-utility for the second-eye model is $50691/QALY. The
quality-of-life gain from the first-eye model is 6.4% and the cost-utility is
$123887, whereas the most clinically simulating combined model yields a
quality-of-life gain of 10.4% and cost-utility of $74169. CONCLUSIONS: By
conventional standards and the most commonly used second-eye and combined models,
intravitreal ranibizumab administered for occult/minimally classic subfoveal
choroidal neovascularization is a cost-effective therapy. Ranibizumab treatment
confers considerably greater value than other neovascular macular degeneration
pharmaceutical therapies that have been studied in randomized clinical trials.

Publication Types: 
    Clinical Trial, Phase III
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17976724 [PubMed - indexed for MEDLINE]

583: Vision Res. 2008 Feb;48(3):470-7. Epub 2007 Oct 31.

Clinical characterization and genetic mapping of North Carolina macular
dystrophy.

Yang Z, Tong Z, Chorich LJ, Pearson E, Yang X, Moore A, Hunt DM, Zhang K.

Department of Ophthalmology and Visual Sciences, University of Utah Health
Sciences Center, Salt Lake City, UT 84132, USA. zhenglin.yang@hmbg.utah.edu

North Carolina macular dystrophy (NCMD) is an autosomal dominant macular disease,
was mapped to 6q14-q16.2, the disease-causing gene has yet not been identified.
It shares phenotypic similarity with age-related macular degeneration including
drusen and choroidal neovascularization. We collected six families with NCMD
including 75 members, and conducted clinical characterization and genetic mapping
for these families. Forty-five patients were diagnosed as NCMD; all six NCMD
families were mapped to MCDR1 locus using genetic linkage analysis. MCDR1
interval was refined to 3 cM (1.8mb) between D6S1716 to D6S1671 via fine mapping 
using microsatellite markers in these six families, all eleven annotated genes
within the interval were analyzed by mutation screening in coding regions, no
mutation was found, suggesting a potential novel gene or a new pathological
mechanism causing NCMD. The refinement of MCDR1 locus will aid the
disease-causing gene identification. Functional studies of NCMD genes should
provide important insights into pathogenetic mechanisms of NCMD and age-related
macular degeneration.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17976682 [PubMed - indexed for MEDLINE]

584: J Clin Invest. 2007 Nov;117(11):3182-4.

Comment on:
    J Clin Invest. 2007 Nov;117(11):3421-6.

Macrophages feel their age in macular degeneration.

Jager MJ, Klaver CC.

Department of Ophthalmology, Leiden University Medical Center, Leiden, The
Netherlands. m.j.jager@lumc.nl

Macular degeneration, during which the posterior part of the eye known as the
macula suffers from thinning, atrophy, and bleeding caused by abnormal
angiogenesis (blood vessel formation), predominantly affects elderly adults and
results in the loss of central vision. In this issue of the JCI, Kelly et al.
investigate the regulation of innate immune cells, specifically macrophages, in
ocular neovascularization following eye injury in mice (see the related article
beginning on page 3421). They found that, as the mice aged, increased expression 
of IL-10 by senescent macrophages and changes in their expression of other
cytokines altered the ability of these cells to restrain trauma-induced
angiogenesis in the eye. These data provide insight into the effect of senescence
on macrophage function and angiogenesis and have important implications for
age-related diseases such as macular degeneration.

Publication Types: 
    Comment

PMID: 17975664 [PubMed - indexed for MEDLINE]

585: Graefes Arch Clin Exp Ophthalmol. 2008 Apr;246(4):515-20. Epub 2007 Oct 31.

Choroidal circulatory disturbances associated with retinal angiomatous
proliferation on indocyanine green angiography.

Koizumi H, Iida T, Saito M, Nagayama D, Maruko I.

Department of Ophthalmology, Fukushima Medical University School of Medicine, 1
Hikarigaoka, Fukushima, 960-1295, Japan.

PURPOSE: To investigate the association between choroidal perfusion and retinal
angiomatous proliferation (RAP). METHODS: We performed indocyanine green
angiography (ICGA) on 26 eyes of 13 consecutive patients with RAP, and 17 eyes of
17 age-matched controls without age-related macular degeneration. In eyes with
RAP and concurrent pigment epithelial detachments (PEDs), we evaluated ICGA
images obtained after the PEDs resolved following treatment. Of the 26 eyes in
the study group, five eyes with stage 3 RAP or a disciform scar and two eyes that
underwent photodynamic therapy were excluded from further evaluation, leaving 19 
eyes (11 eyes with stage 1 or 2 RAP and eight fellow eyes without RAP). RESULTS: 
Early decreased choroidal filling (EDCF) was observed in nine (81.8%) of 11 eyes 
with RAP and five (62.5%) of eight fellow eyes without RAP. Late decreased
choroidal filling (LDCF) occurred in nine (81.8%) of 11 eyes with RAP and four
(50%) of eight fellow eyes without RAP. The incidence of EDCF and LDCF was
significantly higher in eyes with RAP than in the control eyes (p < 0.05, p <
0.01, respectively). CONCLUSIONS: Persistent decreased choroidal filling is
common in early-stage RAP. Clinicians should be aware of this, especially when
considering treatment.

PMID: 17972093 [PubMed - indexed for MEDLINE]

586: Can J Ophthalmol. 2007 Dec;42(6):854-9.

Modified cataract surgery with telescopic magnification for patients with
age-related macular degeneration.

Iizuka M, Gorfinkel J, Mandelcorn M, Lam WC, Devenyi R, Markowitz SN.

Low Vision Service, University Health Network Hospitals, Department of
Ophthalmology and Vision Sciences, University of Toronto, Toronto, ON.

BACKGROUND: The most desirable effect following cataract surgery in the presence 
of age-related macular degeneration (AMD) is to obtain an improvement in distance
resolution acuity, and the only optical solution to this is the use of telescopic
magnification. The purpose of the study was to develop and verify the clinical
utility of inducing low-grade telescopic magnification (<33%) at the time of
cataract surgery by the choice of an appropriate intraocular lens power and
spectacle glasses in patients with AMD and cataract. METHODS: The design was a
prospective, nonrandomized, interventional case series involving 6 patients aged 
74-86 (mean 80; SD 4) years with AMD and cataract. Participants were males and
females, equal in number, who had visual acuity of less than 20/400 in the weaker
eye. Standard cataract surgery was performed in the weaker eye. The power of the 
intraocular lens was derived from the reduced Gullstrand model of the eye in such
a way that at the intraocular lens plane a minus lens was created, which,
together with a plus lens in matching glasses, formed a Galilean telescopic
system with magnification of up to 33%. Outcome measures were visual acuity,
contrast sensitivity, and activities of daily living (ADL) scores. RESULTS: The
mean power of the implanted intraocular lenses was 6.31 (SD 2.42) diopters and,
according to the theoretical derivations, achieved magnification between 20% and 
30% (mean 26%; SD 4.92%). Visual acuity improved for the group from a mean of
20/525 (logMAR 1.48; SD 0.13) to a mean of 20/290 (logMAR 1.20; SD 0.21).
Contrast sensitivity improved significantly (p < 0.001) only in the lower spatial
frequencies. Postoperatively, ADL scores improved significantly in all patients
except one. At the end of the follow-up period, 3 patients reported that they
would like to proceed with similar surgery for the other eye. INTERPRETATION: An 
optimal surgical telescopic device based on low-grade telescopic magnification
may improve functional vision for usage in all tasks in AMD patients. All
patients from this study were satisfied following surgery and viewed study
outcomes as positive and beneficial, and some patients responded with enthusiasm.
Surgeons are encouraged to use this modified technique of cataract surgery in
low-vision patients with AMD and cataract.

PMID: 17965754 [PubMed - indexed for MEDLINE]

587: Br J Ophthalmol. 2008 Jan;92(1):76-80. Epub 2007 Oct 26.

Intravitreal triamcinolone versus bevacizumab for treatment of refractory
diabetic macular oedema (IBEME study).

Paccola L, Costa RA, Folgosa MS, Barbosa JC, Scott IU, Jorge R.

Department of Ophthalmology, School of Medicine of Ribeirão Preto, Ribeirão
Preto, SP, Brazil.

BACKGROUND/AIMS: The aim of this study was to compare the morphological and
visual acuity outcomes associated with a single intravitreal injection of
triamcinolone acetonide versus bevacizumab for the treatment of refractory
diffuse diabetic macular oedema. METHODS: Twenty-eight patients were randomly
assigned to receive a single intravitreal injection of either 4 mg/0.1 ml
triamcinolone acetonide or 1.5 mg/0.06 ml bevacizumab. Comprehensive ophthalmic
evaluation was performed at baseline and at weeks 1, 4, 8 (+/-1), 12 (+/-2) and
24 (+/-2) after treatment. Main outcome measures included central macular
thickness measured with optical coherence tomography (OCT) and best corrected
Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity. RESULTS:
Twenty-six patients (26 eyes) completed all study visits (two patients missed two
consecutive study visits). Central macular thickness was significantly reduced in
the intravitreal triamcinolone group compared with the bevacizumab group at weeks
4, 8, 12 and 24 (p<0.05). Logarithm of the minimum angle of resolution (LogMAR)
best-corrected visual acuity was significantly higher at weeks 8 (0.69;
approximately 20/100(+1)) and 12 (0.74; 20/100(-2)) in the intravitreal
triamcinolone group compared with the bevacizumab group (weeks 8 (0.83;
approximately 20/125(-1)) and 12 (0.86; 20/160(+2))) (p<0.05). Significant change
from baseline in mean intraocular pressure (mmHg) was seen at week 4 (+2.25) only
in the intravitreal triamcinolone group (p<0.0001). No patient had observed
cataract progression during the study. CONCLUSIONS: One single intravitreal
injection of triamcinolone may offer certain advantages over bevacizumab in the
short-term management of refractory diabetic macular oedema, specifically with
regard to changes in central macular thickness. The actual clinical relevance of 
our preliminary findings, however, remains to be determined in future larger
studies.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17965109 [PubMed - indexed for MEDLINE]

588: Br J Ophthalmol. 2008 Feb;92(2):210-2. Epub 2007 Oct 26.

Submacular haemorrhages after intravitreal bevacizumab for large occult choroidal
neovascularisation in age-related macular degeneration.

Goverdhan SV, Lochhead J.

Consultant Ophthalmologist, Department of Ophthalmology, St Mary's Hospital,
Newport PO30 5TG, Isle of Wight, UK.

OBJECTIVE: To report the occurrence of submacular haemorrhages following
intravitreal bevacizumab for occult choroidal neovascularisation (CNV) in
age-related macular degeneration (AMD). METHODS: Retrospective chart review of 53
patients with occult CNV who had received intravitreal bevacizumab 1.25 mg.
Analysis was done in three groups based on mean CNV lesion size: <10 mm(2) (n =
17), >/=10 to <15 mm(2) (n = 17) and >/=15 mm(2) (n = 18). ETDRS derived acuity, 
incidence of fresh macular haemorrhages and haemorrhage size (pre-existing or
fresh) were documented and analysed. RESULTS: The median injection number was 1.0
(range: 1 to 3) with a minimum follow-up of 6 months (range: 4 to 12 months). The
mean presenting size of occult lesions was 13.4 mm(2) (range: 3.0 to 30.3 mm(2)).
Submacular fresh haemorrhages were seen in the absence of pre-existing
haemorrhage in four out of 10 patients in the >/=15 mm(2) CNV size group (40%)
but none in the remaining groups with CNV sizes <15 mm(2) (OR = 20.1, p = 0.01,
95% CI = 0.99 to 409.3). These haemorrhages developed at a median of 14 days.
CONCLUSIONS: Submacular haemorrhages seem to be a significant adverse event
following intravitreal bevacizumab in large occult choroidal neovascularisation
and may affect visual outcomes. Prospective studies are required to establish the
optimal dose of bevacizumab for larger lesion sizes or to identify the most
appropriate anti-VEGF agent in large occult CNV with fibrovascular and serous PED
lesions.

PMID: 17965104 [PubMed - indexed for MEDLINE]

589: Br J Ophthalmol. 2008 Jan;92(1):81-3. Epub 2007 Oct 26.

Trans-Tenon's retrobulbar triamcinolone acetonide injection for macular oedema
related to branch retinal vein occlusion.

Kawaji T, Takano A, Inomata Y, Sagara N, Iwao K, Inatani M, Fukushima M, Tanihara
H.

Department of Ophthalmology and Visual Science, Graduate School of Medical
Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan.
kawag@white.plala.or.jp

BACKGROUND: The aim of the study was to evaluate the safety and effectiveness of 
trans-Tenon's retrobulbar triamcinolone acetonide (TA) injection for macular
oedema associated with branch retinal vein occlusion (BRVO). METHODS: We reviewed
the medical records of 50 consecutive patients with macular oedema associated
with BRVO who were treated with trans-Tenon's retrobulbar TA injection (20 mg) as
initial treatment for a follow-up period of at least 12 months. Foveal thickness 
determined by optical coherence tomography, visual acuity, intraocular pressure
(IOP) and cataract progression were measured. RESULTS: The mean duration between 
oedema onset and TA injection was 4.9 months. Foveal thickness decreased
significantly at 3 months after injection (p<0.0001). Furthermore, the percentage
reduction in foveal thickness in eyes with posterior vitreous detachment (PVD; n 
= 23) was significantly greater than that without PVD (n = 27, p = 0.003).
Improved visual acuity by at least 0.20 log minimum angle of resolution (logMAR) 
was seen in 22 eyes (44%; 11 eyes with PVD and 11 eyes without PVD). After
completion of the 3-month follow-up, 29 eyes (58%) needed additional treatment
including TA injections or pars plana vitrectomy (PPV). PPV seemed to be
effective for macular oedema resistant to TA. IOP elevation and cataract
progression occurred in less than 10% of all patients. CONCLUSIONS: Trans-Tenon's
retrobulbar TA injection appeared safe and relatively effective for macular
oedema associated with BRVO. In eyes resistant to TA injection, PPV may be
effective as an adjunctive treatment.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17965103 [PubMed - indexed for MEDLINE]

590: J AAPOS. 2007 Dec;11(6):618-9. Epub 2007 Oct 25.

Spontaneous separation of epiretinal membrane in a child with Stargardt macular
dystrophy.

Cakir M, Cekiç O, Bayraktar S, Yilmaz OF.

Kuledibi Beyoglu Eye Training and Research Hospital, Istanbul, Turkey.
drmcakir@hotmail.com

We demonstrate optical coherence tomography findings of spontaneous separation of
an epiretinal membrane associated with Stargardt macular dystrophy in a child. A 
period of observation seems appropriate in eyes with an epiretinal membrane
associated with Stargardt's disease, as the membrane may show spontaneous release
and the macular area may improve.

Publication Types: 
    Case Reports

PMID: 17964205 [PubMed - indexed for MEDLINE]

591: Invest Ophthalmol Vis Sci. 2007 Nov;48(11):5315-9.

Coding and noncoding variants in the CFH gene and cigarette smoking influence the
risk of age-related macular degeneration in a Japanese population.

Mori K, Gehlbach PL, Kabasawa S, Kawasaki I, Oosaki M, Iizuka H, Katayama S,
Awata T, Yoneya S.

Department of Ophthalmology, Saitama Medical School, Moroyama, Iruma, Saitama,
Japan. keisuke@saitama-med.ac.jp

PURPOSE: Ethnic variation has been reported in age-related macular degeneration
(AMD)-associated Y402H polymorphism in complement factor H (CFH). This variation 
is evident in the Japanese population. Recently a strong association between a
novel single-nucleotide polymorphism (SNP; rs1410996) in the CFH gene and AMD has
been identified in Caucasian patients. The present study was undertaken to
investigate whether four coding and noncoding variants of the CFH gene, including
rs1410996, are associated with AMD in native, unrelated Japanese patients.
METHODS: A total of 188 patients with AMD and 139 control subjects without AMD
were recruited for the study. Four SNPs (rs800292, rs1061170, rs1410996, and
rs2274700) in the CFH gene were assessed by genotyping assay. The information
regarding systemic conditions and lifestyle including smoking were documented in 
each subject by standardized questionnaire. RESULTS: The intronic SNP (rs1410996)
and the synonymous SNP (rs2274700) were associated with a significant risk of AMD
(P = 2.37 x 10(-5) and 3.52 x 10(-5), respectively). A significant association
was also noted between a coding variant (rs800292, I62V) and AMD (P = 8.63 x
10(-6)). In contrast, the Y402H variant showed no significant association with
AMD (P = 0.101). Two common haplotypes also demonstrated significant association 
with AMD (P = 1.08 x 10(-3) and 2.00 x 10(-5)). Among the environmental factors, 
smoking alone had a significant association with AMD (P = 1.17 x 10(-4)).
CONCLUSIONS: Although the Y402H variant was not significantly associated with
AMD, other coding and noncoding variants in the CFH gene including rs1410996 and 
smoking moderately influenced the risk of AMD in a Japanese population.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17962488 [PubMed - indexed for MEDLINE]

592: Invest Ophthalmol Vis Sci. 2007 Nov;48(11):4963-73.

Optical coherence tomography versus stereoscopic fundus photography or
biomicroscopy for diagnosing diabetic macular edema: a systematic review.

Virgili G, Menchini F, Dimastrogiovanni AF, Rapizzi E, Menchini U, Bandello F,
Chiodini RG.

Department of Ophthalmology, University of Florence, Florence, Italy.
gianni.virgili@unifi.it

PURPOSE: To review systematically the sensitivity and specificity of optical
coherence tomography (OCT) for diagnosing macular edema attributable to diabetic 
retinopathy compared with well-established gold standard tests such as fundus
stereophotography or contact and noncontact fundus biomicroscopy. METHODS:
Medline and Embase were searched electronically and six major ophthalmic journals
from 1998 to 2006 were hand searched. Two reviewers independently assessed trial 
searches, studied quality with the QUADAS (Quality Assessment of Diagnostic
Accuracy Studies) checklist, and extracted data. The target disease was
clinically significant macular edema (CSME) according to Early Treatment of
Diabetic Retinopathy Study (ETDRS) criteria. A bivariate model was used to obtain
summary estimates of sensitivity and specificity and fit a summary receiver
operating characteristic (ROC) curve. RESULTS: Fifteen studies were considered
eligible. These studies were of good quality for most items of the QUADAS
checklist, but most studies did not report masking of examiners and did not
describe how withdrawals and undetermined results were treated. Seven studies
included healthy control subjects, which could have artificially enhanced OCT
diagnostic performance. All but one study included both eyes of the patients
without taking into account the within-subject correlation in statistical
analyses. Sensitivity and specificity data could be extracted from only 6 of 15
studies, because appropriate cross tabulations of index and reference tests were 
not reported by the others. In five of these studies, central retinal thickness
cutoffs between 230 and 300 microm were adopted to define abnormal OCT results
and considered the central type of CSME only, whereas in one study a complex
algorithm accounting for extrafoveal CSME was used. The design of one study was
case-control and was excluded from the meta-analysis. The expected operating
point on the summary ROC, a pooled estimate of all studies, corresponded to a
sensitivity of 0.79 (95% CI: 0.71-0.86), a specificity of 0.88 (95% CI:
0.80-0.93), a positive likelihood ratio of 6.5 (95% CI: 4.0-10.7), and a negative
likelihood ratio of 0.24 (95% CI: 0.17-0.32). These values suggest a good overall
performance of OCT for diagnosing CSME. CONCLUSIONS: OCT performs well compared
with fundus stereophotography or biomicroscopy to diagnose diabetic macular
edema. The quality of reporting of such studies should be improved, and authors
should present cross tabulations of index and reference test results. Data
adjusted for within-subject correlation should also be provided, although this
issue represents a challenge for systematic reviewers.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't
    Review

PMID: 17962446 [PubMed - indexed for MEDLINE]

593: Br J Ophthalmol. 2008 Feb;92(2):191-6. Epub 2007 Oct 25.

The role of dynamic indocyanine green angiography in the diagnosis and treatment 
of retinal angiomatous proliferation.

Bearelly S, Espinosa-Heidmann DG, Cousins SW.

Duke Center for Macular Diseases, Duke University Eye Center, Box 3802 Erwin
Road, Durham, NC 27710, USA.

AIMS: We compared the effectiveness and durability of indocyanine green
angiography (ICG) directed focal thermal laser treatment of the afferent
arteriole in the treatment of retinal angiomatous proliferation (RAP). METHODS:
Sixteen consecutive patients presenting with stage I or II RAP lesions underwent 
optical coherence tomography, fluorescein angiography and dynamic ICG examination
and were evaluated for response to treatment. Two groups were evaluated: focal
laser as initial treatment; and focal laser as salvage treatment after recurrence
with photodynamic therapy (PDT) and intravitreal triamcinolone. Five additional
eyes with stage III RAP were evaluated separately. RESULTS: Seven eyes received
focal laser as initial treatment, and nine eyes received focal laser as salvage
treatment after failure of PDT with triamcinolone. Five of seven eyes in the
initial focal laser group demonstrated resolution of oedema. All five of the
responders recurred (mean 4.4 months). Salvage therapy with PDT and triamcinolone
after focal laser failure transiently closed these recurrences. In contrast,
eight of nine eyes receiving thermal ablation of the RAP lesion after recurrence 
from prior PDT/triamcinolone demonstrated initial improvement of the retinal
oedema. Four eyes demonstrated no recurrence within a year. None of the five eyes
with stage III RAP improved anatomically or visually. CONCLUSION: Focal thermal
laser treatment of RAP arteriole can resolve retinal oedema. However, durability 
was longer in eyes with prior PDT and triamcinolone treatment than those
receiving thermal laser as initial therapy. These results suggest that focal
laser may be useful in treatment of RAP recurrences and that combination therapy 
with PDT/triamcinolone plus focal laser is better than focal laser alone.

Publication Types: 
    Comparative Study
    Evaluation Studies
    Research Support, Non-U.S. Gov't

PMID: 17962393 [PubMed - indexed for MEDLINE]

594: Doc Ophthalmol. 2008 Mar;116(2):129-35. Epub 2007 Oct 25.

Electrophysiological and structural assessment of the central retina following
intravitreal injection of bevacizumab for treatment of macular edema.

Shetty R, Pai SA, Vincent A, Shetty N, Narayana KM, Sinha B, Shetty BK.

Department of Neuro-ophthalmology and Electrophysiology, Narayana Nethralaya,
Super Speciality Eye Hospital and Post Graduate Institute of Ophthalmology,
121/C, Chord Road, Rajajinagar, 1st R Block, Bangalore 560 010, India.
drrohitshetty@yahoo.com

PURPOSE: To evaluate with electrophysiological responses and Optical Coherence
Tomography (OCT), the short term functional and structural effects at the macula 
following intravitreal injection of bevacizumab for macular edema. METHODS:
Prospective, non-randomized, interventional case study. In total, 17 eyes of 17
patients with macular edema due to vein occlusions and diabetic retinopathy
received intravitreal bevacizumab. All Patients underwent complete ophthalmic
examination including Snellen visual acuity testing, Multifocal
Electroretinography (mfERG) and Full Field Electroretinography (FERG), OCT
scanning at baseline at 1 week and 2 months after intravitreal bevacizumab.
RESULTS: FERG did not show any change in waveform parameters following
intravitreal injection of bevacizumab. Average mfERG macular responses within
central 20 degrees showed increased P(1) amplitude (P < 0.05) at 2 months after
treatment as compared to the baseline recordings in all subjects. No changes were
seen in the implicit time. There was 22% improvement in central retinal thickness
(CRT) at 2 months compared to the baseline (P < 001). CONCLUSION: Intravitreal
injection bevacizumab resulted in reduction in the central retinal thickness and 
mild to moderate improvement in the mfERG amplitudes in this short-term study.
The visual acuity changes did not directly correlate with the reduced central
retinal thickness or improvement in mfERG. The short-term results showed no
serious ocular adverse effects. Therefore on short-term follow up the off label
drug showed improvement of macular edema secondary to vein occlusion and diabetic
retinopathy with no demonstrable toxic effects.

PMID: 17960440 [PubMed - indexed for MEDLINE]

595: Ophthalmic Surg Lasers Imaging. 2007 Sep-Oct;38(5):371-7.

Pegaptanib for choroidal neovascularization in treatment-naïve exudative
age-related macular degeneration.

Ehlers JP, Fintak DR, Gupta OP, Regillo CD, Fineman MS, Ho AC.

Retina Service, Wills Eye Institute, Philadelphia, Pennsylvania 19107, USA.

BACKGROUND AND OBJECTIVE: To evaluate the use of intravitreal pegaptanib in the
treatment of choroidal neovascularization secondary to age-related macular
degeneration (AMD) in treatment-naive patients. PATIENTS AND METHODS: In a
consecu-tive, retrospective case series, treatment-naïve patients with exudative 
AMD were treated with intravitreal pegaptanib. Intravitreal injections were
typically given every 6 weeks at the discretion of the treating physician.
Snellen visual acuity (VA), clinical course, and adverse events were monitored. A
minimum of three pegaptanib injections were given. Retreatment criteria included 
persistent submacular fluid, macular edema, new macular hemorrhage, and loss of
vision. RESULTS: The average change in VA for all lesions was a loss of 2.9
lines. Fifteen (14%) patients gained more than 3 lines of VA. The average number 
of in-jections was 4.8. Ninety-two of 111 lesions were able to be categorized by 
size. Sixty-six patients had small lesions (< 4 disc areas) with an average
change of -2.0 lines, and 26 had large lesions (> or = 4 disc areas) with an
average change of -5.4 lines (P < .02). Patients with larger lesions were at
greater risk for severe visual loss (P < .01). The average follow-up was
approximately 31 weeks (range: 12 to 82 weeks) after the first injection.
CONCLUSIONS: Pegaptanib therapy resulted in a 2.9 average line loss in patients
when all lesions were considered. Small lesions responded favorably, with 15% of 
patients gaining more than 3 lines of VA. Larger lesions had an increased risk of
progression and poor visual outcome.

PMID: 17955841 [PubMed - indexed for MEDLINE]

596: Doc Ophthalmol. 2008 Mar;116(2):111-8. Epub 2007 Oct 23.

A 43-year-old man with reduced visual acuity and normal fundus: occult macular
dystrophy--case report.

Lubiński W, Gosławski W, Penkala K, Drobek-Słowik M, Karczewicz D.

Department of Ophthalmology, Pomeranian Medical University, Powstańców Wlkp. 72
str., 70-111 Szczecin, Poland. lubinski@pro.onet.pl

PURPOSE: Occult macular dystrophy (OMD) is an unusual, inherited macular
dystrophy characterized by a slowly progressive decline of visual acuity with
normal fundus and fluorescein angiography (FA). The authors present a 43-year-old
man who was diagnosed as having OMD because of the results of
electrophysiological, psychophysical, optical coherence tomography (OCT) tests.
METHODS: Routine ophthalmological evaluation, FA, visual field tests,
electroretinographic examinations (EOG, ERG, PERG and mfERG recordings according 
to ISCEV standards) and foveal thickness measurements (OCT) were performed.
RESULTS: Funduscopic examinations, FA, full field ERG as well as PERG results
were all normal. In both eyes, the abnormalities were observed in static
perimetry (relative central scotomas), mfERG (significant reduction of P1
amplitude in the central retinas) and OCT (significantly thinner foveal
thickness). CONCLUSIONS: A new case with OMD is added to preceding reports. The
mfERG and OCT tests are important in detection of OMD patients. It can help in
differential diagnosis of amblyopia, optic nerve diseases and non-organic visual 
disorders.

Publication Types: 
    Case Reports

PMID: 17955274 [PubMed - indexed for MEDLINE]

597: Clinics. 2007 Oct;62(5):573-8.

Quality of life in patients with age-related macular degeneration with monocular 
and binocular legal blindness.

Marback RF, Maia OO Jr, Morais FB, Takahashi WY.

Ophthalmology - University of Sao Paulo Medical School General Hospital, São
Paulo/Brazil. robertamarback@uol.com.br

OBJECTIVE: To evaluate the quality of life for persons affected by age-related
macular degeneration that results in monocular or binocular legal blindness.
METHODS: An analytic transversal study using the National Eye Institute Visual
Functioning Questionnaire (NEI VFQ-25) was performed. Inclusion criteria were
persons of both genders, aged more than 50 years old, absence of cataracts,
diagnosis of age-related monocular degeneration in at least one eye and the
absence of other macular diseases. The control group was paired by sex, age and
no ocular disease. RESULTS: Group 1 (monocular legal blindness) was composed of
54 patients (72.22% females and 27.78% males, aged 51 to 87 years old, medium age
74.61 +/- 7.27 years); group 2 (binocular legal blindness ) was composed of 54
patients (46.30% females and 53.70% males aged 54 to 87 years old, medium age
75.61 +/- 6.34 years). The control group was composed of 40 patients (40% females
and 60% males, aged 50 to 81 years old, medium age 65.65 +/- 7.56 years). The
majority of the scores were statistically significantly higher in group 1 and the
control group in relation to group 2 and higher in the control group when
compared to group 1. CONCLUSIONS: It was evident that the quality of life of
persons with binocular blindness was more limited in relation to persons with
monocular blindness. Both groups showed significant impairment in quality of life
when compared to normal persons.

PMID: 17952317 [PubMed - indexed for MEDLINE]

598: Indian J Ophthalmol. 2007 Nov-Dec;55(6):470-2.

Retinal pigment epithelial tears after intravitreal bevacizumab injection for
exudative age-related macular degeneration.

Shaikh S, Olson JC, Richmond PP.

Central Florida Retina Consultants, The University of South Florida College of
Medicine, USA. sshaikhmd@yahoo.com

We report a series of retinal pigment epithelial (RPE) tears after intravitreal
bevacizumab therapy for choroidal neovascularization associated with age-related 
macular degeneration (ARMD). Retinal pigment epithelial tears were estimated to
occur at an incidence of 1.6% in this patient population at our institution.
Ophthalmologists should be aware of this rare but serious finding associated with
exudative macular degeneration therapy.

Publication Types: 
    Case Reports

PMID: 17951911 [PubMed - indexed for MEDLINE]

599: Indian J Ophthalmol. 2007 Nov-Dec;55(6):451-5.

Intravitreal bevacizumab (Avastin) treatment of diffuse diabetic macular edema in
an Indian population.

Kumar A, Sinha S.

Vitreous-Retina Service, Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All 
India Institute of Medical Sciences, New Delhi - 110 029, India.
atulretina@gmail.com

BACKGROUND: To report the anatomic and visual acuity response after intravitreal 
bevacizumab (Avastin) in patients with diffuse diabetic macular edema. Design:
Prospective, interventional case series study. MATERIALS AND METHODS: This study 
included 20 eyes of metabolically stable diabetes mellitus with diffuse diabetic 
macular edema with a mean age of 59 years who were treated with two intravitreal 
injections of bevacizumab 1.25 mg in 0.05 ml six weeks apart. Main outcome
measures were 1) early treatment diabetic retinopathy study visual acuity, 2)
central macular thickness by optical coherence tomography imaging. Each was
evaluated at baseline and follow-up visits. RESULTS: All the eyes had received
some form of laser photocoagulation before (not less than six months ago), but
all of these patients had persistent diffuse macular edema with no improvement in
visual acuity. All the patients received two injections of bevacizumab at an
interval of six weeks per eye. No adverse events were observed, including
endophthalmitis, inflammation and increased intraocular pressure or
thromboembolic events in any patient. The mean baseline acuity was 20/494 (log
Mar=1.338+/-0.455) and the mean acuity at three months following the second
intravitreal injection was 20/295 (log Mar=1.094+/-0.254), a difference that was 
highly significant ( P =0.008). The mean central macular thickness at baseline
was 492 microm which decreased to 369 microm ( P =0.001) at the end of six
months. CONCLUSIONS: Initial treatment results of patients with diffuse diabetic 
macular edema not responding to previous photocoagulation did not reveal any
short-term safety concerns. Intravitreal bevacizumab resulted in a significant
decrease in macular thickness and improvement in visual acuity at three months
but the effect was somewhat blunted, though still statistically significant at
the end of six months.

PMID: 17951903 [PubMed - indexed for MEDLINE]

600: Indian J Ophthalmol. 2007 Nov-Dec;55(6):445-50.

The future implications and indications of anti-vascular endothelial growth
factor therapy in ophthalmic practice.

Hussain N, Ghanekar Y, Kaur I.

Smt. Kanuri Santhamma Retina Vitreous Centre, L.V. Prasad Eye Institute,
Hyderabad, Andhra Pradesh, India. nazimul@lvpei.org

In the last few years anti-vascular endothelial growth factor (VEGF) therapy has 
changed the paradigm in the treatment of neovascular age-related macular
degeneration (ARMD). Besides, its potential use in the treatment of diabetic
retinopathy and other possible proliferative vascular disorders has also shown
promise. Clinical trial results have shown tremendous beneficial effect of
ranibizumab in ARMD. Off-label use of bevacizumab has also shown similar benefit 
but long-term and clinical trial results do not exist. Some of the potential
questions in the use of anti-VEGF are recurring cost, possible long-term effect
on physiological function of VEGF and determination of endpoint of treatment.
Overall, the use of anti-VEGF therapy in ocular angiogenesis has proven to be
beneficial at least now.

Publication Types: 
    Review

PMID: 17951902 [PubMed - indexed for MEDLINE]

601: Indian J Ophthalmol. 2007 Nov-Dec;55(6):441-3.

The economic implications of the use of anti-vascular endothelial growth factor
drugs in age-related macular degeneration.

Azad R, Chandra P, Gupta R.

Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of
Medical Sciences, New Delhi - 110 029, India. rajvardhanazad@hotmail.com

Age-related macular degeneration (ARMD) is the most common cause for visual
impairment in the elderly in western countries. Recently several anti-vascular
endothelial growth factor (VEGF) drugs like pegaptanib sodium (Macugen),
ranibizumab (Lucentis) and bevacizumab (Avastin) are available for use in the
management of wet ARMD. A major limitation of these drugs is that they require
multiple intravitreal injections, every 4 to 6 weeks interval for a period of 2
years. Moreover, most of these drugs are too expensive for the general masses to 
afford in developing nations. Avastin, though used "off-label", offers a
comparable result at affordable cost, however, long term results are awaited. The
drug industry should review the entire pricing policy of these drugs in
developing countries like India, and develop affordable alternative compounds.
The article reviews the economic burden and affordability issues of these
Anti-VEGF drugs in ARMD.

Publication Types: 
    Review

PMID: 17951901 [PubMed - indexed for MEDLINE]

602: Indian J Ophthalmol. 2007 Nov-Dec;55(6):437-9.

Comment in:
    Indian J Ophthalmol. 2008 May-Jun;56(3):255-6; author reply 256.

A comparative debate on the various anti-vascular endothelial growth factor
drugs: pegaptanib sodium (Macugen), ranibizumab (Lucentis) and bevacizumab
(Avastin).

Nagpal M, Nagpal K, Nagpal PN.

Retina Foundation, Ahmedabad, India. drmanishnagpal@yahoo.com

Wet age-related macular degeneration and diabetic retinopathy are pathological
consequences of vascular endothelial growth factor (VEGF) release as a reaction
to deficiency of oxygen and nutrients in the macular cells. Conventional
treatment modalities have been constrained by limited success. Convincing
evidence exists that targeting VEGF signaling is a significant approach for the
therapy of these ocular angiogenesis-dependent disorders. We have come a long way
since the approval of the first angiogenesis inhibitors in medicine. The clinical
use of these drugs has provided enormous tempo to clinical and pharmacological
research. It has also significantly altered patient outcome and expectations. In 
the following brief, we will discuss the development and emergence of these drugs
as well as the anticipated future course based on evidence.

Publication Types: 
    Comparative Study
    Review

PMID: 17951900 [PubMed - indexed for MEDLINE]

603: Indian J Ophthalmol. 2007 Nov-Dec;55(6):431-5.

Use of intravitreal injection of triamcinolone acetonide in the treatment of
age-related macular degeneration.

Gopal L, Sharma T.

Shri Bhagwan Mahavir Vitreoretinal Services, Sankara Nethralaya, Vision Research 
Foundation, 18 College Road, Chennai - 600 006, India. lekhag70@gmail.com

Age-related macular degeneration (AMD) is now considered an important and leading
cause of blindness among elderly patients in developed and developing countries. 
AMD has two forms, dry and wet; both can lead to visual loss. However, occurrence
of subfoveal choroidal neovascular (CNV) membrane in the wet form results in
severe visual impairment. Treatment options for choroidal neovascularization are 
available in order to maintain and in some cases improve vision. Photodynamic
therapy (PDT) has been used to treat both classic and occult membranes. It has
known to cause choroidal hypoperfusion and production of vascular endothelial
growth factor. Intravitreal steroid can possibly reduce the damage caused due to 
these undesirable effects. In the recent past, intravitreal injection of
triamcinolone acetonide (IVTA) has been used extensively as an adjunct to PDT in 
AMD in order to reduce the number of PDT sessions and evaluate possible
beneficial effects on vision. This article reviews the pharmacological attributes
of triamcinolone, available evidence of its use as monotherapy or combination
therapy to treat AMD, ocular side-effects thereof and ongoing clinical trials on 
IVTA.

Publication Types: 
    Review

PMID: 17951899 [PubMed - indexed for MEDLINE]

604: Indian J Ophthalmol. 2007 Nov-Dec;55(6):421-5.

Role of ranibizumab in management of macular degeneration.

Singh RP, Kaiser PK.

Cole Eye Institute, Cleveland Clinic Foundation, USA.

Age-related macular degeneration (AMD) is one of the most common causes of severe
vision loss in the western world. Both animal and human studies have established 
that vascular endothelial growth factor (VEGF) plays an important role in the
pathogenesis of this process. Ranibizumab (Lucentis(TM) Genentech, South San
Francisco, CA) is a monoclonal antibody fragment (Fab) directed toward all
isoforms of VEGF-A that was specifically designed to target wet AMD. The human
antibody fragment is produced by an E. coli expression system and has a molecular
weight of 48kD allowing for excellent retinal penetration. The most common ocular
complaints of patients receiving ranibizumab injections in randomized clinical
trials were transient conjunctival hemorrhage, vitreous floaters, intraocular
inflammation, increased intraocular pressure and eye pain. The rates of serious
adverse events such as retinal detachment, cataract and endophthalmitis were
similar to those that have been reported with other intravitreal injections and
patients should always be treated under strict aseptic conditions to reduce this 
risk. There were no significant non-ocular events found during any study so far
and the risk of thromboembolic events was less than 4% and not different than
sham. The MARINA, ANCHOR and PIER studies validated the safety and efficacy of
ranibizumab amongst a large population with different choroidal neovascular
membrane lesion types against sham or standard of care treatment. These studies
recommended monthly intravitreal ranibizumab for patients. However, the PIER
study reported that an alternative dosing of every three months is acceptable but
less effective than monthly injections.

Publication Types: 
    Review

PMID: 17951897 [PubMed - indexed for MEDLINE]

605: Indian J Ophthalmol. 2007 Nov-Dec;55(6):413-5.

Introduction, mechanism of action and rationale for anti-vascular endothelial
growth factor drugs in age-related macular degeneration.

Kim R.

Retina Vitreous Services, Aravind eye Hospital, Madurai, India. kim@aravind.org

Recent developments may provide an opportunity to improve outcome in individuals 
who develop neovascular age-related macular degeneration (ARMD). Several
therapies have been introduced that show promise for halting the progression of
this disorder. However, data from controlled clinical trials to test the relative
efficacy of different management strategies across the subtypes of disease remain
limited. New treatment modalities that target the neovascularization process,
including leakage from choroidal neovascularization (CNV), are currently being
developed. Vascular endothelial growth factor (VEGF) has been implicated as a key
mediator in the pathogenesis of ARMD-related CNV. Anti-VEGF strategies show
promise as potential therapeutic agents for the treatment of CNV and are
currently undergoing active clinical investigation. Such strategies include
anti-VEGF antibodies, anti-VEGF aptamer, gene therapy and protein kinase C
inhibition. This article reviews the mechanism of action and rationale for
anti-VEGF drugs in ARMD.

Publication Types: 
    Review

PMID: 17951895 [PubMed - indexed for MEDLINE]

606: Am J Ophthalmol. 2007 Dec;144(6):850-857. Epub 2007 Oct 22.

Ranibizumab for predominantly classic neovascular age-related macular
degeneration: subgroup analysis of first-year ANCHOR results.

Kaiser PK, Brown DM, Zhang K, Hudson HL, Holz FG, Shapiro H, Schneider S, Acharya
NR.

Cole Eye Institute, Cleveland, OH 44195, USA. pkkaiser@aol.com

PURPOSE: Subgroup data from a pivotal phase 3 study comparing ranibizumab
(LUCENTIS) with verteporfin (VISUDYNE) photodynamic therapy (PDT) in patients
with predominantly classic choroidal neovascularization (CNV) secondary to
age-related macular degeneration (AMD) were retrospectively analyzed to identify 
patient and disease characteristics that may predict visual acuity (VA) treatment
outcomes. DESIGN: Retrospective subgroup analysis of 12-month data from the
ANCHOR study. METHODS: Univariate analyses were performed to assess VA outcomes
across subgroups based on patients' gender and baseline age, VA score, CNV lesion
size, CNV lesion type, and duration of neovascular AMD, followed by multivariate 
analyses to identify predictors of the VA score change from baseline at 12
months. main outcome measures: Proportion of patients losing <15 letters and
proportion gaining > or =15 letters from baseline VA; mean change from baseline
VA. RESULTS: On average, all subgroups of ranibizumab-treated patients did better
than PDT patients for all three VA outcome measures. In the multivariate
analysis, lower baseline VA score, smaller baseline CNV lesion size, and younger 
baseline age were associated with greater gain of letters with ranibizumab
treatment and less loss of letters with PDT. CONCLUSIONS: Subgroup analysis of
12-month data from the ANCHOR study showed ranibizumab to be superior to PDT in
all subgroups evaluated, and was consistent with the subgroup analysis of
24-month data from the other pivotal phase 3 study of ranibizumab (MARINA) in
showing that the most important predictors of VA outcomes were, in decreasing
order of impact, the patient's baseline VA score, CNV lesion size, and age.

Publication Types: 
    Clinical Trial, Phase III
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17949673 [PubMed - indexed for MEDLINE]

607: Ophthalmologica. 2007;221(6):366-77.

Emerging therapies for neovascular age-related macular degeneration: state of the
art.

Donati G.

Clinique d'Ophtalmologie de Genève, HUG, Geneva, Switzerland.
guy.donati@bluewin.ch

The cornerstone of pharmacotherapeutic treatment for age-related macular
degeneration (AMD) is photodynamic therapy with verteporfin. The recently
approved pegaptanib sodium, which targets vascular endothelial growth factor
(VEGF), reduces vision loss in AMD when given by intravitreal injection every 6
weeks. The early promise of monotherapy with the corticosteroid triamcinolone
acetonide has yet to be borne out in larger clinical trials, but outcomes may be 
improved when it is used in combination with verteporfin therapy. The angiostatic
cortisone anecortave acetate was recently reported to have failed to meet the
primary efficacy criterion in two large, placebo-controlled trials, and its
clinical utility is uncertain. Other potential treatments with varying mechanisms
of action are currently under investigation. To date, no agent has been shown to 
significantly restore lost vision in patients with AMD. Future treatment
strategies are likely to include a combination of treatments to better manage
AMD-associated choroidal neovascularisation and preserve patients' visual acuity.
(c) 2007 S. Karger AG, Basel.

Publication Types: 
    Review

PMID: 17947822 [PubMed - indexed for MEDLINE]

608: Conf Proc IEEE Eng Med Biol Soc. 2006;1:4714-7.

Automated change analysis from fluorescein angiograms for monitoring wet macular 
degeneration.

Narasimha-Iyer H, Can A, Roysam B, Stern J.

Detection and analysis of changes from retinal images is important in clinical
practice, quantitative scoring of clinical trials, computer-assisted reading
centers, and in medical research. This paper presents a fully-automated approach 
for robust detection and classification of changes in longitudinal time-series of
fluorescein angiograms (FA). The changes of interest here are related to the
development of choroidal neo-vascularization (CNV) in wet macular degeneration.
Specifically, the changes in CNV regions as well as the retinal pigment
epithelium (RPE) hypertrophic regions are detected and analyzed to study the
progression of disease and effect of treatment. Retinal features including the
vasculature, vessel branching/crossover locations, optic disk and location of the
fovea are first segmented automatically. The images are then registered to
sub-pixel accuracy using a 12-dimensional mapping that accounts for the unknown
retinal curvature and camera parameters. Spatial variations in illumination are
removed using a surface fitting algorithm that exploits the segmentations of the 
various features. The changes are identified in the regions of interest and a
Bayesian classifier is used to classify the changes into clinically significant
classes. The automated change analysis algorithms were found to have a success
rate of 83%

PMID: 17947113 [PubMed - indexed for MEDLINE]

609: Cochrane Database Syst Rev. 2007 Oct 17;(4):CD005022.

Surgical implantation of steroids with antiangiogenic characteristics for
treating neovascular age-related macular degeneration.

Geltzer A, Turalba A, Vedula SS.

Brown University, 389 Benefit Street, Providence, Rhode Island 02906, USA.
youngheeart@mac.com

BACKGROUND: Neovascular age-related macular degeneration (AMD) is associated with
rapid vision loss due to choroidal neovascularization (CNV), leakage, and
scarring. Steroids have gained attention in their role for the treatment of
neovascular AMD for their antiangiogenic and anti-inflammatory properties.
OBJECTIVES: This review aims to examine effects of steroids with antiangiogenic
properties in the treatment of neovascular AMD. SEARCH STRATEGY: We searched for 
trials in CENTRAL, MEDLINE, EMBASE, and LILACS on 2 October 2006. SELECTION
CRITERIA: We included randomised controlled clinical trials of intra- and
peri-ocular steroids in people diagnosed with neovascular AMD. DATA COLLECTION
AND ANALYSIS: Review authors extracted the data and assessed trial quality
independently. We did not pool data since the included studies evaluated
difference comparisons. MAIN RESULTS: We report the risk of losing three or more 
lines vision at 12 months - "vision loss". One trial (139 people randomized)
reported that a single dose of intravitreal triamcinolone (n = 75) (4 mg) had no 
significant effect on the risk of vision loss compared to placebo (n = 76). (Risk
ratio vision loss 0.97, 95% confidence interval (CI) 0.74 to 1.26). Eyes treated 
with triamcinolone were more likely to develop cataracts and experience increased
intraocular pressure (IOP) compared to untreated eyes. One trial (128 people
randomized) reported the effects of anecortave acetate (3 mg (n = 32), 15 mg (n =
33) or 30 mg (n = 33) single dose with retreatment every six months if indicated)
compared to placebo (n = 30). Risk ratio vision loss 0.80 (95% CI 0.45 to 1.45)
in the 3 mg group, 0.45 (95% CI 0.21 to 0.97) in the 15 mg group and 0.91 (95% CI
0.52 to 1.58) in the 30 mg group. Side effects were similar in all treatment
groups with the anecortave group having a slightly higher incidence of foreign
body sensation compared to placebo. There was a high loss to follow-up. The final
analysis may have been subject to selection bias as participants who were not
selected for retreatment, possibly with worsening disease, were excluded. There
was also a possibility of type I error due to multiple statistical comparisons.
The sample size was estimated on the basis of a single 2-way comparison but three
2-way comparisons were analysed and presented. One trial reported that anecortave
acetate (n = 263) (15 mg administered at beginning of study and six months) gave 
similar results to photodynamic therapy (n = 267) (risk ratio vision loss 1.08,
95% CI 0.91 to 1.29). AUTHORS' CONCLUSIONS: Overall there is weak evidence as to 
the benefits and harms of steroids with antiangiogenic properties for treating
neovascular AMD with only three published trials of variable quality.
Intravitreal triamcinolone injection for neovascular AMD does not appear to
prevent severe vision loss and is associated with increased IOP and higher risk
of cataract formation. Anecortave acetate 15 mg may have a mild benefit in
stabilizing vision, but further better quality evidence is needed. The role of
steroids in combination with other treatment modalities is yet to be determined.

Publication Types: 
    Review

PMID: 17943833 [PubMed - indexed for MEDLINE]

610: Isr Med Assoc J. 2007 Sep;9(9):656-8.

Comment in:
    Isr Med Assoc J. 2007 Sep;9(9):674-5.

Ethnic background as a risk factor for advanced age-related macular degeneration 
in Israel.

Asleh SA, Chowers I.

Department of Ophthalmology, Hadassah-Hebrew University Medical Center,
Jerusalem, Israel.

BACKGROUND: Age-related macular degeneration is the most common cause of legal
blindness in the developed world including Israel. Ethnic background is a risk
factor for advanced AMD in several populations, however the relative prevalence
of this disease in different ethnic groups in the Middle East is unknown.
OBJECTIVES: To compare the prevalence of advanced AMD in Arabs and Jews in
Israel. METHODS: We performed a retrospective analysis of two independent groups 
of patients: the first group comprised a sequential series of Jerusalem residents
who underwent photodynamic therapy for neovascular AMD (PDT group), and the
second group consisted of all individuals in Jerusalem who received a blind
certificate due to AMD (legal blindness group). Control groups were assessed to
exclude inherited ethnic associated bias in the two study groups. RESULTS: The
PDT group included 146 patients: 142 were Jews (97.3%) and 4 were Arabs (2.7%).
The legal blindness group included 340 Jerusalem residents: 326 Jews (96%) and 14
Arabs (4%). The number of Arab AMD patients in the two groups was lower than
expected based on the ethnic composition of the age-matched Jerusalem population 
(P = 0.0002 for the PDT group, and P < 0.0001 for the legal blindness group). By 
contrast, the number of non-AMD Arab patients who were treated in the same clinic
and the number of Arabs who received a blind certificate for diabetic retinopathy
was not different from expected based on their relative number in the Jerusalem
population. CONCLUSIONS: Advanced AMD is less common in the Arab than the Jewish 
population of Jerusalem. Genetic and environmental factors may account for this
difference. A population-based study is required to assess the overall prevalence
of AMD in Jews and Arabs.

PMID: 17939627 [PubMed - indexed for MEDLINE]

611: Am J Ophthalmol. 2007 Dec;144(6):878-885. Epub 2007 Oct 15.

Comment in:
    Am J Ophthalmol. 2008 Aug;146(2):332-3; author reply 333.

Triple therapy of vitrectomy, intravitreal triamcinolone, and macular laser
photocoagulation for intractable diabetic macular edema.

Kang SW, Park SC, Cho HY, Kang JH.

Department of Ophthalmology, Samsung Medical Center, Sungkyunkwan University
School of Medicine, Seoul, Republic of Korea. swkang@smc.samsung.co.kr

PURPOSE: To evaluate the effect of a sequentially combined triple therapy on
intractable diabetic macular edema (DME). DESIGN: Prospective, interventional
case series. METHODS: Twenty-four eyes from 24 subjects, diagnosed with
intractable DME of nontractional origin, were subjected to vitrectomy.
Intravitreal triamcinolone acetonide injection and macular laser photocoagulation
were conducted sequentially at one and 14 days after vitrectomy. Best-corrected
visual acuity (BCVA) and central macular thickness (CMT) were recorded before
surgery and at three, six, and 12 months after triple therapy. RESULTS: The mean 
(+/- standard deviation [SD]) logarithm of the minimum angle of resolution BCVAs 
before and three, six, and 12 months after the triple therapy were 0.88 +/- 0.37,
0.55 +/- 0.33, 0.56 +/- 0.27, and 0.48 +/- 0.28, respectively. The mean (+/- SD) 
CMTs before and three, six, and 12 months after the triple therapy were 514 +/-
187 microm, 253 +/- 138 microm, 219 +/- 95 microm, and 197 +/- 91 microm,
respectively. The changes in both BCVA and CMT at three, six, and 12 months from 
baseline were statistically significant (P < .003). The major adverse events
after triple therapy were development of nuclear sclerotic cataracts (eight among
12 phakic eyes) and elevation of intraocular pressure (eight among 24 eyes).
CONCLUSIONS: The triple therapy may facilitate early recovery of vision and may
improve the long-term outcomes in some patients with DME refractory to
conventional monotherapy.

PMID: 17936715 [PubMed - indexed for MEDLINE]

612: Graefes Arch Clin Exp Ophthalmol. 2008 Feb;246(2):319-21. Epub 2007 Oct 13.

Intravitreal ranibizumab (Lucentis) for choroidal neovascularization associated
with Stargardt's disease.

Querques G, Bocco MC, Soubrane G, Souied EH.

Department of Ophthalmology, Ospedali Riuniti, University of Foggia, Foggia,
Italy. giuseppe.querques@hotmail.it

PURPOSE: To describe a young patient with choroidal neovascularization,
associated with Stargardt's disease, who underwent treatment with intravitreal
ranibizumab. METHODS: A 26-year-old man with a diagnosis of Stargard's disease
presented at our department for sudden decreased vison in his right eye (20/800).
Upon a complete oplthamologic examination, including fluorescein angiography
(FA), indocyanine green angiography (ICGA) and optical coherence tomography
(OCT), the patient was diagnosed with subfoveal CNV of the right eye. Owing to
the subfoveal localization of the CNV, intravitreal ranibizumab injection was
performed on this young patient. RESULTS: Three months after the last
intravitreal injection of ranibizumab, fundus biomicroscopy, FA, ICGA and OCT
revealed the CNV closure and total resolution of the associated cistoid macular
edema and serous retinal detachment, with no recurrence and no complication from 
the intravitreal injection of ranibizumab. Visual acuity improved only to 20/400.
CONCLUSION: Intravitreal ranibizumab injection seems to induce total regression
of CNV complicating Stargardt's disease. Further investigations are required to
confirm our results.

Publication Types: 
    Case Reports

PMID: 17934751 [PubMed - indexed for MEDLINE]

613: Eur J Ophthalmol. 2007 Sep-Oct;17(5):780-4.

Alterations in central retinal sensitivity after intravitreal triamcinolone
injection for diffuse diabetic macular edema.

Bardak Y, Cekiç O, Sahin Tiğ U, Bardak H.

Department of Ophthalmology, Suleyman Demirel University Medical School, Cünür,
Turkey. yavuzbardak@hotmail.com

PURPOSE: To evaluate alterations in central retinal sensitivity following
intravitreal triamcinolone injection in patients with diffuse diabetic macular
edema that persisted after laser treatment. METHODS: Fourteen eyes of 14 patients
that received 4 mg 0.1 cc intravitreal triamcinolone underwent macular threshold 
test using computerized visual field analyzer before and after 1, 2, 3, and 5
months of triamcinolone injection. Pre- and postinjection values of total defect 
depth, total threshold, and best-corrected visual acuity were compared and
correlated. RESULTS: At the last follow-up, compared to baseline, visual acuity
improved from 1.4+/-0.4 (logMAR, mean +/- standard deviation) to 1.0+/0.4
(p=0.01). Total defect depth tended to recover from 148+/-64 dB to 121+/-48 dB
(p=0.12), and total threshold tended to increase from 241+/-87 dB to 271+/-68 dB 
(p=0.16), but these values did not reach significance. There was a significant
correlation between baseline and 5 months postinjection values of total defect
depth (rho=0.60, p=0.02), and of total threshold of light sensitivity (rho=0.55, 
p=0.04). CONCLUSIONS: Best-corrected visual acuity was found improved in patients
with diabetic macular edema 5 months after triamcinolone injection. Improvement
in central retinal sensitivity did not reach significant level at the last
follow-up. Macular threshold test may be a valuable tool in the follow- up of
patients with diffuse diabetic macular edema after intravitreal triamcinolone
injection.

PMID: 17932855 [PubMed - indexed for MEDLINE]

614: Eur J Ophthalmol. 2007 Sep-Oct;17(5):768-75.

Monitoring of photodynamic therapy results in age-related macular degeneration by
means of preferential hyperacuity perimeter.

Wylegala EA, Pilat J, Teper SJ, Wroblewska-Czajka E, Bartusek M.

Department of Nursing and Social Medical Issues, Medical University of Silesia,
Katowice, Poland. okulistyka@o2.pl

PURPOSE: To describe changes revealed by Zeiss Preferential Hyperacuity Perimeter
(PreView PHP) in age-related macular degeneration (AMD), before and after
photodynamic therapy (PDT), and determine usefulness of such monitoring. METHODS:
Forty patients (40 eyes) with subfoveolar choroidal neovascularization (CNV) and 
20 volunteers with cataract (40 eyes) were examined in a prospective study.
Control group was screened for false positive results to evaluate reliability of 
the test. Subfoveolar CNV was confirmed by fluorescein angiography and optical
coherence tomography (OCT). Best-corrected visual acuity (BCVA) and macular
visual field in the PHP (area and intensity of distortion) were assessed 1 day
before and 1 week and 4 weeks after PDT. RESULTS: Four weeks after PDT there was 
improvement in PHP results in 20 eyes (50%), stabilization in 15 eyes (37.5%) and
progression in 5 eyes (12.5%). At this time there was BCVA improvement in 9 eyes 
(22.5%), stabilization in 28 eyes (70%), and worsening in 3 eyes (7.5%). 1 week
after PDT 30 eyes (75%) presented temporary progression in PHP but only 3
patients (7.5%) presented temporary decrease of visual acuity and progression in 
OCT. Correlation coefficient of BCVA and PHP results was low during whole study. 
There was no significant change in control group during observation. 17.5% false 
positive PHP results were obtained at baseline. In the PDT group no false
negative results were noted. CONCLUSIONS: Visual outcome after PDT cannot be
predicted with use of PreView PHP. Temporary progression of changes in PHP 1 week
after PDT can be expected in most cases.

PMID: 17932853 [PubMed - indexed for MEDLINE]

615: Eur J Ophthalmol. 2007 Sep-Oct;17(5):760-7.

One-year results of photodynamic therapy for small predominantly classic
choroidal neovascular membranes secondary to age-related macular degeneration.

Doyle E, Khanwala M, Shah SP, Ong DG, Casswell AG.

Sussex Eye Hospital, Brighton and Sussex University Hospitals NHS Trust,
Brighton, UK. EdRachie@btinternet.com

PURPOSE: To determine the visual and angiographic outcomes of patients with small
predominantly classic choroidal neovascular membranes (CNV) undergoing
photodynamic therapy (PDT). METHODS: The subjects were a cohort of patients with 
age-related predominantly classic CNV with lesion size of greatest linear
diameter of 2000 microm or less treated with PDT. Lesion size and visual acuity
were recorded at baseline and at 3-month intervals. Visual treatment failure was 
defined as either loss of at least 15 letters or visual acuity less than 35
letters on a modified Early Treatment Diabetic Retinopathy Study chart. Lesion
treatment failure was defined as increase in greatest linear diameter (GLD) of at
least 500 microm. RESULTS: Twenty-five eyes of 25 patients were included. Visual 
treatment failure occurred in 16 and mean visual acuity dropped from 58 letters
to 34 letters (p<0.0001). In 11 of these patients this occurred within the first 
3 months. Lesion treatment failure occurred in 18 patients. Mean GLD increased
from 1331 to 2935 microm (p<0.0001). Early growth of the lesion was associated
with poor visual outcome with growth in GLD in the first 3 months of 310 microm
in patients without eventual visual treatment failure and 1131 microm in patients
with eventual visual failure (p=0.027). CONCLUSIONS: Small predominantly classic 
lesions commonly cause visual deterioration if treated with PDT alone. In the
first year over 50% may lose at least 15 letters or drop below 35 letters, with
most visual loss occurring in the first 3 months. Visual loss is associated with 
early lesion growth.

Publication Types: 
    Comparative Study
    Multicenter Study

PMID: 17932852 [PubMed - indexed for MEDLINE]

616: Eur J Ophthalmol. 2007 Sep-Oct;17(5):749-54.

Molecular scanning of the ABCA4 gene in Spanish patients with retinitis
pigmentosa and Stargardt disease: identification of novel mutations.

Stenirri S, Battistella S, Soriani N, Bernal S, Baiget M, Ferrari M, Cremonesi L.

Genomic Unit for Diagnosis of Human Pathologies, San Raffaele Scientific
Institute, Milano, Italy.

PURPOSE: Among the 500 ABCA4 mutations identified so far in the retina-specific
ABC transporter (ABCA4) gene, only 20 have been described in patients with
autosomal recessive retinitis pigmentosa (arRP). In this study the gene was
screened for mutations in a cohort of 25 patients of Spanish origin, to further
assess ABCA4 involvement in retinal dystrophies. METHODS: The 50 exons of the
ABCA4 gene have been analyzed through denaturing high performance liquid
chromatography (DHPLC) and direct sequencing of samples displaying altered
elution profiles. RESULTS: Four new and five known mutations were identified in
our patients; except for one new deletion detected in a patient with Stargardt
disease, all the remaining variations are single nucleotide substitutions
resulting in missense mutations. CONCLUSIONS: The results further underline the
genetic heterogeneity of retinal disorders, suggesting that more than one gene
could differentially contribute to at least some forms of retinal degeneration.
Finding a high proportion of novel mutations merits the use of scanning
methodologies to analyze the whole coding region of the ABCA4 gene.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17932850 [PubMed - indexed for MEDLINE]

617: Appl Opt. 2007 Oct 10;46(29):7244-51.

Nonlinearity in the rotational dynamics of Haidinger's brushes.

Rothmayer M, Dultz W, Frins E, Zhan Q, Tierney D, Schmitzer H.

Xavier University, Cincinnati, Ohio 45207, USA.

Haidinger's brushes are an entoptic effect of the human visual system that
enables us to detect polarized light. However, individual perceptions of
Haidinger's brushes can vary significantly. We find that the birefringence of the
cornea influences the rotational motion and the contrast of Haidinger's brushes
and may offer an explanation for individual differences. We have devised an
experimental setup to simulate various phase shifts of the cornea and found a
switching effect in the rotational dynamics of Haidinger's brushes. In addition, 
age related macular degeneration reduces the polarization effect of the macula
and thus also leads to changes in the brush pattern.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17932536 [PubMed - indexed for MEDLINE]

618: Jpn J Ophthalmol. 2007 Sep-Oct;51(5):368-74. Epub 2007 Oct 5.

Determinants of patient satisfaction with photodynamic therapy for neovascular
age-related macular degeneration or polypoidal choroidal vasculopathy.

Yamashiro K, Tsujikawa A, Nishida A, Kurimoto Y.

Department of Ophthalmology, Kobe City General Hospital, Chuo, Kobe, Japan.
yamashro@kcgh.gr.jp

PURPOSE: To evaluate the determinants of patient satisfaction with photodynamic
therapy (PDT) for neovascular age-related macular degeneration (AMD) or
polypoidal choroidal vasculopathy (PCV). METHODS: Questionnaires were mailed to
69 patients who had undergone PDT for AMD or PCV at the Kobe City General
Hospital. The questionnaire considered the following parameters: subjective
change in visual acuity, subjective change in the relative scotoma in central
vision, subjective change in visual distortion, and patient satisfaction with PDT
scored on a 100-point scale. RESULTS: Nine patients (14%) reported their
subjective visual acuity change as "significantly improved" and 21 (32%) as
"slightly improved"; 18 (27%) reported "no change"; 12 (18%) reported their
visual acuity as "slightly worsened"; and 6 (9%) as "significantly worsened."
Subjective change in the central scotoma was reported improved in 43 patients
(64%) and visual distortion had improved subjectively in 31 patients (47%). The
satisfaction score was 59 +/- 25 in patients who had undergone PDT for AMD and 75
+/- 24 in those with PCV. Not only the visual acuity change but also the
subjective change in central scotoma and visual distortion correlated
significantly with the satisfaction score. CONCLUSIONS: More patients who have
undergone PDT for AMD or PCV perceive improvement in central scotoma and visual
distortion than in visual acuity. Since these subjective changes correlated
significantly with the satisfaction score, subjective change in central scotoma
and visual distortion, in addition to visual acuity, should be taken into account
in evaluating the benefits of PDT.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17926114 [PubMed - indexed for MEDLINE]

619: BMJ. 2007 Oct 13;335(7623):755. Epub 2007 Oct 8.

Comment in:
    BMJ. 2007 Oct 13;335(7623):729.

Dietary antioxidants and primary prevention of age related macular degeneration: 
systematic review and meta-analysis.

Chong EW, Wong TY, Kreis AJ, Simpson JA, Guymer RH.

Centre for Eye Research Australia, University of Melbourne, Victoria 3002,
Australia. twong@unimelb.edu.au

OBJECTIVE: To evaluate the effectiveness of dietary antioxidants in the primary
prevention of age related macular degeneration (AMD). DESIGN: Systematic review
and meta-analysis. DATA SOURCES: Search of seven databases without limits on year
or language of publication, and retrieval of references in pertinent reviews and 
articles. METHODS: Two reviewers independently searched the databases and
selected the studies, using standardised criteria. Randomised clinical trials and
prospective cohort studies were included. Of the 4192 abstracts initially
identified, 12 studies (nine prospective cohort studies and three randomised
clinical trials) met the selection criteria and were included. Data extraction
and study quality evaluation were independently reviewed, using standardised
criteria. Results were pooled quantitatively using meta-analytic methods.
RESULTS: The nine prospective cohort studies included 149 203 people, with 1878
incident cases of early AMD. The antioxidants investigated differed across
studies, and not all studies contributed to the meta-analysis of each
antioxidant. Pooled results from prospective cohort studies indicated that
vitamin A, vitamin C, vitamin E, zinc, lutein, zeaxanthin, alpha carotene, beta
carotene, beta cryptoxanthin, and lycopene have little or no effect in the
primary prevention of early AMD. The three randomised clinical trials did not
show that antioxidant supplements prevented early AMD. CONCLUSIONS: There is
insufficient evidence to support the role of dietary antioxidants, including the 
use of dietary antioxidant supplements, for the primary prevention of early AMD.

Publication Types: 
    Meta-Analysis
    Research Support, Non-U.S. Gov't
    Review

PMID: 17923720 [PubMed - indexed for MEDLINE]

620: Arch Ophthalmol. 2007 Oct;125(10):1396-401.

C-reactive protein level and risk of aging macula disorder: The Rotterdam Study.

Boekhoorn SS, Vingerling JR, Witteman JC, Hofman A, de Jong PT.

Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.

OBJECTIVE: To examine whether C-reactive protein (CRP) level is a risk factor for
aging macula disorder (AMD) in a general population. METHODS: We examined serum
high-sensitivity CRP (HsCRP) levels in 4914 participants of the population-based 
Rotterdam Study at risk for AMD. After a mean follow-up of 7.7 years, 561 cases
of early and 97 cases of late incident AMD (iAMD) were identified. We used Cox
proportional hazards regression models to estimate hazard ratios and
corresponding 95% confidence intervals (CIs). RESULTS: After adjustment for age
and sex, hazard ratios were 1.11 (95% CI, 1.02-1.21) per standard deviation
increase in HsCRP level for early iAMD and 1.28 (95% CI, 1.02-1.60) for late
iAMD. Hazard ratios for early iAMD increased per quartile increase in HsCRP level
as follows: second quartile, 1.19 (95% CI, 0.94-1.52); third quartile, 1.29 (95% 
CI, 1.01-1.64); and fourth quartile, 1.33 (95% CI, 1.05-1.70). The risk of late
iAMD was higher in all upper quartiles of HsCRP. CONCLUSION: Elevated baseline
levels of HsCRP were associated with the development of early and late AMD in
this large population-based cohort.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17923549 [PubMed - indexed for MEDLINE]

621: Arch Ophthalmol. 2007 Oct;125(10):1367-72.

Erratum in:
    Arch Ophthalmol. 2007 Dec;125(12):1646.

Long-term follow-up of macular translocation with 360 degrees retinotomy for
exudative age-related macular degeneration.

Aisenbrey S, Bartz-Schmidt KU, Walter P, Hilgers RD, Ayertey H, Szurman P,
Thumann G.

Department of Ophthalmology, University of Tuebingen, Schleichstrasse 12-16,
72076 Tuebingen, Germany. sabine.aisenbrey@med.uni-tuebingen.de

OBJECTIVE: To assess long-term functional and morphological changes after macular
translocation in patients with exudative age-related macular degeneration.
METHODS: Evaluation of a noncomparative cohort study of 90 patients with a
follow-up of 14 to 79 months (mean, 38.2 months). RESULTS: Visual acuity
increased by 3 or more lines in 15 patients, remained stable in 35 patients, and 
deteriorated in 40 patients at final examination. Pigment epithelium atrophy
extending to the new fovea was detected in 44 patients; in 25 patients this new
atrophy was associated with loss of visual function. CONCLUSIONS: Long-term
follow-up of macular translocation with 360 degrees retinotomy showed
stabilization or improvement in half of the patients. Progressive atrophy of the 
pigment epithelium represented one major limiting factor of the beneficial effect
of the treatment. Macular translocation may be an option for cases of exudative
age-related macular degeneration that are not eligible for or do not respond to
alternative treatments.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17923545 [PubMed - indexed for MEDLINE]

622: Arch Ophthalmol. 2007 Oct;125(10):1357-61.

Comment in:
    Arch Ophthalmol. 2008 Sep;126(9):1314-5; author reply 1315.

Intravitreal bevacizumab vs verteporfin photodynamic therapy for neovascular
age-related macular degeneration.

Bashshur ZF, Schakal A, Hamam RN, El Haibi CP, Jaafar RF, Noureddin BN.

Department of Ophthalmology, American University of Beirut, Beirut, Lebanon.
zb00@aub.edu.lb

OBJECTIVE: To compare verteporfin photodynamic therapy (PDT) with intravitreal
bevacizumab for management of choroidal neovascularization (CNV) associated with 
age-related macular degeneration. METHODS: Patients with predominantly classic
CNV were prospectively randomized to receive standard PDT or intravitreal
bevacizumab injections (2.5 mg). Best-corrected visual acuity (BCVA) measured by 
Snellen charts, central retinal thickness by optical coherence tomography, and
greatest linear dimension of the CNV by fluorescein angiography were compared
between the groups at baseline and at 3 and 6 months. Main outcome measures were 
stability or improvement in BCVA, decrease in central retinal thickness, and
stability in greatest linear dimension. RESULTS: Mean baseline BCVA, central
retinal thickness, and greatest linear dimension were not statistically different
between the bevacizumab (n = 32) and PDT (n = 30) groups. Mean central retinal
thickness was significantly better at 3 and 6 months in the bevacizumab group vs 
the PDT group (P = .04 and P = .002, respectively). At 3 months, mean BCVA and
greatest linear dimension were not significantly different between the 2 groups. 
At 6 months, mean BCVA and greatest linear dimension were significantly better in
the bevacizumab group (P < .001 and P = .02, respectively). CONCLUSION: During 6 
months, intravitreal bevacizumab was superior to PDT in controlling predominantly
classic CNV in age-related macular degeneration. Additional randomized clinical
trials are necessary to determine if this benefit will remain with longer
follow-up.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial

PMID: 17923543 [PubMed - indexed for MEDLINE]

623: Arch Ophthalmol. 2007 Oct;125(10):1323-30.

Incident choroidal neovascularization in fellow eyes of patients with unilateral 
subfoveal choroidal neovascularization secondary to age-related macular
degeneration: SST report No. 20 from the Submacular Surgery Trials Research
Group.

Submacular Surgery Trials Research Group, Solomon SD, Jefferys JL, Hawkins BS,
Bressler NM.

Johns Hopkins University School of Medicine, 550 N Broadway, Ste 115, Baltimore, 
MD 21205-2005, USA. nmboffice@jhmi.edu

OBJECTIVE: To describe incident choroidal neovascular lesions in fellow eyes of
participants in the Submacular Surgery Trials who had age-related macular
degeneration (AMD). METHODS: Review of baseline fluorescein angiograms confirmed 
the absence of neovascular AMD in fellow eyes of 364 participants at risk.
Subjects were eligible for a minimum of 2 years of follow-up with angiograms of
eyes at risk reevaluated to estimate incidence rates of choroidal
neovascularization (CNV) and to characterize these lesions. MAIN OUTCOME
MEASURES: Incidence of CNV during follow-up, characteristics of the incident
lesion (composition, size, and location), and visual acuity at the time of
incidence. RESULTS: Incident lesions were confirmed in 98 fellow eyes of
participants, yielding 2- and 4-year cumulative incidence rates of 22% and 37%.
Incident lesions were predominantly CNV in 87 fellow eyes (90%), extrafoveal in
29 fellow eyes (30%), and juxtafoveal in 9 fellow eyes (9%). Occult without
classic CNV lesions were found in 64 eyes (67%), minimally classic CNV and
predominantly classic CNV lesions in 12 eyes (13%) each, and predominantly blood 
lesions in 4 eyes (4%). Nearly two-thirds of all incident lesions were 3 disc
areas or smaller in size. Median visual acuity decreased from 20/25 at baseline
to 20/250 at the 4-year follow-up in fellow eyes with incident CNV. CONCLUSIONS
AND APPLICATION TO CLINICAL PRACTICE: Frequent angiographic follow-up of fellow
eyes at risk for CNV may lead to earlier detection and treatment of neovascular
AMD and better visual acuity outcomes.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial
    Research Support, N.I.H., Extramural

PMID: 17923538 [PubMed - indexed for MEDLINE]

624: Am J Clin Nutr. 2007 Oct;86(4):1210-8.

Dietary carbohydrate and the progression of age-related macular degeneration: a
prospective study from the Age-Related Eye Disease Study.

Chiu CJ, Milton RC, Klein R, Gensler G, Taylor A.

Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging 
at Tufts University, Boston, MA 02111, USA.

BACKGROUND: Cross-sectional studies indicate that diets that provide a higher
dietary glycemic index (dGI) are associated with a greater risk of age-related
macular degeneration (AMD). No prospective studies have addressed this issue.
OBJECTIVE: The objective was to prospectively evaluate the effect of baseline dGI
on the progression of AMD. DESIGN: dGI was calculated as the weighted average of 
GIs from foods and was evaluated as being above or below the sex median (women:
77.9; men: 79.3) for 3977 participants aged 55-80 y (58% women) in the
Age-Related Eye Disease Study. The 7232 eligible eyes without advanced AMD were
classified into 1 of 3 AMD categories: group 1 (nonextensive small drusen), group
2 (intermediate drusen, extensive small drusen, or pigmentary abnormalities), or 
group 3 (large drusen or extensive intermediate drusen). With the use of
multifailure Cox proportional-hazards regression, we modeled the time to the
maximal progression to evaluate the relation between dGI and the risk of AMD.
RESULTS: Overall, the multivariate-adjusted risk of progression over 8 y of
follow-up (x: 5.4 y) was significantly higher (risk ratio: 1.10; 95% CI: 1.00,
1.20; P = 0.047) in the high-dGI group than in the low-dGI group. The risk of
progression for groups 1, 2, and 3 eyes was 5%, 8%, and 17% greater, respectively
(P for trend < 0.001). The latter gives an estimate that 7.8% of new advanced AMD
cases would be prevented in 5 y if people consumed the low-dGI diet. CONCLUSION: 
Persons at risk of AMD progression, especially those at high risk of advanced
AMD, may benefit from consuming a smaller amount of refined carbohydrates.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, Non-P.H.S.

PMID: 17921404 [PubMed - indexed for MEDLINE]

625: Graefes Arch Clin Exp Ophthalmol. 2008 Apr;246(4):483-9. Epub 2007 Oct 5.

Intravitreal bevacizumab with or without triamcinolone for refractory diabetic
macular edema; a placebo-controlled, randomized clinical trial.

Ahmadieh H, Ramezani A, Shoeibi N, Bijanzadeh B, Tabatabaei A, Azarmina M,
Soheilian M, Keshavarzi G, Mohebbi MR.

Ophthalmic Research Center, Labbafinejad Medical Center, Shaheed Beheshti Medical
University, Tehran, Iran. hahmadieh@hotmail.com

PURPOSE: To evaluate the effect of three intravitreal injections of bevacizumab
(IVB) alone or combined with triamcinolone (IVT) in the first injection for
treatment of refractory diabetic macular edema (DME). METHODS: In this
prospective, placebo-controlled, randomized clinical trial, 115 eyes of 101
patients with refractory DME were included. Subjects were randomly assigned to
one of the three study arms: 1) three injections of IVB (1.25 mg/0.05 ml) at
6-week intervals, 2) combined IVB and IVT (1.25 mg/0.05 ml and 2 mg/0.05 ml
respectively) followed by two injections of IVB at 6-week intervals, and 3) sham 
injection (control group). The primary outcome measure was change in central
macular thickness (CMT). Secondary outcome measures were change in best-corrected
logMAR visual acuity (BCVA ) and incidence of potential adverse events. RESULTS: 
Central macular thickness was reduced significantly in both the IVB and IVB/IVT
groups. At week 24, CMT change compared to the baseline was -95.7 microm (95% CI,
-172.2 to -19.26) in the IVB group, -92.1 microm (95% CI, -154.4 to -29.7) in the
IVB/IVT group, and 34.9 microm (95% CI, 7.9 to 61.9) in the control group. There 
was a significant difference between the IVB and control groups (P = 0.012) and
between the IVB/IVT and control groups (P = 0.022). Improvement of BCVA was
initiated at weeks 6 and 12 in the IVB/IVT and IVB groups respectively. In terms 
of BCVA change compared to the baseline at 24 weeks, the differences between the 
IVB and control groups (P = 0.01) and also between the IVB/IVT and control groups
(P = 0.006) were significant. No significant differences were detected in the
changes of CMT and BCVA between the IVB and IVB/IVT groups (P = 0.99). Anterior
chamber reaction was noticed in eight (19.5%) and seven (18.9%) eyes respectively
in the IVB and IVB/IVT groups the day after injection, and it resolved with no
sequel. Elevation of IOP occurred in three eyes (8.1%) in the IVB/IVT group.
CONCLUSION: Three consecutive intravitreal injections of bevacizumab had a
beneficial effect on refractory DME in terms of CMT reduction and BCVA
improvement. Addition of triamcinolone in the first injection seemed to induce
earlier visual improvement; however, it did not show any significant additive
effect later during follow-up.

Publication Types: 
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial

PMID: 17917738 [PubMed - indexed for MEDLINE]

626: Am J Ophthalmol. 2007 Dec;144(6):838-843. Epub 2007 Oct 4.

Octreotide long-acting repeatable for the treatment of chronic macular edema in
uveitis.

Missotten T, van Laar JA, van der Loos TL, van Daele PL, Kuijpers RW, Baarsma GS,
van Hagen PM.

Department of Uveitis, Rotterdam Eye Hospital, Rotterdam, The Netherlands.
missotten@oogziekenhuis.nl

PURPOSE: To report on the efficacy of the somatostatin analog octreotide
long-acting repeatable (LAR), in the treatment of uveitic chronic macular edema
(CME). DESIGN: Case series, retrospective analysis. METHODS: In 20 patients, 20
episodes of recurrent CME during otherwise quiescent uveitis were treated with
intramuscular octreotide LAR injections. Patients were included if CME control
with acetazolamide or systemic and periocular steroids had failed during previous
CME episodes or if contraindications existed for persistent use of these
therapies. Mean outcome points were CME and visual acuity changes. Correlation of
prognostic factors with these outcomes was analyzed. RESULTS: The included CME
episodes occurred 7.6 +/- 1.4 years after onset of uveitis. Octreotide LAR
treatment started 7.0 +/- 7.3 months after diagnosis of CME. CME decreased in 70%
of episodes, after 2.7 +/- 1.3 months of treatment. After arrest of successful
treatment, CME recurred instantly (27.2%) or within six months (36.4%). In 36.4% 
of successfully treated episodes, CME was absent for more than one year. A
probable prognostic factor for success was the duration of CME before treatment. 
CONCLUSIONS: Octreotide LAR had an edema-reducing effect in 70% of treated CME
episodes. Successful response was related to duration of CME before start of
treatment. The early recurrence of CME (63.6%) after arrest of octreotide LAR
advocates a long-term treatment in recent episodes of macular edema in otherwise 
quiescent uveitis.

PMID: 17916316 [PubMed - indexed for MEDLINE]

627: Am J Ophthalmol. 2007 Dec;144(6):886-892. Epub 2007 Oct 4.

Intravitreal bevacizumab therapy for neovascular age-related macular degeneration
with large submacular hemorrhage.

Stifter E, Michels S, Prager F, Georgopoulos M, Polak K, Hirn C, Schmidt-Erfurth 
U.

Department of Ophthalmology, Medical University of Vienna, Austria.

PURPOSE: To evaluate functional and anatomic effects of intravitreal bevacizumab 
(Avastin; Roche Pharma, Vienna, Austria) in patients with neovascular age-related
macular degeneration (AMD) with large submacular hemorrhages. DESIGN:
Retrospective, clinical study. METHODS: Twenty-one eyes of 19 AMD patients with
choroidal neovascularization and large submacular hemorrhage involving the fovea 
comprising more than 50% of the total lesion area were evaluated. All patients
completed at least four months of follow-up; 12 patients fulfilled 12 months or
more of follow-up. Patients were treated with up to six intravitreal bevacizumab 
injections (1 mg/0.04 ml) at a minimum of four-week intervals. Changes from
baseline visual acuity (VA) scores, retinal measurements by optical coherence
tomography (OCT), angiographic lesion characteristics, and hemorrhage size were
analyzed. A safety assessment was performed at all visits. RESULTS: Intravitreal 
bevacizumab injections were well tolerated in all patients. At month 4, VA was
stable or improved (visual loss of 3 acuity lines or fewer) in 100% and improved 
by at least 3 lines in 9.5%. Comparable results were found at month 12. On
average, the central foveal thickness decreased significantly by 55 microm four
weeks after the first injection (P < .001) and by 52 microm at month 4 (P =
.002). A significant anatomic improvement also was found for maximum retinal
thickness, minimum retinal thickness, and foveal volume (P < .05) and was
maintained during four months of follow-up. Mean size of hemorrhage was
significantly reduced from 19.7 mm(2) at baseline to 2.5 mm(2) at the four-month 
follow-up (P < .001). CONCLUSIONS: Intravitreal bevacizumab seems to be a
promising therapeutic option in eyes with neovascular AMD and large submacular
hemorrhages, with a stabilization in VA and anatomic improvement.

PMID: 17916314 [PubMed - indexed for MEDLINE]

628: Annu Rev Pharmacol Toxicol. 2008;48:61-78.

Pharmacotherapy for the treatment of choroidal neovascularization due to
age-related macular degeneration.

Novack GD.

PharmaLogic Development Inc., San Rafael, CA 94903, USA.
gary_novack@pharmalogic.com

Age-related macular degeneration (AMD) is a progressive, degenerative disease of 
the macula that threatens central vision. It initially occurs in a "dry" form,
and can progress to choroidal neovascularization (CNV) or geographic atrophy. It 
is the leading cause of blindness among European-descended people older than 65
years, with a prevalence of 1.5%. The treatment of CNV in developed nations in
2007 is substantially different than it was in 1997. Focal, photocoagulating,
laser therapy was replaced by intravenous verteporfin and then by intravitreal
pegaptanib, which is now being replaced by intravitreal ranibizumab and off-label
use of bevacizumab. Other than a ranibizumab versus verteporfin trial, there are 
no published comparative studies of the three approved pharmacological treatments
for CNV. Although frequent intravitreal injections are accepted as a current
standard of care, their use is still far from ideal. Thus, there is an
opportunity for improving therapy of CNV with respect to mechanism-targeted
treatments, efficacy, and route of administration.

Publication Types: 
    Review

PMID: 17914929 [PubMed - indexed for MEDLINE]

629: Ann Ophthalmol (Skokie). 2007 Spring;39(1):51-2.

Large subretinal hemorrhage after intravitreal bevacizumab (Avastin) for
age-related macular degeneration.

Chieh JJ, Fekrat S.

Department of Opthalmology, Duke University Medical Center, Durham, NC 27710,
USA.

We report the development of a large subretinal hemorrhage 4 weeks after
intravitreal bevacizumab in an 84-year-old male with 20/70 visual acuity caused
by occult choroidal neovascularization from neovascular age-related macular
degeneration in one eye that was treated with 1.25 mg of intravitreal
bevacizumab.

Publication Types: 
    Case Reports

PMID: 17914205 [PubMed - indexed for MEDLINE]

630: J AAPOS. 2007 Dec;11(6):614-5. Epub 2007 Oct 29.

Subfoveal choroidal neovascularization in a 3-year-old child with North Carolina 
macular dystrophy.

Rhee DY, Reichel E, Rogers A, Strominger M.

Tufts-New England Medical Center, New England Eye Center, Boston, MA 02111, USA.

North Carolina macular dystrophy is characterized by nonprogressive atrophy of
the choroid, choriocapillaris, and the retinal pigment epithelial layer. The
characteristic retinal findings, ranging from scattered drusen to a posterior
staphyloma, have been reported as early as infancy and usually reach their
greatest magnitude in the second decade of life. Herein, we describe a case of a 
3-year-old boy with a documented family history of North Carolina macular
dystrophy who presented with a subfoveal choroidal neovascular membrane in
addition to the macular dystrophic changes.

Publication Types: 
    Case Reports

PMID: 17913524 [PubMed - indexed for MEDLINE]

631: Doc Ophthalmol. 2008 Jan;116(1):57-60. Epub 2007 Oct 3.

Electronegative electroretinogram associated with topiramate toxicity and
vitelliform maculopathy.

Tsui I, Casper D, Chou CL, Tsang SH.

Brown Glaucoma Laboratory at Edward S. Harkness Eye Institute, Columbia
University, New York, NY 10032, USA. irena.tsui@gmail.com

Topiramate is known to cause ocular side effects such as refractive changes and
angle closure. We describe a patient with an electronegative electroretinogram
(ERG) which may have been related to topiramate use. Electronegative ERG's have
been associated with other drugs in humans as well as topiramate use in rabbits. 
However, this would be the first suggestion of causality in humans.

Publication Types: 
    Case Reports
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17912565 [PubMed - indexed for MEDLINE]

632: Hum Mol Genet. 2007 Oct 15;16 Spec No. 2:R174-82.

Genetic susceptibility to age-related macular degeneration: a paradigm for
dissecting complex disease traits.

Swaroop A, Branham KE, Chen W, Abecasis G.

Department of Ophthalmology, University of Michigan, Ann Arbor, MI 48105, USA.
swaroop@umich.edu

Age-related macular degeneration (AMD) is a progressive neurodegenerative
disease, which affects quality of life for millions of elderly individuals
worldwide. AMD is associated with a diverse spectrum of clinical phenotypes, all 
of which include the death of photoreceptors in the central part of the human
retina (called the macula). Tremendous progress has been made in identifying
genetic susceptibility variants for AMD. Variants at chromosome 1q32 (in the
region of CFH) and 10q26 (LOC387715/ARMS2) account for a large part of the
genetic risk to AMD and have been validated in numerous studies. In addition,
susceptibility variants at other loci, several as yet unidentified, make
substantial cumulative contribution to genetic risk for AMD; among these,
multiple studies support the role of variants in APOE and C2/BF genes.
Genome-wide association and re-sequencing projects, together with
gene-environment interaction studies, are expected to further define the causal
relationships that connect genetic variants to AMD pathogenesis and should assist
in better design of prevention and intervention.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Review

PMID: 17911160 [PubMed - indexed for MEDLINE]

633: J R Soc Med. 2007 Oct;100(10):473-7.

Age-related macular degeneration: what do patients find on the internet?

Rennie CA, Hannan S, Maycock N, Kang C.

Southampton Eye Unit, Mailpoint 104, Southampton General Hospital, Tremona Road, 
Southampton, SO16 6YD, UK. chris_rennie@yahoo.com

OBJECTIVE: To assess the quality of information and readability of the top
internet sites for age-related macular degeneration (AMD). DESIGN: An examination
of the technical information provision, quality and readability of websites found
during an internet search for 'age-related macular degeneration'. Setting Six
internet search engines were used to find 26 unique sites on AMD. MAIN OUTCOME
MEASURES: Technical information and quality were assessed using a simple grading 
system. Readability was assessed using a Simple Measure Of Gobbledygook (SMOG)
rating. RESULTS: Twelve organizational, seven academic and seven commercial sites
were identified. The average technical scores were 82.3%, 67.9% and 65.2% for
each type of site, respectively (P=0.097, one way ANOVA). The average quality
scores were 62.2%, 62.6%, and 49.5% for each type of site, respectively (P=0.356,
one-way ANOVA). The average SMOG ratings were 16.3, 16.1, and 16.2 for each type 
of site, respectively (P=0.983, one-way ANOVA). Fifteen of the sites provided
details of new and emerging treatments, with seven providing a detailed
discussion. CONCLUSIONS: Many websites are now meeting the challenge of providing
comprehensive information about AMD and its new treatments. Quality scores were
disappointing, with sites needing to provide more evidence of authorship and
attribution of information. The majority of sites had SMOG scores above 10,
making them difficult for the average person to understand. As physicians we need
to help design and direct patients to sites that provide high quality, current
information.

Publication Types: 
    Evaluation Studies

PMID: 17911131 [PubMed - indexed for MEDLINE]

634: J Clin Invest. 2007 Oct;117(10):2920-8.

Comment in:
    J Clin Invest. 2007 Oct;117(10):2758-62.

CX3CR1-dependent subretinal microglia cell accumulation is associated with
cardinal features of age-related macular degeneration.

Combadière C, Feumi C, Raoul W, Keller N, Rodéro M, Pézard A, Lavalette S,
Houssier M, Jonet L, Picard E, Debré P, Sirinyan M, Deterre P, Ferroukhi T, Cohen
SY, Chauvaud D, Jeanny JC, Chemtob S, Behar-Cohen F, Sennlaub F.

INSERM U543, Laboratoire d'Immunologie Cellulaire, Paris, France.

The role of retinal microglial cells (MCs) in age-related macular degeneration
(AMD) is unclear. Here we demonstrated that all retinal MCs express CX3C
chemokine receptor 1 (CX3CR1) and that homozygosity for the CX3CR1 M280 allele,
which is associated with impaired cell migration, increases the risk of AMD. In
humans with AMD, MCs accumulated in the subretinal space at sites of retinal
degeneration and choroidal neovascularization (CNV). In CX3CR1-deficient mice,
MCs accumulated subretinally with age and albino background and after laser
impact preceding retinal degeneration. Raising the albino mice in the dark
prevented both events. The appearance of lipid-bloated subretinal MCs was
drusen-like on funduscopy of senescent mice, and CX3CR1-dependent MC accumulation
was associated with an exacerbation of experimental CNV. These results show that 
CX3CR1-dependent accumulation of subretinal MCs evokes cardinal features of AMD. 
These findings reveal what we believe to be a novel pathogenic process with
important implications for the development of new therapies for AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17909628 [PubMed - indexed for MEDLINE]

635: J Clin Invest. 2007 Oct;117(10):2758-62.

Comment on:
    J Clin Invest. 2007 Oct;117(10):2920-8.

Overstaying their welcome: defective CX3CR1 microglia eyed in macular
degeneration.

Chen J, Connor KM, Smith LE.

Department of Ophthalmology, Children's Hospital Boston, Harvard Medical School, 
Boston, Massachusetts, USA.

Age-related macular degeneration (AMD), the most common cause of blindness in the
elderly, is characterized by degeneration of the macula and can lead to loss of
fine color vision. Alterations in inflammatory and immune system pathways, which 
arise from genetic differences, predispose individuals to AMD. Yet the mechanism 
of disease progression with respect to inflammation is not fully understood. In
this issue of the JCI, the study by Combadière and colleagues shows that CX3C
chemokine receptor 1-deficient (CX3CR1-deficient) mice have abnormal microglia
that accumulate beneath the retina and contribute to the progression of AMD.

Publication Types: 
    Comment
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17909623 [PubMed - indexed for MEDLINE]

636: Acta Ophthalmol. 2008 Jun;86(4):456-8. Epub 2007 Oct 1.

Resolution of macular oedema in occult choroidal neovascularization under oral
Sorafenib treatment.

Kernt M, Staehler M, Stief C, Kampik A, Neubauer AS.

Department of Ophthalmology, Ludwig-Maximilians University, Munich, Germany.

PURPOSE: To report on the effect of oral nexavar (Sorafenib) treatment in one
patient with neovascular age-related macular degeneration (AMD) and advanced
renal cell cancer (RCC). METHODS: After two intravitreal injections of
bevacizumab (1.25 mg) for occult choroidal neovascularization (CNV) in AMD, the
patient was started on oral Sorafenib (400 mg twice daily) treatment for RCC.
RESULTS: Visual acuity (VA) was 20/80 in the left eye and optical coherence
tomography (OCT) demonstrated persistent central thickening to 251 microm after
bevacizumab. After 6 weeks of oral Sorafenib treatment, VA had increased to 20/70
and a significant decrease in retinal thickness to 208 microm was observed on
OCT. The patient remained stable during a further 3 months of follow-up.
CONCLUSIONS: Resolution of macular oedema and stabilization of VA under oral
treatment with the multikinase inhibitor Sorafenib was observed. This observation
warrants further investigation.

Publication Types: 
    Case Reports

PMID: 17908257 [PubMed - indexed for MEDLINE]

637: Vision Res. 2007 Nov;47(24):3120-3. Epub 2007 Sep 27.

HTRA1 variant increases risk to neovascular age-related macular degeneration in
Chinese population.

Lu F, Hu J, Zhao P, Lin Y, Yang Y, Liu X, Fan Y, Chen B, Liao S, Du Q, Lei C,
Cameron DJ, Zhang K, Yang Z.

Human Molecular Biology & Genetics, Sichuan Academy of Medical Sciences & Sichuan
Provincial People's Hospital, Sichuan 610072, China.

Age-related macular degeneration (AMD) is a leading cause of irreversible visual 
impairment in the world. Advanced AMD can be divided into wet AMD (choroidal
neovascularization) and dry AMD (geographic atrophy, GA). Drusen is characterized
by deposits in the macula without visual loss and is an early AMD sign in the
Caucasian population. rs11200638 in the promoter of HTRA1 has recently been shown
to increases the risk for wet AMD in both Caucasian and Hong Kong Chinese
populations. In order to replicate these results in a different cohort, we
genotyped rs11200638 for 164 Chinese patients (90 wet AMD and 74 drusen) and 106 
normal controls in a Han Mainland Chinese cohort. The genotypes were compared
using chi square analysis for an additive allelic model. rs11200638 was
significantly associated with wet AMD (p=5.00x10(-12)). Unlike in the Caucasian
population, the risk allele of rs11200638 was not associated with drusen in our
Chinese population. These findings confirm the association of HTRA1 with wet AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17904186 [PubMed - indexed for MEDLINE]

638: Graefes Arch Clin Exp Ophthalmol. 2007 Dec;245(12):1877-80. Epub 2007 Sep
28.

Ranibizumab for retinal angiomatous proliferation in neovascular age-related
macular degeneration.

Lai TY, Chan WM, Liu DT, Lam DS.

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong
Kong, Hong Kong Eye Hospital, 147K Argyle Street, Hong Kong, SAR, People's
Republic of China. tyylai@cuhk.edu.hk

BACKGROUND: To report the efficacy of intravitreal injection of ranibizumab
(Lucentis) in the treatment of retinal angiomatous proliferation (RAP) in
neovascular age-related macular degeneration (AMD). METHODS: Case review of four 
consecutive patients who received 3 injections at monthly intervals of
intravitreal ranibizumab injections for RAP. The serial changes in best-corrected
visual acuity (BCVA), optical coherence tomography (OCT), fluorescein angiography
(FA), and indocyanine green angiography (ICGA) are presented. RESULTS: The
baseline mean logMAR BCVA was 0.89 (Snellen equivalent of 20/155). After three
injections of ranibizumab, all four patients had visual improvement and the mean 
logMAR BCVA improved to 0.59 (Snellen equivalent of 20/78). The mean visual
improvement was 3.0 lines. All patients also had complete resolution of
subretinal fluid after treatment, and the mean OCT central foveal thickness
reduced from 438 microm at baseline to 169 microm at 3 months. Follow-up FA and
ICGA at 3 months showed absence of leakage in three patients with minimal leakage
in the remaining patient. One patient had recurrence of RAP at 8 months after
commencement of treatment, and repeat ranibizumab injection resulted in
resolution of the subretinal fluid and pigment epithelial detachment and visual
improvement. CONCLUSIONS: Intravitreal ranibizumab injections appeared to be an
effective treatment for RAP, resulting in visual gain and reduction in macular
thickness. Further long-term studies to evaluate the efficacy of intravitreal
ranibizumab in RAP are warranted.

Publication Types: 
    Case Reports

PMID: 17901972 [PubMed - indexed for MEDLINE]

639: Compr Ther. 2006 Winter;32(4):267-70.

Is transpupillary thermotherapy applicable to the treatment of age-related
macular degeneration with pigment epithelial detachment?

Honda M, Mizota A, Sakuma T, Tanaka M.

Department of Ophthalmology, Juntendo University, Urayasu Hospital, 2-1-1
Tomioka, Urayasu, 279-0021, Japan.

The cause of pigment epithelial tears at the edge of a pigment epithelial
detachment (PED) following transpupillary thermotherapy (TTT) in eyes with a PED 
associated with age-related macular degeneration has not been conclusively
determined. We have treated two eyes that had a PED with TTT. A pigment
epithelial tear developed in one eye but not in the other. Our findings suggest
that pigment epithelial tears are probably related to the shape of the PED, and
TTT should not be applied to a balloon-shaped PED.

Publication Types: 
    Case Reports

PMID: 17898434 [PubMed - indexed for MEDLINE]

640: Invest Ophthalmol Vis Sci. 2007 Oct;48(10):4838-45.

Computer-based test to measure optimal visual acuity in age-related macular
degeneration.

González EG, Tarita-Nistor L, Markowitz SN, Steinbach MJ.

Vision Science Research Program, Toronto Western Hospital, Toronto, Ontario,
Canada. gonzalez@yorku.ca

PURPOSE: The authors present a computer-based method for evaluating the visual
acuity of patients with age-related macular degeneration (AMD). It incorporates
four features known to improve visual acuity: high contrast, white optotypes on a
black background to reduce intraocular scatter, proportional layout to reduce the
effects of crowding, and multiple optotypes to minimize the effects of fixation
instability and to maximize the likelihood of optotype detection. METHODS:
Experiment 1 evaluated the best-eye acuity of 24 patients with AMD using the
ETDRS chart and three versions of the Tumbling E acuity test: multiple black
optotypes on a white background, single white optotype on a black background, and
multiple white optotypes on a black background. Experiment 2 compared the two
White E optotype tests with the ETDRS in patients with AMD, and Experiment 3
measured probability summation in persons with normal vision. RESULTS: Multiple
white optotypes on a black background yielded the highest acuity estimates and
the ETDRS the lowest. The Single E test yielded a lower estimate of acuity than
the two Multiple E tests. The effect of polarity-white on black was better than
black on white-was consistent with results found in persons with healthy retinas.
For patients with AMD, acuity measured with the Multiple E test was independent
of that measured with the ETDRS, but acuity measured with the Single E test
decreased as acuity worsened. For the participants with normal vision, the
differences between the Multiple and Single E tests were within the known limits 
of test-retest variability. CONCLUSIONS: The multiple-optotype, reversed-polarity
test provides a measure of the optimal visual acuity of which a person is capable
and, in this sense, may be a useful tool for assessing rehabilitation progress.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17898311 [PubMed - indexed for MEDLINE]

641: Invest Ophthalmol Vis Sci. 2007 Oct;48(10):4811-7.

Temporal response properties of the macular cone system: effect of normal aging
and age-related maculopathy.

Falsini B, Ziccardi L, Stifano G, Iarossi G, Merendino E, Minnella AM, Fadda A,
Balestrazzi E.

Institute of Ophthalmology, Catholic University, Rome, Italy. md0571@mckink.it

PURPOSE: To evaluate the influence of aging and age-related maculopathy (ARM) on 
the temporal frequency response function (TFR) of macular focal
electroretinography. METHODS: Macular (18 degrees ) focal electroretinograms
(FERGs) in response to sinusoidal flicker, modulated at TFs between 3.7 and 52
Hz, were recorded from 13 young (age range, 14-29 years) and 9 old (age range,
55-80 years) healthy subjects and from 18 patients with ARM (stage 2 disease; age
range, 55-80 years; visual acuity >/=0.4). Amplitude and phase of the
Fourier-analyzed response fundamental (1F) and seconnd harmonic (2F) were
measured. RESULTS: In young healthy subjects, mean 1F TFR showed a maximum
amplitude at 41 Hz, a secondary peak at 3.7 Hz, a minimum at 8 Hz, and a high TF 
(32-52 Hz) roll-off. Mean 1F TFR of old, compared with young, healthy subjects
showed amplitude enhancement at 10 to 14 Hz and a small loss at high TF. Mean 2F 
TFR of young and old healthy subjects had a maximum at 5.7 to 8 Hz and an
attenuation beyond 10 Hz. Mean 1F and 2F TFRs of ARM patients were similar to
those of old healthy subjects but were depressed in mean amplitude. FERG TFR
changes of old healthy subjects and ARM patients were not mimicked by reducing
stimulus retinal illuminance or modulation depth in young healthy subjects.
CONCLUSIONS: FERG temporal properties are affected by normal aging and ARM.
Because FERG TFR is shaped mainly by postreceptoral activity, the findings
suggest that photoreceptor and postsynaptic dysfunction underlie aging- and
ARM-related FERG changes.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17898308 [PubMed - indexed for MEDLINE]

642: Invest Ophthalmol Vis Sci. 2007 Oct;48(10):4694-705.

Chloride channel activity of bestrophin mutants associated with mild or
late-onset macular degeneration.

Yu K, Qu Z, Cui Y, Hartzell HC.

Department of Cell Biology and The Center for Neurodegenerative Disease, Emory
University School of Medicine, Atlanta, Georgia 30322, USA.

PURPOSE: Mutations in the hBest1 (VMD2) gene are linked to various kinds of
macular degeneration, including Best vitelliform macular dystrophy (BVMD) and
adult-onset vitelliform macular dystrophy (AVMD). The age at onset and severity
of disease are quite variable. This study was conducted to examine Cl(-) currents
generated by six hBest1 mutations (E119Q, A146K, T216I, DeltaI295, D312N, and
L567F) found in patients having adult-onset macular dystrophies or in BVMD
patients having normal electro-oculograms (EOGs), to examine the hypothesis that 
the severity of disease is related to the effect of the hBest1 mutation on hBest1
Cl(-) channel function. METHODS: Wild-type (WT) hBest1 was mutated by PCR-based
mutagenesis. WT and mutant channels were expressed in HEK293 cells and Cl(-)
currents analyzed by whole-cell patch clamp. The trafficking of proteins to the
plasma membrane was tested by cell-surface biotinylation. RESULTS: All the
mutations except L567F and T216I produced a defect in Cl(-) channel function. The
D312N and DeltaI295 mutants do not generate functional Cl(-) currents.
Furthermore, they inhibit WT hBest1 function. The amplitudes of currents produced
by the A146K mutant were smaller than WT and had altered anionic selectivity. The
E119Q mutant produced currents similar in amplitude to those of WT, but had
altered relative permeability to large anions. CONCLUSIONS: These findings
support the idea that hBest1 mutations produce variable forms of macular
dystrophy via dysfunction of hBest1 Cl(-) channels. However, because the light
peak of the EOG of some patients with the DeltaI295, D312N, E119Q, and A243V
mutations does not correlate with the Cl(-) channel function, the results also
support the suggestion that the light peak of the EOG may not be generated solely
by hBest1.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 17898294 [PubMed - indexed for MEDLINE]

643: Invest Ophthalmol Vis Sci. 2007 Oct;48(10):4407-20.

SOD2 knockdown mouse model of early AMD.

Justilien V, Pang JJ, Renganathan K, Zhan X, Crabb JW, Kim SR, Sparrow JR,
Hauswirth WW, Lewin AS.

Department of Molecular Genetics, University of Florida, Gainesville, Florida,
USA.

PURPOSE: To test the hypothesis that oxidative injury to the retinal pigment
epithelium (RPE) may lead to retinal damage similar to that associated with the
early stages of age-related macular degeneration (AMD). METHODS: A ribozyme that 
targets the protective enzyme manganese superoxide dismutase (MnSOD) was
expressed in RPE-J cells, and adeno-associated virus (AAV) expressing the
ribozyme gene was injected beneath the retinas of adult C57BL/6 mice. The
RPE/choroid complex was examined for SOD2 protein levels and protein markers of
oxidative damage using immunoblot analysis and LC MS/MS-identification of
proteins and nitration sites. Lipids were extracted from retinal tissue and
analyzed for the bis-retinoid compounds A2E and iso-A2E. The mice were analyzed
by full-field electroretinography (ERG) for light response. Light and electron
microscopy were used to measure cytological changes in the retinas. RESULTS: The 
treatment of RPE-J cells with Rz432 resulted in decreased MnSOD mRNA and protein 
as well as increased levels of superoxide anion and apoptotic cell death. When
delivered by AAV, Rz432 reduced MnSOD protein and increased markers of oxidative 
damage, including nitrated and carboxyethylpyrrole-modified proteins in the
RPE-choroid of mice. Ribozyme delivery caused a progressive loss of
electroretinograph response, vacuolization, degeneration of the RPE, thickening
of Bruch's membrane, and shortening and disorganization of the photoreceptor
outer and inner segments. Progressive thinning of the photoreceptor outer nuclear
layer resulted from apoptotic cell death. Similar to the eyes of patients with
AMD, ribozyme-treated eyes exhibited increased autofluorescence and elevated
levels of A2E and iso-A2E, major bis-retinoid pigments of lipofuscin.
CONCLUSIONS: These results support the hypothesis that oxidative damage to the
RPE may play a role in some of the key features of AMD.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17898259 [PubMed - indexed for MEDLINE]

644: Ophthalmic Epidemiol. 2007 Jul-Aug;14(4):184-7.

Overview of progress in the epidemiology of age-related macular degeneration.

Klein R.

Department of Ophthalmology and Visual Sciences, University of Wisconsin,
Madison, Wisconsin, USA. kleinr@epi.ophth.wisc.edu

PURPOSE: To provide an over-view of progress in the epidemiology of age-related
macular degeneration. METHODS: Review of epidemiological and clinical trial
findings regarding AMD since initial National Eye Institute sponsored
epidemiology meeting in 1982. RESULTS: A growing number new epidemiological
studies have provided data on the prevalence and long-term incidence of AMD.
Despite a similar prevalence of early AMD in whites, blacks, and hispanics,
whites have higher prevalence of late AMD. An age-period cohort effect has been
shown in the Beaver Dam Eye Study suggesting that AMD incidence may be declining 
among younger birth cohorts. Genetic factors such as complement factor H have
been shown to be strongly associated with AMD. Smoking is strongly related to
risk of AMD. Randomized controlled clinical trials have shown the benefits of
zinc-antioxidant supplementation in preventing visual loss in persons with signs 
of early AMD and anti-vascular endothelial growth factor agents in restoring
vision in eyes with neovascular AMD. CONCLUSIONS: Despite remarkable progress in 
understanding AMD, many questions remain that can only be addressed by
continuation of longitudinal population-based studies.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Review

PMID: 17896295 [PubMed - indexed for MEDLINE]

645: J Neuroophthalmol. 2007 Sep;27(3):180-3.

Optic disc edema, cystoid macular edema, and elevated vascular endothelial growth
factor in a patient with POEMS syndrome.

Chong DY, Comer GM, Trobe JD.

Department of Ophthalmology, W. K. Kellogg Eye Center, University of Michigan,
1000 Wall Street, Ann Arbor, MI 48105, USA.

A 48-year-old man with polyneuropathy, organomegaly, endocrinopathy, monoclonal
gammopathy, and skin changes (POEMS) syndrome had bilateral optic disc edema
(ODE), bilateral cystoid macular edema (CME), anasarca, and elevated serum
vascular endothelial growth factor (VEGF). This is the first reported example of 
ophthalmoscopic, angiographic, and optical coherence tomographic evidence of the 
combination of ODE and CME in this syndrome. This combination of features
suggests that the ODE in this condition may be due to increased vascular
permeability.

Publication Types: 
    Case Reports

PMID: 17895817 [PubMed - indexed for MEDLINE]

646: Clin Experiment Ophthalmol. 2007 Sep-Oct;35(7):640-4.

Subthreshold micropulse diode laser photocoagulation for clinically significant
diabetic macular oedema: a three-year follow up.

Sivaprasad S, Sandhu R, Tandon A, Sayed-Ahmed K, McHugh DA.

Kings College Hospital, Denmark Hill, London, UK.

PURPOSE: To report the long-term visual outcome of subthreshold micropulse diode 
laser photocoagulation for clinically significant diffuse diabetic macular oedema
(CSME). DESIGN: Non-comparative case-series. METHODS: The main outcome measures
of this 3-year follow-up study of infrared (810 nm) subthreshold diode micropulse
laser photocoagulation for CSME were visual outcome and the angiographic CSME
status of 19 patients (25 eyes). RESULTS: Visual acuity stabilized or improved in
84% of treated eyes by the end of the first year. The result was maintained in
the second year and by the third year, 92% maintained vision. However, more
patients needed supplementary grid laser in the third year than in the second
year. CSME decreased in 92% of the eyes and resolved in 88% in the first year. By
the second year, 92% showed complete resolution. However, in the third year,
recurrent CSME was noted in 28% of patients. CONCLUSION: This study has the
longest follow up reported so far and demonstrating that subthreshold micropulse 
diode laser photocoagulation has a beneficial long-term effect on visual acuity
and resolution of CSME with minimal chorio-retinal damage.

PMID: 17894684 [PubMed - indexed for MEDLINE]

647: Am J Ophthalmol. 2007 Oct;144(4):627-37.

Anti-VEGF agents in the treatment of neovascular age-related macular
degeneration: applying clinical trial results to the treatment of everyday
patients.

Brown DM, Regillo CD.

Vitreoretinal Consultants, Houston, Texas 77030, USA. dmbmd@houstonretina.com

PURPOSE: The vision gains reported with monthly intravitreal ranibizumab in the
MARINA and ANCHOR trials led to an immediate paradigm shift in the treatment of
neovascular AMD with retina physicians universally switching to the pan-VEGF
blocking agents ranibizumab and bevacizumab, and patients expecting visual
improvement. As these agents are primarily used on a pro re nata (PRN) dosing
schedule (because neither patients nor physicians want monthly injections), the
factors involved in making the treatment and retreatment decisions are very
important in any attempt to maximize vision gain. DESIGN: Analysis of literature,
ongoing clinical trials, and the clinical assessments that can aid clinicians in 
treatment and retreatment decisions. METHODS: Literature review and perspective. 
RESULTS: If a monthly injection protocol is not used, clinicians should use both 
functional and anatomic criteria to attempt to guide treatment and retreatment
decisions. Qualitative optical coherence tomography (OCT) appears to be the most 
sensitive and practical assessment tool to determine anatomic response to
treatment but should be used in conjunction with clinical examination.
CONCLUSIONS: If monthly intravitreal injections are not performed, a combination 
of clinical examination (looking for new hemorrhage) and qualitative OCT (to
assess response to treatment and early signs of recurrent leakage) can be used to
guide anti-vascular endothelial growth factor (anti-VEGF), treatments with the
goal of maintaining a "normal" retinal anatomy in an attempt to maximize the
benefit (visual acuity gains) to risk (number of injections required) ratio.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17893015 [PubMed - indexed for MEDLINE]

648: Vision Res. 2008 Feb;48(3):360-5. Epub 2007 Sep 24.

Maculas, monkeys, models, AMD and aging.

Dawson WW, Dawson JC, Lake KP, Gonzalez-Martinez J.

Department of Ophthalmology, University of Florida, 1600 SW Archer Road, Rm:
M119, Gainesville, FL 32610-0284, USA. wdawson@eye.ufl.edu

Age related macular degeneration (AMD) signs may be found reliably in monkeys
(Macaca mulatta) bred selectively in Florida after 14 generations of inbreeding
in a closed colony at the University of Puerto Rico. Progression, ultrastructure 
and functional losses are parallel to those found in humans.

PMID: 17892891 [PubMed - indexed for MEDLINE]

649: Eye. 2008 Jan;22(1):82-6. Epub 2007 Sep 21.

Intravitreal bevacizumab in the treatment of neovascular age-related macular
degeneration, 6- and 9-month results.

Cleary CA, Jungkim S, Ravikumar K, Kelliher C, Acheson RW, Hickey-Dwyer M.

Department of Ophthalmology, Mater Misericordiae Hospital, Dublin, Ireland.
ucclearly@mac.com

PURPOSE: To evaluate 6- and 9-month follow-up data including the effect on vision
and anatomic outcome in patients treated with intravitreal bevacizumab for
neovascular age-related macular degeneration (AMD). STUDY DESIGN: Interventional 
consecutive retrospective case series. Patients received intravitreal bevacizumab
for the treatment of neovascular AMD including choroidal neovascular membranes,
pigment epithelial detachment, and macular haemorrhage. Ophthalmic evaluation
included log MAR or Snellen acuity, ophthalmic examination, optical coherence
tomography, and fluorescein angiography. Repeat injections were given in the
presence of persistent leakage or retinal oedema. Change in vision and foveal
thickness from baseline was evaluated using the paired Student's t-test. RESULTS:
A total of 112 eyes of 111 patients received injections. Median follow-up was 5
months (range: 1-12 months). Mean log MAR vision pre-injection was 0.84+/-0.03
(n=112); at 3 months was 0.69+/-0.05 (P<0.0001, n=84); at 6 months was
0.74+/-0.06 (P<0.05, n=51); and at 9 months was 0.69+/-0.08 (n=29, P=0.09).
Thirteen of 17 patients who received only one injection maintained improved or
stable vision at 6 months. Mean baseline foveal thickness was 291+/- 9.72 microm 
(n=56); at 3 months was 282.7+/-28 (P<0.05, n=31); and at 6 months was
249.7+/-10.3 (P<0.05, n=12). One case of endophthalmitis, three submacular
haemorrhages, and three retinal pigment epithelial (RPE) tears occurred.
CONCLUSION: Intravitreal bevacizumab is an effective treatment for neovascular
AMD, resulting in improved vision and foveal anatomy at 6 months and even up to 9
months. This treatment is well tolerated in the majority of patients but adverse 
events may include endophthalmitis, RPE tears, and submacular haemorrhage.

Publication Types: 
    Case Reports
    Evaluation Studies

PMID: 17891059 [PubMed - indexed for MEDLINE]

650: Retina. 2007 Sep;27(7):903-7.

Intravitreal bevacizumab treatment for radiation macular edema after plaque
radiotherapy for choroidal melanoma.

Mason JO 3rd, Albert MA Jr, Persaud TO, Vail RS.

Retina Consultants of Alabama, Callahan Eye Foundation Hospital, Birmingham,
Alabama 35233, USA.

PURPOSE: To evaluate the effect of intravitreal bevacizumab treatment on patients
with macular edema (ME) due to radiation retinopathy after plaque radiotherapy
for choroidal melanoma. METHODS: In this retrospective case series, 10
consecutive patients with ME due to radiation retinopathy after plaque
radiotherapy for choroidal melanoma were treated with a single intravitreal
injection of bevacizumab. Postinjection best-corrected visual acuity (BCVA) and
mean foveal thickness measured by ocular coherence tomography were the primary
outcome measures. RESULTS: The mean BCVA at the time of the diagnosis of
choroidal melanoma was 20/25 (range, 20/20 to 20/40). The mean radiation dose to 
the foveola was 4,323 cGy (range, 1,908-7,975 cGy). Radiation ME developed at a
mean of 26 months (range, 17-44 months) after plaque radiotherapy. Choroidal
melanoma regressed in all patients, and there were no neovascular sequelae. At
the time of radiation ME diagnosis, the mean BCVA was 20/100 (range, 20/40 to
20/200). After bevacizumab injection, the mean BCVA was 20/86 at 6 weeks and
20/95 at 4 months. Mean foveal thickness measured by ocular coherence tomography 
was 482 microm before injection, 284 microm 6 weeks after injection, and 449 mum 
4 months after injection. CONCLUSIONS: Intravitreal bevacizumab injection
decreases mean foveal thickness while only modestly improving BCVA on a
short-term basis in patients with radiation-induced ME.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17891015 [PubMed - indexed for MEDLINE]

651: Retina. 2007 Sep;27(7):891-6.

Intravitreal bevacizumab combined with photodynamic therapy for the treatment of 
occult choroidal neovascularization associated with serous pigment epithelium
detachment in age-related macular degeneration.

Ladas ID, Kotsolis AI, Papakostas TD, Rouvas AA, Karagiannis DA, Vergados I.

1st Department of Ophthalmology, Medical School of Athens University, Greece.

PURPOSE: To evaluate the efficacy of intravitreal injection of bevacizumab
combined with photodynamic therapy (PDT) for the treatment of occult choroidal
neovascularization (CNV) associated with serous pigment epithelium detachment
(s-PED) due to age-related macular degeneration (AMD). METHODS: In this
retrospective study, six patients (six eyes) with subfoveal occult CNV associated
with s-PED due to AMD were treated with intravitreal bevacizumab combined with
PDT. All patients were treated at baseline with PDT followed by intravitreal
bevacizumab 1.25 mg 1 hour later. Afterwards, according to the findings of
optical coherence tomography and fluorescein angiography, repeat bevacizumab
injections were given, if necessary, monthly for three doses followed by further 
doses every 3 months. PDT was repeated every 3 months according to the same
criteria. Follow-up time was 9 months. RESULTS: All patients completed their
treatment during the first 3 months from baseline. Best-corrected visual acuity
(BCVA) improved or remained stable related to the baseline values in all patients
at the end of the follow-up time. Mean BCVA improved from 20/67 to 20/42. S-PED
and subretinal fluid decreased or disappeared. The mean central 1-mm retinal
thickness was reduced from baseline value for the 9-month follow-up period by 128
microm. CONCLUSION: Intravitreal bevacizumab combined with PDT seems to be a
promising treatment with good functional and anatomical results for occult CNV
associated with s-PED due to AMD.

PMID: 17891013 [PubMed - indexed for MEDLINE]

652: Retina. 2007 Sep;27(7):879-90.

Macular function in eyes with early age-related macular degeneration with or
without contralateral late age-related macular degeneration.

Parisi V, Perillo L, Tedeschi M, Scassa C, Gallinaro G, Capaldo N, Varano M.

Fondazione per l'Oftalmologia G B Bietti-IRCCS, Rome, Italy. vparisi@tin.it

PURPOSE: To evaluate psychophysical and electrophysiologic responses in eyes with
early age-related macular degeneration (AMD) without a decrease in visual acuity 
and with or without late AMD in the fellow eye. METHODS: Fifteen patients (mean
age: 67.9 +/- 7.20 years) with early AMD in both eyes (AMD1 group, 15 eyes) and
15 patients (mean age: 71.40 +/- 7.06 years) with early AMD in one eye and late
AMD in the fellow eye (AMD2 group, 15 eyes) were enrolled. They were compared to 
15 age-similar normal control subjects. LogMAR visual acuity (VA), macular
sensitivity by MP-1 microperimetry, and multifocal electroretinograms (mfERG)
were assessed in control, AMD1, and AMD2 eyes. mfERG response amplitude density
(RAD, nV/deg2) of the N1-P1 component of first order binary kernels was measured.
RESULTS: When compared to controls, AMD1 and AMD2 eyes showed a significant
(analysis of variance, P < 0.01) decrease in MP-1 microperimetry assessed in the 
0-2.5 and 2.5-5 degrees of the macula, significantly correlated (Pearson test, P 
< 0.01) to the corresponding significant decrease (P < 0.01) in mfERG N1-P1 RADs 
assessed in the 0-2.5 and 2.5-5 degrees. In AMD1 and AMD2 eyes, VA and mfERG
N1-P1 RADs assessed in the 5-20 degrees were similar (P > 0.01) to controls. VA, 
MP-1, and mfERG values were not significantly different in AMD1 and AMD2 eyes.
CONCLUSION: In eyes with early AMD there is a dysfunction of preganglionic
elements in the central 0-5 retinal degrees detectable by mfERG or MP-1
microperimetry. This impairment is not further influenced by the presence of late
AMD in the fellow eye.

PMID: 17891012 [PubMed - indexed for MEDLINE]

653: Retina. 2007 Sep;27(7):873-8.

The significance of early detection of age-related macular degeneration: Richard 
& Hinda Rosenthal Foundation lecture, The Macula Society 29th annual meeting.

Loewenstein A; Richard & Hinda Rosenthal Foundation.

Department of Ophthalmology, Tel Aviv Sourasky Medical Center, Faculty of
Medicine, Tel Aviv University, Israel. anatlow@tasmc.health.gov.il

BACKGROUND: The main cause for visual loss in age-related macular degeneration
(AMD) is the development of choroidal neovascularization (CNV), which has been
shown to occur in 18% of patients over 5 years. Even though satisfactory
treatments for CNV are available, in the majority of cases no improvement in
visual acuity occurs and in those it does it is mostly limited. Early detection
has the potential of significantly improving the final visual outcome of patients
who develop subfoveal CNV. METHODS: This review is a summary of the importance of
early detection in the management of AMD, in view of the current available
treatment methods. It is a review of the results of early detection of AMD using 
the Preferential Hyperacuity Perimeter (PHP). RESULTS: Awareness for symptoms,
use of the Amsler grid and monitoring by an ophthalmologist are not satisfactory 
means for early detection of AMD. The PHP has good sensitivity and specificity in
detecting CNV patient early and differentiate them from intermediate AMD.
CONCLUSION: In an era of excellent treatments available for CNV treatment, early 
detection of CNV by novel technology modalities such as the PHP at a frequency
that allows early detection (approximately 4 times a year) is crucial in the
armamentarium of AMD patient management.

Publication Types: 
    Review

PMID: 17891011 [PubMed - indexed for MEDLINE]

654: Retina. 2007 Sep;27(7):864-72.

Multifocal electroretinography in patients with exudative amd and intravitreal
treatment with pegaptanib sodium.

Lipski A, Bornfeld N, Jurklies B.

Department of Ophthalmology, University Hospital Essen, Germany.
andreas.lipski@uni-duisburg-essen.de

BACKGROUND: To objectively investigate central retinal function in patients with 
choroidal neovascularization (CNV) due to age-related macular degeneration (AMD) 
before and after treatment with pegaptanib sodium (PS). METHODS: Patients with
CNV due to exudative AMD received intravitreal injections of 0.3 mg PS every
sixth week if angiographic activity was evident. Longitudinal observation
included recordings with multifocal electroretinography (mfERG) before the first 
treatment and before each injection at follow-up intervals. RESULTS: During the
observation period of 30.5 +/- 8 weeks (mean +/- SD) a mean number of 5.3 +/- 1.3
injections were applied. Final mean log(MAR) visual acuity decreased,
statistically nonsignificant, from 0.67 +/- 0.3 at baseline to 0.74 +/- 0.16.
mfERG recordings in 12 patients after 25 +/- 9 weeks evinced a decrease in
response density which was statistically significant in the central 5 degrees .
Mean P1-amplitudes of ring 1, 2, and 3 were reduced by 66%, 39% and 30%,
respectively. During follow-up, implicit times of the P1 components remained
stable within 4% of baseline. In three of four patients with vision loss of 2
lines or more, P1-response amplitudes decreased substantially at least 6 weeks
prior vision loss. CONCLUSION: Treatment with PS resulted in a decrease of
central retinal function more obvious in mfERG than in VA longitudinal testing.
Good correlations were seen between changes in mean vision and changes in mfERG
response density components. As a decline in P1-response amplitudes anteceded
vision loss in this study, our results indicate a possible role of mfERG to
predict vision loss during intravitreal pharmacotherapy.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17891010 [PubMed - indexed for MEDLINE]

655: Retina. 2007 Sep;27(7):857-63.

RPE tears after pegaptanib treatment in age-related macular degeneration.

Chang LK, Flaxel CJ, Lauer AK, Sarraf D.

Jules Stein Eye Institute, Department of Ophthalmology, University of California,
Los Angeles 90095, USA.

PURPOSE: To describe retinal pigment epithelial (RPE) tears in patients with
age-related macular degeneration (AMD) status post pegaptanib (Macugen)
injection. METHODS: Six eyes from six patients who developed RPE tears while
undergoing treatment with pegaptanib for AMD-related fibrovascular pigment
epithelial detachment (PED) and occult choroidal neovascularization (CNV) were
identified retrospectively. Diagnosis of pre-pegaptanib fibrovascular PED and
post-pegaptanib RPE tears were made by clinical examination, fluorescein
angiography (FA), and optical coherence tomography (OCT) imaging of the macula.
RESULTS: Four patients developed an RPE tear within 8 weeks after the first
pegaptanib injection, while RPE tears were found in two patients following a
second injection. Only one of the patients reported acute vision loss, although
three of six eyes had a decrease in objective visual acuity in the affected eye
to the count fingers level. All six cases displayed the classic clinical and
angiographic appearance of RPE tears. In addition, OCT imaging showed an
irregular, hyperreflective RPE layer with a focal defect. CONCLUSIONS: RPE tears 
are known to occur in the setting of PED spontaneously or after laser treatment, 
but have only recently been described in association with intravitreal
pegaptanib. OCT imaging of eyes status post pegaptanib therapy may be helpful in 
identifying this complication. Patients with AMD, especially those with occult
CNV and fibrovascular PED, receiving pegaptanib therapy should be monitored for
RPE tears, which may warrant deferral of further injections.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 17891009 [PubMed - indexed for MEDLINE]

656: Retina. 2007 Sep;27(7):851-6.

Treatment of naïve lesions in neovascular age-related macular degeneration with
pegaptanib.

Quiram PA, Hassan TS, Williams GA.

Associated Retinal Consultants, Beaumont Hospital, Royal Oak, Michigan 48073,
USA. pollyquiram@yahoo.com

PURPOSE: To evaluate the safety and efficacy of pegaptanib sodium injection
(Macugen, OSI Eyetech Pharmaceuticals) as primary therapy for previously
untreated choroidal neovascular membranes (CNV) associated with wet age-related
macular degeneration (AMD). METHODS: The authors retrospectively reviewed data of
90 patients with newly diagnosed wet AMD in which pegaptanib was used as primary 
therapy. Inclusion criteria included CNV of any angiographic subtype and size.
Exclusion criteria included any lesion previously treated with photodynamic
therapy (PDT), intravitreal triamcinolone, or thermal laser. Outcome measures
included pre and post-treatment changes in best-corrected visual acuity, lesion
size, lesion angiographic characteristics, and optical coherence tomography (OCT)
measurements. Patients were injected every 6 weeks and fluorescein angiography
(FA) and OCT imaging were performed after every three injections. Safety
assessment was performed by complete ophthalmologic examination pre- and
post-injection. RESULTS: Of the patients undergoing primary treatment with
pegaptanib, the lesion characteristics were 80% (72/90) occult, 13% (12/90)
minimally classic, and 7% (6/90) predominantly classic. Lesion sizes were 50%
(45/90) <or=4 disc areas (DA) and 50% (45/90) >4 DA. The mean follow-up was 9.1
+/- 2 months (range 6-14 months). Gain of >or=3 lines of vision occurred in 20%
(18/90) of patients, stabilization of vision (prevention of three lines of vision
loss) occurred in 70% (63/90) of patients, and loss of >or=3 lines of vision
occurred in 10% (9/90) of patients, resulting in a 90% response rate. In the
patients who gained >or=3 lines of vision, the average number of injections was
3.5. One case of endophthalmitis was recognized. CONCLUSIONS: Pegaptanib as
primary therapy for naïve CNV lesions offers a 90% rate of improvement or
stabilization of vision-outcomes that exceed those reported in the VISION trial.

PMID: 17891008 [PubMed - indexed for MEDLINE]

657: Retina. 2007 Sep;27(7):846-50.

Comment in:
    Retina. 2008 Jun;28(6):911-2; author reply 912.

Ranibizumab for treatment of choroidal neovascularization secondary to
age-related macular degeneration.

Bhatnagar P, Spaide RF, Takahashi BS, Peragallo JH, Freund KB, Klancnik JM Jr,
Cooney MJ, Slakter JS, Sorenson JA, Yannuzzi LA.

Vitreous-Retina-Macula Consultants of New York, New York, USA.

PURPOSE: To evaluate the short-term outcomes after intravitreal ranibizumab
(Lucentis; Genentech, Inc., South San Francisco, CA) injection in patients with
neovascular age-related macular degeneration. METHODS: A review of data for
consecutive patients who received intravitreal ranibizumab injection was
conducted. The main outcome measures were mean visual acuity and central macular 
thickness at 3 months compared with those at baseline. Response to ranibizumab
therapy was evaluated with particular attention to prior treatment with
bevacizumab (Avastin; Genentech, Inc.). RESULTS: Mean baseline visual acuity of
231 eyes of 231 patients was 20/152, and 189 patients (81.8%) had undergone prior
treatment, with 153 (65.4%) having received intravitreal bevacizumab. Mean visual
acuity at 3 months, available for 203 patients (88%), was 20/126 (P = 0.004).
Mean visual acuity for 98 patients treated with bevacizumab within 3 months
before ranibizumab injection was 20/100 at baseline and 20/98 at 3 months (P =
0.35). Mean baseline central macular thickness was 278 microm for all patients
and improved to 211 microm at 3 months (P < 0.001). Macular thickness decrease
was noted irrespective of previous bevacizumab therapy. CONCLUSION: Ranibizumab
therapy was associated with significant improvements in mean visual acuity and
central macular thickness for the group of all patients. Patients who had
received bevacizumab treatment within 3 months before initiating ranibizumab
treatment had stability of, but no improvement in, visual acuity.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17891007 [PubMed - indexed for MEDLINE]

658: Retina. 2007 Sep;27(7):825-31.

Selective photodynamic therapy for neovascular age-related macular degeneration
with polypoidal choroidal neovascularization.

Eandi CM, Ober MD, Freund KB, Slakter JS, Yannuzzi LA.

The LuEsther T. Mertz Retina Research Center of Manhattan Eye, Ear and Throat
Hospital, New York, New York 10021, USA.

PURPOSE: To evaluate the efficacy of selective treatment with indocyanine green
(ICG) angiography-guided photodynamic therapy (PDT) with verteporfin for
polypoidal choroidal vasculopathy (PCV). METHODS: In this retrospective
consecutive series, 30 eyes of 30 patients with PCV were included. Complete
ocular examination, digital fluorescein angiography (FA), ICG angiography, and
optical coherence tomography were performed at baseline and at standard intervals
thereafter. ICG angiography-guided PDT was performed on all eyes. Only the area
of the active PCV or "hot spot" evident on the ICG angiogram was treated. A spot 
size was chosen to cover the active neovascular lesion with a 200-mum border.
Retreatment was performed when angiography revealed a recurrent lesion. RESULTS: 
Thirty eyes with PCV were treated and followed for 1 year. Mean age of the
patients was 75 years (range, 55-90 years). These patients were all classified as
having occult choroidal neovascularization (CNV) with FA and polypoidal CNV with 
ICG angiography. Improvement of vision (>or=3 lines) was achieved in 15 eyes
(50%). Nine eyes had stable vision (30%), and 6 eyes (20%) had a decrease in
vision (>or=3 lines). Repeated treatment was required in 15 eyes (50%) for an
average of 2.2 treatments in 1 year. CONCLUSION: This study indicates that
stabilization or improvement of vision is achieved in most eyes (80%) with
neovascular AMD from PCV after selected ICG angiography-guided PDT. These
outcomes compare very favorably with those in previous reports on the treatment
of occult CNV. Reduced collateral damage to the choriocapillaris and reduced
upregulation of vascular endothelial growth factor are presumed to be the
explanation for this apparently better outcome. Further studies with longer
follow-up are warranted to investigate the long-term efficacy in these
conditions.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17891004 [PubMed - indexed for MEDLINE]

659: Vision Res. 2008 Feb;48(3):339-45. Epub 2007 Sep 20.

Targeting age-related macular degeneration with Alzheimer's disease based
immunotherapies: anti-amyloid-beta antibody attenuates pathologies in an
age-related macular degeneration mouse model.

Ding JD, Lin J, Mace BE, Herrmann R, Sullivan P, Bowes Rickman C.

Department of Ophthalmology, Duke University Medical Center, Albert Eye Research 
Institute, Room 5010, Box 3802, Erwin Road, Durham, NC 27710, USA.

Age-related macular degeneration (AMD) is a late-onset, neurodegenerative retinal
disease that shares several clinical and pathological features with Alzheimer's
disease (AD) including extracellular deposits containing amyloid-beta (Abeta)
peptides. Immunotherapy targeting the Abeta protein has been investigated as a
potential treatment for AD. Here, we present the rationale for extending this
approach to treat AMD. We tested an anti-Abeta antibody administered systemically
in a mouse model of AMD. Histological and functional measurements in treated
animals compared to controls showed that following immunotherapy, the amounts of 
Abeta in the retina and brain were decreased and the ERG deficits in the retina
were attenuated. These data support the hypothesis that Abeta is a therapeutic
target for AMD.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17888483 [PubMed - indexed for MEDLINE]

660: Pharmacoeconomics. 2007;25(10):863-79.

Cost effectiveness of pegaptanib for the treatment of age-related macular
degeneration in the UK.

Wolowacz SE, Roskell N, Kelly S, Maciver FM, Brand CS.

RTI-Health Solutions, Manchester, UK. swolowacz@rti.org

BACKGROUND: Age-related macular degeneration (AMD) is the primary cause of vision
loss in the elderly and results in significant economic and humanistic burden.
The selective vascular endothelial growth factor inhibitor, pegaptanib (Macugen) 
is indicated for patients with neovascular AMD. Guidance is needed regarding the 
cost effectiveness of treatment, any variation between sub-populations of
differing clinical characteristics and the optimum duration of treatment.
OBJECTIVE: To estimate the cost effectiveness of pegaptanib versus best
supportive care (BSC) for AMD from the perspective of the UK government, and to
evaluate the impact of patient characteristics and differing treatment
discontinuation scenarios. METHODS: A cohort of 1000 patients aged >45 years with
a best-corrected visual acuity (VA) in their better-seeing eye of < or =6/12 was 
modelled. Patients were either treated with pegaptanib (0.3mg every 6 weeks for a
maximum of 2 years in their better-seeing eye only) or received BSC (no active
treatment). Supportive services were provided for patients with a VA < or =6/60. 
A 10-year Markov model composed of 12 VA states (defined by individual Snellen
lines) and a dead state was constructed. The model reported herein was used to
support submissions to the National Institute for Health and Clinical Excellence 
(NICE) and the Scottish Medicines Consortium (SMC). NICE guidance is expected to 
be available in October 2007 and the SMC advice was issued on 7 July 2006. SMC
accepted pegaptanib for use in patients with visual acuity between 6/12 and 6/60 
(inclusive) and should be stopped if visual acuity falls below 6/60 during
treatment or where severe visual loss is experienced. Time-dependent transition
probabilities for the loss and gain of Snellen lines were derived from parametric
survival curves fitted to patient-level data from the VISION trials. Survival
curves were fitted with treatment and baseline Snellen scores as covariates;
additional curves were fitted with the addition of age, gender, lesion type or
lesion size as covariates. Mortality rates were adjusted for the age, gender and 
VA of the population. Cost effectiveness was expressed as the incremental cost
(IC) per vision-year saved and IC/QALY. Uncertainty was explored by probabilistic
and univariate sensitivity analysis. Costs (year 2005 values) and outcomes were
discounted at 3.5% per anum. RESULTS: In the base-case analysis, treatment was
targeted to patients with a VA of 6/12 to 6/95 and discontinued after 2 years, or
earlier if VA fell below 6/95 or by > or =6 lines. The IC/QALY was estimated as
8023 pounds(upper 95% CI 20,641 pounds). Cost effectiveness varied by age (age
<75 years = 2033 pounds/QALY; age > or =75 years = 11,657 pounds/QALY) and by
pre-treatment VA (6/12-6/95 = 8023 pounds/QALY; 6/12-6/60 = 6664 pounds/QALY;
6/12-6/24 = 1920 pounds/QALY). Gender and lesion type or size had little effect. 
Cost effectiveness was not sensitive to precise rules for treatment
discontinuation, but was maximised if treatment was discontinued in patients no
longer likely to benefit. CONCLUSIONS: The results suggest that pegaptanib
treatment is likely to be cost effective across all groups studied, and
marginally more cost effective in younger patients and those with better
pre-treatment VA. Cost effectiveness appears to be optimised if treatment is
discontinued after 1 year if individual patients' VA has dropped by > or =6 lines
from pre-treatment levels, or at any time if it drops below 6/95. However, strict
application of discontinuation rules does not appear to be necessary for
pegaptanib to be cost effective. Clinical judgement and patient preference should
be an important determinant in decisions about stopping treatment.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17887807 [PubMed - indexed for MEDLINE]

661: Doc Ophthalmol. 2008 Jan;116(1):13-8. Epub 2007 Sep 21.

Multifocal electroretinography as a predictor of maintenance of vision after
photodynamic therapy for neovascular age-related macular degeneration.

Mackay AM, Brown MC, Grierson I, Harding SP.

Department of Clinical Engineering, Royal Liverpool University Hospital,
Liverpool, UK. alison.mackay70@ntlworld.com

PURPOSE: To investigate the role of multifocal electroretinography (mfERG) in
predicting the outcome of photodynamic therapy (PDT) for neovascular age-related 
macular degeneration (AMD). METHODS: Participants underwent refraction protocol
VA assessment using the ETDRS logMAR chart at 1 m, Contrast Sensitivity (CS)
using the Pelli-Robson chart at 1 m, fundus fluorescein angiography (FA) and
mfERGs in response to 19 segments. Response to PDT was binary (1 = the loss of
less than 15 letters at 12 months, 0 = the loss of 15 letters or more) and was
used as the dependent variable for logistic regression analysis. RESULTS:
Logistic regression modelling identified mfERG central segment amplitude, lesion 
size on FA, VA and CS as predictors of outcome (P = 0.05, 0.02, 0.01, 0.03). The 
model is stable and has excellent discriminability. CONCLUSION: The outcomes of
this study are particularly relevant to patients in the UK who are sometimes
treated with PDT alone. A larger prospective study would facilitate development
of an index to predict outcome of future treatments for AMD.

PMID: 17885777 [PubMed - indexed for MEDLINE]

662: Proc Natl Acad Sci U S A. 2007 Oct 9;104(41):16227-32. Epub 2007 Sep 20.

Comment in:
    Proc Natl Acad Sci U S A. 2007 Oct 23;104(43):16725-6.

A variant of mitochondrial protein LOC387715/ARMS2, not HTRA1, is strongly
associated with age-related macular degeneration.

Kanda A, Chen W, Othman M, Branham KE, Brooks M, Khanna R, He S, Lyons R,
Abecasis GR, Swaroop A.

Department of Ophthalmology and Visual Sciences, University of Michigan, Ann
Arbor, MI 48105, USA.

Genetic variants at chromosomes 1q31-32 and 10q26 are strongly associated with
susceptibility to age-related macular degeneration (AMD), a common blinding
disease of the elderly. We demonstrate, by evaluating 45 tag SNPs spanning HTRA1,
PLEKHA1, and predicted gene LOC387715/ARMS2, that rs10490924 SNP alone, or a
variant in strong linkage disequilibrium, can explain the bulk of association
between the 10q26 chromosomal region and AMD. A previously suggested causal SNP, 
rs11200638, and other examined SNPs in the region are only indirectly associated 
with the disease. Contrary to previous reports, we show that rs11200638 SNP has
no significant impact on HTRA1 promoter activity in three different cell lines,
and HTRA1 mRNA expression exhibits no significant change between control and AMD 
retinas. However, SNP rs10490924 shows the strongest association with AMD (P =
5.3 x 10(-30)), revealing an estimated relative risk of 2.66 for GT heterozygotes
and 7.05 for TT homozygotes. The rs10490924 SNP results in nonsynonymous A69S
alteration in the predicted protein LOC387715/ARMS2, which has a highly conserved
ortholog in chimpanzee, but not in other vertebrate sequences. We demonstrate
that LOC387715/ARMS2 mRNA is detected in the human retina and various cell lines 
and encodes a 12-kDa protein, which localizes to the mitochondrial outer membrane
when expressed in mammalian cells. We propose that rs10490924 represents a major 
susceptibility variant for AMD at 10q26. A likely biological mechanism is that
the A69S change in the LOC387715/ARMS2 protein affects its presumptive function
in mitochondria.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17884985 [PubMed - indexed for MEDLINE]

663: Am J Ophthalmol. 2007 Nov;144(5):741-746. Epub 2007 Sep 20.

Comment in:
    Am J Ophthalmol. 2008 Apr;145(4):765; author reply 765-6.    Am J Ophthalmol. 2008 Jun;145(6):1107; author reply 1107-8.

Posterior vitreomacular adhesion: a potential risk factor for exudative
age-related macular degeneration?

Krebs I, Brannath W, Glittenberg C, Zeiler F, Sebag J, Binder S.

Ludwig Boltzmann Institute for Retinology and Biomicroscopic Laser Surgery,
Vienna, Austria. Ilse.Krebs@wienkav.at

PURPOSE: To compare the state of the posterior vitreous in exudative age-related 
macular degeneration (AMD) with eyes with nonexudative AMD and controls. DESIGN: 
Prospective, observational case series. METHODS: B-scan ultrasonography and
optical coherence tomography (OCT) were performed in 163 eyes from 82 subjects
older than 55 years, 50 eyes with exudative AMD, 57 with nonexudative AMD, and 56
control eyes. Main outcome measures were the number of eyes with complete
posterior vitreous detachment (PVD) by ultrasound and the number of eyes with
central vitreomacular adhesion by OCT. RESULTS: By ultrasonography, 17 (34.0%) of
50 eyes with exudative AMD had PVD as compared with 41 (71.9%) of 57 eyes with
nonexudative AMD (P = .00002) and 34 (60.7%) of 56 controls (P = .017). OCT
detected persistent central vitreoretinal adhesion surrounded by a detached
posterior vitreous cortex in 18 (36%) of 50 eyes with exudative AMD,
significantly higher than in nonexudative AMD (4/57 [7%]; P < .0001) and in
controls (6/56 [10%]; P = .002). CONCLUSIONS: Persistent attachment of the
posterior vitreous cortex to the macula may be another risk factor for the
development of exudative AMD via vitreoretinal traction inducing chronic
low-grade inflammation, by maintaining macular exposure to cytokines or free
radicals in the vitreous gel, or by interfering in transvitreous oxygenation and 
nutrition of the macula. Inducing PVD may provide prophylactic benefit against
exudative AMD.

Publication Types: 
    Comparative Study

PMID: 17884003 [PubMed - indexed for MEDLINE]

664: Graefes Arch Clin Exp Ophthalmol. 2008 Jan;246(1):27-37. Epub 2007 Sep 19.

Characteristics of dynamic processing in the visual field of patients with
age-related maculopathy.

Eisenbarth W, Mackeben M, Poggel DA, Strasburger H.

Generation Research Program, Human Science Center, Ludwig-Maximilians University,
Munich, Germany.

PURPOSE: To investigate the characteristics of dynamic processing in the visual
field of patients with age-related maculopathy (ARM) by measuring motion
sensitivity, double-pulse resolution (DPR), and critical flicker fusion. METHODS:
Fourteen subjects with ARM (18 eyes), 14 age-matched controls (19 eyes), and 7
young controls (8 eyes) served as subjects. Motion contrast thresholds were
determined by a four-alternative forced-choice (4 afc) staircase procedure with a
modification by Kernbach for presenting a plaid (size = 3.8 degrees) moving
within a stationary spatial and temporal Gaussian envelope in one of four
directions. Measurements were performed on the horizontal meridian at 10 degrees,
20 degrees, 30 degrees, 40 degrees, and 60 degrees eccentricity. DPR was defined 
as the minimal temporal gap detectable by the subject using a 9-fold interleaved 
adaptive procedure, with stimuli positioned on concentric rings at 5 degrees, 10 
degrees, and 20 degrees eccentricity on the principal and oblique meridians.
Critical flicker fusion thresholds (CFF) and the Lanthony D-15 color vision test 
were applied foveally, and the subjects were free to use their fovea or whatever 
retinal area they needed to use instead, due to their retinal lesions caused by
ARM. All measurements were performed under photopic conditions. RESULTS: Motion
contrast sensitivity in subjects with ARM was pronouncedly reduced (0.23-0.66 log
units, p < 0.01), not only in the macula but in a region up to 20 degrees
eccentricity. In the two control groups, motion contrast sensitivity
systematically declined with retinal eccentricity (0.009-0.032 log units/degree) 
and with age (0.01 log units/year). Double-pulse thresholds in healthy subjects
were approximately constant in the central visual field and increased outside a
radius of 10 degrees (1.73 ms/degree). DPR thresholds were elevated in subjects
with ARM (by 23-32 ms, p < 0.01) up to 20 degrees eccentricity, and their foveal 
CFFs were increased by 5.5 Hz or 14% (p < 0.01) as compared with age-matched
controls. CONCLUSIONS: Dynamic processing properties in subjects with ARM are
severely impaired in the central visual field up to 20 degrees eccentricity,
which is clearly beyond the borders of the macula.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17882447 [PubMed - indexed for MEDLINE]

665: Vision Res. 2007 Oct;47(23):2943-55. Epub 2007 Sep 18.

Relationship between slow visual processing and reading speed in people with
macular degeneration.

Cheong AM, Legge GE, Lawrence MG, Cheung SH, Ruff MA.

Minnesota Laboratory for Low Vision Research, University of Minnesota,
Minneapolis, MN 55455, USA. cheon015@umn.edu

PURPOSE: People with macular degeneration (MD) often read slowly even with
adequate magnification to compensate for acuity loss. Oculomotor deficits may
affect reading in MD, but cannot fully explain the substantial reduction in
reading speed. Central-field loss (CFL) is often a consequence of macular
degeneration, necessitating the use of peripheral vision for reading. We
hypothesized that slower temporal processing of visual patterns in peripheral
vision is a factor contributing to slow reading performance in MD patients.
METHODS: Fifteen subjects with MD, including 12 with CFL, and five age-matched
control subjects were recruited. Maximum reading speed and critical print size
were measured with rapid serial visual presentation (RSVP). Temporal processing
speed was studied by measuring letter-recognition accuracy for strings of three
randomly selected letters centered at fixation for a range of exposure times.
Temporal threshold was defined as the exposure time yielding 80% recognition
accuracy for the central letter. RESULTS: Temporal thresholds for the MD subjects
ranged from 159 to 5881 ms, much longer than values for age-matched controls in
central vision (13 ms, p<0.01). The mean temporal threshold for the 11 MD
subjects who used eccentric fixation (1555.8 +/- 1708.4 ms) was much longer than 
the mean temporal threshold (97.0 +/- 34.2 ms, p<0.01) for the age-matched
controls at 10 degrees in the lower visual field. Individual temporal thresholds 
accounted for 30% of the variance in reading speed (p<0.05). CONCLUSION: The
significant association between increased temporal threshold for letter
recognition and reduced reading speed is consistent with the hypothesis that
slower visual processing of letter recognition is one of the factors limiting
reading speed in MD subjects.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 17881032 [PubMed - indexed for MEDLINE]

666: Graefes Arch Clin Exp Ophthalmol. 2008 Mar;246(3):353-61. Epub 2007 Sep 18.

Comment in:
    Graefes Arch Clin Exp Ophthalmol. 2008 Aug;246(8):1203; author reply 1205-7.    Graefes Arch Clin Exp Ophthalmol. 2008 Aug;246(8):1209; author reply 1211-4.

Role of retinal hypoxia in diabetic macular edema: a new concept.

Hayreh SS.

Department of Ophthalmology & Visual Sciences, College of Medicine, University of
Iowa, Iowa, IA, USA. Sohan-hayreh@uiowa.edu

BACKGROUND: To report the role of retinal hypoxia in development of diabetic
macular edema and its management--a new concept. CASE REPORT: A 24-year-old
diabetic female was seen with bilateral visual blurring for 3 weeks, associated
with marked diabetic macular edema, diabetic retinopathy, and non-arteritic
anterior ischemic optic neuropathy (NA-AION) in both eyes. She was taking three
blood pressure lowering drugs for diabetic neuropathy and nephropathy. Stopping
two of those arterial hypotensive drugs, without any of the conventional
treatments for diabetic macular edema, resulted in rapid improvement of visual
acuity from counting fingers to 20/50 in the right eye, and from 20/80 to 20/25
in the left eye, and complete resolution of macular edema and improvement of
retinopathy. Similarly, visual field defects in both eyes improved to almost
normal. CONCLUSIONS: The evidence from this diabetic patient suggests that
hypoxia caused by fall in perfusion pressure in the retinal capillaries may be
playing an important role in the development of diabetic macular edema in some,
perhaps many, of these cases.

Publication Types: 
    Case Reports

PMID: 17876597 [PubMed - indexed for MEDLINE]

667: Am J Ophthalmol. 2007 Nov;144(5):747-754. Epub 2007 Sep 17.

Optical coherence tomography findings in persistent diabetic macular edema: the
vitreomacular interface.

Ghazi NG, Ciralsky JB, Shah SM, Campochiaro PA, Haller JA.

Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland 21287, USA.

PURPOSE: To assess the optical coherence tomography (OCT) characteristics of eyes
with persistent clinically significant diabetic macular edema (PDME) after focal 
laser treatment, with emphasis on the vitreomacular interface (VMI)
characteristics. DESIGN: Prospective, observational case series. METHODS: Fifty
eyes with PDME after at least one focal laser treatment were enrolled
prospectively. Slit-lamp biomicroscopy, stereoscopic fundus photography,
fluorescein angiography (FA), and OCT were performed for each eye. The main
outcome measures included the detection rate of VMI abnormalities (VMIA) by OCT
in comparison with biomicroscopy, fundus photography, and FA (traditional
techniques); the relationship between VMIA and the number of focal laser sessions
per eye and FA leakage pattern. RESULTS: Two of 50 eyes were excluded because of 
incomplete data. For the remaining 48 eyes, 25 eyes (52.1%) demonstrated definite
VMIA, including anomalous vitreal adhesions, epiretinal membrane (ERM), or both, 
and six eyes (12.5%) had questionable VMIA. OCT in general was 1.94 times more
sensitive than traditional techniques combined in detecting VMIA (P = .00003).
The number of focal laser sessions and diffuse FA leakage were not associated
with an increased prevalence of VMIA (P = .13 and P = .47, respectively).
CONCLUSIONS: This study demonstrates a high prevalence of VMIA in eyes with PDME 
after focal laser treatment and underscores the superiority of OCT in detecting
these abnormalities. OCT evaluation of eyes with PDME may be helpful in
identifying VMIA, which may impact treatment selection and patient subgroup
stratification.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17869207 [PubMed - indexed for MEDLINE]

668: Ophthalmology. 2008 May;115(5):876-883.e1. Epub 2007 Sep 14.

Macular pigment density and age-related maculopathy in the Carotenoids in
Age-Related Eye Disease Study. An ancillary study of the women's health
initiative.

LaRowe TL, Mares JA, Snodderly DM, Klein ML, Wooten BR, Chappell R; CAREDS
Macular Pigment Study Group.

Collaborators: Blodi B, Eisner A, Gehrs K, Wallace R, Kardon R, Klein ML, Mares
JA, Snodderly DM, Ver Hoeve J, Wooten BR.

Department of Family Medicine, University of Wisconsin-Madison, Madison,
Wisconsin, USA.

PURPOSE: To examine the association between intermediate age-related macular
degeneration (AMD) and the optical density of macular pigment (MPOD), which is
composed of lutein and zeaxanthin from the diet. DESIGN: Cross-sectional cohort
study. PARTICIPANTS: We included 1698 of 2005 women ages 54 to 86 years and
participating in the Carotenoids in Age-Related Eye Disease Study, an ancillary
study of the Women's Health Initiative. METHODS: The MPOD was measured
noninvasively by heterochromatic flicker photometry. Fundus photographs were
taken to document prevalent AMD. MAIN OUTCOME MEASURES: Intermediate AMD (n =
305) and two subtypes-large drusen (n = 233) and pigmentary abnormalities (n =
157). RESULTS: After adjusting for covariates, the odds ratio (OR) and 95%
confidence interval (CI) for AMD among women in quintile (Q) 5 (n = 339) versus 1
(n = 340) for MPOD was 1.4 (0.9, 2.1). However, after excluding women with
possible unstable diets and recent supplement use due to chronic disease history,
associations reversed (OR Q2-5 vs. 1, 0.8; 95% CI, 0.5-1.2), but remained
nonsignificant. Associations also differed between middle-aged (54-69 years) and 
older (> or =70 years) women (P-interaction = 0.09), but less so, after excluding
women who were likely to have unstable diets: adjusted ORs (95% CI) were 0.5
(0.3-1.0; P = 0.08) for intermediate AMD among middle-aged women (n = 516) with
MPOD in Q2 to Q5 versus 1 and 1.0 (0.5-2.0; P = 0.90) for older women (n = 422). 
CONCLUSIONS: The MPOD is not cross-sectionally associated with AMD. The
inconsistency of relationships across age groups and in subgroups of women who
are likely to have more stable diets suggests that cross-sectional associations
may be biased and highlights the need to study these relationships prospectively.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17868874 [PubMed - indexed for MEDLINE]

669: Osaka City Med J. 2007 Jun;53(1):35-47.

Digital image analysis of choroidal hypoperfusion in indocyanine green
angiography using a choroid to disc gray-scale ratio.

Miki N, Kohno T, Shiraki K, Nadachi R, Okazaki Y, Suehiro J, Uenishi Y, Miki T.

Department of Ophthalmology and Visual Sciences, Osaka City University, Graduate 
School of Medicine, Japan. noritomiki@hotmail.com

PURPOSE: To investigate hypoperfusion of the choroidal circulation in the macula,
the brightness of the diffuse fluorescence of indocyanine green (ICG) angiogram
(IA) was measured and the ratio of brightness of the macula to that of the disc
was used for comparison of choroidal perfusion between different angiograms.
METHODS: Ten eyes of 10 young volunteers under 30 years of age (17-28 years old, 
average 24.7 years old), 10 eyes of 10 old volunteers over 60 years old (60-78
years old, average 66.7 years old) and 5 eyes of 5 patients with age-related
macular degeneration (AMD) were examined by IA. The angiograms at 4 and 16
seconds after dye filling were used to measure the brightness of diffuse
fluorescence at the macula and the disc on ICG angiograms with a 256-grade gray
scale using the Topcon IMAGEnet computer system. The ratio (ch/d ratio) of the
averaged brightness of the macula to that of the disc was calculated for each
angiogram. RESULTS: The ch/d ratios of the angiograms 4 seconds after dye filling
were 1.41 in the young volunteers, 1.23 in the old volunteers and 0.52 in the AMD
patients. The ch/d ratios of the angiograms 16 seconds after dye filling were
0.92 in the young volunteers, 1.02 in the old volunteers and 0.80 in AMD. There
were significant differences in the ch/d ratios among the 3 groups 4 seconds
after dye filling (p=0.007, Kruskal-Wallis H test,) but there were no significant
differences 16 seconds after dye filling (p=0.310). CONCLUSION: The ch/d ratio is
an adjunctive method for detecting choroidal hypoperfusion in IA, and may be
helpful for objective evaluation of the choroidal circulation in chorioretinal
diseases.

Publication Types: 
    Clinical Trial
    Comparative Study

PMID: 17867632 [PubMed - indexed for MEDLINE]

670: Scand J Occup Ther. 2008 Jun;15(2):68-74.

A randomized controlled trial of a health-promotion programme and its effect on
ADL dependence and self-reported health problems for the elderly visually
impaired.

Eklund K, Sjöstrand J, Dahlin-Ivanoff S.

Department of Neurology and Physiology, Sahlgrenska Academy at Göteborg
University, Sweden. kajsa.Eklund@gu.se

BACKGROUND: Ageing with visual impairment is associated with a high degree of
disability whereby age-related macular degeneration in particular causes
dependence in activities of daily living (ADL) even at an early stage. AIMS: To
compare an activity-based, health-promotion programme with an individual
programme, targeting the elderly with age-related macular degeneration concerning
the effect on the development of dependence in ADL, general health, and
self-reported health problems. METHODS: A randomized controlled study with a
28-month follow-up. A total of 229 persons were randomized to the study and 131
(57%) were followed up (individual intervention n=69, health-promotion programme 
n=62) at 28-month. RESULTS: The health-promotion group maintained their ADL level
despite a significant decrease in visual acuity, while the individual
intervention group increased its dependence in ADL. General health systematically
dropped to a lower level in both groups, but participants from the
health-promotion group reported fewer health problems. There were significantly
fewer reports of tiredness and dizziness among the health-promotion participants.
CONCLUSION: The health-promotion programme seems to have slowed down the
disablement process among elderly with decreased vision by enabling them to
maintain their ADL level and by reducing self-reported health problems for at
least 28 months following intervention.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial

PMID: 17852958 [PubMed - indexed for MEDLINE]

671: Arch Ophthalmol. 2007 Sep;125(9):1249-54.

Comment in:
    Arch Ophthalmol. 2007 Sep;125(9):1266-8.

Burden and health care resource utilization in neovascular age-related macular
degeneration: findings of a multicountry study.

Soubrane G, Cruess A, Lotery A, Pauleikhoff D, Monès J, Xu X, Zlateva G, Buggage 
R, Conlon J, Goss TF.

Department of Ophthalmology, University Paris XII, Centre Hospitalier
Intercommunal de Créteil, 40 Avenue de Verdun, Créteil, France.
gisele.soubrane@chicreteil.fr

OBJECTIVE: To describe the burden of bilateral neovascular age-related macular
degeneration (NV-AMD) on patient-reported functioning and health resource
utilization. METHODS: A cross-sectional study of 401 patients with bilateral
NV-AMD and 471 elderly control subjects without AMD was conducted in 5 countries.
Subjects completed a telephone survey, including the National Eye Institute
25-Item Visual Function Questionnaire, the EuroQol instrument, the Hospital
Anxiety and Depression Scale, and history of falls, fractures, and health care
resource utilization. RESULTS: The mean age for patients with NV-AMD was 78.1
years, and 65% were women. The patients reported 45% worse vision-related
functioning, 13% worse overall well-being, and 30% more anxiety and 42% more
depression symptoms than controls after adjusting for covariates (all, P < .001).
The effect of NV-AMD was also observed as a doubled fall rate (16% vs 8% [P <
.001]) and a quadrupled need for assistance with daily activities (29% vs 7% [P <
.001]) in the patients compared with controls. CONCLUSIONS: The evidence of
extensive decline in quality of life and increased need of daily living
assistance for patients with NV-AMD compared with a control population
substantiates the need for new treatments that prevent vision loss and
progression to blindness.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 17846366 [PubMed - indexed for MEDLINE]

672: Arch Ophthalmol. 2007 Sep;125(9):1241-7.

Age-related macular degeneration and cancer mortality in the atherosclerosis risk
in communities study.

Cheung N, Shankar A, Klein R, Folsom AR, Couper DJ, Wong TY; Atherosclerosis Risk
in Communities (ARIC) Study Investigators.

Centre for Eye Research Australia, University of Melbourne, Victoria, Australia.

OBJECTIVE: To examine the prospective association of early age-related macular
degeneration (AMD) with cancer mortality. METHODS: A population-based cohort
study of 10 029 persons aged 49 to 73 years free of cancer. The AMD signs were
evaluated from retinal photographs taken in 1993 through 1995. Cancer mortality
was determined from death records. RESULTS: There were 464 cases of early AMD.
Over 10 years, there were 234 cancer deaths (71 lung cancer deaths). After
controlling for age, sex, race, field center, education, smoking status,
pack-years of smoking, body mass index (calculated as weight in kilograms divided
by height in meters squared), and diabetes mellitus, early AMD was associated
with cancer mortality (rate ratio [RR], 1.68; 95% confidence interval [CI],
1.03-2.73). This association was overall stronger in African American individuals
(RR, 3.93; 95% CI, 1.67-9.22) than white individuals (RR, 1.28; 95% CI,
0.71-2.32) and for lung cancer deaths (RR, 2.14; 95% CI, 0.97-4.72) than non-lung
cancer deaths (RR, 1.50; 95% CI, 0.81-2.78). In African American individuals,
early AMD was associated with a 5-fold higher risk of lung cancer deaths (RR,
5.28; 95% CI, 1.52-18.40). CONCLUSIONS: Middle-aged African American individuals 
with early AMD may be at increased risk of dying of cancer, particularly lung
cancer. This association was not present in white individuals and needs
confirmation in other studies.

Publication Types: 
    Multicenter Study
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17846365 [PubMed - indexed for MEDLINE]

673: Arch Ophthalmol. 2007 Sep;125(9):1235-40.

Comment in:
    Arch Ophthalmol. 2007 Sep;125(9):1270-1.

Mitochondrial DNA haplogroups and age-related maculopathy.

Jones MM, Manwaring N, Wang JJ, Rochtchina E, Mitchell P, Sue CM.

Department of Neurogenetics, University of Sydney, Australia.

OBJECTIVE: To investigate whether mitochondrial haplogroups are associated with
age-related maculopathy (ARM). METHODS: We assessed the association between
mitochondrial haplogroups and ARM in a population-based sample of 3509 persons
aged 49 years or older residing west of Sydney. Retinal photographs of both eyes 
were taken (1999-2001) and subsequently graded for ARM following the Wisconsin
grading system. Genetic analysis for mitochondrial DNA haplogroups was performed.
Associations between these genetic markers and risk factors for ARM were
assessed. RESULTS: After adjusting for age, sex, and smoking, haplogroup H was
associated with a reduced prevalence of any (early and late) ARM (odds ratio
[OR], 0.75; 95% confidence interval [CI], 0.58-0.97), early ARM (OR, 0.75; 95%
CI, 0.57-0.98), and large distinct and indistinct soft drusen (OR, 0.70; 95% CI, 
0.56-0.89). Haplogroup J was associated with a higher prevalence of large, soft
distinct drusen (OR, 1.80; 95% CI, 1.18-2.73). Haplogroup U was associated with
an increased prevalence of retinal pigment abnormalities (OR, 1.45; 95% CI,
1.11-1.91). CONCLUSIONS: Our findings of associations between different
haplogroup types and prevalent ARM or ARM lesions suggest that these haplogroups 
may be genetic markers indicative of an individual's susceptibility to ARM.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17846364 [PubMed - indexed for MEDLINE]

674: Arch Ophthalmol. 2007 Sep;125(9):1225-32.

Comment in:
    Arch Ophthalmol. 2008 Sep;126(9):1313; author reply 1313-4.

The relationship of dietary carotenoid and vitamin A, E, and C intake with
age-related macular degeneration in a case-control study: AREDS Report No. 22.

Age-Related Eye Disease Study Research Group, SanGiovanni JP, Chew EY, Clemons
TE, Ferris FL 3rd, Gensler G, Lindblad AS, Milton RC, Seddon JM, Sperduto RD.

The EMMES Corporation, 401 N Washington St, Ste 700, Rockville, MD 20850-1707,
USA. aredspub@emmes.com

OBJECTIVE: To evaluate the relationship of dietary carotenoids, vitamin A,
alpha-tocopherol, and vitamin C with prevalent age-related macular degeneration
(AMD) in the Age-Related Eye Disease Study (AREDS). METHODS: Demographic,
lifestyle, and medical characteristics were ascertained on 4519 AREDS
participants aged 60 to 80 years at enrollment. Stereoscopic color fundus
photographs were used to categorize participants into 4 AMD severity groups and a
control group (participants with < 15 small drusen). Nutrient intake was
estimated from a self-administered semiquantitative food frequency questionnaire 
at enrollment. Intake values were energy adjusted and classified by quintiles.
The relationship between diet and AMD status was assessed using logistic
regression analyses. RESULTS: Dietary lutein/zeaxanthin intake was inversely
associated with neovascular AMD (odds ratio [OR], 0.65; 95% confidence interval
[CI], 0.45-0.93), geographic atrophy (OR, 0.45; 95% CI, 0.24-0.86), and large or 
extensive intermediate drusen (OR, 0.73; 95% CI, 0.56-0.96), comparing the
highest vs lowest quintiles of intake, after adjustment for total energy intake
and nonnutrient-based covariates. Other nutrients were not independently related 
to AMD. CONCLUSION: Higher dietary intake of lutein/zeaxanthin was independently 
associated with decreased likelihood of having neovascular AMD, geographic
atrophy, and large or extensive intermediate drusen.

Publication Types: 
    Multicenter Study
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17846363 [PubMed - indexed for MEDLINE]

675: Ophthalmology. 2008 May;115(5):870-5. Epub 2007 Sep 12.

Subclinical changes in the juvenile crystalline macular dystrophy in
Sjögren-Larsson syndrome detected by optical coherence tomography.

Fuijkschot J, Cruysberg JR, Willemsen MA, Keunen JE, Theelen T.

Department of Pediatric Neurology, Radboud University Nijmegen Medical Center,
Nijmegen, Netherlands.

PURPOSE: To study morphologic changes in the macula by optical coherence
tomography (OCT) in patients with a crystalline macular dystrophy due to the
autosomal recessive neurocutaneous Sjögren-Larsson syndrome (SLS). DESIGN:
Retrospective observational case series. PARTICIPANTS: Twenty-seven eyes of 14
patients, mean age 14.6 (range, 3-24) years, with biochemically and genetically
proven SLS underwent clinical and OCT investigation between September 2004 and
September 2006. METHODS: All patients underwent full ophthalmologic examination
including slit-lamp biomicroscopy and binocular ophthalmoscopy. Optical coherence
tomography of all eyes was performed using the macular thickness map protocol of 
Stratus OCT. MAIN OUTCOME MEASURES: Macular morphology in clinical examination
and OCT. RESULTS: Beside clinically visible perimacular crystalline deposits in
all eyes of all study participants, macular morphology and reflectivity were
significantly changed on OCT compared with healthy eyes. We found focal
hyperreflectivities in all study eyes within the perifoveal ganglion cell layer
and the inner plexiform layer, corresponding to the clinical localization of
retinal crystals. More interestingly, a cystoid foveal degeneration on OCT was
present in the majority of patients with SLS (18/27 eyes, or 67% of all eyes
studied), varying from multiple microcystoid spaces to cystoid foveal atrophy. In
general, patients who were severely affected on OCT showed intense changes on
previously performed cerebral magnetic resonance spectroscopy. CONCLUSIONS:
Patients with SLS show a childhood-onset crystalline macular dystrophy with
cystoid foveal atrophy on OCT in most cases. The intraretinal deposition of lipid
metabolites may lead to Müller cell degeneration with subsequent formation of
cystoid spaces or atrophic changes within the fovea. Because this macular
dystrophy is present in all examined patients with SLS, familiarity with this
maculopathy seems important for the diagnosis of this rare systemic disease.

PMID: 17826835 [PubMed - indexed for MEDLINE]

676: Ophthalmology. 2008 May;115(5):898-903.e4. Epub 2007 Sep 12.

The impact of anchor point on utilities for 5 common ophthalmic diseases.

Lee BS, Kymes SM, Nease RF Jr, Sumner W, Siegfried CJ, Gordon MO.

Department of Ophthalmology and Visual Sciences, Washington University School of 
Medicine, St. Louis, Missouri 63110, USA.

PURPOSE: To elicit utilities on a perfect health and perfect vision scale for 5
common eye diseases. DESIGN: Cross-sectional observational preference study.
PARTICIPANTS: We included 434 patients: 58 with diabetic retinopathy, 99 with
glaucoma, 44 with age-related macular degeneration (AMD), 124 with cataract; 109 
with refractive error. TESTING: Standard gamble utilities were estimated using a 
computer-based preference assessment interview platform. MAIN OUTCOME MEASURES:
Standard gamble utilities, a quality-of-life measure that examines the
willingness to accept a risk of death or unilateral blindness in return for
perfect health or perfect vision. RESULTS: Using the standard policy scale, where
health equivalent to death is 0 and perfect health is 1, participants with
asymptomatic diabetic retinopathy had a utility of 0.93. By comparison,
symptomatic diabetics had a further utility loss of 0.14. Asymptomatic glaucoma
participants had a utility of 0.92 with a decrease of 0.03 for early field loss
and a further decrease of 0.03 with central field loss. Participants with AMD who
had > or =20/100 better-eye visual acuity reported a utility of 0.89, whereas
those with more severe AMD reported 0.76. However, neither clinical cataract
opacity score nor refractive error correlated with utility. Adjustment for age
and comorbidity did not alter these relationships. For the same participants,
utilities measured with different anchor points-monocular blindness as 0 and
perfect vision as 1-were lower, especially among participants with increased
disease severity. The difference between utility assessed on this perfect
vision-blindness scale and the perfect health-death scale ranged from 0.04 for
those with severe refractive error to 0.19 for symptomatic diabetics and 0.37 for
those with severe AMD. CONCLUSIONS: This paper elicits utilities with different
anchor points from a previously unreported sample of 434 patients. Lower utility 
scores normally imply greater benefit with successful treatment or prevention of 
disease, but switching from the conventional policy scale to the perfect vision
scale also consistently results in lower scores. Because most previous ophthalmic
studies have used perfect vision as the upper anchor, the resulting utilities may
not have been accurate.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 17826833 [PubMed - indexed for MEDLINE]

677: Graefes Arch Clin Exp Ophthalmol. 2007 Dec;245(12):1745-7. Epub 2007 Sep 6.

Kallikrein-kinin activation by altered vitreous pH: New perspectives for
treatment and pathogenesis of diabetic macular edema? : Comment on: Gao BB et al.
Extracellular carbonic anhydrase mediates hemorrhagic retinal and cerebral
vascular permeability through prekallikrein activation. Nat Med. 2007
Feb;13(2):181-8.

Zeitz O, Keserü M.

Klinik und Poliklinik für Augenheilkunde, Universitätklinikum Hamburg-Eppendorf, 
Martinitsr. 52, Hamburg 20246, Germany. zeitz@uke.uni-hamburg.de

Recently, Gao et al. published an experimental study based on the pathophysiology
of diabetic macular edema in Nature Medicine (Nat Med. 2007 Feb;13(2):181-8).
They found an increased amount of carbonic anhydrase in the vitreous, which
causes a pH shift. This activates the kallikrein-kinin system and leads to
increased retinal vascular permeability. In this comment the clinical
implications of this article are discussed.

PMID: 17823811 [PubMed - indexed for MEDLINE]

678: Can J Ophthalmol. 2007 Oct;42(5):748-9.

Regression of radiation-induced macular edema after systemic bevacizumab.

Solano JM, Bakri SJ, Pulido JS.

Mayo Clinic, Rochester, MN 55905, USA.

CASE REPORT: A 59-year-old patient with a coexisting primary choroidal melanoma
and colorectal cancer was treated with external beam radiation (EBR) of his
choroidal melanoma and systemic chemotherapy with leukovorin/5 fluorouracil (FU) 
for treatment of his metastatic colorectal cancer. Eight months following EBR, he
showed evidence of radiation retinopathy with macular edema. Optical coherence
tomography (OCT) showed macular edema and subretinal fluid. Subsequently,
systemic bevacizumab (5 mg/kg) was added to his leukovorin/5FU chemotherapy.
After the addition of bevacizumab, OCT showed complete resolution of the macular 
edema and subretinal fluid. COMMENTS: Bevacizumab may have a role in the
treatment of radiation retinopathy, but further investigation is needed before
any definitive conclusions can be made.

Publication Types: 
    Case Reports

PMID: 17823640 [PubMed - indexed for MEDLINE]

679: Ophthalmology. 2007 Sep;114(9):1728-35.

Cone- and rod-mediated dark adaptation impairment in age-related maculopathy.

Owsley C, McGwin G Jr, Jackson GR, Kallies K, Clark M.

Department of Ophthalmology, School of Medicine, University of Alabama at
Birmingham, Birmingham, Alabama 35294-0009, USA. owsley@uab.edu

OBJECTIVE: To examine impairment in cone- versus rod-mediated dark adaptation in 
the parafovea of persons with age-related maculopathy (ARM). DESIGN:
Cross-sectional. PARTICIPANTS: Older adults with ARM at various severity levels
from early to advanced (n = 83) and in good retinal health (n = 43), as
determined by stereo fundus photographs evaluated with the Age-Related Eye
Disease Study severity scale. METHODS: Dark adaptation, both cone- and
rod-mediated components, was measured with a modified Humphrey Field Analyzer
using a target located 12 degrees in the inferior visual field on the vertical
meridian, after exposure to a 98% bleach. Information was collected on
self-reported problems for activities at night or under dim illumination (Low
Luminance Questionnaire [LLQ]) and for activities during daytime conditions
(modified National Eye Institute Visual Function Questionnaire [NEI VFQ]). MAIN
OUTCOME MEASURES: Cone- and rod-mediated parameters of dark adaptation. RESULTS: 
Compared with older adults in normal retinal health, ARM patients had significant
impairments in rod-mediated parameters of dark adaptation (rod-cone break, rod
slope, rod sensitivity) (P<0.0001), which were increasingly abnormal as disease
severity increased. Cone-mediated parameters (cone time constant and cone
sensitivity) were not impaired. Low Luminance Questionnaire scores and NEI VFQ
scores decreased with increased ARM severity (P = 0.0004 and P = 0.0005,
respectively); the percent decrease in LLQ scores as a function of disease
severity was larger in magnitude than the percent decrease in NEI VFQ scores.
CONCLUSIONS: Disturbances in rod-mediated but not cone-mediated dark adaptation
in the parafovea at 12 degrees in the inferior field on the vertical meridian are
characteristic of ARM even in its early phases.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17822978 [PubMed - indexed for MEDLINE]

680: Ophthalmology. 2007 Sep;114(9):1713-21.

Periocular triamcinolone and photodynamic therapy for subfoveal choroidal
neovascularization in age-related macular degeneration.

Neovascular Age-Related Macular Degeneration, Periocular Corticosteroids, and
Photodynamic Therapy (NAPP) Trial Research Group, Gilson MM, Bressler NM, Jabs
DA, Solomon SD, Thorne JE, Wilson DJ.

Johns Hopkins University, Baltimore, Maryland, USA.

PURPOSE: To evaluate fluorescein angiographic and visual acuity (VA) outcomes
from patients enrolled in a trial of a single periocular corticosteroid injection
immediately before photodynamic therapy (PDT) versus PDT alone for subfoveal
choroidal neovascularization secondary to age-related macular degeneration (AMD).
DESIGN: Randomized 2-center clinical trial. PARTICIPANTS: Sixty-seven subjects
with AMD, subfoveal choroidal neovascularization, and best-corrected VA of 20/20 
to 20/320 in the study eye who had received no more than 1 prior PDT treatment.
METHODS: Subjects were randomized to receive PDT alone (no corticosteroid) or a
single periocular corticosteroid injection given via the posterior superior
sub-Tenon's capsule route before PDT (corticosteroid) and assessed 1, 3, and 6
months after enrollment. Best-corrected VA and intraocular pressure (IOP)
measurements were taken during each examination. Color photographs and
fluorescein angiograms were taken at baseline and 3 and 6 months. MAIN OUTCOME
MEASURE: Presence or absence of fluorescein leakage from choroidal
neovascularization 3 months after randomization. RESULTS: Between the 34
participants randomized to periocular corticosteroid and 33 to no corticosteroid,
baseline features appeared balanced. Thirty-three corticosteroid participants and
30 no corticosteroid participants returned for the 3-month follow-up, at which
time 56 had fluorescein leakage. Proportions of participants with leakage at 3
months for the 2 treatment groups did not statistically significantly differ; 94%
of the corticosteroid group and 90% of the no corticosteroid group had
fluorescein leakage at 3 months (P = 0.66). Mean VAs at 3 months after enrollment
were 20/100 and 20/125 in the corticosteroid and no corticosteroid groups,
respectively, decreasing on average 1.5 and 0.9 lines from baseline (P = 0.50).
Adverse events included IOP > 21 mmHg in 7 corticosteroid participants (21%) and 
1 (3%) no corticosteroid participant (P<0.05) and ptosis of the study eyelid in 1
(3%) corticosteroid participant. CONCLUSIONS: In contrast to previously reported 
uncontrolled studies and 1 controlled study, this trial did not find a reduction 
in the amount of fluorescein leakage 3 months after a single periocular injection
of corticosteroid and PDT compared with PDT alone.

Publication Types: 
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17822977 [PubMed - indexed for MEDLINE]

681: Graefes Arch Clin Exp Ophthalmol. 2008 Mar;246(3):339-44. Epub 2007 Sep 6.

Effect of posterior juxtascleral triamcinolone acetonide on the efficacy and
choriocapillaris hypoperfusion of photodynamic therapy.

Iriyama A, Obata R, Inoue Y, Takahashi H, Tamaki Y, Yanagi Y.

Department of Ophthalmology, University of Tokyo School of Medicine, 7-3-1 Hongo,
Bunkyo-ku, Tokyo, 113-8655, Japan.

PURPOSE: To evaluate the effect of posterior juxtascleral triamcinolone acetonide
(TA) injection combined with photodynamic therapy with verteporfin (PDT) for
treating exudative age-related macular degeneration (AMD), the best-corrected
visual acuity (BCVA), the retreatment rates and the rate of choroidal
hypoperfusion were investigated. METHODS: A total of 67 eyes with subfoveal
choroidal neovascularization (CNV) due to AMD were included. Forty-four eyes
underwent PDT alone (PDT-alone group), and 23 eyes underwent PDT with the
posterior juxtascleral injection of TA (PDT+TA group). Every 3 months after the
PDT, the eyes were evaluated with regard to BCVA and requirement for retreatment 
by fluorescein angiography (FA) with the aid of optical coherence tomography
(OCT). Choroiocapillaris hypoperfusion was assessed by indocyanine green
angiography (ICGA) at 3 and 12 months. All patients completed a 1-year follow-up.
RESULTS: At the baseline, there was no difference in lesion type, size or visual 
acuity between the two groups. At 1 year, the change in BCVA was -0.0811
logarithm of the minimum angle of resolution (LogMAR) in the PDT-alone group,
compared with -0.0432 logMAR in the PDT+TA group. There was no significant
difference in the change in BCVA between the two groups (P = 0.6910). The PDT+TA 
group required a lower mean number of treatments (1.64 compared with 2.34 [P =
0.0223]) and showed a higher rate of choriocapillaris occlusion at 3 months, but 
no significant difference at 1 year (P = 0.9243) CONCLUSIONS: Fewer retreatments 
were required in the TA+PDT group. There was no significant difference in the
change in BCVA between the two groups. Adjacent TA may promote short-term
choriocapillaris hypoperfusion.

PMID: 17805556 [PubMed - indexed for MEDLINE]

682: Korean J Ophthalmol. 2007 Sep;21(3):146-50.

Evaluation of the efficacy of vitrectomy for persistent diabetic macular edema
and associated factors predicting outcome.

Song SJ, Sohn JH, Park KH.

Department of Ophthalmology, Kangbuk Samsung Hospital, Sungkyunkwan University
College of Medicine, Seoul, Korea.

PURPOSE: To evaluate the efficacy of vitrectomy for persistent diabetic macular
edema after laser photocoagulation or intravitreal triamcinolone injections and
to determine the demographic and ocular factors that influence functional and
anatomical outcomes. METHODS: We retrospectively evaluated 55 eyes (51 patients) 
that had persistent diffuse macular edema after laser photocoagulation or
intravitreal triamcinolone injections. We compared preoperative and postoperative
best corrected visual acuity and macular thickness by Optical Coherence
Tomography and investigated factors including patient's age, presence of
vitreomacular traction, grade of diabetic retinopathy, and intraoperative
internal limiting membrane removal that may influence the surgical results.
RESULTS: The mean preoperative BCVA (log MAR) was 0.91+/-0.40 (0.8-1.2). The BCVA
improved to 0.72+/-0.39 (0.3-1.2). The mean preoperative macular thickness was
440+/-130 (202-805) micrometer and the mean macular thickness decreased to
306+/-97 (136-580) micrometer postoperatively. The eyes showed statistically
significant improvement in BCVA and central macular thickness (p<0.001).
Preoperative better BCVA was associated with an improved postoperative visual
acuity. (p=0.04). No other covariates were found to be statistically significant 
factors for prognosis of postoperative BCVA. CONCLUSIONS: In eyes with persistent
diabetic macular edema after laser or IVTA injections, vitrectomy was effective
for decreasing macular thickness and improvement of vision. The visual
improvement after vitrectomy was associated with the preoperative better BCVA.

Publication Types: 
    Evaluation Studies

PMID: 17804919 [PubMed - indexed for MEDLINE]

683: Acta Ophthalmol. 2008 May;86(3):292-6. Epub 2007 Sep 4.

Screening for cystoid macular oedema in children with uveitis using the retinal
thickness analyser.

Maca SM, Garhofer G, Kiss C, Barisani-Asenbauer T.

Department of Ophthalmology, Medical University Vienna, Vienna, Austria.

PURPOSE: This study aimed to investigate the retinal thickness analyser (RTA) as 
a means to identify the presence of cystoid macular oedema (CMO) in children with
uveitis, whether the course of CMO can be monitored using this method, and
whether there is a trend towards a correlation between macular oedema and visual 
acuity (VA) in children. METHODS: This prospective, cross-sectional study with
observer-blinded analysis included 25 eyes. Standardized testing for best
corrected distance VA (d-VA), near (reading) VA (n-VA) and slit-lamp examination 
were conducted. Using the RTA, a 3 x 3-mm scan of the macula was obtained, which 
was then used to discern CMO and calculate mean foveal thickness (MFT). RESULTS: 
Macular scanning was possible in all children. Cystoid macular oedema was
discerned in 10 eyes (40%) and ruled out in 15. In CMO eyes, d-VA was 0.5 Snellen
and n-VA was 2 Jaeger; neither result differed significantly from those in eyes
without CMO. Mean foveal thickness correlated with n-VA (r = 0.511, p = 0.015),
but not with d-VA (r = 0.271, p = 0.191). After 3 months of tailored therapy, CMO
was still detectable in six eyes. Changes in d-VA in the CMO and non-CMO groups
were 3 +/- 2.1 and 0.8 +/- 1.8 Snellen, respectively; changes in n-VA were 1 +/- 
1.4 and 0.1 +/- 0.3 Jaeger, respectively. Changes in MFT were - 244.8 +/- 137.4
microm and - 0.8 +/- 18.1 microm, respectively. A statistically significant
correlation was found between the changes in MFT and n-VA (r = 0.629), but not
with that in d-VA (r = 0.292). CONCLUSIONS: We used the RTA to establish the
presence or absence of CMO according to measurements of the macular region. Our
findings show that CMO is a common complication in children with uveitis and can 
be present even in cases with good d-VA. Mean foveal thickness as measured with
the RTA correlates indirectly with n-VA.

PMID: 17803720 [PubMed - indexed for MEDLINE]

684: J Ocul Pharmacol Ther. 2007 Aug;23(4):387-94.

Short-term results of intravitreal bevacizumab for macular edema with retinal
vein obstruction and diabetic macular edema.

Byeon SH, Kwon YA, Oh HS, Kim M, Kwon OW.

Department of Ophthalmology, Institute of Vision Research, Yonsei University
College of Medicine, Seoul, Korea.

OBJECTIVE: The aim of this study was to identify the short-term effect, safety,
and durability of intravitreally injected bevacizumab in patients with macular
edema (ME) caused by retinal vein obstruction (RVO) and diabetic macular edema
(DME). METHODS: We retrospectively evaluated 39 eyes of 36 patients, 14 with ME
caused by RVO and 25 with DME, who received intravitreal bevacizumab (1.25 mg)
and were followed up for at least 3 months. Monthly assessments examined safety, 
best corrected visual acuity with an ETDRS chart (logMAR), and central retinal
thickness (CRT) using optical coherence tomography. RESULTS: No significant
ocular or systemic side-effects were observed. The follow-up period was 5.4 +/-
1.1 months (mean +/- standard deviation). During follow-up, the mean number of
injections was 1.4 +/- 0.5. The baseline mean logMAR was 0.91 +/- 0.51, and the
mean CRT was 552.6 +/- 186.7 microm. At 1, 2, and 3 months, the mean logMAR was
0.67 +/- 0.46 (paired t test, P < 0.001), 0.66 +/- 0.46 (P < 0.001), and 0.69 +/-
0.45 (P < 0.001), respectively, and the mean CRT was 323.1 +/- 151.9 mum (P <
0.001), 324.6 +/- 136.9 mum (P < 0.001), and 382.5 +/- 130.4 microm (P < 0.001), 
respectively. Fourteen (14) of 34 eyes with more than 3 months of follow-up
required a second injection at a mean 3.4 +/- 1.0 months after the initial
injection. For both ME caused RVO and DME patients, a bevacizumab administration 
improved logMAR and CRT at each time point through to 6 months, except for logMAR
in DME at 1 week (P = 0.081), 5 months (P = 0.130) and 6 months (P = 0.759).
CONCLUSIONS: An intravitreal bevacizumab injection for ME caused by RVO and DME
was safe and effective for improving visual acuity and reducing CRT.

PMID: 17803438 [PubMed - indexed for MEDLINE]

685: Mol Immunol. 2007 Sep;44(16):3901-8.

The role of complement system in ocular diseases including uveitis and macular
degeneration.

Jha P, Bora PS, Bora NS.

Department of Ophthalmology, Jones Eye Institute, University of Arkansas for
Medical Sciences, 4301 West Markham, Little Rock, AR 72205, USA.

In the normal eye, the complement system is continuously activated at low levels 
and both membrane-bound and soluble intraocular complement regulatory proteins
tightly regulate this spontaneous complement activation. This allows protection
against pathogens without causing any damage to self-tissue and vision loss. The 
complement system and complement regulatory proteins control the intraocular
inflammation in autoimmune uveitis and play an important role in the development 
of corneal inflammation, age-related macular degeneration and diabetic
retinopathy. The evidence derived from both animal models and patient studies
support the concept that complement inhibition is a relevant therapeutic target
in the treatment of various ocular diseases. Currently, several clinical trials
using complement inhibitors are going on. It is possible that, in the near
future, complement inhibitors might be used as therapeutic agents in eye clinics.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Review

PMID: 17768108 [PubMed - indexed for MEDLINE]

686: Nat Genet. 2007 Oct;39(10):1200-1. Epub 2007 Sep 2.

Variation in complement factor 3 is associated with risk of age-related macular
degeneration.

Maller JB, Fagerness JA, Reynolds RC, Neale BM, Daly MJ, Seddon JM.

Center for Human Genetic Research, Massachusetts General Hospital, Boston,
Massachusetts 02114, USA.

The association of variants in complement factors H and B with age-related
macular degeneration has led to more intense genetic and functional analysis of
the complement pathway. We identify a nonsynonymous coding change in complement
factor 3 that is strongly associated with risk of age-related macular
degeneration in a large case-control sample.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17767156 [PubMed - indexed for MEDLINE]

687: Am J Ophthalmol. 2007 Sep;144(3):449-51.

Intravitreal bevacizumab for the treatment of retinal angiomatous proliferation.

Costagliola C, Romano MR, dell'Omo R, Cipollone U, Polisena P.

Dipartimento di Scienze per la Salute, Università degli Studi del Molise,
Campobasso, Italy.

PURPOSE: To verify the potential efficacy of intravitreal bevacizumab (IVB)
injections for the treatment of retinal angiomatous proliferation (RAP). DESIGN: 
Retrospective interventional case series. METHODS: Four consecutive patients
affected by RAP at different stages and refractory to photodynamic therapy (PDT).
All patients underwent a complete ophthalmic examination including best-corrected
visual acuity (BCVA), fluorescein and indocyanine green angiographies, and
optical coherence tomography (OCT) at baseline, and after one, three, six, nine, 
and 12 months. All patients received IVB injections (1.25 mg/0.05 ml). RESULTS:
The best functional response has been achieved in patients with RAP at stages 1
and 2; whereas in stage 3, a detectable recovery of visual acuity was not
observed. This improvement was stable over the follow-up period with a
concomitant reduction of macular thickness. CONCLUSIONS: The use of IVB in
patients affected by RAP seems to exert morphologic benefits at all RAP stages
that does not always correspond a functional improvement.

PMID: 17765426 [PubMed - indexed for MEDLINE]

688: Semin Ophthalmol. 2007 Jul-Sep;22(3):171-3.

Retinal astrocytic hamartoma with associated macular edema: report of spontaneous
resolution of macular edema as a result of increasing hamartoma calcification.

Iaccheri B, Fiore T, Cagini C, Giansanti F, Androudi S, Brazitikos PD.

Department of Ophthalmology, Monteluce Hospital, University of Perugia, Perugia, 
Italy.

The purpose of this article is to report a case of retinal astrocytic hamartoma
with an associated macular edema and the spontaneous resolution of the latter due
to an increase in hamartoma calcification over a seven-year follow-up period.
Clinical examination, red-free and colour fundus photographs, fluorescein
angiography, and optical coherence tomography were performed during a seven-year 
follow-up. We conclude that retinal astrocytic hamartomas may be associated with 
cystoid macular edema. In some cases, the CME may resolve due to an increase in
tumor calcification. Whether the progressive calcification of the retinal mass
represents an overall positive prognostic factor is still unknown and further
histologic studies are certainly required.

Publication Types: 
    Case Reports

PMID: 17763239 [PubMed - indexed for MEDLINE]

689: Semin Ophthalmol. 2007 Jul-Sep;22(3):155-61.

The coexistence of age-related macular degeneration and retinitis pigmentosa in
three unrelated families.

Sarraf D, Salib DM, Jain A, Quiram PA.

Jules Stein Eye Institute, University of California, Greater LA VA Healthcare
Center, Los Angeles, CA 90095, USA. dsarraf@ucla.edu

PURPOSE: To describe the clinical, electroretinographic (ERG) and genetic
findings in three unrelated families with a coexistence of severe, atrophic
age-related macular degeneration (ARMD) in the first generation and rod-cone
retinitis pigmentosa (RP) in the second generation. METHODS: Patients underwent
complete ophthalmologic examination, fluorescein angiography (FA), Humphrey
visual field (HVF) and ERG analyses. Genetic screening was conducted to search
for mutations of the ABCA4, peripherin/RDS, and GCAP-1 genes. RESULTS: In each of
the three families, the mother demonstrated severe vision loss from geographic
atrophy (GA). At least one child in each family demonstrated clinical and ERG
evidence of rod-cone RP with a flat or severely depressed scotopic response and a
variably depressed photopic response. Genetic screening was negative for known
mutations in ABCA4, peripherin/RDS and GCAP-1 genes. CONCLUSIONS: The coexistence
of ARMD and RP in different members of one family lacks precedent in the
literature. Here we present three families with severe, atrophic ARMD (GA) in the
mothers and rod-cone RP in the children, which may represent a novel phenotype. A
currently unidentified genetic mutation with variable expression and/or gene
manifesting a carrier state may explain the presence of these two diseases in the
same family.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 17763236 [PubMed - indexed for MEDLINE]

690: Semin Ophthalmol. 2007 Jul-Sep;22(3):151-3.

Cystoid macular edema with docetaxel chemotherapy and the fluid retention
syndrome.

Telander DG, Sarraf D.

Department of Ophthalmology, University of California, Davis, Sacramento, CA,
USA.

Docetaxel (Taxotere) is an anticancer agent used to treat a wide range of
malignancies including breast, lung, and prostate cancer. In this report, we
describe a patient with bilateral vision loss due to cystoid macular edema (CME) 
associated with docetaxel therapy. This report documents for the first time the
optical coherence tomography (OCT) findings of CME despite the lack of leakage
with flourescein angiography and its association with the Fluid Retention
Syndrome (FRS). Successful management of CME with oral acetazolamide is also
discussed.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 17763235 [PubMed - indexed for MEDLINE]

691: Ann Ophthalmol (Skokie). 2006 Winter;38(4):339-42.

Is transpupillary thermotherapy applicable to the treatment of age-related
macular degeneration with pigment epithelial detachment?

Honda M, Mizota A, Sakuma T, Tanaka M.

Department of Ophthalmology, Juntendo University, Urayasu Hospital, Urayasu,
Japan.

The cause of pigment epithelial tears at the edge of a pigment epithelial
detachment (PED) following transpupillary thermotherapy in eyes with associated
age-related macular degeneration is unclear. We have treated 2 eyes which had a
PED with TTT. Our findings suggest pigment epithelial tears are probably related 
to the shape of the PED and TTT should not applied to a balloon-shaped PED.

Publication Types: 
    Case Reports

PMID: 17726222 [PubMed - indexed for MEDLINE]

692: Ann Ophthalmol (Skokie). 2006 Winter;38(4):317-20.

Intravitreal triamcinolone for cystoid macular edema related to branch retinal
vein occlusion.

Bearelly S, Cooney MJ, Stinnett S, Fekrat S.

Albert Eye Research Institute, Duke University Eye Center, Department of
Ophthalmology, Durham, NC 27710, USA. beare002@mc.duke.edu

We retrospectively evaluated the effectiveness of intravitreal triamcinolone in
treating 19 eyes with macular edema related to branch retinal vein occlusion
(BRVO). Eyes with nonischemic BRVO respond more favorably than those with
ischemic BRVO. A single injection of intravitreal triamcinolone led to elevated
intraocular pressure in 3 of 19 eyes (16%). Half of phakic eyes had progression
of cataract. Retreatment may be necessary.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17726219 [PubMed - indexed for MEDLINE]

693: Ann Ophthalmol (Skokie). 2006 Winter;38(4):305-10.

Visual acuity and diabetic maculopathy.

Ang GS, Vusirikala B, Mukherji S, Ram AR.

Department of Ophthalmology, Royal Glamorgan Hospital, Llantrisant, South Wales, 
United Kingdom.

We investigated the relationship between visual acuity (VA) and glycosylated
hemoglobin, and the presentation and type of diabetic maculopathy retrospectively
from 2000 to 2003. Data on 103 eyes of 75 patients were gathered. No
statistically significant correlation was found between serum HbA1c with
maculopathy type. VA is a poor predictor for the presence or absence of
clinically significant diabetic maculopathy and type of maculopathy, emphasizing 
the importance of systematic screening for and early treatment of maculopathy
before visual loss.

Publication Types: 
    Comparative Study

PMID: 17726217 [PubMed - indexed for MEDLINE]

694: Klin Oczna. 2007;109(4-6):138-41.

Macular microcirculation blood flow in patients with age related macular
degeneration treated with photodynamic therapy and transpupillary thermotherapy.

Kubicka-Trzaska A.

Department of Ophthalmology, Medical College, Jagiellonian University, Kraków.

PURPOSE: To assess the macular retinal and choroidal microcirculation blood flow 
in patients with exudative age related macular degeneration before and after
photodynamic therapy (PDT) or transpupillary thermotherapy (TTT) with Doppler
laser scanning (HRF--Heidelberg retinal flowmeter). MATERIAL AND METHODS: Thirty 
patients with exudative age-related macular degeneration were included in a
prospective study. The diagnosis was established based on ophthalmic examination 
and fluorescein angiography results. In all cases the subfoveal choroidal
neovascularization (CNV) was present. Control group consists of the fellow eyes
with early stage of AMD (19 eyes) or with disciform scar (11 eyes). In 15 eyes
with active CNV PDT was performed and in remaining 15--TTT. In all cases the
macular blood flow was measured with Heidelberg retina flowmeter (HRF) before
therapy and then 1 week, 4 weeks and 10-12 weeks after treatment. RESULTS: At the
baseline examination in a group of eyes with active CNV the mean values of
macular blood flow were significantly higher comparing to the fellow eyes and
reached respectively: 678.6 +/- 125.0 AU and 298.4 +/- 79.2 AU (p=0.001). Four
weeks after treatment all eyes showed the reduction of macular blood flow
comparing to the baseline values (p=0.001). Ten to twelve weeks after laser
therapy in all cases the increased macular blood flow was detected comparing to
the previous examination (p=0.01). During the follow-up period the macular blood 
flow in the fellow eyes were significantly lower than in treated eyes.
CONCLUSIONS: The measurement of macular blood flow using Doppler scanning laser
(HRF--Heidelberg retinal flowmeter) may act as a non-invasive and useful
diagnostic tool in assessment of CNV activity in patients with exudative
age-related degeneration before and after PDT or TTT.

Publication Types: 
    Comparative Study

PMID: 17725271 [PubMed - indexed for MEDLINE]

695: Can J Ophthalmol. 2007 Oct;42(5):720-6.

Dietary lutein, zeaxanthin, and fats and the progression of age-related macular
degeneration.

Robman L, Vu H, Hodge A, Tikellis G, Dimitrov P, McCarty C, Guymer R.

Centre for Eye Research Australia, University of Melbourne. liubov@unimelb.edu.au

BACKGROUND: To estimate the effect of dietary intake of lutein and zeaxanthin
(L/Z) and fats on the progression of age-related macular degeneration (AMD).
METHODS: Two hundred and fifty-four subjects identified with early age-related
macular degeneration (AMD) were re-examined to determine 7-year AMD progression. 
Intakes of L/Z and fatty acids were estimated from food frequency questionnaires.
Progression was defined by 3 different definitions, 2 quantitative and 1
qualitative, which varied in the stringency of the change required for the AMD to
be deemed to have progressed. Covariates included age, smoking, AMD family
history, source study, and follow-up duration. RESULTS: Energy-adjusted L/Z
intake as a continuous variable was associated with AMD progression in the worse 
affected eye when defined by the most stringent criterion (odds ratio [OR] =
2.65, 95% confidence interval [CI] 1.13-6.22, p = 0.02). Similar associations
were observed for the 2 other progression definitions (p = 0.18 and p = 0.13).
Energy-adjusted omega-3 fatty acid intake modelled as a quintile median was
associated with AMD progression only in the side-by-side assessment (OR = 2.56,
95% CI 1.11-5.91, p = 0.03), with borderline significance in the other 2
definitions (p = 0.05 and p = 0.08). No association of AMD progression was
observed with the intake of either total fat or other subgroups: saturated,
polyunsaturated, or monounsaturated fats; trans fatty acids; or omega-6 fatty
acids. INTERPRETATION: The findings of the study are counterintuitive, suggesting
that increased intakes of dietary L/Z and omega-3 fatty acids are associated with
progression of AMD. These results may indicate that too much of a good thing
might be harmful. It is possible that in this study participants adopted a more
healthy diet, having been aware of their AMD status at the beginning of the
study. This healthy diet was then reflected in the dietary questionnaire
completed at the end of study. However, this explanation may not adequately
explain why those whose AMD had progressed, on the basis of fundus signs and not 
symptoms such as visual acuity decline, adopted a healthier lifestyle more
aggressively than those without progression.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17724493 [PubMed - indexed for MEDLINE]

696: Invest Ophthalmol Vis Sci. 2007 Sep;48(9):4300-7.

Reproducibility of quantitative optical coherence tomography subanalysis in
neovascular age-related macular degeneration.

Joeres S, Tsong JW, Updike PG, Collins AT, Dustin L, Walsh AC, Romano PW, Sadda
SR.

Doheny Image Reading Center, Doheny Eye Institute, Keck School of Medicine,
University of Southern California, Los Angeles, CA 90033, USA.

PURPOSE: To determine the intergrader reproducibility for computer-assisted
grading of optical coherence tomography (OCT) images in eyes with neovascular
age-related macular degeneration (AMD), by using a standardized grading
procedure. METHODS: Sixty OCT image sets (of six radial lines each) were
independently analyzed by two graders using validated custom software (OCTOR) to 
draw boundaries manually on OCT B-scans. Spaces delineated by these boundaries
included retina, subretinal fluid, subretinal tissue, and pigment epithelial
detachments (PEDs). Volume measurements for the nine Early Treatment of Diabetic 
Retinopathy Study (ETDRS) subfields and the mean foveal center point (FCP)
thickness were calculated by the software and compared by using weighted kappa
statistics and intraclass correlation coefficients (ICCs). RESULTS: Intergrader
comparison of the foveal central subfield (FCS) volume, total volume, and mean
FCP thickness showed a high level of agreement and strong correlation between
measurements for all spaces (kappa(weighted) = 0.72-0.97; ICC = 0.92-0.99). The
best agreement was observed for total volume of the combination of all four
graded spaces (kappa(weighted) = 0.97, mean difference = 0.31 mm(3), or 2.51%).
The highest ICCs were seen for FCP thickness measurements. The poorest agreement 
was found for grading of subretinal tissue. Eyes with advanced choroidal
neovascularization (CNV) and poor visibility of the retinal pigment epithelium
(RPE) band appeared to show the greatest intergrader discrepancies. CONCLUSIONS: 
Analysis of OCT images by trained graders using computer-assisted grading
software allows for highly reproducible quantitative measurements, even in eyes
with complex diseases such as neovascular AMD. Quantitative subanalysis may be
useful in studying the differential morphologic effect of therapies on various
anatomic components.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 17724220 [PubMed - indexed for MEDLINE]

697: Invest Ophthalmol Vis Sci. 2007 Sep;48(9):4277-83.

Haplotypes spanning the complement factor H gene are protective against
age-related macular degeneration.

Spencer KL, Hauser MA, Olson LM, Schnetz-Boutaud N, Scott WK, Schmidt S, Gallins 
P, Agarwal A, Postel EA, Pericak-Vance MA, Haines JL.

Center for Human Genetics Research, Vanderbilt University Medical Center,
Nashville, Tennessee 37232, USA.

PURPOSE: Age-related macular degeneration (AMD) is a devastating disorder that
adversely affects the quality of life of nearly 2 million Americans who have
advanced forms of the disease. Besides the well-known risk imparted by carrying
the Y402H variant in the complement factor H (CFH) gene on chromosome 1, recent
evidence of the existence of protective haplotypes spanning CFH has been
reported. METHODS: The haplo.stats program was used to test for association of
the protective haplotypes after adjusting for age in the dataset of 584 sporadic 
cases and 248 control samples. Logistic regression modeling and likelihood ratio 
tests were used to investigate an interaction between a particular haplotype and 
smoking status. The HBAT option of FBAT was used to confirm the associations in
an independent dataset of 201 families. RESULTS: Two protective (P) haplotypes in
a family-based dataset (P1 = CAATTTAG, P = 0.021; and P2 = CGGCTTAG, P = 0.018)
were identified for the first time. Age-adjusted score statistics provided
support for these protective haplotypes in the case-control dataset (P1 frequency
in cases approximately 13%, in controls approximately 20%, P = 0.001; P2
frequency in cases approximately 5%, in controls approximately 8%, P = 0.077).
There was also tentative evidence of an interaction between one of the protective
haplotypes and cigarette smoking (P = 0.04 likelihood ratio test for P2-smoking
interaction). CONCLUSIONS: Replication of the association between the protective 
haplotypes and decreased AMD susceptibility provides increased evidence that
these associations have biological meaning. The suggestion of a haplotype-smoking
interaction adds to the growing body of evidence that smoking is an important
environmental covariate in AMD that should be considered in genetic studies.
Identification of the protective variant(s) carried within these haplotypes is
critical for understanding the etiology of AMD.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 17724217 [PubMed - indexed for MEDLINE]

698: Invest Ophthalmol Vis Sci. 2007 Sep;48(9):4007-11.

Exposure to Chlamydia pneumoniae infection and age-related macular degeneration: 
the Blue Mountains Eye Study.

Robman L, Mahdi OS, Wang JJ, Burlutsky G, Mitchell P, Byrne G, Guymer R, Taylor
H.

Centre for Eye Research Australia, University of Melbourne, Melbourne, Australia.

PURPOSE: To assess cross-sectional and longitudinal associations between exposure
to Chlamydia pneumoniae infection and age-related macular degeneration (AMD) in
the nested case-control sample drawn from the Blue Mountains Eye Study (BMES)
cohort. METHODS: The BMES examined 3654 persons aged 49 to 97 years during 1992
through 1994 (BMES I survey). Survivors from this cohort (n = 2335; 75%) and 1174
persons who moved in this area or reached an eligible age were examined during
1997 through 2000 (BMES II survey, n = 3509). One hundred ninety-seven AMD cases 
and 433 control subjects matched for age, sex and smoking status, were drawn from
the BMES II survey. Photographic macular grading followed the Wisconsin grading
system. Plasma samples were analyzed with an enzyme-linked immunosorbent assay to
determine antibody titers to the elementary bodies from C. pneumoniae AR39.
Associations between seroreactivity to C. pneumoniae and prevalent and incident
AMD were assessed by using logistic regression models. RESULTS: There were 159
early and 38 late AMD cases. Of them, 87 cases of early and 22 of late AMD
developed between the baseline and follow-up examinations. After adjustment for
age, gender, and smoking, no significant association was evident between C.
pneumoniae antibody titer and any prevalent early or late AMD (OR 1.02, 95% CI
0.66-1.56 comparing upper with lower tertile of antibody titer). Findings were
similar when early or late AMD was analyzed separately. Analysis confined to
incident AMD also showed no significant association with the incidence of either 
early (OR 0.92, 95% CI 0.52-1.64) or late (OR 1.85, 95% CI 0.57-6.05) AMD. The
results did not change after adjustment for family history of AMD and
cardiovascular disease. CONCLUSIONS: In this nested case-control sample of an
older Australian population we found no association between C. pneumoniae
antibody titers and early AMD. The study has insufficient power to assess an
association with late AMD.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17724180 [PubMed - indexed for MEDLINE]

699: Invest Ophthalmol Vis Sci. 2007 Sep;48(9):3983-7.

Progression of diabetic macular edema: correlation with blood retinal barrier
permeability, retinal thickness, and retinal vessel diameter.

Sander B, Thornit DN, Colmorn L, Strøm C, Girach A, Hubbard LD, Lund-Andersen H, 
Larsen M.

Department of Ophthalmology, Glostrup Hospital, University of Copenhagen,
Denmark. bisan@glo.regionh.dk

PURPOSE: To study the progression of diabetic macular edema (DME) in relation to 
baseline retinal thickness, retinal vascular leakage, and retinal trunk vessel
diameters. METHODS: In this single-center study, 45 patients were enrolled with
62 eligible eyes defined as having DME of a grade less than clinically
significant macular edema (CSME). From the start, the patients were included in a
multicenter study exploring the effect of ruboxistaurin versus placebo for 3.4
years. Subsequently, the patients were followed up for a mean of 5.7 years by
optical coherence tomography, fundus photography, and vitreous fluorometry.
Baseline values in eyes that progressed to photocoagulation treatment were
compared with values from eyes that did not reach this endpoint. RESULTS: In the 
22 eyes of 18 patients in which CSME was diagnosed and treated, mean retinal
vascular leakage at baseline was 5.6 (95% CI 4.2-7.6) nm/s, whereas eyes that did
not progress to photocoagulation had a significantly lower mean leakage at
baseline of 3.4 (95% CI 2.7-4.3) nm/s. No significant difference was found for
measures of baseline retinal thickness or summarized retinal trunk vessel
diameters. Eyes that progressed to photocoagulation treatment (mean delay to
treatment, 3.6 years) had significantly higher foveal thicknesses than did
nonprogressing eyes, from 18 months after study initiation. CONCLUSIONS:
Progression to photocoagulation treatment for CSME was associated with higher
retinal vascular leakage at baseline, whereas baseline retinal vessel diameters
and retinal thickness were comparable in progressing and nonprogressing eyes.
Baseline leakage was the strongest predictor of progression from non-CSME to
photocoagulation for CSME.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17724176 [PubMed - indexed for MEDLINE]

700: Int J Nanomedicine. 2007;2(1):65-77.

Age-related macular degeneration: a target for nanotechnology derived medicines.

Birch DG, Liang FQ.

Retina Foundation of the Southwest, Dallas, TX 75231, USA.
dbirch@retinafoundation.org

Despite the fact that the retina is a fairly accessible portion of the central
nervous system, there are virtually no treatments for early age-related macular
degeneration (AMD). AMD is a degenerative retinal disease that causes progressive
loss of central vision and is the leading cause of irreversible vision loss and
legal blindness in individuals over the age of 50. Both environmental and genetic
components play a role in its development. AMD is a multifactorial disease with
characteristics that include drusen, hyperpigmentation and/or hypopigmentation of
the retinal pigment epithelium (RPE), geographic atrophy and, in a subset of
patients, late-stage choroidal neovascularization (CNV). Drugs that inhibit
vascular endothelial growth factor (VEGF) have proven effective in treating
late-stage CNV, but optimal means of drug delivery remains to be determined.
Microscopic particles, whose size is on the nanometer scale, show considerable
promise for drug delivery to the retina, for gene therapy, and for powering
prosthetic "artificial retinas." This article summarizes the pathophysiology of
AMD stressing potential applications from nanotechnology.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Review

PMID: 17722514 [PubMed - indexed for MEDLINE]

701: J Cataract Refract Surg. 2007 Sep;33(9):1550-8.

Comment in:
    J Cataract Refract Surg. 2008 May;34(5):717-8; author reply 718.

Clinical pseudophakic cystoid macular edema. Risk factors for development and
duration after treatment.

Henderson BA, Kim JY, Ament CS, Ferrufino-Ponce ZK, Grabowska A, Cremers SL.

Massachusetts Eye and Ear Infirmary, Harvard Medical School, Cambridge,
Massachusetts, USA. bahenderson@eyeboston.com

PURPOSE: To characterize the incidence, duration, and risk factors for and
outcome of cystoid macular edema (CME) after cataract surgery and investigate the
effects of treatment regimens on visual outcome and duration. SETTING:
University-based comprehensive ophthalmology practice. METHODS: This study
included 1659 consecutive cataract surgeries performed by residents between 2001 
and 2006. Cases were classified according to the presence of CME. Subset analysis
excluded patients with diabetes mellitus (DM). The CME groups were analyzed
according to type of treatment to compare duration of CME and final best
corrected visual acuity. RESULTS: The incidence of postoperative CME was 2.35%
(39/1659), and history of retinal vein occlusion (RVO) was predictive of
postoperative CME (odds ratio [OR], 47.12; P<.001). When patients with DM were
excluded, the incidence of CME was 2.14% (29/1357) and history of RVO (OR, 31.75;
P<.001), epiretinal membrane (ERM) (OR, 4.93; P<.03), and preoperative
prostaglandin use (OR, 12.45; P<.04) were predictive of postoperative CME.
Patients with DM and/or intraoperative complications did not have an increased
risk for CME when treated with prophylactic postoperative nonsteroidal
antiinflammatory drugs (NSAIDs) for 3 months. Groups treated with NSAIDs plus a
steroid had significantly shorter resolution times than the untreated group (P = 
.004). CONCLUSIONS: A history of RVO, ERM, and preoperative prostaglandin use
were associated with an increased risk for pseudophakic CME. Treatment with
NSAIDs plus steroids was associated with faster resolution of CME than no
treatment. Treating high-risk patients with NSAIDs after cataract surgery
decreases the incidence of postoperative CME to that of patients who are not at
high risk.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17720069 [PubMed - indexed for MEDLINE]

702: J Cataract Refract Surg. 2007 Sep;33(9):1546-9.

Incidence of visually significant pseudophakic macular edema after uneventful
phacoemulsification in patients treated with nepafenac.

Wolf EJ, Braunstein A, Shih C, Braunstein RE.

Edward S. Harkness Eye Institute, Columbia University College of Physicians and
Surgeons, Department of Ophthalmology, 635 West 165th Street, New York, New York 
10032, USA. ericwolfmd@yahoo.com

PURPOSE: To compare the incidence of visually significant pseudophakic macular
edema after uneventful phacoemulsification in patients treated postoperatively
with topical prednisolone and those treated with topical prednisolone and
nepafenac 0.1% suspension (Nevanac). SETTING: Edward S. Harkness Eye Institute of
Columbia University, New York, New York, USA. METHODS: This retrospective chart
review was of consecutive patients who had phacoemulsification at a single
institute and were given topical prednisolone alone or topical prednisolone and
nepafenac to prevent cystoid macular edema. Data collection included preexisting 
ocular and systemic diseases, concurrent use of ocular and systemic medications, 
surgical technique, intraoperative and postoperative complications, follow-up
visual and ocular assessments, and postoperative optical coherence tomography
(OCT) assessment for macular edema. RESULTS: Postoperatively, 240 patients were
treated with prednisolone and 210 patients, with prednisolone-nepafenac.
Preoperatively, the 2 groups were demographically and clinically comparable in
sex distribution (P = .8400), history of diabetes (P = .7267), hypertension or
cardiac disease (P = .8690), and concurrent use of oral nonsteroidal
anti-inflammatory drugs (P = .7303). Iris manipulation was done in 16 patients in
the prednisolone-alone group and 10 patients in the prednisolone-nepafenac group 
(P = .3876). Capsule staining was done in 5 patients and 4 patients,
respectively. All patients were followed for at least 1 month postoperatively.
Visually significant pseudophakic macular edema was documented by OCT in 5
patients treated with prednisolone alone and in no patients treated with
prednisolone and nepafenac (P = .0354). No significant intraoperative or
postoperative complications were reported. CONCLUSION: Patients treated with
topical prednisolone alone had a significantly higher incidence of visually
significant pseudophakic macular edema after uneventful cataract surgery than
those treated with topical prednisolone and nepafenac.

PMID: 17720068 [PubMed - indexed for MEDLINE]

703: Drug Ther Bull. 2007 Jul;45(7):49-52.

A view on new drugs for macular degeneration.

[No authors listed]

Estimates suggest that in Europe 2.3% of people older than 65 years have
neovascular age-related macular degeneration, which can lead to loss of central
vision. The condition is the leading cause of blindness in the estern world, and 
the third commonest worldwide. It is characterised by growth of new blood vessels
beneath the retina (choroidal neovascularisation), a process stimulated by the
secretion of vascular endothelial growth factor (VEGF).3 Two new drugs,
pegaptanib sodium (Macugen - Pfizer) and ranibizumab (Lucentis -Novartis), that
block the effects of VEGF are now licensed in the UK for patients with
neovascular age-related macular degeneration. A third drug that inhibits VEGF
activity, bevacizumab (Avastin - Roche), is also used for this condition but is
licensed only for metastatic colorectal or breast cancer. Here we consider the
role of pegaptanib, ranibizumab and bevacizumab in patients with neovascular
age-related macular degeneration.

Publication Types: 
    Review

PMID: 17718304 [PubMed - indexed for MEDLINE]

704: Int J Nanomedicine. 2006;1(3):263-8.

Pegaptanib in the treatment of wet, age-related macular degeneration.

Vinores SA.

Wilmer Eye Instutute, Johns Hopkins University School of Medicine, 600 N. Wolfe
Street, Baltimore, MD 21287-9289, USA. svinores@jhmi.edu

Age-related macular degeneration (AMD) is a major cause of severe visual loss
worldwide. Neovascular (wet) AMD accounts for 90% of the visual loss associated
with the disorder and vascular endothelial growth factor (VEGF) has been shown to
play a major role in neovascularization and vascular permeability, the major
causes of visual loss in AMD, making it an ideal target for therapeutic
intervention. To utilize this strategy, pegaptanib, an aptamer that specifically 
binds to and blocks VEGF165, the VEGF isoform primarily responsible for abnormal 
vascular growth and permeability in AMD, was developed. Following encouraging
preclinical trials, clinical trials showed that pegaptanib stabilized vision and 
reduced the risk of severe visual loss in the majority of patients with AMD, with
some patients showing visual improvement. Pegaptanib has maintained a good safety
profile with only occasional adverse effects. Even greater success was achieved
when pegaptanib was used in combination with another therapeutic strategy, such
as photodynamic therapy or bevacizumab, a pan isoform VEGF inhibitor. Further
investigation of pegaptanib for the therapy of wet AMD, particularly in
combination with other modes of therapy, should be encouraged.

Publication Types: 
    Review

PMID: 17717967 [PubMed - indexed for MEDLINE]

705: Ophthalmology. 2008 Feb;115(2):324-333.e2. Epub 2007 Aug 22.

Carotenoids and antioxidants in age-related maculopathy italian study: multifocal
electroretinogram modifications after 1 year.

Parisi V, Tedeschi M, Gallinaro G, Varano M, Saviano S, Piermarocchi S; CARMIS
Study Group.

Fondazione G. B. Bietti-Istituto di Ricovero e Cura a Carattere Scientifico,
Roma, Italy. vparisi@tin.it

OBJECTIVE: To evaluate the influence of short-term carotenoid and antioxidant
supplementation on retinal function in nonadvanced age-related macular
degeneration (AMD). DESIGN: Randomized controlled trial. PARTICIPANTS:
Twenty-seven patients with nonadvanced AMD and visual acuity > or =0.2 logarithm 
of the minimum angle of resolution were enrolled and randomly divided into 2
age-similar groups: 15 patients had oral supplementation of vitamin C (180 mg),
vitamin E (30 mg), zinc (22.5 mg), copper (1 mg), lutein (10 mg), zeaxanthin (1
mg), and astaxanthin (4 mg) (AZYR SIFI, Catania, Italy) daily for 12 months
(treated AMD [T-AMD] group; mean age, 69.4+/-4.31 years; 15 eyes); 12 patients
had no dietary supplementation during the same period (nontreated AMD [NT-AMD]
group; mean age, 69.7+/-6.23 years; 12 eyes). At baseline, they were compared
with 15 age-similar healthy controls. METHODS: Multifocal electroretinograms in
response to 61 M-stimuli presented to the central 20 degrees of the visual field 
were assessed in pretreatment (baseline) conditions and, in nonadvanced AMD
patients, after 6 and 12 months. MAIN OUTCOME MEASURES: Multifocal
electroretinogram response amplitude densities (RAD, nanovolt/deg(2)) of the
N1-P1 component of first-order binary kernels measured from 5 retinal
eccentricity areas between the fovea and midperiphery: 0 degrees to 2.5 degrees
(R1), 2.5 degrees to 5 degrees (R2), 5 degrees to 10 degrees (R3), 10 degrees to 
15 degrees (R4), and 15 degrees to 20 degrees (R5). RESULTS: At baseline, we
observed highly significant reductions of N1-P1 RADs of R1 and R2 in T-AMD and
NT-AMD patients when compared with healthy controls (1-way analysis of variance
P<0.01). N1-P1 RADs of R3-R5 observed in T-AMD and NT-AMD were not significantly 
different (P>0.05) from controls. No significant differences (P>0.05) were
observed in N1-P1 RADs of R1-R5 between T-AMD and NT-AMD at baseline. After 6 and
12 months of treatment, T-AMD eyes showed highly significant increases in N1-P1
RADs of R1 and R2 (P<0.01), whereas no significant (P>0.05) change was observed
in N1-P1 RADs of R3-R5. No significant (P>0.05) changes were found in N1-P1 RADs 
of R1-R5 in NT-AMD eyes. CONCLUSIONS: In nonadvanced AMD eyes, a selective
dysfunction in the central retina (0 degrees -5 degrees ) can be improved by the 
supplementation with carotenoids and antioxidants. No functional changes are
present in the more peripheral (5 degrees -20 degrees ) retinal areas.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial

PMID: 17716735 [PubMed - indexed for MEDLINE]

706: Ophthalmology. 2008 Feb;115(2):319-23. Epub 2007 Aug 13.

Comparison of visual acuity in macular degeneration patients measured with
snellen and early treatment diabetic retinopathy study charts.

Falkenstein IA, Cochran DE, Azen SP, Dustin L, Tammewar AM, Kozak I, Freeman WR.

Joan and Irwin Jacobs Retina Center, Department of Ophthalmology, Shiley Eye
Center, University of California, La Jolla, California 92037, USA.

PURPOSE: To compare the measurements of visual acuity (VA) results measured with 
Snellen and Early Treatment Diabetic Retinopathy Study (ETDRS) charts in eyes
with and without age-related macular degeneration (AMD). DESIGN: Cross-sectional 
study. PARTICIPANTS: One hundred four participants (190 eyes) selected from a
university retina practice; 80 participants (142 eyes) had some degree of AMD.
METHODS: Visual acuity was measured in each patient using standard procedure with
both Snellen and ETDRS charts in random order. Statistical analysis of the
results was performed. MAIN OUTCOME MEASURES: Difference in VA measured by both
charts in logarithm of minimal angle of resolution (logMAR) notations. RESULTS:
Overall, the mean Snellen VA was 0.78 logMAR (= 20/120), and the mean ETDRS VA in
the same eye was 0.54 logMAR (= 20/70; P<0.001). In the low vision group
(<20/200), represented by patients with AMD, the average difference in number of 
lines was considerably larger than in the good vision range (>20/30). On average,
20/200 on Snellen was 20/95 on ETDRS (>3 lines difference), and 20/30 on Snellen 
was 20/25 on ETDRS (<1 line difference). CONCLUSION: Our results show poor
agreement between the Snellen and ETDRS charts, and it was more pronounced in the
group with poor vision. The ETDRS measurements yielded better VA, particularly in
participants with vision <20/200 (representing more advanced AMD patients). We
suggest taking these findings into consideration when comparing outcomes in
clinical practices (which typically measure VA using standard Snellen charts)
with outcomes from clinical trials (which typically measure VA using ETDRS
charts).

Publication Types: 
    Comparative Study
    Research Support, N.I.H., Extramural

PMID: 17706288 [PubMed - indexed for MEDLINE]

707: Graefes Arch Clin Exp Ophthalmol. 2007 Nov;245(11):1713-6. Epub 2007 Aug 18.

Complement factor H variant Y402H and basal laminar deposits in exudative
age-related macular degeneration.

Lommatzsch A, Hermans P, Weber B, Pauleikhoff D.

Department of Ophthalmology, St. Franziskus Hospital, Hohenzollernring 74, 48145 
Münster, Germany.

BACKGROUND: Complement factor H (CFH) polymorphism Y402H has been shown to be
significantly associated with age-related macular degeneration (AMD).
Furthermore, histopathological studies in AMD have implicated basal laminar
deposits (BLD) in the development of choroidal neovascularization (CNV)
membranes. The purpose of this study was to correlate CFH staining in BLD with
the CFH genotype at the tyrosine 402 histidine (Y402H) polymorphism. PATIENTS AND
METHODS: During macular translocation, 21 angiographically confirmed CNV
membranes were extracted in 21 patients. The specimens were analysed
histologically for BLD. The presence of CFH, complement proteins, and vitronectin
was determined by immunohistochemistry. Finally, the CFH Y402H genotype was
established by direct sequencing analysis. RESULTS: Histological examination
demonstrated BLD in all of the excised CNV membranes. By immunostaining CFH was
detected in the peripheral aspect at the inner and outer surface of BLD, which
colocalized with other proteins of the complement cascade (C3, C5b-9). Similarly,
vitronectin was detected in all of the BLD investigated. Four patients were
noncarriers of CFH Y402H polymorphism, nine patients were heterozygous and eight 
patients homozygous for the CFH Y402H polymorphism. CONCLUSIONS: BLD are composed
of different complement factors (factor H, C3, C5b-9) and extracellular matrix
proteins such as vitronectin. The prevalence of homozygous carriers in regard to 
CFH Y402H polymorphism, which is suspicious for AMD, might be associated with
increased secretion of vitronectin in response to dysregulation of the complement
cascade.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17704937 [PubMed - indexed for MEDLINE]

708: Graefes Arch Clin Exp Ophthalmol. 2008 Mar;246(3):345-52. Epub 2007 Aug 18.

Reduction of iatrogenic RPE lesions in AMD patients: evidence for wound healing?

Rabenlehner D, Stanzel BV, Krebs I, Binder S, Goll A.

The Ludwig Boltzmann Institute for Retinology and Biomicroscopic Lasersurgery,
Vienna, Austria. doris.rabenlehner@mediatrain.at

PURPOSE: Our purpose was to study retinal pigment epithelium (RPE) wound healing 
in patients with age-related macular degeneration (AMD). PATIENTS AND METHODS:
Abrasive debridement of nasal RPE was performed with a metal cannula during pars 
plana vitrectomy for foveal choroidal neovascularization (CNV) membrane excision 
combined with simultaneous autologous RPE transplantation. Fundus
autofluorescence, fluorescein angiography images, and red-free pictures were
taken initially within 1-2 weeks postoperatively, subsequently in 2-week
intervals until 3 months, monthly until 6 months, and every 3 months thereafter. 
The borders of these lesions were measured; areas were calculated and compared
using ArchiCad Software. Fourteen eyes of 14 patients suffering from AMD were
included (nine women and four men, mean age 75.6 years +/-6.6 years). RESULTS:
Six of 14 (42.9 %) patients showed a reduction of the RPE debrided area. The size
of these lesions reduced 5.6-20% within 2 postoperative months compared with
their size at first examination (from a mean of 13.7 mm2 +/- 7.2 at baseline to a
mean of 12.8 mm2 +/- 6.7 at 2 months postoperatively). No further reduction of
the lesions was seen after the 2 months. In eight cases, borders of the RPE
debrided areas stayed stable during observation time. CONCLUSIONS: Wound healing 
of abrasively debrided RPE monolayer defects in patients with AMD occurs to a
certain extent in nearly half of the cases. This process seems to stop after 2
months.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17704936 [PubMed - indexed for MEDLINE]

709: Histol Histopathol. 2007 Dec;22(12):1301-8.

Oxidative damage in age-related macular degeneration.

Shen JK, Dong A, Hackett SF, Bell WR, Green WR, Campochiaro PA.

The Department of Ophthalmology, The Johns Hopkins University School of Medicine 
Maumenee, Baltimore, Maryland 21287-9277, USA.

Epidemiologic studies have suggested that elderly patients who consumed diets
rich in antioxidants throughout their lives are less likely to be afflicted with 
age-related macular degeneration (AMD). This led to the Age-Related Eye Disease
Study, which showed that supplements containing antioxidant vitamins and zinc
reduce the risk of progression to severe stages of AMD. Despite these data that
indirectly implicate oxidative damage in the pathogenesis of AMD, there has not
been any direct demonstration of increased oxidative damage in the retinas of
patients with AMD. In this study, we used biomarkers of oxidative damage in
postmortem eyes from patients with AMD and comparably aged patients without AMD
to directly assess for oxidative damage. Sections from 4 eyes with no pathologic 
features of AMD showed no immunofluorescent staining for markers of oxidative
damage, while sections from 8 of 12 eyes with advanced geographic atrophy showed 
evidence of widespread oxidative damage in both posterior and anterior retina.
Only 2 of 8 eyes with choroidal neovascularization and 2 of 16 eyes with diffuse 
drusen and no other signs of AMD showed evidence of oxidative damage. These data 
suggest that widespread oxidative damage occurs in the retina of some patients
with AMD and is more likely to be seen in patients with advanced geographic
atrophy. This does not rule out oxidative damage as a pathogenic mechanism in
patients with CNV, but suggests that a subpopulation of patients with geographic 
atrophy may have a major deficiency in the oxidative defense system that puts the
majority of cells in the retina at risk for oxidative damage.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17701910 [PubMed - indexed for MEDLINE]

710: Drugs Aging. 2007;24(8):643-62.

Targeting vascular endothelial growth factor: a promising strategy for treating
age-related macular degeneration.

Waisbourd M, Loewenstein A, Goldstein M, Leibovitch I.

Ophthalmology Department, Tel-Aviv Sourasky Medical Centre, Tel-Aviv University, 
Tel-Aviv, Israel. mwaisbourd@hotmail.com

Age-related macular degeneration (AMD) is the leading cause of irreversible
visual loss in the industrialised world. While treatment options for advanced AMD
have been rather limited until recently, the introduction of intravitreal
injections of anti-angiogenic agents appears to be a promising and revolutionary 
mode of treatment for this blinding disease. Vascular endothelial growth factor
(VEGF) appears to play a pivotal role in the pathogenesis of choroidal
neovascularisation, one of the cornerstones of advanced AMD. Pegaptanib, the
first anti-VEGF treatment approved for AMD patients, is a VEGF-neutralising
aptamer that specifically inhibits one isoform of VEGF (VEGF-165). Although
evidence suggested that pegaptanib was superior to previous treatment options,
results with this agent were still unsatisfactory. Ranibizumab is a humanised
anti-VEGF monoclonal antibody fragment that inhibits all isotypes of VEGF. This
new drug has demonstrated a high efficacy profile in terms of inhibiting disease 
progression and even improving visual acuity. Bevacizumab is a full-length
anti-VEGF antibody that was originally approved for use in metastatic colon
cancer and is under investigation as a low-cost off-label alternative for
patients with AMD. There is growing evidence that this drug may be an effective
and safe alternative to the more expensive ranibizumab, although prospective
multicentre trials are required to fully investigate this issue. Undoubtedly, the
concept of directly injecting anti-VEGF drugs into the vitreal cavity brings new 
hope to many AMD patients.

Publication Types: 
    Review

PMID: 17702534 [PubMed - indexed for MEDLINE]

711: Int Ophthalmol. 2008 Aug;28(4):291-6. Epub 2007 Aug 16.

Intravitreal triamcinolone acetonide for the management of papillophlebitis and
associated macular edema.

Chang YC, Wu WC.

Department of Ophthalmology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung
Medical University, Kaohsiung, Taiwan.

BACKGROUND: To investigate the efficacy of intravitreal injection of
triamcinolone acetonide in the management of papillophlebitis and associated
cystoid macular edema. METHODS: This study was a retrospective medical records
review of four eyes of four patients (three males and one female) who had
approximately 2-4 months history of papillophlebitis and associated persistent
cystoid macular edema. These patients were treated with a single intravitreal
injection of 4 mg triamcinolone acetonide. Mean follow-up time was 15 +/- 4
months. The outcome measures included best corrected visual acuity (BCVA),
intraocular pressure (IOP), and central retinal thickness by optical coherence
tomography (OCT). RESULTS: The BCVA ranged from 20/100 to 20/60 pre-operation.
The mean gain in BCVA was 7 +/- 1 Snellen lines. All eyes had BCVA of 20/20 at
the last visit. The mean baseline central retinal thickness as measured by OCT
was 529 +/- 53 microm. The mean central retinal thickness by OCT was 235 +/- 15
microm at 1-week follow-up examination. At the last visit the mean central
retinal thickness by OCT was 161 +/- 7 microm. One patient experienced an
increase in IOP after the first injection and another patient had IOP elevation
after the second injection. Both were well controlled with single topical
anti-glaucoma medication. CONCLUSION: Intravitreal injection of triamcinolone
acetonide appears to be an effective treatment for patients with papillophlebitis
and associated cystoid macular edema.

Publication Types: 
    Comparative Study

PMID: 17701380 [PubMed - indexed for MEDLINE]

712: Graefes Arch Clin Exp Ophthalmol. 2008 Jan;246(1):17-25. Epub 2007 Aug 15.

Combined intravitreal bevacizumab and photodynamic therapy for neovascular
age-related macular degeneration.

Ladewig MS, Karl SE, Hamelmann V, Helb HM, Scholl HP, Holz FG, Eter N.

Department of Ophthalmology, University of Bonn, Ernst-Abbe-Strasse 2, 53127,
Bonn, Germany.

BACKGROUND: Our aim was to evaluate the short-term safety and efficacy of
combined photodynamic therapy (PDT) with verteporfin and intravitreal bevacizumab
in neovascular age-related macular degeneration (AMD). METHODS: A prospective
non-randomized interventional case series of 30 eyes of 30 patients with
choroidal neovascularization (CNV) caused by AMD was studied. All patients were
treated with PDT followed by an intravitreal injection of bevacizumab (1.5 mg) on
the same day. Ophthalmic evaluations included determination of best-corrected
visual acuity by using ETDRS charts. CNV lesion characteristics were determined
by fluorescein angiography, and retinal morphology by optical coherence
tomography. Review examinations were performed 1, 4, and 12 weeks following
treatment. RESULTS: The median ETDRS letter scores increased by 3 letters after 4
weeks and 4.3 letters after 12 weeks. Median central retinal thickness decreased 
from the baseline by 145 microm (week 1), 205 microm (week 4), and 171 microm
(week 12), respectively (P < 0.0001, for all comparisons). One patient
experienced a transient moderate vision loss after 4 weeks post treatment.
Leakage on fluorescein angiography was resolved in all patients at week 12. No
significant ocular or systemic side-effects were observed. CONCLUSIONS:
Short-term results suggest that a single PDT in combination with intravitreal
bevacizumab is safe and associated with stabilization of visual acuity and
decrease of intraretinal and subretinal fluid accumulation in the macula. Further
evaluation of this treatment strategy for neovascular AMD appears warranted.

Publication Types: 
    Case Reports

PMID: 17701197 [PubMed - indexed for MEDLINE]

713: Optom Vis Sci. 2007 Aug;84(8):683-8.

Impact of cataract surgery on quality of life in patients with early age-related 
macular degeneration.

Lamoureux EL, Hooper CY, Lim L, Pallant JF, Hunt N, Keeffe JE, Guymer RH.

Department of Ophthalmology, Centre for Eye Research Australia, The University of
Melbourne, Victoria, Australia. ecosse@unimelb.edu.au

PURPOSE: To investigate if cataract surgery improves overall and specific areas
of quality of life (QoL) in patients with early age-related macular degeneration 
(AMD) using the impact of vision impairment (IVI) questionnaire. METHODS:
Patients with visually significant cataract and early AMD, who were being
considered for cataract surgery in the study eye, were recruited. Eligible
patients were randomized to either "early surgery" or "standard surgery"
(standard cataract surgery waiting time of 6 months) groups. The IVI,
sociodemographic, and clinical data were collected. Rasch analysis was used to
estimate QoL person measures at baseline and follow-up. The data were analyzed
using repeated measures ANOVA. Effect sizes were calculated using Cohen's d
coefficient. RESULTS: Fifty six patients (mean age = 78.5 years and visual acuity
= 6/15) had one eye randomly allocated to either the early surgery (n = 29) or
standard surgery (n = 27) groups. At follow-up, significant interaction effects
were found for the overall IVI score [F(1,54) = 17.7; p < 0.001], the emotional
well-being [F(1,54) = 13.4; p = 0.001], mobility and independence [F(1,54) =
13.4; p = 0.001], and reading and accessing information subscales [F(1,54) =
13.1; p = 0.001]. The standard surgery group systematically recorded worse scores
at 6 months on all QoL measures whereas the early surgery group recorded
significant gains (p < 0.001; Cohen's d = 0.66 to 0.91) on all of them. Visual
acuity in the study eye significantly improved in the early surgery group only
(Cohen's d = 1.1; p < 0.05) and improvement in log MAR lines read was identified 
as the single independent predictor of enhanced QoL explaining between 26 and 34%
of the variance in the IVI scores. CONCLUSIONS: Cataract surgery is justified in 
patients with early AMD. It brings significant improvements in visual acuity,
aspects of daily living, and overall QoL.

Publication Types: 
    Randomized Controlled Trial

PMID: 17700333 [PubMed - indexed for MEDLINE]

714: Arch Ophthalmol. 2007 Aug;125(8):1118-21.

Surgical placement of an optical prosthetic device for end-stage macular
degeneration: the implantable miniature telescope.

Colby KA, Chang DF, Stulting RD, Lane SS.

Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical
School, 243 Charles St, Ste 808, Boston, MA 02114, USA. kacolby@meei.harvard.edu

OBJECTIVE: To describe the surgical procedure for placement of an implantable
telescope prosthesis for end-stage age-related macular degeneration. METHODS: As 
part of a phase 2/3 clinical trial for patients with bilateral, irreversible
age-related macular degeneration, the optimal procedure for monocular placement
of the telescope prosthesis was determined. RESULTS: Because of the unique
configuration of the telescope prosthesis, proper wound construction, anterior
chamber management, and device insertion after phacoemulsification are critical
for successful surgery. CONCLUSION: A unique surgical technique ensures
appropriate placement of the telescope prosthesis, while reducing surgical trauma
to the corneal endothelium.

Publication Types: 
    Clinical Trial, Phase II
    Clinical Trial, Phase III
    Randomized Controlled Trial

PMID: 17698761 [PubMed - indexed for MEDLINE]

715: Arch Ophthalmol. 2007 Aug;125(8):1089-95.

Smoking and the long-term incidence of age-related macular degeneration: the Blue
Mountains Eye Study.

Tan JS, Mitchell P, Kifley A, Flood V, Smith W, Wang JJ.

Centre for Vision Research, Westmead Millennium Institute, University of Sydney, 
and Department of Ophthalmology, Westmead Hospital, Hawkesbury Road, Westmead,
New South Wales, Australia.

OBJECTIVE: To assess the association between smoking and long-term incident
age-related macular degeneration (AMD). METHODS: Of 3654 Australians 49 years and
older examined at baseline (January 14, 1992, through December 18, 1993), 2454
were examined 5 years later (January 11, 1997, through February 23, 2000), 10
years later (July 10, 2002, through November 4, 2005), or both. Retinal
photographs were taken to assess AMD. Smoking status was recorded at each
interview. RESULTS: After controlling for age, sex, and other factors, current
smokers had a 4-fold higher risk of late AMD than never smokers (relative risk,
3.9; 95% confidence interval, 1.7-8.8). Past smokers had a 3-fold higher risk of 
geographic atrophy (relative risk, 3.4; 95% confidence interval, 1.2-9.7). Joint 
exposure to current smoking and (1) the lowest level of high-density lipoprotein 
(HDL) cholesterol, (2) the highest total to HDL cholesterol ratio, or (3) low
fish consumption was associated with a higher risk of late AMD than the effect of
any risk factor alone. However, interactions between smoking and HDL cholesterol 
level, ratio of total to HDL cholesterol, and fish consumption were not
statistically significant. CONCLUSION: Smoking strongly increased the long-term
risk of incident late, but not early, AMD, with a possibly greater effect in
persons with a low HDL cholesterol level, a high ratio of total to HDL
cholesterol, and low fish consumption.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17698756 [PubMed - indexed for MEDLINE]

716: Ophthalmology. 2007 Oct;114(10):1860-7. Epub 2007 Aug 15.

A phase II randomized clinical trial of intravitreal bevacizumab for diabetic
macular edema.

Diabetic Retinopathy Clinical Research Network, Scott IU, Edwards AR, Beck RW,
Bressler NM, Chan CK, Elman MJ, Friedman SM, Greven CM, Maturi RK, Pieramici DJ, 
Shami M, Singerman LJ, Stockdale CR.

Jaeb Center for Health Research, 15310 Amberly Drive, Suite 350, Tampa, FL 33647,
USA. drcrnet@jaeb.org

OBJECTIVE: To provide data on the short-term effect of intravitreal bevacizumab
for diabetic macular edema (DME). DESIGN: Randomized phase II clinical trial.
PARTICIPANTS: One hundred twenty-one eyes of 121 subjects (109 eligible for
analysis) with DME and Snellen acuity equivalent ranging from 20/32 to 20/320.
INTERVENTIONS: Random assignment to 1 of 5 groups: (A) focal photocoagulation at 
baseline (n = 19), (B) intravitreal injection of 1.25 mg of bevacizumab at
baseline and 6 weeks (n = 22), (C) intravitreal injection of 2.5 mg of
bevacizumab at baseline and 6 weeks (n = 24), (D) intravitreal injection of 1.25 
mg of bevacizumab at baseline and sham injection at 6 weeks (n = 22), or (E)
intravitreal injection of 1.25 mg of bevacizumab at baseline and 6 weeks with
photocoagulation at 3 weeks (n = 22). MAIN OUTCOME MEASURES: Central subfield
thickness (CST) on optical coherence tomography and best-corrected visual acuity 
(VA) were measured at baseline and after 3, 6, 9, 12, 18, and 24 weeks. RESULTS: 
At baseline, median CST was 411 mum and median Snellen VA equivalent was 20/50.
Compared with group A, groups B and C had a greater reduction in CST at 3 weeks
and about 1 line better median VA over 12 weeks. There were no meaningful
differences between groups B and C in CST reduction or VA improvement. A CST
reduction > 11% (reliability limit) was present at 3 weeks in 36 of 84 (43%)
bevacizumab-treated eyes and 5 of 18 (28%) eyes treated with laser alone, and at 
6 weeks in 31 of 84 (37%) and 9 of 18 (50%) eyes, respectively. Combining focal
photocoagulation with bevacizumab resulted in no apparent short-term benefit or
adverse outcomes. Endophthalmitis developed in 1 eye. The following events
occurred during the first 24 weeks in subjects treated with bevacizumab without
attributing cause to the drug: myocardial infarction (n = 2), congestive heart
failure (n = 1), elevated blood pressure (n = 3), and worsened renal function (n 
= 3). CONCLUSION: These results demonstrate that intravitreal bevacizumab can
reduce DME in some eyes, but the study was not designed to determine whether
treatment is beneficial. A phase III trial would be needed for that purpose.

Publication Types: 
    Clinical Trial, Phase II
    Multicenter Study
    Randomized Controlled Trial
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17698196 [PubMed - indexed for MEDLINE]

717: Am J Ophthalmol. 2007 Oct;144(4):618-26. Epub 2007 Aug 15.

Age-related macular degeneration and the immune response: implications for
therapy.

Nussenblatt RB, Ferris F 3rd.

Laboratory of Immunology, National Eye Institute, National Institutes of Health, 
Bethesda, Maryland 20892, USA. DrBob@nei.nih.gov

PURPOSE: To review the available information concerning the immune mediation of
age-related macular degeneration (AMD) and to speculate on proposed mechanisms
and immunotherapy. DESIGN: Interpretative essay. METHODS: Literature review and
interpretation. RESULTS: An ever-growing body of evidence is gathering concerning
the role of the immune system in AMD. Evidence to date suggests that the
underlying mechanism leading to AMD is the decline of the ocular downregulatory
immune environment. The subsequent activation of the immune system would lead to 
T-cell sensitization. When combined with local antiangiogenic therapy, several
existing immunotherapies may be used to downregulate the immune response,
potentially leading to a more efficient inhibition of choroidal
neovascularization. CONCLUSIONS: The loss of the downregulatory immune
environment is central to the development of AMD, permitting activation of the
immune system. If so, immunotherapy could positively alter the course of the
disease.

Publication Types: 
    Research Support, N.I.H., Intramural
    Review

PMID: 17698021 [PubMed - indexed for MEDLINE]

718: Am J Ophthalmol. 2007 Oct;144(4):592-9. Epub 2007 Aug 15.

Optical coherence tomography identification of occult choroidal
neovascularization in age-related macular degeneration.

Coscas F, Coscas G, Souied E, Tick S, Soubrane G.

Creteil University Eye Clinic, University of Paris XII, Creteil, France.
coscas.f@wanadoo.fr

PURPOSE: To evaluate and describe the various optical coherence tomography (OCT) 
features of occult choroidal neovascularization (CNV) in age-related macular
degeneration (AMD) at the time of diagnosis. DESIGN: Prospective, consecutive,
observational case series. METHODS: One hundred and fifty-three eyes of 130
consecutive patients with subfoveal occult CNV diagnosed on scanning laser
ophthalmoscope (SLO) fluorescein angiography (FA) and SLO indocyanine green
angiography (ICGA) were evaluated with OCT. The diagnostic criteria for occult
CNV on angiography were heterogeneous hyperfluorescence with late leakage in the 
macular region associated with pigment epithelial detachment (PED), stippled
hyperfluorescent dots, and signs of deterioration. OCT findings were evaluated
and described. RESULTS: A PED was observed on OCT in 98% (150 eyes) either as a
limited retinal pigment epithelium (RPE) elevation (54 eyes [35.3%]) or a
complete detachment (96 eyes [62.7%]). Occult CNV corresponded to zones of
hyperreflectivity in contact with the RPE band and was detected in 62.7% of eyes.
In fibrovascular PED (63 eyes [65.5%]), the elevated RPE was highlighted
posteriorly by a moderately reflective band overlying a hyporeflective cavity. In
serous PED, the cavity remained optically empty. The RPE in the detached zone
showed changes such as fragmentation (137 eyes [89.5%]). OCT also showed
intraretinal (122 eyes [79.7%]) and subretinal (64 eyes [41.8%]) fluid.
CONCLUSIONS: Analysis of the various OCT features observed in this study confirms
the polymorphic nature of occult CNV in AMD, their exudative reactions, the
almost constant presence of PED, and the different changes in the RPE band. OCT
examination, therefore, provides valuable data to confirm the features of
subepithelial occult CNV.

PMID: 17698019 [PubMed - indexed for MEDLINE]

719: Methods Inf Med. 2007;46(4):432-9.

Discovery of factors influencing the growth of geographic atrophy in patients
with age-related macular degeneration.

Dreyhaupt J, Dolar-Szczasny J, Bindewald A, Holz FG, Mansmann U.

Institute of Medical Biometry and Informatics, University of Heidelberg, INF 305,
69120 Heidelberg, Germany. dreyhaupt@imbi.uni-heidelberg.de

OBJECTIVES: Identifying factors influencing the growth of geographic atrophy (GA)
in patients with age-related macular degeneration (AMD). METHODS: Data on the
natural course and suspected modifying factors were collected as part of the
multicenter, longitudinal, observational FAM-study in 178 eyes of 114 patients
with atrophic AMD. The endpoint of interest - the size of GA - was measured in
fundus autofluorescence images. The influence of different putative risk factors 
on progression of GA is investigated with a forward selection procedure based on 
the likelihood ratio test. In order to interpret non-significant results of the
forward selection procedure, the power of the tests used was quantified by a
parametric post-hoc bootstrap approach. RESULTS: A mean increase in GA of 1.75
mm(2) per year was estimated for the given population (95% CI: [1.46; 2.02]).
Patient and eye-specific random effects could be assessed. Neither
patient-specific risk factors nor ocular-specific risk factors show any
significant influence on GA growth. The post-hoc bootstrap procedure shows that
only very strong effects can be detected on the basis of the given data. For
example, the hypercholesteremia which would result in an additional increase of
GA by near 4 mm(2) per year can be detected with a power of 80%. CONCLUSIONS: The
use of linear mixed effects regression models offers a convenient way to explore 
sources of variation in the natural course of GA. Data from further follow-up
examinations and data about other putative risk factors than those investigated
will be needed to further investigate of the GA growth process. The procedure
described in this article is easily applicable to other putative risk factors as 
well as to other fields of application.

PMID: 17694237 [PubMed - indexed for MEDLINE]

720: Am J Ophthalmol. 2007 Oct;144(4):608-12. Epub 2007 Aug 9.

LOC387715/HTRA1 variants in polypoidal choroidal vasculopathy and age-related
macular degeneration in a Japanese population.

Kondo N, Honda S, Ishibashi K, Tsukahara Y, Negi A.

Department of Organs Therapeutics, Division of Ophthalmology, Kobe University
Graduate School of Medicine, Kobe, Japan.

PURPOSE: To investigate whether variants in the LOC387715 locus and the HtrA
serine peptidase 1 (HTRA1) gene within the 10q26 locus are associated with
polypoidal choroidal vasculopathy (PCV) and wet age-related macular degeneration 
(AMD) in a Japanese population, and whether genetic diversity exists between PCV 
and wet AMD in this locus. DESIGN: Cross-sectional study. METHODS: We genotyped
243 Japanese individuals, including 76 PCV cases, 73 wet AMD cases, and 94
controls using two single nucleotide polymorphisms (SNPs) that are located in the
LOC387715 locus (rs10490924) or the HTRA1 gene (rs11200638). Genotyping was
performed using TaqMan assays (Applied Biosystems, Foster City, California, USA).
RESULTS: Two SNPs generated highly significant allelic associations with PCV
(rs10490924, P = 5.7 x 10(-6); rs11200638, P = 5.2 x 10(-6)) and AMD (rs10490924,
P = 1.4 x 10(-6); rs11200638, P = 3.4 x 10(-7)). The odds ratios and population
attributable risks were higher for the AMD cases than for the PCV cases.
Homozygotes for the risk allele at rs11200638 had a 6.33-fold increased risk of
PCV and a 13.77-fold increased risk of wet AMD when compared with homozygotes for
the wild-type allele. There were no significant differences in either allelic or 
genotypic frequencies between PCV and AMD cases. CONCLUSIONS: The LOC387715/HTRA1
variants are associated with PCV and wet AMD in the Japanese population. The
associations are stronger in AMD than in PCV. PCV and AMD share common genetic
factors, which suggests that PCV and wet AMD are similar in some pathophysiologic
aspects.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 17692272 [PubMed - indexed for MEDLINE]

721: Forum Nutr. 2007;60:168-75.

Application of nutrigenomics in eye health.

Delcourt C.

Inserm, U593 Epidemiology, Public Health and Development, Université Victor
Segalen Bordeaux 2, Bordeaux, France. Cecile.Delcourt@isped.u-bordeaux2.fr

This paper reviews recent findings on the implication of nutritional and genetic 
factors in age-related eye diseases: age-related macular degeneration (AMD; a
degenerative disease of the retina) and cataract (opacification of the lens).
Because of direct exposure to light, the eye is particularly sensitive to
oxidative stress. Antioxidants, such as vitamin E, C or zinc, clearly have a
protective effect in AMD and probably in cataract. In addition, two carotenoids, 
lutein and zeaxanthin, may play a more specific role in the eye: they accumulate 
in the retina, where they form the macular pigment, and in the lens. Their role
is probably to filter out phototoxic blue light and to quench singlet oxygen.
Finally, docosahexaenoic acid (an omega-3 polyunsaturated fatty acid) is
particularly important for the retina, where it exerts structural, functional and
protective actions. Besides, these diseases are strongly influenced by genetics, 
as demonstrated by familial and twin studies. The apolipoprotein E4 allele is
associated with a reduced risk of AMD, while an association of AMD with
complement factor H polymorphism has recently been demonstrated. Nutrigenomics,
by studying the interactions between genetic variability and nutritional factors,
represents a new challenge in order to account for interindividual variations in 
disease susceptibility. Such potential interactions are presented.

Publication Types: 
    Review

PMID: 17684413 [PubMed - indexed for MEDLINE]

722: Mol Vis. 2007 Jul 24;13:1274-9.

Association of the HTRA1 -625G>A promoter gene polymorphism with exudative
age-related macular degeneration in a Central European population.

Weger M, Renner W, Steinbrugger I, Köfer K, Wedrich A, Groselj-Strele A,
El-Shabrawi Y, Schmut O, Haas A.

Department of Ophthalmology, Medical University of Graz, Austria.

PURPOSE: Exudative age-related macular degeneration (AMD) is one of the most
common causes of severe visual loss. Both environmental and genetic factors, such
as the complement factor H (CFH) 402H allele, have been associated with AMD.
Recently, the HTRA1 -625A allele was identified as a novel risk marker in both a 
North American and a Chinese population. The present study was performed to
evaluate the association of the HTRA1 -625A allele with exudative AMD in a
Central European population. METHODS: The present case-control study included 242
patients with exudative AMD and 157 control subjects. Genotypes of the HTRA1
-625G>A polymorphism were determined by a 5'-exonuclease assay (TaqMan).
Determination of CFH Y402H genotypes was done by allele specific digestion of
polymerase chain products. RESULTS: Carriers of the HTRA1 -625AA genotype were
found significantly more often in AMD patients than among control subjects (27.7%
versus 5.1%; p<0.001). Binary logistic regression analysis binary logistic
regression analysis revealed an odds ratio (OR) of 2.7 (95% confidence interval
(CI): 1.1-6.8) for AMD among subjects heterozygous for the HTRA1 -625A allele
compared to those with the wildtype genotype, when adjusted for CFH Y402H
genotypes (p=0.034). The OR increased to 10.2 (95% CI: 3.0-34.5) among subjects
homozygous for the HTRA1 -625A allele (p<0.001). The OR for AMD among
heterozygous carriers of the CFH 402H variant was 3.6 (95% CI: 1.6-7.8) compared 
to those with the wildtype genotype, when adjusted for HTRA1 -625G>A genotypes
(p=0.001). The OR increased to 9.8 (95% CI: 3.7-25.9) among subjects homozygous
for the CFH 402HH genotype (p<0.001). Interaction terms between CFH and HTRA1
genotypes were not significantly associated with AMD. CONCLUSIONS: Our data
suggest that both the HTRA1 -625A allele and the CFH 402H allele are
independently associated with exudative AMD in a Central European population.

PMID: 17679948 [PubMed - indexed for MEDLINE]

723: Arch Gen Psychiatry. 2007 Aug;64(8):886-92.

Comment in:
    Arch Gen Psychiatry. 2007 Aug;64(8):884-5.    Curr Psychiatry Rep. 2008 Feb;10(1):7.

Preventing depression in age-related macular degeneration.

Rovner BW, Casten RJ, Hegel MT, Leiby BE, Tasman WS.

Department of Psychiatry, Jefferson Hospital for Neuroscience, 900 Walnut St, 4th
Floor, Philadelphia, PA 19107, USA. barry.rovner@jefferson.edu

CONTEXT: Age-related macular degeneration is a prevalent disease of aging that
may cause irreversible vision loss, disability, and depression. The latter is
rarely recognized or treated in ophthalmologic settings. OBJECTIVE: To determine 
whether problem-solving treatment can prevent depressive disorders in patients
with recent vision loss. DESIGN: Randomized, controlled trial. SETTING:
Outpatient ophthalmology offices in Philadelphia, Pennsylvania. PATIENTS: Two
hundred six patients aged 65 years or older with recent diagnoses of neovascular 
age-related macular degeneration in one eye and pre-existing age-related macular 
degeneration in the fellow eye. INTERVENTION: Patients were randomly assigned to 
problem-solving treatment (n = 105) or usual care (n = 101). Problem-solving
treatment therapists delivered 6 sessions during 8 weeks in subjects' homes. MAIN
OUTCOME MEASURES: Outcomes were assessed at 2 months for short-term effects and 6
months for maintenance effects. These included DSM-IV-defined diagnoses of
depressive disorders, National Eye Institute Vision Function Questionnaire-17
scores, and rates of relinquishing valued activities. RESULTS: The 2-month
incidence rate of depressive disorders in problem-solving-treated subjects was
significantly lower than controls (11.6% vs 23.2%, respectively; odds ratio,
0.39; 95% confidence interval, 0.17-0.92; P = .03). Problem-solving treatment
also reduced the odds of relinquishing a valued activity (odds ratio, 0.48; 95%
confidence interval, 0.25-0.96; P = .04). This effect mediated the relationship
between treatment group and depression. By 6 months, most earlier observed
benefits had diminished, though problem-solving treatment subjects were less
likely to suffer persistent depression (chi2(1,3) = 8.46; P = .04). CONCLUSIONS: 
Problem-solving treatment prevented depressive disorders and loss of valued
activities in patients with age-related macular degeneration as a short-term
treatment, but these benefits were not maintained over time. Booster or rescue
treatments may be necessary to sustain problem-solving treatment's preventative
effect. This study adds important new information to the emerging field of
enhanced-care models to prevent or treat depression in older persons. Trial
Registration: clinicaltrials.gov Identifier: NCT00042211.

Publication Types: 
    Randomized Controlled Trial
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17679633 [PubMed - indexed for MEDLINE]

724: Ophthalmology. 2008 Feb;115(2):355-362.e2. Epub 2007 Aug 2.

Three-dimensional imaging of cystoid macular edema in retinal vein occlusion.

Yamaike N, Tsujikawa A, Ota M, Sakamoto A, Kotera Y, Kita M, Miyamoto K,
Yoshimura N, Hangai M.

Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School
of Medicine, Kyoto, Japan.

OBJECTIVE: To study the pathomorphologic features of cystoid macular edema (CME) 
associated with retinal vein occlusion by three-dimensional (3D) optical
coherence tomography (OCT) and to study the relationship of the ocular findings
to visual function. DESIGN: Observational case series. PARTICIPANTS: Twenty eyes 
of 20 patients with retinal vein occlusion. METHODS: A prototype 3D OCT system
based on Fourier-domain OCT technology was fabricated for patient examination in 
this study. This system uses a superluminescent diode, which has a center
wavelength of 830 nm and a bandwidth of 50 nm, as the light source, resulting in 
4.3-microm axial resolution in tissue. Data acquisition rates of approximately 18
700 axial scans per second and a sensitivity of 98 dB were achieved.
Three-dimensional imaging was performed by volume rendering based on the 3D data 
set acquired with a raster scan of 256x256 axial scans. MAIN OUTCOME MEASURES:
Images of CME pathologic features obtained by 3D OCT and by Stratus OCT (Carl
Zeiss, Dublin, CA). RESULTS: The 3D OCT imaging system generates a realistic 3D
image of CME with high resolution. In 16 eyes, 3D OCT showed large foveal cystoid
spaces, most of which were accompanied by small cystoid spaces in the parafoveal 
region. Cystoid spaces were seen often in the inner nuclear layer and outer
plexiform layer, but were detected to some extent in all retinal layers. The 3D
OCT showed clearly a thin back-reflecting line corresponding to the external
limiting membrane (ELM) in 18 eyes; of these, cystoid spaces were located on the 
inside of the ELM in 7 eyes and appeared to be in contact with the ELM in 9 eyes.
In 2 eyes, the ELM line could not be seen clearly beneath the large foveal
cystoid spaces. Integrity of the ELM in the foveal region had a direct
correlation with visual acuity. CONCLUSIONS: Observation of CME using 3D OCT
enabled visualization of its spatial extent in each retinal layer and discernment
of its relationship to the ELM. The use of 3D OCT thus may improve the monitoring
of CME progression and its response to treatment.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17675242 [PubMed - indexed for MEDLINE]

725: Ophthalmology. 2008 Apr;115(4):693-9. Epub 2007 Aug 2.

The LOC387715 polymorphism, inflammatory markers, smoking, and age-related
macular degeneration. A population-based case-control study.

Wang JJ, Ross RJ, Tuo J, Burlutsky G, Tan AG, Chan CC, Favaloro EJ, Williams A,
Mitchell P.

Centre for Vision Research, Department of Ophthalmology and Westmead Millennium
Institute, University of Sydney, Sydney, Australia. jiejin_wang@wmi.usyd.edu.au

OBJECTIVE: To assess combined effects on the risk of age-related macular
degeneration (AMD) by the LOC387715 polymorphism, smoking, and inflammatory or
hemostatic factors. DESIGN: Population-based case-control study. PARTICIPANTS:
Two hundred seventy-eight AMD cases (224 early, 54 late) and 557 controls matched
for age, gender, and smoking, drawn from the Blue Mountains Eye Study cohort.
METHODS: Subjects were genotyped for the LOC387715 Ala69Ser polymorphism (rs#
10490924). Smoking was self-reported. Serum high-sensitivity C-reactive protein
(CRP), interleukin 6 (IL-6), soluble intercellular adhesion molecule 1 (sICAM-1),
fibrinogen, homocysteine, plasminogen activator inhibitor 1 (PAI-1), von
Willebrand factor, and white cell count (WCC) were measured. Combined effects of 
this genetic variant plus any of these study factors on AMD risk were assessed
using logistic regression models, adjusted for age and smoking. We defined
interaction if the influence of 2 factors departed from the multiplicative scale,
confirmed by a statistically significant interaction term. Otherwise, the
combined effect was used. MAIN OUTCOME MEASURES: Age-related macular degeneration
was graded using the Wisconsin grading system. RESULTS: Combined effects on the
likelihood of early or late AMD were demonstrated for the LOC387715 Ala69Ser G/T 
and T/T genotypes with the markers high-sensitivity CRP (odds ratios [ORs], 1.2
for the highest tertile alone, 1.6 for G/T and T/T genotypes alone, and 2.2 for
both G/T and T/T genotypes plus the highest tertile, compared with the G/G
genotype with the 2 lower tertiles), IL-6 (corresponding ORs, 1.1, 1.6, and 2.2),
sICAM-1 (ORs, 1.0, 1.5, and 2.3, respectively), and PAI-1 (ORs, 1.3, 1.7, and
2.3, respectively), but not with WCC, fibrinogen, homocysteine, and von
Willebrand factor. Findings were similar for early and late AMD separately.
Current smokers with G/T and T/T genotypes had strong combined effects on late
AMD risk compared with those who never smoked or past smokers with the G/G
genotype (ORs, 1.2 for current smokers alone, 1.8 for G/T and T/T genotypes
alone, and 6.1 for current smokers plus G/T and T/T genotypes). CONCLUSIONS: We
found no significant interaction but combined effects for the LOC387715 genotypes
with 3 inflammatory markers and PAI-1 on the risk of early or late AMD, and with 
current smoking on the risk of late AMD.

Publication Types: 
    Research Support, N.I.H., Intramural
    Research Support, Non-U.S. Gov't

PMID: 17675241 [PubMed - indexed for MEDLINE]

726: Ophthalmology. 2008 Jan;115(1):116-26. Epub 2007 Aug 6.

Erratum in:
    Ophthalmology. 2008 Sep;115(9):1524. Wong, Tien [corrected to Wong, Tien Y].

The natural history and prognosis of neovascular age-related macular
degeneration: a systematic review of the literature and meta-analysis.

Wong TY, Chakravarthy U, Klein R, Mitchell P, Zlateva G, Buggage R, Fahrbach K,
Probst C, Sledge I.

Centre for Eye Research Australia, University of Melbourne, Melbourne, Australia.

PURPOSE: To describe the natural history and progression of visual loss in eyes
with untreated neovascular age-related macular degeneration (AMD). DESIGN:
Systematic review and meta-analysis. PARTICIPANTS: Four thousand three hundred
sixty-two untreated neovascular AMD patients from published interventional
studies. METHODS: A systematic review of the literature from 1980 to August 2005 
was performed. Studies reporting disease progression outcomes for untreated
patients with neovascular AMD were included. Outcome measures were summarized
using simple counts and means. Random effects meta-analyses were conducted and
tests of heterogeneity were performed where appropriate. MAIN OUTCOME MEASURES:
Changes in visual acuity (VA) loss, development of comorbidities, and fellow eye 
involvement. RESULTS: Fifty-three primary studies were included. Nearly half of
the studies (28) were randomized clinical trials. The quality of the studies was 
high, with over 80% providing level I or II evidence. Mean baseline VA among
study patients was 0.64 logarithm of the minimum angle of resolution (logMAR)
(approximately 20/87 Snellen). The mean VA change in logMAR progressed from 0.1
(1 line lost) at 3 months to 0.3 (2.7 lines lost) after 12 months and 0.4 (4
lines lost) after 24 months. The proportion of patients who developed severe
vision loss (>6 lines) from baseline increased from 21.3% at 6 months to 41.9% by
3 years. The proportion of patients with VA worse than logMAR 1.0 (20/200
Snellen) increased from 19.7% at baseline to 75.7% by 3 years. Neovascular AMD
developed in the fellow eye in 12.2% of patients by 12 months and in 26.8% by 4
years. Meta-analyses of vision outcome by subtype of neovascular AMD were not
possible. CONCLUSIONS: A doubling of the visual angle of presenting VA may be
expected to occur in the year after initial presentation in eyes with untreated
neovascular AMD. No conclusions can be drawn as to the differences in rates of
disease progression by neovascular AMD subtype. The diversity of reporting
formats, paucity of long-term natural history data, and heterogeneity among the
reported clinical studies impose limits to the clear understanding of long-term
prognosis for visual function in neovascular AMD.

Publication Types: 
    Meta-Analysis
    Research Support, Non-U.S. Gov't
    Review

PMID: 17675159 [PubMed - indexed for MEDLINE]

727: Graefes Arch Clin Exp Ophthalmol. 2008 Feb;246(2):245-54. Epub 2007 Aug 3.

Optical coherence tomography analysis of a randomized study combining
photodynamic therapy with intravitreal triamcinolone.

Arias L, Garcia-Arumi J, Ramon JM, Badia M, Rubio M, Pujol O.

Department of Ophthalmology, Bellvitge University Hospital, C/Feixa Llarga, S/N
L'Hospitalet de Llobregat, Barcelona, Spain. luisarias@telefonica.net

BACKGROUND: The objective of the study was to analyze optical coherence
tomography (OCT) scan differences between patients with predominantly classic
subfoveal choroidal neovascularization (CNV) secondary to age-related macular
degeneration (AMD) treated with only photodynamic therapy (PDT) and patients
treated with PDT combined with intravitreal triamcinolone acetonide (IVTA).
METHODS: In this prospective study, 61 patients were randomized to receive PDT (n
= 30) or PDT combined with IVTA (n = 31). They were evaluated every 3 months with
a refraction protocol for best-corrected visual acuity (VA) measured with Early
Treatment Diabetic Retinopathy Study (ETDRS) charts, fluorescein angiography
(FA), and OCT. When measuring foveal thickness on OCT scans, neuroretinal foveal 
thickness (NFT) was differentiated from outer high reflectivity band thickness
(OHRBT). The main outcome measures were mean change in OCT measurements and
correlation of VA and angiographic area of the lesion with OCT measurements.
RESULTS: At the 12-month follow-up, the mean change in NFT was not significantly 
reduced (P = 0.9), but the mean change in OHRBT was significantly lower (P =
0.004) in the group of patients who received combined therapy. There was no
correlation between final VA and NFT in either patient group (P = 0.2). The final
VA was significantly worse in eyes with a thicker OHRBT (P = 0.04) in the group
of patients treated with only PDT. There was no correlation between angiographic 
area and NFT and OHRBT in either patient group (P > 0.3). There was a
statistically significant difference between the pre-treatment angiographic area 
of the lesion and VA at the 12-month follow-up in the combined therapy group (P =
0.01), and more eyes treated with only PDT presented with intraretinal fluid at
the last follow-up (P = 0.01). CONCLUSION: Combined PDT+IVTA therapy was more
effective than PDT alone at reducing OHRBT. This OCT measurement seems to be have
a greater effect on VA than NFT.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial

PMID: 17674020 [PubMed - indexed for MEDLINE]

728: Graefes Arch Clin Exp Ophthalmol. 2008 Jan;246(1):81-7. Epub 2007 Aug 3.

Twelve-month safety of intravitreal injections of bevacizumab (Avastin): results 
of the Pan-American Collaborative Retina Study Group (PACORES).

Wu L, Martínez-Castellanos MA, Quiroz-Mercado H, Arevalo JF, Berrocal MH, Farah
ME, Maia M, Roca JA, Rodriguez FJ; Pan American Collaborative Retina Group
(PACORES).

Collaborators: Wu L, Evans T, Arevalo JF, Sanchez JG, Garcia-Amaris RA, Farah M, 
Maia M, Aggio FB, Quiroz-Mercado H, Fromow-Guerra J, Morales-Canton V,
Dalma-Weiszhausz J, Rodriguez FJ, Infante R, Flores S, Medina D, Berrocal MH,
Cruz-Villegas V, Graue-Wiechers F, Lozano-Rechy D, Robledo V, Roca JA, Reategui
G, Saravia MJ, Martinez-Cartier M, Avila M, Costa RA, Cardillo J.

Instituto de Cirugía Ocular, San José, Costa Rica.

BACKGROUND: Vascular endothelial growth factor (VEGF) plays an important role in 
many diseases of the posterior pole that are characterized by macular edema
and/or intraocular neovascularization. Recently anti-VEGF agents such as
ranibizumab and pegaptanib sodium have been shown to be beneficial in the
treatment of choroidal neovascularization (CNV) secondary to age-related macular 
degeneration (ARMD). However in most parts of the world, both pegaptanib sodium
and ranibizumab are not readily available. Bevacizumab, a humanized recombinant
monoclonal IgG antibody that binds and inhibits all VEGF isoforms, has been
proposed as an alternative treatment option. METHODS: A total of 1,265
consecutive patients were injected with bevacizumab for diseases such as
proliferative diabetic retinopathy, diabetic macular edema, retinal vein
occlusions, and CNV of several etiologies including ARMD at eight Latin American 
institutions from 1 September 2005 to 31 January 2006. Of these 1,265, 92 were
excluded because they were injected once and lost to follow-up. The remaining
1,173 patients constitute the subjects of this retrospective, multicenter, open
label, uncontrolled interventional case series that reports the cumulative
systemic and ocular adverse events following intravitreal bevacizumab during 12
months of follow-up. Patients were examined at baseline and then monthly. If the 
patients were unable to attend the 12-month visit, a telephone interview was
conducted to assess for possible systemic complications. RESULTS: A total of
4,303 intravitreal injections of bevacizumab on 1,310 eyes was reported. All
1,173 patients were accounted for at the 12-month visit. Systemic adverse events 
were reported in 18 (1.5%) patients. These included seven (0.59%) cases of an
acute elevation of systemic blood pressure, six (0.5%) cerebrovascular accidents,
five (0.4%) myocardial infarctions, two (0.17%) iliac artery aneurysms, two
(0.17%) toe amputations and five (0.4%) deaths. Ocular complications included
seven (0.16%) bacterial endophthalmitis, seven (0.16%) tractional retinal
detachments, four (0.09%) uveitis, and a case (0.02%) each of rhegmatogenous
retinal detachment and vitreous hemorrhage. CONCLUSION: Despite the limited
follow-up, repeated intravitreal injections of either 1.25 mg or 2.5 mg of
bevacizumab appears to be safe and well tolerated during the 1st year.

Publication Types: 
    Multicenter Study

PMID: 17674014 [PubMed - indexed for MEDLINE]

729: Eur J Ophthalmol. 2007 Jul-Aug;17(4):615-9.

The diagnostic contribution of indocyanine green to fluorescein angiography in
fellow drusen eyes of patients with wet age-related macular degeneration.

Landa G, Springer A, Bukelman A, Pollack A.

Department of Ophthalmology, Kaplan Medical Center, Rehovot 76100, Israel.
genal@inter.net.il

PURPOSE: To assess the contribution of indocyanine green angiography (ICGA) to
fluorescein angiography (FA) in evaluating fellow drusen eyes of patients with
wet age-related macular degeneration (AMD) in the other eye. METHODS: The records
of paired FA and ICGA of patients with dry AMD in one eye and wet AMD in the
other eye were retrospectively reviewed. Based on color fundus photographs,
drusen were graded to low, moderate, or high grade of severity on FA. The FA and 
ICGA findings were compared. RESULTS: Fifty-two pairs of eyes were included.
Fluorescein angiography showed drusen of low severity in 11 (21.2%) eyes, of
moderate severity in 31 (59.6%), and of high severity in 10 (19.2%). Leakage on
both FA and ICGA was not demonstrated in any case of drusen of low or moderate
severity. Only in 2 out of 10 eyes from the high severity group, 3.8% of the eyes
of the whole study population, did ICGA reveal occult choroidal
neovascularization (CNV) that was not observed on FA. CONCLUSIONS: In selected
eyes with drusen of high grade severity, ICGA may detect occult CNV, unrecognized
clinically or by FA. ICGA had a small contribution to the diagnosis of occult CNV
in fellow drusen eyes with any degree of severity.

PMID: 17671939 [PubMed - indexed for MEDLINE]

730: Doc Ophthalmol. 2007 Sep;115(2):69-76. Epub 2007 Aug 2.

Deficits in the electroretinogram in neovascular age-related macular degeneration
and changes during photodynamic therapy.

Mackay AM, Brown MC, Hagan RP, Fisher AC, Grierson I, Harding SP.

Department of Clinical Engineering, Royal Liverpool University Hospital, Prescot 
Street, Liverpool, UK.

PURPOSE: To describe the deficits in four electroretinography (ERG) modalities in
patients with neovascular age-related macular degeneration (AMD). To describe the
changes in these parameters during a course of verteporfin photodynamic therapy
(PDT). METHODS: Pattern (PERG), multifocal (mfERG) (19 segment simplified test
protocol), flash ERG and flicker ERG were performed in patients with active
neovascular AMD before PDT and compared to fellow eye controls using paired
t-tests. Changes in ERG parameters during the 12 month treatment course were
visualised using 95% confidence intervals of the median difference. The
statistical significance of any changes was quantified using Wilcoxon signed
ranks tests. RESULTS: Fifty patients were recruited and followed. At presentation
all ERG amplitudes were reduced with greater reductions in focal as opposed to
global test protocols (P < 0.05). Over the 12 month course of PDT, PERG P50
amplitude showed a general downward trend and latency remained unchanged. mfERG
p1 amplitude density showed an upward trend at six months before returning to
baseline by 12 months. mfERG ring 2 amplitude density was significantly increased
at 12 months compared to baseline (P = 0.010). Flicker ERG latency was
significantly increased at six months compared to baseline (P = 0.015).
DISCUSSION: The simplified mfERG protocol was tolerated by this patient group,
however, they found the full test protocol demanding. Large deficits in the
retinal ERG function occur in neovascular AMD and involve retinal locations
adjacent to as well as overlying choroidal neovascularisation (CNV). After PDT
there is an improvement in electro-retinal function in retinal locations
overlying the CNV.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17671804 [PubMed - indexed for MEDLINE]

731: Hum Mol Genet. 2007 Oct 15;16(20):2411-22. Epub 2007 Jul 30.

The R345W mutation in EFEMP1 is pathogenic and causes AMD-like deposits in mice.

Fu L, Garland D, Yang Z, Shukla D, Rajendran A, Pearson E, Stone EM, Zhang K,
Pierce EA.

F.M. Kirby Center for Molecular Ophthalmology, University of Pennsylvania School 
of Medicine, Philadelphia, PA 19104, USA.

Age-related macular degeneration (AMD) is the most common cause of vision loss in
developed countries. A defining characteristic of this disorder is the
accumulation of material between Bruch's membrane and the retinal pigment
epithelium (RPE), first as microscopic basal deposits and later as clinically
evident drusen. The pathogenesis of these deposits remains to be defined.
Biochemical and genetic studies have suggested that inflammation and complement
activation may play roles in AMD. Several lines of evidence also suggest that
alterations to the extracellular matrix (ECM) of the RPE and choroid contribute
to the development of AMD. The inherited macular degeneration Doyne honeycomb
retinal dystrophy/Malattia Leventinese is thought to be caused by an R345W
mutation in the EFEMP1 gene (also called fibulin-3). The pathogenicity of this
mutation has been questioned because all individuals identified to date with the 
R345W mutation have shared a common haplotype. We investigated the pathogenicity 
of this mutation in families with early-onset macular degeneration and by
generating Efemp1-R345W knockin mice. Genetic studies show that one of the
identified families with the R345W mutation has a novel haplotype. The mutant
Efemp1-R345W mice develop deposits of material between Bruch's membrane and the
RPE, which resemble basal deposits in patients with AMD. These basal deposits
contain Efemp1 and Timp3, an Efemp1 interacting protein. Evidence of complement
activation was detected in the RPE and Bruch's membrane of the mutant mice. These
results confirm that the R345W mutation in EFEMP1 is pathogenic. Further, they
suggest that alterations in the ECM may stimulate complement activation,
demonstrating a potential connection between these two etiologic factors in
macular degeneration.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17666404 [PubMed - indexed for MEDLINE]

732: Hum Mol Genet. 2007 Oct 15;16(20):2423-32. Epub 2007 Jul 30.

Formation and progression of sub-retinal pigment epithelium deposits in Efemp1
mutation knock-in mice: a model for the early pathogenic course of macular
degeneration.

Marmorstein LY, McLaughlin PJ, Peachey NS, Sasaki T, Marmorstein AD.

Department of Ophthalmology and Vision Science, University of Arizona, Tucson, AZ
85711, USA. Lmarmorstein@eyes.arizona.edu

Malattia leventinese (ML) is a dominantly inherited macular degenerative disease 
characterized by the presence of sub-retinal pigment epithelium (RPE) deposits.
With the exception of an earlier age of onset, ML patients exhibit symptoms and
histopathology compatible with the diagnosis of age-related macular degeneration 
(AMD), the most common cause of incurable blindness. ML is caused by a mutation
(R345W) in the gene EFEMP1 which encodes fibulin-3, a protein of unknown
function. We generated a knock-in mouse carrying the disease-associated mutation 
in the murine Efemp1 gene. Small, isolated sub-RPE deposits developed as early as
4 months of age in both heterozygous and homozygous knock-in mice. Over time
these deposits increased in size and number eventually becoming continuous
sheets. In older mice membranous debris was observed within the deposits and
within Bruch's membrane, and was accompanied by general RPE and choroidal
abnormalities including degeneration, vacuolation, loss or disruption of the RPE 
basal infoldings, choroidal atrophy, and focal thickening of and invasion of
cellular processes into Bruch's membrane. Fibulin-3 was found to accumulate in
the sub-RPE deposits. Thus, the Efemp1 knock-in mice reconstitute the most
important histopathologic symptoms of both ML and AMD. We conclude that these
mice are a valuable tool for studying the primary pathogenic course of basal
deposits associated with macular degeneration and for testing prevention and
treatment strategies for this class of diseases.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, Non-P.H.S.

PMID: 17664227 [PubMed - indexed for MEDLINE]

733: Ophthalmology. 2008 Feb;115(2):334-41. Epub 2007 Jul 30.

Dietary antioxidants and the long-term incidence of age-related macular
degeneration: the Blue Mountains Eye Study.

Tan JS, Wang JJ, Flood V, Rochtchina E, Smith W, Mitchell P.

Department of Ophthalmology, Centre for Vision Research, Westmead Millennium
Institute, Westmead Hospital, University of Sydney, Sydney, Australia.

PURPOSE: To assess the relationship between baseline dietary and supplement
intakes of antioxidants and the long-term risk of incident age-related macular
degeneration (AMD). DESIGN: Australian population-based cohort study.
PARTICIPANTS: Of 3654 baseline (1992-1994) participants initially 49 years of
older, 2454 were reexamined after 5 years, 10 years, or both. METHODS:
Stereoscopic retinal photographs were graded using the Wisconsin Grading System. 
Data on potential risk factors were collected. Energy-adjusted intakes of
alpha-carotene; beta-carotene; beta-cryptoxanthin; lutein and zeaxanthin;
lycopene; vitamins A, C, and E; and iron and zinc were the study factors.
Discrete logistic models assessed AMD risk. Risk ratios (RRs) and 95% confidence 
intervals (CIs) were calculated after adjusting for age, gender, smoking, and
other risk factors. MAIN OUTCOME MEASURES: Incident early, late, and any AMD.
RESULTS: For dietary lutein and zeaxanthin, participants in the top tertile of
intake had a reduced risk of incident neovascular AMD (RR, 0.35; 95% CI,
0.13-0.92), and those with above median intakes had a reduced risk of indistinct 
soft or reticular drusen (RR, 0.66; 95% CI, 0.48-0.92). For total zinc intake the
RR comparing the top decile intake with the remaining population was 0.56 (95%
CI, 0.32-0.97) for any AMD and 0.54 (95% CI, 0.30-0.97) for early AMD. The
highest compared with the lowest tertile of total beta-carotene intake predicted 
incident neovascular AMD (RR, 2.68; 95% CI, 1.03-6.96; P = 0.029, for trend).
Similarly, beta-carotene intake from diet alone predicted neovascular AMD (RR
comparing tertile 3 with tertile 1, 2.40; 95% CI, 0.98-5.91; P = 0.027, for
trend). This association was evident in both ever and never smokers. Higher
intakes of total vitamin E predicted late AMD (RR compared with the lowest
tertile, 2.83; 95% CI, 1.28-6.23; and RR, 2.55; 95% CI, 1.14-5.70 for the middle 
and highest tertiles, respectively; P = 0.22, for trend). CONCLUSIONS: In this
population-based cohort study, higher dietary lutein and zeaxanthin intake
reduced the risk of long-term incident AMD. This study confirmed the Age-Related 
Eye Disease Study finding of protective influences from zinc against AMD. Higher 
beta-carotene intake was associated with an increased risk of AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17664009 [PubMed - indexed for MEDLINE]

734: J Cataract Refract Surg. 2007 Aug;33(8):1436-41.

Optical coherence tomography evaluation of macular edema after
phacoemulsification surgery with intracameral mydriatics.

Johansson M, Lundberg B, Behndig A.

Department of Clinical Sciences/Ophthalmology, Umeå University Hospital, Umeå,
Sweden.

PURPOSE: To quantify the macular edema induced by intracameral mydriatics in
phacoemulsification surgery. SETTING: University hospital eye clinic, Umeå,
Sweden. METHODS: In a randomized study of 22 patients, 11 patients were given 150
muL of a mixture of phenylephrine 1.5% and lidocaine 1% intracamerally for
mydriasis and anesthesia. In a control group (n = 11), conventional topical
mydriatics and intracameral lidocaine were given. Multiple preoperative,
intraoperative, and postoperative variables were recorded. RESULTS: There were no
differences in macular edema between the 2 treatments. A correlation was seen
between macular edema and impaired visual acuity 1 week postoperatively. On the
first postoperative day, a similar correlation was seen between corneal edema and
the degree of visual improvement. CONCLUSIONS: Intracameral lidocaine and
phenylephrine for mydriasis and anesthesia did not induce more significant
macular edema than the standard regimen of topical mydriatics plus intracameral
lidocaine. Macular edema limited visual improvement 1 week after
phacoemulsification, while corneal edema appeared to have a larger effect
immediately after surgery.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17662438 [PubMed - indexed for MEDLINE]

735: Exp Eye Res. 2007 Sep;85(3):366-80. Epub 2007 Jun 14.

Disease susceptibility of the human macula: differential gene transcription in
the retinal pigmented epithelium/choroid.

Radeke MJ, Peterson KE, Johnson LV, Anderson DH.

Center for the Study of Macular Degeneration, Neuroscience Research Institute,
University of California, Santa Barbara, CA 93106, USA. radeke@lifesci.ucsb.edu

The discoveries of gene variants associated with macular diseases have provided
valuable insight into their molecular mechanisms, but they have not clarified why
the macula is particularly vulnerable to degenerative disease. Its predisposition
may be attributable to specialized structural features and/or functional
properties of the underlying macular RPE/choroid. To examine the molecular basis 
for the macula's disease susceptibility, we compared the gene expression profile 
of the human RPE/choroid in the macula with the profile in the extramacular
region using DNA microarrays. Seventy-five candidate genes with differences in
macular:extramacular expression levels were identified by microarray analysis, of
which 29 were selected for further analysis. Quantitative PCR confirmed that 21
showed statistically significant differences in expression. Five genes were
expressed at higher levels in the macula. Two showed significant changes in the
macular:extramacular expression ratio; another two exhibited changes in absolute 
expression level, as a function of age or AMD. Several of the differentially
expressed genes have potential relevance to AMD pathobiology. One is an RPE cell 
growth factor (TFPI2), five are extracellular matrix components (DCN, MYOC, OGN, 
SMOC2, TFPI2), and six are related to inflammation (CCL19, CCL26, CXCL14, SLIT2) 
and/or angiogenesis (CXCL14, SLIT2, TFPI2, WFDC1). The identification of regional
differences in gene expression in the RPE/choroid is a first step in clarifying
the macula's propensity for degeneration. These findings lay the groundwork for
further studies into the roles of the corresponding gene products in the normal, 
aged, and diseased macula.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 17662275 [PubMed - indexed for MEDLINE]

736: Jpn J Ophthalmol. 2007 Jul-Aug;51(4):285-91. Epub 2007 Aug 3.

Long-term follow-up results of pars plana vitrectomy for diabetic macular edema.

Yamamoto T, Takeuchi S, Sato Y, Yamashita H.

Department of Ocular Cellular Engineering, Yamagata University Hospital,
Yamagata, Japan. teiko-y@med.id.yamagata-u.ac.jp

PURPOSE: To analyze the long-term effects of pars plana vitrectomy for diabetic
macular edema. METHODS: Sixty-nine patients (73 eyes) with diabetic macular edema
were examined retrospectively after pars plana vitrectomy. The mean follow-up
time was 24.6 +/- 7.3 months. RESULTS: The postoperative best-corrected visual
acuity (BCVA) at 12 months was significantly better than the preoperative BCVA,
and the improvement was maintained for at least 24 months. The mean central
retinal thickness (RT) at 3 months after surgery was significantly thinner than
the preoperative central RT, and was maintained for at least 24 months in the
cases followed for this period. The postoperative BCVA was significantly worse
than the preoperative BCVA at 2 years after surgery in eyes with a preoperative
BCVA of < or =0.05. In addition, there was lower probability that the
postoperative BCVA would be > or =0.5 in eyes with a preoperative BCVA of <0.3.
CONCLUSIONS: The results indicate that the improvement in the BCVA is attained by
12 months postvitrectomy, and is maintained for at least 24 months. The reduction
in RT can be maintained for up to 24 months. The results also indicate that
vitrectomy should be performed when the preoperative BCVA is >0.05 at worst.

PMID: 17660989 [PubMed - indexed for MEDLINE]

737: Jpn J Ophthalmol. 2007 Jul-Aug;51(4):278-84. Epub 2007 Aug 3.

Recurrence of diabetic macular edema after intravitreous injection of
triamcinolone following vitrectomy.

Shimonagano Y, Doi N, Noda Y, Uemura A, Sakamoto T.

Department of Ophthalmology, Kagoshima University Graduate School of Medical and 
Dental Science, Kagoshima, Japan.

PURPOSE: To evaluate the effects of intravitreous triamcinolone acetonide (TA)
after pars plana vitrectomy (PPV) for diabetic macular edema (DME). METHODS: We
studied a prospective interventional case series. TA was injected intravitreously
after PPV in 28 eyes (PPV+TA group). Eyes with DME that met the same criteria and
had been treated with PPV alone (29 eyes) were used as controls. The
best-corrected visual acuity (VA) and foveal thickness determined by optical
coherence tomography were followed up for over 12 months in both groups.
Chronological changes of VA and foveal thickness between the groups were
evaluated. RESULTS: In the PPV+TA group, VA had improved at 1 month, but worsened
after 3 months. Improvement of foveal thickness was found until 3 months, but not
after 6 months. In controls, both VA and foveal thickness continued to improve.
The VA of the PPV+TA group was significantly better than that of the controls at 
1 and 3 months (P = 0.007 and 0.015, respectively). The foveal thickness of the
PPV+TA group was significantly less than that of controls at 1 month (P =
0.0004). These differences became insignificant thereafter, and foveal thickness 
became significantly worse in the PPV+TA group than in the controls at 12 months 
(P = 0.0002). CONCLUSION: Although adjunctive use of TA after PPV for DME
improved VA and foveal thickness, the effect was transient and foveal thickness
increased significantly compared with the PPV alone group at 12 months
postoperatively.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17660988 [PubMed - indexed for MEDLINE]

738: Hum Genet. 2007 Nov;122(3-4):219-36. Epub 2007 Jul 21.

Progress in defining the molecular biology of age related macular degeneration.

Lotery A, Trump D.

Clinical Neurosciences Division, University of Southampton, Southampton General
Hospital, Southampton, SO16 6YD, UK. a.j.lotery@soton.ac.uk

Age related macular degeneration (AMD) is an extremely prevalent complex genetic 
disorder. Its incidence rises exponentially in the elderly to a frequency of 1 in
2 in the general population by age 85. It affects approximately 25 million people
and is the commonest cause of irreversible visual loss in the Western world. It
is therefore a major public health problem. However, until recently its aetiology
was unknown. Our understanding of both the molecular biology of AMD and the
relevant clinical treatments has progressed dramatically in the last 2 years. Two
genes of large effect have been identified which together contribute to over 70% 
of the population attributable risk of AMD. Treatments which inhibit expression
of vascular endothelial growth factor have been developed which can rescue vision
in the "wet" form of the disease. The association of complement factor H with AMD
highlights the importance of the alternative complement pathway in the
development of AMD whilst the pathophysiology of the serine protease HTRA1 is now
under intensive study. This review will give an insight into these developments
and will summarise our current knowledge of the molecular biology of AMD.

Publication Types: 
    Review

PMID: 17659362 [PubMed - indexed for MEDLINE]

739: Drugs Aging. 2007;24(7):581-602.

Sustained-release ophthalmic drug delivery systems for treatment of macular
disorders: present and future applications.

Booth BA, Vidal Denham L, Bouhanik S, Jacob JT, Hill JM.

Department of Ophthalmology, LSU Health Sciences Center, New Orleans, Louisiana, 
USA.

Macular disease currently poses the greatest threat to vision in aging
populations. Historically, most of this pathology could only be dealt with
surgically, and then only after much damage to the macula had already occurred.
Current pathophysiological insights into macular diseases have allowed the
development of effective new pharmacotherapies. The field of drug delivery
systems has advanced over the last several years with emphasis placed on
controlled release of drug to specific areas of the eye. Its unique location and 
tendency toward chronic disease make the macula an important and attractive
target for drug delivery systems, especially sustained-release systems. This
review evaluates the current literature on the research and development of
sustained-release posterior segment drug delivery systems that are primarily
intended for macular disease with an emphasis on age-related macular
degeneration.Current effective therapies include corticosteroids and
anti-vascular endothelial growth factor compounds. Recent successes have been
reported using anti-angiogenic drugs for therapy of age-related macular
degeneration. This review also includes information on implantable devices
(biodegradable and non-biodegradable), the use of injected particles
(microspheres and liposomes) and future enhanced drug delivery systems, such as
ultrasound drug delivery. The devices reviewed show significant drug release over
a period of days or weeks. However, macular disorders are chronic diseases
requiring years of treatment. Currently, there is no 'gold standard' for therapy 
and/or drug delivery. Future studies will focus on improving the efficiency and
effectiveness of drug delivery to the posterior chamber. If successful,
therapeutic modalities will significantly delay loss of vision and improve the
quality of life for patients with chronic macular disorders.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Review

PMID: 17658909 [PubMed - indexed for MEDLINE]

740: FASEB J. 2007 Dec;21(14):4077-86. Epub 2007 Jul 26.

N-tert-butyl hydroxylamine, a mitochondrial antioxidant, protects human retinal
pigment epithelial cells from iron overload: relevance to macular degeneration.

Voloboueva LA, Killilea DW, Atamna H, Ames BN.

Children's Hospital Oakland Research Institute, Nutrition and Metabolism Center, 
5700 Martin Luther King Jr. Way, Oakland, CA 94609-1673, USA.

Age-related macular degeneration (AMD) is the leading cause of severe visual
impairment in the elderly in developed countries. AMD patients have elevated
levels of iron within the retinal pigment epithelia (RPE), which may lead to
oxidative damage to mitochondria, disruption of retinal metabolism, and vision
impairment or loss. As a possible model for iron-induced AMD, we investigated the
effects of excess iron in cultured human fetal RPE cells on oxidant levels and
mitochondrial cytochrome c oxidase (complex IV) function and tested for
protection by N-tert-butyl hydroxylamine (NtBHA), a known mitochondrial
antioxidant. RPE exposure to ferric ammonium citrate resulted in a time- and
dose-dependent increase in intracellular iron, which increased oxidant production
and decreased glutathione (GSH) levels and mitochondrial complex IV activity.
NtBHA addition to iron-overloaded RPE cells led to a reduction of intracellular
iron content, oxidative stress, and partial restoration of complex IV activity
and GSH content. NtBHA might be useful in AMD due to its potential to reduce
oxidative stress, mitochondrial damage, and age-related iron accumulation, which 
may damage normal RPE function and lead to loss of vision.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 17656467 [PubMed - indexed for MEDLINE]

741: Acta Ophthalmol Scand. 2007 Aug;85(5):486-94.

Guidance for the treatment of neovascular age-related macular degeneration.

Schmidt-Erfurth UM, Richard G, Augustin A, Aylward WG, Bandello F, Corcòstegui B,
Cunha-Vaz J, Gaudric A, Leys A, Schlingemann RO; European Society for Retina
Specialists' Guidelines Committee (EURETINA).

Department of Ophthalmology, Medical University of Vienna, Austria.
Ursula.schmidt-erfurth@meduniwien.ac.at

Neovascular age-related macular degeneration is becoming an increasing
socio-medical problem as the proportion of the aged population is continuously
increasing. However, new insights in the pathogenesis of the disease offer the
opportunity to develop targeted therapies that attack the disease process more
successfully than ever. This review article will focus on summarizing the actual 
options in the management of neovascular age-related macular degeneration and
provide a short overview about recent therapeutic options in clinical and
preclinical evaluation. The recent development of anti-VEGF substances for use in
clinical routine has markedly improved the prognosis of patients with neovascular
AMD. Intravitreal treatment with substances targeting all isotypes of vascular
endothelial growth factor (VEGF), for the first time in the history of AMD
treatments, results in a significant increase in visual acuity in patients with
neovascular AMD. Overall, antiangiogenic approaches provide vision maintenance in
over 90% and substantial improvement in 25-40% of patients. The combination with 
occlusive therapies like photodynamic therapy (PDT) potentially offers a
reduction of re-treatment frequency and long-term maintenance of the treatment
benefit. Further developments interacting with various steps in the angiogenic
cascade are under clinical or preclinical evaluation and may soon become
available. Nevertheless, the growing number of novel therapeutic options will
have to provide proof of concept in randomized controlled clinical trials, a
major challenge in view of the rapidly evolving field. For those therapies, which
are already in clinical use, reasonable diagnostic tools for follow-up need to be
developed, as the burden of continuous clinical monitoring of all patients and
all indications is significant for patients and doctors. Ultimately, economic
issues will be the limiting factor for the clinical availability of different
treatment options.

Publication Types: 
    Review

PMID: 17655610 [PubMed - indexed for MEDLINE]

742: Graefes Arch Clin Exp Ophthalmol. 2008 Jan;246(1):105-14. Epub 2007 Jul 26.

Ocular fundus auto-fluorescence observations at different wavelengths in patients
with age-related macular degeneration and diabetic retinopathy.

Hammer M, Königsdörffer E, Liebermann C, Framme C, Schuch G, Schweitzer D,
Strobel J.

Department of Ophthalmoloy, University of Jena, Bachstr. 18, 07740, Jena,
Germany. martin.hammer@med.uni-jena.de

BACKGROUND: Post-translational protein modification by lipid peroxidation
products or glycation is a feature of aging as well as pathologic processes in
postmitotic cells at the ocular fundus exposed to an oxidative environment. The
accumulation of modified proteins such as those found in lipofuscin and advanced 
glycation end products (AGEs) contribute greatly to the fundus auto-fluorescence.
The distinct fluorescence spectra of lipofuscin and AGE enable their
differentiation in multispectral fundus fluorescence imaging. METHOD: A
dual-centre consecutive case series of 78 pseudo-phacic patients is reported.
Digital colour fundus photographs as well as auto-fluorescence images were taken 
from 33 patients with age related macular degeneration (AMD), 13 patients with
diabetic retinopathy (RD), or from 32 cases without pathologic findings
(controls). Fluorescence was excited at 475-515 nm or 476-604 nm and recorded in 
the emission bands 530-675 nm or 675-715 nm, respectively. Fluorescence images
excited at 475-515 nm were taken by a colour CCD-camera (colour-fluorescence
imaging) enabling the separate recording of green and red fluorescence. The ratio
of green versus red fluorescence was calculated within a representative region of
each image. RESULTS: The 530-675 nm auto-fluorescence in AMD patients was
dominated by the red emission (green vs. red ratio, g/r = 0.861). In comparison, 
the fluorescence of the diabetics was green-shifted (g/r = 0.946; controls: g/r =
0.869). Atrophic areas (geographic atrophy, laser scars) showed massive
hypo-fluorescence in both emission bands. Hyper-fluorescent drusen and exudates, 
unobtrusive in the colour fundus images as well as in the fluorescence images
with emission >667 nm, showed an impressive green-shift in the
colour-fluorescence image. CONCLUSIONS: Lipofuscin is the dominant fluorophore at
long wavelengths (>675 nm or red channel of the colour fluorescence image). In
the green spectral region, we found an additional emission of collagen and
elastin (optic disc, sclera) as well as deposits in drusen and exudates. The
green shift of the auto-fluorescence in RD may be a hint of increased AGE
concentrations.

Publication Types: 
    Multicenter Study

PMID: 17653752 [PubMed - indexed for MEDLINE]

743: Graefes Arch Clin Exp Ophthalmol. 2007 Dec;245(12):1781-7. Epub 2007 Jul 26.

Triamcinolone versus inner-limiting membrane peeling in persistent diabetic
macular edema (TIME study): design issues and implications.

Joussen AM, Weiss C, Bauer D, Hilgers RD; TIME Study group.

Collaborators: Kirchhof B, Lemmen KD, Agostini, Bornfeld, Bunse, Binder, Dahlke, 
Foja, Gandorfer, Groenewald, Hansen, Heimann, Hoerauf, Jochmann, Joussen, Kampik,
Kohen, Lommatzsch, Meier, Müller, Pauleikhoff, Pearce, Requadt, Roider, Stolba,
Ulbig, Wiechens, Wiedemann, Wong.

Department of Ophthalmology, University Hospital Duesseldorf, University of
Duesseldorf, Moorenstrasse 5, 40225 Duesseldorf, Germany. joussena@googlemail.com

AIM: Treatment options for persistent diabetic macular edema remain
disappointing. ILM peeling and intravitreal triamcinolone have been successfully 
used in several case series; however, there is no evidence that one of these
options is superior for specific groups of patients. The triamcinolone versus ILM
peeling in diabetic macular edema study (TIME-study) is designed to investigate
the efficacy of these two treatments in patients with persistent diabetic macular
edema. METHODS: Patients with persistent diabetic macular edema are randomised to
either the control group (no treatment), ppV + ILM peeling, or triamcinolone (4
mg) injection. One hundred thirty-five patients are to be recruited per group and
followed-up for one year. The main endpoints are defined as change in visual
acuity (VA) at 12 months compared to baseline and the change in retinal thickness
after 3 months follow-up. Secondary endpoints include differences in the
functional success and anatomical success and the effect of the treatment on the 
patient's quality of life. Twelve institutions (28 surgeons) in 3 European
countries agreed to contribute to the study. RESULTS: The design issues and
implications of the study are described. CONCLUSIONS: The TIME study is the first
randomised prospective clinical trial to investigate the effectiveness of the two
treatment methods. The results of this study should enable physicians to improve 
therapy and to select cases according to the most promising treatment option.

Publication Types: 
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17653751 [PubMed - indexed for MEDLINE]

744: Graefes Arch Clin Exp Ophthalmol. 2008 Jan;246(1):89-92. Epub 2007 Jul 25.

The prevalence of retinal angiomatous proliferation in age-related macular
degeneration with occult choroidal neovascularization.

Massacesi AL, Sacchi L, Bergamini F, Bottoni F.

Ophthalmology Department, S. Giuseppe Hospital, Milan, Italy.

BACKGROUND: The purpose of the study was to ascertain the prevalence of retinal
angiomatous proliferation (RAP) by means of dynamic indocyanine green angiography
(d-ICGA) in patients with newly diagnosed fibrovascular pigment epithelium
detachment (type 1) or late leakage of undetermined source (type 2) occult
choroidal neovascularization (CNV) on fluorescein angiography. METHODS: We
carried out a review of digital fluorescein and ICG angiograms obtained by
confocal scanning laser ophthalmoscope (HRA; Heidelberg Engineering GmbH,
Dossenheim, Germany) in 253 consecutive patients (270 eyes) with a clinical
diagnosis of type 1 or type 2 occult CNV on fluorescein angiography (1998 through
2003). RESULTS: Sixty eyes had type 1 and 210 eyes type 2 occult CNV on
fluorescein angiography. Overall, 57 cases of RAP were identified in 54 eyes
(20%) with d-ICGA. RAP was present in 6 out of 60 eyes with type 1 (10%) and in
51 out of 210 eyes with type 2 occult CNV (24%). Mean distance of the lesion from
the fovea was 682 +/- 304 microm (mean +/- SD). CONCLUSIONS: d-ICGA is invaluable
for early diagnosis of RAP in exudative age-related macular degeneration (ARMD). 
In our series, up to one fourth of type 2 occult CNV were in fact RAP.

PMID: 17653567 [PubMed - indexed for MEDLINE]

745: Mol Vis. 2007 Jun 28;13:1031-7.

High prevalence of mutations in peripherin/RDS in autosomal dominant macular
dystrophies in a Spanish population.

Gamundi MJ, Hernan I, Muntanyola M, Trujillo MJ, García-Sandoval B, Ayuso C,
Baiget M, Carballo M.

Servicio de Laboratorio, Biología y Genética Molecular Hospital de Terrassa,
Ctra. Torrebonica, Terrassa, Barcelona, Spain.

PURPOSE: Mutations in the peripherin/retinal degeneration slow (RDS) gene are a
known cause of various types of central retinal dystrophies. The purpose of this 
study was to determine the prevalence of mutations in the peripherin/RDS gene in 
Spanish patients with different types of autosomal dominant macular dystrophy.
METHODS: Ophthalmic and electrophysiological examination was performed in
patients from 61 unrelated autosomal dominant macular dystrophy (adMD) Spanish
families. Screening for mutations in the peripherin/RDS gene by denaturing
gradient gel electrophoresis (DGGE) and direct genomic sequencing was performed
in index patients and extended to the family when positive. RESULTS: We report
four novel mutations in peripherin/RDS and a relatively high frequency (23%) of
mutations in this gene in families with adMD. Thirteen different mutations were
found in fifteen adMD families. Three novel missense, four nonsense and a
cis-acting splicing mutation IVS2+2T>C, were found in a Spanish population while 
five more missense mutations were also reported in other populations. The
Arg142Trp and Arg172Trp mutations, present in several populations, were both
detected in two independent Spanish families. All the missense mutations produce 
an amino acid substitution in the second intradiscal loop of the peripherin,
while the nonsense mutations presumably generate a truncated protein.
CONCLUSIONS: A high frequency (23%) of mutations in the peripherin/RDS gene was
found in a cohort of 61 unrelated patients with various types of autosomal
dominant central retinal dystrophies as compared with a low prevalence (1.3%) of 
mutations in this gene causing retinitis pigmentosa in a Spanish population.
Different macular dystrophy phenotypes according to the mutations in
peripherin/RDS are shown. However, a limited phenotype variation was observed for
these mutations within the family.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17653047 [PubMed - indexed for MEDLINE]

746: Invest Ophthalmol Vis Sci. 2007 Aug;48(8):3827-36.

Murine ccl2/cx3cr1 deficiency results in retinal lesions mimicking human
age-related macular degeneration.

Tuo J, Bojanowski CM, Zhou M, Shen D, Ross RJ, Rosenberg KI, Cameron DJ, Yin C,
Kowalak JA, Zhuang Z, Zhang K, Chan CC.

Laboratory of Immunology, National Eye Institute, National Institutes of Health, 
Bethesda, Maryland 20892-1857, USA.

PURPOSE: Senescent Ccl2(-/-) mice are reported to develop cardinal features of
human age-related macular degeneration (AMD). Loss-of-function single-nucleotide 
polymorphisms within CX3CR1 are also found to be associated with AMD. The authors
generated Ccl2(-/-)/Cx3cr1(-/-) mice to establish a more characteristic and
reproducible AMD model. METHODS: Single Ccl2- and Cx3cr1-deficient mice were
crossbred to obtain Ccl2(-/-)/Cx3cr1(-/-) mice. Funduscopy, histopathology,
retinal A2E quantification, proteomics, RT-PCR gene expression assay,
immunochemistry, and Western blotting were used to examine the retina and to
evaluate gene expression within the retinal tissue. RESULTS: By 6 weeks of age,
all Ccl2(-/-)/Cx3cr1(-/-) mice developed AMD-like retinal lesions, including
drusen, retinal pigment epithelium alteration, and photoreceptor degeneration.
Furthermore, choroidal neovascularization occurred in 15% of the mice. These
degenerative lesions progressed with age. A2E, a major lipofuscin fluorophore
that accumulated during AMD progression, was significantly higher in the
Ccl2(-/-)/Cx3cr1(-/-) retina than in the wild-type retina. Complement cofactor
was higher in the Ccl2(-/-)/Cx3cr1(-/-) RPE. Proteomics data indicated that four 
proteins were differentially expressed in Ccl2(-/-)/Cx3cr1(-/-) retina compared
with control. One of these proteins, ERp29, an endoplasmic reticulum protein,
functions as an escort chaperone and in protein folding. CONCLUSIONS: The authors
concluded that Ccl2(-/-)/Cx3cr1(-/-) mice develop a broad spectrum of AMD
abnormalities with early onset and high penetrance. These observations implicate 
certain chemokines and endoplasmic reticulum proteins in AMD pathogenesis.
Similar to the mechanism of neurodegeneration caused by dysfunction of
endoplasmic reticulum proteins, decreased chaperoning may cause misfolded protein
accumulation, leading to drusen formation and retinal degeneration.

Publication Types: 
    Research Support, N.I.H., Intramural

PMID: 17652758 [PubMed - indexed for MEDLINE]

747: Invest Ophthalmol Vis Sci. 2007 Aug;48(8):3783-7.

Ethnic differences in macular pigment density and distribution.

Wolf-Schnurrbusch UE, Röösli N, Weyermann E, Heldner MR, Höhne K, Wolf S.

Klinik und Poliklinik für Augenheilkunde, Inselspital, University Bern, Bern,
Switzerland.

PURPOSE: Many epidemiologic studies suggest a number of risk factors that may be 
associated with progression of age-related maculopathy (ARM). In this study, the 
authors investigate ethnic differences in macular pigment density (MPD) and
macular pigment (MP) distribution. METHODS: Inclusion criteria were healthy
subjects, aged 35 to 49 years, visual acuity >or=20/20, race ethnicity white
non-Hispanic (WNH) or African. All subjects underwent the following examinations:
best-corrected ETDRS visual acuity (VA), measurements of MPD, and spatial
distribution of MP with a modified confocal scanning laser ophthalmoscope
according to a standard protocol. MPD maps were calculated from autofluorescence 
images recorded at 488 nm and 514 nm. Central macular pigment density (MPDc) was 
quantified from MPD maps within 0.5 degrees around the center of the fovea.
RESULTS: In total, 118 healthy subjects (61 women, 57 men) aged 35 to 49 years
(mean, 42.5 +/- 3.6 years) were recruited for the study. Sixty-seven healthy
subjects were WNH and 51 were African. Visual acuity ranged from 20/20 to 20/16
in the study eye. Significant differences were found among MPDc between the group
of WNH (MPDc, 0.36 +/- 0.13 density units [DU]; P < 0.0001) and African subjects 
(MPDc, 0.59 +/- 0.14 DU). A parafoveal ring was significantly more frequent in
African subjects than in WNH subjects (86% [African] vs. 68% [WNH]; P < 0.0001). 
CONCLUSIONS: This study demonstrates that ethnicity plays a role in MPD values
and in MP distribution. The association of different distribution patterns and
their relevance as possible prognostic factors for diseases leading to oxidative 
retinal damage requires further studies.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17652752 [PubMed - indexed for MEDLINE]

748: Invest Ophthalmol Vis Sci. 2007 Aug;48(8):3469-79.

Age-related macular degeneration and retinal protein modification by
4-hydroxy-2-nonenal.

Ethen CM, Reilly C, Feng X, Olsen TW, Ferrington DA.

Department of Biochemistry, University of Minnesota, Minneapolis, Minnesota, USA.

PURPOSE: Oxidative damage to proteins, lipids, and DNA has been suggested to be a
mechanism for age-related macular degeneration (AMD). The retina is particularly 
susceptible to lipid peroxidation due to high concentrations of easily oxidized
polyunsaturated fatty acids in the presence of abundant oxygen. One of the most
toxic products of lipid peroxidation, 4-hydroxy-2-nonenal (HNE), can modify and
inactivate proteins. The hypothesis was that 4-HNE-modified proteins would
accumulate and serve as a marker for progressive stages of AMD. METHODS: Proteins
containing HNE adducts were identified in both the macular and peripheral regions
during four progressive stages of AMD. The proteins were resolved by
two-dimensional (2-D) gel electrophoresis before detection of HNE-adducted
proteins. Modified proteins were identified by matrix-assisted laser desorption
ionization time-of-flight mass spectrometry (MALDI-TOF/MS). The total content of 
HNE adducts was compared using a slot blot immunoassay. One-dimensional Western
blot analysis was used to measure levels of proteins involved in HNE
detoxification. RESULTS: Nineteen proteins that were consistently modified
regardless of stage of AMD or retinal region were identified. These proteins are 
involved in two main functions: energy production and stress response. No change 
in total HNE-adducted protein was observed between regions or stages. Modest
increases in content of proteins involved in HNE detoxification were observed.
CONCLUSIONS: Consistently modified proteins indicate preferred protein targets
for oxidation by HNE. HNE-modified proteins were not different between regions or
stages, suggesting that pathways for detoxification of HNE or removal of damaged 
proteins are adequate. Consistent levels of HNE-modified proteins suggest that
HNE is not a sensitive retinal biomarker for AMD.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17652714 [PubMed - indexed for MEDLINE]

749: Acta Ophthalmol. 2008 Feb;86(1):34-9. Epub 2007 Jul 25.

Correlation between intraretinal changes in diabetic macular oedema seen in
fluorescein angiography and optical coherence tomography.

Soliman W, Sander B, Hasler PW, Larsen M.

Department of Ophthalmology, Glostrup Hospital, University of Copenhagen,
Copenhagen, Denmark. waelsoliman73@yahoo.com

PURPOSE: To study the relationship between intraretinal optical coherence
tomography (OCT) and fluorescein angiography (FA) findings in eyes with diabetic 
macular oedema (DMO). METHODS: We carried out a retrospective observational case 
series. Thirty eyes with previously untreated DMO underwent FA and OCT. The same 
ETDRS template was overlaid on the FA images in order to compare OCT and FA.
Transfoveal linear high-resolution OCT scans (at the 0- and 90-degree meridians) 
and FA pictures were compared according to the ETDRS rings. RESULTS: Six distinct
patterns of intraretinal changes in OCT correlated with changes in FA: (a) focal 
angiographic leakage did not correspond to any obvious intraretinal abnormality
in OCT in four eyes; (b) localized thickening of the outer nuclear layer in OCT
corresponded to focal leaking microaneurysm (focal oedema) in FA in 11 eyes; (c) 
diffuse thickening of the outer nuclear layer in OCT corresponded to diffuse
angiographic leakage in 21 eyes; (d) cystoid expansion of the outer nuclear layer
was found in seven eyes with a petaloid angiographic pattern of leakage; (e)
cystoid expansion of the inner nuclear layer was found in relation to honeycomb
angiographic oedema in five eyes, and (f) serous detachment of the fovea in OCT
did not correspond to any distinct finding in FA in four eyes. CONCLUSIONS:
Intraretinal abnormalities found in OCT correlate systemically with changes in
FA. Very early DMO morphological changes may be seen better with FA than with
OCT. Serous detachment of the fovea is seen in OCT, but not in FA. The
combination of OCT and FA is useful in facilitating understanding of the
pathophysiological changes that occur in DMO.

PMID: 17651471 [PubMed - indexed for MEDLINE]

750: Acta Ophthalmol Scand. 2007 Dec;85(8):877-82. Epub 2007 Jul 25.

Reading performance with low-vision aids and vision-related quality of life after
macular translocation surgery in patients with age-related macular degeneration.

Nguyen NX, Besch D, Bartz-Schmidt K, Gelisken F, Trauzettel-Klosinski S.

Department of Ophthalmology II, University Eye Hospital, Tübingen, Germany.
nhung.nguyen@med.uni-tuebingen.de

PURPOSE: The aim of the present study was to evaluate the power of magnification 
required, reading performance with low-vision aids and vision-related quality of 
life with reference to reading ability and ability to carry out day-to-day
activities in patients after macular translocation. METHODS: This study included 
15 patients who had undergone macular translocation with 360-degree peripheral
retinectomy. The mean length of follow-up was 19.2 +/- 10.8 months (median 11
months). At the final examination, the impact of visual impairment on reading
ability and quality of life was assessed according to a modified 9-item
questionnaire in conjunction with a comprehensive clinical examination, which
included assessment of best corrected visual acuity (BCVA), the magnification
power required for reading, use of low-vision aids and reading speed. Patients
rated the extent to which low vision restricted their ability to read and
participate in other activities that affect quality of life. Responses were
scored on a scale of 1.0 (optimum self-evaluation) to 5.0 (very poor). RESULTS:
In the operated eye, overall mean postoperative BCVA (distance) was not
significantly better than mean preoperative BCVA (0.11 +/- 0.06 and 0.15 +/-
0.08, respectively; p = 0.53). However, 53% of patients reported a subjective
increase in visual function after treatment. At the final visit, the mean
magnification required was x 7.7 +/- 6.7. A total of 60% of patients needed
optical magnifiers for reading and in 40% of patients closed-circuit TV systems
were necessary. All patients were able to read newspaper print using adapted
low-vision aids at a mean reading speed of 71 +/- 40 words per minute. Mean
self-reported scores were 3.2 +/- 1.1 for reading, 2.5 +/- 0.7 for day-to-day
activities and 2.7 +/- 3.0 for outdoor walking and using steps or stairs.
Patients' levels of dependency were significantly correlated with scores for
reading (p = 0.01), day-to-day activities (p < 0.001) and outdoor walking and
using steps (p = 0.001). CONCLUSIONS: The evaluation of self-reported visual
function and vision-related quality of life in patients after macular
translocation is necessary to obtain detailed information on treatment effects.
Our results indicated improvement in patients' subjective evaluations of visual
function, without significant improvement in visual acuity. The postoperative
clinical benefits of treatment coincide with subjective benefits in terms of
reading ability, quality of life and patient satisfaction. Our study confirms the
importance and efficiency of visual rehabilitation with aids for low vision after
surgery.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17651462 [PubMed - indexed for MEDLINE]

751: Clin Experiment Ophthalmol. 2007 Jul;35(5):448-57.

New algorithm for assessing patient suitability for macular translocation
surgery.

Uppal G, Milliken A, Lee J, Acheson J, Hykin P, Tufail A, da Cruz L.

Moorfields Eye Hospital, London, UK. gurmit@orange.net

PURPOSE: We propose a case selection algorithm to assess suitability for macular 
translocation for subfoveal neovascular membrane (CNV) secondary to age-related
macular degeneration. The algorithm is based on preoperative assessment of
residual foveal function, as assessed by a slit-lamp fixation task and duration
of visual loss, in patients with poor acuity. We validate our slit-lamp fixation 
task against an objective analysis (Nidek MP-1 Microperimetry) and proceed to
examine surgical outcomes as selected by the algorithm. METHODS: A prospective
series of 27 consecutive patients with CNV underwent translocation at Moorfields 
Eye Hospital, London between May 2003 and May 2006. RESULTS: Validation of the
slit-lamp fixation task revealed 100% concordance in classification of fixation
between the slit-lamp task and the microperimeter. At an average follow up of
12.2 months, the mean Early Treatment of Diabetic Retinopathy Study distance
acuity improved from logMAR 0.88 to 0.68 (P < 0.03). Sixty-six per cent of
patients achieved an acuity of < or =logMAR 0.8 (6/30), 22% an acuity of < or
=logMAR 0.3 (6/12) and 33% gained three lines of acuity. The mean MN Read reading
acuity improved from logMAR 1.23 to 0.91 (P < 0.01). Forty-four per cent of
patients achieved an acuity of > or =logMAR 0.7 (N10), 15% an acuity of > or
=logMAR 0.4 (N5) and 44% gained three lines of acuity. DISCUSSION: We have
demonstrated a simple case selection algorithm that is based on residual foveal
function and suggests good outcomes. The strongest indicators of foveal function 
are fixation characteristics and duration of visual loss. In contrast to previous
studies, our algorithm suggests good outcomes independently of preoperative
visual acuity and CNV characteristics.

PMID: 17651250 [PubMed - indexed for MEDLINE]

752: J Fr Ophtalmol. 2007 Jun;30(6):616-20.

A novel mutation in the VMD2 gene in an Italian family with Best maculopathy.

Sodi A, Passerini I, Simonelli F, Testa F, Menchini U, Torricelli F.

Department of Oto-Neuro-Ophthalmological Surgical Sciences, University of
Florence, Italy. asodi@tin.it

Vitelliform macular dystrophy (Best disease) is an inherited macular degeneration
in which the primary defect is thought to occur at the level of the retinal
pigment epithelium. The VMD2 gene, considered responsible for the disease, mapped
to the long arm of chromosome 11, and it codifies the bestrophin protein,
probably acting as a transmembrane ionic channel. In the present study, we
screened for mutations the VMD2 gene in Italian patients with Best maculopathy.
Five families with Best disease were recruited from central and southern Italy,
and family members were evaluated by complete ophthalmologic examination and DNA 
analysis by means of DHPLC technology. Some mutations of the VMD2 gene were
identified and among them there was a novel mutation (R218G), probably involving 
a functionally active region of the bestrophin protein. In spite of the small
number of families considered, it was possible to note a significant phenotypic
heterogeneity. First, in one family the R218C mutation was associated with early 
onset of choroidal neovascularization (CNV) in the affected mother and her son,
while no CNV was reported in another family sharing the same mutation. Then a
patient with the R25W mutation showed a multifocal location of the vitelliform
deposits, while another family with the same mutation showed a typical isolated
vitelliform disc in the macular area.

PMID: 17646752 [PubMed - indexed for MEDLINE]

753: Trends Mol Med. 2007 Aug;13(8):345-52. Epub 2007 Jul 17.

Anti-angiogenic therapy of exudative age-related macular degeneration: current
progress and emerging concepts.

Noël A, Jost M, Lambert V, Lecomte J, Rakic JM.

Laboratory of Tumor and Development Biology, Center for Experimental Cancer
Research, Center for Biomedical Integrative Genoproteomics, University of Liège, 
B-4000 Liège, Belgium. agnes.noel@ulg.ac.be

Age-related macular degeneration (AMD) is the leading cause of blindness in
elderly patients. The more aggressive exudative form is characterized by abnormal
blood-vessel development that occurs beneath the retina as a result of choroidal 
neovascularization (CNV). Vascular endothelial growth factor (VEGF) has emerged
as the key mediator of CNV formation; this has led to intensive research on VEGF 
and the recent approval of anti-VEGF compounds by the US Food and Drug
Administration. Despite this successful introduction of anti-angiogenic therapies
into the clinical setting, there is still a lack of treatments that definitively 
reverse damaged vision. Here, we consider the importance of putative molecular
targets other than VEGF that might have been underestimated. Emerging cellular
mechanisms offer additional opportunities for innovative therapeutic approaches.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17644433 [PubMed - indexed for MEDLINE]

754: Eye. 2008 Jun;22(6):799-807. Epub 2007 Jul 20.

Autologous translocation of the choroid and RPE in age-related macular
degeneration: 1-year follow-up in 30 patients and recommendations for patient
selection.

Heussen FM, Fawzy NF, Joeres S, Lux A, Maaijwee K, Meurs JC, Kirchhof B, Joussen 
AM.

Department of Vitreoretinal Surgery, Center of Ophthalmology, University of
Cologne, Cologne, Germany.

AIM: To evaluate the long-term (1 year) functional and anatomical outcome of
autologous translocation of peripheral choroid and retinal pigment epithelium
(RPE) in 30 patients with age-related macular degeneration (AMD). METHODS: After 
the extraction of the neovascular complex, an autologous peripheral
full-thickness graft of RPE and choroid was positioned under the macula.
Functional tests included ETDRS vision, reading (Radner test), and microperimetry
(scanning laser ophthalmoscope). Fluorescein, indocyanine green angiography, and 
autofluorescence were monitored. RESULTS: Preoperative visual acuity ranged from 
20/40 to 20/800 (0.3-1.6 log MAR). Vision ranged from 20/25 to LP (0.1-2.1 log
MAR) 1 year after surgery, with stabilization in six eyes, an increase in five
eyes, and a decrease in 19 eyes. Deterioration mostly occurred within the first 3
months after surgery. In patients who demonstrated vascularization of the graft
after 3 months, this persisted up to 12 months as did fixation when initially
stable. Autofluorescence decreased significantly from 6 to 12 months
postoperatively. Eleven cases showed a recurrence of choroidal neovascularization
(CNV) within this period. CONCLUSION: Patch translocation results in a viable
graft. There is no evidence of graft failure within a 1-year follow-up.
Nevertheless, there is risk for late CNV formation originating from the edges of 
the excision side of the CNV and growing peripheral to the graft.

Publication Types: 
    Evaluation Studies

PMID: 17641681 [PubMed - indexed for MEDLINE]

755: Cochrane Database Syst Rev. 2007 Jul 18;(3):CD004763.

Laser photocoagulation for neovascular age-related macular degeneration.

Virgili G, Bini A.

University of Florence, Department of Ophthalmology, Via le Morgagni 85,
Florence, Italy, 50134. gianni.virgili@unifi.it

BACKGROUND: Laser photocoagulation was the first treatment introduced to try to
halt the progression of neovascular age-related macular degeneration (AMD), in
which newly formed vessels or choroidal neovascularisation (CNV) grow under the
macula leading to the occurrence of a scotoma or blind spot in the central visual
field. OBJECTIVES: The aim of this review was to examine the effects of laser
photocoagulation for neovascular AMD. SEARCH STRATEGY: We searched the CENTRAL,
MEDLINE, EMBASE, LILACS, NRR and ZETOC in March 2007. SELECTION CRITERIA: We
included randomised trials of laser photocoagulation in people with CNV due to
AMD. DATA COLLECTION AND ANALYSIS: Two authors independently extracted the data. 
The risk ratio (RR) of severe visual loss (loss of six or more lines of visual
acuity) was estimated at three months and two years after treatment. MAIN
RESULTS: Fifteen trials were included in the review (2064 participants). Three
types of photocoagulation were used in the trials: direct photocoagulation of the
entire CNV (11 trials), perifoveal photocoagulation (one trial) and grid
photocoagulation (three trials). In 12 trials the control group was observation
only. One trial compared photocoagulation to submacular surgery and two trials
compared different lasers. Data on the progression of visual loss could be
extracted from five of the eight trials of direct photocoagulation of the CNV
versus observation. The treatment effect was in the direction of harm in all
studies at three months follow up (RR 1.41, 95% confidence intervals (CI) 1.08 to
1.82). After two years the treatment effect was in the direction of benefit (RR
0.67, 95% CI 0.53 to 0.83). These studies were clinically heterogeneous with
participants having CNV lesions in different locations and different baseline
visual acuities. There was little evidence of statistical heterogeneity at three 
months but substantial statistical heterogeneity at two years. However, all
treatment effects in the individual trials were in the direction of benefit. One 
study comparing perifoveal photocoagulation or observation of subfoveal CNV found
benefits that were statistically significant only at two years (RR 0.36, 95% CI
0.18 to 0.72). Other comparisons did not demonstrate differences. AUTHORS'
CONCLUSIONS: In the medium to long term laser photocoagulation of CNV slows the
progression of visual loss in people with neovascular AMD. However, it is
associated with an increased risk of visual loss immediately after treatment and 
this period may be longer in people with subfoveal AMD. With the advent of modern
pharmacological therapies, and concern for the impact of iatrogenic scotoma in
subfoveal CNV, laser photocoagulation of subfoveal CNV is not recommended. No
studies have compared photocoagulation with modern pharmacological agents for AMD
for non-subfoveal CNV.

Publication Types: 
    Meta-Analysis
    Review

PMID: 17636773 [PubMed - indexed for MEDLINE]

756: Cochrane Database Syst Rev. 2007 Jul 18;(3):CD002030.

Update of:
    Cochrane Database Syst Rev. 2005;(4):CD002030.

Photodynamic therapy for neovascular age-related macular degeneration.

Wormald R, Evans J, Smeeth L, Henshaw K.

London School of Hygiene & Tropical Medicine, International Centre for Eye
Health, Keppel Street, London, UK, WC1E 7HT. r.wormald@ucl.ac.uk

BACKGROUND: In neovascular age-related macular degeneration (AMD) new vessels
grow under the retina distorting vision and leading to scarring. This is
exacerbated if the blood vessels leak. Photodynamic therapy (PDT) has been
investigated as a way to treat the neovascular membranes without affecting the
retina. OBJECTIVES: The aim of this review was to examine the effects of PDT in
the treatment of neovascular AMD. SEARCH STRATEGY: We searched CENTRAL (Issue 1, 
2007), MEDLINE (1966 to March 2007), EMBASE (1980 to March 2007). We contacted
experts in the field and searched the reference lists of relevant studies.
SELECTION CRITERIA: We included randomised trials of PDT in people with choroidal
neovascularisation due to AMD. DATA COLLECTION AND ANALYSIS: Two authors
independently extracted the data. Risk ratios were combined using a fixed-effect 
model after testing for heterogeneity. MAIN RESULTS: Three published trials were 
identified that randomised 1022 participants to verteporfin therapy compared to
5% dextrose in water. The TAP and VIP trials were performed by the same
investigators using largely the same clinical centres and funded by manufacturers
of verteporfin. Outcome data were available at 12 and 24 months after the first
treatment. Participants received on average five treatments over two years. The
risk ratio of losing three or more lines of visual acuity at 24 months comparing 
the intervention with the control group was 0.77 (95% confidence interval 0.69 to
0.87). The risk ratio of losing six or more lines of visual acuity at 24 months
comparing the intervention with the control group was 0.62 (95% confidence
interval 0.50 to 0.76). The results at 12 months were similar to those at 24
months. The most serious adverse outcome, acute (within seven days of treatment) 
severe visual acuity decrease, occurs in about one in 50 patients. Some outcomes 
from the more recent VIM trial could be included in the meta-analysis but have
not greatly altered the findings. AUTHORS' CONCLUSIONS: Photodynamic therapy in
people with choroidal neovascularisation due to AMD is probably effective in
preventing visual loss though there is doubt about the size of the effect.
Outcomes and potential adverse effects of this treatment should be monitored
closely. Further independent trials of verteporfin are required to establish that
the effects seen in this study are consistent and to examine important issues not
yet addressed, particularly relating to quality of life and cost. However, the
advent of new interventions for AMD make this unlikely.

Publication Types: 
    Meta-Analysis
    Review

PMID: 17636693 [PubMed - indexed for MEDLINE]

757: Int Ophthalmol. 2008 Apr;28(2):95-9. Epub 2007 Jul 20.

Quantitative evaluation of reduction of plaque-like hard exudates in diabetic
macular edema after intravitreal triamcinolone injection.

Cekiç O, Bardak Y, Tiğ US, Yildizoğlu U, Bardak H.

Department of Ophthalmology, Süleyman Demirel University Medical School, Isparta,
Turkey. ocekic@hotmail.com

BACKGROUND: To describe a new method of quantifying the amount of plaque-like
hard exudates after intravitreal triamcinolone acetonide injection in diabetic
macular edema. METHODS: This study included 22 eyes of 14 patients (mean age, 63 
years) with chronic diabetic macular edema and plaque-like hard exudates. The
patients were injected with a single dose of 4 mg intravitreal triamcinolone
acetonide. The optic disc size as relative size unit was taken to quantify the
hard exudates: Total areas of exudates and the optic nerve head were computed
from fundus pictures with a digital analysis program on magnified images. The
former was divided by the latter, and the results were expressed as a percentage 
value. The ratio was used to track improvements in a given eye over 6 months.
RESULTS: Average ratio of hard exudates to optic nerve head area reduced to 81%
of its initial value at 1 month (P=0.007), to 54% at 3 months (P<0.001) and to
41% at 6 months (P<0.001). CONCLUSIONS: The new method allowed detection of a
significant reduction of ratio of hard exudates to optic disc area of diabetic
plaque-like hard exudates following 4 mg intravitreal triamcinolone.

PMID: 17634861 [PubMed - indexed for MEDLINE]

758: Int Ophthalmol. 2008 Apr;28(2):101-9. Epub 2007 Jul 20.

Safety monitoring in bevacizumab (Avastin) treatment: retinal function assessed
by psychophysical (visual fields, colour vision) and electrophysiological
(ERG/EOG) tests in two subgroups of patients.

Ziemssen F, Lüke M, Messias A, Beutel J, Tatar O, Zrenner E, Bartz-Schmidt KU;
Tuebingen Bevacizumab Study Group.

Department for Ophthalmology, Eberhard-Karls University Tuebingen, Tuebingen,
Germany. Focke.Ziemssen@med.uni-tuebingen.de

BACKGROUND: Bevacizumab (Avastin) has been used as off-label treatment for the
specific inhibition of the vascular endothelial growth factor (VEGF). Although
only intravenous administration of the drug is approved in combination therapy of
colorectal carcinoma, promising short-term results have been reported about its
intravitreal administration. However, VEGF is also known to exhibit neurotrophic 
capabilities. Therefore, blockage of all VEGF isoforms by bevacizumab could
induce toxic effects. Missing randomized controlled studies and unclear long-term
risks require further evaluation. METHODS: Intensified monitoring of bevacizumab 
treatment was performed in consecutive patients. In ten patients, the functional 
field score was calculated after obtaining Goldmann visual fields at baseline and
1 year after injection. The other subgroup was examined by means of EOG, ERG and 
colour testing at baseline and 4 months following treatment. Naka-Rushton plots
were calculated to enable statements about retinal function. Lanthony desaturated
D15 test was used for repeated colour testing. RESULTS: Baseline parameters
already disclosed predominant cone dysfunction. Drug-related effects caused a
significant improvement of visual acuity. There was no sign of clinically
relevant retinal toxicity following the bevacizumab injection. No progression of 
visual field defects was seen within the follow-up of 1 year. Performance in EOG 
testing was affected by restricted fixation stability, but no parameter indicated
deterioration within the 4-month-period. CONCLUSIONS: Short-term results
underline that intraocular bevacizumab injection promises to be not only a
cost-effective, but safe treatment option. Assessed functional parameters as
error scores (e.g., Lanthony) corresponded to the impaired retinal function which
was presumed to be disease-related. Further long-term results have to confirm the
good tolerability in repeated treatment.

PMID: 17634860 [PubMed - indexed for MEDLINE]

759: N Engl J Med. 2007 Aug 9;357(6):553-61. Epub 2007 Jul 18.

Complement C3 variant and the risk of age-related macular degeneration.

Yates JR, Sepp T, Matharu BK, Khan JC, Thurlby DA, Shahid H, Clayton DG, Hayward 
C, Morgan J, Wright AF, Armbrecht AM, Dhillon B, Deary IJ, Redmond E, Bird AC,
Moore AT; Genetic Factors in AMD Study Group.

Department of Medical Genetics, Cambridge Institute for Medical Research,
University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom.
jrwy1@cam.ac.uk

BACKGROUND: Age-related macular degeneration is the most common cause of
blindness in Western populations. Susceptibility is influenced by age and by
genetic and environmental factors. Complement activation is implicated in the
pathogenesis. METHODS: We tested for an association between age-related macular
degeneration and 13 single-nucleotide polymorphisms (SNPs) spanning the
complement genes C3 and C5 in case subjects and control subjects from the
southeastern region of England. All subjects were examined by an ophthalmologist 
and had independent grading of fundus photographs to confirm their disease
status. To test for replication of the most significant findings, we genotyped a 
set of Scottish cases and controls. RESULTS: The common functional polymorphism
rs2230199 (Arg80Gly) in the C3 gene, corresponding to the electrophoretic
variants C3S (slow) and C3F (fast), was strongly associated with age-related
macular degeneration in both the English group (603 cases and 350 controls,
P=5.9x10(-5)) and the Scottish group (244 cases and 351 controls, P=5.0x10(-5)). 
The odds ratio for age-related macular degeneration in C3 S/F heterozygotes as
compared with S/S homozygotes was 1.7 (95% confidence interval [CI], 1.3 to 2.1);
for F/F homozygotes, the odds ratio was 2.6 (95% CI, 1.6 to 4.1). The estimated
population attributable risk for C3F was 22%. CONCLUSIONS: Complement C3 is
important in the pathogenesis of age-related macular degeneration. This finding
further underscores the influence of the complement pathway in the pathogenesis
of this disease. Copyright 2007 Massachusetts Medical Society.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17634448 [PubMed - indexed for MEDLINE]

760: Optom Vis Sci. 2007 Jul;84(7):559-72.

Current treatment of age-related macular degeneration.

Zarbin M, Szirth B.

Institute of Ophthalmology and Visual Science, New Jersey Medical School, Newark,
New Jersey 07103, USA. zarbin@umdnj.edu

PURPOSE: To review proved and experimental treatments for exudative and
nonexudative complications of age-related macular degeneration (AMD), to consider
the impact of current therapy on the structure of future clinical trials, and to 
consider the role of improved diagnostic imaging techniques on the effectiveness 
of current therapy as well as the structure of future clinical trials in AMD
patients. RESULTS: Defining the cell biology of choroidal new vessel (CNV)
formation and geographic atrophy will lead to identification of different
biochemical pathways that are the target of AMD treatment. Many treatments and
treatment combinations are under study for AMD, but all work through a finite
number of pathways. Currently, the most effective proved therapy for
AMD-associated CNVs is administered by repeated intravitreal injection of agents 
that inhibit vascular endothelial growth factor, e.g., ranibizumab. Improved drug
delivery will enhance patient satisfaction and possibly will enhance the
effectiveness and reduce the risk of current pharmacotherapy for AMD-associated
CNVs. Combination therapy (e.g., verteporfin-photodynamic therapy + ranibizumab) 
appears to reduce the risk and enhance the effectiveness of CNV treatment
compared with monotherapy with currently available agents. Improved noninvasive
diagnostic imaging may lead to better visual outcomes with existing therapeutic
modalities. Improved imaging also may alter favorably the design of future
clinical trials for AMD-associated CNVs and thus reduce cost and increase the
diversity of sight-saving treatments. CONCLUSIONS: Delineation of the biochemical
basis for CNV formation has led to development of pathway-based pharmacotherapy
for AMD patients. Areas of investigation that will advance the field further
include combination therapy, improved drug delivery, and improved noninvasive,
high-resolution diagnostic imaging. The logistics of future clinical trials will 
be complicated by the need for an active treatment control group, more stringent 
definition of successful treatment, and the increased numbers of patients
required for combination therapy studies.

Publication Types: 
    Review

PMID: 17632299 [PubMed - indexed for MEDLINE]

761: Am J Ophthalmol. 2007 Sep;144(3):404-408. Epub 2007 Jul 12.

Clinical phenotypes associated with the complement factor H Y402H variant in
age-related macular degeneration.

Brantley MA Jr, Edelstein SL, King JM, Apte RS, Kymes SM, Shiels A.

Department of Ophthalmology and Visual Sciences, Washington University School of 
Medicine, St Louis, Missouri 63110, USA. brantley@vision.wustl.edu

PURPOSE: To determine whether the complement factor H (CFH) Y402H variant is
associated with specific age-related macular degeneration (AMD) clinical
phenotypes. DESIGN: Retrospective, case-control study. METHODS: One hundred and
eighty-eight white subjects with AMD and 189 control subjects were genotyped for 
the T-to-C polymorphism in exon 9 of the CFH gene by restriction-fragment length 
analysis and deoxyribonucleic acid (DNA) sequencing using genomic DNA from
mouthwash samples. AMD phenotypes were characterized by clinical examination,
fundus photography, and fluorescein angiography. RESULTS: Heterozygosity for the 
at-risk genotype (TC) increased the likelihood for AMD 2.1-fold (95% confidence
interval [CI], 1.3 to 3.3), whereas homozygosity for the genotype (CC) increased 
the likelihood for AMD 6.5-fold (95% CI, 3.4 to 12.5) in our population. The C
allele was associated significantly with predominantly classic choroidal
neovascularization (odds ratio [OR], 2.01; 95% CI, 1.34 to 3.30). Neovascular
lesion size was similar among the three genotypes (P = .67). CONCLUSIONS: The
Y402H CFH variant carried a significantly increased risk for developing AMD in
our population. Genotype and phenotype correlations regarding choroidal
neovascular lesion type were observed.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 17631852 [PubMed - indexed for MEDLINE]

762: Am J Ophthalmol. 2007 Sep;144(3):414-418. Epub 2007 Jul 13.

Urinary cadmium and age-related macular degeneration.

Erie JC, Good JA, Butz JA, Hodge DO, Pulido JS.

Department of Ophthalmology, Mayo Clinic College of Medicine, Rochester,
Minnesota 55905, USA. erie.jay@mayo.edu

PURPOSE: To evaluate the association between urinary and blood cadmium (Cd)
levels with age-related macular degeneration (AMD). DESIGN: Prospective
case-control study. METHODS: In 53 participants older than 60 years with AMD in
both eyes and in 53 age-matched (+/- 3 years) controls without AMD, Cd levels
were measured in blood and urine specimens (with and without creatinine
adjustment) by using inductively coupled plasma-mass spectrometry. Data on age,
gender, smoking status, and family history were obtained. By using color
stereoscopic fundus photographs, the degree of AMD was graded using the
Age-Related Eye Disease Study's 4-stage AMD severity scale. The inclusion
criterion for AMD cases was a photographic severity level of two to four in both 
eyes. Median blood and urine Cd and median urine Cd/creatinine concentrations in 
cases and controls were compared by using the rank-sum test, stratifying for
smoking status. RESULTS: Current and former smokers with AMD had median urine
Cd/creatinine levels (1.18 microg/g; range, 0.84 to 1.44 microg/g) that were 97% 
higher than smokers without AMD (0.60 microg/g; range, 0.49 to 0.90 microg/g; P =
.02), 111% higher than never smokers with AMD (0.56 microg/g; range, 0.40 to 0.80
microg/g; P < .001) and 107% higher than never smokers without AMD (0.57
microg/g; 0.40 to 0.65 microg/g; P < .001). Blood Cd levels, indicative of
short-term exposure levels, were not associated with AMD (P >/= .06).
CONCLUSIONS: A higher urinary Cd level, which reflects the total body burden of
Cd, was associated with AMD in smokers. Accumulated Cd exposure may be important 
in the development of smoking-related AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17631267 [PubMed - indexed for MEDLINE]

763: Ophthalmology. 2008 Feb;115(2):347-354.e2. Epub 2007 Jul 12.

Quantitative comparison of optical coherence tomography after pegaptanib or
bevacizumab in neovascular age-related macular degeneration.

Joeres S, Kaplowitz K, Brubaker JW, Updike PG, Collins AT, Walsh AC, Romano PW,
Sadda SR.

Doheny Image Reading Center, Doheny Eye Institute, Keck School of Medicine of the
University of Southern California, Los Angeles, California, USA.

PURPOSE: To demonstrate the benefit of enhanced quantitative analysis of optical 
coherence tomography (OCT) images using computer-assisted grading to compare the 
short-term morphologic effects of pegaptanib and bevacizumab treatment for
neovascular age-related macular degeneration (AMD). DESIGN: Retrospective
consecutive case series. PARTICIPANTS: Fifty-three cases with neovascular AMD
undergoing pegaptanib or bevacizumab therapy. METHODS: Fifty-three consecutive
cases of patients who underwent StratusOCT imaging followed by treatment with
either intravitreal pegaptanib (n = 18) or bevacizumab (n = 35) for neovascular
AMD were retrospectively collected. Raw exported StratusOCT images were analyzed 
using publicly available custom software (OCTOR) designed to define the
boundaries of various spaces manually. Changes in thickness and volume of the
retina, subretinal fluid (SRF), subretinal tissue, and pigment epithelial
detachments (PEDs) before treatment and at 3 months after treatment were
calculated and compared between treatment groups. OCTOR software measurements
after manual grading were also compared with the automated StratusOCT output.
MAIN OUTCOME MEASURES: Volume and thickness measurements calculated by the
automated StratusOCT software and the manual grading software OCTOR. RESULTS:
Intravitreal bevacizumab resulted in a statistically significant greater
reduction of total retinal volume than pegaptanib (-0.88+/-1.4 mm(3) vs.
-0.07+/-0.5 mm(3), P = 0.003). Mean foveal central subfield (FCS) retinal volume 
decreased from 0.26+/-0.1 mm(3) to 0.21+/-0.1 mm(3) (P = 0.001) in the
bevacizumab group and remained constant at 0.22+/-0.1 in the pegaptanib group 3
months after injection. Subanalysis of the SRF, subretinal tissue, and PEDs
revealed statistically significant reductions of the total volume of all 3 spaces
after bevacizumab injections but no significant change after pegaptanib
treatment. Automated StratusOCT output measurements of FCS thickness, foveal
center point thickness, and total volume of the retina did not reveal a
statistically significant difference between the treatments. CONCLUSIONS:
Differences in morphologic response between treatments were less apparent on
automated StratusOCT output than on computer-assisted analysis. Although
intravitreal bevacizumab was associated with a greater short-term reduction in
features of exudation than pegaptanib therapy, the retrospective design of the
study limits the significance of this finding. Computer-assisted subanalysis of
OCT data, however, may be a useful tool in more precisely defining the anatomic
effects of therapies for neovascular AMD.

Publication Types: 
    Comparative Study
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17628685 [PubMed - indexed for MEDLINE]

764: Ophthalmology. 2007 Oct;114(10):1868-75. Epub 2007 Jul 12.

Angiographic and optical coherence tomographic results of the MARINA study of
ranibizumab in neovascular age-related macular degeneration.

Kaiser PK, Blodi BA, Shapiro H, Acharya NR; MARINA Study Group.

Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
pkkaiser@aol.com

OBJECTIVE: To assess pharmacodynamic responses to ranibizumab, an inhibitor of
vascular endothelial growth factor A (VEGF-A), in a study of the treatment of
minimally classic or occult with no classic choroidal neovascularization
secondary to age-related macular degeneration (AMD) (designated MARINA [Minimally
Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab in the Treatment of
Neovascular AMD]) and to compare these responses with those in a sham-injection
control group. DESIGN: Retrospective (prespecified and ad hoc) analyses of
24-month data. PARTICIPANTS: Seven hundred sixteen patients, randomized to 0.3-mg
ranibizumab (n = 238), 0.5-mg ranibizumab (n = 240), or a sham injection (n =
238). METHODS: Stereoscopic fundus photography and fluorescein angiography (FA)
were done at baseline and months 3, 6, 12, and 24. Optical coherence tomography
(OCT) was performed at a subset of investigative sites (46 patients) at baseline,
day 7, and months 1 and 12. MAIN OUTCOME MEASURES: Prespecified secondary end
points were mean change from baseline in total area of choroidal
neovascularization and total area of leakage from choroidal neovascularization at
months 12 and 24. Prespecified exploratory FA end points included mean change
from baseline in the areas of the choroidal neovascularization lesion and serous 
sensory retinal detachment (SSRD) at months 12 and 24. Post hoc exploratory FA
outcome measures included the proportion of patients with no leakage from
choroidal neovascularization and mean change from baseline over time in the area 
of subretinal fibrous tissue/disciform scar. The prespecified exploratory end
point for OCT was mean change from baseline over time in center point thickness. 
RESULTS: At 12 and 24 months, statistically significant benefits of ranibizumab
over sham treatment were observed for mean change from baseline in the areas of
choroidal neovascularization lesion, total choroidal neovascularization, leakage 
from choroidal neovascularization, SSRD, and disciform scar/subretinal fibrosis. 
At 12 months (final OCT), the mean change in foveal center point thickness on OCT
was a significant decrease in the ranibizumab group compared with the sham group.
CONCLUSIONS: Patients with minimally classic or occult with no classic
neovascular AMD treated with ranibizumab demonstrated improvement that was
consistent for visual acuity, FA, and OCT outcomes and superior to that in
sham-treated patients.

Publication Types: 
    Case Reports
    Clinical Trial, Phase III
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17628683 [PubMed - indexed for MEDLINE]

765: BioDrugs. 2007;21(4):245-57.

Emerging therapies for the treatment of neovascular age-related macular
degeneration and diabetic macular edema.

Emerson MV, Lauer AK.

Casey Eye Institute, Oregon Health and Science University, Portland, Oregon
97239-4197, USA.

Diabetic macular edema (DME) and choroidal neovascularization (CNV) associated
with age-related macular degeneration (AMD) are the leading causes of vision loss
in the industrialized world. The mainstay of treatment for both conditions has
been thermal laser photocoagulation, while there have been recent advances in the
treatment of CNV using photodynamic therapy with verteporfin. While both of these
treatments have prevented further vision loss in a subset of patients, vision
improvement is rare. Anti-vascular endothelial growth factor (VEGF)-A therapy has
revolutionized the treatment of both conditions. Pegaptanib, an anti-VEGF
aptamer, prevents vision loss in CNV, although the performance is similar to that
of photodynamic therapy. Ranibizumab, an antibody fragment, and bevacizumab, a
full-length humanized monoclonal antibody against VEGF, have both shown promising
results, with improvements in visual acuity in the treatment of both diseases.
VEGF trap, a modified soluble VEGF receptor analog, binds VEGF more tightly than 
all other anti-VEGF therapies, and has also shown promising results in early
trials. Other treatment strategies to decrease the effect of VEGF have used small
interfering RNA to inhibit VEGF production and VEGF receptor production.
Corticosteroids have shown efficacy in controlled trials, including anacortave
acetate in the treatment and prevention of CNV, and intravitreal triamcinolone
acetonide and the fluocinolone acetonide implant in the treatment of DME.
Receptor tyrosine kinase inhibitors, such as vatalanib, inhibit downstream
effects of VEGF, and have been effective in the treatment of CNV in early
studies. Squalamine lactate inhibits plasma membrane ion channels with downstream
effects on VEGF, and has shown promising results with systemic administration.
Initial results are also encouraging for other growth factors, including pigment 
epithelium-derived factor administered via an adenoviral vector. Ruboxistaurin,
which decreases protein kinase C activity, has shown positive results in the
prevention of diabetic retinopathy progression, and the resolution of DME.
Combination therapy has been investigated, and may prove to be quite effective in
the management of both DME and AMD-associated CNV, although ongoing and future
studies will be crucial to treatment optimization for each condition.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17628122 [PubMed - indexed for MEDLINE]

766: Retina. 2007 Jul-Aug;27(6):798-803.

Variability among retina specialists in evaluating fluorescein angiograms of
patients with neovascular age-related macular degeneration.

Zayit-Soudry S, Alfasi M, Goldstein M, Moisseiev J, Axer-Siegel R, Pollack A,
Yassur Y, Loewenstein A.

Department of Ophthalmology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. 
shirizayit@gmail.com

PURPOSE: To determine the rate of agreement among five retina specialists in
classifying various angiographic features of subfoveal choroidal
neovascularization (CNV) secondary to age-related macular degeneration (AMD), as 
evaluated on printed digital fluorescein angiogram (FA) frames, as well as
determination of eligibility for photodynamic treatment (PDT) according to
established guidelines. METHODS: Ninety-two digital FAs demonstrating subfoveal
CNV secondary to AMD were evaluated independently by five retina specialists. The
pattern of classic component could be classified as no classic component,
minimally classic, predominantly classic, or classic only. Each grader was asked 
to determine eligibility of each case to PDT according to established treatment
guidelines, national health insurance guidelines, and one's own personal
judgment. RESULTS: The kappa coefficient of concordance calculated for all five
observers regarding CNV localization was 0.285, indicating fair overall
agreement, and was 0.295, indicating fair agreement, regarding classification of 
leakage pattern. The kappa coefficient of agreement calculated for all five
graders regarding eligibility for treatment according to established
international guidelines, national health insurance, and each grader's own
personal judgment was 0.163, 0.33, and 0.164, respectively, indicating slight to 
fair overall agreement. CONCLUSION: Considerable variability may exist among
retina specialists interpreting FAs and should be considered in the assessment of
treatment guidelines.

PMID: 17621192 [PubMed - indexed for MEDLINE]

767: Retina. 2007 Jul-Aug;27(6):764-9.

Injection of triamcinolone acetonide into the posterior sub-tenon capsule for
treatment of diabetic macular edema.

Toda J, Fukushima H, Kato S.

Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo,
Japan. jtoda-tky@umin.ac.jp

PURPOSE: To compare eyes that received treatment with untreated fellow eyes to
assess the effectiveness of injection of 20 mg of triamcinolone acetonide (TA)
into the posterior sub-Tenon capsule for treatment of diabetic macular edema
(DME). METHODS: Nine adult patients (mean age, 60.4 years) with DME in both eyes 
were followed up for 3 months after unilateral treatment. We compared central
macular thickness before and after treatment with those of the untreated fellow
eye. RESULTS: In 9 eyes injected with 20 mg of TA, the mean central macular
thickness +/- SD was 624.8 +/- 173.7 microm before treatment. In the fellow eyes,
it was 452.8 +/- 235.2 microm. There was no significant difference between the
two groups (P=0.10, unpaired t-test). One month after injection, it was 434.0 +/-
120.7 microm in injected eyes (P=0.017, paired t-test) and 462.2 +/- 232.7 microm
in fellow eyes (P=0.70, paired t-test), and after 3 months, the respective values
were 423.1 +/- 186.3 microm (P=0.052, paired t-test) and 478.3 +/- 269.1 microm
(P=0.65, paired t-test). CONCLUSION: Injection of 20 mg of TA into the posterior 
sub-Tenon capsule effectively reduces macular thickening due to DME, at least in 
the short term.

Publication Types: 
    Case Reports

PMID: 17621188 [PubMed - indexed for MEDLINE]

768: Retina. 2007 Jul-Aug;27(6):759-63.

The behavior of surgically repaired idiopathic macular holes in the setting of
subsequent cystoid macular edema.

Huynh TH, Johnson MW.

W. K. Kellogg Eye Center, Department of Ophthalmology and Visual Sciences,
University of Michigan, Ann Arbor, Michigan 48105, USA.

PURPOSE: To report findings for eyes with surgically repaired idiopathic macular 
hole that subsequently developed cystoid macular edema (CME). METHODS: This study
was a retrospective chart review of six eyes of six consecutive patients
evaluated between January 1997 and October 2000 who had successful macular hole
repair and subsequently developed CME. Patient demographic data, cause and time
course of CME, treatment, and outcomes, including macular hole reopening, were
recorded. RESULTS: CME developed after cataract extraction in five eyes and after
macular hole surgery alone in one eye. Average time from macular hole surgery to 
diagnosis of CME was 11.2 months (range, 2.5-23.0 months). Average duration of
CME was 5.5 months (range, 1.5-17.0 months). Five (83%) of 6 eyes had sustained
closure of the macular hole throughout a mean follow-up period of 31.8 months
(range, 9.5-62.0 months). Patients were treated with topical antiinflammatory
therapy, and all had resolution of CME. CONCLUSIONS: CME developing in eyes with 
surgically repaired idiopathic macular holes responds well to conventional
topical antiinflammatory therapy and is not associated with a high incidence of
macular hole reopening. These results suggest that in most eyes the reparative
mechanisms involved in macular hole closure confer sufficient strength to
withstand the tensile forces associated with CME.

Publication Types: 
    Case Reports

PMID: 17621187 [PubMed - indexed for MEDLINE]

769: Retina. 2007 Jul-Aug;27(6):724-9.

Optical coherence tomography findings during pegaptanib therapy for neovascular
age-related macular degeneration.

Emerson GG, Flaxel CJ, Lauer AK, Stout JT, Emerson MV, Nolte S, Wilson DJ, Klein 
ML.

Casey Eye Institute, Oregon Health & Science University, Portland, OR, USA.

BACKGROUND: To evaluate macular thickness measured by optical coherence
tomography (OCT) during pegaptanib therapy for neovascular age-related macular
degeneration (AMD). METHODS: For this prospective, nonrandomized, observational
case series, 41 eyes from 41 patients with neovascular AMD received intravitreous
pegaptanib (1 mg) injections repeated every 6 weeks. The primary outcome measure 
was central foveal thickness measured by OCT. Secondary outcomes were fluorescein
angiographic leakage and visual acuity. RESULTS: Mean thickness of the central
area on OCT decreased from 340 +/- 24 microm to 299 +/- 14 microm after 12 weeks 
of pegaptanib injections. This represents a reduction in thickening of 32%.
Fluorescein angiograms with definite leakage decreased from 100% to 81%, and mean
visual acuity decreased from 20/116 to 20/120. CONCLUSIONS: Intravitreal
injections of pegaptanib at 6-week intervals result in a moderate reduction of
central foveal thickness in eyes with subfoveal neovascular AMD. This presents a 
modest effect relative to that reported with other anti-angiogenic agents.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17621181 [PubMed - indexed for MEDLINE]

770: Retina. 2007 Jul-Aug;27(6):713-23.

Influence of verteporfin photodynamic therapy on inflammation in human choroidal 
neovascular membranes secondary to age-related macular degeneration.

Tatar O, Adam A, Shinoda K, Yoeruek E, Szurman P, Bopp S, Eckardt C,
Bartz-Schmidt KU, Grisanti S.

University Eye Hospital at the Center for Ophthalmology, Eberhard-Karls
University Tuebingen, Germany.

PURPOSE: To examine the short- and long-term consequences of verteporfin
photodynamic therapy (PDT) on inflammation with regard to infiltration of
macrophages and leukocytes and expression of thy-1 in human choroidal
neovascularization membranes (CNV) secondary to age-related macular degeneration 
(AMD). METHODS: Retrospective review of an interventional case series of 43
patients who underwent removal of CNV. Twenty patients were treated with PDT 3 to
246 days preoperatively. Twenty-three CNV without previous treatment were used as
control. CNV were stained for CD34, CD105, cytokeratin 18, Ki-67, thy-1, an
endothelial cell glycoprotein known to be upregulated only by inflammatory
cytokines, CD68 (macrophages), and CD45 (common leukocyte antigen). RESULTS:
Specimens treated by PDT 3 days previously showed significantly reduced
endothelial thy-1 expression (P = 0.008), leukocyte (P=0.04) and macrophage
(P=0.0063) infiltration, and proliferative activity (P=0.02) compared to control 
CNV. Specimens at longer intervals after PDT, in contrast, disclosed a
significantly increased expression of thy-1 (P=0.004), infiltration with
leukocytes (P=0.044) and macrophages (P=0.01), and proliferative activity
(P=0.03) compared to CNV excised 3 days after PDT. CONCLUSIONS: The rebound
effect after PDT seems to be based on an inflammatory response that contributes
to enhanced proliferation. These data support the need for an anti-inflammatory
therapy as adjuvant to PDT.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17621180 [PubMed - indexed for MEDLINE]

771: Retina. 2007 Jul-Aug;27(6):701-6.

Comment in:
    Retina. 2008 Mar;28(3):527; author reply 527-8.

Standardized visual acuity results associated with primary versus secondary
bevacizumab (avastin) treatment for choroidal neovascularization in age-related
macular degeneration.

Falkenstein IA, Cheng L, Morrison VL, Kozak I, Tammewar AM, Freeman WR.

Joan and Irwin Jacobs Retina Center, Department of Ophthalmology, University of
California at San Diego, La Jolla, California 92037, USA.

PURPOSE: To compare standardized visual outcomes and macular thickness changes
associated with primary and secondary bevacizumab (Avastin; Genentech, Inc.,
South San Francisco, CA) therapy for choroidal neovascularization (CNV) in
age-related macular degeneration (AMD). METHODS: Eighteen eyes received primary
bevacizumab treatment; 20 eyes received pegaptanib (Macugen; Eyetech/OSI
Pharmaceuticals, New York, NY) as initial treatment followed by bevacizumab
therapy. Both medications were injected at 6-week intervals. Best-corrected
visual acuity was measured with the ETDRS chart. Three- and 6-month data were
analyzed for all eyes. RESULTS: Mean visual acuity improvement in the primary
bevacizumab treatment cohort was 1.5 ETDRS lines at 3 months (P = 0.0009) and 2.2
ETDRS lines at 6 months (P=0.0004) compared with -0.4 ETDRS line at 3 months
(P=0.27) and 0.2 ETDRS line at 6 months (P=0.70) in the secondary bevacizumab
treatment group. Mean decrease in retinal thickness was also higher in the
primary bevacizumab treatment group (90.9 microm [P=0.0037] vs 43.8 microm
[P=0.13], respectively) than in the secondary bevacizumab treatment group (73.72 
microm [P=0.051] vs 33.0 microm [P=0.21], respectively) at 3 months and 6 months.
CONCLUSION: Primary bevacizumab therapy resulted in significantly greater visual 
improvement than secondary bevacizumab treatment at 3 months or 6 months. To our 
knowledge, this is the first report comparing primary bevacizumab treatment of
CNV in AMD with secondary bevacizumab treatment after multiple pegaptanib
injections.

Publication Types: 
    Comparative Study

PMID: 17621178 [PubMed - indexed for MEDLINE]

772: Retina. 2007 Jul-Aug;27(6):693-700.

Effect of adjunctive diclofenac with verteporfin therapy to treat choroidal
neovascularization due to age-related macular degeneration: phase II study.

Adjunctive Diclofenac with Verteporfin (ADD-V) Study Group, Boyer DS, Beer PM,
Joffe L, Koester JM, Marx JL, Weisberger A, Yoser SL.

BACKGROUND: To determine short-term effects of topical diclofenac administered in
conjunction with verteporfin therapy for predominantly classic subfoveal
choroidal neovascularization (CNV) due to age-related macular degeneration (AMD).
METHODS: Randomized, multicenter (14), prospective, placebo-controlled,
double-masked clinical trial. Patients (n=61) were randomly assigned to treatment
with diclofenac sodium ophthalmic solution 0.1% or placebo and followed for 12
weeks. Patients instilled diclofenac or placebo two drops four times daily, 2-4
days before verteporfin treatment until 2 weeks after treatment, then two drops
twice daily for 10 weeks. This exploratory study was not powered to detect
differences between treatment groups. Statistical analyses were conducted solely 
to aid interpretation of results. RESULTS: In diclofenac-treated eyes, mean
changes in visual acuity letter score from baseline in the diclofenac and placebo
groups were +1.8 letters and -1.0 at week 1 (P=0.505 between groups). Mean visual
acuity letter scores decreased in both groups at all subsequent visits, with a
mean change at 12 weeks of -7.4 with diclofenac and -2.6 with placebo (P=0.213). 
Percentages of eyes with stable or improved vision (change <or=4 or increase
>or=5 letters) were similar in the diclofenac and placebo groups at all study
visits. No significant between-group differences in changes from baseline in
lesion area, greatest linear dimension (GLD), fluorescein leakage, or retinal
thickness were detected. CONCLUSION: In patients with predominantly classic
subfoveal CNV due to AMD, administration of topical diclofenac with verteporfin
therapy was associated with similar vision outcomes to placebo plus verteporfin
therapy.

Publication Types: 
    Clinical Trial, Phase II
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial

PMID: 17621177 [PubMed - indexed for MEDLINE]

773: Arch Ophthalmol. 2007 Jul;125(7):945-51.

Health-related quality of life and utility in patients with age-related macular
degeneration.

Sahel JA, Bandello F, Augustin A, Maurel F, Negrini C, Berdeaux GH; MICMAC Study 
Group.

Department IV, Hôpital de XV-XX, Paris, France.

OBJECTIVE: To assess the impact of best-eye and worst-eye visual acuity (BEVA and
WEVA, respectively) on health-related quality of life and utility in patients
with wet age-related macular degeneration. DESIGN: This cross-sectional,
prospective, observational, multicenter study was performed in France, Germany,
and Italy. Patients were stratified into 4 severity groups (BEVA, 20/40; WEVA,
20/200). Patients completed the National Eye Institute 25-Item Visual Function
Questionnaire, the Macular Disease Quality of Life Scale, and the Health Utility 
Index 3. Analysis of variance was used to adjust for age, sex, and country.
RESULTS: Patients (N = 360) were mainly female (59.6%), with a mean age of 77
years and mean time since age-related macular degeneration diagnosis of 2.3
years. Health Utility Index 3 scores decreased with VA severity from 0.62 to
0.39. The National Eye Institute 25-Item Visual Function Questionnaire global
score decreased with VA severity from 67.0 to 40.7 and was related to the BEVA (P
< .001) and WEVA (P = .03). Corresponding changes were observed on the general
vision, distance vision, driving, and mental health dimensions. The average
weighted impact score on the Macular Disease Quality of Life varied from -4.6 to 
-2.6, decreasing with VA severity. Both eyes contributed to the average weighted 
impact score. CONCLUSION: The BEVA and WEVAs influenced vision-related quality of
life independently, as measured by the National Eye Institute 25-Item Visual
Function Questionnaire and Macular Disease Quality of Life Scale.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 17620576 [PubMed - indexed for MEDLINE]

774: Arch Ophthalmol. 2007 Jul;125(7):917-24.

Visual impairment, age-related macular degeneration, cataract, and long-term
mortality: the Blue Mountains Eye Study.

Cugati S, Cumming RG, Smith W, Burlutsky G, Mitchell P, Wang JJ.

Centre for Vision Research, Department of Ophthalmology, Westmead Millennium
Institute, University of Sydney, Westmead Hospital, Westmead, New South Wales,
Australia.

OBJECTIVE: To assess the association of visual impairment, age-related macular
degeneration (ARMD), and cataract with long-term mortality. METHODS: At baseline,
3654 persons 49 years and older were examined in the Blue Mountains Eye Study
(1992-1994). Standardized photographic grading was used to assess ARMD and
cataract. Mortality and causes of death occurring between baseline and December
31, 2003, were obtained via data linkage with the Australian National Death
Index. Age-standardized mortality rates were calculated. Hazard ratios (HRs) and 
95% confidence intervals (CIs) were assessed using Cox models. Result
Age-standardized mortality was higher in persons with vs without visual
impairment (54.0% vs 34.0%), ARMD (45.8% vs 33.7%), and cataract (39.2% vs
29.5%). After adjusting for factors that predict mortality, neither visual
impairment (HR, 1.3; 95% CI, 0.98-1.7) nor ARMD (HR, 1.0; 95% CI, 0.8-1.3) was
significantly associated with all-cause mortality in all ages. Among persons
younger than 75 years, however, ARMD predicted higher all-cause mortality (HR,
1.6; 95% CI, 1.0-2.4). Any cataract (HR, 1.3; 95% CI, 1.0-1.5) and cortical (HR, 
1.2; 95% CI, 0.97-1.4), nuclear (HR, 1.2; 95% CI, 0.98-1.5), and posterior
subcapsular (HR, 1.3; 95% CI, 1.0-1.7) cataract were also associated with higher 
all-cause mortality. CONCLUSION: Cataract predicted increased mortality in
persons 49 years and older, and ARMD predicted mortality in persons aged 49 to 74
years.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17620571 [PubMed - indexed for MEDLINE]

775: Graefes Arch Clin Exp Ophthalmol. 2007 Dec;245(12):1765-71. Epub 2007 Jul
10.

Macular thickness after uneventful cataract surgery determined by optical
coherence tomography.

von Jagow B, Ohrloff C, Kohnen T.

Department of Ophthalmology, Johann Wolfgang Goethe-University, Theodor-Stern-Kai
7, 60590 Frankfurt am Main, Germany.

BACKGROUND: Using standardized macular optical coherence tomography (OCT) in the 
postoperative period, subclinical changes in macular thickness can be detected.
With this method, postoperative development of macular thickness in healthy eyes 
is evaluated. The repeatability of the method and the influence of selected
surgical (phaco time and phaco energy) and biometric parameters (axial length and
anterior chamber depth) on the results were assessed. METHODS: In a prospective
study, 33 patients without macular pathology in both eyes were examined.
Phacoemulsification and intraocular lens (IOL) implantation was performed in one 
eye, and the contralateral eye served as control. OCT (StratusOCT; Zeiss, Dublin,
CA, USA), mean minimal foveal thickness (MMFT) and mean foveal thickness (MFT)
were measured preoperatively, at 1 day, 1 week and 6 weeks postoperatively. At
these visits, the best-corrected visual acuity (BCVA) tests and slit-lamp
examination were performed. To assess the influence on foveal thickness ocular
axial length, anterior chamber depth, phacotime and energy were documented.
Statistical analysis using parametric tests was carried out with standard
statistical software (SPSS11, BIAS). RESULTS: MMFT of the operated eyes and the
intraindividual difference of MMFT increased significantly at one day (+12.31 +/-
24.2 microm, P < 0.001) and 6 weeks (+6.76 +/- 22.6 microm, P = 0.009). MFT in
the operated eyes and intraindividual difference of MFT rose significantly at 1
day, 1 week and 6 weeks (1 day: +10.66 +/- 20.8 microm, P = 0,026; 1 week: +15.23
+/- 19.7 microm; 6 weeks: +17.33 +/- 14.81 microm, P < 0.001). Repeatability was 
better for MFT in controls (ICR = 0.92) than for MMFT in controls (ICR = 0.77).
No clinical cystoid macular edema was diagnosed in this study. No correlation
between macular thickening and visual acuity and selected surgical and
biometrical parameters could be found. CONCLUSIONS: After cataract surgery, a
mild increase of foveal thickness without impact on visual acuity could be
observed. This increase may be due to both subclinical changes and to influence
of changes in media opacity on the measurement technique. Surgical and biometric 
parameters such as phacotime and energy and axial length did not correlate to the
degree of macular thickening.

PMID: 17619896 [PubMed - indexed for MEDLINE]

776: Graefes Arch Clin Exp Ophthalmol. 2007 Nov;245(11):1673-80. Epub 2007 Jul
10.

Indocyanine-green-mediated photothrombosis (IMP) with intravitreal triamcinolone 
acetonide for macular edema secondary to group 2A idiopathic parafoveal
telangiectasis without choroidal neovascularization: a pilot study.

Arevalo JF, Sanchez JG, Garcia RA, Wu L, Berrocal MH, Rodriguez FJ, Rodríguez A, 
Novoa LA, Garcia-Amaris R.

Retina and Vitreous Service, Clinica Oftalmológica Centro Caracas, Caracas,
Venezuela. arevalojf@movistar.net.ve

BACKGROUND: The purpose of this study was to determine the feasibility, safety
and clinical effect of indocyanine green (ICG)-mediated photothrombosis (IMP)
combined with intravitreal triamcinolone acetonide (IVTA) in patients with
macular edema secondary to idiopathic parafoveal telangiectasis (IPFT) group 2A
without choroidal neovascularization (CNV). METHODS: Nine eyes of six patients
that were treated with IMP immediately followed by IVTA at a dose of 4 mg
participated in the study. Patients had a mean follow-up of 23.3 months (range
12-36 months). Patients underwent one or two sessions of IMP combined with IVTA
("study group"). An IVTA-only group of 19 eyes from 14 patients with macular
edema secondary to IPFT group 2A that underwent an IVTA 4 mg without IMP
("IVTA-only group") was included for comparison. In addition, a matched control
group of 40 eyes from 20 patients selected retrospectively from our medical
records with macular edema secondary to IPFT group 2A without any therapy was
included ("observation group"). RESULTS: The best-corrected visual acuity (BCVA) 
remained stable in five eyes (55.5%). Four eyes (44.4%) demonstrated improvement 
of BCVA (> or = two ETDRS lines), and no eyes experienced worsening of visual
acuity (> or = two ETDRS lines). A significant decrease in hyperfluorescence was 
not seen with fluorescein angiography (FA), however optical coherence tomography 
(OCT) showed a decrease in the size of inner intraretinal hyporeflective spaces
or cystic edema. Two (22.2%) eyes developed an increase in intraocular pressure. 
However, it was medically controlled with topical anti-glaucoma medications.
Cataract developed in five eyes (55.5%). Six of nine eyes (66.6%) required one
retreatment during the study period. At the last follow-up (mean 21.1 months,
range 12-30 months) in the IVTA-only group, 5 (25.3%) eyes improved BCVA, 11
(57.9%) eyes remained within two lines of baseline BCVA and 3 (15.8%) eyes lost
BCVA. In the observation group, with similar follow-up, 87.5% of eyes showed
either stabilization or deterioration of BCVA over time. CONCLUSIONS: Combined
IMP and IVTA may provide stability or improvement in BCVA and fundus findings in 
eyes with macular edema secondary to IPFT group 2A without CNV at a minimum
follow-up of 12 months.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17619895 [PubMed - indexed for MEDLINE]

777: Am J Clin Nutr. 2007 Jul;86(1):180-8.

Association between dietary glycemic index and age-related macular degeneration
in nondiabetic participants in the Age-Related Eye Disease Study.

Chiu CJ, Milton RC, Gensler G, Taylor A.

Jean Mayer US Department of Agriculture, Human Nutrition Research Center on Aging
at Tufts University, Boston, MA 02111, USA.

BACKGROUND: Age-related macular degeneration (AMD) is the major cause of
irreversible blindness. AMD appears to share several carbohydrate-related
mechanisms and risk factors with diabetes-related diseases, including retinopathy
and cardiovascular disease (CVD); however, to date, only one small study has
addressed this issue. OBJECTIVE: The objective was to test the hypothesis that
dietary glycemic index (dGI), which has been related to the risk of diabetes and 
CVD, is associated with the risk and severity of AMD in nondiabetic elderly
populations. DESIGN: Dietary information was obtained from 4099 participants aged
55-80 y (56% women) in the Age-Related Eye Disease Study (AREDS). A total of 8125
eligible eyes at baseline were classified into 1 of 5 AMD groups according to the
size and extent of drusen, the presence of geographic atrophy, and neovascular
changes. We used a generalized estimating approach to evaluate the relations
between dGI and risk and severity of AMD with eyes as the unit of analysis.
RESULTS: Compared with eyes in the first quintile of dGI, eyes in the fourth and 
fifth quintiles had a significantly or suggestively higher risk of large drusen, 
geographic atrophy, and neovascularization. The multivariate-adjusted odds ratios
(95% CIs) for the highest quintile were 1.42 (1.09, 1.84), 1.78 (0.81, 3.90), and
1.41 (0.95, 2.08), respectively, of which only the odds ratio for large drusen
was significant. A significant positive relation between dGI and severity of AMD 
was also noted (P for trend < 0.001). There was a 49% increase in the risk of
advanced AMD (geographic atrophy plus neovascularization) for persons with a dGI 
higher than the sex median (women: >or=77.9; men: >or=79.3). This result
indicated that 20% of prevalent cases of AMD would have been eliminated if the
AREDS participants consumed diets with a dGI below the median. CONCLUSION: The
association between dGI and AMD from the AREDS cross-sectional analysis at
baseline suggests that a reduction in the dGI, a modifiable risk factor, may
provide a means of diminishing the risk of AMD.

Publication Types: 
    Multicenter Study
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, Non-P.H.S.

PMID: 17616779 [PubMed - indexed for MEDLINE]

778: J Biomed Opt. 2007 May-Jun;12(3):034025.

Complete blood vessel occlusion in the chick chorioallantoic membrane using
two-photon excitation photodynamic therapy: implications for treatment of wet
age-related macular degeneration.

Samkoe KS, Clancy AA, Karotki A, Wilson BC, Cramb DT.

University of Calgary, Department of Chemistry, 2500 University Drive, Northwest,
Calgary, Alberta T2N 1N4, Canada.

Complete blood vessel occlusion is required for the treatment of age-related
macular degeneration (AMD). AMD is the leading cause of blindness in developed
countries and current treatment regimes have potential to cause collateral
damage, or do not remove pre-existing unwanted vasculature. It has been proposed 
that two-photon excitation (TPE) photodynamic therapy (PDT) can be applied to
cause local blood vessel occlusion without damaging surrounding retinal tissues. 
The in ovo chicken chorioallantoic membrane (CAM) is used as the model for
vascularization in the wet form of AMD; novel techniques for the utilization of
the CAM are reported. Complete occlusion of CAM vessels approximately 15 microm
in diameter is achieved using the clinically approved photosensitizer Verteporfin
(Visudyne, QLT, Incorporated, Vancouver, British Columbia, Canada) and TPE
activation. The average and peak irradiances used for treatment are 3.3x10(6)
Wcm(2) and 3.7x10(11) Wcm(2), respectively. A total fluence of 1.1x10(8) Jcm(2)
is the dosage required for successful occlusion, and it is expected that for
optimal conditions it will be much less. These results are the first
proof-of-principle evidence in the literature that indicate TPE-PDT can be used
to occlude small blood vessels. Further investigation will help determine the
utility of TPE-PDT for treating wet AMD, perhaps through targeting feeder
vessels.

Publication Types: 
    In Vitro
    Research Support, Non-U.S. Gov't

PMID: 17614733 [PubMed - indexed for MEDLINE]

779: Ophthalmic Epidemiol. 2007 May-Jun;14(3):127-33.

Depressive symptoms and age-related macular degeneration in older people: the
cardiovascular health study.

Sun C, Tikellis G, Klein R, Steffens DC, Larsen EK, Wong TY.

Centre for Eye Research Australia, University of Melbourne, Australia.

PURPOSE: To examine the association between age-related macular degeneration
(AMD) and depressive symptoms. METHODS: Population-based, cross-sectional study. 
A total of 2,194 persons aged 69-97 years were included in the current analyses. 
During the 1997-1998 examination, retinal photography from one randomly selected 
eye was graded for presence of early and late AMD using a modified Wisconsin AMD 
by Grading System. Depressive symptoms were assessed via a modified version of
the Centers for Epidemiologic Studies Depression (CES-D) scale annually from 1989
through 1997-1998. Depressive symptoms were defined as a CES-D score of >9 (top
quartile of CES-D score) at the 1997-1998 examination. RESULTS: There were 338
(15.6%) individuals with early AMD and 29 (1.3%) with late AMD. Among them, 368
(16.8%) persons had depressive symptoms at the 1997-1998 examination. Depressive 
symptoms were not associated with early AMD (multivariable adjusted odds ratio
[OR]: 0.97; 95% confidence intervals [CI]: 0.69-1.36) or late AMD (OR: 1.15; 95% 
CI: 0.38-3.46). Including persons using anti-depressive medications did not alter
these associations (OR: 0.98; 95% CI: 0.74-1.32 for early AMD and OR: 0.97; 95%
CI: 0.35-2.67 for late AMD). There was no association in multinomial logistic
regression models of increasing quartiles of the CES-D scores with early or late 
AMD status. CONCLUSIONS: Our study did not find an association between early AMD 
and depressive symptoms in older people.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17613847 [PubMed - indexed for MEDLINE]

780: Curr Eye Res. 2007 Jun;32(6):555-64.

Measurement of macular pigment optical density using two different
heterochromatic flicker photometers.

Loane E, Stack J, Beatty S, Nolan JM.

Macular Pigment Research Group, Department of Chemical & Life Sciences, Waterford
Institute of Technology, Waterford, Ireland. eloane@wit.ie

PURPOSE: To compare macular pigment optical density using two different
heterochromatic flicker photometers. METHODS: We measured macular pigment optical
density in 121 healthy subjects using heterochromatic flicker photometry.
RESULTS: The mean (+/-SD) macular pigment optical density measured using the
Maculometer was 0.394 (+/-0.170), and that using the Densitometer was 0.395
(+/-0.189). The difference in measurements on each instrument was influenced by
age and macular pigment levels. CONCLUSIONS: On average, there is no difference
in measurements provided by these two instruments. The Maculometer tends to
underestimate macular pigment in older subjects and/or those with higher macular 
pigment compared with the Densitometer.

Publication Types: 
    Comparative Study

PMID: 17612971 [PubMed - indexed for MEDLINE]

781: Acta Ophthalmol. 2008 Feb;86(1):105-10. Epub 2007 Jul 3.

Intravitreal triamcinolone as adjunctive treatment to laser panretinal
photocoagulation for concomitant proliferative diabetic retinopathy and
clinically significant macular oedema.

Margolis R, Singh RP, Bhatnagar P, Kaiser PK.

Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.

PURPOSE: To evaluate the effect of intravitreal injections of triamcinolone
acetonide (IVTA) combined with panretinal photocoagulation (PRP) on visual acuity
(VA) and foveal thickness in patients with concomitant high-risk proliferative
diabetic retinopathy (PDR) and clinically significant macular oedema (CSMO).
METHODS: This retrospective interventional case series included seven eyes
diagnosed with both high-risk PDR and CSMO that underwent PRP and a single
injection of 4 mg of IVTA. The main outcome measures were VA and foveal
thickness, measured by optical coherence tomography (OCT) before treatment and
throughout the follow-up period. RESULTS: Median follow-up was 301 days (range
180-715 days). Foveal thickness data were available for four of seven eyes.
Before the combined treatment, median LogMAR (logarithm of the minimum angle of
resolution) VA and median foveal thickness were 1 (Snellen 20/200, range
20/40-20/800) and 559 microm (range 333-689 microm), respectively. After
treatment, median vision improved to LogMAR 0.544 (Snellen 20/70, range
20/40-20/1000) (P = 0.13). Vision improved or remained stable in six of seven
eyes. Median foveal thickness at final follow-up was 436 microm (range 259-623
microm) (P = 0.15). Foveal thickness decreased or remained stable in all eyes.
CONCLUSION: The addition of IVTA to PRP in the treatment of eyes with high-risk
PDR and CSMO may prevent PRP-induced foveal thickening and loss of vision.

PMID: 17608830 [PubMed - indexed for MEDLINE]

782: Int Ophthalmol. 2008 Apr;28(2):119-23. Epub 2007 Jun 30.

Polypoidal choroidal vasculopathy coexisting with exudative age-related macular
degeneration.

Chen Y, Wen F, Sun Z, Wu D.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen
University, 54 Xianlie Road, Guangzhou 510060, PR China.

PURPOSE: To report two cases that had polypoidal choroidal vasculopathy (PCV)
coexisting with choroidal neovascularization (CNV) of exudative age-related
macular degeneration (AMD). METHODS: Both of the patients underwent color
photographs, fluorescein and indocyanine green (ICG) angiography. RESULTS: On
fundus examination, a grayish lesion in the foveal area, reddish-orange lesions
and hemorrhagic retinal pigment epithelial detachments (PED) in the
inferotemporal vascular arch were disclosed in the left eye of a patient, and
macular scarring was observed in the fellow eye. ICG angiography revealed a
typical branching vascular network and polyp-like aneurysmal dilations at
terminals of branches in the inferotemporal vascular arcade and a well-demarcated
hyperfluorescent area of CNV in the fovea in the left eye, and staining of
macular scarring was present in the fellow eye. On fundus examination of the
right eye of the other patient a gray-yellow lesion at the fovea, reddish-orange 
lesions in the extramacula were noted, and diffuse drusens were present in the
fellow eye. ICG angiography revealed scattered polyp-like aneurysmal dilations
without identifiable continuous branching vascular network in the extramacula,
and a well-demarcated hyperfluorescence area of CNV in the fovea. CONCLUSIONS:
PCV can coexist with exudative AMD in some patients and the polypoidal lesions
may less involve in the fovea than CNV. Evidence of AMD are present meanwhile in 
the fellow eyes these patients.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 17603771 [PubMed - indexed for MEDLINE]

783: Am J Ophthalmol. 2007 Jul;144(1):134-6.

The effect of intravitreal triamcinolone on foveal edema in exudative macular
degeneration.

Gillies MC, Larsson J.

Department of Clinical Ophthalmology, Save Sight Institute, University of Sydney,
Sydney, Australia. mark@eye.usyd.edu.au

PURPOSE: To evaluate the effect of a single intravitreal injection of
triamcinolone (IVTA) on central macular thickness and visual acuity in eyes with 
minimally classic exudative age-related macular degeneration (AMD). DESIGN:
Retrospective, nonrandomized clinical interventional study. METHODS: Optical
coherence tomography (OCT) and best-corrected logarithm of the minimum angle of
resolution visual acuity were performed at baseline and one month after
treatment. RESULTS: We identified 11 eyes with foveal edema and minimally classic
subfoveal neovascularization treated with an IVTA. Foveal edema decreased
significantly from 401 +/- 98 microm at baseline to 295 +/- 141 microm (mean +/- 
standard deviation; P = .004) at one month. There was, however, no significant
change in visual acuity at one or three months after the intervention.
CONCLUSIONS: This biological effect of IVTA does not support its clinical use,
yet it does warrant further research to determine whether locally delivered
corticosteroids may be synergistic with other treatments. Reduction in foveal
edema is not necessarily associated with improved visual function in exudative
AMD.

PMID: 17601437 [PubMed - indexed for MEDLINE]

784: Am J Ophthalmol. 2007 Jul;144(1):124-6.

Bevacizumab (Avastin) for diabetic macular edema in previously vitrectomized
eyes.

Yanyali A, Aytug B, Horozoglu F, Nohutcu AF.

Department of Ophthalmology, Haydarpasa Numune Education and Research Hospital,
Istanbul, Turkey. ayanyali@hotmail.com

PURPOSE: To report the visual acuity (VA) and foveal thickness (FT) changes after
intravitreal bevacizumab for diabetic macular edema (DME) in previously
vitrectomized eyes. DESIGN: Retrospective, noncomparative, interventional case
series. METHODS: Medical records of 11 eyes of 10 patients who underwent
intravitreal bevacizumab injection for persistent DME were reviewed. This
retrospective study included eyes that had persistent DME despite prior pars
plana vitrectomy with internal limiting membrane removal at our institution with 
optical coherence tomography (OCT) assessment of DME. All eyes received three
intravitreal injections of bevacizumab 1.25 mg/0.05 ml monthly. RESULTS: Mean FT 
was 408 +/- 77 microm at baseline, 453 +/- 97 microm at three months, and 454 +/-
101 microm at six months (P = .172). Mean Early Treatment Diabetic Retinopathy
Study (ETDRS) letter scores were 59 +/- 15 (20/80) at baseline, 59 +/- 16 (20/80)
at three months, 57 +/- 15 (20/80) at six months (P = .398). CONCLUSION: No
change in VA and FT was observed in the short-term after intravitreal bevacizumab
for DME in previously vitrectomized eyes.

PMID: 17601433 [PubMed - indexed for MEDLINE]

785: Am J Ophthalmol. 2007 Jul;144(1):122-4.

Intravitreal bevacizumab (Avastin) injection in ocular ischemic syndrome.

Amselem L, Montero J, Diaz-Llopis M, Pulido JS, Bakri SJ, Palomares P,
Garcia-Delpech S.

Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota, USA.

PURPOSE: To determine whether bevacizumab may improve anatomic and visual
outcomes in patients with ocular ischemic syndrome (OIS). DESIGN: Interventional 
case reports. METHODS: Two patients with OIS presenting with unilateral ocular
pain, iris neovascularization, and macular edema. Intravitreal injection of
bevacizumab (1.25 mg). The main outcome measures were postinjection
best-corrected visual acuity (BCVA), intraocular pressure (IOP), angiographic
findings, and optical coherence tomography (OCT) findings and complications.
RESULTS: One week after treatment, both patients demonstrated regression of the
iris neovascularization and improvement of the macular edema, with no changes in 
BCVA and IOP. One eye was reinjected at four months. After three and seven
months, no significant or systemic adverse events were observed, and no signs of 
new iris neovascularization were present. CONCLUSIONS: Intravitreal bevacizumab
may be useful for the treatment of eyes with iris neovascularization and macular 
edema secondary to OIS.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 17601432 [PubMed - indexed for MEDLINE]

786: Ophthalmology. 2008 Feb;115(2):342-6. Epub 2007 Jun 28.

Comment in:
    Ophthalmology. 2008 Oct;115(10):1853-4; author reply 1854.

Autofluorescence imaging in age-related macular degeneration complicated by
choroidal neovascularization: a prospective study.

Vaclavik V, Vujosevic S, Dandekar SS, Bunce C, Peto T, Bird AC.

Moorfields Eye Hospital, London, United Kingdom. veronikavaclavik@yahoo.co.uk

PURPOSE: To determine if integrity of the retinal pigment epithelium
(RPE)/photoreceptor complex as assessed by autofluorescence imaging can be
predicted on the basis of visual acuity (VA), size, or fluorescein angiographic
characteristics of the lesion in the early stage of choroidal neovascularization 
in age-related macular degeneration (AMD). DESIGN: Prospective, observational,
consecutive case series. PARTICIPANTS: Seventy-nine eyes of 78 patients with
untreated early-stage subfoveal neovascular AMD. METHODS: Digital color fundus
photography and fluorescein angiography were carried out by certified
photographers using the same camera throughout the study. Confocal scanning laser
ophthalmoscopy images were obtained using a retinal angiograph. Autofluorescence 
images were compared with digital fluorescein angiography and fundus color
photographs using IMAGEnet. MAIN OUTCOME MEASURES: Autofluorescence at the macula
was correlated with VA, angiographic lesion characteristics, lesion size, and
length of symptoms. RESULTS: Of the 79 eyes studied, 40 had classic and
predominantly classic choroidal neovascularization, 10 had minimally classic, 29 
had occult, 75 were subfoveal, and 4 were juxtafoveal. In 54 eyes,
autofluorescence was continuous at the central macula, and this correlated
significantly with VA, lesion size, and symptom length but not choroidal
neovascularization type. However, there was considerable overlap between the 2
groups such that the integrity of RPE autofluorescence could not be predicted on 
the basis of these criteria. CONCLUSION: Intact autofluorescence at the macula in
early choroidal neovascularization correlates with VA, lesion size, and symptom
length but not lesion type. None predict with any certainty the integrity of the 
outer retina. Our data suggest that the RPE/photoreceptor complex may be intact
at the macula for several months in the presence of choroidal neovascularization,
suggesting that VA might be rescued if treatment were effective in suppressing
neovascular growth without damaging the RPE/retina complex, although this remains
to be tested. It would be sensible to assess autofluorescence in treatment
protocols to test this concept because it may be a marker for earlier disease and
predict outcomes of treatment.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17599415 [PubMed - indexed for MEDLINE]

787: Ophthalmic Res. 2007;39(4):207-12. Epub 2007 Jun 26.

Comparative study on efficacy of a combination therapy of triamcinolone acetonide
administration with and without vitrectomy for macular edema associated with
branch retinal vein occlusion.

Hirano Y, Sakurai E, Yoshida M, Ogura Y.

Department of Ophthalmology and Visual Science, Nagoya City University Graduate
School of Medical Sciences, Nagoya, Japan. yossyeye@med.nagoya-cu.ac.jp

AIMS: To compare the efficacy ofa combination therapy of triamcinolone acetonide 
(TA) administration with and without vitrectomy in eyes with macular edema
associated with branch retinal vein occlusion over a 1-year period. METHODS: A
retrospective, case-control study was conducted in 15 eyes of 15 patients with
macular edema associated with branch retinal vein occlusion. Eight eyes underwent
simultaneous intravitreal and posterior sub-Tenon capsule injections of TA
(TA-injected group). Seven eyes underwent vitrectomy with intravitreal or
simultaneous posterior sub-Tenon capsule injection of TA (vitrectomy with TA
group). Macular thickness and visual acuity were measured before and at 1, 3, 6
and 12 months after the therapy. RESULTS: Twelve months after the therapy, mean
visual acuity improved significantly from baseline in both the TA-injected (p =
0.0069) and vitrectomy with TA groups (p = 0.0145). Macular thickness also
improved significantly in both the TA-injected (p = 0.0065) and vitrectomy with
TA groups (p = 0.0058). At 12 months after the therapy, there was no significant 
difference in visual acuity and macular thickness between the two groups (p =
0.3308 and 0.3711, respectively). At the early postoperative stage (1 and 3
months after the therapy), the central macular thickness in the TA-injected group
was significantly less than that in the vitrectomy with TA group (p = 0.0140 and 
0.0275, respectively); there was no significant difference in visual acuity
between the two groups (p = 0.0796 and 0.3753, respectively). CONCLUSION: TA
injection without vitrectomy was as effective as a combination therapy of TA
injection with vitrectomy. Copyright (c) 2007 S. Karger AG, Basel.

Publication Types: 
    Comparative Study

PMID: 17596753 [PubMed - indexed for MEDLINE]

788: Indian J Ophthalmol. 2007 Jul-Aug;55(4):277-81.

A pilot trial for comparison of photodynamic therapy and transpupillary
thermotherapy for the management of classic subfoveal choroidal
neovascularization secondary to age-related macular degeneration.

Tewari HK, Prakash G, Azad RV, Talwar D, Kai S.

Centre for Sight, Safdarjang Enclave, New Delhi, India.

AIM: The aim of the study was to compare the visual outcomes of photodynamic
therapy (PDT) with verteporfin and transpupillary thermotherapy (TTT) for classic
subfoveal choroidal neovascularization (CNVM) secondary to age-related macular
degeneration (ARMD). SETTINGS AND DESIGN: Patients with subfoveal classic CNVM
caused by ARMD attending vitreo-retinal services at a tertiary care setup were
included in this nonrandomized, open label, prospective, clinical, comparative
pilot trial. MATERIALS AND METHODS: Standardized refraction, visual acuity
testing, evaluation of fundus and serial color photography and fundus fluorescein
angiography were carried out to evaluate the effects of treatment in 32 eyes each
undergoing either PDT or TTT. Follow-up was carried out at four weeks, 12 weeks
and six months. Retreatment if indicated was carried out three months post
treatment. RESULTS: Stabilization or improvement occurred in 69% of patients
undergoing PDT and 50% patients undergoing TTT at six months of follow-up. Among 
patients with a pretreatment visual acuity greater than or equal to 20/63, only
one out of six patients who underwent PDT had a drop of visual acuity > 2 lines
as compared to four patients (100%) who underwent TTT. (P =0.0476, two-tailed
Fisher's exact test). CONCLUSION: For short-term preservation of vision in
patients of classic CNVM due to ARMD, PDT seems to be better than TTT if the
pre-laser best corrected visual acuity is > 20/63 but both are equally effective 
if pre-laser best corrected visual acuity is < 20/63.

Publication Types: 
    Clinical Trial

PMID: 17595476 [PubMed - indexed for MEDLINE]

789: J Ocul Pharmacol Ther. 2007 Jun;23(3):284-91.

Diclofenac prevents an early event of macular thickening after cataract surgery
in patients with diabetes.

Shimura M, Nakazawa T, Yasuda K, Nishida K.

Department of Ophthalmology, NTT East Japan Tohoku Hospital, Sendai, Japan.
masahiko@v101.vaio.ne.jp

PURPOSE: This study compares the effect of topical diclofenac with that of
betamethasone against postoperative cystoid macular edema (CME) following
cataract surgery in patients with non- and mild nonproliferative diabetic
retinopathy. METHODS: Forty-six (46) consecutive patients with mild
nonproliferative- or nondiabetic retinopathy who had bilateral and symmetrical
cataracts underwent uncomplicated cataract surgery in both eyes (92 eyes in
total). Postoperatively, topical diclofenac was applied 4 times daily for 1 eye, 
and topical betamethasone 4 times daily for the other eye in each patient. Best
corrected logMAR visual acuity (BCVA), averaged foveal thickness (FT) as measured
by optical coherence tomography (OCT), and intraocular pressure (IOP) were
monitored preoperatively, and also postoperatively at 1 day and 1, 4, and 8
weeks. RESULTS: VA in both the diclofenac- and betamethasone-treated eyes
significantly improved following the cataract surgery; however, no statistical
difference of VA was noted between the diclofenac- and betamethasone-treated eyes
throughout the observational period (before and after the surgery until 8 weeks
postoperatively). FT in both eyes increased after the cataract surgery. FT in the
diclofenac-treated eyes did not increase 1 week after surgery, but gradually
increased at week 4 and week 8. In contrast, the FT in the betamethasone-treated 
eyes increased during 1-8 weeks postoperatively. IOP in the diclofenac-treated
eyes decreased with time, but IOP in the betamethasone-treated eyes showed no
change throughout the observational period. CONCLUSIONS: Postoperative macular
thickening following cataract surgery in patients with non- or mild
nonproliferative-diabetic retinopathy cannot be fully suppressed by either
topical diclofenac or betamethasone. Nonetheless, diclofenac protected against an
early event of postoperative CME and also a decrease of IOP.

Publication Types: 
    Clinical Trial
    Comparative Study

PMID: 17593013 [PubMed - indexed for MEDLINE]

790: Cornea. 2007 Jul;26(6):683-4.

Macular edema after corneal graft: a prospective study by optical coherence
tomography.

Genevois O, Benzerroug M, Gardea E, Brasseur G, Muraine M.

Department of Ophthalmology, Rouen University Hospital, Rouen Cedex, France.
oliviergenevois@hotmail.com

PURPOSE: Vision recovery after corneal graft is sometimes limited by the
occurrence of macular edema. The aim of this prospective study of 62 keratoplasty
patients was to assess the incidence of macular edema by using optical coherence 
tomography (OCT 3; Stratus, Carl Zeiss Meditec, Dublin, CA) and to identify
factors associated with edema. METHODS: Sixty-two patients who were all operated 
on by the same surgeon were examined by OCT 3, 1 and 3 months after corneal
graft. RESULTS: The incidence of macular edema after keratoplasty was 9.6%. The
surgical technique (penetrating vs lamellar keratoplasty) had no influence on the
occurrence of edema (P > 0.05), but combined surgery significantly increased the 
risk of developing an edema (P < 0.05). CONCLUSION: Macular edema after
keratoplasty seemed to be less frequent than expected (9.6%) and associated
mainly with combined surgery.

PMID: 17592316 [PubMed - indexed for MEDLINE]

791: Korean J Ophthalmol. 2007 Jun;21(2):95-9.

Diabetic macular edema before and after intravitreal triamcinolone injection.

Ramezani A, Tabatabaie H, Ahmadieh H.

Ophthalmic Research Center, Shaheed Beheshti Medical University, Tehran, Iran.
arramezani@gmail.com

PURPOSE: To compare intravitreal triamcinolone acetonide (IVT) versus natural
course in refractory diabetic macular edema. METHODS: In a prospective
interventional case series, twenty five eyes with refractory DME which had been
allocated to the sham group of a previous clinical trial underwent new
examination and optical coherence tomography about 9 months after their first
enrollment. Twenty eyes that met the inclusion criteria, visual acuity (VA) <
20/50 and central macular thickness (CMT) > 200 microm, were treated by 4 mg IVT.
Evaluations were repeated at 2 and 4 months post-injection to imitate the similar
examination intervals after sham injection. Corrected visual acuity and macular
thickness changes following IVT were compared to the corresponding changes after 
sham injection (the natural course). RESULTS: Visual acuity changes within and
between each period were not statistically significant. Visual acuity decreased
0.08 & 0.09 logMAR by 2 months and 0.06 & 0.04 logMAR by 4 months after sham and 
IVT injections, respectively. The changes of macular thickness after IVT and sham
intervention were not meaningful either. However, the difference between
thickness changes by 4 months (52+/-50 microm increase after sham vs. 262+/-115
microm reduction after IVT) was significant (P=0.014). CONCLUSIONS: Concerning
macular thickness, IVT has beneficial effect on refractory diabetic macular edema
as opposed to observation. However, considering visual acuity, it does not induce
significant difference in comparison to the natural course of the disease.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17592240 [PubMed - indexed for MEDLINE]

792: Invest Ophthalmol Vis Sci. 2007 Jul;48(7):3419-24.

Suprathreshold contrast matching in maculopathy.

Mei M, Leat SJ.

School of Optometry, University of Waterloo, Waterloo, Ontario, Canada.
m2mei@uwaterloo.ca

PURPOSE: To compare suprathreshold contrast perception among three groups of
participants with maculopathy (atrophic age-related macular degeneration [ARMD], 
exudative ARMD, and juvenile macular dystrophy [JMD]) and to compare
suprathreshold contrast matching between controls and subjects with maculopathy. 
METHODS: Three groups of subjects with macular disorders (13 atrophic ARMD, 14
exudative ARMD, and 8 JMD) and one group of control subjects (15 subjects 50
years and older) participated. Contrast sensitivity (CS) up to 8.53 cycles per
degree (cpd) was measured with a temporal two-alternative forced-choice staircase
procedure. Suprathreshold contrast matching was measured using a method of
limits. A 0.58 cpd sine-wave grating was the standard; the subject was asked to
match the contrast of gratings of different spatial frequencies. RESULTS:
Subjects with maculopathy showed marked deficits of contrast threshold.
Suprathreshold contrast constancy was shown, though deficits were observed in
absolute matches compared with control subjects. The slopes of matched contrast
against standard contrast for the subjects with maculopathy were significantly
different from those for the controls, and these differences were in the
direction that implies compensation for differences in thresholds. There were no 
significant differences among the three groups of subjects with maculopathy.
CONCLUSIONS: In this study, the authors observed a degree of contrast constancy
in subjects with maculopathy, though there were still deficits compared with
control subjects. This is discussed in terms of gain of the visual system
adjusting to compensate for CS losses (though incompletely) or contrast
overconstancy, present in normal peripheral vision, which helps to compensate for
CS loss.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 17591917 [PubMed - indexed for MEDLINE]

793: Invest Ophthalmol Vis Sci. 2007 Jul;48(7):3318-23.

Effect of posture on the diurnal variation in clinically significant diabetic
macular edema.

Polito A, Polini G, Chiodini RG, Isola M, Soldano F, Bandello F.

Department of Ophthalmology, University of Udine, Udine, Italy.
apolito32@yahoo.it

PURPOSE: To investigate the role of posture and other systemic factors in the
diurnal variation of clinically significant diabetic macular edema (CSDME).
METHODS: Ten eyes of 10 diabetic subjects with CSDME underwent four OCT foveal
thickness measurements with StratusOCT at 9 AM and 12, 3, and 6 PM consecutively 
on two different days, with the subject in an upright position on one and in a
recumbent position on the other. For the "recumbent-position" measurements, the
patients were admitted the night before and remained in bed during the entire day
of testing. Clinical laboratory results at baseline included HbA1c, urinary
albumin, and serum creatinine. Refraction and Early Treatment Diabetic
Retinopathy Study (ETDRS) visual acuity were also measured before each OCT
measurement was taken. Variations in blood pressure, body temperature, plasma
glucose, renin, aldosterone, and cortisol levels were measured and then
correlated with macular thickness. RESULTS: Foveal thickening decreased in all
cases over the course of the day. The decrease, however, was significantly
greater for the upright-position measurements (relative mean +/- SD decrease of
20.6% +/- 6.5% in the upright position and 6.2% +/- 4.6% in the recumbent
position). Visual acuity improved by at least 1 ETDRS line in three eyes in the
upright position as opposed to only one eye in the recumbent position. There
seemed to be no association between any of the systemic factors studied and
foveal thickening, with the exception of cortisol. CONCLUSIONS: The results
support the hypothesis that posture and hydrostatic pressure play a major role in
determining time-related shifts in CSDME and suggest that the forces of
Starling's law can in part, account for CSDME formation.

PMID: 17591904 [PubMed - indexed for MEDLINE]

794: Invest Ophthalmol Vis Sci. 2007 Jul;48(7):3283-91.

High-resolution imaging with adaptive optics in patients with inherited retinal
degeneration.

Duncan JL, Zhang Y, Gandhi J, Nakanishi C, Othman M, Branham KE, Swaroop A,
Roorda A.

Department of Ophthalmology, University of California, San Francisco School of
Medicine, San Francisco, California 94143-0730, USA. duncanj@vision.ucsf.edu

PURPOSE: To investigate macular photoreceptor structure in patients with
inherited retinal degeneration using high-resolution images and to correlate the 
findings with clinical phenotypes and genetic mutations. METHODS: Adaptive optics
scanning laser ophthalmoscopy (AOSLO) images of photoreceptors were obtained in
16 eyes: five with retinitis pigmentosa (RP), three with cone-rod dystrophy
(CRD), and eight without retinal disease. A quadratic model was used to
illustrate cone spacing as a function of retinal eccentricity. Cone spacing at 1 
degrees eccentricity was compared with standard measures of central visual
function, including best-corrected visual acuity (BCVA), foveal threshold, and
multifocal electroretinogram (mfERG) amplitude and timing. Intervisit variations 
were studied in one patient with RP and one patient with CRD. Screening of
candidate disease genes identified mutations in two patients, one with RP (a
rhodopsin mutation) and the other with CRD (a novel RPGR-ORF15 mutation).
RESULTS: Cone spacing values were significantly different from normal for
patients with RP (P = 0.01) and CRD (P < 0.0001) and demonstrated a statistically
significant correlation with foveal threshold (P = 0.0003), BCVA (P = 0.01), and 
mfERG amplitude (P = 0.008). Although many RP patients showed normal cone spacing
within 1 degrees of fixation, cones could not be unambiguously identified in
several retinal regions. Cone spacing increased in all CRD patients, even those
with early disease. Little variation was observed in cone spacing measured during
two sessions fewer than 8 days apart. CONCLUSIONS: AOSLO images can be used to
study macular cones with high resolution in patients with retinal degeneration.
The authors present the first report of cone structure in vivo in patients with
mutations in rhodopsin and RPGR-ORF15 and show that macular cones display
distinct characteristics, depending on the underlying disease. AOSLO imaging,
therefore, can provide new insight into possible mechanisms of cone vision loss
in patients with retinal degeneration.

PMID: 17591900 [PubMed - indexed for MEDLINE]

795: Invest Ophthalmol Vis Sci. 2007 Jul;48(7):3005-13.

Genetics of pigment changes and geographic atrophy.

Thompson CL, Jun G, Klein BE, Klein R, Capriotti J, Lee KE, Iyengar SK.

Department of Epidemiology and Biostatistics, Case Western Reserve University,
Cleveland, Ohio 44106-7281, USA.

PURPOSE: Studies of age-related macular degeneration (AMD) often involve persons 
with both choroidal neovascularization and geographic atrophy (GA), but few
genome-wide scans (GWSs) have discriminated between these two outcomes. METHODS: 
To comprehend the role of pigmentary abnormalities (PA) and GA in AMD, the
authors analyzed the data from a previous GWS on AMD (FARMS [Family Age-Related
Maculopathy Study]sample of 34 extended families) looking only at PA. Presented
are new GWS data from the full Beaver Dam Eye Study (BDES) family cohort,
including longitudinal data at baseline and 5- and 10-year follow-up. A linkage
analysis for PA/GA was performed on both samples for 338 markers covering all
autosomes. Another linkage analysis using the rate of change along the PA/GA
scale was performed with the BDES sample. RESULTS: Analysis of the FARMS sample
provided evidence for linkage with P < 0.01 in the 1q25, 5p13, 6q21-23, and 11q14
regions. The most significant peak was found on chromosome 1, near complement
factor H (CFH), with P= 6.20 x 10(-4). Analysis using the rate of change in BDES 
replicated the peaks in 5p13 and 6q21-23, suggesting that these loci may
contribute to the rate of progression of PA/GA. Association analysis of CFH
polymorphisms suggest that CFH may play a role in the development of pigmentary
abnormalities and may modify the progression along the PA/GA scale. CONCLUSIONS: 
These findings suggest a complex, heterogeneous model for PA/GA.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 17591865 [PubMed - indexed for MEDLINE]

796: Br J Ophthalmol. 2008 Jan;92(1):84-8. Epub 2007 Jun 25.

Central visual field impairment during and following cystoid macular oedema.

Kiss CG, Barisani-Asenbauer T, Simader C, Maca S, Schmidt-Erfurth U.

Department of Ophthalmology & Optometry at the Medical University of Vienna,
Vienna, Austria.

AIM: To determine differential light threshold values obtained with the Micro
Perimeter 1 (MP1) in uveitis patients suffering from cystoid macular oedema (CMO)
and to compare these measures to retinal thickness. METHODS: Static threshold
perimetry was performed with the MP1 Microperimeter in 27 eyes of 21 patients
with a history of chronically recurring CMO. Active CMO was confirmed in 19 eyes.
Eight eyes with a history of recurrent CMO were found to have normal foveal
contours in optical coherence tomography (OCT). Differential light threshold
values (MP1) were compared with the corresponding retinal thickness measures
(OCT). RESULTS: Mean differential threshold values within the central two degrees
of the stimulation pattern were reduced compared with normal values and ranged
from 5.8 to 9.5 dB in CMO eyes and from 9.3 to 12.9 dB in eyes with a normal
foveal contour but a history of previous CMO. The corresponding mean retinal
thickness ranged from 390 (SD 90) to 389 (88) microm (at 0 degrees and 1 degree, 
respectively) for active CMO and from 199 (36) to 211 (33) microm in eyes with
normal fovea following CMO resolution. Statistical correlations between mean
differential sensitivity threshold and retinal thickness were only weak and
showed no association. CONCLUSIONS: Active CMO causes a marked reduction in
central retinal sensitivity. In addition, following the resolution of the CMO, a 
substantial impairment of central retinal sensitivity remains. Morphology in
terms of retinal thickness in OCT does not correlate with visual function in
terms of retinal sensitivity in these patients.

PMID: 17591669 [PubMed - indexed for MEDLINE]

797: Hum Mol Genet. 2007 Sep 1;16(17):2135-48. Epub 2007 Jun 25.

Complement factor H and hemicentin-1 in age-related macular degeneration and
renal phenotypes.

Thompson CL, Klein BE, Klein R, Xu Z, Capriotti J, Joshi T, Leontiev D, Lee KE,
Elston RC, Iyengar SK.

Department of Epidemiology and Biostatistics, Case Western Reserve University,
Cleveland, OH 44106, USA.

In this study, we investigated the associations of complement factor H (CFH) and 
hemicentin-1 (HMCN1) with age-related macular degeneration (AMD) and renal
function. Three scales, measuring the course of AMD and drusen development, were 
examined in two samples: the Family Age-Related Macular degeneration Study
(FARMS), consisting of families ascertained through a single individual with
severe AMD, and an unascertained population-based family cohort, the Beaver Dam
Eye Study (BDES), which was also used to assess longitudinal changes in AMD and
associations with renal function. Associations were performed by a regression
accounting for known risk factors as well as familial and sibling effects. Strong
evidence of the association of rs1061170 (Y402H) variation with AMD was confirmed
(P = 9.15 x 10(-5) in BDES, P = 0.016 in FARMS). This association was observed in
multiple AMD scales, suggesting that its role is not phenotype-specific.
Polymorphisms in both CFH and HMCN1 appeared to influence the longitudinal rate
of change of AMD. The rs1061170 polymorphism was also associated with a reduction
in estimated glomerular filtration rate (eGFR) (P = 0.046). Another CFH
polymorphism, rs800292, was similarly associated with eGFR [beta = -0.90 (P =
0.022)]. Associations between rs743137 (P = 0.05) and rs680638 (P = 0.022) in
HMCN1 with calculated creatinine clearance progression were also observed. Both
genes appear to play a role in both AMD and renal pathophysiology. These findings
support evidence for common pathways influencing ocular and renal function and
suggest that further work is required on their common determinants.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 17591627 [PubMed - indexed for MEDLINE]

798: Int Ophthalmol. 2008 Feb;28(1):7-17. Epub 2007 Jun 23.

A randomized, placebo-controlled clinical trial of intravitreal triamcinolone for
refractory diabetic macular edema.

Dehghan MH, Ahmadieh H, Ramezani A, Entezari M, Anisian A.

Ophthalmic Research Centre of Shaheed Beheshti Medical University, Labbafinejad
Medical Centre, Pasdaran Ave. Boostan 9 St., Tehran, 16666, Iran.

PURPOSE: To evaluate the effect of intravitreal triamcinolone acetonide (IVT) on 
refractory diabetic macular edema (DME). METHODS: In a prospective,
placebo-controlled, randomized clinical trial, 88 eyes of 61 patients with
clinically significant macular edema that would have responded unfavourably to
laser photocoagulation were randomly assigned to two groups. The treatment group 
(45 eyes) received 4 mg IVT and the control group (43 eyes) received a placebo
subconjunctival injection. The primary outcome was central macular thickness
(CMT) measured by optical coherence tomography. Complete examination was repeated
at 2 and 4 months post-intervention. RESULTS: The mean (SD) CMT before the
intervention and at the 2- and 4-month follow-ups was 393 (151), 293 (109) and
362 (119) microm in the treatment group and 393 (166), 404 (134) and 405 (160)
microm in the placebo group, respectively. The second month difference was
significant (P=0.01). The difference between visual acuity changes (0.15
logarithm of the minimum angle of resolution, logMAR) was significant at 2 months
(P=0.02) but reduced to 0.11 logMAR (P=0.08) after 4 months. Reduction for hard
exudates and petaloid pattern were significantly greater in cases at 4 months.
CONCLUSIONS: The therapeutic effect of IVT on DME is greatest at 2 months and
decreases up to the fourth month post-intervention. However, in terms of cystoid 
macular edema and hard exudates, the effect is maintained up to 4 months.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17589809 [PubMed - indexed for MEDLINE]

799: Exp Eye Res. 2007 Aug;85(2):202-18. Epub 2007 May 3.

Age-related changes in human macular Bruch's membrane as seen by
quick-freeze/deep-etch.

Huang JD, Presley JB, Chimento MF, Curcio CA, Johnson M.

Department of Biomedical Engineering, Northwestern University, 2145 Sheridan
Road, Evanston, IL 60208-3107, USA.

Lipid-containing inclusions have been observed in human Bruch's membrane (BrM)
and are postulated to be associated with age-related maculopathy (ARM), a major
cause of legal blindness in developed countries. The dehydration associated with 
specimen preparation for thin-section transmission electron microscopy causes
loss of these inclusions. Better preservation of the ultrastructure of the
inclusions and tissue is achieved by using a quick-freeze/deep-etch preparation. 
We use this technique to examine normal human macular BrM in order to
characterize the deposition of the lipid-rich inclusions and their age-related
accumulation within different layers of the tissue. We find that various
inclusions mentioned in other studies can be formed by combinations of three
basic structures: lipoprotein-like particles (LLPs), small granules (SGs) and
membrane-like structures. These inclusions are associated with collagen and
elastic fibrils by fine filaments. In younger eyes, these inclusions are found
mostly in the elastic (EL) and outer collageneous layer (OCL) and occupy a small 
fraction of the interfibrillar spacing. As age increases, LLPs and SGs gradually 
fill the interfibrillar spacing of the EL and inner collageneous layer (ICL) of
the tissue, and later form a new sublayer, the lipid wall, within the boundary
region between the basal lamina of retinal pigment epithelium (RPE) and ICL.
Because the formation of the lipid wall only occurs after these inclusions fill
the ICL, and it seems unlikely that the LLPs can pass through the packed layer,
this result suggests a possible RPE origin of the LLPs that make up the lipid
wall.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17586493 [PubMed - indexed for MEDLINE]

800: Eye. 2008 Jun;22(6):792-8. Epub 2007 Jun 22.

Quality of life in patients with age-related macular degeneration: results from
the VISION study.

Leys A, Zlateva G, Shah SN, Patel M.

Department of Opthalmology, University Hospital Leuven, Leuven, Belgium.

PURPOSE: To assess the impact of treatment with pegaptanib sodium vs usual care
on vision-related quality of life (VRQoL) in patients with age-related macular
degeneration (AMD). METHODS: VRQoL was a secondary end point in the trial, a
prospective, randomized, double-masked, multicentre, dose-ranging study. Three
doses of pegaptanib (0.3, 1, and 3 mg) were compared with usual care with respect
to changes in VRQoL as indicated by the 25-item National Eye Institute Visual
Function Questionnaire (NEI-VFQ 25), administered at baseline and weeks 30 and
54. Four of the NEI-VFQ 25 domains were prospectively designated as primary: near
vision, distance vision, role limitations, and dependency. Between-group
differences were assessed using an analysis of covariance model with age, gender,
and baseline score as covariates. RESULTS: NEI-VFQ 25 data were available for 569
subjects. At week 54, improvements in the distance vision and role limitations
domains were greater in pegaptanib than usual care arms. No substantial increase 
in ocular pain was noted in pegaptanib-treated patients. No clear superiority of 
any particular dosage strength of pegaptanib was demonstrated, and no significant
differences or trends favoured usual care on any domain score or the NEI-VFQ 25
composite score. The greatest VRQoL benefit was seen in responders (lost<3 lines)
to treatment. CONCLUSION: The VISION trial provided evidence of trends in
quality-of-life benefit associated with effective treatment of AMD using
pegaptanib. Treatment with pegaptanib is expected to contribute significantly to 
VRQoL improvement for responder patients.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17585313 [PubMed - indexed for MEDLINE]

801: Br J Ophthalmol. 2008 Jan;92(1):89-92. Epub 2007 Jun 21.

Vision-related quality of life in patients with diabetic macular oedema.

Hariprasad SM, Mieler WF, Grassi M, Green JL, Jager RD, Miller L.

Department of Ophthalmology and Visual Science, University of Chicago, 5841 South
Maryland, MC 2114, Chicago, IL 60637, USA. retina@uchicago.edu

AIMS: The aim of this study was to determine the impact of diabetic macular
oedema (DME) on the quality of life (QOL) in patients with type 2 diabetes
mellitus. METHODS: The study was a prospective, consecutive, non-comparative case
series. An observational study evaluated the quality of vision and
vision-specific QOL using the 25-item National Eye Institute Visual Function
Questionnaire (NEI VFQ-25). Mean VFQ-25 subscale scores in type 2 diabetic study 
patients were compared with mean VFQ-25 subscale score in groups of patients with
type 1 diabetic retinopathy (T1DR) and varying degrees of age-related macular
degeneration (ARMD), glaucoma and cataracts and in reference populations.
RESULTS: Thirty-three patients completed the NEI VFQ-25. The mean age of the
study population was 64 years. When performing a comparison of those patients
with DME versus those with isolated T1DR we found that for the general health
subscale, the DME versus T1DR group means were 42+/-4.4 versus 61+/-1.0
respectively. The DME versus T1DR quality of vision categorical mean scores were 
69+/-4.1 versus 93+/-3.9. The DME versus T1DR VR-QOL categorical mean scores were
62+/-5.0 versus 93+/-1.0. The DME group was significantly worse in each of these 
three categories compared with the T1DR group (p<0.01). An additional analysis
was performed to examine the differences in VR-QOL in the DME group versus
varying common ocular diseases, including age-related macular degeneration
(ARMD), glaucoma, cataracts and disease-free reference groups. The mean values of
VFQ-25 subscale in the DME group were significantly lower then the glaucoma group
in ten of 12 subscales, the cataract group in 11 of 12 subscales, and the
reference group in 12 of 12 subscales. However, the mean values of VFQ-25
subscale in the DME group were only significantly different from the ARMD group
in three of 12 subscales. CONCLUSIONS: Type 2 diabetes patients with macular
oedema experience a decreased VR-QOL compared with type 1 diabetic patients with 
diabetic retinopathy, glaucoma or cataracts. However, VR-QOL in type 2 diabetic
patients with macular oedema was similar to those individuals with ARMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17584999 [PubMed - indexed for MEDLINE]

802: Graefes Arch Clin Exp Ophthalmol. 2007 Nov;245(11):1667-72. Epub 2007 Jun
22.

Combined photodynamic therapy and intravitreal triamcinolone for neovascular
age-related macular degeneration: effect of initial visual acuity on treatment
response.

Schadlu R, Kymes SM, Apte RS.

Department of Ophthalmology and Visual Sciences, Washington University in St.
Louis School of Medicine, Barnes Retina Institute, St. Louis, MO 63110, USA.

PURPOSE: To evaluate visual outcomes in combination therapy with photodynamic
therapy (PDT) and intravitreal triamcinolone acetonide (IVTA) for subfoveal
choroidal neovascularization (CNV) from age-related macular degeneration (AMD).
METHODS: Charts of 39 eyes from 38 patients with exudative AMD treated with PDT
and 4 mg of triamcinolone acetate injected intravitreally were reviewed
retrospectively. Visual data, angiographic lesion type, prior PDT exposure,
number of treatments, and follow-up were recorded. Snellen visual acuities were
converted to LogMAR for all calculations. Lines of vision lost or gained pertain 
to calculated ETDRS lines of vision (via LogMAR). RESULTS: Twenty-two of the
choroidal neovascular membranes were occult, and 17 were classified as
predominantly classic. Mean follow-up was 43 weeks. The average number of
treatments was 2.23. At final follow-up, 11 eyes (28.21%) experienced improved
visual acuity, 8 eyes (20.51%) were stable, and 20 eyes (51.28%) had worsened. No
significant difference in treatment response was found between angiographic
subtypes (p > 0.59). Lack of previous PDT exposure did not improve treatment
outcomes (p > 0.77). Pre-treatment visual acuity (PTVA) was determined as a
strong predictor of treatment outcome in our study cohort. Visual acuity of
20/200 or worse was associated with a 40.9% chance of some improvement and a
35.75% chance of three or more lines of improvement. Visual acuity better than
20/200 was associated with an 89.4% chance of no improvement and a 58.8% chance
of three or more lines of visual loss. CONCLUSION: Counter to previously reported
results with combination therapy, the majority of our patients (72%) did not
demonstrate improved vision and 51% lost vision. When PTVA was accounted for,
selected patients benefitted significantly from treatment. PTVA may be a useful
and simple patient selection tool for combination treatment with PDT and IVTA.

PMID: 17583819 [PubMed - indexed for MEDLINE]

803: Ophthalmology. 2008 Jan;115(1):141-6. Epub 2007 Jun 20.

One-year outcomes of photodynamic therapy in age-related macular degeneration and
polypoidal choroidal vasculopathy in Japanese patients.

Gomi F, Ohji M, Sayanagi K, Sawa M, Sakaguchi H, Oshima Y, Ikuno Y, Tano Y.

Department of Ophthalmology, Osaka University Medical School, Suita, Osaka,
Japan. fgomi@ophthal.med.osaka-u.ac.jp

PURPOSE: To determine the prevalence of polypoidal choroidal vasculopathy (PCV)
in Japanese patients presumed to have age-related macular degeneration (AMD) and 
compare 1-year outcomes after photodynamic therapy between PCV and choroidal
neovascularization secondary to AMD. DESIGN: Prospective interventional study.
PARTICIPANTS: Ninety-three consecutive patients (93 eyes) met the inclusion
criteria: at least 50 years old, best-corrected visual acuity (VA) of 34 to 73 on
the Early Treatment Diabetic Retinopathy Study (ETDRS) letter chart, a subfoveal 
lesion 5400 mum or smaller in greatest linear dimension (GLD) on fluorescein
angiography (FA), and eligibility for photodynamic therapy. METHODS: Indocyanine 
green angiography was performed in all participants, and PCV and AMD were
differentiated, treated with photodynamic therapy, and the patients observed for 
1 year. The GLD was determined by FA for AMD and by indocyanine green angiography
for PCV, and the diameter of the laser spot size was chosen, with an extra 1000
microm added to the GLD. Photodynamic therapy was repeated if leakage occurred on
FA at 3-month follow-up visits. MAIN OUTCOME MEASURES: Prevalence of PCV at
baseline and visual and angiographic changes 1 year after photodynamic therapy in
PCV and AMD. RESULTS: Using indocyanine green angiography, 36 eyes (39%) were
diagnosed with PCV and 54 eyes (58%) with choroidal neovascularization secondary 
to AMD. The median change in VA using the ETDRS letter score from baseline to 1
year was -7.0 in AMD eyes and +8.0 in PCV eyes (Mann-Whitney rank sum test;
P<0.001). The VA improved (> or =15 letters) in AMD and PCV by 6% and 25%,
respectively, and decreased (> or =15 letters) by 31% and 8%, respectively.
Fluorescein leakage stopped at 1 year in 86% of PCV and 61% of AMD eyes (P =
0.031). Polypoidal choroidal vasculopathy recurred in 2 PCV eyes (5.6%), and a
new PCV lesion developed in 1 PCV eye (2.8%) and 2 AMD eyes (3.7%) on indocyanine
green angiography at 1 year. CONCLUSION: The prevalence of PCV meeting the
treatment criteria for photodynamic therapy for presumed AMD is high in Japanese 
patients. Photodynamic therapy is more efficacious for PCV than for AMD, which
may explain the good results in Japanese patients. Further study should assess
the long-term clinical results.

PMID: 17582498 [PubMed - indexed for MEDLINE]

804: Biochemistry. 2007 Jul 17;46(28):8451-61. Epub 2007 Jun 20.

Biochemical analysis of a common human polymorphism associated with age-related
macular degeneration.

Yu J, Wiita P, Kawaguchi R, Honda J, Jorgensen A, Zhang K, Fischetti VA, Sun H.

Department of Physiology and Jules Stein Eye Institute, David Geffen School of
Medicine at UCLA, Los Angeles, California 90095, USA.

Age-related macular degeneration (AMD) is the leading cause of irreversible
blindness in developed countries. A large number of human genetic studies have
associated a common variant (Y402H) of complement factor H (CFH) with a highly
significant increase in AMD risk. CFH is a modular protein with 20 homologous
short consensus repeats (SCRs). The Y402H variant is located in SCR7 of both CFH 
and factor H-like protein 1 (FHL-1), a splice variant of CFH (containing SCR1-7) 
with unique biochemical properties. Because SCR7 is known to bind to heparin,
C-reactive protein (CRP), and M protein from Streptococcus pyogenes, it has been 
hypothesized that the AMD-associated polymorphism may affect interactions with
these CFH ligands. In this study, we tested this hypothesis in the context of
full-length CFH (SCR1-20) and FHL-1. We systematically analyzed the interactions 
of the Y402 and H402 variants of CFH and FHL-1 with heparin, CRP, and several
bacterial ligands: M6 protein of Streptococcus pyogenes, PspC of Streptococcus
pneumoniea, and BbCRASP-1 of Borrelia burgdorferi. In comparing the Y and H
variants of CFH and FHL-1, we found no significant difference in their protein
secretion, cofactor activity, or interactions with heparin, BbCRASP-1, or PspC,
but a significant difference in binding to CRP and M6 protein. This study reveals
the fundamental properties of a common polymorphism of CFH and lays the
groundwork for elucidating the role of CFH in AMD pathogenesis.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17580967 [PubMed - indexed for MEDLINE]

805: Ophthalmologica. 2007;221(4):227-32.

Intraobserver repeatability of automated versus adjusted optical coherence
tomography measurements in patients with neovascular age-related macular
degeneration.

Tatlipinar S, Shah SM, Campochiaro PA, Nguyen QD.

Retina Service, Wilmer Eye Institute, Johns Hopkins University School of
Medicine, 600 North Wolfe Street, Baltimore, MD 21287, USA.

AIM: To assess the intraobserver repeatability of automated versus adjusted
optical coherence tomography (OCT) measurements in patients with neovascular
age-related macular degeneration (NVAMD). METHODS: Ten eyes with NVAMD from 10
consecutive patients underwent two OCT measurements within 5 days by a single
operator. Automated and adjusted central 1-mm foveal thickness and automated and 
adjusted total macular volume were measured in each study eye. The term
'adjusted' refers to manually corrected values, in which the interface landmarks 
for measurements are selected by the operator using Stratus scan profiling and
custom software. Bland-Altman method and bootstrap comparison of intraclass
correlations (ICCs) were used for repeatability analysis. RESULTS: Bland-Altman
comparison did not reveal any statistically significant difference in any
parameter, when results at first and second examination were compared (p > 0.05),
indicating that the repeated measurements are similar. Further analysis was
conducted using the bootstrap comparison of ICCs. The difference between adjusted
and automated foveal thickness ICCs (r = 0.945 and 0.635, respectively) was
significant (p = 0.031), indicating higher repeatability for adjusted foveal
thickness. The ICCs for adjusted and automated total macular volume (r = 0.873
and 0.863, respectively) showed no statistically significant difference (p =
0.881). CONCLUSION: The repeatability of adjusted retinal thickness measurements,
in which the errors of retinal boundary detection by OCT analysis software is
corrected by the operator using scan profiling, is found to be higher than that
of automated ones in this small group of NVAMD patients when performed by a
single experienced operator. Copyright (c) 2006 S. Karger AG, Basel.

Publication Types: 
    Comparative Study
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17579287 [PubMed - indexed for MEDLINE]

806: Hum Mol Genet. 2007 Aug 15;16(16):1986-92. Epub 2007 Jun 18.

Protective effect of complement factor B and complement component 2 variants in
age-related macular degeneration.

Spencer KL, Hauser MA, Olson LM, Schmidt S, Scott WK, Gallins P, Agarwal A,
Postel EA, Pericak-Vance MA, Haines JL.

Center for Human Genetics Research, Vanderbilt University Medical Center,
Nashville, TN, USA.

Age-related macular degeneration (AMD) is a devastating disorder of the central
retina, causing significant visual impairment for 7.5 million elderly Americans. 
Abnormal regulation of the complement system likely caused by the Y402H
polymorphism in the complement factor H gene is a recognized risk factor for AMD,
as is the A69S variant in the poorly characterized LOC387715 gene. Recently,
polymorphisms in the factor B (CFB) and complement component 2 (CC2) genes were
associated with decreased susceptibility to AMD. To validate this association in 
independent family-based and case-control Caucasian data sets, we genotyped two
single-nucleotide polymorphisms (SNPs) in CC2 and four SNPs in CFB. The R32Q
variant of CFB was significantly associated with protection from AMD in the
family-based data set (P = 0.025). Three SNPs in CC2 and CFB were strongly
associated with decreased risk of AMD in the case-control data set (CC2 E318D: P 
= 0.02; CC2 rs547154: P = 9 x 10(-6); and CFB R32Q P = 2 x 10(-5)). The minor
alleles at CC2 rs547154 and CFB R32Q are present in 4% of cases versus 10% of
controls, and as these SNPs are in strong linkage disequilibrium (r(2)=0.92),
these results likely represent the same protective signal. After controlling for 
age, Y402H, A69S and smoking, the effect of CFB R32Q remained quite strong (OR
0.21, 95% confidence interval 0.11-0.39; P < 10(-4)). Likelihood ratio testing
and conditional analyses in the case-control data set suggest that a weaker,
independent protective effect exists for CC2 E318D.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 17576744 [PubMed - indexed for MEDLINE]

807: Ophthalmology. 2008 Jan;115(1):127-33. Epub 2007 Jun 14.

Comparison of methods to identify incident cataract in eyes of patients with
neovascular maculopathy: Submacular Surgery Trials Report No. 18.

Submacular Surgery Trials Research Group, Mann AL, Bressler SB, Hawkins BS,
Holekamp N, Bressler NM.

Submacular Surgery Trials Chair's Office, Wilmer Eye Institute, Johns Hopkins
University, 550 North Broadway, Suite 115, Baltimore, MD 21205, USA.
sstchairman@jhmi.edu

PURPOSE: To describe and compare methods used to monitor development and
progression of presumed vision-limiting lens opacity in study eyes of Submacular 
Surgery Trials (SST) patients. DESIGN: Prospective study of patients enrolled in 
a set of randomized clinical trials. PARTICIPANTS: Patients enrolled in the SST
who were phakic in the study eye at the time of enrollment (n = 690). In a subset
of 114 patients, lens photographs were obtained at baseline and 2 years after
enrollment. METHODS: Data collection at baseline and annual follow-up
examinations included ocular history, ophthalmologic examination including the
SST ophthalmologist's assessment of presence or absence of vision-limiting
opacity, fundus photography, and lens photography (13 of 27 clinics only). All
photographs were assessed by masked graders centrally using the Lens Opacities
Classification System III (LOCS III). kappa statistics were calculated to compare
LOCS III cataract classifications with fundus photograph quality and with the
ophthalmologist's assessment of lens opacity, with the LOCS III classification
considered the gold standard. MAIN OUTCOME MEASURE: Incidence of cataract in
study eyes. RESULTS: Baseline lens photographs were available and graded for 312 
(45%) of 690 patients with phakic study eyes; 2-year lens photographs were
available for 156 (23%) of 690 initially phakic eyes. Both baseline and 2-year
lens photographs were available for 114 eyes that remained phakic. Submacular
surgery was associated with significant progression of nuclear color and nuclear 
opalescence characteristics within 2 years of enrollment. The reliability of
fundus photograph quality versus cataract classification using a 4.5 LOCS III
score threshold for cataract was poor to good at each time point and for all
groups (kappa, 0-0.51), but sensitivity of the photograph quality score as a
surrogate was low, and both positive and negative predictive values were low.
Agreement between the ophthalmologists' assessments of lens opacity and the 4.5
LOCS III score threshold for cataract was good (kappa, 0.42-0.78). CONCLUSIONS:
In the SST, clinical identification of severe cataract (LOCS III scores of 4.5 or
worse for nuclear opacity or nuclear color) by the examining ophthalmologist was 
valid based on comparison with LOCS III scores and may be an adequate method to
use in similar trials.

Publication Types: 
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17574675 [PubMed - indexed for MEDLINE]

808: Appl Psychophysiol Biofeedback. 2007 Dec;32(3-4):185-9. Epub 2007 Jun 16.

Microperimetric biofeedback in AMD patients.

Vingolo EM, Cavarretta S, Domanico D, Parisi F, Malagola R.

Department of Ophthalmology, Inherited Retinal Diseases Unit, La Sapienza
University of Rome, Ospedale A. Fiorini, Terracina, Italy. evingolo@rdn.it

To analyse biofeedback training by microperimeter MP-1 (Nidek Technologies) on
patients with Age Related Maculopathy (AMD). We enrolled 15 patients (10 female
and 5 male) and examined total of 27 eyes with AMD. All the patient underwent 10 
training sessions of 10 min for each eye, performed once a week using the MP-1
biofeedback examination. Statistical analysis was performed using Student's
t-test. p values less than 0.05 were considered statistically significant. All
patients displayed an improvement in visual acuity, fixation behaviour, retinal
sensitivity an reading speed. The mean character size value improved from 36.4 to
11.7; this result was statistically significant (p = 0.031). A biofeedback
examination using the MP-1 microperimeter can help the brain to memorize the
final fixation location by increasing attention modulation, thereby providing an 
efficient preferred retinal locus for visual tasks in patients with macular
disease and central scotoma.

Publication Types: 
    Clinical Trial

PMID: 17574525 [PubMed - indexed for MEDLINE]

809: Ophthalmology. 2008 Jan;115(1):18-25. Epub 2007 Jun 18.

Eye-related medicare costs for patients with age-related macular degeneration
from 1995 to 1999.

Coleman AL, Yu F.

Jules Stein Eye Institute and University of California Los Angeles Department of 
Ophthalmology, Los Angeles, California 90095-7004, USA. coleman@jsei.ucla.edu

OBJECTIVE: Age-related macular degeneration (AMD) is the leading cause of
blindness and severe visual impairment among the elderly in the United States.
This study aims to assess eye-related Medicare costs from 1995 to 1999 in
patients with both nonneovascular and neovascular AMD as compared with controls, 
and to delineate whether variations exist across demographic and clinical
subgroups in eye-related Medicare costs over 5 years. DESIGN: Retrospective,
observational, population-based analysis. PARTICIPANTS: Five percent random
sample of Medicare beneficiaries. METHODS: Data were obtained from the 5% random 
sample of Medicare beneficiaries with diagnoses of nonneovascular and neovascular
AMD. A control group was selected based on diagnoses of blepharitis, chronic
conjunctivitis, or blepharoconjuctivitis and no diagnosis of AMD. Eye-related
claims were totaled and compared for each group over the 5-year study period.
Demographic and clinical factors potentially influencing eye-related costs were
also examined. MAIN OUTCOME MEASURES: Eye-related Medicare costs during the
5-year study period. RESULTS: Median eye-related Medicare costs were estimated at
$1607 for neovascular AMD patients, $832 for nonneovascular AMD patients, and
$658 for controls. Cost differences across groups were significant based on
univariate and multivariate analyses (P<0.001). In linear regression analysis,
males and blacks had significantly lower eye-related Medicare costs than females 
and whites, respectively (P<0.001). CONCLUSIONS: Age-related macular degeneration
represented a significant economic burden to the U.S. health care system for a
single ophthalmic disease entity based on Medicare reimbursed eye-related costs
before the availability of photodynamic therapy and anti-vascular endothelial
growth factor therapy. Given that direct eye-related costs associated with the
treatment of neovascular AMD are estimated at $569 million annually before the
availability of therapy for subfoveal lesions, effective therapeutic measures may
be associated with substantial cost offsets.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17572499 [PubMed - indexed for MEDLINE]

810: J Hum Genet. 2007;52(7):636-41. Epub 2007 Jun 14.

Association of the HTRA1 gene variant with age-related macular degeneration in
the Japanese population.

Mori K, Horie-Inoue K, Kohda M, Kawasaki I, Gehlbach PL, Awata T, Yoneya S,
Okazaki Y, Inoue S.

Department of Ophthalmology, Saitama Medical University, Faculty of Medicine, 38 
Morohongo, Moroyama, Iruma, Saitama, 350-0495, Japan. keisuke@saitama-med.ac.jp

The purpose of this investigation was to determine whether the high-temperature
requirement A-1 (HTRA1) gene polymorphism is associated with age-related macular 
degeneration (AMD) in native, unrelated Japanese patients. A total of 123
patients with AMD and 133 control subjects without AMD were recruited for this
study. The single-nucleotide polymorphism (SNP) rs11200638 in the HTRA1 gene was 
assessed using a TaqMan assay. The risk A allele frequencies in the AMD cases and
control patients were 0.577 and 0.380, respectively, and were associated with a
significant risk of developing AMD (p=7.75x10(-6)). The results were more
significant in subtype analyses with wet AMD (p=5.96x10(-7)). We conclude that
the rs11200638 variant in the HTRA1 gene is strongly associated with AMD in the
Japanese population. This result supports the hypothesis that the HTRA1 gene may 
increase susceptibility to AMD development and can participate in a potential new
molecular pathway for AMD pathogenesis by extending this association across
diverse ethnicities.

PMID: 17568988 [PubMed - indexed for MEDLINE]

811: Optom Vis Sci. 2007 Jun;84(6):487-95.

Visual acuity and fixation characteristics in age-related macular degeneration.

Cacho I, Dickinson CM, Reeves BC, Harper RA.

Faculty of Life Sciences, Moffat Building, The University of Manchester,
Manchester, UK. i.cacho@manchester.ac.uk

PURPOSE: To compare "single letter" (SL) acuity, "crowded letter" (CL) acuity,
and "repeated letter" (RL) acuity for patients with age-related macular
degeneration (AMD) and investigate if differences between these visual acuities
are associated with fixation characteristics. METHODS: A total of 243 patients
with AMD had their best-corrected visual acuity measured on an ETDRS chart. SL,
CL, and RL acuities were measured using Landolt C targets on a monitor.
Fifty-degree-field red-free fundus photographs were taken and a static target was
used to calculate the Preferred Retinal Locus (PRL) distance and direction from
the fovea. Quality of fixation (consistency and oculomotor response) was also
assessed using a fundus camera and a dynamic target. RESULTS: RL acuity was
almost always better than CL acuity and SL acuity was almost always better than
CL acuity. The mean (+/-SD) RL-CL and SL-CL acuity differences were -0.13
(+/-0.15) logMAR and -0.11 (+/-0.13) logMAR respectively. The median PRL distance
was 3.73 degrees and the preferred retinal areas for the location of the PRL were
the left (left quadrant of visual field; 39.5% of cases) and superior (inferior
quadrant of visual field; 25.4%). Visual acuity was significantly associated with
PRL distance but PRL distance only explained 10% of the variation in visual
acuity. PRL distance was found to be a significant but weak predictor of the
SL-CL acuity difference but fixation quality was not a good predictor of the
RL-CL acuity difference. CONCLUSIONS: Although the acuity measured under
different stimulus conditions varies, the absolute differences are small. This
suggests that these techniques would not be helpful in determining fixation
characteristics, or predicting the outcome of rehabilitation in individual
patients with AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17568318 [PubMed - indexed for MEDLINE]

812: Br J Ophthalmol. 2007 Dec;91(12):1602-6. Epub 2007 Jun 13.

Histopathological findings in postmortem eyes after photodynamic therapy for
choroidal neovascularisation in age-related macular degeneration: report of two
cases.

Kang SJ, Schmack I, Benson HE, Grossniklaus HE.

LF Montgomery Ophthalmic Pathology Laboratory, Emory Eye Center, 1365-B Clifton
Road NE, Atlanta, GA 30322, USA. ophtheg@emory.edu

BACKGROUND: To report the histopathological findings after photodynamic therapy
(PDT) in eyes obtained postmortem with choroidal neovascularisation (CNV)
secondary to age-related macular degeneration (AMD). METHODS: Two eyes were
obtained postmortem from two patients with CNV secondary to AMD. Both of the
patients had been treated with PDT. Serial sections through the posterior poles
were obtained and stained with haematoxylin-eosin, periodic acid-Schiff, Masson
trichrome or phosphotungstic acid haematoxylin (PTAH). Two-dimensional
reconstructions were prepared and compared with fluorescein angiograms. RESULTS: 
The interval between PDT and death was 3 months and 17 months in each patient,
respectively. Light-microscopic examination showed that CNV enveloped with
retinal pigment epithelium (RPE) in both eyes. The average size of the CNV was
550 x 280 microm. One eye had combined (subRPE/subretinal) growth pattern CNV,
and the other eye had both type I (subRPE) and combined growth pattern CNV. All
specimens contained fibrous proliferation and patent vascular channels within the
CNV, and there was no thrombus formation within the vascular channels. No
apparent abnormalities in the choroid were observed by light microscopy.
CONCLUSIONS: Although involution with fibrous tissue proliferation occurred, PDT 
did not result in permanent occlusion of the vascular channels in the CNV. Our
findings indicate that PDT may accelerate involution of CNV, thus limiting its
size and preserving photoreceptors.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 17567659 [PubMed - indexed for MEDLINE]

813: Semin Ophthalmol. 2007 Apr-Jun;22(2):105-8.

Intravitreal bevacizumab for macular edema due to occlusive vasculitis.

Margolis R, Lowder CY, Sears JE, Kaiser PK.

Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.

Systemic vasculitides can cause retinal vascular pathology, including cotton-wool
spots, retinal hemorrhages, vascular occlusion, and capillary nonperfusion. Two
main causes of visual decline include macular edema and retinal
neovascularization. Presumably, both of these complications are caused by
increased intraocular levels of vascular growth and permeability factors. We
report a patient with occlusive retinal vasculitis associated with mixed
connective tissue disease who was treated with intravitreal bevacizumab for
chronic macular edema. One month after treatment, visual acuity improved from
20/80 to 20/60, and foveal thickness decreased from 543 microns to 306 microns.
This effect persisted for at least 3 months after treatment. No complications,
including increased retinal ischemia, were observed.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 17564933 [PubMed - indexed for MEDLINE]

814: Semin Ophthalmol. 2007 Apr-Jun;22(2):87-8.

Intravitreous vascular endothelial growth factor (VEGF) inhibitor therapy for
tamoxifen induced macular edema.

Bourla DH, Gonzales CR, Mango CW, Moral JN, Wirthlin RS, Schwartz SD.

Jules Stein Eye Institute, Department of Ophthalmology, University of California,
Los Angeles, CA 90095, USA. bourla@jsei.ucla.edu

A 59-year-old male patient with tamoxifen induced macular edema in both eyes was 
treated with intravitreous sodium pegaptanib. Follow-up clinical examination,
OCT, and FA demonstrated reduced edema and leakage with improvement in visual
acuity.

Publication Types: 
    Case Reports

PMID: 17564928 [PubMed - indexed for MEDLINE]

815: Semin Ophthalmol. 2007 Apr-Jun;22(2):75-9.

The use of intravitreal etanercept in diabetic macular oedema.

Tsilimbaris MK, Panagiotoglou TD, Charisis SK, Anastasakis A, Krikonis TS,
Christodoulakis E.

Retina Service, Department of Ophthalmology, University Hospital of Heraklion,
Crete, Greece. tsilimb@med.uoc.gr

The aim of this pilot study was to investigate the effect of intravitreal
administration of etanercept in refractory diabetic macular edema. Seven patients
diagnosed with diabetic macular edema, refractory to previous treatment, were
enrolled. They all received 2 consecutive intravitreal injections of 2.5 mg (0, 1
ml) of Etanercept (Enbrel), with a two-week interval. In all patients visual
acuity assessment, fundoscopy and fluorescein angiography were performed prior to
the first injection, weekly for the first month, as well as 2 and 3 months
following the first injection. No adverse reactions or adverse events were
noticed in any patient. Analysis of the data indicates a trend for improvement of
visual acuity, a slight worsening of hard exudates and fluorescein leakage, while
hemorrhages remained stable, 3 months after initiation of therapy. However, no
statistical significance has been reached. This small pilot study did not reveal 
any improvement in the clinical course of patients with refractory diabetic
macular edema after the intravitreal injection of etanercept. Further research is
warranted in order to obtain conclusive results concerning the role of anti-TNF
therapy in diabetic macular edema.

PMID: 17564925 [PubMed - indexed for MEDLINE]

816: Mol Vis. 2007 May 23;13:772-8.

Oxidized phospholipids in the macula increase with age and in eyes with
age-related macular degeneration.

Suzuki M, Kamei M, Itabe H, Yoneda K, Bando H, Kume N, Tano Y.

Department of Ophthalmology, Osaka University Medical School, Suita, Japan.
msuzuki@ophthal.med.osaka-u.ac.jp

PURPOSE: There is good evidence that oxidative stress is involved in the
pathogenesis of age-related macular degeneration (AMD). Because AMD has risk
factors and histopathology similar to with atherosclerosis, we hypothesized that 
oxidized phospholipids, which contribute to the pathogenesis of atherosclerosis, 
would accumulate in the eyes of AMD patients. To test this hypothesis, we
investigated whether oxidized phospholipids were present in normal eyes and
whether the level changed with increasing age. We then, we determined whether the
levels of oxidized phospholipids were higher in eyes with AMD. METHODS: Twenty
normal human donor eyes and six eyes with AMD were studied. Immunohistochemistry 
was performed on a tissue strip from the macular region using an antibody against
oxidized phosphatidylcholine. Western blot analysis was also performed on
proteins extracted from the posterior retina of donor eyes. The immunoreactivity 
of the specimens and the bands were quantified with NIH image software. RESULTS: 
Immunohistochemistry showed oxidized phosphatidylcholine was present in the
photoreceptors and retinal pigment epithelium of the normal human macular area,
and their levels increased with age. Eyes with AMD showed more intense
immunoreactivity for oxidized phospholipids than age-matched normal eyes.
CONCLUSIONS: These findings suggest that oxidative stress is involved in the
pathogenesis of AMD possibly by oxidizing phospholipids in the photoreceptors as 
demonstrated in the arterial intima of patients with atherosclerosis. It is
likely that controlling oxidation of phospholipids may be a potential treatment
for AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17563727 [PubMed - indexed for MEDLINE]

817: Arch Ophthalmol. 2007 Jun;125(6):759-64.

Treatment of cystoid macular edema in retinitis pigmentosa with intravitreal
triamcinolone.

Scorolli L, Morara M, Meduri A, Reggiani LB, Ferreri G, Scalinci SZ, Meduri RA.

Department of Pathophysiological Optics, University of Bologna, Via Zuccardi
Merli 1, 40141 Bologna, Italy. luciascorolli@yahoo.it

OBJECTIVE: To evaluate the results of treatment with intravitreal triamcinolone
acetonide injection in patients with cystoid macular edema secondary to retinitis
pigmentosa. METHODS: This prospective, nonrandomized comparative trial included
20 eyes of 20 patients with cystoid macular edema secondary to retinitis
pigmentosa (group A) and 20 eyes of 20 control individuals (group B) with the
same characteristics who declined treatment. All treated eyes received an
intravitreal injection of 0.1 mL of triamcinolone acetonide (4 mg). The total
follow-up was 12 months. The main outcome measures were best-corrected visual
acuity, central macular thickness measured by optical coherence tomography, and
intraocular pressure. RESULTS: No statistically significant changes were observed
in best-corrected visual acuity. Central macular thickness showed statistical
differences between the 2 groups. Intraocular pressure showed a statistically
significant increase after the first day, at 1 month, and at 3 months in both
groups but no significant increase afterward. CONCLUSIONS: Intravitreal
triamcinolone administration may be useful for select cases of cystoid macular
edema in patients with retinitis pigmentosa but its efficacy seems to be limited 
over time. Therefore, to obtain a good anatomical result and an improvement of
best-corrected visual acuity, further treatment would be necessary after 6
months.

Publication Types: 
    Clinical Trial
    Comparative Study

PMID: 17562986 [PubMed - indexed for MEDLINE]

818: Graefes Arch Clin Exp Ophthalmol. 2007 Nov;245(11):1681-9. Epub 2007 Jun 12.

Retinal pigment epithelium and choroid translocation in patients with exudative
age-related macular degeneration: long-term results.

Maaijwee K, Heimann H, Missotten T, Mulder P, Joussen A, van Meurs J.

Department of Vitreoretinal Surgery, the Rotterdam Eye Hospital, Rotterdam, The
Netherlands. kmaaijwee@hotmail.com

BACKGROUND: To study the results of the translocation of a free autologous
retinal pigment epithelium (RPE)-choroid graft after removal of a subfoveal
choroidal neovascular membrane in patients with exudative age-related macular
degeneration (AMD), and to determine whether preoperative variables may predict
visual outcome at 1 year after surgery. METHODS: Prospective interventional case 
series of 84 eyes of 83 consecutive eligible patients with exudative AMD with a
minimal follow-up of 1 year after surgery. Of this group, 45, 24 and 11 patients 
reached a follow-up of respectively 2, 3 and 4 years. Pre- and postoperative
evaluation included ETDRS visual acuity (VA), fixation testing and color fundus
photography. Preoperative fluorescein angiograms were assessed by masked readers 
for lesion size, size of hemorrhage and lesion composition according to the MPS
criteria. The relationship between lesion composition adjusted for preoperative
delay and VA, lesion size, percentage of blood, and visual outcome at 1 year
after surgery was analyzed. RESULTS: The mean VA (logMAR) improved slightly at 1 
and 2 years (0.89, Delta = -0.06), 3 years (0.79, Delta = -0.16) and 4 years
(0.74, Delta = -0.21) after surgery. Five patients had a preoperative VA better
than 20/80, compared to 19 out of 84, six out of 45, four out of 24 and two out
of 11 after 1, 2, 3 and 4 years respectively. Fixation was located on the graft
in 62 patients (74%) up to the last examination. Predominantly classic and occult
lesions had a significant better prognosis than minimally classic or hemorrhagic 
(> or = 50% blood) lesions. Retinal detachment occurred in seven patients; two
caused by rhegmatogenous detachment and five caused by proliferative
vitreoretinopathy. In 11 eyes, a recurrent or persisting neovascular membrane was
observed. CONCLUSION: An autologous free RPE-choroid graft may stabilize or
improve vision in patients with exudative AMD up to 4 years after surgery.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17562066 [PubMed - indexed for MEDLINE]

819: Curr Med Res Opin. 2007 Jun;23(6):1253-8. Epub 2007 Apr 25.

The effect of intravitreal triamcinolone on intraocular pressure.

Kramar M, Vu L, Whitson JT, He YG.

Department of Ophthalmology, University of Texas Southwestern Medical Center at
Dallas, Dallas, TX 75390, USA.

OBJECTIVE: To evaluate the effect of triamcinolone acetonide (ITA) on intraocular
pressure (IOP) following intravitreal injection, and, in those patients who
experience post-injection elevation of IOP, to determine the time course, effect 
of multiple injections, and risk factors for the pressure rise. METHODS: A
retrospective chart review of 85 consecutive patients who received ITA (0.1 mL of
40 mg/mL solution) at the University of Texas South-western Medical Center
between January 2002 and April 2004 was performed. Patient age, history of
open-angle glaucoma (OAG), previous intraocular surgery, prior steroid exposure, 
type of retinal pathology treated, pre- and post-injection IOP, and
post-injection glaucoma medications were tabulated. Patients with previous
exposure to topical, intraocular or systemic steroids, and those without at least
16 weeks of follow-up were excluded. A student's paired t-test was used for
statistical analysis. RESULTS: Seventy-seven eyes of 70 patients were included.
Forty-eight eyes (62.3%) experienced an increase in IOP of at least 5 mmHg.
Twenty-five eyes (32.5%) experienced elevation in IOP of 5-9 mmHg, and 23 eyes
(29.9%) experienced an increase in IOP of > or = 10 mmHg during the review
period. The mean time for elevations of 5-9 mmHg and > or = 10 mmHg to occur
following injection were 6.9 weeks and 8.8 weeks, respectively. Fifty percent of 
eyes (3/6) in patients with OAG experienced a maximum IOP level of > 30 mmHg. Of 
all eyes with IOP elevation following injection, 32.5% required topical glaucoma 
therapy. Thirteen eyes received a second ITA injection. All eight eyes with IOP
elevation after the first injection experienced another rise in IOP after the
second. Of the five eyes which had no rise in IOP after the first injection, four
had no rise after the second. At the final visit, 50% of eyes (3/6) with OAG
required additional glaucoma medication compared to baseline. No patients
required surgery for IOP control during the period under review. CONCLUSIONS: ITA
is frequently associated with a significant elevation in IOP, typically within
the first 2-months after injection. Most patients who do not have an elevated IOP
after an initial injection will not experience a pressure rise after an
additional one. About one-third will require topical glaucoma therapy for IOP
control. Patients with OAG may be more difficult to control and require a longer 
duration of therapy. The inconsistent post-injection follow-up visit intervals
among patients in this retrospective review may have affected our results, as
some patients with maximum IOP changes may have been missed between office
visits. In addition, practice patterns among treating physicians typically differ
as to thresholds for the treatment of elevated IOP. A randomized, prospective,
controlled trial could better address these issues.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17559723 [PubMed - indexed for MEDLINE]

820: Ocul Immunol Inflamm. 2007 Mar-Apr;15(2):71-9.

Erratum in:
    Ocul Immunol Inflamm. 2007 Jul-Aug;15(4):369. Anthi, Koutsandrea [corrected to
Chrysanthi, Koutsandrea].

Course of macular edema in uveitis under medical treatment.

Markomichelakis NN, Halkiadakis I, Pantelia E, Georgalas E, Chrysanthi K,
Theodossiadis P, Moschos M, Theodossiadis G, Kouvatseas G.

Ocular Immunology and Inflammation Service, Department of Ophthalmology, General 
Hospital of Athens, Athens, Greece. marnik@otenet.gr

OBJECTIVE: To describe the response of uveitic macular edema to various treatment
methods using optical coherence tomography (OCT). METHODS: This is a prospective 
study of consecutive uveitis patients with macular edema in at least one eye. The
patients received medical treatment. Best corrected Snellen Visual Acuity (BCVA) 
and tomographic features of the macula, including macular thickness measurement, 
were obtained at one, three, six, and 12 months after commencing treatment.
RESULTS: Eighty-one eyes of 58 patients were analyzed. Complete resolution of
macular edema occurred in 38 eyes (47%). The average BCVA was 20/34 logarithm of 
minimum angle of resolution (-logMAR, 0.2 +/- 0.3) upon study entry and 20/27
(-logMAR, 0.13 +/- 0.29) upon study completion. The difference was statistically 
significant (p = 0.04). The corresponding mean retinal thickness at the central
fovea was 319 +/- 150 microm at the beginning of the study compared to 241 +/-
125 microm at 12 months (p < 0.001). A weak but statistically significant
correlation between the reduction of macular thickness and the improvement of
BCVA (r = 0.3, p = 0.01) was found. Thirteen of the 43 eyes (30%) with persistent
macular edema had a more than 15% reduction of macular thickness compared to
baseline, whereas 10 eyes (23, 3%) had a more than 15% increase in macular
thickness. Statistical analysis indicated that the presence of an epiretinal
membrane and an OCT pattern of diffuse macular edema was a significant factor
associated with medical treatment failure. CONCLUSION: This study demonstrates
the overall favorable visual prognosis of uveitic macular edema under medical
treatment. The presence of an epiretinal membrane is an important factor
associated with medical treatment failure.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17558831 [PubMed - indexed for MEDLINE]

821: Retina. 2007 Jun;27(5):621-8.

Evaluation of costs for cystoid macular edema among patients after cataract
surgery.

Schmier JK, Halpern MT, Covert DW, Matthews GP.

Exponent Inc., 1800 Diagonal Road, Alexandria, VA 22314, USA.
jschmier@exponent.com

PURPOSE: Little is known about the costs of cystoid macular edema (CME), an
important complication associated with cataract surgery. The purpose of this
analysis was to estimate the cost of treatment for CME in the United States.
METHODS: Data were analyzed from the 1997 through 2001 Medicare 5% Beneficiary
Encrypted Files. Beneficiaries who underwent cataract surgery were identified and
stratified by diagnosis of CME (cases) or no diagnosis of CME (controls) within 1
year after surgery. Claims and reimbursements for ophthalmic care were
identified. Subgroup analyses explored CME costs among beneficiaries with
diabetes versus those without diabetes. RESULTS: Of 139,759 beneficiaries with
cataract surgery, 1.95% (2,720) were diagnosed with CME. Annual total ophthalmic 
claims were 41% ($3,298) higher for cases than for controls; payments were 47%
($1,092) higher (both P < 0.0001). Approximately 16% (23,122) of cataract
patients had diabetes. The rate of CME diagnosis was significantly higher for
diabetics than for nondiabetics (3.05% vs. 1.73%, respectively). Differences in
claims and payments between cases and controls were similar for diabetic and
nondiabetic subgroups. CONCLUSION: CME is associated with substantial costs.
Therapies that prevent or decrease CME severity are likely to result in cost
savings, particularly among diabetic beneficiaries. Further analyses should
explore the relationship of comorbidities to costs among CME patients.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17558326 [PubMed - indexed for MEDLINE]

822: Retina. 2007 Jun;27(5):584-8.

Long-term visual outcomes after vitrectomy for macular edema with foveal
hemorrhage in branch retinal vein occlusion.

Kumagai K, Furukawa M, Ogino N, Larson E, Uemura A.

Shinjo Ophthalmologic Institute, 889 Mego, Shimoki-takata-cho, Miyazaki 880-0035,
Japan. kumagai3@f8.dion.ne.jp

PURPOSE: To determine the long-term visual outcomes after vitreous surgery for
macular edema with foveal hemorrhage associated with branch retinal vein
occlusion (BRVO). METHODS: One hundred twenty eyes of 120 patients underwent pars
plana vitrectomy with or without internal limiting membrane (ILM) peeling for
macular edema with foveal hemorrhage due to BRVO with a minimum 12 months of
follow-up. Simultaneous cataract extraction with intraocular lens implantation
was performed on 117 phakic eyes. RESULTS: Follow-up after surgery ranged from 12
months to 129 months (average, 48 months). Visual acuity improved in 71% of cases
at the 1-year visit. Mean visual acuity significantly increased from 0.24
(median, 0.3) before surgery to 0.57 (median, 0.7) 1 year after surgery (P <
0.0001) and 0.66 (median, 0.9) at the final visit (P < 0.0001). There was a
significant difference between visual acuity at 1 year after surgery and visual
acuity at the final visit (P < 0.0001). Of 120 patients, 95 (79%) had final
visual acuity of > or =0.5, and 55 (46%) had final visual acuity of > or =1.0.
ILM removal did not seem to have significant beneficial effects on visual
outcomes in this series. No serious complications occurred during the follow-up
period. CONCLUSION: After vitreous surgery for macular edema with foveal
hemorrhage associated with BRVO, visual acuity continued to improve beyond 1 year
after surgery. A randomized, multicenter clinical trial is warranted to determine
the efficacy of this procedure.

PMID: 17558320 [PubMed - indexed for MEDLINE]

823: Retina. 2007 Jun;27(5):557-66.

Long-term outcomes of pars plana vitrectomy with internal limiting membrane
removal in diabetic macular edema.

Yanyali A, Horozoglu F, Celik E, Nohutcu AF.

Department of Ophthalmology, Haydarpasa Numune Education and Research Hospital,
Caddebostan 81060, Istanbul, Turkey. ayanyali@hotmail.com

PURPOSE: To report the long-term visual results and anatomical outcome as
assessed by optical coherence tomography (OCT) after pars plana vitrectomy (PPV) 
with removal of the internal limiting membrane (ILM) in diabetic macular edema
(DME). METHODS: Medical records of 27 eyes of 27 patients who underwent PPV with 
ILM removal for DME attributable to diffuse leakage were reviewed. This
retrospective study included eyes that underwent PPV with ILM removal at our
institution with preoperative and postoperative OCT assessment of DME. None of
the eyes had OCT evidence of anteroposterior vitreomacular traction. Main outcome
measures were foveal thickness and visual acuity changes. RESULTS: Foveal
thickness decreased by at least 20% in 22 eyes (81.4%) and increased by at least 
20% in 3 eyes (11.1%) with PPV and ILM removal (mean follow-up +/- SD, 27.6 +/-
7.2 months; range, 12-38 months). Mean foveal thickness decrease +/- SD was 178
+/- 164 microm (43.6%), with a mean preoperative foveal thickness +/- SD of 408
+/- 121 microm compared with a mean postoperative foveal thickness +/- SD of 230 
+/- 74 microm (P < 0.001). Recurrence of DME was observed at postoperative month 
24 in 2 eyes and postoperative month 30 in 1 eye. Visual acuity improved by > or 
=2 lines in 10 eyes (37%) and decreased by > or =2 lines in 3 eyes (11.1%). Mean 
best-corrected logMAR (logarithm of the minimum angle of resolution) visual
acuity +/- SD was 0.75 +/- 0.35 preoperatively and 0.63 +/- 0.33 postoperatively 
(P = 0.033). CONCLUSION: PPV with ILM removal appears to be effective in reducing
DME and improving visual acuity, and its effectiveness is maintained in the long 
term. Recurrence of DME may be observed in the late postoperative period.

PMID: 17558316 [PubMed - indexed for MEDLINE]

824: Retina. 2007 Jun;27(5):541-51.

Retinal pigment epithelial tears after intravitreal bevacizumab injection for
neovascular age-related macular degeneration.

Chan CK, Meyer CH, Gross JG, Abraham P, Nuthi AS, Kokame GT, Lin SG, Rauser ME,
Kaiser PK.

Southern California Desert Retina Consultants, Palm Springs, CA 92263, USA.
Pschan@aol.com

PURPOSE: To study retinal pigment epithelium (RPE) tears after off-label
intravitreal bevacizumab (Avastin; Genentech, Inc., South San Francisco, CA)
injection for neovascular age-related macular degeneration. Eyes with a
vascularized pigment epithelial detachment (PED) that developed an RPE tear were 
compared with eyes with a vascularized PED but without an RPE tear. METHODS: Nine
retina specialists across the United States and in Europe participated in this
retrospective case series. All eyes that received intravitreal bevacizumab
injection for choroidal neovascularization (CNV) over 12 months (October 2005 to 
September 2006) were included. Eyes without all three confirmed tests
(fluorescein angiography, fundus photography, and optical coherence tomography)
were excluded from analysis. Statistical analyses were performed on multiple
characteristics of eyes with a vascularized PED that did and did not develop an
RPE tear. RESULTS: Among 2,785 intravitreal bevacizumab injections for 1,064
eyes, RPE tears were found in 22 eyes in 22 patients (2.2%). A vascularized PED
was present in 21 of 22 eyes that developed an RPE tear (17.1% of PED eyes; 15,
100% occult CNV; 6, predominantly occult CNV). Mean interval from bevacizumab
injections to RPE tears was 37.3 days. Mean follow-up time was 124.9 days. Mean
subfoveal PED size was larger for eyes with tears than for those without tears
(13.97 mm vs 9.9 mm, respectively; P = 0.01; odds ratio, 1.09). There was
substantially smaller mean ratio of CNV size to PED size for eyes with tears than
for those without tears (27.9% vs 67.6%, respectively; P = 0.005). Mean
pre-bevacizumab injection best-corrected Snellen visual acuity was 20/162, and
mean post-RPE tear best-corrected visual acuity was 20/160 (P = 0.48).
CONCLUSION: Large PED size is a predictor for RPE tears, and a small ratio of CNV
size to PED size (<50%) is more common in eyes with RPE tears. Vision may be
preserved despite RPE tears.

Publication Types: 
    Case Reports
    Multicenter Study

PMID: 17558314 [PubMed - indexed for MEDLINE]

825: Retina. 2007 Jun;27(5):535-40.

Retinal pigment epithelium tears after intravitreal injection of bevacizumab
(avastin) for neovascular age-related macular degeneration.

Ronan SM, Yoganathan P, Chien FY, Corcóstegui IA, Blumenkranz MS, Deramo VA,
Elner SG, Fastenberg DA, Johnson MW, López M, Mateo C, Moshfeghi DM, Navarro R,
Rosenblatt BJ, Sanislo SR, Saxe SJ, Zacks DN.

Kellogg Eye Center, Department of Ophthalmology and Visual Science, University of
Michigan, 1000 Wall Street, Ann Arbor, MI 48105, USA.

BACKGROUND: Intravitreal bevacizumab (Avastin, Genentech, Inc., South San
Francisco, CA) treatment of neovascular age-related macular degeneration (AMD)
has become an important part of clinical retinal practice. We describe retinal
pigment epithelium (RPE) tears that were noted after intravitreal injection of
bevacizumab. METHODS: In this multimember, retrospective case series, data on
eyes that developed RPE tears after intravitreal bevacizumab injection were
collected and analyzed. Previous treatments, type of lesion, time to tear, and
preinjection and final visual acuities were all compared. The total numbers of
bevacizumab injections were available from all four institutions and compiled to 
estimate the incidence rate. RESULTS: Four retina centers administered a total of
1,455 intravitreal 1.25-mg bevacizumab injections for neovascular AMD during the 
9-month study period. Twelve patients presented with RPE tears within 4 days to 8
weeks of injection (mean +/- SD, 24.3 +/- 15.2 days from injection to tear). In
each case, the RPE tear was preceded by an RPE detachment, and all had a
component of serous sub-RPE fluid. On the basis of our collective data, we
estimate an incidence rate of approximately 0.8%. CONCLUSIONS: RPE tears can
occur after intravitreal injection of bevacizumab. The low incidence of this
adverse event should not preclude anti-vascular endothelial growth factor therapy
counseling for patients with neovascular AMD, but eyes with serous RPE
detachments appear to be most vulnerable to this adverse event.

Publication Types: 
    Case Reports
    Multicenter Study

PMID: 17558313 [PubMed - indexed for MEDLINE]

826: BMC Ophthalmol. 2007 Jun 7;7:10.

Single-session photodynamic therapy combined with intravitreal bevacizumab and
triamcinolone for neovascular age-related macular degeneration.

Ahmadieh H, Taei R, Soheilian M, Riazi-Esfahani M, Karkhaneh R, Lashay A,
Azarmina M, Dehghan MH, Moradian S.

Ophthalmic Research Center, Shaheed Beheshti Medical University, Labbafinejad
Medical Center, Tehran, Iran. hahmadieh@hotmail.com

BACKGROUND: To evaluate the efficacy of triple therapy consisting of
single-session photodynamic therapy (PDT), intravitreal bevacizumab (IVB) and
intravitreal triamcinolone (IVT) as initial pulse therapy followed by repeat
intravitreal bevacizumab injections for maintenance treatment in neovascular
age-related macular degeneration (AMD). METHODS: In a prospective interventional 
case series, patients with subfoveal choroidal neovascularization (CNV) secondary
to AMD underwent pulse therapy with single-session PDT according to the standard 
protocol followed by 1.25 mg IVB and 2 mg IVT 48 hours later. Best corrected
visual acuity (BCVA) was assessed and optical coherence tomography (OCT) and
fluorescein angiography (FA) were performed prior to treatment. BCVA and OCT
measurements were repeated at 6 week intervals and FA was obtained after 12 weeks
and when necessary thereafter. Repeat injections of IVB were performed based on
fluorescein angiographic evidence of CNV leakage. RESULTS: This series included
17 eyes of 17 patients with mean age of 67.6 +/- 7.2 years. Mean follow up
duration was 50.4 +/- 15.5 weeks. Mean BCVA prior to treatment was 0.74 +/- 0.33 
logMAR which improved to 0.52 +/- 0.36 logMAR after 12 weeks (P = 0.012) and 0.41
+/- 0.38 logMAR after 24 weeks (P = 0.001). Mean pretreatment central macular
thickness (CMT) was 395 +/- 181 micro which was significantly reduced to 217 +/- 
69 micro (P = 0.005), 231 +/- 79 micro (P = 0.028) and 221 +/- 87 micro (P =
0.05) six, twelve and twenty-four weeks after initial treatment respectively.
Visual acuity improvement and CMT reduction was maintained during the follow-up
period. IVB injections were repeated once, twice and three times in 10, 7 and 2
eyes at a mean interval of 20.2 +/- 10.1, 19 +/- 13.7 and 15 +/- 1.4 weeks after 
initial therapy, respectively. CONCLUSION: Initial pulse triple therapy
consisting of single-session PDT combined with IVB and IVT improves vision and
reduces CMT in neovascular AMD. Repeat IVB injections maintain the visual gain
from the initial combination therapy.

Publication Types: 
    Clinical Trial

PMID: 17555600 [PubMed - indexed for MEDLINE]

827: Jpn J Ophthalmol. 2007 May-Jun;51(3):210-5. Epub 2007 Jun 7.

Photodynamic therapy for age-related macular degeneration in Japanese patients:
results after one year.

Ogino T, Takeda M, Imaizumi H, Okushiba U.

Department of Ophthalmology, Sapporo City General Hospital, Sapporo, Japan.
oginot@sapmed.ac.jp

PURPOSE: To evaluate the effects of photodynamic therapy (PDT) with verteporfin 1
year after treatment in Japanese patients with age-related macular degeneration
(AMD) and subfoveal choroidal neovascularization. METHODS: Between May 2004 and
March 2005, PDT was performed on 102 eyes of 98 patients (60 men and 38 women)
with AMD and subfoveal choroidal neovascularization. Patients were followed for
at least 12 months after PDT. RESULTS: The mean visual acuities in logarithm of
the minimum angle of resolution (logMAR) units were 0.978 at baseline, 0.919 at 3
months, 0.895 at 6 months, 0.892 at 9 months, and 0.874 at 12 months. After PDT, 
the logMAR visual acuity improved by >0.3 logMAR units or more in 28 eyes (27%)
and deteriorated by >0.3 logMAR units or more in 13 eyes (13%). Stable or
improved vision was achieved in 93% of patients with polypoidal choroidal
vasculopathy (PCV). CONCLUSIONS: The visual outcome in our patients was similar
to that of an earlier major Japanese study, and similar to or better than
outcomes in Western studies. Differences between Caucasians and Japanese might
influence the characteristics of PCV. It is possible that PDT is more effective
for AMD patients with PCV than for other AMD patients. Further observations and
longer follow-up are necessary. Copyright (c) Japanese Ophthalmological Society
2007.

PMID: 17554484 [PubMed - indexed for MEDLINE]

828: Jpn J Ophthalmol. 2007 May-Jun;51(3):204-9. Epub 2007 Jun 7.

Results of visual acuity and foveal thickness in diabetic macular edema after
vitrectomy.

Shimonagano Y, Makiuchi R, Miyazaki M, Doi N, Uemura A, Sakamoto T.

Department of Ophthalmology, Faculty of Medicine, Kagoshima University Graduate
School of Medicine and Dental Sciences, Kagoshima, Japan.

PURPOSE: To report results of an investigation of visual acuity (VA) and foveal
thickness in diabetic macular edema (DME) patients after vitrectomy. METHODS: A
retrospective study was performed of the records of 47 patients (61 eyes) who
received pars plana vitrectomy (PPV) for DME. All eyes were followed up for over 
6 months (mean, 24.8 months; range, 6-60 months). VA and foveal thickness
evaluated by optical coherence tomography were reviewed preoperatively and
postoperatively. RESULTS: Twenty-four-month follow-up data were available for 46 
of the 61 eyes (75%). VA at the final examination had improved by 0.2 log units
or more in 34 of the 61 eyes (56%), remained unchanged in 21 eyes (34%), and
worsened in six eyes (10%). Mean foveal thickness decreased by more than 20% of
the preoperative value in 50 of the 61 eyes (82%), remained unchanged in ten eyes
(16%), and increased by more than 20% in one eye (2%) at the final examination.
Postoperative best-corrected visual acuity (BCVA) at both 12 and 24 months was
significantly better than preoperative BCVA (P < 0.0001). Foveal thickness at 3
months or later significantly decreased from the preoperative value (P < 0.0001),
but remained unchanged in comparison with postoperative 12 months and 24 months
values (P = 0.19). Preoperative VA and presence of cystoid macular edema (CME)
were independently associated with final visual acuity (P = 0.001). CONCLUSIONS: 
PPV for DME effectively improved VA and reduced foveal thickness for a longer
postoperative period. Better preoperative VA was associated with better final
postoperative VA. The eyes without CME tended to have better final postoperative 
VA. Copyright (c) Japanese Ophthalmological Society 2007.

PMID: 17554483 [PubMed - indexed for MEDLINE]

829: Ophthalmic Surg Lasers Imaging. 2007 May-Jun;38(3):226-8.

Extrafoveal choroidal neovascularization secondary to wet age-related macular
degeneration treated with intravitreal bevacizumab.

Mones JM, Lopez MA, Prieto JA, Rodriguez JP.

Instituto de Microcirugía Ocular, Barcelona, Spain.

Considering the risk of recurrence of extrafoveal or juxtafoveal lesions after
thermal laser treatment and the risk of poor response to photodynamic therapy, it
seems reasonable to discuss with the patient the risks and benefits of
antiangiogenic therapy. A case of age-related macular degeneration with an
extrafoveal choroidal neovascularization treated with a single injection of
intravitreal bevacizumab is described. The patient showed both anatomic and
visual acuity improvement at 1 month following treatment that persisted even at
the 8-month follow-up visit. Further studies are needed to validate the real
risk-benefit ratio of intravitreal bevacizumab for extrafoveal exudative lesions 
versus the current treatments available.

Publication Types: 
    Case Reports

PMID: 17552389 [PubMed - indexed for MEDLINE]

830: Ophthalmic Surg Lasers Imaging. 2007 May-Jun;38(3):219-25.

The relationship between retrobulbar and choroidal hemodynamics in
non-neovascular age-related macular degeneration.

Rechtman E, Harris A, Siesky B, Kagemann L, Danis RP, Sines D, Ciulla TA.

Goldschleger Eye Institute, Tel-Hashomer, Israel.

BACKGROUND AND OBJECTIVE: To evaluate the relationship between retrobulbar and
choroidal hemodynamics in non-neovascular age-related macular degeneration.
PATIENTS AND METHODS: Thirteen patients with age-related macular degeneration
were assessed by both color Doppler imaging and scanning laser ophthalmoscope
indocyanine green (ICG) angiography. Color Doppler imaging was used to measure
peak systolic and end diastolic velocity (from which the resistance index, a
measure of the resistance to flow downstream, was calculated) in the retrobulbar 
vessels. Scanning laser ophthalmoscope ICG angiograms were analyzed by area
dilution analysis for quantitative choroidal fluorescence intensity assessment.
Color Doppler imaging parameters were correlated with scanning laser
ophthalmoscope ICG area dilution analysis parameters. RESULTS: A good correlation
was found between the posterior ciliary arteries resistance index and scanning
laser ophthalmoscope ICG area dilution analysis fluorescence duration.
CONCLUSIONS: Scanning laser ophthalmoscope ICG area dilution analysis "duration" 
may serve as an alternative to color Doppler imaging in assessing the resistance 
to blood flow in the posterior ciliary arteries.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17552388 [PubMed - indexed for MEDLINE]

831: J Exp Med. 2007 Jun 11;204(6):1245-8. Epub 2007 Jun 4.

Complement factor H and the hemolytic uremic syndrome.

Atkinson JP, Goodship TH.

Division of Rheumatology, Washington University School of Medicine, St. Louis, MO
63110, USA. jatkinso@im.wustl.edu

Immune recognition is coupled to powerful proinflammatory effector pathways that 
must be tightly regulated. The ancient alternative pathway of complement
activation is one such proinflammatory pathway. Genetic susceptibility factors
have been identified in both regulators and activating components of the
alternative pathway that are associated with thrombotic microangiopathies,
glomerulonephritides, and chronic conditions featuring debris deposition. These
observations indicate that excessive alternative pathway activation promotes
thrombosis in the microvasculature and tissue damage during debris accumulation. 
Intriguingly, distinct genetic changes in factor H (FH), a key regulator of the
alternative pathway, are associated with hemolytic uremic syndrome (HUS),
membranoproliferative glomerulonephritis (dense deposit disease), or age-related 
macular degeneration (AMD). A mouse model of HUS designed to mirror human
mutations in FH has now been developed, providing new understanding of the
molecular pathogenesis of complement-related endothelial disorders.

Publication Types: 
    Review

PMID: 17548524 [PubMed - indexed for MEDLINE]

832: Ophthalmology. 2007 Jun;114(6):1190-6.

Randomized trial of peribulbar triamcinolone acetonide with and without focal
photocoagulation for mild diabetic macular edema: a pilot study.

Diabetic Retinopathy Clinical Research Network, Chew E, Strauber S, Beck R,
Aiello LP, Antoszyk A, Bressler N, Browning D, Danis R, Fan J, Flaxel C, Friedman
S, Glassman A, Kollman C, Lazarus H.

OBJECTIVE: To provide pilot data on the safety and efficacy of anterior and
posterior sub-Tenon injections of triamcinolone either alone or in combination
with focal photocoagulation in the treatment of mild diabetic macular edema
(DME). DESIGN: Prospective, phase II, multicenter, randomized clinical trial.
PARTICIPANTS: One hundred nine patients (129 eyes) with mild DME and visual
acuity 20/40 or better. METHODS: The participants were assigned randomly to
receive either focal photocoagulation (n = 38), a 20-mg anterior sub-Tenon
injection of triamcinolone (n = 23), a 20-mg anterior sub-Tenon injection
followed by focal photocoagulation after 4 weeks (n = 25), a 40-mg posterior
sub-Tenon injection of triamcinolone (n = 21), or a 40-mg posterior sub-Tenon
injection followed by focal photocoagulation after 4 weeks (n = 22). Follow-up
visits were performed at 4, 8, 17, and 34 weeks. MAIN OUTCOME MEASURES: Change in
visual acuity and retinal thickness measured with optical coherence tomography
(OCT). RESULTS: At baseline, mean visual acuity in the study eyes was 20/25 and
mean OCT central subfield thickness was 328 mum. Changes in retinal thickening
and in visual acuity were not significantly different among the 5 groups at 34
weeks (P = 0.46 and P = 0.94, respectively). There was a suggestion of a greater 
proportion of eyes having a central subfield thickness less than 250 mum at 17
weeks when the peribulbar triamcinolone was combined with focal photocoagulation.
Elevated intraocular pressure and ptosis were adverse effects attributable to the
injections. CONCLUSIONS: In cases of DME with good visual acuity, peribulbar
triamcinolone, with or without focal photocoagulation, is unlikely to be of
substantial benefit. Based on these results, a phase III trial to evaluate the
benefit of these treatments for mild DME is not warranted.

Publication Types: 
    Clinical Trial, Phase II
    Multicenter Study
    Randomized Controlled Trial
    Research Support, N.I.H., Extramural

PMID: 17544778 [PubMed - indexed for MEDLINE]

833: Ophthalmology. 2007 Jun;114(6):1179-85.

Verteporfin therapy and intravitreal bevacizumab combined and alone in choroidal 
neovascularization due to age-related macular degeneration.

Lazic R, Gabric N.

Eye Clinic Svjetlost, Zagreb, Croatia. ratimir.lazic@svjetlost.hr

OBJECTIVE: To evaluate the efficacy and safety of photodynamic therapy (PDT) with
verteporfin combined with intravitreal bevacizumab in choroidal
neovascularization (CNV) owing to age-related macular degeneration (AMD) in
comparison with individual monotherapies used as controls. DESIGN: Randomized
controlled pilot clinical trial. PARTICIPANTS: Males or females, aged > or =50
years, with minimally classic or occult CNV owing to AMD in at least 1 eye that
had never been treated previously. METHODS: One hundred sixty-five eyes in 165
subjects (53 males, 112 females) aged between 60 and 87 years (mean [standard
deviation]: 75.7 [6.0] years) were randomly assigned to receive either a single
PDT session with verteporfin (PDT group; n = 55), or a single administration of
intravitreal bevacizumab (1.25 mg; BEV group; n = 55), or their combination (COMB
group; n = 55). In the COMB group, bevacizumab was administered within 1 hour of 
PDT. Subjects were followed up at 1 and 3 months after treatment. Ophthalmic
evaluations including optical coherence tomography, fluorescein angiography, and 
visual acuity (VA) and central foveal thickness (CFT) measurements were performed
at each visit. MAIN OUTCOME MEASURES: Changes from baseline in best-corrected VA 
and CFT measured at 1- and 3-month follow-up visits. RESULTS: One hundred
fifty-six subjects (54 BEV, 50 PDT, and 52 COMB) completed the study. At the
3-month follow-up, significant improvements in best-corrected VA were observed in
the BEV and COMB groups (0.079 and 0.223 logarithm of the minimum angle of
resolution [logMAR], respectively; P<0.0001 for both). In the PDT group, a slight
worsening was noted. Significant reductions of CFT were observed in the 3 groups 
(-34.0 microm [BEV], -59.6 microm [COMB], and -50.5 microm [PDT]; P<0.0001 for
all). At the 1-month follow-up, 46 subjects (16 BEV, 29 COMB, and 1 PDT) had an
improvement >0.2 logMAR in best-corrected VA; at 3-month follow-up, this
improvement persisted in 23 subjects (1 BEV, 22 COMB, and 0 PDT). CONCLUSIONS:
Significant improvements in best-corrected VA after 1 month and their maintenance
over a 3-month period were observed after verteporfin PDT combined with
intravitreal bevacizumab. These results should be confirmed in larger and
long-term prospective randomized trials.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial

PMID: 17544776 [PubMed - indexed for MEDLINE]

834: Ophthalmology. 2007 Jun;114(6):1164-9.

A case-control study of drug risk factors for age-related macular degeneration.

Douglas IJ, Cook C, Chakravarthy U, Hubbard R, Fletcher AE, Smeeth L.

Department of Epidemiology and Population Health, London School of Hygiene and
Tropical Medicine, London, United Kingdom.

OBJECTIVE: To investigate the association between age-related macular
degeneration (AMD) and exposure to antacids, antithyroids, thyroid hormones, and 
thiazide diuretics. DESIGN: Matched case-control study. PARTICIPANTS:
Population-based participants were selected from the United Kingdom General
Practice Research Database. A total of 18,007 people with diagnosed AMD were
compared with 86 169 controls matched for age, gender, and general practice.
METHODS: Conditional logistic regression was used to determine the association
between exposure to each drug group of interest and a diagnosis of AMD, adjusting
for relevant confounding variables. MAIN OUTCOME MEASURES: The primary outcome
was the odds ratio for the association between exposure to antacids,
antithyroids, thyroid hormones, or thiazide diuretics and AMD. Secondary analyses
were conducted to assess the effect of recent exposure to the drugs of interest, 
the total number of prescriptions received, and restricting the data set to
participants with more than 2 years of observation time. RESULTS: The crude odds 
ratios for association between any record of drug exposure and AMD were as
follows: 1.34 (95% confidence interval [CI], 1.29-1.39) for antacids; 1.15 (95%
CI, 0.92-1.44) for antithyroids; 1.34 (95% CI, 1.29-1.39) for thyroid hormones;
and 1.13 (95% CI, 1.08-1.17) for thiazide diuretics. After adjusting for
consultation rate, observation time, diabetes, heart failure, hyperlipidemia,
cardiovascular drug use, atherosclerosis, hypertension, aspirin use, hormone
replacement therapy use, body mass index, alcohol consumption, and smoking, the
odds ratios reduced to: 1.06 (95% CI, 1.02-1.10) for antacids, 0.98 (95% CI,
0.78-1.24) for antithyroids, 0.99 (95% CI, 0.92-1.06) for thyroid hormones, and
0.98 (95% CI, 0.94-1.02) for thiazides. Secondary analyses were consistent with
these findings for all 4 drug categories. CONCLUSIONS: No association was
detected between short- and medium-term use of antithyroids, thyroid hormones,
and thiazide diuretics and the risk of AMD. Short- and medium-term use of
antacids seems to be associated with a small increase in the risk of this
disease. However, this increased risk is likely the result of residual
confounding by smoking or uncontrolled confounding resulting from socioeconomic
status. No conclusions could be drawn regarding longer-term use of each drug
category.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17544775 [PubMed - indexed for MEDLINE]

835: Clin Experiment Ophthalmol. 2007 May-Jun;35(4):330-4.

Factors influencing poor visual outcome in patients treated with photodynamic
therapy for choroidal neovascularization secondary to age-related macular
degeneration.

Manku KK, Rotchford A, Whitaker J, Amoaku WM.

Queens Medical Centre, Nottingham, UK. ravkiran@optusnet.com.au

BACKGROUND: This study evaluated patients with choroidal neovascular membranes
secondary to age-related macular degeneration for factors that may predict the
visual outcome after photodynamic therapy. METHODS: A retrospective review of 172
eyes of 172 consecutive patients who received photodynamic therapy for
predominantly classic with and without occult, minimally classic and occult
choroidal neovascular membranes secondary to macular degeneration in private
practice from June 2000 to September 2004 was undertaken. All eyes had a baseline
vision of 6/12 to 6/60. Classification of lesion composition, retreatment and
follow up adhered to published photodynamic therapy guidelines. The primary
outcomes measured were effects of patient age, baseline visual acuity, lesion
composition and lesion size on final visual acuity and loss of less than 15
letters of logMAR at 12 months. RESULTS: All eyes were followed up for 12 months.
Baseline mean logMAR visual acuity was logMAR 0.64. Using multivariate logistic
regression, loss of logMAR vision at 12 months was independently associated with 
increasing age (P=0.004), better baseline vision (P=0.009) and increasing lesion 
size (P=0.035). However, there was no association with lesion composition
(P=0.16). At 12 months the loss of 15 letters or less was found in 101 (59.7%;
95% confidence interval: 51.0-66.2%) of all patients. CONCLUSIONS: This study
found no statistically significant association between lesion composition defined
on fluorescein angiography and loss of visual acuity compared with previous
studies. Factors associated with an increased rate of loss of 15 letters were
increasing age of the patient, increasing lesion size and better baseline logMAR 
vision.

PMID: 17539784 [PubMed - indexed for MEDLINE]

836: Clin Exp Optom. 2007 Jul;90(4):263-71.

Age-related maculopathy in the light of ischaemia.

Feigl B.

Institute of Health and Biomedical Innovation and School of Optometry, Queensland
University of Technology, Brisbane, Australia. b.feigl@qut.edu.au

This manuscript focuses on the pathogenesis of age-related maculopathy (ARM) and 
the documentation of new treatments in ARM. Ischaemia will be given special
consideration, as it is believed to play a central role in both early ARM and
late ARM or age-related macular degeneration (AMD). Reduced choroidal and retinal
blood flow causes ischaemia of Bruch's membrane, retinal pigment epithelium and
neuroretina in the early course of ARM. This is thought to be the primary trigger
of the condition. Chronic ischaemia upregulates vascular endothelial growth
factor (VEGF), which induces abnormal vessel growth in neovascular AMD. The role 
of ischaemia in neovascular AMD is supported by the evidence of effective new
treatments targeting VEGF.

Publication Types: 
    Review

PMID: 17535365 [PubMed - indexed for MEDLINE]

837: Eur J Ophthalmol. 2007 May-Jun;17(3):451-3.

Macular hole and intravitreal injection of triamcinolone acetonide for macular
edema due to central retinal vein occlusion.

Lattanzio R, Ramoni A, Scotti F, Introini U.

Department of Ophthalmology, San Raffaele Scientific Institute, Milano, Italy.
lattanzio.rosangela@hsr.it

PURPOSE: To report a case of macular hole progression after intravitreal
injection of triamcinolone acetonide (IVTA) for chronic macular edema secondary
to nonischemic central retinal vein occlusion (CRVO). METHODS: A 33-year-old
woman with massive macular edema after CRVO underwent IVTA. Optical coherence
tomography (OCT) and fluorescein angiography were performed before and after the 
procedure. RESULTS: At the 1-week IVTA injection control, the patient's
best-corrected visual acuity improved from 20/400 to 20/200 and OCT detected a
progression of macular hole stage. CONCLUSIONS: IVTA steroid injection may
provide a significant improvement in macular edema, but injection-related
complications may occur such as this uncommon macular reaction resulting in
permanent visual loss.

Publication Types: 
    Case Reports

PMID: 17534835 [PubMed - indexed for MEDLINE]

838: Prog Retin Eye Res. 2007 Sep;26(5):516-54. Epub 2007 Mar 6.

Transplantation of the RPE in AMD.

Binder S, Stanzel BV, Krebs I, Glittenberg C.

Department of Ophthalmology, Rudolf Foundation Clinic, Hospital of the City of
Vienna, Vienna, Austria. susanne.binder@wienkav.at

The retinal pigment epithelium (RPE) maintains retinal function as the metabolic 
gatekeeper between photoreceptors (PRs) and the choriocapillaries. The RPE and
Bruch's membrane (BM) suffer cumulative damage over lifetime, which is thought to
induce age-related macular degeneration (AMD) in susceptible individuals. Unlike 
palliative pharmacologic treatments, replacement of the RPE has a curative
potential for AMD. This article reviews mechanisms leading to RPE dysfunction in 
aging and AMD, laboratory studies on RPE transplantation, and surgical techniques
used in AMD patients. Future strategies using ex vivo steps prior to
transplantation, BM prosthetics, and stem cell applications are discussed. The
functional peculiarity of the macular region, epigenetic phenomena leading to an 
age-related shift in protein expression, along with the accumulation of
lipofuscin may affect the metabolism in the central RPE. Thickening of BM with
age decreases its hydraulic conductivity. Drusen are deposits of extracellular
material and formed in part by activation of the alternative complement pathway
in individuals carrying a mutant allele of complement factor H. AMD likely
represents an umbrella term for a disease entity with multifactorial etiology and
manifestations. Presently, a slow progressing (dry) non-neovascular atrophic form
and a rapidly blinding neovascular (wet) form are discerned. No therapy is
currently available for the former, while RPE transplantation and promising
(albeit non-causal) anti-angiogenic therapies are available for the latter. The
potential of RPE transplantation was demonstrated in animal models. Rejection of 
allogeneic homologous transplants in patients focused further studies on
autologous sources. In vitro studies elucidated cell adhesion and wound healing
mechanisms on aged human BM. Currently, autologous RPE, harvested from the
midperiphery, is being transplanted as a cell suspension or a patch of RPE and
choroid in AMD patients. These techniques have been evaluated from several
groups. Autologous RPE transplants may have the disadvantage of carrying the same
genetic information that may have led to AMD manifestation. An intermittent
culturing step would allow for in vitro therapy of the RPE, its rejuvenation and 
prosthesis of BM to improve the success RPE transplants. Recent advances in stem 
cell biology when combined with lessons learned from studies of RPE
transplantation are intriguing future therapeutic modalities for AMD patients.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17532250 [PubMed - indexed for MEDLINE]

839: J Cataract Refract Surg. 2007 Jun;33(6):1101-3.

Bilateral cystoid macular edema after phacoemulsification in post-laser in situ
keratomileusis eyes.

Chalioulias K, Tsaloumas M.

Sellyoak Hospital, Raddlebarn Road, Birmingham, West Midlands, United Kingdom.
k_chal@hotmail.com

We report a case of a 66-year-old man who had bilateral laser in situ
keratomileusis and 6 months later, uneventful simultaneous bilateral cataract
surgery. One week postoperatively, the visual acuity was reduced and 4 weeks
later, the patient was referred to our clinic with a macular hemorrhage in the
right eye and bilateral cystoid macular edema. He was treated with bilateral
sub-Tenon's triamcinolone, which had to be repeated in both eyes, and is still
being followed.

Publication Types: 
    Case Reports

PMID: 17531708 [PubMed - indexed for MEDLINE]

840: Ann Epidemiol. 2007 Aug;17(8):615-21. Epub 2007 May 25.

Modeling smoking history: a comparison of different approaches in the MARS study 
on age-related maculopathy.

Neuner B, Wellmann J, Dasch B, Behrens T, Claes B, Dietzel M, Pauleikhoff D,
Hense HW.

Institute of Epidemiology and Social Medicine, University of Muenster, Muenster, 
Germany. neuner@uni-muenster.de

PURPOSE: Smoking is an established risk factor for the development of age-related
maculopathy (ARM), and its end stage, age-related macular degeneration (AMD). We 
evaluated the benefit of various smoking-related variables in modeling the
association of smoking with ARM and AMD in a mixed sample of current, former, and
never smokers. METHODS: This was a cross-sectional study in participants of the
Muensteraner Altern- und Retina-Studie (MARS). Participants were classified
according to the Rotterdam classification system as healthy, or having ARM or
AMD. Using multinomial logistic regression techniques, the association with
number of cigarettes, years of smoking, pack-years and time since cessation in
former smokers were evaluated. RESULTS: Mean age of the 982 participants (58.6%
females) was 70.9 +/- 5.5 years. ARM was present in 483 (49.2%) and AMD in 285
(29.0%) individuals. The adjusted prevalence odds ratio (OR) in current smokers
versus never smokers was 2.61 (95% confidence interval [CI] 1.34-5.09) for ARM
and 3.94 (95% CI 1.91-8.14) for AMD. This effect decreased in former smokers with
an OR = 0.55 (95% CI 0.33-0.99) per log-transformed time since smoking cessation 
for ARM and an OR = 0.52 (95% CI 0.30-0.90) for AMD. CONCLUSIONS: By including a 
variable for time since smoking cessation, we were able to handle current,
former, and never smokers in one model that estimates the association of smoking 
with ARM or AMD. Logarithmical transformation of the time since smoking cessation
seemed to increase the model fit and to reflect a non-linear protective effect of
smoking cessation on the onset of ARM and AMD in former smokers.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17531503 [PubMed - indexed for MEDLINE]

841: Invest Ophthalmol Vis Sci. 2007 Jun;48(6):2831-6.

Effects of periocular administration of triamcinolone acetonide on
leukocyte-endothelium interactions in the ischemic retina.

Mizuno S, Nishiwaki A, Morita H, Miyake T, Ogura Y.

Department of Ophthalmology and Visual Sciences, Nagoya City University Graduate 
School of Medical Sciences, Nagoya, Japan. simon@pp24.so-net.ne.jp

PURPOSE: Recent studies have reported that intravitreal or posterior sub-Tenon's 
injection of triamcinolone acetonide (TA) is effective in the treatment of
macular edema resulting from retinal microcirculatory disturbances such as
diabetic retinopathy and retinal vein occlusion. The effects of periocular
administration of TA on leukocyte-endothelium interactions were studied after
transient retinal ischemia. METHODS: Transient retinal ischemia was induced by
temporary ligation of the optic nerve sheath for 60 minutes in male Long-Evans
rats. After the induction of ischemia, experimental eyes received a periocular
injection of TA (2 mg). In control animals, the same volume of saline was
administered. Leukocyte dynamics were evaluated in the retinal microcirculation
using acridine orange digital fluorography. Also, retinal thickness was studied
by using optical coherence tomography and a histologic METHOD: The retinal mRNA
expression of P-selectin and intercellular adhesion molecule (ICAM)-1 was
semiquantitatively studied with RT-PCR. RESULTS: The leukocytes rolling along
retinal vein linings increased after ischemia in the vehicle-treated rats (32.5
+/- 2.1 cells/min). No rolling leukocytes, however, were seen in the TA-treated
rats. The number of accumulated leukocytes was significantly lower in the
TA-treated rats (831 +/- 99 cells/mm2) than in the control (971 +/- 81 cells/mm2,
P < 0.05). The treatment decreased the retinal thickness and the mRNA expression 
of P-selectin and ICAM-1. CONCLUSIONS: The present study demonstrated that the
periocular injection of TA effectively decreased retinal thickness and inhibited 
leukocyte-endothelium interactions in the retina after ischemia. Downregulation
of adhesion molecules of retinal vascular endothelium induced by TA may play a
role in the course.

PMID: 17525219 [PubMed - indexed for MEDLINE]

842: Invest Ophthalmol Vis Sci. 2007 Jun;48(6):2806-13.

Evaluating retinal function in age-related maculopathy with the ERG photostress
test.

Binns AM, Margrain TH.

School of Optometry and Vision Sciences, Cardiff University, Cardiff, Wales,
United Kingdom. binnsAM@cf.ac.uk

PURPOSE: To evaluate the diagnostic potential of the electroretinogram (ERG)
photostress test and the focal cone ERG in age-related maculopathy (ARM).
METHODS: The cohort comprised 31 patients with ARM and 27 age-matched control
subjects. The ERG photostress test was used to monitor cone adaptation after
intense light adaptation. Focal 41- and 5-Hz cone ERGs were recorded monocularly 
(central 20 degrees) to assess steady state retinal function. Univariate analysis
identified electrophysiological parameters that differed between groups, and
receiver operating characteristic (ROC) curves were constructed to assess their
diagnostic potential. Logistic regression analysis determined the diagnostic
potential of a model incorporating several independent predictors of ARM.
RESULTS: The rate of recovery of the ERG photostress test was reduced (recovery
was slower) in subjects with ARM. The parameter exhibited good diagnostic
potential (P = 0.002, area under ROC curve = 0.74). The implicit times of the
5-Hz (a-wave, P = 0.002; b-wave, P < 0.001) and the 41-Hz (P < 0.001) focal cone 
ERGs were increased, and the 41-Hz focal cone ERG amplitude (P = 0.003) and focal
to full-field amplitude ratio (P = 0.001) were reduced in the ARM group. Logistic
regression analysis identified three independent predictors of ARM, including the
rate of recovery of the ERG photostress test. CONCLUSIONS: Early ARM has a marked
effect on the kinetics of cone adaptation. The clinical application of the ERG
photostress test increases the sensitivity and specificity of a model for the
diagnosis of ARM. Improved assessment of the functional integrity of the central 
retina will facilitate early diagnosis and evaluation of therapeutic
interventions.

PMID: 17525216 [PubMed - indexed for MEDLINE]

843: Invest Ophthalmol Vis Sci. 2007 Jun;48(6):2782-91.

Dendritic and synaptic plasticity of neurons in the human age-related macular
degeneration retina.

Sullivan RK, Woldemussie E, Pow DV.

School of Biomedical Sciences, University of Newcastle, Newcastle, NSW,
Australia.

PURPOSE: To determine whether structural plasticity is evident in human retinal
tissues in response to age-related macular degeneration (AMD). Remodeling events 
such as sprouting of neuronal processes and the reconnection of synapses are
essential elements in repairing any damage to adult nervous tissues such as might
occur in response to insults such as strokes or in AMD. METHODS: The anatomic
architecture of normal and AMD-affected human retinas was examined in the
central, midperipheral, and far-peripheral regions. The retina, by virtue of its 
well-organized laminar structure, allows the identification and analysis of
abnormal projections or connections of neuronal elements. RESULTS: In
AMD-afflicted retinas, but not in normal aged human retinas, a large number of
photoreceptor synapses across the entire retina retract into the outer nuclear
layer. This event evokes the subsequent outgrowth of dendrites from the
postsynaptic bipolar cells, again across the entire retina, and the subsequent
reformation of synaptic contacts between photoreceptor and bipolar cells.
CONCLUSIONS: These findings illustrate that there are anatomic changes in the AMD
retina at all eccentricities, not just in the macular region. Aged human retinal 
neurons have the capacity to form new synapses, and this finding may be important
when investigating possible means of repairing the damaged human retina.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17525213 [PubMed - indexed for MEDLINE]

844: Am J Ophthalmol. 2007 Jun;143(6):1026-9.

Alcohol consumption and the 15-year cumulative incidence of age-related macular
degeneration.

Knudtson MD, Klein R, Klein BE.

Department of Ophthalmology and Visual Sciences, University of Wisconsin School
of Medicine and Public Health, Madison, Wisconsin 53726, USA.
knudtson@epi.ophth.wisc.edu

PURPOSE: To investigate alcohol consumption as a risk factor for the 15-year
cumulative incidence and progression of age-related macular degeneration (AMD).
DESIGN: Prospective population-based study in Beaver Dam, WI with four
examinations at five-year intervals initiated in 1988 (n = 3,509 contributed data
for this analysis). METHODS: History of alcohol consumption was obtained via
questionnaire. Cumulative incidence of early AMD, exudative AMD, pure geographic 
atrophy, and progression of AMD were assessed from fundus photographs taken at
each examination. RESULTS: Heavy drinking (four or more drinks daily) at baseline
was related to the 15-year cumulative incidence of pure geographic atrophy in men
(odds ratio, 9.2; 95% confidence interval, 1.7 to 51.2). There were no consistent
associations with the amount of beer, wine, or liquor consumption and the
incidence or progression of AMD. CONCLUSIONS: Alcohol consumption is unlikely to 
strongly increase (or decrease) the risk of AMD.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 17524768 [PubMed - indexed for MEDLINE]

845: Drugs. 2007;67(8):1199-206; discussion 1207-9.

Ranibizumab.

Blick SK, Keating GM, Wagstaff AJ.

Wolters Kluwer Health/Adis, Auckland, New Zealand. demail@adis.co.nz

Ranibizumab is the antigen-binding fragment of a recombinant, humanised
monoclonal antibody, which binds with high affinity to, and inhibits the activity
of, all active forms of vascular endothelial growth factor A, an important
mediator in the development of choroidal neovascularisation. Well designed, phase
III trials in patients with neovascular (wet) age-related macular degeneration
(AMD) indicated that monthly intravitreal injections of ranibizumab 0.3 or 0.5 mg
for up to 2 years maintained or improved visual acuity to a greater extent than
sham injection, verteporfin photodynamic therapy or sham photodynamic therapy. In
patients with predominantly classic wet AMD who received ranibizumab in
combination with verteporfin therapy, preliminary results indicate that
combination therapy is superior to that of verteporfin therapy alone. Most
serious ocular adverse events, which were uncommon, were associated with either
the injection procedure or ranibizumab.

Publication Types: 
    Review

PMID: 17521219 [PubMed - indexed for MEDLINE]

846: J Exp Med. 2007 Jun 11;204(6):1249-56. Epub 2007 May 21.

Spontaneous hemolytic uremic syndrome triggered by complement factor H lacking
surface recognition domains.

Pickering MC, de Jorge EG, Martinez-Barricarte R, Recalde S, Garcia-Layana A,
Rose KL, Moss J, Walport MJ, Cook HT, de Córdoba SR, Botto M.

Molecular Genetics and Rheumatology Section, Faculty of Medicine, Imperial
College, London W12 0NN, England, UK. matthew.pickering@imperial.ac.uk

Factor H (FH) is an abundant serum glycoprotein that regulates the alternative
pathway of complement-preventing uncontrolled plasma C3 activation and
nonspecific damage to host tissues. Age-related macular degeneration (AMD),
atypical hemolytic uremic syndrome (aHUS), and membranoproliferative
glomerulonephritis type II (MPGN2) are associated with polymorphisms or mutations
in the FH gene (Cfh), suggesting the existence of a genotype-phenotype
relationship. Although AMD and MPGN2 share pathological similarities with the
accumulation of complement-containing debris within the eye and kidney,
respectively, aHUS is characterized by renal endothelial injury. This
pathological distinction was reflected in our Cfh association analysis, which
demonstrated that although AMD and MPGN2 share a Cfh at-risk haplotype, the
haplotype for aHUS was unique. FH-deficient mice have uncontrolled plasma C3
activation and spontaneously develop MPGN2 but not aHUS. We show that these mice,
transgenically expressing a mouse FH protein functionally equivalent to
aHUS-associated human FH mutants, regulate C3 activation in plasma and
spontaneously develop aHUS but not MPGN2. These animals represent the first model
of aHUS and provide in vivo evidence that effective plasma C3 regulation and the 
defective control of complement activation on renal endothelium are the critical 
events in the molecular pathogenesis of FH-associated aHUS.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17517971 [PubMed - indexed for MEDLINE]

847: Prog Retin Eye Res. 2007 Jul;26(4):437-51. Epub 2007 Mar 27.

Management of neovascular age-related macular degeneration.

Schmidt-Erfurth UM, Pruente C.

Department of Ophthalmology, Medical University of Vienna, Waehringer Guertel
18-20, A 1090 Vienna, Austria. ursula.schmidt-erfurth@meduniwien.ac.at

Neovascular age-related macular degeneration (AMD) is becoming an increasing
socio-medical problem as the proportion of the aged population is continuously
increasing. However, new insights in the pathogenesis of the disease offer the
opportunity to develop targeted therapies that attack the disease process more
successfully than ever. This review article will focus on summarizing the actual 
options in the management of neovascular AMD and provide a short overview about
recent therapeutic options in clinical and preclinical evaluation. The recent
development of anti-VEGF substances for use in clinical routine has markedly
improved the prognosis of patients with neovascular AMD. Intravitreal treatment
with substances targeting all isotypes of vascular endothelial growth factor
(VEGF), for the first time in the history of AMD treatments, results in a
significant increase in visual acuity in patients with neovascular AMD. Overall, 
anti-angiogenic approaches provide vision maintenance in over 90% and substantial
improvement in 25-40% of patients. The combination with occlusive therapies like 
photodynamic therapy (PDT) potentially offers a reduction of re-treatment
frequency and long-term maintenance of the treatment benefit. Further
developments interacting with various steps in the angiogenic cascade are under
clinical or preclinical evaluation and may soon become available. Nevertheless,
the growing number of novel therapeutic options will have to provide proof of
concept in randomized controlled clinical trials, a major challenge in view of
the rapidly evolving field. For those therapies, which are already in clinical
use, reasonable diagnostic tools for follow-up need to be developed, as the
burden of continuous clinical monitoring of all patients and all indications is
significant for patients and doctors. Ultimately, economic issues will be the
limiting factor for the clinical availability of different treatment options.

Publication Types: 
    Review

PMID: 17512238 [PubMed - indexed for MEDLINE]

848: Acta Ophthalmol Scand. 2007 Aug;85(5):526-33. Epub 2007 May 18.

Treatment of choroidal neovascularization using intravitreal bevacizumab.

Pedersen R, Soliman W, Lund-Andersen H, Larsen M.

Department of Ophthalmology, Glostrup Hospital, University of Copenhagen,
Glostrup, Denmark.

PURPOSE: This study aimed to assess the pharmacodynamic profile of intravitreal
bevacizumab in relation to best corrected visual acuity (BCVA), foveal thickness,
and other aspects of macular morphology after intravitreal injection of
bevacizumab in eyes with subretinal choroidal neovascularization (CNV). METHODS: 
A retrospective observational, uncontrolled case series including 26 eyes in 25
patients followed for up to 6 months after intravitreal injection of bevacizumab 
1 mg repeated as deemed necessary after monthly assessments by biomicroscopy,
optical coherence tomography, colour fundus photography, fluorescein angiography 
and BCVA determination. At follow-up, cases were classified by morphological
treatment response (reduction or elimination of pathological neovascular leakage,
retinal thickening or serous retinal detachment) or absence of response
(deterioration or lack of improvement). Primary disease entities included
age-related macular degeneration (22 eyes, four of which had evidence of retinal 
angiomatous proliferation), idiopathic peripapillary neovascularization (one
eye), and angioid streaks (three eyes in two patients). RESULTS: One month after 
the first injection, apparent morphological improvement was observed in 24/26
eyes and mean BCVA had improved by 3.1 +/- 7.8 letters (p = 0.05). Of these 24
responders, which included all primary diagnoses, 11 (46%) demonstrated BCVA
improvement of >or= 5 letters. The two non-responders (7.7%) had lost > 3 lines
of vision at 2 months follow-up. Overall, 18 eyes completed 6 months follow-up,
with a mean BCVA improvement of 0.5 +/- 12.7 letters, and 22 eyes completed 3
months follow-up, with a mean BCVA improvement of 2.0 +/- 11.0 letters. Two
months after the first injection, 11 (46%) of the 24 responders demonstrated
signs of recurrent CNV activity, defined as decreased BCVA and/or increased
retinal thickness and/or fluorescein angiographic CNV leakage. No serious
drug-related adverse events were observed during the course of the study.
CONCLUSIONS: Overall mean BCVA remained stable throughout the study.
Morphological signs of reduced CNV activity were seen in the majority of eyes at 
2-4 weeks after intravitreal bevacizumab injection. Half the responders showed
signs of renewed CNV activity at 2 months after their first injection. All
first-injection responders were also second-injection responders.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17511757 [PubMed - indexed for MEDLINE]

849: Ophthalmology. 2007 Sep;114(9):1702-12. Epub 2007 May 23.

Pegaptanib 1-year systemic safety results from a safety-pharmacokinetic trial in 
patients with neovascular age-related macular degeneration.

Macugen AMD Study Group, Apte RS, Modi M, Masonson H, Patel M, Whitfield L,
Adamis AP.

Department of Ophthalmology and Visual Sciences, Washington University in St.
Louis School of Medicine, St. Louis, Missouri 63110, USA.

OBJECTIVE: To characterize the safety, tolerability, and pharmacokinetics of the 
pegylated anti-vascular endothelial growth factor (VEGF) aptamer pegaptanib
sodium in subfoveal choroidal neovascularization secondary to age-related macular
degeneration (AMD). DESIGN: Prospective 2-cohort study: (1) open-label cohort and
(2) randomized, double-masked, uncontrolled multicenter trial. PARTICIPANTS: In
the combined cohorts, 147 subjects with any angiographic subtype of subfoveal
choroidal neovascularization secondary to AMD and best-corrected visual acuities 
(VAs) in the study eye of 20/40 to 20/320 and in the fellow eye of 20/800 or
better received pegaptanib sodium. INTERVENTION: Subjects were randomized to
receive intravitreous pegaptanib sodium (1 mg or 3 mg [3- and 10-fold higher than
the 0.3-mg approved dose]) every 6 weeks for 54 weeks. MAIN OUTCOME MEASURES:
Safety assessments included blood chemistries, urinalyses, vital signs,
electrocardiograms, serum antipegaptanib antibody assays, adverse events, VAs,
and intraocular pressures. After the first, fourth, and eighth injections, serial
blood samples were obtained for quantification of pegaptanib plasma
concentrations. RESULTS: No antipegaptanib immunoglobulin G (IgG) or IgM
antibodies were detected. Few systemic adverse events were noted. Mild or
moderate ocular adverse events related to the injection procedure were reported
in most patients. Pegaptanib did not accumulate in plasma after multiple doses;
systemic exposures were similar after the first, fourth, and eighth doses. The
mean apparent terminal half-life was 10 days. Evaluation of blood pressure (BP)
and urine protein, both of which are known to be affected by systemic VEGF
inhibition, indicated no evidence of a pegaptanib treatment effect on these
parameters. Mean BP at the end of year 1 remained below 140 mmHg (systolic) and
90 mmHg (diastolic), levels considered hypertension by the American College of
Cardiology. CONCLUSIONS: At doses up to 10-fold higher than the 0.3-mg dose
approved for the treatment of AMD, pegaptanib sodium was well tolerated, with no 
detectable clinical evidence of systemic VEGF inhibition (i.e., no clinically
meaningful changes in proteinuria or mean BP) and no clinically relevant ocular
inflammation. Most ocular adverse events were related to the injection procedure 
itself and were mild or moderate in severity.

Publication Types: 
    Clinical Trial, Phase III
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17509689 [PubMed - indexed for MEDLINE]

850: Am J Ophthalmol. 2007 Jul;144(1):15-22. Epub 2007 May 23.

Clinical characteristics of exudative age-related macular degeneration in
Japanese patients.

Maruko I, Iida T, Saito M, Nagayama D, Saito K.

Department of Ophthalmology, Fukushima Medical University School of Medicine,
Fukushima, Japan.

PURPOSE: To clarify the clinical characteristics of exudative age-related macular
degeneration (AMD) in Japanese patients. DESIGN: Retrospective, observational,
consecutive case series. METHODS: Two hundred and eighty-nine patients with
neovascular AMD were examined. RESULTS: The authors classified the patients into 
three subtypes of neovascular AMD: polypoidal choroidal vasculopathy (PCV),
retinal angiomatous proliferation (RAP), and typical AMD. One hundred and
fifty-eight patients (54.7%) were diagnosed with PCV and 102 patients (35.3%)
with typical AMD. RAP was observed in 13 patients (4.5%). In 16 patients (5.5%), 
one eye had PCV and the other eye had typical AMD. Most patients with PCV and
typical AMD had unilateral disease (81.6% and 94.1%, respectively) with a male
preponderance (77.8% and 71.6%, respectively). Nine of 13 patients with RAP were 
female (69.2%). Patients with RAP were older (mean, 80.3 years for men and 75.3
years for women) than patients with other subtypes. Serous and hemorrhagic
pigment epithelial detachment developed in 69 patients (43.7%) with PCV, 22
patients (21.6%) with typical AMD, and nine patients (69.2%) with RAP. In the
patients with unilateral disease in each subtype, large drusen in the unaffected 
eye were seen in 24.0% with PCV, 30.2% with typical AMD, and 77.8% with RAP.
CONCLUSIONS: Neovascular AMD in Japanese patients has different demographic
features compared with that in White patients. In Japanese patients, there is a
preponderance of PCV, male gender, unilaterality, and absence of drusen in the
second eye, with the exception of RAP.

PMID: 17509509 [PubMed - indexed for MEDLINE]

851: Am J Ophthalmol. 2007 Jul;144(1):37-44. Epub 2007 May 23.

Optical coherence tomography reader agreement in neovascular age-related macular 
degeneration.

Zhang N, Hoffmeyer GC, Young ES, Burns RE, Winter KP, Stinnett SS, Toth CA, Jaffe
GJ.

Duke University Eye Center and the OCT Reading Center at Duke, Duke University
Medical Center, Durham, North Carolina 27710, USA.

PURPOSE: To determine the interreader and intrareader agreement at the Optical
Coherence Tomography (OCT) Reading Center at Duke for images produced for an
interventional neovascular age-related macular degeneration (AMD) clinical trial.
DESIGN: Retrospective, observational case series. METHODS: OCT was performed
using the Stratus OCT Fast Macular Thickness Map (Carl Zeiss Meditec, Dublin,
California, USA) scan mode and a 7-mm line scan centered on the fovea.
Experienced OCT readers, certified to grade scans according to a standardized
protocol, independently determined whether a scan was gradable. If gradable, each
of the scans was graded for multiple morphologic characteristics. In addition,
retinal thickness, subretinal fluid thickness, and choroidal neovascularization
(CNV) thickness at the fovea were measured for each gradable scan. Interreader
agreement was determined among three reader pairs. Readers regraded a subset of
scans and intrareader agreement was determined. RESULTS: The interreader
agreement was high for scan gradability and scan grades among three reader pairs,
ranging from 84% to 100% and from 84% to 96%, respectively. Similarly, the
intrareader agreement for scan gradability and scan grade, including comparison
of adjudicated scan grades with readjudicated scan grades, was high and ranged
from 91% to 100% and from 79% to 98%, respectively, except for scan grades of
retinal pigment epithelium atrophy, when CNV was present. Highly reproducible
results also were found for quantitative thickness measurements. CONCLUSIONS:
Well-trained OCT readers can grade independently, with a high level of
interreader and intrareader agreement, multiple morphologic parameters of OCT
scans obtained from eyes with neovascular AMD. Reproducible Stratus OCT scan data
will be valuable to monitor treatment efficacy in interventional clinical trials 
of neovascular AMD.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 17509508 [PubMed - indexed for MEDLINE]

852: Int Ophthalmol. 2007 Oct;27(5):313-9. Epub 2007 May 16.

Hemodynamic response to intravitreal triamcinolone in eyes with macular edema:
intravitreal triamcinolone and ocular blood flow.

Cekiç O, Bardak Y, Tiğ SU, Demirkol A, Ekim MM, Altintaş O, Yeşildağ A, Oyar O.

Department of Ophthalmology, Süleyman Demirel University Medical School, Isparta,
Turkey. ocekic@hotmail.com

PURPOSE: To assess ocular hemodynamic response to intravitreal triamcinolone in
patients with macular edema due to diabetes or retinal vein occlusion. METHODS:
Forty-three patients that were injected by intravitreal triamcinolone acetonide
(0.1 cc 4 mg) for unilateral macular edema due to diabetes mellitus (n = 17) and 
occlusion of retinal vein (n = 26) underwent ocular hemodynamic evaluation by
color Doppler imaging (CDI) before and one, two and three months after injection.
Non-injected fellow eyes as well as 16 healthy volunteers were also evaluated.
RESULTS: In patients with diabetic macular edema, there was no hemodynamic
difference between eyes to be injected and non-injected at baseline (P > 0.23).
Compared to controls, a significant difference existed in the ophthalmic artery
resistant index (P = 0.001) and end-diastolic velocity (P < 0.001) in diabetics. 
At one month, compared to fellow eyes, change in end diastolic velocity from
baseline in treated eyes was significantly decreased in posterior ciliary
arteries (0.68 +/- 0.34 cm/s [mean +/- SEM] vs. -1.04 +/- 0.81 cm/s, P = 0.012). 
Throughout the study period, no significant alteration from baseline in the
resistant index of any artery was noted in treated diabetic eyes (P > 0.05). In
eyes with retinal vein occlusion, baseline CDI evaluation demonstrated reduced
posterior ciliary arteries systolic flow velocity compared to fellow and control 
eyes (13.24 +/- 1.04 cm/s, 16.37 +/- 0.76 cm/s and 14.33 +/- 1.41 cm/s,
respectively, P = 0.007). Increased peak systolic velocity in the posterior
ciliary arteries at one week (P = 0.02), one month (P = 0.005) and two months (P 
= 0.04), and increase in central retinal artery resistant index at one month was 
noted (P = 0.05). CONCLUSION: Intravitreal triamcinolone temporarily changed
central retinal artery blood flow and posterior ciliary arteries' peak systolic
blood velocity in eyes with retinal vein occlusion whilst no response of blood
flow to triamcinolone injection but only transiently altered end diastolic blood 
velocity in posterior ciliary arteries was observed in diabetic eyes.

PMID: 17505781 [PubMed - indexed for MEDLINE]

853: Ophthalmic Res. 2007;39(3):139-42. Epub 2007 May 15.

Vascular endothelial growth factor and basic fibroblast growth factor in
exudative age-related macular degeneration and diffuse diabetic macular edema.

Jonas JB, Neumaier M.

Department of Ophthalmology, Faculty of Clinical Medicine Mannheim, University of
Heidelberg, Mannheim, Germany.

BACKGROUND: To evaluate the concentrations of vascular endothelial growth factor 
(VEGF) and basic fibroblast growth factor (bFGF) in neovascular or edematous
retinal diseases. METHODS: In the clinical comparative interventional study, VEGF
and bFGF concentrations in aqueous humor samples of 35 patients with exudative
age-related macular degeneration (AMD), 21 patients with diabetic macular edema
and 24 patients of a control group were measured using a solid-phase
chemiluminescence immunoassay. RESULTS: Concentrations of VEGF and bFGF,
respectively, were significantly higher in the diabetic group (184.7 +/- 107.0
and 5.0 +/- 10.2 pg/l) than in the AMD group (107.7 +/- 73.0 pg/l, p = 0.002; 2.2
+/- 7.4 pg/l, p = 0.002) and the control group (71.5 +/- 94.7 pg/l, p = 0.001;
0.00 pg/l, p = 0.001). The two latter groups did not vary significantly (p =
0.10). CONCLUSIONS: VEGF and bFGF are present in considerably higher
concentrations in eyes with diabetic macular edema than in eyes with exudative
AMD or normal eyes. The differences were more marked for VEGF than for bFGF.

Publication Types: 
    Clinical Trial

PMID: 17505145 [PubMed - indexed for MEDLINE]

854: Br J Ophthalmol. 2007 Dec;91(12):1644-9. Epub 2007 May 15.

Comment in:
    Br J Ophthalmol. 2007 Dec;91(12):1575-6.

Association between integrity of foveal photoreceptor layer and visual acuity in 
branch retinal vein occlusion.

Ota M, Tsujikawa A, Murakami T, Kita M, Miyamoto K, Sakamoto A, Yamaike N,
Yoshimura N.

Department of Ophthalmology, Kyoto University Graduate School of Medicine,
Sakyo-ku, Kyoto 606-8507, Japan.

AIM: To study the correlation between integrity of the photoreceptor layer after 
resolution of macular oedema (MO) associated with branch retinal vein occlusion
(BRVO) and final visual acuity (VA), and to determine prognostic factors for
visual outcome. METHODS: We retrospectively studied 46 eyes from 46 patients with
resolved MO secondary to BRVO, the foveal thickness of which was less than 250
microm at final observation. We assessed the status of the third high reflectance
band (HRB) in the fovea using optical coherence tomography (OCT) at final
observation, and studied OCT images taken at the initial visit in the hope of
identifying a factor that would be prognostic of visual outcome. RESULTS: No
differences were found in initial VA or in foveal thickness between eyes with or 
without complete third HRB at final observation. However, final VA in eyes
without a complete HRB was significantly poorer (p<0.002). Additionally, initial 
status of the third HRB in the parafoveal area of unaffected retina was
associated with final VA; lack of visualisation of the third HRB at 500 microm (p
= 0.0104) or 1000 microm (p = 0.0167) from the fovea on initial OCT images was
associated with poor visual recovery after resolution of the MO. CONCLUSION:
Integrity of the photoreceptor layer in the fovea is associated with VA in
resolved MO, and status of the third HRB before treatment might be predictive of 
visual outcome.

PMID: 17504858 [PubMed - indexed for MEDLINE]

855: Br J Ophthalmol. 2007 Nov;91(11):1499-503. Epub 2007 May 15.

Microperimetry and fundus autofluorescence in patients with early age-related
macular degeneration.

Midena E, Vujosevic S, Convento E, Manfre' A, Cavarzeran F, Pilotto E.

Department of Ophthalmology, University of Padova, Via Giustiani 2, 35128 Padova,
Italy. edoardo.midena@unipd.it

BACKGROUND: Early age-related macular degeneration (AMD) has been correlated with
different functional alterations, but the exact relationship between fundus
lesions and overlying sensitivity is not well known. The aim of this study was to
compare fundus-related sensitivity (microperimetry) and fundus autofluorescence
(FAF) of the macular area with drusen and pigment abnormalities in early AMD.
METHODS: 13 consecutive patients with early AMD and visual acuity of 20/20 were
studied by means of microperimetry, which automatically analyses macular light
differential threshold and fixation patterns. Fundus colour photo and FAF of the 
macular area were recorded on the same day. Microperimetry was exactly
(topographically) superimposed over FAF images. RESULTS: Macular sensitivity
significantly decreased over large drusen (11.2 +/- 5.6 dB, p<0.0001) and over
pigment abnormalities (13.1 +/- 3.6 dB, p<0.0001). When both characteristics were
present the reduction was greater if compared with its absence (9.6 +/- 4.3
versus 15.0 +/- 4.5 dB, p<0.0001). Sensitivitity reduction was significant in
areas with altered FAF when compared with areas with normal FAF (p<0.0001).
CONCLUSIONS: Increased FAF in early AMD has a functional correlate exactly
quantified by microperimetry. In retinal areas affected by early AMD retinal
sensitivity deteriorates, despite good visual acuity. Microperimetry may allow
the early detection of functional impairment caused by these lesions. Both
microperimetry and FAF may be useful to monitor AMD progression.

PMID: 17504849 [PubMed - indexed for MEDLINE]

856: Br J Ophthalmol. 2007 Oct;91(10):1303-7. Epub 2007 May 15.

Burden of illness, visual impairment and health resource utilisation of patients 
with neovascular age-related macular degeneration: results from the UK cohort of 
a five-country cross-sectional study.

Lotery A, Xu X, Zlatava G, Loftus J.

University of Southampton, Southampton Eye Unit, Southampton General Hospital,
Tremona Road, Southampton SO16 6YD, UK. a.j.lotery@soton.ac.uk

BACKGROUND/AIMS: Quantitative data regarding the impact of neovascular
age-related macular degeneration (NV-AMD) on individuals and society is a
prerequisite for rational decision-making processes when evaluating alternative
treatments for the disease. METHODS: 75 bilateral NV-AMD (patients) and 91
elderly non-AMD (controls) subjects forming the UK cohort of an international
cross-sectional, observational study were independently analysed. Subjects
completed a telephone survey including the National Eye Institute Visual Function
Questionnaire (NEI-VFQ-25), the EuroQol (EQ-5D), the Hospital Anxiety and
Depression Scale (HADS), history of falls and health resource utilisation.
RESULTS: Patients with NV-AMD reported substantially worse vision-related
functioning and overall well-being, including higher depression scores, than
controls after adjusting for age, gender and co-morbidities (adjusted mean
scores: NEI-VFQ-25 overall 52.7 vs 90.7, p<0.0001; EQ-5D 0.67 vs 0.77, p =
0.0273; HADS depression 6.8 vs 4.0, p = 0.0026). Significantly more patients
reported a need for assistance with daily activities compared with controls
(25.3% vs 6.6%, p = 0.003). Total annual healthcare utilisation costs were more
than sevenfold higher for patients with AMD compared with controls ( pound
3,823.89 vs pound 517.05, respectively; p<0.0001) CONCLUSIONS: Patients with
NV-AMD show a significant decline in quality of life and increased need for daily
living assistance compared to a control population without AMD. With the
availability of effective new therapies there is a need for improved early access
to treatment.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17504847 [PubMed - indexed for MEDLINE]

857: Arch Ophthalmol. 2007 May;125(5):671-9.

The relationship of dietary lipid intake and age-related macular degeneration in 
a case-control study: AREDS Report No. 20.

SanGiovanni JP, Chew EY, Clemons TE, Davis MD, Ferris FL 3rd, Gensler GR, Kurinij
N, Lindblad AS, Milton RC, Seddon JM, Sperduto RD; Age-Related Eye Disease Study 
Research Group.

AREDS Coordinating Center, The EMMES Corporation, 401 N. Washington Street,
Rockville, MD 20850, USA. aredspub@emmes.com

OBJECTIVE: To evaluate the association of lipid intake with baseline severity of 
age-related macular degeneration (AMD) in the Age-Related Eye Disease Study
(AREDS). METHODS: Age-Related Eye Disease Study participants aged 60 to 80 years 
at enrollment (N = 4519) provided estimates of habitual nutrient intake through a
self-administered semiquantitative food frequency questionnaire. Stereoscopic
color fundus photographs were used to categorize participants into 4 AMD severity
groups and a control group (participants with <15 small drusen). RESULTS: Dietary
total omega-3 long-chain polyunsaturated fatty acid (LCPUFA) intake was inversely
associated with neovascular (NV) AMD (odds ratio [OR], 0.61; 95% confidence
interval [CI], 0.41-0.90), as was docosahexaenoic acid, a retinal omega-3 LCPUFA 
(OR, 0.54; 95% CI, 0.36-0.80), comparing highest vs lowest quintile of intake,
after adjustment for total energy intake and covariates. Higher fish consumption,
both total and broiled/baked, was also inversely associated with NV AMD (OR,
0.61; 95% CI, 0.37-1.00 and OR, 0.65; 95% CI, 0.45-0.93, respectively). Dietary
arachidonic acid was directly associated with NV AMD prevalence (OR, 1.54; 95%
CI, 1.04-2.29). No statistically significant relationships existed for the other 
lipids or AMD groups. CONCLUSION: Higher intake of omega-3 LCPUFAs and fish was
associated with decreased likelihood of having NV AMD.

Publication Types: 
    Multicenter Study
    Research Support, N.I.H., Extramural

PMID: 17502507 [PubMed - indexed for MEDLINE]

858: Arch Ophthalmol. 2007 May;125(5):661-9.

Association between vitamin D and age-related macular degeneration in the Third
National Health and Nutrition Examination Survey, 1988 through 1994.

Parekh N, Chappell RJ, Millen AE, Albert DM, Mares JA.

The Cancer Institute of New Jersey, University of Medicine and Dentistry of New
Jersey, New Brunswick, NJ, USA.

OBJECTIVE: To evaluate the associations between levels of vitamin D
(25-hydroxyvitamin D) in serum and prevalent age-related macular degeneration
(AMD). METHODS AND DESIGN: Cross-sectional associations of serum vitamin D and
early and advanced AMD, assessed from nonmydriatic fundus photographs, were
evaluated in the third National Health and Nutrition Examination Survey, a
multistage nationally representative probability sample of noninstitutionalized
individuals (N = 7752; 11% with AMD). RESULTS: Levels of serum vitamin D were
inversely associated with early AMD but not advanced AMD. The odds ratio (OR) and
95% confidence interval (CI) for early AMD among participants in the highest vs
lowest quintile of serum vitamin D was 0.64 (95% CI, 0.5-0.8; P trend <.001).
Exploratory analyses were conducted to evaluate associations with important food 
and supplemental sources of vitamin D. Milk intake was inversely associated with 
early AMD (OR, 0.75; 95% CI, 0.6-0.9). Fish intake was inversely associated with 
advanced AMD (OR, 0.41; 95% CI, 0.2-0.9). Consistent use vs nonuse of vitamin D
from supplements was inversely associated with early AMD only in individuals who 
did not consume milk daily (early AMD: OR, 0.67; 95% CI, 0.5-0.9). CONCLUSION:
This study provides evidence that vitamin D may protect against AMD. Additional
studies are needed to confirm these findings.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17502506 [PubMed - indexed for MEDLINE]

859: Arch Ophthalmol. 2007 May;125(5):641-5.

Human retinal pigment epithelium cell changes and expression of
alphaB-crystallin: a biomarker for retinal pigment epithelium cell change in
age-related macular degeneration.

De S, Rabin DM, Salero E, Lederman PL, Temple S, Stern JH.

Center for Neuropharmacology and Neuroscience and Department of Ophthalmology,
Albany Medical College, 42 New Scotland Avenue, Albany, NY 12208, USA.

OBJECTIVE: To examine changes in the retinal pigment epithelium (RPE) in eyes
with age-related macular degeneration (AMD) and specifically to characterize
alphaB-crystallin expression in RPE cells as a biomarker in this disease.
METHODS: Maculae from human patients diagnosed as having AMD or from age-matched 
control eyes were isolated, cryosectioned, and analyzed immunohistochemically for
alphaB-crystallin and for cell type-specific markers. RESULTS: In eyes with dry
and wet AMD, alphaB-crystallin was heterogeneously expressed by a subpopulation
of RPE cells in the macular region (frequently in cells adjacent to drusen) and
in areas of RPE hypertrophy associated with wet AMD. In contrast,
alphaB-crystallin was not detected at significant levels in control RPE.
CONCLUSION: Accompanying the formation of drusen in early-stage and late-stage
AMD, RPE cells undergo change to express alphaB-crystallin. CLINICAL RELEVANCE:
The detection of alphaB-crystallin in the RPE of patients with early and advanced
AMD implicates this as an AMD biomarker. Sporadic expression of alphaB-crystallin
by RPE cells localized adjacent to drusen in early AMD indicates that changes in 
the gene expression of RPE cells accompany early stages of the disease and
introduces novel potential targets for AMD therapy.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17502503 [PubMed - indexed for MEDLINE]

860: Arch Ophthalmol. 2007 May;125(5):624-7.

Effect of eccentric and inconsistent fixation on retinal optical coherence
tomography measures.

Campbell RJ, Coupland SG, Buhrmann RR, Kertes PJ.

Department of Ophthalmology, Queen's University, Hotel Dieu Hospital, 166 Brock
Street, Kingston, Ontario, Canada. rob.campbell@queensu.ca

OBJECTIVE: To assess the relative stabilities of optical coherence tomography
(OCT)-based retinal volume and central foveal thickness measurements in the
setting of eccentric or inconsistent fixation. METHODS: Ten healthy right eyes
underwent multiple macular OCT centered at fixation. To model the effect of
eccentric or inconsistent fixation, OCT was repeated with scan centers precisely 
shifted by 0.50, 1.00, and 1.50 mm in each of 4 directions. At each scan
location, retinal volumes within a series of radii of the scan center, as well as
central foveal thickness, were calculated. The main outcome measure was the
percentage effect of decentered scanning on each OCT-based variable. RESULTS:
Central foveal thickness was the variable most affected in this model of
eccentric and inconsistent fixation. This variable demonstrated changes from
baseline-centered scans of up to 69.4%. Retinal volumes within a radii of the
scan center measuring 1.11 mm or greater were least affected by decentered
scanning, demonstrating maximum changes from baseline-centered scans of only
15.7% (P<.001 vs foveal thickness). CONCLUSION: Optical coherence
tomography-based retinal volume quantification provides a more stable measure
than foveal thickness in the setting of eccentric or inconsistent fixation as may
occur in the setting of macular pathologic conditions.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17502500 [PubMed - indexed for MEDLINE]

861: Arch Ophthalmol. 2007 May;125(5):619-23.

Optimal optical coherence tomography-based measures in the diagnosis of
clinically significant macular edema: retinal volume vs foveal thickness.

Campbell RJ, Coupland SG, Buhrmann RR, Kertes PJ.

Department of Ophthalmology, Queen's University, Hotel Dieu Hospital, 166 Brock
Street, Kingston, Ontario, Canada. rob.campbell@queensu.ca

OBJECTIVE: To compare optical coherence tomography-based measures of retinal
thickness and volume as quantitative tests for clinically significant macular
edema (CSME). DESIGN: Diagnostic validation study. METHODS: Sixty-five eyes with 
diabetic retinopathy underwent stereo photographic and optical coherence
tomographic examination. Stereo photographs were examined in a masked fashion to 
determine the presence or absence of CSME according to criteria from the Early
Treatment Diabetic Retinopathy Study. Optical coherence tomography-based
measurements of central foveal thickness as well as retinal volumes within a
series of radii of fixation were generated. The main outcome measures were areas 
under receiver operating characteristic curves. Likelihood ratios, sensitivities,
and specificities for the diagnosis of CSME were also evaluated. RESULTS: Retinal
volumes within radii of 0.50 mm and 1.11 mm of fixation and central foveal
thickness were the best variables for discriminating between those with and
without CSME as evidenced by analysis of receiver operating characteristic
curves. There were no significant differences among these 3 variables in their
performance as diagnostic tests for CSME. CONCLUSIONS: Optical coherence
tomography-based retinal volume and central foveal thickness variables display
comparable abilities to discriminate between those with and without CSME. Both
measures may have clinical applications as quantitative diagnostic tests for
CSME.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Validation Studies

PMID: 17502499 [PubMed - indexed for MEDLINE]

862: J Diabetes Complications. 2007 May-Jun;21(3):172-80.

Diabetic macular edema and its relationship to renal microangiopathy: a sample of
Type I diabetes mellitus patients in a 15-year follow-up study.

Romero P, Baget M, Mendez I, Fernández J, Salvat M, Martinez I.

Servicio de Oftalmología, Institut Català de la Retina, Departamento de Medicina 
y Cirugía, Hospital Universitario Sant Joan de Reus, Universidad Rovira y
Virgili, Spain. promero@grupsagessa.com

PURPOSE: In the present study, our objective was to determine the epidemiological
risk factors for the development of diabetic macular edema, especially attendant 
on renal diabetic lesion (microalbuminuria or overt nephropathy) in 112 Type I
diabetic patients after 15 years. METHODS: This is a 15-year follow-up study of a
cohort of 112 consecutive Type I (insulin-dependent) diabetes mellitus patients
without diabetic retinopathy or nephropathy who were enrolled in 1990. We studied
the incidence of diabetic macular edema and its risk factors. The epidemiological
risk factors included in the study were as follows: gender, diabetes duration,
glycated hemoglobin (HbA1c) levels, arterial hypertension, macroangiopathy,
triglyceride levels, fractions of cholesterol [high-density lipoprotein
cholesterol and low-density lipoprotein (LDL) cholesterol], and cigarette
smoking. RESULTS: The incidence of diabetic macular edema after 15 years was as
follows: the focal form of diabetic macular edema was present in 13 (11.6%)
patients and the diffuse form of macular edema was present in 10 (8.9%) patients,
among 23 (20.5%) patients. The following factors were significant in the
development of diabetic macular edema: high levels of LDL-cholesterol (P=.013),
high levels (>7.5%) of HbA1c (P=.021), the presence of macroangiopathy (P=.022), 
the severity of diabetic retinopathy (P=.029), the presence of arterial
hypertension (P=.037), and the presence of overt nephropathy (P=.047).
Microalbuminuria was not significant in logistic regression (P=.587), and
cigarette smoking was not significant (P=.976). The relationship between diabetic
macular edema and duration of diabetes presented two peaks of incidence: first in
patients with 15-20 years' duration of diabetes mellitus, and second in patients 
with >35 years' duration. CONCLUSIONS: In summary, our data suggest that better
control of glycemia, LDL-cholesterol levels, and blood pressure in Type I
diabetes mellitus patients may be beneficial in reducing the incidence of
diabetic macular edema. Finally, our data validate the current guidelines for
ophthalmologic care for the detection of diabetic macular edema over the
long-term course of diabetes.

PMID: 17493551 [PubMed - indexed for MEDLINE]

863: J Am Geriatr Soc. 2007 May;55(5):740-6.

Bone mineral density and age-related maculopathy in older women.

Seitzman RL, Mangione CM, Cauley JA, Ensrud KE, Stone KL, Cummings SR, Hochberg
MC, Hillier TA, Yu F, Coleman AL; Study of Osteoporotic Fractures Research Group.

Department of Ophthalmology, Jules Stein Eye Institute, David Geffen School of
Medicine, University of California at Los Angeles, Los Angeles, California 90095,
USA. seitzman@ucla.edu

OBJECTIVES: To determine whether bone mineral density (BMD) is associated with
age-related maculopathy (ARM) risk in older women. DESIGN: Cross-sectional
analysis at Year 10 (1997/98) of the Study of Osteoporotic Fractures (SOF).
SETTING: Four clinical centers in the United States. PARTICIPANTS: One thousand
forty-two randomly sampled SOF participants who attended the Year 10 clinic
visit. MEASUREMENTS: ARM status was determined from fundus photographs using a
modification of the Wisconsin Age-Related Maculopathy Grading System 6-level
severity scale used in the National Health and Nutrition Examination Survey III. 
Total hip BMD was measured at Year 10 using dual-energy x-ray absorptiometry.
Information on potential confounders, including age, reproductive hormone
exposures, body mass index, smoking, alcohol consumption, nutrition, education,
diabetes mellitus, hypertension, and physical activity, was ascertained with
questionnaires. RESULTS: The prevalence of ARM was 50% (46% had early ARM and 4% 
had late ARM). After potential confounder adjustment, greater BMD was associated 
with lower odds of ARM (odds ratio (OR) per 1 standard deviation increase in
BMD=0.82, 95% confidence interval (CI)=0.70-0.96). Women in the highest quartile 
of BMD had lower odds of ARM than those in the lowest quartile (OR=0.63, 95%
CI=0.41-0.97) and those in the lowest three quartiles combined (OR=0.66, 95%
CI=0.48-0.91). CONCLUSION: Higher levels of BMD may be associated with lower risk
for ARM. The underlying mechanism is unknown, although BMD may be a marker for
lifetime endogenous estrogen exposure. Future studies are needed to replicate
these findings and further investigate the nature of the relationship between BMD
and ARM.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17493194 [PubMed - indexed for MEDLINE]

864: Aust Fam Physician. 2007 May;36(5):359-61.

Comment in:
    Aust Fam Physician. 2007 Oct;36(10):791.    Aust Fam Physician. 2007 Sep;36(9):680.

Age related macular degeneration - new developments in treatment.

Smith TC, Lee L.

City Eye Centre, Brisbane, Queensland, Australia. tsmith@med.usyd.edu.au

BACKGROUND: Age related macular degeneration (AMD) is a common condition seen in 
general practice. Over the past few years, new understanding of the condition has
seen the rapid development of increasingly effective treatments. OBJECTIVE: This 
article discusses the pathogenesis of AMD and how this relates to the most up to 
date treatments for the disease. It aims to provide general practitioners with
timely information regarding these significant advances, which may assist in the 
management of patients with AMD. DISCUSSION: Increasingly, AMD sufferers
independently source information about the latest treatments. Consequently GPs
are likely to hear more questions from their patients regarding treatment
options. Antivascular endothelial growth factor drugs show exciting potential for
an often debilitating condition. However, early referral and treatment is vital
to successful outcomes and GPs can play an essential role in this process. As
well, they can serve to provide ongoing information and counselling to their
patients with AMD.

Publication Types: 
    Review

PMID: 17492074 [PubMed - indexed for MEDLINE]

865: Eye. 2008 Jun;22(6):768-76. Epub 2007 May 11.

Age-related macular degeneration: a perspective on genetic studies.

Patel N, Adewoyin T, Chong NV.

Laser and Retinal Research Unit, Kings College Hospital, London, UK.

AIM: Age-related macular degeneration (AMD) is a common macular disease in the
developed world and recent studies have shown that specific genes may be
associated with it and may contribute to a higher risk of developing AMD.
OBJECTIVE: Our objective was to review systematically recent publications related
to the genetics of AMD and provide relevant information that would help both
scientists and clinicians in advising patients. METHOD: A systematic search was
performed on PubMed, Medline, and National Library of Medicine as well as ARVO
abstracts using key words relevant to the genetic associations of AMD. RESULTS:
The most important genetic associations in AMD involved the complement factor H
(CFH) gene, which showed that possession of the variant Y402H polymorphism
significantly increases the risk for AMD. Protective genes have also been
identified such as those on either factor B (BFor complement factor B (CFB)) or
complement component 2 (C2) genes. The genes involved in inherited macular
dystrophies such as ATP-binding cassette, subfamily A (ABC1), member 4 (ABCA4),
vitelliform macular dystrophy (VMD2), tissue inhibitor of matrix
metalloproteinase-3 (TIMP3), and EFEMP1have yielded some important information
but further confirmatory work has yet to establish a clear association with AMD. 
CONCLUSION: Patients with AMD possess specific genetic variants of the CFHgene,
which put them at a higher risk of developing the disease. Other unaffected
individuals may possess certain protective genetic variants, which could prevent 
them from developing AMD. Further research will no doubt shed light on other such
mechanisms and these will be useful in identifying possible direct targets for
drugs or indirectly through modulation of the genes responsible for disease
presentation.

Publication Types: 
    Review

PMID: 17491602 [PubMed - indexed for MEDLINE]

866: Postgrad Med J. 2007 May;83(979):301-7.

Age-related macular degeneration and recent developments: new hope for old eyes?

Morris B, Imrie F, Armbrecht AM, Dhillon B.

Princess Alexandra Eye Pavilion,Edinburgh, UK. bridcmorris@yahoo.com

Age-related macular degeneration (AMD) is the commonest cause of blindness in the
population over 60 years of age and accounts for over 50% of those registered
blind in the UK. The incidence is increasing and as older generations live longer
a growing number of patients will be affected in the future. Affected patients
lose central vision, important in all aspects of everyday life. This review
outlines risk factors for AMD, clinical features, treatment and management
strategies for patients, families and physicians caring for those with AMD.
Recent trials are included along with practical clinical advice. While there is
no curative treatment at present, intervention can reduce the risk of developing 
AMD and limit disease progression if it occurs. These modalities are discussed
here. As new discoveries in the field of genetics and novel therapies emerge, a
brighter future seems certain for the ageing population.

Publication Types: 
    Review

PMID: 17488857 [PubMed - indexed for MEDLINE]

867: Ind Health. 2007 Apr;45(2):371-3.

Macular degeneration in an arc welder.

Kim EA, Kim BG, Yi CH, Kim IG, Chae CH, Kang SK.

Occupational Safety and Health Research Institute, Korea Occupational Safety and 
Health Agency, Incheon, Korea.

A male welder who had been working in an industrial machine plant for more than
20 years experienced acute intense pain in his left eye with continuous
lacrimation while performing arc welding in 1997. Later in 1997, at the age of 39
yr, macular edema was found in his left eye. He was diagnosed with macular
degeneration (MD) of the left eye in 2002, and with right eye MD in 2004.
Radiation in the visible and near infrared (IR) spectra penetrates the eye and is
absorbed by the retina, possibly causing thermal or photochemical damage. Such
retinal damage may be permanent and, therefore, sight-threatening. The young age 
and history of an acute painful eye injury are not consistent with age related
macular degeneration (AMD) but rather is likely maculopathy caused by welding arc
exposure.

Publication Types: 
    Case Reports

PMID: 17485886 [PubMed - indexed for MEDLINE]

868: Mil Med. 2007 Apr;172(4):405-10.

Evaluation of digital fundus images as a diagnostic method for surveillance of
diabetic retinopathy.

Chun DW, Bauer RM, Ward TP, Dick JS 2nd, Bower KS.

Ophthalmology Service, Walter Reed Army Medical Center, Washington, DC 20307,
USA.

OBJECTIVE: The goal was to evaluate a digital imaging system for diagnosing and
grading diabetic retinopathy (DR) and cystoid macular edema (CME). METHODS: A
single 45 degrees, nonmydriatic, digital color photograph was taken of 231 eyes
of 120 patients with diabetes mellitus. The images were graded for DR and CME by 
a remote ophthalmologist, and the results were compared with dilated
ophthalmoscopy performed by a retina specialist. RESULTS: For DR, the level of
agreement between digital image review and ophthalmoscopy was moderate (kappa =
0.44). The sensitivity and specificity of digital image review were 0.60 and
1.00, respectively. For CME, the level of agreement was moderate (kappa = 0.60). 
The sensitivity and specificity of digital image review were 0.60 and 0.99,
respectively. CONCLUSION: A single 45 degrees, nonmydriatic, digital image is not
reliable as the sole modality for DR screening. However, with modifications, it
may be useful where access to an experienced ophthalmologist is limited.

Publication Types: 
    Evaluation Studies
    Research Support, U.S. Gov't, Non-P.H.S.

PMID: 17484313 [PubMed - indexed for MEDLINE]

869: Ann Acad Med Singapore. 2007 Apr;36(4):293-7.

Pars plana vitrectomy and internal limiting membrane peeling for macular oedema
secondary to retinal vein occlusion: a pilot study.

Liang XL, Chen HY, Huang YS, Au Eong KG, Yu SS, Liu X, Yan H.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen
University, Guangzhou, China. Liangxlsums@yahoo.com.cn

INTRODUCTION: Macular oedema is the main cause of visual impairment following
retinal vein occlusion. The purpose of this study was to evaluate the anatomical 
and functional outcome of pars plana vitrectomy and internal limited membrane
(ILM) peeling for macular oedema secondary to retinal vein occlusion. CLINICAL
PICTURE: This pilot study is a prospective nonrandomised series of 11 eyes of 11 
patients with macular oedema secondary to retinal vein occlusion. The
best-corrected visual acuity (BCVA), foveal thickness on optical coherence
tomography, fundus fluorescein angiography (FFA) and multifocal
electroretinography were evaluated. TREATMENT AND OUTCOME: All 11 patients
underwent pars plana vitrectomy with ILM peeling. The mean postoperative
follow-up was 13.5 months (range, 1.5 to 24). The mean thickness at the foveal
centre decreased from 794 +/- 276 microm preoperatively to 373 +/- 150 microm,
302 +/- 119 microm, 249 +/- 203 microm and 185 +/- 66 microm at 1 week, 1 month, 
3 months and the final visit postoperatively, respectively (all P <0.001, paired 
t- test, compared to preoperative thickness). Postoperative FFA demonstrated
markedly reduced leakage in the macular region. At the final visit, BCVA improved
2 lines or more in 72.7% (8/11) of patients and was unchanged in 27.3% (3/11)
patients. Complications included cataract in 7 patients and vitreous haemorrhage,
recurrence of macular oedema and visual field defect in 1 case each. CONCLUSION: 
Pars plana vitrectomy and ILM peeling rapidly reduced the macular oedema caused
by retinal vein occlusion, with improvement in BCVA.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17483861 [PubMed - indexed for MEDLINE]

870: Optometry. 2007 May;78(5):213-9.

LAST II: Differential temporal responses of macular pigment optical density in
patients with atrophic age-related macular degeneration to dietary
supplementation with xanthophylls.

Richer S, Devenport J, Lang JC.

Department of Veterans Affairs, Medical Center Eye Clinic, North Chicago,
Illinois 60064-3095, USA. Stuart.Richer1@va.gov

BACKGROUND: Age-related macular degeneration (ARMD) is the leading cause of
vision loss in aging Western societies. The objective of the Lutein Antioxidant
Supplementation Trial (LAST) was to determine whether specific dietary
interventions increased macular pigment optical density (MPOD) and visual
function in patients with atrophic ARMD. The current objective of LAST II is to
discern those specific characteristics that increase MPOD, i.e., that might
differentiate a responder from a nonresponder. METHODS: The LAST study was a
prospective, 12-month, randomized, double-masked, placebo-controlled trial
conducted at an urban midwestern Veterans Administation Hospital from August 1999
to May 2001. Ninety patients with atrophic ARMD entered the study and were
assigned randomly to 1 of 3 groups. Patients in group 1 received 10 mg lutein; in
group 2, 10 mg lutein in combination with vitamins, minerals, and antioxidants;
and in group 3, maltodextrin placebo. Changes in macular MPOD over time were
evaluated. Characteristics potentially influencing MPOD included age, weight
(body mass index), initial baseline values of macular pigment, and combining
xanthophylls with other nutrients. RESULTS: MPOD increased with supplementation
and declined slightly without supplementation (regression slopes not equal to
zero in supplemented groups, P < 0.02). The highest increases in MPOD over time
occurred in patients with lower baseline values of MPOD. Statistically
significant increases in MPOD density were observed in the lutein group for
patients with baseline MPOD <or=0.3 optical density units and up to 0.2 optical
density units in the lutein plus antioxidant group. Further analysis found that
none of the subjects' eyes in the lowest quartile of baseline MPOD were in the
lowest quartile for change in MPOD. CONCLUSION: Noteworthy is the observation
that those individuals with lowest MPOD, and in greatest need of supplementation,
were also most likely to benefit from either the lutein or the lutein plus
antioxidant supplementation. For those individuals who responded to
supplementation, their macular pigment optical density had not ceased to increase
at 12 months' duration of supplementation. The inference is that if a deficiency 
in macular pigment optical density is accurately diagnosed, effective
interventions should be able to re-establish this prophylactic barrier.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, Non-P.H.S.

PMID: 17478338 [PubMed - indexed for MEDLINE]

871: Exp Eye Res. 2007 Jul;85(1):34-43. Epub 2007 Mar 19.

Enhanced accumulation of A2E in individuals homozygous or heterozygous for
mutations in BEST1 (VMD2).

Bakall B, Radu RA, Stanton JB, Burke JM, McKay BS, Wadelius C, Mullins RF, Stone 
EM, Travis GH, Marmorstein AD.

Department of Ophthalmology and Vision Science, University of Arizona, Tucson, AZ
85724, USA.

Best vitelliform macular dystrophy (BMD) is an autosomal dominant inherited
macular degenerative disease caused by mutations in the gene BEST1 (formerly
VMD2). Prior reports indicate that BMD is characterized histopathologically by
accumulation of lipofuscin in the retinal pigment epithelium (RPE). However, this
accumulation has not been quantified and the chemical composition of lipofuscin
in BMD has not been examined. In this study we characterize the histopathology of
a donor eye from a rare individual homozygous for a mutation (W93C) in BEST1. We 
find that this individual's disease was not any more severe than has been
described for heterozygotes. We then used this tissue to quantify lipofuscin
accumulation by enriching intracellular granules from RPE cells on sucrose
gradients and counting the granules in each density fraction. Granules from the
homozygous donor eye as well as a donor eye from an individual heterozygous for
the mutation T6R were compared with age-matched control eyes. Interestingly, the 
least dense fraction, representing classical lipofuscin granules was either not
present or significantly diminished in the BMD donor eyes and the
autoflourescence associated with lipofuscin had shifted to denser fractions.
However, a substantial enrichment for granules in fractions of higher density was
also noted in the BMD samples. Inspection of granules from the homozygous donor
eye by electron microscopy revealed a complex abnormal multilobular structure.
Analysis of granules by HPLC indicated a approximately 1.6- and approximately
fourfold overall increase in A2E in the BMD eyes versus age-matched control eyes,
with a shift of A2E to more dense granules in the BMD donor eyes. Despite the
increase in A2E and total intracellular granules, the RPE in the homozygous donor
eyes was relatively well preserved. Based on these data we conclude that the
clinical and histopathologic consequences to the homozygous donor were not any
more severe than has been reported previously for individuals who are established
or presumptive heterozygotes. We find that A2E is a component of the lipofuscin
accumulated in BMD and that it is more abundant than in control eyes suggesting
that the etiology of BMD is similar to Stargardt's disease and Stargardt-like
macular dystrophy. Finally, the changes we observe in the granules suggest that
the histopathology and eventual vision loss associated with BMD may be due to
defects in the ability of the RPE to fully degrade phagocytosed photoreceptor
outer segments.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17477921 [PubMed - indexed for MEDLINE]

872: Br J Ophthalmol. 2007 Sep;91(9):1177-82. Epub 2007 May 2.

Pegaptanib and ranibizumab for neovascular age-related macular degeneration: a
systematic review.

Takeda AL, Colquitt J, Clegg AJ, Jones J.

Southampton Health Technology Assessments Centre, Wessex Institute for Health
Research and Development, Mailpoint 728, Boldrewood, University of Southampton,
Southampton, UK. a.l.takeda@soton.ac.uk

AIMS: To assess the clinical effectiveness of pegaptanib sodium and ranibizumab
for neovascular age-related macular degeneration (AMD). METHODS: A systematic
review of randomised controlled trials (RCTs) identified through searching 12
electronic databases, bibliographies and consultation with experts and
manufacturers. RCTs were eligible if they assessed the effects of pegaptanib or
ranibizumab with best supportive care, sham injection or photodynamic therapy
(PDT) on patients with subfoveal choroidal neovascularisation associated with wet
AMD and examined outcomes including visual acuity and adverse events. RESULTS:
Three RCTs of ranibizumab (MARINA, ANCHOR, FOCUS) and two of pegaptanib (VISION
study) met the inclusion criteria. The RCTs included patients with different
lesion types. The studies showed statistically significant benefit on different
measures of visual acuity for patients receiving pegaptanib, ranibizumab or
ranibizumab with PDT compared to control (sham injection, PDT or sham injection
with PDT) after 12 months. These differences appeared to be clinically
significant. Although adverse events were common among those receiving pegaptanib
or ranibizumab, they were considered mild to moderate in nature. Meta-analysis of
ranibizumab trials and indirect comparison of the two drugs were not possible due
to differences in the study populations' lesion types. However, results from the 
RCTs of ranibizumab tended to show a greater effect on visual acuity than results
from the RCT of pegaptanib. CONCLUSIONS: Pegaptanib and ranibizumab appear to
slow or stop the progression of neovascular AMD. Uncertainty remains over the
relative benefits of pegaptanib compared with ranibizumab and other unlicensed
drugs (eg, Avastin), due to the nature of the evidence. Head-to-head RCTs and
economic evaluations comparing these alternatives are needed.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17475698 [PubMed - indexed for MEDLINE]

873: Am J Ophthalmol. 2007 Jul;144(1):1-6. Epub 2007 May 2.

Comment in:
    Am J Ophthalmol. 2007 Jul;144(1):117-9.

Statin use and the five-year incidence and progression of age-related macular
degeneration.

Klein R, Knudtson MD, Klein BE.

Department of Ophthalmology, University of Wisconsin School of Medicine and
Public Health, Madison, Wisconsin 53726, USA. kleinr@epi.ophth.wisc.edu

PURPOSE: To examine the association of hydroxymethylglutaryl-coenzyme A (HMG-CoA)
reductase inhibitors (statins) with the five-year incidence of age-related
macular degeneration (AMD). DESIGN: Population-based cohort study. METHODS:
settings: Beaver Dam, Wisconsin. study population: Participants included persons 
53 to 96 years of age at examination in 1998 to 2000 (n = 2,962), of whom 2,204
participated in a follow-up five years later. observation procedures:
Standardized procedures were used for physical examinations, blood collection,
and questionnaire administration. AMD was determined by grading images of the
posterior pole using a standard protocol. Standard univariate and multivariate
analyses were performed. main outcome measures: Incident early and late AMD and
progressed AMD. RESULTS: There were 1,347 and 1,638 persons not using statins and
339 and 429 using statins at the 1998 to 2000 examination at risk of early and
late AMD, respectively. The unadjusted five-year incidence of early and late AMD,
respectively, was 5.9% and 1.8% in those not using statins and 6.8% and 2.3% in
those using statins. While controlling for age, gender, smoking status, and
multivitamin use, a history of statin use was not associated with the five-year
incidence of early AMD (odds ratio [OR] 1.16, 95% confidence interval [CI] 0.71
to 1.91, P = .55), progression of AMD (OR 1.16, 95% CI 0.75 to 1.78, P = .51) or 
incidence of late AMD (OR 1.27, 95% CI 0.60 to 2.69. P = .53). CONCLUSION: These 
findings do not show an association between statin use and the incidence or
progression of AMD over a five-year period.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17475196 [PubMed - indexed for MEDLINE]

874: J Glaucoma. 2007 Mar;16(2):220-4.

Intraocular pressure after intravitreal injection of triamcinolone acetonide
following vitrectomy for macular edema.

Yamashita T, Uemura A, Kita H, Sakamoto T.

Department of Ophthalmology, Kagoshima University Graduate School of Medical and 
Dental Sciences Kagoshima, Japan. take1@m.kufm.kagoshima-u.ac.jp

PURPOSE: To evaluate long-term intraocular pressure (IOP) response after
intravitreal injections of different doses of triamcinolone acetonide (TA) upon
completion of pars plana vitrectomy (PPV) for macular edema secondary to diabetic
retinopathy or retinal vein occlusion. PATIENTS AND METHODS: Retrospective,
consecutive, comparative, interventional case series. Twenty-seven eyes of 25
consecutive patients with macular edema associated with diabetic retinopathy
(n=18) or retinal vein occlusion (n=9), who underwent PPV for the treatment of
macular edema between January 2003 and December 2003, were included. Upon
completion of vitrectomy, different doses of TA were injected into the vitreous
cavity: 14 eyes with 5 mg of TA (group 1) and 13 eyes with 10 mg of TA (group 2).
The main outcome measure was IOP. RESULTS: All patients were followed up for at
least 12 months. Preoperative IOP was 12.6+/-2.6 mm Hg (mean+/-standard
deviation) in group 1 and 13.2+/-2.1 mm Hg in group 2. Postoperatively, IOP
increased to a mean maximum of 20.6+/-5.5 mm Hg in group 1 and 31.5+/-3.5 mm Hg
in group 2 (P<0.01 for both groups). The difference between groups was also
significant (P<0.05). Five of 14 eyes (36%) in group 1 and 10 of 13 eyes (77%) in
group 2 had an elevation of IOP exceeding 21 mm Hg (P=0.03). The median interval 
from surgery to reach maximal IOP was 7 days in both groups. The significant IOP 
elevation lasted for 3 months in group 1 and 6 months in group 2. CONCLUSIONS:
After injecting of TA into the vitreous cavity upon completion of PPV for macular
edema, a dose-dependent IOP elevation was observed, starting from early
postoperative days and returning to normal values after several months. These
results show that intravitreal TA injection in the vitrectomized eyes might have 
different IOP changes from in the nonvitrectomized eyes.

PMID: 17473734 [PubMed - indexed for MEDLINE]

875: Surv Ophthalmol. 2007 May-Jun;52(3):266-78.

Is significant relevant? Validity and patient benefit of randomized controlled
clinical trials on age-related macular degeneration.

Joussen AM, Lehmacher W, Hilgers RD, Kirchhof B.

Department of Ophthalmology, University of Düsseldorf, Düsseldorf, Germany.

A large variety of new treatment options for different forms of age-related
macular degeneration (ARMD) are becoming available. Not all new therapies may
meet the expectations of patients and ophthalmologists. Despite the given
statistical significant priority of treatment investigations, the endpoints may
not be relevant to the patient's requirements. Therefore, questions inevitably
arise regarding patient's benefit and the validity of the randomized controlled
trials. The randomized controlled trial is regarded as the "gold standard" in
terms of evaluating the effectiveness of interventions. The external validity of 
randomized controlled trials may be compromised, if, for example, patients
assigned to the study group are unrepresentative of the reference population.
This review aims to analyze problems with external validity in the randomized
controlled trials on ARMD and surveys the endpoints of clinical studies with
respect to the patient benefit.

Publication Types: 
    Review

PMID: 17472802 [PubMed - indexed for MEDLINE]

876: Trans Am Ophthalmol Soc. 2006;104:232-40.

Senile panretinal cone dysfunction in age-related macular degeneration (AMD): a
report of 52 amd patients compared to age-matched controls.

Ronan S, Nusinowitz S, Swaroop A, Heckenlively JR.

Department of Ophthalmology and Visual Science, Kellogg Eye Center, University of
Michigan, Ann Arbor, Michigan, USA.

PURPOSE: To test if patients with age-related macular degeneration (AMD) have
normal panretinal function using standardized full-field electroretinograms
(ERGs). METHODS: This is a retrospective study evaluating electroretinographic
studies performed in patients with AMD to assess their panretinal function.
Fifty-two individuals 55 years or older had standardized ERG testing and fundus
photographs. RESULTS: The study group was aged 57 to 93 years old with a mean of 
75.7, and the controls ranged from 79 to 87 years with a mean of 81.4. On
average, the photopic, scotopic, dark-adapted bright-flash, and flicker function 
response amplitudes are lower with longer implicit times in the study group than 
the controls. The most pronounced differences were seen with the bright-flash
dark-adapted a-waves and the photopic b-wave amplitudes. Forty-three of 104 eyes 
had abnormal photopic b-wave ERGs of more than 2 SD compared to controls. The
mean of the photopic b-wave amplitudes for the study group was 76.7 +/- 36.2 muV 
(1 SD) compared to 91.4 +/- 16.9 muV (1 SD) for the control group. This finding
was statistically significant with P = .0269 by the Student t test and P = .0336 
by the Wilcoxon test. CONCLUSIONS: There is a subgroup of AMD patients with a
panretinal cone dysfunction on ERG in association with their macular
degeneration. Previous studies have shown varied results when looking at ERG
changes in AMD, likely reflecting the underlying complexity of this disorder.
Using standardized ERG to identify a more homogeneous subgroup of AMD patients
with panretinal dysfunction will aid in better characterizing subtypes clinically
and is likely to be valuable in identifying new genes contributing to AMD.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17471344 [PubMed - indexed for MEDLINE]

877: Trans Am Ophthalmol Soc. 2006;104:221-31.

Preliminary analysis of the final multicenter investigation of rheopheresis for
age related macular degeneration (AMD) trial (MIRA-1) results.

Pulido JS, Winters JL, Boyer D.

Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota, USA.

PURPOSE: To present an initial evaluation of the final data from the Multicenter 
Investigation of Rheopheresis for age-related macular degeneration (AMD) (MIRA-1)
trial. This was a 12-month randomized, prospective, multicenter, double-masked,
placebo-controlled, Food and Drug Administration approved clinical trial designed
to compare rheopheresis treatment with placebo-control treatment. METHODS:
Patients that had nonexudative age-related macular degeneration (AMD) and certain
hemorheologic abnormalities were randomized to either rheopheresis or sham
treatment in a 2:1 fashion. Best-corrected visual acuity was determined before
and at 3, 6, 9, and 12 months following treatment. Adverse events were also
recorded. RESULTS: A total of 216 patients were randomized. Of these, 18 were not
included in the vision or adverse events evaluation because they did not complete
one treatment. This decreased the number of patients that were evaluated for
adverse events to 198 patients. In this group, there were 27 serious adverse
events, but only 1.8 % of treatments were suspended because of adverse events. At
12 months, there were 104 treated patients and 63 placebo patients that had
follow-up. The treated patients had a logMAR vision improvement of 0.02 +/-
0.213, and the placebo patients had a vision improvement of 0.02 +/- 0.20. This
was not statistically significant (P = .977). The repeated measure P value for
the entire time interval was not significant (P = .69). There appeared to be
patients entered into the study that did not meet inclusion criteria. Excluding
37% of the treated patients and 29% of the placebo data from the analysis, there 
appeared to be statistically significant improvement in the treated patients
compared to the control patients at 1 year with a P value of .001 (repeated
measures P value = .01). CONCLUSIONS: At best this was a flawed study in that 37%
of the treated cases did not meet inclusion criteria, and at worst there was no
evidence of effect. Even though the number of serious adverse events is small,
because this study did not show an effect in the intent-to-treat group,
rheopheresis should not be performed for AMD outside of an approved randomized
controlled trial.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial

PMID: 17471343 [PubMed - indexed for MEDLINE]

878: Trans Am Ophthalmol Soc. 2006;104:161-6.

The impact of optical coherence tomography on surgical decision making in
epiretinal membrane and vitreomacular traction.

Do DV, Cho M, Nguyen QD, Shah SM, Handa JT, Campochiaro PA, Zimmer-Galler I, Sung
JU, Haller JA.

Retina Division, Wilmer Eye Institute, Johns Hopkins University School of
Medicine, Baltimore, Maryland, USA.

PURPOSE: To compare retinal surgeons' recommendations for management of
epiretinal membranes (ERM) and vitreomacular traction syndrome (VMT) based on
clinical examination alone, with management based on examination supplemented by 
optical coherence tomography (OCT). METHODS: A prospective, masked clinical case 
series was conducted. Surgeons first assessed, on the basis of clinical
examination only, whether ERM, VMT, or macular edema was present, questionably
present, or absent and made a provisional management recommendation. The retina
specialist then reviewed the OCT images, determined the presence or absence of
ERM, VMT, or associated macular edema, and made a final management
recommendation. RESULTS: Eighty-four eyes of 73 patients were examined. ERM was
identified in 66 (78.6%) of 84 using clinical examination compared to 72 (85.7%) 
of 84 using OCT (P = .06). VMT was identified in five (6%) of 84 using clinical
examination compared to 18 (21.4%) of 84 using OCT (P < .005). Macular edema was 
identified in 57 (67.9%) of 84 using clinical examination compared to 70 (83.3%) 
of 84 using OCT (P =.003). Surgical intervention was recommended in 33 cases: 19 
(57.6%) based on clinical examination alone and 14 (42.4%) based on the
combination of clinical examination and OCT findings. CONCLUSIONS: OCT is more
sensitive than clinical examination in detecting ERM, VMT, and associated macular
edema. OCT influenced the recommendation for surgical intervention in 42.4% of
patients scheduled for surgery.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17471336 [PubMed - indexed for MEDLINE]

879: Ophthalmic Physiol Opt. 2007 May;27(3):225-31.

Investigation of the effect of simulated lens yellowing, transparency loss and
refractive error on in vivo resonance Raman spectroscopy.

Hogg RE, Zlatkova MB, Chakravarthy U, Anderson RS.

Department of Ophthalmology and Vision Science, Queen's University, Belfast, UK. 
r.e.hogg@qub.ac.uk

PURPOSE: To separately investigate the impact of simulated age-related lens
yellowing, transparency loss and refractive error on measurements of macular
pigment (MP) using resonance Raman spectroscopy. METHODS: Two healthy young
subjects with clear media underwent Raman spectroscopy under the following
conditions: age-related lens yellowing was simulated using seven broad-band
yellow filters with transmittance at 488 nm ranging from 0.54 to 0.90; cataract
was simulated using five white filters of increasing opacity (scatter filters),
the transmittance of which ranged from 0.42 to 0.86, each of which reduced peak
contrast sensitivity by approximately 0.1 log units over the previous filter.
Refractive error up to +6.25 D was achieved using soft contact lenses. RESULTS:
The Raman signal declined steadily to an average value of 43% of the starting
value with the densest yellow filter in place. The white scatter filters produced
a progressive linear reduction in signal resulting in almost complete signal loss
with the densest filter. Refractive error resulted in an initial slight
improvement in Raman count up to a value of +2.00 D followed by a decline
thereafter. CONCLUSIONS: These results imply that lens yellowing and increasing
scatter has an influence on the Raman signal and suggest that studies using this 
technology to estimate MP levels in older populations should carefully account
for the status of the lens.

PMID: 17470234 [PubMed - indexed for MEDLINE]

880: Coll Antropol. 2007 Jan;31 Suppl 1:107-10.

Incidence of age related macular degeneration in correlation with age, sex and
occupation.

Njirić S, Misljenović T, Mikulicić M, Pavicević L.

Eye Polyclinic "Dr. L. Pavicević", Rijeka, Croatia. snjiric2@net.hr

This study assesses the relation between age related macular degeneration (ARMD) 
and age, sex and occupation. It is designed as a retrospective study conducted on
patients presenting to the Eye Polyclinic "Dr. L. Pavicević", Rijeka, Croatia,
during the years 1995, 2000 and 2005, and included total of 6617 patients. The
number of patients diagnosed with ARMD, their age and sex distribution, as well
as the correlation between occupation type (indoor/outdoor) and the incidence of 
ARMD were analyzed. The results of our study show that the incidence of ARMD is
slightly increased in female vs. male, strongly age related, as expected, and
significantly increased in patients with outdoor type of occupation. Besides, an 
increasing trend of incidence is noted.

PMID: 17469763 [PubMed - indexed for MEDLINE]

881: Coll Antropol. 2007 Jan;31 Suppl 1:77-81.

Intravitreal bevacizumab (Avastin) in treatment of neovascular age-related
macular degeneration.

Lazić R, Gabrić N, Dekaris I, Sarić B, Gavrić M.

Eye Clinic 'Svjetlost", Zagreb, Croatia. ratimir.lazic@svjetlost.hr

To evaluate the efficacy and safety of intravitreal bevacizumab in treatment of
minimally classic and occult choroidal neovascularization secondary to
age-related macular disease 48 eyes of 48 patients (mean age of 74.8) included in
this prospective, noncomparative, interventional case series. Median follow-up
was 18 weeks (6-24). Intravitreal bevacizumab injection of 0.05 mL (1.25 mg) was 
administered at baseline and in 6 week intervals until leakage resolved, and
repeated in case of leakage recurrence. Visual acuity (VA) improved in the
majority of patients (mean baseline VA = 1.078 log MAR) by mean increase of 1.32 
lines (last follow-up) (p = 0.001). Central foveal thickness and total macular
volume decreased by 51 microm (p = 0.01) and 0.84 mm3 (p < 0.0001) respectively. 
No serious complications were observed. As initial therapy, intravitreal
bevacizumab appears to be safe and effective. A significant functional and
anatomical improvement was noted in majority of patients and maintained during
follow-up.

PMID: 17469757 [PubMed - indexed for MEDLINE]

882: Coll Antropol. 2007 Jan;31 Suppl 1:71-5.

Photodynamic therapy combined with intravitreal bevacizumab (Avastin) in
treatment of choroidal neovascularization secondary to age-related macular
degeneration.

Lazić R, Gabrić N, Dekaris I, Gavrić M, Bosnar D.

Eye Clinic "Svjetlost", Zagreb, Croatia. ratimir.lazic@svjetlost.hr

To evaluate photodynamic therapy with verteporfin combined with intravitreal
bevacizumab in minimally classic and occult choroidal neovascularization
secondary to age-related macular degeneration. 46 eyes of 46 patients (mean age
74.5) included in this prospective, noncomparative, interventional case series.
Median follow-up was 24 weeks (12-36). Verteporfin photodynamic therapy (PDT) was
followed by 0.05 mL (1.25 mg) of bevacizumab injected intravitreally within 24
hours and again after 6 weeks. Whole procedure was repeated in 3-month intervals 
in case of leakage. Visual acuity (VA) improved in majority of patients (baseline
VA 1.041 log MAR) by mean increase of 1.45 lines (last follow-up) (p = 0.001).
Central foveal thickness (CFT) and total macular volume (TMV) decreased by 53
microm (p = 0.03) and 1.04 mm3 (p < 0.001) respectively. No serious complications
were observed. Combined treatment may improve outcome of monotherapy. Significant
improvement in VA, CFT and TMA was noted in majority of patients and maintained
during follow-up.

PMID: 17469756 [PubMed - indexed for MEDLINE]

883: Coll Antropol. 2007 Jan;31 Suppl 1:69-70.

Prednisolone neuroprotective therapy in age-related macular degeneration.

Vojniković B, Spanjol J.

Eye Polyclinic "Dr. B. Vojniković", Rijeka, Croatia. decv@decv.com

134 patients with Age-related Macular Degeneration (AMD) (aging 47-75 years) were
treated in therapy procedure with parabulbar injections of Methylprednisolone
Acetate and Prednisolone Acetate. In the first group of patients with AMD (n = 71
patients) were treated with Methylprednisolone acetate, and second group (n = 63 
patients) with Prednisolone acetate. Each patient was given doses of 60 mg,
through two weeks, 10 mg every second day. It's estimated in all patients
ameliorate in macular threshold, so that it's in the group with
Methylprednisolone treatment, ameliorate effect begins after first week, than in 
second group, treated with Prednisolone, initial ameliorate effect is after
second week. Complete effect in both groups is after 2 months. It can be
concluded that the treatment of AMD with glucocorticoids has the ameliorate
effect in vision loss and it is decided that earlier effect in the group treated 
with Methylprednisolone, is probably of higher affinity for glucocorticoid
receptors.

Publication Types: 
    Clinical Trial

PMID: 17469755 [PubMed - indexed for MEDLINE]

884: Coll Antropol. 2007 Jan;31 Suppl 1:43-4.

Ultraviolet sun radiation and incidence of age-related macular degeneration on
Croatian Island Rab.

Vojniković B, Njirić S, Coklo M, Spanjol J.

Eye Polyclinic "Dr. B. Vojniković", Rijeka, Croatia. decv@decv.com

This epidemiological study is completed on island Rab, located in North Adriatic 
Sea. For this study it is important that Adriatic Sea has one of the highest
solar radiations in geographical area of Europe. The aim of this epidemiological 
study is to estimate correlation between incidence of Age-Related Macular
Degeneration (AMD) and exposure of sunlight in two different populations on
island Rab. In the first group of population of island Rab, agriculturists and
fishermen (n = 1300), incidence of AMD was in 18%, but in urban population only
2.5%. It is very interesting that correlation exists between incidence of AMD and
exfoliation syndrome. In the group of chronic exposure to sunlight
(agriculturists and fishermen) exfoliation syndrome exists in 28%, but in urban
population it has never been seen. The age in both populations was 45-65 years.
We can conclude that there is a very significant correlation between chronic
exposure to sunlight and appearance of AMD.

PMID: 17469748 [PubMed - indexed for MEDLINE]

885: Coll Antropol. 2007 Jan;31 Suppl 1:33-8.

Long-term exposure to solar ultraviolet radiation as a risk factor for
age-related macular degeneration.

Plestina-Borjan I, Klinger-Lasić M.

Department of Ophthalmology, Split University School of Medicine, Split, Croatia.
iplestina@krizine.kbsplit.hr

A clinical epidemiological study has been conducted as apart of research project 
investigating chronic exposure to solar ultraviolet radiation (UVR) as a factor
contributing to the onset of age-related macular degeneration (ARMD). The study
included 623 subjects older than 50 from two different geographic areas, one with
high solar radiation (the island of Solta - Region 1) and the other (Zagreb and
its surroundings - Region 2) with low solar radiation. Individual exposure to UVR
was assessed according to global exposure to sunlight, on the basis detailed
history of life-long exposure to sunlight, with special reference to professional
history and geophysical specificities of the respective areas. Different grades
of ARMD were based on the fundus photographs and flourescein angiography.
Statistically significant relation was found between ARMD and mean daily exposure
(in hours) to solar radiation in Region 1 (chi2 = 186.22; p = 0.000), Region 2
(chi2 = 25.66; p = 0.000) and in both regions together (chi2 = 216.43; p =
0.000). ARMD is more frequent in the subjects belonging to the Region 1 and with 
the same exposure to sunlight (8 hours and more) which goes in favor of their
increased UVR exposure. The results support a relationship between long-term
sunlight exposure and increased risk of ARMD.

PMID: 17469746 [PubMed - indexed for MEDLINE]

886: Coll Antropol. 2007 Jan;31 Suppl 1:3-5.

Age-related macular degeneration is not macular process only--peripheral retina
is attacked too.

Vojniković B.

Eye Polyclinic "Dr. B. Vojniković", Rijeka, Croatia. decv@decv.com

On a small island of Rab, geographical latitude 44 degrees 40' N, with the
highest solar radiation among Adriatic islands, 1371 patients were examined in
2003-2005 period, with the aim of estimating the frequency of the patients number
with Age-related Macular Degeneration (AMD), and further if the peripheral retina
is damaged similarly as the macular region. In the first group of agriculturists 
and fishermen (n = 1300) we estimated the AMD, initial and middle stage of AMD,
in 18% of population, but in urban population only by 2 patients. Perimetric
analysis with computerized Kowa perimeter, estimated that the peripheral retina
is affected similarly as the macular region. Author concludes that for this
reason, the usual term of "Age-related Macular Degeneration" should necessarily
be named with the suffix "Peripheral", or "Age-related Retinopathy".

PMID: 17469740 [PubMed - indexed for MEDLINE]

887: Ophthalmology. 2007 May;114(5):890-4.

Comment in:
    Ophthalmology. 2008 Feb;115(2):417-8; author reply 418.

Optical coherence tomographic pattern may predict visual outcome after
intravitreal triamcinolone for diabetic macular edema.

Gibran SK, Khan K, Jungkim S, Cleary PE.

Eye, Ear, Nose and Throat Centre, Queens Medical Centre, Nottingham, United
Kingdom.

OBJECTIVE: To identify an optical coherence tomography (OCT) pattern predictive
of visual outcome in patients with diabetic macular edema (DME) who underwent a
single dose of intravitreal triamcinolone. DESIGN: Retrospective case analysis
with prospective data collection for controls. PARTICIPANTS: Ninety-three cases
and 25 controls. METHODS: Two independent masked observers retrospectively
examined preoperative macular OCTs of 93 eyes of 93 patients who were given a
single dose (4 mg in 0.1 ml) of intravitreal triamcinolone for DME and
categorized them as belonging to 2 groups: 1, comprised of eyes with high
reflectivity (bright colors) from inner retinal layers, and 2, comprised of eyes 
that had low reflectivity (darker colors) from inner retinal layers. Logarithm of
the minimum angle of resolution visual acuity (VA) and macular thickness measured
by OCT were assessed preoperatively and postoperatively at 1 and 3 months. MAIN
OUTCOME MEASURES: Optical coherence tomographic appearance of inner retinal
layers. RESULTS: All patients completed 3 months of follow-up. In group 1, 45 of 
51 eyes (88%) experienced visual improvement of > or =2 lines on an Early
Treatment Diabetic Retinopathy Study (ETDRS) chart at 1 month of follow-up.
Forty-four of 51 patients (86%) experienced visual improvement of > or =2 lines
on an ETDRS chart at 3 months of follow-up. In group 2, 18 of 42 patients (43%)
experienced visual improvement of > or =1 lines on an ETDRS chart at 1 and 3
months of follow-up. For the remaining patients, VA remained unchanged during the
postoperative course of 3 months. CONCLUSIONS: Patients in whom OCT demonstrated 
the high reflectivity of inner retinal layers achieved greater VA though macular 
thickness decreased significantly after intravitreal triamcinolone in both
groups. It may be hypothesized that a lower optical reflectivity of inner retinal
layers is related to the atrophy of the inner retinal layers, thus resulting in a
failure of VA recovery in these patients. The level of reflectivity from inner
retinal layers on OCT may provide objective criteria in predicting the response
of DME to intravitreal triamcinolone and help in preoperative counseling of
patients with DME.

PMID: 17467527 [PubMed - indexed for MEDLINE]

888: Ophthalmology. 2007 May;114(5):860-5.

Comment in:
    Ophthalmology. 2008 Aug;115(8):1437-8; author reply 1438.    Ophthalmology. 2008 May;115(5):921-2; author reply 922.

The IOL-Vip System: a double intraocular lens implant for visual rehabilitation
of patients with macular disease.

Orzalesi N, Pierrottet CO, Zenoni S, Savaresi C.

University Eye Clinic, San Paolo Hospital, Milan, Italy. nicola.orzalesi@unimi.it

PURPOSE: To investigate the efficacy of a new surgical and rehabilitative
procedure designed to improve vision in patients with central scotoma due to
macular diseases. DESIGN: Case series of 40 consecutive surgical and
rehabilitative procedures. PARTICIPANTS: Forty eyes of 35 consecutive patients
with a stable central scotoma due to macular disease underwent
phacoemulsification cataract surgery with the implant of the IOL-Vip System.
METHODS: The IOL-Vip System consists of a biconcave high minus-power intraocular 
lens (IOL) in the capsular bag and a biconvex high plus-power IOL in the anterior
chamber, reproducing an intraocular Galilean telescope with x1.3 magnification
for distance. Selection of the candidate patients was carried out by means of a
low-vision diagnostic and rehabilitative program (IOL-Vip software) that
evaluates the residual visual function of patients and prognosis for visual
improvement based on simulation of the postoperative condition. The software also
designs the rehabilitation strategies based on preoperative and postoperative
training of the preferred retinal locus. MAIN OUTCOME MEASURES: Best-corrected
visual acuity (BCVA), evaluated by means of the Early Treatment Diabetic
Retinopathy Study charts and procedure; reading magnification; and reading
distance. RESULTS: All patients showed an improvement of visual acuity (VA) due
to the surgical and rehabilitative procedure, confirming or exceeding the
preoperative expected results. Mean postoperative BCVA was 0.77 (logarithm of the
minimum angle of resolution), compared with 1.28 preoperatively. The mean
postoperative best reading magnification gain was x6.2, and the mean
postoperative reading distance gain was 7.66 cm. No cases of intraoperative or
postoperative complications were detected, and the implant was subjectively well 
tolerated in both monocular and binocular procedures. CONCLUSION: In this pilot
study, the IOL-Vip System was shown to be effective and apparently well tolerated
in improving the vision of patients with macular disease. Best-corrected VA,
reading magnification, and reading distance improved in all cases of this
low-vision patient series.

PMID: 17467525 [PubMed - indexed for MEDLINE]

889: Curr Opin Genet Dev. 2007 Jun;17(3):228-33. Epub 2007 Apr 27.

Two genetic pathways for age-related macular degeneration.

DeWan A, Bracken MB, Hoh J.

Department of Epidemiology and Public Health, Yale University, 60 College Street,
New Haven, CT 06520, USA.

The discovery of strong associations of the His402 variant of complement factor H
(CFH) and the change in the promoter region of HtrA serine peptidase 1 (HTRA1)
with age-related macular degeneration (AMD) have altered our conception of the
pathophysiology of this disease. The complement system has been placed at the
center of a flurry of research interest, and a similar growth in attention to the
serine proteases is not far behind. The specific role of these variants in
causing AMD is unknown, but they will undoubtedly lead to a deeper understanding 
of the biological mechanisms and will point to new avenues for pharmacologic
management. Furthermore, these variants will enable clinicians and investigators 
to identify people at high risk for this condition, thereby establishing the
preconditions for preventing the disease.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Review

PMID: 17467263 [PubMed - indexed for MEDLINE]

890: J Cataract Refract Surg. 2007 May;33(5):804-7.

Preoperative topical indomethacin to prevent pseudophakic cystoid macular edema.

Yavas GF, Oztürk F, Küsbeci T.

Afyon Kocatepe University, Faculty of Medicine, Department of Ophthalmology,
Afyonkarahisar, Turkey. gkumbar@ttnet.net.tr

PURPOSE: To evaluate the effectiveness of a nonsteroidal antiinflammatory drug
(NSAID) on pseudophakic cystoid macular edema (CME) and determine the efficacy
when used preoperatively and after uneventful phacoemulsification surgery.
SETTING: Department of Ophthalmology, Kocatepe University, School of Medicine,
Afyonkarahisar, Turkey. METHODS: One hundred seventy-nine eyes of 189 patients
having uneventful phacoemulsification surgery were enrolled in the study. After
surgery, all patients used topical steroids and antibiotics 4 times daily.
Sixty-one eyes, chosen randomly, received a topical NSAID (indomethacin) 4 times 
daily for 3 days preoperatively and 1 month postoperatively. Sixty eyes received 
topical indomethacin 4 times daily for 1 month postoperatively. Fifty-eight eyes 
served as a control group and received only topical steroids and antibiotics. At 
the third postoperative month, visual acuity, fluorescein angiograms, and macular
thresholds were evaluated. Statistical analysis was by chi-square and 1-way
analysis of variance tests. RESULTS: Cystoid macular edema was not seen in the
group receiving indomethacin preoperatively and postoperatively. The incidence of
angiographic CME was 15.0% in the group receiving postoperative indomethacin and 
32.8% in the control group (P<.001). Mean sensitivity in the macular threshold
test did not show a significant change between groups (P = .83). Postoperative
visual acuity was significantly higher in the group receiving preoperative
indomethacin (P<.001). CONCLUSION: Nonsteroidal antiinflammatory drugs decreased 
the incidence of CME, and their efficacy increased when begun preoperatively.

Publication Types: 
    Randomized Controlled Trial

PMID: 17466852 [PubMed - indexed for MEDLINE]

891: Expert Opin Ther Targets. 2007 May;11(5):625-39.

New therapeutic targets in atrophic age-related macular degeneration.

Petrukhin K.

Columbia University, Department of Ophthalmology, Eye Institute Annex, New York, 
NY 10032, USA. kep4@columbia.edu

Age-related macular degeneration (AMD) is the leading cause of blindness in
developed countries. There is no effective treatment for the most prevalent
atrophic (dry) form of AMD. Atrophic AMD is triggered by abnormalities in the
retinal pigment epithelium (RPE) that lies beneath the photoreceptor cells and
normally provides critical metabolic support to these light-sensing cells.
Secondary to RPE dysfunction, macular rods and cones degenerate leading to the
irreversible loss of vision. Oxidative stress, formation of drusen, accumulation 
of lipofuscin, local inflammation and reactive gliosis represent the pathologic
processes implicated in pathogenesis of atrophic AMD. This review discusses
potential target areas for small-molecule and biologic intervention, which may
lead to development of new therapeutic treatments for atrophic AMD.

Publication Types: 
    Review

PMID: 17465722 [PubMed - indexed for MEDLINE]

892: Eye. 2008 Jun;22(6):849-54. Epub 2007 Apr 27.

An analysis of the CFH Y402H genotype in AMD patients and controls from the UK,
and response to PDT treatment.

Goverdhan SV, Hannan S, Newsom RB, Luff AJ, Griffiths H, Lotery AJ.

Clinical Neurosciences Division, University of Southampton, Southampton General
Hospital, Southampton, UK.

AIM: Mutation in the complement factor H (CFH) gene is an important risk factor
for age-related macular degeneration (AMD). In this study, we identified the
strength of the CFH Y402H gene variant association in a UK AMD cohort and tested 
the hypothesis that this variant may influence the biological response of
choroidal neovascularisation (CNV) following photodynamic therapy (PDT) for CNV. 
METHODS: A total of 557 cases with AMD and 551 normal controls were genotyped for
the CFH Y402H (1277 C/T) variant using the 5' nuclease TaqMan assay for allelic
discrimination. The CFH gene association for AMD, for the different CNV subtypes 
and for patients needing PDT was estimated. Twenty-seven PDT-treated patients
were followed up for 15 months with ETDRS-derived vision, clinical examination,
and fundus angiography. Individuals with different CFH genotypes were then
analysed for any association with visual change following PDT. RESULTS: The risk 
association for AMD with the CFH CC genotype (odd ratio (OR)=3.62, Pc<0.0001) was
similar to that reported in other Caucasian cohorts. The magnitude and strength
of this association was stronger in AREDS stages 2-4 (ORs=4.48, 2.69, and 5.17). 
ORs for the risk of predominantly classic CNV were significantly raised for both 
the CC (OR=17.87, P<0.0001) and CT (OR=9.06, P=0.0002) genotypes. The number of
patients carrying the high-risk C allele was 70.4% in those requiring PDT as
compared to 52.3% in the non-PDT group (OR=2.16, P=0.011), and presence of the CC
genotype significantly increased the risk of PDT (OR=5.48, P=0.015). The degree
of visual loss following PDT was significantly higher in the CFH CC genotype
group (P=0.038); 50% of CC cases (n=13) and 45% of the CT cases (n=12) lost 15 or
more ETDRS letters at final follow-up. CONCLUSION: In this UK cohort of AMD
patients, the CFH Y402H variant was significantly enriched in patients with
predominantly classic CNV. Patients homozygous for the CFH Y402H genotype seem to
have worse visual acuity after PDT.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17464302 [PubMed - indexed for MEDLINE]

893: Retina. 2007 Mar;27(3):342-8.

Photodynamic therapy with verteporfin for choroidal neovascularization associated
with retinal pigment epithelial detachment in age-related macular degeneration.

Pece A, Isola V, Vadalà M, Calori G.

Department of Ophthalmology, Ospedale di Melegnano, Milan, Italy.
pece.retina@mclink.it

PURPOSE: To assess the effectiveness of photodynamic therapy (PDT) with
verteporfin for choroidal neovascularization (CNV) associated with retinal
pigment epithelium detachment (PED) in age-related macular degeneration. METHODS:
Thirty eyes of 26 patients with CNV and PED were treated with PDT. The eyes were 
divided in two groups based on CNV location in relation to PED; group 1 included 
13 eyes with CNV within PED, and group 2 included 17 eyes with CNV at the edge of
PED. The median follow-up was 16 months. RESULTS: Patients received a mean +/- SD
of 2.83 +/- 1.26 treatments (range, 1-6 treatments). In the whole cohort, the
mean preoperative visual acuity changed from 20/144 (0.86 +/- 0.42 logarithm of
minimal angle of resolution [logMAR]) to 20/182 (0.96 +/- 0.51 logMAR; P = 0.39) 
at month 18. Five eyes (16%) gained a mean of 1.5 Snellen lines from baseline.
Twelve eyes (40%) lost a mean of 1.7 Snellen lines of visual acuity. Vision in 13
eyes (44%) remained stable. In group 1, the mean visual acuity at month 12 was
20/303 (1.18 +/- 0.51 logMAR) and significantly (P = 0.015) worse than that,
20/110 (0.74 +/- 0.42 logMAR), in group 2. CONCLUSION: PDT can improve or
stabilize visual function in 60% of eyes with vascularized PED. CNV at the edge
of PED appears to respond more favorably to PDT. Appropriate patient selection
and prompt treatment are essential to obtain the best outcomes after verteporfin 
therapy.

PMID: 17460590 [PubMed - indexed for MEDLINE]

894: Retina. 2007 Mar;27(3):269-75.

Role of genetic factors and inflammation in age-related macular degeneration.

Moshfeghi DM, Blumenkranz MS.

Department of Ophthalmology, Stanford University School of Medicine, Stanford,
California, USA. dariusm@stanford.edu

Complement factor H (CFH) has been implicated in the predisposition to advanced
forms of age-related macular degeneration (AMD). The purpose of this review is to
highlight recent discoveries implicating single nucleotide polymorphisms on 1q32,
6p21, and 10q26 in the risk for development of AMD. In addition, the central role
of CFH in the complement cascade and its role in the inflammatory hypothesis for 
AMD are reviewed.

Publication Types: 
    Review

PMID: 17460581 [PubMed - indexed for MEDLINE]

895: Korean J Ophthalmol. 2007 Mar;21(1):55-60.

Therapeutic effect of diode laser photodynamic therapy with ICG dye in ARMD: a
case report.

Yoon CK, Kyoung SE, Chang MH.

Department of Ophthalmology, Dankook University College of Medicine, Cheonan,
Korea.

PURPOSE: To evaluate the diode laser photodynamic therapy efficacy on choroidal
neovascularization (CNV) in the treatment of three patients with age-related
macular degeneration (ARMD). METHODS: The authors selected three patients with
ARMD whose vision has decreased due to CNV, and applied diode laser treatment
after injecting an indocyanine green (ICG) solution. The patients were followed
for at least three months after treatment, and examinations included evaluating
vision changes and possible leakage on fluorescein angiography (FAG). RESULTS:
The final vision of two patients improved by more than one line on the Early
Treatment Diabetic Retinopathy Study (ETDRS) chart after at least three months of
follow-up. However, the final vision of the third patient decreased by one line
on ETDRS chart. FAG was done in all patients, and in two of the patients, there
was no evidence of leakage at the laser-applied site. In the other patient, there
was evidence of minimal leakage, with the area of leakage decreasing by more than
fifty percent. Side effects of ICG were not found during or after the
photodynamic therapy sessions. CONCLUSIONS: The photodynamic usage of ICG
treatment of CNV in patients with ARMD, was effective in preventing or improving 
the visual outcome. Compared to the widely used verteporfin, ICG is more stable
and is more cost effective. The authors therefore came to a conclusion that ICG
can be very useful in the treatment of CNV. However, further studies are
necessary.

Publication Types: 
    Case Reports

PMID: 17460435 [PubMed - indexed for MEDLINE]

896: Korean J Ophthalmol. 2007 Mar;21(1):18-20.

Early versus late intravitreal triamcinolone acetonide for macular edema
associated with branch retinal vein occlusion.

Oh JY, Seo JH, Ahn JK, Heo JW, Chung H.

Department of Ophthalmology, Seoul National University College of Medicine,
Chongno-gu, Seoul, Korea.

PURPOSE: To compare the effect of early versus late intravitreal injection of
triamcinolone in patients with macular edema due to branch retinal vein occlusion
(BRVO). METHODS: Twenty eyes of 20 patients with macular edema from BRVO,
including 10 with duration after onset of or <or= 3 months and 10 with duration
of 3 months, were treated using a single intravitreal triamcinolone injection (4 
mg/0.1 ml). Best-corrected visual acuity and foveal thickness by optical
coherence tomography were measured 1, 3, and 6 months post-injection. RESULTS: In
patients that received treatment after a disease duration of <or= 3 months,
visual acuity and foveal thickness significantly improved from baseline over 6
months of follow-up. However, in those with a duration of >3 months, improvements
in visual acuity and foveal thickness, though apparent at 1 month, were not
maintained at 3 and 6 months post-triamcinolone. CONCLUSIONS: Intravitreal
triamcinolone is more effective in patients with BRVO who are treated earlier.

Publication Types: 
    Controlled Clinical Trial

PMID: 17460427 [PubMed - indexed for MEDLINE]

897: Korean J Ophthalmol. 2007 Mar;21(1):11-7.

Laser photocoagulation combined with intravitreal triamcinolone acetonide
injection in proliferative diabetic retinopathy with macular edema.

Choi KS, Chung JK, Lim SH.

Department of Ophthalmology, Soonchunhyang University, College of Medicine,
Yongsan-gu, Seoul, Korea. ckseek@naver.com

PURPOSE: To evaluate therapeutic effects and usefulness of a combination
treatment of intravitreal injection of triamcinolone acetonide (IVTA) and
panretinal photocoagulation (PRP) in patients with clinically significant macular
edema secondary to proliferative diabetic retinopathy (PDR). METHODS: Visual
acuity test, fundoscopy, fluorescein angiography, and optical coherence
tomography (OCT) were taken in 20 patients (20 eyes) of macular edema and PDR. A 
combination of intravitreal injection of triamcinolone acetonide and PRP was
performed in 10 patients (10 eyes) and a combination of focal or grid laser
photocoaqulation and PRP in the remaining 10 eyes. The postoperative outcomes
were compared between the two combination treatments by best corrected visual
acuity (BCVA), tonometry, fluorescein angiography, and OCT at 2 weeks, 1, 2, and 
3 months. RESULTS: Average BCVA (log MAR) significantly improved from
preoperative 0.56-/+0.20 to 0.43-/+0.08 at 1 month (P=0.042) and it was
maintained until 3 months after a combination of IVTA and PRP in 10 eyes
(P=0.007). The thickness of fovea decreased from average 433.3-/+114.9 micrometer
to average 279.5-/+34.1 micrometer at 2 weeks after combined treatment of IVTA
and PRP (P=0.005), which was significantly maintained until 3 months, but there
was a transient visual disturbance and no significant difference in thickness of 
the fovea before and after treatment in the groups with PRP and focal or grid
laser photocoagulation. CONCLUSIONS: A combination of IVTA and PRP might be an
effective treatment modality in the treatment of macular edema and PDR and
prevent the subsequent PRP-induced macular edema result in visual dysfunction. In
combination with PRP, IVTA might be more effective than focal or grid laser
photocoagulation and PRP for reducing diabetic macular edema and preventing
aggravation of macular edema without transient visual disturbance in patients
requiring immediate PRP.

PMID: 17460426 [PubMed - indexed for MEDLINE]

898: Invest Ophthalmol Vis Sci. 2007 May;48(5):2278-84.

IDOCS: intelligent distributed ontology consensus system--the use of machine
learning in retinal drusen phenotyping.

Thomas G, Grassi MA, Lee JR, Edwards AO, Gorin MB, Klein R, Casavant TL, Scheetz 
TE, Stone EM, Williams AB.

Department of Computer Science, University of Iowa, Iowa City, Iowa, USA.

PURPOSE: To use the power of knowledge acquisition and machine learning in the
development of a collaborative computer classification system based on the
features of age-related macular degeneration (AMD). METHODS: A vocabulary was
acquired from four AMD experts who examined 100 ophthalmoscopic images. The
vocabulary was analyzed, hierarchically structured, and incorporated into a
collaborative computer classification system called IDOCS. Using this system,
three of the experts examined images from a second set of digital images compiled
from more than 1000 patients with AMD. Images were annotated, and features were
identified and defined. Decision trees, a machine learning method, were trained
on the data collected and used to extract patterns. Interrelationships between
the data from the different clinicians were investigated. RESULTS: Six drusen
classes in the structured vocabulary were largely sufficient to describe all the 
identified features. The decision trees classified the data with 76.86% to 88.5% 
accuracy and distilled patterns in the form of hierarchical trees composed of 5
to 15 nodes. Experts were largely consistent in their characterization of soft,
and to a lesser extent, hard drusen, but diverge in definition of other drusen.
Size and crystalline morphology were the main determinants of drusen type across 
all experts. CONCLUSIONS: Machine learning is a powerful tool for the
characterization of disease phenotypes. The creation of a defined feature set for
AMD will facilitate the development of an IDOCS-based classification system.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17460291 [PubMed - indexed for MEDLINE]

899: Invest Ophthalmol Vis Sci. 2007 May;48(5):1983-8.

Circulating inflammatory markers and hemostatic factors in age-related
maculopathy: a population-based case-control study.

Wu KH, Tan AG, Rochtchina E, Favaloro EJ, Williams A, Mitchell P, Wang JJ.

the Center for Vision Research, Department of Ophthalmology, University of
Sydney, Westmead Hospital, Westmead, NSW, Australia.

PURPOSE: To examine the relationship between circulating inflammatory markers,
hemostatic factors, and age-related maculopathy (ARM). METHODS: A
population-based, cross-sectional case-control study drawn from the Blue
Mountains Eye Study included 159 early and 38 late ARM cases, and 433 controls
matched for age, gender, and smoking. ARM lesions were assessed from retinal
photographs according to the Wisconsin ARM grading system. Circulating
inflammatory markers (high-sensitivity C-reactive protein [hsCRP], intercellular 
adhesion molecule [ICAM]-1, and interleukin [IL]-6), white cell count (WCC), and 
hemostatic factors (fibrinogen, homocysteine, plasminogen activator inhibitor
[PAI]-1 and von Willebrand factor [vWF]) were assessed. Age, gender, current
smoking, body mass index, hypertension, history of stroke, and cardiovascular
events were adjusted for. Adjusted mean levels of each marker were compared
between persons with early ARM, those with late ARM, and control subjects, and
are presented as probabilities. Adjusted associations with ARM were examined
continuously (per SD), and are presented as odds ratios (ORs) and 95% confidence 
intervals (CIs). Summarizing z scores for inflammation and hemostatic dysfunction
were calculated. RESULTS: Increased PAI-1 level was associated with both early
(OR 1.2, 95% CI 1.0-1.4 per SD increase) and late ARM (OR 1.3, 95% CI 0.9-1.9 per
SD increase). Elevated ICAM-1 level was marginally associated with late ARM (OR
1.3, 95% CI 1.0-1.7 per SD increase). No other significant associations were
found between the remaining inflammatory or hemostatic markers and either early
or late ARM. Summarized z scores for inflammatory or hemostatic markers also did 
not suggest any associations. CONCLUSIONS: There was no consistent pattern of
association found between ARM and circulating inflammatory markers or hemostatic 
factors in this population-based case-control study.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17460250 [PubMed - indexed for MEDLINE]

900: Invest Ophthalmol Vis Sci. 2007 May;48(5):1976-82.

Rasch analysis of the daily living tasks dependent on vision (DLTV).

Denny F, Marshall AH, Stevenson MR, Hart PM, Chakravarthy U.

Centre for Vision Sciences, School of Mathematics and Physics, Queen's University
of Belfast, Belfast Northern Ireland, United Kingdom.

PURPOSE: To examine internal consistency, refine the response scale, and obtain a
linear scoring system for the visual function instrument, the Daily Living Tasks 
Dependent on Vision (DLTV). METHODS: Data were available from 186 participants
with a clinical diagnosis of AMD who completed the 22-item DLTV (DLTV-22)
according to four-point ordinal response scale. An independent group of 386
participants with AMD were administered a reduced version of the DLTV with 11
items (DLTV-11), according to a five-point response scale. Rasch analysis was
performed on both datasets and used to generate item statistics for measure
order, response odds ratios per item and per person, and infit and outfit mean
square statistics. The Rasch output from the DLTV-22 was examined to identify
redundant items and for factorial validity and person item measure separation
reliabilities. RESULTS: The average rating for the DLTV-22 changed monotonically 
with the magnitude of the latent person trait. The expected versus observed
average measures were extremely close, with step calibrations evenly separated
for the four-point ordinal scale. In the case of the DLTV-11, step calibrations
were not as evenly separated, suggesting that the five-point scale should be
reduced to either a four- or three-point scale. Five items in the DLTV-22 were
removed, and all 17 remaining items had good infit and outfit mean squares. PCA
with residuals from Rasch analysis identified two domains containing 7 and 10
items each. The domains had high person separation reliabilities (0.86 and 0.77
for domains 1 and 2, respectively) and item measure reliabilities (0.99 and 0.98 
for domains 1 and 2, respectively). CONCLUSIONS: With the improved internal
consistency, establishment of the accuracy and precision of the rating scale for 
the DLTV and the establishment of a valid domain structure we believe that it
constitutes a useful instrument for assessing visual function in older adults
with age-related macular degeneration.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17460249 [PubMed - indexed for MEDLINE]

901: Ann N Y Acad Sci. 2007 Apr;1100:213-7.

The importance of serum lipids in exudative diabetic macular edema in type 2
diabetic patients.

Uçgun NI, Yildirim Z, Kiliç N, Gürsel E.

Gazi University, Faculty of Medicine, Department of Medical Biochemistry, 06510
Beşevler, Ankara, Turkey.

To evaluate the relationship between serum lipid levels and exudative diabetic
maculopathy in patients with nonproliferative diabetic retinopathy, 27 patients
with exudative diabetic macular edema were included in group A and 27 patients
without exudative diabetic macular edema were included in group B. All 54
patients have nonproliferative diabetic retinopathy. Blood cholesterol,
triglyceride, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein
(LDL) cholesterol, very low-density lipoprotein (VLDL) cholesterol, hemoglobin
A1c (HbA1c), and hemoglobin levels were measured in patients in group A and group
B. The mean concentration of cholesterol in group A (224.30 +/- 49.49 mg/dL), in 
group B (197.78 +/- 41.49 mg/dL); triglyceride in group A (199.11 +/- 90.51
mg/dL), in group B (160.78 +/- 65.30 mg/dL); HDL in group A (43.48 +/- 10.62
mmol/L), in group B (42.37 +/- 10.92 mmol/L); LDL in group A (150.59 +/- 43.96
mg/dL), in group B (124.37 +/- 40.28 mg/dL); VLDL in group A (40.52 +/- 16.54
mg/dL), in group B (37.89 +/- 23.70 mg/dL); HbA1c in group A (9.62 +/- 2.50), in 
group B (7.36 +/- 1.62 g/dL); and hemoglobin in group A (13.46 +/- 1.6 g/dL), in 
group B (13.90 +/- 1.77 g/dL). Serum cholesterol (P = 0.38), LDL (P = 0.026), and
HbA1c (P = 0.000) levels were different between the two groups. Triglyceride,
HDL, VLDL, and hemoglobin levels were not different between the two groups. We
must consider regulation of high blood sugar and elevated total serum cholesterol
or LDL levels in patients with macular edema and high hard exudates.

PMID: 17460181 [PubMed - indexed for MEDLINE]

902: Ophthalmology. 2007 Dec;114(12):2162-7. Epub 2007 Apr 25.

Intravitreal triamcinolone plus sequential grid laser versus triamcinolone or
laser alone for treating diabetic macular edema: six-month outcomes.

Lam DS, Chan CK, Mohamed S, Lai TY, Lee VY, Liu DT, Li KK, Li PS, Shanmugam MP.

Department of Ophthalmology and Visual Sciences, Chinese University of Hong Kong,
Hong Kong, China. dennislam_pub@cuhk.edu.hk

OBJECTIVE: To evaluate the efficacy of sequential intravitreal triamcinolone
acetonide (TA) injection followed by grid laser photocoagulation for treating
diabetic macular edema (DME). DESIGN: Prospective, 3-armed, randomized clinical
trial. PARTICIPANTS: One hundred eleven eyes of 111 patients with DME involving
the fovea. INTERVENTION: Patients were randomized to grid laser photocoagulation 
(37 eyes), 4 mg of intravitreal TA (38 eyes), or 4 mg of intravitreal TA combined
with sequential grid laser about 1 month later (36 eyes). MAIN OUTCOME MEASURES: 
Central foveal thickness (CFT) as measured by optical coherence tomography,
logarithm of the minimum angle of resolution (logMAR) best-corrected visual
acuity (BCVA), and side effect profiles. The 6-month results are reported.
RESULTS: All patients completed 6 months' follow-up. Baseline mean (+/- standard 
deviation) CFTs were 385+/-100 microm, 396+/-91 microm, and 424+/-108 microm for 
the laser, intravitreal TA, and combined groups, respectively (P = 0.24). After
treatment, significant CFT reductions were noted in both the intravitreal TA and 
combined groups at all follow-up visits (P<0.01) but not in the laser group. Mean
CFT improved significantly to minimums of 267+/-75 microm and 256+/-73 microm for
the intravitreal TA and combined groups, respectively, but the difference between
the 3 groups was not significant at 6 months. The standardized change in macular 
thickening at 17 weeks was significantly greater in the combined group versus the
intravitreal TA group (P = 0.007), suggesting that combined treatment might
prolong the effects of intravitreal TA. Mean baseline logMAR BCVAs were
0.64+/-0.37, 0.72+/-0.34, and 0.69+/-0.34 in the laser, intravitreal TA, and
combined groups, respectively (P = 0.67). Best-corrected visual acuity improved
significantly at 4 and 9 weeks for the intravitreal TA group but did not change
significantly in the other 2 groups. No significant difference in BCVA was
observed between the 3 groups at any time point. CONCLUSIONS: Contrary to the
results of a recent study, combined treatment of intravitreal TA plus grid laser 
did not yield better CFT reduction or BCVA improvement at 6 months than
intravitreal TA alone. Grid laser alone was significantly worse than the 2 other 
treatment modalities.

Publication Types: 
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17459479 [PubMed - indexed for MEDLINE]

903: Acta Ophthalmol Scand. 2007 Nov;85(7):795-8. Epub 2007 Apr 24.

Full-thickness macular hole in a patient with diabetic cystoid macular oedema
treated by intravitreal triamcinolone injections.

Lecleire-Collet A, Offret O, Gaucher D, Audren F, Haouchine B, Massin P.

Department of Ophthalmology, Lariboisière Hospital, University of Paris, Paris,
France. colletamelie@hotmail.com

PURPOSE: Full-thickness macular hole associated with diabetic macular oedema is a
rare feature and its pathogenesis remains incompletely elucidated. We report the 
occurrence of a full-thickness macular hole, documented with optical coherence
tomography (OCT), in a patient with diabetic cystoid macular oedema treated by
intravitreal triamcinolone injections. CASE REPORT: A 48-year-old woman with
refractory diabetic cystoid macular oedema underwent successive intravitreal
triamcinolone injections, which were followed by a progressive thinning of the
neurosensory retina at the fovea, and then by a full-thickness macular hole,
associated with a perifoveal posterior hyaloid detachment, visible on OCT. During
pars plana vitrectomy, a thin epiretinal macular membrane was diagnosed and
removed. DISCUSSION: Pathogenesis of the present full-thickness macular hole
associated with diabetic macular oedema is different from that of idiopathic
macular holes because anteroposterior vitreous tractions were not involved in its
formation. Recurrent intravitreal triamcinolone injections may have had an
indirect role in the development of the macular hole, by favouring the rupture of
distended Muller cells and intraretinal pseudocysts.

Publication Types: 
    Case Reports

PMID: 17459030 [PubMed - indexed for MEDLINE]

904: Klin Monatsbl Augenheilkd. 2007 Apr;224(4):311-3.

Bartonella henselae infection presenting as a unilateral acute maculopathy.

Wimmersberger Y, Baglivo E.

Clinique d'Ophtalmologie, Hôpitaux Universitaires de Genève, Geneva, Switzerland.

BACKGROUND: The purpose of this article is to report an unusual ocular
manifestation of cat scratch disease (CSD) presenting as a unilateral acute
maculopathy (UAM). We describe and review the clinical, laboratory, fluorescein
angiography (FA), indocyanine green angiography (ICG) and optical coherence
tomography (OCT) records of a patient with CSD. HISTORY AND SIGNS: A 30-year-old 
Chinese woman presented with a painless progressive visual loss affecting her
left eye. Fundus examination of the left eye disclosed rare vitreous cells and a 
deep-creamy choroidal macular lesion with satellite foci of choroiditis. THERAPY 
AND OUTCOME: FA revealed an early hypofluorescence of the lesion, becoming
progressively hyperfluorescent with a leakage on the late phase. The ICG
disclosed an early hypofluorescence of the macular lesion with a mild staining of
its periphery on the late frames. Hypofluorescent satellite lesions were visible 
both on the early and late frames. The OCT disclosed a serous retinal detachment 
at the level of the whitish lesion. Serologies for Bartonella henselae (BH)
became positive (IgG 1: 512, IgM < 1:20) confirming an active or recent
infection. CONCLUSIONS: Ocular manifestations of CSD can appear as a UAM with
satellite lesions. CSD should be ruled out in patients manifesting such clinical 
features.

Publication Types: 
    Case Reports

PMID: 17458800 [PubMed - indexed for MEDLINE]

905: Klin Monatsbl Augenheilkd. 2007 Apr;224(4):297-9.

Intravitreal triamcinolone acetonide for serous retinal pigment epithelial
detachments in exudative age-related macular degeneration.

Sutter FK, Kurz-Levin MM, Scherrer M, Barthelmes D, Fleischhauer JC, Helbig H.

Augenklinik, Universitätsspital, Zürich, Switzerland. florian.sutter@usz.ch

BACKGROUND: Due to the high risk of RPE tears PDT is usually not performed in
eyes with serous RPE detachments (sRPED). For this reason this subform of
exudative AMD was so far untreatable. PATIENTS AND METHODS: We report on a
prospective uncontrolled observational case series. 20 eyes of 20 patients with
subfoveal sRPED demonstrated by OCT were treated between June 2005 and April 2006
with intravitreal triamcinolone acetonide (IVTA). In 15 cases there was a primary
sRPED, in 5 cases it had developed after one or more sessions of photodynamic
therapy with Visudyne. RESULTS: There was a trend for better average visual
acuity in the group with primary sRPED from 0.73 logMAR (0.19 Snellen equivalent)
at baseline (n = 15) to 0.68 logMAR (0.21 Snellen) after one month (n = 15) (p = 
0.19) and to 0.60 logMAR (0.25 Snellen) after three months (n = 14) (p = 0.41).
The maximal height of sRPED decreased to an average of 35.3 % after one month (n 
= 15) and increased again to 56.9 % after 3 months (n = 14). One patient was lost
to follow-up. In the group of eyes with sRPED after PDT, one eye developed an RPE
tear with severe vision loss two weeks after IVTA. In the remaining four eyes
average visual acuity improved from 0.90 logMAR (0.13 Snellen) at baseline to
0.73 logMAR (0.19 Snellen) after one month and to 0.80 logMAR (0.16 Snellen)
after 3 months. Complete resolution of sRPED was observed in 8/20 eyes (4/5 eyes 
with sRPED after PDT and 4/15 eyes with primary sRPED). CONCLUSIONS: IVTA seems
to be a therapeutic option in otherwise untreatable eyes with sRPED.

PMID: 17458796 [PubMed - indexed for MEDLINE]

906: Klin Monatsbl Augenheilkd. 2007 Apr;224(4):279-81.

First clinical experience with anecortave acetate (Retaane).

Hayek S, Scherrer M, Barthelmes D, Fleischhauer JC, Kurz-Levin MM, Menghini M,
Helbig H, Sutter FK.

Augenklinik, UniversitätsSpital, Zürich, Switzerland.

BACKGROUND: Anecortave acetate is an angiostatic cortisene which is injected as a
posterior juxtascleral depot and has been shown to be effective in the treatment 
of exudative age-related macular degeneration (AMD). The compound is not yet
approved in Switzerland but can be used as "compassionate use" in individual
cases. PATIENTS AND METHODS: An uncontrolled case series with standardised
documentation of ETDRS visual acuity, near acuity, need for magnification and
fluorescein angiography was performed. RESULTS: 22 eyes of 19 patients (8 male,
11 female, average age 78.8 years) were treated with a posterior juxtascleral
depot injection (PJD) of 15 mg anecortave acetate. The mean change in visual
acuity after 3 months in eyes treated with anecortave acetate was -2.6 ETDRS
letters corresponding to 0.52 Snellen lines. 3/20 eyes gained more than 1 line.
11/20 eyes showed stable visual acuity (+/- 1 Snellen line, +/- 5 ETDRS letters).
5/20 eyes developed moderate vision loss (one to two Snellen lines, 6-10 ETDRS
letters). 1/20 lost 18 ETDRS letters (> 3 Snellen lines). There were no moderate 
or severe adverse events. CONCLUSIONS: A PJD of 15 mg anecortave acetate is safe 
and well tolerated. In eyes with occult CNV without recent progression or with
residual neovascular activity after photodynamic therapy anecortave acetate may
be an alternative therapeutic option before considering intravitreal anti-VEGF
agents due to the much less invasive character and lower risk profile.

Publication Types: 
    Clinical Trial

PMID: 17458792 [PubMed - indexed for MEDLINE]

907: Sleep Breath. 2007 Dec;11(4):253-7.

Central serous chorioretinopathy and risk for obstructive sleep apnea.

Leveque TK, Yu L, Musch DC, Chervin RD, Zacks DN.

Department of Ophthalmology and Visual Sciences, Kellogg Eye Center, 1000 Wall
St., Ann Arbor, MI 48105, USA. thelleal@med.umich.edu

Patients with obstructive sleep apnea (OSA), in comparison to controls, have
increased levels of circulating epinephrine and norepinephrine, both of which are
risk factors for the development of central serous chorioretinopathy (CSCR). The 
aim of this pilot study was to investigate the frequency of symptoms that suggest
OSA in CSCR patients and normal controls. The Berlin Questionnaire, a validated
research tool to assess risk for OSA, was administered to 29 patients who met the
criteria for active, acute, non-steroid-induced CSCR and 29 controls matched for 
age and sex. In this retrospective case-controlled study, the main outcome
measure was increased risk for OSA. The mean age of the patients was 47.8 years
(range 29-72) and the mean age of controls was 47.3 years (range 25-70).
Seventy-six percent (22) of both groups were men. Survey scores showed 58.6% (17)
of patients with CSCR to be at an increased risk for OSA compared to 31.0% (nine)
of controls. A conditional logistic regression analysis showed that the CSCR
group had a higher proportion with an increased risk for OSA compared to the
control group (odds ratio=3.67; 95% CI: 1.02, 13.14; P = 0.046). Patients with
CSCR may be more likely than other adults to have OSA, and screening for this
sleep disorder should be considered in this population. Further research is
warranted to determine whether sleep apnea may contribute to the development of
CSCR, and to assess whether treatment of sleep apnea might offer a new
therapeutic option for some patients with CSCR.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17457629 [PubMed - indexed for MEDLINE]

908: Indian J Ophthalmol. 2007 May-Jun;55(3):207-11.

Visual acuity and contrast sensitivity outcomes in Indian eyes undergoing
photodynamic therapy with intravitreal injection of triamcinolone acetonide in
age-related macular degeneration.

Kumar A, Sinha S, Kumar V.

Vitreous-Retina Service, Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All 
India Institute of Medical Sciences, New Delhi, India. akum66mm@del6.vsnl.net.in

PURPOSE: To evaluate photodynamic therapy (PDT) with verteporfin along with
intravitreal triamcinolone acetonide (IVTA) in the treatment of neovascular
age-related macular degeneration (AMD). MATERIALS AND METHODS: This prospective
interventional case series included 23 patients (23 eyes) of choroidal
neovascularization due to neovascular AMD who were treated with PDT with
verteporfin followed by an injection of 4 mg IVTA. The main outcome measures were
visual acuity (VA), contrast sensitivity, retreatment frequency with PDT (and
triamcinolone) and frequency of side-effects. RESULTS: Twenty-three eyes
underwent PDT with verteporfin followed by IVTA one week later. All patients were
followed up for one year. Initial VA ranged from 20/32 to 20/800 and final VA
ranged from 20/40 to 20/500 at the end of 12 months. VA stabilized (that is
loss/gain < 2 lines) in 19 (82%) eyes. Contrast sensitivity also improved in
16/23 eyes (70%). Lesion type and patient's age had no influence on the outcome, 
but baseline VA had a borderline statistically significant effect (P =0.059). Six
eyes (27%) had an increase in intraocular pressure that required therapy. There
were no cases of endophthalmitis, but four eyes (18%) developed significant
cataract that required surgery during the follow-up period. CONCLUSION: The
combination of PDT along with IVTA improves contrast sensitivity and stabilizes
vision during one-year follow-up.

PMID: 17456939 [PubMed - indexed for MEDLINE]

909: JAMA. 2007 Apr 25;297(16):1793-800.

Erratum in:
    JAMA. 2007 Jun 20;297(23):2585.

Comment in:
    JAMA. 2007 Oct 10;298(14):1637; author reply 1637.

Association of CFH Y402H and LOC387715 A69S with progression of age-related
macular degeneration.

Seddon JM, Francis PJ, George S, Schultz DW, Rosner B, Klein ML.

Ophthalmic Epidemiology and Genetics Service, Department of Ophthalmology,
Tufts-New England Medical Center, Boston, MA 02111, USA. jseddon@earthlink.net

CONTEXT: Studies have reported that single-nucleotide polymorphisms in the genes 
CFH and LOC387715 are associated with age-related macular degeneration (AMD).
OBJECTIVE: To assess whether these genetic variants have prognostic importance
for progression to advanced AMD and related visual loss. DESIGN, SETTING, AND
PARTICIPANTS: Prospective analysis of 1466 white participants in the Age-Related 
Eye Disease Study (AREDS), a US multicenter clinical trial conducted from 1990 to
2001 with a mean follow-up time of 6.3 years. Age-related macular degeneration
status was determined by grading of fundus photographs. Progression (n = 281) was
defined as newly diagnosed advanced AMD (geographic atrophy, exudative disease,
or AMD causing visual loss) in one or both eyes during the course of the study.
Genotypic analysis was conducted in 2006. MAIN OUTCOME MEASURE: Incidence rates
of dry and neovascular advanced AMD. RESULTS: The CFH Y402H and LOC387115 A69S
polymorphisms were each independently related to progression from early or
intermediate stages to advanced stages of AMD, controlling for demographic
factors, smoking, body mass index, and AREDS vitamin-mineral treatment
assignment, with odds ratios (ORs) of 2.6 (95% confidence interval [CI], 1.7-3.9)
for CFH and 4.1 (95% CI, 2.7-6.3) for LOC387715 for the homozygous risk genotypes
(P<.001 for trend for each additional risk allele for both genes). The effect of 
LOC387715 was stronger for progression to neovascular disease (OR, 6.1; 95% CI,
3.3-11.2) compared with geographic atrophy (OR, 3.0; 95% CI, 1.4-6.5) relative to
no progression for the homozygous risk state. The presence of all adverse factors
(both risk genotypes, smoking, and body mass index > or =25) increased risk
19-fold. Smoking and high body mass index increased odds of progression within
each risk genotype. Genetic plus nongenetic risk scores provided an area under
the receiver operating characteristic curve of up to 0.78. CONCLUSIONS: Common
polymorphisms in the genes CFH and LOC387715 are independently related to AMD
progression after adjustment for other known AMD risk factors. Presence of these 
polymorphisms plus smoking [corrected] and body mass index of 25 or higher,
controlling for AREDS vitamin-mineral treatment, identifies [corrected] patients 
who are highly susceptible to developing advanced states [corrected] of this
visually disabling disease.

Publication Types: 
    Multicenter Study
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17456821 [PubMed - indexed for MEDLINE]

910: Curr Eye Res. 2007 Mar;32(3):241-7.

Evaluation of macular changes after uncomplicated phacoemulsification surgery by 
optical coherence tomography.

Perente I, Utine CA, Ozturker C, Cakir M, Kaya V, Eren H, Kapran Z, Yilmaz OF.

Beyoglu Eye Research and Training Hospital, Istanbul, Turkey.

PURPOSE: To evaluate the effect of uncomplicated phacoemulsification surgery on
macula by optical coherence tomography (OCT). METHODS: A total of 110 eyes of 102
patients who underwent uncomplicated phacoemulsification and foldable intraocular
lens implantation at Beyoglu Eye Research and Training Hospital between February 
and March 2005 and who were without any systemic disease, fundus or other ocular 
pathology were included. Postoperatively, topical prednisolone acetate (6 x 1)
and ofloxacine (5 x 1) was started, and by decreasing the dosage progressively,
treatment was continued for 6 weeks. Full ophthalmologic and OCT examinations
were done preoperatively and at the postoperative 1st day, 1st week, 1st, 3rd,
and 6th months. Mean retinal thicknesses, volumetric analyses at central fovea,
superior, inferior, temporal, and nasal macular quadrants, and thinnest foveal
retinal thicknesses were recorded. Preoperative and postoperative measurements
were analyzed statistically by using ANOVA test, paired samples t-test with
Bonferroni correction, and Pearson's correlation test. RESULTS: The mean central 
foveal retinal thickness was preoperatively 202.4 +/- 25.9 micro m,
postoperatively 200.4 +/- 26.1 micro m at 1st day (p = 0.29), 208.4 +/- 27.6
micro m at 1st week (p = 0.29), 226.2 +/- 54.9 micro m at 1st month, 215.2 +/-
24.0 micro m at 3rd month, 213.5 +/- 29.4 micro m at 6th month (p < 0.001).
Perifoveal macular thicknesses at superior, inferior, temporal, and nasal
quadrants were 264.9 +/- 28.8 micro m, 266.1 +/- 29.5 micro m, 255.0 +/- 31.3
micro m, 260.3 +/- 34.0 micro m, respectively, preoperatively; 287.9 +/- 28.4
micro m, 288.0 +/- 26.3 micro m, 286.8 +/- 33.1 micro m, 272.0 +/- 32.4 micro m, 
respectively, at postoperative 1st month (p < 0.001). The change in mean central 
foveal thickness, foveal thinnest retinal thickness, mean perifoveal retinal
thickness and volumetric analyses was insignificant at postoperative 1st day (p >
0.05), and significant at 1st week, 1st, 3rd, and 6th months (p < 0.05 for all
measurements). CONCLUSIONS: Statistically significant increase in macular
thickness was detected at postoperative early periods, after the 1st week after
uncomplicated cataract operation. The increase in macular thickness starts from
parafoveal regions. Longer follow-up of patients is required for the macular
consequences, and different treatment protocols should be studied in a randomized
controlled fashion.

PMID: 17453944 [PubMed - indexed for MEDLINE]

911: Int Ophthalmol. 2007 Oct;27(5):299-306. Epub 2007 Apr 24.

Two-year results of intravitreal triamcinolone acetonide injection for the
treatment of diabetic macular edema.

Batioğlu F, Ozmert E, Parmak N, Celik S.

Department of Ophthalmology, Faculty of Medicine, Ankara University, Mamak
Street, Ankara 06100, Turkey. fbatioglu@gmail.com

PURPOSE: To investigate 2-year results of intravitreal triamcinolone acetonide
injection for the treatment of diffuse diabetic macular edema unresponsive to
previous laser photocoagulation. METHOD: The study included 75 eyes of 75
diabetic patients with clinically significant diffuse macular edema that had
failed to respond to previous laser photocoagulation. An intravitreal injection
of triamcinolone acetonide at the dose of 4 mg/0.1 ml was administered.
Best-corrected visual acuity was measured as the logarithm of the minimum angle
of resolution (logMAR), and central macular thickness was obtained by optical
coherence tomography at each visit. Intraocular pressure and lenticular status
were also evaluated. Differences among measurements were evaluated by Friedman
two-way analysis of variance by ranks. Mean follow-up period was 24.7 +/- 5.9
months. RESULTS: The mean central macular thickness, which was obtained 3 days, 1
month, 3 months, 6 months, 9 months, 12 months, 18 months and 24 months
postoperatively, was significantly different from the baseline measurement (P <
0.001). Mean best-corrected logMAR visual acuity improved significantly from
baseline at the 1- month and 3-month follow-up intervals (P < 0.05), but there
was no significant change at the 6- month, 9-month, 12-month, 18-month or
24-month follow-up periods (P > 0.05). During the follow-up, 29 (38.7%) eyes
received re-injection of intravitreal triamcinolone. Twenty-one (28%) eyes
developed intraocular pressure values higher than 21 mmHg, and 18 (24%) eyes
developed cataract. Thirteen (17.3%) eyes required cataract and/or glaucoma
surgery. CONCLUSIONS: In refractory diabetic macular edema, intravitreal
triamcinolone effectively reduces foveal thickness and improves visual acuity in 
the short term, but with the extended follow-up, the number of recurrences and
steroid-related complications were shown to increase. Nevertheless, it may be a
therapeutic option in some patients that do not respond to previous laser
photocoagulation.

PMID: 17453151 [PubMed - indexed for MEDLINE]

912: Am J Ophthalmol. 2007 May;143(5):889-90. Epub 2006 Dec 29.

Age-related macular degeneration in very old individuals with family history.

Geirsdottir A, Stefansson E, Jonasson F, Helgadottir G, Sigurdsson H.

Department of Ophthalmology, Landspitali-University Hospital, Reykjavik, Iceland.

PURPOSE: To study age-related macular degeneration (AMD) in old and very old
individuals with family history of AMD to find the proportion of those with early
and advanced AMD. DESIGN: Retrospective cross-sectional cohort study of
individuals with family history of AMD. METHODS: Database of 897 AMD patients
ages 75 to 102 years with family history of AMD was compiled. Color fundus
photographs were graded in a masked fashion according to the International
Classification of AMD. RESULTS: With increasing age, a gradually larger
proportion of participants had advanced AMD; 54% (469 of 863) of all those 75
years and older had advanced AMD, 64% (258 of 406) of all those 85 years and
older, 74% (37 of 50) of all those 95 years and older, and all (eight of eight)
100 years and older had advanced AMD. CONCLUSIONS: All the centenarians in the
present study had advanced AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17452183 [PubMed - indexed for MEDLINE]

913: Ideggyogy Sz. 2007 Mar 30;60(3-4):169-72.

Association of apolipoprotein E polymorphism with age-related macular
degeneration and Alzheimer's disease in south-western Hungary.

Kovács KA, Pámer Z, Kovács A, Fekete S, Miseta A, Kovács B, Kovács GL.

Department of Ophthalmology, University of Pécs, Pécs.

BACKGROUND: Age-related macular degeneration (AMD) and Alzheimer dementia (AD)
show similarities (advanced age, formation of deposits of similar content).
Recently apolipoprotein E 2 (apoE 2) has been associated with AMD, while apoE4
with AD. The question of coexistence, especially with respect to the genetic
background has not been studied earlier. We investigated, therefore, the
occurrence of AMD in AD patients and compared their lipid profile and apoE
polymorphism. METHODS:- 49 AMD, 32 AD and 27 control patients were examined (risk
factors, visual acuity, slit lamp biomicroscopy, fundoscopy). Following
measurement of triglyceride, total and HDL cholesterol levels, apoE mutation
analysis was performed. RESULTS: AMD was found in 8% of the cooperating AD
patients. The prevalence of the apoE 4 isoforms in the AMD, AD and the control
patients was 2%, 47% and 22%, while that of apoE 2 was 17%, 6% and 7%,
respectively. The prevalence of apoE 3 isoform was 82%, 41% and 71%,
respectively. Triglyceride, total and HDL cholesterol were in the reference
range; however, AD patients were characterized by a lower total cholesterol
value. CONCLUSION: The new finding of this publication is the rare occurrence of 
AMD among AD patients. The higher frequency of apoE 4 among the AD population,
and the higher frequency of apoE 2 among AMD patients in the South-Western region
of Hungary confirms the findings of other investigators.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 17451062 [PubMed - indexed for MEDLINE]

914: Br J Ophthalmol. 2007 May;91(5):649-54.

Two-year results of surgical removal of choroidal neovascular membranes related
to non-age-related macular degeneration.

Essex RW, Tufail A, Bunce C, Aylward GW.

Moorfields Eye Hospital, City Road, London EC1V 2PD, UK.

PURPOSE: To present the 2-year outcomes of surgical removal of non-age-related
macular degeneration (AMD)-related choroidal neovascular membranes and to
evaluate any association between visual outcome and baseline clinical factors.
METHODS: Retrospective consecutive case series. All patients who had surgery for 
non-AMD-related choroidal neovascularisation (CNV) between November 1997 and
March 2003 under the care of a single surgeon (WA) were included in the study.
Baseline data including patient age, duration of subfoveal CNV, preoperative
visual acuity (VA), lesion size, lesion components and aetiology were collected. 
The primary outcome was VA change with secondary outcomes retinal detachment,
operative peripheral retinal break formation, CNV recurrence and cataract.
RESULTS: A total of 52 eyes were included in the study. The aetiology of CNV was:
punctate inner choridopathy 21 (40%); idiopathic 8 (15%); pathologic myopia 6
(12%); ocular histoplasmosis syndrome 1 (2%); and other 16 (31%). The mean age of
patients was 41(range 14-72) years. 24-month follow-up was available for 41 (80%)
eyes. The mean logMAR equivalent baseline acuity was 1.1 and mean lesion size 1.2
disc areas. An improvement in VA >1 Snellen line was noted in 26 (63%) eyes,
whereas 10 (24%) eyes remained the same (within 1 line) and 5 (12%) lost >1 line 
of acuity. Improvement in VA was associated with worse baseline VA (84% for eyes 
with VA <or=6/36 vs 31% for those with VA>6/36, p=0.001). No evidence of
association between 2-year visual outcome and any other baseline factor under
study was observed. Peripheral retinal breaks were noted in 5 (10%) eyes at the
time of surgery, and 3 (5.8%) eyes developed postoperative retinal detachments.
Persistent/recurrent CNV was noted in 17 (33%) eyes. The median time to
presentation of CNV in these eyes was 27 (range 2-172) weeks. Five eyes underwent
cataract surgery during the follow-up period. The mean age of these patients was 
significantly higher than the mean age of those who did not require cataract
surgery (57 vs 37 years, p=0.014). CONCLUSIONS: Surgical excision of
non-AMD-related CNV resulted in improvement of VA in the majority of eyes. Worse 
presenting acuity was associated with better visual improvements.

PMID: 17446505 [PubMed - indexed for MEDLINE]

915: Ophthalmology. 2007 Nov;114(11):2061-9. Epub 2007 Apr 18.

Relationship of macular microcirculation and retinal thickness with visual acuity
in diabetic macular edema.

Sakata K, Funatsu H, Harino S, Noma H, Hori S.

Department of Ophthalmology, Tokyo Women's Medical University, Tokyo, Japan.
sakata@oph.twmu.ac.jp

PURPOSE: To assess perifoveal capillary blood flow velocity (BFV), capillary
occlusion, and retinal thickness at the central fovea in diabetic patients with
or without clinically significant macular edema; to examine the relationships of 
these variables with visual acuity (VA); and to identify their contributions to
visual outcome and diabetic macular edema. DESIGN: Comparative cross-sectional
prospective study. PARTICIPANTS AND CONTROLS: Diabetic patients with clinically
significant macular edema (CSME) (n = 22), matched diabetic patients without CSME
(n = 22), and healthy volunteers (n = 16). METHODS: Capillary BFV was measured by
fluorescein angiography using a scanning laser ophthalmoscope and was analyzed by
the tracing method. Severity of perifoveal capillary abnormalities was classified
by the size and outline of the foveal avascular zone (FAZ) and extent of foveal
capillary loss. Macular thickness was measured by optical coherence tomography.
Each subject underwent a complete ophthalmic evaluation, and best-corrected VA
(BCVA) was converted to the logarithm of the minimum angle of resolution scale.
MAIN OUTCOME MEASURES: Relationship of perifoveal capillary BFV, capillary
occlusion, and foveal thickness with VA. RESULTS: Best-corrected VA significantly
differed among all 3 groups (P<0.0001). Best-corrected VA correlated negatively
with BFV (r = -0.644, P<0.0001) among all subjects and positively with retinal
thickness at the central fovea in diabetic patients with CSME (r = 0.640, P =
0.0013). There was a positive correlation between BCVA and severity in the size
of the FAZ (r = 0.484, P = 0.0015), outline of the FAZ (r = 0.542, P = 0.0004),
and extent of foveal capillary loss (r = 0.585, P = 0.0001) among all diabetic
subjects. Multiple regression analysis showed that retinal thickness at the
central fovea was the only variable that significantly predicted VA (standardized
regression coefficient, 0.635; P = 0.0001). CONCLUSIONS: Best-corrected VA was
associated with perifoveal capillary BFV, severity of perifoveal capillary
occlusion, and retinal thickness at the central fovea in diabetic patients, but
the greatest contributing factor was only the retinal thickness.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 17445900 [PubMed - indexed for MEDLINE]

916: Ophthalmologica. 2007;221(3):143-52.

Inflammation in dry age-related macular degeneration.

Rodrigues EB.

Retina Department, Ophthalmology Service, Hospital Regional São José, Instituto
de Olhos Florianópolis/Centro Oftalmológico, Florianópolis, Brazil.
edubrodriguess@yahoo.com.br

PURPOSE: To summarize the current information regarding the role of immune and
inflammatory response in the pathogenesis of dry age-related macular degeneration
(ARMD). METHODS: A Pubmed search was conducted of the period January 1999 to
2005. Relevant information in the literature on the role of inflammation in early
dry ARMD was reviewed. RESULTS: Some important evidence for inflammation in early
ARMD consists in the isolation of immunoglobulins, complement proteins, cytokines
and activated microglia, in retinal pigment epithelium (RPE) cells and drusen.
Pivotal mechanisms in early ARMD include the accumulation of debris and proteins 
along the RPE surface, followed by immune-complex deposition and complement
activation. In contrast, the role of other plasma enzymes such as
kallikrein-kinin-bradykinin, the Hageman factor, peptides and coagulation
proteins in drusen formation and ARMD has yet to be determined. CONCLUSION: A
clear role for inflammatory mediators and cells has been established in recent
years. Future studies should elucidate further mechanisms in ARMD development.
Copyright (c) 2007 S. Karger AG, Basel.

Publication Types: 
    Review

PMID: 17440275 [PubMed - indexed for MEDLINE]

917: Ann Med. 2006;38(8):592-604.

Extended haplotypes in the complement factor H (CFH) and CFH-related (CFHR)
family of genes protect against age-related macular degeneration:
characterization, ethnic distribution and evolutionary implications.

Hageman GS, Hancox LS, Taiber AJ, Gehrs KM, Anderson DH, Johnson LV, Radeke MJ,
Kavanagh D, Richards A, Atkinson J, Meri S, Bergeron J, Zernant J, Merriam J,
Gold B, Allikmets R, Dean M; AMD Clinical Study Group.

Department of Ophthalmology and Visual Sciences, Cell Biology and Functional
Genomics Laboratory, The University of Iowa, 11190E PFP, 200 Hawkins Drive, Iowa 
City, Iowa 52240, USA. gregory-hageman@uiowa.edu

BACKGROUND: Variants in the complement factor H gene (CFH) are associated with
age-related macular degeneration (AMD). CFH and five CFH-related genes (CFHR1-5) 
lie within the regulators of complement activation (RCA) locus on chromosome
1q32. Aims and Methods. In this study, the structural and evolutionary
relationships between these genes and AMD was refined using a combined genetic,
molecular and immunohistochemical approach. RESULTS: We identify and characterize
a large, common deletion that encompasses both the CFHR1 and CFHR3 genes. CFHR1, 
an abundant serum protein, is absent in subjects homozygous for the deletion.
Genotyping analyses of AMD cases and controls from two cohorts demonstrates that 
deletion homozygotes comprise 1.1% of cases and 5.7% of the controls
(chi-square=32.8; P= 1.6 E-09). CFHR1 and CFHR3 transcripts are abundant in
liver, but undetectable in the ocular retinal pigmented epithelium/choroid
complex. AMD-associated CFH/CFHR1/CFHR3 haplotypes are widespread in human
populations. CONCLUSION: The absence of CFHR1 and/or CFHR3 may account for the
protective effects conferred by some CFH haplotypes. Moreover, the high
frequencies of the 402H allele and the delCFHR1/CFHR3 alleles in African
populations suggest an ancient origin for these alleles. The considerable
diversity accumulated at this locus may be due to selection, which is consistent 
with an important role for the CFHR genes in innate immunity.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17438673 [PubMed - indexed for MEDLINE]

918: Mol Vis. 2007 Apr 4;13:545-8.

HTRA1 promoter polymorphism predisposes Japanese to age-related macular
degeneration.

Yoshida T, DeWan A, Zhang H, Sakamoto R, Okamoto H, Minami M, Obazawa M, Mizota
A, Tanaka M, Saito Y, Takagi I, Hoh J, Iwata T.

National Institute of Sensory Organs, National Hospital Organization Tokyo
Medical Center, Tokyo, Japan.

PURPOSE: To study the effect of candidate single nucleotide polymorphisms (SNPs) 
on chromosome 10q26, recently shown to be associated with wet age-related macular
degeneration (AMD) in Chinese and Caucasian cohorts, in a Japanese cohort.
METHODS: Using genomic DNA isolated from peripheral blood of wet AMD cases and
age-matched controls, we genotyped two SNPs, rs10490924, and rs11200638, on
chromosome 10q26, 6.6 kb and 512 bp upstream of the HTRA1 gene, respectively,
using temperature gradient capillary electrophoresis (TGCE) and direct
sequencing. Association tests were performed for individual SNPs and jointly with
SNP complement factor H (CFH) Y402H. RESULTS: The two SNPs, rs10490924 and
rs11200638, are in complete linkage disequilibrium (D'=1). Previous sequence
comparisons among seventeen species revealed that the genomic region containing
rs11200638 was highly conserved while the region surrounding rs10490924 was not. 
The allelic association test for rs11200638 yielded a p-value <10(-11). SNP
rs11200638 conferred disease risk in an autosomal recessive fashion: Odds ratio
was 10.1 (95% CI 4.36, 23.06), adjusted for SNP CFH 402, for those carrying two
copies of the risk allele, whereas indistinguishable from unity if carrying only 
one risk allele. CONCLUSIONS: The HTRA1 promoter polymorphism, rs11200638, is a
strong candidate with a functional consequence that predisposes Japanese to
develop neovascular AMD.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17438519 [PubMed - indexed for MEDLINE]

919: Curr Opin Ophthalmol. 2007 May;18(3):240-4.

Treatment of neovascular age-related macular degeneration: past, present and
future directions.

Smith BT, Joseph DP, Grand MG.

Barnes Retina Institute, Washington University Department of Ophthalmology and
Visual Sciences, St Louis, Missouri, USA. smithbradleythomas@Msn.com

PURPOSE OF REVIEW: The treatment options of choroidal neovascularization due to
age-related macular degeneration have expanded. Prior to ocular photodynamic
therapy the only available treatment was laser photocoagulation. Clinicians and
patients were not particularly enthusiastic despite its ability to stabilize
vision. The purpose of the review is to review the past and current concepts of
neovascular age-related macular degeneration therapy and to provide a short
overview of upcoming treatments. RECENT FINDINGS: Photodynamic therapy provided
us with the first realistic means to address subfoveal choroidal
neovascularization lesions from age-related macular degeneration. Antivascular
endothelial growth factors now allow better visual outcomes than mere
stabilization of vision and other promising treatments are undergoing study at
this time. SUMMARY: Age-related macular degeneration therapy has undergone a
significant revolution in recent years. Understanding the historical perspective 
of treatment provides a better appreciation of current therapies. Still there is 
no cure for this disease and more promising treatments are currently under
investigation.

Publication Types: 
    Review

PMID: 17435433 [PubMed - indexed for MEDLINE]

920: Curr Opin Ophthalmol. 2007 May;18(3):235-9.

Drug delivery methods for posterior segment disease.

Hsu J.

Retina Service, Wills Eye Institute, Philadelphia, PA 19107, USA.
jasonhsu.md@comcast.net

PURPOSE OF REVIEW: New pharmacotherapies for posterior segment diseases of the
eye have been recently introduced which use novel drug delivery methods. The
various current and potential future methods will be discussed. RECENT FINDINGS: 
Drug delivery systems have been developed which can provide controlled release of
drug for potentially long periods of time. Ideal candidates for these devices are
chronic conditions that require repeated local administration of drug, such as
noninfectious intermediate or posterior uveitis, neovascular age-related macular 
degeneration, and persistent macular edema due to diabetic retinopathy or venous 
occlusive disease. Recently, Retisert (Bausch & Lomb, Rochester, New York, USA), 
a nonbiodegradable fluocinolone acetonide implant, was approved for use in
noninfectious uveitis affecting the posterior segment and is currently in
clinical trials for the treatment of macular edema. A biodegradable dexamethasone
implant is currently in clinical trials for the treatment of uveitis and diabetic
macular edema. SUMMARY: With the development of therapeutic agents that require
repeated administration comes a need for new strategies to improve safety and
maximize efficacy. Novel drug delivery systems involving nonbiodegradable or
biodegradable implants, microparticulates or nanoparticulates, liposomes, or
transscleral iontophoresis may provide the solution.

Publication Types: 
    Review

PMID: 17435432 [PubMed - indexed for MEDLINE]

921: Curr Opin Ophthalmol. 2007 May;18(3):220-3.

Nutritional supplementation in age-related macular degeneration.

Coleman H, Chew E.

Division of Epidemiology and Clinical Research, National Eye Institute/National
Institutes of Health, Bethesda, Maryland, USA.

PURPOSE OF REVIEW: This review assesses the current status of the knowledge of
the role of nutrition in age-related macular degeneration - a leading cause of
vision loss in the persons with European ancestry. RECENT FINDINGS: We will
evaluate the different nutritional factors and both observational and
interventional studies used to assess the association of nutrition with
age-related macular degeneration. Persons with intermediate risk of age-related
macular degeneration or advanced age-related macular degeneration in one eye are 
recommended to take the formulation proven in the Age-Related Eye Disease Study
(AREDS) to be successful in preventing the development of advanced age-related
macular degeneration by 25%. The formulation consists of vitamins C, E,
beta-carotene and zinc. In addition, observational data suggest that high dietary
intake of macular xanthophylls lutein and zeaxanthin are associated with a lower 
risk of advanced age-related macular degeneration. Similarly, long-chain
polyunsaturated fatty acids derived from fish consumption are also associated
with a decreased risk of advanced age-related macular degeneration. SUMMARY:
Persons with intermediate age-related macular degeneration or advanced
age-related macular degeneration (neovascular or central geographic atrophy) in
one eye should consider taking the AREDS-type supplements. Further evaluation of 
nutritional factors, specifically, lutein/zeaxanthin and omega-3 fatty acids will
be tested in a multicenter controlled, randomized trial - the Age-Related Eye
Disease Study 2 (AREDS2).

Publication Types: 
    Review

PMID: 17435429 [PubMed - indexed for MEDLINE]

922: Curr Opin Ophthalmol. 2007 May;18(3):206-11.

Pharmacoeconomics and macular degeneration.

Brown GC, Brown MM, Brown H, Godshalk AN.

Center for Value-Based Medicine, Flourtown, Pennsylvania 19031, USA.
gbrown@valuebasedmedicine.com

PURPOSE OF REVIEW: To describe pharmacoeconomics and its relationship to drug
interventions. RECENT FINDINGS: Pharmacoeconomics is the branch of economics
which applies cost-minimization, cost-benefit, cost-effectiveness and
cost-utility analyses to compare the economics of different pharmaceutical
products or to compare drug therapy to other treatments. Among the four
instruments, cost-utility analysis is the most sophisticated, relevant and
clinically applicable as it measures the value conferred by drugs for the monies 
expended. Value-based medicine incorporates cost-utility principles but with
strict standardization of all input and output parameters to allow the
comparability of analyses, unlike the current situation in the healthcare
literature. SUMMARY: Pharmacoeconomics is assuming an increasingly important role
with regard to whether drugs are listed on the drug formulary of a country or
province. It has been estimated that the application of standardized, value-based
medicine drug analyses can save over 35% from a public healthcare insurer drug
formulary while maintaining or improving patient care.

Publication Types: 
    Review

PMID: 17435427 [PubMed - indexed for MEDLINE]

923: Curr Opin Ophthalmol. 2007 May;18(3):201-5.

Age-related macular degeneration: the costs to society and the patient.

Gupta OP, Brown GC, Brown MM.

Retina Service, Wills Eye at Thomas Jefferson University, Philadelphia, USA.
ogupta@hotmail.com

PURPOSE OF REVIEW: The current literature was reviewed to assess the patient and 
societal costs associated with age-related macular degeneration (ARMD). RECENT
FINDINGS: An increasing number of studies discuss the growing direct
ophthalmologic, direct nonophthalmologic, and indirect costs associated with
ARMD. Most reports, however, focus on only one of these aspects. The prevalence
of this debilitating disease will increase as life expectancy increases. SUMMARY:
ARMD continues to be a major public health problem in developed countries. The
treatment and management of exudative ARMD are changing dramatically. These
therapies will likely become a more significant portion of the overall healthcare
burden of ARMD. To date, no comprehensive study exists that attempts to calculate
the total cost of ARMD.

Publication Types: 
    Review

PMID: 17435426 [PubMed - indexed for MEDLINE]

924: Curr Opin Ophthalmol. 2007 May;18(3):194-200.

Value-based medicine and interventions for macular degeneration.

Brown MM, Brown GC, Brown H.

Center for Value-Based Medicine, Flourtown, USA. mbrown@valuebasedmedicine.com

PURPOSE OF REVIEW: The aim of this article is to review the patient value
conferred by interventions for neovascular macular degeneration. RECENT FINDINGS:
Value-based medicine is the practice of medicine based upon the patient value
(improvement in quality of life and length of life) conferred by an intervention.
For ophthalmologic interventions, in which length-of-life is generally
unaffected, the value gain is equivalent to the improvement in quality of life.
Photodynamic therapy delivers a value gain (improvement in quality of life) of
8.1% for the average person with classic subfoveal choroidal neovascularization, 
while laser photocoagulation for the same entity confers a 4.4% improvement in
quality of life. Preliminary data suggest the value gain for the treatment of
occult/minimally classic choroidal neovascularization with ranibizumab is greater
than 15%. The average value gain for statins for the treatment of hyperlipidemia 
is 3.9%, while that for the use of biphosphonates for the treatment of
osteoporosis is 1.1% and that for drugs to treat benign prostatic hyperplasia is 
1-2%. SUMMARY: Interventions, especially ranibizumab therapy, for neovascular
macular degeneration appear to deliver an extraordinary degree of value compared 
with many other interventions across healthcare.

Publication Types: 
    Review

PMID: 17435425 [PubMed - indexed for MEDLINE]

925: Br J Ophthalmol. 2007 Sep;91(9):1244-6. Epub 2007 Apr 12.

Comment in:
    Br J Ophthalmol. 2008 Jul;92(7):1010.    Br J Ophthalmol. 2008 Jun;92(6):866-7.

Ranibizumab (Lucentis) versus bevacizumab (Avastin): modelling cost
effectiveness.

Raftery J, Clegg A, Jones J, Tan SC, Lotery A.

Wessex Institute for Health R&D, Medical School, University of Southampton,
Southampton, UK. raftery@soton.ac.uk

Two new drugs provide startling benefits in the treatment of age-related macular 
degeneration (AMD). The clinical and cost effectiveness of ranibizumab (Lucentis)
was compared to that of bevacizumab (Avastin), which costs up to 100 times less. 
A cost effectiveness model was developed to assess the cost per quality adjusted 
life year (QALY) over 10 years. For predominantly classic AMD, the efficacy of
bevacizumab relative to ranibizumab would have to be around 40% for the latter to
achieve 30 k pounds per QALY, a NICE threshold. Similar but worse results applied
to the other main forms of AMD, minimally occult and occult with no classic
lesions. The price of ranibizumab would have to be drastically reduced for it to 
be cost effective. Continued unlicensed use of bevacizumab raises ethical, legal 
and policy questions. Public pressure may be the most potent weapon in persuading
Genentech to license bevacizumab for AMD.

Publication Types: 
    Comparative Study

PMID: 17431015 [PubMed - indexed for MEDLINE]

926: Clin Experiment Ophthalmol. 2007 Apr;35(3):287-8.

In vivo microscopy of Best's Vitelliform Macular Dystrophy: optical coherence
tomography study of combined stage III and IV lesions.

Arora R, Das S, Shroff D, Narula R, Chauhan D.

A 35-year-old man presented with decreased vision in both eyes. Fundus
biomicroscopy of the right eye revealed a pseudohypopyon along with an area of
hyperpigmentation and scarring at the macula (combined stage III and IVb Best's
Vitelliform Macular Dystrophy [BVMD]). The left eye showed the presence of a
pseudohypopyon along with macular atrophy (combined stage III and IVa). On
optical coherence tomography both eyes had a neurosensory retinal detachment with
an optically clear subretinal zone, an accumulation of material between
neurosensory retina and the retinal pigment epithelium corresponding to the
pseudohypopyon and subfoveal photoreceptor atrophy. We document on optical
coherence tomography the transition of BVMD from stage III to IV (in the form of 
the combined stage). These new findings may be considered unique for this stage
of BVMD, and would help in a further understanding of the disease as it passes
through its various stages.

Publication Types: 
    Case Reports
    Letter

PMID: 17430522 [PubMed - indexed for MEDLINE]

927: Clin Experiment Ophthalmol. 2007 Apr;35(3):220-4.

Measurement of retinal thickness from three-dimensional images obtained from C
scan images from the optical coherence tomography ophthalmoscope.

Mizota A, Sakuma T, Miyauchi O, Honda M, Tanaka M.

Department of Ophthalmology, Juntendo University Urayasu Hospital, Tomioka,
Urayasu, Japan. mizota@juntendo-urayasu.jp

BACKGROUND: One of the unique features of the optical coherence tomography (OCT) 
ophthalmoscope is that it can record C scan images of the retina. The purpose of 
this study was to determine the best recording time to measure the retinal
thickness with the OCT ophthalmoscope. In addition, the accuracy of the
measurements was examined by comparing the values obtained by the OCT
ophthalmoscope with those obtained with the Stratus OCT Model 3000 (OCT III)
assuming that the OCT III gives an accurate measurement of retinal thickness.
METHODS: The topography mode of the OCT ophthalmoscope was used. First, the
average retinal thickness recorded with 2-s scans was compared with that recorded
with 4-s scans for a recording area of 15 degreesx15 degrees. Next, the average
retinal thickness recorded by the OCT ophthalmoscope was compared with that
obtained by the Fast Macular Thickness program of the OCT III in patients with
macular oedema. RESULTS: The mean retinal thickness of the central area was 208.1
microm for both 2 and 4 s recording times. The average retinal thickness obtained
by the OCT ophthalmoscope was highly correlated and not significantly different
from the values obtained by the OCT III. The largest differences obtained by the 
two instruments were seen in the parts of the retina with accumulation of hard
exudates. CONCLUSIONS: Accurate measurements of retinal thickness can be obtained
with the OCT ophthalmoscope by 2-s scans, and thus, the OCT ophthalmoscope can be
a valuable instrument for clinical assessments of retinal thickness.

PMID: 17430507 [PubMed - indexed for MEDLINE]

928: Cardiovasc Hematol Agents Med Chem. 2007 Apr;5(2):147-54.

Current and emerging concepts in the management of neovascular age-related
macular degeneration.

Maloney SC, Godeiro KD, Odashiro AN, Burnier MN Jr.

The Henry C Witelson Ocular Pathology Laboratory and Registry, McGill University 
Montreal Quebec, Montreal, Quebec, Canada. shawn.maloney@mail.mcgill.ca

Age-related macular degeneration (AMD) is the leading cause of blindness in the
elderly worldwide. The more severe form of the disease, known as neovascular AMD,
is characterized by aberrant growth of blood vessels from the choroid into the
subretinal space. This pathologic choroidal neovascularization can have drastic
consequences, often seriously impairing vision in affected individuals. Current
treatment approaches focus on combination therapies that include photodynamic
therapy in conjunction with numerous forms of antiangiogenic or anti-inflammatory
drug intervention. To date, however, no adequate treatment is available for the
majority of affected individuals. The threat of a rapidly aging population
provides the impetus for aggressive efforts to control the prevalence and
progression of this disease. This review will outline the currently available
pharmacotherapies, discussing the justification for their use as well as their
shortcomings. Furthermore, drugs that are currently under investigation as
monotherapies and adjuncts will be highlighted. The potential for alternate
targets will also be examined, with a focus on the most promising candidates.

Publication Types: 
    Review

PMID: 17430137 [PubMed - indexed for MEDLINE]

929: J Opt Soc Am A Opt Image Sci Vis. 2007 May;24(5):1468-80.

Imaging polarimetry in patients with neovascular age-related macular
degeneration.

Elsner AE, Weber A, Cheney MC, VanNasdale DA, Miura M.

School of Optometry, Indiana University, Bloomington 47405, USA, and University
Hospital RWTH Aachen, Germany. aeelsner@indiana.edu

Imaging polarimetry was used to examine different components of neovascular
membranes in age-related macular degeneration. Retinal images were acquired with 
a scanning laser polarimeter. An innovative pseudocolor scale, based on cardinal 
directions of color, displayed two types of image information: relative phases
and magnitudes of birefringence. Membranes had relative phase changes that did
not correspond to anatomical structures in reflectance images. Further, membrane 
borders in depolarized light images had significantly higher contrasts than those
in reflectance images. The retinal birefringence in neovascular membranes
indicates optical activity consistent with molecular changes rather than merely
geometrical changes.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 17429494 [PubMed - indexed for MEDLINE]

930: Cell Cycle. 2007 May 2;6(9):1122-5. Epub 2007 May 16.

HTRA1 variant confers similar risks to geographic atrophy and neovascular
age-related macular degeneration.

Cameron DJ, Yang Z, Gibbs D, Chen H, Kaminoh Y, Jorgensen A, Zeng J, Luo L,
Brinton E, Brinton G, Brand JM, Bernstein PS, Zabriskie NA, Tang S, Constantine
R, Tong Z, Zhang K.

Department of Ophthalmology and Visual Sciences, Moran Eye Center, University of 
Utah School of Medicine, Salt Lake City, Utah, USA.

Age-related macular degeneration (AMD) is the most common cause of irreversible
visual impairment in the developed world. The two forms of advanced AMD,
geographic atrophy (GA) and choroidal neovascularization (wet AMD), represent two
types of degenerative processes in the macula that lead to loss of central
vision. Soft confluent drusen, characterized by deposits in macula without visual
loss are considered a precursor of advanced AMD. A single nucleotide
polymorphism, rs11200638, in the promoter of HTRA1 has been shown to increases
the risk for wet AMD. However, its impact on soft confluent drusen and GA or the 
relationship between them is unclear. To better understand the role the HTRA1
polymorphism plays in AMD subtypes, we genotyped an expanded Utah population with
658 patients having advanced AMD or soft confluent drusen and 294 normal controls
and found that the rs11200638 was significantly associated with GA. This
association remains significant conditional on LOC387715 rs10490924. In addition,
rs11200638 was significantly associated with soft confluent drusen, which are
strongly immunolabeled with HTRA1 antibody in an AMD eye with GA similar to wet
AMD. Two-locus analyses were performed for CFH Y402H variant at 1q31 and the
HTRA1 polymorphism. Together CFH and HTRA1 risk variants increase the odds of
having AMD by more than 40 times. These findings expand the role of HTRA1 in AMD.
Understanding the underlying molecular mechanism will provide an important
insight in pathogenesis of AMD.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17426452 [PubMed - indexed for MEDLINE]

931: Retina. 2007 Apr-May;27(4):483-9.

Effect of tinted optical filters on visual acuity and contrast sensitivity in
patients with inflammatory cystoid macular edema.

Valentincic NV, Berendschot TT, Hawlina M, Kraut A, Rothova A.

Eye Clinic, University Medical Centre, Ljubljana, Slovenia. vid.val@siol.net

PURPOSE: To ascertain the effect of tinted optical filters (TFs) on visual
function in patients with inflammatory cystoid macular edema (CME). METHODS: A
prospective study included 14 patients with inflammatory CME and best-corrected
visual acuity between 0.1 and 0.8 (CME group) and 16 sex-, age-, and
best-corrected visual acuity-matched patients with macular disorders but no CME
(non-CME group). All patients from both groups underwent the following tests:
determination of visual acuity at distance, contrast sensitivity (CS) testing;
and subjective grading of each TF for best-corrected visual acuity and CS
compared with no TFs. All tests were performed with the following TFs: Corning
photochromic filter with a cutoff at 450 nm; Zeiss filter with a cutoff at 560
nm; and cheap widely available yellow filter with a cutoff at 489 nm. RESULTS:
Without TFs, the CME and non-CME groups did not differ in best-corrected visual
acuity (P = 0.79). Using the TFs, a clinically significant improvement was not
achieved by any patient. However, using the definition of any improvement,
best-corrected visual acuity with all TFs showed a significant improvement in the
CME group compared with no TFs (P < 0.01). The CME group rated the Corning
photochromic filter with a cutoff of 450 nm significantly higher than the other
TFs when determining visual acuity (P = 0.05) and CS (P = 0.01) in contrast to no
improvement in the non-CME group. CONCLUSION: Although the use of TFs for the CME
patients was not associated with criteria of clinically significant improvement, 
our results indicate that visual acuity and CS in patients with inflammatory CME 
might benefit from the use of TFs.

PMID: 17420703 [PubMed - indexed for MEDLINE]

932: Retina. 2007 Apr-May;27(4):458-61.

Photodynamic therapy and high-dose intravitreal triamcinolone to treat exudative 
age-related macular degeneration: 2-year outcome.

Ruiz-Moreno JM, Montero JA, Zarbin MA.

Department of Ophthalmology, Miguel Hernández University School of Medicine,
Alicante, Spain. jm.ruiz@umh.es

PURPOSE: To evaluate the efficacy of photodynamic therapy (PDT) and high-dose
intravitreal triamcinolone acetonide (TA) injection to treat choroidal
neovascularization (CNV) associated with age-related macular degeneration (AMD)
at the 2-year follow-up. METHODS: In this prospective, consecutive, comparative, 
nonrandomized, interventional case series, 30 eyes of 30 consecutive patients
with subfoveal CNV associated with AMD were treated by PDT followed by
intravitreal injection of 19.4 +/- 2.1 mg TA. Fifteen eyes were naive to
treatment (group 1), and 15 had been treated previously by PDT alone (group 2). A
group of 15 eyes of 15 patients treated by PDT alone served as controls. The
number of Snellen lines gained or lost and PDT sessions were evaluated. RESULTS: 
Best-corrected visual acuity (BCVA) did not change significantly in group 1 from 
baseline (0.0 +/- 3.4 Snellen line; range, -5 to 9 Snellen lines; P = 0.81);
group 2 lost an average -0.6 +/- 2.5 line (range, -7 to 3 Snellen lines) (P =
0.41), and the control group lost an average of -2.2 +/- 3.4 lines (range, -8 to 
2 Snellen lines) (P = 0.03, Wilcoxon signed rank test). The average number of PDT
sessions during the 24-month follow-up was 1.9, 1.2, and 3.9 for group 1, group
2, and the control group, respectively. CONCLUSION: Two years after combined
PDT/high-dose intravitreal TA to treat AMD-associated CNV, final BCVA was stable,
and the need for retreatment was reduced compared with historical controls.

PMID: 17420698 [PubMed - indexed for MEDLINE]

933: Retina. 2007 Apr-May;27(4):445-50.

Intravitreal bevacizumab for refractory pigment epithelial detachment with occult
choroidal neovascularization in age-related macular degeneration.

Chen E, Kaiser RS, Vander JF.

Retina Service, Wills Eye Hospital, Philadelphia, Pennsylvania 19107, USA.

PURPOSE: New medications targeting vascular endothelial growth factor show
promise in the treatment of wet macular degeneration. This study describes the
clinical response and optical coherence tomography (OCT) findings for patients
with refractory pigment epithelial detachment (PED) and occult choroidal
neovascular membranes (CNVMs) who were treated with intravitreal bevacizumab.
METHODS: A retrospective analysis of data for 10 patients with fibrovascular
PEDs, initially treated with intravitreal pegaptanib, thermal laser, or
photodynamic therapy with or without triamcinolone acetonide administration, was 
performed. All patients were refractory to previous treatment. They received
monthly injections of bevacizumab and were followed by clinical examination,
angiography, and OCT. RESULTS: Nine of 10 patients had stable or improved vision.
Angiogram findings showed resolution of leakage from CNVMs. OCT demonstrated
resolution of the subretinal or intraretinal fluid but persistence of the PED
itself. Vision improvement was correlated with OCT changes. CONCLUSION:
Intravitreal bevacizumab may be a viable option in treating patients with
fibrovascular PEDs. OCT findings suggest that visual improvement is secondary to 
resolution of subretinal and intraretinal edema without resolution of the PED.

PMID: 17420696 [PubMed - indexed for MEDLINE]

934: Retina. 2007 Apr-May;27(4):439-44.

Intravitreal bevacizumab (Avastin) treatment of neovascular age-related macular
degeneration.

Emerson MV, Lauer AK, Flaxel CJ, Wilson DJ, Francis PJ, Stout JT, Emerson GG,
Schlesinger TK, Nolte SK, Klein ML.

Macular Degeneration Center, Casey Eye Institute, Oregon Health & Science
University, Portland, Oregon, USA.

PURPOSE: To report the change in visual acuity and central retinal thickness by
optical coherence tomography (OCT) after intravitreal injections of bevacizumab
for the treatment of neovascular age-related macular degeneration (AMD). METHODS:
A retrospective case series in a university-based practice evaluated patients
with subfoveal choroidal neovascularization (CNV) due to AMD. Patients received
intravitreal injections (1.25 mg) of bevacizumab and were monitored monthly with 
determination of best-corrected ETDRS visual acuity and OCT for persistence of
retinal thickening. Eyes were retreated on an "as needed" basis, defined by
presence of intraretinal or subretinal fluid. Patients were monitored every 2
months to 3 months for persistence of angiographic leakage. RESULTS: Seventy-nine
eyes of 74 consecutive patients received the initial injection of bevacizumab
between August 1, 2005, and January 30, 2006. Sixty-eight eyes (86%) of 64
patients had at least 3 months of follow-up. Mean central retinal thickness +/-
SD decreased from 304 +/- 83 microm at baseline to 237 +/- 105 microm at 3 months
(P = 0.00002). Mean ETDRS visual acuity gained 4 letters from 20/100 at baseline 
to 20/80-1 at 3 months (P = 0.040). Twenty eyes (25%) appeared to have a
sustained response to a single injection and did not require further injections
through 3 months. Two patients had a potentially drug-related adverse event
(ischemic stroke and myocardial infarction). No serious injection-related adverse
events occurred. CONCLUSIONS: Intravitreal bevacizumab injection affects a rapid 
decrease in retinal thickness to normal or near-normal levels and improvement in 
visual acuity in eyes with CNV due to AMD. The sustainability of changes in
retinal thickness and visual acuity in response to bevacizumab treatment warrant 
further investigation and long-term follow-up.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17420695 [PubMed - indexed for MEDLINE]

935: Retina. 2007 Apr-May;27(4):432-8.

Intravitreal bevacizumab for previously treated choroidal neovascularization from
age-related macular degeneration.

Goff MJ, Johnson RN, McDonald HR, Ai E, Jumper JM, Fu A.

Pacific Vision Foundation, California Pacific Medical Center, San Francisco,
California, USA.

PURPOSE: To report the optical coherence tomography (OCT) findings and visual
results in a series of patients treated with intravitreal bevacizumab for
choroidal neovascularization (CNV) associated with age-related macular
degeneration (AMD), and to determine if a difference in treatment effect exists
between previously treated and treatment naïve patients. METHODS: A retrospective
review of all patients treated with intravitreal bevacizumab for CNV from AMD
with visual acuity greater than or equal to 20/320 between September 2005 and
February 2006 was performed. OCT data recorded included central macular thickness
and the presence or absence of cystic intraretinal fluid, subretinal fluid, or
pigment epithelial detachment at the time of the initial injection, at 1-week,
1-month, and 3-month intervals, as well as at the end of follow-up. Visual acuity
measurements were recorded using Early Treatment Diabetic Retinopathy Study
charts. Any ocular or systemic adverse events were recorded. Statistical analysis
was performed to determine if OCT and visual acuity results were significant and 
to determine if a difference in outcomes existed between previously treated
patients and treatment naïve patients. RESULTS: Fifty-four eyes of 51 patients
treated with intravitreal bevacizumab for CNV from AMD were identified. A total
of 178 injections were performed. Mean number of days of follow-up was 138 with
91% of patients having at least 90 days of follow-up. Seventy percent of patients
had undergone previous treatment for CNV. The mean number of intravitreal
bevacizumab injections per eye was 3.3. Combined treatment with photodynamic
therapy was provided in 20% of cases at the initial intravitreal injection. OCT
data for all patients revealed an initial mean thickness of 362 mum, which was
decreased at 1 week to 278 microm (P = 0.001), 235 microm at 1 month (P <
0.0001), 238 microm at 3 months (P = 0.0004), and 244 microm for the end of
follow-up (P < 0.0001). Cystic retinal edema, subretinal fluid, and pigment
epithelial detachment resolved in the majority of cases, but pigment epithelial
detachment frequently took longer to resolve. Initial mean visual acuity was
20/125 (logMAR 0.8), and final mean visual acuity was 20/100 (logMAR 0.7) (P =
0.03). There was no difference in OCT or visual acuity outcomes (P = 0.62 and P =
0.28, respectively) between previously treated and treatment naïve patients.
There was no difference in OCT or visual acuity outcomes (P = 0.67 and P = 0.21, 
respectively) between patients who received combination therapy and those who
received monotherapy with intravitreal bevacizumab. No systemic or ocular adverse
events were recorded. CONCLUSION: Intravitreal bevacizumab for CNV from AMD
results in a rapid decrease in OCT-measured retinal thickness in a majority of
cases. Visual acuity also improved in this series, suggesting a potential
corresponding visual benefit. This series suggests that previously treated and
treatment naïve patients have similar outcomes.

PMID: 17420694 [PubMed - indexed for MEDLINE]

936: Retina. 2007 Apr-May;27(4):426-31.

Comment in:
    Retina. 2008 May;28(5):782; author reply 782-3.

Rebound macular edema following bevacizumab (Avastin) therapy for retinal venous 
occlusive disease.

Matsumoto Y, Freund KB, Peiretti E, Cooney MJ, Ferrara DC, Yannuzzi LA.

Vitreous-Retina-Macula Consultants of New York, and LuEsther T. Mertz Retinal
Research Center, Manhattan Eye, Ear and Throat Hospital, New York, New York
10022, USA.

BACKGROUND: Bevacizumab, a humanized monoclonal antibody to vascular endothelial 
growth factor (VEGF), has been given via intravitreal injection as an off-label
therapy for both neovascular age-related macular degeneration and for macular
edema secondary to retinal vascular disease. The authors describe three patients 
with macular edema secondary to retinal venous occlusion whose edema initially
responded to intravitreal bevacizumab but subsequently recurred in excess of that
observed before treatment. METHODS: This is a retrospective case series of three 
patients with macular edema secondary to retinal vein occlusion treated with
intravitreal bevacizumab. RESULTS: In all three patients, the rebound retinal
edema observed was more pronounced than that present before treatment.
CONCLUSION: These cases suggest a potential limitation of using relatively
short-acting VEGF antagonists in retinal vascular disease of a chronic nature.
Frequent repeated injections may be required to prevent a rebound effect with no 
clearly defined endpoint. Until the long-term safety of multiple injections of
these agents is established, the authors recommend caution in using this
treatment strategy.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 17420693 [PubMed - indexed for MEDLINE]

937: Retina. 2007 Apr-May;27(4):419-25.

Intravitreal bevacizumab (Avastin) in the treatment of macular edema secondary to
branch retinal vein occlusion.

Rabena MD, Pieramici DJ, Castellarin AA, Nasir MA, Avery RL.

California Retina Consultants and Research Foundation, Santa Barbara, CA 93103,
USA.

PURPOSE: To report the authors' experience after intravitreal bevacizumab
(Avastin, Genentech) injection in patients with macular edema (ME) secondary to
branch retinal vein occlusive disease (BRVO). METHODS: A consecutive
retrospective review of patients with ME secondary to BRVO who were treated with 
intravitreal bevacizumab (1.25 mg/0.05 mL). Patients underwent complete
ophthalmic evaluation, which included nonstandardized Snellen visual acuity
testing, optical coherence tomography (OCT), and/or angiographic testing at
baseline and follow-up visits. RESULTS: There were 27 consecutive patients who
received intravitreal bevacizumab injections. The mean length of follow-up was
5.3 months (median 6 months, range 3-8 months). The mean visual acuity improved
from 20/200(-) at baseline to 20/100(-) at 1 month and 20/100(+) at 3 months and 
last follow-up (P < 0.001). The mean central 1 mm macular thickness was 478
microm at baseline and decreased to 310, 336, and 332 microm at 1 month, 3
months, and last follow-up (P < 0.001). Patients received an average of two
injections (range one to three). No adverse side effects were observed following 
injections. CONCLUSION: The observed anatomic (by ophthalmic examination, OCT,
and/or fluorescence angiography) and visual acuity improvements and lack of
serious adverse side effects after intravitreal bevacizumab injection
demonstrates, in principle, the potential of bevacizumab for the treatment of ME 
in this setting.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 17420692 [PubMed - indexed for MEDLINE]

938: Retina. 2007 Apr-May;27(4):399-413.

Tumor necrosis factor antagonists: preliminary evidence for an emerging approach 
in the treatment of ocular inflammation.

Theodossiadis PG, Markomichelakis NN, Sfikakis PP.

Second Department of Ophthalmology, Laikon Hospital, Athens University Medical
School, Greece.

The anti-tumor necrosis factor (TNF) monoclonal antibody infliximab and the
soluble TNF receptor etanercept inhibit the pleiotropic actions of TNF and are
widely used for the treatment of rheumatoid arthritis (RA), juvenile idiopathic
arthritis (JIA), spondyloarthropathies (SpA), Crohn's disease, and psoriasis with
an acceptable safety profile. A pathogenetic role of TNF in ocular inflammatory
conditions has recently emerged from small trials reporting preliminary results
on the efficacy of these agents in patients with noninfectious uveitis,
regardless of the origin of the disease. The authors review the published
experience, derived mostly from investigator-sponsored trials and uncontrolled
case series, on the use of TNF antagonists in approximately 280 patients with
various ocular conditions who were inadequately controlled on currently available
therapy. These reports suggest that TNF antagonists, mainly infliximab, which may
have better efficacy than etanercept, are useful in the treatment of ocular
inflammation associated with Adamantiades-Behçet's disease, RA, JIA, SpA,
Crohn's, sarcoidosis, and Graves' disease ophthalmopathy. Infliximab was also
beneficial in small numbers of patients with idiopathic uveitis or scleritis,
birdshot retinochoroiditis, uveitic and diabetic cystoid macular edema, and
age-related macular degeneration. The currently available data are nonrandomized 
and thus preliminary, providing the foundation and justification for randomized
trials to assess efficacy and safety. Until such results are available, knowledge
regarding the use of anti-TNF regimens in ophthalmology is incomplete. However,
the preliminary evidence points to a growing optimism for targeting TNF in
patients with ocular inflammation.

Publication Types: 
    Review

PMID: 17420690 [PubMed - indexed for MEDLINE]

939: Arch Ophthalmol. 2007 Apr;125(4):534-43.

Subclinical atherosclerotic cardiovascular disease and early age-related macular 
degeneration in a multiracial cohort: the Multiethnic Study of Atherosclerosis.

Klein R, Klein BE, Knudtson MD, Cotch MF, Wong TY, Liu K, Burke GL, Saad MF,
Jacobs DR Jr, Sharrett AR.

Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison
53726-2397, USA. kleinr@epi.ophth.wisc.edu

OBJECTIVE: To investigate the relationship of subclinical atherosclerotic
cardiovascular disease (CVD) and its risk factors with age-related macular
degeneration (AMD) in the Multiethnic Study of Atherosclerosis. METHODS: This
study included 6176 white, black, Hispanic, and Chinese participants aged 44 to
84 years from 6 communities in the United States. Measurements of subclinical CVD
were performed according to standardized protocols. Fundus images were graded
using the Wisconsin Age-Related Maculopathy Grading System. RESULTS: In analyses 
controlled for age, sex, race/ethnicity, and study location, early AMD was
associated with a higher serum high-density lipoprotein cholesterol level (odds
ratio per 15 mg/dL, 1.16; 95% confidence interval, 1.01-1.36) and the presence of
echolucent carotid artery plaque (odds ratio for present vs no plaque, 0.37; 95% 
confidence interval, 0.18-0.74) in the whole cohort. Interactions of
race/ethnicity and early AMD were found for carotid intima-media thickness,
increasing severity of maximum carotid artery stenosis, serum triglyceride level,
subclinical CVD severity, and Agatston calcium score. CONCLUSION: Few
associations were found between subclinical CVD and CVD risk factors with early
AMD. The findings of associations of early AMD with some signs of subclinical
atherosclerotic CVD are different among the 4 racial/ethnic groups, which
suggests that care must be taken in generalizing from one racial/ethnic group to 
another.

Publication Types: 
    Multicenter Study
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17420374 [PubMed - indexed for MEDLINE]

940: Arch Ophthalmol. 2007 Apr;125(4):515-9.

Estimation of systemic complement C3 activity in age-related macular
degeneration.

Sivaprasad S, Adewoyin T, Bailey TA, Dandekar SS, Jenkins S, Webster AR, Chong
NV.

Laser and Retinal Research Unit, King's College Hospital, King's College London, 
England. senswathi@aol.com

OBJECTIVES: To determine the role of systemic complement activation in the
pathogenesis of age-related macular degeneration and to examine whether serum C3a
des Arg reflects systemic complement activation, independent of individual
complement component levels. METHODS: Plasma complement C3a des Arg levels and a 
single nucleotide polymorphism at position 402 of the complement factor H gene
(CFH) were determined in 3 groups of subjects: 42 subjects with early age-related
maculopathy, 42 subjects with neovascular (wet) age-related macular degeneration,
and a control group of 38 subjects with no clinical evidence of age-related
changes at the macula. RESULTS: The median (range) of plasma complement C3a des
Arg levels in the age-related maculopathy and neovascular age-related macular
degeneration groups were 52.6 (2.8-198.1) ng/mL and 60.9 (3.1-173.1) ng/mL,
respectively. The levels were significantly raised compared with the control
group (n = 38), which had a median (range) plasma complement C3a des Arg level of
40.3 (6.1-81.7) ng/mL (analysis of variance, P = .02). The concentration of
plasma C3a des Arg did not differ significantly between those with different CFH 
genotypes (P = .07). CONCLUSION: Systemic activation of the complement system may
contribute to the pathogenesis of age-related macular degeneration independent of
CFH polymorphism. CLINICAL RELEVANCE: The results of this study may be relevant
to aiming new treatment strategies toward reducing systemic low-grade
inflammation.

PMID: 17420372 [PubMed - indexed for MEDLINE]

941: Arch Ophthalmol. 2007 Apr;125(4):469-80.

Comparison of the modified Early Treatment Diabetic Retinopathy Study and mild
macular grid laser photocoagulation strategies for diabetic macular edema.

Writing Committee for the Diabetic Retinopathy Clinical Research Network, Fong
DS, Strauber SF, Aiello LP, Beck RW, Callanan DG, Danis RP, Davis MD, Feman SS,
Ferris F, Friedman SM, Garcia CA, Glassman AR, Han DP, Le D, Kollman C, Lauer AK,
Recchia FM, Solomon SD.

OBJECTIVE: To compare 2 laser photocoagulation techniques for treatment of
diabetic macular edema: the modified Early Treatment Diabetic Retinopathy Study
(ETDRS) direct/grid photocoagulation technique and a potentially milder (but
potentially more extensive) mild macular grid (MMG) laser technique in which
microaneurysms are not treated directly and small mild burns are placed
throughout the macula, whether or not edema is present. METHODS: Two hundred
sixty-three subjects (mean age, 59 years) with previously untreated diabetic
macular edema were randomly assigned to receive laser photocoagulation by either 
the modified ETDRS (162 eyes) or MMG (161 eyes) technique. Visual acuity, fundus 
photographs, and optical coherence tomography measurements were obtained at
baseline and at 3.5, 8, and 12 months. Treatment was repeated if diabetic macular
edema persisted. MAIN OUTCOME MEASURE: Change in optical coherence tomography
measurements at 12-month follow-up. RESULTS: Among eyes with a baseline central
subfield thickness of 250 microm or greater, central subfield thickening
decreased by an average of 88 microm in the modified ETDRS group and by 49 microm
in the MMG group at 12-month follow-up (adjusted mean difference, 33 microm; 95% 
confidence interval, 5-61 microm; P = .02). Weighted inner zone thickening by
optical coherence tomography decreased by 42 microm in the modified ETDRS group
and by 28 microm in the MMG group (adjusted mean difference, 14 microm; 95%
confidence interval, 1-27 microm; P = .04); maximum retinal thickening (maximum
thickening of the central and 4 inner subfields) decreased by 66 and 39 microm,
respectively (adjusted mean difference, 27 microm; 95% confidence interval, 6-47 
microm; P = .01), and retinal volume decreased by 0.8 and 0.4 mm3, respectively
(adjusted mean difference, 0.3 mm3; 95% confidence interval, 0.02-0.53 mm3; P =
.03). At 12 months, the mean change in visual acuity was 0 letters in the
modified ETDRS group and 2 letters worse in the MMG group (adjusted mean
difference, 2 letters; 95% confidence interval, -0.5 to 5 letters; P = .10).
CONCLUSIONS: At 12 months after treatment, the MMG technique was less effective
at reducing optical coherence tomography-measured retinal thickening than the
more extensively evaluated current modified ETDRS laser photocoagulation
approach. However, the visual acuity outcome with both approaches is not
substantially different. Given these findings, a larger long-term trial of the
MMG technique is not justified. APPLICATION TO CLINICAL PRACTICE: Modified ETDRS 
focal photocoagulation should continue to be a standard approach for treating
diabetic macular edema. TRIAL REGISTRATION: clinicaltrials.gov Identifier:
NCT00071773.

Publication Types: 
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, N.I.H., Extramural

PMID: 17420366 [PubMed - indexed for MEDLINE]

942: J Clin Epidemiol. 2007 May;60(5):456-60. Epub 2006 Dec 11.

A randomized trial of Pegaptanib sodium for age-related macular degeneration used
an innovative design to explore disease-modifying effects.

Mills E, Heels-Ansdell D, Kelly S, Guyatt G.

Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, 
Canada. millsej@mcmaster.ca

OBJECTIVE: Effectively evaluating disease-modifying effects in clinical trials
has posed a problem for clinical trialists and drug development. One method that 
has been proposed to evaluate disease-modifying effects has been the
re-randomization of active group participants to discontinue the intervention
after a period sufficient to produce therapeutic effects. We aimed to determine
if this design would permit inferences regarding disease modification in a trial 
evaluating Pegaptanib sodium, an intra-ocular injection, for the treatment of
age-related macular degeneration. STUDY DESIGN AND SETTING: In two identically
designed trials, 1,186 patients were randomized to receive 54 weeks of treatment.
After 54 weeks, 1,053 were re-randomized to either stay on treatment or
discontinue treatment. Patients were seen at multicenter outpatient clinics.
RESULTS: We found that patients randomized to discontinue treatment after 54
weeks of treatment and followed for a further 48 weeks, were significantly
different than the control group (sham) in loss of 15 letters of vision (Relative
Risk 0.70, 95% Confidence Interval 0.57-0.88, P=0.002), indicating that treatment
is disease modifying. This effect was consistent throughout our sensitivity
analyses. CONCLUSION: This trial is the first example of a clinical trial
evaluating disease-modifying effects and this design should influence drug
discovery to determine further therapeutic potential of pharmacologic
interventions.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial

PMID: 17419956 [PubMed - indexed for MEDLINE]

943: Eye. 2008 Jul;22(7):975-7. Epub 2007 Apr 6.

Correlation between microaneurysm closure rate and reduction in macular thickness
following laser photocoagulation of diabetic macular edema.

Sachdev N, Gupta V, Abhiramamurthy V, Singh R, Gupta A.

Department of Ophthalmology, Post Graduate Institute of Medical Education and
Research, Chandigarh, India.

AIM: To correlate the microaneurysmal closure rate measured on fundus fluorescein
angiography (FFA) with reduction in macular thickness observed on optical
coherence tomography (OCT) following laser photocoagulation of diabetic macular
edema. MATERIALS AND METHODS: A prospective observational case series. Fifty
patients (50 eyes) of type II diabetes mellitus with clinically significant
macular oedema (CSME) underwent focal/grid laser photocoagulation. OCT and FFA
were performed at baseline and at 2 and 12 weeks following laser photocoagulation
to measure the change in macular thickness and the number of leaking
microaneurysms respectively. Statistical analysis was performed using
paired-ttest and Pearson's correlation test. RESULTS: A significant reduction in 
macular thickness was seen at both 2 (P=0.02) and 12 weeks (P<0.0001), most
remarkably in the central 1 mm quadrant. However, microaneurysm closure was only 
0.67% at 2 weeks, which increased to 89.6% by 12 weeks. The change in retinal
thickness correlated significantly with the decrease in the number of leaking
microaneurysms at 12 weeks (r=0.597, P<0.0001), but not at 2 weeks (r=-0.228,
P=0.112). On OCT, the final reduction in retinal thickness achieved at 12 weeks
from baseline correlated significantly with the initial decrease in retinal
thickness at 2 weeks (r=0.66, P<0.0001). However, on FFA, the final closure rate 
of leaking microaneurysms at 12 weeks from baseline did not correlate with the
initial closure rate at 2 weeks (r=-0.039, P=0.413). Conclusion: Following laser 
photocoagulation for CSME, an OCT at 2 weeks is more informative and better
correlates with the final outcome than an FFA at 2 weeks.

PMID: 17417620 [PubMed - indexed for MEDLINE]

944: Ann Ophthalmol (Skokie). 2006 Fall;38(3):239-41.

Photodynamic therapy and intravitreal triamcinolone for extrafoveal choroidal
neovascularization in neovascular age-related macular degeneration.

Etter J, Fekrat S.

Albert Eye Research Institute, Duke University Eye Center, Durham, NC 27710, USA.

We report a case of extrafoveal choroidal neovascularization (CNV) secondary to
neovascular age-related macular degeneration treated with photodynamic therapy
(PDT) and intravitreal triamcinolone. Nine months following PDT and intravitreal 
triamcinolone, no ophthalmoscopic or angiographic evidence of recurrent CNV in
the left eye was found. The intraocular pressure (IOP) increased from 10 mmHg on 
presentation to 20 mmHg at 9 months. No IOP-lowering agents were required. The
mild nuclear sclerosis remained unchanged.

Publication Types: 
    Case Reports

PMID: 17416961 [PubMed - indexed for MEDLINE]

945: Ann Ophthalmol (Skokie). 2006 Summer;38(2):153-5.

A case of cystoid macular edema treated by intravitreal triamcinolone in a
patient with systemic lupus erythematosis.

Gupta A, Charles S.

Manchester Royal Eye Hospital, Manchester, United Kingdom. abha16@hotmail.com

We describe the use of intravitreal triamcinolone in the treatment of macular
edema associated with systematic lupus erythematosus providing short-term
resolution of cystoid macular edema and increase in visual acuity. No side
effects from the injection have been seen as yet. We suggest this treatment to be
considered in patients for whom laser treatment may be inappropriate or not
feasible, or even as an alternative/safer option for all patients.

Publication Types: 
    Case Reports

PMID: 17416949 [PubMed - indexed for MEDLINE]

946: Ann Ophthalmol (Skokie). 2006 Summer;38(2):107-10.

Visual acuity in central and branch vein retinal occlusion in the presence of
macular edema: 1 year of follow-up.

Recupero SM, Perdicchi A, Scuderi GL, Amodeo S, Medori EM, Leonardi A.

Department of Ophthalmology II University of Rome "La Sapienza" Sant' Andrea
Hospital, Rome, Italy.

One year after laser treatment of 117 eyes with central or branch retinal vein
occlusion in the presence of macular edema, visual acuity was equally improved in
the central retinal vein occlusion laser-treated and branch retinal vein
occlusion non-laser-treated eyes. We concluded that fluorangiographically evident
ischemic areas or significant macular edema are indications for laser therapy,
and that a poor long-term functional prognosis is always related to more severe
macular damage at the onset.

PMID: 17416938 [PubMed - indexed for MEDLINE]

947: Arch Med Res. 2007 May;38(4):398-402.

Macular edema in unregulated type 2 diabetic patients following glycemic control.

Kayýkçýolu O, Ozmen B, Seymenoglu G, Tunali D, Kafesçiler SO, Güclü F, Hekimsoy
Z.

Ophthalmology Department, Celal Bayar University Medical Faculty, Manisa, Turkey.
orkayikciogluq@yahoo.com

BACKGROUND: We undertook this study to evaluate the changes in macular edema of
uncontrolled type 2 diabetes mellitus patients with the regulation of
hyperglycemia. METHODS: The study population was comprised of 35 type 2 diabetes 
mellitus patients who had poorly regulated blood glucose values. Ophthalmic
examinations including baseline and 6-month macular edema index values of
patients by Heidelberg Retinal Tomography (HRT) macular module were done.
RESULTS: Twenty four (68.6%) female patients and 11 (31.4%) male patients with a 
mean age of 50.7 +/- 10.3 (mean +/- SD) years and mean diabetic duration of 9.8
+/- 7.5 years participated in the study. Twenty two (62.9%) did not have diabetic
retinopathy (DR), whereas 13 (37.2%) had background DR with macular edema. There 
was a significant correlation between duration of diabetes and HRT-II macula
edema index for the right and left eyes (r = 0.40, p = 0.21 and r = 0.40, p =
0.22, respectively). CONCLUSIONS: Macular edema did not change significantly by
regulation of glycemic control in the study group.

PMID: 17416286 [PubMed - indexed for MEDLINE]

948: Eur J Ophthalmol. 2007 Mar-Apr;17(2):230-7.

Intravitreal bevacizumab therapy for choroidal neovascularization secondary to
age-related macular degeneration: 6-month results of an open-label uncontrolled
clinical study.

Giansanti F, Virgili G, Bini A, Rapizzi E, Giacomelli G, Donati MC, Verdina T,
Menchini U.

Department of Oto-Neuro-Ophthalmological Surgical Sciences, Eye Clinic,
University of Florence, Viale Morgagni 85, 50134 Florence, Italy.
fabriziogiansanti@interfree.it

PURPOSE: To investigate the 6-month safety and clinical outcomes of intravitreal 
injections of bevacizumab administered to treat choroidal neovascularization
secondary to age-related macular degeneration. METHODS: Twenty-seven patients
underwent 1.25 mg intravitreal injections of bevacizumab at baseline. A similar
intravitreal injection was administered to all eyes at 1 and 2 month follow-up
visits. At baseline and at each follow-up visit (1, 2, 3, and 6 months), patients
underwent best-corrected visual acuity (BCVA) measurement, fluorescein
angiography, indocyanine green angiography, and optical coherence tomography.
Laboratory testing, visual field analyses, and endothelial cell counts were
performed at baseline and third and sixth months. RESULTS: At 3 months, the mean 
BCVA remained substantially stable at 20/100. Mean central retinal thickness
(CRT) decreased from 373 to 279 microm (p<0.01). Mean lesion greatest linear
dimension (GLD) decreased from 4087 to 3782 microns (p<0.01). At 6 months, mean
BCVA slightly decreased from 20/100(-1) to 20/125(-3) (not significant, p=0.40). 
Mean CRT was still inferior to baseline (305 microm, p<0.01). Mean lesion GLD was
4186 microm, not different from baseline values (p=0.59), but superior to 3-month
mean GLD (p<0.01). Significant visual field defects or endothelial cell losses
were not detected at 3 and 6 months. Laboratory testing did not reveal any
clinically significant deviations compared to baseline values. CONCLUSIONS:
Intravitreal therapy using bevacizumab over 6 months showed stabilization of
visual acuity and choroidal neovascularization activity; the safety data were
convincing.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 17415697 [PubMed - indexed for MEDLINE]

949: Acta Ophthalmol Scand. 2007 Sep;85(6):613-7. Epub 2007 Apr 4.

Enhanced optical coherence patterns of diabetic macular oedema and their
correlation with the pathophysiology.

Soliman W, Sander B, Jørgensen TM.

Department of Ophthalmology, Glostrup Hospital, University of Copenhagen,
Glostrup, Denmark. waelsoliman73@yahoo.com

PURPOSE: To describe different patterns of diabetic macular oedema (DMO) using a 
computerized alignment and averaging of sequences in optical coherence tomography
(OCT) B-scans and to show the correlation of these patterns with the
pathophysiology of the condition. METHODS: We carried out a prospective,
uncontrolled study, including 46 human subjects with untreated DMO. Enhanced OCT 
images were produced. We correlated different OCT patterns of DMO with ETDRS
visual acuity and with the thickness of the central 1-mm of the macula. We also
correlated these patterns with theories of the pathophysiology of DMO. RESULTS:
Enhanced OCT images enabled us to examine how different layers of the macula were
affected. The external limiting membrane (ELM) was clearly seen in all stages,
including advanced stages. The sequence of DMO events in different macular layers
can be divided into five patterns. Morphologically, DMO starts at the outer
nuclear layer/Henle's layer. As the oedema progresses, cysts are seen in the
fovea and the DMO spreads further into the inner nuclear layer. The ELM seems to 
act as a barrier for proteins and plays an important role in the development of
DMO. CONCLUSIONS: Enhanced OCT revealed new details of DMO pathophysiology. The
different morphological patterns of DMO seen in enhanced OCT may represent
different levels of severity of the disease.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17408388 [PubMed - indexed for MEDLINE]

950: Graefes Arch Clin Exp Ophthalmol. 2007 Oct;245(10):1475-85. Epub 2007 Apr 4.

Glycoxidized particles mimic lipofuscin accumulation in aging eyes: a new
age-related macular degeneration model in rabbits.

Yasukawa T, Wiedemann P, Hoffmann S, Kacza J, Eichler W, Wang YS, Nishiwaki A,
Seeger J, Ogura Y.

Department of Ophthalmology and Eye Clinic, University of Leipzig Medical
Faculty, Leipzig, Germany. yasukawa@med.nagoya-cu.ac.jp

PURPOSE: The biogenesis of drusen, a hallmark of age-related macular degeneration
(AMD), is still unclear. Lipofuscin, which extensively accumulates with age in
RPE cells, is hardly soluble, derived in part from oxidation byproducts of the
photoreceptor outer segments. The purpose of the current study is to develop a
new AMD model in rabbits using glycoxidized particles as imitation lipofuscin,
and determine whether accumulation of lipofuscin as insoluble material may play a
role in drusen biogenesis and other pathogenesis of AMD. METHODS: To mimic the
accumulation of insoluble lipofuscin, glycoxidized microspheres (glycox-MS) were 
made through a glycoxidation process with albumin and glycolaldehyde,
alpha-hydroxy aldehyde. As a control, microspheres made with glutaraldehyde (cMS)
and soluble glycoxidized (glycox-) albumin were prepared. Each material was
implanted into the subretinal space in rabbits. The implanted area was assessed
by funduscopy, fluorescein angiography, histology, and transmission electron
microscopy (TEM). RESULTS: Compared with control microspheres, glycox-MS
stagnated for a prolonged period in the cytoplasm of RPE cells. Eyes implanted
with glycox-MS produced drusen-like deposits at a significantly higher frequency,
when compared with the controls. Glycox-MS were observed at the margin of or
beneath the drusen-like deposits in all cases. In some eyes with glycox-MS,
late-onset sub-RPE choroidal neovascularization was observed, while control
groups did not have these findings. CONCLUSIONS: These results suggest that the
accumulation of indigestible granules such as lipofuscin in RPE or subsequent
depositions toward Bruch's membrane may play a role in drusen biogenesis as a
trigger of inflammation or via other mechanisms. This model of AMD may be useful 
to elucidate drusen biogenesis and pathogenesis of AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17406884 [PubMed - indexed for MEDLINE]

951: Graefes Arch Clin Exp Ophthalmol. 2007 Oct;245(10):1441-5. Epub 2007 Apr 4.

Subtype lesions of neovascular age-related macular degeneration in Chinese
patients.

Liu Y, Wen F, Huang S, Luo G, Yan H, Sun Z, Wu D.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen
University, 54 Xianlie Road, Guangzhou 510060, People's Republic of China.

PURPOSE: To identify the subtype frequency and clinical features of neovascular
age-related macular degeneration (AMD) in Chinese patients. METHODS: From January
2003 to August 2006, we investigated prospectively 155 newly diagnosed patients
with presumed neovascular AMD. Fundus fluorescein angiography (FFA) and
indocyanine green angiography (ICGA) were performed in both eyes of all patients.
Subtype frequency and clinical features were recorded according to their
angiograms. RESULTS: Three subtypes of lesion were noted, which were polypoidal
choroidal vasculopathy (PCV), retinal angiomatous proliferation (RAP) and mixed
lesions. Of the 155 patients, 105 (67.7%) had choroidal neovascularization (CNV) 
of the typical type seen in AMD, 38 (24.5%) had PCV and seven (4.5%) had RAP. In 
five (3.2%) additional cases, mixed lesions were noted. In 38 cases (47 eyes)
with PCV, the rates of subfoveal, juxtafoveal and extrafoveal lesion were
respectively 29.8% (14 eyes), 8.5% (four eyes), and 61.7% (29 eyes), compared
with 75.6%, 14.6% and 9.8% for CNV lesion (P < 0.01). The percentage of subfoveal
lesion in PCV group was significantly lower than that in the CNV group (P <
0.01). The location of the RAP lesion was subfoveal in two (28.6%) eyes,
juxtafoveal in three (42.9%) eyes and extrafoveal in two (28.6%) eyes. The five
eyes with mixed lesions were all PCV coexisting with CNV at the same eye, and in 
all of the five cases, CNV was subfoveal while PCV was extrafoveal. CONCLUSIONS: 
In this hospital-based study, PCV accounts for 24.5% of neovascular AMD and is
the most common subtype, RAP is less frequent (4.5%), and mixed lesions are much 
less common in Chinese patients. PCV is least likely to involve the fovea in
neovascular AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17406882 [PubMed - indexed for MEDLINE]

952: Br J Ophthalmol. 2007 Oct;91(10):1323-6. Epub 2007 Apr 3.

Efficacy and safety of multiple intravitreal triamcinolone injections for
refractory diabetic macular oedema.

Gillies MC, Islam FM, Zhu M, Larsson J, Wong TY.

Save Sight and Eye Health Institute, Department of Clinical Ophthalmology,
University of Sydney, GPO Box 4337, Sydney NSW 2001, Australia.
mark@eye.usyd.edu.au

AIM: The efficacy and safety of repeated injections of intravitreal triamcinolone
(IVTA) for diabetic macular oedema is unclear, with results of previous reports
conflicting. METHODS: This is a prospective, observational case series of 27 eyes
receiving IVTA for diabetic macular oedema. LogMAR visual acuity (VA) and central
macular thickness (CMT) were measured at baseline and in 3 to 6 monthly intervals
for up to 24 months, then correlated with the number of IVTA injections given.
RESULTS: One IVTA injection was required in 6 (18%) eyes, 2 in 8 (24%) eyes, 3 in
13 (39%) eyes and 4-5 in 6 (18%) eyes. VA improved in all patients, but neither
the final improvement in VA nor the absolute improvement in CMT from baseline to 
24 months correlated with the number of injections received (p = 0.44 and 0.84,
respectively). Cataract surgery was more frequent in eyes receiving more
injections (p = 0.01). CONCLUSIONS: This study suggests that repeated injections 
of IVTA continue to be as effective as the first over a 2-year period. The
probability of cataract surgery increases with an increasing number of
injections.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17405800 [PubMed - indexed for MEDLINE]

953: Eye. 2008 Jun;22(6):834-7. Epub 2007 Mar 30.

Full macular translocation following photodynamic therapy in neovascular
age-related macular degeneration.

Suesskind D, Voelker M, Bartz-Schmidt KU, Gelisken F.

Center for Ophthalmology, University of Tuebingen, Tuebingen, Germany.

PURPOSE: To report the long-term functional and anatomical outcome of full
macular translocation (FMT) in eyes with neovascular age-related macular
degeneration (AMD) following photodynamic therapy (PDT). METHODS: Twelve eyes of 
12 consecutive patients with neovascular AMD who were PDT-nonresponders and
underwent FMT were analysed. Best-corrected visual acuity (BCVA) measurement,
fundus photography, and fluorescein angiography at baseline and at follow-up
examinations in 3 months intervals were performed. Primary end point was change
of BCVA from baseline to last visit. RESULTS: Totally 12 eyes of 12 patients were
analysed. Mean time interval between the last PDT and FMT was 3.7 months (range
1-10 months). Mean follow-up after FMT was 25.6 months. BCVA ranged at baseline
from 20/1000 to 20/80 (mean 20/230). At the last visit, mean BCVA was by 20/185. 
BCVA improved in 50% (6/12) of eyes by more than 1 line. Twenty five per cent
(3/12) of eyes had final BCVA within +/-1 line from baseline. In 25% (3/12) of
eyes the BCVA decreased by more than 1 line. One eye had recurrent CNV. In four
eyes a cystoid macular oedema developed. No retinal detachment or disturbing
diplopia was noted. CONCLUSIONS: In the present study, FMT in PDT-nonresponders
stabilised or improved visual acuity in the majority of the eyes in a mean
follow-up period of nearly 2 years. FMT can be considered as a therapeutical
option in eyes who are nonresponders to the PDT in neovascular AMD.

PMID: 17401325 [PubMed - indexed for MEDLINE]

954: Eye. 2008 Jan;22(1):132-7. Epub 2007 Mar 30.

Macular pigment in the human retina: histological evaluation of localization and 
distribution.

Trieschmann M, van Kuijk FJ, Alexander R, Hermans P, Luthert P, Bird AC,
Pauleikhoff D.

Department of Ophthalmology, St Franziskus Hospital, Münster, Germany.

PURPOSE: Clinical investigations have demonstrated variation in both the peak
optical density and the spatial distribution of macular pigment. To confirm these
impressions histologically, the present study examined the distribution of
macular pigment in the human retina. MATERIALS AND METHODS: The macular retina of
11 donor eyes of different ages (28-91 years) were examined histologically on 100
microm vibratome sections directly, without further staining. Measurements were
made in two dimensions: (1) adding the number of macular sections with visible
macular pigment, and (2) direct measurement of the extension of macular pigment
in the foveolar section, which visibly contained the most macular pigment.
RESULTS: The measurements with two methods demonstrated good correlation. The
macula demonstrated a variation in the spatial extension of the visible macular
pigment between 200 and 900 microm diameter around the centre of the fovea, which
was also found when direct measurements were taken. There was no correlation with
the donor age. The main location of macular pigment was in the layer of the
fibres of Henle in the fovea and in the inner nuclear layer at the parafoveal
site. CONCLUSIONS: Histologically, a wide variation of the spatial distribution
of macular pigment was found that confirms clinical observations. The primary
localization of human macular pigment is in the inner retinal layers.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17401321 [PubMed - indexed for MEDLINE]

955: Ophthalmology. 2007 Sep;114(9):1722-7. Epub 2007 Apr 2.

Elevated C-reactive protein levels in patients with polypoidal choroidal
vasculopathy and patients with neovascular age-related macular degeneration.

Kikuchi M, Nakamura M, Ishikawa K, Suzuki T, Nishihara H, Yamakoshi T, Nishio K, 
Taki K, Niwa T, Hamajima N, Terasaki H.

Department of Ophthalmology, Nagoya University Graduate School of Medicine,
Nagoya, Japan.

PURPOSE: To determine the relationship between systemic C-reactive protein (CRP) 
levels and polypoidal choroidal vasculopathy (PCV) and advanced neovascular
age-related macular degeneration (AMD) in Japanese patients. DESIGN: Case-control
study. PARTICIPANTS: Ninety-seven patients with PCV, 176 with advanced
neovascular AMD, and 262 control subjects without any macular abnormality were
studied. METHODS: Color fundus photographs of the macular area were taken from
both eyes in all subjects. Indocyanine green angiography and fluorescein
angiography were performed for diagnosis. The CRP level was measured by a
high-sensitivity assay using a latex aggregation immunoassay, and the levels in
patients with PCV and neovascular AMD were compared with that in the control
group using the Kruskal-Wallis test. Associations between CRP and PCV or
neovascular AMD were compared using logistic regression analysis by computing the
odds ratios (ORs) and 95% confidence intervals (CIs) after the study populations 
were divided into quartiles. MAIN OUTCOME MEASURES: The CRP levels in patients
with PCV, patients with neovascular AMD, and control subjects. Standard
univariate and multivariate analyses between groups. RESULTS: Median CRP levels
were significantly higher in cases with PCV (0.94 mg/l) or with advanced
neovascular AMD (0.95 mg/l) than in control subjects (0.43 mg/l) (P<0.001 for
Kruskal-Wallis test). After adjusting for baseline characteristics such as age,
gender, smoking status, alcohol use, body mass index, history, and use of
antiinflammatory drugs, the increase in risk was significant for the highest
quartile of CRP for both PCV (OR, 3.53; 95% CI, 1.49-8.40) and neovascular AMD
(OR, 4.08; 95% CI, 1.94-8.56), and for the third quartile of CRP for neovascular 
AMD (OR, 2.29; 95% CI, 1.07-4.91). The trends for an increase in risk of disease 
with increase in CRP were statistically significant for both PCV (P = 0.001) and 
neovascular AMD (P<0.001). CONCLUSIONS: The significant associations between
elevated serum CRP levels and PCV or neovascular AMD in the Japanese strongly
suggest that inflammatory processes are involved in the pathogenesis of PCV and
neovascular AMD.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 17400294 [PubMed - indexed for MEDLINE]

956: Mol Immunol. 2007 Jul;44(13):3398-406. Epub 2007 Mar 30.

Defective complement control of factor H (Y402H) and FHL-1 in age-related macular
degeneration.

Skerka C, Lauer N, Weinberger AA, Keilhauer CN, Sühnel J, Smith R,
Schlötzer-Schrehardt U, Fritsche L, Heinen S, Hartmann A, Weber BH, Zipfel PF.

Department of Infection Biology, Leibniz Institute for Natural Products Research 
and Infection Biology, Hans Knöll Institute, Jena, Germany.

The common variant in the human complement Factor H gene (CFH), with Tyr402His,
is linked to age-related macular degeneration (AMD), a prevalent disorder leading
to visual impairment and irreversible blindness in elderly patients. Here we show
that the risk variant CFH 402His displays reduced binding to C reactive protein
(CRP), heparin and retinal pigment epithelial cells. This reduced binding can
cause inefficient complement regulation at the cell surface, particularly when
CRP is recruited to injured sites and tissue. In addition, we identify the Factor
H-like protein 1 (FHL-1), an alternative splice product of the CFH gene as an
additional protein that includes the risk residue 402, and thus confers risk for 
AMD. FHL-1 is expressed in the eye and the FHL-1 402His risk variant shows
similar reduced cell binding and likely reduced complement regulatory functions
on the cell surface. CFH and FHL-1 may act in concert in the eye and the reduced 
surface binding may result in inappropriate local complement control, which in
turn can lead to inflammation, disturbance of local physiological homeostasis and
progression to cell damage. As a consequence, these processes may lead to AMD
pathogenesis.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17399790 [PubMed - indexed for MEDLINE]

957: Ophthalmology. 2007 Apr;114(4):743-50.

Primary intravitreal bevacizumab (Avastin) for diabetic macular edema: results
from the Pan-American Collaborative Retina Study Group at 6-month follow-up.

Arevalo JF, Fromow-Guerra J, Quiroz-Mercado H, Sanchez JG, Wu L, Maia M, Berrocal
MH, Solis-Vivanco A, Farah ME; Pan-American Collaborative Retina Study Group.

Retina and Vitreous Service, Clinica Oftalmológica Centro Caracas, Caracas,
Venezuela. arevalojf@movistar.net.ve

PURPOSE: To report the 6-month anatomic and best-corrected visual acuity (BCVA)
response after primary intravitreal bevacizumab (Avastin) in patients with
diabetic macular edema (DME). DESIGN: Interventional retrospective multicenter
study at 6 centers from 6 countries of patients with DME. PARTICIPANTS: We
reviewed the clinical records of 88 consecutive patients (110 eyes) with DME.
Seventy-eight eyes of 64 consecutive patients with a minimum follow-up of 6
months and mean age of 59.7+/-9.3 years were included in this analysis.
INTERVENTION: Patients were treated with at least one intravitreal injection of
1.25 mg or 2.5 mg of bevacizumab and underwent Early Treatment Diabetic
Retinopathy Study (ETDRS) BCVA testing, ophthalmoscopic examination, optical
coherence tomography (OCT), and fluorescein angiography (FA) at baseline and
follow-up visits. Repeated-measures analysis of variance was used to compare mean
values. MAIN OUTCOME MEASURES: Changes in BCVA, OCT, and FA. RESULTS: Mean
follow-up was 6.31+/-0.81 months (range, 6-9). Sixteen (20.5%) eyes needed a
second injection at a mean of 13.8 weeks (range, 4-28), and 6 eyes needed a third
injection (7.7%) at a mean of 11.5 weeks (range, 5-20). The mean baseline BCVA
was 0.87 (logarithm of the minimum angle of resolution), and the final mean BCVA 
was 0.6, a difference that was statistically significant (P<0.0001). Final BCVA
analysis by subgroups demonstrated that 32 (41.1%) eyes remained stable, 43
(55.1%) improved > or =2 ETDRS lines of BCVA, and 3 (3.8%) decreased > or =2
ETDRS lines of BCVA. Mean central macular thickness at baseline by OCT was
387.0+/-182.8 mum and decreased to a mean of 275.7+/-108.3 at end of follow-up
(P<0.0001). No ocular or systemic adverse events were observed. CONCLUSIONS:
Primary intravitreal bevacizumab at doses of 1.25 to 2.5 mg seem to provide
stability or improvement in VA, OCT, and FA in DME at 6 months. Follow-up is
still short to make any specific treatment recommendations; however, the results 
appear promising. Evaluation in a multicenter randomized controlled clinical
trial with longer follow-up is needed.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 17398322 [PubMed - indexed for MEDLINE]

958: Ophthalmology. 2007 Apr;114(4):738-42.

Association of complement factor H Y402H gene polymorphism with different
subtypes of exudative age-related macular degeneration.

Wegscheider BJ, Weger M, Renner W, Steinbrugger I, März W, Mossböck G, Temmel W, 
El-Shabrawi Y, Schmut O, Jahrbacher R, Haas A.

Department of Ophthalmology, Medical University Graz, Graz, Austria.

OBJECTIVE: Exudative age-related macular degeneration (AMD) is a common cause for
a severe central visual loss. The complement system has been implicated in the
pathogenesis of drusen. Recently, a complement factor H (CFH) polymorphism, which
is characterized by a tyrosine (Y)-to-histidine (H) exchange at position 402 of
the CFH gene, has been suggested as a major risk factor for AMD in a North
American population. The aim of the present study was to investigate a
hypothesized association between the CFH Y402H polymorphism and the presence of
exudative AMD in a Central European population of Caucasoid descent as well as to
determine the genotype distribution among different types of exudative AMD.
DESIGN: Retrospective case-control study. PARTICIPANTS: The study cohort
consisted of 179 patients with exudative AMD and 163 controls. METHODS:
Determination of genotypes was carried out by allele-specific digestion of
polymerase chain reaction products. MAIN OUTCOME MEASURES: Genotypes of CFH Y402H
polymorphism. RESULTS: The prevalence of the CFH 402HH genotype was significantly
higher in patients with exudative AMD than among controls (35.2% vs. 8.6%;
P<0.001). Homozygosity for the CFH Y402H polymorphism was associated with an odds
ratio of 5.78 (95% confidence interval, 3.09-10.83) for exudative AMD. Subgroup
analysis revealed that the CFH 402HH genotype was significantly more prevalent in
eyes with predominantly classic with no occult choroidal neovascularization (CNV)
than in those with either retinal angiomatous proliferation, occult with no
classic CNV, or predominantly classic with occult CNV. CONCLUSION: Our data
suggest that the CFH Y402H polymorphism is a major risk factor for exudative AMD 
in a Central European population.

PMID: 17398321 [PubMed - indexed for MEDLINE]

959: J Cataract Refract Surg. 2007 Apr;33(4):682-5.

Comment in:
    J Cataract Refract Surg. 2007 Nov;33(11):1837-8; author reply 1838.

Successful treatment of cystoid macular edema with valdecoxib.

Reis A, Birnbaum F, Hansen LL, Reinhard T.

Eye Clinic, University of Freiburg, Freiburg, Germany. reis@augenwerk.li

PURPOSE: To evaluate the safety and efficacy of the COX-2 inhibitor valdecoxib in
treating macular edema after cataract surgery. SETTING: University Eye Clinic,
Freiburg, Germany and Reis Medical Institution, Liechtenstein. METHODS: The COX-2
inhibitor valdecoxib (Bextra) was administered systemically to patients with
significant visual loss resulting from macular edema in a prospective clinical
trial. RESULTS: Ten patients were enrolled. Valdecoxib was tolerated well and led
to a significant visual improvement within 10 days of therapy in all patients.
CONCLUSION: The fast and persistent control of macular edema with valdecoxib
warrants further investigation.

Publication Types: 
    Clinical Trial

PMID: 17397743 [PubMed - indexed for MEDLINE]

960: Ophthalmic Surg Lasers Imaging. 2007 Mar-Apr;38(2):164-6.

Intravitreal bevacizumab for macular edema from idiopathic juxtafoveal retinal
telangiectasis.

Moon SJ, Berger AS, Tolentino MJ, Misch DM.

Center for Retina and Macular Disease, Winter Haven, Florida, 33880, USA.

To assess the potential visual benefit of intravitreal bevacizumab in a patient
with idiopathic juxtafoveal retinal telangiectasis refractory to focal laser
treatment, an intravitreal injection of bevacizumab (1.25 mg) was given. Within 1
week, visual acuity improved from 20/50 to 20/25 and optical coherence tomography
demonstrated complete resolution of macular edema. There was no adverse effect.
The macular edema recurred after 3 months, requiring a repeat injection of
bevacizumab with subsequent resolution of macular edema. An intravitreal
injection of bevacizumab may provide potential short-term visual benefit in
patients with macular edema from idiopathic juxtafoveal retinal telangiectasis.

Publication Types: 
    Case Reports

PMID: 17396701 [PubMed - indexed for MEDLINE]

961: Ophthalmic Surg Lasers Imaging. 2007 Mar-Apr;38(2):126-34.

Computerized detection and measurement of drusen in age-related macular
degeneration.

Friberg TR, Huang L, Palaiou M, Bremer R.

UPMC Eye Center, Department of Ophthalmology, University of Pittsburgh School of 
Medicine, Pittsburgh, Pennsylvania 15213, USA.

BACKGROUND AND OBJECTIVE: The authors used a drusen detection algorithm to
quantitate drusen on digitized images and determined its precision and accuracy. 
PATIENTS AND METHODS: Fundus images from 349 participants in the Age-Related Eye 
Disease Study trial were digitized and analyzed with the Drusen Analyzer (IRIDEX 
Corporation, Mountain View, CA). The size, number, and area of the drusen in two 
macular regions were computed by two readers using an interactive approach.
Measurements were compared to data generated by reading center methods. RESULTS: 
For the Analyzer, inter-observer agreement was 0.79 (SE = 0.02) and 0.86 (SE =
0.01) (kappa statistic). Intra-observer precision was 0.835 and 0.880 (Spearman
coefficients). Categorical agreement (weighted kappa) between the Analyzer and
reading center results for the two regions was (0.76, 0.58) and (0.68, 0.68) for 
readers A and B. The time required to quantitate an image using the Analyzer was 
105 +/- 52 and 218 +/- 102 seconds for the two regions, respectively.
CONCLUSIONS: Quantitative detection of drusen can be performed reproducibly and
efficiently. Comparisons to more labor intensive reading center techniques
suggest that the results are similar but that the algorithm is more sensitive and
precise.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17396693 [PubMed - indexed for MEDLINE]

962: Mol Vis. 2007 Mar 1;13:318-29.

Proteomic and phototoxic characterization of melanolipofuscin: correlation to
disease and model for its origin.

Warburton S, Davis WE, Southwick K, Xin H, Woolley AT, Burton GF, Thulin CD.

Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT
84602, USA. sarah.warburton@gmail.com <sarah.warburton@gmail.com>

PURPOSE: Melanolipofuscin (MLF) is a complex granule, exhibiting properties of
both melanosomes and lipofuscin (LF) granules, which accumulates in retinal
pigment epithelial (RPE) cells and may contribute to the etiology of age-related 
macular degeneration (AMD). MLF accumulation has been reported by Feeney-Burns to
more closely reflect the onset of AMD than the accumulation of lipofuscin. In an 
effort to assess the possible contribution MLF may have to the onset of AMD, we
analyzed the phototoxicity and protein composition of MLF and compared those
results to that of LF. METHODS: Specifically, we observed the accumulation of MLF
in human RPE from different decades of life, and assessed the phototoxicity of
these granules. We also employed fluorescence spectroscopy, atomic force
microscopy, transmission and scanning electron microscopy and proteomic analysis 
to examine the composition of MLF granules in an effort to ascertain their
origin. RESULTS: Our results show that MLF granules are phototoxic and their
accumulation more closely reflects the onset of AMD than does LF accumulation.
Our compositional analysis of MLF has shown that while these granules contain
some similarities to LF granules, MLF is substantially different. Of significant 
interest is the finding that MLF, in contrast to LF, does not contain
photoreceptor-specific proteins, suggesting that MLF may not originate from the
phagocytosis of photoreceptor outer segments. Instead the presence of RPE- and
melanosome-specific proteins would suggest that MLF accumulates as a result of
the melanosomal autophagocytosis of RPE cells. CONCLUSIONS: Our results provide
significant insight into understanding the formation and toxicity of MLF and
suggest a possible contribution to the etiology of retinal diseases.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17392682 [PubMed - indexed for MEDLINE]

963: Invest Ophthalmol Vis Sci. 2007 Apr;48(4):1801-7.

Scavenger receptors for oxidized lipoprotein in age-related macular degeneration.

Kamei M, Yoneda K, Kume N, Suzuki M, Itabe H, Matsuda K, Shimaoka T, Minami M,
Yonehara S, Kita T, Kinoshita S.

Department of Ophthalmology, Graduate School of Medicine, Osaka University, 2-2
Yamadaoka, Suita, Osaka 565-0871, Japan. mkamei@ophthal.med.osaka-u.ac.jp

PURPOSE: The accumulation of macrophages is known to be involved in the
pathogenesis of age-related macular degeneration (AMD), but the reasons why
macrophages accumulate in AMD lesions have not been determined. Because the
histopathology of AMD has some factors common with those of atherosclerosis, the 
authors hypothesized that macrophages accumulate to take up oxidized lipoproteins
in the eyes of patients with AMD, as has been demonstrated in atherosclerosis.
METHODS: Immunohistochemistry was performed on 10 surgically excised choroidal
neovascular (CNV) membranes from eyes with AMD. An antibody against oxidized
lipoprotein and antibodies against the scavenger receptors SR-PSOX and LOX-1 were
used. Antibodies against cytokeratin, CD68, and von Willebrand factor were used
to identify retinal pigment epithelium (RPE), macrophages, and vascular
endothelial cells, respectively. RT-PCR was performed to detect the mRNAs of the 
scavenger receptors in the CNV membranes. RESULTS: Oxidized lipoproteins were
immunohistochemically detected in the CNV membranes. Intense immunostaining was
observed at the surface of the CNV membranes with the SR-PSOX antibody, whereas
LOX-1 immunostaining was weak. Cells expressing scavenger receptors were found to
be predominantly macrophages with a minority of RPE. Both SR-PSOX and LOX-1 mRNAs
were detected in CNV membranes. CONCLUSIONS: Oxidized lipoproteins are present in
AMD lesions. Macrophages and RPE in the CNV membranes express cell surface
scavenger receptors for oxidized lipoproteins. These findings suggest that
macrophages may accumulate to take up oxidized lipoproteins in AMD and that the
control of oxidative stress and macrophage responses may therefore be potential
treatments for AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17389514 [PubMed - indexed for MEDLINE]

964: Invest Ophthalmol Vis Sci. 2007 Apr;48(4):1767-72.

Synergies of VEGF inhibition and photodynamic therapy in the treatment of
age-related macular degeneration.

Zuluaga MF, Mailhos C, Robinson G, Shima DT, Gurny R, Lange N.

Laboratory of Pharmaceutics and Biopharmaceutics, Section of Pharmaceutical
Sciences, University of Geneva, 30 Quai Ernest-Ansermet, CH-1211 Geneva,
Switzerland.

PURPOSE: Photodynamic therapy (PDT) and the administration of compounds acting
against vascular endothelial growth factor (anti-VEGF) are approved for the
treatment of choroidal neovascularization (CNV) secondary to age-related macular 
degeneration (AMD). Experimental evidence that the combined use of both treatment
options may improve therapeutic outcome is presented. METHODS: Fertilized chick
eggs were incubated until day 12 of embryo development (EDD12) and were treated
by PDT using two different photosensitizing agents (liposomal formulation of
BPD-MA; m-THPP encapsulated in polymeric nanoparticles) and were visualized using
an epifluorescence microscope. Vascular occlusion of the treated zones of the
chorioallantoic membrane (CAM) was assessed by fluorescence angiography 24 and 48
hours after treatment. Alternatively, PDT-treated areas were exposed to a soluble
VEGF receptor antagonist (sFlt-1) 6 hours after treatment and were analyzed.
RESULTS: Vascular occlusion in the PDT-treated areas was observed with both
photosensitizers 24 hours after treatment. Reperfusion of preexisting blood
vessels and first signs of revascularization were visible 48 hours after PDT.
Topical administration of sFlt-1 to the treated areas augmented occlusion and
limited subsequent angiogenesis in a dose-dependent manner. CONCLUSIONS: The
combined use of PDT and of agents targeting angiogenic cytokines may
synergistically improve therapeutic outcome after combined treatment in patients 
with CNV secondary to AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17389510 [PubMed - indexed for MEDLINE]

965: Invest Ophthalmol Vis Sci. 2007 Apr;48(4):1498-503.

Anxiety and depression prevalence rates in age-related macular degeneration.

Augustin A, Sahel JA, Bandello F, Dardennes R, Maurel F, Negrini C, Hieke K,
Berdeaux G.

Augenklinik, Karlsruhe, Germany.

PURPOSE: To estimate the prevalence rates of depression and anxiety in patients
with wet age-related macular degeneration (AMD) and the relationship with visual 
acuity and to develop a simple algorithm for depression screening. METHODS: This 
cross-sectional, prospective, observational, multicenter study was performed in
France, Germany, and Italy. Retina specialists at 10 centers per country each
enrolled 12 consecutive patients with wet ARMD. Patients were stratified into
four severity groups by using best eye (BE) and worst eye (WE) visual acuity (VA)
thresholds (BE:VA 20/40 and WE:VA 20/200). Patients rated themselves on the
Hospital Anxiety and Depression Scale (HADS). Analysis of variance was performed 
to estimate the effect of VA severity levels on HADS scores adjusted on age,
gender, and country. RESULTS: Patients (females 60%) were recruited, with a mean 
age of 77 years and 2.3 years' disease duration. Mean BE:VA at inclusion was 0.49
logMar (logarithm of the minimum angled of resolution) and WE:VA 1.0 logMar. The 
prevalence of severe depression increased from 0% (BE:VA > or = 20/40+WE:VA > or 
= 20/200) to 7.6% (BE:VA < 20/40+WE:VA < 20/200), whereas anxiety was unrelated
to VA loss. Moreover, total depression scores were strongly associated with VA
severity (P = 0.006), but not total anxiety scores (P = 0.840). Responses to two 
HADS items ("I still enjoy things I used to enjoy"; "I can enjoy a good book or
radio or television program") identified 95% of severely to moderately depressed 
patients. CONCLUSIONS: Self-rated depression in patients with AMD was associated 
with VA severity level. It should, therefore, be relatively easy for
ophthalmologists to implement the screening procedure and refer identified
patients to psychiatrists for proper assessment and treatment.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 17389477 [PubMed - indexed for MEDLINE]

966: Invest Ophthalmol Vis Sci. 2007 Apr;48(4):1472-5.

Is pseudophakia a risk factor for neovascular age-related macular degeneration?

Sutter FK, Menghini M, Barthelmes D, Fleischhauer JC, Kurz-Levin MM, Bosch MM,
Helbig H.

Department of Ophthalmology, University Hospital, CH-8049 Zurich, Switzerland.
florian.sutter@usz.ch

PURPOSE: To examine the possible association between pseudophakia and neovascular
age-related macular degeneration (AMD). METHODS: Reports of all patients
undergoing fluorescein angiography in the authors' department over a 6-year
period were retrospectively reviewed. Four hundred ninety-nine patients with
recent onset of neovascular AMD in one eye and early age-related maculopathy
(ARM) in the fellow eye were included in the study. Lens status (phakic or
pseudophakic) in both eyes at the time of onset of neovascular AMD and the time
between cataract surgeries (if performed) and onset of neovascular AMD were
determined. RESULTS: There was no significant difference in lens status between
eyes with neovascular AMD and fellow eyes with early ARM (115/499 [23.0%] vs.
112/499 [22.4%] pseudophakic; P = 0.88, odds ratio 1.035, 95% CI 0.770-1.391).
Subgroup analysis revealed no difference between the groups with large drusen,
small drusen, or pigmentary changes only (respectively, 20.3% vs. 19.6%
pseudophakic, P = 0.92; 20.5% vs. 23.3% pseudophakic, P = 0.84; 33.3% vs. 31.7%
pseudophakic, P = 1.0). Pseudophakic eyes with neovascular AMD had not been
pseudophakic for a significantly longer period at the time of onset of
neovascular AMD than their pseudophakic fellow eyes at the same time point (225.9
+/- 170.4 vs. 209.9 +/- 158.2 weeks, P = 0.27). CONCLUSIONS: The results do not
support the hypothesis that pseudophakia is a major risk factor for the
development of neovascular AMD.

PMID: 17389473 [PubMed - indexed for MEDLINE]

967: Am J Ophthalmol. 2007 Apr;143(4):701-4. Epub 2006 Nov 28.

Anatomical and visual outcome of retinal angiomatous proliferation treated with
photodynamic therapy and intravitreal triamcinolone.

van de Moere A, Kak R, Sandhu SS, Talks SJ.

Department of Ophthalmology, Royal Victoria Infirmary, Newcastle upon Tyne,
United Kingdom.

PURPOSE: To evaluate the efficacy and safety of photodynamic therapy (PDT) with
verteporfin combined with intravitreal triamcinolone (TA) in retinal angiomatous 
proliferation (RAP). DESIGN: Retrospective, consecutive, noncomparative case
series. METHODS: Patients newly diagnosed with RAP underwent indocyanine green
angiography (ICGA)-guided PDT with verteporfin, immediately followed by
intravitreal TA. Complete ocular examination, fluorescein angiography (FA), ICGA,
and optical coherence tomography (OCT) were performed at baseline and follow-up
visits every three months. RESULTS: Seventeen eyes of seventeen patients
underwent this simultaneous combined treatment. All patients had 12 months of
follow-up. Complete resolution of angiographic leakage was achieved in 83% at 12 
months. Visual acuity improved in 35%, and was stable in 47%. Eleven patients
developed recurrent leakage after six to 12 months, which settled completely
after repeat combined treatment. CONCLUSIONS: This simultaneous combined
treatment in patients with RAP was effective in reducing or eliminating retinal
edema, regression of neovascularization, and stabilizing or improving visual
acuity.

PMID: 17386286 [PubMed - indexed for MEDLINE]

968: Am J Ophthalmol. 2007 Apr;143(4):685-7. Epub 2006 Dec 20.

Statins and the long-term risk of incident age-related macular degeneration: the 
Blue Mountains Eye Study.

Tan JS, Mitchell P, Rochtchina E, Wang JJ.

Centre for Vision Research, Department of Ophthalmology, Westmead Millennium
Institute, University of Sydney, Australia.

PURPOSE: To assess the relationship between statin use and the long-term
incidence of age-related macular degeneration (AMD). DESIGN: Population-based
cohort study. METHODS: Of 3,654 baseline (1992 to 1994) participants in the Blue 
Mountains Eye Study initially aged 49+ years, 2,335 were reexamined after five
years (1997 to 1999) and 1,952 after 10 years (2002 to 2004). Stereoscopic
macular photographs were graded using the Wisconsin Age-related Maculopathy
Grading System. History, physical examination, and fasting blood samples provided
data on possible risk factors. Discrete linear logistic models were used to
assess risk of incident AMD. RESULTS: After controlling for age, gender, and
other confounding factors, compared with nonusers, statin users had a reduced
risk of developing indistinct soft drusen, the principal late AMD precursor
lesion (hazard ratio, 0.33; 95% confidence interval, 0.13 to 0.84). CONCLUSIONS: 
Statin use was not significantly associated with overall early AMD incidence, but
was protective for indistinct soft drusen, a key late AMD precursor lesion.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17386278 [PubMed - indexed for MEDLINE]

969: Am J Ophthalmol. 2007 Apr;143(4):566-83.

Comment in:
    Am J Ophthalmol. 2007 Apr;143(4):679-80.

An optical coherence tomography-guided, variable dosing regimen with intravitreal
ranibizumab (Lucentis) for neovascular age-related macular degeneration.

Fung AE, Lalwani GA, Rosenfeld PJ, Dubovy SR, Michels S, Feuer WJ, Puliafito CA, 
Davis JL, Flynn HW Jr, Esquiabro M.

Pacific Eye Associates, California Pacific Medical Center, San Francisco,
California, USA.

PURPOSE: To evaluate an optical coherence tomography (OCT)-guided,
variable-dosing regimen with intravitreal ranibizumab for the treatment of
patients with neovascular age-related macular degeneration (AMD). DESIGN:
Open-label, prospective, single-center, nonrandomized, investigator-sponsored
clinical study. METHODS: In this two-year study, neovascular AMD patients with
subfoveal choroidal neovascularization (CNV) (n = 40) and a central retinal
thickness of at least 300 microm as measured by OCT were enrolled to receive
three consecutive monthly intravitreal injections of ranibizumab (0.5 mg).
Thereafter, retreatment with ranibizumab was performed if one of the following
changes was observed between visits: a loss of five letters in conjunction with
fluid in the macula as detected by OCT, an increase in OCT central retinal
thickness of at least 100 microm, new-onset classic CNV, new macular hemorrhage, 
or persistent macular fluid detected by OCT at least one month after the previous
injection of ranibizumab. RESULTS: At month 12, the mean visual acuity improved
by 9.3 letters (P < .001) and the mean OCT central retinal thickness decreased by
178 microm (P < .001). Visual acuity improved 15 or more letters in 35% of
patients. These visual acuity and OCT outcomes were achieved with an average of
5.6 injections over 12 months. After a fluid-free macula was achieved, the mean
injection-free interval was 4.5 months before another reinjection was necessary. 
CONCLUSION: This OCT-guided, variable-dosing regimen with ranibizumab resulted in
visual acuity outcomes similar to the Phase III clinical studies, but required
fewer intravitreal injections. OCT appears useful for determining when
retreatment with ranibizumab is necessary.

Publication Types: 
    Clinical Trial
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17386270 [PubMed - indexed for MEDLINE]

970: Br J Ophthalmol. 2007 Sep;91(9):1173-6. Epub 2007 Mar 23.

Types of choroidal neovascularisation in newly diagnosed exudative age-related
macular degeneration.

Cohen SY, Creuzot-Garcher C, Darmon J, Desmettre T, Korobelnik JF, Levrat F,
Quentel G, Paliès S, Sanchez A, de Gendre AS, Schluep H, Weber M, Delcourt C.

Centre Ophtalmologique d'Imagerie et de Laser, 11 Rue Antoine Bourdelle, 75015
Paris, France. sycohen@club-internet.fr

AIM: To describe the types and location of choroidal neovascularisation (CNV) in 
exudative age-related macular degeneration (AMD), including vascularised pigment 
epithelial detatchments (PED), and most recently described subtypes, such as
retinal choroidal anasmostosis, also termed "retinal angiomatous proliferation"
(RAP). METHODS: Prospective multicentre consecutive descriptive case series. A
total of 207 consecutive cases of newly diagnosed exudative AMD undergoing
fluorescein angiography (FA) were recruited by 7 French referral hospital-based
or private centres. Indocyanine green angiography (ICG) also was performed, when 
judged necessary by investigators. Types and location of CNV were classified by
two independent experts and adjudicated by a third when discordant. RESULTS: All 
patients had FA, while ICG was performed in 50% of subjects. A total of 17.6% had
classic CNV only, 5.4% and 8.3% had predominantly and minimally classic CNV,
respectively. Occult CNV could be classified in occult CNV without PED (32.7%)
and occult CNV with PED, ie, vascularised PED (23.9%). RAP was observed in 15.1% 
of cases, and accounted for 30% of vascularised PED. In 5.8% of the cases there
was haemorrhagic AMD and 4.8% had fibrovascular scars. Lesions were mainly
subfoveal (80%). Agreement between the centre's ophthalmologist and the final
validated expert classification was moderate (kappa = 0.52 for location and 0.59 
for type of lesion). CONCLUSION: This study confirms that newly diagnosed cases
of exudative AMD are mainly occult and subfoveal. RAP appeared as a common lesion
in patients with newly diagnosed exudative AMD.

Publication Types: 
    Multicenter Study

PMID: 17383997 [PubMed - indexed for MEDLINE]

971: Br J Ophthalmol. 2007 Aug;91(8):1073-6. Epub 2007 Mar 23.

Matrix bound SFD mutant TIMP-3 is more stable than wild type TIMP-3.

Majid MA, Smith VA, Newby AC, Dick AD.

Bristol Eye Hospital, Lower Maudlin Street, Bristol BS1 2LX, UK.

BACKGROUND: Sorsby's fundus dystrophy (SFD) is a degenerative retinopathy
characterised by accumulation of mutant TIMP-3 protein in Bruch's membrane. AIM: 
To compare the stability of matrix bound SFD mutant TIMP-3s with wild type
TIMP-3. METHODS: COS-7 cells were transfected with plasmids containing wild type,
Ser 181, Gly-167, Ser-156, and Tyr-168 TIMP-3 cDNA. The cells and their matrices 
were subsequently harvested and homogenised. After measuring the bound wild type 
and SFD mutant TIMP-3 concentrations by ELISA, aliquots of the homogenates were
heated to 100 degrees C. The rates of denaturation of the TIMP proteins at this
temperature were monitored by reverse zymography. RESULTS: Over a period of 24 h 
at 100 degrees C the biological activity of both wild type and SFD mutant TIMP-3 
was lost. Over a period of 6 h at this temperature the biological activity of the
SFD mutant TIMP-3s was fully retained whereas that of the wild type TIMP-3 was
lost. CONCLUSION: Matrix bound SFD mutant TIMP-3s are thermodynamically more
stable than wild type. This may explain why SFD starts earlier in life than age
related macular degeneration.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17383996 [PubMed - indexed for MEDLINE]

972: Ophthalmologica. 2007;221(2):118-31.

Current treatment approaches in diabetic macular edema.

Meyer CH.

Department of Ophthalmology, Philipps University, Marburg, Germany.
meyer_eye@yahoo.com

PURPOSE: To review current treatment approaches in diabetic macular edema (DME). 
METHODS: The underlying pathopathology, classifications and diagnostic
examination techniques including fluorescein angiography, optical coherence
tomography and stereoscopic biomicroscopy. Treatment modalities with focal or
grid argon laser photocoagulation, pars plana vitrectomy with and without peeling
of the inner limiting membrane (ILM), as well as intravitreal injections using
triamcinolone acetonide or novel vascular endothelial growth factor (VEGF)
inhibitors are described. RESULTS: DME results from a series of biochemical and
cellular changes, causing progressive leakage and exudation. Focal and grid
photocoagulation remains the standard care for diabetic maculopathy. However, the
availability of new agents raises the possibility of improvements if significant 
benefits can be validated in randomized clinical trials. Posterior vitreous
attachments play a critical role through several mechanical or physiological
mechanisms. Vitrectomy without ILM removal seems to be effective in reducing the 
retinal thickness and improving visual acuity. CONCLUSION: A proper evaluation of
the vitreous and retina is fundamental to select the most appropriate treatment
approach in DME. While small microaneurysms with focal DME may be treated by
conventional focal photocoagulation, diffuse DME which do not respond to grid
photocoagulation may benefit from intravitreal injections using triamcinolone
acetonide or novel VEGF inhibitors. Eyes with DME and additional vitreous
traction may benefit from pars plana vitrectomy without ILM peeling. A
combination of laser, pharmacological and surgical treatment modalities may be
necessary to maintain central vision in eyes with DME. Copyright (c) 2007 S.
Karger AG, Basel.

Publication Types: 
    Review

PMID: 17380066 [PubMed - indexed for MEDLINE]

973: J Gerontol B Psychol Sci Soc Sci. 2007 Mar;62(2):P90-7.

Age-related macular degeneration and change in psychological control: role of
time since diagnosis and functional ability.

Wahl HW, Schilling O, Becker S.

Institute of Psychology, Department of Psychological Aging Research, University
of Heidelberg, Bergheimer Str. 20, 69115 Heidelberg, Germany.
h.w.wahl@psychologie.uni-heidelberg.de

We apply the life-span theory of control proposed by Heckhausen and Schulz to
study the change in use of control strategies related to age-related macular
degeneration (AMD). A mixed-model approach considers nonlinear relations of rate 
of change in the use of control strategies with time since diagnosis and
functional ability. Data stem from a sample of 90 individuals with AMD (age,
M=79.5 years at Time 1), of whom 71 were assessed two times over 1 year.
Compensatory primary control strategies increased shortly after the diagnosis,
whereas the increase in compensatory secondary control strategies was related to 
functional loss in instrumental daily activities. Findings provide support for
the critical role of compensatory control strategies in the event that
individuals with AMD are faced with anticipated or real functional loss.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17379677 [PubMed - indexed for MEDLINE]

974: Angiogenesis. 2007;10(2):119-32. Epub 2007 Mar 13.

Molecular genetics of AMD and current animal models.

Edwards AO, Malek G.

Department of Ophthalmology, Mayo Clinic, 200 First Street, SW, Rochester, MN
55905, USA.

During the past few years systematic investigation into the epidemiology,
genetics, and pathophysiology of age-related macular degeneration (AMD) has
provided important new insight into this leading cause of vision loss in older
persons. These studies provide a view of AMD as a complex trait influenced by
well-established genetic and environmental risks that leads to the deposition of 
inflammatory deposits in the outer retina. This maculopathy leads to visual
dysfunction through a variety of mechanisms and complications that can be
observed in both humans and animal models. In this review, the risks associated
with AMD in humans and the animal models used to study AMD and its complications 
will be summarized. No effort has been made to perform a comprehensive citation
of all areas of AMD genetics and animal models, but rather a selection of
observations and supporting references illustrative of the current state of the
field is presented.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17372852 [PubMed - indexed for MEDLINE]

975: Trends Genet. 2007 May;23(5):225-31. Epub 2007 Mar 26.

The challenge of modeling macular degeneration in mice.

Marmorstein AD, Marmorstein LY.

Department of Ophthalmology and Vision Science, University of Arizona, 655 North 
Alvernon Way, Suite 108, Tucson, AZ 85711, USA. amarmorstein@eyes.arizona.edu

Macular degenerations (MD), age-related or inherited, interfere with the ability 
to read, drive and recognize faces. Understanding this class of diseases has been
challenging because the mouse, the mammal most amenable to genetic manipulation, 
lacks a macula. Here we discuss whether we can model MD in the mouse, present
criteria for an 'ideal' mouse model of MD and discuss how mouse models have
contributed to our knowledge of MD by contrasting how well they meet the 'ideal' 
criteria with how informative they have actually been. By modeling MD in mice, we
can learn about aspects of MD that an animal with a macula would be unable to
teach us.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17368622 [PubMed - indexed for MEDLINE]

976: Ophthalmology. 2007 Aug;114(8):1574-1579.e1. Epub 2007 Mar 23.

Comment in:
    Ophthalmology. 2008 Mar;115(3):585.

Intravitreal bevacizumab for treatment of uveitic macular edema.

Cordero Coma M, Sobrin L, Onal S, Christen W, Foster CS.

Massachusetts Eye Research and Surgery Institute, Cambridge, Massachusetts 02142,
USA.

PURPOSE: To evaluate the short-term safety and efficacy of intravitreal
bevacizumab for the treatment of cystoid macular edema (CME) secondary to
uveitis. DESIGN: Retrospective, noncomparative, interventional case series.
PARTICIPANTS: Thirteen patients undergoing treatment for recalcitrant uveitic
macular edema at one referral center. METHODS: Charts of patients who received
one 2.5-mg intravitreal injection of bevacizumab in one eye were reviewed for
clinical information including best-corrected Snellen visual acuity (VA),
examination findings, optical coherence tomography (OCT) results, and fluorescein
angiography results. Kaplan-Meier survival analysis was used to calculate
probability success rates. The statistical significance of change in mean retinal
thickness and VA was assessed using repeated-measures analysis of variance. MAIN 
OUTCOME MEASURES: Assessments of changes in best-corrected Snellen VA and OCT
retinal thickness were made. RESULTS: Six (46.15%) patients had a decrease in
foveal thickness at the end of the follow-up, whereas 5 (38.4%) patients had an
improvement of VA by > or =2 lines 84 days or more after the injection. Mean
retinal thickness showed a significant decrease over the follow-up (P<0.02). The 
change in mean logarithm of the minimum angle of resolution VA over the follow-up
was not significant (P>0.05). Survival analysis showed that the probability of
any improvement in VA increased progressively starting at 6 weeks and reached 81%
at 14 weeks. No significant ocular or systemic adverse effects were observed.
CONCLUSIONS: These results suggest that a single intravitreal injection of
bevacizumab is well tolerated and is associated with short-term improvement in VA
and decreased OCT retinal thickness in a considerable proportion of patients with
uveitic CME resistant to conventional therapy. Further evaluation of intravitreal
bevacizumab for uveitic CME in controlled randomized studies is warranted.

PMID: 17363060 [PubMed - indexed for MEDLINE]

977: J Mol Biol. 2007 Apr 27;368(2):564-81. Epub 2007 Feb 22.

Associative and structural properties of the region of complement factor H
encompassing the Tyr402His disease-related polymorphism and its interactions with
heparin.

Fernando AN, Furtado PB, Clark SJ, Gilbert HE, Day AJ, Sim RB, Perkins SJ.

Department of Biochemistry and Molecular Biology, Darwin Building, University
College London, Gower Street, London WC1E 6BT, UK.

Factor H (FH) is a major complement control protein in serum. The seventh short
complement regulator (SCR-7) domain of the 20 in FH is associated with
age-related macular degeneration through a Tyr402His polymorphism. The
recombinant SCR-6/8 domains containing either His402 or Tyr402 and their
complexes with a heparin decasaccharide were studied by analytical
ultracentrifugation and X-ray scattering. The sedimentation coefficient is
concentration dependent, giving a value of 2.0 S at zero concentration and a
frictional ratio f/f(o) of 1.2 for both allotypes. The His402 allotype showed a
slightly greater self-association than the Tyr402 allotype, and small amounts of 
dimeric SCR-6/8 were found for both allotypes in 50 mM, 137 mM and 250 mM NaCl
buffers. Sedimentation equilibrium data were interpreted in terms of a
monomer-dimer equilibrium with a dissociation constant of 40 microM for the
His402 form. The Guinier radius of gyration R(G) of 3.1-3.3 nm and the R(G)/R(O) 
ratio of 2.0-2.1 showed that SCR-6/8 is relatively extended in solution. The
distance distribution function P(r) showed a maximum dimension of 10 nm, which is
less than the length expected for a linear domain arrangement. The constrained
scattering and sedimentation modelling of FH SCR-6/8 showed that bent SCR
arrangements fit the data better than linear arrangements. Previously identified 
heparin-binding residues were exposed on the outside curvature of this bent
domain structure. Heparin caused the formation of a more linear structure,
possibly by binding to residues in the linker. It was concluded that the His402
allotype may self-associate more readily than the Tyr402 allotype, SCR-6/8 is
partly responsible for the folded-back structure of intact FH, and SCR-6/8
changes conformation upon heparin binding.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17362990 [PubMed - indexed for MEDLINE]

978: Clin Experiment Ophthalmol. 2007 Mar;35(2):186-7.

Erythropoietin levels in aqueous humour in eyes with exudative age-related
macular degeneration and diabetic retinopathy.

Jonas JB, Neumaier M.

The purpose of this study was to evaluate whether the concentration of
erythropoietin as another potent ischemia-induced angiogenic factor is elevated
in eyes with neovascular (age-related macular degeneration [AMD]) or oedematous
(diabetic retinopathy) maculopathies. The clinical comparative study included 28 
patients with diabetic macular oedema, 59 patients with exudative AMD, and 49
patients with cataract. For all patients, aqueous humour was collected during
cataract surgery or during an intravitreal injection of triamcinolone acetonide. 
Erythropoietin levels were measured using a solid-phase chemiluminescence
immunoassay. The mean concentration of erythropoietin was significantly higher in
the diabetic group (60.1 +/- 46.7 mUnits/mL; P < 0.001) than in the age-related
macular degeneration group (22.9 +/- 23.2 mUnits/mL) and in the control group
(22.0 +/- 21.0 mUnits/mL; P < 0.001). The two latter groups did not vary
significantly (P = 0.41). The results indicate that erythropoietin may be present
in considerably higher concentrations in eyes with diabetic macular oedema than
in eyes with exudative AMD or normal eyes.

Publication Types: 
    Letter

PMID: 17362463 [PubMed - indexed for MEDLINE]

979: Clin Experiment Ophthalmol. 2007 Mar;35(2):167-73.

Surgical treatment of age-related macular degeneration: will there be a role in
the future?

Wong D, Durnian JM.

University of Hong Kong, Li Ka Shing Faculty of Medicine, Pok Fu Lam, Hong Kong, 
China. saihungdavid@mac.com

Surgical treatment has been shown to be able to improve vision that is lost as a 
result of age-related macular degeneration. Surgery is complex, such that
improvement has always to be weighed against risk of complications. The
availability of Ranibizumab and Bevacizumab is set to dramatically alter our
management options. Surgical treatment will have a limited role to play in the
next few years.

Publication Types: 
    Review

PMID: 17362461 [PubMed - indexed for MEDLINE]

980: Can J Ophthalmol. 2007 Feb;42(1):116-22.

Surgical macular decompression for macular edema in retinal vein occlusion.

Mandelcorn MS, Mandelcorn E, Guan K, Adatia FA.

Department of Ophthalmology and Vision Sciences, University of Toronto, Ontario, 
Canada. mark.mandelcorn@utoronto.ca

BACKGROUND: Recently, a number of surgical and laser approaches have been used to
improve visual outcome in cases of central retinal vein occlusion (CRVO) and
branch retinal vein occlusion (BRVO). Intravitreal steroid injection alone
appears to offer only temporary improvement at best. Radial optic neurotomy for
CRVO and arteriovenous adventitial sheathotomy for BRVO are the most frequently
utilized surgical procedures for these conditions, but evidence regarding
efficacy is still lacking. We have suggested that macular decompression by
internal limiting membrane (ILM) peeling may reduce macular edema and hemorrhage 
and improve visual acuity by relieving elevated intraretinal tissue pressure and 
facilitating egress of blood and extracellular fluid out of inner retinal layers 
into the vitrectomized vitreous cavity. METHODS: 50 cases of severe visual loss
due to macular edema caused by CRVO or BRVO, not eligible for laser
photocoagulation, underwent pars plana vitrectomy with removal of preretinal
hyaloid, peeling of the ILM stained with indocyanine green dye, air-fluid
exchange, and postoperative prone positioning. RESULTS: In all cases,
intraretinal blood and retinal thickening diminished within 6 weeks of surgery.
Visual acuity improved in 87% of CRVO cases and 68% of BRVO cases. Vision
improved and stabilized at 39 days after surgery. Average improvement was 2.6
lines with a 6-line improvement in 1 case. There was no difference in outcome
between cases with ischemic or nonischemic features on fluorescein angiography.
INTERPRETATION: Macular decompression using vitrectomy and ILM peeling is
effective in the treatment of severe visual loss due to macular edema in CRVO and
in those BRVO cases that do not qualify for laser photocoagulation.

PMID: 17361252 [PubMed - indexed for MEDLINE]

981: Can J Ophthalmol. 2007 Feb;42(1):107-9.

Fluorescein angiographic findings in cases with intermediate uveitis in the
inactive phase.

Gürlü VP, Alimgil ML, Esgin H.

Department of Ophthalmology, Trakya University, Edirne, Turkey.
gurluvuslat@yahoo.com

BACKGROUND: To determine fundus fluorescein angiography (FA) findings in cases
with intermediate uveitis in the inactive phase. METHODS: This prospective study 
included all eligible cases with a diagnosis of intermediate uveitis that were
treated at the uvea unit of Trakya University ophthalmology department between
January 2002 and January 2004. Study criteria included patients in the inactive
phase who had no complaints, no biomicroscopic or ophthalmoscopic inflammatory
findings in the anterior and posterior segments, and no period of inflammation
that had occurred within the previous 6 months. Cases receiving immunosuppressive
treatment were not excluded. FA was performed in all cases, which were evaluated 
by 2 independent observers. RESULTS: A total of 21 eyes from 21 cases with
intermediate uveitis were included in the study. FAs of the cases were taken
approximately 8.8 (SD 5.4) months (range 6-23 months) after the last activation. 
In these FAs, no pathological findings were identified in 5 eyes (23.8%); optic
disc hyperfluorescence was observed in 14 eyes (66.7%); large vein staining was
observed in 2 eyes (9.5%); peripheral venous leakage was observed in 6 eyes
(28.6%); and cystoid macular edema was observed in 5 eyes (23.8%).
INTERPRETATION: These findings indicate that retinal vascular inflammatory
changes persist in cases with intermediate uveitis even if the clinical
manifestations have been treated.

PMID: 17361250 [PubMed - indexed for MEDLINE]

982: J Biol Chem. 2007 Jun 29;282(26):18960-8. Epub 2007 Mar 13.

Structure shows that a glycosaminoglycan and protein recognition site in factor H
is perturbed by age-related macular degeneration-linked single nucleotide
polymorphism.

Herbert AP, Deakin JA, Schmidt CQ, Blaum BS, Egan C, Ferreira VP, Pangburn MK,
Lyon M, Uhrín D, Barlow PN.

Edinburgh Biomolecular NMR Unit, School of Chemistry and School of Biological
Sciences, University of Edinburgh, West Mains Road, Edinburgh EH9 3JJ, Scotland, 
United Kingdom.

A common single nucleotide polymorphism in the factor H gene predisposes to
age-related macular degeneration. Factor H blocks the alternative pathway of
complement on self-surfaces bearing specific polyanions, including the
glycosaminoglycan chains of proteoglycans. Factor H also binds C-reactive
protein, potentially contributing to noninflammatory apoptotic processes. The at 
risk sequence contains His (rather than Tyr) at position 402 (384 in the mature
protein), in the seventh of the 20 complement control protein (CCP) modules
(CCP7) of factor H. We expressed both His(402) and Tyr(402) variants of CCP7,
CCP7,8, and CCP6-8. We determined structures of His(402) and Tyr(402) CCP7 and
showed them to be nearly identical. The side chains of His/Tyr(402) have similar,
solvent-exposed orientations far from interfaces with CCP6 and -8. Tyr(402) CCP7 
bound significantly more tightly than His(402) CCP7 to a heparin affinity column 
as well as to defined-length sulfated heparin oligosaccharides employed in gel
mobility shift assays. This observation is consistent with the position of the
402 side chain on the edge of one of two glycosaminoglycan-binding surface
patches on CCP7 that we inferred on the basis of chemical shift perturbation
studies with a sulfated heparin tetrasaccharide. According to surface plasmon
resonance measurements, Tyr(402) CCP6-8 binds significantly more tightly than
His(402) CCP6-8 to immobilized C-reactive protein. The data support a causal link
between H402Y and age-related macular degeneration in which variation at position
402 modulates the response of factor H to age-related changes in the
glycosaminoglycan composition and apoptotic activity of the macula.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17360715 [PubMed - indexed for MEDLINE]

983: Int Ophthalmol. 2005 Dec;26(6):207-14. Epub 2007 Feb 14.

Intravitreal triamcinolone as an adjunct in the treatment of concomitant
proliferative diabetic retinopathy and diffuse diabetic macular oedema. Combined 
IVTA and laser treatment for PDR with CSMO.

Kaderli B, Avci R, Gelisken O, Yucel AA.

Department of Ophthalmology, Uludag University Hospital, 16059 Gorukle, Bursa,
Turkey.

PURPOSE: To investigate if triamcinolone acetonide (TA) can be an adjunct to
laser treatment in patients with concomitant non-high-risk proliferative diabetic
retinopathy (PDR) and diffuse clinically significant diabetic macular oedema
(CSMO). METHODS: This prospective, interventional and comparative clinical study 
included 32 eyes of 16 patients with bilateral concomitant non-high-risk PDR and 
diffuse CSMO. Each patient received 4 mg intravitreal TA for the eye with worse
visual acuity (study group) and macular focal and grid laser photocoagulation
(MP) for the other eye (control group). One month later, each patient received
four sessions of panretinal photocoagulation for both eyes plus MP for the eyes
in the study group. The visual and angiographic results of both groups were
compared. RESULTS: In the study group, the mean visual acuity (VA) improved from 
0.12 +/- 2.3 lines at the baseline to 0.19 +/- 3.1 (P = 0.004), 0.20 +/- 3.2 (P =
0.004), 0.19 +/- 3.6 (P = 0.009) and 0.19 +/- 3.3 lines (P = 0.091) at the 1-,
3-, 6- and 9-month follow-up intervals, respectively. The macular oedema was
found to be resolved in 11 eyes (69%) and decreased in five eyes (31%). In the
control group, the mean VA deteriorated progressively from 0.41 +/- 3.1 lines at 
the baseline to 0.20 +/- 3.1 lines (P = 0.026) at the end of the study and the
macular oedema decreased only in three eyes (19%) at the sixth follow-up month.
CONCLUSIONS: During the follow-up period of the study, intravitreal TA as an
adjunct in the treatment of concomitant non-high-risk PDR and diffuse CSMO led to
a more-favourable clinical outcome than conventional laser treatment.

Publication Types: 
    Controlled Clinical Trial

PMID: 17356929 [PubMed - indexed for MEDLINE]

984: Ann Pharmacother. 2007 Apr;41(4):614-25. Epub 2007 Mar 13.

Bevacizumab for neovascular ocular diseases.

Lynch SS, Cheng CM.

Department of Clinical Pharmacy, University of California, San Francisco, CA
94143, USA. lynchs@pharmacy.ucsf.edu

OBJECTIVE: To review the efficacy and safety of off-label use of bevacizumab for 
neovascular ocular diseases. DATA SOURCES: A PubMed (1966-January 2007) search
was conducted using the terms human, intravitreal, bevacizumab, macular, and
retinopathy. Meeting abstracts from the American Academy of Ophthalmology, Retina
Society, Macula Society, and Association for Research in Vision and Ophthalmology
were reviewed. STUDY SELECTION AND DATA EXTRACTION: Controlled studies,
unpublished reports involving 100 or more subjects, and published reports
describing 5 or more subjects were reviewed. Only English-language articles were 
considered. DATA SYNTHESIS: Intravitreal bevacizumab has been evaluated in 133
patients in unpublished controlled studies. Over 3500 patients have been
evaluated in open-label studies with duration of follow-up ranging from 3 months 
to 1 year. The most common use was neovascular age-related macular degeneration
(AMD). Other conditions studied included diabetic retinopathy, pathological
myopia, neovascular glaucoma, and macular edema due to diabetes, retinal vein
occlusion, or uveitis. Statistically significant improvements in visual acuity,
as well as decreases in retinal thickness and the extent of choroidal
neovascularization, were noted. Intravitreal bevacizumab was well tolerated over 
the short term. In a registry compiling adverse experiences of 7113 intravitreal 
injections, rates of adverse events were less than or equal to 0.21%.
CONCLUSIONS: Uncontrolled studies support a benefit of intravitreal bevacizumab
in neovascular AMD for 3 months to 1 year. Low cost is a significant advantage of
bevacizumab. Patients should discuss the potential risks and benefits of
intravitreal bevacizumab and other available therapies with their physicians
before receiving treatment. Controlled trials are needed to characterize the
safety and efficacy of intravitreal bevacizumab and determine the optimal
treatment regimen.

Publication Types: 
    Review

PMID: 17355998 [PubMed - indexed for MEDLINE]

985: Curr Med Res Opin. 2007 Mar;23(3):477-87.

Verteporfin photodynamic therapy and anti-angiogenic drugs: potential for
combination therapy in exudative age-related macular degeneration.

Kaiser PK.

Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
pkkaiser@aol.com

OBJECTIVE: To discuss the rationale for combining anti-angiogenic treatment with 
verteporfin (Visudyne) photodynamic therapy in the management of choroidal
neovascularization (CNV) due to age-related macular degeneration (AMD) and
evaluate available evidence for the therapeutic benefits of such approaches.
SCOPE: The Medline and EMBASE databases were searched in October 2006 to retrieve
relevant articles. Additional articles were obtained from the reference lists of 
retrieved articles, as well as from recent scientific meetings and company
websites. FINDINGS: Treatments for CNV due to AMD can be directed at either the
vascular component of CNV (the new vessels that proliferate and leak blood and
fluid) or the angiogenic component that leads to the development of the
condition. Verteporfin targets the vascular component, whereas anti-angiogenic
agents (such as pegaptanib and ranibizumab) target key mediators of the
angiogenic cascade. The different mechanisms of action of these approaches offer 
the potential for additive or synergistic effects with combination therapy. In
addition, anti-angiogenic agents might counteract upregulation of angiogenic
factors (including VEGF) that occur after verteporfin photodynamic therapy.
Results from preclinical and clinical studies of the combination of ranibizumab
or pegaptanib with verteporfin warrant continued investigation. CONCLUSIONS: The 
use of anti-angiogenic agents in combination with verteporfin may have the
potential to improve visual outcomes and reduce the number of treatments in eyes 
with CNV due to AMD, and requires further evaluation in randomized, controlled
clinical trials.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17355729 [PubMed - indexed for MEDLINE]

986: Arch Ophthalmol. 2007 Mar;125(3):333-9.

Beta carotene supplementation and age-related maculopathy in a randomized trial
of US physicians.

Christen WG, Manson JE, Glynn RJ, Gaziano JM, Chew EY, Buring JE, Hennekens CH.

Division of Preventive Medicine, Department of Medicine, Brigham and Women's
Hospital, 900 Commonwealth Ave E, Boston, MA 02215-1204, USA.
wchristen@rics.bwh.harvard.edu

OBJECTIVE: To test whether beta carotene supplementation affects the incidence of
age-related maculopathy (ARM) in a large-scale randomized trial. DESIGN:
Randomized, double-masked, placebo-controlled trial among 22 071 apparently
healthy US male physicians aged 40 to 84 years. Participants were randomly
assigned to receive beta carotene (50 mg every other day) or placebo. Main
Outcome Measure Incident ARM responsible for a reduction in best-corrected visual
acuity to 20/30 or worse. RESULTS: After 12 years of treatment and follow-up,
there were 162 cases of ARM in the beta carotene group vs 170 cases in the
placebo group (relative risk [RR], 0.96; 95% confidence interval [CI],
0.78-1.20). The results were similar for the secondary end points of ARM with or 
without vision loss (275 vs 274 cases; RR, 1.01; 95% CI, 0.86-1.20) and advanced 
ARM (63 vs 66 cases; RR, 0.97; 95% CI, 0.69-1.37). CONCLUSIONS: These randomized 
data relative to 12 years of treatment among a large population of apparently
healthy men indicate that beta carotene supplementation has no beneficial or
harmful effect on the incidence of ARM. Long-term supplemental use of beta
carotene neither decreases nor increases the risk of ARM.

Publication Types: 
    Randomized Controlled Trial
    Research Support, N.I.H., Extramural

PMID: 17353403 [PubMed - indexed for MEDLINE]

987: Arch Ophthalmol. 2007 Mar;125(3):318-24.

Effect of ruboxistaurin in patients with diabetic macular edema: thirty-month
results of the randomized PKC-DMES clinical trial.

PKC-DMES Study Group.

OBJECTIVE: To evaluate the safety and efficacy of orally administered
ruboxistaurin (RBX) as a mesylate salt in patients with diabetic macular edema
(DME). DESIGN: Multicenter, double-masked, randomized, placebo-controlled study
of 686 patients receiving placebo or RBX orally (4, 16, or 32 mg/d) for 30
months. At baseline, patients had DME farther than 300 mum from the center of the
macula, an Early Treatment Diabetic Retinopathy Study retinopathy severity level 
from 20 to 47A without prior photocoagulation, and an Early Treatment Diabetic
Retinopathy Study visual acuity of 75 or more letters in the study eye. The
primary study outcome was progression to sight-threatening DME or application of 
focal/grid photocoagulation for DME. Main Outcome Measure Masked grading of
stereoscopic fundus photographs. RESULTS: The delay in progression to the primary
outcome was not statistically significant (32 mg of RBX vs placebo, P = .14
[unadjusted]; Cox proportional hazards model adjusted for covariates, hazards
ratio = 0.73; 95% confidence interval, 0.53-1.0; P = .06). However, application
of focal/grid photocoagulation prior to progression to sight-threatening DME
varied by site, and a secondary analysis of progression to sight-threatening DME 
alone showed that 32 mg of RBX per day reduced progression, compared with placebo
(P = .054 [unadjusted]; Cox proportional hazards model, hazards ratio = 0.66; 95%
confidence interval, 0.47-0.93; P = .02). CONCLUSIONS: Although progression to
the primary outcome was not delayed, daily oral administration of RBX may delay
progression of DME to a sight-threatening stage. Ruboxistaurin was well tolerated
in this study.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17353401 [PubMed - indexed for MEDLINE]

988: Arch Ophthalmol. 2007 Mar;125(3):309-17.

Randomized controlled study of an intravitreous dexamethasone drug delivery
system in patients with persistent macular edema.

Kuppermann BD, Blumenkranz MS, Haller JA, Williams GA, Weinberg DV, Chou C,
Whitcup SM; Dexamethasone DDS Phase II Study Group.

Department of Ophthalmology, University of California, Irvine, 118 Med Surge I,
Irvine, CA 92697-4375, USA. bdkupper@uci.edu

OBJECTIVE: To evaluate a dexamethasone intravitreous drug delivery system (DDS)
in patients with persistent (> or =90 days despite treatment) macular edema.
METHODS: This 6-month study randomized 315 patients with persistent macular edema
with best-corrected visual acuity (BCVA) of 20/40 to 20/200 in the study eye to
observation or a single treatment with dexamethasone DDS, 350 or 700 microg. MAIN
OUTCOME MEASURES: Proportion of patients achieving a BCVA improvement of 10 or
more letters or 15 or more letters, safety measures, change in fluorescein
angiographic leakage, and central retinal thickness. RESULTS: At day 90 (primary 
end point), an improvement in BCVA of 10 letters or more was achieved by a
greater proportion of patients treated with dexamethasone DDS, 700 microg (35%)
or 350 microg (24%), than observed patients (13%; P<.001 vs 700-microg group; P =
.04 vs 350-microg group); an improvement in BCVA of 15 letters or more was
achieved in 18% of patients treated with dexamethasone DDS, 700 microg, vs 6% of 
observed patients (P = .006). Results were similar in patients with diabetic
retinopathy, vein occlusion, or uveitis or Irvine-Gass syndrome. During 3 months 
of observation, 11% of treated patients and 2% of observed patients had
intraocular pressure increases of 10 mm Hg or higher. CONCLUSION: In persistent
macular edema, a single dexamethasone DDS treatment produced statistically
significant BCVA improvements 90 days after treatment and was well tolerated for 
180 days. Application to Clinical Practice Dexamethasone DDS, 700 microg, may
have potential as a treatment for persistent macular edema.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17353400 [PubMed - indexed for MEDLINE]

989: Arch Ophthalmol. 2007 Mar;125(3):300-5.

High-sensitivity C-reactive protein, other markers of inflammation, and the
incidence of macular degeneration in women.

Schaumberg DA, Christen WG, Buring JE, Glynn RJ, Rifai N, Ridker PM.

Division of Preventive Medicine, 900 Commonwealth Ave E, Boston, MA 02215, USA.
dschaumberg@rics.bwh.harvard.edu

OBJECTIVE: To investigate whether high-sensitivity C-reactive protein (hsCRP) and
other biomarkers of inflammation predict age-related macular degeneration (AMD). 
METHODS: We measured hsCRP, soluble intercellular adhesion molecule-1 (sICAM-1), 
and fibrinogen levels in baseline plasma samples from 27 687 participants with a 
mean age of 54.6 years and initially free of AMD in the Women's Health Study. We 
prospectively ascertained 150 cases of AMD with vision loss of 20/30 or worse in 
the affected eye by self-report confirmed with review of medical records during
275 852 person-years of follow-up (mean = 10 years) and used proportional hazards
models to examine the relationship between these biomarkers and AMD. RESULTS:
After adjustment for multiple risk factors, the hazard ratio (HR) (95% confidence
interval [CI]) of AMD, contrasting the highest vs lowest quintile of hsCRP, was
3.09 (1.39-6.88) (P trend = .02). In similar models, the HR (95% CI) for sICAM-1 
was 1.87 (0.97-3.58) (P trend = .07). The relationship between fibrinogen and AMD
was J-shaped, with an HR (95% CI) of 2.01 (1.07-3.75) for women in the highest
fifth vs second fifth. CONCLUSION: Elevated circulating levels of hsCRP, sICAM-1,
and fibrinogen precede the development of visually significant AMD in women,
providing further support for the hypothesis that inflammation may play a role in
AMD.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17353399 [PubMed - indexed for MEDLINE]

990: Ophthalmology. 2007 Aug;114(8):1520-5. Epub 2007 Mar 13.

Reproducibility of macular thickness and volume using Zeiss optical coherence
tomography in patients with diabetic macular edema.

Diabetic Retinopathy Clinical Research Network, Krzystolik MG, Strauber SF,
Aiello LP, Beck RW, Berger BB, Bressler NM, Browning DJ, Chambers RB, Danis RP,
Davis MD, Glassman AR, Gonzalez VH, Greenberg PB, Gross JG, Kim JE, Kollman C.

Jaeb Center for Health Research, 15310 Amberly Drive, Suite 350, Tampa, FL 33647,
USA.

PURPOSE: To evaluate optical coherence tomography (OCT) reproducibility in
patients with diabetic macular edema (DME). DESIGN: Prospective 1-day
observational study. PARTICIPANTS: Two hundred twelve eyes of 107 patients with
DME involving the macular center by clinical examination and OCT central subfield
thickness of > or =225 microm. METHODS: Retinal thickness was measured with the
OCT3 system, and scans were evaluated by a reading center. Reproducibility of
retinal thickness measurements was assessed, and 95% confidence intervals (CIs)
for a change in thickness were estimated. MAIN OUTCOME MEASURES: Reproducibility 
of OCT-measured central subfield thickness. RESULTS: Reproducibility was better
for central subfield thickness than for center point thickness (half-width of the
95% CI for absolute change, 38 microm vs. 50 microm, and for relative change, 11%
vs. 17%, respectively; P<0.001). The median absolute difference between replicate
measurements of the central subfield was 7 microm (2%). Half-widths of the 95% CI
for a change in central subfield thickness were 22, 23, 33, and 56 microm for
scans with central subfield thicknesses of <200, 200 to <250, 250 to <400, and > 
or =400 microm, respectively. When expressed as percentage differences between 2 
measurements, half-widths of the 95% CI for a change in central subfield
thickness were 10%, 10%, 10%, and 13% for scans with central subfield thicknesses
of <200, 200 to <250, 250 to <400, and > or =400 microm, respectively. We were
unable to identify an effect on reproducibility of central subfield measurements 
with respect to the presence of cystoid abnormalities, subretinal fluid,
vitreomacular traction, or reduced visual acuity. Reproducibility was better when
both scans had a standard deviation (SD) of the center point of <10.0%
(half-width of the 95% CI for change, 33 microm vs. 56 microm; P<0.001).
CONCLUSIONS: Reproducibility is better for central subfield thickness
measurements than for center point measurements, and variability is less with
retinal thickness when expressed as a percent change than when expressed as an
absolute change. A change in central subfield thickness exceeding 11% is likely
to be real. Scans with an SD of the center point of > or =10.0% are less
reproducible and should be viewed with caution when assessing the validity of an 
observed change in retinal thickness in patients with DME.

Publication Types: 
    Evaluation Studies
    Multicenter Study
    Research Support, N.I.H., Extramural

PMID: 17353052 [PubMed - indexed for MEDLINE]

991: Mayo Clin Proc. 2007 Mar;82(3):301-7.

Relationship between age-related macular degeneration-associated variants of
complement factor H and LOC387715 with coronary artery disease.

Pulido JS, McConnell JP, Lennon RJ, Bryant SC, Peterson LM, Berger PB, Somers V, 
Highsmith WE.

Department of Ophthalmology, Mayo Clinic College of Medicine, Rochester, Minn
55905, USA.

OBJECTIVE: To determine whether either of the gene variants associated with
age-related macular degeneration is associated with coronary artery disease
(CAD). PATIENTS AND METHODS: This study consisted of 493 patients who underwent
clinically indicated coronary angiography between June 1, 1998, and January 1,
1999. The Y402H variant of the complement factor H (CFH) gene and the A69S
variant of the LOC387715 gene locus were examined by restriction fragment length 
polymorphism. Multiple logistic regression models were used to assess the
association of CFH and LOC gene variants with CAD. Covariates with
well-established associations with CAD were also evaluated. RESULTS: Seventy
patients (14%) were homozygous for the histidine variant (HH) of CFH, 237 (48%)
were heterozygous for the histidine variant (HY), and 186 (38%) were homozygous
for the tyrosine variant (YY). Three hundred eight patients (62%) were homozygous
for the alanine allele of LOC387715, 170 (34%) were heterozygous for Ala and Ser 
alleles, and 15 (3%) were homozygous for the serine variant. The overall
association of the CFH genotype with CAD was not statistically significant
(P=.08). However, some evidence (P=-.046) suggested that CAD was increased for
the HH genotype compared to the homozygous wild-type YY genotype (odds ratio,
1.95; 95% confidence interval, 1.01-3.76). Male sex, hypertension, low-density
lipoprotein cholesterol, high-density lipoprotein cholesterol, and age were other
variables that demonstrated significant associations with CAD. The overall effect
of the LOC genotype was not statistically significant (P=-.06). Heterozygosity
for the serine variant was (P=-.02) associated with the absence of CAD vs the AS 
genotype (odds ratio, 0.59; confidence interval, 0.38-0.91; P=-.02). CONCLUSION: 
The CFH genotype may have an independent association with CAD, although our
evidence did not show statistical significance. Controlling for known risk
factors, the age-related macular degeneration-associated HH variant appears to be
associated with CAD. The LOC387715 gene may also play a role in CAD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17352366 [PubMed - indexed for MEDLINE]

992: Graefes Arch Clin Exp Ophthalmol. 2007 Dec;245(12):1831-6. Epub 2007 Mar 9.

Quality of life in a prospective, randomised pilot-trial of photodynamic therapy 
versus full macular translocation in treatment of neovascular age-related macular
degeneration--a report of 1 year results.

Lüke M, Ziemssen F, Bartz-Schmidt KU, Gelisken F.

University Eye Hospital, Centre for Ophthalmology, Eberhard-Karls University of
Tuebingen, Schleichstr. 12-16, 72076 Tuebingen, Germany.
matthias.lueke@med.uni-tuebingen.de

PURPOSE: To assess visual function and its effects on vision-targeted,
health-related quality of life (QOL) of patients with neovascular age-related
macular degeneration (AMD) treated with photodynamic therapy (PDT) or full
macular translocation (FMT). METHODS: Fifty patients with predominantly classic
subfoveal choroidal neovascularisation (CNV) secondary to AMD were randomised to 
PDT or FMT. To test the vision-targeted QOL, the 39-item National Eye Institute
Visual Function Questionnaire (NEI-VFQ-25 plus supplement) was administered prior
to and 1 year after therapy. The change of vision-related QOL at 1 year in
comparison to baseline was defined as primary end point. RESULTS: The
vision-related subscales showed a stabilisation or even higher mean scores at 1
year in both treatment groups. A significant improvement in the quality of the
subject's vision-related subscales was only observed after FMT correlating with a
more frequent increase in visual acuity. Comparing the results of the QOL scores 
after 1 year, the improvement of the subscale scores general vision (p = 0.03),
mental health (p = 0.02) and dependency (p = 0.03) were significantly higher in
the FMT arm. CONCLUSIONS: FMT and PDT can achieve a stabilisation in
vision-related QOL, in which FMT was superior to the PDT after 1 year. The
discrepancy between the amount of patients with an increased visual acuity after 
FMT and a moderate improvement in QOL might be caused by the onset of
complications related to this surgical procedure. Besides visual acuity, the
impact of therapy-related complications has to be taken into consideration when
evaluating new therapeutic concepts in exudative AMD.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial

PMID: 17347809 [PubMed - indexed for MEDLINE]

993: Hum Hered. 2007;63(3-4):212-8. Epub 2007 Mar 7.

The LOC387715 gene, smoking, body mass index, environmental associations with
advanced age-related macular degeneration.

Francis PJ, George S, Schultz DW, Rosner B, Hamon S, Ott J, Weleber RG, Klein ML,
Seddon JM.

Macular Degeneration Center, Casey Eye Institute, Oregon Health and Science
University, Portland, OR 97239, USA.

BACKGROUND AND AIMS: Age-related macular degeneration (AMD) is the leading cause 
of blindness in the Western World. It is now evident that both genetic and
environmental factors contribute to disease susceptibility. We tested the
hypotheses that (a) a common coding SNP in the LOC387715 gene is associated with 
advanced AMD (geographic atrophy or choroidal neovascularization), and (b) that
modifiable environmental exposures alter AMD susceptibility associated with this 
SNP. METHODS: A case-control association analysis was performed on participants
(530 advanced AMD cases and 280 controls) ascertained as part of the multi-center
Age-Related Eye Disease Study. AMD status was determined by the reading center
from fundus photographs using the AREDS AMD grading categorization. Environmental
risk factor exposure data was collected from participants whose DNA was also
genotyped for the LOC387715 gene SNP rs10490924. Multivariate logistic regression
analyses were performed. RESULTS AND CONCLUSIONS: The number of risk alleles at
the LOC387715 SNP was associated with advanced AMD, with odds ratios (OR) = 3.0
(95% confidence interval (CI) 2.1-4.3) for the GT heterozygous genotype and OR = 
12.1 (5.6-26.5) for the homozygous TT risk genotype, after controlling for
demographic and behavioral risk factors. The LOC387715 SNP was associated with
both forms of advanced AMD. Current cigarette smoking and body mass index were
independently related to AMD, controlling for genotype. However, there was no
statistical interaction between LOC387715 genotype and smoking with regard to
advanced AMD development.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17347568 [PubMed - indexed for MEDLINE]

994: Am J Clin Nutr. 2007 Mar;85(3):762-9.

Effect of dietary lutein and zeaxanthin on plasma carotenoids and their transport
in lipoproteins in age-related macular degeneration.

Wang W, Connor SL, Johnson EJ, Klein ML, Hughes S, Connor WE.

Department of Medicine, Oregon Health and Science University, Portland, OR
97239-3098, USA. wangwe@ohsu.edu

BACKGROUND: Low dietary intakes and low plasma concentrations of lutein and
zeaxanthin are associated with an increased risk of age-related macular
degeneration (AMD). No studies have challenged AMD patients with a diet high in
lutein and zeaxanthin. OBJECTIVE: The objective was to examine the effect of
diets low or high in lutein and zeaxanthin on plasma carotenoids and their
transport in AMD patients. DESIGN: Seven AMD patients and 5 control subjects were
fed a low-lutein, low-zeaxanthin diet ( approximately 1.1 mg/d) for 2 wk, which
was followed by a high-lutein, high-zeaxanthin diet ( approximately 11 mg/d) for 
4 wk. Ten subjects continued the diet for 8 wk. Plasma and lipoprotein
carotenoids were measured by HPLC. RESULTS: The high-lutein, high-zeaxanthin diet
resulted in 2- to 3-fold increases in plasma concentrations of lutein and
zeaxanthin and other carotenoids, except lycopene, in the AMD patients and the
control subjects. With this diet, 52% of the lutein and 44% of the zeaxanthin
were transported by HDL; approximately 22% of lutein and zeaxanthin was
transported by LDL. Only 20-25% of alpha-carotene, beta-carotene, and lycopene
was transported by HDL; 50-57% was transported by LDL. CONCLUSIONS: The AMD
patients and control subjects responded similarly to a diet high in lutein and
zeaxanthin; plasma carotenoid concentrations increased greatly in both groups,
and the transport of carotenoids by lipoproteins was not significantly different 
between the groups. This finding suggests that abnormalities in the metabolism of
lutein and zeaxanthin in AMD may reside in the uptake of lutein and zeaxanthin
from the plasma and transport into the retina.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17344498 [PubMed - indexed for MEDLINE]

995: Exp Eye Res. 2007 May;84(5):850-7. Epub 2007 Jan 27.

Nuclear kinesis, neurite sprouting and abnormal axonal projections of cone
photoreceptors in the aged and AMD-afflicted human retina.

Pow DV, Sullivan RK.

School of Biomedical Sciences, University of Newcastle, Callaghan, NSW 2308,
Australia. david.pow@newcastle.edu.au

Tissues often respond to damage by recapitulating developmental programs. We have
investigated whether anatomical signs of developmental recapitulation are evident
in cone photoreceptors of the aged and AMD-afflicted human retina. Radial
migration of cell nuclei mediated by microtubules is a characteristic feature of 
cells in the developing retina. Similarly, neurite outgrowth is a feature of
developing neurons. We have examined whether nuclear kinesis and neurite
outgrowth from cone photoreceptors is evident. Calbindin-positive cone
photoreceptor nuclei are normally positioned as a single layer of somata at the
outer border of the outer nuclear layer. In AMD-afflicted retinae, many nuclei
are translocated, with some somata abutting the outer plexiform layer (OPL) and
others outside the outer limiting membrane whilst many nuclei are present at
intermediate levels. The axonal processes of many cones were also aberrant,
displaying tortuous pathways as they projected to the OPL, with occasional
evidence for bifurcation at points where the axon changed direction. We suggest
that tangential extension of collateral neurites and the rapid retraction of the 
original process may give rise to the tortuous axonal projections observed. Since
microtubules are key mediators of both neurite extension and nuclear kinesis we
examined expression of microtubule associated protein 2 (MAP2) which is an
important regulator of neurite extension. The strong expression of MAP2 observed 
in those cells with aberrant morphologies supports the notion that abnormal
microtubule-mediated remodelling events are present in the AMD retina and to a
lesser extent in normal aged retinas, allowing cone photoreceptors to
recapitulate two key features of development.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17343852 [PubMed - indexed for MEDLINE]

996: J Ocul Pharmacol Ther. 2007 Feb;23(1):54-6.

Infrared spectroscopic examination of aqueous humor.

Weissbrodt D, Mueller R, Perrin J, Backhaus J, Jonas JB.

Mannheim University of Applied Sciences, Institute for Instrumental Analysis,
Mannheim, Germany.

OBJECTIVE: The aim of this study was to report on a new technique for examining
aqueous humor. PARTICIPANTS: Aqueous humor samples obtained from 198 patients
(cataract: n=66 eyes; age-related macular degeneration [AMD]: n=66; diabetic
macular edema: n=66) were in vitro examined by mid infrared spectroscopy. After
training and validating the technique, 66 samples were taken for the final
independent prediction. RESULTS: In computerized analysis of the spectrometric
data, 22 (100%) cataract eyes were diagnosed as the cataract group, 17 (77%)
diabetic macular edema eyes were diagnosed as the diabetic macular edema group,
and 14 (64%) eyes with AMD were diagnosed as the AMD group. Mid infrared
spectrometry could statistically significantly (P=0.004) differentiate between
the 3 study groups. CONCLUSIONS: Mid infrared spectroscopic examination of
aqueous humor may be able to differentiate eyes with cataract, AMD, or diabetic
macular edema.

PMID: 17341151 [PubMed - indexed for MEDLINE]

997: J Ocul Pharmacol Ther. 2007 Feb;23(1):46-53.

Evaluation of subretinal triamcinolone acetonide in patients with exudative
age-related macular degeneration.

Kozak I, Cheng L, Falkenstein I, Tammewar AM, Freeman WR.

Jacobs Retina Center at Shiley Eye Center, University of California at San Diego,
La Jolla, CA 92037, USA.

PURPOSE: The aim of this paper was to present the results of subretinal delivery 
of triamcinolone acetonide (TCA) in humans with choroidal neovascularization
(CNV) caused by age-related macular degeneration (AMD). METHODS: Twenty two (22) 
eyes of 22 patients underwent pars plana vitrectomy with subretinal TCA
administration. Two milligrams (2 mg) of preservative-free TCA were delivered
through a 32-gauge automatic subretinal injector in 20 microL of volume. Visual
acuity, fluorescein angiography (FA), and intraocular pressure (IOP) were
recorded and compared pre- and postoperatively. RESULTS: Preoperative
average+/-standard deviation visual acuity in the treated eye was 1.408+/-0.129
(logMAR; median 20/400) and 1.403+/-0.114 (logMAR; median 20/300) postoperatively
(P=0.51). The mean area of pre- and postoperative FA leakage in the operated eyes
was 21.31+/-1.125 and 19.29+/-1.108 mm2, respectively (P=0.04). The average IOP
value before treatment was 15.3+/-0.78 mmHg. Three (3) months after surgery, it
was 20.5+/-2.04 mmHg (P=0.02). Six (6) months and 1 year after surgery, the
average IOP was 17.0+/-0.66 mmHg (P=0.9) and 15.6+/-1.02 mmHg (P=0.6),
respectively. CONCLUSIONS: Subretinal TCA stabilizes visual acuity, decreases FA 
leakage in eyes with CNV owing to AMD, and does not increase IOP, as seen with
intravitreous injections.

Publication Types: 
    Evaluation Studies

PMID: 17341150 [PubMed - indexed for MEDLINE]

998: J Immunol. 2007 Mar 15;178(6):3831-6.

Y402H polymorphism of complement factor H affects binding affinity to C-reactive 
protein.

Laine M, Jarva H, Seitsonen S, Haapasalo K, Lehtinen MJ, Lindeman N, Anderson DH,
Johnson PT, Järvelä I, Jokiranta TS, Hageman GS, Immonen I, Meri S.

Department of Bacteriology and Immunology, Haartman Institute, University of
Helsinki, Haartmaninkatu 3, FI-00014 Helsinki, Finland.

Complement factor H (FH) is an important regulator of the alternative complement 
pathway. The Y402H polymorphism within the seventh short consensus repeat of FH
was recently shown to be associated with age-related macular degeneration, the
most common cause of irreversible blindness in the Western world. We examined the
effects of this polymorphism on various FH functions. FH purified from sera of
age-related macular degeneration patients homozygous for the FH(402H) variant
showed a significantly reduced binding to C-reactive protein (CRP), an acute
phase protein, as compared with FH derived from unaffected controls homozygous
for the FH(402Y) variant. Strongly reduced binding to CRP was also observed with 
a recombinant fragment of FH (short consensus repeat 5-7) containing the same
amino acid change. Because the interaction of CRP and FH promotes
complement-mediated clearance of cellular debris in a noninflammatory fashion, we
propose that the reduced binding of FH(402H) to CRP could lead to an impaired
targeting of FH to cellular debris and a reduction in debris clearance and
enhanced inflammation along the macular retinal pigmented epithelium-choroid
interface in individuals with age-related macular degeneration.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17339482 [PubMed - indexed for MEDLINE]

999: Ophthalmology. 2007 Jun;114(6):1157-63. Epub 2007 Mar 6.

Cigarette smoking and age-related macular degeneration in the EUREYE Study.

Chakravarthy U, Augood C, Bentham GC, de Jong PT, Rahu M, Seland J, Soubrane G,
Tomazzoli L, Topouzis F, Vingerling JR, Vioque J, Young IS, Fletcher AE.

Department of Ophthalmology, Queen's University of Belfast, Belfast, United
Kingdom.

OBJECTIVE: To examine the association between cigarette smoking and age-related
maculopathy (ARM) including age-related macular degeneration (AMD) in the
European population. DESIGN: Cross-sectional study. PARTICIPANTS: Four thousand
seven hundred fifty randomly sampled > or =65-year-olds from 7 study centers
across Europe (Norway, Estonia, United Kingdom, France, Italy, Greece, and
Spain). METHODS: Participants underwent an eye examination and digital retinal
photography. The images were graded at a single center. Smoking history was
ascertained by a structured questionnaire administered by trained fieldworkers.
Multinomial and binary logistic regressions were used to examine the association 
between smoking history and ARM grade and type of AMD, taking account of
potential confounders and the multicenter study design. MAIN OUTCOME MEASURES:
Photographic images were graded according to the International Classification
System for ARM and stratified using the Rotterdam staging system into 5 exclusive
stages (ARM 0-3 and ARM 4, also known as AMD). Age-related macular degeneration
also was classified as neovascular AMD or geographic atrophy (GA). RESULTS: One
hundred fifty-eight cases were categorized as AMD (109 neovascular AMD and 49
GA); 2260 had no signs of ARM (ARM 0). Current smokers had increased odds of
neovascular AMD (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.4-4.8) or 
GA (OR, 4.8; 95% CI, 2.1-11.1), whereas for ex-smokers the odds were around 1.7. 
Compared with people with unilateral AMD, those with bilateral AMD were more
likely to have a history of heavy smoking in the previous 25 years (OR, 5.1; 95% 
CI, 1.3-20.0). The attributable fraction for AMD due to smoking was 27% (95% CI, 
19%-33%). There was no consistent association with ARM grades 1 to 3 and smoking.
CONCLUSIONS: These findings highlight the need for increasing public awareness of
the risks associated with smoking and the benefit of quitting smoking. Patients
with unilateral disease who are current smokers should be advised of the risk of 
second-eye disease.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 17337063 [PubMed - indexed for MEDLINE]

1000: Graefes Arch Clin Exp Ophthalmol. 2007 Sep;245(9):1273-80. Epub 2007 Feb
28.

Intravitreal bevacizumab (Avastin) in combination with verteporfin photodynamic
therapy for choroidal neovascularization associated with age-related macular
degeneration (IBeVe Study).

Costa RA, Jorge R, Calucci D, Melo LA Jr, Cardillo JA, Scott IU.

U.D.A.T. Macular Imaging & Treatment Division, Hospital de Olhos de Araraquara,
Rua Padre Duarte 989 apto 172, Araraquara, SP 14801-310, Brazil.
roger.retina@globo.com

BACKGROUND: A novel alternative for combined treatment using verteporfin
photodynamic therapy (PDT) has emerged as preliminary safety and efficacy data of
the intravitreal use of the anti-angiogenic bevacizumab became available. In the 
current study we investigate the feasibility of intravitreal bevacizumab combined
with verteporfin PDT for the treatment of choroidal neovascularization (CNV)
secondary to age-related macular degeneration (AMD). METHODS: A single-centre,
prospective, open-label study of 11 patients with documented CNV progression
after PDT treatment who underwent combined PDT and intravitreal injection of 1.5 
mg of bevacizumab was undertaken. Standardized ophthalmic evaluation was
performed at baseline and at weeks 1, 2, 12 and 24. Clinical evidence of
complications and changes in logarithm of the minimum angle of resolution
(logMAR) best-corrected visual acuity (BCVA) using Early Treatment Diabetic
Retinopathy Study (ETDRS) charts and in fluorescein leakage from CNV were
evaluated. RESULTS: The mean (+/-SD) age of the 11 patients was 74 (+/-5) years. 
Seven eyes had been treated with one previous PDT session and four eyes had two
previous PDT sessions. The mean baseline logMAR ETDRS BCVA was 1.031 (Snellen
equivalent, 20/200(-2)). At follow-up weeks 1, 2, 12 and 24, the mean logMAR
ETDRS BCVA (Snellen equivalent) was 0.944 (20/160(-2)), 0.924 (20/160(-1)), 0.882
(20/160(+1)), and 0.933 (20/160(-2)), respectively. The change in BCVA from
baseline was significant at each study follow-up interval (P < or = 0.001); at 12
and 24 weeks, the mean change in BCVA from baseline was an improvement of 1.49
and of 0.98 ETDRS line, respectively. Fluorescein leakage from CNV was absent in 
all eyes at week 12. One additional treatment session was required in seven
(63.6%) eyes at week 24 due to recurrent fluorescein leakage from CNV ("minimum" 
[<50% of the leaking area noted at baseline], n = 4; and "moderate" [>50% of the 
leaking area noted at baseline], n = 3). No progression of the neovascular lesion
was observed at week 24. No safety issues were identified throughout the period
of the study. CONCLUSIONS: The overall changes in vision and fluorescein leakage 
from CNV throughout the study suggest that a possible synergistic effect may
arise from the combination of intravitreal bevacizumab with verteporfin PDT for
the treatment of neovascular AMD.

Publication Types: 
    Clinical Trial

PMID: 17333238 [PubMed - indexed for MEDLINE]

1001: Eye. 2008 Jun;22(6):782-9. Epub 2007 Mar 2.

Optical coherence tomography on autologous translocation of choroid and retinal
pigment epithelium in age-related macular degeneration.

Joeres S, Llacer H, Heussen FM, Weiss C, Kirchhof B, Joussen AM.

Department of Vitreoretinal Surgery, Center for Ophthalmology, University of
Cologne, Cologne, Germany.

PURPOSE: To analyse structural changes after autologous translocation of choroid 
and retinal pigment epithelium (RPE) in patients with age-related macular
degeneration (AMD) using optical coherence tomography (OCT). METHODS: We
performed a prospective nonrandomised study in 29 consecutive patients, who
underwent submacular surgery with translocation of an autologous full-thickness
graft of RPE, Bruch's membrane, and choroid. All patients had recent loss of
reading vision due to AMD. OCT was performed before surgery and at 3- and 6-
month follow-up to analyse the morphological appearance of the graft and the
overlying retina. RESULTS: Maximum retinal thickness decreased from mean 408
microm (standard deviation (SD) 127 microm) preoperative to mean 373 microm (SD
104 microm) at 6-month follow-up (P=0.094). In 11 cases (40%), a nearly
physiological shape of the retina was seen at this time point. A macular hole
persisted in two eyes after silicone oil removal. In most eyes, the highly
reflective band of the graft presumably corresponding to RPE was continuous with 
the surrounding RPE band in all six OCT scans. Eyes with flat appearance of the
graft at 6-month follow-up (<300 microm) showed a significantly better functional
outcome than eyes with more prominent grafts. Interestingly, most patients did
not complain about metamorphopsia, even though the graft was prominent or
wrinkled in some cases. CONCLUSION: OCT is a useful tool in monitoring intra- and
subretinal changes after subretinal surgery with graft translocation. We
demonstrated that graft translocation may lead to a normalisation of retinal
thickness and stabilisation of visual acuity.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17332766 [PubMed - indexed for MEDLINE]

1002: Ophthalmology. 2007 Aug;114(8):1499-504. Epub 2007 Feb 28.

Axial length measurement in eyes with diabetic macular edema: a-scan ultrasound
versus IOLMaster.

Attas-Fox L, Zadok D, Gerber Y, Morad Y, Eting E, Benamou N, Pras E, Segal O,
Avni I, Barkana Y.

Department of Ophthalmology, Assaf Harofeh Medical Center, Zerifin, Israel.

OBJECTIVE: To compare axial length (AL) measurements obtained with ultrasound
(US) and IOLMaster (software version 3.01.0294; Carl Zeiss Meditec, Jena,
Germany) in eyes with diabetic clinically significant macular edema (CSME) and to
examine the correlation between measurement difference and foveal thickness.
DESIGN: Prospective nonrandomized clinical study. PARTICIPANTS: Twenty-three
healthy eyes of 23 participants and 21 eyes with CSME of 21 diabetic outpatients.
METHODS: The authors prospectively measured AL using US and IOLMaster in eyes of 
both groups. Foveal thickness was measured with optical coherence tomography. The
difference between both methods was assessed using the t test, and its
correlation to foveal thickness was evaluated by Pearson coefficient. MAIN
OUTCOME MEASURE: Difference in AL measurements between IOLMaster and US. RESULTS:
Mean+/-standard deviation foveal thickness in healthy and CSME eyes was 201+/-26 
microm (range, 156-240) and 475+/-106 microm (range, 331-758), respectively. Mean
AL by US and IOLMaster in healthy eyes was 23.17+/-1.07 mm (range, 21.17-25.18)
and 23.25+/-1.10 mm (range, 21.17-25.26), respectively (P = 0.51); in CSME eyes, 
it was 23.02+/-0.97 mm (range, 21.53-24.81) and 23.27+/-0.924 mm (range,
21.9-25.13), respectively (P<0.001). Correlation between AL difference and foveal
thickness was poor in both healthy (r = 0.18, P = 0.40) and CSME (r = 0.02, P =
0.93) eyes. CONCLUSIONS: Axial length measurements using applanation A-scan US
and IOLMaster in eyes with CSME differ statistically and clinically
significantly. This is likely a result of the fundamentally different methodology
of the 2 methods in measuring eyes with a pathologically thickened retina. A
conversion formula based on foveal thickness can not be provided at present.

Publication Types: 
    Comparative Study

PMID: 17331581 [PubMed - indexed for MEDLINE]

1003: Mol Vis. 2007 Feb 7;13:196-205.

An update on the genetics of age-related macular degeneration.

Scholl HP, Fleckenstein M, Charbel Issa P, Keilhauer C, Holz FG, Weber BH.

Department of Ophthalmology, University of Bonn, Bonn, Germany.
hendrik.scholl@ukb.uni-bonn.de <hendrik.scholl@ukb.uni-bonn.de>

Age-related macular degeneration (AMD) is a genetically complex disorder of the
photoreceptor-RPE-Bruch's membrane-choriocapillaris complex. Family and twin
studies have shown that the susceptibility for this disease is genetically
influenced. The heritability has been estimated to be up to 71%. Linkage and
association studies have identified several chromosomal regions that are likely
to contain susceptibility loci with strongest evidence found on chromosome 1q31
and 10q26. Variants in the complement factor H (CFH) gene have been shown by
several independent studies to be associated with an increased risk for AMD in
Caucasian populations. These findings imply that the innate immune system may
play a significant role in AMD pathogenesis. The LOC387715/HTRA1 locus within
10q26 has been identified as a second major locus contributing to AMD
pathogenesis. The two late forms of AMD, choroidal neovascularization and
geographic atrophy, have not been found to be different in risk allele
distribution. Variants within CFH and LOC387715/HTRA1 may contribute to the
increased risk of late AMD largely through their impact on precursors, such as
drusen and/or other RPE/Bruch's membrane changes. Considering variants at CFH,
LOC387715/HTRA1 and complement component 2-complement factor B (C2-FB), high-risk
homozygotes at all three loci may have a 250-fold increased risk compared to
baseline. However, the identification of genetic factors has not resulted in
therapeutic strategies to modify the disease so far and additional genetic and
environmental factors are yet to be discovered in order to influence the onset
and the progression of AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17327825 [PubMed - indexed for MEDLINE]

1004: Invest Ophthalmol Vis Sci. 2007 Mar;48(3):1416-23.

Visual loss and visual hallucinations in patients with age-related macular
degeneration (Charles Bonnet syndrome).

Abbott EJ, Connor GB, Artes PH, Abadi RV.

University of Manchester, Faculty of Life Sciences, Manchester, England, United
Kingdom.

PURPOSE: The condition in which visual hallucinations (VHs) are solely associated
with a visual impairment is termed Charles Bonnet Syndrome (CBS). The study was
undertaken to investigate whether the extent of visual acuity (VA) loss and
central visual field loss predisposes a patient with age-related macular
degeneration (AMD) to develop a CBS VH and, in addition, whether the progression 
in loss is mirrored in the complexity of the VHs reported. VH phenomenology and
CBS prevalence were also examined. METHODS: Sixty-six patients (age range, 63-96 
years, mean +/- SD 81.2 +/- 7.1 years) with bilateral AMD were questioned as to
whether they had experienced any hallucinatory episodes exclusive to vision. The 
four-point primary inclusion criterion ensured that all patients had bilateral
AMD, a bilateral central scotoma, best monocular VA poorer than or equal to 0.6
logMAR (logarithm of the minimum angle of resolution) and intact cognition (using
the Mini Mental State Examination for the Blind and the Telephone Interview for
Cognitive Status). The patients who did not report VH were classified into the
non-VH group, with the remainder in the VH group. An extended Institute of
Psychiatry Structural Interview characterized the phenomenology of the VH. A
secondary inclusion criterion subdivided the VH group into the apparent CBS
group, in which personal medical history may have contributed to VH generation,
and the manifest CBS group, where VHs were solely as a result of the visual loss.
RESULTS: Fifty-three patients met the primary inclusion criterion: 32 were
classified into the non-VH group and 21 into the VH group. The VH group were
slightly younger (median difference, 4 years, P = 0.03) and appeared to have a
lower VA (median difference, 0.20 logMAR, P = 0.08) and a more extensive visual
field loss (P = 0.06) than did the non-VH group. However, when these variables
were evaluated simultaneously by logistic regression, only age emerged as a
statistically significant predictor of VH (odds ratio 0.88, 95% confidence
interval [CI] 0.8-0.99, P = 0.03). The prevalence of apparent CBS and manifest
CBS in the AMD population was found to be 25% and 15%, respectively. With no
clinical and phenomenological differences between the two CBS groups, the
secondary inclusion criterion was withdrawn, the VH group was renamed the CBS
group, and a prevalence of 40% was recalculated. Of the 82 visual phenomena
experienced by the CBS group, 21 were classified as simple VHs and 39 as complex 
VHs, with the remainder classified as either entopic phenomena or visual
inference. Patients who experienced both simple and complex VHs appeared to have 
a greater visual field loss (P = 0.06) compared with those patients who reported 
either solely simple or solely complex VHs. CONCLUSIONS: The extent of visual
loss did not appear to be a predictor for the likelihood of a patient with AMD
experiencing a CBS VH, nor was the progression of loss reflected in the
complexity of the VHs reported.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17325191 [PubMed - indexed for MEDLINE]

1005: Invest Ophthalmol Vis Sci. 2007 Mar;48(3):1128-32.

The LOC387715 polymorphism and age-related macular degeneration: replication in
three case-control samples.

Ross RJ, Bojanowski CM, Wang JJ, Chew EY, Rochtchina E, Ferris FL 3rd, Mitchell
P, Chan CC, Tuo J.

Laboratory of Immunology, National Eye Institute, National Institutes of Health, 
Bethesda, Maryland, USA.

PURPOSE: Age-related macular degeneration (AMD) is a multifactorial blinding
disease in the elderly. LOC387715 harbors a single-nucleotide polymorphism that
has an association with AMD. This study was conducted to confirm the association 
between LOC387715 and AMD and to refine estimates of the impact of this gene
variation in using samples from three studies: an Australian population-based
study and two U.S. clinic-based case-control studies. METHODS: Cases and controls
were collected from a National Eye Institute (NEI) clinical protocol (n = 240),
the Age-Related Eye Disease Study (AREDS; n = 488), and the Blue Mountains Eye
Study (BMES; n = 851). After DNA extraction, subjects were genotyped for the
LOC387715 Ala69Ser polymorphism (rs10490924). RESULTS: The combined NEI and AREDS
samples yielded odds ratios (ORs) of 2.61 (95% CI 1.89-3.61, P = 1.42 x 10(-9))
and 8.59 (95% CI 4.49-16.5, P = 3.56 x 10(-13)) for the heterozygous and
homozygous risk alleles, respectively. The corresponding odds ratios in the BMES 
sample were 1.69 (95% CI: 1.25-2.28, P = 0.0007) and 2.20 (95% CI: 1.05-4.62, P =
0.038) for the heterozygous and homozygous groups. Neither set of samples showed 
statistically significant interaction with smoking, although there appeared to be
a trend of interaction between smoking and LOC387715 for risk of advanced AMD.
CONCLUSIONS: Although these data from three case-control samples support an AMD
genetic risk marker harbored within LOC387715, the nested case-control data from 
the population-based BMES samples showed lower estimates than from the
clinic-based samples. This may be because the BMES samples consisted of largely
early AMD cases while the clinic-based AMD samples consisted exclusively of
advanced cases.

Publication Types: 
    Multicenter Study
    Research Support, N.I.H., Intramural
    Research Support, Non-U.S. Gov't

PMID: 17325155 [PubMed - indexed for MEDLINE]

1006: Invest Ophthalmol Vis Sci. 2007 Mar;48(3):1012-7.

Estrogen receptor alpha gene polymorphisms associated with incident aging macula 
disorder.

Boekhoorn SS, Vingerling JR, Uitterlinden AG, Van Meurs JB, van Duijn CM, Pols
HA, Hofman A, de Jong PT.

Department of Epidemiology and Biostatistics, Erasmus Medical Center, Rotterdam, 
The Netherlands.

PURPOSE: It has been suggested that early menopause increases the risk of
aging-macula disorder (AMD), the major cause of incurable blindness with a dry
and wet late subtype, and that exposure to endogenous or postmenopausal exogenous
estrogens reduces this risk. This study was undertaken to investigate whether
genetic variations in the estrogen receptor alpha (ESR1) gene are associated with
incident AMD. METHODS: In the Rotterdam Study, a prospective population-based
cohort study of participants aged 55 years and older, associations between ESR1
PvuII-XbaI haplotypes and incident early or late AMD were studied in 4571
participants after a mean follow-up time of 7.7 years. Cox proportional hazards
regression was used to estimate hazard ratios (HRs) and corresponding 95%
confidence intervals (CIs), with adjustment for the most common confounders.
RESULTS: ESR1 PvuII-XbaI haplotype 1 was a risk factor for late AMD. Persons with
two copies of haplotype 1 were at 3.20 (95% CI, 1.47-6.99) times higher risk for 
late AMD than noncarriers of haplotype 1, after adjustment for age and sex. This 
increase was more pronounced for wet AMD (hazard ratio [HR] 4.29; 95% CI,
1.47-12.49) after adjustment for age, sex, smoking, and complement factor H
genotype. Correction for additional confounders, including age at menopause, use 
of hormone replacement therapy, blood pressure, and body mass index did not
essentially alter the findings. CONCLUSIONS: Persons with one or two copies of
ESR1 PvuII-XbaI haplotype 1 have an increased risk of late AMD, especially of the
wet form.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17325140 [PubMed - indexed for MEDLINE]

1007: Invest Ophthalmol Vis Sci. 2007 Mar;48(3):1007-11.

Prevalence of early and late age-related macular degeneration in a rural
population in northern India: the INDEYE feasibility study.

Gupta SK, Murthy GV, Morrison N, Price GM, Dherani M, John N, Fletcher AE,
Chakravarthy U.

Department of Community Ophthalmology, Dr Rajendra Prasad Centre for Ophthalmic
Sciences, All India Institute of Medical Sciences, New Delhi, India.

PURPOSE: To assess the prevalence of age-related macular degeneration (AMD) in a 
rural population in Northern India. METHODS: In a pilot feasibility study, 1443
people (median age, 60 years; 52% women), were identified from enumeration of the
50+ age group in 11 randomly sampled villages from a rural, periurban district of
Haryana, Northern India. Of those identified, 87% attended an eye examination
that included digital fundus photography. Fundus images were graded at a single
reading center using definitions from the Wisconsin Age-Related Maculopathy
Grading System. RESULTS: Fundus photographs were available for 1101 participants.
Overall, 28.8% of participants had ungradable fundus images due to cataract.
Including all with ungradable images in the denominator, the prevalence of soft
drusen was 34.0% (95% confidence interval [CI] 26.1-42.9); of soft indistinct
drusen, 2.2% (95% CI, 1.1-4.4); and of pigmentary irregularities, 10.8% (95% CI, 
7.1-16.1). There were 15 (1.4%) cases of late-stage AMD (95% CI, 0.8-2.3) with
the prevalence rising from 0.4% in the 50- to 59-year age range to 4.6% in those 
aged 70 years or older. CONCLUSIONS: Drusen and pigmentary irregularities are
common among the rural northern Indian population. The prevalence of late AMD is 
similar to that encountered in Western settings and is likely to contribute
significantly to the burden of vision loss in older people in the developing
world.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17325139 [PubMed - indexed for MEDLINE]

1008: Invest Ophthalmol Vis Sci. 2007 Mar;48(3):968-77.

Relationship of Basal laminar deposit and membranous debris to the clinical
presentation of early age-related macular degeneration.

Sarks S, Cherepanoff S, Killingsworth M, Sarks J.

Prince of Wales Medical Research Institute, Randwick, NSW, Australia.
shsarks@bigpond.net.au

PURPOSE: To correlate basal laminar deposit (BLamD) and membranous debris,
including basal linear deposit (BLinD), with the evolution of early age-related
macular degeneration (AMD). METHODS: A clinicopathologic collection of 132 eyes
with a continuous layer of BLamD was reviewed. The thickness and type of BLamD
and the sites of membranous debris deposition were correlated with the clinical
progression of the disease. RESULTS: Two types of BLamD, termed early and late,
were identified based on light microscopic appearance by using the picro-Mallory 
stain. The progressive accumulation of late type BLamD correlated well with
increasing BLamD thickness, advancing RPE degeneration, poorer vision, increasing
age, and clinically evident pigment changes. Membranous debris initially
accumulated diffusely as BLinD, most eyes with BLinD and early BLamD remaining
funduscopically normal. However, membranous debris also formed focal collections 
as basal mounds internal to the RPE basement membrane and as soft drusen external
to the basement membrane. Eyes in which membranous debris remained confined to
basal mounds belonged to older patients with poorer vision, whereas patients with
soft drusen were younger and had better vision. CONCLUSIONS: The presence of
BLinD and early BLamD define threshold AMD, which manifests clinically as a
normal fundus. Although late BLamD correlates most closely with clinical pigment 
abnormalities, it is the quantity and sites of membranous debris accumulation
that appear to determine whether the disease develops pigment changes only or
follows the alternative pathway of soft drusen formation with its attendant
greater risk of choroidal neovascularization (CNV).

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17325134 [PubMed - indexed for MEDLINE]

1009: Ophthalmology. 2007 Mar;114(3):561-70.

Autologous transplantation of the retinal pigment epithelium and choroid in the
treatment of neovascular age-related macular degeneration.

MacLaren RE, Uppal GS, Balaggan KS, Tufail A, Munro PM, Milliken AB, Ali RR,
Rubin GS, Aylward GW, da Cruz L.

Moorfields Eye Hospital, City Road, London, UK. robert.maclaren@moorfields.nhs.uk

PURPOSE: To assess excision of choroidal new vessels (CNV) combined with
autologous transplantation of the equatorial retinal pigment epithelium (RPE) as 
a means of restoring vision for patients with acute neovascular age-related
macular degeneration (AMD). DESIGN: Prospective interventional cohort study.
PARTICIPANTS: Twelve patients were recruited into an ethics committee approved
trial with informed consent between 2004 and 2005. All had <6 months of acute
visual loss owing to subfoveal neovascular AMD and were ineligible for
photodynamic therapy. METHODS: Patients underwent submacular removal of CNV
through a single retinotomy. A full-thickness patch graft of RPE, Bruch's
membrane, and choroid was harvested from the superior equatorial retina and
transplanted into the subfoveal space. The graft was flattened under heavy
liquid, before silicone oil exchange. Removal of silicone oil and cataract
surgery were performed 3 months later. All patients underwent cataract grading,
full refraction, optical coherence tomography, fundus autofluorescence, and
fluorescein and indocyanine angiography preoperatively and again 6 months
postoperatively. Retinal pigment epithelium samples from 3 patients were tested
for ex vivo gene transfer using a recombinant lentiviral vector. MAIN OUTCOME
MEASURES: Six months after surgery, successful transplantation was determined by 
the presence of a pigmented subfoveal graft showing RPE autofluorescence and
choroidal reperfusion. Visual outcome was assessed by subjective refraction and
microperimetry of the retina overlying the graft. RESULTS: Successful viable
grafts were seen in 11 patients. Three patients had good visual function on the
grafts, with mean logarithm of the minimum angle of resolution (logMAR) improving
from 0.88 to 0.79 and maintained beyond 1 year. Operative complications occurred 
in 8 patients, including retinal detachment in 5 patients and hemorrhage
affecting the graft in 4 patients. The mean visual acuity over the whole cohort
fell from logMAR 0.82 to 1.16. The excised RPE choroid could also be genetically 
modified outside the eye with a viral vector applied within the time frame of the
operation. CONCLUSIONS: Autologous RPE transplantation can in principle restore
vision in neovascular AMD, but surgical complications remain high. The
possibility for ex vivo gene transfer to the free graft of RPE may widen the
scope of this procedure to include gene therapy or adjunctive molecular
treatments for AMD.

Publication Types: 
    In Vitro
    Research Support, Non-U.S. Gov't

PMID: 17324698 [PubMed - indexed for MEDLINE]

1010: Ophthalmology. 2007 Mar;114(3):551-60.

Autologous translocation of the choroid and retinal pigment epithelium in
patients with geographic atrophy.

Joussen AM, Joeres S, Fawzy N, Heussen FM, Llacer H, van Meurs JC, Kirchhof B.

Department of Ophthalmology, University of Duesseldorf, Duesseldorf, Germany.
Joussena@googlemail.com

PURPOSE: To evaluate the functional and anatomical outcomes of autologous
translocation of peripheral choroid and retinal pigment epithelium (RPE) in
patients with geographic atrophy. DESIGN: Prospective nonrandomized study.
PARTICIPANTS: Twelve consecutive patients with geographic atrophy secondary to
age-related macular degeneration presenting with recent loss of reading vision.
METHODS: An autologous peripheral full-thickness graft of RPE, Bruch's membrane, 
and choroid was positioned under the macula in patients with geographic atrophy. 
MAIN OUTCOME MEASURES: Functional tests included Early Treatment Diabetic
Retinopathy Study distant vision, reading (Radner Test, measured as logarithm of 
the reading acuity determination [logRAD]), threshold static perimetry, and
determination of the point of fixation. Fluorescein and indocyanine green
angiography, autofluorescence, and optical coherence tomography served to
evaluate the anatomical outcome in a 6-month follow-up (12 months in 7 patients).
RESULTS: Preoperative visual acuity (VA) ranged from 20/800 to 20/40 (mean,
0.6+/-0.4 logarithm of the minimum angle of resolution), and reading vision from 
1.1 to 0.5 logRAD (mean, 0.8+/-0.2). Three patients were unable to read. Six
months after surgery, VA ranged from hand movements to 20/32, with an increase of
> or =5 letters in 2 eyes. Two patients without reading ability preoperatively
were able to read after surgery. Reading was possible in a total of 8 patients
after 6 months (1.3-0.4 logRAD). In 7 patients who were observed for 1 year, VA
remained stable (+/-1 line) in 5 eyes and decreased in 2 eyes between 6 months'
and 1 year's follow-up. In all eyes but 2, revascularization was visible on
indocyanine green angiography as early as 3 weeks after surgery. Autofluorescence
of the RPE was independent of revascularization of the graft and persisted
throughout follow-up. Four eyes had unstable fixation and/or extrafoveal fixation
before surgery. Two of these eyes stabilized during follow-up. Areas overlying
atrophic areas demonstrated low threshold sensitivities that persisted after
translocation of a free graft with only limited recovery. Revisional surgery due 
to proliferative vitreoretinopathy was required in 5 eyes. CONCLUSIONS: The
translocation of a full-thickness graft usually results in a vascularized and
functioning graft in patients with geographic atrophy, although is associated
with a high risk of complications and visual loss. Longer follow-up is necessary 
to learn about the long-term survival and functionality of the graft.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17324697 [PubMed - indexed for MEDLINE]

1011: BMC Ophthalmol. 2007 Feb 26;7:3.

TOZAL Study: an open case control study of an oral antioxidant and omega-3
supplement for dry AMD.

Cangemi FE.

Vitreo-Retinal Associates of New Jersey, Ridgewood, New Jersey 07450, USA.
franciscangemi@aol.com

BACKGROUND: The primary objective of this prospective study was to measure the
change from baseline in visual function--Best-Corrected Visual Acuity (BCVA) via 
the Early Treatment Diabetic Retinopathy Study (ETDRS) chart, contrast
sensitivity, central 10 degree visual fields and retinal imaging (angiograms and 
photographs) at 6 months in subjects with atrophic (dry) age-related macular
degeneration treated with a targeted nutritional supplement. METHODS: 37 mixed
gender patients with a mean age of 76.3 +/- 7.8 years were enrolled at 5
independent study sites and received standard of care with a novel formulation of
a nutritional supplement. Results were compared to a placebo cohort constructed
from the literature that was matched for inclusion and exclusion criteria. A
paired t-test was used to test a null hypothesis and a two-sided alpha level of
0.05 was used to determine statistical significance. RESULTS: 76.7% of subjects
receiving the nutritional supplement demonstrated stabilization or improvement of
BCVA at 6 months. Subjects gained an average of 0.0541 logMAR or one-half of a
line of visual acuity (VA) over the 6-month period. There was a statistically
significant improvement in VA from baseline with P = .045. The results provide
strong evidence that the treatment being studied produces an improvement in VA.
CONCLUSION: Treatment with this unique nutritional supplement increased VA above 
the expected baseline decrease in the majority of patients in this population
with dry macular degeneration. The results of the TOZAL study agree with the LAST
and CARMIS studies and are predictive for positive visual acuity outcomes in the 
AREDS II trial. However, patients will likely require supplementation for longer 
than 6 months to effect changes in additional visual parameters.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17324285 [PubMed - indexed for MEDLINE]

1012: Acta Ophthalmol Scand. 2007 Aug;85(5):563-5. Epub 2007 Feb 27.

Visual acuity change after intravitreal bevacizumab for exudative age-related
macular degeneration in relation to subfoveal membrane type.

Jonas JB, Libondi T, Ihloff AK, Harder B, Kreissig I, Schlichtenbrede F, Sauder
G, Spandau UH.

Department of Ophthalmology, Faculty of Clinical Medicine Mannheim, University of
Heidelberg, Mannheim, Germany. Jost.Jonas@augen.ma.uni-heidelberg.de

PURPOSE: To examine an association between the subfoveal neovascular membrane
type and visual acuity change after intravitreal bevacizumab injection for
exudative age-related macular degeneration (AMD). METHODS: We carried out a
clinical, retrospective, interventional case-series study including 66
consecutive patients (67 eyes) with exudative AMD who received an intravitreal
injection of 1.5 mg bevacizumab. Study subgroups included the occult type without
or with minimally classic subfoveal neovascularization (n = 28 eyes, 42%),
predominantly or purely classic subfoveal neovascularization (n = 22 eyes, 33%), 
and eyes with retinal pigment epithelium detachment (n = 17 eyes, 25%). Follow-up
was >or= 2 months. RESULTS: The maximal visual acuity (VA) gain (mean +/-
standard deviation - 0.07 +/- 0.30 logMAR, 0.5 +/- 2.9 Snellen lines; p = 0.87), 
and VA gain at 1 month (p = 0.10), 2 months (p = 0.77) and 3 months (p = 0.35)
after the injection did not vary significantly between the three study subgroups.
Correspondingly, a multivariate analysis did not reveal a statistically
significant (p = 0.57) influence of subfoveal lesion type on gain in VA.
CONCLUSIONS: Visual improvement after intravitreal bevacizumab does not differ
markedly between various types of subfoveal neovascularization in AMD.

Publication Types: 
    Case Reports

PMID: 17324219 [PubMed - indexed for MEDLINE]

1013: Br J Ophthalmol. 2007 Mar;91(3):391-3.

The Amsler chart: absence of evidence is not evidence of absence.

Crossland M, Rubin G.

UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK.
m.crossland@ucl.ac.uk

Early detection of the onset or progression of macular disease is likely to
become increasingly important as new treatment modalities are introduced. Current
best practice involves issuing patients with an Amsler chart for daily or weekly 
observation with the instruction to attend for immediate assessment should any
new distortion be perceived. However the sensitivity of Amsler charts in
detecting macular disease can be less than 50%, implying that presentation may be
delayed in over half of patients with advancing disease relying on the Amsler
chart to detect progression. A likely explanation for this is the phenomenon of
perceptual completion whereby regular objects are "filled-in" across the scotoma.
Although alternative tests have been developed and shown to have greater
sensitivity, at present no straightforward, cheap, home-based test of macular
disease progression is available. The development of such a self-diagnostic tool 
should be a research priority.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17322466 [PubMed - indexed for MEDLINE]

1014: Ophthalmology. 2007 Jun;114(6):1170-8. Epub 2007 Feb 23.

A value-based medicine comparison of interventions for subfoveal neovascular
macular degeneration.

Brown GC, Brown MM, Brown HC, Kindermann S, Sharma S.

Center for Value-Based Medicine, Flourtown, Pennsylvania 19031, USA.
gbrown@valuebasedmedicine.com

OBJECTIVE: To perform a value-based medicine analysis of clinical trials that
evaluate the interventions of laser photocoagulation, intravitreal pegaptanib
therapy, and photodynamic therapy (PDT) with verteporfin for the treatment of
classic subfoveal choroidal neovascularization. DESIGN: Reference case
cost-utility analysis using value-based medicine principles, which use
patient-based utility values and standardized, input variable criteria.
PARTICIPANTS: Data from participants in the Macular Photocoagulation Study,
Pegaptanib for Neovascular Age-Related Macular Degeneration Study, and the
Treatment of Age-Related Macular Degeneration with Photodynamic Therapy Study.
METHODS: Visual data were converted to a value-based format using time tradeoff
utility analysis values from patients with macular degeneration. Costs were
obtained from 2005 Medicare data. Outcomes (quality-adjusted life-years [QALYs]) 
and costs were discounted at a 3% annual rate. MAIN OUTCOME MEASURES:
Interventional QALYs gained, percent improvement in quality of life, and dollars 
spent per QALY gained. RESULTS: Laser photocoagulation confers a 4.4% (P = 0.03
versus pegaptanib therapy) improvement in quality of life for the reference case,
whereas pegaptanib therapy confers a 5.9% improvement and PDT confers an 8.1% (P 
= 0.0002 versus pegaptanib therapy) improvement. The cost-utility associated with
laser photocoagulation is $8179, that for pegaptanib therapy is $66978, and that 
for PDT is $31544. All sensitivity analyses remain within the conventional
standards of cost-effectiveness. CONCLUSIONS: Photodynamic therapy confers
greater patient value than intravitreal pegaptanib therapy and laser
photocoagulation for the treatment of classic subfoveal choroidal
neovascularization. Despite the fact that laser photocoagulation is the most
cost-effective intervention, both PDT and pegaptanib therapy deliver greater
value, and thus are both preferred over laser photocoagulation. Using an economic
measure, photodynamic therapy is the preferred treatment among these 3
interventions.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 17320964 [PubMed - indexed for MEDLINE]

1015: Ophthalmology. 2007 Jul;114(7):1319-26. Epub 2007 Feb 22.

Cost-effectiveness of vitamin therapy for age-related macular degeneration.

Rein DB, Saaddine JB, Wittenborn JS, Wirth KE, Hoerger TJ, Narayan KM, Clemons T,
Sorensen SW.

RTI International, Research Triangle Park, North Carolina, USA. drein@rti.org

OBJECTIVE: To determine the cost-effectiveness of vitamin therapy (antioxidants
plus zinc) for all indicated patients diagnosed with age-related macular
degeneration (AMD). DESIGN: We compared the impacts of vitamin therapy with those
of no vitamin therapy using a computerized, stochastic, agent-based model. The
model simulated the natural history of AMD and patterns of ophthalmic service use
in the United States in a cohort from age 50 years until 100 or death.
PARTICIPANTS AND/OR CONTROLS: The model created 20 million simulated individuals.
These individuals each received both the intervention (vitamin therapy after
diagnosis) and the control (no vitamin therapy). Expected outcomes generated when
vitamins were taken after diagnosis were compared with the expected outcomes
generated when they were not. METHODS: The model created individuals
representative of patients in the U.S. Incidence of early AMD was based on
published studies, as was vision loss and response to choroidal
neovascularization therapies. Post-incident disease progression was governed by
previously unpublished data drawn from the Age-Related Eye Disease Study. MAIN
OUTCOME MEASURES: Extent of disease progression, years and severity of visual
impairment, cost of ophthalmic care and nursing home services, and
quality-adjusted life years (QALYs). Costs and benefits were considered from the 
health care perspective and discounted using a 3% rate. The analysis was run for 
50 years starting in 2003. RESULTS: Compared with no therapy, vitamin therapy
yielded a cost-effectiveness ratio of $21,387 per QALY gained and lowered the
percentage of patients with AMD who ever developed visual impairment in the
better-seeing eye from 7.0% to 5.6%. CONCLUSIONS: Our model demonstrates that
vitamin therapy for AMD improves quality of life at a reasonable cost.

Publication Types: 
    Controlled Clinical Trial
    Research Support, U.S. Gov't, P.H.S.

PMID: 17320962 [PubMed - indexed for MEDLINE]

1016: Graefes Arch Clin Exp Ophthalmol. 2007 Jul;245(7):1037-40. Epub 2007 Feb
21.

RPE-rip after intravitreal bevacizumab (Avastin) treatment for vascularised PED
secondary to AMD.

Gamulescu MA, Framme C, Sachs H.

University Eye Clinic, Franz-Josef-Strauss Allee 11, 93053 Regensburg, Germany.
gamulescu@eye-regensburg.de

BACKGROUND: Retinal pigment epithelial (RPE)-rips in age-related macular
degeneration (AMD)-associated pigment epithelial detachment (PED) occur in the
natural course of the disease but also after therapy (e.g. laser
photocoagulation, photodynamic therapy), possibly triggered by the specific
therapy. We report here on four patients that received intravitreal bevacizumab
(Avastin) for AMD-associated vascularised PED and developed RPE-rips during the
follow-up. METHODS: The case reports of four consecutive patients that developed 
RPE-rips after intravitreal injection of bevacizumab at 1 mg/0.1 ml were
reviewed. RESULTS: The RPE-rips occurred in all patients between 1 week and 1
month following intravitreal injection. Two of the four patients improved in
vision despite the rip, but 3 months after the initial intervention, three
patients suffered deterioration in visual acuity and had to be re-injected.
CONCLUSION: Improvement in visual acuity may occur following intravitreal
bevacizumab despite RPE-rips, but the patients need close follow-up and eventual 
re-treatment in the case of deterioration.

Publication Types: 
    Case Reports

PMID: 17318562 [PubMed - indexed for MEDLINE]

1017: Am J Ophthalmol. 2007 Mar;143(3):516-8. Epub 2006 Nov 13.

Optical coherence tomography findings in occult macular dystrophy.

Brockhurst RJ, Sandberg MA.

Berman-Gund Laboratory for Study of Retinal Degenerations, Harvard Medical
School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts 02114, USA.

PURPOSE: To determine the basis for unexplained visual acuity loss in selected
patients. DESIGN: Observational study of patients with unexplained reduced visual
acuity. METHODS: We used optical coherence tomography (OCT) to evaluate foveal
structure in eight patients. These patients had corrected visual acuities of
20/25 to count fingers in one or both eyes and a normal ocular examination. We
recorded foveal cone electroretinograms (ERGs) as an objective measure of foveal 
function. RESULTS: Seven patients showed reduced foveal thickness associated with
thinning of the outer nuclear layer (ONL), and five of these patients also had
reduced foveal cone ERGs. One patient had normal tomograms and reduced foveal
ERGs. CONCLUSIONS: Unexplained reductions in visual acuity may result from
photoreceptor loss or foveal malfunction without photoreceptor loss, which are
indicators of occult macular dystrophy. OCT and the foveal cone ERG together
appear to be sufficient to identify the basis for visual acuity loss in these
patients.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17317401 [PubMed - indexed for MEDLINE]

1018: Am J Ophthalmol. 2007 Mar;143(3):510-2. Epub 2006 Nov 13.

Intravitreal bevacizumab (Avastin) for neovascular age-related macular
degeneration: a short-term study.

Chen CY, Wong TY, Heriot WJ.

Center for Eye Research Australia, University of Melbourne, Melbourne, Victoria, 
Australia.

PURPOSE: To report the short-term study of intravitreal bevacizumab (Avastin) in 
the treatment of neovascular age-related macular degeneration (AMD). DESIGN:
Interventional, consecutive, prospective case series. METHODS: One hundred and
two eyes of 102 patients with neovascular AMD received monthly intravitreal
bevacizumab (Avastin) (1.25 mg) until resolution of macular edema, subretinal
fluid, and/or pigment epithelial detachment. Outcome measures included visual
acuity (VA) and central retinal thickness as defined from optical coherence
tomography (OCT). RESULTS: Mean VA was 20/80 and OCT central retinal thickness
was 251.0 +/- 74.6 microm before injection and improved to 20/63 and 214.9 +/-
41.7 microm at six weeks (P < .001), 20/50 and 204.8 +/- 33.6 microm at 10 weeks 
(P < .001), and remained stable at 20/50 and 210 microm after 14 weeks (P < .05).
No significant ocular or systemic side effects were observed. CONCLUSIONS:
Intravitreal bevacizumab (Avastin) appears to be beneficial and well tolerated in
the treatment of neovascular AMD in the short term. Further comparative
evaluation against other antivascular endothelial growth factor (VEGF) agents and
dosing schedule is warranted.

PMID: 17317398 [PubMed - indexed for MEDLINE]

1019: Am J Ophthalmol. 2007 Mar;143(3):505-7. Epub 2006 Dec 28.

Retinal pigment epithelial tear after intravitreal ranibizumab.

Bakri SJ, Kitzmann AS.

Department of Ophthalmology, Mayo Clinic College of Medicine, Rochester,
Minnesota 55905, USA. bakri.sophie@mayo.edu

PURPOSE: To report two cases of a retinal pigment epithelial (RPE) tear after
intravitreal injection of 0.05 mg ranibizumab. DESIGN: Observational case report.
METHODS: Two patients with choroidal neovascularization (CNV) resulting from
age-related macular degeneration (AMD) were treated with an intravitreal
injection of ranibizumab. RESULTS: Both patients were found to have a RPE tear on
follow-up visits at one month, confirmed by optical coherence tomography (OCT)
and by fluorescein or indocyanine green angiography. CONCLUSIONS: RPE tears may
occur after intravitreal injection of ranibizumab. Further study is needed to
determine whether CNV membranes associated with pigment epithelial detachments
(PED) are more likely to develop RPE tears after treatment with anti-vascular
endothelial growth factor (anti-VEGF) agents.

Publication Types: 
    Case Reports

PMID: 17317396 [PubMed - indexed for MEDLINE]

1020: Am J Ophthalmol. 2007 Mar;143(3):504-5. Epub 2006 Dec 8.

Retinal pigment epithelium tears following ranibizumab for exudative age-related 
macular degeneration.

Carvounis PE, Kopel AC, Benz MS.

Cullen Eye Institute, Baylor College of Medicine, Houston, Texas, USA.

PURPOSE: To report two cases of retinal pigment epithelium (RPE) tears following 
intravitreous ranibizumab injection for age-related macular degeneration
(AMD)-associated serous pigment epithelium detachment (PED). DESIGN:
Noncomparative case series. METHODS: The charts of two patients who received
intravitreous ranibizumab for AMD-associated PED and developed RPE tears were
reviewed. Fundus photography, fluorescein angiography and optical coherence
tomography performed prior to injection and upon follow-up confirmed the
diagnosis. RESULTS: Two patients with serous PED and occult choroidal
neovascularization associated with AMD developed RPE tears within four weeks of
injection with ranibizumab. CONCLUSIONS: RPE tears may complicate ranibizumab
intravitreous injection for the treatment of AMD-associated PEDs. Further studies
need be undertaken to determine whether this complication may also occur when
treating choroidal neovascular membranes not associated with PED and whether
certain angiographic subtypes are more susceptible to this complication.

Publication Types: 
    Case Reports

PMID: 17317395 [PubMed - indexed for MEDLINE]

1021: Am J Ophthalmol. 2007 Mar;143(3):473-83. Epub 2007 Jan 10.

Cardiovascular disease, its risk factors and treatment, and age-related macular
degeneration: Women's Health Initiative Sight Exam ancillary study.

Klein R, Deng Y, Klein BE, Hyman L, Seddon J, Frank RN, Wallace RB, Hendrix SL,
Kuppermann BD, Langer RD, Kuller L, Brunner R, Johnson KC, Thomas AM, Haan M.

Department of Ophthalmology and Visual Sciences, University of Wisconsin,
Madison, Wisconsin 53726, USA. kleinr@epi.ophth.wisc.edu

PURPOSE: To examine the association of cardiovascular disease (CVD), CVD risk
factors, and CVD treatment with age-related macular degeneration (AMD). DESIGN:
Observational analysis of a randomized clinical trial. METHODS: SETTINGS: The
Women's Health Initiative Sight Examination (WHISE), an ancillary study to the
Women's Health Initiative's clinical trial of hormone replacement therapy. STUDY 
POPULATION: A total of 4,288 women age 63 years and older. OBSERVATION
PROCEDURES: Information on CVD and its risk factors were obtained from a
standardized questionnaire and examination. MAIN OUTCOME MEASURE: AMD as
determined by standardized grading of fundus photographs. RESULTS: Prevalence of 
any AMD was 21.4% (n = 919). Of those with AMD, 5.8% (n = 53) had signs of
exudative AMD (n = 39) or pure geographic atrophy (n = 14), limiting the power to
examine associations. Significant associations between late AMD and CVD risk
factors were (odds ratio [OR], 95% confidence interval [CI]) older age (1.19,
1.13 to 1.27, P < .0001), more pack years smoked (1.02 per pack-year smoked,
1.003 to 1.03, P = .01), systolic blood pressure (0.84 per 10 mm Hg, 0.71 to
0.995, P = .04), report of taking calcium channel blockers (2.49, 1.21 to 5.12, P
= .04), self-reported history of diabetes (2.00, 1.01 to 3.96, P = .05), and
greater body mass index (1.05 per 1 kg/m, 1.001 to 1.10, P = .05). History of
myocardial infarction, stroke, use of statins, or white blood cell count was not 
associated with AMD. CONCLUSIONS: Results suggest that smoking, use of calcium
channel blockers, diabetes, and obesity are risk factors for late AMD in women.
However, the association of late AMD with systolic blood pressure and the effects
of other CVD risk factors on early AMD need to be further explored.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17317391 [PubMed - indexed for MEDLINE]

1022: Br J Ophthalmol. 2007 Jul;91(7):966-70. Epub 2007 Feb 21.

Fine-scale linkage disequilibrium mapping of age-related macular degeneration in 
the complement factor H gene region.

Ennis S, Goverdhan S, Cree A, Hoh J, Collins A, Lotery A.

Genetic Epidemiology and Bioinformatics Group, Human Genetics Division (MP 808), 
Southampton General Hospital, Southampton, UK.

AIM: To present results from a nested association study of the complement factor 
H (CFH) gene region using a novel methodology that uses a high-resolution genetic
linkage disequilibrium map to estimate a point location for a causal mutation.
METHOD: Age-related macular degeneration (AMD) case-control data from a
genomewide single-nucleotide polymorphism (SNP) panel were used to identify the
target interval to be genotyped at higher density in a second independent panel. 
The pattern of linkage disequilibrium (LD) and segmental duplications across this
region are described in detail. RESULT: Data were consistent with other studies
in that strong association between the Y402H variant and AMD is observed.
However, composite likelihood analysis, which combines association data from all 
SNPs in the region, and uses genetic locations on a high-resolution LD map, gave 
a point location for a causal variant between exons 1 and 2 of the CFH gene.
CONCLUSION: The findings are consistent with evidence that, in addition to the
widely described Y402H variant, there is at least one and, most probably, several
other mutations in the CFH gene which determine disease manifestation in AMD. A
genetic model in which multiple mutations contribute to a varying degree to
disease aetiology has been previously well described in ophthalmic genetics, and 
is typified by the COL2A1 and ABCA4 genes.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17314151 [PubMed - indexed for MEDLINE]

1023: Exp Eye Res. 2007 Apr;84(4):772-80. Epub 2007 Jan 9.

Comment in:
    Exp Eye Res. 2008 May;86(5):860-1; author reply 862-3.

High concentration of zinc in sub-retinal pigment epithelial deposits.

Lengyel I, Flinn JM, Peto T, Linkous DH, Cano K, Bird AC, Lanzirotti A,
Frederickson CJ, van Kuijk FJ.

Division of Pathology, Institute of Ophthalmology, 11-43 Bath Street, University 
College London, and Department of Research and Development, Moorfields Eye
Hospital, London EC1V 9EL, UK. i.lengyel@ucl.ac.uk

One of the hallmarks of age-related macular degeneration (AMD), the leading cause
of blindness in the elderly in Western societies, is the accumulation of
sub-retinal pigment epithelial deposits (sub-RPE deposits), including drusen and 
basal laminar deposits, in Bruch's membrane (BM). The nature and the underlying
mechanisms of this deposit formation are not fully understood. Because we know
that zinc contributes to deposit formation in neurodegenerative diseases, we
tested the hypothesis that zinc might be involved in deposit formation in AMD.
Using zinc specific fluorescent probes and microprobe synchrotron X-ray
fluorescence we showed that sub-RPE deposits in post-mortem human tissues contain
unexpectedly high concentrations of zinc, including abundant bio-available (ionic
and/or loosely protein bound) ions. Zinc accumulation was especially high in the 
maculae of eyes with AMD. Internal deposit structures are especially enriched in 
bio-available zinc. Based on the evidence provided here we suggest that zinc
plays a role in sub-RPE deposit formation in the aging human eye and possibly
also in the development and/or progression of AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, Non-P.H.S.

PMID: 17313944 [PubMed - indexed for MEDLINE]

1024: Int J Clin Pract. 2007 Mar;61(3):501-9.

Ranibizumab for the treatment of neovascular AMD.

Kaiser PK, Do DV.

Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.

Age-related macular degeneration (AMD) is the leading cause of adult blindness
among individuals aged 50 and older in the Western world, with the neovascular
form of AMD responsible for the most severe and rapid visual loss. Although
monotherapy with currently available treatments can slow the rate of loss of
vision in eyes with neovascular AMD, they do not significantly improve vision.
Vascular endothelial growth factor-A (VEGF-A) plays a critical role in the
pathogenesis of neovascular AMD, and ranibizumab is a promising new treatment
that targets all VEGF-A isoforms and their biologically active degradation
products. Clinical trials have reported that ranibizumab treatment resulted in
greater proportions of patients achieving a < 15 letter loss of visual acuity and
improved vision at 12 and 24 months than control groups. The incidence of serious
ocular and systemic adverse events was low in all ranibizumab trials to date.
Currently, ranibizumab is the only treatment for neovascular AMD to demonstrate
significant improvement in vision for many patients and represents a major
advance in treating neovascular AMD.

Publication Types: 
    Review

PMID: 17313620 [PubMed - indexed for MEDLINE]

1025: Ophthalmology. 2007 Jul;114(7):1327-31. Epub 2007 Feb 16.

Complement factor H polymorphism in age-related macular degeneration.

Narayanan R, Butani V, Boyer DS, Atilano SR, Resende GP, Kim DS, Chakrabarti S,
Kuppermann BD, Khatibi N, Chwa M, Nesburn AB, Kenney MC.

Department of Ophthalmology, University of California Irvine Medical Center,
Irvine, California, USA.

PURPOSE: To determine the association between complement factor H (CFH)
polymorphism T1277C (tyrosine-402 --> histidine-402) and phenotypic variations of
age-related macular degeneration (AMD). DESIGN: Cross-sectional observational
study. PARTICIPANTS: Subjects with dry or wet AMD and a control population
consisting of age-matched non-AMD subjects from 2 clinical facilities examined
during the period January 1, 1999 through December 31, 2002. METHODS: Total DNA
isolated from the leukocytes of 66 AMD subjects and 58 age-matched control
subjects was studied. The CFH gene was amplified by polymerase chain reaction and
analyzed by Nla III restriction fragment length analysis. MAIN OUTCOME MEASURES: 
Incidence of CHF polymorphism with the occurrence of AMD. RESULTS: Among the AMD 
patients, 15 had dry and 51 had wet AMD. For the CFH gene, the T1277C variant
showed the genotype distribution as CC, TC, and TT. There was a strong
association between homozygous C and AMD compared with the control population
(odds ratio [OR] = 3.4; 95% confidence interval [CI], 1.32-8.74; P = 0.0053).
Furthermore, dry AMD had a stronger association (OR, 8.32; 95% CI, 2.30-30.11; P 
= 0.001) than wet AMD (OR, 2.49; 95% CI, 0.90-6.84; P = 0.039) compared with the 
control population. Homozygous T was more prevalent in the control subjects
compared with AMD patients (OR, 5; 95% CI, 2.18-11.43; P = 0.00005). CONCLUSIONS:
Complement factor H polymorphism T1277C (tyrosine-402 --> histidine-402) is
strongly associated with both dry and wet AMD and points to a possible role for
inflammation in the pathogenesis of AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17306880 [PubMed - indexed for MEDLINE]

1026: Ophthalmology. 2007 May;114(5):847-54. Epub 2007 Feb 16.

Relative cost of a line of vision in age-related macular degeneration.

Smiddy WE.

Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami
Miller School of Medicine, Miami, Florida, USA. wsmiddy@med.miami.edu

PURPOSE: To quantitate the relative cost of new therapies for age-related macular
degeneration (AMD) versus saved vision. DESIGN: Systematic review. METHODS:
Landmark AMD treatment studies were reviewed to quantitate the visual benefit.
For comparison, representative treatment studies for common retinal conditions
including retinal detachment, macular hole (MH), epiretinal membrane (ERM), and
diabetic retinopathy were also reviewed. MAIN OUTCOME MEASURES: Several
parameters to estimate Snellen lines of vision saved were defined and tabulated
for each condition. A regimen of office visits, ancillary testing, and treatments
was outlined. Costs for this were tabulated using Medicare-allowable costs, and
costs of visual benefit (per line of vision) for each condition were calculated. 
Life expectancy was factored in to calculate the cost of a line of vision for
each year (line-year). The proportions of costs allocated to professional,
technical, and pharmaceutical expenses were tabulated for each therapy. RESULTS: 
The cost per line of vision saved for AMD therapies ranged from $997 for laser
for extrafoveal choroidal neovascularization, to $5509 for photodynamic therapy
for occult lesions, to $12 482 for pegaptanib injections. This compares to $651
for retinal detachment repair, $1658 for MH repair, $2411 for ERM peeling, $5458 
for diabetic macular edema laser, $594 for panretinal photocoagulation, and $2984
to $4178 for diabetic vitrectomy. The costs per line-years ranged from $77 to
$1248 for AMD, and $21 to $194 for the comparison conditions. The proportion of
costs for pegaptanib treatment was 17% for professional fees and 70% for
pharmaceutical fees. Assumptions incorporated in estimating costs for pegaptanib 
could easily have doubled because second-year costs might approximate first-year 
costs and the maintenance of treatment effect has not been well established.
CONCLUSIONS: Although correctly heralded as a breakthrough in macular
degeneration treatment, new pharmacologic therapies for AMD are extremely
expensive and some yield marginal visual dividends. As in all fields of medicine 
that provide care to elderly patients, these costs should be considered as they
relate to health care costs for the individual patient and payors, and must be
considered in a larger perspective of health care benefit apportionment.

Publication Types: 
    Review

PMID: 17306878 [PubMed - indexed for MEDLINE]

1027: Exp Eye Res. 2007 Apr;84(4):718-28. Epub 2006 Dec 19.

Changes in macular pigment optical density and serum concentrations of its
constituent carotenoids following supplemental lutein and zeaxanthin: the LUNA
study.

Trieschmann M, Beatty S, Nolan JM, Hense HW, Heimes B, Austermann U, Fobker M,
Pauleikhoff D.

Institute of Ophthalmology, St. Franziskus Hospital, and Institute of
Epidemiology, University of Münster, Germany. meiketri@aol.com

Macular pigment (MP), consisting of lutein (L) and zeaxanthin (Z), is believed to
protect the retina from photo-oxidative damage. The current study investigates,
in terms of MP optical density (MPOD) and serum concentrations of its constituent
carotenoids, response to supplemental L and Z, and co-antioxidants. An
intervention (I) group, consisting of 108 subjects (mean [+/-SD] age: 71.5
[+/-7.1] years), of which 92.6% exhibited features of age-related macular
degeneration (AMD), received a daily supplement consisting of 12 mg L and 1 mg Z,
both provided as ester 120 mg vitamin C, 17.6 mg vitamin E, 10 mg zinc, 40 microg
selenium (Ocuvite Luteintrade mark) for a period of 6 months. MPOD was measured, 
by 2-wavelength autofluorescence (AF), on five occasions during the period of
supplementation, and once again 3 months following discontinuation of the
supplement. A control (C) group of 28 subjects (mean [+/-SD] age: 71.0 [+/-8.1]
years), who received no dietary supplementation or modification, was examined at 
baseline and once again after a mean of 29.4 (+/-9.3) weeks. At baseline, mean
(+/-SD) MPOD (at 0.5 degrees) was 0.504 (+/-0.197) and 0.525 (+/-0.189) in the I 
and C groups, respectively. There was a statistically significant increase in
MPOD (at 0.5 degrees) for the I group (0.1 [+/-0.009]; p<0.0008), whereas no
significant increase was seen in the C group (0.03 [+/-0.02]; p>0.05), over the
period of supplementation. In order to classify supplemented subjects into
quartiles, in terms of MPOD response, we calculated the difference between MPOD
(at 0.5 degrees) at visit 6 and at baseline (visit 1). Quartile 1 (the
"non-responder" quartile) displayed no increase in MPOD (at 0.5 degrees), in
spite of rises seen in serum concentrations of L and Z. The three "responder"
quartiles reached similar final plateaus of MPOD (at 0.5 degrees), reflected in
final mean (+/-SEM) values of 0.59 (+/-0.04) optical density unit (ODU), 0.64
(+/-0.03) ODU and 0.64 (+/-0.03) ODU for quartiles 2, 3 and 4, respectively.
Subjects with low baseline MPOD were more likely to exhibit a dramatic rise in
MPOD, or to exhibit no rise in MPOD, in response to supplements than subjects
with medium to high baseline MPOD values. Supplementation with 12 mg L and 1 mg
Z, combined with co-antioxidants, resulted in an increase of MPOD at 0.5 degrees 
eccentricity in a majority of subjects, including those afflicted with AMD.
However, there remains a substantial proportion of subjects for whom, in spite of
rises in serum concentrations of L and Z in these subjects, MPOD augmentation in 
response to supplemental L, Z and co-antioxidants could not be detected over the 
study period, thus indicating that intestinal malabsorption of these carotenoids 
is not responsible for the lack of a macular response to such supplements.
Further, our results suggest that saturable mechanisms play a role in the retinal
capture and/or stabilisation of the macular carotenoids.

PMID: 17306793 [PubMed - indexed for MEDLINE]

1028: Am J Ophthalmol. 2007 Apr;143(4):601-6. Epub 2007 Feb 15.

Clinical, anatomic, and electrophysiologic evaluation following intravitreal
bevacizumab for macular edema in retinal vein occlusion.

Pai SA, Shetty R, Vijayan PB, Venkatasubramaniam G, Yadav NK, Shetty BK, Babu RB,
Narayana KM.

Department of Vitreoretinal Surgery, Narayana Nethralaya, Superspeciality Eye
Hospital, Bangalore, India. sudhirshiv@yahoo.com <sudhirshiv@yahoo.com>

PURPOSE: To investigate clinical, anatomic, and electrophysiologic response after
single intravitreal injection of bevacizumab for macular edema attributable to
retinal vein occlusion. DESIGN: Prospective nonrandomized, interventional case
series. METHODS: Twenty-one patients with macular edema attributable to vein
occlusion received intravitreal injection of bevacizumab 1.25 mg. Nine patients
had central retinal vein occlusion (CRVO), and 12 patients had branch retinal
vein occlusion (BRVO). Complete ophthalmic examination including optical
coherence tomography (OCT) was done at baseline and follow-up visits. Fifteen
patients underwent fluorescein angiography at baseline. Selected patients
underwent electroretinography (ERG) and visual evoked potential (VEP) at baseline
and follow-up. Follow-up was for 12 weeks. RESULTS: At baseline, mean visual
acuity was 20/381 (median, 20/400) and showed improvement to mean 20/135 (median,
20/60) after one month, (P = .001). At 12 weeks, mean visual acuity was 20/178
(median, 20/80) (P = .001). The mean central retinal thickness (CRT) was 647.81
microm (median, 609.00 microm) at baseline and decreased to mean 293.43 microm
(median, 222.00 microm) at one month (P = .001). At 12 weeks, mean CRT was 320.90
mum (median, 280.00 microm) (P = .001). ERG and VEP showed no worsening of the
waveforms. There was no significant difference in the visual outcome between the 
BRVO and CRVO groups. CONCLUSION: Intravitreal injection of bevacizumab appears
to result in significant short-term improvement of visual acuity and macular
edema secondary to vein occlusion. The present report confirms the previous
studies. No ocular toxicity or adverse effects were observed. However,
prospective, randomized, controlled long-term studies are required with an
adequate number of patients.

PMID: 17306753 [PubMed - indexed for MEDLINE]

1029: Acta Ophthalmol Scand. 2007 Mar;85(2):188-91.

Leucine 7-proline 7 polymorphism in the signal peptide of neuropeptide Y is not a
risk factor for exudative age-related macular degeneration.

Kaarniranta K, Holopainen JM, Karvonen MK, Koulu M, Kallio J, Pesonen U,
Teräsvirta M, Uusitalo H, Immonen I.

Department of Ophthalmology, University of Kuopio, Kuopio, Finland.
kaarnira@messi.uku.fi

PURPOSE: Because of the regulatory role of neuropeptide Y (NPY) in angiogenesis, 
we set out to determine the presence of the leucine 7-proline 7 (Leu7Pro)
polymorphism in exudative age-related macular degeneration (AMD) patients and to 
analyse its implications. METHODS: Genotype analysis of the Leu7Pro polymorphism 
in the signal peptide region of the human prepro-NPY was performed in blood
samples from exudative AMD patients (n = 240) and control subjects (n = 79).
RESULTS: In all, 11% of exudative AMD patients and 14% of control subjects
exhibited the NPY signal peptide Leu7Pro polymorphism. There were no
statistically significant differences in Leu7Pro polymorphism frequency between
the exudative AMD and control cases, as analysed by Fisher's exact two-sided
test. CONCLUSIONS: Leu7Pro polymorphism in the signal peptide region of the human
prepro-NPY is not a risk factor for exudative AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17305733 [PubMed - indexed for MEDLINE]

1030: Eye. 2007 Dec;21(12):1511-5. Epub 2007 Feb 16.

Plasma levels of matrix metalloproteinase-2 and -9 (MMP-2 and MMP-9) in
age-related macular degeneration.

Chau KY, Sivaprasad S, Patel N, Donaldson TA, Luthert PJ, Chong NV.

Institute of Ophthalmology, University College, London, UK.

BACKGROUND: Several studies indicate that age-related macular degeneration (AMD) 
and atherosclerosis may share common pathogenetic pathways. The aim of this study
was to determine the role of systemic matrix metalloproteinases (MMPs) in AMD,
given that MMPs are implicated in the pathogenesis of atherosclerosis. METHODS:
This study determined the plasma matrix metalloproteinases (MMP-2 and MMP-9)
levels in three groups of subjects: group 1 included subjects with age-related
maculopathy (ARM), group 2 included subjects with choroidal neovascularization
(CNV) owing to AMD and group 3 consisted of age-matched controls. RESULTS: The
mean plasma levels of MMP-2 were not significantly different in the three groups.
In contrast, the mean plasma MMP-9 levels were significantly higher in ARM and
CNV groups compared to that of the control group. However, there was no
significant difference in MMP-9 levels between ARM and CNV groups. CONCLUSION:
This is the first study that reveals a link between raised plasma MMP-9 levels
with AMD. Further studies are required to identify the factors that contribute to
this association.

PMID: 17304258 [PubMed - indexed for MEDLINE]

1031: Am J Ophthalmol. 2007 Apr;143(4):596-600. Epub 2007 Feb 14.

The macular automated photostress test.

Dhalla MS, Fantin A, Blinder KJ, Bakal JA.

Barnes Retina Institute, St Louis, Missouri, USA. Mandeep.S.Dhalla@gmail.com
<Mandeep.S.Dhalla@gmail.com>

PURPOSE: To introduce a standardized macular photostress test using an automated 
perimeter as a method to quantify macular disease severity and as a tool to
distinguish optic neuropathy from macular pathology. DESIGN: Prospective
interventional pilot study. METHODS: Twenty-five bilaterally pseudophakic
subjects aged range, 65 to 84: 15 patients with varying severity of
non-neovascular age-related macular degeneration (AMD), five patients with no
ocular disease, and five patients with moderate primary open-angle glaucoma
(POAG). Previously reported normative values served as controls for this study.
Patients underwent foveal threshold testing using the Humphrey Visual Field
Perimeter Model 750 (Carl Zeiss Meditec, Inc, Dublin, California, USA). Baseline 
measurements were compared to threshold sensitivity after photostress at one
minute and then two-minute intervals until sensitivity returned to baseline. Main
outcome measures were baseline foveal threshold sensitivity, foveal threshold
depression, and recovery following photostress. RESULTS: Automated macular
photostress testing in macular disease (AMD) causes a decrease (P < .001) in
baseline foveal sensitivity and a delay (P < .001) in recovery time to baseline
sensitivity. Optic nerve pathology (POAG) does not affect (P = .343) the foveal
response curve. CONCLUSIONS: The macular automated photostress (MAP) test is an
inexpensive, noninvasive, and readily accessible adjunct for evaluating patients 
with macular disease. This standardized protocol is useful in objectively
defining disease severity, may be used to follow response to treatment, and could
aid in distinguishing optic neuropathy from macular pathology.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17303062 [PubMed - indexed for MEDLINE]

1032: Am J Ophthalmol. 2007 Apr;143(4):584-95. Epub 2007 Feb 14.

Comment in:
    Am J Ophthalmol. 2007 Apr;143(4):681-2.

Adult retinal pigment epithelial transplantation in exudative age-related macular
degeneration.

Tezel TH, Del Priore LV, Berger AS, Kaplan HJ.

Department of Ophthalmology & Visual Sciences, Kentucky Lions Eye Center,
University of Louisville School of Medicine, Louisville, Kentucky, USA.

PURPOSE: To improve visual function by retinal pigment epithelial (RPE) cell
transplantation and systemic immunosuppression at the time of surgical removal of
subfoveal choroidal neovascularization in exudative age-related macular
degeneration (AMD). DESIGN: An interventional case series of RPE transplantation 
in exudative AMD. METHODS: Twelve patients (one eye only) underwent subfoveal
membranectomy with transplantation of a sheet of adult human allogeneic RPE cells
at a single institution and were followed for one year. Eligibility criteria
included age >60, best-corrected acuity < or =20/63 and subfoveal
neovascularization < or =9 disk areas on preoperative fluorescein angiography.
All patients were started on triple immunosuppression postoperatively. The
primary outcome measure was best-corrected vision, with contrast sensitivity and 
reading speed as secondary outcome measures. RESULTS: The best-corrected visual
acuity (P = .085), contrast sensitivity (P = .204), and the reading speed (P =
.077) did not change significantly at one year compared with preoperative values.
Transplants showed no signs of rejection in patients who were able to continue
the immunosuppressants for six months. Postoperative surgical complications
included cataract progression requiring surgery (three of eight phakic eyes),
retinal detachment (three eyes), intraoperative retinal breaks (two eyes), and
macular pucker (two eyes). None of the patients developed cystoid macular edema
on postoperative fluorescein angiography or postoperative inflammation.
CONCLUSIONS: A sheet of adult human allogeneic RPE can be transplanted into the
subretinal space in AMD patients at the time of subfoveal membranectomy. Systemic
immune suppression appeared to prevent rejection of the transplanted tissue, but 
did not lead to an improvement in visual function.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17303061 [PubMed - indexed for MEDLINE]

1033: Korean J Ophthalmol. 2006 Dec;20(4):220-4.

A Korean family with an early-onset autosomal dominant macular dystrophy
resembling North Carolina macular dystrophy.

Kim SJ, Woo SJ, Yu HG.

Department of Ophthalmology, Seoul National University College of Medicine,
Seoul, Korea.

PURPOSE: To characterize and report the phenotype of a Korean family with an
early-onset autosomal dominant macular dystrophy resembling North Carolina
macular dystrophy (NCMD). METHODS: Five members of a Korean family were examined 
clinically and underwent fundus photography, fluorescein angiography, indocyanine
green angiography, optical coherence tomography, full field electroretinogram
(ERG), multifocal ERG, electro-oculography (EOG), a color vision test, and a
visual field test. RESULTS: Visual acuity ranged from 20/200 to 20/20. Fundus
findings demonstrated varying degrees of involvement ranging from drusen only to 
chorioretinal involvement. Central scotoma corresponded to retinal lesions in two
patients. Full field ERG was normal but multifocal ERG showed decreased amplitude
and delayed implicit time in the macular area. EOG was normal except in one
patient. Color vision tests were also normal. CONCLUSIONS: The phenotype of this 
Korean family is consistent with NCMD. Linkage analysis is required to confirm
the diagnosis.

PMID: 17302207 [PubMed - indexed for MEDLINE]

1034: Korean J Ophthalmol. 2006 Dec;20(4):210-4.

Arteriovenous sheathotomy for persistent macular edema in branch retinal vein
occlusion.

Sohn JH, Song SJ.

Hangil Eye Hospital, Incheon, Korea.

PURPOSE: To evaluate the efficacy of arteriovenous (AV) sheathotomy with internal
limiting membrane peeling for persistent or recurrent macular edema after
intravitreal triamcinolone injection and/or laser photocoagulation in branch
retinal vein occlusion. METHODS: Twenty-two eyes with branch retinal vein
occlusion (BRVO) with recurrent macular edema underwent vitrectomy with AV
sheathotomy and internal limiting membrane peeling. All eyes had previous
intravitreal triamcinolone injection and/or laser photocoagulation for macular
edema. The best corrected visual acuity (BCVA), fluorescein angiography and
optical coherence tomography (OCT) before and after surgery were compared.
RESULTS: The mean preoperative BCVA (log MAR) were 0.79 +/- 0.29 and
postoperative BCVA (log MAR) at 3 months was 0.57 +/- 0.33. And improvement of
visual acuity > or = 2 lines was observed in 10 eyes (45%). The mean preoperative
fovea thickness measured by OCT was 595.22 +/- 76.83 microm (510-737 microm) and 
postoperative fovea thickness was 217.60 +/- 47.33 microm (164-285 microm).
CONCLUSIONS: Vitrectomy with AV sheathotomy can be one treatment option for the
patients with recurrent macular edema in BRVO.

PMID: 17302205 [PubMed - indexed for MEDLINE]

1035: Korean J Ophthalmol. 2006 Dec;20(4):205-9.

Intravitreal versus posterior subtenon injection of triamcinolone acetonide for
diabetic macular edema.

Choi YJ, Oh IK, Oh JR, Huh K.

Department of Ophthalmology, Korea University College of Medicine, Seoul, Korea.

PURPOSE: To compare the short-term effects of intravitreal versus posterior
subtenon injection of triamcinolone acetonide for diabetic macular edema.
METHODS: This is a prospective and interventional study. Sixty eyes of 60
patients who had diffuse diabetic macular edema were assigned to receive a single
intravitreal injection (4 mg) or a single posterior subtenon injection (40 mg) of
triamcinolone acetonide. The central retinal thickness was measured using optical
coherent tomography before injection and at 1 and 3 months after injection.
Visual acuity and intraocular pressure (IOP) were also measured. RESULTS: Both
intravitreal and posterior subtenon injections of triamcinolone acetonide
resulted in significant improvements in visual acuity at 1 month and 3 months
after injection. Both groups resulted in a significant decrease in central
macular thickness (CMT) at 1 month and 3 months post-injection. IOP in the
intravitreal injection group was significantly higher than in the posterior
subtenon injection group at 3 months after injection. CONCLUSIONS: The posterior 
subtenon injection of triamcinolone acetonide had a comparable effect to the
intravitreal triamcinolone injection and showed a lower risk of elevated IOP.
Posterior subtenon injection of triamcinolone acetonide may be a good alternative
for the treatment of diffuse diabetic macular edema.

PMID: 17302204 [PubMed - indexed for MEDLINE]

1036: Clin Experiment Ophthalmol. 2007 Jan-Feb;35(1):89-93.

Comment in:
    Clin Experiment Ophthalmol. 2007 Jan-Feb;35(1):3-4.

Chlamydia pneumoniae and age-related macular degeneration: a role in pathogenesis
or merely a chance association?

Guymer R, Robman L.

Centre for Eye Research Australia, University of Melbourne, East Melbourne,
Victoria, Australia. rhg@unimelb.edu.au

The role of inflammation in the aetiology of age-related macular degeneration
(AMD) has become very topical as the discovery that genetic variation in
complement pathway genes influences the risk of developing AMD. Complement factor
H gene, an inhibitor of the alternative complement activation pathway along with 
other complement pathway genes factor F (BF) and C2 show significant contribution
to the risk of AMD. The alternative complement pathway is activated by a trigger,
which is often microbial in nature. One current model of AMD aetiology implicates
aberrant regulation of the alternative pathway of complement, in combination with
some unknown infectious agents. Chlamydia pneumoniae could be one such potential 
trigger of the alternative complement pathway and several investigations have
linked C. pneumoniae to AMD. However, there are only a few studies to date and
numbers in most studies are small. Also there are many difficulties in verifying 
laboratory techniques for the detection of C. pneumoniae chronic infection. As
such we need to be cautious not to over interpret the current results. However,
the findings certainly give impetus for further work on C. pneumoniae and AMD.
This paper provides an overview of work in this area.

Publication Types: 
    Review

PMID: 17300581 [PubMed - indexed for MEDLINE]

1037: Clin Experiment Ophthalmol. 2007 Jan-Feb;35(1):24-31.

Photodynamic therapy with verteporfin for choroidal neovascularization due to
age-related macular degeneration and other causes: a New Zealand outcomes study.

Sharp DM, Lai S, Markey CM.

Retina specialists, Parnell, New Zealand. dianne@retinaspecialists.co.nz

PURPOSE: To assess the efficacy and safety of photodynamic therapy (PDT) for
choroidal neovascularization (CNV) secondary to age-related macular degeneration 
(AMD) and other conditions by analysing visual acuity changes. METHODS: A
retrospective review of patients treated with PDT was conducted. CNV was
confirmed on fluorescein angiography. Visual acuity outcomes were recorded at
3-monthly intervals to a maximum of 48 months. The primary outcome measure was
the proportion of patients avoiding moderate visual loss (losing less than three 
lines of visual acuity relative to baseline) at 12 months. RESULTS: A total of
343 patients receiving PDT were followed up for a mean of 14.9 months. Two
hundred and eighty-five (83%) patients presented with CNV due to AMD and 58
patients (17%) due to other causes. Seventy per cent of patients with CNV
secondary to AMD avoided moderate visual loss at both 12 and 24 months. Secondary
outcomes (including mean change in visual acuity, proportion of patients with
stable or improved vision and proportion of patients with severe vision loss)
also compared favourably with the Treatment of Age-Related Macular Degeneration
with Photodynamic Therapy (TAP) Investigation. Of patients with CNV secondary to 
causes other than AMD, 76% avoided moderate visual loss at both 12 and 24 months.
The safety profile identified one severe adverse reaction, with development of a 
serous pigment epithelial detachment and subsequent rip. CONCLUSION: The results 
of this present retrospective, open-label, clinical practice study in New Zealand
are consistent with the findings of multicentre randomized, placebo-controlled
trials and confirm the treatment benefit of PDT in a clinical setting.

PMID: 17300567 [PubMed - indexed for MEDLINE]

1038: Clin Experiment Ophthalmol. 2007 Jan-Feb;35(1):18-23.

Evaluating the use of a scanning laser-derived oedema index to grade diabetic
retinopathy and maculopathy.

Styles CJ, Park SJ, McGhee CN, Gamble G, Donaldson ML.

Department of Ophthalmology, University of Auckland, Auckland, New Zealand.
caroline.styles@faht.scot.ngs.uk

PURPOSE: To evaluate the Heidelburg Retina Tomograph II (HRTII) retinal module as
a tool for grading severity of retinopathy in a diabetic retinal screening and
treatment service. METHODS: Seventy-seven consecutive patients with type 2
diabetes underwent scanning laser tomography using the HRTII. Scan data were
analysed using the proprietary macular module software and oedema indices
calculated for each of nine topographic macular zones. Two consultant
ophthalmologists, masked to the result of the HRTII scans, graded each subject
for severity of retinopathy and presence of macular oedema. The oedema indices
were analysed statistically to determine whether these correlated with severity
of retinopathy and presence of macular oedema. RESULTS: There is an increased
oedema index in severe non-proliferative diabetic retinopathy in the outer
temporal zone compared with lesser grades of diabetic retinopathy (P = 0.001). In
patients with clinically detectable macular oedema, the oedema index from the
500-microm-diameter central zone was significantly higher than those without (P =
0.03). CONCLUSION: The scanning laser-derived oedema index differentiated between
moderate and severe non-proliferative diabetic retinopathy in this series and
detected diabetic macular oedema. Further development of this technology may
provide an important tool to supplement retinal photographic surveillance in eye 
clinics overwhelmed by an increasing prevalence of type 2 diabetes.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17300566 [PubMed - indexed for MEDLINE]

1039: Eur J Clin Nutr. 2007 Nov;61(11):1341-4. Epub 2007 Feb 14.

Dietary fat and the risk of age-related maculopathy: the POLANUT study.

Delcourt C, Carrière I, Cristol JP, Lacroux A, Gerber M.

Inserm, Research Unit U593 for Epidemiology, Public Health and Development,
Bordeaux, France. Cecile.Delcourt@isped.u-bordeaux2.fr

This study aimed at assessing the associations of dietary fat with the risk of
age-related maculopathy (ARM), in the framework of a population-based study from 
southern France. Nutritional data were collected using a dietitian-administered
food-frequency questionnaire. ARM was classified from retinal photographs using
the international classification and included neovascular age-related macular
degeneration, geographic atrophy, soft indistinct drusen, soft distinct drusen
associated with pigmentary abnormalities. After multivariate adjustment, high
total, saturated and monounsaturated fat intake were associated with increased
risk for ARM (odds ratio (OR)=4.74, P=0.007; OR=2.70, P=0.04; and OR= 3.50,
P=0.03, respectively). Total polyunsaturated fatty acid was not significantly
associated with ARM. Total and white fish intake was not significantly associated
with ARM, but fatty fish intake (more than once a month versus less than once a
month) was associated with a 60% reduction in risk for ARM (OR=0.42, P=0.01).

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17299457 [PubMed - indexed for MEDLINE]

1040: Arch Ophthalmol. 2007 Feb;125(2):160-4.

Contributions of genetics to our understanding of inherited monogenic retinal
diseases and age-related macular degeneration.

Bok D.

Jules Stein Eye Institute, Department of Neurobiology, David Geffen School of
Medicine, University of California-Los Angeles, 100 Stein Plaza, Los Angeles, CA 
90095, USA. bok@sei.ucla.edu

Molecular genetics has contributed greatly to our understanding of inherited
ocular disease. Prior to the development of recombinant DNA technology, basic and
clinical scientists were limited to a description and classification of
phenotypes based on morphology, biochemistry, and physiology. Progress was
severely hampered by the dearth of genetic information. The pace of progress
accelerated in the 1990s after the first disease-causing allele for retinitis
pigmentosa was reported. The years 1990 through 2000 featured the identification 
and characterization of multiple gene alleles underlying retinitis pigmentosa and
allied monogenic diseases. A second leap in our understanding occurred in the
past year. Age-related macular degeneration-which was, until now, refractory to
the identification of genes involving significant segments of the patient
population-is finally yielding its secrets. However, some genes have no known
function. Indeed this is the case for the majority of genes putatively identified
by the Human Genome Project. Answers to these questions will come through an
amalgamation of genetics, cell biology, physiology, and other disciplines.
Collaboration among investigators in these disciplines is already occurring out
of sheer fascination over this interesting and important topic. In the end,
patients with inherited ocular disease will be the final and highly deserving
beneficiaries.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Review

PMID: 17296891 [PubMed - indexed for MEDLINE]

1041: Eur J Ophthalmol. 2007 Jan-Feb;17(1):75-83.

The nature and frequency of neovascular age-related macular degeneration.

Iranmanesh R, Eandi CM, Peiretti E, Klais CM, Garuti S, Goldberg DE, Slakter JS, 
Yannuzzi LA.

The LuEsther T. Mertz Retina Research Center of Manhattan Eye, Ear and Throat
Hospital, New York, USA.

PURPOSE: This study was designed to evaluate the frequency and nature of
neovascularization in age-related macular degeneration (ARMD) utilizing the
combination of digital imaging techniques, fluorescein angiography (FA),
indocyanine green (ICG) angiography, and optical coherence tomography (OCT).
METHODS: A complete clinical examination was performed on 100 eyes of 93
consecutive newly diagnosed patients with neovascular ARMD. Digital fluorescein
angiography, ICG angiography, and OCT were also used in evaluating those
patients. Comparison of the imaging techniques to determine their value in
studying the nature of the lesions. RESULTS: On the basis of existing fluorescein
standards, 15 eyes were diagnosed with classic choroidal neovascularization
(CNV), 15 with minimally classic CNV, and 70 with occult CNV. ICG angiography was
superior for detecting the active vascular component in polypoidal CNV (16 eyes) 
and retinal angiomatous proliferation (14 eyes). OCT was more sensitive than FA
for determining the presence of cystoid macular edema evident in the vast
majority of eyes with retinal angiomatous proliferation (RAP). CONCLUSIONS: These
results suggest that FA, ICG angiography, and OCT, when used in combination, will
assist clinicians in best determining the precise nature of the neovascular
process in ARMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17294386 [PubMed - indexed for MEDLINE]

1042: J Biol Chem. 2007 Apr 13;282(15):10894-900. Epub 2007 Feb 9.

The factor H variant associated with age-related macular degeneration (His-384)
and the non-disease-associated form bind differentially to C-reactive protein,
fibromodulin, DNA, and necrotic cells.

Sjöberg AP, Trouw LA, Clark SJ, Sjölander J, Heinegård D, Sim RB, Day AJ, Blom
AM.

Department of Laboratory Medicine, University Hospital Malmö, Lund University,
S-205 02 Malmo, Sweden.

Recently, a polymorphism in the complement regulator factor H (FH) gene has been 
associated with age-related macular degeneration. When histidine instead of
tyrosine is present at position 384 in the seventh complement control protein
(CCP) domain of FH, the risk for age-related macular degeneration is increased.
It was recently shown that these allotypic variants of FH, in the context of a
recombinant construct corresponding to CCPs 6-8, recognize polyanionic structures
differently, which may lead to altered regulation of the alternative pathway of
complement. We show now that His-384, corresponding to the risk allele, binds
C-reactive protein (CRP) poorly compared with the Tyr-384 form. We also found
that C1q and phosphorylcholine do not compete with FH for binding to C-reactive
protein. The interaction with extracellular matrix protein fibromodulin, which we
now show to be mediated, at least in part, by CCP6-8 of FH, occurs via the
polypeptide of fibromodulin and not through its glycosaminoglycan modifications. 
The Tyr-384 variant of FH bound fibromodulin better than the His-384 form.
Furthermore, we find that CCP6-8 is able to interact with DNA and necrotic cells,
but in contrast the His-384 allotype binds these ligands more strongly than the
Tyr-384 variant. The variations in binding affinity of the two alleles indicate
that complement activation and local inflammation in response to different
targets will differ between His/His and Tyr/Tyr homozygotes.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, Non-P.H.S.

PMID: 17293598 [PubMed - indexed for MEDLINE]

1043: Exp Eye Res. 2007 Apr;84(4):737-44. Epub 2006 Dec 23.

Heterotypic RPE-choroidal endothelial cell contact increases choroidal
endothelial cell transmigration via PI 3-kinase and Rac1.

Peterson LJ, Wittchen ES, Geisen P, Burridge K, Hartnett ME.

Department of Ophthalmology, 6135 Neuroscience Research Building, University of
North Carolina, 103 Mason Farm Road, CB#7041, 6135 NSRB, Chapel Hill, NC
27599-7041, USA.

Age-related macular degeneration (AMD) is the major cause of non-preventable
blindness. Severe forms of AMD involve breaching of the retinal pigment
epithelial (RPE) barrier by underlying choroidal endothelial cells (CECs),
followed by migration into, and subsequent neovascularization of the neurosensory
retina. However, little is known about the interactions between RPE and CECs and 
the signaling events leading to CEC transmigration. While soluble chemotactic
factors secreted from RPE can contribute to inappropriate CEC transmigration,
other unidentified stimuli may play an additional role. Using a coculture model
that maintains the natural structural orientation of CECs to the basal aspect of 
RPE, we show that "contact" with RPE and/or RPE extracellular matrix increases
CEC transmigration of the RPE barrier. From a biochemical standpoint, contact
between CECs and RPE results in an increase in the activity of the GTPase Rac1
within the CECs; this increase is dependent on upstream activation of PI 3-K and 
Akt1. To confirm a link between these signaling molecules and increased CEC
transmigration, we performed transmigration assays while inhibiting both PI 3-K
and Rac1 activity, and observed that both decreased CEC transmigration. We
hypothesize that contact between CECs and RPE stimulates a signaling pathway
involving PI 3-K, Akt1, and Rac1 that facilitates CEC transmigration across the
RPE barrier, an important step in the development of neovascular AMD.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17292356 [PubMed - indexed for MEDLINE]

1044: Health Care Financ Rev. 2006 Spring;27(3):37-47.

Resource utilization and costs of age-related macular degeneration.

Halpern MT, Schmier JK, Covert D, Venkataraman K.

Exponent Inc., Alexandria, VA 22314, USA. mhalpern@exponent.com

Data were analyzed from the 1999-2001 Medicare Beneficiary Encrypted Files for
patients with age-related macular degeneration (AMD), an ophthalmic condition
characterized by central vision loss. Classifying AMD subtype by International
Classification of Diseases, Ninth Revision, Clinical Modifications (ICD-9-CM)
(Centers for Disease Control and Prevention, 2003) code, resource utilization
rates increased with disease progression. Individuals with more severe disease
(wet only or wet and dry AMD) had greater costs than did those with less severe
disease (drusen only or dry only). Costs among patients with wet disease
increased yearly at rates exceeding inflation, possibly due in part to increased 
rates of treatment with photodynamic therapy among these individuals and the
aging of the population.

PMID: 17290647 [PubMed - indexed for MEDLINE]

1045: Retina. 2007 Feb;27(2):216-21.

Evidence for the effect of omega-3 fatty acids on progression of age-related
macular degeneration: a systematic review.

Hodge WG, Barnes D, Schachter HM, Pan YI, Lowcock EC, Zhang L, Sampson M,
Morrison A, Tran K, Miguelez M, Lewin G.

Department of Ophthalmology, Ottawa Hospital Eye Institute, The University of
Ottawa, Ottawa, Ontario, Canada. whodge@ottawahospital.on.ca

BACKGROUND: As part of a larger systematic review on the effect of omega-3 fatty 
acids on eye health, the aim of this report was to appraise and synthesize the
evidence for the effects of omega-3 fatty acids in slowing down the progression
of age-related macular degeneration (AMD) and/or decreasing the rate of
progression to advanced forms of AMD. METHODS: A comprehensive search was
undertaken in six databases (MEDLINE, PreMEDLINE, EMBASE, Cochrane Central
Register of Controlled Trials, CAB Health, and Dissertation Abstracts). RESULTS: 
Two unique studies, one randomized clinical trial (RCT) and one prospective
cohort study, satisfied the eligibility criteria and were included in the review.
The RCT reported evidence on the effect of omega-3 fatty acids in slowing down
the progression of AMD. The prospective cohort study addressed the question: what
is the evidence that omega-3 fatty acids decrease the rate of progression to
advanced forms of AMD? CONCLUSIONS: Clinical research on this topic is scarce.
Only two studies were eligible to be included in this review. Although one study 
result indicated efficacy of preventing AMD progression to its advanced form,
this result needs to be duplicated and supported by future research.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, U.S. Gov't, P.H.S.
    Review

PMID: 17290205 [PubMed - indexed for MEDLINE]

1046: Retina. 2007 Feb;27(2):204-10.

Designing clinical trials for age-related geographic atrophy of the macula:
enrollment data from the geographic atrophy natural history study.

Sunness JS, Applegate CA, Bressler NM, Hawkins BS.

Richard E. Hoover Rehabilitation Services for Low Vision and Blindness, Greater
Baltimore Medical Center, Baltimore, Maryland 21204, USA. jsunness@gbmc.org

PURPOSE: To derive information from the Geographic Atrophy (GA) Natural History
Study that is relevant to recruiting patients and designing clinical trials for
GA. METHODS: A prospective natural history study with annual follow-up enrolled
patients with GA and no choroidal neovascularization (CNV) in at least one eye.
Characteristics of recruited and enrolled patients are analyzed, in the context
of progression data from the study. RESULTS: The data show that GA from
age-related macular degeneration (AMD) was seen in 82% of the referred patients, 
there was an attrition rate of 14%, and 60% of the patients with GA from AMD had 
bilateral GA without CNV. Within the 83 patients in the bilateral GA group with
follow-up, 50 patients (60%) met both the proposed visual acuity and the proposed
GA area criteria for a treatment trial in one or both eyes. CONCLUSION: These
data should be helpful in planning future treatment trials for GA.

Publication Types: 
    Multicenter Study
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17290203 [PubMed - indexed for MEDLINE]

1047: Retina. 2007 Feb;27(2):180-9.

Early treatment of severe cystoid macular edema in central retinal vein occlusion
with posterior sub-tenon triamcinolone acetonide.

Lin JM, Chiu YT, Hung PT, Tsai YY.

Department of Ophthalmology, China Medical University Hospital, Taichung, Taiwan.

PURPOSE: To evaluate the clinical outcomes of posterior sub-Tenon (PST) injection
of triamcinolone acetonide (TA) in the early treatment of severe cystoid macular 
edema (CME) in central retinal vein occlusion (CRVO). METHODS: In a
noncomparative, prospective study, 18 eyes of 18 patients with severe CME
(central macular thickness, CMT >450 microm) secondary to recent-onset CRVO (the 
onset of symptoms < or =4 weeks) and a decrease in visual acuity (< or =80
letters of Early Treatment Diabetic Retinopathy Study [ETDRS] scores, 20/50) were
included. PST injection of 40 mg of TA was given under topic anesthesia. All
patients received three biweekly injections and were evaluated at baseline and at
1 day, 1, 2, 4, 6, and 8 weeks, and 3, 6, and 9 months after injection. The main 
outcome measures were ETDRS scores, CMT, intraocular pressure (IOP), cataract
progression, and frequency of complications. RESULTS: The mean age of the 18
patients was 61.17 years (range, 24-81 years) and the mean duration of symptoms
was 15.28 days (range, 9-28 days). Eight eyes were diagnosed with ischemic CRVO
and 10 eyes with nonischemic CRVO. Mean baseline ETDRS visual acuity (VA) score
was 36.89 +/- 18.22 in all affected eye. There was a significant improvement in
VA at 1, 3, 6, and 9 months of follow-up. The mean VA at these time points were
46.61 +/- 20.21, 58.11 +/- 22.19, 59.39 +/- 22.98, and 58.67 +/- 23.27 (all P <
0.001), respectively. Both nonischemic and ischemic eyes benefited with a
statistically significant VA improvement at each time point. A comparison of the 
gain in VA between two subgroups was not significant at 1 and 3 months (P >
0.05), but was statistically significant at 6 and 9 months (P = 0.009 and 0.008, 
respectively). VA gain of 10 or more letters was found in all nonischemic eyes
(10/10) and 3 ischemic eyes (3/8) at the 9-month follow-up. Two ischemic eyes
were found to have no gain of letters in VA at the 9-month follow-up. The mean
baseline CMT for all eyes was 566 +/- 42 microm. There was a 29% reduction with a
mean CMT of 404 +/- 49 microm (P < 0.001) at 1 month, 51% reduction with a mean
CMT of 278 +/- 40 microm (P < 0.001) at 3 months, 61% reduction with a mean CMT
of 222 +/- 56 microm (P < 0.001) at 6 months, and 63% reduction with a mean CMT
of 210 +/- 30 microm (P < 0.001) at 9 months. Both nonischemic and ischemic eyes 
demonstrated a statistically significant reduction in CMT (all P < 0.001). A
comparison of the reduction in CMT between these two subgroups was not
significant at each visit (all P > 0.05). For both subgroups, there was no
statistically significant difference in IOP change at baseline, 1 week, 1, 3, 6, 
and 9 months of follow-up. Only two patients required topic antiglaucoma drops
for elevated IOP. Three patients developed a recurrence of CME accompanied with
visual decrease. No cataract progression or other complications were observed.
CONCLUSIONS: PST injection of TA is effective in reversing CME and improving
visual acuity in recent-onset CRVO in the first 9 months. Patients with
nonischemic CRVO may respond more favorably than patients with ischemic CRVO.
Early treatment may be better for visual improvement before longstanding macular 
edema results in irreversible photoreceptor damage. Further study with longer
follow-up period is necessary.

PMID: 17290200 [PubMed - indexed for MEDLINE]

1048: Retina. 2007 Feb;27(2):174-9.

Triamcinolone acetonide-assisted pars plana vitrectomy improves residual
posterior vitreous hyaloid removal: ultrastructural analysis of the inner
limiting membrane.

Matsumoto H, Yamanaka I, Hisatomi T, Enaida H, Ueno A, Hata Y, Sakamoto T, Ogino 
N, Ishibashi T.

Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu
University, Fukuoka, Japan.

OBJECTIVE: To determine whether triamcinolone acetonide (TA) can facilitate
residual posterior vitreous hyaloid removal in pars plana vitrectomy (PPV), we
examined the ultrastructure of inner limiting membrane (ILM) removed in
TA-assisted PPV for diabetic macular edema (DME). PATIENTS AND METHODS: In this
retrospective series of 38 eyes of 37 patients who underwent PPV and ILM removal 
for diffuse DME with posterior hyaloid attachment, 24 eyes underwent standard PPV
without TA (control group), and 14 eyes underwent TA-assisted PPV (TA group).
Excised ILMs during PPV were examined by transmission electron microscopy
(control group, n = 20; TA group, n = 10) or scanning electron microscopy
(control group, n = 4; TA group, n = 4). RESULTS: Transmission electron
microscopy clearly demonstrated that the ratio of the posterior vitreous hyaloid 
remaining on ILM was significantly lower (P = 0.0187) in the TA group than in the
control group and also that TA-assisted PPV successfully removed posterior
hyaloid in five of seven eyes with TA granules remaining on the retinal surface
even after surgical separation of the posterior vitreous. Scanning electron
microscopy enabled spatial analysis of the residual posterior hyaloid on ILM,
which appeared in a patchy fashion in the control group. CONCLUSIONS: TA-assisted
PPV clearly demonstrated the residual posterior hyaloid on ILM and allowed more
efficient removal of the posterior hyaloid than standard PPV.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 17290199 [PubMed - indexed for MEDLINE]

1049: Retina. 2007 Feb;27(2):159-64.

Intraocular triamcinolone acetonide for pseudophakic cystoid macular edema:
optical coherence tomography and multifocal electroretinography study.

Koutsandrea C, Moschos MM, Brouzas D, Loukianou E, Apostolopoulos M, Moschos M.

Department of Ophthalmology, University of Athens, Athens, Greece.

PURPOSE: To evaluate pseudophakic cystoid macular edema (CME) by optical
coherence tomography (OCT) and multifocal electroretinography (mf-ERG) and
determine the efficacy of intravitreal triamcinolone acetonide injections.
METHODS: In this nonrandomized retrospective study, 14 eyes of 14 patients with
persistent pseudophakic CME were treated with triamcinolone acetonide injection
and were followed up for 1 year. All patients underwent complete ophthalmologic
examination including determination of best-corrected visual acuity, slit-lamp
examination, tonometry, and funduscopy. Results of OCT and mf-ERG were also
recorded before and after the injection. RESULTS: Visual acuity and mf-ERG values
increased in all patients after intravitreal triamcinolone acetonide injections. 
OCT showed improvement of the retinal thickness in the macular area. Temporary
increase of intraocular pressure was controlled with topical use of antiglaucoma 
drops. CONCLUSION: Intravitreal triamcinolone acetonide injection is a promising 
therapeutic tool for chronic pseudophakic edema resistant to other medical
treatment. However, further study is needed to assess the treatment's long-term
efficacy, its safety, and the need for retreatment.

PMID: 17290196 [PubMed - indexed for MEDLINE]

1050: Retina. 2007 Feb;27(2):141-9.

Intravitreal bevacizumab (avastin) for central and hemicentral retinal vein
occlusions: IBeVO study.

Costa RA, Jorge R, Calucci D, Melo LA Jr, Cardillo JA, Scott IU.

U.D.A.T.--Macular Imaging aaaa Treatment Division, Hospital de Olhos de
Araraquara, Araraquara, São Paulo, Brazil. roger.retina@globo.com

PURPOSE: To evaluate the safety, visual acuity changes, and morphologic effects
associated with intravitreal bevacizumab injections for the management of macular
edema due to ischemic central or hemicentral retinal vein occlusion (RVO).
METHODS: In this prospective, open-label study, 7 consecutive patients (7 eyes)
with macular edema associated with ischemic central or hemicentral RVO were
treated with intravitreal injections of 2.0 mg (0.08 mL) of bevacizumab at
12-week intervals. Standardized ophthalmic evaluation was performed at baseline
and at weeks 1, 6, and 12 after each injection. Clinical evidence of toxicity and
complications as well as changes in logarithm of minimum angle of resolution
Early Treatment Diabetic Retinopathy Study best-corrected visual acuity (BCVA),
central macular thickness (CMT) and total macular volume (TMV) shown by optical
coherence tomography (OCT), and dye leakage shown by fluorescein angiography were
evaluated. RESULTS: The median age of the 7 patients was 65 years (range, 58-74
years), and the median duration of symptoms before injection was 7 months (range,
2.5-16 months). At baseline, mean BCVA was 1.21 (Snellen equivalent,
approximately 20/320) in the affected eye. Mean baseline CMT and TMV were 730.1
microm and 17.1 mm(3), respectively. Fluorescein leakage was observed in the
macula and affected retinal quadrants in all seven eyes. Six patients completed
the 25-week follow-up examination with reinjections performed at weeks 12 and 24.
The most common adverse events were conjunctival hyperemia and subconjunctival
hemorrhage at the injection site. At the last follow-up, mean BCVA in the
affected eye was 0.68 (Snellen equivalent, 20/100(+1). No patient had a decrease 
in BCVA. Mean CMT and TMV at the 25-week follow-up were 260.3 microm and 9.0
mm(3), respectively; fluorescein leakage within the macula and affected retinal
quadrants as compared with baseline was markedly reduced in all patients. Coupled
with fluorescein angiographic findings, OCT data suggest a trend of macular edema
recurrence between 6 weeks and 12 weeks after injection. CONCLUSIONS:
Intravitreal bevacizumab injections of 2.0 mg at 12-week intervals were well
tolerated and were associated with short-term BCVA stabilization or improvement
and favorable macular changes in all patients with ischemic RVO and associated
macular edema.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17290194 [PubMed - indexed for MEDLINE]

1051: Retina. 2007 Feb;27(2):133-40.

Triple therapy for choroidal neovascularization due to age-related macular
degeneration: verteporfin PDT, bevacizumab, and dexamethasone.

Augustin AJ, Puls S, Offermann I.

Department of Ophthalmology, Klinikum Karlsruhe, Karlsruhe, Germany.
106020.560@compuserve.com

PURPOSE: To evaluate the efficacy and safety of triple therapy with verteporfin
photodynamic therapy (PDT), dexamethasone, and bevacizumab in choroidal
neovascularization (CNV) secondary to age-related macular degeneration (AMD).
METHODS: This prospective, noncomparative, interventional case series included
104 patients. Verteporfin PDT was administered with a reduced light dose (42
J/cm, accomplished by light delivery time of 70 seconds). Approximately 16 hours 
after PDT, dexamethasone (800 microg) and bevacizumab (1.5 mg) were injected
intravitreally. Patients attended follow-up visits every 6 weeks, undergoing
visual acuity and intraocular pressure measurement, slit-lamp and ophthalmoscopic
examination, and optical coherence tomography (OCT). Fluorescein angiography was 
performed every 3 months or earlier if OCT showed significant edema. RESULTS: All
104 patients received one triple therapy cycle (5 patients received a second
triple treatment due to remaining CNV activity). The triple therapy was
complemented in 18 patients (17.3%) by an additional intravitreal injection of
bevacizumab. The mean follow-up period was 40 weeks (range, 22-60 weeks). Mean
increase in visual acuity was 1.8 lines (P < 0.01). Mean decrease in retinal
thickness was 182 microm (P < 0.01). No serious adverse events have been
observed. CONCLUSION: In most patients with CNV due to AMD, triple therapy
results in significant and sustained visual acuity improvement after only one
cycle of treatment. In addition, the therapy offers a good safety profile,
potentially lower cost compared with therapies that must be administered more
frequently, and convenience for patients.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17290193 [PubMed - indexed for MEDLINE]

1052: FEBS Lett. 2007 Mar 6;581(5):885-90. Epub 2007 Feb 2.

Transformation of the proteasome with age-related macular degeneration.

Ethen CM, Hussong SA, Reilly C, Feng X, Olsen TW, Ferrington DA.

Department of Biochemistry, Molecular Biology, and Biophysics, University of
Minnesota, Minneapolis, MN 55455, USA.

The proteasome mediates pathways associated with oxidative stress and
inflammation, two pathogenic events correlated with age-related macular
degeneration (AMD). In human donor eyes corresponding to four stages of AMD, we
found the proteasomal chymotrypsin-like activity increased in neurosensory retina
with disease progression. Increased activity correlated with a dramatic increase 
in the inducible subunits of the immunoproteasome, which was not due to an
increase in CD45 positive immune cells in the retina. The novel observation of
proteasome transformation may reflect retinal response to local inflammation or
oxidative stress with AMD.

Publication Types: 
    In Vitro
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17289037 [PubMed - indexed for MEDLINE]

1053: Graefes Arch Clin Exp Ophthalmol. 2007 Aug;245(8):1225-7.

Retinal pigment epithelial tear following intravitreal ranibizumab injections for
neovascular age-related macular degeneration.

Lee GK, Lai TY, Chan WM, Lam DS.

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong
Kong, Hong Kong Eye Hospital, 147K Argyle Street, Hong Kong, People's Republic of
China.

BACKGROUND: To report the development of retinal pigment epithelial (RPE) tear
after intravitreal injection of ranibizumab (Lucentis, Novartis, Basel,
Switzerland). METHODS: Case report with presentation of the fundus photography,
fluorescein angiography (FA) and optical coherence tomography (OCT) findings.
RESULTS: A 70-year-old man received intravitreal injections of ranibizumab for
the treatment of occult choroidal neovascularisation (CNV) with fibrovascular
pigment epithelial detachment due to age-related macular degeneration. One day
after the third intravitreal ranibizumab injection, fundus examination showed a
RPE defect at the foveal region. FA and OCT confirmed the presence of RPE tear
sparing the fovea. No further progression of the RPE tear was observed after
withholding subsequent ranibizumab injection and his right eye visual acuity
remained at 20/100 at 3 months from the last injection. CONCLUSIONS: As with
other anti-vascular endothelial growth factor treatment for CNV, RPE tear might
occur after intravitreal ranibizumab injection even after previous uneventful
intravitreal injections.

Publication Types: 
    Case Reports

PMID: 17287977 [PubMed - indexed for MEDLINE]

1054: J Med Genet. 2007 Mar;44(3):e70. Epub 2007 Feb 7.

New VMD2 gene mutations identified in patients affected by Best vitelliform
macular dystrophy.

Marchant D, Yu K, Bigot K, Roche O, Germain A, Bonneau D, Drouin-Garraud V,
Schorderet DF, Munier F, Schmidt D, Le Neindre P, Marsac C, Menasche M, Dufier
JL, Fischmeister R, Hartzell C, Abitbol M.

Centre de recherche thérapeutique en ophtalmologie, équipe d'accueil 2502 MENRT, 
Université René Descartes Paris V, Faculté de Médecine Necker-Enfants Malades,
Paris, France.

PURPOSE: The mutations responsible for Best vitelliform macular dystrophy (BVMD) 
are found in a gene called VMD2. The VMD2 gene encodes a transmembrane protein
named bestrophin-1 (hBest1) which is a Ca(2+)-sensitive chloride channel. This
study was performed to identify disease-specific mutations in 27 patients with
BVMD. Because this disease is characterised by an alteration in Cl(-) channel
function, patch clamp analysis was used to test the hypothesis that one of the
VMD2 mutated variants causes the disease. METHODS: Direct sequencing analysis of 
the 11 VMD2 exons was performed to detect new abnormal sequences. The mutant of
hBest1 was expressed in HEK-293 cells and the associated Cl(-) current was
examined using whole-cell patch clamp analysis. RESULTS: Six new VMD2 mutations
were identified, located exclusively in exons four, six and eight. One of these
mutations (Q293H) was particularly severe. Patch clamp analysis of human
embryonic kidney cells expressing the Q293H mutant showed that this mutant
channel is non-functional. Furthermore, the Q293H mutant inhibited the function
of wild-type bestrophin-1 channels in a dominant negative manner. CONCLUSIONS:
This study provides further support for the idea that mutations in VMD2 are a
necessary factor for Best disease. However, because variable expressivity of VMD2
was observed in a family with the Q293H mutation, it is also clear that a
disease-linked mutation in VMD2 is not sufficient to produce BVMD. The finding
that the Q293H mutant does not form functional channels in the membrane could be 
explained either by disruption of channel conductance or gating mechanisms or by 
improper trafficking of the protein to the plasma membrane.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17287362 [PubMed - indexed for MEDLINE]

1055: J Hum Genet. 2007;52(4):384-7. Epub 2007 Feb 7.

Assessment of the contribution of the LOC387715 gene polymorphism in a family
with exudative age-related macular degeneration and heterozygous CFH variant
(Y402H).

Shastry BS.

Department of Biological Sciences, Oakland University, Rochester, MI, USA.
shastry@oakland.edu

Age-related macular degeneration (AMD) is a common cause of visual impairment in 
the elderly population in developed countries. The etiology of AMD is not
completely understood but environmental and genetic factors have been implicated 
in the disease. Recently it has been documented that variations in the complement
factor H (CFH) and LOC 387715 genes are the major risk factors that predispose
individuals to dry and wet AMD. To investigate further the genetic contribution
to AMD, we have analyzed the LOC 387715 gene in a non-smoking family with an
exudative AMD and a heterozygous mutation (Y402H) in the CFH gene. Direct
sequencing of the amplified product of exon 1 of the LOC 387715 gene identified a
previously reported missense mutation (A69S) in this family. The affected
individual is homozygous for the mutation and this sequence alteration was not
identified in six age-matched controls. On the basis of this and other results it
is tempting to speculate that the combined effect of variants in the CFH and LOC 
387715 genes may contribute to the AMD phenotype in this family. Further studies 
on these and other susceptibility genes may provide clues on variable phenotypes,
new preventive strategies and treatment options for AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17285240 [PubMed - indexed for MEDLINE]

1056: Am J Ophthalmol. 2007 Apr;143(4):607-15. Epub 2007 Feb 5.

Changes in select redox proteins of the retinal pigment epithelium in age-related
macular degeneration.

Decanini A, Nordgaard CL, Feng X, Ferrington DA, Olsen TW.

Department of Ophthalmology, University of Minnesota, Minneapolis, Minnesota
55455, USA.

PURPOSE: To examine changes of select reduction-oxidation (redox) sensitive
proteins from human donor retinal pigment epithelium (RPE) at four stages of
age-related macular degeneration (AMD). DESIGN: Experimental study. METHODS:
Human donor eyes were obtained from the Minnesota Lions Eye Bank and graded using
the Minnesota Grading System (MGS) into four stages that correspond to stages
defined by the age-related eye disease study (AREDS). Protein content in RPE
homogenates was measured using Western immunoblotting with protein-specific
antibodies. RESULTS: The content of several antioxidant enzymes and specific
proteins that facilitate refolding or degradation of oxidatively damaged proteins
increased significantly in MGS stage 3. These proteins are involved in the
primary (copper-zinc superoxide dismutase [CuZnSOD], manganese superoxide
dismutase [MnSOD], and catalase) and secondary (heat shock protein [HSP] 27, HSP 
90, and proteasome) defense against oxidative damage. Additionally, the insulin
pro-survival receptor exhibited disease-related upregulation. CONCLUSIONS: The
pattern of protein changes identified in human donor tissue graded using the MGS 
support the role of oxidative mechanisms in the pathogenesis and progression of
AMD. The MGS uses nearly identical clinical definitions and grading criteria of
AMD that are used in the AREDS, so our results apply to clinical and
epidemiologic studies using similar definitions. Results from our protein
analysis of human donor tissue helps to explain altered oxidative stress
regulation and cell-survival pathways that occur in progressive stages of AMD.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 17280640 [PubMed - indexed for MEDLINE]

1057: Ophthalmic Surg Lasers Imaging. 2007 Jan-Feb;38(1):87-8.

Use of the Honan balloon as a compression device for intravitreal triamcinolone
acetonide injection.

Hernaez-Ortega MC, Soto-Pedre E.

European Innovative Biomedicine Institute, Cantabria, Spain.

Obtaining a lower intraocular pressure (IOP) before an intravitreal injection is 
important to avoid the danger of an immediate increase in IOP. This article
describes the use of the Honan balloon to reduce the IOP before an intravitreal
triamcinolone acetonide injection instead of the other procedures described in
the literature, which may increase the risk of complications. The results of the 
technique in 19 patients with retinal vein occlusion are reported. Honan balloon 
was applied at 30 mm Hg for 10 minutes and the injection was then performed no
more than 5 minutes after the removal of the Honan balloon. In no more than 10
minutes, this procedure resulted in a significant reduction in IOP. No
complications such as central retinal artery occlusion were observed after the
injection.

PMID: 17278546 [PubMed - indexed for MEDLINE]

1058: Ophthalmic Surg Lasers Imaging. 2007 Jan-Feb;38(1):64-8.

Large submacular hemorrhage following PDT with verteporfin in patients with
occult CNVM secondary to age-related macular degeneration.

Chaudhry NA, Lavaque AJ, Tom DE, Liggett PE.

New England Retina Associates, Hamden, Connecticut 06518, USA.

A review of the charts for all patients who developed large submacular
hemorrhages following photodynamic therapy for choroidal neovascular membranes
secondary to age-related macular degeneration yielded three patients who met the 
criteria for a large submacular hemorrhage. All three patients were treated for
exudative age-related macular degeneration and were taking warfarin for chronic
anticoagulation. Before photodynamic therapy, the international normalized ratio 
ranged from 1.2 to 1.6. All three patients had received at least one previous
verteporfin treatment in the study eye. All three hemorrhages were not noted
immediately after photodynamic therapy and were documented within 1 to 2 weeks
following the procedure. Patients with age-related macular degeneration who are
receiving warfarin therapy and undergoing repeat verteporfin treatments appear to
be at risk for submacular hemorrhages.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17278540 [PubMed - indexed for MEDLINE]

1059: Ann Biomed Eng. 2007 Apr;35(4):615-30. Epub 2007 Feb 3.

Protein transport to choroid and retina following periocular injection:
theoretical and experimental study.

Mac Gabhann F, Demetriades AM, Deering T, Packer JD, Shah SM, Duh E, Campochiaro 
PA, Popel AS.

Department of Biomedical Engineering, The Wilmer Eye Institute, Johns Hopkins
University School of Medicine, 720 Rutland Ave, #613 Traylor, Baltimore, MD
21205, USA. feilim@jhu.edu

Ocular neovascularization is a major cause of blindness in several diseases
including age-related macular degeneration (choroidal neovascularization) and
diabetic retinopathy (retinal neovascularization). Antiangiogenic agents with
clinically significant effects exist, but a key question remains: how to
effectively deliver drugs to the site of neovascularization. Periocular delivery 
of drugs or proteins is less invasive and safer than intravitreous delivery, but 
little is known regarding how and to what extent agents access intraocular
tissues after periocular injection. We present a computational model of drug or
protein transport into the eye following periocular injection to quantify
movement of macromolecules across the sclera of the mouse eye. We apply this
model to the movement of green fluorescent protein (GFP) across the mouse eye and
fit the results of in vivo experiments to find transport parameters. Using these 
parameters, the model gives the profile of interstitial GFP concentration across 
the sclera, choroid and retina. We compare this to predictions of transport
following intravitreous injections. We then scale up the model to estimate the
transport of GFP into the human choroid and retina; the thicker sclera decreases 
transscleral delivery. This is the first model of ocular drug delivery to
explicitly account for transport properties of each eye layer.

PMID: 17277991 [PubMed - indexed for MEDLINE]

1060: Mol Vis. 2007 Jan 26;13:96-101.

Partial paternal uniparental disomy (UPD) of chromosome 1 in a patient with
Stargardt disease.

Riveiro-Alvarez R, Valverde D, Lorda-Sanchez I, Trujillo-Tiebas MJ, Cantalapiedra
D, Vallespin E, Aguirre-Lamban J, Ramos C, Ayuso C.

Fundacion Jimenez Diaz, Genetics, Reyes Catolicos 2, Madrid, Spain.
rriveiro@fjd.es

PURPOSE: Stargardt disease (STGD) is the most common juvenile macular dystrophy, 
characterized by central visual impairment. All recessively inherited cases are
thought to be due to mutations in the ABCA4 gene, mapped to 1p21-p13. METHODS: To
describe a form of non-mendelian inheritance in a patient with STGD identified
through the course of a conventional mutational screening performed on 77 STGD
families. DNA from the patient and relatives was analyzed for variants in all 50 
exons of the ABCA4 gene by screening on the ABCR400 microarray; results were
confirmed by direct sequencing. Haplotype analyses, standard and high-resolution 
(HR) karyotypes, and multiplex ligation-dependent probe amplification (MLPA) were
also performed. RESULTS: A patient with STGD caused by the homozygous
p.Arg1129Leu mutation in the ABCA4 gene was found to be the daughter of a
noncarrier mother and a father who was heterozygous for this change. Haplotype
analysis suggested that no maternal ABCA4 allele was transmitted to the patient. 
Microsatellite markers spanning the entire chromosome 1 identified a homozygous
region of at least 4.4 Mb, involving the ABCA4 gene. The cytogenetic study
revealed normal female karyotype. Further evaluation with MLPA showed the patient
had a normal dosage for both copies of the ABCA4 gene, thus suggesting partial
paternal isodisomy but not a maternal microdeletion. CONCLUSIONS: We report that 
recessive STGD can rarely be inherited from only one unaffected carrier parent in
a non-mendelian manner. This study also demonstrates that genomic alterations
contribute to only a small fraction of disease-associated alleles for ABCA4.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 17277736 [PubMed - indexed for MEDLINE]

1061: Lancet. 2007 Feb 3;369(9559):425-35.

Erratum in:
    Lancet. 2007 Jun 23;369(9579):2078. Wong, Tien [corrected to Wong, Tien Yin].

The eye in hypertension.

Wong TY, Mitchell P.

Centre for Eye Research Australia, University of Melbourne, Australia.
twong@unimelb.edu.au

Hypertension has a range of effects on the eye. Hypertensive retinopathy refers
to retinal microvascular signs that develop in response to raised blood pressure.
Signs of hypertensive retinopathy are frequently seen in adults 40 years and
older, and are predictive of incident stroke, congestive heart failure, and
cardiovascular mortality--independently of traditional risk factors. Hypertension
is also a major risk factor for the development of other retinal vascular
diseases, such as retinal vein and artery occlusion, and ischaemic optic
neuropathy. High blood pressure increases the risk of both development of
diabetic retinopathy and its progression. Adequate control of blood pressure has 
been proven in randomised clinical trials to reduce vision loss associated with
diabetic retinopathy. Finally, hypertension has been implicated in the
pathogenesis of glaucoma and age-related macular degeneration. Recognition of the
ocular effects of blood pressure could allow physicians to better manage patients
with hypertension, and to monitor its end-organ effects.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Review

PMID: 17276782 [PubMed - indexed for MEDLINE]

1062: J Cataract Refract Surg. 2007 Feb;33(2):348-9.

Cystoid macular edema following photorefractive keratectomy complicated by
presumptive infectious keratitis.

Hasan SA, Stewart MW.

Department of Ophthalmology, Mayo Clinic, Jacksonville, Florida 32224, USA.
hasan.saiyid@mayo.edu

A 71-year-old man developed cystoid macular edema (CME) following photorefractive
keratectomy (PRK). He had a history of CME following cataract surgery in both
eyes, which had responded well to topical steroid and nonsteroidal
antiinflammatory drops. The cataract surgery in the left eye had resulted in a
hyperopic surprise, with secondary anisometropia and visual discomfort. For this 
reason, the patient elected to have PRK. Three weeks after the procedure, he
returned, complaining of visual loss. Optical coherence tomography and
fluorescein angiography confirmed the presence of CME. This responded well to
topical and sub-Tenon's corticosteroids and nonsteroidal antiinflammatory drops.

Publication Types: 
    Case Reports

PMID: 17276286 [PubMed - indexed for MEDLINE]

1063: Transfus Apher Sci. 2007 Feb;36(1):5-12. Epub 2007 Feb 2.

Update on multi-center clinical trials in the United States.

Afenyi-Annan A, Brecher ME, Bandarenko N.

University of North Carolina Hospitals, 101 Manning Drive, 1021 East Wing, Blood 
Bank, CB#7525, Chapel Hill, NC 27514, USA. araba_afenyi-annan@med.unc.edu

This article reviews numerous multi-center clinical trials, either ongoing or in 
planning stages, which involve diverse clinical applications and emerging
technologies in apheresis and transfusion medicine. The investigations summarized
herein involve the following specific areas: platelet dosing strategy, thrombotic
thrombocytopenia purpura, inflammatory bowel disease, seven-day platelet storage,
dendritic cell vaccines, and age-related macular degeneration.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Review

PMID: 17276142 [PubMed - indexed for MEDLINE]

1064: Ophthalmology. 2007 May;114(5):881-9. Epub 2007 Feb 1.

Analysis of macular edema after cataract surgery in patients with diabetes using 
optical coherence tomography.

Kim SJ, Equi R, Bressler NM.

Retina Division, Wilmer Eye Institute (Department of Ophthalmology), Johns
Hopkins University School of Medicine, Baltimore, Maryland, USA.

OBJECTIVE: To assess the incidence or progression of macular edema (ME) after
cataract surgery in diabetic patients using optical coherence tomography (OCT)
and correlating this with degree of diabetic retinopathy or other risk factors.
DESIGN: Prospective cohort study. PARTICIPANTS: Fifty diabetic eyes undergoing
cataract surgery. METHODS: Each eye underwent 7-field fundus photography no more 
than 3 months before surgery. Optical coherence tomography testing was performed 
within 4 weeks before surgery and at 1- and 3-month postoperative visits.
Best-corrected visual acuity (BCVA) was recorded at each visit. Macular edema was
defined as an increase of center point thickness on OCT > 30% from preoperative
baseline. MAIN OUTCOME MEASURES: Changes in foveal thickness and BCVA. RESULTS:
The incidence of ME on OCT was 22% (95% confidence interval, 13%-35%). The
average increase in center point thickness at 1 month for eyes with ME was 202
microm, which resulted in a nearly 1-line loss of vision (0.07 logarithm of the
minimum angle of resolution [logMAR] units) compared with eyes without ME gaining
>2 lines of vision (0.24 logMAR units) (P>0.001). Eyes with no diabetic
retinopathy developed minimal thickening of 18 mum and 14 mum at 1 and 3 months, 
respectively, associated with approximately 2 and 3 lines of improved vision,
respectively (0.22 and 0.26 logMAR units). Eyes with moderate or severe
nonproliferative diabetic retinopathy or proliferative diabetic retinopathy
developed thickening of 145 mum and 131 mum at 1 and 3 months, respectively,
associated with <1 and 2 lines of improved visual acuity, respectively (0.08 and 
0.17 logMAR units). This difference (P = 0.05) in thickening (127 microm and 117 
mum at 1 and 3 months, respectively) was correlated inversely with visual
improvement (r = -0.662). Both duration of diabetes > or = 10 years (P = 0.04)
and insulin dependence (P = 0.007) were associated with reduced visual
improvement. CONCLUSIONS: Diabetic eyes have a high incidence of increased center
point thickness on OCT after cataract surgery, associated with a loss of vision
at 1 month, with limited visual recovery at 3 months. Treatment to prevent this
might improve outcomes in similar individuals after surgery.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17275910 [PubMed - indexed for MEDLINE]

1065: Ophthalmology. 2007 Jun;114(6):1143-50. Epub 2007 Feb 1.

Cardiovascular risk factors and the long-term incidence of age-related macular
degeneration: the Blue Mountains Eye Study.

Tan JS, Mitchell P, Smith W, Wang JJ.

Centre for Vision Research, Department of Ophthalmology, Westmead Millennium
Institute, University of Sydney, Westmead, Australia.

PURPOSE: To assess the relationship between cardiovascular disease and
cardiovascular risk factors, other than smoking, and risk of long-term incident
age-related macular degeneration (AMD). DESIGN: Population-based cohort study.
PARTICIPANTS: There were 3654 baseline (1992-1994) participants aged > or = 49
years included in the Blue Mountains region, west of Sydney, Australia. Of these,
2335 (75% of survivors) were reexamined after 5 years (1997-1999) and 1952 (76%
of survivors) after 10 years (2002-2004). METHODS: Stereoscopic color fundus
photographs were graded using the Wisconsin Age-related Maculopathy Grading
System. History, physical examination, and fasting blood samples provided data on
possible risk factors. Age-related macular degeneration incidence was calculated 
using the Kaplan-Meier survival approach. Discrete linear logistic models were
used to assess risk of incident AMD. Relative risks (RR) and 95% confidence
intervals (CI) are presented after adjusting for age, gender, smoking, and other 
risk factors. MAIN OUTCOME MEASURE: Incident early and late AMD. RESULTS:
Increasing high-density lipoprotein (HDL) cholesterol was inversely related to
incident late AMD (RR per standard deviation [SD] increase, 0.74; 95% CI,
0.56-0.99). Elevated total/HDL cholesterol ratio predicted late AMD (RR per SD
increase, 1.35; 95% CI, 1.07-1.70) and geographic atrophy (GA; RR per SD, 1.63;
95% CI, 1.18-2.25). Diabetes predicted incident GA (RR, 3.89; 95% CI,
1.36-11.08), but not neovascular AMD. History of stroke (RR 2.01; 95% CI,
1.12-3.58), or any cardiovascular disease (stroke, myocardial infarction, or
angina; RR, 1.57; 95% CI, 1.13-2.16) predicted incident early AMD and incident
indistinct soft or reticular drusen (RR, 2.38; 95% CI, 1.33-4.27 for stroke; RR, 
1.80; 95% CI, 1.28-2.52 for any cardiovascular disease). Neither pulse pressure, 
systolic or diastolic blood pressure, or presence of hypertension at baseline
were associated with incident AMD. CONCLUSIONS: Our findings provide some
evidence of links between cardiovascular risk factors and AMD. Further
prospective evaluation of these relationships is warranted, as these findings
could have therapeutic implications.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17275090 [PubMed - indexed for MEDLINE]

1066: Int J Oncol. 2007 Mar;30(3):537-48.

Apoptosis signalling mechanisms in human cancer cells induced by Calphostin-PDT.

Olivo M, Ali-Seyed M.

Division of Medical Sciences, National Cancer Centre, 11 Hospital Drive,
Singapore 169610. dmsmcd@nccs.com.sg

Photodynamic therapy (PDT) is a promising treatment that is approved by the US
FDA for the treatment of oesophageal and lung cancer as well as for age-related
macular degeneration. In this study, using standard tissue culture techniques,
the photo cytotoxicity and apoptotic mechanisms of Calphostin C (Cal C), a
perylenequinone microbial compound in combination with visible light dose was
examined in different tumor cell lines. Our results demonstrated both a time and 
drug-light dose dependence in Cal-C-PDT induced photo toxicity and apoptotic cell
death. The induction of apoptosis by Cal C-PDT was found to transit to necrotic
cell death at higher drug and light doses. The detection of apoptosis in
irradiated tumor cells was performed using various approaches including cell
morphology analysis, flow cytometry [DNA fragmentation and phosphatidylserine
(PS) externalization] and biochemical assays (activation of caspases).
Time-course analysis of Cal C cellular uptake and distribution showed a rapid
increase within the cellular compartments. The activation of caspases and nuclear
fragmentation was evidenced at a maximum time point of 3 h after irradiation. By 
the use of specific caspase substrates, significant activation of caspase-8 and
-3 was found. Mitochondrial involvement during Cal C-PDT-induced apoptosis was
proven by a rapid reduction of the mitochondrial membrane potential. Furthermore,
Cal C-PDT also enhanced FasL expression, which then induced Fas
signalling-dependent cell death in NPC and colon cancer cell lines tested. Our
results contribute to a deeper understanding of the processes involved in
apoptotic cell death following photodynamic treatment with Cal C.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17273754 [PubMed - indexed for MEDLINE]

1067: Ophthalmology. 2007 Feb;114(2):334-9.

Intravitreal triamcinolone acetonide for the treatment of immune recovery uveitis
macular edema.

Morrison VL, Kozak I, LaBree LD, Azen SP, Kayicioglu OO, Freeman WR.

Jacobs Retina Center, Department of Ophthalmology, University of California, San 
Diego, La Jolla, California 92093, USA.

PURPOSE: To evaluate the use of intravitreal triamcinolone (IVTA) for the
treatment of macular edema secondary to immune recovery uveitis (IRU) in patients
with AIDS. DESIGN: Prospective, consecutive, interventional case series.
PARTICIPANTS: Eight eyes of 7 patients receiving 13 injections. METHODS:
Prospective, consecutive, interventional case series of 13 injections involving 8
eyes in 7 patients who underwent an intravitreal injection of 20 mg decanted
triamcinolone acetate for fluorescein angiographically proven IRU-related macular
edema. MAIN OUTCOME MEASURES: The primary outcome measure was vision (using the
Early Treatment Diabetic Retinopathy Study chart). Other outcome measures
included fluorescein angiography and optical coherence tomography. RESULTS:
Visual acuity improved at all time points and was statistically significant at
the 1-month and 3-month follow-up examinations. The average visual improvement
was 3 lines at 3 months. Retinal volume and thickness improvement were
statistically significant at all time points. All patients had a minimum
follow-up of 9 months, and there were no cases of cytomegalovirus reactivation.
CONCLUSIONS: Previous studies showed that treatment with sub-Tenon repository
steroids for the treatment of macular edema of IRU was only marginally effective.
However, the current study shows that IVTA can be an effective short-term
treatment for macular edema secondary to IRU in patients with AIDS. Longer
follow-up is needed to assess the durability of the effect and to monitor for
longer-term complications and outcomes.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 17270681 [PubMed - indexed for MEDLINE]

1068: Ophthalmology. 2007 Feb;114(2):278-82.

Cataract surgery is associated with a higher rate of photodynamic therapy for
age-related macular degeneration.

Kaiserman I, Kaiserman N, Elhayany A, Vinker S.

Department of Ophthalmology, Barzilai Medical Center, Ashkelon, Israel.
Igor@Dr-Kaiserman.com

PURPOSE: To investigate the association between cataract surgery and the rate of 
photodynamic therapy (PDT) for age-related macular degeneration (AMD). DESIGN:
Observational population-based retrospective case-control study. PARTICIPANTS:
All members in a district of the largest health maintenance organization (HMO) in
Israel > 50 years old on January 1, 2001, who did not terminate their membership 
through May 31, 2005 (139 894 members). METHODS: All PDT procedures for AMD
performed in the study population between January 1, 2001 and May 31, 2005 (283
patients) and all cataract surgeries performed between January 1, 2001 and
December 31, 2003 (5913 patients) were documented. We extracted clinical
information from the chronic disease registry of the HMO as well as demographic
and socioeconomic information. For each patient that underwent cataract surgery, 
5 HMO members matched in age, gender, chronic diseases (systemic hypertension,
diabetes, hyperlipemia, and ischemic heart disease), place of residence, country 
of birth and socioeconomic status, who did not undergo cataract surgery, were
randomly chosen as controls (n = 29 565). MAIN OUTCOME MEASURES: The rate for
undergoing PDT at different time periods after cataract surgery. RESULTS: Fifty
(0.85%) cataract patients and 94 control cases (0.32%) underwent PDT after
cataract surgery (P<0.0001, chi-square test). A significant rise in PDT rate was 
noticed in cataract patients compared to controls during the first 6 months after
surgery (P = 0.004, chi-square test). Between 6 and 12 months postoperatively,
the PDT rates were similar in both groups. However, a more significant rise in
PDT rates occurred between 1 and 1.5 years after surgery (P<0.0001, chi-square
test). The Kaplan-Meier PDT-free survival curve of cataract patients was
significantly worse than that of the controls (P<0.0001, chi-square test; P =
33.7, log-rank test). The hazard ratio for cataract patients compared to controls
to undergo PDT after surgery was 2.7 (confidence interval = 2.4-5.7). The most
significant factors to reduce the time to PDT were advanced age followed by
having had cataract surgery, place of birth, socioeconomic status, and
hyperlipidemia (Cox proportional hazards survival regression). CONCLUSIONS: We
identified an increased rate of PDT, presumably for subfoveal AMD, 1 to 1.5 years
after cataract surgery.

PMID: 17270677 [PubMed - indexed for MEDLINE]

1069: Ophthalmology. 2007 Feb;114(2):271-7.

The long-term natural history of geographic atrophy from age-related macular
degeneration: enlargement of atrophy and implications for interventional clinical
trials.

Sunness JS, Margalit E, Srikumaran D, Applegate CA, Tian Y, Perry D, Hawkins BS, 
Bressler NM.

Richard E. Hoover Rehabilitation Services for Low Vision and Blindness, Greater
Baltimore Medical Center, Baltimore, Maryland 21204, USA. jsunness@gbmc.org

PURPOSE: To report the enlargement rate of geographic atrophy (GA) over time, its
relationship to size of atrophy at baseline and to prior enlargement rate, and
the implications for designing future treatment trials for GA. DESIGN:
Prospective natural history study of GA resulting from age-related macular
degeneration. PARTICIPANTS: Two hundred twelve eyes of 131 patients were included
in the analysis. METHODS: Annual follow-up included stereo color fundus
photographs. The areas of GA were identified and measured, and the rate of
enlargement of the atrophy was assessed. Sample sizes for clinical trials using
systemic treatment and uniocular treatment were determined. MAIN OUTCOME MEASURE:
Rate of enlargement of the atrophy. RESULTS: The median overall enlargement rate 
was 2.1 mm2/year (mean, 2.6 mm2/year). Eyes with larger areas of atrophy at
baseline tended to have larger enlargement rates, but knowledge of prior rates of
enlargement was the most significant factor in predicting subsequent enlargement 
rates. There was high concordance between the enlargement rates in the 2 eyes of 
patients with bilateral GA (correlation coefficient, 0.76). To detect a 25%
reduction in enlargement rate for a systemic treatment (alpha, 0.05; power, 0.80;
losses to follow-up, 15%), 153 patients each in a control and treatment group
would be required for a trial with a 2-year follow-up period for each patient.
For a uniocular treatment, 38 patients with bilateral GA would be required, with 
the untreated eye serving as a control for the treated eye. CONCLUSIONS:
Treatment trials for GA with an outcome variable of change in enlargement rate
are feasible.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17270676 [PubMed - indexed for MEDLINE]

1070: Ophthalmology. 2007 Feb;114(2):253-62.

Fifteen-year cumulative incidence of age-related macular degeneration: the Beaver
Dam Eye Study.

Klein R, Klein BE, Knudtson MD, Meuer SM, Swift M, Gangnon RE.

Department of Ophthalmology and Visual Sciences, University of Wisconsin School
of Medicine and Public Health, Madison, Wisconsin 53726-2336, USA.
kleinr@epi.ophth.wisc.edu

PURPOSE: To describe the 15-year cumulative incidence of signs of early and late 
age-related macular degeneration (AMD). DESIGN: Population-based cohort study.
PARTICIPANTS: We included 3917 persons, 43 to 86 years of age at the time of a
baseline examination in 1988 through 1990 and with information collected in
follow-up in 1993 through 1995, and/or 1998 through 2000, and/or 2003 through
2005. METHODS: Grading of stereoscopic fundus photographs using the Wisconsin
Age-Related Maculopathy Grading System. MAIN OUTCOME MEASURES: Cumulative
incidence of drusen type and size, pigmentary abnormalities, geographic atrophy, 
and exudative AMD accounting for competing risk of death. RESULTS: The 15-year
cumulative incidence was 14.3% for early AMD (the presence of either soft
indistinct drusen or the presence of pigmentary abnormalities together with any
type of drusen) and 3.1% for late AMD (presence of exudative AMD or geographic
atrophy). There was an increased incidence of AMD lesions with age (P<0.05).
Individuals > or = 75 years of age at baseline had significantly (P<0.01) higher 
15-year incidences of the following characteristics than people 43 to 54 years of
age: larger drusen (125 mum in diameter, 24.1% vs 10.6%), soft indistinct drusen 
(18.7% vs 6.5%), retinal pigmentary abnormalities (20.2% vs 3.7%), exudative
macular degeneration (4.4% vs 0.4%), and pure geographic atrophy (3.2% vs 0%).
Controlling for age, compared with those with small numbers of only small hard
drusen (1-2), those with large numbers of only hard drusen (> or =8) had an
increased 15-year age-adjusted incidence of both soft indistinct drusen (16.3% vs
4.7%) and pigmentary abnormalities (10.6% vs 2.7%). Eyes with soft indistinct
drusen or pigmentary abnormalities at baseline were more likely to develop late
AMD at follow-up than eyes without these lesions (17.8% vs 1.2% and 12.9% vs
1.7%, respectively). CONCLUSIONS: We document the long-term incidence of signs of
AMD and a continuum from small hard drusen to late AMD in older persons in the
population. The 15-year cumulative incidence of late AMD in people > or = 75
years of age (8%) indicates a public health problem of significant proportions
because the United States population this age is expected to increase by 54%
between 2005 and 2025.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17270675 [PubMed - indexed for MEDLINE]

1071: Ophthalmology. 2007 Feb;114(2):246-52.

Subgroup analysis of the MARINA study of ranibizumab in neovascular age-related
macular degeneration.

Boyer DS, Antoszyk AN, Awh CC, Bhisitkul RB, Shapiro H, Acharya NR; MARINA Study 
Group.

Retina-Vitreous Associates, Beverly Hills, California, USA. vitdoc@aol.com

OBJECTIVE: An examination of clinically relevant subgroups of patients in the
MARINA study of ranibizumab in treatment of minimally classic or occult with no
classic choroidal neovascularization (CNV) secondary to age-related macular
degeneration (AMD) was done. Objectives were to determine the effectiveness of
ranibizumab across subgroups, compare the effectiveness of ranibizumab with that 
of sham injection within subgroups, and evaluate the relationship between
selected baseline characteristics and visual acuity (VA) outcomes. DESIGN:
Retrospective subgroup analyses of 24-month data from the MARINA study.
PARTICIPANTS AND CONTROLS: Seven hundred sixteen patients were randomly assigned 
to 0.3 mg ranibizumab (n = 238), 0.5 mg ranibizumab (n = 240), or sham treatment 
(n = 238). METHODS: Efficacy outcomes were compared across subgroups based on
patients' gender, age, baseline VA score, baseline CNV lesion size, CNV lesion
type, and duration of neovascular AMD using univariate analyses. Multivariate
analyses were performed on the change from baseline to 24 months in VA score to
assess further the correlation between baseline characteristics and VA outcome.
MAIN OUTCOME MEASURES: Proportion of patients losing <15 letters from baseline,
proportion gaining > or =15 letters from baseline, and mean VA score change from 
baseline. RESULTS: For each of the 3 VA end points, all subgroups of
ranibizumab-treated patients did better on average than the sham-treated
patients. Increasing age, larger CNV lesion size at baseline, and a higher
baseline VA score were all associated with greater loss of letters in the sham
group or less gain of letters in the ranibizumab groups. However, the net benefit
of ranibizumab versus sham treatment was greater in patients who scored higher
than in those who scored lower in baseline VA. CONCLUSIONS: This subgroup
analysis of 24-month data from the MARINA study indicates that ranibizumab
treatment was associated with an average increase from baseline VA in all
subgroups evaluated, and that ranibizumab treatment was superior to sham
treatment across all subgroups. The most important predictors of VA outcomes
were, in decreasing order of importance, baseline VA score, CNV lesion size, and 
age.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial

PMID: 17270674 [PubMed - indexed for MEDLINE]

1072: Saudi Med J. 2007 Feb;28(2):221-4.

Enhanced susceptibility of low-density lipoprotein to oxidation in wet type
age-related macular degeneration in male patients.

Javadzadeh A, Ghorbanihaghjo A, Rashtchizadeh N, Rafeey M, Rahimi-Ardabili B.

Department of Ophthalmology, Nikookari Hospital-Drug of Applied Research Center, 
Tabriz University of Medical Sciences, Tabriz, Iran. javadzadehalireza@yahoo.com

OBJECTIVE: To determine the susceptibility of low-density lipoprotein (LDL) to
oxidation in the plasma of male patients with wet type age related macular
degeneration (AMD) and in a similar control group, in order to evaluate the LDL
oxidative status as risk factor of AMD. METHODS: We conducted this study in the
Retina Service, Department of Ophthalmology, Nikookari Eye Hospital-Drug of
Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
during the period between October 2004 and December 2005. Sixty male patients
with AMD (mean age 67 +/- 16 years) with BMI 4.1 +/- 1.3 were selected as the
patient group. The control group consisted of 60 males, apparently healthy, and
without ophthalmologic signs and family history of AMD. Low-density lipoprotein
was isolated by gradient ultracentrifugation and susceptibility of LDL to in
vitro copper-mediated oxidation was assayed by measuring conjugated dienes
production (lag phase duration) at 234 nm. Lipid and lipoproteins were determined
by standard methods. RESULTS: Comparing with control, significant reduction in
the duration of lag phase (p<0.004) and a significant increase in LDL-C
concentrations (p=0.006), were noticed. No significant change in cholesterol
(p>0.3), triglyceride (p>0.1) and high density lipoprotein cholesterol (p>0.1)
levels were found between control and patient groups. A significant negative
correlation between Lag phase and LDL-C levels (p=0.004, r=-0.364) was found in
the patient group. CONCLUSION: The increased LDL concentration and enhanced
susceptibility of LDL to oxidation may play a roll in the wet type AMD process.

PMID: 17268700 [PubMed - indexed for MEDLINE]

1073: Eur J Clin Nutr. 2007 Sep;61(9):1121-7. Epub 2007 Jan 31.

Effect of lutein and antioxidant dietary supplementation on contrast sensitivity 
in age-related macular disease: a randomized controlled trial.

Bartlett HE, Eperjesi F.

Opthalmic Research Group, School of Life and Health Sciences, Aston University,
Aston Triangle, Birmingham, UK. H.E.Bartlett@aston.ac.uk

OBJECTIVE: The aim of the study is to determine the effect of lutein combined
with vitamin and mineral supplementation on contrast sensitivity in people with
age-related macular disease (ARMD). DESIGN: A prospective, 9-month, double-masked
randomized controlled trial. SETTING: Aston University, Birmingham, UK and a UK
optometric clinical practice. SUBJECTS: Age-related maculopathy (ARM) and
atrophic age-related macular degeneration (AMD) participants were randomized
(using a random number generator) to either placebo (n=10) or active (n=15)
groups. Three of the placebo group and two of the active group dropped out.
INTERVENTIONS: The active group supplemented daily with 6 mg lutein combined with
vitamins and minerals. The outcome measure was contrast sensitivity (CS) measured
using the Pelli-Robson chart, for which the study had 80% power at the 5%
significance level to detect a change of 0.3 log units. RESULTS: The CS score
increased by 0.07+/-0.07 and decreased by 0.02+/-0.18 log units for the placebo
and active groups, respectively. The difference between these values is not
statistically significant (z=-0.903, P=0.376). CONCLUSION: The results suggest
that 6 mg of lutein supplementation in combination with other antioxidants is not
beneficial for this group. Further work is required to establish optimum dosage
levels.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17268417 [PubMed - indexed for MEDLINE]

1074: Biomaterials. 2007 Apr;28(13):2192-201. Epub 2007 Jan 11.

Spatial cues for the enhancement of retinal pigment epithelial cell function in
potential transplants.

Lee CJ, Fishman HA, Bent SF.

Department of Chemical Engineering, Stanford University, Stanford, CA 94305-5025,
USA.

Retinal pigment epithelial (RPE) cellular morphology and function are vital to
the health of the retina. In age-related macular degeneration, RPE dysfunction
and changes in Bruch's membrane occur. Thus, a potential cure is a dual-layer
biomimetic transplant consisting of a layer of healthy RPE cells cultured on a
support membrane. In this study, we investigated human anterior lens capsule as a
replacement for Bruch's membrane and also explored different seeding methods as
ways of inducing the desired cellular morphology and function. Using in vitro
assays, we demonstrated that RPE cells cultured on lens capsule exhibited
epithelial characteristics, such as the presence of actin belts and the formation
of tight junctions in the monolayer. Bovine photoreceptor outer segments were
also incubated with the RPE cells in order to quantify the binding and ingestion 
activity of the RPE cells. With these assays, we determined that cells seeded by 
centrifugation appeared to possess the most epithelial-like morphology, with the 
shortest overall length and the smallest elongation. They also exhibited enhanced
metabolic activity, with a 1.5-fold increase over conventional gravity seeding.
Thus, the spatial cues provided by centrifugation may assist cells in assuming
native RPE function. Therefore, a dual-layer transplant, with RPE cells organized
by centrifugation onto lens capsule, appears promising in achieving native
retinal function.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17267030 [PubMed - indexed for MEDLINE]

1075: Vis Neurosci. 2006 Nov-Dec;23(6):863-70.

Postreceptoral adaptation abnormalities in early age-related maculopathy.

Feigl B, Brown B, Lovie-Kitchin J, Swann P.

Institute of Health and Biomedical Innovation, School of Optometry, Queensland
University of Technology, Victoria Park Road, Kelvin Grove Q 4059, Australia.
b.feigl@qut.edu.au

Age-related maculopathy (ARM) has become the major cause of blindness in the
Western World. Currently its pathogenesis and primary site of functional damage
is not fully understood but ischemia is believed to play a major role. Early
detection and precise monitoring of progression of ARM are main goals of current 
research due to lack of sufficient treatment options, especially in the dry,
atrophic form of this disease. We applied the multifocal electroretinogram
(mfERG) that can detect any local functional deficit objectively in the central
retina. We recorded two paradigms in early ARM patients, the fast flicker and the
slow flash paradigm which both represent fast adaptation processes of the
proximal retina but under differing photopic conditions and stimulation rates. By
subtracting the waveform responses we extracted a late component in the
difference waveform that was significantly reduced in the early ARM group
compared to a healthy control group (p < or = 0.05). We propose that this
multifocal nonlinear analysis permits the detection of adaptative deficits and
provides topographic mapping of retinal dysfunction in early ARM. The difference 
waveform component we extracted with this novel approach might indicate early
functional loss in ARM caused by ischemia in postreceptoral layers such as
bipolar cells and inner plexiform regions.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17266778 [PubMed - indexed for MEDLINE]

1076: Genet Epidemiol. 2007 Apr;31(3):224-37.

Evidence for association between multiple complement pathway genes and AMD.

Dinu V, Miller PL, Zhao H.

Program in Computational Biology and Bioinformatics, Yale University, New Haven, 
Connecticut 06520-8009, USA. valentin.dinu@yale.edu

In this paper we explore the use of biological knowledge to supplement
statistical analysis in identifying genes associated with disease. It has been
previously found that the 402H variant in complement factor H (CFH) is associated
with risk for developing age related macular degeneration (AMD). By focusing on
the single nucleotide polymorphisms (SNPs) in the complement pathway, we were
able to use the genotype data from a recently published AMD genome wide
association study to identify two additional genes, C7 and MBL2, as potentially
associated with subtypes of AMD. Two SNPs situated in introns of C7 and MBL2
could help differentiate between two forms of AMD: wet (more severe form of AMD) 
and dry (milder form of AMD). We identified a C7 haplotype associated with
protection against developing wet AMD among individuals with homozygous CFH risk 
allele 402H (p-value 0.001 for wet AMD versus dry AMD, odds ratio (OR) 0.16, OR
95% CI 0.05-0.49) as well as among individuals with at least one CFH risk allele 
(p-value 0.007 for wet AMD versus dry AMD, OR 0.35, OR 95% CI 0.16-0.77). The
fact that the statistical scores for the C7 and MBL2 SNPs were significant (low
false discovery rate) at the pathway level, but not significant at the genome
level suggests that focusing at the pathway level can be beneficial for
identifying SNP signals that would be lost at the genome-wide level.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 17266113 [PubMed - indexed for MEDLINE]

1077: Clin Rheumatol. 2007 Aug;26(8):1248-53. Epub 2007 Jan 31.

Chloroquine-induced bull's eye maculopathy in rheumatoid arthritis: related to
disease duration?

Shinjo SK, Maia OO Jr, Tizziani VA, Morita C, Kochen JA, Takahashi WY, Laurindo
IM.

Division of Rheumatology, School of Medicine, University of São Paulo, Av. Dr.
Arnaldo, 455, Sala 3133, CEP 01246-903, São Paulo, SP, Brazil.
samuel.shinjo@terra.com.br

Chloroquine diphosphate has been used in the treatment of various rheumatic
diseases, including rheumatoid arthritis. The most important of its side effects 
is retinopathy. If not diagnosed early, this lesion can evolve into irreversible 
bull's eye maculopathy and visual loss. The aim of this study was to define the
outcome of chloroquine-induced maculopathy after cessation of chloroquine therapy
and also to identify the risk factors involved in case of retinopathy evolution. 
The design of this cohort study was longitudinal and retrospective. Over the
period spanning 2000 to 2005, out of 607 medical records of patients with
rheumatoid arthritis followed in our Division of Rheumatology, 27 had been
diagnosed with chloroquine-induced maculopathy through clinical funduscopy with
pupil dilation. In all cases, there was immediate chloroquine intake cessation.
After a mean time of 5 years, 16 of these patients were available for follow-up
and underwent a new ophthalmologic evaluation by funduscopy, using biomicroscopy 
and angiofluorescein when necessary. Sequelae maculopathy were reconfirmed in all
16 cases, but progression to advanced stage (bull's eye maculopathy) was found in
half of the cohort, even though chloroquine had been suspended. All patients
complained of visual alterations, but without progression. Comparison between
patient groups with and without bull's eye maculopathy revealed a statistically
significant longer rheumatoid arthritis disease history in the former group.
Also, the bull's eye group had higher dose intakes of chloroquine and over a
longer period compared to the other group, but not statistically significant.
This study corroborates the progression of maculopathy even after cessation of
chloroquine intake, pointing out the need for careful screening in the high-risk 
patients. Furthermore, it indicates that duration of rheumatoid arthritis disease
could be a possible factor linked to worse prognosis of chloroquine-induced
maculopathy.

PMID: 17264974 [PubMed - indexed for MEDLINE]

1078: Lab Invest. 2007 Mar;87(3):227-30. Epub 2007 Jan 29.

Antiangiogenesis to treat cancer and intraocular neovascular disorders.

Shojaei F, Ferrara N.

Genentech Inc., South San Francisco, CA 94080, USA.

Identification and characterization of several important regulators of
angiogenesis, and FDA approval of the first antiangiogenic drugs, has opened a
new era in the therapy of cancer and neovascular age-related macular
degeneration. This brief review focuses on the progress in targeting one of the
major regulators of angiogenesis, VEGF-A, and also discusses potential cellular
and molecular mechanisms underlying resistance to antiangiogenic treatments.

Publication Types: 
    Review

PMID: 17259997 [PubMed - indexed for MEDLINE]

1079: Am J Ophthalmol. 2007 Feb;143(2):344-6. Epub 2006 Sep 29.

Elevated serum homocysteine, low serum vitamin B12, folate, and age-related
macular degeneration: the Blue Mountains Eye Study.

Rochtchina E, Wang JJ, Flood VM, Mitchell P.

Department of Ophthalmology, Centre for Vision Research, Westmead Millennium
Institute, University of Sydney, Sydney, Australia.

PURPOSE: To assess associations between increased serum homocysteine, low vitamin
B12, low folate, and age-related macular degeneration (AMD). DESIGN:
Population-based, cross-sectional analysis. METHODS: Serum homocysteine, vitamin 
B12, and folate were measured in 2,335 participants of the Blue Mountains Eye
Study second survey. AMD detected from retinal photographs included atrophic or
neovascular lesions. RESULTS: After adjusting for age, gender, and smoking in
logistic regression models, homocysteine >15 micromol/l was associated with an
increased likelihood of AMD in participants aged <75 years (odds ratio [OR] 3.21,
95% confidence interval [95% CI] 1.09 to 9.43). A similar association was found
for vitamin B12 <125 pmol/l (OR 2.30, 95% CI 1.08 to 4.89) among all
participants. In participants with homocysteine < or =15 micromol/l, low serum
B12 was associated with nearly four-fold higher odds of AMD (OR 3.74, 95% CI 1.06
to 13.24). Folate was not statistically significantly associated with AMD.
CONCLUSIONS: Increased homocysteine and low vitamin B12 were independently
associated with an increased risk of AMD in this study population.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17258528 [PubMed - indexed for MEDLINE]

1080: Am J Ophthalmol. 2007 Feb;143(2):342-4. Epub 2006 Oct 17.

Perimetric sensitivity with the micro perimeter 1 and retinal thickness in
patients with branch retinal vein occlusion.

Yamaike N, Kita M, Tsujikawa A, Miyamoto K, Yoshimura N.

Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School
of Medicine, Kyoto, Japan.

PURPOSE: To evaluate the relationship between retinal sensitivity and thickness
of the macular edema associated with branch retinal vein occlusion (BRVO).
DESIGN: Prospective case series. METHODS: We prospectively examined 15 eyes of 15
patients with macular edema associated with BRVO. In each patient, retinal
sensitivity in the macular area was examined with the Micro Perimeter 1 (MP-1);
retinal thickness was measured by optical coherence tomography (OCT). Eyes with
marked retinal hemorrhage or macular nonperfusion were excluded from the current 
study. RESULTS: Retinal sensitivity measured with the MP-1 was significantly
correlated with retinal thickness in the fovea (R(2) = 0.460) and in all
extrafoveal regions (R(2) = 0.383 to 0.794). In four eyes treated with
triamcinolone acetonide, retinal sensitivity showed marked improvement in
parallel with the reduction of the macular edema. CONCLUSIONS: Retinal
sensitivity in the macular area correlates linearly and negatively with increased
retinal thickness in eyes with BRVO.

PMID: 17258527 [PubMed - indexed for MEDLINE]

1081: Vision Res. 2007 Mar;47(5):714-22. Epub 2007 Jan 24.

Elovl4 haploinsufficiency does not induce early onset retinal degeneration in
mice.

Li W, Chen Y, Cameron DJ, Wang C, Karan G, Yang Z, Zhao Y, Pearson E, Chen H,
Deng C, Howes K, Zhang K.

Genetics of Development and Diseases Branch, National Institute of Diabetes and
Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.

ELOVL4 was first identified as a disease-causing gene in Stargardt macular
dystrophy (STGD3, MIM 600110.) To date, three ELOVL4 mutations have been
identified, all of which result in truncated proteins which induce autosomal
dominant juvenile macular degenerations. Based on sequence homology, ELOVL4 is
thought to be another member within a family of proteins functioning in the
elongation of long chain fatty acids. However, the normal function of ELOVL4 is
unclear. We generated Elovl4 knockout mice to determine if Elovl4 loss affects
retinal development or function. Here we show that Elovl4 knockout mice, while
perinatal lethal, exhibit normal retinal development prior to death at day of
birth. Further, postnatal retinal development in Elovl4 heterozygous mice appears
normal. Therefore haploinsufficiency for wildtype ELOVL4 in autosomal dominant
macular degeneration likely does not contribute to juvenile macular degeneration 
in STGD3 patients. We found, however, that Elovl4+/- mice exhibit enhanced ERG
scotopic and photopic a and b waves relative to wildtype Elovl4+/+ mice
suggesting that reduced Elovl4 levels may impact retinal electrophysiological
responses.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, N.I.H., Intramural
    Research Support, Non-U.S. Gov't

PMID: 17254625 [PubMed - indexed for MEDLINE]

1082: Cornea. 2007 Feb;26(2):182-4.

Central corneal thickness in patients with neovascular age-related macular
degeneration.

Kymionis GD, Panagiotoglou TD, Yoo SH, Tsiklis NS, Christodoulakis E,
Hajithanasis GC, Tsilimbaris MK, Pallikaris IG.

Department of Ophthalmology, Institute of Vision and Optics, University of Crete,
Crete, Greece. kymionis@med.uoc.gr

PURPOSE: To compare the central corneal thickness (CCT) measurements of patients 
with neovascular age-related macular degeneration (AMD) and control subjects.
METHODS: The CCT value (measured with ultrasound corneal pachymetry) of 130 eyes 
(130 patients, 1 eye from each patient) with neovascular AMD (AMD group) and 98
eyes (98 patients, 1 eye from each patient) of similar age, sex, and eye's axial 
length healthy control subjects (normal group) was compared. RESULTS: The mean
age (AMD group: 69.1 years vs. control group: 69.5 years, P = 0.81), sex (AMD
group: 77 women, 59% vs. control group: 59 women, 60%, P = 0.77), and eye's axial
length (AMD group: 25.05-mm vs. control group: 24.61-mm, P = 0.38) of patients
with neovascular AMD and healthy control subjects were comparable. There were no 
statistically significant differences in the mean CCT measurements in the
neovascular AMD group in comparison with the control group (549.44 vs. 544.35
microm, P = 0.11). CONCLUSIONS: CCT measurements do not differ in patients with
neovascular AMD compared with healthy control subjects.

PMID: 17251809 [PubMed - indexed for MEDLINE]

1083: Dev Ophthalmol. 2007;39:88-95.

Diffuse diabetic macular edema: pathology and implications for surgery.

Gandorfer A.

Vitreoretinal and Pathology Unit, Augenklinik der Ludwig-Maximilians-Universität,
München, Germany. arnd.gandorfer@med.uni-muenchen.de

Diffuse diabetic macular edema represents a common problem in diabetic patients. 
It is characterized by widespread and poorly demarcated leakage in the macular
area. The vitreomacular interface in eyes with diffuse diabetic macular edema is 
composed of (1) a layer of native vitreous collagen covering the internal
limiting membrane, (2) fibroblasts and fibrous astrocytes embedded in native
vitreous collagen, and (3) mostly multilayered cellular membranes situated on a
layer of vitreous collagen in eyes with tangential vitreomacular traction. Given 
the poor response of diffuse diabetic macular edema to grid laser
photocoagulation, vitreoretinal surgical techniques including removal of the
vitreous cortex and the internal limiting membrane of the retina have been
proposed. In this chapter, the pathology of diffuse diabetic macular edema and
the implications for surgery are discussed.

Publication Types: 
    Review

PMID: 17245080 [PubMed - indexed for MEDLINE]

1084: Dev Ophthalmol. 2007;39:69-87.

Benefits and limitations in vitreoretinal surgery for proliferative diabetic
retinopathy and macular edema.

Joussen AM, Joeres S.

Department of Ophthalmology, University of Duesseldorf, Duesseldorf, Germany.
joussena@googlemail.com

Surgical therapy for diabetic retinopathy has been refined since the 1960s (Early
Treatment Diabetic Retinopathy Study). While the Early Treatment Diabetic
Retinopathy Study abstained from panretinal photocoagulation at the time of
surgery, today, endophotocoagulation is the most important singular reason for
vitrectomy, e.g., in vitreous hemorrhage. Despite improved techniques, the
surgical prognosis is lagging behind patient expectations, especially in cases of
advanced proliferative stages. The following review addresses current surgical
options and indications of diabetic retinopathy/maculopathy.

Publication Types: 
    Review

PMID: 17245079 [PubMed - indexed for MEDLINE]

1085: Dev Ophthalmol. 2007;39:1-12.

Pathophysiology of diabetic macular edema.

Joussen AM, Smyth N, Niessen C.

Department of Ophthalmology, University of Duesseldorf, Duesseldorf, Germany.
joussena@googlemail.com

Diabetic maculopathy is the leading cause of visual loss in diabetic patients.
The pathogenesis is not fully understood and a satisfactory therapy is currently 
not available. Malfunction of the blood-retinal barrier plays a central role in
the disease and leads to retinal edema and secondary photoreceptor dysfunction.
Diabetic vascular leakage and macular edema are regulated by a distinct
combination of direct paracellular transport, alterations in endothelial
intercellular junctions and endothelial cell death. The distribution and
relevance of these three factors to diabetic maculopathy varies over the course
of the disease. Cumulative endothelial cell death will become more relevant after
prolonged diabetic conditions. This article reviews the current knowledge on the 
pathogenic mechanisms of diabetic macular edema.

Publication Types: 
    Review

PMID: 17245075 [PubMed - indexed for MEDLINE]

1086: Acta Ophthalmol Scand. 2007 Feb;85(1):88-91.

Intraocular lens power calculation for combined cataract surgery, vitrectomy and 
peeling of epiretinal membranes for macular oedema.

Kovács I, Ferencz M, Nemes J, Somfai G, Salacz G, Récsán Z.

Department of Ophthalmology, Semmelweis University, Budapest, Hungary.
kovacsilles@yahoo.com

PURPOSE: This study aimed to compare preoperatively calculated and
postoperatively achieved refraction following phacoemulsification and intraocular
lens (IOL) implantation combined with pars plana vitrectomy with internal
limiting membrane or epiretinal membrane removal. METHODS: Twelve eyes of 12
patients who underwent a combined procedure were enrolled in this study.
Ultrasound axial length and macular thickness (optical coherence tomography, OCT)
measurements were performed pre- and postoperatively. Intraocular lens power was 
calculated with the SRK/T formula and the planned refraction was compared with
results of postoperative automatic refractometry. Comparisons between IOL
calculations using the measured axial length and calculations using an adjusted
axial length (by adding the macular thickness measured on OCT to the ultrasound
axial length) were also performed. RESULTS: Axial length increased (p = 0.02),
whereas macular thickness decreased (p = 0.002). The planned refraction was 0.63 
+/- 0.38 dioptres, whereas the postoperative refraction error was - 0.16 +/- 0.48
D (p = 0.02), with a mean difference of - 0.79 +/- 0.24 D. During case-to-case
comparisons, differences were observed between IOL calculations using the
measured axial length and calculations using an adjusted axial length (0.63 +/-
0.38 D versus 0.13 +/- 0.48 D, p = 0.005). Correlation analysis showed a
significant relationship between the 'adjusted planned' and the measured
postoperative ametropia (r = 0.93, p < 0.001). CONCLUSIONS: The observed myopic
shift due to erroneous IOL calculation results from underestimation of the axial 
length due to a thicker macula and calls for preoperative adjustment of
ultrasound axial length when biometry is performed by this method.

PMID: 17244217 [PubMed - indexed for MEDLINE]

1087: Acta Ophthalmol Scand. 2007 Feb;85(1):32-9.

Topography of diabetic macular oedema compared with fluorescein angiography.

Neubauer AS, Chryssafis C, Priglinger SG, Haritoglou C, Thiel M, Welge-Lüssen U, 
Kampik A, Ulbig MW.

Department of Ophthalmology, Ludwig-Maximilians-University, Munich, Germany.
aljoscha.neubauer@med.uni-muenchen.de

PURPOSE: To compare the amount and pattern of fluorescein leakage in diabetic
macular oedema with the retinal thickness maps obtained with the retinal
thickness analyser (RTA) and optical coherence tomography (OCT). METHODS: A
consecutive series of 30 eyes from 30 patients with diabetic macular oedema was
included. On fluorescein angiography (FA) the macula was analysed in 10 subfields
as defined by the ETDRS. The amount and source of leakage for each field were
determined. Retinal thickness was measured by OCT and RTA maps in each of the 10 
fields and compared with the FA grading. RESULTS: Foveal retinal thickness on OCT
was most influenced by the overall FA leakage, which was the only significant
covariate on multivariate analysis. The source and amount of leakage correlated
significantly with the topography of retinal thickness in the four peripheral
fields between 1500 microm and 3000 microm from the macular centre (r = 0.54, p =
0.002). The mean amount and source of leakage in those fields also showed the
highest correlation with central macular thickness on OCT (r = 0.46, p = 0.01).
Similar results were obtained by RTA when excluding ischaemic cases (r = 0.44, p 
= 0.04). For both instruments, FA leakage within the four central fields < 1500
microm did not correlate significantly with retinal thickness. Thickness by OCT
and RTA were highly correlated with one another for central macular measurements 
(r = 0.73, p < 0.001), but correlated poorly in the peripheral fields. Overall,
OCT measurements correlated more highly with FA. CONCLUSIONS: Optical coherence
tomography and RTA thickness measurements can be used to identify patients for
further examination. Fluorescein angiography leakage in the outer ETDRS fields
correlates best with central thickness and retinal thickness topography by OCT.

Publication Types: 
    Comparative Study

PMID: 17244207 [PubMed - indexed for MEDLINE]

1088: Acta Ophthalmol Scand. 2007 Feb;85(1):27-31.

Identification of diabetic macular oedema using retinal thickness measurements.

Knudsen LL.

Department of Ophthalmology, Aalborg Sygehus South, Aarhus University Hospital,
Aalborg, Denmark. ul9204@aas.nja.dk

BACKGROUND: Identification of clinically significant macular oedema (CSMO)
involves human depth perception, which is subject to a degree of uncertainty.
However, although the ability to obtain objective thickness measurements of the
central macular region may be advantageous, the topography of the macular region 
suggests that average thickness measurements represent a simplification of the
topographic profile of the region. This study explored the applicability of
additional sub-analysis of central macular thickness measurements. METHODS: The
study included 47 eyes of 47 normal subjects and 158 ocular examinations of 38
eyes from 22 diabetic subjects with and without CSMO. All eyes underwent central 
macular thickness measurements using retinal thickness analysis equipment. Eyes
of diabetes subjects were classified as being without CSMO (n = 53), with focal
CSMO (n = 50) and with diffuse CSMO (n = 55). The central macular region was
subdivided into narrow concentric rings around the foveola, using a new
invention, and the thicknesses of the individual concentric rings were
calculated. The sensitivity and specificity of the CSMO diagnosis were
established using the average thickness and the thicknesses of the concentric
rings. RESULTS: The average thickness of the central macular region was found to 
be 165.1 microm in eyes of normal subjects and 192.3 microm in eyes without CSMO.
It increased non-significantly to 198.2 microm in eyes with focal CSMO and
significantly to 236.9 microm in eyes with diffuse CSMO. Sensitivity for focal
CSMO was 48.0% with average thickness measurements and 83.6% with concentric
rings. Corresponding values for detection of diffuse CSMO were 91.7% and 96.1%,
respectively. Specificity was 77.4% with average thickness measurements and 79.7%
with concentric rings. CONCLUSIONS: Thickness measurements of the central macular
region can be used to distinguish between eyes with and without diffuse CSMO, but
not between eyes with and without focal CSMO. Additional sub-analysis based on
concentric rings around the foveola seems to be a useful clinical tool that
increases diagnostic certainty in these eyes.

PMID: 17244206 [PubMed - indexed for MEDLINE]

1089: Acta Ophthalmol Scand. 2007 Feb;85(1):21-6.

Short-term effects of intravitreal triamcinolone on retinal vascular leakage and 
trunk vessel diameters in diabetic macular oedema.

Vinten M, Larsen M, Lund-Andersen H, Sander B, La Cour M.

Department of Ophthalmology, Glostrup Hospital, University of Copenhagen,
Denmark. vinten@oftalmolognet.dk

PURPOSE: To assess retinal vascular permeability and vessel diameter changes
after intravitreal triamcinolone acetonide (IVTA) injection in eyes with
persistent foveal thickening after photocoagulation for diabetic macular oedema
(DMO). METHODS: We calculated the blood-retinal barrier permeability as measured 
by vitreous fluorophotometry, artery and venous vessel diameter at the temporal
vascular arcades as measured on digital fundus photos, and retinal thickness as
measured by optical coherence tomography. Seven patients with type 2 diabetes and
DMO were examined immediately before and 1 week after IVTA 2 mg. The study was
designed as an open-label interventional case series using the fellow eyes as
untreated controls. RESULTS: One week after IVTA, we observed that, compared with
baseline values, blood-retinal barrier permeability had decreased to 27.2 +/-
3.6% (p < 0.0001), retinal artery diameter had decreased to 94.9 +/- 0.02% (p =
0.05), retinal vein diameter had decreased to 89.2 +/- 0.03% (p = 0.02) and
foveal thickness had decreased to 68.7 +/- 6.9% (p = 0.004). Visual acuity (VA)
improved by 7.4 +/- 2.2 letters (p = 0.01). No significant change was observed in
control eyes except that mean VA deteriorated by 2.6 +/- 0.9 letters (p = 0.03). 
Changes in permeability were closely correlated to changes in retinal thickness
(R = 0.84) and venoule diameter (R = 0.93) in treated eyes. CONCLUSIONS:
Intravitreal injection of triamcinolone acetonide in eyes with DMO is followed by
a marked reduction in retinal vascular leakage and a concomitant reduction in
retinal vessel calibre.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17244205 [PubMed - indexed for MEDLINE]

1090: Acta Ophthalmol Scand. 2007 Feb;85(1):6-20.

Comment in:
    Acta Ophthalmol Scand. 2007 Feb;85(1):5.

New therapies for neovascular age-related macular degeneration: critical
appraisal of the current evidence.

Virgili G, Do DV, Bressler NM, Menchini U.

Department of Oto-Neuro-Ophthalmological Surgical Sciences, University of
Florence, Florence, Italy. gianni.virgili@unifi.it

During the past 20 years, several multicentre clinical trials have investigated
different therapies for neovascular age-related macular degeneration (AMD). These
landmark studies have provided the scientific community with powerful data
regarding the ability of laser photocoagulation, verteporfin therapy, pegaptanib 
sodium and submacular surgery to treat particular choroidal neovascular lesion
types. Accurate interpretation of data from these trials is essential to enable
clinicians to make informed decisions about therapeutic interventions.
Furthermore, several new treatment options are likely to become available in the 
next few years and clinicians will have to decide how effective these therapies
may be, and how (or if) they should be used in clinical practice. It is therefore
timely to review the strengths and weaknesses of the body of evidence for the
currently available therapeutic options for patients with choroidal
neovascularization due to AMD. Evaluation of the quality of reporting in past
clinical trials will also enable critical review of new studies that will be
published in the future. This review summarizes the design, reporting and results
of key randomized clinical trials, in addition to evaluating the available
evidence for new therapies and identifying the important issues that need to be
considered when evaluating their efficacy.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17244204 [PubMed - indexed for MEDLINE]

1091: Ophthalmology. 2007 Jun;114(6):1151-6. Epub 2007 Jan 22.

Independent effects of complement factor H Y402H polymorphism and cigarette
smoking on risk of age-related macular degeneration.

Scott WK, Schmidt S, Hauser MA, Gallins P, Schnetz-Boutaud N, Spencer KL, Gilbert
JR, Agarwal A, Postel EA, Haines JL, Pericak-Vance MA.

Center for Human Genetics, Duke University Medical Center, Durham, North Carolina
27710, USA. bill.scott@duke.edu

OBJECTIVE: To examine the potential gene-environment interaction between
cigarette smoking and the complement factor H (CFH) T1277C polymorphism, 2 strong
risk factors for age-related macular degeneration (AMD). DESIGN: Retrospective
case-control study. PARTICIPANTS: A university clinic-based sample of 599 people 
with AMD and 242 controls. METHODS: Standard criteria were used to rate disease
severity (grades 1-5) from fundus photographs. Individuals were classified as
"ever smokers" or "never smokers" based on self-reported lifetime smoking of at
least 100 cigarettes. Intensity of smoking was evaluated by calculating
pack-years of smoking, which was analyzed as a continuous variable, and by
categorizing individuals as smoking more or less than the median 30 pack-years.
T1277C genotypes were determined by sequencing the polymorphic site. Generalized 
estimating equations were used to analyze the effects of smoking and genotype,
controlling for age and gender and adjusting for correlations among related
subjects. MAIN OUTCOME MEASURE: Age-related macular degeneration affection
status. RESULTS: Interaction terms between T1277C genotype and smoking variables 
were not statistically significant, indicating a multiplicative relationship
between risk factors. Effects of both T1277C genotype and cigarette smoking were 
stronger when comparing neovascular (grade 5) AMD with grade 1 controls than when
comparing all cases (grades 3-5) with grades 1 to 2 controls. CONCLUSION: These
results suggest that cigarette smoking and T1277C are independent risk factors
for AMD and that both risk factors are associated more strongly with neovascular 
AMD than all forms of AMD combined.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 17241667 [PubMed - indexed for MEDLINE]

1092: Surv Ophthalmol. 2007 Jan;52 Suppl 1:S79-90.

Anecortave acetate for the treatment of exudative age-related macular
degeneration--a review of clinical outcomes.

Russell SR, Hudson HL, Jerdan JA; Anecortave Acetate Clinical Study Group.

Center for Macular Degeneration and Department of Ophthalmology and Visual
Sciences, The University of Iowa Hospitals and Clinics, Iowa City, USA.

PURPOSE: The angiostatic cortisene anecortave acetate was evaluated in three
safety and efficacy studies of patients with subfoveal choroidal
neovascularization secondary to exudative age-related macular degeneration.
METHODS: The Anecortave Acetate Monotherapy Trial enrolled 128 patients
randomized to anecortave acetate (3 mg, 15 mg, or 30 mg) or vehicle administered 
as a sub-Tenon's posterior juxtascleral depot (PJD) at 6-month intervals. The
Anecortave Acetate and photodynamic therapy (PDT) with verteporfin Combination
Trial enrolled 136 patients randomized to PDT with verteporfin followed by a
single depot administration of anecortave acetate (15 mg or 30 mg) or vehicle.
The Anecortave Acetate 15 mg versus PDT Comparison Trial enrolled 530 patients to
receive either anecortave acetate 15 mg every 6 months + sham PDT every 3 months 
or PDT with verteporfin every 3 months + sham PJD administration every 6 months. 
RESULTS: Anecortave acetate 15 mg was statistically superior to vehicle in the
monotherapy trial at both 12 and 24 months for maintenance of vision and
inhibition of CNV lesion growth. In the combination trial, a trend favored adding
either anecortave acetate 15 mg or 30 mg to PDT for these two measures of
clinical efficacy, but this short-duration study did not achieve statistical
significance. Anecortave acetate 15 mg is comparable to PDT for maintaining
vision over the 24-month period in the comparison trial. CONCLUSIONS: Anecortave 
acetate is safe and effective treatment for exudative age-related macular
degeneration.

Publication Types: 
    Review

PMID: 17240260 [PubMed - indexed for MEDLINE]

1093: Surv Ophthalmol. 2007 Jan;52 Suppl 1:S70-8.

Clinical safety profile of posterior juxtascleral depot administration of
anecortave acetate 15 mg suspension as primary therapy or adjunctive therapy with
photodynamic therapy for treatment of wet age-related macular degeneration.

Regillo CD, D'Amico DJ, Mieler WF, Schneebaum C, Beasley CH, Sullins GT.

Retina Service, Wills Eye Hospital, Philadelphia, Pennsylvania 19107, USA.

OBJECTIVES: Safety data for anecortave acetate 15 mg suspension (Retaane 15 mg,
Alcon Research, Ltd., Ft. Worth, TX 76134) as primary or adjunctive therapy with 
photodynamic therapy are available for 358 patients with age-related macular
degeneration who received this novel cortisene during clinical trials in which
the drug was administered via posterior juxtascleral depot every 6 months for 2
years. METHODS: Detailed ophthalmic examinations, physical examinations, and
adverse event reporting were used to characterize the clinical safety of
anecortave acetate 15 mg and were monitored by an Independent Safety Committee.
RESULTS: Anecortave acetate 15 mg was safe and well tolerated in the overall
patient population. No serious, treatment-related deaths were reported. Ocular
adverse events assessed as related to anecortave acetate 15 mg were non-serious
with one exception (retinal detachment), mild to moderate in intensity with one
exception, generally resolved with or without treatment, and did not interrupt
patient participation in the studies with two exceptions. CONCLUSIONS: Anecortave
acetate 15 mg is safe and well-tolerated when administered as a posterior
juxtascleral depot at 6-month intervals for use as primary therapy or as
adjunctive therapy with PDT.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17240259 [PubMed - indexed for MEDLINE]

1094: Surv Ophthalmol. 2007 Jan;52 Suppl 1:S20-5.

Quality of life and health economic assessments of age-related macular
degeneration.

Covert D, Berdeaux G, Mitchell J, Bradley C, Barnes R.

Alcon Research, Ltd., Fort Worth, Texas 76134-2099, USA.

In this article, we review measures of patient-reported outcomes that can show
whether a treatment for age-related macular degeneration also provides
patient-perceived benefits. In addition, we look at health economic measurements 
currently being used to develop cost-effectiveness models for age-related macular
degeneration.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17240252 [PubMed - indexed for MEDLINE]

1095: Am J Ophthalmol. 2007 Mar;143(3):463-72. Epub 2006 Dec 22.

Progression of geographic atrophy and impact of fundus autofluorescence patterns 
in age-related macular degeneration.

Holz FG, Bindewald-Wittich A, Fleckenstein M, Dreyhaupt J, Scholl HP,
Schmitz-Valckenberg S; FAM-Study Group.

Department of Ophthalmology, University of Bonn, Bonn, Germany.
Frank.Holz@ukb.uni-bonn.de

PURPOSE: To test if fundus autofluorescence (FAF) patterns around geographic
atrophy (GA) have an impact on GA progression rates over time in atrophic
age-related macular degeneration (AMD). DESIGN: Prospective longitudinal
multicenter natural history study. METHODS: Standardized digital FAF images were 
obtained from 195 eyes of 129 patients with GA using confocal scanning laser
ophthalmoscopy (excitation 488 nm, emission >500 nm). Areas of GA were quantified
and patterns of abnormal FAF in the junctional zone were classified. Repeated FAF
images were obtained over a median follow-up period of 1.80 years (interquartile 
range [IQR], 1.28 to 3.34). RESULTS: Areas of GA (median, 7.04 mm(2) at baseline;
IQR, 3.12 to 10.0) showed a median enlargement of 1.52 mm(2)/year (IQR, 0.81 to
2.33). Progression rates in eyes with the banded (median 1.81 mm(2)/year) and the
diffuse FAF pattern (1.77 mm(2)/year) were significantly higher compared to eyes 
without FAF abnormalities (0.38 mm(2)/year) and focal FAF patterns (0.81
mm(2)/year, P < .0001). Within the group of the diffuse pattern, eyes with a
diffuse trickling pattern could be identified that exhibited an even higher
spread rate (median 3.02 mm(2)/year) compared to the other diffuse types (1.67
mm(2)/year, P = .001). CONCLUSIONS: The results indicate that distinct phenotypic
FAF patterns have an impact on disease progression in eyes with atrophic AMD and 
may therefore serve as prognostic determinants. The findings underscore the
relevance of FAF imaging and the pathogenetic role of excessive retinal pigment
epithelium (RPE) lipofuscin (LF) accumulation in GA. Natural history data and
identification of high-risk characteristics will be helpful to design
interventional studies aiming at slowing the spread of atrophy.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17239336 [PubMed - indexed for MEDLINE]

1096: Ophthalmic Physiol Opt. 2007 Jan;27(1):93-9.

Reading performance with various lamps in age-related macular degeneration.

Eperjesi F, Maiz-Fernandez C, Bartlett HE.

Ophthalmic Research Group, School of Life and Health Sciences, Aston University, 
Birmingham B4 7ET, UK. f.eperjesi@aston.ac.uk

The purpose of this study was to determine if there was an objective difference
in reading between four commonly available lamps, of varying spectral radiance,
for 13 subjects with age-related maculopathy (ARM) or non-exudative age-related
macular degeneration (AMD)--logMAR visual acuity between 0.04 and 0.68. At a
constant illuminance of 2000 lux, there was no interaction between ARM and AMD
subgroups and no statistically significant difference between the lamps: standard
(clear envelope) incandescent, daylight simulation (blue tint envelope)
incandescent, compact fluorescent and halogen incandescent, for any reading
outcome measure (threshold print size p = 0.67, critical print size p = 0.74,
acuity reserve p = 0.84 and mean reading rate p = 0.78). For lamps typically used
in low-vision rehabilitation, a clinically significant effect of spectral
radiance on reading for people with ARM or non-exudative AMD is unlikely.

Publication Types: 
    Clinical Trial
    Comparative Study

PMID: 17239195 [PubMed - indexed for MEDLINE]

1097: J Immunol. 2007 Feb 1;178(3):1783-90.

CD59, a complement regulatory protein, controls choroidal neovascularization in a
mouse model of wet-type age-related macular degeneration.

Bora NS, Kaliappan S, Jha P, Xu Q, Sivasankar B, Harris CL, Morgan BP, Bora PS.

Department of Ophthalmology, Jones Eye Institute, Pat and Willard Walker Eye
Research Center, University of Arkansas for Medical Sciences, Little Rock, AR
72205, USA. NBora@UAMS.edu

We have shown that membrane attack complex (MAC) formation via the activation of 
the alternative pathway plays a central role in the laser-induced choroidal
neovascularization (CNV). This study was undertaken to understand the role of a
complement regulatory protein, CD59, which controls MAC assembly and function, in
this model. CNV was induced by laser photocoagulation in C57BL/6 and Cd59a(-/-)
mice using an argon laser. Animals from each group were sacrificed on day 1, 3,
5, and 7 postlaser. Retinal pigment epithelium-choroid-scleral tissue was
examined to determine the incidence and size of CNV complex, and semiquantitative
RT-PCR and Western blot analysis for CD59a was studied. Recombinant soluble mouse
CD59a-IgG2a fusion (rsCD59a-Fc) protein was injected via i.p. or intravitreal
routes 24 h before laser. Our results demonstrated that CD59a (both mRNA and
protein) was down-regulated during laser-induced CNV. Cd59a(-/-) mice developed
CNV complex early in the disease process. Increased MAC deposition was also
observed in these Cd59a(-/-) mice. Administration of rsCD59a-Fc inhibited the
development of CNV complex in the mouse model by blocking MAC formation and also 
inhibited expression of angiogenic growth factors. These data provide strong
evidence that CD59a plays a crucial role in regulating complement activation and 
MAC formation essential for the release of growth factors that drive the
development of laser-induced CNV in mice. Thus, our results suggest that the
inhibition of complement by soluble CD59 may provide a novel therapeutic
alternative to current treatment.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17237428 [PubMed - indexed for MEDLINE]

1098: Br J Ophthalmol. 2007 Aug;91(8):1062-4. Epub 2007 Jan 17.

Cystoid puncture for chronic cystoid macular oedema.

Singh RP, Margolis R, Kaiser PK.

Digital Optical Coherence, Tomography Reading Center (DOCTR), 9500 Euclid Avenue,
Cleveland, OH 44195, USA.

OBJECTIVE: To evaluate the new surgical technique of cystoid macular oedema
puncture (CMOP) in patients with longstanding cystoid macular oedema refractory
to standard treatments. DESIGN: Interventional, retrospective case series
METHODS: Retrospective review of patients with chronic cystoid macular oedema
from vascular retinopathy for whom maximal medical or surgical treatment failed
and who underwent pars plana vitrectomy and CMOP. Clinical findings,
best-corrected Snellen visual acuity, stereo colour fundus photography,
intravenous fluorescein angiograms, and optical coherence tomography were
obtained before and after treatment to evaluate the efficacy and safety of the
treatment. RESULTS: Seven patients were included in the study. Cystoid macular
oedema was due to diabetic retinopathy in five patients, central retinal vein
occlusion in one patient and branch retinal vein occlusion in one patient.
Preoperative intravitreal steroids failed for all patients, and three patients
also had focal grid photocoagulation. Previous pars plana vitrectomy, with
elevation of the posterior hyaloid, internal limiting membrane peeling, and
intravitreal steroid injection, had failed in three patients. The median time to 
CMOP was 488 days. Resolution or improvement of cystoid oedema occurred in all
patients as determined by fluorescein angiography or optical coherence
tomography, or both. However, visual acuity was unchanged in five patients,
declined in one patient and stable in one patient. CONCLUSIONS: Although cystoid 
macular oedema does improve quantitatively after CMOP, the technique fails to
improve visual acuity in patients.

PMID: 17229807 [PubMed - indexed for MEDLINE]

1099: Br J Ophthalmol. 2007 Jun;91(6):753-6. Epub 2007 Jan 17.

Comment in:
    Br J Ophthalmol. 2007 Jun;91(6):707-8.

Recurrence of choroidal neovascularisation after photodynamic therapy in patients
with age-related macular degeneration.

Potter MJ, Szabo SM.

Department of Ophthalmology and Visual Sciences, University of British Columbia, 
Vancouver, British Columbia, Canada. mpotter@eyecarecentre.org

AIM: To determine the incidence of recurrence of choroidal neovascularisation
(CNV) 18 months after cessation of photodynamic therapy (PDT) with verteporfin
monotherapy in patients with age-related macular degeneration (AMD). METHODS:
This was a prospective interventional cohort study. The sample consisted of 108
individuals with CNV secondary to AMD which was treated with PDT. Data on
demographics, pre-PDT and post-PDT Early Treatment of Diabetic Retinopathy Study 
(ETDRS) acuity, pre-PDT lesion size and composition were collected for each
participant. All participants returned for fundus photographs and ETDRS acuity
measurements 18 months after their final PDT, which were compared with the same
measurements from the final treatment session to determine recurrence status.
Recurrences were classified primarily on the basis of haemorrhage and increased
lesion size. RESULTS: Recurrences were observed in 36 of 108 (33%) eyes. 23 of 36
(64%) recurrences were clinically meaningful. Of the explanatory variables
considered, only final PDT acuity was significantly different between those that 
recurred (45.5 ETDRS letters) and those that did not (38.4 letters; p = 0.03).
CONCLUSION: CNV recurrences are common after PDT for AMD, occurring in 33% of
eyes in this study. Visual acuity measured at the final PDT treatment visit may
be a predictor of subsequent recurrence.

Publication Types: 
    Clinical Trial

PMID: 17229805 [PubMed - indexed for MEDLINE]

1100: Br J Ophthalmol. 2007 Jun;91(6):766-72. Epub 2007 Jan 17.

Quality of life and relative importance: a comparison of time trade-off and
conjoint analysis methods in patients with age-related macular degeneration.

Aspinall PA, Hill AR, Dhillon B, Armbrecht AM, Nelson P, Lumsden C, Farini-Hudson
E, Brice R, Vickers A, Buchholz P.

Heriot-Watt University, Riccarton, Edinburgh EH14 3AZ, Scotland, UK.
p.a.aspinall@sbe.hw.ac.uk

AIM: To investigate the relative priorities in quality of life (QoL) in patients 
with age-related macular degeneration (AMD). METHODS: Measures of visual
function, QoL and utility associated with visual loss were obtained from 122
patients with AMD classified according to macular morphology. The two methods of 
utility assessment were time trade-off (TTO) and conjoint analysis (CA), which
have been recommended by the UK's National Institute of Clinical Excellence as
techniques for the assessment of healthcare priorities. RESULTS: Results show
that the two methods for assessing utility are poorly related: TTO relates
moderately to visual function and disease severity but CA does not. CA identified
two different subgroups of patients: one with outdoor mobility and the other with
reading as their main priority. CONCLUSION: Further work is needed and caution
required in interpreting data obtained using these methodologies for determining 
their relative importance in vision-related QoL studies.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 17229802 [PubMed - indexed for MEDLINE]

1101: Int J Clin Pract. 2007 Jan;61(1):88-97.

Erratum in:
    Int J Clin Pract. 2007 Apr;61(4):711.

Diabetic macular oedema: a clinical overview.

Girach A, Lund-Andersen H.

Lilly Research Labs, Surrey, UK. girach.aniz@lilly.com

Diabetic retinopathy is the leading cause of blindness in working aged-adults in 
westernised countries. Diabetic macular oedema (DMO) is a manifestation of
diabetic retinopathy and is the leading cause of the visual impairment that
occurs with diabetic retinopathy. There are multiple ways of classifying DMO;
however, none appear to be wholly satisfactory. DMO occurs more frequently in
type 2 diabetes mellitus, and appears to be more prevalent as the duration of
diabetes increases, and as the severity of diabetic retinopathy worsens. There
are multiple risk factors in common with diabetic retinopathy, such as
hyperglycaemia, hypertension and dyslipidaemia; however, specific factors such as
the presence of renal disease appear to be more significantly associated with
DMO. Whereas the gold standard for diagnosis of DMO is via clinical examination, 
there is considerable variability involved, and hence, this has led to the advent
of more objective methods of quantifying the degree of retinal thickness, such as
optical coherence tomography. Laser photocoagulation appears to be the only
universally acceptable treatment of choice to date; however, this is a
destructive therapy, and its side effects coupled with the suboptimal efficacy
has led to the advent of potential new therapies which will undoubtedly
compliment the existing approaches, in the future management of a patient with
DMO.

Publication Types: 
    Review

PMID: 17229183 [PubMed - indexed for MEDLINE]

1102: Graefes Arch Clin Exp Ophthalmol. 2007 Mar;245(3):451-6. Epub 2007 Jan 17.

Intravitreal triamcinolone acetonide in the management of cystoid macular edema
in Behçet's disease.

Atmaca LS, Yalçindağ FN, Ozdemir O.

Department of Ophthalmology, Ankara University Medical School, Ankara, Turkey.
leylaatmaca@ttnet.net.tr

PURPOSE: To determine the efficacy of intravitreal triamcinolone acetonide (ivTA)
injection in the management of cystoid macular edema (CME) due to uveitis in
patients with Behçet's disease. METHODS: Ten eyes of seven patients with CME
associated with Behçet's disease were included in the study. A quantity of 4 mg
of triamcinolone acetonide was injected intravitreally in all of the eyes. The
maculas of the patients were evaluated with optical coherence tomography (OCT)
and fluorescein angiography (FA). The change in visual acuity, fluorescein
leakage, macular thickness, and potential complications were assessed. RESULTS:
The mean follow-up was 15.6 months (range 7-19 months). There was an increase of 
more than two Snellen lines in the visual acuity in seven of the ten eyes (70%)
at the last examination. Macular edema regressed completely in eight of the ten
eyes (80%) at the last visit on OCT and FA. The mean central macular thickness
assessed by OCT was 406 mum before treatment and 186.9 mum at the last visit. The
intraocular pressure (IOP) exceeded 21 mmHg in six eyes of five patients (60%)
during the follow-up. At the last visit, the IOP was less than 21 mmHg in five
eyes with medication. One eye underwent glaucoma filtration surgery. Four eyes of
three patients had cataract progression. In four eyes of four patients (40%), a
second ivTA injection was given due to relapsing CME. CONCLUSION: Intravitreal
triamcinolone acetonide (ivTA) may be beneficial in the management of CME in
patients with Behçet's disease. Repeated ivTA injections might be required if CME
reoccurs.

PMID: 17226025 [PubMed - indexed for MEDLINE]

1103: Can J Ophthalmol. 2006 Dec;41(6):727-32.

Benefits of stereopsis when identifying clinically significant macular edema via 
teleophthalmology.

Rudnisky CJ, Tennant MT, de Leon AR, Hinz BJ, Greve MD.

Department of Opthalmology, University of Alberta, Edmonton, Canada.
crudnisk@ualberta.ca

BACKGROUND: The need to incorporate stereopsis into a teleophthalmology system is
controversial. Detection of hard exudate in the macula is suggested by some as an
adequate surrogate for direct observation of retinal thickening. This study was
designed to determine how accurate the detection of hard exudate is as a
surrogate for stereoscopic detection of clinically significant macular edema
(CSME).METHODS: 120 patients with diabetes underwent clinical retinal examination
with contact-lens biomicroscopy by a retinal specialist. The presence or absence 
of CSME was recorded. On the same day as clinical grading, 30 degrees
stereoscopic digital photographs of the macula were captured. At least 2 months
after clinical examination, the digital images were viewed by masked graders for 
the presence or absence of hard exudate and retinal thickening. RESULTS: 207 eyes
of 106 patients had complete data sets for both diagnostic modalities. The
sensitivity of hard exudate (93.9%) in predicting the presence of CSME was
similar to that of direct stereoscopic observation of retinal thickening (90.9%),
with p = 0.5. On the other hand, digital stereopsis was significantly more
specific (92.9%) than was hard exudate (81.6%) in predicting the presence of CSME
(p < 0.001). This difference was maintained even when controlling for image
quality. INTERPRETATION: Although the presence of hard exudate within the macula 
is a sensitive surrogate marker for CSME, it is less specific than stereoscopic
evaluation. Any American Telemedicine Association category 3 teleophthalmology
system that utilizes hard exudate as a surrogate marker for CSME may refer
patients unnecessarily for clinical evaluation.

PMID: 17224954 [PubMed - indexed for MEDLINE]

1104: Can J Ophthalmol. 2006 Dec;41(6):699-703.

Cystoid macular edema after phacoemulsification: risk factors and effect on
visual acuity.

Gulkilik G, Kocabora S, Taskapili M, Engin G.

SSK Vakif Gureba Education Hospital, Istanbul, Turkey. g.gulkilik@excite.com

BACKGROUND: To determine the incidence and risk factors for cystoid macular edema
(CME) after phacoemulsification surgery and its effect on visual acuity. METHODS:
This prospective study evaluated 98 eyes of 98 patients (43 women) with a mean
(SD) age of 61.8 (11.3) years. Phacoemulsification was performed with temporal
clear corneal incision and implantation of foldable hydrophilic acrylic
intraocular lens in the bag. Postoperative visits were on day 1, week 1, and at
1, 3, and 6 months. In addition, at week 10 all patients had fundus fluorescein
angiography, and presence of CME was determined. Age, sex, iris colour,
pseudoexfoliation, type of cataract, phaco time, status of the posterior
vitreous, iris trauma, severity of anterior chamber reaction, and visual acuities
were evaluated. RESULTS: No major intraoperative complications occurred.
Twenty-five (25.5%) eyes were CME(+), and 73 (74.4%) eyes were CME(-). CME
occurred in 70% of patients with iris trauma and 20.5% of patients with no iris
trauma. CME was more common in patients who had postoperative anterior chamber
inflammation of 2+ or more than in patients with less inflammation (43.2% vs.
11.5%). Complete posterior vitreous detachment had some apparent protective
effect against CME development. The mean visual acuities of CME(+) patients were 
lower than those of CME(-) patients in all postoperative periods. The difference 
was significant in the third month (p < 0.05). INTERPRETATION: CME after
phacoemulsification was associated with iris trauma and severe postoperative
inflammation. Complete posterior vitreous detachment had some apparent protective
effect against CME development. CME may be associated with decreased visual
acuity.

PMID: 17224950 [PubMed - indexed for MEDLINE]

1105: Eye. 2008 Jun;22(6):777-81. Epub 2007 Jan 12.

Lack of benefit of early awareness to age-related macular degeneration.

Cervantes-Castañeda RA, Banin E, Hemo I, Shpigel M, Averbukh E, Chowers I.

Department of Ophthalmology, Hadassah - Hebrew University Medical Center,
Jerusalem, Israel.

AIMS: To assess the rate of early awareness to the presence of age-related
macular degeneration (AMD) and whether it enables early detection of transition
to neovascular AMD (NVAMD) as compared with patients whose first presentation to 
an ophthalmologist is already at the neovascular stage of disease. METHODS: A
retrospective analysis of 268 eyes of 268 consecutive patients with newly
diagnosed NVAMD that were treated in a tertiary referral centre was performed.
Patients were classified into those who were unaware (Group 1), or aware (Group
2), of the fact that they had AMD before diagnosis of NVAMD. Visual acuity,
lesion size and composition, and demographics were compared between both groups. 
RESULTS: In all, 185 patients (69%) and 83 patients (31%) were classified to
Groups 1 and 2, respectively. Patients in Groups 1 and 2 had similar demographic 
characteristics, presenting visual acuity and lesion size, and lesion
compositions. Group 1 patients were more likely to have a positive history for
smoking (41 vs26% in Group 2, P=0.03), whereas Group 2 patients were more likely 
to have positive family history for AMD (20 vs10%, P=0.02). Conclusions: These
data suggest that current screening methods fail to identify the majority of
patients with AMD before the development of NVAMD. The findings also demonstrate 
that in the routine clinical setting, prior awareness of AMD may not facilitate
early detection of treatable choroidal neovascularization lesions.

PMID: 17220824 [PubMed - indexed for MEDLINE]

1106: Graefes Arch Clin Exp Ophthalmol. 2007 May;245(5):627-36. Epub 2007 Jan 12.

Müller cells as players in retinal degeneration and edema.

Reichenbach A, Wurm A, Pannicke T, Iandiev I, Wiedemann P, Bringmann A.

Paul Flechsig Institute of Brain Research, Faculty of Medicine, University of
Leipzig, Jahnallee 59, 04109, Leipzig, Germany.

BACKGROUND: Under normal conditions, Müller cells support neuronal activity and
the integrity of the blood-retinal barrier, whereas gliotic alterations of Müller
cells under pathological conditions may contribute to retinal degeneration and
edema formation. A major function of Müller cells is the fluid absorption from
the retinal tissue, which is mediated by transcellular water transport coupled to
currents through potassium channels. METHODS: Alterations of retinal Müller cells
under pathological conditions were investigated by immunohistochemistry and
recording their behavior under osmotic stress. RESULTS: In animal models of
various retinopathies, e.g., retinal ischemia, ocular inflammation, retinal
detachment, and diabetes, it was found that Müller cells decrease the expression 
of their major potassium channel (Kir4.1). This alteration is associated with an 
impairment of the rapid water transport across Müller cell membranes, as
recognizable in the induction of cellular swelling under hypoosmolar conditions. 
Osmotic swelling of Müller cells is also induced by oxidative stress and by
inflammatory mediators such as arachidonic acid and prostaglandins. CONCLUSIONS: 
The data suggest that a disturbed fluid transport through Müller cells is (in
addition to vascular leakage) a pathogenic factor contributing to the development
of retinal edema. Pharmacological re-activation of the retinal water clearance by
Müller cells may represent an approach to the development of new edema-resolving 
drugs. Triamcinolone acetonide, which is clinically used to resolve edema,
prevents osmotic swelling of Müller cells as it induces the release of endogenous
adenosine and subsequent A1 receptor activation which results in the opening of
ion channels. Apparently, triamcinolone resolves edema by both inhibition of
vascular leakage and stimulation of retinal fluid clearance by Müller cells.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17219109 [PubMed - indexed for MEDLINE]

1107: Graefes Arch Clin Exp Ophthalmol. 2007 Aug;245(8):1085-95.

Full macular translocation versus photodynamic therapy with verteporfin in the
treatment of neovascular age-related macular degeneration: 1-year results of a
prospective, controlled, randomised pilot trial (FMT-PDT).

Gelisken F, Voelker M, Schwabe R, Besch D, Aisenbrey S, Szurman P, Grisanti S,
Herzau V, Bartz-Schmidt KU.

Centre for Ophthalmology, University of Tuebingen, Schleichstr. 12, 72076
Tuebingen, Germany. Faik.Gelisken@med.uni-tuebingen.de

BACKGROUND: The purpose of this study was to compare full macular translocation
(FMT) with photodynamic therapy (PDT) in the treatment of neovascular age-related
macular degeneration (AMD). METHODS: In a prospective, randomised, non-masked,
mono-center, pilot-trial, 50 eyes of 50 patients were assigned to either FMT or
PDT. Baseline and control examinations in 3-monthly intervals over a 12-month
period included standardized protocol refraction, visual acuity testing and
fluorescein angiography. Primary outcome measurements were made to establish the 
change in distant visual acuity from the baseline to the 12-month examination.
The statistical analyses were carried out on the intent-to-treat principle.
RESULTS: The improvement of one or more ETDRS lines was 56% (14/25) of the eyes
in the FMT and 16% (4/25) of the eyes in the PDT arm (P = 0.007). Twenty eyes
(80%) in the FMT and 16 eyes (64%) in the PDT group had less than three ETDRS
lines of vision loss (P = 0.35). Retinal detachment (six eyes) and diplopia (five
patients) were recorded in the FMT group. None of the eyes treated in the FMT
group had phtysis. CONCLUSION: This pilot study showed that no statistically
significant difference existed between the FMT and PDT in terms of the vision
loss of less than three ETDRS lines in eyes with neovascular AMD. The chance of
vision improvement was significantly higher for the patients in the FMT group.
However, in the era of promising therapy with anti-vascular endothelial growth
factor for neovascular AMD, FMT should not be offered as a standard primary
procedure for neovascular AMD.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17219106 [PubMed - indexed for MEDLINE]

1108: Retina. 2007 Jan;27(1):21-9.

Fundus microperimetry patterns of fixation in type 2 diabetic patients with
diffuse macular edema.

Carpineto P, Ciancaglini M, Di Antonio L, Gavalas C, Mastropasqua L.

From the Department of Medicine and Aging Sciences, Section of Ophthalmology,
University G. d'Annunzio Chieti-Pescara, Chieti, Italy. p.carpineto@unich.it

BACKGROUND: Recently developed fundus microperimetry (MP-1; Nidek Technologies,
Srl. Vigonza PD, Italy) was used to evaluate fixation patterns and retinal
sensitivity in patients who had clinically significant macular edema with a
diffuse pattern and type 2 diabetes mellitus. METHODS: In a prospective,
observational case series study, 84 consecutive patients with type 2 diabetes (84
eyes) who had clinically significant macular edema with a diffuse pattern were
studied by means of MP-1. Main outcome measures were fixation stability and
position and mean retinal sensitivities within the central 2 degrees and 8
degrees areas. Logarithm of the minimum angle of resolution (logMAR)
best-corrected visual acuity (BCVA) was evaluated by means of an Early Treatment 
of Diabetic Retinopathy Study chart. Foveal thickness was measured by Stratus
optical coherence tomography (OCT; Carl Zeiss Meditec, Inc., Dublin, CA). Age,
duration of diabetes, hemoglobin A1c (HbA1c) levels, duration of symptoms,
history of panretinal photocoagulation, vitreomacular adhesion, and cystoid
macular changes were documented. Patients were grouped according to both position
of fixation (central or eccentric) and stability of fixation (stable or
unstable). Statistical analyses included independent samples t-test, binomial
test, Bonferroni correction for multiple comparisons, and generalized linear
model univariate analysis. RESULTS: Of 84 eyes, 44 (52.4%) had central fixation, 
and 40 (47.6%) had eccentric fixation. Of 84 eyes, 34 (40.5%) had stable
fixation, and 50 (59.5%) had unstable fixation. In the whole sample, mean central
2 degrees retinal sensitivity +/- SD was 6.26 +/- 3.19 dB (range, 0-14.80 dB),
and mean central 8 degrees retinal sensitivity +/- SD was 7.62 +/- 2.55 (range,
3.85-14.90 dB); logMAR BCVA ranged from 0.1 to 1.3 (mean +/- SD, 0.6 +/- 0.29).
Mean OCT foveal thickness +/- SD was 300.77 +/- 66.93 m (range, 220-525 m). Both 
comparisons between groups (stable vs. unstable and central vs. eccentric) showed
statistically significant differences in mean logMAR BCVA, mean central 2 degrees
and 8 degrees retinal sensitivities, and mean OCT foveal thickness. Duration of
symptoms was significantly longer and HbA1c levels were higher in the groups with
deterioration of stability or centrality of fixation. The prevalence of cystoid
macular changes was significantly higher in the groups with eccentric or unstable
fixation (P < 0.001). Generalized linear model statistical analysis showed that
logMAR BCVA was significantly associated with stability of fixation (P = 0.020), 
mean central 8 degrees retinal sensitivity (P < 0.001), and mean OCT foveal
thickness (P < 0.001). The interaction between stability of fixation and mean OCT
foveal thickness showed a statistically significant association with logMAR BCVA 
(P = 0.003). Some eyes with eccentric fixation presented with stable fixation,
especially in the presence of long-lasting symptoms, and had better visual acuity
than eyes with central, but unstable fixation. CONCLUSION: Visual acuity, central
retinal sensitivity, foveal thickness, duration of symptoms, HbA1c levels, and
presence of cystoid macular changes were strongly associated with fixation
impairment in type 2 diabetic patients who had clinically significant macular
edema with a diffuse pattern. Stability of fixation and foveal thickness play a
major role in conditioning BCVA.

PMID: 17218911 [PubMed - indexed for MEDLINE]

1109: Retina. 2007 Jan;27(1):13-20.

Short-term effects of focal argon laser treatment in diabetic maculopathy as
demonstrated by optical coherence tomography.

Sandhu SS, Birch MK, Griffiths PG, Talks SJ.

Department of Ophthalmology, Royal Victoria Infirmary, Newcastle upon Tyne,
United Kingdom.

PURPOSE: To assess the short-term effects of argon laser on retinal thickening as
demonstrated by optical coherence tomography (OCT). METHODS: A prospectively
collected consecutive series of patients undergoing routine focal argon laser
treatment for sight-threatening diabetic maculopathy had bilateral OCT performed 
before laser treatment and 1 hour, 24 hours, and 2 weeks after treatment. The
main outcome measure was change in retinal thickness in the region of laser
treatment. RESULTS: Forty-six eyes were analyzed. There was a small increase in
retinal thickness in the treated area 1 hour after laser treatment, with a mean
change from before laser treatment of +2.6 microm (95% confidence interval [CI], 
+0.2 to + 5.0). However, there was a larger change 24 hours after treatment of
+39.0 microm (95% CI, +31.6 to + 46.4) and a significant decrease 2 weeks after
treatment of -14.6 microm (95% CI, -21.6 to -7.7) from before laser treatment
values. CONCLUSION: Focal argon laser treatment remains the first-line treatment 
for sight-threatening diabetic maculopathy. This study shows that in the
short-term, areas of retinal thickening worsen before settling in response to
argon laser treatment as demonstrated by OCT.

PMID: 17218910 [PubMed - indexed for MEDLINE]

1110: Hum Mutat. 2007 Apr;28(4):406-13.

Case-control genetic association study of fibulin-6 (FBLN6 or HMCN1) variants in 
age-related macular degeneration (AMD).

Fisher SA, Rivera A, Fritsche LG, Keilhauer CN, Lichtner P, Meitinger T, Rudolph 
G, Weber BH.

Department of Medical and Molecular Genetics, Guy's King's and St Thomas' School 
of Medicine, King's College London, London, United Kingdom.

This article reports a well-powered age-related macular degeneration (AMD)
case-control association study in the HMCN1 gene, showing that common variants do
not account for a substantial proportion of AMD cases. Thus, the consistent
linkage peak observed by several genome-wide linkage scans within the 1q32 region
is unlikely to be attributed to polymorphisms at the HMCN1 locus. In addition,
the analysis provides comprehensive data suggesting that low-frequency variants
encoding possible functional amino acid polymorphisms in the HMCN1 gene may not
contribute substantially to disease, although HMCN1 mutations may still confer
disease susceptibility in a small subset of patients. Interestingly, the HMCN1
p.Gln5346Arg mutation, which is thought to be a causal mutation in a large AMD
pedigree segregating the disease as a single-gene trait, appears to occur in our 
control cohort as a low-frequency polymorphism with an allele frequency of
approximately 0.0026. Copyright 2007 Wiley-Liss, Inc.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17216616 [PubMed - indexed for MEDLINE]

1111: Doc Ophthalmol. 2007 Jan;114(1):37-44. Epub 2007 Jan 10.

Intravitreal use of bevacizumab (Avastin) for choroidal neovascularization due to
ARMD: a preliminary multifocal-ERG and OCT study. Multifocal-ERG after use of
bevacizumab in ARMD.

Moschos MM, Brouzas D, Apostolopoulos M, Koutsandrea C, Loukianou E, Moschos M.

Department of Ophthalmology, University of Athens, Athens, Greece.
moschosmarilita@yahoo.fr

PURPOSE: To evaluate by MFERG and OCT the macular function before and after
intravitreal use of bevacizumab (Avastin) in eyes suffering from CNV due to ARMD.
METHODS: Eighteen eyes with subfoveal CNV due to ARMD were studied before and
after intravitreal use of bevacizumab with MFERG and OCT. The post treatment
follow up was three months. RESULTS: Before treatment, OCT shows an increase of
the retinal thickening of the fovea and the electrical response densities in the 
fovea and parafovea were decreased in all patients. Three months after treatment,
OCT showed a real resolution of the subretinal fluid. The electrical responses in
the fovea and parafovea remained the same or slightly improved in some cases. The
intraocular pressure remained normal and no inflammation was observed.
CONCLUSION: The intravitreal use of bevacizumab may provide anatomical correlates
that support the concept of disease amelioration but the functional improvement
of the macula three months after treatment is not obvious. However the method is 
promising and needs further evaluation.

PMID: 17216267 [PubMed - indexed for MEDLINE]

1112: Br J Ophthalmol. 2007 Jun;91(6):743-5. Epub 2007 Jan 10.

Continued use of dorzolamide for the treatment of cystoid macular oedema in
patients with retinitis pigmentosa.

Fishman GA, Apushkin MA.

Department of Ophthalmology and Visual Sciences, University of Illinois at
Chicago, Chicago, IL 60612, USA. gerafish@uic.edu

AIM: To determine the value of a topical carbonic anhydrase inhibitor for
extended treatment of cystoid macular oedema (CME) in patients with retinitis
pigmentosa (RP). METHOD: Eight patients with RP and foveal cystic-appearing
lesions observed on fundus examination and by optical coherence tomography (OCT) 
testing were treated with a topical form of carbonic anhydrase inhibitor.
RESULTS: Foveal cystic-like spaces were documented by OCT testing in all eight
patients before treatment. All patients had a significant reduction in their
foveal thickness (FT) and foveal zone thickness (FZT) in at least one eye after
using 2% dorzolamide three times a day for 1 or 2 months. Six patients had an
improvement in both eyes. After an additional 6-13 months of the same treatment
regimen, out of six patients who had a sustained reduction in FT and FZT in at
least one eye, four had this reduction in both eyes. While they were still taking
Trusopt, a recurrence (rebound) of CME in both eyes was observed in two patients,
whereas one patient had a sustained improvement in one eye and rebound of CME in 
the other eye. Out of 8 patients, 3 showed an improvement in their visual acuity 
by > or =7 letters, in at least one eye, on Snellen acuity charts, which was
determined as clinically significant. CONCLUSION: Results from this study suggest
that patients with RP could potentially sustain a beneficial effect from
continued treatment with a topical form of carbonic anhydrase inhibitor.

Publication Types: 
    Clinical Trial
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17215269 [PubMed - indexed for MEDLINE]

1113: Arch Ophthalmol. 2007 Jan;125(1):68-73.

Apolipoprotein e gene and age-related maculopathy in older individuals: the
cardiovascular health study.

Tikellis G, Sun C, Gorin MB, Klein R, Klein BE, Larsen EK, Siscovick DS, Hubbard 
LD, Wong TY.

Centre for Eye Research Australia, University of Melbourne, Victoria, Australia.

OBJECTIVE: To examine the association between the apolipoprotein E (APOE) gene
and age-related maculopathy (ARM) in an older population. METHODS: Two thousand
one hundred seventy persons 65 years and older sampled from 4 US communities had 
ARM signs assessed from retinal photographs using a modified Wisconsin
Age-Related Maculopathy Grading System. DNA extracted from blood samples was
analyzed for common APOE alleles. RESULTS: After controlling for age, sex,
cigarette smoking, and other factors, white participants carrying the epsilon2
allele had an increased risk of late ARM (odds ratio, 2.53 [95% confidence
interval, 1.08-5.90]) while carriers of the epsilon4 allele had a lower risk of
late ARM (odds ratio, 0.69 [95% confidence interval, 0.19-2.50]). There were too 
few late ARM cases in African American individuals for analysis. CONCLUSION: APOE
polymorphism is associated with late ARM in older white persons 65 years and
older. Consistent with previous studies, the APOE epsilon2 allele is associated
with a significant increased risk of late ARM development, whereas the epsilon4
allele may confer some protection.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17210854 [PubMed - indexed for MEDLINE]

1114: Arch Ophthalmol. 2007 Jan;125(1):63-7.

Neovascular age-related macular degeneration and its association with LOC387715
and complement factor H polymorphism.

Shuler RK Jr, Hauser MA, Caldwell J, Gallins P, Schmidt S, Scott WK, Agarwal A,
Haines JL, Pericak-Vance MA, Postel EA.

Eye Center and Center for Human Genetics, Duke University, Durham, NC, USA.

OBJECTIVE: To compare phenotypes of 2 age-related macular degeneration (AMD)
susceptibility genes: LOC387715 and complement factor H (CFH). METHODS:
Phenotypes of 755 AMD cases were characterized. The number of LOC387715 (T allele
at rs10490924, or A69S) and CFH (T1277C at rs1061170, or Y402H) risk alleles were
determined in each case. Individuals were divided into 5 groups by genotype:
group 1, LOC-/- CFH-/-; group 2, LOC+/- CFH-/- or LOC+/+ CFH-/-; group 3, LOC-/- 
CFH+/- or LOC-/- CFH+/+; group 4, LOC+/- CFH+/-, LOC+/+ CFH+/-, or LOC+/- CFH+/+;
and group 5, LOC+/+ CFH+/+. RESULTS: Signs of neovascular AMD including grade (P 
= .002), pigment epithelial detachment (P = .001), and subretinal hemorrhage
(P<.001) demonstrated significant association with groups 2, 4, and 5 vs groups 1
and 3. Group 5 had a significantly younger mean age (72.3 years) compared with
other groups (P = .002). CONCLUSIONS: The AMD cases possessing the LOC387715
(rs10490924) variant may have a higher risk of neovascular AMD. Individuals with 
AMD who are homozygous for both variants might be at greater risk for earlier
onset of neovascular AMD.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17210853 [PubMed - indexed for MEDLINE]

1115: Arch Ophthalmol. 2007 Jan;125(1):55-62.

Comment in:
    JAMA. 2007 Jan 24;297(4):401-2.

A prospective study of 2 major age-related macular degeneration susceptibility
alleles and interactions with modifiable risk factors.

Schaumberg DA, Hankinson SE, Guo Q, Rimm E, Hunter DJ.

Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Mass, USA.
dschaumberg@rics.bwh.harvard.edu

OBJECTIVES: To delineate the magnitude of susceptibility to age-related macular
degeneration (AMD) due to common variants in the gene for complement factor H
(CFH) and the predicted gene LOC387715 and to determine whether these variants
interact with modifiable risk factors. METHODS: We compared cases who developed
AMD (n = 457) with 1071 age- and sex-matched control subjects in a prospective
nested case-control study within the Nurses' Health Study and the Health
Professionals Follow-up Study. We determined the incidence rate ratios and 95%
confidence intervals (CIs) for AMD for each genotype and examined the
interactions with modifiable risk factors. RESULTS: Participants with 1 or 2
copies of the Y402H variant of CFH were, respectively, 1.98 (95% CI, 1.64-2.40)
and 3.92 (95% CI, 2.69-5.76) times more likely to develop AMD, whereas the
incident rate ratios (95% CIs) for 1 and 2 copies of LOC387715 A69S were 2.38
(1.92-2.96) and 5.66 (3.69-8.76), respectively. The fraction of AMD cases
attributable to these 2 variants was 63% (95% CI, 58%-68%). Subjects homozygous
for both risk alleles had a 50-fold increased risk of AMD (95% CI, 10.8-237), and
cigarette smoking and obesity multiplied the risks associated with these
variants. CONCLUSION: Age-related macular degeneration has emerged as a
paradigmatic example of a common disease caused by the interplay of genetic
predisposition and exposure to modifiable risk factors.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 17210852 [PubMed - indexed for MEDLINE]

1116: Arch Ophthalmol. 2007 Jan;125(1):49-54.

Cigarette smoking, CFH, APOE, ELOVL4, and risk of neovascular age-related macular
degeneration.

DeAngelis MM, Ji F, Kim IK, Adams S, Capone A Jr, Ott J, Miller JW, Dryja TP.

Department of Ophthalmology, Harvard Medical School, and Massachusetts Eye and
Ear Infirmary, Boston, USA. margaret_deangelis@hms.harvard.edu

OBJECTIVE: To examine if the genes encoding complement factor H (CFH),
apolipoprotein E (APOE), and elongation of very-long-chain fatty acids-like 4
(ELOVL4) confer risk of neovascular age-related macular degeneration (AMD) in an 
independent or interactive manner when controlling for smoking exposure. METHODS:
We studied 103 unrelated patients with neovascular AMD who each had at least 1
sibling with normal maculae. Smoking histories were obtained. Genotyping was
performed by analyzing amplified genomic fragments from CFH, APOE, and ELOVL4 by 
direct sequencing or by restriction endonuclease digests. Conditional logistic
regression analysis was used to build a multifactor model. RESULTS: For CFH, only
the CC genotype carried a statistically significant elevation of disease risk
(odds ratio, 49.37; 95% confidence interval, 6.20-393.22; P<.001). No significant
association was observed between neovascular AMD and APOE or ELOVL4. No
significant interactions were found between smoking and having the CFH or APOE
genotype nor were significant interactions found between the CFH, ELOVL4, and
APOE genotypes. CONCLUSIONS: Smoking and having the CFH CC genotype independently
increase risk of neovascular AMD. APOE and ELOVL4 genotypes do not seem to modify
risk. CLINICAL RELEVANCE: Smoking 10 pack-years or more and having the CFH CC
genotype increase one's risk of neovascular AMD 144-fold compared with smoking
less than 10 pack-years and having the CT or TT genotype.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17210851 [PubMed - indexed for MEDLINE]

1117: Arch Ophthalmol. 2007 Jan;125(1):21-9.

A clinician's view of the molecular genetics of age-related maculopathy.

Gorin MB.

Departments of Ophthalmology, The David Geffen School of Medicine at UCLA, Los
Angeles, Calif, USA. gorin@jsei.ucla.edu

Molecular genetic studies of age-related maculopathy (ARM), including
family-based linkage studies and case-control association studies, have yielded
valuable insights into the risks of developing this condition and potential
disease-causing mechanisms. Variants in the complement factor H gene and
LOC387715 have consistently been shown to be major risk factors for ARM.
Additional genes, and environmental, behavioral, and dietary factors, also play a
major role in ARM pathogenesis. The present studies are a starting point toward
our understanding of the causes of ARM and for future therapeutic studies. As
clinicians, we can already begin to use our knowledge of ARM genetics to counsel 
and care for our patients at risk.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Review

PMID: 17210848 [PubMed - indexed for MEDLINE]

1118: Am J Clin Nutr. 2007 Jan;85(1):304S-307S.

Multivitamin-multimineral supplements and eye disease: age-related macular
degeneration and cataract.

Seddon JM.

Epidemiology Unit, Massachusetts Eye and Ear Infirmary, Harvard Medical School,
Boston, MA 02114, USA. jseddon@earthlink.net

The prevalence and effects of age-related macular degeneration (AMD) and cataract
are increasing dramatically as the proportion of elderly in our population
continues to rise. A multivitamin-multimineral supplement with a combination of
vitamin C, vitamin E, beta-carotene, and zinc (with cupric oxide) is recommended 
for AMD but not cataract. Weak support exists for multivitamins or other vitamin 
supplements from observational studies of cataract. The results of observational 
studies suggest that a healthy lifestyle with a diet containing foods rich in
antioxidants, particularly lutein and zeaxanthin, as well as n-3 fatty acids,
appears beneficial for AMD and possibly cataract. The Age-Related Eye Disease
Study II will evaluate some of these additional nutrients as dietary supplements 
in a randomized trial.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17209215 [PubMed - indexed for MEDLINE]

1119: Br J Ophthalmol. 2007 Dec;91(12):1593-5. Epub 2007 Jan 3.

The North Jutland County Diabetic Retinopathy Study (NCDRS) 2. Non-ophthalmic
parameters and clinically significant macular oedema.

Knudsen LL, Lervang HH, Lundbye-Christensen S, Gorst-Rasmussen A.

Department of Ophthalmology, Aarhus University Hospital, Aalborg Sygehus Syd,
Hobrovej 18-22, DK-9100 Aalborg, Denmark. u19204@aas.nja.dk

BACKGROUND: The influence of non-ophthalmic parameters on the prevalence of
clinically significant macular oedema has not been unambiguously established. The
present study was initiated with the aim of clarification. METHODS: This
cross-sectional study comprised 656 type 1 and 328 type 2 diabetic subjects
undergoing retinopathy screening in the county of North Jutland. The association 
between the presence of clinically significant macular oedema and blood pressure,
HbA1c, BMI, age, onset of diabetes, duration of diabetes, blood-pressure-reducing
medication, lipid-lowering medication, neuropathy and urinary albumin excretion
was explored using multiple logistic regression analysis. RESULTS: We found no
significant association between the presence of clinically significant macular
oedema and any of the examined parameters in type 1 diabetic subjects. In type 2 
diabetic subjects, the duration of diabetes, HbA1c, neuropathy and increased
urinary albumin excretion was significantly associated with the presence of
clinically significant macular oedema. CONCLUSIONS: The risk factors for
clinically significant macular oedema differ in type 1 and type 2 diabetic
subjects and can account only in part for this manifestation.

PMID: 17202201 [PubMed - indexed for MEDLINE]

1120: Psychol Aging. 2006 Dec;21(4):703-14.

Modeling late-life adaptation in affective well-being under a severe chronic
health condition: the case of age-related macular degeneration.

Schilling OK, Wahl HW.

Department of Psychological Aging Research, Institute of Psychology, University
of Heidelberg, Heidelberg, Germany.
oliver.schilling@psychologie.uni-heidelberg.de

Age-related macular degeneration (AMD) was used as a case model to longitudinally
study adaptation in affective well-being under a prevalent chronic health
condition. Measures of positive and negative affect, obtained at 5 subsequent
measurement occasions with 3-month intervals in between, were analyzed in 90
older adults diagnosed with AMD. The authors proposed a pattern of adaptation
that shows initial decline in affective well-being after disease outbreak,
followed by a turnaround into a restorative phase of increase, implying nonlinear
intraindividual trajectories, with changes substantially related to disease
duration. Analysis was conducted by means of a nonlinear mixed models approach.
Results confirmed the hypothesized adaptation pattern for positive affect but not
for negative affect, which was found more stable across measurement occasions.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17201491 [PubMed - indexed for MEDLINE]

1121: Can J Occup Ther. 2006 Dec;73(5):272-80.

Health education for people with macular degeneration: learning experiences and
the effect on daily occupations.

Eklund K, Ivanoff SD.

Division of Occupational Therapy, Institute of Neurosciences and Physiology,
Sahlgrenska Academy at Göteborg University, Sweden. kajsa.eklund@fhs.gu.se

BACKGROUND: Discovering New Ways, a program for people with macular degeneration,
was developed based on a health education model incorporating occupation.
PURPOSE: The purpose of this study was to evaluate the participants' learning
experience in the program and the significance for their daily occupations.
METHOD: Within an experimental design format, a content analysis was performed.
Ninety-two people with macular degeneration were interviewed 1 and 16 months
after the intervention. RESULTS: Participants in the individual intervention
program stated that they mastered occupational tasks as a result of the provision
of assistive devices. Participants in the health education program stated that
the problem-solving toolbox provided them with hope and confidence to master
daily occupations. The participants'experience of learning within the health
education program has provided important feedback regarding the structure of the 
health education model and its learning process. PRACTICE IMPLICATIONS: The
health education model may be seen as a model to design early interventions for
individuals with health conditions which can impact occupational performance.

PMID: 17201100 [PubMed - indexed for MEDLINE]

1122: Int J Geriatr Psychiatry. 2007 Aug;22(8):789-93.

Dissatisfaction with performance of valued activities predicts depression in
age-related macular degeneration.

Rovner BW, Casten RJ, Hegel MT, Hauck WW, Tasman WS.

Department of Psychiatry and Neurology, Jefferson Medical College, Philadelphia, 
PA 19107, USA. barry.rovner@jefferson.edu

OBJECTIVE: To determine whether dissatisfaction with performance of valued
activities predicts depression in patients with age-related macular degeneration 
(AMD). PATIENTS: Two hundred and six patients with newly diagnosed neovascular
AMD in one eye and pre-existing AMD in the fellow eye who were participating in a
clinical trial of a psychosocial intervention to prevent depression. MEASURES:
Structured clinical evaluations of vision function, depression, visual acuity,
contrast sensitivity and medical morbidity. Subjects were classified as
dissatisfied if they indicated that they were dissatisfied with their performance
of a valued activity. RESULTS: Subjects who were dissatisfied with performance of
valued activities (n = 71) had similar demographic characteristics to satisfied
subjects (n = 135) but had worse visual acuity (p < 0.054), greater medical
comorbidity (p < 0.006), and lower vision function (p < 0.001). Dissatisfied
subjects were almost 2.5 times more likely (OR = 2.41; [95% CI 1.02, 5.65]; p =
0.044) to become depressed within 2 months than satisfied subjects independent of
baseline visual acuity, vision function, and medical comorbidity. CONCLUSION:
Dissatisfaction with performance of valued activities in older persons with AMD
predicts depression over a 2-month period. Assessing the ability to pursue valued
activities may identify patients at risk for depression and prompt clinicians to 
initiate rehabilitative interventions and careful surveillance for depression.

Publication Types: 
    Randomized Controlled Trial
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17199237 [PubMed - indexed for MEDLINE]

1123: Ophthalmology. 2007 Jan;114(1):99-103.

Population-based study of early age-related macular degeneration: role of the
complement factor H Y402H polymorphism in bilateral but not unilateral disease.

Tedeschi-Blok N, Buckley J, Varma R, Triche TJ, Hinton DR.

Department of Preventive Medicine, Keck School of Medicine, University of
Southern California, Los Angeles, California 90033, USA.

OBJECTIVE: Recently, a strong association has been observed for the complement
factor H (CFH) Tyr402His polymorphism with early and advanced age-related macular
degeneration (AMD) in independent non-Hispanic White, clinic-based, case-control 
studies. These studies suggest the CFH His402 allele is a major risk allele in
early and advanced AMD, explaining 43% to 70% of all AMD in older adults. We
utilized a population-based case-control study design of early AMD among
Latinos/Hispanics to evaluate the CFH Tyr402His polymorphism for an association
with early AMD phenotypes. DESIGN: Retrospective population-based case-control
study. PARTICIPANTS: This study cohort consists of 285 early AMD cases and 570
controls matched on age, birthplace, and smoking status. METHODS: Genotype
determination was performed by allele-specific digestion of polymerase chain
reaction products. MAIN OUTCOME MEASURES: Complement factor H Tyr402His
polymorphism. RESULTS: We observed no overall statistically significant
association with early AMD among Latinos. However, a subset of early AMD cases
that have bilateral, not unilateral, intermediate-to-large soft macular drusen
were 1.7 times more likely to carry either the homozygous or heterozygous His402 
genotype. CONCLUSIONS: Our data suggest that the CFH Tyr402His is not a major
risk factor for overall early AMD in this Latino population, but may play a role 
in susceptibility to phenotypes of early AMD likely to progress to late AMD.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17198853 [PubMed - indexed for MEDLINE]

1124: Ophthalmology. 2007 Jan;114(1):92-8.

Ten-year incidence and progression of age-related maculopathy: the blue Mountains
Eye Study.

Wang JJ, Rochtchina E, Lee AJ, Chia EM, Smith W, Cumming RG, Mitchell P.

Centre for Vision Research, Department of Ophthalmology, Westmead Millennium
Institute, University of Sydney, Sydney, Australia. jiejin_wang@wmi.usyd.edu.au

PURPOSE: To assess the 10-year incidence of age-related maculopathy (ARM) in an
older Australian cohort. DESIGN: Population-based cohort study. PARTICIPANTS:
Three thousand six hundred fifty-four Blue Mountains Eye Study participants > or 
=49 years old were examined during 1992 through 1994; 2335 (75% of survivors)
were reexamined after 5 years (1997-1999) and 1952 (76% of survivors) after 10
years (2002-2004). METHODS: The same graders performed retinal photographic
grading in all examinations, using the Wisconsin Age-Related Maculopathy Grading 
System. Photographs of participants with ARM lesions at any of the examinations
were subsequently regraded using a side-by-side comparison method. MAIN OUTCOME
MEASURES: The diagnosis of incident late ARM was given if neovascular ARM or
geographic atrophy was detected at either follow-up examination in persons free
of these lesions at baseline. Incident early ARM was diagnosed if early ARM (soft
indistinct or reticular drusen or combined soft distinct drusen and retinal
pigment abnormality) was present in persons free of early and late ARM at
baseline. Age-related maculopathy incidence was calculated using Kaplan-Meier
methods to incorporate information from both 5- and 10-year examinations.
Discrete logistic models were used to assess the risk of incident late ARM
according to various baseline factors, including early ARM lesion
characteristics. RESULTS: After excluding 72 late ARM cases present at baseline, 
2395 of 3582 subjects at risk of late ARM (67%) were reexamined at either
follow-up time point or both follow-up time points. Over the 10-year period, 72
of 2395 subjects (3.7%) developed late ARM and 266 of 2255 subjects (14.1%)
developed early ARM. After age standardization to the Beaver Dam Eye Study
population, our 10-year incidences of late and early ARM were 2.8% and 10.8%,
respectively. Baseline age and early ARM lesion characteristics and severity were
strong predictors of late ARM incidence. CONCLUSIONS: Long-term follow-up of this
older population confirms that the risk of ARM progression is related strongly to
the severity of early-stage lesions. The study provides evidence-based criteria
for identifying persons at high risk of developing late ARM.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17198852 [PubMed - indexed for MEDLINE]

1125: Ophthalmology. 2007 Jan;114(1):86-91.

Age-related macular degeneration and risk of coronary heart disease: the
Atherosclerosis Risk in Communities Study.

Wong TY, Tikellis G, Sun C, Klein R, Couper DJ, Sharrett AR.

Centre for Eye Research Australia, University of Melbourne, Melbourne, Australia.
twong@unimelb.edu.au

OBJECTIVE: To examine the association of age-related macular degeneration (AMD)
with incident coronary heart disease (CHD) and all-cause mortality. DESIGN:
Population-based prospective cohort study. PARTICIPANTS: From the Atherosclerosis
Risk in Communities Study (n = 12 536; age range, 49-73 years). METHODS:
Participants had retinal photographs of one eye taken between 1993 and 1995.
Photographs were evaluated for the presence of early and late AMD signs according
to the Wisconsin grading system. Incident CHD events (acute myocardial
infarction, silent myocardial infarction, fatal CHD, and cardiac
revascularization procedures) and all-cause mortality were identified
prospectively using standardized methods. MAIN OUTCOME MEASURES: Incident CHD
events and all-cause mortality. RESULTS: Of 11,414 persons at risk of CHD, there 
were 555 (4.9%) with AMD at baseline, of whom 540 were early AMD and 15 were late
AMD cases. Over a 10-year follow-up, 922 persons developed an incident CHD event.
After controlling for age, gender, race, systolic and diastolic blood pressure,
pack-years of cigarette smoking, and other variables, early AMD was not
associated with incident CHD (relative risk, 1.08; 95% confidence interval,
0.82-1.42). However, individuals with late AMD were significantly more likely to 
have an incident CHD event, with 4 CHD events among the 15 participants with late
AMD at baseline (10-year cumulative incidence, 30.9%) as compared with 918 CHD
events among the 11 399 participants without late AMD (incidence of 10.0%; P =
0.049, Fisher exact test). In the full cohort (n = 12 536), early AMD was not
significantly associated with all-cause mortality. However, individuals with late
AMD were more likely to die (10-year cumulative mortality rate, 23.5%) than those
without late AMD (mortality rate, 8.9%; P = 0.088, Fisher exact test).
CONCLUSIONS: These data provide no evidence of an association between early AMD
signs with incident CHD and all-cause mortality in middle-aged persons.
Individuals with late AMD appear to have a higher rate of CHD events than those
without late AMD, but due to a small number of late AMD cases, this finding
should be interpreted cautiously.

Publication Types: 
    Multicenter Study
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17198851 [PubMed - indexed for MEDLINE]

1126: Arch Iran Med. 2007 Jan;10(1):14-9.

Therapeutic effect of macular grid photocoagulation in treatment of nonexudative 
age-related macular degeneration.

Nili-Ahmadabadi M, Espandar L, Mansoori MR, Karkhane R, Riazi M, Ardestani E.

Department of Ophthalmology, Tehran University of Medical Sciences, Tehran, Iran.

BACKGROUND: To investigate the effect of prophylactic subthreshold laser macular 
grid photocoagulation on drusen area and to evaluate the visual outcome and
incidence of choroidal neovascularization in patients with soft drusen
maculopathy. METHODS: In a nonrandomized nonmasked clinical trial, 18 patients
(36 eyes) with bilateral soft drusen maculopathy were studied. For each patient, 
one eye was treated with 48 subthreshold (invisible end-point) applications of
532-nm KTP-laser in a macular grid pattern and the fellow eye was observed. Soft 
drusen areas were calculated and compared between the two groups at baseline and 
follow-up visits at 3, 6, 12, and 30 months of therapy. Best corrected visual
acuity was also compared in observed and laser-treated eyes. Reduction of drusen 
area, change in visual acuity, and rate of CNV were assessed in both groups.
RESULTS: At baseline, there was no significant difference in the mean drusen
surface area between the two groups (P = 0.90). The mean surface area of soft
drusen in treated eyes was 6.51 mm(2) after 30 months and 7.58 mm(2) (P = 0.50)
in the control eyes. There was a trend towards reduction in the mean soft drusen 
area after 30 months from baseline in laser-treated eyes (6.51 vs. 6.97 mm(2)).
In treated eyes, there was no statistically significant difference between the
mean best corrected visual acuity at the baseline (0.28 logMAR) and after 30
months (0.32 logMAR) (P = 0.40). CONCLUSION: Subthreshold macular grid
photocoagulation with 532-nm KTP-laser did not seem to reduce drusen surface area
significantly and did not improve best corrected visual acuity after 30 months.
No exudative lesion developed in laser-treated eyes.

Publication Types: 
    Clinical Trial

PMID: 17198447 [PubMed - indexed for MEDLINE]

1127: Invest Ophthalmol Vis Sci. 2007 Jan;48(1):396-404.

Acceleration of age-related changes in the retina in alpha-tocopherol transfer
protein null mice fed a Vitamin E-deficient diet.

Tanito M, Yoshida Y, Kaidzu S, Chen ZH, Cynshi O, Jishage K, Niki E, Ohira A.

Department of Ophthalmology, Shimane University School of Medicine, Shimane,
Japan.

PURPOSE: To assess the role of vitamin E (VE) in age-related changes in the
retinal tissues by using a mouse model of severe VE deficiency. METHODS: Pups of 
alpha-tocopherol transfer protein null (a-TTP(-)(/)(-)) mice were fed a
VE-deficient diet for 4 or 18 months (VE (-) group). Wild-type C57BL/6 mice were 
fed a 0.002% alpha-tocopherol-supplemented diet (VE (+) group). In various ocular
tissues, the VE levels were measured by high-performance liquid chromatography;
the fatty acid composition by gas chromatography (GC); and the
hydroxyoctadecadienoic acid and 8-iso-prostaglandin F(2)(alpha) levels, which are
biomarkers for lipid peroxidation, by GC-mass spectrometry. The retinal structure
was assessed by light, electron, and fluorescence microscopy. RESULTS: The
alpha-tocopherol level in the retinas obtained from 4-month-old VE (-) animals
was 71-fold lower than that in the retinas obtained from the VE (+) group. In
addition, gamma-tocopherol was not detected; thus, the VE (-) group demonstrated 
a more severe VE deficiency than ever reported. In this group, the concentration 
of n-3 polyunsaturated fatty acids decreased (0.3- to 0.9-fold), whereas that of 
other classes of fatty acids was unchanged or increased. At 18 months of age, the
number of the outer nuclear layer (ONL) nuclei was observed to be 17% lower in
the VE (-) than in the VE (+) group (P < 0.05). Electron microscopy revealed
larger amounts of matrix between the ONL nuclei indicating the Müller cell
hypertrophy, greatly expanded rod outer segment discs, and a larger number of
inclusion bodies in the retinal pigment epithelium (RPE; P < 0.05) in the VE (-) 
group. Fluorescence microscopy revealed that the autofluorescence signal was
increased in the RPE layer in this group. When the observations of the
18-month-old animals were compared to those of the 4-month-old animals, the
hydroxyoctadecadienoic acid and 8-iso-prostaglandin F(2)(alpha) levels were found
to be increased in the retina and RPE obtained from both the VE (-) and VE (+)
groups; however, the age-related increases were more remarkable in the VE (-)
group (2.6- to 43.5-fold) than in the VE (+) group (0.8- to 8.7-fold).
CONCLUSIONS: The combined use of a-TTP(-)(/)(-) mice and a VE-deficient diet
leads to a severe deficiency of VE, enhances lipid peroxidation in the retina,
and accelerates degenerative damage of the retina with age.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17197560 [PubMed - indexed for MEDLINE]

1128: Invest Ophthalmol Vis Sci. 2007 Jan;48(1):96-103.

Public health impact of neovascular age-related macular degeneration treatments
extrapolated from visual acuity.

Bandello F, Lafuma A, Berdeaux G.

Department of Ophthalmology, University of Udine, Udine, Italy.

PURPOSE: To estimate the potential public health impact of treatment with new
medications intended to preserve vision in patients with neovascular age-related 
macular degeneration (AMD). METHODS: A Markov model was used to simulate the
natural history of AMD over the lifetime of patients with diagnosed neovascular
AMD from clinical trials and epidemiologic surveys. It applied to a cohort of
patients aged 75 years, with newly diagnosed neovascular AMD in one eye, whose
visual acuity was 0.7 logMAR. Probabilities were calculated for the risk of AMD
in the remaining eye and for premature mortality. Results of the model were
expressed as the duration of low vision (worse eye VA>1.0 and better eye VA>0.7
logMAR) and blindness (bilateral VA >1.0 logMAR). Health consequences of
blindness and low vision were estimated for depression, hip fractures,
institutionalization, and life expectancy. RESULTS: For AMD patients with a 50%
probability of VA >1.0 logMAR at 1 year, in one eye, the probability of lifetime 
bilateral blindness was >47%. The patients would live approximately 7 years with 
monocular vision >1.0 logMAR and an additional 4 years with bilateral blindness
and a >15% probability of depression due to AMD. Life expectancy was decreased by
approximately 2 years, >90/1000 patients would sustain a new hip fracture, and
1.5% of the patients would require institutional care for visual impairment due
to AMD. To achieve a defined public health outcome (visual impairment and
consequent comorbidity), it was necessary for the VA effectiveness of new
treatments to increase in parallel with disease severity. CONCLUSIONS:
Comorbidity related to visual impairment contributes significantly to the public 
health impact of AMD. Aggressive lesions need highly effective treatments. Models
may be used to compare the public health impact of placebo-controlled clinical
trial results.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17197522 [PubMed - indexed for MEDLINE]

1129: Neurosci Lett. 2007 Feb 27;414(1):71-4. Epub 2006 Dec 27.

A polymorphism of LOC387715 gene is associated with age-related macular
degeneration in the Japanese population.

Tanimoto S, Tamura H, Ue T, Yamane K, Maruyama H, Kawakami H, Kiuchi Y.

Department of Ophthalmology and Visual Science, Graduate School of Biomedical
Sciences, Hiroshima University, Japan. stanimo@hiroshima-u.ac.jp

Age-related macular degeneration (AMD) is one of the leading causes of blindness 
among older adults in developed countries and also in Japan. Previous research
suggests that AMD is etiologically a complex disease, caused by multiple genes
and environmental factors. Association studies have identified that a complement 
factor H gene (CFH) variant is a major risk factor for AMD in Caucasians.
However, we and two other groups have reported no association between CFH and AMD
in the Japanese population. Recent studies have suggested that LOC387715 on
chromosome 10q26 may be the second major risk loci for AMD in Caucasians. In this
study, we examined the association between LOC387715 and AMD in Japanese, and our
results show that polymorphism of the LOC387715 gene is associated with AMD in
Japanese as well as in Caucasians. Our data show a disease odds ratio of 6.20
(95% CI: 2.87-13.40) conferred by homozygosity for risk alleles at LOC387715
compared with the non-risk genotype. A polymorphism of LOC387715 gene is
associated with AMD in the Japanese population.

PMID: 17194541 [PubMed - indexed for MEDLINE]

1130: Eur J Ophthalmol. 2006 Nov-Dec;16(6):883-6.

Optical coherence tomography and focal electroretinogram evaluation of cystoid
macular edema secondary to retinitis pigmentosa treated with intravitreal
triamcinolone: case report.

Minnella AM, Falsini B, Bamonte G, Montrone L, Petroni S, Zinzanella G,
Balestrazzi E.

Institute of Ophthalmology, Catholic University, Roma, Italy.
aminnella@fastwebnet.it

PURPOSE: To assess macular structure and function by optical coherence tomography
(OCT) and focal electroretinogram (FERG) before and after intravitreal
triamcinolone acetonide (IVTA) administration for cystoid macular edema (CME) in 
a patient with retinitis pigmentosa (RP). METHODS: A 33-year-old man with RP and 
refractory bilateral macular edema was treated with IVTA in his left eye and
evaluated with visual acuity, OCT, and FERG for 6 months. RESULTS. Compared to
the fellow eye, after IVTA mean retinal thickness significantly decreased, while 
FERG amplitude and phase did not show significant changes at the end of
follow-up. Visual acuity showed a significant tendency to improve. CONCLUSIONS:
In this case report, IVTA improved macular anatomy and visual acuity; this
result, however, was not associated with a similar electrophysiologic response.

Publication Types: 
    Case Reports

PMID: 17191201 [PubMed - indexed for MEDLINE]

1131: Eur J Ophthalmol. 2006 Nov-Dec;16(6):841-6.

Long-term visual outcomes of vitrectomy for cystoid macular edema due to
nonischemic central retinal vein occlusion.

Furukawa M, Kumagai K, Ogino N, Uemura A, Larson E.

Department of Ophthalmology, Kami-iida First General Hospital, Nagoya, Japan.

PURPOSE: To report the long-term surgical outcome of vitrectomy for cystoid
macular edema due to nonischemic central retinal vein occlusion (CRVO). METHODS: 
A retrospective chart review of 25 consecutive eyes (25 patients) with cystoid
macular edema due to nonischemic CRVO treated with vitrectomy was performed. All 
patients underwent a pars plana vitrectomy with the creation of a posterior
vitreous detachment if still attached. Simultaneous phacoemulsification with
intraocular lens implantation was also performed in phakic eyes. The main outcome
measures were best-corrected visual acuity (BCVA) and changes in macular edema
shown by contact-lens biomicroscopy. The mean follow-up time was 49 months
(range, 16-108). RESULTS: The median BCVA before surgery was 0.31 and the median 
BCVA at last follow-up was 0.67. The BCVA at the last follow-up improved at least
two Snellen lines in 17 (68%), remained unchanged in 4 (16%), and worsened in 4
(16%). The BCVA was 20/40 or better in 3 eyes (12%) preoperatively and in 18 eyes
(72%) at the last follow-up. During the follow-up, four patients progressed to
ischemic CRVO; one of them had neovascular glaucoma requiring surgical
intervention. CONCLUSION: The data indicate that vitrectomy appears to be a
possibly effective treatment in some eyes with cystoid macular edema associated
with nonischemic CRVO.

PMID: 17191190 [PubMed - indexed for MEDLINE]

1132: Eur J Ophthalmol. 2006 Nov-Dec;16(6):824-34.

Verteporfin therapy and triamcinolone acetonide: convergent modes of action for
treatment of neovascular age-related macular degeneration.

Augustin AJ, Schmidt-Erfurth U.

Department of Ophthalmology, Klinikum Karlsruhe, Karlsruhe, Germany.
106020.560@compuserve.com

PURPOSE: Choroidal neovascularization associated with age-related macular
degeneration is the primary cause of blindness in the elderly in developed
countries, due to a number of pathogenic effects, including angiogenesis,
cell-mediated inflammation, leukocyte adhesion and extravasation, and matrix
remodeling. METHODS: By producing photochemical effects at the site of target
tissue (lesion), photodynamic therapy (PDT) can induce vascular damage and blood 
flow stasis, leading to occlusion of vascularization and lesion leakage. RESULTS:
PDT with verteporfin (Visudyne, Novartis) has been shown to be safe and effective
in reducing the risk of vision loss in patients with classic containing subfoveal
CNV and occult with no classic CNV. However, in predominantly occult CNV, the
treatment may be most effective in smaller lesions, and less in larger lesions.
Most important, visual acuity rarely is improved. CONCLUSIONS: Pilot studies and 
large case series suggest that a combination of PDT and intravitreal
triamcinolone acetonide has the potential to improve visual outcomes and reduce
the need for additional treatments. Randomized, prospective clinical trials are
underway to confirm the efficacy and safety of this novel treatment modality.

Publication Types: 
    Review

PMID: 17191188 [PubMed - indexed for MEDLINE]

1133: Am J Ophthalmol. 2007 Jan;143(1):184-5. Epub 2006 Sep 1.

Comment in:
    Am J Ophthalmol. 2007 Aug;144(2):334; author reply 334-5.

Bilateral macular lesions in a 10-year-old girl.

Radhakrishnan S, Bala E, Peachey NS, Lewis H, Traboulsi EI.

Cole Eye Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland,
OH 44195, USA.

PURPOSE: To report a previously undescribed macular dystrophy. DESIGN: Single
descriptive case report. METHODS: Presentation of clinical findings, including
ophthalmoscopy, fluorescein angiography, full-field and multifocal
electroretinography (ERG), optical coherence tomography (OCT), and visual fields.
RESULTS: A 10 year-old Caucasian girl had peculiar reddish blotchy macular
lesions bilaterally, associated with decreased visual acuity, and no family
history of similar lesions. Fluorescein angiography was inconclusive and showed
mottled hyperfluorescence in the macula. The full-field electroretinogram was
normal, but multifocal ERG revealed diminished waveforms centrally. CONCLUSION:
This is possibly a new macular dystrophy, the nature of which remains to be
determined.

Publication Types: 
    Case Reports
    Research Support, N.I.H., Extramural
    Research Support, U.S. Gov't, Non-P.H.S.

PMID: 17188069 [PubMed - indexed for MEDLINE]

1134: Am J Ophthalmol. 2007 Jan;143(1):176-8. Epub 2006 Sep 1.

Intravitreal prednisolone sodium succinate reduces diabetic macular edema without
intraocular pressure rise.

La Heij EC, Lundqvist IJ, Berendschot TT, Hardy E, Liem AT, Hendrikse F.

Eye Research Institute Maastricht, Department of Ophthalmology, University
Hospital Maastricht, P. Debyelaan 25, 6202 AZ Maastricht, The Netherlands.
ela@soog.azm.nl

PURPOSE: To evaluate the six-month results of patients treated with intravitreal 
prednisolone sodium succinate injections for persistent diabetic macular edema.
DESIGN: Retrospective, noncontrolled, clinical case series. METHODS: Nineteen
eyes had intravitreal injections with prednisolone sodium succinate. Need for
retreatment was based on fluorescein angiographic or optical coherence tomography
evidence of persisting macular edema. RESULTS: Mean visual acuity at six weeks,
three months, and six months after injection was significantly better than the
mean preoperative visual acuity (P = .015, P = .004, and P = .031, respectively).
In none of the studied eyes intraocular pressure exceeded 22 mm Hg. No other
adverse events, such as endophthalmitis or retinal detachment, occurred.
CONCLUSIONS: In this small pilot study, mean visual acuity improvement was
statistically significant up to six months postoperatively. Current results
suggest that intravitreal injection of the solution of prednisolone sodium
succinate may be a safe and good alternative in eyes with macular edema.

PMID: 17188065 [PubMed - indexed for MEDLINE]

1135: Am J Ophthalmol. 2007 Jan;143(1):171-3. Epub 2006 Sep 28.

Photoreceptor status after resolved macular edema in branch retinal vein
occlusion treated with tissue plasminogen activator.

Murakami T, Tsujikawa A, Ohta M, Miyamoto K, Kita M, Watanabe D, Takagi H,
Yoshimura N.

Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School
of Medicine, Sakyo-ku, Kyoto 606-8507, Japan.

PURPOSE: To evaluate the integrity of photoreceptors in macular edema (ME)
associated with branch retinal vein occlusion after intravitreal tissue
plasminogen activator. DESIGN: Retrospective, interventional case series.
METHODS: Nineteen eyes with ME by branch retinal vein occlusion were treated with
intravitreal tissue plasminogen activator injection. We assessed visual acuity
(VA) and the presence or absence in the fovea of a third high reflectance band
(HRB) by optical coherence tomography at the final visit. RESULTS: No differences
were found in age, preoperative VA, and foveal thickness between the groups with 
or without the third HRB. After treatment, the mean VA improved significantly (P 
< .05) in both groups. At the final visit, the mean VA in the group without HRB
was significantly poorer than the group with HRB (P = .0042); foveal thickness
did not differ between the groups. CONCLUSIONS: The integrity of the third HRB in
the fovea is associated with VA after the resolution of ME.

PMID: 17188062 [PubMed - indexed for MEDLINE]

1136: Am J Ophthalmol. 2007 Jan;143(1):169-70. Epub 2006 Sep 7.

Comment in:
    Am J Ophthalmol. 2007 Aug;144(2):330; author reply 330-1.

Visual hallucinations after intravitreal injection of bevacizumab in vascular
age-related macular degeneration.

Meyer CH, Mennel S, Hörle S, Schmidt JC.

Department of Ophthalmology, Philipps University, Robert-Koch-Strasse 4, 35037
Marburg, Germany. meyer_eye@yahoo.com

PURPOSE: To describe transient structured visual hallucinations in a patient with
vascular age-related macular degeneration (AMD), following an intravitreal
Avastin-injection. DESIGN: Interventional case reports. METHODS: A fully alert
83-year-old woman with disciform scar right eye (OD) and occult choroidal
neovascularization (CNV) left eye (OS) experienced a progressive visual loss to
20/800 OD and 20/400 OS. A coherent 84-year-old woman with occult CNV both eyes
(OU) experienced decreased vision of 20/800 OU. After both patients gave informed
consent, an uneventful intravitreal injection of 1.25 mg Avastin was performed in
the left eyes. RESULTS: One day and three days after an uneventful intravitreal
injection both patients experienced structured hallucinations including trees,
faces, and water for approximately 15 to 30 minutes. CONCLUSIONS: We report a
typical symptoms of Charles-Bonnet syndrome (CBS) in patients with severe AMD
after intravitreal Avastin-injections. The reduced retinal edema and realignment 
of the photoreceptors may promote the release phenomenon and trigger
hallucinatory episodes.

Publication Types: 
    Case Reports

PMID: 17188061 [PubMed - indexed for MEDLINE]

1137: Am J Ophthalmol. 2007 Jan;143(1):157-9. Epub 2006 Aug 31.

Is early age-related macular degeneration associated with cerebral MRI changes?
The Atherosclerosis Risk in Communities study.

Grosso A, Mosley TH, Klein R, Couper DJ, Tikellis G, Wong TY; Atherosclerosis
Risk in Communities Study.

Centre for Eye Research Australia, University of Melbourne, 32 Gisborne Street,
Victoria 3002, Australia.

PURPOSE: To examine the relation of early age-related macular degeneration (AMD) 
with cerebral magnetic resonance imaging (MRI) changes. DESIGN: Population-based,
cross-sectional study. METHODS: A sample of 1,684 persons ages 51 to 72 years
with no history of stroke had cerebral MRI and retinal photography. MRI scans
were graded for severity of white matter lesions (WML), sulcal widening (SW), and
ventricular enlargement (VE). AMD was graded from retinal photographs. RESULTS:
After adjustment for age, gender, race, or center, early AMD (5.0% of
participants) was not significantly associated with WML (odds ratio [OR] 1.0, 95%
confidence intervals [CI], 0.6 to 1.6), SW (OR 0.6, 95% CI, 0.4 to 1.2), or VE
(OR 1.0, 95% CI, 0.6 to 1.8). CONCLUSIONS: These data showed no statistically
significant association of early AMD with cerebral MRI changes, but the study was
limited by a small number of cases with wide CIs. Further studies may clarify
these associations.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17188055 [PubMed - indexed for MEDLINE]

1138: Am J Ophthalmol. 2007 Jan;143(1):83-89. Epub 2006 Oct 20.

Progressive visual loss in subfoveal exudation in age-related macular
degeneration: a meta-analysis using Lineweaver-Burke plots.

Shah AR, Del Priore LV.

Department of Ophthalmology, Columbia University, 635 West 165th Street, New
York, NY 10032, USA.

PURPOSE: To analyze the randomized clinical trials in exudative age-related
macular degeneration (AMD) to reveal apparent differences in the behavior of
untreated control eyes among these trials. Herein we test the hypothesis that the
behavior of untreated control eyes is actually the same in all studies, with
apparent differences arising from differences in the time of entry of eyes into
clinical trials. DESIGN: Retrospective meta-analysis of prior clinical trials.
METHODS: Control eye data from six AMD studies (Macular Photocoagulation Study,
Subfoveal Surgery Trial, Photodynamic Therapy [TAP] With Visudyne, pegaptanib
trial for neovascular AMD, anecortave acetate trial, and 360 degree Macular
Translocation Study) were plotted on a double reciprocal plot of 1/(Letters Lost)
vs 1/(Months After Enrollment). To account for differences in time of entry into 
clinical trials, we introduced a horizontal translation factor to shift each data
subset horizontally to maximize r(2) for the cumulative trend line. RESULTS:
Cumulative data for untreated control eyes fits a straight line on a double
reciprocal plot (r(2) = .9521); an untreated eye would eventually deteriorate to 
a final vision of 20/640. The slope of the line predicts that patients would
experience half of the maximum final vision within 10.88 months after exudation
onset. CONCLUSIONS: The pattern of vision loss experienced in AMD eyes with
subfoveal neovascularization is uniform across a wide range of clinical trials,
with apparent differences arising from differences in the time of entry of
patients into clinical trials.

Publication Types: 
    Meta-Analysis
    Research Support, Non-U.S. Gov't

PMID: 17188044 [PubMed - indexed for MEDLINE]

1139: Ophthalmology. 2007 Apr;114(4):732-7. Epub 2006 Dec 20.

Comment in:
    Ophthalmology. 2007 Sep;114(9):1793.

Age-related macular degeneration is associated with incident myocardial
infarction among elderly Americans.

Duan Y, Mo J, Klein R, Scott IU, Lin HM, Caulfield J, Patel M, Liao D.

Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033,
USA.

OBJECTIVE: To investigate whether age-related macular degeneration (AMD) is
associated with the development of myocardial infarction (MI) among elderly
Americans. DESIGN: Population-based cross-sectional and cohort study.
PARTICIPANTS: Five percent random sample of 2000 to 2003 Medicare enrollees.
METHODS: The cross-sectional study included the first 2-year (2000 and 2001)
enrollees who were aged > or =65 years (n = 1,519,086). The cohort study included
only baseline MI-free enrollees (n = 1445677). MAIN OUTCOME MEASURES: Chronic
conditions (AMD and type, history of MI, hypertension, and diabetes) were defined
based on any occurrence of relevant International Classification of Diseases 9
codes in relevant diagnosis fields of the baseline Medicare claim files. A total 
of 56611 incident MI cases were identified from the follow-up data (2002 and
2003). RESULTS: Baseline mean age was 76 years, with 60% women and 88% whites.
The prevalence of neovascular AMD was 2.2% (2.3% in women vs. 1.7% in men and
2.3% in whites vs. 1.2% in blacks; P<0.01 for both gender and race differences). 
The prevalence of nonneovascular AMD was 8.8% (9.9% in women vs. 7.3% in men and 
9.5% in whites vs. 4.3% in blacks; P<0.01 for both gender and race differences). 
Baseline age-, gender-, and race-adjusted prevalences of hypertension, diabetes, 
and history of MI were 75%, 33%, and 5.00%, respectively, in the neovascular AMD 
group. In contrast, they were 73%, 27%, and 4.68% in the nonneovascular AMD
group, and 65%, 25%, and 4.54% in the non-AMD group (P<0.01 for comparing the
prevalence in neovascular and nonneovascular AMD vs. non-AMD groups).
Prospectively, baseline age-, gender-, race-, hypertension-, and
diabetes-adjusted 2-year incident odds ratios and 95% confidence intervals of MI 
associated with AMD are 1.19 (1.16-1.22) for all persons with AMD, 1.26
(1.20-1.33) for neovascular AMD, and 1.18 (1.14-1.21) for nonneovascular AMD.
CONCLUSIONS: AMD is associated with older age, female gender, being white, and
having a history of MI, hypertension, and diabetes. Furthermore, presence of AMD,
especially neovascular AMD, is prospectively associated with a higher risk of
incident MI. These findings, if confirmed by other studies that control for
smoking and other lifestyle covariables, suggest the possibility of shared common
antecedents between MI and AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17187863 [PubMed - indexed for MEDLINE]

1140: Graefes Arch Clin Exp Ophthalmol. 2007 Jul;245(7):941-8. Epub 2006 Dec 21.

Intravitreal bevacizumab (Avastin) for occult choroidal neovascularization in
age-related macular degeneration.

Aisenbrey S, Ziemssen F, Völker M, Gelisken F, Szurman P, Jaissle G, Grisanti S, 
Bartz-Schmidt KU.

Center of Ophthalmology, University of Tuebingen, Schleichstrasse 12, 72076
Tuebingen, Germany. sabine.aisenbrey@med.uni-tuebingen.de

BACKGROUND: The purpose of the study is to report data on short-term safety of
intravitreal bevacizumab treatment and its effect on visual function, central
retinal thickness, and angiographical changes of occult choroidal
neovascularization due to age-related macular degeneration. METHODS: A
consecutive interventional case series of 30 patients with active subfoveal
occult choroidal neovascularization secondary to age-related macular degeneration
was followed after one intravitreal injection of 1.25 mg bevacizumab at baseline 
and subsequent injections following standardized criteria. At baseline and
follow-up visits patients had visual acuity assessment, intraocular pressure
measurement, fluorescein angiography, and optical coherence tomography imaging.
RESULTS: No serious ocular or systemic adverse events were identified. A
significant increase of intraocular pressure or signs of retinal toxicity or
endophthalmitis were not detected in any patient. Optical coherence tomography
revealed significant decrease (p < 0.001) in central retinal thickness after 1
week, 4 weeks, and 12 weeks, respectively. Fluorescein leakage decreased within 1
week and improvement was maintained at week 12 in the majority of patients.
Visual acuity improved or remained stable in 29 of 30 patients; improvement of 3 
or more lines was seen in 14 of 30 patients; one patients showed improvement of 6
lines. No patient had severe vision loss of 6 lines or more; moderate vision loss
of 3 lines was seen in one patient. Re-injections of bevacizumab according to
standard criteria were performed one to two times during the follow-up period of 
12 weeks with a re-injection interval of 4 to 18 weeks (median 8 weeks).
CONCLUSIONS: Short-term results suggest that intravitreal injection of
bevacizumab is well tolerated and for the majority of patients with occult
choroidal neovascularization in AMD results in improvement of visual acuity,
decrease in central retina thickness, and reduction of angiographic leakage of
the lesion. Bevacizumab as intravitreal treatment may provide a novel therapeutic
option for selected patients with exudative AMD. Randomized prospective
multicenter trials seem justified to further evaluate long term effects and
impact of intravitreal bevacizumab on different subtypes of AMD compared to
established therapies.

PMID: 17186262 [PubMed - indexed for MEDLINE]

1141: Health Qual Life Outcomes. 2006 Dec 21;4:97.

Quality of life in age-related macular degeneration: a review of the literature.

Mitchell J, Bradley C.

Department of Psychology, Royal Holloway, University of London, Egham, Surrey,
TW20 0EX, UK. j.mitchell@rhul.ac.uk

BACKGROUND: The Age-related Macular Degeneration Alliance International
commissioned a review of the literature on quality of life (QoL) in macular
degeneration (MD) with a view to increasing awareness of MD, reducing its impact 
and improving services for people with MD worldwide. METHOD: A systematic review 
was conducted using electronic databases, conference proceedings and key journal 
hand search checks. The resulting 'White Paper' was posted on the AMD Alliance
website and is reproduced here. REVIEW: MD is a chronic, largely untreatable eye 
condition which leads to loss of central vision needed for tasks such as reading,
watching TV, driving, recognising faces. It is the most common cause of blindness
in the Western world. Shock of diagnosis, coupled with lack of information and
support are a common experience. Incidence of depression is twice that found in
the community-dwelling elderly, fuelled by functional decline and loss of leisure
activities. Some people feel suicidal. MD threatens independence, especially when
comorbidity exacerbates functional limitations. Rehabilitation, including low
vision aid (LVA) provision and training, peer support and education, can improve 
functional and psychological outcomes but many people do not receive services
likely to benefit them. Medical treatments, suitable for only a small minority of
people with MD, can improve vision but most limit progress of MD, at least for a 
time, rather than cure. The White Paper considers difficulties associated with
inappropriate use of health status measures and misinterpretation of utility
values as QoL measures: evidence suggests they have poor validity in MD.
CONCLUSION: There is considerable evidence for the major damage done to QoL by MD
which is underestimated by health status and utility measures. Medical treatments
are limited to a small proportion of people. However, much can be done to improve
QoL by early diagnosis of MD with good communication of prognosis and continuing 
support. Support could include provision of LVAs, peer support, education and
effective help in adjusting to MD. It is vital that appropriate measures of
visual function and QoL be used in building a sound evidence base for the
effectiveness of rehabilitation and treatment.

Publication Types: 
    Review

PMID: 17184527 [PubMed - indexed for MEDLINE]

1142: Ophthalmologica. 2007;221(1):57-61.

Pneumatic displacement of submacular hemorrhage due to age-related macular
degeneration.

Ron Y, Ehrlich R, Axer-Siegel R, Rosenblatt I, Weinberger D.

Department of Ophthalmology, Rabin Medical Center, Beilinson Campus, Petah Tiqva,
Israel. yoninadi@netvision.net.il

PURPOSE: Subretinal hemorrhage is one of the most serious complications of
exudative age-related macular degeneration (AMD). Treatment with vitreous surgery
with or without plasminogen activator, fluid-gas exchange, or perfluorocarbon
yields only a small improvement in visual acuity. PATIENTS AND METHODS: The files
of 24 patients with submacular hemorrhage secondary to AMD who were treated by
injection of perfluoropropane gas (C(3)F(8)) (11 patients) or sulfur hexafluoride
(SF(6)) (13 patients) were reviewed for visual acuity before and after the
procedure and time of treatment from onset of symptoms. RESULTS: For the whole
sample, pneumatic displacement led to a statistically significant improvement in 
mean visual acuity (p = 0.015). A significant difference between pre- and
postoperative visual acuity was found for the patients treated with SF(6) (p =
0.034), but not for the patients treated with C(3)F(8) (p = 0.245). CONCLUSION:
The use of gas injection to displace submacular hemorrhage can significantly
improve visual acuity. Copyright 2007 S. Karger AG, Basel.

PMID: 17183203 [PubMed - indexed for MEDLINE]

1143: Clin Experiment Ophthalmol. 2006 Dec;34(9):893-4.

Bilateral macular cyst after lightning visualized with optical coherence
tomography.

Rivas-Aguiño PJ, Garcia RA, Arevalo JF.

The authors report a 14-year-old girl who was struck by lightning with bilateral 
macular cyst that was diagnosed with optical coherence tomography (OCT). Her
fundus examination revealed bilateral macular lesions that simulated macular
holes. The Watzke-Allen sign was negative in the right eye and positive in the
left eye. Fluorescein angiography showed a foveal window defect in both eyes. OCT
demonstrated a small foveal cyst evident as a hyporeflective lucency, visible
just anterior to the retinal pigment epithelium/choriocapillaris complex in both 
eyes. OCT seems to be useful in the evaluation of lighting maculopathy to
rule-out full-thickness macular hole in these cases, and avoid unnecessary
surgery.

Publication Types: 
    Case Reports
    Letter

PMID: 17181625 [PubMed - indexed for MEDLINE]

1144: Jpn J Ophthalmol. 2006 Nov-Dec;50(6):529-31. Epub 2006 Dec 18.

Pars plana vitrectomy with removal of posterior hyaloid face in treatment of
refractory diabetic macular edema resistant to triamcinolone acetonide.

Higuchi A, Ogata N, Jo N, Wada M, Matsumura M.

Department of Ophthalmology, Kansai Medical University, Moriguchi, Osaka, Japan.

BACKGROUND: Triamcinolone acetonide (TA) has recently been used to treat diabetic
macular edema (DME) but its effectiveness is limited. CASES: Three patients
(three eyes) with unresolved diffuse DME who did not respond to a posterior
sub-Tenon's injection of TA underwent vitrectomy. OBSERVATIONS: Intraoperatively,
it was found that all of the eyes had a posterior hyaloid face that was adherent 
to a large area of the posterior pole retina, although this had not been detected
by slit-lamp biomicroscopy or optical coherence tomography. After vitrectomy and 
removal of the posterior hyaloid face, there was a significant reduction in the
central macular thickness of all three eyes and an improvement in the visual
acuity of the patients. CONCLUSIONS: When TA treatment is not effective for DME, 
vitrectomy with the complete removal of the posterior hyaloid face, including
removal of the internal limiting membrane, should be considered.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 17180527 [PubMed - indexed for MEDLINE]

1145: Jpn J Ophthalmol. 2006 Nov-Dec;50(6):524-8. Epub 2006 Dec 18.

Verteporfin therapy for neovascular age-related macular degeneration in Indian
eyes.

Hussain N, Das T, Khanna R, Sumasri K, Mohan Ram LS.

Smt. Kanuri Santhamma Retina Vitreous Centre, Hyderabad, Andhra Pradesh, India.
nazimul@lvpei.org

PURPOSE: To determine visual outcome after a 12-month follow-up period of
verteporfin therapy for subfoveal choroidal neovascularization (CNV) secondary to
age-related macular degeneration (AMD) in Indian patients. METHODS: Twenty-five
patients (26 eyes) who completed a 12-month follow-up after photodynamic therapy 
for subfoveal CNV secondary to AMD were included in the study. The follow-up
schedule was every month for 2 months and then every 3 months thereafter until 12
months. Improvement in visual acuity was defined as a >or=10-letter gain, and
deterioration as a >or=10-letter loss in the Early Treatment Diabetic Retinopathy
Study chart at 4 m. RESULTS: The mean age of the 25 patients was 62.3 +/- 9
years. There were 17 male patients (68%). The mean initial letter acuity was 28. 
4 +/- 14.1, and the final letter acuity was 25.5 +/- 18.4 at 12 months. Initial
visual acuity was >or=20/40 in seven eyes, 20/50-20/80 in nine eyes, and
20/100-20/200 in ten eyes; seven eyes had a >or=10-letter gain, and three eyes
had a >or=10-letter loss. At the end of 12 months, six eyes had a >or=10-letter
gain and ten eyes had a >or=10-letter loss. CONCLUSION: Photodynamic therapy
appears to preserve the vision in subfoveal CNV secondary to AMD in the eyes of
Indian patients.

PMID: 17180526 [PubMed - indexed for MEDLINE]

1146: Curr Eye Res. 2006 Dec;31(12):1047-9.

Optical coherence tomography of peripheral retinal lesions in enucleated human
eye specimens with histologic correlation II.

Ghazi NG, Knape RM.

Department of Ophthalmology, University of Virginia Health System,
Charlottesville, Virginia 22908, USA. ngg6f@virginia.edu

PURPOSE: To report optical coherence tomography (OCT)-histologic correlations of 
two peripheral retinal lesions (PRLs) and to emphasize the feasibility of OCT
imaging in fixed tissue specimens. METHODS: We studied seven formalin-fixed human
eyes two of which contained two common peripheral retinal lesions. OCT scans were
performed through these lesions and the vitreous base area, and the images were
correlated with corresponding histologic sections. RESULTS: Two PRLs including a 
retinal break and pars plana cysts in addition to the pars plicata and anterior
vitreous were successfully imaged. Their optical characteristics correlated well 
with histology. OCT findings that may help differentiate the hyaloid face and
vitreous skirt were also observed. CONCLUSIONS: The correlation between OCT
images and corresponding histologic sections demonstrates the feasibility of OCT 
imaging in fixed tissue specimens. Optical characteristics of the vitreous noted 
in this study may be helpful in understanding disease processes involving the
vitreomacular interface.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17169843 [PubMed - indexed for MEDLINE]

1147: Mol Vis. 2006 Dec 5;12:1536-42.

Association of complement factor H polymorphisms with exudative age-related
macular degeneration.

Chen LJ, Liu DT, Tam PO, Chan WM, Liu K, Chong KK, Lam DS, Pang CP.

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong
Kong, Hong Kong. lijia_chen@yahoo.com <lijia_chen@yahoo.com>

PURPOSE: Variants in the complement factor H (CFH) gene have been reported to be 
associated with age-related macular degeneration (AMD). We conducted a
case-control association study to investigate the association of 6 single
nucleotide polymorphisms (SNPs) in CFH with exudative AMD in the Chinese
population. METHODS: We recruited 163 cases and 244 controls, all ethnic Chinese,
with complete ophthalmic examination including fundus investigation. Cigarette
smoking was recorded. Six SNPs (dbSNP ID: rs3753394, rs800292, rs1061147,
rs1061170, rs380390, and rs1329428) in the CFH gene were genotyped by Taqman
assays. RESULTS: Y402H (1277 T>C) has low frequencies in our study population,
5.8% in patients and 3.9% in controls. It was not associated with exudative AMD
adjusted for age, gender and smoking. Significant associations were detected for 
AMD with rs3753394 (p=0.003, p(corr)=0.018), rs800292 (p=0.00053,
p(corr)=0.0032), and rs1329428 (p=0.00092, p(corr)=0.0028), p(corr) values
obtained after adjustment for multicomparison. A haplotype containing these four 
SNPs (TGTC) was found to confer a significantly increased likelihood of exudative
AMD with an odds ratio of 1.68 (95% CI: 1.26-2.23) p=0.0003 (p(corr)=0.0026 after
correction by permutation test). Logistic regression analysis detected no
interactions between the SNPs and age, gender or smoking. CONCLUSIONS: We have
found differences in the association between the CFH gene and exudative AMD in
Chinese from Caucasians and Japanese. We detected SNP rs3753394 in the CFH
promoter carrying a significantly increased risk for exudative AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17167412 [PubMed - indexed for MEDLINE]

1148: Br J Ophthalmol. 2007 May;91(5):602-4. Epub 2006 Dec 13.

Histological findings of a choroidal neovascular membrane removed at the time of 
macular translocation in a patient previously treated with intravitreal
bevacizumab treatment (Avastin).

Gibran SK, Sachdev A, Stappler T, Newsome R, Wong D, Hiscott P.

St Paul's Eye Unit, Royal Liverpool Hospital, Liverpool L7 8XP, UK.
syedgibran@yahoo.com

AIM: To report the findings in a patient treated by repeated intravitreal
bevacizumab (Avastin) injections, followed by macular relocation and excision of 
subfoveal choroidal neovascular membrane (CNV). METHODS: Histopathological
evaluation of the CNV specimen, including immunohistochemical assessment.
RESULTS: During surgical excision, the CNV seemed to be avascular and its
underlying bed did not bleed. Histopathological examination revealed that the CNV
comprised avascular fibrous subretinal tissue containing fibroblastic retinal
pigment epithelial (RPE) cells, fragments of irregular thickened Bruch's membrane
and fibrotic choroidal tissue containing some medium-sized vessels but no
choriocapillaris. CONCLUSIONS: The development of an RPE tear during the course
of Avastin treatment may reflect contraction of the avascular subretinal tissue, 
whereas the lack of capillaries in both choroidal and subretinal components may
be caused by the increased access of Avastin to the choriocapillaris in the
presence of the RPE tear.

Publication Types: 
    Case Reports

PMID: 17166893 [PubMed - indexed for MEDLINE]

1149: Ann Acad Med Singapore. 2006 Nov;35(11):821-30.

Macular carotenoids and age-related maculopathy.

O'Connell E, Neelam K, Nolan J, Au Eong KG, Beatty S.

Department of Ophthalmology, Waterford Regional Hospital, Waterford, Republic of 
Ireland. dreamonnoconnell@iolfree.ie

Lutein (L) and zeaxanthin (Z) are concentrated at the macula, where they are
collectively known as macular pigment (MP), and where they are believed to play a
major role in protecting retinal tissues against oxidative stress. Whilst the
exact pathogenesis of age-related maculopathy (ARM) remains unknown, the
disruption of cellular processes by oxidative stress may play an important role. 
Manipulation of dietary intake of L and Z has been shown to augment MP, thereby
raising hopes that dietary supplementation with these carotenoids might prevent, 
delay, or modify the course of ARM. This article discusses the scientific
rationale supporting the hypothesis that L and Z are protective against ARM, and 
presents the recent evidence germane to this theory.

Publication Types: 
    Review

PMID: 17160199 [PubMed - indexed for MEDLINE]

1150: Curr Opin Ophthalmol. 2007 Feb;18(1):9-12.

Is cataract surgery a risk factor for progression of macular degeneration?

Patel JI.

Ophthalmology Department, Royal Perth Hospital, Perth, Australia.
jigs37@hotmail.com

PURPOSE OF REVIEW: There is a suggestion of increased risk or progression of
age-related macular degeneration after cataract surgery, which is related to the 
increased exposure of the retina to short-wavelength light. RECENT FINDINGS: Cell
culture and animal work has described retinal and retinal pigment epithelium
phototoxicity on acute light exposure. Clinical studies suggest that the use of
short-wavelength-blocking intraocular lenses can help but may also affect visual 
function and circadian rhythm. SUMMARY: Evidence to date fails to prove
conclusively that light alone or cataract surgery can induce or cause the
progression of age-related macular degeneration. A randomized clinical study of
the use of short-wavelength (blue)-blocking lenses to prove or disprove the
ability of these intraocular lenses to help in preventing progression of
age-related macular degeneration is needed.

Publication Types: 
    Review

PMID: 17159440 [PubMed - indexed for MEDLINE]

1151: Arch Ophthalmol. 2006 Dec;124(12):1701-7.

Diurnal variation in retinal thickening measurement by optical coherence
tomography in center-involved diabetic macular edema.

Diabetic Retinopathy Clinical Research Network, Danis RP, Glassman AR, Aiello LP,
Antoszyk AN, Beck RW, Browning DJ, Ciardella AP, Kinyoun JL, Murtha TJ, Topping
TM, Shami M, Sharuk GS, Wells JA 3rd.

Jaeb Center for Health Research, Tampa, FL 33647, USA. drcrnet@jaeb.org

OBJECTIVE: To evaluate diurnal variation in retinal thickness measured with
optical coherence tomography (OCT) in patients with center-involved diabetic
macular edema. METHODS: Serial OCT3 measurements were performed in 156 eyes of 96
subjects with clinically diagnosed diabetic macular edema and OCT central
subfield retinal thickness of 225 microm or greater at 8 am. Central subfield
thickness was measured from OCT3 retinal thickness maps at 6 points over a single
day between 8 am and 4 pm. A change in central subfield thickening (observed
thickness minus mean normal thickness) of at least 25% and of at least 50 microm 
at 2 consecutive points or between 8 am and 4 pm was considered to have met the
composite outcome threshold. RESULTS: At 8 am, the mean central subfield
thickness was 368 microm and the mean visual acuity was 66 letters (approximately
20/50). The mean change in relative central subfield retinal thickening between 8
am and 4 pm was a decrease of 6% (95% confidence interval, -9% to -3%) and the
mean absolute change was a decrease of 13 microm (95% CI, -17 to -8). The
absolute change was significantly greater in retinas that were thicker at 8 am
(P<.001) but the relative change was not (P = .14). The composite threshold of
reduction in central subfield thickening (as defined above) was observed in 5
eyes of 4 subjects (3% of eyes; 95% CI, 1% to 8%) while 2 eyes of 2 subjects (1%;
95% CI, 0% to 5%) had an increase in central subfield thickening of this same
magnitude. The maximum decrease was observed at 4 pm in all 5 eyes. CONCLUSION:
Although on average there are slight decreases in retinal thickening during the
day, most eyes with diabetic macular edema have little meaningful change in OCT
central subfield thickening between 8 am and 4 pm.

Publication Types: 
    Multicenter Study
    Research Support, N.I.H., Extramural

PMID: 17159029 [PubMed - indexed for MEDLINE]

1152: Am J Ophthalmol. 2007 Feb;143(2):206-211. Epub 2006 Nov 9.

Effects of long-term zinc supplementation on plasma thiol metabolites and redox
status in patients with age-related macular degeneration.

Moriarty-Craige SE, Ha KN, Sternberg P Jr, Lynn M, Bressler S, Gensler G, Jones
DP.

Department of Medicine, Emory University School of Medicine, Atlanta, Georgia,
USA.

PURPOSE: To determine the effects of zinc supplementation on plasma thiol
metabolites and their redox status in a cohort of patients with age-related
macular degeneration (AMD). DESIGN: Randomized clinical trial that evaluated the 
effects of high doses of zinc and antioxidants on plasma biomarkers of oxidative 
stress. METHODS: This was an ancillary study of the Age-Related Eye Disease Study
(AREDS). Subjects with AMD were randomized to one of four treatment groups: (1)
antioxidants (vitamin C, 500 mg; vitamin E, 400 IU; and beta carotene, 15 mg),
(2) zinc (80 mg zinc oxide, 2 mg cupric oxide), (3) antioxidants plus zinc, or
(4) placebo. At 20 and 80 months after randomization, blood specimens were
collected and analyzed for glutathione (GSH), oxidized glutathione (GSSG),
cysteine (Cys), and cystine (CySS). RESULTS: Although zinc supplementation had no
apparent effect on plasma thiol/disulfide redox status at the first blood draw,
the group of patients receiving zinc supplementation at the second blood draw had
significantly less CySS compared with those not receiving zinc (54.9 vs 64.1
microM; P = .01). There was a time-dependent oxidation of the plasma GHS pool and
was not affected by zinc supplementation. CONCLUSIONS: Because increased CySS
level is associated with aging, oxidative stress, and age-related diseases, the
apparent prevention of increased CySS by zinc supplementation warrants additional
investigation.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17157802 [PubMed - indexed for MEDLINE]

1153: Am J Ophthalmol. 2007 Feb;143(2):212-216. Epub 2006 Nov 13.

Serum dehydroepiandrosterone sulphate level in age-related macular degeneration.

Tamer C, Oksuz H, Söğüt S.

Ophthalmology Department, Mustafa Kemal University, Antakya, Turkey.
cengavertamer@yahoo.ca

PURPOSE: To evaluate plasma dehydroepiandrosterone sulphate (DHEAS) levels in
patients diagnosed with age-related macular degeneration (AMD) and controls.
DESIGN: Case-controlled, prospective, comparative noninterventional study.
METHODS: This study involved 32 men and 35 women with exudative AMD, 37 men and
38 women with nonexudative AMD, and 32 men and 32 women of an age-matched control
group. The Wisconsin Age-Related Maculopathy Grading System was used to asses the
severity of AMD lesions. DHEAS levels were measured and compared according to a
gender based subdivision. Analysis of variance was used to assess the association
between DHEAS and AMD. Linear regression model was used to examine the relation
among DHEAS level and AMD severity scale. RESULTS: Mean +/- SD of DHEAS levels in
exudative AMD, nonexudative AMD, and controls in men was 2.67 +/- 0.68
micromol/l, 2.89 +/- 0.95 micromol/l, and 4.43 +/- 1.44 micromol/l, respectively 
(P = .001), and in women was 1.64 +/- 0.72 micromol/l, 1.85 +/- 0.73 micromol/l, 
and 2.78 +/- 0.91 micromol/l, respectively (P = .001). Post hoc Tukey analyses
revealed a significant reduction in serum DHEAS level in both AMD groups,
compared with controls for men and women (P = .001), while no difference was
found between AMD groups in both men and women (P = .668 and 0.49, respectively).
Regression analyses revealed an inverse correlation among serum DHEAS level and
AMD severity scale both in men and women (P = .006 and .007, respectively).
CONCLUSIONS: This study suggests an inverse correlation between serum DHEAS level
and AMD severity scale with a considerably reduced DHEAS level in AMD.

Publication Types: 
    Comparative Study

PMID: 17157799 [PubMed - indexed for MEDLINE]

1154: Am J Ophthalmol. 2006 Dec;142(6):1081-3. Epub 2006 Aug 2.

Age-related macular degeneration is associated with an increased risk of hip
fractures in the Medicare database.

Anastasopoulos E, Yu F, Coleman AL.

Center for Eye Epidemiology, Jules Stein Eye Institute, University of California 
at Los Angeles, School of Medicine, Los Angeles, California 90095, USA.

PURPOSE: To explore the relationship between age-related macular degeneration
(AMD) and incident hip fractures in the Medicare population. DESIGN: Prospective 
cohort study. METHODS: With a 5% random sample of Medicare beneficiaries in 1995,
8596 cases were coded with exudative AMD; 26,942 cases were coded with atrophic
AMD, and 1,013,748 cases were coded without AMD. The Medicare claims from 1996 to
1999 were evaluated for hip fracture codes. The relationship between AMD and
incident hip fractures was analyzed with multiple logistic regression models,
with adjustment for baseline, ocular, and systemic covariates. RESULTS: In
adjusted analyses, the risk of hip fractures was similar in cases that were coded
with exudative AMD (odds ratio, 1.03; 95% confidence interval (CI), 0.95, 1.12)
compared with cases with no AMD but was significantly higher in cases that were
coded with atrophic AMD (odds ratio, 1.11; 95% CI, 1.06, 1.16). CONCLUSION:
Medicare patients with a code for atrophic AMD had an 11% greater risk of hip
fractures than did patients without a code for AMD over a four-year follow-up
period.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17157603 [PubMed - indexed for MEDLINE]

1155: Am J Ophthalmol. 2006 Dec;142(6):1076-9. Epub 2006 Sep 5.

Prevalence of age-related macular degeneration in Greece: the Thessaloniki Eye
Study.

Topouzis F, Coleman AL, Harris A, Anastasopoulos E, Yu F, Koskosas A, Pappas T,
Mavroudis L, Wilson MR.

II Department of Ophthalmology, Aristotle University of Thessaloniki,
Thessaloniki, Greece. ftopouzis@otenet.ge

PURPOSE: To estimate the age- and gender-specific prevalence of age-related
macular degeneration (AMD) in a population-based sample of subjects 60 years of
age or older in Thessaloniki, Greece. DESIGN: Cross-sectional population-based
study. METHODS: A total of 2554 subjects randomly identified from municipality
registers in Thessaloniki underwent a complete ophthalmologic examination.
RESULTS: Of the 3617 eligible subjects, 2554 (71%) participants completed a
clinical examination. The prevalence was 2.5% for AMD, 1.4% for neovascular (NV) 
AMD, and 1.3% for geographic atrophy (GA). Bilateral AMD was present in 40% of
AMD cases. The prevalence of AMD, NV, GA, and bilateral AMD increased with
increasing age (P< .0001). No gender-specific statistically significant
differences were noted. Of all participants with AMD, 67% were unaware of the
diagnosis. CONCLUSIONS: The prevalence of AMD in Greece is comparable to that in 
other Caucasian populations. A dramatic increase in prevalence in people older
than 80 years of age was observed.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17157601 [PubMed - indexed for MEDLINE]

1156: Am J Ophthalmol. 2006 Dec;142(6):1074-6. Epub 2006 Aug 31.

Polymorphisms in Complement Factor H and Hemicentin-1 genes in a Japanese
population with dry-type age-related macular degeneration.

Fuse N, Miyazawa A, Mengkegale M, Yoshida M, Wakusawa R, Abe T, Tamai M.

Department of Ophthalmology, Tohoku University Graduate School of Medicine,
Sendai, Miyagi, Japan. fusen@oph.med.tohoku.ac.jp

PURPOSE: To determine whether polymorphisms in the Complement Factor H (CFH) gene
and the Hemicentin-1 gene at the ARMD1 locus are associated with dry age-related 
macular degeneration (AMD) in Japanese patients. DESIGN: Clinically relevant
laboratory investigation. METHODS: Eighty unrelated Japanese patients with dry
AMD and 196 Japanese control patients were studied. Two exons of the CFH gene and
four exons of the Hemicentin-1 gene were amplified by polymerase chain reaction
and sequenced directly. RESULTS: For the CFH gene, the frequency of the
previously reported Tyr402His variant was not significantly higher in the AMD
group than in the control group (P = .31). In the Hemicentin-1 gene, three
sequence alterations (Asp5088Val, IVS99-13C/T, and His5245Gln) were detected, and
the originally reported Gln5346Arg was not detected. CONCLUSION: The CFH gene and
Hemicentin-1 genes do not appear to be involved in a statistically significant
fraction of dry AMD cases in the Japanese population.

PMID: 17157600 [PubMed - indexed for MEDLINE]

1157: Am J Ophthalmol. 2006 Dec;142(6):1068-70.

Retinal pigment epithelium tear after intravitreal bevacizumab for exudative
age-related macular degeneration.

Spandau UH, Jonas JB.

Department of Ophthalmology, Faculty of Clinical Medicine Mannheim of the
Ruprecht-Karls-University Heidelberg, Heidelberg, Germany.
Ulrich.Spandu@augen.ma.uni-heidelberg.de

PURPOSE: To report on the development of retinal pigment epithelium tears after
intravitreal injections of bevacizumab as treatment of exudative age-related
macular degeneration (AMD). DESIGN: Interventional case series. METHODS: The
study included 63 patients who received an intravitreal injection of 1.5 mg
bevacizumab as treatment of a detachment of the retinal pigment epithelium
attributable to AMD and who had a follow-up of at least two months. RESULTS: Four
patients (6%) developed a tear of the retinal pigment epithelium in the
parafoveal region. Compared with the baseline value, visual acuity at the end of 
follow-up remained stable in three patients and declined in the fourth patient.
CONCLUSIONS: Intravitreal injections of bevacizumab may be followed by a tear of 
the retinal pigment epithelium in eyes with exudative AMD and a retinal pigment
epithelium detachment.

PMID: 17157597 [PubMed - indexed for MEDLINE]

1158: Am J Ophthalmol. 2006 Dec;142(6):976-82. Epub 2006 Sep 7.

Trends in cost of major eye diseases to Medicare, 1991 to 2000.

Salm M, Belsky D, Sloan FA.

University of Mannheim, Institute for the Economics of Aging, Mannheim, Germany.

PURPOSE: To estimate impacts of physician-diagnosed eye diseases (age-related
macular degeneration (AMD), cataract, diabetic retinopathy, and glaucoma) on
Medicare payments in the periods 1991 to 1995 and 1996 to 2000. DESIGN: A
retrospective cohort study to estimate program payments per capita and in total
for each of the major eye diseases and the four eye diseases in total. METHODS:
Data from the 1994 and 1999 National Long-Term Care Survey (NLTCS) and medical
claims to Medicare from 1991 to 2000 were merged with the NLTCS. Medicare
payments for eye-related procedures on persons with and without major eye
diseases as reported on Medicare claims and self-reported data from NLTCS.
RESULTS: Overall, the burden of major eye diseases was to increase Medicare
spending by 4.8 billion dollars (1999 USD) in 1991 to 1995 and by 4.5 billion
dollars in 1996 to 2000. The most expensive eye disease was cataract, costing
Medicare 3.8 billion dollars in 1991 to 1995 and 3 billion dollars in 1996 to
2000. CONCLUSIONS: Prevalence of major eye diseases increased over time, but the 
effect of major eye diseases on Medicare payments decreased, mainly as a result
of lower payments for cataract surgery in the later years.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 17157582 [PubMed - indexed for MEDLINE]

1159: Ophthalmic Surg Lasers Imaging. 2006 Nov-Dec;37(6):524-6.

Monoscopic versus stereoscopic photography in screening for clinically
significant macular edema.

Welty CJ, Agarwal A, Merin LM, Chomsky A.

Vanderbilt Eye Institute, Nashville, Tennessee 37232-8808, USA.

The purpose of the study was to determine whether monoscopic photography could
serve as an accurate tool when used to screen for clinically significant macular 
edema. In a masked randomized fashion, two readers evaluated monoscopic and
stereoscopic retinal photographs of 100 eyes. The photographs were evaluated
first individually for probable clinically significant macular edema based on the
Early Treatment Diabetic Retinopathy Study criteria and then as stereoscopic
pairs. Graders were evaluated for sensitivity and specificity individually and in
combination. Individually, reader one had a sensitivity of 0.93 and a specificity
of 0.77, and reader two had a sensitivity of 0.88 and a specificity of 0.94. In
combination, the readers had a sensitivity of 0.91 and a specificity of 0.86.
They correlated on 0.76 of the stereoscopic readings and 0.92 of the monoscopic
readings. These results indicate that the use of monoscopic retinal photography
may be an accurate screening tool for clinically significant macular edema.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17152553 [PubMed - indexed for MEDLINE]

1160: Ophthalmic Surg Lasers Imaging. 2006 Nov-Dec;37(6):462-7.

Preoperative visual acuity as a prognostic indicator for laser treatment of
macular edema due to branch retinal vein occlusion.

Subramanian ML, Heier JS, Esrick E, Devaiah AK, Topping TM, Frederick AR, Morley 
MG.

Ophthalmic Consultants of Boston, USA.

BACKGROUND AND OBJECTIVE: To determine the visual outcome of laser treatments for
macular edema due to branch retinal vein occlusion (BRVO) in patients with a
preoperative visual acuity (VA) of 20/200 or worse compared to patients with a
preoperative VA of better than 20/200. PATIENTS AND METHODS: Records of 88
patients with macular edema secondary to BRVO undergoing laser treatment from
1984 to 2003 were reviewed. Mean VA was measured before and after each treatment 
and after the final treatment. RESULTS: All patients received between one and
five laser treatments. Preoperative VA was better than 20/200 in 56 patients
(group 1) and 20/200 or worse in 32 patients (group 2). Patients in group 1 had a
mean improvement of 0.48 lines and 57% had a final VA of 20/40 or better.
Patients in group 2 had a mean improvement of 1.69 lines and 20% had a final VA
of 20/40 or better. CONCLUSIONS: Patients with poor VA (20/200 or worse)
secondary to macular edema due to BRVO responded positively to laser treatment.
The level of preoperative VA can be a useful predictor of visual outcome. These
patients should consider laser treatment before alternative, more aggressive
approaches.

PMID: 17152539 [PubMed - indexed for MEDLINE]

1161: Ophthalmic Surg Lasers Imaging. 2006 Nov-Dec;37(6):455-61.

Combined photodynamic therapy and intravitreal triamcinolone acetonide injection 
for neovascular age-related macular degeneration with pigment epithelium
detachment.

Axer-Siegel R, Ehrlich R, Avisar I, Kramer M, Rosenblatt I, Priel E, Weinberger
D.

Department of Ophthalmology Rabin Medical Center, Beilinson Campus, Petah Tiqva, 
Israel.

BACKGROUND AND OBJECTIVE: To report the outcome of combined verteporfin
photodynamic therapy (PDT) and intravitreal triamcinolone acetonide (IVTA) for
the treatment of choroidal neovascularization (CNV) with serous pigment
epithelium detachment (PED) due to age-related macular degeneration (AMD).
PATIENTS AND METHODS: The files of all consecutive patients with CNV and serous
PED who received PDT and IVTA either primarily (primary treatment group) or
following previous unsuccessful PDT (secondary treatment group) were reviewed for
visual and angiographic results. RESULTS: Ten patients (11 eyes) were included.
Mean number of PDT sessions was 3.18; 8 eyes received one IVTA injection and 3
eyes received two IVTA injections. Thirty-six percent of patients retained their 
initial visual acuity after a mean follow-up of 15.3 months. Loss of 3 or more
Snellen lines was noted in 2 of 3 eyes in the primary treatment group and 5 of 8 
eyes in the secondary treatment group. Increased intraocular pressure developed
in 3 patients and was controlled by topical medications. CONCLUSIONS: Although
combined PDT and IVTA may be considered for CNV with serous PED in patients with 
poor prognosis with PDT alone, the regimen as administered in this small series
was not beneficial. Further studies are required to determine whether alternate
sequences, timing, or doses would yield a better outcome.

PMID: 17152538 [PubMed - indexed for MEDLINE]

1162: Ophthalmic Surg Lasers Imaging. 2006 Nov-Dec;37(6):446-54.

Safety and efficacy of intravitreal bevacizumab followed by pegaptanib
maintenance as a treatment regimen for age-related macular degeneration.

Hughes MS, Sang DN.

Schepens Eye Research Institute and the Department of Ophthalmology, Harvard
Medical School, Boston, Massachusetts, USA.

BACKGROUND AND OBJECTIVE: Vascular endothelial growth factor (VEGF)-A, both
necessary and sufficient in promoting ocular neovascularization, is an attractive
therapeutic target. Combining nonselective and selective VEGF blockade may
provide clinical benefit with minimal risks in the treatment of neovascular
age-related macular degeneration (AMD). PATIENTS AND METHODS: Twenty patients
with all subtypes of neovascular AMD and a broad range of baseline vision were
treated with intravitreal bevacizumab followed by pegaptanib sodium for 54 weeks.
Visual acuity measurements, biomicroscopy, funduscopy, fluorescein angiography,
optical coherence tomography, and adverse event assessments were performed.
RESULTS: Mean visual acuity improved from approximately 20/200 at baseline to
20/80. All patients experienced an improvement in retinal thickness, ranging from
-47 to -297 microns. Adverse events were limited to transient irritation or
redness. No significant elevation in intraocular pressure occurred following
either bevacizumab or pegaptanib injections. CONCLUSIONS: Nonselective VEGF
blockade with bevacizumab induction and selective VEGF165 blockade with
pegaptanib as maintenance therapies may offer clinically meaningful outcomes with
acceptable safety profiles in patients with AMD.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 17152537 [PubMed - indexed for MEDLINE]

1163: Retina. 2006 Nov-Dec;26(9):1056-62.

Impact of visual impairment on use of caregiving by individuals with age-related 
macular degeneration.

Schmier JK, Halpern MT, Covert D, Delgado J, Sharma S.

Exponent Inc, Alexandria, VA, USA. jschmier@exponent.com

BACKGROUND: To assess the patient-reported use of caregiving among individuals
with age-related macular degeneration (AMD) and evaluate the impact of visual
impairment level on this use. METHODS: A survey including the AMD Health and
Impact Questionnaire and the Daily Living Tasks Dependent on Vision Questionnaire
(DLTV) was mailed to members of the Macular Degeneration Partnership. The study
was approved by an institutional review board, and respondents provided consent
before participating. Responses were analyzed by estimated visual acuity
determined by scores from the DLTV. Deidentified data were analyzed using SAS
Version 8.2 (SAS Institute, Cary, NC). RESULTS: Of 803 respondents, 56% were
male, and the mean age was 73 years. Use of paid and unpaid help significantly
increased as visual acuity decreased. Using a national average for caregiver
time, annual costs for caregiving ranged from 225 to 47,086 US dollar depending
on visual acuity. CONCLUSION: There are substantial differences in caregiver
support with increased AMD severity. Delaying progression of AMD could result in 
considerable cost savings.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17151494 [PubMed - indexed for MEDLINE]

1164: Retina. 2006 Nov-Dec;26(9):1042-8.

Self-reported acute decrease in visual acuity after photodynamic therapy for
age-related macular degeneration.

Recchia FM, Greenbaum S, Recchia CA, Ruby AJ, Alldredge CD, Hassan TS.

Department of Ophthalmology and Associated Retinal Consultants, PC, William
Beaumont Hospital, Royal Oak, MI, USA. franco.recchia@vanderbilt.edu

PURPOSE: To evaluate the incidence of self-reported decrease in visual acuity
within 7 days of photodynamic therapy (PDT) for choroidal neovascularization
secondary to age-related macular degeneration (AMD) and to describe the
anatomical and clinical course of patients with documented significant visual
loss. METHODS: Consecutive records of all patients with exudative AMD treated
with PDT over a 16-month period at a community-based retina referral practice
were reviewed for instances of self-reported visual change within 7 days of
treatment. The primary outcome measure was Snellen visual acuity. Secondary
outcome measures were fluorescein angiography (FA) and anatomical findings.
RESULTS: Among 1,894 PDT treatments performed for 821 patients, there were 32
instances (for 30 patients) of self-reported visual change within 7 days of PDT. 
A decrease in > or =2 lines of Snellen visual acuity was documented for 10
patients (1.2% of patients or 0.5% of treatments), and all occurred within 3 days
of PDT (median, 1 day) in all patients. Median pre-PDT vision was 20/60 (range,
20/50 to 20/200). Vision within 3 days after PDT was 20/100 or worse in all 10
cases and counting fingers or worse in 3. Subretinal hemorrhage occurred in four 
cases. FA of eyes without hemorrhage showed a circular area of choroidal
hypoperfusion (corresponding to the PDT spot) in all five eyes with persistence
of the hypofluorescence up to 4 months later. Visual improvement after the
initial acute decrease was seen in 3 patients (30%; 95% confidence interval,
7-65%) by 3 months after PDT. CONCLUSIONS: Acute visual decrease after PDT for
AMD is uncommon. Visual recovery may occur in some patients, but a precise
estimate is difficult to determine given the small sample size.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17151492 [PubMed - indexed for MEDLINE]

1165: Retina. 2006 Nov-Dec;26(9):999-1005.

Intravitreal bevacizumab (Avastin) therapy for persistent diffuse diabetic
macular edema.

Haritoglou C, Kook D, Neubauer A, Wolf A, Priglinger S, Strauss R, Gandorfer A,
Ulbig M, Kampik A.

Department of Ophthalmology, Ludwig-Maximilians-University, Munich, Germany.
Haritoglou@med.uni-muenchen.de

PURPOSE: To evaluate the efficacy of bevacizumab (Avastin; Genentech, Inc., South
San Francisco, CA) for the treatment of diabetic macular edema. METHODS: This
prospective, consecutive, noncomparative case series included 51 consecutive
patients (26 females and 25 males; mean age, 64 years) with diffuse diabetic
macular edema. Inclusion criteria were determined independently of the size of
edema, retinal thickness, visual acuity, age, metabolic control, type of
diabetes, or previous treatments beyond a 6-month period. At each visit, patients
underwent complete eye examination, including determination of best-corrected
visual acuity, slit-lamp examination, intraocular pressure measurement,
stereoscopic biomicroscopy of the macula, retinal thickness measurement by
optical coherence tomography, fluorescein angiography, and fundus photography.
After written informed consent was obtained, all patients were treated with a
0.05-mL injection containing 1.25 mg of bevacizumab. RESULTS: All patients
completed 6 weeks of follow-up; 23 (45%) completed 12 weeks of follow-up. Sixteen
patients (70%) had received at least two intravitreal injections. All patients
had undergone previous treatments, such as focal laser therapy (35%),
full-scatter panretinal laser therapy (37%), vitrectomy (12%), and intravitreal
injection of triamcinolone (33%). The mean diameter of the foveal avascular zone 
was 503 micro m, with 49% with values of >500 micro m. At baseline, mean visual
acuity +/- SD was 25.88 +/- 14.43 ETDRS letters (0.86 +/- 0.38 logMAR of Snellen 
letters). Mean central retinal thickness by optical coherence tomography +/- SD
was 501 +/- 163 micro m (range, 252-1,031 micro m). Mean visual acuity +/- SD
increased to 0.75 +/- 0.37 logMAR of Snellen letters at 6 weeks after injection
(P = 0.001), with some regression to 0.84 +/- 0.41 logMAR of Snellen letters
after 12 weeks. Changes in ETDRS letters were not significant throughout
follow-up. Mean retinal thickness +/- SD decreased to 425 +/- 180 micro m at 2
weeks (P = 0.002), 416 +/- 180 micro m at 6 weeks (P = 0.001), and 377 +/- 117
micro m at 12 weeks (P = 0.001). Changes of retinal thickness and visual acuity
correlated weakly (r = -0.480 and P = 0.03 at 6 weeks; r = -0.462 and P = 0.07 at
12 weeks). The increase of visual acuity after 6 weeks as measured by ETDRS
charts could be predicted best by baseline visual acuity. No other factors
investigated, such as age, thickness by optical coherence tomography, or previous
treatments, were predictive for the increase in visual acuity. CONCLUSION: Even
in cases of diffuse diabetic macular edema not responding to previous treatments 
such as photocoagulation, intravitreal injection of triamcinolone, or vitrectomy,
improvement of visual acuity and decrease of retinal thickness could be observed 
after intravitreal injection of bevacizumab. Although our follow-up period was
too short to provide specific treatment recommendations, the short-term results
encourage further prospective studies with different treatment groups and longer 
follow-up.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 17151486 [PubMed - indexed for MEDLINE]

1166: Retina. 2006 Nov-Dec;26(9):994-8.

Visual improvement following intravitreal bevacizumab (Avastin) in exudative
age-related macular degeneration.

Yoganathan P, Deramo VA, Lai JC, Tibrewala RK, Fastenberg DM.

Department of Ophthalmology, North Shore-Long Island Jewish Health System, Great 
Neck, NY, USA.

PURPOSE: To study the visual and anatomic outcome of intravitreal bevacizumab
injection in the treatment of exudative age-related macular degeneration (AMD).
METHODS: Retrospective review of patients who received one or more intravitreal
bevacizumab injections for exudative AMD. Outcome measures include standardized
visual acuity, optical coherence tomography (OCT), macular thickness and volume, 
intraocular pressure, and blood pressure at 24 or more weeks follow-up. RESULTS: 
Fifty eyes of 48 patients were identified. Patients were observed for a median
length of follow-up of 34 weeks (range, 24-50 weeks). Thirty-six eyes (72%) had
prior treatment with pegaptanib (Macugen) and/or photodynamic therapy (PDT) and
14 eyes (28%) were treatment-naive. Mean visual acuity increased by 6.5 letters
(P < 0.01) at 4 weeks and 5.3 letters (P < 0.01) at 24 weeks after initial
bevacizumab injection. At 24 weeks, naive eyes had a mean increase of 14.2
letters (P < 0.001) and previously treated eyes had a mean increase of 2.8
letters (P = 0.06). Overall, mean OCT macular thickness and volume decreased by
73 micro m (P < 0.001) and 1.0 mm3 (P < 0.001) respectively at last follow-up. At
last follow-up, all eyes received an average of 3.5 injections and experienced an
average of 1.08 recurrences. There was no incidence of severe vision loss or
adverse effect. CONCLUSION: Intravitreal bevacizumab has the potential for
improvement in vision in both naive and previously treated eyes for at least 6
months. The benefit is more pronounced in eyes without prior pegaptanib and/or
PDT.

PMID: 17151485 [PubMed - indexed for MEDLINE]

1167: Retina. 2006 Nov-Dec;26(9):988-93.

Combined photodynamic therapy with verteporfin and intravitreal bevacizumab for
choroidal neovascularization in age-related macular degeneration.

Dhalla MS, Shah GK, Blinder KJ, Ryan EH Jr, Mittra RA, Tewari A.

Barnes Retina Institute, St Louis, MO, USA.

PURPOSE: To examine the 7-month results for patients treated with combined
photodynamic therapy (PDT) with verteporfin and intravitreal bevacizumab for
choroidal neovascularization (CNV) secondary to age-related macular degeneration 
(AMD). METHODS: This is a retrospective series of 24 eyes with juxtafoveal or
subfoveal CNV secondary to AMD. Patients were treated with PDT with verteporfin
and 1.25 mg of intravitreal bevacizumab. All patients were naive to treatment and
had either treatment within a 14-day interval. Main outcome measures were visual 
acuity stabilization (defined as no change or a gain in visual acuity) and
retreatment rate. RESULTS: At the 7-month follow-up, 20 (83%) of 24 patients had 
stabilization of visual acuity. Sixteen eyes (67%) had improvement in visual
acuity. Mean improvement in visual acuity (n = 24) was 2.04 Snellen lines.
Fifteen eyes (63%) required only a single combined treatment for CNV resolution. 
There were no complications, including endophthalmitis, uveitis, and ocular
hypertension. CONCLUSION: The results of this study suggest that combined
treatment of PDT with verteporfin and intravitreal bevacizumab may be useful in
treating neovascular AMD by reducing retreatment rates and improving visual
acuity. Further investigation with large, controlled trials is warranted to
outline the appropriate treatment paradigm for combination therapy.

Publication Types: 
    Clinical Trial

PMID: 17151484 [PubMed - indexed for MEDLINE]

1168: Retina. 2006 Nov-Dec;26(9):985-7.

No association of complement factor H gene polymorphism and age-related macular
degeneration in the Japanese population.

Uka J, Tamura H, Kobayashi T, Yamane K, Kawakami H, Minamoto A, Mishima HK.

Department of Ophthalmology and Visual Science, Graduate School of Biomedical
Sciences, Hiroshima University, Hiroshima, Japan.

PURPOSE: The aim of this study was to determine whether genetic polymorphism of
complement factor H (CFH) is associated with age-related macular degeneration
(AMD) in the Japanese population. METHODS: Genomic DNA was examined in a cohort
of 67 Japanese patients with AMD and 107 controls. TT/TC/CC genotypes on exon 9
were screened for sequence alternation by polymerase chain reaction analysis and 
through sequencing. RESULTS: The mean ages +/- SD of AMD patients and control
subjects were 73 +/- 8.5 years and 72 +/- 8.7 years, respectively. There was no
significant difference between CFH genotypes in the AMD group (TT, 76%; TC, 19%; 
CC, 5%) and the control group (TT, 80%; TC, 17%; CC, 3%). The frequencies of T
and C alleles were 86% and 14%, respectively, in the AMD group and 89% and 11%,
respectively, in the control group. CONCLUSION: CFH gene polymorphism is not
associated with AMD in the Japanese population. Moreover, the frequency of the C 
allele is low among the Japanese population.

PMID: 17151483 [PubMed - indexed for MEDLINE]

1169: Br J Ophthalmol. 2007 May;91(5):600-1. Epub 2006 Dec 6.

Use of optical coherence tomography, fluorescein angiography and indocyanine
green angiography in a screening clinic for wet age-related macular degeneration.

Talks J, Koshy Z, Chatzinikolas K.

Department of Ophthalmology, Royal Victoria Infirmary, Newcastle upon Tyne NE1
4LP, UK. james.talks@newcastle.ac.uk

AIMS: To assess the utility of optical coherence tomography (OCT) in a nurse-led,
fast-track clinic for new age-related macular degeneration (AMD) referrals, and
to see how often indocyanine green angiography (ICGA) led to an additional
diagnosis to that provided by fundus fluorescein angiography (FFA). METHOD:
Retrospective audit of a consecutive series of 134 new patients referred with
suspected wet AMD. When visual acuity was >or=6/60 an OCT was performed. If the
OCT was consistent with "wet" AMD, the patient underwent simultaneous FFA/ICGA.
The sensitivity and specificity of this clinic was calculated. The number of
additional diagnoses made using ICGA was recorded. RESULTS: 23/134 (17.16%)
patients had OCT only and were not subsequently found to have wet AMD. FFA/ICGA
was performed in 111 patients, showing wet AMD in 90 (81%) patients. OCT as used 
in our clinic had a sensitivity of 1 and a specificity of 0.65 for detecting wet 
AMD. ICGA provided additional diagnoses in 19 (14.17%) patients. ICGA detected a 
specific vascular abnormality in 58% of the occult lesions. CONCLUSIONS: OCT
proved to be an effective screening tool for wet AMD in this clinic, with
excellent sensitivity and reasonable specificity. ICGA provided an additional
diagnosis in a significant number of cases, but did not define a vascular
abnormality in all occult cases.

Publication Types: 
    Evaluation Studies

PMID: 17151058 [PubMed - indexed for MEDLINE]

1170: Ophthalmic Genet. 2006 Dec;27(4):151-5.

Mutation screen of the cone-specific gene, CLUL1, in 376 patients with
age-related macular degeneration.

Sturgill GM, Pauer GJ, Bala E, Simpson E, Yaniglos SS, Crabb JW, Hollyfield JG,
Lewis H, Peachey NS, Hagstrom SA.

Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, 
OH, USA.

Clusterin is a secreted glycoprotein expressed ubiquitously in many tissues that 
appears to function as a molecular chaperone capable of protecting stressed
proteins. It is upregulated in many different forms of neurodegeneration and is
thought to represent a defense response against neuronal damage. Clusterin has
been found to be a common protein identified in drusen preparations isolated from
the retina of donor eyes of patients with age-related macular degeneration (AMD),
the leading cause of blindness in the elderly population of developed countries. 
A retina-specific clusterin-like protein (CLUL1) showing nearly 25% identity to
clusterin at the protein level was recently cloned and shown to be expressed
specifically in cone photoreceptor cells. For these reasons, we investigated
CLUL1 as a candidate gene for AMD. A mutation screen of the entire coding region 
of the CLUL1 gene in 376 unrelated patients with AMD uncovered three sequence
variations, one isocoding change and two intronic changes. One intronic change
appears significantly less frequent in patients with the more severe forms of AMD
than in control subjects, suggesting that this variant may reduce the risk for
AMD or may be linked to a nearby variant that may reduce AMD risk. Variant
alleles of the CLUL1 gene were found; however, none are considered pathogenic.
None of the variants identified are predicted to create or destroy splice donor
or acceptor sites based on splice-site prediction software.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, Non-P.H.S.

PMID: 17148042 [PubMed - indexed for MEDLINE]

1171: J Med Genet. 2006 Dec;43(12):e57.

A novel locus on 19q13 associated with autosomal-dominant macular dystrophy in a 
large Greek family.

Yang Z, Kitsos G, Tong Z, Payne M, Gorezis S, Psilas K, Grigoriadou M, Zhao Y,
Kamaya S, Aperis G, Petersen MB, Zhang K.

OBJECTIVE: To describe the clinical features of and genetic locus associated with
autosomal-dominant macular dystrophy (MCDR5) in a large Greek family. METHODS: 26
members of a single family underwent clinical examinations and venepuncture. A
genomewide linkage scan using 400 microsatellite markers distributed with an
average spacing of 10 cM throughout the human genome. RESULTS: 14 members of the 
study family exhibited clinical features of the disease including decreased
central vision and macular abnormalities in the posterior pole of the retina.
Analysis of loci known to be associated with macular dystrophy did not show
positive linkage. A genomewide linkage scan showed linkage to chromosome 19q,
with a two-point maximum LOD score of 5.809 at theta = 0 between the disease and 
marker locus D19S412. On the basis of recombination events, the disease interval 
was localised between markers D19S420 and D19S540 on chromosome 19q, at a span of
about 3.8 cM, in an area known to contain 120 known genes/transcripts. Eleven of 
these genes/transcripts were sequenced, and no disease-causing mutation was
identified. CONCLUSIONS: This study describes a new locus on 19q associated with 
autosomal-dominant macular dystrophy, designated as MCDR5. Additional study of
other family members will be necessary to further narrow the interval and
identify the responsible gene. The study of MCDR5 will aid in elucidation of the 
underlying pathogenic mechanisms for this and other macular diseases, including
age-related macular degeneration.

Publication Types: 
    Letter
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17142619 [PubMed - indexed for MEDLINE]

1172: Metabolism. 2006 Dec;55(12):1681-8.

Association of manganese superoxide dismutase gene polymorphism (V16A) with
diabetic macular edema in Korean type 2 diabetic patients.

Lee SJ, Choi MG.

Department of Endocrinology and Metabolism, College of Medicine, Hallym
University, ChunCheon Sacred Heart Hospital, Kangwon-Do 200-704, South Korea.
leesj@hallym.ac.kr

This study was designed to investigate whether V16A polymorphism of the manganese
superoxide dismutase (Mn-SOD) gene is associated with the development of type 2
diabetes mellitus and with progression of diabetic retinopathy (DR) and diabetic 
macular edema (DME). We simultaneously analyzed insertion/deletion polymorphism
of the angiotensin-converting enzyme (ACE) gene in the 16th intron to avoid its
confounding effect. A total of 192 nondiabetic subjects and 304 type 2 diabetic
patients were included in the study. Diabetic retinopathy was classified as
nonretinopathy, nonproliferative retinopathy, and proliferative retinopathy.
Diabetic macular edema was defined as thickening of the retina and/or hard
exudates within a 1-disk diameter of the center of the macula. Diabetic macular
edema was further classified into focal, diffuse, and ischemic types. The A
allele frequency of the Mn-SOD gene was not different between nondiabetic and
type 2 diabetic subjects, between the normotensive and hypertensive groups,
between the DR (-) and DR (+) groups, and among the stages of DR. In the DR (+)
group, the DME (+) group had a lower A allele frequency than that of the DME (-) 
group. In the DME (+) group, focal, diffuse, and ischemic types were found in 8, 
23, and 6 patients, respectively. The A allele frequency of each type was 0.188, 
0.109, and 0.0. The D allele frequency of the angiotensin-converting enzyme gene 
did not differ in any of the comparisons. Clinical and laboratory parameters of
the A allele carriers were not different from those of the noncarriers except for
the prevalence of hypertension and DME. Hypertension, diabetic duration, and
insulin therapy were related to DR. The A allele, hypertension, and insulin
therapy were associated with DME. In conclusion, our results suggest that V16A
polymorphism of the Mn-SOD gene is not related to the development of diabetes and
progression of DR, but is associated with DME in Korean type 2 diabetic patients.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17142144 [PubMed - indexed for MEDLINE]

1173: Med Hypotheses. 2007;68(5):1047-55. Epub 2006 Dec 4.

Apolipoprotein E epsilon4 offers protection against age-related macular
degeneration.

Friedman DA, Lukiw WJ, Hill JM.

Department of Ophthalmology, LSU Health Sciences Center, New Orleans, LA
70112-2234, United States.

BACKGROUND: In many previous studies, age-related macular degeneration (ARMD) has
been linked to a variety of different risk factors. The publications have debated
whether apolipoprotein E (apoE) epsilon4 serves as a potential protective factor 
in the development of the disease. Other studies have classified the behavior of 
this protein in different pathologies, including Alzheimer's disease (AD) and
cardiovascular disease. The general behavior of the epsilon4 isoform of ApoE is
different than the predominant epsilon3 isoform. HYPOTHESIS: We propose that the 
general characteristics and molecular behavior of apoE epsilon4 cause it to be a 
protective factor against the development of ARMD by preventing cumulative
effects of oxidative retinal damage. EVALUATION OF HYPOTHESIS: Review of the
literature related to ARMD and ApoE, using OVID as our main database, led to the 
development of several theories regarding ApoE epsilon4's behavior compared to
epsilon3 and potential explanation of its protective characteristics.
CONSEQUENCES OF HYPOTHESIS: We relate these theories to the potential behavior of
ApoE epsilon4 in other situations including choroidal neovascularization,
Alzheimer's Disease (AD), cardiovascular disease, herpes simplex virus infection,
and smoking. DISCUSSION: The potential implications of this theory could be used 
as a branching point for further studies that examine the role of the different
apoE isoforms, in relation to the other risk factors for ARMD.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17141963 [PubMed - indexed for MEDLINE]

1174: Int Ophthalmol. 2005 Aug-Oct;26(4-5):135-41. Epub 2006 Dec 1.

Dilute triamcinolone-assisted peeling of the internal limiting membrane in cases 
of diffuse diabetic macular oedema.

Avci R, Avci B, Kaderli B.

Ophthalmology Department, Uludag University Hospital, Bursa, Turkey.
ravci@uludag.edu.tr

PURPOSE: In this study we evaluated the efficiency of diluted triamcinolone
particles in peeling of the internal limiting membrane (ILM) in cases of diffuse 
diabetic macular oedema. METHODS: A prospective observational study of thirteen
consecutive patients with diffuse diabetic macular oedema who had undergone ILM
peeling aided by use of a diluted (1 mg mL(-1)) suspension of triamcinolone
particles (0.05 mg). The results were assessed by measurement of visual acuity
and intraocular pressure, by ophthalmoscopy, and by fluorescein angiography.
RESULTS: ILM peeling in all eyes could be performed easily and completely with
the aid of triamcinolone particles homogeneously dispersed over the macular ILM. 
During the peeling procedure, triamcinolone particles resulted in clear contrast 
between the peeled and unpeeled ILM thus enabling us to easily find the edge of
the ILM and to be able to continue peeling at further attempts. In twelve of the 
thirteen eyes the macular oedema was completely resolved or reduced. Visual
acuity improved by at least two lines in nine eyes (70%). The intraocular
pressure increase did not exceed 21 mmHg in any of the patients. CONCLUSIONS: The
diluted triamcinolone suspension enables good visualisation of the ILM during the
ILM peeling procedure in cases of diffuse diabetic macular oedema. Use of a
diluted suspension may reduce the risk of intraocular pressure increase and the
potential toxicity of triamcinolone.

PMID: 17139528 [PubMed - indexed for MEDLINE]

1175: Graefes Arch Clin Exp Ophthalmol. 2007 Feb;245(2):215-20.

Intravitreal bevacizumab for exudative age-related macular degeneration after
multiple treatments.

Aggio FB, Farah ME, Silva WC, Melo GB.

Vision Institute, Federal University of São Paulo, São Paulo, Brazil.
aggio@oftalmo.epm.br

BACKGROUND: Photodynamic therapy with verteporfin (PDT) significantly reduces the
risk of vision loss in patients with exudative age-related macular degeneration
(AMD). Indocyanine green-mediated photothrombosis (IMP) and trans-pupillary
thermotherapy (TTT) may also be beneficial for selective cases of exudative AMD. 
However, a substantial subset of patients responds poorly to these treatments.
Intravitreal bevacizumab (IVB) has been recently used in the treatment of
exudative AMD, showing both visual and anatomic improvement in the majority of
cases. METHODS: This interventional retrospective case series reports the effects
of IVB in 17 eyes with subfoveal neovascular AMD that had undergone repeated PDT 
(combined or not with triamcinolone acetonide) or PDT followed by either IMP or
TTT with poor results. The main outcome measures were visual acuity and
tomographic signs of intra/subretinal fluid, as well as central retinal
thickness. RESULTS: Most patients received a single IVB injection. The mean
follow-up was 4.47 months. The mean logMAR visual acuity changed from 1.17 +/-
0.40 to 1.06 +/- 0.44 (P = 0.17). The mean central retinal thickness decreased
from 404.05 +/- 245.26 to 280.23 +/- 143.14 microm (P = 0.032). At the end of the
study, lack of tomographic signs of intra/ subretinal fluid was noted in four
(23.5%) eyes. No ocular or systemic side effects were identified. CONCLUSIONS:
Short-term results with IVB for the treatment of exudative AMD have been
promising. However, the chronic retinal and pigment epithelium changes frequently
present in eyes that underwent multiple previous treatments may limit complete
visual recovery. To our knowledge, this is the first report on the use of IVB for
this particular group of AMD patients.

PMID: 17139490 [PubMed - indexed for MEDLINE]

1176: Surv Ophthalmol. 2006 Nov-Dec;51(6):576-86.

Unraveling a complex genetic disease: age-related macular degeneration.

Chamberlain M, Baird P, Dirani M, Guymer R.

Centre for Eye Research Australia, University of Melbourne, 32 Gisborne Street,
East Melbourne, Australia 3002.

In most of the Western world, age-related macular degeneration (AMD) remains the 
largest single cause of severe visual impairment, and its prevalence continues to
increase. It is considered to be a complex disease, in which multiple genes and
environment play a role in pathogenesis. Several environmental insults are
implicated with smoking, serum cholesterol, hypertension, sunlight exposure, and 
many other factors being variously associated with disease pathogenesis. Until
recently, there have been relatively few breakthroughs to further our
understanding of the genetics of AMD, despite remarkable progress in molecular
genetic techniques over the last 20 years, and the fact that many rare inherited 
macular diseases have had their causative genes mapped. Development of new tools 
such as high-density single-nucleotide polymorphism chips and microarrays have
changed the face of genetic research, but have yet to directly translate into
improved clinical outcomes in ophthalmology. However with the recent finding of
the Tyr402His polymorphism in the complement factor H gene being implicated in
AMD, we are about to witness a new wave of research in this disease. Not only
does the identification of a biologically plausible gene identify a new pathway, 
but it also identifies new biological mechanisms for disease, avenues to pursue
treatment, and a better understanding of how the environment interacts with the
genetic background to create disease. This article aims to review the process of 
gene discovery in complex disease, why the search for genes remains difficult,
how to translate laboratory findings to a clinical setting, and how these
findings will impact on disease treatment and public health issues.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17134647 [PubMed - indexed for MEDLINE]

1177: Ophthalmology. 2007 Mar;114(3):525-36. Epub 2006 Nov 21.

Comment in:
    Curr Diab Rep. 2008 Aug;8(4):255-6.    Ophthalmology. 2008 Feb;115(2):416-7; author reply 417.

Relationship between optical coherence tomography-measured central retinal
thickness and visual acuity in diabetic macular edema.

Diabetic Retinopathy Clinical Research Network, Browning DJ, Glassman AR, Aiello 
LP, Beck RW, Brown DM, Fong DS, Bressler NM, Danis RP, Kinyoun JL, Nguyen QD,
Bhavsar AR, Gottlieb J, Pieramici DJ, Rauser ME, Apte RS, Lim JI, Miskala PH.

Jaeb Center for Health Research, 15310 Amberly Drive, Suite 350, Tampa, FL 33647,
USA. drcrnet@jaeb.org

OBJECTIVE: To compare optical coherence tomography (OCT)-measured retinal
thickness and visual acuity in eyes with diabetic macular edema (DME) both before
and after macular laser photocoagulation. DESIGN: Cross-sectional and
longitudinal study. PARTICIPANTS: Two hundred ten patients (251 eyes) with DME
enrolled in a randomized clinical trial of laser techniques. METHODS: Retinal
thickness was measured with OCT and visual acuity was measured with the
electronic Early Treatment of Diabetic Retinopathy procedure. MAIN OUTCOME
MEASURES: Optical coherence tomography-measured center point thickness and visual
acuity. RESULTS: The correlation coefficients for visual acuity versus OCT center
point thickness were 0.52 at baseline and 0.49, 0.36, and 0.38 at 3.5, 8, and 12 
months after laser photocoagulation. The slope of the best fit line to the
baseline data was approximately 4.4 letters (95% confidence interval, 3.5-5.3) of
better of visual acuity for every 100-mum decrease in center point thickness at
baseline with no important difference at follow-up visits. Approximately one
third of the variation in visual acuity could be predicted by a linear regression
model that incorporated OCT center point thickness, age, hemoglobin A1C, and
severity of fluorescein leakage. The correlation between change in visual acuity 
and change in OCT center point thickening 3.5 months after laser treatment was
0.44, with no important difference at the other follow-up times. A subset of eyes
showed paradoxical improvements in visual acuity with increased center point
thickening (7%-17% at the 3 time points) or paradoxical worsening of visual
acuity with a decrease in center point thickening (18%-26% at the 3 time points).
CONCLUSIONS: There is modest correlation between OCT-measured center point
thickness and visual acuity, and modest correlation of changes in retinal
thickening and visual acuity after focal laser treatment for DME. However, a wide
range of visual acuity may be observed for a given degree of retinal edema. Thus,
although OCT measurements of retinal thickness represent an important tool in
clinical evaluation, they cannot substitute reliably as a surrogate for visual
acuity at a given point in time. This study does not address whether short-term
changes on OCT are predictive of long-term effects on visual acuity.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial
    Research Support, N.I.H., Extramural

PMID: 17123615 [PubMed - indexed for MEDLINE]

1178: Invest Ophthalmol Vis Sci. 2006 Dec;47(12):5495-504.

Autofluorescence characteristics of early, atrophic, and high-risk fellow eyes in
age-related macular degeneration.

Smith RT, Chan JK, Busuoic M, Sivagnanavel V, Bird AC, Chong NV.

Department of Ophthalmology, Columbia University, Harkness Eye Institute, New
York, New York 10032, USA. rts1@columbia.edu

PURPOSE: To assess the relationships of drusen, pigment, and focally increased
autofluorescence (FIAF) and the reticular pattern of hypoautofluorescence, to
distinguish the combined photographic and AF characteristics of early, atrophic, 
and high-risk fellow eyes in AMD. METHODS: In a retrospective interinstitutional 
clinical study, AF and color photograph pairs of 221 eyes were examined: 166 eyes
of 83 patients with bilateral large, soft drusen, with and without geographic
atrophy (GA), and 55 fellow eyes of 55 patients with unilateral choroidal
neovascularization (CNV). Forty-two eyes (one eye from each of 42 patients with
early or atrophic AMD) were divided into four groups: 14 with drusen only, 9 with
drusen and pigment abnormalities, 11 fellow eyes of patients with unilateral GA, 
and 8 eyes of patients with bilateral GA (acronyms for the groups: D-D, D-Pig,
D-GA and GA-GA, respectively). The 55 fellow eyes of patients with CNV were
divided into three groups: 19 eyes with no FIAF (CNV-0), 16 with FIAF without
reticular AF (CNV-1), and 20 eyes with reticular AF and/or pseudodrusen (CNV-R). 
Image pairs of eyes with FIAF were registered, and drusen, pigment, and FIAF were
segmented using automated background leveling and thresholding. All 221 eyes were
surveyed for reticular AF and reticular pseudodrusen. The main outcome measures
were (1) the fraction and relative probability of FIAF colocalizing with drusen
and pigment and (2) the presence or absence of reticular AF and reticular
pseudodrusen. RESULTS: The mean fractions of FIAF that colocalized with large
drusen were: D-D group, 0.46 +/- 0.21; D-Pig group, 0.42 +/- 0.29; D-GA group,
0.13 +/- 0.09; and GA-GA group, 0.11 +/- 0.12. Comparisons between groups showed 
significant differences when comparing either the D-D group or the D-Pig group
with either the D-GA group or the GA-GA group (P between 0.0001 and 0.015),
whereas other comparisons were nonsignificant (Mann-Whitney rank sum test). The
mean probabilities of FIAF colocalizing with large drusen relative to chance
(1.0) were: D-D group, 4.7 +/- 2.5; D-Pig group, 4.3 +/- 2.3; D-GA group, 1.4 +/-
0.8; and GA-GA group, 1.8 +/- 1.3, with similar significant differences as for
the colocalization fractions. The mean probability of FIAF colocalizing with
small to intermediate drusen in the D-D group was 1.5 +/- 1.3, which was not
significantly different from chance. In the D-Pig group, the median probability
of FIAF colocalizing with pigment abnormalities was 10.0 (range, 1.1-51.0). The
AF patterns in 15 of 19 eyes in the CNV-0 group were normal; the remainder had
nonreticular hypoautofluorescence only. In the CNV-1 group, the relations of FIAF
with drusen and pigment were similar to those in the early AMD groups. CNV-R
comprised 20 of 55 eyes in the CNV group, but reticular autofluorescence and/or
pseudodrusen were found in only 14 of 166 eyes of the early and atrophic groups. 
Of the 34 total eyes with reticular AF or pseudodrusen, 28 had both, 4 had
reticular AF only, and 2 had reticular pseudodrusen only. CONCLUSIONS: There are 
clear relationships between AF patterns and clinical AMD status. In early AMD,
FIAF's colocalization with large, soft drusen and hyperpigmentation is several
times greater than chance, suggesting linked disease processes. In advanced
atrophic AMD, FIAF is found mostly adjacent to drusen and GA, suggesting that
dispersal of drusen-associated lipofuscin is a marker of atrophic disease
progression. In the neovascular case, a large group of fellow eyes have no FIAF
abnormalities, suggesting that lipofuscin is not a major determinant of CNV.
However, reticular hypoautofluorescence, consistent with widespread inflammatory 
damage to the RPE, appears to be a highly sensitive imaging marker for the
disease that determines reticular pseudodrusen and is strongly associated with
CNV.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17122141 [PubMed - indexed for MEDLINE]

1179: Invest Ophthalmol Vis Sci. 2006 Dec;47(12):5460-8.

Dynamic and quantitative analysis of choroidal neovascularization by fluorescein 
angiography.

Shah SM, Tatlipinar S, Quinlan E, Sung JU, Tabandeh H, Nguyen QD, Fahmy AS,
Zimmer-Galler I, Symons RC, Cedarbaum JM, Campochiaro PA.

Retinal Imaging Research and Reading Center, Wilmer Eye Institute, Johns Hopkins 
University School of Medicine, Baltimore, Maryland 21287-9277, USA.

PURPOSE: In this study, the authors sought to develop and characterize techniques
for measuring changes in choroidal neovascularization (CNV) lesion size and
fluorescence over time for quantitative analysis of fluorescein angiograms.
METHODS: Initial assessment of the quantitative technique was made by
retrospectively analyzing digital fluorescein angiograms taken before and 3
months after photodynamic therapy (PDT) for CNV (6 patients, group 1). The method
was then applied prospectively to digital fluorescein angiograms (baseline and
day 71) obtained on 12 patients taking part in a clinical trial investigating the
effect of vascular endothelial growth factor (VEGF) Trap in CNV (group 2). Two
masked observers, with the use of image processing, measured the area of
hyperfluorescence and fluorescence intensity above background. Values for each
image were plotted against time after dye injection to generate curves, and each 
area under the curve (AUC) was calculated. RESULTS: The physician who treated the
patients in group 1 judged the condition of three patients to be improved and of 
three to be worse 3 months after PDT. Masked retrospective grading of fluorescein
angiograms showed an 11% decrease in AUC for fluorescence area and a 32% decrease
in AUC for fluorescence intensity in the three patients whose conditions
clinically improved but increases of 131% and 292% in the three patients whose
conditions clinically worsened. In group 2, a 38% decrease in AUC for
fluorescence intensity and a 19% decrease in AUC for fluorescence area were
observed in patients who received VEGF Trap compared with increases of 66% (P =
0.004, Mann-Whitney U test) and 21% (P = 0.07) for patients who received placebo.
Macular volume decreased by 11% in VEGF Trap-treated patients and increased by
10% in placebo-treated patients (P = 0.03). CONCLUSIONS: This study reports a
technique for analysis of change in fluorescence area and intensity over time
during fluorescein angiography (FA) using a continuous scale and its application 
in a clinical setting and a clinical trial. Compared with previous techniques
making use of categorical scales, this approach provides an advantage for
evaluating responses to treatment that may improve the value of FA as an outcome 
measure in clinical trials.

Publication Types: 
    Clinical Trial, Phase I
    Randomized Controlled Trial
    Research Support, N.I.H., Extramural

PMID: 17122137 [PubMed - indexed for MEDLINE]

1180: Invest Ophthalmol Vis Sci. 2006 Dec;47(12):5453-9.

Expanded genome scan in extended families with age-related macular degeneration.

Barral S, Francis PJ, Schultz DW, Schain MB, Haynes C, Majewski J, Ott J, Acott
T, Weleber RG, Klein ML.

Laboratory of Statistical Genetics, Rockefeller University, New York, New York,
USA.

PURPOSE: To investigate further the genetic contribution to age-related macular
degeneration (AMD), increasing the power of a previous analysis and reproducing
the original findings. METHODS: A large cohort of families with this condition
was assembled, and an expanded genome scan was performed with 556 microsatellite 
markers. In 2003, the results were reported of a genome-wide linkage analysis of 
70 of these pedigrees. Members of 51 new families have now been ascertained and
many of the original pedigrees expanded. Parametric and nonparametric linkage
analyses were performed with a denser map of markers. In addition, analyses were 
performed with the sample stratified by age at ascertainment and by two major
advanced phenotypes for the disease: neovascular AMD (choroidal
neovascularization) and geographic atrophy. RESULTS: The results corroborate the 
macular degeneration-susceptibility loci consistently reported by the authors and
others in genome-wide scans. New loci were identified, including the finding of a
two-point HLOD of 3.70 at 6q25.2. CONCLUSIONS: The results suggest that the use
of families enriched in predisposition to AMD has legitimacy. Genetic analyses of
a genome-wide scan performed on our large cohort of families add further
confirmatory evidence that susceptibility loci lie on 1q, 3p, 9q, and 10q.
Furthermore, new loci have been identified, including a locus on 6q.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17122136 [PubMed - indexed for MEDLINE]

1181: Invest Ophthalmol Vis Sci. 2006 Dec;47(12):5234-42.

The effect of lutein and zeaxanthin supplementation on metabolites of these
carotenoids in the serum of persons aged 60 or older.

Khachik F, de Moura FF, Chew EY, Douglass LW, Ferris FL 3rd, Kim J, Thompson DJ.

Department of Chemistry and Biochemistry, Joint Institute for Food Safety and
Applied Nutrition (JIFSAN), University of Maryland, College Park, MD 20742-2021, 
USA. khachik@umd.edu

PURPOSE: To investigate the effect of lutein supplementation at doses of 2.5,
5.0, and 10 mg/d for 6 months on distribution of these carotenoids and their
metabolites in the serum of elderly human subjects, with and without age-related 
macular degeneration. To determine whether supplementation with lutein can
interact with the serum levels of other dietary carotenoids, retinol, and
alpha-tocopherol. METHODS: Forty-five subjects received daily supplements of
lutein (containing 5% zeaxanthin) for 6 months and were followed up for another 6
months after supplementation. Blood was collected at various intervals and
lutein, zeaxanthin, and their metabolites in the sera were quantified by
normal-phase high-performance liquid chromatography (HPLC)-UV/visible detection. 
Other dietary carotenoids, retinol, and alpha-tocopherol were identified and
quantified on a C18 reversed phase HPLC column. RESULTS: After 6 months of
supplementation with 10 mg of lutein, the increases in the mean serum levels from
baseline were: 210 to 1000 nM/L (P < 0.0001) for lutein and 56 to 95 nM/L (P <
0.0001) for zeaxanthin. Similarly, the mean concentrations (nM/L) of carotenoid
metabolites increased from 49 to 98 (P < 0.0001) for
3-hydroxy-beta,epsilon-caroten-3'-one (3'-oxolutein); 31 to 80 (P < 0.0001) for
3'-hydroxy-epsilon,epsilon-caroten-3-one; and 19 to 25 (P < 0.0001) for
epsilon,epsilon-carotene-3,3'-dione. The serum levels of these carotenoids
gradually decline within 6 months after supplementation. CONCLUSIONS: The
increase in the serum levels of lutein/zeaxanthin correlates with increases in
the serum levels of their metabolites that have previously been identified in the
ocular tissues. Elderly human subjects with and without AMD can safely take
supplements of lutein up to 10 mg/d for 6 months with no apparent toxicity or
side effects.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17122108 [PubMed - indexed for MEDLINE]

1182: Invest Ophthalmol Vis Sci. 2006 Dec;47(12):5227-33.

Erratum in:
    Invest Ophthalmol Vis Sci. 2007 Jan;48(1):17. de Monastario, Francisco [corrected
to de Monasterio, Francisco].

Dose-ranging study of lutein supplementation in persons aged 60 years or older.

Rosenthal JM, Kim J, de Monasterio F, Thompson DJ, Bone RA, Landrum JT, de Moura 
FF, Khachik F, Chen H, Schleicher RL, Ferris FL 3rd, Chew EY.

Clinical Trials Branch, Division of Epidemiology and Clinical Research, National 
Eye Institute, National Institutes of Health, Bethesda, Maryland, USA.

PURPOSE: To examine the dose-response relationship between oral lutein
supplementation and serum lutein concentrations in persons aged 60 years and
older, with or without age-related macular degeneration (AMD). METHODS:
Forty-five participants with no AMD, large drusen, or advanced AMD, were
randomized to receive one of three doses (2.5, 5, or 10 mg) of lutein for 6
months and to be observed for 6 additional months after the cessation of lutein
supplementation. RESULTS: The mean age of the participants (33 women) was 71
years (range: 60-91). The serum lutein concentrations of each dose group were
similar before supplementation, increased at 1 month, and peaked by 3 months.
Median serum concentrations of the 2.5-, 5-, and 10-mg groups from baseline to
month 6 increased from 18.7 to 35.1 microg/dL (2-fold increase), from 17.8 to
59.2 microg/dL (2.9-fold increase), and from 15.1 to 66.8 microg/dL (4-fold
increase), respectively (all P < 0.001). The increases in lutein serum
concentrations did not vary with AMD disease severity (P = 0.98). No toxicity was
observed with any dose of lutein. No significant changes were detected in visual 
acuity or visual field tests. CONCLUSIONS: Increasing doses of lutein supplements
significantly increased the serum levels of lutein and zeaxanthin, and doses up
to 10 mg were safely administered. A long-term large clinical trial is necessary 
to investigate the safety and efficacy of lutein in reducing the risk of the
development of advanced AMD.

Publication Types: 
    Randomized Controlled Trial
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17122107 [PubMed - indexed for MEDLINE]

1183: Graefes Arch Clin Exp Ophthalmol. 2007 Jun;245(6):767-73. Epub 2006 Nov 22.

Influence of macular pigment and melanin on incident early AMD in a white
population.

Kanis MJ, Berendschot TT, van Norren D.

Department of Ophthalmology, University Medical Center Utrecht, AZU E03.136, 3508
GA, Utrecht, The Netherlands. M.J.Kanis@umcutrecht.nl

BACKGROUND: The protective effect of macular pigment (MP) and melanin against
age-related macular degeneration (AMD) is still controversial from
cross-sectional studies. In an attempt to clarify this issue, we performed a
population-based longitudinal study. METHODS: MP optical density (MPOD) and
melanin optical density (MOD) data were collected during the second follow-up
phase of the Rotterdam Study in 1999 in a random subset of 435 participants. Data
from 419 participants (98% white) was available for analysis. AMD diagnosis was
based on standardized fundus photographs according to the International
Classification System, and AMD cases were subdivided into five mutually exclusive
stages. In the three follow-up phases, incident AMD (iAMD), defined as absence of
any AMD at baseline and the presence of stage 2 or higher at follow-up, was
determined. We used Cox regression analysis to study the effect of an assumedly
stable MPOD and MOD on early iAMD. RESULTS: During a mean follow-up of 9.82
years, 13 male and 17 female participants developed early iAMD and two male
participants late iAMD. Because only two participants developed late iAMD, we had
to restrict our analyses to early iAMD. Cox regression analysis adjusted for age 
and gender showed no significant effect of MPOD [hazard ratio (HR) 0.37; 95%
confidence interval (CI) 0.04, 3.57] and MOD (HR 0.56; 95% CI 0.09, 3.60) on
early iAMD. Additional adjustment for smoking did not change these associations. 
CONCLUSIONS: This unique but quantitatively limited material leads to the
conclusion that no major protective effect of MPOD or MOD was seen on early iAMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17119995 [PubMed - indexed for MEDLINE]

1184: Qual Life Res. 2007 Apr;16(3):533-43. Epub 2006 Nov 22.

Determinants of health related quality of life and health state utility in
patients with age related macular degeneration: the association of contrast
sensitivity and visual acuity.

Bansback N, Czoski-Murray C, Carlton J, Lewis G, Hughes L, Espallargues M, Brand 
C, Brazier J.

Health Economics and Decision Science, ScHARR (School of Health and Related
Research), The University of Sheffield, Regent Court, 30 Regent Street,
Sheffield, S1 4DA, UK. n.j.bansback@sheffield.ac.uk

BACKGROUND: There has been increasing interest in the use of measures of health
related quality of life (HRQoL) and health state utility values in Age Related
Macular Degeneration (ARMD). Visual acuity has been found to be an important
determinant of such measures in previous studies. More recently, another measure 
of visual impairment, contrast sensitivity has received considerable attention.
We designed a study to examine whether the contribution of contrast sensitivity
in explaining HRQoL and health utilities over and above that of visual acuity.
METHODS: 209 patients with unilateral or bilateral ARMD were recruited into a
cross-sectional study of patients from a large teaching hospital. Patients
underwent visual tests (near and distant visual acuity, contrast sensitivity) and
completed a vision function questionnaire, the VF-14, HUI3, and time trade-off.
RESULTS: Using multivariate regression analysis, the study revealed that contrast
sensitivity remained a statistically significant predictor of all outcome
measures even when visual acuity was included. This result was supported by the
correlation coefficients between measures. CONCLUSIONS: The measurement of
contrast sensitivity appears to be better related to a person's HRQoL and health 
utility. Future studies should consider incorporating contrast sensitivity in
addition to visual acuity. Studies, in particular economic evaluations, may
underestimate the effect of treatment unless contrast sensitivity is considered.

Publication Types: 
    Evaluation Studies
    Research Support, Non-U.S. Gov't

PMID: 17119846 [PubMed - indexed for MEDLINE]

1185: Arq Bras Oftalmol. 2006 Jul-Aug;69(4):539-44.

Retinal thickness assessed by optical coherence tomography (OCT) in pseudophakic 
macular edema.

Bonanomi MT, Nicoletti AG, Carricondo PC, Buzalaf F, Kara-José N Jr, Gomes AM,
Nakashima Y.

Hospital das Clínicas, Department of Ophthalmology, Universidade de São Paulo,
São Paulo, SP, Brasil. mtbonanomi@uol.com.br

PURPOSE: To evaluate the usefulness of the optical coherence tomography (OCT)
retinal map in angiographic pseudophakic macular edema (ACME). METHODS: This is a
prospective analysis of a group of 36 pseudophakic eyes at the fifth
postoperative week, submitted to optical coherence tomography 2 macular map and
fluorescein angiography on the same day and, a control group of twenty-two 20/20 
vision eyes with a minimum 6-month postoperative period, submitted to optical
coherence tomography 2 macular map only. Exclusion criteria were diabetes, any
macular pathology and unreadable optical coherence tomography or angiogram. The
angiograms were divided into three groups according to the edema intensity: Group
I: level 0 (absence of angiographic pseudophakic macular edema); group II: levels
1 and 2 (incomplete and complete perifoveal angiographic pseudophakic macular
edema respectively) and group III: levels 3 and 4 (up to one disc diameter and
greater than one disc diameter angiographic pseudophakic macular edema area
respectively). The nine zones of the optical coherence tomography macular map
were compared between the control and the three subgroups of the study group and,
between group I and groups II and III. RESULTS: Among the 36 eyes, 23 (64%) were 
classified as group I, 10 (28%) as group II and three (8%) as group III. The mean
thickness of the fovea zone was 185+/-15 microm for the control group, 189+/-24
microm for group I, 213+/-33 microm for group II and 455+/-38 microm for group
III. Significant differences: between group III and the control or group I for
all zones (p<0.01) and, between group II and control or group I for the fovea and
temporal inner zones (p<0.05). CONCLUSION: The optical coherence tomography
retinal map is useful in angiographic pseudophakic macular edema diagnosis.

Publication Types: 
    Evaluation Studies

PMID: 17119727 [PubMed - indexed for MEDLINE]

1186: Graefes Arch Clin Exp Ophthalmol. 2007 Jan;245(1):68-73. Epub 2006 Nov 18.

Intravitreally administered bevacizumab (Avastin) in minimally classic and occult
choroidal neovascularization secondary to age-related macular degeneration.

Lazic R, Gabric N.

Eye Clinic Svjetlost, Bukovacka 27, 10000 Zagreb, Croatia.
ratimir.lazic@svjetlost.hr

BACKGROUND: Anti-vascular endothelial growth factor (anti-VEGF) agents have been 
shown to be effective in the treatment of neovascular age-related macular
degeneration (AMD). Efficacy and safety of intravitreally administered
bevacizumab (Avastin), a humanized monoclonal anti-VEGF, was assessed in
minimally classic and occult subfoveal choroidal neovascularization (CNV) due to 
AMD. METHODS: A prospective interventional study was carried out. Bevacizumab
(1.25 mg) was administered intravitreally on a 6-week basis until macular edema, 
subretinal fluid, and/or pigment epithelial detachment had resolved.
Administration was repeated in case of relapse. Ophthalmic evaluations included a
complete ophthalmic examination, measurement of the visual acuity (VA), optical
coherence tomography, and fluorescein angiography. Main outcome measures were the
changes between baseline and last follow-up visit in best-corrected VA, central
foveal thickness (CFT) and total macular volume (TMV). RESULTS: From 102 patients
[mean age (range) 74.8 (61-85) years], 102 eyes were included. Median (range)
duration of follow-up was 18 (6-24) weeks. Statistically significant changes from
baseline were observed in best-corrected VA [increase of 1.29 lines (P=0.001)],
CFT [reduction of 56 microm (P=0.01)] and TMV [reduction of 0.80 mm(3)
(P<0.0001)]. Positive results were obtained in 65/102 (64%) patients after two to
three injections as a mean. In a substantial proportion of patients (38%)
followed up for at least 18 weeks, recurrence of leakage requiring additional
injections was observed. Treatment was well tolerated; two pigment epithelium
rips and ten posterior vitreous detachments were reported. CONCLUSIONS:
Short-term results suggest that intravitreally administered bevacizumab (Avastin)
is effective in minimally classic and occult CNV due to AMD. Significant
improvements in VA, CFT and TMV were obtained and maintained during follow-up. In
some patients, however, recurrence of leakage requiring additional intravitreal
injection occurred. Maintenance of the effect of bevacizumab and its safety after
repeated and prolonged administration have to be investigated in well-controlled 
studies.

PMID: 17111146 [PubMed - indexed for MEDLINE]

1187: Am J Epidemiol. 2007 Feb 15;165(4):375-82. Epub 2006 Nov 16.

Association between circulating white blood cell count and long-term incidence of
age-related macular degeneration: the Blue Mountains Eye Study.

Shankar A, Mitchell P, Rochtchina E, Tan J, Wang JJ.

Department of Community, Occupational, and Family Medicine, National University
of Singapore, Republic of Singapore. ashankar@nus.edu.sg

Inflammatory processes are implicated in the development and progression of
age-related macular degeneration (AMD). However, there are limited data on
longitudinal associations between systemic markers of inflammation and AMD. The
authors examined the prospective relation between the circulating white blood
cell (WBC) count and early and late AMD in a population-based cohort of 3,654
participants, aged 49-97 years, in the Blue Mountains region, Australia. The main
outcome of interest was the 10-year incidence of early and late AMD among
individuals free from corresponding disease at the baseline (1992-1994). An
elevated baseline WBC count was associated with early AMD incidence, independent 
of smoking and other major confounders. The multivariable relative risk comparing
tertile 3 of WBC count (>6.7 x 10(9) cells/liter) with tertile 1 (</=5.5 x 10(9) 
cells/liter) was 1.85 (95% confidence interval: 1.33, 2.58). The association
between WBC count and early AMD was present consistently in analyses of different
early AMD lesions, including incident pigmentary abnormalities and soft
indistinct/reticular drusen. Moreover, this association persisted in subgroup
analyses by gender and smoking. An elevated WBC count at baseline was not
consistently associated with late AMD incidence. This study provides
population-based evidence supporting a longitudinal association between the
circulating WBC count, a widely available marker of inflammation, and incidence
of early AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17110636 [PubMed - indexed for MEDLINE]

1188: Exp Eye Res. 2007 Feb;84(2):378-80. Epub 2006 Nov 14.

Fibulin-5 distribution in human eyes: relevance to age-related macular
degeneration.

Mullins RF, Olvera MA, Clark AF, Stone EM.

Fibulin-5 is an extracellular matrix glycoprotein that participates in
elastogenesis. Mutations in the gene for fibulin-5 have been found to be
associated with age-related macular degeneration. Little is known, however, about
the expression of this gene in normal eyes or eyes with age-related macular
degeneration. In this study, we evaluated the expression of the fibulin-5 protein
in human donor eyes and localized this protein to Bruch's membrane and the
intercapillary pillars of the choriocapillaris in normal eyes. In eyes with
age-related macular degeneration, fibulin-5 was localized to pathologic basal
deposits beneath the retinal pigment epithelium as well as some small drusen.
These results suggest that fibulin-5 may promote extracellular deposit formation 
in macular degeneration.

Publication Types: 
    Letter
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17109857 [PubMed - indexed for MEDLINE]

1189: Expert Opin Pharmacother. 2006 Dec;7(17):2355-68.

A review of drug options in age-related macular degeneration therapy and
potential new agents.

Yeoh J, Sims J, Guymer RH.

Centre for Eye Research Australia, The University of Melbourne, Australia.

Age-related macular degeneration (AMD) is the leading cause of legal blindness in
people > 50 years of age in the developed world. AMD is both a debilitating and
costly disease for the individual and the community. Greater understanding of the
mechanisms and pathways involved in causing the visual loss in AMD has resulted
in the advent of several newer and more effective treatment options, making it an
exciting time in the management of AMD. This paper will examine the principles
behind the existing drug therapies available, as well as those being developed in
the management or prophylaxis of AMD and its vision-threatening complications.

Publication Types: 
    Review

PMID: 17109611 [PubMed - indexed for MEDLINE]

1190: Doc Ophthalmol. 2007 Jan;114(1):1-7. Epub 2006 Nov 16.

Intraocular triamcinolone acetonide for macular edema due to CRVO. A
multifocal-ERG and OCT study.

Moschos MM, Brouzas D, Loukianou E, Apostolopoulos M, Moschos M.

Department of Ophthalmology, University of Athens, Athens, Greece.
moschosmarilita@yahoo.fr

PURPOSE: To investigate the effectiveness of intravitreal triamcinolone acetonide
in the treatment of cystoid macular edema due to central retinal vein occlusion
(CRVO). A noncomparative, prospective, interventional case series. METHODS: In
this study 15 eyes of 15 patients (9 males and 6 females) with macular edema due 
to non-ischemic CRVO were treated with intravitreal injection of 4 mg
triamcinolone acetonide and followed-up for 1 year. Examination included
measurement of best-corrected visual acuity (BCVA) for distance, measurement of
intraocular pressure (IOP), fluorescein angiography, foveal retinal thickness
measurement by optical coherence tomography (OCT), and multifocal
electroretinography recordings (MFERG) preoperatively 3, 6 and 12 months
postoperatively. RESULTS: The visual acuity increased to a significant degree at 
3 months, to a smaller degree at 6 months but at 12 months there was no
significant improvement. The OCT macula thickness improved to a significant level
all the follow-up period but with less significance at 12 months. The MFERG
recordings from the fovea showed significant improvement at 3 and 6 months. The
MFERG from the parafovea area showed significant improvement at 3 and 6 and to a 
smaller degree at 12 months. The intraocular pressure increased at 3 and 6 months
but returned to pretreatment level at 12 months. CONCLUSION: Intravitreal
injection of triamcinolone acetonide leads to a significant improvement of mean
VA in patients with macular edema due to CRVO. However, this significant effect
is not permanent and persists for a maximum of 3-6 months. Thereafter all the
indexes tend to deteriorate.

PMID: 17109155 [PubMed - indexed for MEDLINE]

1191: Br J Ophthalmol. 2007 Jun;91(6):761-5. Epub 2006 Nov 15.

Predictive factors for short-term visual outcome after intravitreal triamcinolone
acetonide injection for diabetic macular oedema: an optical coherence tomography 
study.

Brasil OF, Smith SD, Galor A, Lowder CY, Sears JE, Kaiser PK.

The Cleveland Clinic, Cole Eye Institute, Cleveland, Ohio 44195, USA.

AIM: To evaluate the predictive factors for visual outcome after intravitreal
triamcinolone acetonide injection to treat refractory diabetic macular oedema
(DME). METHODS: A retrospective chart review of patients with DME who met the
following inclusion criteria was performed: clinically significant diabetic
macular oedema, receipt of a 4 mg/0.1 ml intravitreal triamcinolone acetonide
injection and an optical coherence tomography (OCT) of the macula performed up to
10 days before injection. All patients received a full ophthalmic examination
including best-corrected Snellen visual acuity (VA). The main outcome measure was
the mean change in vision 3 months after injection. RESULTS: Data from 73 eyes of
59 patients were analysed. After a mean follow-up of 324 days, the mean change in
vision was -0.075 logarithm of minimum angle of resolution (logMAR) units, with
27.3% improving > or =3 lines, 6.8% declining > or =3 lines and 60.2% remaining
stable within 1 line of baseline vision. Statistical analysis was performed using
multivariate generalised estimating equations on the basis of data from 52 eyes
of 42 patients. Factors associated with an improvement in vision 3 months after
injection were worse baseline VA (-0.27 logMAR units/unit increase in baseline
VA, p = 0.002) and presence of subretinal fluid (-0.17 logMAR units, p = 0.06).
The presence of cystoid macular oedema negatively affected the visual outcome
(0.15 logMAR units, p = 0.03). In addition, the presence of an epiretinal
membrane (ERM) was associated with less visual improvement. ERM modified the
effect of baseline VA as demonstrated by a significant interaction between these 
two variables (0.34 logMAR units/unit increase in baseline VA, p = 0.04).
CONCLUSIONS: OCT factors and baseline VA can be useful in predicting the outcomes
of VA 3 months after intravitreal triamcinolone acetonide injection in patients
with refractory DME.

PMID: 17108013 [PubMed - indexed for MEDLINE]

1192: Optom Vis Sci. 2006 Nov;83(11):789-96.

Reading with central scotomas: is there a binocular gain?

Kabanarou SA, Rubin GS.

Institute of Ophthalmology, London, United Kingdom. stamatina_k@hotmail.com

PURPOSE: The purpose of this study was to compare reading performance under
binocular versus monocular viewing conditions in patients with bilateral
age-related macular degeneration (AMD). METHODS: Twenty-two patients with AMD
participated. Distance acuity, reading acuity, and contrast sensitivity were
recorded binocularly and monocularly with the better eye. An infrared eye tracker
recorded eye movements during reading. Reading speed and reading eye movement
parameters, including number of fixations and regressions, fixation duration, and
number of saccades to find the next line, were calculated for both viewing
conditions. The difference between binocular and monocular performance (binocular
gain) was computed. Regression analysis was used to determine whether intraocular
differences in distance and reading acuity and contrast sensitivity were
predictive of binocular gain. RESULTS: Reading speed when using both eyes was
highly correlated with the reading speed for the better eye. There was a small,
but not significant, advantage of binocular viewing (6.9 words/minute, p = 0.33).
No significant difference was detected in any eye movement parameters when
comparing both eyes with the better eye. Although some patients showed either
positive or negative binocular gain, the amount of gain was not predicted by
intraocular differences in acuity or contrast sensitivity. CONCLUSIONS: Overall, 
there was no significant difference between binocular and monocular reading
performance in patients with AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17106405 [PubMed - indexed for MEDLINE]

1193: Ann Acad Med Singapore. 2006 Oct;35(10):701-5.

Retrospective review of eyes with neovascular age-related macular degeneration
treated with photodynamic therapy with verteporfin and intravitreal
triamcinolone.

Fackler TK, Reddy S, Bearelly S, Stinnett S, Fekrat S, Cooney MJ.

Duke Eye Center, Albert Eye Research Institute, North Carolina, USA.

AIM: To review the outcomes of eyes with neovascular age-related macular
degeneration (AMD) treated with photodynamic therapy (PDT) with verteporfin and
intravitreal triamcinolone acetonide injection. MATERIALS AND METHODS: We
retrospectively reviewed the outcomes of consecutive eyes with neovascular AMD
that received an intravitreal triamcinolone injection within 1 week of their
first PDT and had at least 6 months of follow-up. Eyes were retreated with PDT at
3-month intervals if angiographic leakage was present. RESULTS: Twenty-six eyes
from 24 patients were identified. The mean visual acuity at baseline was 20/118
(median 20/112). The mean visual acuity decreased to 20/138 at 9 months (P =
0.24, n = 15) and to 20/174 at 12 months (P = 0.23, n = 8). The change in visual 
acuity from baseline was not statistically significant at any time point. The
mean central foveal thickness by OCT measured 342 microm at baseline and
decreased to 296 microm at 12 months (P = 0.31). Sixty-two per cent of eyes
required no additional PDT at 12 months. Nineteen per cent of 26 eyes had a rise 
in intraocular pressure that was controlled with topical medication alone.
CONCLUSION: Photodynamic therapy with verteporfin combined with intravitreal
triamcinolone injection in the treatment of neovascular AMD may be superior to
PDT alone by decreasing visual loss and reducing the number or retreatments.

PMID: 17102894 [PubMed - indexed for MEDLINE]

1194: Arch Ophthalmol. 2006 Nov;124(11):1593-600.

Localization of multifocal electroretinogram abnormalities to the lesion site:
findings in a family with Best disease.

Glybina IV, Frank RN.

Kresge Eye Institute, Wayne State University School of Medicine, Detroit, MI
48201, USA. iglybina@med.wayne.edu

OBJECTIVE: To determine the association between multifocal electroretinogram
(mfERG) abnormalities and macular lesions, as shown by retinal photography and
optical coherence tomography (OCT), in a 3-generation family with vitelliform
macular dystrophy. METHODS: Five family members were examined using OCT, mfERG,
and retinal photography. To localize mfERG abnormalities in relation to retinal
findings, we overlaid the mfERG trace arrays on the retinal images and aligned
the mfERGs and OCT images in the 180 degrees meridian. RESULTS: Family members
had typical macular lesions, normal full-field ERGs, and reduced
electro-oculogram light-dark ratios. The OCT images demonstrated variable lesion 
severity. Some individuals with good vision and normal-appearing fundi showed OCT
abnormalities of the choroid and retinal pigment epithelium. The overlay
technique revealed that the depressed mfERGs corresponded with the lesions
detected by OCT and retinal photography. The latencies of mfERG components in the
2 central stimulus rings in our patients were often prolonged. CONCLUSIONS: The
mfERG abnormalities matched the localization of the macular lesions in our
patients. The latencies of the mfERG N1 and P1 components in the first 2
concentric stimulus rings were often significantly (>2 SDs) delayed, an
observation that has not been previously reported, to our knowledge.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 17102007 [PubMed - indexed for MEDLINE]

1195: Arch Ophthalmol. 2006 Nov;124(11):1532-42.

Erratum in:
    Arch Ophthalmol. 2007 Jan;125(1):138.

Ranibizumab combined with verteporfin photodynamic therapy in neovascular
age-related macular degeneration: year 1 results of the FOCUS Study.

Heier JS, Boyer DS, Ciulla TA, Ferrone PJ, Jumper JM, Gentile RC, Kotlovker D,
Chung CY, Kim RY; FOCUS Study Group.

Ophthalmic Consultants of Boston, Boston, MA 02114, USA. jsheier@eyeboston.com

OBJECTIVE: To investigate the safety and efficacy of intravitreal ranibizumab
treatment combined with verteporfin photodynamic therapy (PDT) in patients with
predominantly classic choroidal neovascularization secondary to age-related
macular degeneration. METHODS: In this 2-year, phase I/II, multicenter,
randomized, single-masked, controlled study, patients received monthly
ranibizumab (0.5 mg) (n = 106) or sham (n = 56) injections. The PDT was performed
7 days before initial ranibizumab or sham treatment and then quarterly as needed.
MAIN OUTCOMES MEASURES: Proportion of patients losing fewer than 15 letters from 
baseline visual acuity at 12 months (primary efficacy outcome) and the incidence 
and severity of adverse events. RESULTS: At 12 months, 90.5% of the
ranibizumab-treated patients and 67.9% of the control patients had lost fewer
than 15 letters (P<.001). The most frequent ranibizumab-associated serious ocular
adverse events were intraocular inflammation (11.4%) and endophthalmitis (1.9%;
4.8% if including presumed cases). On average, patients with serious inflammation
had better visual acuity outcomes at 12 months than did controls. Key serious
nonocular adverse events included myocardial infarctions in the PDT-alone group
(3.6%) and cerebrovascular accidents in the ranibizumab-treated group (3.8%).
CONCLUSION/APPLICATION TO CLINICAL PRACTICE: Ranibizumab + PDT was more
efficacious than PDT alone for treating neovascular age-related macular
degeneration. Although ranibizumab treatment increased the risk of serious
intraocular inflammation, affected patients, on average, still experienced visual
acuity benefit.

Publication Types: 
    Clinical Trial, Phase I
    Clinical Trial, Phase II
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17101999 [PubMed - indexed for MEDLINE]

1196: Ann Med. 2006;38(7):450-71.

Age-related macular degeneration--emerging pathogenetic and therapeutic concepts.

Gehrs KM, Anderson DH, Johnson LV, Hageman GS.

Department of Ophthalmology and Visual Sciences, The University of Iowa, Iowa
City, IA 52240, USA.

Today, the average life expectancy in developed nations is over 80 years and
climbing. And yet, the quality of life during those additional years is often
significantly diminished by the effects of age-related, degenerative diseases,
including age-related macular degeneration (AMD), the leading cause of blindness 
in the elderly worldwide. AMD is characterized by a progressive loss of central
vision attributable to degenerative and neovascular changes in the macula, a
highly specialized region of the ocular retina responsible for fine visual
acuity. Estimates gathered from the most recent World Health Organization (WHO)
global eye disease survey conservatively indicate that 14 million persons are
blind or severely visually impaired because of AMD. The disease has a tremendous 
impact on the physical and mental health of the geriatric population and their
families and is becoming a major public health burden. Currently, there is
neither a cure nor a means to prevent AMD. Palliative treatment options for the
less prevalent, late-stage 'wet' form of the disease include anti-neovascular
agents, photodynamic therapy and thermal laser. There are no current therapies
for the more common 'dry' AMD, except for the use of antioxidants that delay
progression in 20%-25% of eyes. New discoveries, however, are beginning to
provide a much clearer picture of the relevant cellular events, genetic factors, 
and biochemical processes associated with early AMD. Recently, compelling
evidence has emerged that the innate immune system and, more specifically,
uncontrolled regulation of the complement alternative pathway plays a central
role in the pathobiology of AMD. The complement Factor H gene--which encodes the 
major inhibitor of the complement alternative pathway--is the first gene
identified in multiple independent studies that confers a significant genetic
risk for the development of AMD. The emergence of this new paradigm of AMD
pathogenesis should hasten the development of novel diagnostic and therapeutic
approaches for this disease that will dramatically improve the quality of our
prolonged lifespan.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Review

PMID: 17101537 [PubMed - indexed for MEDLINE]

1197: Exp Eye Res. 2007 Jan;84(1):135-42. Epub 2006 Nov 13.

Clathrin and adaptin accumulation in drusen, Bruch's membrane and choroid in AMD 
and non-AMD donor eyes.

Bando H, Shadrach KG, Rayborn ME, Crabb JW, Hollyfield JG.

Cole Eye Institute (i-31), Department of Ophthalmology, Cleveland Clinic
Foundation Lerner College of Medicine of Case Western Reserve University, 9500
Euclid Avenue, Cleveland, OH 44195, USA.

Clathrin was identified in a recent proteomic analysis of Bruch's membrane from
age-related macular degeneration (AMD) donor eyes. The present study was
conducted to determine the localization of clathrin in AMD tissues and to compare
this distribution and relative content with that in non-AMD control tissues. The 
distribution of adaptin, which is functionally linked to clathrin, was also
evaluated. Human eyes were from donors between 66 and 94 years of age; 13 eyes
were from donors with AMD and 13 from non-AMD donors. Bruch's membrane and
choroid from the macula of each donor eye were prepared for immunohistochemistry 
and Western blotting. Differences in immunoreactivity were quantitated. Drusen,
Bruch's membrane and choroid from AMD tissues showed greater immunoreactivity for
clathrin and adaptin than did non-AMD tissues. Western blots also showed more
intense clathrin and adaptin immunoreactivity in AMD tissues than were present in
non-AMD samples. This study suggests that accumulation of clathrin and adaptin in
drusen, Bruch's membrane and choroid may reflect a higher rate of clathrin
mediated endocytosis in AMD tissues. Alternatively, the accumulation of these
proteins in these extracellular compartments may reflect a higher susceptibility 
to oxidative damage.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17097084 [PubMed - indexed for MEDLINE]

1198: Graefes Arch Clin Exp Ophthalmol. 2007 Mar;245(3):360-8. Epub 2006 Nov 9.

Comparative evaluation of vitrectomy and dye-enhanced ILM peel with grid laser in
diffuse diabetic macular edema.

Kumar A, Sinha S, Azad R, Sharma YR, Vohra R.

Vitreous-Retina Service, Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All 
India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India.
akum66mm@yahoo.co.in

BACKGROUND: The purpose of this study is to compare the effectiveness of pars
plana vitrectomy (PPV) and dye-enhanced peeling of the internal limiting membrane
(ILM) with modified grid laser photocoagulation in patients with diffuse diabetic
macular edema and to determine if any correlation exists between improvement in
visual acuity (functional improvement) and reduction in foveal thickness and
macular volume (anatomical improvement). DESIGN: This is a randomized,
prospective, comparative, interventional study. METHOD: In this study 24 eyes of 
24 patients with metabolically stable diabetes and with diffuse diabetic macular 
edema were evaluated. The patients were randomized to either pars plana
vitrectomy with removal of ILM which was done in 12 eyes (ILM group) and modified
grid laser photocoagulation carried out in the remaining 12 eyes (laser group).
Main outcome measures were (1) the postoperative visual acuity in the form of
ETDRS log MAR values, (2) foveal thickness and (3) macular volume as measured by 
optical coherence tomography. The correlation between improvement in visual
acuity and the reduction of foveal thickness and macular volume in both the
groups were also evaluated. The results were all subjected to statistical
analysis. RESULTS: The ETDRS log MAR visual acuity difference between the two
groups at the end of 6 months was not clinically significant (P = 0.525).
However, foveal thickness and macular volume decreased significantly more in the 
ILM group compared to the laser group (P = 0.001, P < 0.001, Mann Whitney U
test). There was no correlation between the improvement in visual acuity and the 
reduction of foveal thickness (r = -0.158, P = 0.6) (ILM group), r = -0.155, P = 
0.7) (laser group) in both groups. CONCLUSIONS: PPV with ILM peeling was shown to
be beneficial by inducing a statistically significant reduction of macular
thickness and macular volume. Visual acuity also demonstrated a trend towards
improvement in both the ILM peel group and the grid laser group; however, the
comparative VA outcome analysis between the two groups was not significantly
different. Besides, there was also no correlation between the reductions of
foveal thickness and macular volume with the improvement in visual acuity in
either of the groups.

Publication Types: 
    Comparative Study
    Evaluation Studies
    Randomized Controlled Trial

PMID: 17093998 [PubMed - indexed for MEDLINE]

1199: Am J Clin Nutr. 2006 Nov;84(5):1107-22.

Predictors of optical density of lutein and zeaxanthin in retinas of older women 
in the Carotenoids in Age-Related Eye Disease Study, an ancillary study of the
Women's Health Initiative.

Mares JA, LaRowe TL, Snodderly DM, Moeller SM, Gruber MJ, Klein ML, Wooten BR,
Johnson EJ, Chappell RJ; CAREDS Macular Pigment Study Group and Investigators.

Department of Ophthalmology and Visual Sciences, University of Wisconsin,
Madison, WI, USA. jmarespe@facstaff.wisc.edu

BACKGROUND: Lifestyle, diet, and physical and health predictors of xanthophyll
carotenoids in the retina are poorly understood. OBJECTIVE: We aimed to
investigate the predictors of the density of lutein and zeaxanthin in the macula 
of the retina. DESIGN: Macular pigment optical density (MPOD) was measured by
heterochromatic flicker photometry. Relations to dietary lutein and zeaxanthin
and to other predictors were measured in 1698 women aged 53-86 y. The women were 
members of observational study cohorts of the Women's Health Initiative at Iowa
City, IA, Madison, WI, or Portland, OR, and participated in the Carotenoids in
Age-Related Eye Disease Study (2001-2004). RESULTS: MPOD at 0.5 degrees from the 
foveal center was 30% higher in women in the highest quintile for lutein and
zeaxanthin intake [x (+/-SD): 0.40 +/- 0.21] than in women in the lowest quintile
(0.31 +/- 0.21) and 20% higher after adjustment for other predictors. Dietary
intake of lutein, zeaxanthin, fiber, and polyunsaturated fatty acids (% of
energy) together explained 3% of the variability in MPOD. Higher waist
circumference and diabetes, which are related to lower MPOD, together with study 
site explained an additional 5% of variation. The total explained variability
increased to 12% when lutein and zexanthin concentrations obtained from the
serum, which were collected 4-7 y earlier, were added to the model. CONCLUSIONS: 
MPOD is directly related to dietary intake of lutein and zeaxanthin but even more
strongly to serum concentrations, which may reflect unmeasured physical and
medical factors that influence the uptake, distribution, and utilization of
lutein and zeaxanthin. Higher abdominal body fat and diabetes are related to
lower MPOD. Unknown predictors of retinal carotenoids remain.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 17093164 [PubMed - indexed for MEDLINE]

1200: Am J Clin Nutr. 2006 Nov;84(5):971-4.

Lutein and zeaxanthin intakes and risk of age-related macular degeneration and
cataracts: an evaluation using the Food and Drug Administration's evidence-based 
review system for health claims.

Trumbo PR, Ellwood KC.

Division of Nutrition Programs and Labeling, Food and Drug Administration,
College Park, MD, USA. paula.trumbo@fda.gov

The labeling of health claims that meet the significant scientific agreement
standard and of qualified health claims on conventional foods and dietary
supplements requires premarket approval by the Food and Drug Administration
(FDA). The FDA conducts an evidence-based review to ascertain whether sufficient 
evidence exists to support a significant scientific agreement standard or a
qualified health claim. The FDA recently reviewed intervention and observational 
studies that evaluated the role of lutein and zeaxanthin in reducing the risk of 
age-related macular degeneration and cataracts. On the basis of this
evidence-based review, the FDA concluded that no credible evidence exists for a
health claim about the intake of lutein or zeaxanthin (or both) and the risk of
age-related macular degeneration or cataracts.

Publication Types: 
    Review

PMID: 17093145 [PubMed - indexed for MEDLINE]

1201: Eye. 2007 Dec;21(12):1455-63. Epub 2006 Nov 10.

Using contrast sensitivity to estimate the cost-effectiveness of verteporfin in
patients with predominantly classic age-related macular degeneration.

Bansback N, Davis S, Brazier J.

Health Economics and Decision Science, ScHARR (School of Health and Related
Research), University of Sheffield, Sheffield, UK. n.j.bansback@sheffield.ac.uk

AIMS: To re-evaluate the cost-effectiveness of photodynamic therapy with
verteporfin (Visudyne, Novartis AG, Switzerland) in patients with predominantly
classic and classic choroidal neovascularization (CNV) owing to age-related
macular degeneration (AMD), using new evidence on the impact of contrast
sensitivity on health status. METHOD: A health economic model is used to
synthesise the evidence on contrast sensitivity and treatment rates from the TAP 
Investigation with health state utilities and costs. Impairment of visual
function is estimated using a Markov model to predict transitions between states 
of contrast sensitivity. Each state is associated with costs and a health state
utility. Total expected costs and benefits for a cohort of patients over a
defined number of cycles are calculated. The expected health state utility for
each disease state was estimated using results from a study of 209 patients with 
AMD in Sheffield. The model includes the costs associated with treatment and
monitoring in the verteporfin treatment arm and costs offset by delaying the
deterioration of visual function. RESULTS: Beyond 3 years, the annual costs of
the verteporfin arm are estimated to be less than the annual costs of the control
arm, owing to the cost associated with higher blindness prevalence in the control
arm. Over time, the results show that both the incremental utility and cost
decreases. By 10 years, the estimated incremental cost-effectiveness is
approximately pound20 996 per Quality-Adjusted Life Years. CONCLUSION: The
results of this study suggest that the verteporfin therapy in the treatment for
patients with predominantly classic and classic CNV owing to AMD is encouraging.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17086167 [PubMed - indexed for MEDLINE]

1202: Exp Eye Res. 2007 Jan;84(1):61-74. Epub 2006 Nov 1.

Risk factors for age-related maculopathy are associated with a relative lack of
macular pigment.

Nolan JM, Stack J, O' Donovan O, Loane E, Beatty S.

Macular Pigment Research Group, Department of Chemical and Life Sciences,
Waterford Institute of Technology, Cork Road, Waterford, Ireland. jnolan@wit.ie

Macular pigment (MP) is composed of the two dietary carotenoids lutein (L) and
zeaxanthin (Z), and is believed to protect against age-related maculopathy (ARM).
This study was undertaken to investigate MP optical density with respect to risk 
factors for ARM, in 828 healthy subjects from an Irish population. MP optical
density was measured psychophysically using heterochromatic flicker photometry,
serum L and Z were quantified by HPLC, and dietary intake of L and Z was assessed
using a validated food-frequency questionnaire. Clinical and personal details
were also recorded, with particular attention directed towards risk factors for
ARM. We report a statistically significant age-related decline in MP optical
density (r2=0.082, p<0.01). Current and past smokers had lower average MP optical
density than never smokers and this difference was statistically significant
(p<0.01). Subjects with a confirmed family history of ARM had significantly lower
levels of MP optical density than subjects with no known family history of
disease (p<0.01). For each of these established risk factors, their statistically
significant negative association with MP persisted after controlling for the
other two, and also after controlling for other potentially confounding variables
such as sex, cholesterol, dietary and serum L (p<0.01). In the absence of retinal
pathology, and in advance of disease onset, the relative lack of MP seen in
association with increasing age, tobacco use and family history of ARM supports
the hypothesis that the enhanced risk that these variables represent for ARM may 
be attributable, at least in part, to a parallel deficiency of macular
carotenoids.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17083932 [PubMed - indexed for MEDLINE]

1203: Acta Ophthalmol Scand. 2006 Dec;84(6):812-4.

Vitrectomy for non-ischaemic macular oedema in retinal vein occlusion.

Hvarfner C, Larsson J.

Department of Ophthalmology, Lund University Hospital, Sweden.
charlotte.hvarfner@med.lu.se

PURPOSE: To evaluate the effect of vitrectomy in eyes with non-ischaemic macular 
oedema secondary to hemi and central retinal vein occlusion. METHODS: This
retrospective study analysed the outcome of eight patients with non-ischaemic
macular oedema without posterior vitreous detachment. Six patients had a central 
retinal vein occlusion and two had a hemi retinal vein occlusion. A standard
three-port vitrectomy was performed in all patients. Retinal mapping by optical
coherence tomography and visual acuity (VA) testing were performed before
vitrectomy and at 1, 2 and 12 months postoperatively. RESULTS: At the 1-month
follow-up there was a statistically significant reduction in retinal thickness
(Wilcoxon; p = 0.04) that persisted at 2 months (Wilcoxon; p = 0.04). However, at
12 months there was no difference compared with baseline. LogMAR VA was
significantly improved at 1 month (Wilcoxon p = 0.04), but at 2 and 12 months
there was no difference compared with baseline. CONCLUSIONS: Vitrectomy in hemi
and central retinal vein occlusion has the potential to reduce macular oedema and
improve VA in the early postoperative phase but does not seem to improve the
longterm outcome of the disease.

Publication Types: 
    Case Reports

PMID: 17083544 [PubMed - indexed for MEDLINE]

1204: Acta Ophthalmol Scand. 2006 Dec;84(6):722-33.

Comment in:
    Acta Ophthalmol Scand. 2007 Mar;85(2):234; author reply 234-5.

Intravitreal steroids in the management of macular oedema.

Sivaprasad S, McCluskey P, Lightman S.

Department of Clinical Ophthalmology, Institute of Ophthalmology, Moorfields Eye 
Hospital, London, UK.

The use of intravitreal corticosteroids in the management of macular oedema has
recently gained widespread acceptance. New long-acting steroid preparations and
methods of delivery have facilitated the use of these new modalities. This review
describes the various types of macular oedema for which this therapeutic option
is used and the results.

Publication Types: 
    Review

PMID: 17083528 [PubMed - indexed for MEDLINE]

1205: Disabil Rehabil. 2006 Nov 15;28(21):1331-7.

Impact of visual impairment on service and device use by individuals with
age-related macular degeneration (AMD).

Schmier JK, Halpern MT, Covert DW, Delgado J, Sharma S.

Exponent Inc., Alexandria, Virginia 22314, USA. jschmier@exponent.com

PURPOSE: To assess the patient-reported use of services, supplements, and devices
among individuals with age-related macular degeneration (AMD) and evaluate the
impact of visual impairment level on this use. METHOD: Data for this study were
collected using two instruments, the AMD Health and Impact Questionnaire and the 
Daily Living Tasks Dependent on Vision questionnaire (DLTV). Both questionnaires 
were mailed to members of the Macular Degeneration Partnership. The study was
approved by an IRB and respondents provided consent before participating.
Respondents' visual acuity (VA) was estimated using scores from the DLTV, while
use of services and devices was collected from the AMD Questionnaire.
De-identified data were analysed in SAS. RESULTS: Of 803 respondents, 56% were
male and the mean age was 73 years. Use of services (e.g., counseling,
rehabilitation), and devices significantly increased as VA decreased. Using
standard US costs, costs for services, supplements, and devices ranged from
506-1619 US dollars depending on VA. CONCLUSION: There are substantial
differences in service and device use with increased AMD severity. Delaying
progression of AMD could result in considerable cost savings.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17083181 [PubMed - indexed for MEDLINE]

1206: Proc Natl Acad Sci U S A. 2006 Nov 14;103(46):17456-61. Epub 2006 Nov 1.

Individuals homozygous for the age-related macular degeneration risk-conferring
variant of complement factor H have elevated levels of CRP in the choroid.

Johnson PT, Betts KE, Radeke MJ, Hageman GS, Anderson DH, Johnson LV.

Center for the Study of Macular Degeneration, Neuroscience Research Institute,
University of California, Santa Barbara, CA 93106-5060, USA.

Polymorphisms in the complement factor H gene (CFH) are associated with a
significantly increased risk for, or protection against, the development of
age-related macular degeneration (AMD). The most documented risk-conferring
single-nucleotide polymorphism results in a tyrosine-to-histidine substitution at
position 402 (Y402H) of the CFH protein. In this work, we examined the ocular
distributions and relative abundance of CFH, several CFH-binding proteins, and
abundant serum proteins in the retinal pigmented epithelium (RPE), Bruch's
membrane, and choroid (RPE-choroid) in CFH homozygotes possessing either the
"at-risk" 402HH or "normal" 402YY variants. Although CFH immunoreactivity is high
in the choroid and in drusen, no differences in CFH-labeling patterns between
genotypes are apparent. In contrast, at-risk individuals have significantly
higher levels of the CFH-binding protein, C-reactive protein (CRP), in the
choroidal stroma. Immunoblots confirm that at-risk individuals have approximately
2.5-fold higher levels of CRP in the RPE-choroid; no significant differences in
the levels of CFH or other serum proteins are detected. Similarly, we find no
differences in CFH transcription levels in the RPE-choroid nor evidence for local
ocular CRP transcription. Increased levels of CRP in the choroid may reflect a
state of chronic inflammation that is a by-product of attenuated CFH
complement-inhibitory activity in those who possess the CFH at-risk allele.
Because the CRP-binding site in CFH lies within the domain containing the Y402H
polymorphism, it is also possible that the AMD risk-conferring allele alters the 
binding properties of CFH, thereby leading to choroidal CRP deposition,
contributing to AMD pathogenesis.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17079491 [PubMed - indexed for MEDLINE]

1207: Br J Ophthalmol. 2006 Dec;90(12):1461-3. Epub 2006 Oct 31.

Physical activity and the 15-year cumulative incidence of age-related macular
degeneration: the Beaver Dam Eye Study.

Knudtson MD, Klein R, Klein BE.

Department of Ophthalmology and Visual Sciences, University of Wisconsin School
of Medicine and Public Health,, Madison, WI 53726-2336, USA.
knudtson@epi.ophth.wisc.edu

BACKGROUND: Cardiovascular disease and age-related macular degeneration (AMD) may
share common risk factors. Physical activity improves the cardiovascular risk
profile; however, there have been few studies investigating a relationship
between physical activity and the long-term incidence of AMD. METHODS: The
15-year cumulative incidence of AMD was determined through four examination
phases at 5-year intervals of a population-based study conducted in Beaver Dam,
Wisconsin, USA, initiated in 1988-90 (n = 3874 men and women between ages 43 and 
86 years). Early AMD (pigment abnormalities or soft indistinct drusen), exudative
AMD and geographic atrophy were determined by grading stereoscopic colour fundus 
photographs. Measures of physical activity were obtained through a questionnaire 
administered at the baseline examination. RESULTS: After controlling for age,
sex, history of arthritis, systolic blood pressure, body mass index, smoking and 
education, people with an active lifestyle (defined as regular activity > or =3
times/week) at baseline were less likely to develop exudative AMD (odds ratio
(OR) 0.3, 95% confidence interval (CI) 0.1 to 0.7) compared with people without
an active lifestyle. After multivariate adjustment, increased categories of
number of blocks walked per day decreased the risk of exudative AMD (OR 0.7, 95% 
CI 0.6 to 0.97). Physical activity was not related to the incidence of early AMD 
or pure geographic atrophy. CONCLUSIONS: These data show a protective effect of
physical activity for incident exudative AMD, independent of body mass index and 
other confounders. They also suggest a possible modifiable behaviour that might
be protective against developing AMD.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17077116 [PubMed - indexed for MEDLINE]

1208: Br J Ophthalmol. 2007 Apr;91(4):449-54. Epub 2006 Oct 31.

Comment in:
    Br J Ophthalmol. 2007 Apr;91(4):407-8.

Pretreatment of posterior subtenon injection of triamcinolone acetonide has
beneficial effects for grid pattern photocoagulation against diffuse diabetic
macular oedema.

Shimura M, Nakazawa T, Yasuda K, Shiono T, Nishida K.

Department of Ophthalmology, NTT East Japan Tohoku Hospital, 2-29-1, Yamato,
Wakabayashi, Sendai, Miyagi 984-8560, Japan. masahiko@v101.vaio.ne.jp

AIM: To prospectively evaluate the efficacy of subtenon injection of
triamcinolone acetonide (TA) before laser grid pattern photocoagulation (G-PC)
for the treatment of diffuse diabetic macular oedema (DDME). METHODS: 42 eyes of 
37 consecutive patients with DDME were studied. 1 week before G-PC, 21 eyes
received TA subtenon injection, and the other eyes served as control. The
clinical course of visual acuity (VA) and foveal thickness (FT) was monitored for
up to 24 weeks after G-PC. Mean deviation (MD) of perimetry with 30-2 program on 
Humphrey Perimeter (Zeiss-Humphrey, Dublin, California, USA) was also measured.
The average laser intensity was recorded. RESULTS: After TA injection, FT and VA 
were improved, and subsequent G-PC maintained the improvement for up to 24 weeks 
without recurrence of diffuse diabetic macular oedema. In contrast, G-PC without 
TA injection induced transient worsening of FT and VA, then both were gradually
improved. At 24 weeks after G-PC, MD in the TA-injected eyes was better than
those in control. The required laser intensity in TA-injected eyes was less than 
that for control. CONCLUSION: Subtenon injection of TA prior to G-PC allows for
treatment with a lower intensity of laser spots and also prevents the decrease in
central visual field sensitivity, all of which have clinical advantages for G-PC.

Publication Types: 
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 17077114 [PubMed - indexed for MEDLINE]

1209: J Ocul Pharmacol Ther. 2006 Oct;22(5):370-6.

Visual acuity change after intravitreal triamcinolone in various types of
exudative age-related macular degeneration.

Jonas JB, Strueven V, Kamppeter BA, Harder B, Spandau UH, Schlichtenbrede F.

Department of Ophthalmology, Faculty of Clinical Medicine Mannheim of the
University of Heidelberg, Heidelberg, Germany.
Jost.Jonas@augen.ma.uni-heidelberg.de

OBJECTIVE: The aim of this study was to compare the visual acuity change after an
intravitreal high-dose injection of triamcinolone acetonide (TA) in various types
of exudative age-related macular degeneration (AMD). PARTICIPANTS: The
interventional comparative case series study included 142 patients (146 eyes)
with progressive exudative AMD differentiated into the occult type (n = 78;
53.4%), minimal classic type (n = 45; 30.8%), predominantly classic type (n = 17;
11.6%), and the purely classic type (n = 6; 4.1%). Mean follow-up was 9.7 +/- 7.0
months (3-35.7 months). METHODS: Single intravitreal injection of approximately
20 mg of TA. Outcome measures: Visual acuity, intraocular pressure (IOP).
RESULTS: Gain in visual acuity measured at 1 month (P = 0.20), 2 months (P =
0.43), and at 3 months (P = 0.38) after the intravitreal injection of
triamcinolone and maximal gain in visual acuity during the whole follow-up (P =
0.81) did not vary significantly between the 4 study groups. Correspondingly, the
size of a retinal pigment epithelium detachment was not significantly associated 
with the change in visual acuity at 1 month (P = 0.62), 2 months (P = 0.24), 3
months (P = 0.96), or the maximal gain in visual acuity during follow-up (P =
0.93). The amount of rise in IOP, compared with the baseline value (6.5 +/- 7.4
mmHg), was statistically not associated with the type of subfoveal membrane (P = 
0.20; 95% confidence interval: -0.52, 2.45). CONCLUSIONS: The change in visual
acuity and the rise in IOP in patients with exudative AMD receiving an
intravitreal triamcinolone monotherapy is statistically independent of the type
of subfoveal membrane, including the size of a retinal epithelium detachment.

Publication Types: 
    Clinical Trial
    Comparative Study

PMID: 17076632 [PubMed - indexed for MEDLINE]

1210: Ophthalmology. 2006 Nov;113(11):1974-86.

Laser treatment in patients with bilateral large drusen: the complications of
age-related macular degeneration prevention trial.

Complications of Age-Related Macular Degeneration Prevention Trial Research
Group.

OBJECTIVE: To evaluate the efficacy and safety of low-intensity laser treatment
in the prevention of visual acuity (VA) loss among participants with bilateral
large drusen. DESIGN: Multicenter randomized clinical trial. One eye of each
participant was assigned to treatment, and the contralateral eye was assigned to 
observation. PARTICIPANTS: A total of 1052 participants who had > or =10 large
(>125 microm) drusen and VA> or =20/40 in each eye enrolled through 22 clinical
centers. INTERVENTION: The initial laser treatment protocol specified 60 barely
visible burns applied in a grid pattern within an annulus between 1500 and 2500
mum from the foveal center. At 12 months, eyes assigned to treatment that had
sufficient drusen remaining were retreated with 30 burns by targeting drusen
within an annulus between 1000 and 2000 mum from the foveal center. MAIN OUTCOME 
MEASURE: Proportion of eyes at 5 years with loss of > or =3 lines of VA from
baseline. Secondary outcome measures included the development of choroidal
neovascularization or geographic atrophy (GA), change in contrast threshold,
change in critical print size, and incidence of ocular adverse events. RESULTS:
At 5 years, 188 (20.5%) treated eyes and 188 (20.5%) observed eyes had VA scores 
> or = 3 lines worse than at the initial visit (P = 1.00). Cumulative 5-year
incidence rates for treated and observed eyes were 13.3% and 13.3% (P = 0.95) for
choroidal neovascularization and 7.4% and 7.8% (P = 0.64) for GA, respectively.
The contrast threshold doubled in 23.9% of treated eyes and in 20.5% of observed 
eyes (P = 0.40). The critical print size doubled in 29.6% of treated eyes and in 
28.4% of observed eyes (P = 0.70). Seven treated eyes and 14 observed eyes had an
adverse event of a > or =6-line loss in VA in the absence of late age-related
macular degeneration or cataract. CONCLUSION: As applied in the Complications of 
Age-Related Macular Degeneration Prevention Trial, low-intensity laser treatment 
did not demonstrate a clinically significant benefit for vision in eyes of people
with bilateral large drusen.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial
    Research Support, N.I.H., Extramural

PMID: 17074563 [PubMed - indexed for MEDLINE]

1211: Eye. 2008 Jan;22(1):120-7. Epub 2006 Oct 27.

Evaluation of arteriovenous crossing sheathotomy for decompression of branch
retinal vein occlusion.

Avci R, Inan UU, Kaderli B.

Department of Ophthalmology, Uludag University School of Medicine, Bursa, Turkey.
ravci@uludag.edu.tr

PURPOSE: To report the effects of arteriovenous adventitial sheathotomy on
anatomical and functional improvements in patients with macular oedema due to
branch retinal vein occlusion (BRVO). METHODS: Pars plana vitrectomy and
arteriovenous sheathotomy was performed on 11 patients with BRVO who had vision
loss due to macular oedema. Ten patients with macular oedema due to BRVO and who 
have been treated with grid laser photocoagulation were included in the control
group. The measurement of visual acuity with ETDRS chart was taken preoperatively
and at 1, 3, 6, and 9 months follow-up in the study group and at 1, 3, 6, and 9
months after grid laser in the control group. RESULTS: The mean preoperative
logMAR visual acuity was 0.84+/-0.3 in the surgical group and 1.06+/-0.4 in the
control group. The postoperative mean logMAR visual acuity was 0.41+/-0.2,
0.40+/-0.2, 0.40+/-0.3, and 0.36+/-0.3 at 1, 3, 6, and 9 months follow-up,
respectively. In the control group the postlaser mean logMAR visual acuity was
0.92+/-0.3, 0.87+/-0.4, 0.85+/-0.3, and 0.82+/-0.3 at 1, 3, 6, and 9 months
follow-up, respectively. The improvements of visual acuity in both groups were
statistically significant when compared to pretreatment (P=0.003 and P=0.007 at 9
months in the study and control group, respectively). CONCLUSION: Arteriovenous
sheathotomy for decompression of BRVO in patients who have vision loss due to
macular oedema was safe and effective for anatomical and functional improvement
and resulted in significantly better visual outcomes than a matched control group
of laser-treated eyes.

Publication Types: 
    Evaluation Studies

PMID: 17072289 [PubMed - indexed for MEDLINE]

1212: Prog Retin Eye Res. 2006 Nov;25(6):539-62. Epub 2006 Oct 30.

Maculoplasty for age-related macular degeneration: reengineering Bruch's membrane
and the human macula.

Del Priore LV, Tezel TH, Kaplan HJ.

Department of Ophthalmology, The Edward S. Harkness Eye Institute, Columbia
University, NY, USA. lvdelpriore@gmail.com

Age-related macular degeneration (AMD) is the leading cause of blindness in the
western world. Over the last decade, there have been significant advances in the 
management of exudative AMD with the introduction of anti-VEGF drugs; however,
many patients with exudative AMD continue to lose vision and there are no
effective treatments for advanced exudative AMD or geographic atrophy. Initial
attempts at macular reconstruction using cellular transplantation have not been
effective in reversing vision loss. Herein we discuss the current status of
surgical attempts to reconstruct damaged subretinal anatomy in advanced AMD. We
reinforce the concept of maculoplasty for advanced AMD, which is defined as
reconstruction of macular anatomy in patients with advanced vision loss.
Successful maculoplasty is a three-step process that includes replacing or
repairing damaged cells (using transplantation, translocation or stimulation of
autologous cell proliferation); immune suppression (if allografts are used to
replace damaged cells); and reconstruction or replacement of Bruch's membrane (to
restore the integrity of the substrate for proper cell attachment). In the
current article we will review the rationale for maculoplasty in advanced AMD,
and discuss the results of initial clinical attempts at macular reconstruction.
We will then discuss the role of Bruch's membrane damage in limiting transplant
survival and visual recovery, and discuss the effects of age-related changes
within human Bruch's membrane on the initial attachment and subsequent
proliferation of transplanted cells. We will discuss attempts to repair Bruch's
membrane by coating with extracellular matrix ligands, anatomic reconstitution of
the inner collagen layer, and the effects of Bruch's membrane reconstruction of
ultrastuctural anatomy and subsequent cell behavior. Lastly, we will emphasize
the importance of continued efforts required for successful maculoplasty.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17071125 [PubMed - indexed for MEDLINE]

1213: Ophthalmology. 2007 Jan;114(1):104-7. Epub 2006 Oct 27.

Correlation between optical coherence tomography and fluorescein angiography
findings in diabetic macular edema.

Otani T, Kishi S.

Department of Ophthalmology, Gunma University School of Medicine, Maebashi,
Japan. otanito@showa.gunma-u.ac.jp

OBJECTIVE: To report the relationship between the findings of third-generation
optical coherence tomography (OCT) and fluorescein angiography (FA) in eyes with 
diabetic macular edema (DME). DESIGN: Small case series. PARTICIPANTS: Four eyes 
with DME. METHODS: We compared findings from late-phase FA with corresponding
cross-sectional OCT images using 5-mm-long horizontal and vertical scans. MAIN
OUTCOME MEASURES: Fluorescein angiography and OCT findings in DME. RESULTS:
Fluorescein angiography showed dye pooling within the cystic spaces with a
petalloid pattern in the foveal area in all eyes; 3 eyes had cystic spaces
primarily in the outer plexiform layer (OPL) on OCT. In 16 perifoveal areas in 4 
eyes, FA showed hyperfluorescence with a honeycomb pattern in 7 areas, petalloid 
pattern in 3, and diffuse pattern in 3. The remaining 3 perifoveal areas had no
hyperfluorescence. Optical coherence tomography showed that the perifoveal areas 
with a honeycomb pattern of hyperfluorescence had not only swelling of the OPL
but also cystoid spaces located in the inner nuclear layer (INL). The perifoveal 
areas with no honeycomb pattern but petalloid or diffuse hyperfluorescence had
only retinal swelling of the OPL. In the remaining 3 perifoveal areas without
hyperfluorescence, OCT showed almost normal retinal structures. CONCLUSIONS:
Diabetic macular edema typically showed 2 patterns of dye pooling on late-phase
FA (i.e., petalloid in the fovea and honeycomb in the perifoveal area). The dye
pooling corresponded to large cystic spaces in the OPL, and the honeycomb pattern
to small cystic spaces in the INL.

Publication Types: 
    Case Reports
    Comparative Study

PMID: 17070586 [PubMed - indexed for MEDLINE]

1214: Invest Ophthalmol Vis Sci. 2006 Nov;47(11):4956-61.

The bestrophin mutation A243V, linked to adult-onset vitelliform macular
dystrophy, impairs its chloride channel function.

Yu K, Cui Y, Hartzell HC.

Department of Cell Biology, The Center for Neurodegenerative Disease, Emory
University School of Medicine, 615 Michael Street, Atlanta, GA 30322, USA.

PURPOSE: It has been proposed that Best vitelliform macular dystrophy (BVMD) is
caused by dysfunction in the Cl(-) channel function of human bestrophin-1
(hBest1), but some patients with BVMD who have the hBest1 A243V mutation have
normal electro-oculograms, suggesting that this mutation may not affect Cl(-)
channel function. The purpose of this study was to determine whether the A243V
mutation affects the Cl(-) channel function of hBest1. METHODS: Wild-type alanine
at position 243 was changed to valine by PCR-based mutagenesis. Wild-type (WT)
and A243V hBest1 were transfected into HEK-293 cells, and Cl(-) currents were
measured with the whole-cell patch-clamp technique. The trafficking of proteins
to the plasma membrane was tested by cell-surface biotinylation. RESULTS: WT
hBest1 induced Ca(2+)-activated Cl(-) currents in HEK cells that were >1 nA in
amplitude. The currents produced by the A243V mutant, however, were only
approximately 10% as large as WT. This was not due to the inability of the A243V 
mutant to reach the plasma membrane, as shown by cell-surface biotinylation. The 
A243V mutation changed channel anion selectivity. The WT current exhibited a
relative permeability P(X)/P(Cl) order of SCN(-) > or = I(-) > or = NO(3)(-) >
Br(-) > Cl(-) > HCO(3)(-) and a relative conductance G(X)/G(Cl) order of NO(3)(-)
> SCN(-) > I(-) > or = Br(-) > or = Cl(-) > HCO(3)(-). However, the A243V current
exhibited different sequences: P(X)/P(Cl) was SCN(-) > NO(3)(-) > I(-) > Br(-) > 
Cl(-) > HCO(3)(-) and G(X)/G(Cl) was SCN(-) > NO(3)(-) > or = I(-) > or = Br(-) >
Cl(-) > HCO(3)(-). Unlike several other hBest1 mutations that have
dominant-negative effects on wild-type channels, the A243V-mutation did not
influence the wild-type current when A243V and WT hBest1 were transfected
together. CONCLUSIONS: The disease-causing A243V mutation is associated with
altered hBest1 Cl(-) channel activity. The absence of a dominant negative effect 
of A243V is consistent with the more mild symptoms associated with this mutation.
These results are interpreted in terms of the hypotheses that bestrophins are
Cl(-) channels and regulators of Ca signaling.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17065513 [PubMed - indexed for MEDLINE]

1215: Invest Ophthalmol Vis Sci. 2006 Nov;47(11):4660-4.

Iron induced oxidative damage as a potential factor in age-related macular
degeneration: the Cogan Lecture.

Dunaief JL.

F. M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University 
of Pennsylvania, 305 Stellar-Chance Labs, 422 Curie Boulevard, Philadelphia, PA
19104, USA. jdunaief@mail.med.upenn.edu

Iron is a potent generator of oxidative damage whose levels increase with age,
potentially exacerbating age-related diseases. Several lines of evidence suggest 
that iron accumulation may be a factor in age-related macular degeneration (AMD).
AMD retinas have more iron within the photoreceptors, RPE, and drusen than do
age-matched control retinas. Accelerated AMD-like maculopathy develops in
patients with retinal iron overload from the hereditary disease
aceruloplasminemia. Mice with retinal iron overload resulting from knockout of
ceruloplasmin and its homologue hephaestin exhibit retinal degeneration with some
features of AMD, including subretinal neovascularization, accumulation of RPE
lipofuscin and sub-RPE deposits, and RPE/photoreceptor death. Increased
understanding of the mechanisms of retinal iron homeostasis may help in the
development of therapies to prevent iron overload. For example, herein it is
shown that one regulator of systemic iron homeostasis, HFE, is expressed in the
RPE. Thus, patients with the common disease hereditary hemochromatosis, which is 
often caused by an HFE mutation, may have retinal iron overload predisposing to
AMD. Preliminary data suggest that iron chelation can reduce RPE iron overload in
mice and protect them from degeneration, suggesting that iron-binding drugs may
one day prove useful in reducing RPE oxidative stress and decreasing the risk of 
AMD progression.

Publication Types: 
    Lectures
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17065470 [PubMed - indexed for MEDLINE]

1216: Expert Opin Emerg Drugs. 2006 Nov;11(4):725-40.

Emerging drugs for age-related macular degeneration.

Augustin AJ, Offermann I.

Eye Clinic, Department of Ophthalmology, Moltkestrasse 90, 76133 Karlsruhe,
Germany. 106020.560@compuserve.com

Age-related macular degeneration (AMD) is a leading cause of blindness that until
recently had no recognised drug treatment. In wet AMD, choroidal
neovascularisation (CNV) causes a profound loss of central vision. CNV is a
complex process in which tissue ischaemia and/or inflammation is thought to
trigger production of angiogenic signal molecules. The release of VEGF appears to
be particularly important. Verteporfin photodynamic therapy was the first drug
therapy to be licensed for the treatment of some types of wet AMD. Other
treatments directly targeting VEGF or other aspects of angiogenesis, such as
pegaptanib, ranibizumab and anecortave acetate, have either recently been
licensed or are in the advanced stages of development. These and other promising 
treatment options such as combination strategies are reviewed.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17064228 [PubMed - indexed for MEDLINE]

1217: Int Ophthalmol. 2005 Jun;26(3):93-9. Epub 2006 Oct 25.

The correlation between optical coherence tomographic features and severity of
retinopathy, macular thickness and visual acuity in diabetic macular edema.

Alkuraya H, Kangave D, Abu El-Asrar AM.

Department of Ophthalmology, College of Medicine, King Saud University, Riyadh,
Saudi Arabia.

PURPOSE: To investigate the correlation between the features of optical coherence
tomography (OCT) and the severity of concurrent retinopathy, central macular
thickness (CMT), and best-corrected visual acuity in clinically significant
diabetic macular edema. METHODS: In a prospective study, OCT was performed in 55 
eyes of 55 patients with clinically significant diabetic macular edema, in 58
eyes of 30 patients with diabetes without retinopathy, and in 40 eyes of 21
healthy control subjects. The OCT features were categorized into: type 1,
sponge-like retinal swelling; type 2, cystoid macular edema; type 3, serous
retinal detachment; and type 4, vitreofoveal traction. RESULTS: The CMT in eyes
with diabetic macular edema was significantly higher than in eyes of healthy
controls or in eyes of diabetic patients without retinopathy (P < 0.001). Visual 
acuity correlated with CMT in diabetic macular edema (r = 0.558, P < 0.001). The 
prevalence of OCT type 1 was significantly higher in eyes with mild-to-moderate
non-proliferative retinopathy (NPDR) than in eyes with severe NPDR to
proliferative retinopathy (PDR) (P = 0.0069). The prevalence of OCT types 3 and 4
was significantly higher in eyes with severe NPDR to PDR than in eyes with
mild-to-moderate NPDR (P = 0.0056). OCT type 1 showed the least CMT (P < 0.001)
and the best visual acuity (P = 0.002). CONCLUSIONS: There was a significant
correlation between OCT patterns of clinically significant diabetic macular edema
and severity of retinopathy, CMT, and visual acuity.

PMID: 17063373 [PubMed - indexed for MEDLINE]

1218: Eur J Ophthalmol. 2006 Sep-Oct;16(5):774-5.

Bevacizumab for occult subfoveal neovascularization in age-related macular
degeneration.

Jonas JB, Harder B, Spandau UH, Kamppeter BA, Libondi T, Sauder G.

Department of Ophthalmology, Faculty of Clinical Medicine Mannheim,
Ruprecht-Karls-University of Heidelberg, Heidelberg, Germany.
Jost.Jonas@augen.ma.uni-heidelberg.de

PURPOSE: To report on the treatment of exudative age-related macular degeneration
by intravitreal bevacizumab (Avastin). METHODS: A 78-year-old patient experienced
a progressive loss of visual acuity in her right eye due to an occult subfoveal
neovascular membrane in age-related macular degeneration. She received an
intravitreal injection of 1.5 mg bevacizumab. RESULTS: Within 4 weeks after the
injection, visual acuity improved from 0.40 to 0.60 with complete resolution of
subretinal and intraretinal leakage and edema as shown on optical coherence
tomography. Pre-existing metamorphopsias disappeared. Intraocular pressure
remained in the normal range. During the follow-up, there were no sings of
intraocular inflammation or any other intraocular pathology induced by the
intravitreal injection. CONCLUSIONS: Intravitreal bevacizumab may potentially be 
helpful in the treatment of exudative age-related macular degeneration and may
deserve further evaluation.

Publication Types: 
    Case Reports

PMID: 17061237 [PubMed - indexed for MEDLINE]

1219: Eur J Ophthalmol. 2006 Sep-Oct;16(5):718-21.

Comparison of topical and subconjunctival anesthesia in intravitreal injection
administrations.

Kaderli B, Avci R.

Department of Ophthalmology, Uludag University Hospital, Bursa, Turkey.
drkaderli@yahoo.com

PURPOSE: To compare the effectiveness of topical and subconjunctival anesthesia
in intravitreal injection administrations. METHODS: Twenty-eight patients from a 
university clinic with bilateral diabetic macular edema were prospectively
randomized to receive intravitreal injection of 4 mg triamcinolone under topical 
anesthesia for one eye and subconjunctival anesthesia for the other eye by using 
lidocaine 4%. Patients were asked to grade the pain they experienced during
administration of both anesthesia and intravitreal injection by using a 4-point
pain scale: from 0=no pain to 3=severe pain. Complications that developed during 
both procedures were recorded. RESULTS: The mean pain score experienced during
subconjunctival injections was 0.78+/-0.62, whereas no anesthesia-related pain
was reported in the topical group. The mean pain score experienced during
intravitreal injection was 1.64+/-0.67 in the topical and 0.85+/-0.52 in the
subconjunctival group (p<0.001). The mean total pain scores of both procedures
were 0.82+/-0.34 in the topical and 0.82+/-0.51 in the subconjunctival group
(p>0.05). Nine eyes (32%) developed subconjunctival haemorrhage after
subconjunctival injection, whereas no anesthesia-related complication developed
in the topical group. Subconjunctival haemorrhage was also observed in 5 eyes
(18%) in the topical group and in 11 eyes (40%) in the subconjunctival group
(p>0.05) after intravitreal injection. CONCLUSIONS: Although subconjunctival
anesthesia provides better pain control during intravitreal injections, its
application is more painful and leads to subconjunctival haemorrhage. Moreover,
the mean total pain scores are similar in both methods. Therefore, topical
anesthesia may be more suitable for daily practice.

Publication Types: 
    Randomized Controlled Trial

PMID: 17061223 [PubMed - indexed for MEDLINE]

1220: Eur J Ophthalmol. 2006 Sep-Oct;16(5):711-7.

Optical coherence tomography evaluation of macular edema after intravitreal
triamcinolone acetonide in patients with parafoveal telangiectasis.

Cakir M, Kapran Z, Basar D, Utine CA, Eroglu F, Perente I.

Beyoglu Eye Research and Training Hospital, Istanbul, Turkey.
drmcakir@hotmail.com

PURPOSE: Parafoveal telangiectasis (PT) is a developmental or acquired
microvascular abnormality of the macula. Leakage of the abnormal parafoveal
capillaries leads to macular edema with subsequent decrease in visual acuity.
Intravitreal triamcinolone acetonide is recently widely used in the management of
intraocular proliferative, edematous, and neovascular diseases. METHODS: This
report presents the evaluation of three cases with PT in whom intravitreal
triamcinolone acetonide (IVTA) injection was performed. Fundus fluorescein
angiography (FA) and optical coherence tomography (OCT) were used in follow-up of
the patients. RESULTS: Following pars plana intravitreal injection of 4 mg of
triamcinolone acetonide, the patients had angiographic improvement of the macular
edema and minimal decrease in retinal thickness on OCT, accompanied by
improvement in visual acuity and subjective visual assessment. CONCLUSIONS: The
results of the present study on parafoveal capillary telangiectasis suggest that 
the intravitreal injection of triamcinolone acetonide may be a therapeutic option
to increase visual acuity and decrease vascular leakage on FA. Following IVTA
procedure, follow-up of these patients with both OCT and FA is important for
correct clinical evaluation. Future studies on this method seem to be warranted.

Publication Types: 
    Case Reports

PMID: 17061222 [PubMed - indexed for MEDLINE]

1221: Eur J Ophthalmol. 2006 Sep-Oct;16(5):705-10.

Retinal angiomatous proliferation treated with a combination of intravitreal
triamcinolone acetonide and photodynamic therapy with verteporfin.

Mantel I, Ambresin A, Zografos L.

University Eye Clinic, Hôpital Jules Gonin, Lausanne, Switzerland.
irmela.mantel@ophtal.vd.ch

PURPOSE: Retinal angiomatous proliferation (RAP) is a particularly aggressive
form of exudative age-related macular degeneration. Response to laser
photocoagulation or to photodynamic therapy (PDT) alone is often disappointing.
The purpose of this study was to determine whether intravitreal triamcinolone
acetate (TA) injections followed by PDT in eyes with early stage RAP may be
effective. METHODS: Prospective uncontrolled study, enrolling 11 patients (11
eyes) with stage 2 RAP, treated with intravitreal TA injection followed by PDT.
Patients with large pigment epithelium detachment, RAP stage 3, or pre-existing
glaucoma and known steroid responders were excluded. All patients underwent a
complete ophthalmic examination including fluorescein and indocyanine green (ICG)
angiography and optical coherence tomography (OCT-3) at baseline and at 1, 3, 6, 
and 12 months. Informed consent was obtained from all patients. RESULTS: Mean
follow-up was 14.9 months (range 6 C21 months). Mean age was 82 years. In four
patients a small pigment epithelium detachment was found on tomography. Initial
visual acuity (VA) ranged from 0.1 to 0.6 on the Snellen scale. After calculating
the logarithmic values the authors found an initial mean VA of logMAR 0.61, which
improved by 1.5, 0.9, and 0.9 log lines after 3, 6, and 12 months, respectively. 
Although the VA gain from baseline tended to decrease with time, only 2 patients 
(18%) had an actual loss of acuity>or=3 lines). Retreatment was required in 5
eyes. CONCLUSIONS: In this prospective pilot study examining the use of
intravitreal TA followed by PDT with verteporfin in eyes with stage 2 RAP,
without a large pigment epithelium detachment, the authors found a potential
benefit in terms of stabilization or even improvement of vision.

PMID: 17061221 [PubMed - indexed for MEDLINE]

1222: Eur J Ophthalmol. 2006 Sep-Oct;16(5):686-94.

Is there any relationship between photodynamic therapy for exudative age-related 
macular degeneration and choroidal neovascolarization recurrence? A rationale for
combined treatments.

Piermarocchi S, Sartore M, Lo Giudice G, Monterosso G, Pilotto E, Segato T.

Department of Ophthalmology, University of Padova, Italy.
stefano.piermarocchi@unipd.it

PURPOSE: Photodynamic therapy (PDT) is the treatment of choice for subfoveal
choroidal neovascularization (CNV) in age-related macular degeneration (ARMD).
Interpretation of PDT mechanism of action is not yet fully understood and causes 
of CNV recurrences are unclear. The authors have conducted a retrospective
analysis of fluorescein and indocyanine green angiographies in patients treated
with multiple PDT in order to identify risk factors for recurrence. METHODS: A
total of 342 eyes of 342 patients (207 women and 135 men) with ARMD and subfoveal
CNV were treated with at least two PDT. Angiographic (fluorescein and indocyanine
green) features of recurrences were confronted to pretreatment examinations in
all patients. RESULTS: Post-PDT angiographies showed in all eyes a dark circle
corresponding to the laser spot even 1 year after treatment. Persistence or
progressive regrowth of CNV developed in an area adjacent or corresponding to the
original lesion, without any specific relationship with the location of
fluorescein and indocyanine green late leakage or with presence of abnormal
fluorescence due to pigment abnormalities. At the 3-month angiographic follow-up,
23 patients (6.7%) showed a recurrent CNV resembling shape and dimension of the
laser spot used for the PDT treatment. CONCLUSIONS: The authors failed to
identify angiographic signs helpful to predict the risk of CNV persistence or
recurrence. PDT leaves minor but persistent changes in the choroidal vasculature 
within the treatment area. In some cases, the recurrent CNV seems to be related
to the laser spot of the PDT.

PMID: 17061219 [PubMed - indexed for MEDLINE]

1223: Graefes Arch Clin Exp Ophthalmol. 2007 May;245(5):619-26. Epub 2006 Oct 13.

Analysis of IgG antibody patterns against retinal antigens and antibodies to
alpha-crystallin, GFAP, and alpha-enolase in sera of patients with "wet"
age-related macular degeneration.

Joachim SC, Bruns K, Lackner KJ, Pfeiffer N, Grus FH.

Department of Ophthalmology, Johannes Gutenberg-University, Langenbeckstrasse 1, 
55101, Mainz, Germany.

BACKGROUND: The aim of this study was to compare the IgG antibody patterns
against retinal antigens in sera of patients with age-related macular
degeneration (AMD) and healthy subjects to learn more about possible
immunological aspects of this disease and to identify some of the most important 
antigens. METHODS: Sera of 140 patients were analyzed: healthy volunteers (CO,
n=101) and patients with "wet" age-related macular degeneration (AMD, n=39). The 
sera were tested against western blots of bovine retinal antigens. The IgG
antibody patterns were analyzed by multivariate statistical techniques and some
antigens were identified via LC-MS/MS. RESULTS: All patients showed complex
patterns of IgG antibodies against retinal antigens. The discriminant analysis
revealed a statistical significant difference between the antibody profiles of
the AMD and the CO group (P=0.000023). Not only up-regulations of
antigen-antibody-reactivities in the AMD group at some molecular weight ranges,
e.g. at 46 and 52 kDa, could be seen, but also down-regulations, e.g. at 18 and
36 kDa. The 18 kDa antigen band was identified as alphaB-crystallin, the band at 
46 kDa as alpha-enolase, and one at 52 kDa as glial fibrillary acidic protein.
CONCLUSIONS: We could demonstrate that both groups (wet AMD and CO) show complex 
IgG antibody patterns against retinal antigens, which are highly specific for
each group. This provides further hints for the immunological basis of the
disease. These changes in the antibody profiles in "wet" AMD could represent a
secondary response to retinal damage or can play a causative role in the disease.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 17058093 [PubMed - indexed for MEDLINE]

1224: Trans Am Ophthalmol Soc. 2005;103:173-84; discussion 184-6.

The burden of age-related macular degeneration: a value-based medicine analysis.

Brown GC, Brown MM, Sharma S, Stein JD, Roth Z, Campanella J, Beauchamp GR.

Center for Value-Based Medicine, Flourtown, Pennsylvania, USA.

PURPOSE: To assess the quality-of-life loss and the macroeconomic financial
consequences associated with age-related macular degeneration (ARMD). METHODS:
Time tradeoff utility analysis was performed to assess the quality-of-life
diminution caused by ARMD (both dry and neovascular) in cohorts consisting of (1)
patients with ARMD, (2) ophthalmologists asked to assume they had various degrees
of severity of ARMD, (3) healthcare providers asked to assume they had various
degrees of severity of ARMD, and (4) participants from the general community
asked to assume they had various degrees of severity of ARMD. ARMD was classified
according to vision in the better-seeing eye as (1) mild: 20/20 to 20/40, (2)
moderate: 20/50 to 20/100, (3) severe: < or = 20/200, or (4) very severe: < or = 
20/800. RESULTS: Mild ARMD caused a 17% decrement in the quality of life of the
average patient, similar to that encountered with moderate cardiac angina or
symptomatic human immunodeficiency virus syndrome. Moderate ARMD caused a 32%
decrease in the average patient's quality of life, similar to that associated
with severe cardiac angina or a fractured hip. Severe ARMD caused a 53% decrease 
in quality, more than that of dialysis, and very severe ARMD caused a 60%
decrease in the average ARMD patient's quality of life, similar to that
encountered with end-stage prostate cancer or a catastrophic stroke that leaves a
person bedridden, incontinent, and requiring constant nursing care. Patients with
varying degrees of severity of ARMD were found to have quality-of-life impairment
ranging from 96% to 750% greater than that estimated by treating ophthalmologists
for the same condition. An economic analysis based upon losses to the gross
domestic product suggests that ARMD has approximately a $30 billion annual
negative impact. The return on investment is therefore potentially high for both 
treatment with current ARMD therapies and the research costs invested in the
development of new ARMD treatment modalities. CONCLUSIONS: ARMD is a major public
health problem that has a devastating effect upon patients and marked adverse
financial consequences for the economy.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17057801 [PubMed - indexed for MEDLINE]

1225: Trans Am Ophthalmol Soc. 2005;103:98-107; discussion 107.

Vitrectomy for the treatment of submacular hemorrhages from macular degeneration:
a comparison of submacular hemorrhage/membrane removal and submacular tissue
plasminogen activator-assisted pneumatic displacement.

Thompson JT, Sjaarda RN.

Retina Specialists, Greater Baltimore Medical Center, Baltimore, Maryland, USA.

PURPOSE: To evaluate two techniques for treatment of large submacular hemorrhages
resulting from choroidal neovascularization associated with age-related macular
degeneration. METHODS: Retrospective consecutive case series of 42 eyes of 42
patients who presented with submacular hemorrhages of at least 12 disc areas
associated with visual loss of 3 months or less duration. One of two treatments
was performed: (1) vitrectomy with removal of the submacular
hemorrhage/neovascular membrane complex using subretinal forceps (SRH group), or 
(2) vitrectomy with injection of subretinal tissue plasminogen activator (TPA)
followed by air-fluid exchange to achieve pneumatic displacement of the
hemorrhage (TPA group). RESULTS: The mean visual acuity in the SRH group improved
from 20/1000 -1 to 20/640 -2 at 3 months and 20/640 at 1 year and at the final
examination at a mean of 2.92 years (P = .048). The mean visual acuity in the TPA
group remained stable initially with a visual acuity of 20/500 preoperatively and
20/640 +2 at 3 months. The visual acuity in the TPA group deteriorated to 20/1000
-2 at 1 year and 20/1000 +2 at the final examination at a mean of 2.3 years (P = 
.031). Visual acuity improved by at least .3 logMAR units (3 lines) in 44% of the
SRH group at 3 months and in 48% at 1 year and at the final examination compared 
with 20% of the TPA group at 3 months and 13% at 1 year and at the final
examination (P = .042 comparing SRH and TPA groups at 1 year and final
examination). CONCLUSIONS: Vitrectomy with removal of the subretinal neovascular 
membrane/hemorrhage complex resulted in better visual results than displacement
of the subretinal hemorrhage primarily due to continuing declines in the TPA
group.

Publication Types: 
    Comparative Study
    Evaluation Studies

PMID: 17057793 [PubMed - indexed for MEDLINE]

1226: Trans Am Ophthalmol Soc. 2005;103:37-44; discussion 44-5.

Analysis of Hemicentin-1, hOgg1, and E-selectin single nucleotide polymorphisms
in age-related macular degeneration.

Bojanowski CM, Tuo J, Chew EY, Csaky KG, Chan CC.

National Eye Institute, National Institutes of Health, Bethesda, Maryland, USA.

PURPOSE: Age-related macular degeneration (AMD) is a common disease in which both
environmental and genetic factors have been implicated. Various single nucleotide
polymorphisms (SNPs) have been correlated, through candidate gene association
studies, with age-related diseases, including AMD. Recently we identified an
association between AMD and two SNPs in CX3CR1, which encodes a chemokine
receptor. This study investigates the Hemicentin-1 (an extracellular matrix
protein) Q5345R, hOgg1 (DNA repair gene) S326C, and E-selectin (an adhesion
molecule) S149R SNPs in association with AMD. METHODS: Genomic DNA was extracted 
from peripheral blood of 89 patients with advanced AMD, 97 age-matched controls
without clinical AMD, and 170 random unscreened healthy volunteers. DNA was
subjected to polymerase chain reaction amplification coupled with the restriction
fragment length polymorphism assay. RESULTS: The distribution of the Hemicentin-1
Q5345R, hOgg1 S326C, and E-selectin S149R SNPs did not differ significantly (all 
P values > .05) between the AMD patients and controls. Hemincentin-1 5345R was
not found in any subject. hOgg1 326C allele frequency was 21.35% (38 of 178) in
the AMD group compared with 19.12% (65 of 340) in the random controls and 19.59% 
(38 of 194) in the age-matched controls. E-selectin 149R allele frequencies were 
8.99% (16 of 178) in AMD cases, 9.41% (32 of 340) in random controls, and 10.82% 
(21 of 194) in age-matched controls. CONCLUSIONS: We were not able to demonstrate
an association between the Hemicentin-1, hOgg1, and E-selectin SNPs and AMD
development in the currently available cases and controls. Further candidate
genes, particularly those involved in extracellular matrix, oxidative stress, and
immune system functions, are currently being screened in our laboratory.

Publication Types: 
    Research Support, N.I.H., Intramural

PMID: 17057786 [PubMed - indexed for MEDLINE]

1227: Graefes Arch Clin Exp Ophthalmol. 2007 Mar;245(3):338-44. Epub 2006 Oct 20.

Amplitude calculation in multifocal ERG: comparison of repeatability in 30 Hz
flicker and first order kernel stimulation.

Mazinani BA, Repas T, Weinberger AW, Vobig MA, Walter P.

Department of Ophthalmology, RWTH Aachen University, Pauwelsstrasse 30, 52057,
Aachen, Germany. bmazinani@gmx.de

BACKGROUND: In multifocal flicker stimulation, each step of the M-sequence
consists of four consecutive flashes with a frequency of 30 Hz. The resulting
amplitudes can be calculated by means of a discrete fourier transformation (DFT).
With this method, amplitudes can be calculated without having to localise peaks
and troughs and set cursors. The purpose of this study is to compare the re-test 
stability of this method to conventional mfERG stimulation. METHODS: We examined 
27 healthy subjects using a RETI-scan device (Roland Consult, Wiesbaden). We used
61 hexagons within a 30 deg. visual field. We compared the classic first order
kernel (FOK) stimulation with the multifocal 30 Hz Flicker (mfFlicker-ERG)
stimulation. Repeatability was calculated using coefficients of variation.
RESULTS: Both methods had coefficients of 15% for the sum P1-amplitude and the
DFT results, respectively. The amplitudes calculated by flicker and DFT were
approximately 25% smaller than the FOK amplitudes. CONCLUSIONS: This study showed
no difference of re-test repeatability between the mfFlicker-ERG and the
conventional first order kernel method. Since the mfFlicker-ERG method does not
require a definition of peaks and troughs in order to calculate the amplitudes,
we believe that a common source of error is eradicated, especially when dealing
with distorted or atypical curves.

Publication Types: 
    Comparative Study

PMID: 17053898 [PubMed - indexed for MEDLINE]

1228: Science. 2006 Nov 10;314(5801):992-3. Epub 2006 Oct 19.

A variant of the HTRA1 gene increases susceptibility to age-related macular
degeneration.

Yang Z, Camp NJ, Sun H, Tong Z, Gibbs D, Cameron DJ, Chen H, Zhao Y, Pearson E,
Li X, Chien J, Dewan A, Harmon J, Bernstein PS, Shridhar V, Zabriskie NA, Hoh J, 
Howes K, Zhang K.

Department of Ophthalmology and Visual Sciences, Moran Eye Center, University of 
Utah School of Medicine, Salt Lake City, UT 84132, USA.

Age-related macular degeneration (AMD) is the most common cause of irreversible
vision loss in the developed world and has a strong genetic predisposition. A
locus at human chromosome 10q26 affects the risk of AMD, but the precise gene(s) 
have not been identified. We genotyped 581 AMD cases and 309 normal controls in a
Caucasian cohort in Utah. We demonstrate that a single-nucleotide polymorphism,
rs11200638, in the promoter region of HTRA1 is the most likely causal variant for
AMD at 10q26 and is estimated to confer a population attributable risk of 49.3%. 
The HTRA1 gene encodes a secreted serine protease. Preliminary analysis of
lymphocytes and retinal pigment epithelium from four AMD patients revealed that
the risk allele was associated with elevated expression levels of HTRA1 mRNA and 
protein. We also found that drusen in the eyes of AMD patients were strongly
immunolabeled with HTRA1 antibody. Together, these findings support a key role
for HTRA1 in AMD susceptibility and identify a potential new pathway for AMD
pathogenesis.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17053109 [PubMed - indexed for MEDLINE]

1229: Science. 2006 Nov 10;314(5801):989-92. Epub 2006 Oct 19.

HTRA1 promoter polymorphism in wet age-related macular degeneration.

Dewan A, Liu M, Hartman S, Zhang SS, Liu DT, Zhao C, Tam PO, Chan WM, Lam DS,
Snyder M, Barnstable C, Pang CP, Hoh J.

Department of Epidemiology and Public Health, Yale University, 60 College Street,
New Haven, CT 06520, USA.

Age-related macular degeneration (AMD), the most common cause of irreversible
vision loss in individuals aged older than 50 years, is classified as either wet 
(neovascular) or dry (nonneovascular). Inherited variation in the complement
factor H gene is a major risk factor for drusen in dry AMD. Here we report that a
single-nucleotide polymorphism in the promoter region of HTRA1, a serine protease
gene on chromosome 10q26, is a major genetic risk factor for wet AMD. A
whole-genome association mapping strategy was applied to a Chinese population,
yielding a P value of <10(-11). Individuals with the risk-associated genotype
were estimated to have a likelihood of developing wet AMD 10 times that of
individuals with the wild-type genotype.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17053108 [PubMed - indexed for MEDLINE]

1230: Annu Rev Med. 2007;58:491-504.

Targeting VEGF-A to treat cancer and age-related macular degeneration.

Ferrara N, Mass RD, Campa C, Kim R.

Genentech, Inc., South San Francisco, California 94080, USA. nf@gene.com

Inhibiting angiogenesis is a promising strategy to treat cancer and several other
disorders, including intraocular neovascular syndromes. The identification of
vascular endothelial growth factor (VEGF)-A as a major regulator of normal and
pathological angiogenesis has enabled significant progress toward effective
treatments for such disorders. Several VEGF inhibitors have been recently
approved by the U.S. Food and Drug Administration for the treatment of cancer and
the neovascular form of age-related macular degeneration. This review summarizes 
the basic biology of VEGF-A and illustrates the clinical progress in targeting
this molecule.

Publication Types: 
    Review

PMID: 17052163 [PubMed - indexed for MEDLINE]

1231: Br J Ophthalmol. 2007 May;91(5):576-8. Epub 2006 Oct 18.

Assessment of the contribution of CFH and chromosome 10q26 AMD susceptibility
loci in a Russian population isolate.

Fisher SA, Rivera A, Fritsche LG, Babadjanova G, Petrov S, Weber BH.

Department of Medical and Molecular Genetics, Guy's King's and St Thomas' School 
of Medicine, King's College, London, UK.

BACKGROUND/AIMS: A strong association has been confirmed between age-related
macular degeneration (AMD) and variants at two independent loci including
Tyr402His in the complement factor H (CFH) on 1q32 and Ser69Ala at LOC387715, a
hypothetical gene on chromosome 10q26. The contribution of both loci to AMD was
investigated in an isolated north-west Russian population. METHODS: Together with
a PLEKHA1 variant at 10q26, the CFH Tyr402His and LOC387715 Ser69Ala
polymorphisms were genotyped in 155 patients with AMD and 151 age-matched
controls. chi(2) and Mantel-Haenszel (M-H) score tests were used to test for
association. Sex-adjusted ORs were calculated. RESULTS: The frequency of the
Tyr402His C allele was significantly higher in patients with AMD compared with
controls (p(M-H)=0.0035). The increased risk observed in patients homozygous for 
the C allele (OR(HOM)=2.71, 95% CI 1.25 to 5.90) in this indigenous Russian
population was considerably lower than that observed in previous western
Caucasian populations. A significant increase in the frequency of the LOC387715
variant was observed in patients with late-stage AMD compared with controls
(p(M-H)=0.007), with a homozygous OR of 3.47 (95% CI 1.01 to 11.9), although this
association was not seen with early-stage AMD. CONCLUSION: The CFH gene
contributes to AMD in this Russian population, although the risk conferred is
considerably lower in this population than that found in other Western
populations. A contribution of LOC387715 to disease in this population is also
likely to be of weak effect.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17050575 [PubMed - indexed for MEDLINE]

1232: Expert Opin Biol Ther. 2006 Nov;6(11):1237-45.

Ranibizumab: treatment in patients with neovascular age-related macular
degeneration.

Pieramici DJ, Avery RL.

The California Retina Consultants and Research Foundation, 515 East Micheltorena 
St, Suite C, Santa Barbara, California 93103, USA.

Vascular endothelial growth factor (VEGF)-A is a major regulator of angiogenesis 
and vascular permeability implicated in the development of diseases involving
pathological angiogenesis and increased vascular permeability, such as
neovascular age-related macular degeneration (AMD). LUCENTIS (ranibizumab), a
humanized antigen-binding fragment (Fab) that neutralizes all VEGF-A isoforms and
their biologically active degradation products, was recently approved by the FDA.
Ranibizumab is the first FDA-approved treatment for neovascular AMD that
maintains or improves vision in > or = 90% patients and provides a > or =
15-letter improvement in visual acuity for a quarter to a third of patients with 
all choroidal neovascularisation subtypes. Ranibizumab was associated with a < or
= 1.7% rate of key serious ocular adverse events, such as endophthalmitis and
uveitis, in two pivotal Phase III trials.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17049020 [PubMed - indexed for MEDLINE]

1233: Ophthalmic Res. 2006;38(6):324-8. Epub 2006 Oct 13.

Repeated intravitreal injection of triamcinolone for exudative age-related
macular degeneration.

Jonas JB, Spandau UH, Kamppeter BA, Vossmerbaeumer U, Harder B.

Department of Ophthalmology, Faculty of Clinical Medicine Mannheim, University of
Heidelberg, Mannheim, Germany. Jonst.Jonas@augen.ma.uni-heidelberg.de

BACKGROUND: Intravitreal triamcinolone acetonide has been discussed as treatment 
for exudative age-related macular degeneration (AMD). Objectives: To give an
updated report on repeated intravitreal injections of triamcinolone acetonide
(IVTA) for the treatment of exudative AMD. METHODS: The case-series study
included 24 patients (24 eyes) with progressive exudative AMD who had shown an
increase in, or stabilization of, visual acuity after a first IVTA, and who
eventually experienced a deterioration of visual acuity. The 24 (6.5%) eyes were 
selected out of a total group of 369 eyes who had received IVTA for exudative AMD
within the last 5 years. All patients of the study received a second IVTA
(approximately 20 mg) 3.7-38.5 months after the first injection. Main outcome
measure was visual acuity. RESULTS: After the first injection, best corrected
visual acuity improved significantly (p = 0.001) from 0.75 +/- 0.34 logMAR to a
minimum of 0.58 +/- 0.30 logMAR during follow-up, with 10 (42%) eyes improving in
visual acuity by two or more Snellen lines. Towards the end of follow-up after
the first injection, best corrected visual acuity decreased significantly (p =
0.03) compared with the baseline value. After the second injection, visual acuity
did not change markedly from baseline to a mean maximal visual acuity during
follow-up. Comparing the last postoperative examination at the end of the
follow-up after the second IVTA with the preoperative examination, a
significantly (p = 0.001) higher number of eyes lost in visual acuity [19 (79%)
eyes] than gained in visual acuity [3 (12%) eyes]. CONCLUSIONS: In selected eyes 
with an increase in visual acuity after a first IVTA (20 mg), repeated IVTA
temporarily stabilizes visual acuity with a drop in visual acuity towards the end
of follow-up. Copyright 2006 S. Karger AG, Basel.

PMID: 17047404 [PubMed - indexed for MEDLINE]

1234: Comput Biol Med. 2007 Jun;37(6):836-41. Epub 2006 Oct 13.

Classification of macular and optic nerve disease by principal component
analysis.

Kara S, Güven A, Içer S.

Department of Electronics Engineering, Erciyes University, 38039 Kayseri, Turkey.
kara@erciyes.edu.tr

In this study, pattern electroretinography (PERG) signals were obtained by
electrophysiological testing devices from 70 subjects. The group consisted of
optic nerve and macular diseases subjects. Characterization and interpretation of
the physiological PERG signal was done by principal component analysis (PCA).
While the first principal component of data matrix acquired from optic nerve
patients represents 67.24% of total variance, the first principal component of
the macular patients data matrix represents 76.81% of total variance. The basic
differences between the two patient groups were obtained with first principal
component, obviously. In addition, the graphic of second principal component vs. 
first principal component of optic nerve and macular subjects was analyzed. The
two patient groups were separated clearly from each other without any hesitation.
This research developed an auxiliary system for the interpretation of the PERG
signals. The stated results show that the use of PCA of physiological waveforms
is presented as a powerful method likely to be incorporated in future medical
signal processing.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17046736 [PubMed - indexed for MEDLINE]

1235: Am J Ophthalmol. 2006 Dec;142(6):961-9. Epub 2006 Aug 2.

Vascular endothelial growth factor is a critical stimulus for diabetic macular
edema.

Nguyen QD, Tatlipinar S, Shah SM, Haller JA, Quinlan E, Sung J, Zimmer-Galler I, 
Do DV, Campochiaro PA.

The Wilmer Eye Institute, The Johns Hopkins University School of Medicine,
Baltimore, Maryland 21287-9277, USA.

PURPOSE: The role of vascular endothelial growth factor (VEGF) in diabetic
macular edema (DME) was tested with ranibizumab, a specific antagonist of VEGF.
DESIGN: A nonrandomized clinical trial. METHODS: Ten patients with chronic DME
received intraocular injections of 0.5 mg of ranibizumab at baseline and at one, 
two, four, and six months. The primary outcome was change in foveal thickness
between baseline and seven months, and the secondary outcome measures were
changes from baseline in visual acuity and macular volume. RESULTS: Mean values
at baseline were 503 microm for foveal thickness, 9.22 mm3 for macular volume,
and 28.1 letters (20/80) read on an Early Treatment Diabetic Retinopathy Study
(ETDRS) visual acuity chart. At seven months (one month after the fifth
injection), the mean foveal thickness was 257 microm, which was a reduction of
246 microm (85% of the excess foveal thickness present at baseline; P = .005 by
Wilcoxon signed-rank test for likelihood that this change is due to ranibizumab
rather than chance). The macular volume was 7.47 mm3, which was a reduction of
1.75 mm3 (77% of the excess macular volume at baseline; P = .009). Mean visual
acuity was 40.4 letters (20/40), which was an improvement of 12.3 letters (P =
.005). The injections were well-tolerated with no ocular or systemic adverse
events. CONCLUSION: Intraocular injections of ranibizumab significantly reduced
foveal thickness and improved visual acuity in 10 patients with DME, which
demonstrated that VEGF is an important therapeutic target for DME. A randomized, 
controlled, double-masked trial is needed to test whether intraocular injections 
of ranibizumab provide long-term benefit to patients with DME.

Publication Types: 
    Clinical Trial
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17046701 [PubMed - indexed for MEDLINE]

1236: J Am Geriatr Soc. 2006 Oct;54(10):1557-62.

Age-related macular degeneration: self-management and reduction of depressive
symptoms in a randomized, controlled study.

Brody BL, Roch-Levecq AC, Kaplan RM, Moutier CY, Brown SI.

Department of Ophthalmology, Shiley Eye Center, University of California at San
Diego, La Jolla, CA 92093, USA.

OBJECTIVES: To assess the effectiveness of a self-management program for
age-related macular degeneration (AMD) in reducing depressive symptoms. DESIGN:
Analysis of 6-month follow-up for a subset of participants in a randomized,
controlled trial who were clinically depressed at baseline. SETTING: University
ophthalmology clinic. PARTICIPANTS: Thirty-two depressed older adult volunteers
(mean age 81.5) with advanced AMD who had been randomized to a self-management
program (n=12) or one of two control conditions (n=20). Subjects were included if
at baseline they met criteria from the Structured Clinical Interview for the
Diagnostic and Statistical Manual of Mental Disorders, Axis, I, Fourth Edition,
Research Version, for major or minor depressive disorder with significant
depressive symptoms (>or=5 points) on the 15-item Geriatric Depression Scale
(GDS-15). INTERVENTION: AMD self-management program consisting of cognitive and
behavioral elements including health education and enhancement of problem-solving
skills. MEASUREMENTS: Primary outcome measure was GDS-15. Secondary outcome
measures included National Eye Institute Visual Function Questionnaire (NEI-VFQ) 
and AMD Self-Efficacy Questionnaire. RESULTS: At 6-month follow-up, the
self-management group had a significantly greater reduction in depressive
symptoms on the GDS-15 than the controls (P=.03). The mean reduction of 2.92
points in the self-management group was more than the 2-point change threshold
considered to be clinically meaningful. Change on the NEI-VFQ was nonsignificant.
Reduction in depressive symptoms was associated with greater self-efficacy in the
self-management group. CONCLUSION: These findings may support the effectiveness
of an AMD self-management program for depressed older adults with advanced vision
loss from AMD.

Publication Types: 
    Randomized Controlled Trial
    Research Support, N.I.H., Extramural

PMID: 17038074 [PubMed - indexed for MEDLINE]

1237: Br J Ophthalmol. 2007 Mar;91(3):349-53. Epub 2006 Oct 11.

Autologous retinal pigment epithelium-choroid sheet transplantation in age
related macular degeneration: morphological and functional results.

Treumer F, Bunse A, Klatt C, Roider J.

Department of Ophthalmology, University of Schleswig-Holstein, Campus Kiel,
Hegewischstr, 2, 24105 Kiel, Germany. f.treumer@ophthalmol.uni-kiel.de

OBJECTIVE: To evaluate the outcome of autologous retinal pigment epithelium
(RPE)-choroid sheet transplantation after removal of a subfoveal choroidal
neovascularisation (CNV) in patients with age related macular degeneration (AMD).
METHODS: RPE-choroid sheet transplantation was performed in 10 consecutive
patients with exudative AMD (n = 9) or geographic atrophy (n = 1). After CNV
extraction, an autologous RPE-choroid patch was translocated from the
midperiphery under the macula. Follow-up was between 6 and 12 months. Visual
acuity testing and microperimetry (Nidek-MP1) as well as autofluorescence,
fluorescein and indocyanine green (ICG) angiography were performed and the data
were analysed retrospectively. RESULTS: Visual acuity (logarithm of minimum angel
of resolution) before operation ranged from 0.7 to 1.8 (mean 1.37) and after
operation from 0.4 to 1.6 (mean 1.24). Visual acuity after operation improved in 
seven patients (by a mean of 0.26), remained stable in one patient and decreased 
in two patients. Microperimetry showed light sensitivity and fixation on the
sheet in five cases. ICG angiography demonstrated perfusion through the
RPE-choroid graft in nine patients. Postoperative complications included retinal 
detachment (n = 1) and epiretinal membrane formation (n = 2). The patient with
geographic atrophy developed a CNV after surgery. CONCLUSIONS: Autologous
RPE-choroid sheet transplantation is feasible and a comparatively safe procedure.
Microperimetry showed fixation and light perception over the graft with a
moderate increase in mean visual acuity.

Publication Types: 
    Evaluation Studies

PMID: 17035275 [PubMed - indexed for MEDLINE]

1238: Br J Ophthalmol. 2007 Apr;91(4):430-3. Epub 2006 Oct 11.

Is early age-related macular degeneration related to carotid artery stiffness?
The Atherosclerosis Risk in Communities Study.

Cheung N, Liao D, Islam FM, Klein R, Wang JJ, Wong TY.

Centre for Eye Research Australia, University of Melbourne, 32 Gisborne Street,
Melbourne, Victoria 3002, Australia.

BACKGROUND/ PURPOSE: Atherosclerosis and vascular stiffness have been implicated 
in the pathogenesis of age-related macular degeneration (AMD). The association of
carotid artery stiffness, a measure of arterial elasticity reflecting early
atherosclerosis, with early AMD, was examined in this study. METHODS: A
population-based, cross-sectional study of 9954 middle-aged people (age range
51-72 years). The presence of AMD signs was determined from fundus photographs
according to the Wisconsin grading protocol. Carotid arterial stiffness was
measured from high-resolution ultrasonic echo tracking of the left common carotid
artery, and was defined as an adjusted arterial diameter change (AADCmu). A
smaller AADC reflects greater carotid artery stiffness. The associations of pulse
pressure and carotid artery intima-media thickness (IMT) with early AMD signs
were also analysed. RESULTS: In the study population, 454 (4.6%) had early AMD.
The mean (SD) AADC was 403 (127) mu. After adjusting for age, sex, race/centre,
education, cigarette smoking, fasting glucose, lipid profile and inflammatory
markers, a smaller AADC was found to be not associated with early AMD (odds ratio
0.94; 95% confidence interval, 0.71 to 1.25) or its component lesions. Other
measures of arterial stiffness (pulse pressure) and atherosclerosis (carotid IMT)
were also not associated with early AMD. CONCLUSIONS: Carotid artery stiffness
was not associated with signs of early AMD in this middle-aged population. These 
data provide no evidence of a link between age-related elastoid changes and early
atherosclerotic processes in the carotid arteries and early AMD.

Publication Types: 
    Multicenter Study
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17035267 [PubMed - indexed for MEDLINE]

1239: Nat Rev Neurosci. 2006 Nov;7(11):860-72. Epub 2006 Oct 11.

Macular degeneration: recent advances and therapeutic opportunities.

Rattner A, Nathans J.

Department of Molecular Biology and Genetics, Howard Hughes Medical Institute,
Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.

The central retina mediates high acuity vision, and its progressive dysfunction
due to macular degeneration is the leading cause of visual disability among
adults in industrialized societies. Here, we summarize recent progress in
understanding the pathophysiology of macular degeneration and the implications of
this new knowledge for treatment and prevention. The past decade has witnessed
remarkable advances in this field, including the development of new, non-invasive
retinal imaging technologies, the development of animal models for macular
disease, and the isolation of many of the genes responsible for both early- and
late-onset macular diseases. These advances have set the stage for the
development of effective mechanism-based therapies.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Review

PMID: 17033682 [PubMed - indexed for MEDLINE]

1240: Retina. 2006 Oct;26(8):922-7.

Optical coherence tomography in the diagnosis and monitoring of cystoid macular
edema in patients with retinitis pigmentosa.

Chung H, Hwang JU, Kim JG, Yoon YH.

Department of Ophthalmology, Asan Medical Center, University of Ulsan, College of
Medicine, Seoul, Korea.

PURPOSE: To identify cystoid macular edema (CME) in patients with retinitis
pigmentosa (RP) using optical coherence tomography (OCT) and to evaluate response
to acetazolamide by serial OCT. METHODS: Twenty-nine consecutive RP patients were
included in the study. Patients with CME were treated with acetazolamide (125 or 
250 mg/d for 4-12 months). OCT, fluorescein angiography, and determination of
best-corrected visual acuity (BCVA) were performed initially and throughout the
follow-up period. RESULTS: Ten of the 29 patients had CME by OCT. Of these 10
patients, 5 had various degrees of fluorescein leakage by fluorescein
angiography. After acetazolamide treatment, six patients had significant
decreases in macular edema in at least one eye by follow-up OCT. In six patients,
visual acuity improved by > or =1 line in at least one eye. The change of central
foveal thickness shown by OCT was significantly correlated with the change of
logMAR of BCVA (Pearson correlation coefficient [r] = 0.576; P = 0.008). We
observed no differences in the change of central foveal thickness by OCT
(Mann-Whitney test; P = 1.000) and in the change of logMAR of BCVA (Mann-Whitney 
test; P = 0.106) between patients treated with 125 mg/d acetazolamide and those
treated with 250 mg/d acetazolamide. CONCLUSIONS: These results indicate that OCT
is a valuable tool in the detection and follow-up of CME in RP patients.
Treatment with acetazolamide resulted in marked improvement in OCT-diagnosed CME 
in RP, but visual improvement was variable.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17031294 [PubMed - indexed for MEDLINE]

1241: Retina. 2006 Oct;26(8):896-901.

Intravitreal triamcinolone acetonide treatment of macular edema associated with
central retinal vein occlusion.

Goff MJ, Jumper JM, Yang SS, Fu AD, Johnson RN, McDonald HR, Ai E.

Pacific Vision Foundation, California Pacific Medical Center, San Francisco,
California, USA.

PURPOSE: To evaluate treatment of macular edema associated with central retinal
vein occlusion (CRVO) using intravitreal triamcinolone acetonide. METHODS:
Retrospective review of data for 29 eyes of 29 patients with CRVO and macular
edema treated with intravitreal triamcinolone acetonide. Initial visual acuity,
intraocular pressure, and history of glaucoma were recorded. Final visual acuity,
intraocular pressure, and adverse events were recorded during the treatment
period. RESULTS: Twenty-nine eyes were treated with intravitreal injection. The
mean follow-up was 348 days. The median initial Early Treatment Diabetic
Retinopathy Study visual acuity was 20/250 (median logMAR, 1.1). The median
visual acuity 3 months after injection was 20/125 (median logMAR, 0.8). This
difference was statistically significant. The median final visual acuity was
20/250 (median logMAR, 1.1). This difference in visual acuity was not
statistically significant. Elevated intraocular pressure, excluding that related 
to neovascularization, occurred in 5 of 22 patients. Subgroup analysis revealed
that patients who received multiple injections had better outcomes. CONCLUSION:
Intravitreal triamcinolone acetonide may improve vision transiently but does not 
appear to result in a sustained visual acuity benefit for patients with macular
edema associated with CRVO. Repeated injections may be necessary. The risk of
glaucoma is significant, and additional study is required to further characterize
this and other risks.

PMID: 17031289 [PubMed - indexed for MEDLINE]

1242: Retina. 2006 Oct;26(8):889-95.

One-year safety and efficacy of intravitreal triamcinolone acetonide for the
management of macular edema secondary to central retinal vein occlusion.

Gregori NZ, Rosenfeld PJ, Puliafito CA, Flynn HW Jr, Lee JE, Mavrofrides EC,
Smiddy WE, Murray TG, Berrocal AM, Scott IU, Gregori G.

Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami
Miller School of Medicine, Miami, Florida 33136, USA.

PURPOSE: To evaluate the safety and efficacy of intravitreal triamcinolone
acetonide (IVTA) as treatment for macular edema associated with central retinal
vein occlusion (CRVO). METHODS: A retrospective review was performed of data for 
40 consecutive patients (40 eyes) with CRVO and macular edema treated with IVTA
at the Bascom Palmer Eye Institute (Miami, FL). RESULTS: Median duration of
symptoms before the first injection was 3 months (range, 1 day to 8 years).
Median Snellen visual acuity was 20/400 at baseline (range, 20/60 to light
perception; n = 40), 20/300 at 1 month (P = 0.010; n = 37), 20/300 at 3 months (P
= 0.007; n = 33), 20/400 at 6 months (P = 0.726; n = 28), and 8/200 at 1 year (P 
= 0.569; n = 17). Vision improved by > or =3 lines in 21% of eyes at 1 month, 27%
at 3 months, 14% at 6 months, and 12% at 1 year. Visual acuity was unchanged from
baseline in 71% of eyes at 6 months and 1 year. By 1 year, 50% of eyes received
more than one injection (mean = 1.6 injections; range 1-4 injections). Overall,
intraocular pressure increased by > or =10 mmHg in 24% of eyes at 1 year.
Trabeculectomy was performed on 2 of 12 eyes with preexisting open-angle
glaucoma. CONCLUSION: IVTA can substantially improve vision in some patients, but
most patients have stable visual acuity compared with baseline at 1 year despite 
repeated injections.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17031288 [PubMed - indexed for MEDLINE]

1243: Retina. 2006 Oct;26(8):877-81.

Evaluation of anterior chamber inflammatory activity in eyes treated with
intravitreal bevacizumab.

Kiss C, Michels S, Prager F, Weigert G, Geitzenauer W, Schmidt-Erfurth U.

Department of Ophthalmology and Optometry, Medical University of Vienna, Vienna, 
Austria.

PURPOSE: To evaluate the effect of intravitreal bevacizumab on anterior chamber
inflammatory activity. METHODS: Sixty-one consecutive patients with neovascular
age-related macular degeneration were examined before, 1 day, and 1 week after
intravitreal administration of 1 mg of bevacizumab (0.04 mL) for neovascular
age-related macular degeneration. The intravitreal injection was performed under 
sterile conditions. Twenty-one fellow eyes served as controls. The anterior
chamber inflammatory activity was evaluated using biomicroscopy and the laser
flare meter (Kowa FM-500, Kowa Company, Ltd., Tokyo, Japan). RESULTS: None of the
61 consecutive patients had a significant, clinically detectable inflammatory
response within 1 week of follow-up. Anterior chamber inflammatory activity
measured by the laser flare meter ranged from 1.9 counts/ms to 70.0 counts/ms
(mean +/- SD, 13.2 +/- 16.9 counts/ms; 95% confidence interval [CI], 7.8-18.6)
before treatment. One day and 1 week after injection, values were between 3.2
counts/ms and 30.0 counts/ms (mean +/- SD, 9.1 +/- 6.2 counts/ms; 95% CI,
7.2-11.1) and 2.0 counts/ms and 25.1 counts/ms (mean +/- SD, 7.3 +/- 4.6
counts/ms; 95% CI, 5.8-8.8), respectively. There was a significant reduction of
anterior chamber flare at 1 week compared with baseline (P = 0.031). The control 
eyes had constantly low flare measures. CONCLUSION: No inflammatory response was 
detected clinically and by the laser flare meter after intravitreal bevacizumab
administration. The slight reduction in anterior chamber flare could be due to
the known antiinflammatory effect of anti-vascular endothelial growth factor
therapy.

PMID: 17031286 [PubMed - indexed for MEDLINE]

1244: Retina. 2006 Oct;26(8):859-70.

Comment in:
    Retina. 2007 Oct;27(8):1154-6; author reply 1156-8.

Development of ranibizumab, an anti-vascular endothelial growth factor antigen
binding fragment, as therapy for neovascular age-related macular degeneration.

Ferrara N, Damico L, Shams N, Lowman H, Kim R.

Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA. nf@gene.com

BACKGROUND: Angiogenesis is a key aspect of the wet form of age-related
neovascular (AMD), the leading cause of blindness in the elderly population.
Substantial evidence indicated that vascular endothelial growth factor (VEGF)-A
is a major mediator of angiogenesis and vascular leakage in wet AMD. VEGF-A is
the prototype member of a gene family that includes also PlGF, VEGF-B, VEGF-C,
VEGF-D and the orf virus-encoded VEGF-E. Several isoforms of VEGF-A can be
generated due to alternative mRNA splicing. Various VEGF inhibitors have been
clinically developed. Among these, ranibizumab is a high affinity recombinant Fab
that neutralizes all isoforms of VEGF-A. The article briefly reviews the biology 
of VEGF and then focuses on the path that led to clinical development of
ranibizumab. RESULTS: The safety and efficacy of ranibizumab in the treatment of 
neovascular AMD have been evaluated in two large phase III, multicenter,
randomized, double-masked, controlled pivotal trials in different neovascular AMD
patient populations. Combined, the trial results indicate that ranibizumab
results not only in a slowing down of vision loss but also in a significant
proportion of patients experiencing a clinically meaningful vision gain. The
visual acuity benefit over control was observed regardless of CNV lesion type.
Furthermore, the benefit was associated with a low rate of serious adverse
events. CONCLUSIONS: Ranibizumab represents a novel therapy that, for the first
time, appears to have the potential to enable many AMD patients to obtain a
meaningful and sustained gain of vision. On June 30 2006, ranibizumab was
approved by the US Food and Drug Administration for the treatment of wet AMD.

Publication Types: 
    Review

PMID: 17031284 [PubMed - indexed for MEDLINE]

1245: Ophthalmology. 2006 Nov;113(11):2002.e1-12. Epub 2006 Oct 5.

Systemic bevacizumab (Avastin) therapy for neovascular age-related macular
degeneration: twenty-four-week results of an uncontrolled open-label clinical
study.

Moshfeghi AA, Rosenfeld PJ, Puliafito CA, Michels S, Marcus EN, Lenchus JD,
Venkatraman AS.

Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami
Miller School of Medicine, Miami, Florida 33136, USA.

PURPOSE: To evaluate the safety, efficacy, and durability of bevacizumab for the 
treatment of subfoveal choroidal neovascularization (CNV) in patients with
neovascular age-related macular degeneration (AMD). DESIGN: Open-label,
single-center, uncontrolled clinical study. PARTICIPANTS: Age-related macular
degeneration patients with subfoveal CNV (n = 18) and best-corrected visual
acuity (VA) letter scores of 70 to 20 (approximate Snellen equivalent,
20/40-20/400). METHODS: Patients were treated at baseline with an intravenous
infusion of bevacizumab (5 mg/kg) followed by 1 or 2 additional doses given at
2-week intervals. Safety assessments were performed at all visits. Ophthalmologic
evaluations included protocol VA measurements, ocular examinations, and optical
coherence tomography (OCT) imaging at each visit. Retreatment with bevacizumab
was performed if there was evidence of recurrent CNV. MAIN OUTCOME MEASURES:
Assessments of safety and changes from baseline in VA scores and OCT measurements
were performed through 24 weeks. RESULTS: No serious ocular or systemic adverse
events were identified through 24 weeks. The only adverse event identified was a 
mild elevation of mean systolic and diastolic blood pressure measurements (+11
mmHg, P = 0.004; +8 mmHg, P<0.001) evident by 3 weeks and easily controlled with 
antihypertensive medications. By 24 weeks, the systolic and diastolic mean blood 
pressures were at or below baseline measurements. Visual acuity in the study eyes
improved within the first 2 weeks, and by 24 weeks, the mean VA letter score
increased by 14 letters in the study eyes (P<0.001), and the mean OCT central
retinal thickness measurement decreased by 112 microm (P<0.001). By 24 weeks,
retreatment was needed for only 6 of the 18 study eyes, and after retreatment,
the recurrent leakage was eliminated, with restoration of any lost VA.
CONCLUSIONS: Systemic bevacizumab therapy for neovascular AMD was well tolerated 
and effective for all 18 patients through 24 weeks. By 6 months, most patients
did not require any additional treatment beyond the initial 2 or 3 infusions.
Despite these impressive results, it is unlikely that systemic bevacizumab will
be studied in a large clinical trial because of the potential risks associated
with systemic anti-VEGF therapy and the perception that intravitreal therapy is
safer.

Publication Types: 
    Case Reports
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 17027972 [PubMed - indexed for MEDLINE]

1246: Eye. 2008 Feb;22(2):256-60. Epub 2006 Oct 6.

Risk factors for cystoid macular oedema in patients with uveitis.

van Kooij B, Probst K, Fijnheer R, Roest M, de Loos W, Rothova A.

Department of Ophthalmology, FC Donders Institute of Ophthalmology, University
Medical Center, Utrecht, The Netherlands. b.vankooij@ oogh.azu.nl

PURPOSE: To determine ophthalmologic and systemic factors associated with the
presence of cystoid macular oedema (CMO) in patients with uveitis. METHODS:
Retrospective cross-sectional study in which 97 consecutive patients with uveitis
filled in an extensive questionnaire for the presence of cardiovascular diseases 
and its risk factors. An analysis of the ophthalmologic and questionnaire data
was conducted. RESULTS: CMO was present in 44% (43/97) of patients. Its presence 
was strongly associated with increasing age (P=0.001) and age at onset of uveitis
(P<0.001). For patients older than 50 years, the risk of having CMO was 3.8-fold 
(95% confidence intervals 1.6-9.0) larger than for younger patients. The most
frequent anatomic location of uveitis associated with CMO was panuveitis (49%).
Papillary leakage on fluorescein angiography was associated with CMO (P<0.001),
independently of other risk factors. After adjustment for age, multivariate
logistic regression showed no association between cardiovascular disease and its 
risk factors and the presence of CMO. CONCLUSIONS: Age, independent of duration
of uveitis, was a major risk factor for the presence of CMO in uveitis. A
positive correlation between CMO and papillary leakage on angiography was noted.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17024221 [PubMed - indexed for MEDLINE]

1247: Eye. 2007 Nov;21(11):1412-5. Epub 2006 Oct 6.

The -174G/C interleukin-6 promoter polymorphism influences the development of
macular oedema following uncomplicated phacoemulsification surgery.

Masood I, Negi A, Vernon SA, Comeglio P, Child AH.

Department of Ophthalmology, Queen's Medical Centre, Derby Road, Nottingham, UK. 
imranmasood777@hotmail.com

AIM: To determine whether the functional -174 G/C interleukin-6 gene polymorphism
is a risk factor for the development of cystoid macular oedema (CMO) following
routine uncomplicated phacoemulsification surgery in patients with no established
risk factors. METHODS: A total of 40 patients who underwent routine
phacoemulsification surgery as part of a randomised controlled trial comparing
the use of postoperative steroid drops against a single sub-tenon injection of
triamcinolone were genotyped for the IL-6 -174G/C polymorphism. All patients
underwent fluorescein angiography at 30 days and anterior chamber flare
measurements pre-operatively and at day 1, 7, and 30. RESULTS: Angiographic CMO
developed in 14 patients of the 40 studied. 9 out of the 14 patients carried the 
GG genotype (Fisher's exact test P=0.05, Hazard ratio for GG genotype; 4.05
(1.02-16.00)). There was no difference in flare measurements between the GG and
Non-GG (GC/CC) group. The two groups were otherwise well matched in terms of age,
sex, phacoemulsification energy used intraoperatively, and proportion of patients
receiving postoperative triamcinolone or steroid drops. CONCLUSION: The -174G/C
interleukin-6 promoter gene variant appears to modulate the response to
phacoemulsification surgery and to influence the development of postoperative
CMO. These data suggest a genetic predisposition to this complication.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17024220 [PubMed - indexed for MEDLINE]

1248: J Proteome Res. 2006 Oct;5(10):2599-610.

Erratum in:
    J Proteome Res. 2007 Apr;6(4):1615. Strunnikova, Nataly [added]; Hoffman, Eric
[corrected to Hoffman, Eric P].

Comment in:
    J Proteome Res. 2006 Oct;5(10):2501.

Secreted proteome profiling in human RPE cell cultures derived from donors with
age related macular degeneration and age matched healthy donors.

An E, Lu X, Flippin J, Devaney JM, Halligan B, Hoffman EP, Strunnikova N, Csaky
K, Hathout Y.

Center for Genetic Medicine, Children's National Medical Center, and Program in
Biochemistry and Molecular Genetics, Institute of Biomedical Science, The George 
Washington University, Washington, DC, USA.

Age-related macular degeneration (AMD) is characterized by progressive loss of
central vision, which is attributed to abnormal accumulation of macular deposits 
called "drusen" at the interface between the basal surface of the retinal pigment
epithelium (RPE) and Bruch's membrane. In the most severe cases, drusen deposits 
are accompanied by the growth of new blood vessels that breach the RPE layer and 
invade photoreceptors. In this study, we hypothesized that RPE secreted proteins 
are responsible for drusen formation and choroidal neovascularization. We used
stable isotope labeling by amino acids in cell culture (SILAC) in combination
with LC-MS/MS analysis and ZoomQuant quantification to assess differential
protein secretion by RPE cell cultures prepared from human autopsy eyes of AMD
donors (diagnosed by histological examinations of the macula and genotyped for
the Y402H-complement factor H variant) and age-matched healthy control donors. In
general, RPE cells were found to secrete a variety of extracellular matrix
proteins, complement factors, and protease inhibitors that have been reported to 
be major constituents of drusen (hallmark deposits in AMD). Interestingly, RPE
cells from AMD donors secreted 2 to 3-fold more galectin 3 binding protein,
fibronectin, clusterin, matrix metalloproteinase-2 and pigment epithelium derived
factor than RPE cells from age-matched healthy donors. Conversely, secreted
protein acidic and rich in cysteine (SPARC) was found to be down regulated by
2-fold in AMD RPE cells versus healthy RPE cells. Ingenuity pathway analysis
grouped these differentially secreted proteins into two groups; those involved in
tissue development and angiogenesis and those involved in complement regulation
and protein aggregation such as clusterin. Overall, these data strongly suggest
that RPE cells are involved in the biogenesis of drusen and the pathology of AMD.

Publication Types: 
    Research Support, N.I.H., Intramural
    Research Support, Non-U.S. Gov't

PMID: 17022631 [PubMed - indexed for MEDLINE]

1249: N Engl J Med. 2006 Oct 5;355(14):1432-44.

Comment in:
    N Engl J Med. 2006 Oct 5;355(14):1409-12.    N Engl J Med. 2006 Oct 5;355(14):1493-5.    N Engl J Med. 2007 Feb 15;356(7):747-8; author reply 749-50.    N Engl J Med. 2007 Feb 15;356(7):748-9; author reply 749-50.

Ranibizumab versus verteporfin for neovascular age-related macular degeneration.

Brown DM, Kaiser PK, Michels M, Soubrane G, Heier JS, Kim RY, Sy JP, Schneider S;
ANCHOR Study Group.

Vitreoretinal Consultants, Methodist Hospital, Houston, TX 77030, USA.
dmbmd@houstonretina.com

BACKGROUND: We compared ranibizumab--a recombinant, humanized, monoclonal
antibody Fab that neutralizes all active forms of vascular endothelial growth
factor A--with photodynamic therapy with verteporfin in the treatment of
predominantly classic neovascular age-related macular degeneration. METHODS:
During the first year of this 2-year, multicenter, double-blind study, we
randomly assigned patients in a 1:1:1 ratio to receive monthly intravitreal
injections of ranibizumab (0.3 mg or 0.5 mg) plus sham verteporfin therapy or
monthly sham injections plus active verteporfin therapy. The primary end point
was the proportion of patients losing fewer than 15 letters from baseline visual 
acuity at 12 months. RESULTS: Of the 423 patients enrolled, 94.3% of those given 
0.3 mg of ranibizumab and 96.4% of those given 0.5 mg lost fewer than 15 letters,
as compared with 64.3% of those in the verteporfin group (P<0.001 for each
comparison). Visual acuity improved by 15 letters or more in 35.7% of the 0.3-mg 
group and 40.3% of the 0.5-mg group, as compared with 5.6% of the verteporfin
group (P<0.001 for each comparison). Mean visual acuity increased by 8.5 letters 
in the 0.3-mg group and 11.3 letters in the 0.5-mg group, as compared with a
decrease of 9.5 letters in the verteporfin group (P<0.001 for each comparison).
Among 140 patients treated with 0.5 mg of ranibizumab, presumed endophthalmitis
occurred in 2 patients (1.4%) and serious uveitis in 1 (0.7%). CONCLUSIONS:
Ranibizumab was superior to verteporfin as intravitreal treatment of
predominantly classic neovascular age-related macular degeneration, with low
rates of serious ocular adverse events. Treatment improved visual acuity on
average at 1 year. (ClinicalTrials.gov number, NCT00061594
[ClinicalTrials.gov].). Copyright 2006 Massachusetts Medical Society.

Publication Types: 
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17021319 [PubMed - indexed for MEDLINE]

1250: N Engl J Med. 2006 Oct 5;355(14):1419-31.

Comment in:
    N Engl J Med. 2006 Oct 5;355(14):1409-12.    N Engl J Med. 2006 Oct 5;355(14):1493-5.    N Engl J Med. 2007 Feb 15;356(7):747-8; author reply 749-50.    N Engl J Med. 2007 Feb 15;356(7):748-9; author reply 749-50.

Ranibizumab for neovascular age-related macular degeneration.

Rosenfeld PJ, Brown DM, Heier JS, Boyer DS, Kaiser PK, Chung CY, Kim RY; MARINA
Study Group.

Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami
Miller School of Medicine, Miami, FL 33136, USA. prosenfeld@med.miami.edu

BACKGROUND: Ranibizumab--a recombinant, humanized, monoclonal antibody Fab that
neutralizes all active forms of vascular endothelial growth factor A--has been
evaluated for the treatment of neovascular age-related macular degeneration.
METHODS: In this multicenter, 2-year, double-blind, sham-controlled study, we
randomly assigned patients with age-related macular degeneration with either
minimally classic or occult (with no classic lesions) choroidal
neovascularization to receive 24 monthly intravitreal injections of ranibizumab
(either 0.3 mg or 0.5 mg) or sham injections. The primary end point was the
proportion of patients losing fewer than 15 letters from baseline visual acuity
at 12 months. RESULTS: We enrolled 716 patients in the study. At 12 months, 94.5%
of the group given 0.3 mg of ranibizumab and 94.6% of those given 0.5 mg lost
fewer than 15 letters, as compared with 62.2% of patients receiving sham
injections (P<0.001 for both comparisons). Visual acuity improved by 15 or more
letters in 24.8% of the 0.3-mg group and 33.8% of the 0.5-mg group, as compared
with 5.0% of the sham-injection group (P<0.001 for both doses). Mean increases in
visual acuity were 6.5 letters in the 0.3-mg group and 7.2 letters in the 0.5-mg 
group, as compared with a decrease of 10.4 letters in the sham-injection group
(P<0.001 for both comparisons). The benefit in visual acuity was maintained at 24
months. During 24 months, presumed endophthalmitis was identified in five
patients (1.0%) and serious uveitis in six patients (1.3%) given ranibizumab.
CONCLUSIONS: Intravitreal administration of ranibizumab for 2 years prevented
vision loss and improved mean visual acuity, with low rates of serious adverse
events, in patients with minimally classic or occult (with no classic lesions)
choroidal neovascularization secondary to age-related macular degeneration.
(ClinicalTrials.gov number, NCT00056836 [ClinicalTrials.gov].). Copyright 2006
Massachusetts Medical Society.

Publication Types: 
    Clinical Trial, Phase III
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17021318 [PubMed - indexed for MEDLINE]

1251: Ophthalmic Surg Lasers Imaging. 2006 Sep-Oct;37(5):399-405.

A spreadsheet template for the analysis of optical coherence tomography in the
longitudinal management of diabetic macular edema.

Browning DJ, Fraser CM, Powers ME.

Charlotte Eye, Ear, Nose, and Throat Associates, PA, Charlotte, North Carolina,
USA.

BACKGROUND AND OBJECTIVE: To provide a tool for analyzing optical coherence
tomography data in patients with diabetic macular edema. PATIENTS AND METHODS:
Retrospective series of 206 patients with diabetic macular edema involving at
least one eye and receiving focal laser photocoagulation, intravitreal
triamcinolone acetonide injection, or vitrectomy, membrane peeling, and
intravitreal triamcinolone acetonide injection, and of untreated fellow eyes
without diabetic macular edema. Main outcome measures included foveal subfield
mean thickness and thickening relative to normal (microns), total macular volume 
and its increase relative to normal (mm3), visual acuity (Snellen decimal), and
intraocular pressure (mm Hg). RESULTS: The authors demonstrate a graphical
display of data based on a spreadsheet template for the longitudinal management
of diabetic macular edema. Complex relationships of ocular response and
interventions are concisely displayed. CONCLUSION: A graphical display of optical
coherence tomography, visual acuity, and intraocular pressure data is a practical
aid in the management of diabetic macular edema.

Publication Types: 
    Case Reports

PMID: 17017466 [PubMed - indexed for MEDLINE]

1252: Ophthalmic Surg Lasers Imaging. 2006 Sep-Oct;37(5):423-4.

Macular hole formation following thermal laser photocoagulation in a patient with
choroidal neovascular membrane and age-related macular degeneration.

Iranmanesh R, Reddy S, Peiretti E, Slakter JS.

Vitreous-Retina-Macula Consultants of New York, 460 Park Avenue, 5th Floor, New
York, NY 10022, USA.

A woman with age-related macular degeneration and an extrafoveal choroidal
neovascularization was treated with thermal laser photocoagulation. Three years
later, an optical coherence tomography image showed a full-thickness macular hole
with some contracture toward the adjacent atrophic laser scar, suggestive of some
presumptive tangential forces.

Publication Types: 
    Case Reports

PMID: 17017203 [PubMed - indexed for MEDLINE]

1253: Ophthalmic Surg Lasers Imaging. 2006 Sep-Oct;37(5):406-14.

Fundus autofluorescence before and after photodynamic therapy for choroidal
neovascularization secondary to age-related macular degeneration.

Framme C, Bunse A, Sofroni R, Thalhammer T, Walter A, Sachs HG, Gabel VP.

University Eye Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93042
Regensburg, Germany.

BACKGROUND AND OBJECTIVE: To describe fundus autofluorescence patterns in
choroidal neovascularization secondary to age-related macular degeneration before
and after photodynamic therapy (PDT). PATIENTS AND METHODS: Sixty-eight
consecutive eyes were indicated for PDT after standard fluorescein angiography,
which showed completely classic choroidal neovascularization (CNV) (n=52), occult
with no classic CNV (n=7), and predominantly classic CNV (n=9). Standardized PDT 
was performed and patients were examined 2 to 3 months later. Angiography and
autofluorescence measurements were performed again and compared with preoperative
values. RESULTS: At baseline, autofluorescence was mainly decreased in areas of
completely classic CNV (79%), but showed a regular or mottled pattern in occult
CNV. A slightly increased (50%) or normal (50%) autofluorescence was seen at the 
rim of the classic lesions within the junctional zone. Membrane demarcation was
improved (90%) in classic membranes 2 to 3 months after PDT. After PDT for occult
membranes, a transformation into classic membranes with residual leakage and need
for further PDT was observed (6 of 7 eyes), showing the described
autofluorescence patterns. For the mixed type of CNV, both described patterns of 
autofluorescence distribution were found. CONCLUSION: Especially classic CNVs
reveal distinct characteristics of significantly decreased autofluorescence,
presumably due to their localization above the retinal pigment epithelium level, 
leading to blockage of autofluorescence. Autofluorescence patterns after PDT
included enhanced demarcation of the membrane, suggesting reactive retinal
pigment epithelial changes. Autofluorescence might be an interesting tool to
distinguish noninvasively between classic and occult CNV in age-related macular
degeneration and to monitor changes after PDT.

PMID: 17017200 [PubMed - indexed for MEDLINE]

1254: Ophthalmic Surg Lasers Imaging. 2006 Sep-Oct;37(5):370-7.

Serial optical coherence tomography of subthreshold diode laser micropulse
photocoagulation for diabetic macular edema.

Luttrull JK, Spink CJ.

BACKGROUND AND OBJECTIVE: To use serial optical coherence tomography (OCT) to
evaluate low-intensity, high-density subthreshold diode laser micropulse
photocoagulation treatment of clinically significant diabetic macular edema.
PATIENTS AND METHODS: Eighteen consecutive eyes of 14 patients with clinically
significant diabetic macular edema and a minimum foveal thickness of 223 microm
or greater were prospectively evaluated by OCT preoperatively and 1, 4, and 12
weeks following treatment. RESULTS: Overall, estimated macular edema 3 months
postoperatively (minimum foveal thickness--223 microm) was reduced a mean of 24% 
(P = .02). Eleven eyes treated for recurrent or persistent clinically significant
diabetic macular edema following prior treatment more than 3 months before study 
entry were most improved, with a mean reduction in estimated macular edema 3
months postoperatively of 59%. No treatment complications were observed. No
patient demonstrated laser lesions following treatment. CONCLUSIONS:
Low-intensity, high-density subthreshold diode laser micropulse photocoagulation 
can reduce or eliminate clinically significant diabetic macular edema measured by
OCT. Further study is warranted.

PMID: 17017196 [PubMed - indexed for MEDLINE]

1255: Ophthalmic Surg Lasers Imaging. 2006 Sep-Oct;37(5):358-63.

ICG angiography-guided photodynamic therapy for large pigment epithelial
detachments in age-related macular degeneration.

Wygnanski-Jaffe T, Desatnik H, Alhalel A, Goldstein M, Lowenstein A, Zolf R,
Moisseiev J.

Department of Ophthalmology, The Goldschleger Eye Institute, Sheba Medical
Center, Tel Hashomer, Israel.

BACKGROUND AND OBJECTIVE: To evaluate the role of photodynamic therapy (PDT) in
the management of vascularized pigment epithelial detachment in age-related
macular degeneration (AMD) when the pigment epithelial detachment is the
predominant component of the neovascular complex. PATIENTS AND METHODS: Seventeen
eyes of 17 patients underwent indocyanine green angiography-guided PDT and had at
least 6 months of follow-up. Data retrieved included visual acuity and
angiographic features prior to the treatment, number of PDT sessions, visual
acuity, angiographic outcomes at the end of the follow-up, length of follow-up,
and status of the fellow eye. in the series, with an average age of 77 years and 
a mean follow-up time of 11 months. Six (35%) of the patients lost less than 3
lines of visual acuity, 6 (35%) lost between 3 and 6 lines, and 5 (30%) lost 6 or
more lines. Angiographic outcomes were categorized as failures in 14 (82%) of the
treated eyes and successful in 3 (17%) eyes. CONCLUSIONS: In 82% of the eyes, PDT
failed to flatten the pigment epithelial detachment or prevent growth of the
choroidal neovascular membrane. Visual acuity outcomes correlated poorly with
angiographic outcomes. PDT does not seem to improve the prognosis of eyes with
large pigment epithelial detachments in AMD.

PMID: 17017194 [PubMed - indexed for MEDLINE]

1256: Eye. 2008 Feb;22(2):219-22. Epub 2006 Sep 29.

Outcome of intravitreal triamcinolone acetonide in postoperative cystoid macular 
oedema.

Konstantopoulos A, Williams CP, Luff AJ.

Southampton Eye Unit, Southampton University Hospitals NHS Trust, Southampton,
Hampshire, UK. ariskons@yahoo.com

AIMS: To assess the efficacy and safety of intravitreal triamcinolone in the
treatment of postoperative cystoid macular oedema (CMO). METHODS: A retrospective
case series review of 21 eyes (20 patients) that had an intravitreal injection of
triamcinolone 4 mg for postoperative CMO. Diagnosis was confirmed by fundus
fluorescein angiography and/or optical coherence tomography in all eyes. RESULTS:
Mean age of patients was 71.1 years. CMO had developed following routine
phacoemulsification cataract extraction (13 eyes), phacoemulsification cataract
extraction complicated by posterior capsule tear and vitreous loss (two eyes),
vitrectomy (three eyes), or planned combined phacoemulsification and vitrectomy
(three eyes). Mean duration of CMO before triamcinolone injection was 4.9 months.
Mean duration of follow-up was 7.4 months. Two eyes required a repeat injection. 
Mean logarithm of minimum angle of resolution (LogMAR) visual acuity (VA) before 
treatment was 0.53; at 1 month post injection, this increased significantly to
0.33 (P<0.001). Improvement in VA was maintained throughout follow-up; at 6
months or later, mean LogMAR VA was significantly better than baseline (0.33 vs
0.53, P=0.02). At the latest review, 43% of eyes had improved Snellen VA by two
or more lines and 86% by one or more lines compared to baseline. The remaining
14% had reduced Snellen VA compared to baseline. In the post-injection period,
33% of eyes developed an intraocular pressure of 22 mm Hg or higher and all
responded well to short-term topical agents. There were no other post-injection
complications.CONCLUSION: Intravitreal triamcinolone results in a rapid
improvement in VA that may be sustained for more than 6 months.

PMID: 17016463 [PubMed - indexed for MEDLINE]

1257: Jpn J Ophthalmol. 2006 Sep-Oct;50(5):479-82.

Postoperative assessment of retinal function using a multifocal electroretinogram
after the removal of subfoveal choroidal neovascularization secondary to
age-related macular degeneration.

Obata R, Yanagi Y, Tamaki Y.

Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo,
Japan. robata-tky@umin.ac.jp

PURPOSE: To assess retinal function in a macular lesion with multifocal
electroretinography (mfERG) after successful surgical removal of choroidal
neovascularization (CNV). METHODS: We prospectively studied 15 patients (15 eyes)
who underwent surgical removal of subfoveal CNV secondary to age-related macular 
degeneration. Three and 6 months after surgery, retinal thickness in the
parafoveal lesion and the size of the serous retinal detachment (SRD) were
measured. The mfERG was also recorded, and the data from each of six concentric
ring annuli were averaged. RESULTS: After surgery, the parafoveal retinal
thickness significantly decreased compared with the preoperative value, and SRD
was not recognized in any patient. The change in the amplitude of the P1-wave
within 2 degrees to 15 degrees in diameter positively correlated with the
decrease in the parafoveal retinal thickness. Additionally, amplitude within 8
degrees to 24 degrees in diameter positively correlated with the size of the
preoperative SRD. CONCLUSION: mfERG is helpful to quantitatively and objectively 
assess the effect of the surgical removal of CNV on retinal function, not only in
the fovea but also in the entire macular area. Copyright Japanese
Ophthalmological Society 2006.

Publication Types: 
    Comparative Study

PMID: 17013704 [PubMed - indexed for MEDLINE]

1258: Ophthalmology. 2006 Oct;113(10):1706-12.

A pilot study of multiple intravitreal injections of ranibizumab in patients with
center-involving clinically significant diabetic macular edema.

Chun DW, Heier JS, Topping TM, Duker JS, Bankert JM.

Ophthalmic Consultants of Boston, Boston, Massachusetts 02114, USA.

OBJECTIVE: To evaluate the biologic activity of multiple intravitreal injections 
of ranibizumab in patients with center-involving clinically significant diabetic 
macular edema (DME) and to report any associated adverse events. DESIGN:
Single-center, open-label, dose-escalating pilot study. PARTICIPANTS: A total of 
10 eyes of 10 patients (mean age, 69.3 years [range, 59-81]) with DME involving
the center of the macula and best-corrected visual acuity (BCVA) in the study eye
between 20/63 and 20/400. INTERVENTION: Three intravitreal injections of
ranibizumab (0.3 mg or 0.5 mg each injection) administered on day 0, month 1, and
month 2, and observation until month 24. MAIN OUTCOME MEASURES: Primary end
points were the frequency and severity of ocular and systemic adverse events.
Secondary end points were BCVA and measurement of retinal thickness by optical
coherence tomography. RESULTS: Of the 10 patients enrolled, 5 received 0.3-mg and
5 received 0.5-mg ranibizumab. Intravitreal injections of ranibizumab were well
tolerated. No systemic adverse events were reported. Five occurrences of mild to 
moderate ocular inflammation were reported. At month 3, 4 of 10 patients gained >
or =15 letters, 5 of 10 gained > or =10 letters, and 8 of 10 gained > or =1
letters. At month 3, the mean decrease in retinal thickness of the center point
of the central subfield was 45.3+/-196.3 microm for the low-dose group and
197.8+/-85.9 microm for the high-dose group. CONCLUSIONS: Ranibizumab appears to 
be a well-tolerated therapy for patients with DME. This pilot study demonstrates 
that ranibizumab therapy has the potential to maintain or improve BCVA and reduce
retinal thickness in patients with center-involved clinically significant DME.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 17011952 [PubMed - indexed for MEDLINE]

1259: Am J Ophthalmol. 2006 Oct;142(4):688-9.

Comment in:
    Am J Ophthalmol. 2007 Aug;144(2):335; author reply 335-6.

Retinal vascular abnormalities and prevalence of age-related macular degeneration
in adult Chinese: the Beijing Eye Study.

Xu L, Wang S, Li Y, Jonas JB.

Beijing Institute of Ophthalmology, Beijing Tongren Eye Center and Capital
University of Medical Science, Beijing, China.

PURPOSE: To evaluate whether retinal vessel abnormalities are associated with
early or late age-related macular degeneration (AMD) in adult Chinese. DESIGN:
Population-based prevalence study. METHODS: The Beijing Eye Study included 4439
(83.4%) subjects of 5324 living in a rural area or urban region of Greater
Beijing, age older than 40+ years, and invited to participate. The participants
underwent a detailed ophthalmic examination, including fundus photography. The
photographs were graded using the Wisconsin Age-Related Maculopathy Grading
system for evaluation of AMD, and using the Atherosclerosis Risk in Communities
protocol for assessment of retinal vascular abnormalities. We examined focal and 
generalized arteriolar narrowing, arteriolar sheathing, and arteriovenous
crossing abnormalities. RESULTS: Fundus photographs were available for 8655 eyes 
of 4376 (98.6%) subjects. Neither early nor late AMD was significantly (P > .15) 
associated with any of the retinal vascular abnormalities. CONCLUSIONS: Retinal
vascular abnormalities are not markedly associated with the prevalence of early
or late AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17011870 [PubMed - indexed for MEDLINE]

1260: Am J Ophthalmol. 2006 Oct;142(4):683-4.

Progression of choroidal neovascularization following injection of pegaptanib
sodium (macugen) in two eyes with neovascular age-related macular degeneration.

Williams AJ, Fekrat S.

Albert Eye Research Institute, Duke University Eye Center, Duke University
Medical Center, Durham, NC 27710, USA.

PURPOSE: To describe two cases of neovascular age-related macular degeneration
(AMD) that progressed despite a single intravitreal injection of pegaptanib
sodium (Macugen) six weeks earlier. DESIGN: Interventional case report. METHODS: 
A 62-year-old man and a 76-year-old woman with occult and minimally classic
lesions, respectively, each received a single injection of intravitreal
pegaptanib. RESULTS: Within six weeks of an intravitreal pegaptanib injection,
the choroidal neovascularization (CNV) progressed. In one eye, the chronic occult
lesion developed subfoveal classic CNV. In the other eye, the classic component
of the minimally classic lesion tripled in size. CONCLUSIONS: A single dose of
intravitreal pegaptanib was not effective in these two patients at six weeks.
This report reminds the ophthalmologist to consider obtaining a fluorescein
angiogram during follow-up after an intravitreal pegaptanib injection to monitor 
CNV lesion characteristics, particularly if the visual acuity decreases.

Publication Types: 
    Case Reports

PMID: 17011868 [PubMed - indexed for MEDLINE]

1261: Am J Ophthalmol. 2006 Oct;142(4):660-8.

Antivascular endothelial growth factor agents and their development: therapeutic 
implications in ocular diseases.

Kaiser PK.

Cleveland Clinic, Cleveland, OH, USA. pkkaiser@aol.com

PURPOSE: To provide an overview of angiogenesis and vascular endothelial growth
factor (VEGF) and discusses the development approach, safety, and efficacy
results of current and emerging anti-VEGF therapies for ocular diseases. DESIGN: 
Analysis of literature and current clinical trials of antiangiogenic agents for
age-related macular degeneration (AMD). METHODS: Literature review. RESULTS:
There are several novel antiangiogenic molecules that target vascular endothelial
growth factor and are being used in the management of AMD. Large scale, Phase III
trials have shown promising results in improving vision in this devastating
disease. CONCLUSIONS: Therapies that target VEGF have shown tremendous promise as
treatments for AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17011860 [PubMed - indexed for MEDLINE]

1262: Am J Ophthalmol. 2006 Oct;142(4):620-4.

Reading performance of patients with uveitis-associated cystoid macular edema.

Kiss CG, Barisani-Asenbauer T, Maca S, Richter-Mueksch S, Radner W.

Department of Ophthalmology and Optometry, Medical University of Vienna, Vienna, 
Austria.

PURPOSE: To evaluate the extent of the visual impairment caused by
uveitis-associated cystoid macular edema (CME) and compare the results with
lesion size. DESIGN: Observational case series. METHODS: setting: Uveitis
outpatient clinic of the Department of Ophthalmology and Optometry, Medical
University of Vienna. patient population: CME was verified in 30 eyes of 30
consecutive uveitis patients with optical coherence tomography and lesion size
was assessed with retinal thickness analyzer. main outcome measures: Distance
visual acuity (VA) (measured with Early Treatment Diabetic Retinopathy Study
charts), reading acuity, and reading speed (tested with Radner Reading Charts).
Results were compared with nonaffected partner eyes. RESULTS: Distance VA was
logMAR 0.22 +/- 0.15 in CME eyes vs -0.02 +/- 0.17 in healthy controls. Reading
acuity was 75% of logMAR in CME eyes vs 92% of logMAR in control eyes (P = .01). 
The mean reading speed was 148.4 +/- 36.6 words per minute in patients with CME
vs 168.9 +/- 36.3 in patients without CME (P = .04). Reading acuity correlated
with both lesion size and distance VA (r = 0.61; P = .01 and r = 0.53; P = .028, 
respectively). Neither anatomical classification of uveitis nor gender or age had
a significant influence on the evaluated parameters. CONCLUSIONS: Reading acuity 
and reading speed were considerably more impaired than distance visual acuity.
The assessed parameters showed a better correlation to lesion size and seem to be
a better reflection of macular dysfunction. Analyzing reading function is an
important factor when following patients with CME and evaluating success of
treatment modalities.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17011854 [PubMed - indexed for MEDLINE]

1263: Prostaglandins Leukot Essent Fatty Acids. 2006 Dec;75(6):413-8. Epub 2006
Oct 2.

Changes in endocannabinoid and palmitoylethanolamide levels in eye tissues of
patients with diabetic retinopathy and age-related macular degeneration.

Matias I, Wang JW, Moriello AS, Nieves A, Woodward DF, Di Marzo V.

Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio
Nazionale delle Ricerche, Via Toiano 6, 80072 Arco Felice, Pozzuoli (Napoli),
Italy.

Cannabinoid receptors and the endocannabinoids (anandamide
(N-arachidonoylethanolamine--AEA) and 2-arachidonoylglycerol (2-AG)), as well as 
the AEA congener, palmitoylethanolamide (PEA), are involved in ocular physiology.
We measured endocannabinoid and PEA levels by isotope-dilution liquid
chromatography-mass spectrometric analysis in post-mortem eye tissues of patients
with diabetic retinopathy (DR) or age-related macular degeneration (AMD). In eyes
with DR, significantly enhanced levels of AEA were found in the retina (
approximately 1.8-fold), ciliary body ( approximately 1.5-fold) and, to a lesser 
extent, cornea ( approximately 1.3-fold). Surprisingly, 2-AG levels were
significantly higher ( approximately 3-fold) only in the iris, whereas PEA levels
only slightly increased ( approximately 1.3-fold) in the ciliary body. In eyes
with AMD, significantly enhanced levels of AEA were found in the choroid (
approximately 1.3-fold), ciliary body ( approximately 1.4-fold) and cornea (
approximately 1.4-fold), whereas in the retina only a trend towards an increase (
approximately 1.5-fold) was observed. The tissue- and disease-selective nature of
the changes observed suggests that the compounds analyzed here may play different
roles in the control of eye function under different pathological conditions.

PMID: 17011761 [PubMed - indexed for MEDLINE]

1264: Graefes Arch Clin Exp Ophthalmol. 2007 May;245(5):651-5. Epub 2006 Sep 28.

Intravitreal bevacizumab therapy for neovascular age-related macular
degeneration: a pilot study.

Abrahám-Marin ML, Cortés-Luna CF, Alvarez-Rivera G, Hernández-Rojas M,
Quiroz-Mercado H, Morales-Cantón V.

Asociación para evitar la Ceguera en México, Hospital Luis Sánchez Bulnes,
Vicente García Torres #46, Colonia San Lucas Coyoacán, 04030, Mexico, Mexico.
maura.abraham@gmail.com

PURPOSE: To evaluate the efficacy and safety of intravitreal bevacizumab therapy 
for neovascular age-related macular degeneration (ARMD). METHODS: Patients with
diagnosis of neovascular ARMD without any other ocular pathology were injected
with 2.5 mg of intravitreal bevacizumab. A complete ophthalmic examination was
undertaken in all patients, including best corrected visual acuity (BCVA), slit
lamp biomicroscopy and ocular fundus examination. Ophthalmic follow-up
evaluations included visual acuity measurements, optical coherence tomography
(OCT) imaging, and fluorescein angiography at first, second and fourth week post 
injection. RESULTS: 39 eyes of 39 patients were injected. The median age was 76
years-old (range 65-90), median visual acuity was 1.18 logMAR (range 0.18-3.00)
and median retinal thickness was 388 microns (range 157-1237). By the fourth week
of treatment, the median visual acuity was 0.88 (range 0.18-2.78) and median
retinal thickness was 247 microns (range 108-1262). Statistically significant
differences were found in visual acuity and retinal thickness before and after
intravitreal injection (p=0.002, p<0.001, Wilcoxon rank test). CONCLUSIONS: Our
results suggest that intravitreal bevacizumab is well tolerated and is associated
with improvement in BCVA and decreased mean retinal thickness by OCT. Further
controlled and long term evaluation of intravitreal bevacizumab for the treatment
of neovascular ARMD is warranted.

Publication Types: 
    Clinical Trial

PMID: 17006681 [PubMed - indexed for MEDLINE]

1265: Br J Ophthalmol. 2007 Mar;91(3):345-8. Epub 2006 Sep 27.

Pars plana vitrectomy with intravitreal triamcinolone: effect on uveitic cystoid 
macular oedema and treatment limitations.

Gutfleisch M, Spital G, Mingels A, Pauleikhoff D, Lommatzsch A, Heiligenhaus A.

Department of Ophthalmology, St Franziskus Hospital, Hohenzollernring, Muenster, 
Germany.

OBJECTIVE: To investigate the effect of pars plana vitrectomy (PPV) in
combination with intraoperative intravitreal triamcinolone acetonide injection on
the course of cystoid macular oedema (CME) in patients with uveitis. METHODS:
Patients with uveitis with CME (n = 19) not responding to systemic
corticosteroids and/or immunosuppression combined with acetazolamide were
retrospectively studied after PPV with additional intravitreal injection of 4 mg 
triamcinolone acetonide. Patients had chronic anterior uveitis (n = 4),
intermediate uveitis (n = 9), posterior uveitis (n = 3) or panuveitis (n = 3).
Visual acuity tests, tonometry, fluorescein angiographic appearance and
postoperative complications were analysed. Mean follow-up was 14 months (SD 4.6).
RESULTS: CME improved in 58% of the patients within the first 6 weeks
postoperatively. After 12 months, CME was further improved in 44% and worsened in
another 12%. Improvement of visual acuity was noted in 42% after 3 months and in 
28% after 12 months. Cataract progressed in 85% of the phacic patients
postoperatively. Increased intraocular pressure was detected in 27% at 2 weeks
and in 11% at 12 months after surgery. CONCLUSION: Uveitic CME that is
unresponsive to systemic immunosuppression and acetazolamide may improve after
PPV with additional intravitreal triamcinolone application. The effect seems to
be transient in many of the patients. Frequent complications were cataract
formation and ocular hypertension.

Publication Types: 
    Evaluation Studies

PMID: 17005547 [PubMed - indexed for MEDLINE]

1266: Korean J Ophthalmol. 2006 Sep;20(3):156-61.

Intravitreal triamcinolone reinjection for refractory diabetic macular edema.

Ramezani A, Ahmadieh H, Tabatabaei H.

Ophthalmic Research Center, Shaheed Beheshti University of Medical Sciences,
Tehran, Iran. arramezani@gmail.com

PURPOSE: To evaluate the effect of intravitreal triamcinolone acetonide (IVT)
reinjection on clinical and optical coherence tomographic features in refractory 
diabetic macular edema. METHODS: In a prospective interventional case series, all
IVT treated patients enrolled in a previous clinical trial were recalled to have 
a new ophthalmologic examination and optical coherence tomography (OCT)
performed. Eyes found suitable for reinjection received 4 mg IVT. Complete
clinical examination and OCT were repeated at 2 and 4 months post-injection. The 
changes were statistically analyzed using a paired t test and were compared to
the results of the first injections. RESULTS: Of all returning patients, 12 cases
with complete records were considered candidates for reinjection. Visual acuity
(VA) changes were not significant after the first and second interventions,
although there was a relative improvement (0.14 logMAR) 2 months after the first 
injection. Reductions of central macular thickness (CMT) were 43 +/- 69 microm,
and 40 +/- 69 microm after the first injection and 27 +/- 48 microm, 49 +/- 58
microm after the reinjection at 2 & 4 months, respectively. None of the mentioned
changes was significant. After the second injection, however, intraocular
pressure was elevated at both 2 & 4 months (3.6 & 2.4 mmHg respectively, P <
0.05). Two months after the first administration, intraocular pressure was found 
to be raised significantly (5.58 mmHg, P = 0.001). CONCLUSIONS: The transient
beneficial effects of IVT on diabetic macular edema are not repeated with second 
injections. However, IVT-related ocular hypertension is more persistent after
reinjection. Korean

Publication Types: 
    Clinical Trial
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 17004629 [PubMed - indexed for MEDLINE]

1267: Invest Ophthalmol Vis Sci. 2006 Oct;47(10):4624-31.

Severity staging by early features of age-related maculopathy exhibits weak
relationships with functional deficits on SWS grating acuity.

Beirne RO, Hogg RE, Stevenson MR, Zlatkova MB, Chakravarthy U, Anderson RS.

Vision Science Research Group, School of Biomedical Sciences, University of
Ulster, Northern Ireland, United Kingdom. r.beirne@ulster.ac.uk

PURPOSE: To examine the relationship between short-wavelength-sensitive (SWS)
resolution acuity and epidemiologically defined stages of early age-related
maculopathy (ARM). METHODS: Subjects consisted of 88 adults aged 51 to 87 years. 
Psychophysical testing was undertaken in only one eye of each subject (the study 
eye). All study eyes had a LogMAR acuity of 0.30 (20/40 Snellen) or better. SWS
and achromatic grating resolution acuity were measured at 6 degrees eccentricity 
from the fovea. Stereoscopic color fundus photographs centered on the macula were
taken on both eyes of each subject and were graded using the Wisconsin
Age-Related Maculopathy Grading System (WARMGS). After grading, features of ARM
were combined to assign a severity stage from 0 to 5 using the methods described 
by the Rotterdam Eye Study. Relationships between visual function, study eye ARM 
stage, and fellow eye status were examined with the use of standard statistical
analysis. RESULTS: Although SWS resolution acuity was significantly reduced in
eyes classified as having any ARM compared with eyes classified as having no ARM 
(P = 0.002), there was no relationship between the severity of functional
deficits and the morphologic severity from stage 1 to stage 4. On reassigning
subject eyes to a revised severity staging (stage 0, stages 1 to 4 combined, and 
stage 5), SWS acuity was significantly different among these three groups (P <
0.001). No significant relationship was found between achromatic resolution
acuity and ARM staging. The status of the fellow eye (advanced macular
degeneration present or absent) was not significantly related to visual function 
in the study eye. CONCLUSIONS: Significant functional deficits in SWS resolution 
acuity were found in eyes with ARM features, but the severity of functional loss 
did not correlate well with the currently accepted method of assigning a
morphologic severity stage. Longitudinal studies may reveal further information
on the relationships between functional deficits, ARM status, disease
progression, and outcome.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17003460 [PubMed - indexed for MEDLINE]

1268: Invest Ophthalmol Vis Sci. 2006 Oct;47(10):4569-78.

Intravitreal bevacizumab for choroidal neovascularization caused by AMD (IBeNA
Study): results of a phase 1 dose-escalation study.

Costa RA, Jorge R, Calucci D, Cardillo JA, Melo LA Jr, Scott IU.

U.D.A.T. Macular Imaging and Treatment Division, Hospital de Olhos de Araraquara,
Araraquara, SP, Brazil. roger.retina@globo.com

PURPOSE: To evaluate the safety of three dose regimens of intravitreal
bevacizumab (Avastin; Genentech, Inc., South San Francisco, CA) for the
management of choroidal neovascularization (CNV) associated with age-related
macular degeneration (AMD). METHODS: This was a prospective, nonrandomized
open-label study of 45 patients with AMD and subfoveal CNV. A standardized
ophthalmic evaluation was performed at baseline and at weeks 1, 6, and 12 (+/-1) 
after a single intravitreous injection (1.0, 1.5, or 2.0 mg) of bevacizumab. Main
outcomes measures include clinical evidence of toxicity and complications.
Changes in best corrected visual acuity (BCVA) and lesion characteristics-macular
morphology were also evaluated. RESULTS: The most common adverse events were
conjunctival hyperemia and subconjunctival hemorrhage at the injection site. Mean
BCVA improved from baseline throughout the study (P < 0.001; ANOVA with
Geisser-Greenhouse correction). Compared with baseline, BCVA was improved at week
1 (P = 0.001), week 6 (P < 0.001), and week 12 (P = 0.001; Dunnett test). At week
12, the lesion area and CNV area were stable or decreased in 79.1% (34/43) and in
74.4% (32/43) of patients, respectively, with no deterioration of macular
architecture observed in 83.7% (36/43). A dose-related change in BCVA (in Early
Treatment Diabetic Retinopathy Study [ETDRS] lines) was observed at week 12 (1.0 
mg [+0.3 line]; 1.5 mg [+0.6 line]; and 2.0 mg [+1.0 line]; P = 0.02;
nonparametric test for ordered groups). CONCLUSIONS: A single intravitreal
bevacizumab injection was well tolerated and, except for minor transient local
adverse events, no other adverse events were observed. In the short-term,
treatment was associated with vision stabilization or improvement and no
unfavorable neovascular lesion-macular changes in most patients.

Publication Types: 
    Clinical Trial, Phase I
    Research Support, Non-U.S. Gov't

PMID: 17003454 [PubMed - indexed for MEDLINE]

1269: Invest Ophthalmol Vis Sci. 2006 Oct;47(10):4270-6.

Estimating the yearly number of eyes with treatable neovascular age-related
macular degeneration using a direct standardization method and a markov model.

Korobelnik JF, Moore N, Blin P, Dharmani C, Berdeaux G.

Department of Ophthalmology, CHU (Centre Hospitalier Universitaire) de Bordeaux, 
Hopital Pellegrin, Bordeaux, France.

PURPOSE: To estimate the number of treatable eyes with neovascular subfoveal
age-related macular degeneration (ARMD) in France. METHODS: A literature search
for studies documenting neovascular ARMD incidence rates and direct
standardization according to age and gender were performed. Projection to the
year 2025 was based on OECD (Organization for Economic and Co-operation
Development) data. A cohort of patients aged 75 years was simulated by a
seven-state Markov model. The mean treatment duration was fixed arbitrarily at 2 
years. The probability of ARMD in the second eye was fixed at 30% at 5 years.
Monthly mortality incidence was modeled from INSEE (Institut National de la
Statistique et des Etudes Economiques) mortality tables. The time horizon of the 
model was 25 years. Sensitivity analyses were performed. RESULTS: Based on the
Rotterdam Study, 30,192 citizens per year will develop ARMD in one eye. Among
them, 17,585 will be neovascular and 13,805 neovascular subfoveal ARMD. Taking
into account the second eye, mortality, and a 2-year treatment duration, the
number of neovascular subfoveal treatable eyes yearly would be 37,019 by 2025.
Treatment duration was the most sensitive parameter. The number of eyes would be 
18,899, 53,204, 67,535, and 80,162, for treatment lasting 1, 3, 4, and 5 years,
respectively. A 2% yearly increase is expected up to 2025, due to population
aging and the 1950s baby boom. CONCLUSIONS: According to the study model, the
yearly number of subfoveal neovascular ARMD treatable eyes in France will be
37,019 by 2025. Average treatment duration was the most sensitive parameter.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17003415 [PubMed - indexed for MEDLINE]

1270: Invest Ophthalmol Vis Sci. 2006 Oct;47(10):4194-8.

Analysis of the Y402H variant of the complement factor H gene in age-related
macular degeneration.

Baird PN, Islam FM, Richardson AJ, Cain M, Hunt N, Guymer R.

Centre for Eye Research Australia, University of Melbourne, East Melbourne,
Victoria. pnb@unimelb.edu.au

PURPOSE: Recent studies in U.S. populations have indicated that the Y402H variant
of the complement factor H (CFH) gene contains a major risk susceptibility allele
for age-related macular degeneration (AMD). This study was conducted to ascertain
whether this is also true in a non-U.S. population and also whether the at-risk
allele is associated with the clinical phenotype of disease and the age at
diagnosis. METHODS: Two hundred thirty-six unrelated individuals with AMD and 144
unrelated but ethnically matched control subjects were recruited and examined.
All subjects completed a standard questionnaire, were given a fundus examination,
and provided a blood sample for DNA extraction. Alleles of Y402H in the CFH gene 
were determined by use of a MALDI-TOF-based approach followed by statistical
analysis. RESULTS: Individuals with AMD who had at least one copy of the C allele
of Y402H had an increased risk of disease (odds ratio [OR] 2.98; 95% confidence
interval [CI] 1.81-4.93) compared with cases with the T allele. On subgroup
analysis, this risk was found to be most significant in individuals with
neovascular disease (OR 4.34; 95% CI 1.94, 9.71). In addition, individuals with
neovascular disease who were homozygous CC presented with a significant 7.0-year 
earlier age at diagnosis relative to those individuals who were homozygous TT.
The population-attributable risk for the C allele ranged between 47% to 69%,
depending on the AMD disease subtype. CONCLUSIONS: The C allele of Y402H
represents a significant risk factor in individuals with AMD, and this effect is 
most pronounced in individuals with neovascular disease.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17003406 [PubMed - indexed for MEDLINE]

1271: Hum Mol Genet. 2006 Nov 1;15(21):3206-18. Epub 2006 Sep 25.

CFH, ELOVL4, PLEKHA1 and LOC387715 genes and susceptibility to age-related
maculopathy: AREDS and CHS cohorts and meta-analyses.

Conley YP, Jakobsdottir J, Mah T, Weeks DE, Klein R, Kuller L, Ferrell RE, Gorin 
MB.

Department of Health Promotion and Development, School of Nursing, University of 
Pittsburgh, The Eye and Ear Institute Building, 203 Lothrop Street, Pittsburgh,
PA 15261, USA

Age-related maculopathy (ARM) is an important cause of visual impairment in the
elderly population. It is of crucial importance to identify genetic factors and
their interactions with environmental exposures for this disorder. This study was
aimed at investigating the CFH, ELOVL4, PLEKHA1 and LOC387715 genes in
independent cohorts collected using different ascertainment schemes. The study
used a case-control design with subjects originally recruited through the
Cardiovascular Health Study (CHS) and the Age-Related Eye Disease Study (AREDS). 
CFH was significantly associated with ARM in both cohorts (P</=0.00001). A
meta-analysis confirmed that the risk allele in the heterozygous or homozygous
state (OR, 2.4 and 6.2; 95% CI, 2.2-2.7 and 5.4-7.2, respectively) confers
susceptibility. LOC387715 was also significantly associated with ARM in both
cohorts (P</=0.00001) and a meta-analysis confirmed that the risk allele in the
heterozygous and homozygous state (OR, 2.5 and 7.3; 95% CI, 2.2-2.9 and 5.7-9.4, 
respectively) confers susceptibility. Both CFH and LOC387715 showed an
allele-dose effect on the ARM risk, individuals homozygous at either locus were
at more than two-fold risk compared to those heterozygous. PLEKHA1, which is
closely linked to LOC387715, was significantly associated with ARM status in the 
AREDS cohort, but not the CHS cohort and ELOVL4 was not significantly associated 
with ARM in either cohort. Joint action of CFH and LOC387715 was best described
by independent multiplicative effect without significant interaction in both
cohorts. Interaction of both genes with cigarette smoking was insignificant in
both cohorts. This study provides additional support for the CFH and LOC387715
genes in ARM susceptibility via the evaluation of cohorts that had different
ascertainment schemes regarding ARM status and through the meta-analyses.

Publication Types: 
    Meta-Analysis
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17000705 [PubMed - indexed for MEDLINE]

1272: Nat Genet. 2006 Oct;38(10):1173-7. Epub 2006 Sep 24.

Erratum in:
    Nat Genet. 2007 Apr;39(4):567.

A common CFH haplotype, with deletion of CFHR1 and CFHR3, is associated with
lower risk of age-related macular degeneration.

Hughes AE, Orr N, Esfandiary H, Diaz-Torres M, Goodship T, Chakravarthy U.

Department of Medical Genetics, Queen's University, Belfast, Belfast BT12 6BL,
UK. A.Hughes@qub.ac.uk

Age-related macular degeneration (AMD; OMIM #603075) is the most frequent cause
of visual impairment in the elderly population, with severe disease affecting
nearly 10% of individuals of European descent over the age of 75 years. It is a
complex disease in which genetic and environmental factors contribute to
susceptibility. Complement factor H (CFH) has recently been identified as a major
AMD susceptibility gene, and the Y402H polymorphism has been proposed as the
likely causative factor. We genotyped polymorphisms spanning the cluster of CFH
and five CFH-related genes on chromosome 1q23 in 173 individuals with severe
neovascular AMD and 170 elderly controls with no signs of AMD. Detailed analysis 
showed a common haplotype associated with decreased risk of AMD that was present 
on 20% of chromosomes of controls and 8% of chromosomes of individuals with AMD. 
We found that this haplotype carried a deletion of CFHR1 and CFHR3, and the
proteins encoded by these genes were absent in serum of homozygotes. The
protective effect of the deletion haplotype cannot be attributed to linkage
disequilibrium with Y402H and was replicated in an independent sample.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16998489 [PubMed - indexed for MEDLINE]

1273: Ophthalmology. 2006 Dec;113(12):2310-6. Epub 2006 Sep 25.

Multifocal choroiditis with panuveitis incidence of ocular complications and of
loss of visual acuity.

Thorne JE, Wittenberg S, Jabs DA, Peters GB, Reed TL, Kedhar SR, Dunn JP.

Department of Ophthalmology, Johns Hopkins University School of Medicine,
Baltimore, Maryland 21205, USA. jthorne@jhmi.edu

PURPOSE: To estimate the incidences of ocular complications and vision loss in
patients with multifocal choroiditis with panuveitis (MFCPU) and to describe the 
association between therapy and the incidences thereof. DESIGN: Retrospective
cohort study. PARTICIPANTS: Sixty-six patients (122 eyes) with MFCPU evaluated
from January 1984 through June 2005 at a single-center academic practice.
METHODS: Demographic and clinical information on patients diagnosed with MFCPU
was collected and entered into a computerized database for statistical analyses. 
MAIN OUTCOME MEASURES: Development of ocular complications, including choroidal
neovascularization, epiretinal membrane, and cystoid macular edema (CME), and
loss of visual acuity (VA) to 20/50 or worse and to 20/200 or worse. RESULTS:
Among affected eyes of patients with MFCPU, frequencies of VAs of 20/50 or worse 
and of 20/200 or worse at presentation were 55% and 38%, respectively. Choroidal 
neovascularization was observed in 22% of affected eyes at presentation and was
the leading cause of poor VA at presentation. The incidence rates of vision loss 
to 20/50 or worse and to 20/200 or worse were 0.19/eye-year (EY) and 0.12/EY in
affected eyes and 0.07/person-year (PY) and 0.04/PY in better-seeing eyes.
Choroidal neovascularization was the most common cause of incident vision loss,
with approximately 45% of incident vision loss attributed to new-onset or
recurrent choroidal neovascularization. Presence of epiretinal membrane and CME
also was associated with the development of vision loss during follow-up. When
taken in combination, the incidence of any posterior pole complication was
0.13/EY in affected eyes. Use of immunosuppressive drug therapy (but not low-dose
corticosteroid therapy) was associated with an 83% reduction in the risk of
posterior pole complications (P = 0.004) and with a 92% reduction in the risk of 
20/200 or worse VA in affected eyes (P = 0.05). Of the 6 eyes with recurrent
choroidal neovascularization, only one recurrence was observed, in a patient
receiving immunosuppressive drug therapy. CONCLUSIONS: Treatment with
immunosuppressive drugs may improve VA outcomes among patients with MFCPU by
reducing the risk of sight-threatening posterior pole complications, including
new-onset choroidal neovascularization and recurrent choroidal neovascularization
among eyes with existing choroidal neovascularization.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 16996607 [PubMed - indexed for MEDLINE]

1274: Ophthalmology. 2006 Dec;113(12):2237-42. Epub 2006 Sep 25.

Subthreshold grid laser treatment of macular edema secondary to branch retinal
vein occlusion with micropulse infrared (810 nanometer) diode laser.

Parodi MB, Spasse S, Iacono P, Di Stefano G, Canziani T, Ravalico G.

Eye Clinic, Azienda Ospedaliero-Universitaria di Trieste, Trieste, Italy.
maubp@yahoo.it

PURPOSE: To compare the effectiveness of subthreshold grid laser treatment (SGLT)
with an infrared micropulse diode laser with that of threshold grid laser
treatment (TGLT) for macular edema secondary to branch retinal vein occlusion
(BRVO). DESIGN: Randomized clinical trial. PARTICIPANTS: Thirty-six patients (36 
eyes) were randomized either to infrared SGLT (17 eyes) or to krypton TGLT (19
eyes). METHODS: Complete ophthalmic examinations, including determination of
visual acuity (VA) with Early Treatment Diabetic Retinopathy Study charts,
optical coherence tomography (OCT), and fluorescein angiography, were performed
at the time of the study entry and at 6-month intervals, with a planned follow-up
of 24 months. MAIN OUTCOME MEASURES: Primary: decrease in mean foveal thickness
(FT) on OCT. Secondary: changes of the total macular volume (TMV) over the
follow-up, proportion of eyes that gained at least 10 letters (approximately > or
=2 lines of VA gain) at the 12- and 24-month examinations, and timing of macular 
edema resolution. RESULTS: Changes in mean FT and TMV from the initial values
were statistically significant for TGLT from the 6-month examination (P<0.001)
and for SGLT from the 12-month examination (P<0.001). After 1 year, there was no 
difference in mean FT and TMV between the 2 groups. At the 12-month examination, 
10 patients of the SGLT group (59%) and 11 of the TGLT group (58%) gained at
least 10 letters (2 lines) in VA. At the 24-month examination, this gain was
achieved by 11 patients (65%) of the SGLT group and 11 (58%) of the TGLT group.
Moreover, at the 24-month examination 59% and 26% gained 3 lines in the SGLT and 
TGLT groups, respectively. CONCLUSIONS: Resolution of macular edema and VA
improvement are similar to those obtained with conventional TGLT, but SGLT is not
associated with biomicroscopic and angiographic signs. A multicenter randomized
clinical trial would be needed to ascertain the real efficacy and the most
appropriate settings of SGLT for macular edema secondary to BRVO.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial

PMID: 16996596 [PubMed - indexed for MEDLINE]

1275: Ophthalmology. 2006 Dec;113(12):2251-8. Epub 2006 Sep 25.

Gaze changes with binocular versus monocular viewing in age-related macular
degeneration.

Kabanarou SA, Crossland MD, Bellmann C, Rees A, Culham LE, Rubin GS.

Institute of Ophthalmology, London, United Kingdom. stamatina_k@hotmail.com

PURPOSE: To determine and explain gaze changes during binocular versus monocular 
viewing in patients with age-related macular degeneration (AMD). DESIGN:
Cross-sectional study. PARTICIPANTS: Twenty-nine patients with bilateral
late-stage AMD. METHODS: Distance acuity and fundus pathologic features were
evaluated. Eye position was recorded while viewing a circular fixation target
under monocular and binocular viewing conditions using an infrared eye tracker
(SMI Gazetracker, SensoMotoric, Germany; Eyelink Software 2.04). Gaze changes
were quantified by calculating the mean x-coordinate and y-coordinate eye
position of the center of the bivariate contour ellipse area for a 30-second
fixation task under both viewing conditions. Retinal loci used for monocular
fixation for each eye were determined using the scanning laser ophthalmoscope
(SLO; SLO 101, Rodenstock, Munich, Germany). MAIN OUTCOME MEASURE: Gaze position.
RESULTS: Nine patients showed no shift in gaze position from monocular to
binocular viewing. Three patients demonstrated a shift in both eyes, and 17
patients demonstrated a shift in only 1 eye. The mean shift was 4.7+/-5 degrees
(standard deviation). The shift in gaze position in the worse eye was predictive 
of the distance between the 2 monocular preferred retinal loci (PRLs; better and 
worse eye; r(2) = 0.59; P<0.0001), whereas there was no association between the
shift in gaze position in the better eye and distance (r(2) = 0.00; P = 0.91).
CONCLUSIONS: Most AMD patients shift gaze position in 1 or both eyes when viewing
binocularly compared with monocularly. These changes suggest that different
retinal locations are used for fixation under the 2 viewing conditions. The SLO
data showed that these patients are likely to demonstrate monocular PRLs that
fall on noncorresponding areas. These results may have implications for the
effective development of eccentric viewing and binocular behavior of AMD
patients.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16996593 [PubMed - indexed for MEDLINE]

1276: Ophthalmology. 2006 Nov;113(11):1987-2001. Epub 2006 Sep 20.

Implantable miniature telescope for the treatment of visual acuity loss resulting
from end-stage age-related macular degeneration: 1-year results.

Hudson HL, Lane SS, Heier JS, Stulting RD, Singerman L, Lichter PR, Sternberg P, 
Chang DF; IMT-002 Study Group.

Retina Centers, Tucson, Arizona, USA.

PURPOSE: To evaluate the safety and efficacy of an implantable visual prosthetic 
device (IMT; VisionCare Ophthalmic Technologies, Saratoga, CA) in patients with
bilateral, end-stage age-related macular degeneration (AMD). DESIGN: Prospective,
open-label, multicenter clinical trial with fellow eye controls. PARTICIPANTS: A 
total of 217 patients (mean age, 76 years) with AMD and moderate to profound
bilateral central visual acuity loss (20/80-20/800) resulting from bilateral
untreatable geographic atrophy, disciform scars, or both were enrolled. METHODS: 
A visual prosthetic device (implantable telescope), designed to enlarge retinal
images of the central visual field, was implanted monocularly in the capsular bag
after lens extraction. Fellow eyes were not implanted to provide peripheral
vision and served as controls. Study patients participated in 6 visual
rehabilitation visits after surgery. MAIN OUTCOME MEASURES: Best-corrected
distance visual acuity (BCDVA) and best-corrected near visual acuity (BCNVA),
quality-of-life scores from the National Eye Institute 25-item Visual Function
Questionnaire (NEI VFQ-25) and the Activities of Daily Life scale, endothelial
cell density (ECD), and incidence of complications and adverse events. RESULTS:
At 1 year, 67% of implanted eyes achieved a 3-line or more improvement in BCDVA
versus 13% of fellow eye controls (P<0.0001). Fifty-three percent of implanted
eyes achieved a 3-line or more improvement in both BCDVA and BCNVA versus 10% of 
fellow eyes (P<0.0001). Mean BCDVA and BCNVA improved 3.5 lines and 3.2 lines,
respectively, in implanted eyes versus 0.8 lines and 1.8 lines, respectively, in 
fellow eyes (P<0.0001). Change in visual acuity was not related to lesion type.
Mean NEI VFQ-25 scores improved by more than 7 points from baseline (P<0.01) on 7
of 8 relevant subscales. Eleven eyes did not receive the device because of an
aborted procedure. Endothelial cell density was reduced by 20% at 3 months and
25% at 1 year. The decrease in ECD was correlated with postsurgical edema
(P<0.0001), and there was no evidence that endothelial cell loss is accelerated
by ongoing endothelial trauma after implantation. CONCLUSIONS: This implantable
visual prosthesis can improve visual acuity and quality of life in patients with 
moderate to profound visual impairment caused by bilateral, end-stage AMD.

Publication Types: 
    Controlled Clinical Trial
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 16989902 [PubMed - indexed for MEDLINE]

1277: Am J Ophthalmol. 2006 Nov;142(5):839-48. Epub 2006 Sep 20.

A novel His158Arg mutation in TIMP3 causes a late-onset form of Sorsby fundus
dystrophy.

Lin RJ, Blumenkranz MS, Binkley J, Wu K, Vollrath D.

Department of Genetics, Stanford University School of Medicine, Stanford,
California 94305-5120, USA.

PURPOSE: To describe the phenotype and genotype of a family with suspected Sorsby
fundus dystrophy (SFD). DESIGN: Case reports and results of deoxyribonucleic acid
(DNA) analysis. METHODS: Clinical features were determined by complete
ophthalmologic examination or by review of medical records. Mutational analysis
of the tissue inhibitor of metalloproteinase (TIMP)3 gene was performed by DNA
resequencing. Biochemical properties of the mutant TIMP3 protein were studied,
and phylogenetic and molecular modeling analyses of TIMP proteins were performed.
RESULTS: Fundi of four affected family members demonstrated active or regressed
bilateral choroidal neovascularization, whereas another affected individual
displayed severe diffuse pigmentary degeneration associated with nyctalopia
characteristic of SFD. Onset of disease occurred in the fifth to seventh decades 
of life. A heterozygous His158Arg mutation was found in seven affected family
members and was absent from an unaffected member and 98 unrelated controls.
Bioinformatic analyses indicate that histidine 158 is an evolutionarily conserved
residue in most vertebrate TIMP homologs and predict that substitution by
arginine disrupts TIMP3 function. The mutant protein appears to be expressed by
fibroblasts from an affected family member. Molecular modeling suggests that
TIMP3 residue 158 may be part of a protein-protein interaction interface.
CONCLUSION: A novel mutation in TIMP3 causes a late-onset form of SFD in this
family. His158Arg is the first reported TIMP3 SFD coding sequence mutation that
does not create an unpaired cysteine. Further study of this unusual mutation may 
provide insight into the mechanism of SFD pathogenesis.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16989765 [PubMed - indexed for MEDLINE]

1278: Am J Ophthalmol. 2006 Nov;142(5):788-93. Epub 2006 Sep 20.

Comment in:
    Am J Ophthalmol. 2007 Aug;144(2):335; author reply 335-6.    Am J Ophthalmol. 2008 Aug;146(2):329.

Prevalence of age-related maculopathy in the adult population in China: the
Beijing eye study.

Li Y, Xu L, Jonas JB, Yang H, Ma Y, Li J.

Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Capital
University of Medical Science, Beijing, China.

OBJECTIVE: To evaluate the prevalence of age-related maculopathy (ARM) in adult
Chinese living in rural or urban regions of mainland China. DESIGN:
Population-based prevalence study. METHODS: The study included 4439 subjects
(aged 40 or more years) out of 5324 subjects invited to participate (response
rate 83.4%). It was held in rural and urban regions of Greater Beijing. The
participants underwent a detailed ophthalmic examination including fundus
photography. All fundus photographs were graded by the Wisconsin Age-Related
Maculopathy Grading System. RESULTS: Fundus photographs were available for 4376
(98.6%) subjects. Early ARM was present in 122 (1.4%) of 8655 (95% confidence
interval [CI] 1.16% to 1.66%) eyes or 63 (1.4%) of 4376 (95% CI 1.09% to 1.79%)
subjects, late ARM in 12 (0.14%) of 8655 (95% CI 0.06% to 0.22%) eyes or seven
(0.2%) of 4376 (95% CI 0.04% to 0.28%) subjects, and exudative ARM as part of
late ARM in seven (0.1%) of 8655 (95% CI 0.02% to 0.14%) eyes or six (0.1%) of
4376 (95% CI 0.03% to 0.25%) subjects. The prevalence of early ARM, late ARM, and
exudative ARM, respectively, increased from 0.61%, 0.07%, and 0.07% in the
40-to-44-year age group, to 1.66%, 0.26%, and 0.26% in the 55-to-59-year group,
and to 2.99%, 0.90%, and 0.60% in the group aged 75 years and older. ARM was
causative for visual impairment (best-corrected visual acuity in the better eye, 
<20/60 and > or =20/400) or blindness (visual acuity <20/400) in one subject
(0.023%). CONCLUSIONS: Visual impairment due to ARM was relatively uncommon in
the adult Chinese population in rural and urban regions.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16989759 [PubMed - indexed for MEDLINE]

1279: Prescrire Int. 2006 Aug;15(84):127-9.

Pegaptanib: new drug. In macular degeneration: too many risks for too little
benefit.

[No authors listed]

(1) Age-related macular degeneration with vascular proliferation can markedly
hamper vision. In patients with subfoveolar involvement, verteporfin photodynamic
therapy slows the loss of visual acuity on the EDTRS scale in about 15% of
patients after 2 years of follow-up. (2) Pegaptanib, a vascular endothelial
growth factor (VEGF) inhibitor, has been approved for the treatment of the
neovascular form of age-related macular degeneration. (3) Two double-blind
placebo-controlled trials involved a total of 1208 patients. When pegaptanib was 
injected into the eye every 6 weeks, at a dose of 0.3 mg, visual loss measured
one year after beginning treatment was slowed in about 15% more patients on
pegaptanib than on placebo. Efficacy during the second year is uncertain.
Pegaptanib has not been compared with other treatments, nor has it been assessed 
in combination with verteporfin. (4) A variety of ocular adverse events were
reported during clinical trials, three of which were serious and each affected
about 1% of patients: endophthalmia, retinal detachment, and cataracts. Transient
ocular hypertension occurred in about 15% of patients. A few cases of retinal
arterial and venous thrombosis have been described. No long-term adverse effects 
were reported after clinical trials, but hypersensitivity reactions were reported
post-approval. (5) Treatment with pegaptanib involves an intraocular injection
every 6 weeks under local anaesthesia and under conditions of surgical asepsis.
(6) In practice, an indirect comparison suggests that intraocular pegaptanib is
no more effective than verteporfin photodynamic therapy. In contrast, adverse
events are more numerous and treatment is less convenient.

PMID: 16989023 [PubMed - indexed for MEDLINE]

1280: Br J Ophthalmol. 2007 Apr;91(4):546-50. Epub 2006 Sep 20.

Histological evidence for revascularisation of an autologous retinal pigment
epithelium--choroid graft in the pig.

Maaijwee KJ, van Meurs JC, Kirchhof B, Mooij CM, Fischer JH, Mackiewicz J, Kobuch
K, Joussen AM.

Department of Vitreoretinal Surgery, Center of Ophthalmology, University of
Cologne, Germany.

BACKGROUND: Translocation of a free autologous graft consisting of retinal
pigment epithelium (RPE), Bruch's membrane, choriocapillaris and choroid in
patients with exudative age-related macular degeneration is currently being
evaluated in clinical practice. Angiographic studies in these patients suggest
that their grafts become revascularised. AIM: To investigate the histological
evidence of revascularisation of the graft in a porcine model. METHODS: In 11
pigs (11 eyes), an RPE-choroid graft was translocated from the mid-periphery to
an intact or an intentionally damaged RPE and Bruch's membrane at the recipient
site. The eyes were enucleated 1 week or 3 months after surgery. Tissue sections 
were evaluated using immunohistochemistry. RESULTS: Bridging vessels between
recipient layer and graft were identified from 1 week to 3 months after surgery. 
This reconnection occurred regardless of whether the Bruch's membrane of the
recipient site was left intact or intentionally damaged at the time of
transplantation. The vasculature of the graft appeared open and perfused. Vessels
with transcapillary pillars and conglomerates of small new vessels were present
in the graft. CONCLUSIONS: This study showed histological evidence for
revascularisation by angiogenesis of a free autologous RPE-choroid graft.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16987900 [PubMed - indexed for MEDLINE]

1281: Am J Ophthalmol. 2006 Nov;142(5):794-99. Epub 2006 Sep 15.

Intravitreal triamcinolone acetonide for diffuse diabetic macular edema: phase 2 
trial comparing 4 mg vs 2 mg.

Audren F, Lecleire-Collet A, Erginay A, Haouchine B, Benosman R, Bergmann JF,
Gaudric A, Massin P.

Department of Ophthalmology, Hôpital Lariboisière, Assistance Publique-Hôpitaux
de Paris, Université Paris, Paris, France.

PURPOSE: To prospectively compare the efficacy and safety of 4 vs 2 mg
intravitreal triamcinolone acetonide (TA) injection for diabetic macular edema.
DESIGN: Interventional case series. METHODS: PATIENTS: Thirty-two patients with
diabetic macular edema unresponsive to laser photocoagulation. INTERVENTION:
Patients were randomly assigned to receive 4 or 2 mg intravitreal TA in one eye
(16 patients in each group). MAIN OUTCOME MEASURES: The main outcome was central 
macular thickness (CMT) measured by optical coherence tomography (OCT) at four,
12, and 24 weeks. Secondary outcomes were gain in Early Treatment Diabetic
Retinopathy Study (ETDRS) scores, intraocular pressure (IOP), cataract
progression, and duration of effect. RESULTS: Before injection, mean (+/- SD) CMT
was 564.5 +/- 119 microm and 522.9 +/- 148.5 microm in the 4- and 2-mg groups,
respectively. At four, 12, and 24 weeks after injection, it was 275.0 +/- 79.8,
271.4 +/- 128.7, and 448.7 +/- 146.4 microm, respectively, in the 4-mg group, and
267.3 +/- 82.4, 289.8 +/- 111.4, and 394.7 +/- 178.9 microm, respectively, in the
2-mg group. At no time was the difference in CMT between both groups
statistically significant (P> 0.3). The between-group differences in the gain in 
the ETDRS score and in IOP were not statistically significant either. Diabetic
macular edema recurred after a median period of 20 weeks vs 16 weeks in the 4-
and 2-mg groups, respectively (P = 0.11). CONCLUSIONS: In the short term,
intravitreal injection of 4 or 2 mg TA does not have different effects on CMT,
visual acuity, or IOP.

Publication Types: 
    Clinical Trial, Phase II
    Randomized Controlled Trial

PMID: 16978576 [PubMed - indexed for MEDLINE]

1282: Graefes Arch Clin Exp Ophthalmol. 2006 Oct;244(10):1233-9. Epub 2006 Sep
15.

Three-dimensional imaging of pigment epithelial detachment in age-related macular
degeneration using optical coherence tomography, retinal thickness analysis and
topographic angiography.

Ahlers C, Michels S, Beckendorf A, Birngruber R, Schmidt-Erfurth U.

Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.
christian.ahlers@meduniwien.ac.at

INTRODUCTION: New diagnostic tools such as the retinal thickness analyzer (RTA), 
optical coherence tomography (OCT), and topographic angiography (TAG) were
introduced into clinical ophthalmology during the last years giving the examiner 
new insights into anatomical and functional aspects of macular disease. In this
study, advantages and disadvantages of the new imaging methods have been
evaluated in patients with serous (sPED) and fibrovascular pigment epithelial
detachments (fPED) secondary to age-related macular degeneration (AMD). METHODS: 
TAG, using fluorescein angiography (FA), provides a three-dimensional profile of 
the fluorescein pattern based on the analysis of a set of 32 confocal images over
a depth of 4 mm. RTA and OCT provide cross-sectional images of the neurosensory
retina and the retinal pigment epithelium-choriocapillary complex as well as
retinal thickness data encoded in a false color map. We compared and evaluated
these modalities in 15 patients with fPED and 15 patients with sPED secondary to 
AMD. RESULTS: In patients with classic fPED, TAG detected neovascular structures 
and delineated their configuration. In sPEDs, pooling of extravascular fluid was 
detected in a dome-shaped configuration. OCT provided detailed information on the
neurosensory retina's structures but failed to detect the neovascular membrane in
fPED. Mapping the retinal thickness, RTA and OCT both failed to detect the PED
and showed typical algorithm error-based patterns. CONCLUSION: TAG OCT and RTA
are useful imaging modalities in the evaluation of AMD cases. TAG visualizes the 
vascular configuration, dynamic perfusion, and leakage changes. OCT and RTA are
able to complementarily document intra-, subretinal, and sub-RPE fluid
accumulation secondary to CNV. However, OCT seems to be more efficient in imaging
AMD-related pathologies than RTA, as this modality is often compromised by intra-
or subretinal structural abnormalities. Nevertheless, all modalities may provide 
further valuable insight into AMD pathogenesis, enhance diagnostic quality, and
improve the assessment of therapeutic effects.

Publication Types: 
    Comparative Study

PMID: 16977431 [PubMed - indexed for MEDLINE]

1283: Br J Ophthalmol. 2007 Mar;91(3):354-9. Epub 2006 Sep 14.

Prevalence of reticular pseudodrusen in age-related macular degeneration with
newly diagnosed choroidal neovascularisation.

Cohen SY, Dubois L, Tadayoni R, Delahaye-Mazza C, Debibie C, Quentel G.

Centre Ophtalmologique d'Imagerie et de Laser, 11 Rue Antoine Bourdelle, 75015
Paris, France. sycohen@club-internet.fr

AIM: To investigate the prevalence of reticular pseudodrusen (RPD) in eyes of
patients presenting with newly diagnosed choroidal neovascularisation (CNV) in
age-related macular degeneration (AMD), and to analyse the association between
RPD, age-related maculopathy (ARM) and AMD. METHOD: Two observational consecutive
prospective series. In series 1, patients with AMD with newly diagnosed CNV were 
sampled to determine the incidence of RPD. Eyes with and without RPD were
compared by the Mann-Whitney non-parametric test and Fisher's exact test for age,
sex of patients, the eye involved and type of CNV. Series 2 comprised 100
patients referred for fundus photography, fluorescein and/or indocyanine green
angiography, for whom pictures showed RPD. This second cohort was then selected
from a larger group of patients. RESULTS: Patients with newly diagnosed CNV in
series 1 comprised 67 women and 33 men, aged 57-96 years (mean 79.5). CNV was
"classic" (32 eyes), "occult" (41) or exhibited vascularised pigment epithelial
detachment (PED, 11), retinal angiomatous proliferation (RAP) with or without PED
(13), or haemorrhagic or fibrovascular scarring (3). In all, 24 (24%) eyes had
RPD. The prevalence of RAP was significantly higher in eyes with RPD than in
those without (p = 0.0128), despite the small number of patients with RAP. In
series 2, 100 patients with RPD were enrolled in 3 months, and corresponded to 8%
of the overall cases referred to our centre (Centre Ophtalmologique d'Imagerie et
de Laser, Paris, France). There were 77 women and 23 men, aged 54-93 years (mean 
79.2). Eyes with RPD (n = 155) usually exhibited signs of ARM or AMD, including
soft drusen (101 eyes) and/or retinal pigment epithelium abnormalities (70),
geographical atrophy (27) and/or CNV (61). In both studies, examination of
blue-light fundus pictures was extremely helpful in diagnosing RPD. CONCLUSION:
RPD have a high prevalence among patients with AMD with newly diagnosed CNV (24% 
of cases). RPD were commonly associated with ARM or AMD. This study suggests that
eyes with RPD could be classified as a phenotype of ARM.

PMID: 16973663 [PubMed - indexed for MEDLINE]

1284: Br J Ophthalmol. 2007 Feb;91(2):199-203. Epub 2006 Sep 14.

A prospective randomised trial of different doses of intravitreal triamcinolone
for diabetic macular oedema.

Lam DS, Chan CK, Mohamed S, Lai TY, Li KK, Li PS, Tsang CW, Chan WM, Shanmugam
MP.

Department of Ophthalmology & Visual Sciences, The Chinese University of Hong
Kong, Hong Kong. dennislam_pub@cuhk.edu.hk

OBJECTIVE: To compare the safety and efficacy of different doses of intravitreal 
triamcinolone (ivTA) in treating clinically significant diabetic macular oedema
(CSMO). METHODS: 63 eyes of 63 patients with CSMO and central foveal thickness
(CFT) of > or =250 microm on optical coherence tomography were randomised to
receive 4 mg (n = 23), 6 mg (n = 20) or 8 mg (n = 20) ivTA. Patients were
followed up for 6 months, and changes in best-corrected visual acuity (BCVA),
optical coherence tomography CFT, standardised change in macular thickness
(SCMT), and side effects such as intraocular pressure and cataractogenesis were
compared between the three groups. RESULTS: After ivTA injection, improvements of
BCVA and CFT occurred in all groups. The mean BCVA improvement at 6 months was
significantly higher for the 8 mg group compared with the 4 mg group, with 9.9
and 3.1 improvement in letters on the Early Treatment of Diabetic Retinopathy
Study chart, respectively (p = 0.047). The mean SCMT at 6 months for the 4, 6 and
8 mg groups was 28.7%, 42.3% and 60.5%, respectively (p = 0.06). The proportion
of eyes with SCMT > or =75% at 6 months was higher in the 8 mg group, but the
difference failed to reach significance (p = 0.06). Ocular hypertensive responses
(>21 mm Hg) occurred in 39%, 30% and 55% of eyes in the 4, 6, and 8 mg groups,
respectively (p = 0.27). CONCLUSIONS: Higher doses of ivTA may prolong the
duration of visual benefit in diabetic CSMO and seemed to result in more
sustained reduction in macular oedema. Further studies are warranted to
investigate the optimum dose of ivTA in treating diabetic CSMO.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16973659 [PubMed - indexed for MEDLINE]

1285: Doc Ophthalmol. 2006 Sep;113(2):71-81. Epub 2006 Sep 14.

A comparison of pattern and multifocal electroretinography in the evaluation of
age-related macular degeneration and its treatment with photodynamic therapy.

Neveu MM, Tufail A, Dowler JG, Holder GE.

Moorfields Eye Hospital, London, EC1V 2PD, UK.

This study compares pattern electroretinography (PERG) and multifocal
electroretinography (mfERG) measures in 13 patients with predominantly classic
choroidal neovascularisation (CNV) associated with age-related macular
degeneration (ARMD, 9/13 unilateral, 4/13 bilateral), assesses the usefulness of 
each test in monitoring disease progression, and identifies electrophysiological 
predictors of outcome following treatment with photodynamic therapy (PDT). PERG
and mfERGs were recorded at presentation, 2 weeks post-treatment, and at 3
monthly intervals for 2 years. The PERG was detectable in 8/13 patients with
unilateral disease; the mfERG was detectable in 12/13 patients. P50 and N95
amplitudes increased in 6/8 patients and mfERG p1 increased in 7/13 patients at 2
years. PERG amplitudes correlated strongly with mfERG amplitudes in patients with
unilateral disease. PERG P50 and mfERG p1 amplitude correlated with visual acuity
at 2 years (R = 0.68, R = 0.82, respectively). The largest PERG P50 and mfERG p1 
amplitude difference between treated and fellow eyes of all the groups on initial
visit was associated with a poor visual outcome (P50 64% difference; p1 29%
difference) whereas those with the smallest P50 and p1 amplitude difference was
associated with improved vision at 2 years (P50 30% difference; p1 21%
difference). The PERG and mfERG provide an objective measure of central retinal
function in the progression of ARMD. A detectable PERG on presentation was the
single best indicator of improved function and visual acuity at 2 years. The
mfERG demonstrated disease progression from central retina into the paramacular
regions over 2 years. Patients with poor visual outcomes had the largest
inter-ocular amplitude difference on presentation, suggesting that such patients 
may have a worse prognosis following treatment.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16972084 [PubMed - indexed for MEDLINE]

1286: Genet Couns. 2006;17(2):149-53.

Ectrodactyly, ectodermal dysplasia, macular degeneration syndrome: a further
contribution.

Yildirim MS, Ogun TC, Kamiş U.

Department of Medical Genetics, Meram Medical Faculty of Selcuk University,
Konya, Turkey. drmselman@hotmail.com

EEM syndrome is a rare condition characterised by ectodermal dysplasia,
ectrodactyly and macular dystrophy. Additional abnormalities such as alopecia,
cataract, absent eyebrows, and oligodontia may occur. We report two brothers and 
a sister born to consanguineous parents with EEM syndrome. EEM syndrome differs
from other ectrodactly syndromes by the characteristic findings in the ocular
fundus showing extensive retinochoroidal atrophy with diffuse retinal
pigmentation and mild arteriolar attenuation at the posterior pole. In contrast
to other ectrodactyly syndromes autosomal recessive inheritance is most likely.

Publication Types: 
    Case Reports

PMID: 16970031 [PubMed - indexed for MEDLINE]

1287: Arch Ophthalmol. 2006 Sep;124(9):1276-85.

Use of iris pigment epithelium to replace retinal pigment epithelium in
age-related macular degeneration: a gene expression analysis.

Cai H, Shin MC, Tezel TH, Kaplan HJ, Del Priore LV.

Department of Ophthalmology, Harkness Eye Institute, Columbia University, 635 W. 
165th Street, New York, NY 10032, USA.

OBJECTIVE: To determine the gene expression profiles of primary retinal pigment
epithelium (RPE) and iris pigment epithelium (IPE) using microarrays. METHODS:
Primary RPE and IPE from 6 human donor eyes were collected, and total RNA was
isolated. Differences in gene expression were determined using a human genechip
(human U95Av2 [12 600 probes]; Affymetrix Inc, Santa Clara, Calif). RESULTS:
Hierarchical cluster analysis differentiated the gene expression profiles of RPE 
and IPE clusters into 2 distinct groups. A mean +/- SD of 5308 +/- 416 gene
probes were expressed in RPE vs 6130 +/- 205 in IPE. Sixty-eight genes were
expressed only in RPE; 154 genes were expressed only in IPE. Twenty-two
additional genes had greater than 3-fold increased expression in RPE vs IPE, and 
147 genes had greater than 3-fold decreased expression in RPE vs IPE. CONCLUSION:
There are major differences in the gene expression profiles of primary RPE vs
IPE.Clinical Relevance The different gene expression profiles of primary RPE vs
IPE harvested from the same donor eyes infer that it may be difficult for IPE to 
replace all aspects of damaged RPE function in transplantation studies.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 16966623 [PubMed - indexed for MEDLINE]

1288: Acta Ophthalmol Scand. 2006 Oct;84(5):636-41.

The prevalence of age-related maculopathy (ARM) in an urban Norwegian population:
the Oslo Macular study.

Björnsson OM, Syrdalen P, Bird AC, Peto T, Kinge B.

Department of Ophthalmology, Rikshospitalet, Oslo, Norway.
olafur.bjornsson@retinaklinikken.no

PURPOSE: To examine the prevalence of early and late age-related maculopathy
(ARM) in citizens aged 51 years and older in the city of Oslo and its
surroundings. METHODS: We selected a random sample of 800 subjects, using a
cross-sectional study design. A total of 459 of the 770 eligible subjects agreed 
to participate, giving an attendance rate of 59.6%. Stereoscopic colour digital
photographs were obtained and graded at a certified reading centre using the
International Classification Grading System for ARM. RESULTS: Early ARM in either
eye was found in 43.1% (95% CI 38.5-47.7) of subjects aged 51 years and older.
This was due to a much higher prevalence of pigmentary changes, predominantly
hyperpigmentation in all age groups, than previously reported; 37.5% of people
aged 51-60 years of age had pigmentary changes > or = 63 microm, increasing to
66.0% in the oldest age group. In people aged 71 years and older, geographic
atrophy (GA) was found in either eye in 3.6% (95% CI 0.4-6.8) and exudative
macular degeneration (AMD) was found in either eye in 2.9% (95% CI 0.0-5.7) of
subjects. CONCLUSION: To our knowledge, this is the first published study to rely
solely on digital photography for grading purposes in a population-based study.
Early ARM was found to have a higher prevalence than previously reported in other
populations. Exudative AMD and GA had similar prevalences to those described in
the literature, although the prevalence of GA tended to be higher than previously
reported in some surveys.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16965494 [PubMed - indexed for MEDLINE]

1289: Acta Ophthalmol Scand. 2006 Oct;84(5):624-30.

Intravitreal triamcinolone acetonide for diffuse diabetic macular oedema: 6-month
results of a prospective controlled trial.

Audren F, Erginay A, Haouchine B, Benosman R, Conrath J, Bergmann JF, Gaudric A, 
Massin P.

Department of Ophthalmology, Lariboisière Hospital, University of Paris, Paris,
France.

PURPOSE: To evaluate prospectively the efficacy and safety of one intravitreal
injection of 4 mg triamcinolone acetonide for refractory diffuse diabetic macular
edema. METHODS: Seventeen patients with bilateral diabetic macular edema
unresponsive to laser photocoagulation. In all patients, one eye was injected,
and the other served as a control. The intervention consisted in intravitreal
injection of 4 mg triamcinolone acetonide. The main outcome measure was central
macular thickness (CMT) at 4, 12 and 24 weeks, measured by Optical Coherence
Tomography. Secondary outcomes were Early Treatment Diabetic Rentinopathy Study
(ETDRS) scores, intraocular pressure and cataract PROGRESSION. RESULTS: Before
injection, mean +/- SD CMT was 566.4 +/- 182.4 mum in injected eyes. Four, 12,
and 24 weeks after injection, it was 228.4 +/- 47.5 mum, 210.9 +/- 87.2 mum and
358.5 +/- 160.5 mum respectively. CMT was significantly lower in injected eyes
vs. control eyes except 24 weeks after injection because of a recurrence of
macular edema in 9/17 injected eyes. Mean +/- SD gain in ETDRS score was
significantly better in injected eyes vs. control eyes 4, 12 and 24 weeks after
TA injection. In 9 of the 17 injected eyes, intraocular pressure exceeded 24 mmHg
and was controlled by topical medication. CONCLUSION: In the short-term,
intravitreal injection of triamcinolone effectively reduces macular thickening
due to diffuse diabetic macular edema and improves visual acuity in most cases.
The long-term effect of this treatment and predictive factors of visual recovery 
remain to be elucidated.

Publication Types: 
    Randomized Controlled Trial

PMID: 16965492 [PubMed - indexed for MEDLINE]

1290: Methods Inf Med. 2006;45(4):414-8.

Markov models for repeated ordinal data.

Wellmann J.

University of Münster, Institute of Epidemiology and Social Medicine, Domagkstr. 
3, 48149 Münster, Germany. wellmann@uni-muenster.de

OBJECTIVES: To demonstrate the application of Markov models, especially for
ordinal outcomes, within the context of regression models for correlated data.
METHODS: A brief review of regression methods for correlated data is given. A
proportional odds model and a continuation ratio model is applied to repeated
measurements of macular pigment density, obtained in an intervention study on the
supplementation of macular carotenoids. The correlation between repeated
assessments is assumed to follow a first-order Markov model. The models are
implemented with standard statistical software. RESULTS: Both models, though not 
directly comparable, provide a similar conclusion. The application of these
models with standard statistical software is straightforward. CONCLUSIONS: Markov
models can be valuable alternatives to random effects modes or procedures based
on generalized estimation equations.

PMID: 16964358 [PubMed - indexed for MEDLINE]

1291: Retina. 2006 Sep;26(7):803-10.

The impact of auditory and haptic feedback on computer task performance in
patients with age-related macular degeneration and control subjects with no known
ocular disease.

Scott IU, Jacko JA, Sainfort F, Leonard VK, Kongnakorn T, Moloney KP.

Department of Ophthalmology, Penn State College of Medicine, Hershey,
Pennsylvania 17033-0850, USA. iscott@psu.edu

PURPOSE: To determine the impact of auditory and haptic (tactile) feedback on
computer task performance of patients with age-related macular degeneration (AMD)
compared to controls. METHODS: Thirty patients with AMD and 29 similarly aged
controls with no known ocular disease completed timed computer icon "drag and
drop" tasks under all four possible conditions of presence or absence of auditory
and haptic feedback in a two-factor repeated measures design. Patient recruitment
was stratified by best eye acuity: 20/20-20/50; 20/60-20/100; <20/100. Controls
had best eye acuity>or=20/30. Task completion time was quantified using final
target highlight time (FTHT) and total trial time, measured in milliseconds.
RESULTS: Mean+/-standard deviation (SD) FTHT with neither feedback type in the
three patient and control groups was, respectively: 1,110+/-356, 1,682+/-1,069,
1,763+/-831, 924+/-533. Auditory feedback improved performance [%FTHT decrease,
p-value] in all groups, respectively: 18%, P=0.018; 38%, P=0.054; 57%, P=0.001;
19%, P=0.001. Haptic feedback improved performance in the worst acuity AMD group 
and controls: 46%, P=0.009; 17%, P=0.038. In the worst acuity AMD group, auditory
and/or haptic feedback was associated with a 4-6 second mean (for each task)
reduction in total trial time. CONCLUSION: Auditory and haptic feedback can
substantially increase performance speed of computer "drag and drop" tasks for
patients with AMD, particularly in those patients with the most compromised
vision.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, Non-P.H.S.

PMID: 16963855 [PubMed - indexed for MEDLINE]

1292: Retina. 2006 Sep;26(7):786-91.

Interferon alfa-2a: a new treatment option for long lasting refractory cystoid
macular edema in uveitis? A pilot study.

Deuter CM, Koetter I, Guenaydin I, Stuebiger N, Zierhut M.

Department of Ophthalmology I, University of Tuebingen, Germany.
christoph.deuter@med.uni-tuebingen.de

PURPOSE: To perform a prospective pilot study to evaluate interferon alfa-2a (IFN
alfa-2a) for the treatment of refractory cystoid macular edema (CME) in
endogenous uveitis. METHODS: IFN alfa-2a was administered at an initial dose of 3
or 6 million IU (depending on body weight) per day subcutaneously. Afterwards IFN
alfa-2a was tapered slowly over 6 months and finally discontinued. If CME
relapsed IFN alfa-2a was reinstituted and tapered slowly again to evaluate the
lowest maintenance dose to keep remission. RESULTS: A total of 15 eyes of 8
patients with refractory CME due to intermediate or posterior uveitis were
included. Ineffective pretreatment consisted of systemic steroids and
acetazolamide (all patients) and at least one additional immunosuppressant (6
patients). Six of 8 patients (11 eyes) responded well to IFN alfa-2a and CME
resolved completely during 6 months treatment. One patient was lost to follow-up 
after IFN alfa-2a was stopped. In 1 patient (1 eye) even 19 months after
cessation of IFN alfa-2a no recurrence of CME occurred. In 4 patients (8 eyes)
IFN alfa-2a had to be reinstituted because CME relapsed. All 4 patients responded
again. During a mean follow-up period of 16.4 months since restart of therapy we 
succeeded in all 4 patients to taper IFN alfa-2a to maintenance doses between 1.5
million IU every second and every sixth day without a recurrence of CME in any of
the 8 eyes. CONCLUSION: IFN alfa-2a can be a treatment option for patients with
otherwise treatment resistant uveitic CME.

PMID: 16963852 [PubMed - indexed for MEDLINE]

1293: Vis Neurosci. 2006 May-Aug;23(3-4):549-54.

Macular pigment and color discrimination.

Moreland JD, Westland S.

MacKay Institute, Keele University, United Kingdom.

An earlier modeling study of the effect of changes in macular pigment optical
density (MPOD) on a wide range of surface colors is re-examined. That study
reported changes in local chromaticity variance and in color spacing, some of
which were incompatible with tritan-like confusions in normals associated with
high-simulated MPOD. This disagreement might have arisen through the use of the
von Kries correction for adaptation. The analysis is repeated, using 1782
reflectance spectra of natural and man-made colors. These colors are segregated
into an array of 25 equally populated cells in an analogue of the MacLeod-Boynton
cone excitation diagram. Removing the von Kries correction restores compatibility
with other experimental data. Differences between the results for normal and
anomalous trichromats, noted in the earlier study, are confirmed. An analysis of 
local chromaticity variance across color space indicates the presence of
systematic patterns. The earlier study also reported differences in results
across observer types (for example, between normals and protanomals) and this is 
addressed here by utilizing fundamentals defined by a variable photopigment
template. Chromaticities are computed for the same 1782 reflectance spectra for
normals and for a set of protanomals (for whom the anomalous L pigment is shifted
between the normal L and M spectral locations). Colors are segregated into an
array of 100 cells in an analogue of the MacLeod-Boynton cone excitation diagram.
Changes in chromaticity variance with MPOD for these cells are mapped for normals
and protanomals. Variance along the L/(L + M) axis is sensitive to the number of 
cells used for segmentation. It also increases with MPOD for normal observers but
this trend reverses as the wavelength of maximum sensitivity of the L cone shifts
towards shorter wavelengths (protanomalous locations).

Publication Types: 
    Comparative Study

PMID: 16961994 [PubMed - indexed for MEDLINE]

1294: Br J Ophthalmol. 2007 Apr;91(4):491-6. Epub 2006 Sep 6.

Fundus autofluorescence in exudative age-related macular degeneration.

McBain VA, Townend J, Lois N.

Ophthalmology Department, Grampian University Hospitals NHS Trust, Foresterhill, 
Aberdeen AB25 2ZD, UK.

AIM: To evaluate the distribution of fundus autofluorescence in patients with
age-related macular degeneration and choroidal neovascularisation (CNV). METHODS:
Colour fundus photographs, fundus fluorescein angiograms (FFA) and fundus
autofluorescence images were obtained from a group of 40 patients (43 eyes) with 
age-related macular degeneration and purely classic or occult CNV. Only patients 
with newly diagnosed CNV and in whom autofluorescence images were obtained within
2 weeks from FFA were included. The distribution of autofluorescence was
qualitatively evaluated, and the findings compared with those from colour fundus 
photographs and FFA. RESULTS: 29 (67%) eyes had classic CNV and 14 (33%) had
occult CNV. In 26 (90%) eyes with classic CNV, a low autofluorescence signal was 
detected at the site of the CNV; in 7 (50%) eyes with occult CNV, multiple foci
of low autofluorescence signal were detected. Outside the area affected by the
lesion, homogeneous autofluorescence was observed in most of the cases (n = 33,
77%). Similarly, homogeneous autofluorescence was commonly observed in fellow
eyes (62%). A pattern of focal increased autofluorescence was rarely seen in eyes
with CNV (n = 4, 9%) or in fellow eyes (n = 4, 15%). In 11 of 43 (25%) eyes,
areas of increased autofluorescence, other than a pattern of focal increased
autofluorescence, were detected. In four patients, autofluorescence images had
been obtained before the development of CNV; in none was any increased
autofluorescence detected before the formation of CNV. CONCLUSIONS: Distinct
patterns of autofluorescence were observed in eyes with pure classic and occult
CNV. Increased autofluorescence was rarely seen in eyes with CNV and in fellow
eyes, suggesting that increased autofluorescence, and thus, retinal pigment
epithelium lipofuscin, may not play an essential part in the formation of CNV.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16956913 [PubMed - indexed for MEDLINE]

1295: Ophthalmologica. 2006;220(5):291-5.

Further support for the common variants in complement factor H (Y402H) and
LOC387715 (A69S) genes as major risk factors for the exudative age-related
macular degeneration.

Shastry BS.

Department of Biological Sciences, Oakland University, Rochester, MI 48309-4401, 
USA. shastry@oakland.edu

In developed countries, age-related macular degeneration (ARMD) is a common cause
of blindness in the elderly. It is a clinically complex and genetically
heterogeneous disorder. The etiology of the disorder may involve interactions
between genetic and environmental factors. Recently it has been reported that a
polymorphism in the complement factor H (CFH) and LOC387715 gene may determine
the susceptibility of individuals to ARMD. In order to replicate and to determine
the frequency of this polymorphism in ARMD patients, we have analyzed two
unrelated families having exudative ARMD. Our analysis has identified the same
common polymorphism (Y402H) in the CFH gene in one family and the A69S
polymorphism in the LOC387715 gene in the second family. These results further
support the notion that CFH and LOC387715 genes are the major risk factors for
ARMD. Copyright 2006 S. Karger AG, Basel.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16954704 [PubMed - indexed for MEDLINE]

1296: Eur J Ophthalmol. 2006 Jul-Aug;16(4):573-81.

Pars plana vitrectomy and removal of the internal limiting membrane in diabetic
macular edema unresponsive to grid laser photocoagulation.

Yanyali A, Horozoglu F, Celik E, Ercalik Y, Nohutcu AF.

Department of Ophthalmology, Haydarpasa Numune Education and Research Hospital,
Caddebostan 81060, Istanbul, Turkey. ayanyali@hotmail.com

PURPOSE: To evaluate the effectiveness of pars plana vitrectomy (PPV) with
removal of the internal limiting membrane (ILM) in diabetic patients with macular
edema unresponsive to grid laser photocoagulation. METHODS: In this randomized
controlled study, 20 eyes of 10 patients with diabetic macular edema unresponsive
to grid laser photocoagulation were evaluated. PPV with ILM removal was performed
randomly in one eye each of 10 patients and taken as the study group; the
untreated fellow eyes were taken as the control group. Main outcome measures were
foveal thickness changes measured with optical coherence tomography and
preoperative and post-operative visual acuity. Mann-Whitney U, Wilcoxon, and
chi-square tests were used in statistical analysis. RESULTS: The mean age of the 
patients was 61.5+/-6 years (range 51 to 71). All patients were followed up for
12 months. In the study group, mean foveal thickness was 391.3+/-91.6 microm
preoperatively and 225.5+/-49.4 microm postoperatively (p=0.009). In the control 
group, mean foveal thickness was 356.2+/-140 microm at baseline and 318.4+/-111.1
microm at 12-month follow-up (p=0.138). Mean decrease in foveal thickness was
165.8+/-114.8 microm in the study group and 37.8+/-71.2 microm in the control
group (p=0.016). In the study group, best-corrected log-MAR visual acuity was
0.71+/-0.43 preoperatively and 0.54+/-0.45 postoperatively (p=0.125). In the
control group, best-corrected logMAR visual acuity was 0.43+/-0.44 at baseline
and 0.59+/-0.55 at 12-month follow-up (p=0.235). In the study group, visual
acuity improved by two or more lines in 4 eyes (40%) and remained stable in 6
eyes (60%). In the control group, visual acuity improved by two or more lines in 
1 eye (10%) and decreased by two or more lines in 3 eyes (30%). CONCLUSIONS: PPV 
with ILM removal appears to be an effective procedure for reducing diabetic
macular edema unresponsive to grid laser photocoagulation. A further study with a
large number of patients is required to assess the effectiveness and safety of
this procedure.

Publication Types: 
    Randomized Controlled Trial

PMID: 16952097 [PubMed - indexed for MEDLINE]

1297: Eur J Ophthalmol. 2006 Jul-Aug;16(4):566-72.

Follow-up after intravitreal triamcinolone acetonide for diabetic macular edema.

Jonas JB, Spandau UH, Kamppeter BA, Vossmerbauemer U, Harder B.

Department of Ophthalmology, Faculty of Clinical Medicine Mannheim,
Universitäts-Augenklinik, Ruprecht-Karls-University of Heidelberg,
Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
Jost.Jonas@augen.ma.uni-heidelberg.de

PURPOSE: To report on the follow-up of patients who received an intravitreal
high-dosage injection of triamcinolone acetonide (IVTA) as treatment of diffuse
diabetic macular edema. METHODS: The clinical interventional case-series study
included 109 eyes (90 patients) with diffuse diabetic macular edema who
consecutively received an IVTA of about 20 mg. Mean follow-up was 11.2 +/- 6.2
months. RESULTS: Visual acuity improved significantly (p<0.001) from 0.89 +/-
0.33 logMAR to a best minimum of 0.65 +/- 0.35 logMAR. An increase in best visual
acuity by at least 1 Snellen line, 2 lines, and 3 lines was found in 91 (83%)
eyes, 68 (62%) eyes, and 45 (41%) eyes, respectively. Differences in visual
acuity between baseline and follow-up examinations were significant for
measurements performed at 1 month (p<0.001), 2 months (p<0.001), 3 months
(p<0.001), and at 6 months (p=0.001) after the injection. At 9 months after the
injection, mean visual acuity regressed significantly so that visual acuity at 9 
months (p=0.83) and at 12 months after the injection (p=0.58) compared with
baseline values did not differ significantly. Forty-seven (43%) eyes developed a 
rise in intraocular pressure (pressure >21 mmHg) for 6 to 8 months after the
injection. No other severe complications were detected. CONCLUSIONS: The duration
of a visual acuity increase and intraocular pressure rise after high-dosage IVTA 
in diffuse diabetic macular edema is about 6 to 8 months. Compared with data in
the literature, the high-dosage IVTA may not have a markedly higher profile of
side effects than low-dosage IVTA.

PMID: 16952096 [PubMed - indexed for MEDLINE]

1298: Strabismus. 2006 Sep;14(3):151-62.

Results of compensatory extraocular muscle surgery after macular translocation.

De Clippeleir L, Stalmans P, Dieltiëns M, Baekeland L, Beelen L, Janssens H, van 
Lammeren M.

Department of Ophthalmology, Catholic University of Louvain, Louvain, Belgium.
declippeleir@uz.kuleuven.ac.be

PURPOSE: Macular translocation is an optional surgical treatment for age-related 
macular degeneration. However, this technique induces postoperative torsional
complaints and surgical counterrotation of the globe is mandatory. The purpose of
this study is to report the effect of compensatory extraocular muscle surgery
upon the torsional complaints in patients who underwent a macular translocation
procedure. DESIGN: The pre- and postoperative data on the first 35 patients in
our department who underwent a counterrotation procedure after macular
translocation surgery are reviewed. METHODS: From November 2001 to January 2005, 
35 patients underwent a macular translocation procedure, with subsequent
extraocular muscle surgery to counterrotate the eye. Three types of rectus muscle
transposition procedures were used: full-tendon transposition of two opposite
rectus muscles, "crossed" half-tendon transposition of all rectus muscles ('split
& cross' procedure), and "uncrossed" half-tendon transposition of all rectus
muscles ('split & neighbor cross' procedure). In the majority of patients these
procedures were associated with oblique muscle surgery. RESULTS: With the
selected procedures, retinal excyclodeviations are easier to correct then retinal
incyclodeviations. In our hands, full-tendon transposition of two opposite rectus
muscles with or without associated oblique muscle surgery, never corrects more
than 30 degrees. 'Split & cross' procedures combined with oblique muscle surgery 
are sufficient for retinal excyclodeviations of 30-45 degrees and for
incyclodeviations of up to 30 degrees; 'split & neighbor cross' procedures
combined with oblique muscle surgery are sufficient for retinal excyclodeviations
of 45-65 degrees and for incyclodeviations of up to 40 degrees . CONCLUSIONS: The
effect of the various procedures appears to be predictable. It is possible to
select a surgical procedure as a function of the amount of retinal
cyclodeviation.

PMID: 16950744 [PubMed - indexed for MEDLINE]

1299: Eye. 2008 Feb;22(2):194-9. Epub 2006 Sep 1.

Comparison of visual acuity outcomes in predominantly classic vs occult lesions
in age-related macular degeneration treated with photodynamic therapy.

Potter MJ, Szabo SM, Li WW.

Department of Ophthalmology and Visual Sciences, University of British Columbia, 
Columbia, Canada. mpotter@ interchange.ubc.ca

PURPOSE: To determine if patients with occult with no classic and predominantly
classic (PC) choroidal neovascular membranes have clinically equivalent visual
outcomes after treatment with photodynamic therapy (PDT) with verteporfin.
METHODS: This is a retrospective, observational cohort study. Two hundred and
seventy-seven consecutive patients with occult or PC choroidal neovascularization
secondary to age-related macular degeneration treated with PDT were included. The
main outcome was the difference in mean change in Early Treatment of Diabetic
Retinopathy Study (ETDRS) acuity lost from baseline in occult vs PC lesions, with
the minimal clinically important difference (MCID) set at 7.5 letters. RESULTS:
At baseline, 131 patients had occult and 146 had PC choroidal neovascularization.
Twelve-month follow-up data were available for 94 occult and 110 PC participants.
Occult patients lost an average of 8.7 letters (1.9 lines), and patients in the
PC group an average of 10.0 ETDRS letters (two lines) over 12 months. The mean
letters lost at 12 months was not significantly different between the groups, and
the MCID was not detected (difference=1.3 letters; P=0.411; 95% confidence
interval (-2.3, 5.6)). Patients with occult lesions required a mean of 2.99
treatments vs a mean of 2.96 treatments in the PC group (out of a possible 4;
P=0.172). CONCLUSION: We were not able to detect a clinically important
difference in mean change in visual acuity with PDT treatment between patients
with occult and PC lesions.

Publication Types: 
    Comparative Study

PMID: 16946758 [PubMed - indexed for MEDLINE]

1300: Graefes Arch Clin Exp Ophthalmol. 2007 Mar;245(3):437-42. Epub 2006 Aug 31.

Redistribution of the neurosensory retina in inferior limited macular
translocation: an evaluation using image registration.

Denion E, Ordonez JR, Klein JC, Glacet-Bernard A, Walter T, Caputo G.

Ecole Nationale Supérieure des Mines de Paris, Centre de Morphologie
Mathématique, 35 Rue Saint Honoré, 77305, Fontainebleau Cedex, France.
edenion@wanadoo.fr

BACKGROUND: The present work aims to demonstrate the role of redistribution of
the neurosensory retina (RNR)-that is, retinal tissue stretching and
compression-in inferior limited macular translocation (LMT), to perform
displacement mapping all over the area centralis, and to try and improve
displacement evaluation precision. METHODS: Using piecewise linear image
registration (through Matlab) on indocyanine green angiographic frames, we have
evaluated the deformation (on both the retinal and choroido-scleral layer) of a
pre-operative grid superimposed on the area centralis, plotted displacement
vectors all over the area centralis, and calculated a scale ratio between pre-
and post-operative frames. The scale ratio tests whether or not the same physical
distance is represented by the same distance on these frames. RESULTS: The
choroido-scleral layer is not deformed following surgery. The retinal layer shows
areas of stretching and compression, demonstrating the RNR. Displacement vectors 
feature a rotating pattern around the optic disk (except if a macular fold
exists) and a positive naso-temporal gradient. The median scale ratio is 3.8%
(2.5% to 5.8%). CONCLUSIONS: LMT involves RNR accounting for inferior retinal
displacement, despite the supposedly limited internal scleral shortening. Our
study confirms that the optic disk temporal edge is the displacement axis (except
if a macular fold exists). Our method, unaffected by a non-zero scale ratio,
provides more precision than previously published.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16944187 [PubMed - indexed for MEDLINE]

1301: Hum Mol Genet. 2006 Oct 1;15(19):2955-61. Epub 2006 Aug 29.

VEGF polymorphisms are associated with neovascular age-related macular
degeneration.

Churchill AJ, Carter JG, Lovell HC, Ramsden C, Turner SJ, Yeung A, Escardo J,
Atan D.

Molecular Ophthalmology, University of Bristol, and West Midlands Regional
Genetics Laboratory, Birmingham Womans Hospital NHS Trust, UK.
a.j.churchill@bristol.ac.uk

Age-related macular degeneration (AMD) is the most common cause of blindness in
the elderly. Linkage has been shown to the vascular endothelial growth factor
(VEGF) gene and ocular levels of VEGF are raised in individuals with the
neovascular form of disease. To examine the role of VEGF further, we conducted a 
case-control study where 45 individuals with neovascular AMD and 94 age-matched
controls were genotyped for 14 single nucleotide polymorphisms (SNPs) in the VEGF
promoter and gene. The single SNP +674 CC genotype was significantly associated
with AMD (OR=2.40, 95%CI 1.09-5.26, P=0.027). Haplotype analysis of SNPs +674,
+4618, +5092, +9162 and +9512 revealed that CTCCT and TCACC were associated with 
AMD (OR=15.77, 95% CI 1.91-130.24, P=0.0161 and OR=9.95, 95%CI 3.22-30.74,
P=0.000053, respectively). The haplotype TCACT was associated with the control
group (P=0.0001832). Furthermore, haplotype analysis of promoter SNPs revealed
that possession of the -460T, -417T, -172C, -165C, -160C, -152G, -141A, -116A,
+405C haplotype was strongly associated with AMD (OR=18.24, 95%CI 2.25-148.25,
P=0.0074). This is the most extensive analysis of the VEGF gene in AMD,
demonstrating a clear association with the exudative form of disease, thereby
creating the possibility for predictive testing. Smoking, high fat intake and
hypertension are negative environmental risk factors in AMD, whereas increased
consumption of dietary antioxidants can have a protective effect. Identification 
of those at risk in the population would allow individual counselling with
lifestyle advice to reduce the risks of blindness. (Genbank accession nos M63971 
and AF437895).

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16940309 [PubMed - indexed for MEDLINE]

1302: Proc Natl Acad Sci U S A. 2006 Sep 5;103(36):13480-4. Epub 2006 Aug 25.

Erratum in:
    Proc Natl Acad Sci U S A. 2006 Oct 17;103(42):15722.

Carboxyethylpyrrole oxidative protein modifications stimulate neovascularization:
Implications for age-related macular degeneration.

Ebrahem Q, Renganathan K, Sears J, Vasanji A, Gu X, Lu L, Salomon RG, Crabb JW,
Anand-Apte B.

Cole Eye Institute and Lerner Research Institute, Cleveland Clinic Foundation,
and Department of Chemistry, Case Western Reserve University, Cleveland, OH
44195, USA.

Choroidal neovascularization (CNV), the advanced stage of age-related macular
degeneration (AMD), accounts for >80% of vision loss in AMD. Carboxyethylpyrrole 
(CEP) protein modifications, uniquely generated from oxidation of
docosahexaenoate-containing lipids, are more abundant in Bruch's membrane from
AMD eyes. We tested the hypothesis that CEP protein adducts stimulate
angiogenesis and possibly contribute to CNV in AMD. Human serum albumin (HSA) or 
acetyl-Gly-Lys-O-methyl ester (dipeptide) were chemically modified to yield
CEP-modified HSA (CEP-HSA) or CEP-dipeptide. The in vivo angiogenic properties of
CEP-HSA and CEP-dipeptide were demonstrated by using the chick chorioallantoic
membrane and rat corneal micropocket assays. Low picomole amounts of CEP-HSA and 
CEP-dipeptide stimulated neovascularization. Monoclonal anti-CEP antibody
neutralized limbal vessel growth stimulated by CEP-HSA, whereas anti-VEGF
antibody was found to only partially neutralize vessel growth. Subretinal
injections of CEP-modified mouse serum albumin exacerbated laser-induced CNV in
mice. In vitro treatments of human retinal pigment epithelial cells with
CEP-dipeptide or CEP-HSA did not induce increased VEGF secretion. Overall, these 
results suggest that CEP-induced angiogenesis utilizes VEGF-independent pathways 
and that anti-CEP therapeutic modalities might be of value in limiting CNV in
AMD.

Publication Types: 
    Comparative Study
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16938854 [PubMed - indexed for MEDLINE]

1303: Nat Genet. 2006 Sep;38(9):1049-54. Epub 2006 Aug 27.

CFH haplotypes without the Y402H coding variant show strong association with
susceptibility to age-related macular degeneration.

Li M, Atmaca-Sonmez P, Othman M, Branham KE, Khanna R, Wade MS, Li Y, Liang L,
Zareparsi S, Swaroop A, Abecasis GR.

Department of Biostatistics, 1420 Washington Heights, University of Michigan, Ann
Arbor, Michigan 48109, USA.

In developed countries, age-related macular degeneration is a common cause of
blindness in the elderly. A common polymorphism, encoding the sequence variation 
Y402H in complement factor H (CFH), has been strongly associated with disease
susceptibility. Here, we examined 84 polymorphisms in and around CFH in 726
affected individuals (including 544 unrelated individuals) and 268 unrelated
controls. In this sample, 20 of these polymorphisms showed stronger association
with disease susceptibility than the Y402H variant. Further, no single
polymorphism could account for the contribution of the CFH locus to disease
susceptibility. Instead, multiple polymorphisms defined a set of four common
haplotypes (of which two were associated with disease susceptibility and two
seemed to be protective) and multiple rare haplotypes (associated with increased 
susceptibility in aggregate). Our results suggest that there are multiple disease
susceptibility alleles in the region and that noncoding CFH variants play a role 
in disease susceptibility.

Publication Types: 
    Comparative Study
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16936733 [PubMed - indexed for MEDLINE]

1304: Nat Genet. 2006 Sep;38(9):1055-9. Epub 2006 Aug 27.

Common variation in three genes, including a noncoding variant in CFH, strongly
influences risk of age-related macular degeneration.

Maller J, George S, Purcell S, Fagerness J, Altshuler D, Daly MJ, Seddon JM.

Center for Human Genetic Research, Massachusetts General Hospital, 185 Cambridge 
St., Boston, Massachusetts 02114, USA.

Age-related macular degeneration (AMD) is a common, late-onset disease with
seemingly typical complexity: recurrence ratios for siblings of an affected
individual are three- to sixfold higher than in the general population, and
family-based analysis has resulted in only modestly significant evidence for
linkage. In a case-control study drawn from a US-based population of European
descent, we have identified a previously unrecognized common, noncoding variant
in CFH, the gene encoding complement factor H, that substantially increases the
influence of this locus on AMD, and we have strongly replicated the associations 
of four other previously reported common alleles in three genes (P values ranging
from 10(-6) to 10(-70)). Despite excellent power to detect epistasis, we observed
purely additive accumulation of risk from alleles at these genes. We found no
differences in association of these loci with major phenotypic categories of
advanced AMD. Genotypes at these five common SNPs define a broad spectrum of
interindividual disease risk and explain about half of the classical sibling risk
of AMD in our study population.

Publication Types: 
    Comparative Study
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16936732 [PubMed - indexed for MEDLINE]

1305: Invest Ophthalmol Vis Sci. 2006 Sep;47(9):3729-35.

Analysis of CFH, TLR4, and APOE polymorphism in India suggests the Tyr402His
variant of CFH to be a global marker for age-related macular degeneration.

Kaur I, Hussain A, Hussain N, Das T, Pathangay A, Mathai A, Hussain A, Nutheti R,
Nirmalan PK, Chakrabarti S.

Kallam Anji Reddy Molecular Genetics Laboratory, Hyderabad, India.

PURPOSE: To screen polymorphisms in complement factor-H (CFH), toll-like receptor
4 (TLR4), and APOE genes as potential risk factors for age-related macular
degeneration (AMD) in Indian patients. METHODS: One hundred patients with AMD and
120 normal control subjects were screened for the polymorphisms by restriction
digestion and resequencing. Five intragenic SNPs in CFH were screened to generate
haplotype data in cases and controls. The data were analyzed in conjunction with 
data from other populations based on genotype and haplotype frequencies, and odds
ratios were computed to estimate the risk of AMD in the different genotypes.
RESULTS: Significant association was noted with the CFH variant (Tyr402His) among
AMD cases (P = 1.19 x 10(-7)). Individuals homozygous for the mutant genotype CC 
had a significantly higher risk (P < 0.0001) of AMD (OR = 11.52; 95% CI
5.05-26.28) than those carrying a single copy of the C allele (OR = 1.51; 95% CI 
0.82-2.80), after adjusting for age, gender, and diabetes. Linkage disequilibrium
and haplotype analysis at the CFH locus indicated the C-G-T-C-A-G to be a risk
haplotype (P = 0.0003). No significant differences were observed in the genotype 
frequencies of APOE polymorphisms among patients and control subjects (P = 0.76).
The carriers of epsilon4 allele had a reduced risk (P = 0.03) of AMD (OR = 0.42, 
95% CI 0.19-0.91). TLR4 did not exhibit any association with AMD. CONCLUSIONS:
The CFH polymorphism Tyr402His appears indicative of AMD pathogenesis. Diabetes, 
age, and gender in the presence of the homozygous "CC" genotype in CFH carry an
increased risk of AMD. Hence this polymorphism could be used as a potential
marker for predictive testing across continents.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16936080 [PubMed - indexed for MEDLINE]

1306: Am J Ophthalmol. 2006 Sep;142(3):441-7.

Risk factors for photodynamic therapy of predominantly classic choroidal
neovascularization in age-related macular degeneration.

Kaiserman I, Kaiserman N, Elhayany A, Vinker S.

Department of Ophthalmology, Barzilai Medical Center, Ashkelon, Israel.
Igor@Dr-Kaiserman.com

PURPOSE: To investigate the influence of various risk factors for age-related
macular degeneration (AMD) on the rate of undergoing photodynamic therapy (PDT). 
DESIGN: An observational population based cohort study. METHODS: Settings: A
district of the largest health maintenance organization (HMO) in Israel. Study
Population: All HMO members in the district, older than 50 years on January 1,
2001, who did not terminate their membership until May 31, 2005 (139,894
members); of those, 283 underwent PDT for AMD during the study period (775
procedures). Observation Procedures: We extracted information from the chronic
disease registry of the HMO as well as demographic information including age,
gender, country of birth, place of residency, and social security economic
status. Main Outcome Measures: Effect of various risk factors for AMD on the rate
of PDT. RESULTS: The age-adjusted proportion of patients requiring PDT was
significantly higher in hypertensives (P = .03, chi2 test), in hyperlipidemics (P
= .002), in ischemic heart disease patients (P = .002) and among males (P = .03) 
and Ashkenazi Jews (P = .02). No significant difference in PDT rates was noted in
diabetics, congestive heart failure (CHF), and chronic renal failure (CRF)
patients. PDT rates were lower in the lower socioeconomic class (P = .002).
Logistic regression found a significant effect of age, hyperlipidemia,
hypertension, socioeconomic status, and gender on the rate of PDT, while ischemic
heart disease (IHD), diabetes, CHF, CRF, place of birth, and place of residence
did not contribute significantly to the model. CONCLUSIONS: Advanced age,
hypertension, hyperlipidemia, male gender, and socioeconomic status are risk
factors for undergoing PDT for predominantly classic neovascular AMD.

PMID: 16935589 [PubMed - indexed for MEDLINE]

1307: Am J Ophthalmol. 2006 Sep;142(3):419-28.

Risk factors for five-year incident age-related macular degeneration: the
Reykjavik Eye Study.

Arnarsson A, Sverrisson T, Stefánsson E, Sigurdsson H, Sasaki H, Sasaki K,
Jonasson F.

Department of Ophthalmology, University of Iceland, Reykjavik, Iceland.

PURPOSE: To establish risk factors for five-year incidence of age-related macular
degeneration (AMD). DESIGN: Population-based, prospective cohort study, and risk 
analysis. METHODS: A random sample from the Reykjavik Population Census for
individuals 50 years and older was selected. We took fundus stereo color
photographs and used standard grading system to study the five-year incidence of 
drusen, pigmentary abnormalities, and AMD and to examine possible risk factors. A
questionnaire including information on disease, medication, diet, and lifestyle
from the Reykjavik Eye Study database provided additional information. RESULTS:
Current alcohol consumption decreased the risk for drusen. Being married rather
than divorced or widowed decreased the risk for soft drusen; being single
decreased the risk of hypopigmentation as compared with being divorced or
married. Both consuming dietary fiber-rich vegetables and meat and meat products 
once a week or less frequently was a risk factor for developing soft drusen and
decreased the risk of pigmentary abnormalities. Those who had smoked 20
pack-years or more as compared with nonsmokers had decreased survival rate over
the five years (odds ratio (OR) 0.46, 95% confidence interval (CI) 0.27 to 0.80; 
P = .006). CONCLUSIONS: Risk factors for drusen appear to differ from risk
factors for pigmentary abnormalities. The effect of smoking on developing AMD is 
partly masked by selective mortality.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16935586 [PubMed - indexed for MEDLINE]

1308: Am J Ophthalmol. 2006 Sep;142(3):405-12.

Optical coherence tomographic patterns of diabetic macular edema.

Kim BY, Smith SD, Kaiser PK.

Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA.

PURPOSE: To describe various morphologic patterns of diabetic macular edema (DME)
demonstrated by optical coherence tomography (OCT) and correlate them with visual
acuity. DESIGN: Retrospective, observational, case series. METHODS: A
retrospective review of all patients with DME who underwent OCT evaluation and
met the study inclusion criteria between May 1998 and December 2002 at the Cole
Eye Institute was performed. The OCT scans were evaluated for the presence of
diffuse retinal thickening (DRT), cystoid macular edema (CME), posterior
hyaloidal traction (PHT), serous retinal detachment (SRD), and traction retinal
detachment (TRD). Additionally, the retinal thickness was measured and visual
acuity evaluated. RESULTS: Two hundred seventy-six OCT scans of 164 eyes of 119
patients were identified. OCT revealed five morphologic patterns of DME: DRT
(269, 97%), CME (152, 55%), SRD without PHT (19, 7.0%), PHT without TRD (35,
12.7%), and PHT with TRD (8, 2.9%). Mean retinal thickness varied depending on
the morphologic pattern. The mean visual acuities (Snellen equivalent) also
varied between groups. Increasing retinal thickness in all patterns was
significantly correlated with worse visual acuity (P < .005). The OCT patterns
containing CME (P = .01) and PHT without TRD (P = .02) were also significantly
associated with worse vision. CONCLUSIONS: DME exhibits at least five different
morphologic patterns on OCT. There is a significant correlation between retinal
thickness and visual acuity.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16935584 [PubMed - indexed for MEDLINE]

1309: Ophthalmology. 2006 Nov;113(11):2012-9. Epub 2006 Aug 28.

Proton beam irradiation for neovascular age-related macular degeneration.

Zambarakji HJ, Lane AM, Ezra E, Gauthier D, Goitein M, Adams JA, Munzenrider JE, 
Miller JW, Gragoudas ES.

Retina Service, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology,
Harvard Medical School, Boston, Massachusetts 02114, USA.

OBJECTIVE: To evaluate safety and visual outcomes after proton therapy for
subfoveal neovascular age-related macular degeneration (AMD). DESIGN: Randomized 
dose-ranging clinical trial. PARTICIPANTS: One hundred sixty-six patients with
angiographic evidence of classic choroidal neovascularization resulting from AMD 
and best-corrected visual acuity of 20/320 or better. METHODS: Patients were
assigned randomly (1:1) to receive 16-cobalt gray equivalent (CGE) or 24-CGE
proton radiation in 2 equal fractions. Visual acuity was measured using
standardized protocol refraction. Complete ophthalmological examinations, color
fundus photography, and fluorescein angiography were performed before and 3, 6,
12, 18, and 24 months after treatment. MAIN OUTCOME MEASURE: Proportion of eyes
losing 3 or more lines of vision from baseline. Kaplan-Meier statistics were used
to compare cumulative rates of vision loss between the 2 treatment groups.
RESULTS: At 12 months after treatment, 36 eyes (42%) and 27 eyes (35%) lost 3 or 
more lines of vision in the 16-CGE and 24-CGE groups, respectively. Rates
increased to 62% in the 16-CGE group and 53% in the 24-CGE group by 24 months
after treatment (P = 0.40). Radiation complications developed in 15.7% of
patients receiving 16 CGE and 14.8% of patients receiving 24 CGE. CONCLUSIONS: No
significant differences in rates of visual loss were found between the 2 dose
groups. Proton radiation may be useful as an adjuvant therapy or as an
alternative for patients who decline or are not appropriate for approved
therapies.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16935343 [PubMed - indexed for MEDLINE]

1310: Ophthalmology. 2006 Nov;113(11):2048-53. Epub 2006 Aug 28.

Comment in:
    Ophthalmology. 2007 Aug;114(8):1590; author reply 1590.

Early effects of intravitreal triamcinolone on macular edema: mechanistic
implication.

Miyamoto N, Iossifov D, Metge F, Behar-Cohen F.

INSERM U598 and University René Descartes, Paris, France.

PURPOSE: To evaluate the early effects of intravitreal triamcinolone acetonide
(TA) on cystoid macular edema associated with retinal vein occlusion and diabetic
retinopathy. DESIGN: Prospective, interventional, small case series.
PARTICIPANTS: Four patients with cystoid macular edema resulting from retinal
vein occlusion or diabetic retinopathy of more than 4 months' duration and
evaluated as suitable for treatment with intravitreous injection of TA. METHODS: 
After ophthalmic examination, including visual acuity assessment, intraocular
pressure (IOP) measurement, and optical coherence tomography (OCT) analysis, the 
patients received a single intravitreal injection of 4 mg TA. After the
injection, consecutive visual acuity assessment, IOP measurement, and OCT
analysis were performed after 1 hour, 6 hours, 1 week, and 2 weeks. MAIN OUTCOME 
MEASURE: Optical coherence tomography assessment of macular thickness. RESULTS:
Macular thickness and edema initially were reduced as early as 1 hour after TA
injection. A further continuous decrease was observed during the 2 weeks after
treatment. CONCLUSIONS: This rapid effect of intravitreal TA is interpreted to
indicate that nongenomic effects on retinal or retinal pigment epithelial cell
membranes, or both, may be responsible for this phenomenon. Identifications of
these mechanisms may help design alternative, more specific drugs for the
treatment of macular edema.

Publication Types: 
    Case Reports

PMID: 16935337 [PubMed - indexed for MEDLINE]

1311: Ophthalmology. 2006 Nov;113(11):2020-5. Epub 2006 Aug 28.

Cataract surgery and the 10-year incidence of age-related maculopathy: the Blue
Mountains Eye Study.

Cugati S, Mitchell P, Rochtchina E, Tan AG, Smith W, Wang JJ.

Centre for Vision Research, Department of Ophthalmology and the Westmead
Millennium Institute, University of Sydney, Sydney, Australia.

PURPOSE: To assess the long-term (10-year) risk of late age-related maculopathy
(ARM) in eyes that had previously undergone cataract surgery (before the baseline
examination). DESIGN: Population-based cohort study. PARTICIPANTS: In the Blue
Mountains Eye Study (BMES) cohort, 2335 of 3654 baseline participants > or =49
years old (75% of survivors) were reexamined after 5 years and 1952 (76% of
survivors) were reexamined after 10 years. METHODS: At the baseline examination, 
nonphakic (aphakic or pseudophakic) eyes were identified at slit-lamp examination
and confirmed at lens photographic grading. Side-by-side grading of baseline and 
follow-up stereoretinal photographs was performed using the Wisconsin ARM grading
system. Eye-specific data were analyzed using Kaplan-Meier estimates and
generalized estimating equation models, adjusting for correlation between the 2
eyes. MAIN OUTCOME MEASURES: Incident late ARM was defined if either neovascular 
ARM or geographic atrophy developed in eyes without either lesion at baseline.
RESULTS: After excluding eyes with either late ARM lesion at baseline or that had
missing photographs at either examination, 4763 eyes were considered at risk of
incident late ARM, including 132 eyes that had cataract surgery before the
baseline examination. Late ARM developed in 10 of 132 nonphakic eyes (7.6%)
compared to 96 of 4631 phakic eyes (2.1%). After adjusting for baseline age,
gender, smoking, and presence of early ARM lesions, nonphakic (cataract surgical)
eyes had a 3-fold risk of developing late-stage ARM (odds ratio [OR], 3.3; 95%
confidence interval [CI], 1.1-9.9) or neovascular ARM (OR, 3.4; 95% CI, 1.1-10.9)
compared to phakic eyes. CONCLUSIONS: Our findings support the hypothesis that
the long-term risk of developing late ARM is higher in cataract surgical eyes,
consistent with findings from the Beaver Dam Eye Study.

PMID: 16935334 [PubMed - indexed for MEDLINE]

1312: Ophthalmol Clin North Am. 2006 Sep;19(3):381-91, vi.

Squalamine lactate for exudative age-related macular degeneration.

Connolly B, Desai A, Garcia CA, Thomas E, Gast MJ.

Retina Associates of Western New York, 890 Westfall Road, Suite D, Rochester, NY 
14618, USA. drbpconn@yahoo.com

Squalamine lactate inhibits angiogenesis by a long-lived, intracellular mechanism
of action. The drug is taken up into activated endothelial cells through
caveolae, small invaginations in the cellular membrane. Subsequently, the drug
binds to and "chaperones" calmodulin to an intracellular membrane compartment and
blocks angiogenesis at several levels. A series of basic investigations,
preclinical studies, and human clinical trials have begun to establish the proof 
of concept, efficacy, and safety parameters for use of squalamine lactate as a
therapeutic agent for exudative age-related macular degeneration and several
types of malignancies.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 16935213 [PubMed - indexed for MEDLINE]

1313: Ophthalmol Clin North Am. 2006 Sep;19(3):361-72.

Ranibizumab: Phase III clinical trial results.

Rosenfeld PJ, Rich RM, Lalwani GA.

Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami
Miller School of Medicine, 900 NW 17th Street, Miami, FL 33136, USA.
prosenfeld@med.miami.edu

Ranibizumab therapy is the first treatment for neovascular AMD to improve vision 
for most patients. The benefits apply to all angiographic subtypes of neovascular
AMD and across all lesion sizes. Although the pivotal phase III trials (MARINA
and ANCHOR) used monthly injections of ranibizumab for 2 years, the ongoing PIER,
PrONTO, and SAILOR trials are investigating less frequent dosing regimens, and
preliminary results from the PrONTO study suggest that fewer injections will most
likely result in visual acuity improvements similar to the results from the phase
III trials. When comparing the ANCHOR results with the FOCUS results, it also
becomes apparent that the combination of ranibizumab with PDT does not
necessarily result in better visual acuity outcomes, and the use of PDT may even 
reduce the visual acuity benefits achieved with ranibizumab alone (see Figs.
1-3). It seems unlikely that combination therapy provides any significant
advantage over ranibizumab alone unless the combination of PDT and ranibizumab
can decrease the need for frequent retreatment. The results from the PrONTO Study
already suggest that less frequent treatment with ranibizumab is possible by
using a variable dosing regimen with OCT. Ranibizumab also seems to be safe, with
the 2-year MARINA data showing no increase in the incidence of systemic adverse
events that could be associated with anti-VEGF therapy, such as myocardial
infarction and stroke. There was a hint of a safety concern, however, in the
pooled 1-year safety results from the MARINA and ANCHOR trials. Although the
combined rate of myocardial infarction and stroke during the first year of the
ANCHOR and MARINA trials was similar in the control and the 0.3-mg ranibizumab
arms (1.3% and 1.6% respectively), these adverse events were slightly higher in
the 0.5-mg ranibizumab arm (2.9%). These differences are not statistically
significant, however, and probably do not represent a dose-dependent increase in 
risk because the 2-year results from the MARINA trial with the same monthly
injection regimen showed no increased risk of thromboembolic events. In December 
2005, Genentech submitted a Biologics License Application to the FDA for the use 
of ranibizumab in the treatment of neovascular wet AMD based on 1-year clinical
efficacy and safety data from the two pivotal phase III trials, ANCHOR and
MARINA, and the phase I-II FOCUS trial. Genentech has been granted a 6-month
Priority Review from the FDA with a decision anticipated 6 months from the
December submission date or by the end of June 2006 [29]. By the summer of 2006, 
this revolutionary therapy should be available for the treatment of neovascular
AMD. At that time, the major dilemma facing most retina specialists will be
whether to use intravitreal ranibizumab or intravitreal bevacizumab, the low cost
alternative, for the treatment of neovascular AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 16935211 [PubMed - indexed for MEDLINE]

1314: Ophthalmol Clin North Am. 2006 Sep;19(3):353-60.

Pegaptanib (Macugen): treating neovascular age-related macular degeneration and
current role in clinical practice.

Vavvas D, D'Amico DJ.

Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical
School, 243 Charles Street, Boston, MA 02114, USA.

Repeated Macugen intravitreal injections, well tolerated and safe when performed 
according to protocol, is the first successful pharmacotherapy for wet AMD.
Macugen has already had a significant impact on neovascular AMD management, in
regard to both individual patients with AMD lesions that would become amenable to
treatment, and in its effects on visual function and its preservation in the
aging United States population. Although results and delivery method are not
optimal, the positive outcomes indicate the beginning, and not the limit, of
pharmacotherapy for AMD. The benefits of Macugen therapy for AMD strongly
outweigh the risks. It is pointed out by some that the overall magnitude of the
efficacy results is very similar to the PDT trials and question why there is so
much enthusiasm about a treatment that entails intravitreal injections every 6
weeks instead of PDT every 12 weeks. In all fairness, PDT is not equally
efficacious across the lesion subtypes and sizes, whereas Macugen has effect with
all lesion subtypes. In addition, these studies widen the armamentarium and open 
up the possibility of combination therapy in attacking neovascularization through
multiple ways.

Publication Types: 
    Review

PMID: 16935210 [PubMed - indexed for MEDLINE]

1315: Ophthalmol Clin North Am. 2006 Sep;19(3):335-44.

Role of vascular endothelial growth factor in ocular angiogenesis.

Shams N, Ianchulev T.

Ophthalmic Medicine, Genentech, One DNA Way, South San Francisco, CA 94080-4990, 
USA.

VEGF-A is a critical regulator of ocular angiogenesis and vascular permeability
and is involved in the pathogenesis of several ocular diseases involving
neovascularization or increased vascular permeability, such as neovascular AMD,
diabetic ME, and diabetic retinopathy. Currently available therapies for
neovascular AMD, such as laser photocoagulation, PDT with verteporfin, and
pegaptanib sodium, slow visual loss but do not improve vision for most patients. 
In contrast, an emerging anti-VEGF agent, ranibizumab, improved vision in 25% to 
34% of treated patients in one clinical trial, rather than slowing visual loss
and is the first treatment for neovascular AMD to demonstrate visual improvement 
in a substantial number of patients. This represents a major advance in the
treatment of ocular diseases involving neovascularization or increased vascular
permeability and provides hope to patients with these debilitating diseases.
Since the submission of this article, ranibizumab was approved by the FDA for the
treatment of neovascular AMD.

Publication Types: 
    Review

PMID: 16935208 [PubMed - indexed for MEDLINE]

1316: J Cataract Refract Surg. 2006 Sep;32(9):1521-6.

Cystoid macular edema after pars plana vitrectomy for retained lens fragments.

Cohen SM, Davis A, Cukrowski C.

Department of Ophthalmology, University of South Florida, Tampa, USA.
scohen@hsc.usf.edu

PURPOSE: To describe the incidence and clinical course in patients with cystoid
macular edema (CME) following pars plana vitrectomy (PPV) for retained lens
fragments. SETTING: Retina group, private practice. METHODS: This retrospective
study reviewed the medical records of 91 patients who had PPV for retained lens
fragments. The patients were followed for at least 6 months. Patients with
concomitant eye diseases that adversely affected macular examination or macular
function were excluded. RESULTS: Four (8%) of 50 eyes with a sulcus-fixated
posterior chamber intraocular lens (PC IOL) implanted at cataract extraction and 
19 (46%) of 41 eyes with aphakia or an anterior chamber IOL developed CME
(P</=.001, chi-square test). The CME developed a mean of 4 months after PPV.
Treatment consisted of steroid eyedrops in all eyes; 17 eyes were also treated
with a topical cyclooxygenase inhibitor, and 5 eyes received posterior
sub-Tenon's steroid injections. The CME resolved a mean of 2 months after 1
treatment course in 12 eyes, which had a final visual acuity of 20/40 or better. 
The CME resolved, recurred, and then resolved in 6 eyes. In these eyes, the first
incidence lasted a mean of 4 months. The second episode occurred a mean of 5
months after the initial episode resolved and took a mean of 3 months to resolve.
Final visual acuity was 20/40 or better in 5 of these eyes. The CME persisted in 
5 eyes that were followed for a mean of 30 months. None of these eyes had an
acuity of 20/40 or better. CONCLUSIONS: Sulcus placement of a PC IOL at cataract 
extraction was associated with a reduced risk for CME. The prognosis for eyes
that develop CME after PPV for retained lens fragments is guarded. Long-term
therapy should be considered because of the high rate of recurrence.

PMID: 16931266 [PubMed - indexed for MEDLINE]

1317: J Cataract Refract Surg. 2006 Sep;32(9):1438-44.

Nonproliferative diabetic retinopathy and macular edema progression after
phacoemulsification: prospective study.

Romero-Aroca P, Fernández-Ballart J, Almena-Garcia M, Méndez-Marín I,
Salvat-Serra M, Buil-Calvo JA.

Universidad Rovira i Virgili (Romero-Aroca, Fernández-Ballart), Catalonia, Spain.
promero@grupsagessa.com

PURPOSE: To determine the incidence of diabetic retinopathy (DR) progression
after phacoemulsification in patients with type II diabetes. SETTING: Service of 
Ophthalmology, University of Sant Joan, Barcelona, Spain. METHODS: This
prospective study evaluated 132 patients with diabetes mellitus who had monocular
phacoemulsification. A control group comprised the patients' contralateral eyes. 
Data analysis included preoperative retinal findings and DR status; hemoglobin
A1c (HbA1c), low-density lipoprotein cholesterol, and triglycerides levels;
insulin treatment; and arterial hypertension. RESULTS: Postoperative visual
acuity increased by 2 or more lines in 105 patients (79.55%); the mean
postoperative acuity was 0.63 +/- 0.28 (SD). Diabetic retinopathy in the operated
eye progressed in 31 patients (23.48%) and in the fellow eye in 28 patients
(21.21%). The progression was associated with high levels of HbA1c and diabetes
mellitus duration in both groups. Diabetic macular edema occurred in the operated
eye in 8 patients (6.06%) and in the fellow eye in 6 patients (4.54%).
Pseudophakic macular edema developed in 2 eyes (1.52%). The progression of
diabetic macular edema was not associated with the risk factors studied.
CONCLUSION: Uneventful phacoemulsification cataract surgery may not cause DR
progression.

PMID: 16931253 [PubMed - indexed for MEDLINE]

1318: Br J Ophthalmol. 2006 Sep;90(9):1197-202.

A reference standard for the measurement of macular oedema.

Goatman KA.

Department of Radiology, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD,
UK. k.a.goatman@abdn.ac.uk

Macular oedema is associated with several conditions that lead to blindness.
Accurate measurement of macular thickness is important in order to follow disease
progression and evaluate treatments. Four techniques are examined to determine
the best reference standard for the detection and quantification of macular
oedema: ultrasound, optical coherence tomography, the retinal thickness analyser,
and the scanning laser ophthalmoscope. The three optical techniques have the
highest resolution and sensitivity, in particular optical coherence tomography.
Ultrasound can be useful where dense opacities preclude optical imaging.

Publication Types: 
    Review

PMID: 16929064 [PubMed - indexed for MEDLINE]

1319: Br J Ophthalmol. 2006 Sep;90(9):1188-96.

Evolving European guidance on the medical management of neovascular age related
macular degeneration.

Chakravarthy U, Soubrane G, Bandello F, Chong V, Creuzot-Garcher C, Dimitrakos SA
2nd, Korobelnik JF, Larsen M, Monés J, Pauleikhoff D, Pournaras CJ, Staurenghi G,
Virgili G, Wolf S.

Queen's University and Royal Victoria Hospitals, Belfast, UK.

BACKGROUND: Until recently, only two options were available for the treatment of 
choroidal neovascularisation (CNV) associated with age related macular
degeneration (AMD)-thermal laser photocoagulation and photodynamic therapy with
verteporfin (PDT-V). However, new treatments for CNV are in development, and data
from phase III clinical trials of some of these pharmacological interventions are
now available. In light of these new data, expert guidance is required to enable 
retina specialists with expertise in the management of AMD to select and use the 
most appropriate therapies for the treatment of neovascular AMD. METHODS:
Consensus from a round table of European retina specialists was obtained based on
best available scientific data. Data rated at evidence levels 1 and 2 were
evaluated for laser photocoagulation, PDT-V, pegaptanib sodium, and ranibizumab. 
Other treatments discussed are anecortave acetate, triamcinolone acetonide,
bevacizumab, rostaporfin (SnET2), squalamine, and transpupillary thermotherapy.
RESULTS: PDT-V is currently recommended for subfoveal lesions with predominantly 
classic CNV, or with occult with no classic CNV with evidence of recent disease
progression and a lesion size <or=4 Macular Photocoagulation Study (MPS) disc
areas (DA). The new classes of anti-angiogenic agents-namely, pegaptanib sodium
and ranibizumab (the latter when peer reviewed phase III data become available)
are recommended for subfoveal lesions with any proportion of classic CNV or
occult with no classic CNV. For juxtafoveal classic CNV, PDT-V or anti-angiogenic
therapy should be considered if the new vessels are so close to the fovea that
laser photocoagulation would almost certainly extend under the centre of the
foveal avascular zone. For all other well demarcated juxtafoveal lesions and for 
extrafoveal classic lesions, laser photocoagulation remains the standard
treatment. Therapy should be undertaken within 1 week of the fluorescein
angiogram on which the clinical decision to treat is based. At each follow up,
fluorescein angiography should be performed and best corrected visual acuity
measured as a minimum requirement. CONCLUSIONS: These recommendations provide
evidence based guidance for the choice and use of non-surgical therapies for the 
management of neovascular AMD. Revisions of the recommendations may be required
as new data become available.

Publication Types: 
    Consensus Development Conference

PMID: 16929063 [PubMed - indexed for MEDLINE]

1320: Br J Ophthalmol. 2006 Sep;90(9):1115-8.

Subretinal membranes are associated with abnormal degrees of pupil "evasion": an 
index of clinical macular dysfunction.

Zaidi FH, Bremner FD, Gregory-Evans K, Cocker KD, Moseley MJ.

Department of Ophthalmology and Visual Neuroscience, Imperial College London, UK.
fhz12@hotmail.com

AIM: To assess whether macular dysfunction caused by unilateral subretinal
neovascular membranes (SRNs) is associated with pupil "evasion" (that is,
increased initial rate of re-dilation following a brief light stimulus). METHODS:
Comparative observational series. 20 eyes of 10 participants, all with unilateral
SRNs and healthy fellow eyes. Dynamic infrared pupillography at seven stimulus
intensities (duration 1100 ms, intensities over 2 log unit range). Pupil evasion 
ratio (PEVR; defined as the ratio of light response amplitude to amount of
recovery at the mid-time point of re-dilation expressed as a percentage) was
calculated for each stimulus intensity (mean of five recordings). RESULTS:
Inter-eye PEVR is significantly reduced in eyes with SRN (that is, greater pupil 
evasion in SRN eyes: range p = 0.002 to p = 0.05 (paired t test)) and is most
apparent at higher stimulus intensities. CONCLUSIONS: PEVR is a novel parameter
that is analogous to the pupil escape ratio, but measured following a short
rather than a sustained light stimulus. PEVR is significantly altered by macular 
disease. Clinically PEVR may be used to detect occult unilateral or asymmetric
maculopathy in situations such as ocular media opacities like cataract, when
pupil reactions are unaffected or augmented, while other tests of retinal
function are diminished. PEVR represents altered neuronal firing in cones and
macular ganglion cells.

Publication Types: 
    Evaluation Studies
    Research Support, Non-U.S. Gov't

PMID: 16929060 [PubMed - indexed for MEDLINE]

1321: Clin Experiment Ophthalmol. 2006 Aug;34(6):625-6.

Choroidal neovascular membrane in radiation retinopathy.

Berker N, Aslan O, Batman C, Elgin U, Ozkan SS.

Radiation retinopathy can occur years after the initial radiotherapy of the
cancers of head and neck. It generally has a fulminant course, and can cause a
variety of severe retinal abnormalities. Choroidal neovascularization has been
rarely reported in radiation retinopathy. In this case report, a 21-year-old boy 
is presented who developed fulminant radiation retinopathy and choroidal
neovascular membrane 4 years after receiving radiotherapy for his nasopharyngeal 
carcinoma.

Publication Types: 
    Case Reports
    Letter

PMID: 16925720 [PubMed - indexed for MEDLINE]

1322: Clin Experiment Ophthalmol. 2006 Aug;34(6):590-5.

Retinal autoantibody profile in early age-related macular degeneration:
preliminary findings from the Blue Mountains Eye Study.

Cherepanoff S, Mitchell P, Wang JJ, Gillies MC.

Save Sight Institute, University of Sydney, Sydney New South Wales, Australia.
cherepanoff@yahoo.com

BACKGROUND: To compare the retinal autoantibody profile in individuals with and
without early age-related macular degeneration (AMD) and to determine whether
baseline autoantibodies are associated with progression to advanced AMD 5 and 10 
years later. METHODS: Western immunoblotting was used to detect the presence of
retinal autoantibodies in the baseline serum of 47 individuals with early AMD and
16 healthy controls from the Blue Mountains Eye Study. Autoantibody isotype, IgG 
subclass distribution and target antigens in the early AMD group were compared
with the control group. The association between baseline autoantibodies and
progression to advanced AMD 5 and 10 years later was evaluated using the
chi-square test. RESULTS: Retinal autoantibodies were found in a higher
proportion of the early AMD group compared with controls (57%vs. 25%, chi2=5.028,
P=0.025). Autoantibodies targeted a range of retinal polypeptides in both AMD
cases and controls. The commonest polypeptide antigens occurred between 20-35 kDa
and 50-60 kDa. More than one IgG subclass was often present in participants with 
autoantibodies. Over a 10-year period, 11 participants (23.4%) with early AMD
progressed to advanced AMD. No association was found between baseline
autoantibodies and the development of advanced AMD over 10 years (chi2=0.16,
Fisher's exact P=0.59). CONCLUSIONS: The retinal autoantibody profile in early
AMD is complex, both in terms of antigenic targets and immunoglobulin isotypes.
Detection of potential disease-associated autoantibodies will require a larger
sample size and full characterization of the retinal antigens involved.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16925708 [PubMed - indexed for MEDLINE]

1323: Annu Rev Med. 2007;58:477-90.

Macular degeneration.

Stone EM.

The Carver Family Center for Macular Degeneration, The Howard Hughes Medical
Institute, The University of Iowa Carver College of Medicine, Iowa City, Iowa
52245, USA. edwin-stone@uiowa.edu

Macular degeneration is a term that describes a large group of conditions that
are collectively the most common cause of irreversible vision loss in the
developed world. Approximately one in three people will be affected to some
degree by the time they reach 75 years of age. Many forms of macular degeneration
have a significant genetic component, and a large amount of progress has recently
been made in understanding the genes involved. In the future, genetic testing may
allow specific preventive treatments to be delivered to individuals at risk,
decades before the disease would ordinarily become manifest.

Publication Types: 
    Review

PMID: 16922634 [PubMed - indexed for MEDLINE]

1324: Mol Vis. 2006 Aug 11;12:902-8.

Microarray-based mutation analysis of the ABCA4 gene in Spanish patients with
Stargardt disease: evidence of a prevalent mutated allele.

Valverde D, Riveiro-Alvarez R, Bernal S, Jaakson K, Baiget M, Navarro R, Ayuso C.

Departmento de Bioquímica, Genética e Inmunología, Facultad de Biología,
Universidad de Vigo, Vigo, Spain. dianaval@uvigo.es

PURPOSE: To evaluate, in a pool of affected families, the mutation spectrum in
Stargardt patients from Spain, using the ABCR400 microarray that contains
described sequence variants in the gene encoding for the photoreceptor specific
ATP-binding cassette transporter (ABCA4). METHODS: We analyzed 76 Spanish
patients with STGD1 for a population-specific survey on the sequence variations
in the ABCA4 gene, using the ABCR400 microarray. RESULTS: Potential
disease-associated alleles were identified in 91 of the 152 STGD1 chromosomes
studied, resulting in a detection rate of 60%. The two mutant alleles were found 
in 33/76 patients (43%), whereas in 25/76 cases (33%) only one allele could be
identified. In the remaining 18 patients no mutations were found. In total, we
identified 40 sequence variations that could be related to the disease. The vast 
majority of these substitutions (35/40) were missense mutations. Three frameshift
mutations and two splicing variants were also found. CONCLUSIONS: We identified a
major disease-associated allele, R1129L, which accounted for 24% of the mutated
alleles detected, and a high frequency (12%) of complex alleles.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16917483 [PubMed - indexed for MEDLINE]

1325: Am J Epidemiol. 2006 Nov 1;164(9):813-22. Epub 2006 Aug 17.

Association between apolipoprotein E polymorphisms and age-related macular
degeneration: A HuGE review and meta-analysis.

Thakkinstian A, Bowe S, McEvoy M, Smith W, Attia J.

Clinical Epidemiology Unit, Faculty of Medicine, Ramathibodi Hospital, Mahidol
University, Bangkok, Thailand.

A possible association between apolipoprotein E polymorphisms and age-related
macular degeneration has been investigated numerous times, with conflicting
results. A previous analysis pooling results from four studies (Schmidt et al.,
Ophthalmic Genet 2002;23:209-23) suggested an association, but those
investigators did not document allele frequencies, the magnitude of the
association, or the possible genetic mode of action. Thus, the authors searched
MEDLINE from 1966 to December 2005 for any English-language studies reporting
genetic associations. Data and study quality were assessed in duplicate. Pooling 
was performed while checking for heterogeneity and publication bias. Frequencies 
of the E2 and E4 alleles in Caucasians were approximately 8% and 15%,
respectively. Allele- and genotype-based tests of association indicated a risk
effect of up to 20% for E2 and a protective effect of up to 40% for E4. E2
appeared to act in a recessive mode and E4 in a dominant mode. There appears to
be a differential effect of the E2 and E4 alleles on the risk of age-related
macular degeneration, although the possibility of survivor bias needs to be ruled
out more definitively.

Publication Types: 
    Review

PMID: 16916985 [PubMed - indexed for MEDLINE]

1326: Optom Vis Sci. 2006 Aug;83(8):546-9.

Successful treatment of retinal angiomatous proliferation by photodynamic
therapy.

Gómez-Ulla F, Abraldes MJ, Fernández M, Olmedo M.

Universidad de Santiago de Compostela, Hospital Provincial de Conxo, Spain.

PURPOSE: The purpose of this study is to describe a patient with retinal
angiomatous proliferation (RAP) treated successfully by photodynamic therapy.
METHODS: A 74-year-old white woman was referred to our clinic for evaluation as a
result of progressive decrease of vision in the right eye. Visual acuity was
20/100 in the affected right eye. The findings of fluorescein and indocyanine
green angiography were consistent with a diagnosis of RAP, and cystoid macular
edema was also revealed by optical coherence tomography (OCT). Photodynamic
therapy (PDT) was carried out because of visual deterioration and localization of
the RAP. RESULTS: The RAP was treated with PDT, and an improvement in visual
acuity to 20/60 was noted 4 months after treatment and 20/40 after 6 months. The 
resolution of the lesion was confirmed by fluorescein angiography, indocyanine
green angiography, and OCT. CONCLUSIONS: Photodynamic therapy can be effective
for the treatment of RAP when it is associated with visual acuity decrease and is
located near the fovea.

Publication Types: 
    Case Reports

PMID: 16909080 [PubMed - indexed for MEDLINE]

1327: Arch Ophthalmol. 2006 Aug;124(8):1151-62.

Associations between intermediate age-related macular degeneration and lutein and
zeaxanthin in the Carotenoids in Age-related Eye Disease Study (CAREDS):
ancillary study of the Women's Health Initiative.

Moeller SM, Parekh N, Tinker L, Ritenbaugh C, Blodi B, Wallace RB, Mares JA;
CAREDS Research Study Group.

Author Affiliations: Departments of Ophthalmology and Visual Sciences.

OBJECTIVE: To evaluate the relationship between dietary lutein plus zeaxanthin
and intermediate age-related macular degeneration (AMD). DESIGN: Women aged 50 to
79 years in Iowa, Wisconsin, and Oregon with intake of lutein plus zeaxanthin
above the 78th (high) and below the 28th (low) percentiles at baseline in the
Women's Health Initiative Observational Study were recruited 4 to 7 years later
into the Carotenoids in Age-Related Eye Disease Study (CAREDS), when the presence
of AMD was determined by fundus photographs. Logistic regression analyses
examined the prevalence of AMD in 1787 CAREDS participants, after accounting for 
potential covariates. RESULTS: The prevalence of intermediate AMD was not
statistically different between the high and low lutein plus zeaxanthin intake
recruitment groups after adjusting for age (odds ratio, 0.96; 95% confidence
interval, 0.75-1.23). Limiting analyses to women younger than 75 years with
stable intake of lutein plus zeaxanthin, without a history of chronic diseases
that are often associated with diet changes, substantially lowered odds ratios
(0.57; 95% confidence interval, 0.34-0.95). Exploratory analyses of advanced AMD 
in 34 participants resulted in protective, but statistically nonsignificant,
associations in the overall sample and in women younger than 75 years.
CONCLUSION: Diets rich in lutein plus zeaxanthin may protect against intermediate
AMD in healthy women younger than 75 years.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16908818 [PubMed - indexed for MEDLINE]

1328: Hum Mol Genet. 2006 Sep 15;15(18):2784-90. Epub 2006 Aug 11.

Systematic review and meta-analysis of the association between complement factor 
H Y402H polymorphisms and age-related macular degeneration.

Thakkinstian A, Han P, McEvoy M, Smith W, Hoh J, Magnusson K, Zhang K, Attia J.

Centre for Clinical Epidemiology and Biostatistics, School of Medical Practice
and Population Health, University of Newcastle, NSW, Australia, and Clinical
Epidemiology Unit, Ramathibodi Hospital, Bangkok, Thailand.
ammarin.thakkinstian@newcastle.edu.au

Age-related macular degeneration (AMD) is the leading cause of blindness in the
developed world and complement factor H (CFH) polymorphism has been found to
associated with the AMD. We performed a meta-analysis to estimate the magnitude
of the gene effect and the possible mode of action. A meta-analysis of eight
studies assessing association between the CFH Y402H polymorphism and AMD was
performed. Data extraction and study quality assessment were performed in
duplicate, and heterogeneity and publication bias were explored. There was strong
evidence for association between CFH and AMD, with those having CC and TC
genotypes being roughly six and 2.5 times more likely to have AMD than patients
with TT genotype, suggesting a co-dominant, multiplicative genetic model. The
population attributable risk for the CC/TC genotype is 58.9%, i.e. the CFH
polymorphism is involved in over half of all AMD. This meta-analysis summarizes
the strong evidence for an association between CFH and AMD and indicates a
multiplicative model with each C allele increasing the odds of AMD by
approximately 2.5-fold. This result is at least as important at the population
level as ApoE4 and Alzheimer's disease, playing a role in almost 60% of AMD at
the population level.

Publication Types: 
    Meta-Analysis
    Review

PMID: 16905558 [PubMed - indexed for MEDLINE]

1329: PLoS Med. 2006 Aug;3(8):e310.

Comment in:
    PLoS Med. 2006 Aug;3(8):e364.

Macrophages inhibit neovascularization in a murine model of age-related macular
degeneration.

Apte RS, Richter J, Herndon J, Ferguson TA.

Department of Ophthalmology, Washington University School of Medicine, St. Louis,
Missouri, USA. apte@vision.wustl.edu

BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of
blindness in people over 50 y of age in at least three continents. Choroidal
neovascularization (CNV) is the process by which abnormal blood vessels develop
underneath the retina. CNV develops in 10% of patients with AMD but accounts for 
up to 90% of the blindness from AMD. Although the precise etiology of CNV in AMD 
remains unknown, the macrophage component of the inflammatory response, which has
been shown to promote tumor growth and support atherosclerotic plaque formation, 
is thought to stimulate aberrant angiogenesis in blinding eye diseases. The
current theory is that macrophage infiltration promotes the development of
neovascularization in CNV. METHODS AND FINDINGS: We examined the role of
macrophages in a mouse model of CNV. IL-10(-/-) mice, which have increased
inflammation in response to diverse stimuli, have significantly reduced CNV with 
increased macrophage infiltrates compared to wild type. Prevention of macrophage 
entry into the eye promoted neovascularization while direct injection of
macrophages significantly inhibited CNV. Inhibition by macrophages was mediated
by the TNF family death molecule Fas ligand (CD95-ligand). CONCLUSIONS: Immune
vascular interactions can be highly complex. Normal macrophage function is
critical in controlling pathologic neovascularization in the eye. IL-10 regulates
macrophage activity in the eye and is an attractive therapeutic target in order
to suppress or inhibit CNV in AMD that can otherwise lead to blindness.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16903779 [PubMed - indexed for MEDLINE]

1330: Eye. 2008 Jan;22(1):60-4. Epub 2006 Aug 11.

Intravitreal triamcinolone acetonide for macular oedema owing to retinal vein
occlusion.

Patel PJ, Zaheer I, Karia N.

Department of Ophthalmology, Southend Hospital NHS Trust, Prittlewell Chase,
Westcliff-On-Sea, Southend, Essex, UK.

PURPOSE: To assess the long-term safety and efficacy of intravitreal
triamcinolone acetonide injection in the management of macular oedema caused by
central, hemi-, and branch retinal vein occlusion (CRVO, HRVO, or BRVO). METHODS:
This prospective, interventional case series included 13 patients (13 eyes) with 
retinal vein occlusion and macular oedema. They received an intravitreal
injection of 4 mg triamcinolone acetonide. Follow-up was for 1 year with repeat
injections where appropriate. Outcome measures were visual acuity and macular
thickness measured using ocular coherence tomography (OCT). RESULTS: There were
four patients with CRVO, one with HRVO, and eight with BRVO (13 eyes). Mean
duration of symptoms before intravitreal triamcinolone acetonide injection was
6.8 months (SD 4.5 months). Eight eyes (62%) responded well with improved visual 
acuity and macular thickness 1-3 months postinjection. All eight eyes developed
recurrent macular oedema and five received repeat injections. Three patients
declined a second injection. No improvement in visual acuity or OCT macular
thickness was seen after the second injection with visual acuity returning to
baseline levels at 1-year follow-up. Three eyes (23%) showed no response to the
initial injection (no improvement in macular thickness or visual acuity). Seven
patients (54%) had a rise in intraocular pressure with six (46%) requiring
treatment. CONCLUSIONS: Intravitreal injection of triamcinolone acetonide is
effective as a short-term treatment of macular oedema owing to retinal vein
occlusion, improving both visual acuity and macular thickness. However, this
effectiveness is not maintained after 1 year despite repeat injections.

PMID: 16902493 [PubMed - indexed for MEDLINE]

1331: Gerontology. 2006;52(6):353-8. Epub 2006 Aug 11.

Relation of age-related macular degeneration and cognitive impairment in an older
population.

Pham TQ, Kifley A, Mitchell P, Wang JJ.

Centre for Vision Research, Department of Ophthalmology, University of Sydney,
Westmead Millennium Institute, Westmead, Australia.

BACKGROUND: The aetiology of age-related macular degeneration (AMD) and cognitive
impairment is poorly understood. A link between cognitive impairment and AMD has 
been proposed although only a weak association was found in population-based
studies. PURPOSE: To assess cross-sectional associations between AMD and
cognitive impairment in an older Australian population. METHODS: The Blue
Mountains Eye Study examined 3,509 persons aged 49+ years during 1997-2000. AMD
lesions were assessed from retinal photographs using the Wisconsin System.
Mini-mental state examination (MMSE), demographics, lifestyle factors and medical
history were collected at interview. MMSE score was categorised as high-normal
(28-30), low-normal (24-27) and impaired (< 24). A modified MMSE excluded five
vision related items and was dichotomised as normal (18-22) and impaired (0-17). 
Logistic regression was used to assess associations after adjusting for age, sex,
visual impairment, stroke, current smoking status, hypertension, alcohol
consumption and post-high-school qualification. RESULTS: Prevalence rates for
late and early AMD were 1.5% (n = 50) and 8.3% (n = 273), respectively. Cognitive
impairment was present in 18.0% in persons with late AMD and 8.4% with early AMD,
compared to 2.6% in persons without AMD. After multivariate adjustment, late AMD 
was associated with low normal MMSE (odds ratio (OR): 2.2, 95% confidence
interval (CI): 1.1-5.0) and cognitive impairment (OR: 3.7, CI: 1.3-10.6). Using
the modified MMSE, the multivariate association between late AMD and cognitive
impairment remained (OR: 2.2, CI: 1.0-5.0). No significant association was found 
between cognitive impairment and early AMD. CONCLUSIONS: We found a significant, 
cross-sectional association between late AMD and cognitive impairment in a sample
of older Australians that appeared to be independent of visual impairment. The
association was weaker but remained significant after excluding vision-related
items from the MMSE. Copyright (c) 2006 S. Karger AG, Basel.

PMID: 16902306 [PubMed - indexed for MEDLINE]

1332: Ophthalmic Surg Lasers Imaging. 2006 Jul-Aug;37(4):333-5.

Optical coherence tomography findings in ocular decompression retinopathy.

Bui CM, Recchia FM, Recchia CC, Kammer JA.

Vanderbilt Eye Institute, Nashville, Tennessee 37232, USA.

Three days following trabeculectomy surgery, a 47-year-old woman experienced a
decline in visual acuity to 20/400. Fundus findings were consistent with
decompression retinopathy, and optical coherence tomography revealed macular
thickening, cystoid macular edema, and neurosensory macular detachment. The
foveal anatomy normalized following topical treatment, and visual acuity returned
to 20/30 by 10 weeks postoperatively. Both macular detachment and cystoid macular
edema may contribute to acute decline in visual acuity in decompression
retinopathy. Optical coherence tomography facilitated the prompt detection of
treatable pathology, which resolved following appropriate medical therapy.

Publication Types: 
    Case Reports

PMID: 16898399 [PubMed - indexed for MEDLINE]

1333: Ophthalmic Surg Lasers Imaging. 2006 Jul-Aug;37(4):278-83.

Photodynamic therapy for choroidal neovascularization associated with submacular 
hemorrhage in age-related macular degeneration.

Bakri SJ, Nickel J, Yoganathan P, Beer PM.

Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota, USA.

BACKGROUND AND OBJECTIVE: To describe visual acuity results after photodynamic
therapy (PDT) with verteporfin for choroidal neovascularization in age-related
macular degeneration (AMD) associated with large submacular hemorrhage (SMH).
PATIENTS AND METHODS: Eyes that had AMD, at least 12 months' follow-up, and SMH
of at least 2.5 mm2, and had received no other treatment modality in conjunction 
with PDT, were divided into two groups: eyes with spontaneous SMH that was
treated with PDT and eyes with SMH that occurred following PDT treatment. The
presence of SMH did not preclude the patients from undergoing further PDT.
RESULTS: Mean acuity of the spontaneous SMH group was 20/294 initially and 20/252
after 12 months. Mean acuity of the post-PDT SMH group was 20/336 initially and
20/406 after 12 months. Initial and 12-month acuities in both groups were not
statistically different. Mean size of the hemorrhage was 11.5 mm2 in the
spontaneous SMH group and 17.8 mm2 in the post-PDT SMH group. Subgroup analysis
showed no statistically significant difference between initial and final visual
acuities, regardless of the presence of blood under the fovea. Analysis by size
of the SMH showed only the spontaneous SMH group with hemorrhages over 10 mm2 to 
have a statistically significant difference in visual acuity at 12 months (P=
.0001; initial acuity, 20/230; 12-month acuity, 20/456). CONCLUSION: Eyes treated
with PDT for choroidal neovascularization associated with submacular hemorrhage
and AMD maintained stable vision over 12 months.

PMID: 16898387 [PubMed - indexed for MEDLINE]

1334: Ophthalmic Surg Lasers Imaging. 2006 Jul-Aug;37(4):272-7.

Transpupillary thermotherapy with indocyanine green dye enhancement for the
treatment of occult subfoveal choroidal neovascularization in age-related macular
degeneration.

Kim JE, Shah KB, Han DP, Connor TB Jr.

The Eye Institute, Medical College of Wisconsin, Milwaukee 53226, USA.

BACKGROUND AND OBJECTIVES: Transpupillary thermotherapy (TTT) with indocyanine
green (ICG) dye enhancement (TTT+) and TTT alone were compared for safety and
effectiveness as a treatment of occult subfoveal choroidal neovascularization in 
age-related macular degeneration. PATIENTS AND METHODS: Twenty-one patients were 
randomized to receive TTT (12 eyes) or TTT+ (9 eyes) and observed for at least 6 
months. ETDRS visual acuity and fluorescein and ICG angiography were obtained
every 3 months. RESULTS: The median initial visual acuity was 20/80 in the TTT
group and 20/100 in the TTT+ group. At 6 months, loss of less than 3 lines of
visual acuity was present in 7 of 12 eyes (58%) in the TTT group and 5 of 9 eyes 
(56%) in the TTT+ group. At the final examination, there was no active choroidal 
neovascularization exudation in 6 of 12 eyes (50%) in the TTT group and 5 of 9
eyes (56%) in the TTT+ group. The median final visual acuity was 20/125 in the
TTT group and 20/160 in the TTT+ group. Ocular or systemic complications were not
encountered in either group. CONCLUSION: TTT with ICG dye enhancement was as safe
and effective as TTT alone in this study. However, modifications of treatment
protocol would be needed to see whether there is any advantage to using ICG dye
enhancement.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16898386 [PubMed - indexed for MEDLINE]

1335: Jpn J Ophthalmol. 2006 Jul-Aug;50(4):354-60.

Polypoidal choroidal vasculopathy and retinochoroidal anastomosis in Japanese
patients eligible for photodynamic therapy for exudative age-related macular
degeneration.

Obata R, Yanagi Y, Kami J, Takahashi H, Inoue Y, Tamaki Y.

Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, and
Department of Ophthalmology, Saitama Red-Cross Hospital, Saitama, Japan.
robata-tky@umin.ac.jp

PURPOSE: To determine the percentage of Japanese patients with age-related
macular degeneration (AMD) who are eligible for photodynamic therapy (PDT) with
verteporfin who have either polypoidal choroidal vasculopathy (PCV) or choroidal 
neovascularization (CNV) with retinochoroidal anastomosis (RCA). METHODS: The
medical charts of 82 consecutive patients (83 eyes) with subfoveal CNV due to AMD
were reviewed. Initially, we determined which of these eyes were eligible for PDT
by using the criteria reported by two large randomized control studies, that is, 
the Treatment of Age-related Macular Degeneration with Photodynamic Therapy (TAP)
study and the Verteporfin in Photodynamic Therapy (VIP) study. Among the
PDT-eligible patients, the percentage of eyes with PCV or CNV with RCA was
determined by indocyanine green angiography (ICGA). RESULTS: In total, 36 eyes
(43%) of the 83 eyes were PDT-eligible; 17 (20%) based on the TAP study criteria,
and 19 (23%) based on the VIP study criteria. Among these PDT-eligible eyes, ICGA
revealed that 12 (33%) had PCV and 2 (6%) had CNV with RCA. CONCLUSIONS: With
ICGA, PCV or CNV with RCA were recognized in a substantial proportion of cases
eligible for PDT based on the two clinical studies. Considering that the
treatment efficacy of PDT for PCV or RCA has not been established, detection of
PCV or RCA prior to PDT with ICGA is highly recommended. Copyright (c) Japanese
Ophthalmological Society 2006.

Publication Types: 
    Comparative Study

PMID: 16897221 [PubMed - indexed for MEDLINE]

1336: Jpn J Ophthalmol. 2006 Jul-Aug;50(4):349-53.

Long-term retention of dye after indocyanine green-assisted internal limiting
membrane peeling.

Ashikari M, Ozeki H, Tomida K, Sakurai E, Tamai K, Ogura Y.

Department of Ophthalmology and Visual Science, Nagoya City University Graduate
School of Medical Science, Nagoya, Japan. ma-kou@t-gh.bias.ne.jp

PURPOSE: To evaluate dye retention in the fundus after indocyanine green
(ICG)-assisted internal limiting membrane peeling. METHODS: Ten eyes with stage 3
or 4 nondiabetic idiopathic macular hole (MH group) and six eyes with diffuse
diabetic macular edema (DM group) were studied. The fundus was examined with
780-nm infrared illumination by a scanning laser ophthalmoscope (SLO) after
ICG-assisted internal limiting membrane peeling. The postoperative follow-up
period ranged from 6 to 12 months (mean+/-SD, 3.7+/-2.6 months). RESULTS:
Fluorescence from ICG was detected in all studied eyes in both groups up to 6
months after surgery. At 9 months after surgery, ICG fluorescence was visible in 
all eyes of the DM group, but in only one-third of eyes of the MH group. No
fluorescence was detected in fellow eyes that had not been operated on.
CONCLUSION: The present study using SLO revealed that ICG remains in the fundus
for over 6 months after surgery. The results also suggested that a longer time
might be required for dye clearance from the diabetic retina than from the
nondiabetic retina. Copyright (c) Japanese Ophthalmological Society 2006.

Publication Types: 
    Comparative Study

PMID: 16897220 [PubMed - indexed for MEDLINE]

1337: Graefes Arch Clin Exp Ophthalmol. 2007 Jan;245(1):59-67. Epub 2006 Aug 2.

Prospective optical coherence tomographic evaluation of the efficacy of oral and 
posterior subtenon corticosteroids in patients with intermediate uveitis.

Venkatesh P, Abhas Z, Garg S, Vohra R.

Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of
Medical Sciences, New Delhi, India. venkyprao@yahoo.com

PURPOSE: To prospectively evaluate the efficacy of oral corticosteroids and
posterior subtenon injection in the treatment of macular edema in patients with
intermediate uveitis using optical coherence tomography (OCT). METHODS:
Twenty-two patients with intermediate uveitis were treated with posterior
subtenon injection when the disease was unilateral (group A, n=11) or with oral
steroids when the disease was bilateral (group B, n=11). Changes in macular
thickness from baseline was determined using OCT in both groups at day 0, day 3, 
day 14, 6 weeks and 12 weeks. RESULTS: Statistically significant improvement in
Snellen visual acuity in group A was seen at 6 weeks and in group B at 2 weeks.
In patients receiving oral corticosteroids, foveal thickness decreased by 63% by 
day 3. In those treated with posterior subtenon injection, even at day 14 only a 
55% reduction of foveal thickness was evident. Spearman's correlation coefficient
for visual acuity and foveal thickness was found to be significant. CONCLUSION:
OCT confirms a significantly more rapid decrease in macular edema in patients
treated with oral corticosteroids. A short course of oral steroids may be useful 
in enabling earlier visual recovery in patients treated with posterior subtenon
injection for unilateral uveitic macular edema.

Publication Types: 
    Comparative Study

PMID: 16896918 [PubMed - indexed for MEDLINE]

1338: Ophthalmology. 2006 Oct;113(10):1743-7. Epub 2006 Aug 7.

Minimal depression and vision function in age-related macular degeneration.

Rovner BW, Casten RJ, Hegel MT, Tasman WS.

Department of Psychiatry, Jefferson Medical College, Philadelphia, Pennsylvania, 
USA. barry.rovner@jefferson.edu

OBJECTIVE: To evaluate the impact of minimal depression on subjective and
objective vision function measures in age-related macular degeneration (AMD).
DESIGN: Prospective cross-sectional study. PARTICIPANTS: Two hundred six
outpatients with newly diagnosed neovascular AMD in one eye and preexisting AMD
in the fellow eye. METHODS: Structured clinical evaluations of visual acuity
(VA), contrast sensitivity, vision function, and depression. MAIN OUTCOME
MEASURES: The 17-item National Eye Institute Visual Function Questionnaire (NEI
VFQ 17), Melbourne Low-Vision Index (MLVI), Chronic Disease Score, and Hamilton
Depression Rating Scale. RESULTS: Minimally depressed subjects had significantly 
worse vision function on both the NEI VFQ 17 and performance-based tasks of the
MLVI than nondepressed subjects, independent of severity of VA, contrast
sensitivity, and medical status. CONCLUSIONS: Minimally depressed patients with
AMD, who would not be considered depressed according to current diagnostic
standards, suffer decrements in vision function that cannot be accounted for by
the severity of their eye disease or general medical problems. These data
emphasize the need to assess depressive symptoms in research studies that use
vision function outcome measures and in clinical practice to identify excess
vision-related disability in patients with AMD.

Publication Types: 
    Randomized Controlled Trial
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16893569 [PubMed - indexed for MEDLINE]

1339: Korean J Ophthalmol. 2006 Jun;20(2):99-103.

Triamcinolone-induced intraocular pressure elevation: intravitreal injection for 
macular edema and posterior subtenon injection for uveitis.

Jea SY, Byon IS, Oum BS.

Department of Ophthalmology, College of Medicine, Pusan National University,
Busan, Korea. jea-sy@hanmail.net

PURPOSE: To assess the effect of intravitreal and posterior subtenon injections
of triamcinolone acetonide (TA) on intraocular pressure (IOP). METHODS: we
reviewed 42 consecutive eyes after intravitreal TA injection (IVTA) and 43 eyes
following posterior subtenon TA injection (PSTA). All cases had a minimum
follow-up time of three months. After injection, the value and time of the
maximal IOP, the amount of IOP elevation and the needs of the medication were
assessed. RESULTS: The lOP increased significantly (p < 0.001) from 16.3 +/- 2.5 
mmHg preoperatively to a mean maximum of 21.7 +/- 5.3 mmHg in the IVTA group, and
from 15.3 +/- 4.5 mmHg to 20.6 +/- 3.0 mmHg in the PSTA group. An elevation in
the IOP of more than 5 mmHg from the baseline lOP was seen in 52.4% of the IVTA
group at a mean time of 3.1 weeks postoperatively, and 44.2% of the PSTA group
displayed an IOP elevation at 5.9 weeks. CONCLUSIONS: Both developed significant 
elevations of IOP, but this appeared at a later date in the PSTA group. Careful
follow-up after local injection of steroids is necessary.

Publication Types: 
    Comparative Study

PMID: 16892645 [PubMed - indexed for MEDLINE]

1340: Ophthalmology. 2006 Oct;113(10):1713-9. Epub 2006 Aug 4.

Comparison of the magnitude and time course of macular thinning induced by
different interventions for diabetic macular edema: implications for sequence of 
application.

Browning DJ, Fraser CM, Powers ME.

Charlotte Eye, Ear, Nose, and Throat Associates, Charlotte, North Carolina, USA. 
djbrowning@carolina.rr.com

PURPOSE: To determine estimates of the magnitude and time course of macular
thinning induced by three interventions for diabetic macular edema (DME). DESIGN:
Retrospective observational case series. PARTICIPANTS: Two hundred eleven eyes of
133 patients of a private retina practice, each diagnosed with DME in > or =1
eye. METHODS: Review of clinical charts and optical coherence tomography
measurements of eyes receiving focal laser photocoagulation, intravitreal
triamcinolone injection (IVTA), or vitrectomy compared to untreated fellow eyes
without DME. MAIN OUTCOME MEASURES: Central subfield mean thickness (CSMT; in
micrometers), total macular volume (cubic millimeters), visual acuity, and rates 
of increased macular thickening at follow-up. RESULTS: At 6 months follow-up,
predicted change in CSMT is 0 mum for untreated fellow eyes without DME, -28 mum 
for eyes receiving focal laser, -83 mum for eyes receiving triamcinolone, and -92
mum for eyes receiving vitrectomy. The predicted change in Early Treatment
Diabetic Retinopathy Study letters read at 6 months is 0 for untreated fellow
eyes without DME, 0 for eyes receiving focal laser, +3 for eyes receiving IVTA,
and -1 for eyes receiving vitrectomy. Increased thickening of the macula after
interventions designed to thin it were 25.4% for focal laser, 3.8% for IVTA, and 
19.0% for vitrectomy. CONCLUSIONS: Interventions for DME differ in effect size,
durability of effects, and potential for subsequent increases in macular
thickness. A prospective study to elucidate a preferred sequence of interventions
in DME may be worthwhile.

Publication Types: 
    Comparative Study

PMID: 16889833 [PubMed - indexed for MEDLINE]

1341: Mol Vis. 2006 Jul 20;12:796-801.

Analysis of variants in the complement factor H, the elongation of very long
chain fatty acids-like 4 and the hemicentin 1 genes of age-related macular
degeneration in the Finnish population.

Seitsonen S, Lemmelä S, Holopainen J, Tommila P, Ranta P, Kotamies A, Moilanen J,
Palosaari T, Kaarniranta K, Meri S, Immonen I, Järvelä I.

Department of Ophthalmology, University of Helsinki, Helsinki, Finland.

PURPOSE: A strong association of a Tyr402His polymorphism in the complement
factor H (CFH) gene and a Met299Val polymorphism in the elongation of very long
chain fatty acids-like 4 (ELOVL4) gene with age-related macular degeneration
(AMD) has been identified in Caucasian populations in the United States. Earlier 
a Gln5345Arg variant in the hemicentin 1 (HMCN1) gene was reported in a large AMD
family in the United States. We wanted to investigate whether the polymorphisms
of the CFH and the ELOVL4 genes or the mutation of the HMCN1 gene are associated 
with AMD in patients originating from the Finnish population with characteristics
of a genetic isolate. METHODS: The material consisted of familial (n=181) and
sporadic cases (n=154) with AMD, a control group with no AMD (non-AMD controls,
n=105), and a control group of anonymous blood donors (blood donor controls, n
=350). The DNA of the subjects was sequenced to analyze the variants of the three
genes. RESULTS: We detected a strong association between the C/C-genotype
compared to the T/T-genotype of Tyr402His polymorphism (first base of the
Tyr-codon changes) of the CFH gene and AMD in the AMD cases compared to the
non-AMD (p=8.86x10(-12)) or to blood donor controls (p=2.02x10(-13)). The
frequency of the C/C genotype was significantly increased in both familial cases 
compared to non-AMD controls with non-adjusted odds ratio (OR) 10.1 (confidence
intervals [CI] 95% 4.64-22.2) or compared to blood donor controls with
non-adjusted OR 5.50 (CI 95% 3.17-9.55) and in sporadic cases with non-adjusted
OR 9.33 (CI 95% 4.10-21.3; non-AMD-controls), OR 5.06 (CI 95% 2.75-9.28; blood
donor controls). Frequency of C allele differed significantly between cases and
controls (p=1.32x10(-11); non-AMD-controls and p=3.94x10(-14); blood donor
controls). No association with AMD was detected with Met299Val polymorphism in
the ELOVL4 gene in the familial or sporadic cases compared to non-AMD or blood
donor controls. None of our subjects (258 AMD cases, 72 non-AMD controls) had the
Gln5345Arg variant in the HMCN1 gene. CONCLUSIONS: The CFH gene polymorphism
seems to be an important etiologic factor for AMD also in the isolated Finnish
population.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16885922 [PubMed - indexed for MEDLINE]

1342: Br J Ophthalmol. 2006 Nov;90(11):1357-60. Epub 2006 Aug 2.

Intravitreal triamcinolone and laser photocoagulation for retinal angiomatous
proliferation.

Krieglstein TR, Kampik A, Ulbig M.

Department of Ophthalmology, Ludwig-Maximilians-University of Munich,
Mathildenstr. 8, 80336 Munich, Germany. Tina.Krieglstein@med.uni-muenchen.de

BACKGROUND: Recently, the entity of retinal angiomatous proliferation (RAP) as a 
subtype of exudative age-related macular degeneration was described, but no
treatment options have been established as yet. The only two therapeutic
modalities being discussed are surgical lysis of the feeding arteriole and
draining venule, and the use of photodynamic therapy combined with intravitreal
triamcinolone injection. AIM: To examine focal laser treatment of early
extrafoveal intraretinal neovascularisation of RAP. METHODS: Prospective case
series. We included 13 consecutive patients with an extrafoveal RAP stage I
lesion. All patients underwent a complete ophthalmic examination, including
fluorescein angiography and optical coherence tomography (OCT) III before
treatment and at 2 weeks, 1, 2 and 4 months afterwards. In cases with marked
macular oedema (>350 mum retinal thickening in OCT III, r = 12), intravitreal
injection of 4 mg triamcinolone was given before focal laser treatment to reduce 
the oedema. RESULTS: This case series indicates anatomical improvement or
stabilisation in patients with an extrafoveal RAP lesion after treatment. Initial
visual acuity ranged from 0.1 to 0.6 on the Snellen chart. By calculating
logarithmic values, visual acuity was seen to be improved in five cases (2 to 5
log lines), deteriorated in four cases (-2 to 5 log lines) and stabilised in four
cases (-1 to +1 log line change). Exudation on fluorescein angiography was
stopped in 11 cases. CONCLUSIONS: This preliminary case series suggests laser
photocoagulation combined with prior intravitreal triamcinolone injection as a
viable treatment option for RAP stage I. In cases with marked macular oedema,
intravitreal triamcinolone injection improved visual acuity. For long-term
stabilisation, additional laser treatment is mandatory. These preliminary results
warrant a more detailed prospective clinical trial.

PMID: 16885191 [PubMed - indexed for MEDLINE]

1343: Bioorg Med Chem Lett. 2006 Oct 1;16(19):5001-4. Epub 2006 Aug 1.

Identification of potent agonists of photoreceptor-specific nuclear receptor
(NR2E3) and preparation of a radioligand.

Wolkenberg SE, Zhao Z, Kapitskaya M, Webber AL, Petrukhin K, Tang YS, Dean DC,
Hartman GD, Lindsley CW.

Department of Medicinal Chemistry, Technology Enabled Synthesis Group, Merck &
Co., Inc., PO Box 4, West Point, PA 19486, USA. scott_wolkenberg@merck.com

Agonists of NR2E3 (PNR, RNR) have been identified and optimized to EC(50)< 200
nM. A tritiated analogue of one agonist was prepared to aid in the development of
a binding assay.

PMID: 16879962 [PubMed - indexed for MEDLINE]

1344: Exp Eye Res. 2007 Feb;84(2):229-45. Epub 2006 Jul 31.

Nutritional antioxidants and age-related cataract and maculopathy.

Chiu CJ, Taylor A.

The Laboratory for Nutrition and Vision Research, USDA Human Nutrition Research
Center on Aging, Tufts University, 711 Washington Street, Boston, MA 02111, USA.

Loss of vision is the second greatest, next to death, fear among the elderly.
Age-related cataract (ARC) and maculopathy (ARM) are two major causes of
blindness worldwide. There are several important reasons to study relationships
between risk for ARC/ARM and nutrition: (1) because it is likely that the same
nutritional practices that are associated with prolonged eye function will also
be associated with delayed age-related compromises to other organs, and perhaps, 
aging in general, (2) surgical resources are insufficient to provide economic and
safe surgeries for cataract and do not provide a cure for ARM, and (3) there will
be considerable financial savings and improvements in quality of life if health
rather than old age is extended, particularly given the rapidly growing elderly
segment of our population. It is clear that oxidative stress is associated with
compromises to the lens and retina. Recent literature indicates that antioxidants
may ameliorate the risk for ARC and ARM. Given the association between oxidative 
damage and age-related eye debilities, it is not surprising that over 70 studies 
have attempted to relate antioxidant intake to risk for ARC and ARM. This article
will review epidemiological literature about ARC and ARM with emphasis on roles
for vitamins C and E and carotenoids. Since glycation and glycoxidation are major
molecular insults which involve an oxidative stress component, we also review new
literature that relates dietary carbohydrate intake to risk for ARC and ARM. To
evaluate dietary effects as a whole, several studies have tried to relate dietary
patterns to risk for ARC. We will also give some attention to this emerging
research. While data from the observational studies generally support a
protective role for antioxidants in foods or supplements, results from
intervention trials are less encouraging with respect to limiting risk for
ARC/ARM prevalence or progress through antioxidant supplementations, or
maintaining higher levels of antioxidants either in diet or blood. Without more
information it is difficult to parse these results. It would be worthwhile to
determine why the various types of studies are not yielding similar results.
However, there are many common insults and mechanistic compromises that are
associated with aging, and proper nutrition early in life may address some of
these compromises and provide for extended youthful function later in life.
Indeed, proper nutrition, possibly including use of antioxidant supplements for
the nutritionally impoverished, along with healthy life styles may provide the
least costly and most practical means to delay ARC and ARM. Further studies
should be devoted to identifying the most effective strategy to prevent or delay 
the development and progress of ARC/ARM. The efforts should include identifying
the right nutrient(s), defining useful levels of the nutrient(s), and determining
the age when the supplementation should begin.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, Non-P.H.S.
    Review

PMID: 16879819 [PubMed - indexed for MEDLINE]

1345: Acta Ophthalmol Scand. 2006 Aug;84(4):466-74.

Optical coherence tomography: a key to the future management of patients with
diabetic macular oedema.

Massin P, Girach A, Erginay A, Gaudric A.

Department of Ophthalmology, Lariboisiere Hospital, Paris, France.
p.massin@lrb.aphp.fr

Diabetic macular oedema is a major cause of visual loss in patients with
diabetes. It usually results from the breakdown of the inner blood-retinal
barrier. Early detection of retinal abnormalities is vital in preventing diabetic
macular oedema and subsequent loss of vision, whilst assessment of retinal
thickness is important for treatment and follow-up. Until recently, however, the 
methods available for detecting and evaluating diabetic macular oedema were
slit-lamp biomicroscopy and stereoscopic photography, both of which are limited
in detecting earlier retinal changes. Optical coherence tomography (OCT) is a new
diagnostic imaging modality that provides high-resolution, cross-sectional images
of the eye. It is proving to be an accurate tool for the early diagnosis,
analysis and monitoring of retinopathy, with high repeatability and resolution.
It allows not only the qualitative diagnosis of diabetic macular oedema, but also
the quantitative assessment of oedema. This article reviews the future role of
OCT in the management of patients with diabetic macular oedema.

Publication Types: 
    Review

PMID: 16879566 [PubMed - indexed for MEDLINE]

1346: Acta Ophthalmol Scand. 2006 Aug;84(4):452-65; 451.

From basic to clinical research: a journey with the retina, the retinal pigment
epithelium, the cornea, age-related macular degeneration and hereditary
degenerations, as seen in the rear view mirror.

Nilsson SE.

Department of Ophthalmology, Linköping University, Linköping, Sweden.
nilsson.s.e@telia.com

PURPOSE: This Acta Ophthalmologica Award and Gold Medal Honorary Lecture (the
Lundsgaard Gold Medal Honorary Lecture) reviews some of the work I have carried
out with my mentors and many of my wonderful collaborators and research students 
over more than 40 years, also including related work by other groups. It
concentrates on the basic electrophysiology and ultrastructure of the retina and 
the retinal pigment epithelium (RPE), as well as covering basic and clinical
aspects of the cornea, contact lenses, age-related macular degeneration (AMD) and
hereditary diseases. METHODS: The review describes research performed using light
and electron microscopy, basic and clinical electrophysiology, genetics and
biochemistry in animal experiments and in research on patients. It also outlines 
clinically used techniques, such as laser and photodynamic treatment and scanning
laser ophthalmoscopy. RESULTS: The paper reports on the following subjects: the
mechanisms behind some of the electrical potentials originating in the retina and
the RPE and the use of these potentials in hereditary diseases; corneal receptors
for lectins and presumably for bacteria; the turnover of the photoreceptor outer 
segment and the formation of lipofuscin, including the relation of these
processes to AMD; certain treatments for AMD, and hereditary degenerations in
animal models, such as the RPE65 gene mutation in Briard dogs, which makes them a
model of Leber's congenital amaurosis. The dogs are now treated successfully with
gene therapy in the USA, and a clinical trial is in preparation. CONCLUSIONS:
During the last 40 years we have had the good fortune to experience a dramatic
growth in knowledge and understanding within ophthalmic science of basic
mechanisms. Huge progress has been made in diagnostics and clinical
ophthalmological treatments, much to the benefit of our patients. Even a small
contribution made by my group to these developments has been well worth the
effort, particularly as scientific work is not just deeply satisfying: it is also
fun!

Publication Types: 
    Biography
    Historical Article
    Lectures
    Portraits

Personal Name as Subject: 
    Nilsson SE

PMID: 16879565 [PubMed - indexed for MEDLINE]

1347: Invest Ophthalmol Vis Sci. 2006 Aug;47(8):3603-11.

Haploinsufficiency is not the key mechanism of pathogenesis in a heterozygous
Elovl4 knockout mouse model of STGD3 disease.

Raz-Prag D, Ayyagari R, Fariss RN, Mandal MN, Vasireddy V, Majchrzak S, Webber
AL, Bush RA, Salem N Jr, Petrukhin K, Sieving PA.

NIDCD/NEI, National Institutes of Health, Bethesda, MD 20892, USA.

PURPOSE: Autosomal dominant Stargardt-like (STGD3) disease results from mutations
in the ELOVL4 gene (elongation of very-long-chain fatty acids). This study was
undertaken to characterize a mouse model with a targeted deletion of Elovl4 and
to explore the role of this gene in retinal/macular degeneration. METHODS: A
construct targeted to exon 2 of the Elovl4 gene was used to suppress expression
of the gene. Elovl4 homozygous pups were nonviable and were not available for
study. Hence, the analysis was performed on heterozygous Elovl4(+/-) mice 16 to
22 month of age and littermate wild-type (WT) control mice of the same age.
Characterization included examining gene message and protein levels,
electroretinogram (ERG), retinal morphology and ultrastructure, and plasma and
retinal fatty acid composition. RESULTS: Although the level of Elovl4 mRNA was
reduced in Elovl4(+/-) retinas, only minimal morphologic abnormalities were
found, and the retinal (ERG) function was essentially normal in Elovl4(+/-)
retinas compared with the WT control retinas. Systemic fatty acid profiles of
Elovl4(+/-) mice were unremarkable, although the concentration of several fatty
acids was significantly lower in Elovl4(+/-) retinas, particularly the
monounsaturated fatty acids. CONCLUSIONS: The detailed characterization of this
animal model provides the first in vivo evidence that Elovl4 haploinsufficiency
is not the underlying key disease mechanism in STGD3. The results are consistent 
with a dominant negative mechanism for the deletion mutation. The Elovl4 knockout
mouse is one of three complementary animal models that will help elucidate the
disease mechanism.

Publication Types: 
    Research Support, N.I.H., Intramural

PMID: 16877435 [PubMed - indexed for MEDLINE]

1348: Invest Ophthalmol Vis Sci. 2006 Aug;47(8):3496-504.

Inhibition of choroidal neovascularization by adenovirus-mediated delivery of
short hairpin RNAs targeting VEGF as a potential therapy for AMD.

Cashman SM, Bowman L, Christofferson J, Kumar-Singh R.

Department of Ophthalmology, Tufts University School of Medicine, Boston, MA
02111, USA.

PURPOSE: Choroidal neovascularization (CNV) is the leading cause of blindness in 
age-related macular degeneration (AMD). Several lines of evidence implicate
increased levels of vascular endothelial growth factor (VEGF) in retinal pigment 
epithelium (RPE) from patients with AMD. Current approaches to attenuate VEGF or 
its receptors, including the use of small interfering (si)RNA, show significant
promise, but still have limited efficacy and require repeat administrations,
using procedures associated with multiple complications. The goal of this study
was to develop an approach for long-term endogenous expression of short hairpin
(sh)RNA that would significantly attenuate VEGF and hence act as a potential
therapy for AMD. METHODS: Several shRNAs expressed from recombinant adenovirus
were developed. These shRNAs were expressed in human RPE cells in the presence of
adenovirus vectors overexpressing VEGF, and the amount of VEGF attenuation was
evaluated. Adenovirus vectors expressing VEGF were subsequently injected into the
subretinal space of mice, and induction of CNV was measured in the presence of
adenovirus vectors expressing shRNA targeting VEGF. RESULTS: Potent shRNA
sequences were identified that were able to silence VEGF in human RPE cells. When
expressed from adenovirus backbones, these shRNA constructs silenced VEGF by 94% 
at a 1:5 molar ratio (VEGF to shRNA) and 64% at a 1:0.05 molar ratio. Adenovirus 
vectors expressing high levels of VEGF could induce CNV in mice within 5 days.
Co-injection of VEGF-expressing viruses into mice with shRNA targeting VEGF led
to a substantial (84%) reduction in CNV. CONCLUSIONS: shRNA targeting VEGF from
adenovirus vectors allows potent attenuation of VEGF and prevents CNV. This
approach shows promise as a therapy for AMD.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16877421 [PubMed - indexed for MEDLINE]

1349: Invest Ophthalmol Vis Sci. 2006 Aug;47(8):3242-6.

Association of the Y402H polymorphism in complement factor H gene and neovascular
age-related macular degeneration in Chinese patients.

Lau LI, Chen SJ, Cheng CY, Yen MY, Lee FL, Lin MW, Hsu WM, Wei YH.

Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.

PURPOSE: Age-related macular degeneration (AMD), with its complex traits and
multiple risk factors, is the leading cause of blindness in the elderly. A strong
association between a coding variant, Y402H, in the complement factor H gene
(CFH) and AMD has been recently identified in white patients. This study was
conducted to investigate the association between the Y402H polymorphism in CFH
and neovascular AMD in Chinese patients. METHODS: One hundred sixty-three Chinese
patients with neovascular AMD and 232 age-matched healthy controls were enrolled 
in the study. Genomic DNA from white blood cells was extracted. The Y402H
polymorphism in CFH, with the substitution of T to C at nucleotide position 1277 
in exon 9, was determined by polymerase chain reaction-restriction fragment
length polymorphism analysis. The association between the genetic polymorphism
and the disease was examined by chi(2) test and logistic regression. RESULTS: The
frequency of the risk allele, 1277C, was 11.3% in AMD patients compared with 2.8%
in controls (P < 0.00001). Genotype frequency differed significantly between the 
two groups (1277TT 81.0%, 1277TC 15.3%, and 1277CC 3.7% in the AMD group; 1277TT 
94.4%, 1277TC 5.6%, and 1277CC 0% in the control group; P < 0.0001). The 1277C
allele significantly increased the risk for neovascular AMD and had an odds ratio
of 4.4 (95% confidence interval [95% CI], 2.3-8.5; P < 0.00001). CONCLUSIONS: The
allele frequency of Y402H polymorphism in CFH has an ethnic variation, with much 
lower 1277C frequency in Chinese than in white patients. Despite this, the
polymorphism is significantly associated with neovascular AMD in the Chinese
population.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16877387 [PubMed - indexed for MEDLINE]

1350: Curr Eye Res. 2006 Jul-Aug;31(7-8):635-44.

The rod-mediated multifocal electroretinogram in aging and in early age-related
maculopathy.

Feigl B, Brown B, Lovie-Kitchin J, Swann P.

Institute of Health and Biomedical Innovation, Queensland University of
Technology, Kelvin Grove, Australia. b.feigl@qut.edu.au

PURPOSE: To measure function with the rod-mediated multifocal electroretinogram
(mfERG) in younger and older subjects with normal vision and with early
age-related maculopathy (ARM). METHODS: Thirty subjects were studied: 10 healthy 
subjects with a mean age of 31 years (young group), 10 healthy subjects with a
mean age of 71 years (old group), and 10 early ARM subjects with a mean age of 71
years (early ARM group). The influence of cataract was approximated by retesting 
five subjects of the young group through an 0.3 neutral density filter (ND filter
group). We analyzed first-order N1P1-amplitude and P1-implicit time (P1-IT) mfERG
responses and correlated them with funduscopic changes as defined by the
Age-Related Eye Disease Study (AREDS) group. RESULTS: Averaged concentric ring
P1-ITs were significantly delayed in the old (p = 0.02) and early ARM (p < 0.001)
compared with the young group and in the early ARM group compared with the old
and ND group (p < or = 0.01). There were no significant differences in
N1P1-amplitudes between groups, but there was a significant location effect for
all groups with highest mean amplitudes for the most peripheral ring of hexagons 
(p < 0.01). Significantly delayed overall P1-ITs (p < 0.05) were correlated with 
progressive funduscopic changes. CONCLUSIONS: Aging and early ARM affects the
rod-mediated mfERG, and there is good correlation with funduscopic changes.
Although a lens effect cannot be excluded, a neuronal transmission alteration at 
the postreceptoral level is suggested.

Publication Types: 
    Comparative Study

PMID: 16877272 [PubMed - indexed for MEDLINE]

1351: Curr Eye Res. 2006 Jul-Aug;31(7-8):629-34.

Effect of niacin on retinal vascular diameter in patients with age-related
macular degeneration.

Barakat MR, Metelitsina TI, DuPont JC, Grunwald JE.

Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania,
Philadelphia, Pennsylvania 19104, USA.

PURPOSE: Niacin is a B vitamin well-known for causing vasodilation and flushing. 
The purpose of this study was to investigate its effect on the retinal
vasculature of patients with age-related macular degeneration (AMD). METHODS:
Twelve patients with AMD were enrolled in a double-blind, randomized,
placebo-controlled, crossover trial. Fundus photographs of the posterior pole
were taken at baseline, 30 min, and 90 min after a single dose of niacin or
placebo. The protocol was repeated after a washout period using the alternate
study drug. The diameters of two veins and one artery on each image were
measured. RESULTS: An analysis of variance for repeated measures comparing the
effects of niacin with those of placebo demonstrated a significant increase in
the inferior temporal retinal artery diameter (p = 0.01), with a 5.3 +/- 7.7%
increase at 30 min (p = 0.05) and 5.8 +/- 5.0% increase at 90 min (p = 0.003). No
significant changes were observed in the temporal retinal veins. CONCLUSIONS: Our
results suggest that niacin produces vasodilatation of retinal arterioles.
Further studies are needed to ascertain whether niacin treatment may be
beneficial in retinal ischemic diseases.

Publication Types: 
    Randomized Controlled Trial

PMID: 16877271 [PubMed - indexed for MEDLINE]

1352: Ophthalmology. 2006 Aug;113(8):1446-9.

Impact of macular edema on visual acuity in uveitis.

Lardenoye CW, van Kooij B, Rothova A.

Department of Ophthalmology, St. Elisabeth Hospital, Tilburg, The Netherlands.

OBJECTIVE: To investigate the impact of cystoid macular edema (CME) on visual
acuity in patients with uveitis. DESIGN: Cross-sectional study. PARTICIPANTS: The
data from 529 patients (842 eyes) with uveitis were analyzed. MAIN OUTCOME
MEASURES: We recorded gender and age of the patients, anatomic site and diagnosis
of uveitis, associations with systemic diseases, onset and duration of uveitis,
presence of CME, best-corrected visual acuity, and the causes of decrease in
visual acuity. RESULTS: Cystoid macular edema was noted in 175 (33%) of all
uveitis patients, of whom 77 (44%) had visual acuity of 20/60 or less in at least
1 eye. The mean visual acuity for eyes with CME was significantly worse than for 
eyes without CME (0.25 vs. 0.4; P = 0.003). Of all uveitis patients, 185 (35%)
had visual acuity of 20/60 or less in at least 1 eye, which was caused by CME in 
77 (42%) patients. Poor visual acuity in patients with CME was associated with
the advanced age of the patients, chronic inflammation, and various specific
uveitis entities. The development of visually impaired or blind eyes in patients 
with panuveitis and intermediate uveitis was caused in most cases by CME (59% and
85%, respectively). CONCLUSIONS: Cystoid macular edema was a major cause of
visual loss in patients with uveitis. The unsatisfactory visual acuity in
patients with uveitis underlines the need for improved management of this
complication.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16877081 [PubMed - indexed for MEDLINE]

1353: Ophthalmology. 2006 Aug;113(8):1385-91.

Relationship between macular microcirculation and progression of diabetic macular
edema.

Sakata K, Funatsu H, Harino S, Noma H, Hori S.

Department of Ophthalmology, Tokyo Women's Medical University, Tokyo, Japan.
sakata@oph.twmu.ac.jp

PURPOSE: To investigate the relationship between blood flow velocity in
perifoveal capillaries and retinal thickness at the central fovea in diabetic
patients with clinically significant macular edema to elucidate the pathogenesis 
of diabetic macular edema. DESIGN: Comparative, cross-sectional, prospective
study. PARTICIPANTS: Participants included diabetic patients with clinically
significant macular edema (n = 22), matched diabetic patients without clinically 
significant macular edema (n = 22), and healthy volunteers (n = 16). METHODS:
Perifoveal capillary blood flow velocity was measured with fluorescein
angiography using a scanning laser ophthalmoscope and was analyzed by the tracing
method. The severity of perifoveal capillary abnormalities among diabetic
patients without clinically significant macular edema was classified by the size 
and outline of the foveal avascular zone and extent of foveal capillary loss at
the baseline by the use of fluorescein angiograms. Retinal thickness at the
central fovea was measured by optical coherence tomography. MAIN OUTCOME
MEASURES: Relationship between perifoveal capillary blood flow velocity and
retinal thickness at the central fovea. RESULTS: Perifoveal capillary blood flow 
velocity was significantly slower in the patients with clinically significant
macular edema (0.94+/-0.09 mm/second) compared with the patients without
clinically significant macular edema (1.22+/-0.20 mm/second) and the healthy
volunteers (1.49+/-0.11 mm/second; P<0.0001). Capillary blood flow velocity
negatively correlated with retinal thickness at the central fovea (r = -0.4018,
P<0.0001). Capillary blood flow velocity varied among diabetic patients without
clinically significant macular edema, and there were significant negative
correlations between capillary blood flow velocity and the size of the foveal
avascular zone (r = -0.52, P = 0.01), the outline of the foveal avascular zone (r
= -0.44, P = 0.04), and the extent of foveal capillary loss (r = -0.51, P =
0.01). CONCLUSIONS: The reduction of perifoveal capillary blood flow velocity may
occur before the increase of retinal thickness at the central fovea in the
diabetic patients. It is possible that long-term reduction of blood flow velocity
increases retinal thickness of the macula and may play an important role in the
development and the progression of diabetic macular edema.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 16877077 [PubMed - indexed for MEDLINE]

1354: Am J Ophthalmol. 2006 Aug;142(2):318-20.

Intravitreal tissue plasminogen activator to treat macular edema associated with 
branch retinal vein occlusion.

Murakami T, Takagi H, Kita M, Nishiwaki H, Miyamoto K, Ohashi H, Watanabe D,
Yoshimura N.

Department of Ophthalmology and Visual Sciences, Graduate School of Medicine,
Kyoto University, Kyoto, Japan.

PURPOSE: To evaluate the efficacy of intravitreal tissue plasminogen activator
(tPA) injection for branch retinal vein occlusion (BRVO). DESIGN: Retrospective, 
interventional case series. METHODS: Seventeen eyes presenting with macular edema
caused by BRVO were treated with an intravitreal tPA (Monteplase, 40 k IU)
injection. We assessed the visual acuity (VA) and foveal thickness measured with 
optical coherence tomography. RESULTS: The mean duration of symptoms before
surgery was 3.6 +/- 3.8 weeks. The mean logMAR VA significantly improved from
0.603 +/- 0.327 at baseline to 0.388 +/- 0.248 (P < .01) at one month and 0.359
+/- 0.319 (P < .05) at six months. The mean foveal thickness significantly
decreased from 738 +/- 156 microm at baseline to 454 +/- 213 microm (P < .001) at
one month and 253 +/- 164 microm (P < .001) six months. CONCLUSION: Intravitreal 
tPA injection may be an effective treatment for resolving macular edema and
improving the VA in BRVO.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 16876516 [PubMed - indexed for MEDLINE]

1355: Ophthalmology. 2006 Sep;113(9):1522.e1-1522.e14. Epub 2006 Jul 28.

A phase I trial of an IV-administered vascular endothelial growth factor trap for
treatment in patients with choroidal neovascularization due to age-related
macular degeneration.

Nguyen QD, Shah SM, Hafiz G, Quinlan E, Sung J, Chu K, Cedarbaum JM, Campochiaro 
PA; CLEAR-AMD 1 Study Group.

Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore,
Maryland MD 21287-9277, USA.

OBJECTIVES: To assess the safety, pharmacokinetics, and biological activity of IV
administration of vascular endothelial growth factor trap (VEGF Trap), a
recombinant protein containing the binding domains of VEGF receptors 1 and 2, in 
patients with neovascular age-related macular degeneration (AMD). DESIGN:
Randomized, multicenter, placebo-controlled clinical trial. PARTICIPANTS:
Twenty-five patients were enrolled (11 male, 14 female); 19 received VEGF Trap
(0.3 [n = 7], 1.0 [n = 7], or 3.0 mg/kg [n = 5]), and 6 received a placebo.
METHODS: Patients were randomized to receive a placebo or 0.3-, 1.0-, or
3.0-mg/kg VEGF Trap--a single IV dose followed by a 4-week observation period and
then 3 doses 2 weeks apart. MAIN OUTCOME MEASURES: Safety and biological
activity, including change in excess retinal thickness and volume assessed by
optical coherence tomography and visual acuity (VA) measured by the Early
Treatment Diabetic Retinopathy Study protocol. RESULTS: The majority of adverse
events attributable to VEGF Trap were mild to moderate in severity, but 2 of 5
patients treated with 3.0 mg/kg experienced dose-limiting toxicity (1 with grade 
4 hypertension and 1 with grade 2 proteinuria); therefore, all patients in the
3.0 mg/kg-dose group were withdrawn from the study. The mean percent changes in
excess retinal thickness were -12%, -10%, -66%, and -60%, respectively, for the
placebo and 0.3-, 1.0-, and 3.0-mg/kg groups at day 15 (P<0.02 by analysis of
covariance [ANCOVA]) and -5.6%, +47.1%, and -63.3% for the placebo and 0.3- and
1.0-mg/kg groups at day 71 (P<0.02, ANCOVA). A significant change in VA was not
noted in this small study. CONCLUSIONS: The maximum tolerated dose of IV VEGF
Trap in this study population was 1.0 mg/kg. This dose resulted in elimination of
about 60% of excess retinal thickness after either single or multiple
administrations. Alternative routes of delivery to increase the therapeutic
window are being explored.

Publication Types: 
    Clinical Trial, Phase I
    Multicenter Study
    Randomized Controlled Trial
    Research Support, N.I.H., Extramural

PMID: 16876249 [PubMed - indexed for MEDLINE]

1356: Ophthalmology. 2006 Oct;113(10):1748-51. Epub 2006 Jul 26.

Comparison of visual acuity loss in patients with different stages of Stargardt's
disease.

Kim LS, Fishman GA.

Department of Ophthalmology and Visual Sciences, University of Illinois at
Chicago, Chicago, Illinois, USA.

PURPOSE: To investigate a previously reported observation that the presence of
diffuse, as compared with localized, fundus flecks is an indicator of a more
severe course for visual acuity (VA) loss beyond 20/200 in patients with
Stargardt's disease. DESIGN: Retrospective clinic-based cross-sectional study.
PARTICIPANTS: Four hundred five patients with Stargardt's disease. METHODS:
Visual acuity in 405 patients with Stargardt's disease was analyzed at their
initial and most recent visits. The stage of Stargardt's disease and appearance
of the macula were recorded. The diagnosis and stage of Stargardt's disease were 
based on the extent and appearance of fundus flecks. MAIN OUTCOME MEASURES:
Best-corrected VA, stage of Stargardt's disease, and appearance of the macula at 
the initial and most recent visits were used in the cross-sectional analysis.
RESULTS: At their initial visit, 199 patients were identified as having stage 1
Stargardt's disease, of whom 97.5% maintained 20/200 or better VA in at least one
eye. One hundred eighty-five were identified as having stage 2 or stage 2-3
Stargardt's disease combined, of whom 83.2% maintained 20/200 VA or better.
Patients with stage 1 were more likely to maintain 20/200 or better VA in at
least one eye when compared with patients with stage 2/stage 2-3 Stargardt's
disease (chi2(1) = 21.25, P<0.001). Ninety-nine percent of stage 1 patients and
94.1% of stage 2/stage 2-3 patients maintained 20/400 or better VA in at least
one eye (chi2(1) = 5.72, P = 0.017). CONCLUSIONS: Patients with stage 1
Stargardt's disease exhibiting fundus flecks limited to the posterior pole are
more likely to maintain a level of VA at 20/200 or better when compared with
patients with stage 2/stage 2-3 disease who have diffuse fundus flecks.
Nevertheless, over 80% of the patients with stage 2/stage 2-3 Stargardt's disease
still maintained VA of 20/200 or better. Only 5.9% of patients with stage 2/stage
2-3 had VA levels worse than 20/400. In our cohort of patients with Stargardt's
disease and diffuse fundus flecks, the majority of patients did not lose VA to a 
greater extent than those with localized flecks.

Publication Types: 
    Comparative Study
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16872677 [PubMed - indexed for MEDLINE]

1357: J Am Geriatr Soc. 2006 Jul;54(7):1130-5.

Age-related macular degeneration: a practical approach to a challenging disease.

Bourla DH, Young TA.

Jules Stein Eye Institute, Retina Division, David Geffen School of Medicine,
University of California at Los Angeles, Los Angeles, California 90095, USA.

Age-related macular degeneration (AMD) is the leading cause of blindness in older
North Americans. The clinical spectrum, risk factors, pathophysiology, and
potential therapeutic options for AMD warrant a careful review. Despite the
growth in treatment options for this disease, there is no current curative
therapy. Of critical importance is attention to modifiable risk
factors--improvements in cardiovascular status, including smoking cessation, and 
routine ophthalmic monitoring for opportunities to provide early intervention. In
addition, a low-vision assessment to investigate the potential use of visual
assistive devices may be beneficial to any patient who has experienced a decrease
in vision. Finally, education regarding the clinical course of age-related
macular degeneration and accurate information with respect to the known benefits 
of available treatments will impart a better understanding of this disease to
patients.

Publication Types: 
    Review

PMID: 16866687 [PubMed - indexed for MEDLINE]

1358: Hum Mutat. 2006 Sep;27(9):921-5.

Ethnic variation in AMD-associated complement factor H polymorphism p.Tyr402His.

Grassi MA, Fingert JH, Scheetz TE, Roos BR, Ritch R, West SK, Kawase K, Shire AM,
Mullins RF, Stone EM.

Department of Ophthalmology and Visual Sciences, Carver College of Medicine,
University of Iowa, Iowa City 52242, USA.

Age-related macular degeneration (AMD) is the most common cause of irreversible
visual loss in the developed world. Previous studies have demonstrated that the
c.1204T>C, p.Tyr402His allelic variant in the complement factor H (CFH) gene is
associated with an approximately three-fold increased risk for AMD in Caucasians 
of predominantly European descent. Both the prevalence as well as the phenotypic 
spectrum of AMD varies widely among persons of different ethnicities. We
hypothesized that populations with a lower prevalence of AMD might also have a
lower prevalence of the CFH risk allele. In this study we sought to determine the
frequency of this sequence variant in control populations of Caucasians, African 
Americans, Hispanics, Somalis, and Japanese. Normal control populations were
assembled for each ethnic group: Caucasian (n=148), Somali (n=128), African
American (n=75), Hispanic (n=81), and Japanese (n=82). Individuals were genotyped
using a restriction digest assay and the frequency of the C allele at nucleotide 
position 1204 of the CFH gene was determined. A bioinformatic approach was used
to identify SNPs in linkage disequilibrium with rs1061170 (c.1204T>C,
p.Tyr402His) from the human haplotype map project database (HapMap) in order to
validate the findings. We found widely discordant frequencies of the risk allele 
between some of the different ethnic groups: Japanese 0.07+/-0.02, Hispanics
0.17+/-0.03, African-Americans 0.35+/-0.04, Caucasians 0.34+/-0.03, and Somalis
0.34+/-0.03. Allele frequencies generated by analysis of the HapMap database were
consistent with these findings. This study suggests that there are other yet
unidentified genetic factors important in the pathogenesis of AMD that may
mitigate the effects of c.1204T>C, p.Tyr402His variant. (c) 2006 Wiley-Liss, Inc.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 16865697 [PubMed - indexed for MEDLINE]

1359: Graefes Arch Clin Exp Ophthalmol. 2007 Jan;245(1):18-23. Epub 2006 Jul 25.

Effect of uncomplicated phacoemulsification on the central retina in diabetic and
non-diabetic subjects.

Degenring RF, Vey S, Kamppeter B, Budde WM, Jonas JB, Sauder G.

Department of Ophthalmology Cologne-Merheim, Cologne Hospitals, Cologne, Germany.
robert.degenring@kliniken-koeln.de

BACKGROUND: The purpose of this study was to evaluate the subclinical influence
of uncomplicated cataract surgery on foveal thickness and volume in the early
postoperative period. METHODS: In a prospective study, 108 eyes were assessed by 
optical coherence tomography preoperatively and 1 day, 1 week and 4 weeks after
uncomplicated small incisional phacoemulsification with endocapsular intraocular 
lens (IOL) implantation under topical anesthesia. The study included 24 eyes of
diabetic patients. Eyes with diseases predisposing them for postoperative macular
edema, preexisting macular edema, and eyes that developed cystoid macular edema
during follow-up were excluded. Main outcome measures were minimal foveal
thickness (MFT) and foveal volume. Secondary outcome measure was VA. RESULTS:
Visual acuity (LogMAR) increased significantly (p<0.001) from 0.43+/-0.21 to
0.11+/-0.15 4 weeks after surgery, with a significantly (p=0.001) higher increase
in VA for nondiabetic subjects. MFT increased from 183+/-27 mum preoperatively to
191+/-37 mum 4 weeks after surgery (p=0.001), with diabetic patients showing a
tendency toward a more pronounced increase in minimal retinal thickness than
nondiabetic subjects (p=0.058). One day and 1 week after surgery, MFT
measurements were not significantly different from preoperative results. Foveal
volume showed a significant increase at 1 week and 4 weeks after surgery
(p<0.001), independent of the presence of diabetes (p=0.565). The proportion of
patients exhibiting subclinical macular swelling was about 1/5 in the nondiabetic
group and 1/3 in the diabetic group. Mean duration of surgery was 11.5+/-6.6 min.
CONCLUSION: Foveal thickness and foveal volume demonstrate a subclinical increase
within 4 weeks after uncomplicated cataract surgery in up to 1/3 of the patients.
The amount and frequency of early postoperative subclinical retinal thickening
was higher than expected.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 16865374 [PubMed - indexed for MEDLINE]

1360: Ann Acad Med Singapore. 2006 Jun;35(6):420-4.

The role of optical coherence tomography (OCT) in the diagnosis and management of
retinal angiomatous proliferation (RAP) in patients with age-related macular
degeneration.

Politoa A, Napolitano MC, Bandello F, Chiodini RG.

Department of Ophthalmology, University of Udine, Udine, Italy.
antonio_polito@hotmail.com

INTRODUCTION: The aim of this review was to describe the use of optical coherence
tomography (OCT) in the diagnosis and management of retinal angiomatous
proliferation (RAP) in patients with age-related macular degeneration (AMD).
MATERIALS AND METHODS: We reviewed the tomographic characteristics of the eyes
affected by RAP seen at our institution and imaged by OCT. Some eyes with RAP
were also studied with OCT prior to and after laser treatment to determine the
tomographic changes following laser photocoagulation. RESULTS: In this
preliminary report, OCT showed a typical pattern of structural changes in RAP:
increased foveal thickness, cystoid macular oedema (CME) consisting of large
central cysts and smaller cystoid spaces located mainly in the outer retinal
layers, serous retinal detachment and a highly reflective intraretinal mass
overlying a highly or moderately elevated retinal pigment epithelium (RPE). This 
mass corresponded to the hot spot observed on ICG angiography. After successful
laser photocoagulation, significant decrease in foveal thickness, complete
resolution of CME and retinal detachment with thinning of the neurosensory retina
overlying the treated area could be observed. CONCLUSIONS: OCT appears to be
useful in evaluating and documenting RAP in AMD patients both before and after
laser photocoagulation. Longitudinal studies are required to determine its exact 
place and utility in clinical practice.

Publication Types: 
    Review

PMID: 16865194 [PubMed - indexed for MEDLINE]

1361: Ann Acad Med Singapore. 2006 Jun;35(6):408-10.

A novel mutation of the VMD2 gene in a Chinese family with best vitelliform
macular dystrophy.

Li Y, Wang G, Dong B, Sun X, Turner MJ, Kamaya S, Zhang K.

Beijing Institute of Ophthalmology, China.

INTRODUCTION: In this paper, we report a novel VMD2 gene mutation in a Chinese
family with Best vitelliform macular dystrophy. MATERIALS AND METHODS:
Ophthalmologic examination and optical coherence tomography (OCT) were performed 
in 2 members of this family. Mutational screening was performed by single-strand 
conformation polymorphism (SSCP) and direct sequencing of PCR-amplified DNA
fragments, corresponding to the 11 exons of the gene. RESULTS: Sequence analysis 
identified a previously unreported C to G change, predicting a Phe-113-Leu
substitution. Both the proband and his sister harboured this novel mutation. Each
had bilateral vitelliform lesions. CONCLUSIONS: A novel mutation in the VMD2 gene
(C427G) was found in Chinese patients with Best vitelliform macular dystrophy.

PMID: 16865191 [PubMed - indexed for MEDLINE]

1362: Clin Geriatr Med. 2006 Aug;22(3):659-75.

Innovations in eye surgery.

Singh RP, Lewis H.

Cole Eye Center, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH
44195, USA.

The field of ophthalmology has undergone revolutionary changes during the past
few decades. Advancements in understanding the pathophysiology of eye diseases,
superior surgical instrumentation and surgeon skills, and cotreatment with
medical therapies have enhanced outcomes. The geriatric population,
preferentially affected by these illnesses, has seen a meaningful visual benefit 
from these surgical innovations. Most importantly, these improvements have led to
increases in quality-of-life measures and mental and physical well-being of aging
patients.

Publication Types: 
    Review

PMID: 16860252 [PubMed - indexed for MEDLINE]

1363: Arch Iran Med. 2006 Jul;9(3):261-5.

Multifocal electroretinogram in clinically significant diabetic macular edema.

Farahvash MS, Mohammadzadeh S.

Department of Ophthalmology, Eye Research Center, Tehran, Iran. farahva@yahoo.com

OBJECTIVE: To explore the multifocal electroretinogram in patients with
nonproliferative diabetic retinopathy with clinically-significant macular edema. 
METHODS: Forty-one eyes with clinically significant macular edema were tested.
The latencies and amplitudes of average responses of 5 eccentric rings from 0 to 
26 degrees relative to the fixation point were compared with normal values
obtained from 13 nondiabetic subjects. RESULTS: Local electroretinogram responses
were significantly delayed and decreased in amplitude in patients with
clinically-significant macular edema. CONCLUSION: Multifocal electroretinogram
can be used to quantify the visual function in clinically significant macular
edema.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 16859063 [PubMed - indexed for MEDLINE]

1364: Int J Geriatr Psychiatry. 2006 Aug;21(8):746-51.

Depression in late-life: shifting the paradigm from treatment to prevention.

Whyte EM, Rovner B.

University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
whyteem@upmc.edu

Late-life depression is very common and is associated with high rates of
morbidity and mortality. While the field of geriatric psychiatry is focused on
depression treatment, prevention is an enticing option. Prevention of late-life
depression would decrease both emotional suffering and depression-associated
morbidity and mortality and may decrease dependence on non-mental health
professionals to detect depression and to initiate a treatment referral. This
paper will review current thinking on prevention research with a particular focus
on its application to late-life depression. To illustrate these issues, we
discuss recent and ongoing clinical trials of interventions to prevent depression
in two populations of older persons: those with age-related macular degeneration 
(AMD) and those with cerebrovascular disease.

Publication Types: 
    Research Support, N.I.H., Extramural
    Review

PMID: 16858747 [PubMed - indexed for MEDLINE]

1365: Eye. 2006 Sep;20(9):985-7. Epub 2006 Jul 21.

Comment in:
    Eye. 2007 Jun;21(6):890-1; author reply 891.

Bevacizumab: a new way of doing business?

Canning C, Lotery A.

Southampton Eye Unit, Southampton General Hospital, Southampton, UK.

This review highlights the history of the development of treatments for choroidal
neovascularization (wct AMD). It examines how drug therapies have evolved for the
management of age-related macular degeneration (AMD) and the value of randomised 
clinical trials in determining efficacy. Finally it examines the emerging
practice of utilising bevacizumab for the treatment of choroidal
neovascularization despite the lack of any phase III clinical trial data.

Publication Types: 
    Review

PMID: 16858443 [PubMed - indexed for MEDLINE]

1366: Br J Ophthalmol. 2006 Nov;90(11):1361-2. Epub 2006 Jul 19.

High incidence of vitreomacular traction in recurrent choroidal
neovascularisation after repeated photodynamic therapy.

Schmidt JC, Mennel S, Hörle S, Meyer CH.

Department of Ophthalmology, Philipps-University Marburg, Robert-Koch-Strasse 4, 
35037 Marburg, Germany.

BACKGROUND: The causes of recurrent choroidal neovascularisation (CNV) after
photodynamic therapy (PDT) remain controversial. Subretinal surgery was carried
out after unsuccessful PDT. AIMS: To determine intraoperatively the status of the
posterior vitreous interface. DESIGN: Interventional case series. METHODS:
Conventional three-port vitrectomy was carried out in 10 eyes with CNV that had
undergone 1-4 PDT sessions. The vitreous cutter was held close to the edge of the
optic nerve to evaluate the status of the posterior vitreous. RESULTS: Lesion
size showed an increase from 1.5 (standard deviation (SD) 0.53) to 2.3 (SD 0.83) 
macular photocoagulation study disc diameters, between the first and the last
PDT. Intraoperative findings during vitrectomy showed little liquefaction of the 
vitreous gel and an incomplete posterior-vitreous detachment, with remarkably
firm attachments at the macula in all cases (10/10). CONCLUSION: We determined an
abnormally high incidence of vitreous attachments in eyes with recurrent CNV.
Vitreomacular attachments may trigger the progression or recurrence of CNV.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16854830 [PubMed - indexed for MEDLINE]

1367: Br J Ophthalmol. 2006 Nov;90(11):1344-9. Epub 2006 Jul 19.

Comment in:
    Br J Ophthalmol. 2006 Nov;90(11):1333-4.    Br J Ophthalmol. 2006 Nov;90(11):1440-1.

The International Intravitreal Bevacizumab Safety Survey: using the internet to
assess drug safety worldwide.

Fung AE, Rosenfeld PJ, Reichel E.

Pacific Eye Associates, 2100 Webster Street, Suite 214, San Francisco, CA 94115, 
USA. annefungmd@yahoo.com

AIM: Off-label intravitreal injections of bevacizumab (Avastin) have been given
for the treatment of neovascular and exudative ocular diseases since May 2005.
Since then, the use of intravitreal bevacizumab has spread worldwide, but the
drug-related adverse events associated with its use have been reported only in a 
few retrospective reviews. The International Intravitreal Bevacizumab Safety
Survey was initiated to gather timely information regarding adverse events from
doctors around the world via the internet. METHODS: An internet-based survey was 
designed to identify adverse events associated with intravitreal bevacizumab
treatment. The survey web address was disseminated to the international
vitreoretinal community via email. Rates of adverse events were calculated from
participant responses. RESULTS: 70 centres from 12 countries reported on 7113
injections given to 5228 patients. Doctor-reported adverse events included
corneal abrasion, lens injury, endophthalmitis, retinal detachment, inflammation 
or uveitis, cataract progression, acute vision loss, central retinal artery
occlusion, subretinal haemorrhage, retinal pigment epithelium tears, blood
pressure elevation, transient ischaemic attack, cerebrovascular accident and
death. None of the adverse event rates exceeded 0.21%. CONCLUSION: Intravitreal
bevacizumab is being used globally for ocular diseases. Self-reporting of adverse
events after intravitreal bevacizumab injections did not show an increased rate
of potential drug-related ocular or systemic events. These short-term results
suggest that intravitreal bevacizumab seems to be safe.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 16854824 [PubMed - indexed for MEDLINE]

1368: JAMA. 2006 Jul 19;296(3):301-9.

Complement factor H polymorphism, complement activators, and risk of age-related 
macular degeneration.

Despriet DD, Klaver CC, Witteman JC, Bergen AA, Kardys I, de Maat MP, Boekhoorn
SS, Vingerling JR, Hofman A, Oostra BA, Uitterlinden AG, Stijnen T, van Duijn CM,
de Jong PT.

Department of Epidemiology and Biostatistics, Erasmus Medical Center, Rotterdam, 
The Netherlands.

CONTEXT: The evidence that inflammation is an important pathway in age-related
macular degeneration (AMD) is growing. Recent case-control studies demonstrated
an association between the complement factor H (CFH) gene, a regulator of
complement, and AMD. OBJECTIVES: To assess the associations between the CFH gene 
and AMD in the general population and to investigate the modifying effect of
smoking, serum inflammatory markers, and genetic variation of C-reactive protein 
(CRP). DESIGN, SETTING, AND PARTICIPANTS: Population-based, prospective cohort
study of individuals aged 55 years or older (enrollment between March 20, 1990,
and July 31, 1993, and 3 follow-up examinations that were performed between
September 1, 1993, and December 31, 2004) in Rotterdam, the Netherlands. The CFH 
Y402H polymorphism was determined in a total of 5681 individuals. Information on 
smoking, erythrocyte sedimentation rate, CRP serum levels, and haplotypes of the 
CRP gene were assessed at baseline. MAIN OUTCOME MEASURES: All severity stages of
prevalent and incident AMD, graded according to the international classification 
and grading system for AMD. RESULTS: The frequency of CFH Y402H was 36.2%
(4116/11,362 alleles). At baseline, there were 2062 persons (36.3%) with any type
of AMD (prevalent cases), including 78 (1.4%) with late AMD (stage 4). During
follow-up (mean, 8 years; median, 10 years), 1649 (35.5%) of 4642 participants
progressed to a higher stage of AMD (incident cases), including 93 (5.6%) who
developed late AMD. The odds ratio (OR) of AMD increased in an allele-dose manner
with 2.00 (95% confidence interval [CI], 1.56-2.55) for stage 2 AMD, 4.58 (95%
CI, 2.82-7.44) for stage 3 AMD, and 11.02 (95% CI, 6.82-11.81) for stage 4 (late,
vision threatening) AMD for homozygous persons. Cumulative risks calculated by
Kaplan-Meier analysis of late AMD by age 95 years were 48.3% for homozygotes,
42.6% for heterozygotes, and 21.9% for noncarriers. The population-attributable
risk for CFH Y402H was 54.0%. Elevated erythrocyte sedimentation rates further
increased the OR to 20.2 (95% CI, 9.5-43.0), elevated serum CRP levels to 27.7
(95% CI, 10.7-72.0), and smoking to 34.0 (95% CI, 13.0-88.6) for homozygotes
compared with noncarriers without these determinants. The CRP haplotypes
conferring high levels of CRP significantly increased the effect of CFH Y402H
(P<.01). CONCLUSIONS: The CFH Y402H polymorphism may account for a substantial
proportion of AMD in individuals similar to those in the Rotterdam Study and may 
confer particular risk in the presence of environmental and genetic stimulators
of the complement cascade.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16849663 [PubMed - indexed for MEDLINE]

1369: Ann Pharmacother. 2006 Jul-Aug;40(7-8):1322-6. Epub 2006 Jul 18.

Pegaptanib: a novel approach to ocular neovascularization.

Chapman JA, Beckey C.

Veterans Affairs Medical Center, West Palm Beach, FL 33410, USA.
Julie.chapman3@med.va.gov

OBJECTIVE: To review pegaptanib, a novel aptamer for the treatment of age-related
macular degeneration (AMD). DATA SOURCES: A literature search using MEDLINE
(1980-January 2006) and the Cochrane Database of Systematic Reviews (1978-January
2006) for peer-reviewed, English-language publications was conducted. Abstracts
from recent meetings, including the Association for Research in Vision and
Ophthalmology and American Society of Retinal Specialists, were reviewed for
relevant abstracts and poster presentations. STUDY SELECTION AND DATA EXTRACTION:
Pharmacokinetic and pharmacology data were extracted from animal and human
studies, and double-blind, randomized, controlled trials were included to
describe the efficacy and adverse effects of pegaptanib. DATA SYNTHESIS: The
efficacy of pegaptanib has been evaluated in 2 concurrent, prospective,
randomized, double-blind trials. Patients with AMD were randomly assigned to
receive placebo or pegaptanib intravitreous injection into 1 eye every 6 weeks
for 48 weeks. The effectiveness of pegaptanib was realized as early as week 6 and
continued through week 54. At week 54, 38% of patients receiving pegaptanib 0.3
mg were classified as legally blind versus 56% of those receiving the sham
injection. CONCLUSIONS: Pegaptanib, a new inhibitor of ocular neovascularization,
provides patients with an alternative to photodynamic therapy with verteporfin
and offers a novel approach to future drug developments for AMD. Pegaptanib
offers the advantage of not requiring photodynamic therapy in conjunction with
drug delivery and may be a viable option for institutions where this service is
not easily accessible. Results of clinical trials have shown that pegaptanib is
effective in delaying progression of AMD.

Publication Types: 
    Review

PMID: 16849623 [PubMed - indexed for MEDLINE]

1370: Kaohsiung J Med Sci. 2006 Jul;22(7):321-30.

Intravitreal triamcinolone acetonide for patients with macular edema due to
branch retinal vein occlusion.

Cheng KC, Wu WC.

Department of Ophthalmology, Kaohsiung Medical University Hospital, Taiwan.

We designed a case series study to evaluate the outcome of intravitreal
triamcinolone acetonide for the treatment of macular edema due to branch retinal 
vein occlusion (BRVO). The prospective comparative nonrandomized clinical
interventional study included 27 patients (27 eyes) with macular edema due to
BRVO. The study group consisted of 16 patients who had accepted an intravitreal
injection (IVI) of 4 mg triamcinolone acetonide. The control group included 11
patients without IVI of triamcinolone acetonide. The mean follow-up was 103.00
+/- 36.24 days in the study group and 94.55 +/- 36.31 days in the control group. 
In the study group, visual acuity measurements improved significantly (p < 0.001)
from 0.77 +/- 0.43 logarithm of minimal angle of resolution (logMAR)
preoperatively to a best postoperative visual acuity of 0.44 +/- 0.43 logMAR.
Fourteen eyes (87.5%) gained improvement in visual acuity, with 10 eyes (62.5%)
showing an increase in visual acuity of at least two Snellen lines. All 16
patients showed significant macular edema resolution in optical coherence
tomography examination (p < 0.001) and perivascular leakage decrease in
fluorescein angiography post-IVI. In the control group, baseline best-corrected
visual acuity and best-corrected visual acuity during the follow-up did not vary 
significantly (p = 0.294). In conclusion, IVI of triamcinolone acetonide can lead
to an increase in visual acuity and a resolution of macular edema in patients
with BRVO.

PMID: 16849100 [PubMed - indexed for MEDLINE]

1371: Ann Intern Med. 2006 Jul 18;145(2):98-106.

Comment in:
    Surv Ophthalmol. 2007 Sep-Oct;52(5):551-3.

Summary for patients in:
    Ann Intern Med. 2006 Jul 18;145(2):I37.

Age-related macular degeneration and risk for stroke.

Wong TY, Klein R, Sun C, Mitchell P, Couper DJ, Lai H, Hubbard LD, Sharrett AR;
Atherosclerosis Risk in Communities Study.

Centre for Eye Research Australia, University of Melbourne, East Melbourne,
Victoria, Australia. twong@unimelb.edu.au

BACKGROUND: Age-related macular degeneration (AMD) affects 7 million persons 40
years of age and older in the United States. Risk factors for the disease are
similar to those for stroke. OBJECTIVE: To determine what relationship, if any,
exists between AMD and incident clinical stroke. DESIGN: Prospective cohort
study. SETTING: The population-based Atherosclerosis Risk in Communities Study,
which was conducted in Minnesota, Maryland, Mississippi, and North Carolina.
PATIENTS: 10 405 persons between 49 and 73 years of age who had no history of
stroke or coronary heart disease. MEASUREMENTS: Participants had retinal
photographs taken between 1993 and 1995. A standardized protocol was used to
evaluate the photographs for the presence of drusen and other signs of AMD.
Incident stroke events were identified and validated by reviewing case records.
RESULTS: There were 498 early-stage and 10 late-stage cases of AMD in the cohort 
(n = 508). Over a 10-year period, 241 persons had an incident stroke event. After
adjusting for age, sex, ethnicity, and site, the authors found that persons with 
early-stage AMD had a higher cumulative incidence of stroke than those without
the disease (4.08% vs. 2.14%). The presence of early-stage AMD was associated
with a higher adjusted risk for stroke (hazard ratio, 1.87 [95% CI, 1.21 to
2.88]). Further adjustment for systolic blood pressure, diabetes, cigarette
smoking, and use of antihypertensive medications did not substantially alter this
association (hazard ratio, 1.85 [CI, 1.19 to 2.87]). The authors found that the
association between early-stage AMD and stroke varied by study site and patient
ethnicity. Multivariable-adjusted hazard ratios were 3.15 and 1.07 in samples of 
white patients in Minnesota and Maryland, respectively; 3.77 in a sample of
African-American patients in Mississippi; and 0.33 in a sample of mostly white
patients (91%) in North Carolina. No site included sufficient numbers of both
African-American and white patients to determine whether ethnicity contributed to
the observed differences by study site. LIMITATIONS: There were few cases of
late-stage AMD, and the cohort assembly method prohibited full understanding of
variation by ethnicity and site. CONCLUSION: Middle-aged persons with signs of
early-stage AMD have a higher risk for stroke independent of traditional stroke
risk factors.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16847292 [PubMed - indexed for MEDLINE]

1372: Pharmacol Rep. 2006 May-Jun;58(3):353-63.

Age-related macular degeneration (AMD): pathogenesis and therapy.

Nowak JZ.

Department of Pharmacology, Medical University, Zeligowskiego 7/9, PL 90-752
Łódź, Poland. jznowak@pharm.am.lodz.pl

Age-related macular degeneration (AMD) is a disease leading to severe visual loss
and legal blindness in the elderly population. Its pathogenesis, likely
multifactorial, involving a complex interaction of metabolic, functional, genetic
and environmental factors, remains poorly understood. For these reasons currently
used therapeutic approaches are insufficiently effective. Although major
abnormalities are seen in four functionally interrelated tissues, i.e.,
photoreceptors, retinal pigment epithelium (RPE), Bruch's membrane and
choriocapillaries, the impairment of RPE cell functions is an early and crucial
event in the molecular pathways leading to clinically relevant AMD changes. RPE
progressively degenerate, which results in a progressive irreversible
degeneration of photoreceptors. Four processes: lipofuscinogenesis, drusogenesis,
inflammation and neovascularization, specifically contribute to the development
of two forms of AMD, the dry form (non-exudative; geographic atrophy) and the wet
form (exudative, neovascular). This paper briefly describes major molecular and
cellular events leading to AMD, and presents currently used and new experimental,
forthcoming therapeutic strategies.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 16845209 [PubMed - indexed for MEDLINE]

1373: Proc Natl Acad Sci U S A. 2006 Jul 25;103(30):11282-7. Epub 2006 Jul 14.

Drusen, choroidal neovascularization, and retinal pigment epithelium dysfunction 
in SOD1-deficient mice: a model of age-related macular degeneration.

Imamura Y, Noda S, Hashizume K, Shinoda K, Yamaguchi M, Uchiyama S, Shimizu T,
Mizushima Y, Shirasawa T, Tsubota K.

Department of Ophthalmology, Keio University School of Medicine, 35-Shinanomachi,
Shinjuku-ku, Tokyo 160-8582, Japan. imamura@sc.itc.keio.ac.jp

Oxidative stress has long been linked to the pathogenesis of neurodegenerative
diseases; however, whether it is a cause or merely a consequence of the
degenerative process is still unknown. We show that mice deficient in Cu,
Zn-superoxide dismutase (SOD1) have features typical of age-related macular
degeneration in humans. Investigations of senescent Sod1(-/-) mice of different
ages showed that the older animals had drusen, thickened Bruch's membrane, and
choroidal neovascularization. The number of drusen increased with age, and
exposure of young Sod1(-/-) mice to excess light induced drusen. The retinal
pigment epithelial cells of Sod1(-/-) mice showed oxidative damage, and their
beta-catenin-mediated cellular integrity was disrupted, suggesting that oxidative
stress may affect the junctional proteins necessary for the barrier integrity of 
the retinal pigment epithelium. These observations strongly suggest that
oxidative stress may play a causative role in age-related retinal degeneration,
and our findings provide evidence for the free radical theory of aging. In
addition, these results demonstrate that the Sod1(-/-) mouse is a valuable animal
model to study human age-related macular degeneration.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16844785 [PubMed - indexed for MEDLINE]

1374: Exp Eye Res. 2006 Nov;83(5):1031-40. Epub 2006 Jul 12.

The regulation of vascular endothelial growth factors (VEGF-A, -C, and -D)
expression in the retinal pigment epithelium.

Ikeda Y, Yonemitsu Y, Onimaru M, Nakano T, Miyazaki M, Kohno R, Nakagawa K, Ueno 
A, Sueishi K, Ishibashi T.

Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu
University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
ymoc1@pathol1.med.kyushu-u.ac.jp

The vascular endothelial growth factor (VEGF) family plays an essential role in
vascular development, angiogenesis and lymphangiogenesis. VEGF-A is a key
regulator of endothelial cell functions and VEGF-C and VEGF-D are known to
stimulate both angiogenesis and lymphangiogenesis. In a surgically removed
subretinal vascular membrane of an age-related macular degeneration (AMD)
patient, both VEGF-C and VEGF-D were confirmed, in addition to VEGF-A, to be
markedly positive in the retinal pigment epithelium (RPE). There is no lymph
vessel in ocular tissue, so it is possible that VEGF-C and VEGF-D expression in
the RPE play some role in ocular angiogenesis, as well as VEGF-A. Next, we
assessed the transition of VEGF-A, -C, and -D expression on several conditions,
in human RPE. Hypoxia proverbially induced VEGF-A mRNA expression, meanwhile
VEGF-C and VEGF-D mRNA expression was down-regulated. The Ca(2+) deprivation from
culture medium strongly up-regulated VEGF-A and VEGF-D mRNA expression. Culture
on plastic flasks precoated with poly-2-hydroxyethyl methacrylate up-regulated
VEGF-D expression. Meanwhile, no significant change of VEGF-C mRNA expression was
found in the blockade of cell-cell and/or cell-matrix adhesion. These findings
suggest the possibility that VEGF-C and VEGF-D expression in RPE modify the
ocular angiogenesis as angiogenic stimulators.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16842779 [PubMed - indexed for MEDLINE]

1375: Am J Clin Nutr. 2006 Jun;83(6 Suppl):1494S-1498S.

Erratum in:
    Am J Clin Nutr. 2006 Dec;84(6):1555.

Potential role of dietary n-3 fatty acids in the prevention of dementia and
macular degeneration.

Johnson EJ, Schaefer EJ.

Carotenoid & Health and Lipid Metabolism Laboratories, Jean Mayer U.S. Department
of Agriculture Human Nutrition Research Center on Aging at Tufts University,
Boston, MA 02111, USA. elizabeth.johnson@tufts.edu

Dementia and age-related macular degeneration (AMD) are major causes of
disability in the elderly. n-3 Fatty acids, particularly docosahexaenoic acid
(DHA), are highly concentrated in brain and retinal tissue and may prevent or
delay the progression of dementia and AMD. Low dietary intakes and plasma
concentrations have been reported to be associated with dementia, cognitive
decline, and AMD risk. The major dietary sources of DHA are fish and fish oils,
although dietary supplements are available. At this point, it is not possible to 
make firm recommendations regarding n-3 fatty acids and the prevention of
dementia and AMD. Our own unpublished observations from the Framingham Heart
Study suggest that > or =180 mg/d of dietary DHA (approximately 2.7 fish
servings/wk) is associated with an approximately 50% reduction in dementia risk. 
At least this amount of DHA is generally found in one commercially available 1-g 
fish oil capsule given daily.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, U.S. Gov't, Non-P.H.S.
    Review

PMID: 16841859 [PubMed - indexed for MEDLINE]

1376: Br J Ophthalmol. 2006 Oct;90(10):1256-8. Epub 2006 Jul 12.

Seasonal variations of acute massive submacular haemorrhage associated with
age-related macular degeneration.

Iguchi Y, Ito Y, Kikuchi M, Ishikawa K, Oshima H, Yatsuya H, Terasaki H.

Department of Ophthalmology, Nagoya University School of Medicine, Nagoya, Japan.

AIMS: To determine whether there is a seasonal variation in the onset of acute,
massive submacular haemorrhage associated with age-related macular degeneration. 
METHODS: Sixty eyes of 59 patients diagnosed between April 1998 and March 2005,
were studied retrospectively. For each patient, the month and season of onset of 
the submacular haemorrhage and the mean monthly ambient temperature in Nagoya
were analysed. Any history of systemic hypertension was also recorded, and the
seasonal variations were also investigated in hypertensive and non-hypertensive
groups. RESULTS: The number of cases peaked in winter with a trough in summer,
and this seasonal variation was significant (Roger's R = 12.03, p<0.01). The
monthly incidence was inversely correlated with the temperature (Spearman's rank 
correlation coefficient r = 0.89, p<0.01). The seasonal variations were
significant in the hypertensive group but not in the non-hypertensive group.
CONCLUSION: The considerable seasonal variations suggests that the mechanism for 
the haemorrhage is strongly correlated with the systemic blood pressure.

PMID: 16837537 [PubMed - indexed for MEDLINE]

1377: Curr Med Res Opin. 2006 Jul;22(7):1311-8.

The economic impact of blue-light filtering intraocular lenses on age-related
macular degeneration associated with cataract surgery: a third-party payer's
perspective.

Reddy P, Gao X, Barnes R, Fairchild C, Boci K, Waycaster C, Pashos C.

Abt Associates Inc., HERQuLES, 181 Spring Street, Lexington MA 02421, USA.
prabashni_reddy@abtassoc.com

OBJECTIVES: Epidemiological data support an association between age-related
macular degeneration (AMD) and cataract surgery that may be attributed to
post-operative blue light exposure. By limiting the retina's blue light exposure,
new blue-light filtering intraocular lenses (BLF IOLs) have the potential to
reduce the development of AMD following cataract surgery. In the current economic
healthcare environment, there is increased interest in the cost impact of new
medical technologies. The objective of this analysis was to evaluate the cost
impact of a BLF IOL versus a non-BLF IOL in cataract surgery. METHODS: An
economic model was developed to emulate three age-specific cohorts and to assess 
the clinical and economic outcomes over 5 years. Data from the published
literature was supplemented with clinical expert opinion. Key literature inputs
involved the risk of AMD after cataract surgery as well as laboratory and animal 
data on the effectiveness of the BLF IOL in reducing the risk of AMD. Clinical
experts provided information on the management of AMD. Direct medical costs
including the cost of the IOL, monitoring, and AMD prophylaxis and treatment were
incorporated into the model. All costs were standardized to 2004 US dollars.
Age-stratified sensitivity analyses were conducted. RESULTS: In the BLF IOL
group, the 5-year age-stratified incidence of AMD ranged from 0.58 to 9.23 per
100 eyes, compared with 1.69 to 24.55 per 100 eyes in the non-BLF IOL group. The 
incremental cost of the BLF was offset by reduced costs associated with averted
AMD treatment. Estimated savings with BLF IOLs per 100 eyes were $4275, $29 997, 
and $111 734 in the 55 to 64 year-old, 65 to 74 year-old, and >or= 75-year-old
cohorts, respectively; these findings remained robust throughout the sensitivity 
analyses. CONCLUSION: Limitations of this analysis include the lack of
prospective clinical trial data that definitively demonstrate the efficacy of a
BLF IOL in preventing AMD. Moreover, the efficacy data used to populate the model
were derived from laboratory and animal studies. Thus, based on preliminary data,
this study suggests that the economic benefits of implanting BLF IOLs during
cataract surgery are observed in all patients over a 5-year timeframe although
cost savings are greatest in patients >or= 75 years.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16834830 [PubMed - indexed for MEDLINE]

1378: Eur J Neurol. 2006 Jul;13(7):736-41.

Color vision and macular recovery time in epileptic adolescents treated with
valproate and carbamazepine.

Verrotti A, Lobefalo L, Tocco AM, Spalice A, Gallenga PE, Chiarelli F, Iannetti
P.

Department of Pediatrics, University of Chieti, Chieti, Italy. averrott@unich.it

Visual dysfunction has been reported in patients diagnosed with epilepsy. Some of
these visual disturbances may be attributable to either the disease process, or
the anticonvulsant therapy prescribed to control the seizures. The aims of our
study were to evaluate whether color vision and macular function are impaired in 
epileptic adolescents, to study if the monotherapy with valproic acid (VPA) and
carbamazepine (CBZ) can affect color vision and macular function and to determine
the possible relationship between color vision, retinal function and
antiepileptic drugs (AEDs) dosage and their serum concentrations. We examined 45 
(16 male and 29 female, mean age +/- SD, 15.71 +/- 2.01 years) Caucasian
epileptic patients suffering from various types of cryptogenic epilepsy before
the beginning of therapy and after 1 year of VPA or CBZ monotherapy and 40 sex-
and age-matched healthy controls. Color vision was assessed by Farnsworth Munsell
(FM) 100-hue test and total error score (TES) was evaluated. This test consists
of colored caps: the testee has to arrange the caps according to their colors
macular function was assessed by nyctometry evaluating initial recovery time
(IRT) and summation method (SM). This test evaluates visual acuity after a period
of intense illumination of macula. Analysis of variance was used to evaluate the 
difference between controls and patients; moreover, Pearson's correlation test
have been performed. Before the beginning of therapy, there were no differences
in color vision and macular function between controls and epileptic patients.
After 1 year, the patients, treated with VPA or CBZ, showed a deficit in FM
100-hue test. At nyctometry, all patients showed no significant variation of
macular function between baseline evaluation and second evaluation at end of the 
follow-up. Our study demonstrates that, in our group of epileptic patients,
epilepsy per se does not affect color vision and retinal function. In contrast,
after 1 years of therapy with VPA and CBZ these patients showed a deficit in FM
100-hue test although nyctometry evaluation continued to be normal allowing to
exclude an impairment in macular function. Further investigations are required to
determine the pathophysiological alteration(s) that are at the basis of color
perception defects.

Publication Types: 
    Clinical Trial
    Comparative Study

PMID: 16834703 [PubMed - indexed for MEDLINE]

1379: Isr Med Assoc J. 2006 Jun;8(6):383-7.

Erratum in:
    Isr Med Assoc J. 2006 Aug;8(8):588.

Comment in:
    Isr Med Assoc J. 2006 Jun;8(6):426-7.

The transient efficacy of a single intravitreal triamcinolone acetonide injection
for diabetic macular edema.

Desatnik H, Habot-Wilner Z, Alhalel A, Moroz I, Glovinsky J, Moisseiev J.

Goldschleger Eye Institute, Sheba Medical Center, Tel Hashomer, Israel.

BACKGROUND: The major cause of visual impairment in diabetic patients is macular 
edema. The failure of laser photocoagulation in a large subgroup of patients with
clinically significant diabetic macular edema has prompted interest in other
treatment methods. OBJECTIVES: To evaluate the long-term efficacy and safety of
an intravitreal injection of triamcinolone acetonide for clinically significant
diabetic macular edema. METHODS: In a retrospective case series 31 diabetic
patients with persistent, recurrent or diffuse clinically significant diabetic
macular edema received a single 4 mg (0.1 ml) intravitreal triamcinolone
acetonide injection and were followed for at least 6 months. The main outcome
measures evaluated were classified as primary: visual acuity and central macular 
thickness, and secondary: intraocular pressure and cataract progression.
Statistical analysis included Student's t-test, chi-square test and the MacNamar 
test. RESULTS: Best visual acuity results were observed 2.6 +/- 2.4 months
post-injection. At that time the mean foveal thickness had decreased by 37% from 
a baseline of 455 +/- 100 to 288 +/- 99 mu (P< 0.001) and the mean visual acuity 
improved from 6/42 to 6/23 (P< 0.001). Final mean visual acuity after an average 
of 10 +/- 1.8 months follow-up (range 6-13 months) was identical to the baseline,
although mean foveal thickness was still significantly lower than the initial
thickness (368 +/- 166 vs. 455 +/- 100 mu, P< 0.01). Statistical analysis did not
identify any pre-injection prognostic factors for improved visual acuity. The
only complications that occurred were elevated intraocular pressure in 42% of
patients and cataract progression in 21%. There was no endophthalmitis.
CONCLUSIONS: Intravitreal injection of triamcinolone acetonide for clinically
significant diabetic macular edema is effective in reducing foveal thickness and 
improving visual acuity in the short term. Longer follow-up revealed that visual 
acuity returned to pre-injection values, even though a modest decrease in the
foveal thickness persisted. Further studies are needed to evaluate the long-term 
efficacy in conjunction with laser photocoagulation treatment.

PMID: 16833165 [PubMed - indexed for MEDLINE]

1380: J Occup Environ Med. 2006 Jul;48(7):656.

Parkinson's disease, macular degeneration and cutaneous signs of mercury
toxicity.

Dantzig PI.

OBJECTIVE: The objective of this study was to determined if there was a
relationship between Grover's disease and Parkinson disease. METHODS: Fourteen
patients with Parkinson disease and 14 control patients were randomly selected
and examined for cutaneous eruptions and blood mercury levels. RESULTS: Of the 14
patients with Parkinson's disease, 13 had Grover's disease and detectable blood
mercury. None of the patients in the control group had a cutaneous eruption and
only 2of the 14 had detectable blood mercury. CONCLUSION: Mercury may play a role
in the etiology of Parkinson disease and Grover's disease.

Publication Types: 
    Letter

PMID: 16832218 [PubMed - indexed for MEDLINE]

1381: Arch Ophthalmol. 2006 Jul;124(7):1038-45.

Macular pigment: a review of current knowledge.

Whitehead AJ, Mares JA, Danis RP.

Department of Ophthalmology, University of Wisconsin-Madison, 406 Science Drive, 
Madison, WI 53711, USA.

The existence of the macula lutea of the human retina has been known for more
than 200 years. It is established that the xanthophylls lutein and zeaxanthin are
responsible for the yellow color. The effect of macular photopigments on
blue-light filtration and color perception is well established. It has been
postulated that the pigment might serve to reduce chromatic aberration and to
improve visual acuity. The antioxidant capabilities of these xanthophylls
combined with their ability to trap short-wavelength light may serve to protect
the outer retina, retinal pigment epithelium, and choriocapillaris from oxidative
damage. Current ideas on the pathophysiology of age-related macular degeneration 
may be compatible with the proposed function of lutein and zeaxanthin. This
review will summarize our knowledge about macular pigment regarding current
efforts in research and the epidemiology of age-related eye disease.

Publication Types: 
    Review

PMID: 16832030 [PubMed - indexed for MEDLINE]

1382: Arch Ophthalmol. 2006 Jul;124(7):995-1001.

Cigarette smoking, fish consumption, omega-3 fatty acid intake, and associations 
with age-related macular degeneration: the US Twin Study of Age-Related Macular
Degeneration.

Seddon JM, George S, Rosner B.

Massachusetts Eye and Ear Infirmary and Channing Laboratory, Harvard Medical
School, 243 Charles Street, Boston, MA, USA. johanna_seddon@meei.harvard.edu

OBJECTIVE: To evaluate modifiable risk and protective factors for age-related
macular degeneration (AMD) among elderly twins. METHODS: The US Twin Study of
Age-Related Macular Degeneration comprises elderly male twins from the National
Academy of Sciences-National Research Council World War II Veteran Twin Registry.
To determine genetic and environmental risk factors for AMD, twins were surveyed 
for a prior diagnosis of AMD and underwent an eye examination, fundus
photography, and food frequency and risk factor questionnaires. This
environmental component of the study includes 681 twins: 222 twins with AMD
(intermediate or late stages) and 459 twins with no maculopathy or early signs.
Risk for AMD according to cigarette smoking and dietary fat intake was estimated 
using logistic regression analyses. RESULTS: Current smokers had a 1.9-fold
increased risk (95% confidence interval, 0.99-3.68, P = .06) of AMD while past
smokers had about a 1.7-fold increased risk (95% confidence interval, 1.2-2.6, P 
= .009). Increased intake of fish reduced risk of AMD, particularly for 2 or more
servings per week (P trend = .04). Dietary omega-3 fatty intake was inversely
associated with AMD (odds ratio, 0.55; 95% confidence interval, 0.32-0.95)
comparing the highest vs lowest quartile. Reduction in risk of AMD with higher
intake of omega-3 fatty acids was seen primarily among subjects with low levels
(below median) of linoleic acid intake, an omega-6 fatty acid (P trend<.001). The
attributable risk percentage was 32% for smoking and the preventive fraction was 
22% for higher omega-3 intake. CONCLUSIONS: This study of twins provides further 
evidence that cigarette smoking increases risk while fish consumption and omega-3
fatty acid intake reduce risk of AMD.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Twin Study

PMID: 16832023 [PubMed - indexed for MEDLINE]

1383: Arch Ophthalmol. 2006 Jul;124(7):988-92.

Hormone therapy and age-related macular degeneration: the Women's Health
Initiative Sight Exam Study.

Haan MN, Klein R, Klein BE, Deng Y, Blythe LK, Seddon JM, Musch DC, Kuller LH,
Hyman LG, Wallace RB.

Department of Epidemiology, University of Michigan, 611 Church Street, Ann Arbor,
MI 48104, USA. mnhaan@umich.edu

OBJECTIVE: To determine the effectiveness of treatment with conjugated equine
estrogens (CEE) or with CEE combined with progestin (CEE + P) on age-related
macular degeneration (AMD). METHODS: In an ancillary study to the Women's Health 
Initiative clinical trial of hormone therapy, 4262 women 65 years and older
underwent fundus photography for the determination of AMD. Participants were
recruited from April 2000 to June 2002 at 21 clinical sites an average of 5 years
after randomization. Participants were randomized to treatment with CEE, CEE + P,
or placebo. Participants had been treated for an average of 5 years at the
ophthalmic evaluation for AMD. RESULTS: The overall prevalence of any AMD was
21.0%. No association was found between CEE + P (odds ratio [OR], 0.91; 95%
confidence interval [CI], 0.75-1.11) or CEE alone (OR, 0.98; 95% CI, 0.78-1.25)
and early-stage AMD. The CEE + P was associated with a reduced risk of soft
drusen (OR, 0.83; 95% CI, 0.68-1.00) after adjustment for covariates and with a
reduced risk of neovascular AMD (OR, 0.29; 95% CI, 0.09-0.92). CONCLUSIONS:
Treatment with CEE alone or CEE + P does not affect early- or late-stage AMD.
Treatment with CEE + P may reduce the risk of soft drusen or neovascular AMD.

Publication Types: 
    Multicenter Study
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16832022 [PubMed - indexed for MEDLINE]

1384: Arch Ophthalmol. 2006 Jul;124(7):981-6.

Dietary fatty acids and the 5-year incidence of age-related maculopathy.

Chua B, Flood V, Rochtchina E, Wang JJ, Smith W, Mitchell P.

Centre for Vision Research, Department of Ophthalmology, University of Sydney Eye
Clinic, Westmead Hospital, Hawkesbury Road, Westmead, NSW 2145, Australia.

OBJECTIVE: To assess longitudinal associations between dietary fat and incident
age-related maculopathy (ARM) in an older, population-based, historical cohort.
METHODS: A total of 3654 persons, 49 years or older, participated in the Blue
Mountains Eye Study (1992-1994); 2335 (75.1% of survivors) were reexamined after 
5 years (1997-1999). Dietary data were collected from 2895 people (79%) at
baseline by means of a semiquantitative food frequency questionnaire to calculate
dietary fat intakes. Presence of ARM was graded from retinal photographs
(Wisconsin ARM Grading System). Logistic regression adjusted for age, sex,
vitamin C intake, and smoking. RESULTS: Participants with the highest vs lowest
quintiles of n-3 polyunsaturated fat intake had lower risk of incident early ARM 
(odds ratio [95% confidence interval], 0.41 [0.22-0.75). A 40% reduction of
incident early ARM was associated with fish consumption at least once a week
(odds ratio [95% confidence interval], 0.58 [0.37-0.90]), whereas fish
consumption at least 3 times per week could reduce the incidence of late ARM
(odds ratio [95% confidence interval], 0.25 [0.06-1.00]). We found no association
between incident ARM and butter, margarine, or nut consumption. CONCLUSIONS: A
regular diet high in n-3 polyunsaturated fat, especially from fish, suggests
protection against early and late ARM in this older Australian cohort. Our study 
could not confirm deleterious effects of higher polyunsaturated fat intakes
reported by other clinic-based studies.

PMID: 16832021 [PubMed - indexed for MEDLINE]

1385: Retina. 2006 Jul-Aug;26(6):666-72.

Issues in quantifying atrophic macular disease using retinal autofluorescence.

Sunness JS, Ziegler MD, Applegate CA.

Richard E. Hoover Rehabilitation Services for Low Vision and Blindness, the
Greater Baltimore Medical Center, Maryland 21204, USA. jsunness@gbmc.org

PURPOSE: To demonstrate the potential and limits of autofluorescence imaging in
identifying and delineating areas of atrophy. METHODS: Fundus photographs and
infrared scanning laser ophthalmoscope (SLO) imaging, SLO macular perimetry, and 
SLO autofluorescence imaging results were compared for two patients with
geographic atrophy (GA) from age-related macular degeneration, one patient with
pigmentary alteration of the retina, and two patients with Stargardt disease. The
main outcome measure in this case series was the presence of reduced
autofluorescence. RESULTS: Drusen may become undetectable during autofluorescence
imaging for some patients, allowing simple identification of areas of GA with
areas of reduced autofluorescence. In other patients, drusen themselves have
decreased autofluorescence, despite having intact retinal function in the retina 
overlying them. Some patients may have areas of reduced autofluorescence that
persist for many years, without evidence of the development of atrophy. In
Stargardt disease, decreased autofluorescence can easily detect and delineate
areas of scotoma. Areas with mottled autofluorescence may have overlying
function, but the function may not be adequate to support a fixation locus in
that area. CONCLUSIONS: Using decreased autofluorescence to delineate areas of
atrophy may be helpful in atrophic macular disorders. For GA, correlation with
fundus photographs or macular perimetry findings may be necessary to
differentiate between drusen and atrophy. For Stargardt disease, the nature of
areas of decreased autofluorescence may help explain visual function of those
areas.

Publication Types: 
    Comparative Study
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16829810 [PubMed - indexed for MEDLINE]

1386: Retina. 2006 Jul-Aug;26(6):602-12.

Photodynamic therapy and high-dose intravitreal triamcinolone to treat exudative 
age-related macular degeneration: 1-year outcome.

Ruiz-Moreno JM, Montero JA, Barile S, Zarbin MA.

Department of Ophthalmology, Miguel Hernández University School of Medicine,
Alicante, Spain. jm.ruiz@umh.es

PURPOSE: To evaluate the efficacy of photodynamic therapy with verteporfin (PDT) 
and high-dose intravitreous triamcinolone acetonide to treat choroidal new
vessels (CNVs) associated with age-related macular degeneration (AMD). METHODS:
In this prospective, consecutive, comparative, nonrandomized, interventional case
series, 30 consecutive eyes of 30 patients with subfoveal CNVs associated with
AMD were treated with PDT followed by the intravitreal injection of 19.4 +/- 2.1 
mg /0.1 mL triamcinolone 5 days later. Fifteen eyes had received no previous
treatment (group 1), and 15 had been treated previously with PDT alone (group 2).
A group of 15 eyes of 15 patients treated with PDT alone, matched for age and CNV
composition and size, served as controls. Changes in best-corrected visual acuity
(BCVA; logMAR), the number of Snellen lines improved or lost, and the number of
PDT sessions were considered as primary outcome indicators. RESULTS: Group 1
improved an average of 0.7 +/- 3.7 Snellen lines (range, -5 to 10) (P = 0.62),
group 2 lost an average of -0.7 +/- 1.5 Snellen lines (range, -5 to 1) (P =
0.08), and the control group lost an average of -2.2 +/- 0.4 Snellen lines
(range, -9 to 4) (P = 0.06; Wilcoxon signed rank test). The average number of PDT
treatments during the 12-month follow-up was 1.6, 1.2, and 2.8 for group 1, group
2, and the control group, respectively. Intraocular pressure rose in 8 (57%) of
14 eyes in group 1 and in 7 (50%) of 14 eyes in group 2. Cataracts developed in 4
eyes (31%) in group 1 and in 4 eyes (33%) in group 2. CONCLUSION: Combined
PDT/intravitreal triamcinolone acetonide as treatment for AMD-associated CNVs was
associated with improved final BCVA and reduced the need for retreatment compared
with historical controls.

Publication Types: 
    Clinical Trial

PMID: 16829800 [PubMed - indexed for MEDLINE]

1387: Ophthalmology. 2006 Sep;113(9):1504-7. Epub 2006 Jul 7.

Complement factor H increases risk for atrophic age-related macular degeneration.

Postel EA, Agarwal A, Caldwell J, Gallins P, Toth C, Schmidt S, Scott WK, Hauser 
MA, Haines JL, Pericak-Vance MA.

Duke University Eye Center, Durham, North Carolina, USA. poste002@mc.duke.edu

OBJECTIVE: To determine if the complement factor H gene (CFH) determines risk for
development of geographic atrophy (GA). DESIGN: Retrospective case-control study.
PARTICIPANTS AND CONTROLS: The independent case-control data set contained 647
age-related macular degeneration (AMD) cases (grades 3, 4, or 5) and 163 controls
(grades 1 or 2). METHODS: To determine if CFH had any effect on determining risk 
for development of GA in an independent case-control data set of 647 AMD cases
and 163 controls, the rs1061170 single-nucleotide polymorphism was tested for
association, separating grades and analyzing them independently against the
controls. Odds ratios were calculated using standard logistic regression models. 
MAIN OUTCOME MEASURES: The outcome variable was AMD affection status, and
genotypes were coded according to a log-additive model. RESULTS: There were 407
grade 5, 107 grade 4, 133 grade 3, 35 grade 2, and 128 grade 1 individuals. There
was significant association with AMD when comparing grades 3, 4, and 5 versus the
controls. The highest odds ratio was obtained when analyzing the grade-4 cases
versus the grade-1 controls (OR = 3.217, P<0.0001). CONCLUSIONS: Our results
indicate that CFH increases the risk of developing GA (grade 4) as well as
neovascular (grade 5) and milder (grade 3) disease. Although neovascular disease 
is responsible for the majority of severe vision loss with AMD, GA is also a
significant cause of vision loss, and without effective treatment. Therefore, an 
attempt to clarify its pathogenesis is of the utmost importance.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 16828512 [PubMed - indexed for MEDLINE]

1388: Ophthalmology. 2006 Sep;113(9):1481-7. Epub 2006 Jul 7.

Retinal vessel signs and 10-year incident age-related maculopathy: the Blue
Mountains Eye Study.

Liew G, Kaushik S, Rochtchina E, Tan AG, Mitchell P, Wang JJ.

Centre for Vision Research, Department of Ophthalmology and Westmead Millennium
Institute, University of Sydney, Westmead, NSW, Australia.

OBJECTIVE: To examine whether retinal vessel signs are independent predictors of 
the long-term development of age-related maculopathy (ARM). DESIGN: Prospective
population-based cohort study. PARTICIPANTS: Blue Mountains Eye Study
participants aged > or =49 years (n = 3654) were examined during 1992 through
1994; 2335 (75% of survivors) were reexamined after 5 years and 1952 (76% of
survivors) were reexamined after 10 years. METHODS: Baseline focal arteriolar
narrowing and arteriovenous (AV) nicking were assessed and vessel calibers were
measured from retinal photographs. A side-by-side grading method was used to
assess ARM incidence. Eye-specific data were analyzed using generalized
estimating equation models, adjusting for age, gender, smoking, and blood
pressure. MAIN OUTCOME MEASURES: Incident early ARM (soft indistinct or reticular
drusen or combined soft distinct drusen and retinal pigment abnormality) was
defined in eyes free of both early and late ARM at baseline. Incident late ARM
(either geographic atrophy or neovascular macular degeneration) was defined in
eyes free of these 2 lesions at baseline. RESULTS: Over a 10-year period,
incident late ARM developed in 106/4745 eyes at risk of late ARM (2.2%). Eyes
with mild (2.7%) or severe (4.6 %) AV nicking were more likely to develop late
ARM than eyes without this sign (1.5%). The adjusted odds ratio (OR) was 1.4, 95%
confidence interval (CI) 0.8 to 2.4 for mild and OR 2.6, 95% CI 1.2 to 5.5 for
severe AV nicking. Eyes with focal narrowing were also more likely to develop
late ARM (7.6% vs. 1.8%), adjusted OR 2.2, 95% CI 1.1 to 4.1. Incident early ARM 
developed in 398/4490 eyes at risk of early ARM (8.9%). Severe AV nicking, but
not focal arteriolar narrowing, was associated with an increased long-term risk
of early ARM (13.6% vs. 8.2%; OR 1.5; 95% CI 1.0-2.3). Neither arteriolar nor
venular caliber was significantly associated with the incidence of either early
or late ARM. CONCLUSIONS: These 10-year incidence data confirm our previous
observation that structural retinal arteriolar changes may either contribute to
ARM progression or share common pathologic pathways with ARM, independent of
traditional vascular risk factors.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16828507 [PubMed - indexed for MEDLINE]

1389: Ophthalmology. 2006 Sep;113(9):1533-8. Epub 2006 Jul 7.

Intravitreal triamcinolone for refractory diabetic macular edema: two-year
results of a double-masked, placebo-controlled, randomized clinical trial.

Gillies MC, Sutter FK, Simpson JM, Larsson J, Ali H, Zhu M.

Save Sight Institute, Department of Clinical Ophthalmology and Eye Health,
University of Sydney, Sydney, Australia. mark@eye.usyd.edu.au

OBJECTIVE: To report 2-year safety and efficacy outcomes from a trial of
intravitreal triamcinolone acetonide (TA) injections (4 mg) in eyes with diabetic
macular edema and impaired vision that persisted or recurred after laser
treatment. DESIGN: Prospective, double-masked, placebo-controlled, randomized
clinical trial. PARTICIPANTS AND CONTROLS: Sixty-nine eyes of 43 patients were
entered into the study, with 34 eyes randomized to receive active treatment and
35 placebo. Two-year data were available for 60 of 69 (87%) eyes of 35 of 41
(85%) patients; 9 eyes of 6 patients were lost to follow-up, of which 6 received 
a placebo and 3 received intravitreal TA. INTERVENTION: Triamcinolone acetonide
(0.1 ml) was injected through the pars plana using a 27-gauge needle. Eyes
randomized to placebo received a subconjunctival injection of saline. MAIN
OUTCOME MEASURES: Improvement of best-corrected logarithm of the minimum angle of
resolution visual acuity (VA) by > or =5 letters after 2 years and incidence of
moderate or severe adverse events. RESULTS: Improvement of > or =5 letters'
best-corrected VA was found in 19 of 34 (56%) eyes treated with intravitreal TA, 
compared with 9 of 35 (26%) eyes treated with the placebo (z(generalized
estimating equation) = 2.73, P = 0.006). The mean improvement in VA was 5.7
letters (95% confidence interval, 1.4-9.9) more in the intravitreal TA-treated
eyes than in those treated with the placebo. An increase of intraocular pressure 
(IOP) of > or =5 mmHg was observed in 23 of 34 (68%) treated versus 3 of 30 (10%)
untreated eyes (P<0.0001). Glaucoma medication was required in 15 of 34 (44%)
treated versus 1 of 30 (3%) untreated eyes (P = 0.0002). Cataract surgery was
performed in 15 of 28 (54%) treated versus 0 of 21 (0%) untreated eyes
(P<0.0001). Two eyes in the intravitreal TA-treated group required
trabeculectomy. There was one case of infectious endophthalmitis in the treatment
group. CONCLUSION: Intravitreal TA improves vision and reduces macular thickness 
in eyes with refractory diabetic macular edema. This beneficial effect persists
for up to 2 years with repeated treatment. Progression of cataract and elevation 
of IOP commonly occur but appear manageable. Spontaneous improvement over years
can still occur in eyes that are apparently severely affected by diabetic macular
edema.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16828501 [PubMed - indexed for MEDLINE]

1390: Ophthalmology. 2006 Sep;113(9):1508.e1-25. Epub 2006 Jul 7.

Year 2 efficacy results of 2 randomized controlled clinical trials of pegaptanib 
for neovascular age-related macular degeneration.

VEGF Inhibition Study in Ocular Neovascularization (V.I.S.I.O.N.) Clinical Trial 
Group, Chakravarthy U, Adamis AP, Cunningham ET Jr, Goldbaum M, Guyer DR, Katz B,
Patel M.

Centre for Vision Sciences, The Queen's University of Belfast and The Royal
Victoria Hospital, Belfast, United Kingdom.

OBJECTIVE: To evaluate the efficacy of a second year of pegaptanib sodium therapy
in patients with neovascular age-related macular degeneration (AMD). DESIGN: Two 
concurrent, multicenter, randomized, double-masked, sham-controlled studies
(V.I.S.I.O.N. [Vascular Endothelial Growth Factor Inhibition Study in Ocular
Neovascularization] trials). PARTICIPANTS: Patients with all angiographic
neovascular lesion compositions of AMD were enrolled. In combined analyses, 88%
(1053/1190) were re-randomized at week 54, and 89% (941/1053) were assessed at
week 102. INTERVENTIONS: At week 54, those initially assigned to pegaptanib were 
re-randomized (1:1) to continue or discontinue therapy for 48 more weeks (8
injections). Those initially assigned to sham were re-randomized to continue
sham, discontinue sham, or receive 1 of 3 pegaptanib doses. MAIN OUTCOME
MEASURES: Mean change in visual acuity (VA) over time and mean change in the
standardized area under the curve of VA and proportions of patients experiencing 
a loss of > or =15 letters from week 54 to week 102; losing <15 letters
(responders) from baseline to week 102; gaining > or =0, > or =1, > or =2, and > 
or =3 lines of VA; and progressing to legal blindness (20/200 or worse). RESULTS:
In combined analysis, mean VA was maintained in patients continuing with 0.3-mg
pegaptanib compared with those discontinuing therapy or receiving usual care. In 
patients who continued pegaptanib, the proportion who lost >15 letters from
baseline in the period from week 54 to week 102 was half (7%) that of patients
who discontinued pegaptanib or remained on usual care (14% for each).
Kaplan-Meier analysis showed that patients continuing 0.3-mg pegaptanib for a
second year were less likely to lose > or =15 letters than those re-randomized to
discontinue after 1 year (P<0.05). The proportion of patients gaining vision was 
higher for those assigned to 2 years of 0.3-mg pegaptanib than receiving usual
care. Progression to legal blindness was reduced for patients continuing 0.3-mg
pegaptanib for 2 years. CONCLUSIONS: Continuing visual benefit was observed in
patients who were randomized to receive therapy with pegaptanib in year 2 of the 
V.I.S.I.O.N. trials when compared with 2 years' usual care or cessation of
therapy at year 1.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16828500 [PubMed - indexed for MEDLINE]

1391: Eye. 2008 Jan;22(1):42-8. Epub 2006 Jul 7.

Aqueous humour levels of cytokines are correlated to vitreous levels and severity
of macular oedema in branch retinal vein occlusion.

Noma H, Funatsu H, Yamasaki M, Tsukamoto H, Mimura T, Sone T, Hirayama T, Tamura 
H, Yamashita H, Minamoto A, Mishima HK.

Department of Ophthalmology and Visual Science, Graduate School of Biomedical
Sciences, Hiroshima University, Minami-ku, Hiroshima, Japan. noma-hide@umin.ac.jp

AIM: To investigate whether the aqueous levels of vascular endothelial growth
factor (VEGF) and interleukin-6 (IL-6) are correlated to the vitreous levels of
these substances and to the severity of macular oedema in branch retinal vein
occlusion (BRVO). METHODS: Aqueous and vitreous samples were obtained during
cataract and vitreous surgery from 24 patients (24 eyes) with macular oedema in
BRVO. The VEGF and IL-6 levels in aqueous humour, vitreous fluid, and plasma were
determined by enzyme-linked immunosorbent assay. The degree of retinal ischaemia 
was evaluated in terms of the area of capillary nonperfusion using the Scion
Image. The severity of macular oedema was evaluated using the OCT. RESULTS: The
aqueous level of VEGF was significantly correlated with the vitreous level of
VEGF (P<0.0001). Vitreous levels of VEGF and IL-6 were significantly correlated
with the nonperfusion area of BRVO (P<0.0001, P=0.0061, respectively), as were
the aqueous levels of VEGF and IL-6 (P<0.0001, P=0.0267, respectively).
Furthermore, the vitreous levels of VEGF and IL-6 and the aqueous level of VEGF
were significantly correlated with the severity of macular oedema of BRVO
(P=0.0001, P=0.0331, P=0.0272, respectively). CONCLUSION: Our results suggest
that the aqueous level of VEGF may reflect its vitreous level. Measurement of the
aqueous level of VEGF may be clinically useful to indicate the severity of
macular oedema with BRVO.

PMID: 16826241 [PubMed - indexed for MEDLINE]

1392: Br J Ophthalmol. 2006 Dec;90(12):1524-30. Epub 2006 Jul 6.

Different transitions of multifocal electroretinogram recordings between patients
with age-related macular degeneration and polypoidal choroidal vasculopathy after
photodynamic therapy.

Imai H, Honda S, Nakanishi Y, Yamamoto H, Tsukahara Y, Negi A.

Department of Organ Therapeutics, Division of Ophthalmology, Kobe University
Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
h-i@excite.co.jp

AIM: To compare and evaluate the transitions in retinal function after
photodynamic therapy (PDT) between age-related macular degeneration (AMD) and
polypoidal choroidal vasculopathy (PCV) using multifocal electroretinograms
(mfERGs). METHODS: 10 eyes with choroidal neovascularisation (CNV) secondary to
AMD and 11 eyes with CNV secondary to PCV were included in the study. mfERGs were
recorded before PDT, and 1 week and 3 months after PDT. mfERG recordings were
acquired by a Veris system (V.3.1.3) using a 103 hexagon stimulus. The
first-order kernel was used to calculate amplitudes and latencies. Mean
amplitudes and latencies from two central rings rated 0-4 degrees of visual angle
were analysed and compared with each disease. RESULTS: In AMD, the mean first
negative peak (N1) amplitudes tended to decrease, and the mean first positive
peak (N1P1) amplitudes reduced to significant levels (p = 0.047) 1 week after
PDT. 3 months after PDT, there were no significant differences in the mean N1 and
N1P1 amplitudes compared with pre-PDT values. In PCV, there were no significant
changes in the mean N1 and N1P1 amplitudes 1 week after treatment. However, 3
months after PDT, mean amplitudes showed significant increases in N1 (p = 0.008) 
and N1P1 (p = 0.006) amplitudes compared with pre-PDT values. CONCLUSIONS: mfERG 
recording transitions are different between patients with AMD and those with PCV.
In patients with AMD, these results may show transient impairments in retinal
function 1 week after PDT, but in those with PCV, the efficacy of PDT is superior
to the impairment after PDT.

Publication Types: 
    Comparative Study
    Evaluation Studies

PMID: 16825279 [PubMed - indexed for MEDLINE]

1393: Environ Mol Mutagen. 2006 Oct;47(8):594-602.

An apolipoprotein E variant may protect against age-related macular degeneration 
through cytokine regulation.

Bojanowski CM, Shen D, Chew EY, Ning B, Csaky KG, Green WR, Chan CC, Tuo J.

Laboratory of Immunology, National Eye Institute, National Institutes of Health, 
Bethesda, Maryland 20892-1857, USA.

Age-related macular degeneration (AMD) is the leading cause of visual impairment 
and blindness among the elderly in Western countries. Genetic factors, age,
cigarette smoking, nutrition, and exposure to light have been identified as AMD
risk factors. In this study, we investigated the association between ApoE
C112R/R158C single nucleotide polymorphisms (which determine the E2, E3, and E4
isoforms) and age-related macular degeneration (AMD), and the mechanism
underlying the association. Genomic DNA was extracted from 133 clinically
screened controls, 94 volunteers with a younger mean age, 120 patients with
advanced AMD, and 40 archived ocular AMD slides for single nucleotide
polymorphism typing. The effects of recombinant ApoE isoforms on CCL2 (a
chemokine), CX3CR1 (a chemokine receptor), and VEGF (a cytokine) expression in
cultured human retinal pigment epithelium (RPE) cells were tested and serum
cholesterol profiles of the clinically screened subjects were analyzed. ApoE112R 
(E4) distribution differed significantly between AMD patients and controls.
ApoE112R allele frequency was 10.9% in the AMD group when compared with 16.5% in 
the younger controls and 18.8% in the clinically screened controls. The
pathologically diagnosed archived AMD cases had the lowest allele frequency of
5%. No significant differences in ApoE158C (E2) distribution were observed among 
the groups. A meta-analysis of 8 cohorts including 4,289 subjects showed a strong
association between AMD and 112R, but not 158C. In vitro studies found that
recombinant ApoE suppresses CCL2 and VEGF expression in RPE cells. However, the
E4 isoform showed more suppression than E3 in both cases. These results further
confirm the association between ApoE112R and a decreased risk of AMD development.
The underlying mechanisms may involve differential regulation of both CCL2 and
VEGF by the ApoE isoforms.

Publication Types: 
    Meta-Analysis

PMID: 16823865 [PubMed - indexed for MEDLINE]

1394: Surv Ophthalmol. 2006 Jul-Aug;51(4):316-63.

The genetics of age-related macular degeneration: a review of progress to date.

Haddad S, Chen CA, Santangelo SL, Seddon JM.

Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital,
Boston, 02114, USA.

Age-related macular degeneration (AMD) is the leading cause of vision loss and
blindness among older adults in the USA and throughout the developed world.
Etiological research suggests that AMD is a complex disease, caused by the
actions and interactions of multiple genes and environmental factors. Familial
aggregation studies, twin studies, and segregation analyses have provided strong 
evidence for the heritability of AMD, and linkage and association studies have
been conducted to localize the disease-causing genes. Whole genome linkage scans 
have implicated nearly every chromosome in the human genome, with the most
replicated signals residing on 1q25-31 and 10q26. Association studies have
identified a major risk variant within the complement factor H gene (CFH), and
recent reports suggest that PLEKHA1/LOC387715 and the BF/C2 regions may be major 
risk loci for AMD as well. Several other genes have had at least one positive
association finding and deserve further exploration. Among these, apolipoprotein 
E (APOE) may be a minor risk locus. Additional genes will likely be identified,
and future studies should explore the potential interactions of these genes with 
other genes as well as environmental factors.

Publication Types: 
    Meta-Analysis
    Review

PMID: 16818082 [PubMed - indexed for MEDLINE]

1395: Insight. 2006 Jan-Mar;31(1):11-4.

Macugen treatment for wet age-related macular degeneration.

Tobin KA.

Massachusetts Eye and Ear Infirmary, 243 Charles St, Boston, MA 02114, USA.
Kathleen_Tobin@MEEI.Harvard.edu

Macugen (pegaptanib sodium), manufactured by Eyetech Pharmaceuticals, Inc., and
Pfizer, Inc., is the first treatment approved by the U.S. Food and Drug
Administration for all forms of wet macular degeneration. Although the cause of
wet macular degeneration is not known, it is believed that vascular endothelial
growth factor (VEGF) induces angiogenesis, resulting in a neovascular process,
the hallmark of wet macular degeneration. Macugen is a VEGF antagonist. In two
controlled, double-blinded identical studies, Macugen 0.3 mg was shown to slow
the progression of wet macular degeneration. Using strict aseptic technique,
Macugen 0.3 mg is administered via intravitreal injection every six weeks for one
to two years. Serious adverse reactions include endophthalmitis, retinal
detachment, and iatrogenic traumatic cataract. Macugen is administered after a
topical anesthetic, a subconjuctival block, or a combination of both is used to
numb the injection site on the temporal sclera. Post-procedure patients may
initially complain of transient vision loss, burning, pressure, eye pain, or
"floaters". At time of discharge, patients should be informed of the signs and
symptoms of infection and instructed in the administration of antibiotic drops
and in proper follow-up care. Most patients are seen for follow up one week after
injection and again in five weeks for additional treatment.

Publication Types: 
    Review

PMID: 16817567 [PubMed - indexed for MEDLINE]

1396: Hum Hered. 2006;61(3):157-65. Epub 2006 Jun 30.

CFH gene variant, Y402H, and smoking, body mass index, environmental associations
with advanced age-related macular degeneration.

Seddon JM, George S, Rosner B, Klein ML.

Epidemiology Unit, Massachusetts Eye and Ear Infirmary, Harvard Medical School,
243 Charles Street, Boston, MA 02114, USA. Johanna_Seddon@meei.harvard.edu

OBJECTIVES: We tested the hypothesis that modifiable lifestyle factors alter the 
genetic susceptibility associated with a common coding variant in the complement 
factor H (CFH) gene, Y402H, for the leading cause of blindness among the elderly,
age-related macular degeneration (AMD). METHODS: In this case-control association
analysis, Caucasian participants in the multicenter Age-Related Eye Disease Study
with advanced AMD (n = 574 cases) or no AMD (n = 280 controls) were evaluated.
AMD status was determined by grading of fundus photographs. Risk factors
including cigarette smoking and body mass index (BMI) were assessed and DNA
specimens were genotyped for the variant in the CFH gene. Unconditional logistic 
regression analyses were performed. Attributable risks and multivariable AMD risk
scores were calculated. RESULTS: The number of risk alleles for Y402H was
associated with advanced AMD, with odds ratios (OR) of 2.7 (95% confidence
interval (CI) 1.8-3.8) for the CT heterozygous genotype and OR 7.4 (4.7-11.8) for
the homozygous CC risk genotype, after controlling for demographic and behavioral
risk factors. Current cigarette smoking (OR 5.1) and high BMI > or =30 (OR 2.1)
were independently related to AMD, controlling for genotype. The association
between AMD and BMI varied dependent on genotype (P interaction = 0.006 for the
CT vs. TT genotype). The CC genotype plus higher BMI (OR 5.9) or smoking (OR
10.2) conferred the greatest risks. Gene plus environment risk scores provided an
area under the receiver operating characteristic (ROC) curve of 0.70-0.75.
CONCLUSIONS: Genetic and environmental factors are independently related to
advanced AMD, and modifiable factors alter genetic susceptibility. The AMD risk
score identifies a highly susceptible population. Copyright (c) 2006 S. Karger
AG, Basel.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16816528 [PubMed - indexed for MEDLINE]

1397: Ophthalmology. 2006 Jul;113(7):1165-72; quiz 1172-3, 1178.

Efficacy of omega-3 fatty acids in preventing age-related macular degeneration: a
systematic review.

Hodge WG, Schachter HM, Barnes D, Pan Y, Lowcock EC, Zhang L, Sampson M, Morrison
A, Tran K, Miguelez M, Lewin G.

Department of Ophthalmology, University of Ottawa Eye Institute, Ottawa, Canada. 
whodge@ottawahospital.on.ca

TOPIC: What is the evidence for efficacy of dietary and/or supplemental omega-3
fatty acids in preventing age-related macular degeneration (AMD)? CLINICAL
RELEVANCE: Age-related macular degeneraion is the leading cause of blindness and 
vision impairment in persons older than 50 years living in North America. There
is no cure for AMD, and treatment does not usually restore vision but only
prevents disease progression to a modest degree. omega-3 fatty acids are
considered potentially important antioxidants and are being considered as an arm 
of the Age-Related Eye Disease Study II clinical trial. METHODS/LITERATURE
REVIEWED: Keywords were searched in Medline, Pre-Medline, Embase, and the
Cochrane Library on Ovid. There was no restriction on the year or language of
publication. RESULTS: There were 6 observational studies found, but the specific 
outcomes, exposures, and covariates studied all varied greatly. CONCLUSION: There
is some clinical evidence for protection of AMD from omega-3 fatty acids.
However, the results are not consistent. Hence, our conclusion is that this issue
is neither clearly supported nor refuted by the present world literature. This is
an intriguing and extremely important question but needs further study first with
prospective cohort designs and, if positive, randomized clinical trials.

Publication Types: 
    Review

PMID: 16815401 [PubMed - indexed for MEDLINE]

1398: Am J Ophthalmol. 2006 Jul;142(1):192-4.

Distinct cytokine and chemokine profiles in the aqueous of patients with uveitis 
and cystoid macular edema.

van Kooij B, Rothova A, Rijkers GT, de Groot-Mijnes JD.

F. C. Donders Institute of Ophthalmology, Utrecht, The Netherlands.
b.vankooij@oogh.azu.nl

PURPOSE: To investigate the global cytokine and chemokine expression pattern in
the aqueous humor of uveitis patients and relate them to clinical features.
DESIGN: Cross-sectional study. METHODS: In 31 aqueous humor samples from uveitis 
patients, the concentration of mediators was measured by a multiplex immunoassay.
Eleven control samples were included. RESULTS: Uveitis samples had higher levels 
of interleukin-6, interleukin-8, soluble intercellular adhesion molecule, soluble
vascular cell adhesion molecule (sVCAM), and interferon-inducible protein-10
(IP-10) than nonuveitis controls. Active uveitis samples had higher levels of
interleukin-6, interleukin-10, interferon-gamma, sVCAM, regulated on activation, 
normal T cell expressed and secreted (RANTES), and IP-10 than quiescent uveitis
samples. Infectious uveitis was associated with higher levels of interleukin-10
than noninfectious uveitis (P < .03 for all subgroups). No significant
differences were found between cystoid macular edema (CME) and non-CME samples.
CONCLUSIONS: Elevated levels of specific mediators were found in active and in
infectious uveitis, but not in CME. Mediator profiles might lead to a better
understanding of the pathogenesis of uveitis.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16815285 [PubMed - indexed for MEDLINE]

1399: Am J Ophthalmol. 2006 Jul;142(1):160-2.

Retinal pigment epithelial tears after pegaptanib injection for exudative
age-related macular degeneration.

Singh RP, Sears JE.

Retina Service, Cole Eye Center, Cleveland Clinic Foundation, Cleveland, Ohio
44195, USA.

PURPOSE: To report two cases of retinal pigment epithelium (RPE) tears following 
intravitreal pegaptanib injections for occult choroidal neovascularization.
DESIGN: Noncomparative case series. METHODS: The charts of two patients with
pigment epithelial tears after receiving intravitreal pegaptanib were reviewed.
Approval from the institutional review board and informed consent were obtained
before chart review. Fundus photos, intravenous fluorescein angiograms, and
optical coherence tomography (OCT) were obtained before and after therapy
confirmed the diagnosis. RESULTS: Two patients had turbid pigment epithelial
detachments (PEDs) and occult choroidal neovascular membranes (CNVMs) treated
with intravitreal pegaptanib. Both patients developed RPE tears weeks following
one intravitreal pegaptanib injection. CONCLUSIONS: This report describes the
development of RPE tears after intravitreal pegaptanib injection. Caution should 
be taken in cases of turbid pigment epithelial detachments in the monocular
patient when treatment with intravitreal pegaptanib is entertained. Future
studies should be performed to evaluate which subtypes of lesions are most
susceptible to this devastating visual complication.

Publication Types: 
    Case Reports

PMID: 16815269 [PubMed - indexed for MEDLINE]

1400: Am J Ophthalmol. 2006 Jul;142(1):17-30.

Autologous translocation of the choroid and retinal pigment epithelium in
age-related macular degeneration.

Joussen AM, Heussen FM, Joeres S, Llacer H, Prinz B, Rohrschneider K, Maaijwee
KJ, van Meurs J, Kirchhof B.

Department of Vitreoretinal Surgery, Center for Ophthalmology, University of
Cologne, Cologne, Germany. JoussenA@googlemail.com

PURPOSE: To evaluate the autologous translocation of peripheral choroid and
retinal pigment epithelium (RPE) in 45 eyes of 43 patients with age-related
macular degeneration (AMD). DESIGN: Prospective nonrandomized study. METHODS: All
patients had visual loss due to AMD (n = 5 classic membranes, n = 14 occult, n = 
2 mixed, n = 16 pigment epithelial detachment (PED), n = 5 subretinal hemorrhage,
n = 3 geographic atrophy). After extraction of the neovascular complex, an
autologous peripheral full-thickness explant of RPE, Bruch membrane, and choroid 
was translocated from the midperiphery to the macula. RESULTS: Preoperative
distant visual acuity ranged from 20/800 to 20/40. Reading vision ranged from 1.4
logarithm of reading acuity determination (logRAD) to 0.5 logRAD (0.04 to 0.32
Snellen equivalent). Revision surgery was required in 22 eyes as a result of
proliferative vitreoretinopathy (PVR), retinal detachment, macular pucker, or
vitreous hemorrhage. In eight patients, the patch was renewed. At six months,
distant visual acuity ranged from light perception to 20/50 (increase of 15
letters in four eyes). Reading vision ranged from 1.4 to 0.4 logRAD. Visual
outcome was unrelated to the type of AMD. Vascularization of the transplant was
visible on indocyanine green (ICG) angiography in 40 of 42 eyes. In most
patients, autofluorescence of the pigment epithelium was coincident with
revascularization of the graft. Fixation on the patch was positively related to
visual acuity. CONCLUSIONS: Autologous translocation of a full-thickness
transplant of choroid and RPE usually results in a vascularized and functioning
graft. Vascularization was even achieved in patients with geographic atrophy.
Fixation stability and microperimetry before the patch translocation may be
helpful in selecting patients who will profit from surgery.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16815247 [PubMed - indexed for MEDLINE]

1401: Am J Ophthalmol. 2006 Jul;142(1):10-16.

Photodynamic therapy with verteporfin and intravitreal triamcinolone acetonide in
the treatment of neovascular age-related macular degeneration.

Ergun E, Maár N, Ansari-Shahrezaei S, Wimpissinger B, Krepler K, Wedrich A, Stur 
M.

Department of Ophthalmology, Sanatorium Hera, Vienna, Austria.
erdem.ergun@chello.at

PURPOSE: To examine the efficacy of photodynamic therapy (PDT) with verteporfin
and intravitreal triamcinolone acetonide in the treatment of neovascular
age-related macular degeneration (AMD). DESIGN: Retrospective, interventional
case series. METHODS: Sixty eyes of 56 patients with neovascular AMD were treated
with PDT with verteporfin followed by an intravitreal injection of 4 mg
triamcinolone acetonide. The main outcome measures were visual acuity (VA),
retreatment frequency with PDT (and triamcinolone), and frequency of side
effects. RESULTS: Mean follow-up was 15.9 months (range 12 to 30 months, median
15 months). Twenty-three (38.3%) of 60 eyes had a stable result at 12 months'
follow-up (that is, loss/gain <three lines) and 34 (56.7%) of 60 had a loss of 3 
lines or more. Three patients (5%) had an improvement of 3 lines or more. Lesion 
type, patient age, and lesion size had no influence on the outcome, but baseline 
VA had a statistically significant effect (P = .006). The median number of
PDT-intravitreal triamcinolone acetonide treatments was one. One-third (20 of 60)
of all eyes had an increase in intraocular pressure (IOP) that required therapy. 
There were no cases of endophthalmitis, but 13 patients (21.6%) developed severe 
cataract that required surgery. CONCLUSIONS: The combination of PDT and
intravitreal triamcinolone acetonide requires careful consideration as a
treatment option for neovascular AMD. In our case series, this treatment
combination did not prevent a considerable decrease in VA. The main benefit of
this combination treatment was a low number of verteporfin treatments. Baseline
VA was the main predictor of the final outcome.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16815246 [PubMed - indexed for MEDLINE]

1402: Am J Ophthalmol. 2006 Jul;142(1):1-9.

Comment in:
    Am J Ophthalmol. 2006 Jul;142(1):141-3.

Intravitreal bevacizumab for the management of choroidal neovascularization in
age-related macular degeneration.

Bashshur ZF, Bazarbachi A, Schakal A, Haddad ZA, El Haibi CP, Noureddin BN.

Department of Ophthalmology, American University of Beirut, Beirut, Lebanon.
zb00@aub.edu.lb

PURPOSE: To investigate the efficacy and safety of intravitreal bevacizumab for
managing choroidal neovascularization (CNV) due to age-related macular
degeneration (AMD). DESIGN: Prospective interventional case series. METHODS:
Seventeen eyes of 17 patients with subfoveal CNV due to AMD participated in this 
study at the American University of Beirut Ophthalmology Clinics. All patients
had failed, refused, or were not eligible for photodynamic therapy. All eyes
received a baseline eye examination, which included best-corrected visual acuity 
(BCVA), dilated fundus examination, ocular coherence tomography (OCT) imaging,
and fluorescein angiography. An intravitreal injection of bevacizumab (2.5 mg/0.1
ml) was given at baseline and followed by two additional injections at four-week 
intervals. BCVA, OCT, and fluorescein angiography were repeated four weeks after 
each injection. Main outcome measures were improvement in BCVA and central
retinal thickness (CRT). RESULTS: Mean baseline BCVA was 20/252 (median 20/200), 
and baseline CRT was 362 microm (median 350 microm). Improvement in VA and CRT
occurred by the fourth week. At 12 weeks, mean BCVA was 20/76 (P < .001) and
median BCVA was 20/50 (P < .001). Both mean and median CRT decreased to 211
microm (P < .001). Thirteen (76%) of 17 eyes had total resolution of subretinal
fluid, and four eyes (24%) had BCVA better than 20/50. No systemic or ocular side
effects were noted at any time. CONCLUSION: Eyes with CNV due to AMD treated with
intravitreal bevacizumab had marked anatomic and visual improvement. Further
studies are necessary to confirm the long-term efficacy and safety of this
treatment.

PMID: 16815245 [PubMed - indexed for MEDLINE]

1403: Kidney Int. 2006 Jul;70(1):12-3.

Comment on:
    Kidney Int. 2006 Jul;70(1):42-50.

Factor H genotype-phenotype correlations: lessons from aHUS, MPGN II, and AMD.

Goodship TH.

Institute of Human Genetics, University of Newcastle upon Tyne, Newcastle upon
Tyne, UK. t.h.j.goodship@ncl.ac.uk

Missense mutations in the C-terminal region of Factor H are associated with
atypical hemolytic uremic syndrome, whereas homozygous Factor H deficiency is
more frequently associated with membranoproliferative glomerulonephritis type II 
(MPGN II). The report of Licht et al. of a mutation in the complement-regulatory 
N-terminal region of Factor H in MPGN II provides additional insight into the
pathogenesis of this condition.

Publication Types: 
    Comment

PMID: 16810287 [PubMed - indexed for MEDLINE]

1404: J Ocul Pharmacol Ther. 2006 Jun;22(3):200-7.

Intravitreal triamcinolone acetonide for diabetic macular edema: a prospective,
randomized study.

Jonas JB, Kamppeter BA, Harder B, Vossmerbaeumer U, Sauder G, Spandau UH.

Department of Ophthalmology, Faculty of Clinical Medicine Mannheim of the
Ruprecht-Karls-University of Heidelberg, Germany.
Jost.Jonas@augen.ma.uni-heidelberg.de

PURPOSE: The aim of this study was to examine the visual outcome of patients
receiving an intravitreal injection of triamcinolone acetonide (TA) as treatment 
of diffuse diabetic macular edema (DDME). METHODS: This prospective,
placebo-controlled, randomized, clinical interventional study included 40 eyes
(38 patients) with DDME, with 28 (70%) eyes randomized to treatment and 12 (30%) 
eyes randomized to receive a placebo injection. Thirty-six (36) (90%) eyes
completed the 3-month study visit, and 32 (80%) eyes completed the 6-month study 
visit. The treatment group received an intravitreal injection of approximately 20
mg of TA. RESULTS: Visual acuity increased significantly (P < 0.001) in the study
group by 3.4 +/- 2.5 Snellen lines. In the control group, visual acuity did not
change significantly (P = 0.07) during follow-up. Difference in change of best
visual acuity was significant (P < 0.001) between both groups. At 3 months after 
baseline, 11 (11/26; 42%) eyes and 10 (10/26; 39%) eyes, respectively, improved
by at least 2 and 3 lines, respectively, in the study group, versus 2 (2/10; 20%)
eyes and 1 (1/10; 10%) eye in the control group. At 6 months after baseline, 11
(11/23; 48%) eyes and 9 (9/23; 39%) eyes, respectively, improved by at least 2
and 3 lines, respectively, in the study group, versus 0 (0%) eyes and 0 (0%) eyes
in the control group. The difference was significant for the 2-line improvement
(P = 0.01) and 3-line improvement (P = 0.03). CONCLUSIONS: Using a dosage of
approximately 20 mg of intravitreal TA, visual acuity temporarily increases for 6
months after injection.

Publication Types: 
    Randomized Controlled Trial

PMID: 16808682 [PubMed - indexed for MEDLINE]

1405: J Ocul Pharmacol Ther. 2006 Jun;22(3):194-9.

Duration of the effect of intravitreal triamcinolone acetonide in eyes with
exudative age-related macular degeneration.

Jonas JB, Spandau UH, Kamppeter BA, Degenring RF, Kreissig I, Akkoyun I,
Vossmerbaeumer U.

Department of Ophthalmology, Faculty of Clinical Medicine Mannheim of the
Ruprecht-Karls-University of Heidelberg, Germany.

OBJECTIVE: The aim of this study was to evaluate the duration of the effect of an
intravitreal injection of approximately 20 mg of triamcinolone acetonide (TA) on 
visual acuity and intraocular pressure (IOP) in patients with exudative
age-related macular degeneration (AMD) with subfoveal choroidal
neovascularization. PARTICIPANTS: The prospective, clinical, interventional, case
series study included 69 patients (71 eyes) with exudative AMD who showed an
increase in visual acuity by at least 2 Snellen lines after an intravitreal
injection of approximately 20 mg TA. Mean follow-up was 11.5 +/- 7.4 months
(3.3-35.7 months). The main outcome measure was visual acuity. RESULTS: Within
the first week after the injection, visual acuity and IOP started to increase
significantly (P < 0.001) by reaching a plateau-like maximum at 1-6 months after 
the injection. Visual acuity and IOP returned to baseline values 7-9 months after
the injection. Increase of IOP was statistically (P = 0.72) independent of the
change in visual acuity. CONCLUSIONS: In patients with exudative AMD, who have
shown an increase of at least 2 Snellen lines in visual acuity, the effect of
intravitreal TA (dosage approximately 20 mg) lasts 7-9 months with respect to an 
increase in visual acuity and IOP.

PMID: 16808681 [PubMed - indexed for MEDLINE]

1406: Expert Opin Biol Ther. 2006 Jul;6(7):717-26.

Application of encapsulated cell technology for retinal degenerative diseases.

Tao W.

Neurotech USA, Inc., 6 Blackstone Valley Place, Suite 500, Lincoln, RI 02865,
USA. w.tao@neurotechusa.com

Ophthalmic disorders represent a rapidly growing disease area that is associated 
with the ageing population. Their sight is threatened by age-related macular
degeneration, diabetic retinopathy, glaucoma and/or retinitis pigmentosa (RP).
Few effective treatments for these disorders are available at present, in part
due to lack of effective delivery of therapeutic molecules to the retina.
Encapsulated cell technology (ECT) allows the controlled, continuous and
long-term administration of protein drugs in the eye, where therapeutic agents
are needed, and does not subject the host to the systemic exposure. Furthermore, 
the implants can be retrieved, providing an added level of safety. Ciliary
neurotrophic factor (CNTF) has been shown to protect the retina from degeneration
in 13 animal models, and ECT-based delivery of CNTF protected photoreceptors in
the rcd1 dog model of RP.

Publication Types: 
    Review

PMID: 16805711 [PubMed - indexed for MEDLINE]

1407: Invest Ophthalmol Vis Sci. 2006 Jul;47(7):3044-51.

Diabetic macular edema: correlation between microperimetry and optical coherence 
tomography findings.

Vujosevic S, Midena E, Pilotto E, Radin PP, Chiesa L, Cavarzeran F.

Fondazione G. B. Bietti per l'Oftalmologia, IRCCS (Istituto di Ricovero e Cura a 
Carattere Scientifico), Roma, Italy. stelavu@hotmail.com

PURPOSE: To compare the changes in macular sensitivity (microperimetry) and
macular thickness with different degrees of diabetic macular edema. METHODS:
Sixty-one eyes of 32 consecutive diabetic patients were included in this
cross-sectional study. All included eyes underwent functional and morphologic
examination of the macular area. Best corrected visual acuity (ETDRS charts),
macular sensitivity, and macular thickness were quantified. Lesion-related
macular sensitivity and retinal fixation were investigated with an advanced,
automatic microperimeter. Optical coherence tomography (OCT) was used to quantify
macular thickness. RESULTS: The 61 included eyes were graded, by two retinal
specialists, for diabetic macular edema as follows: 16 were graded as no macular 
edema (NE), 30 as non-clinically significant macular edema (NCSME), and 15 as
clinically significant macular edema (CSME). Macular thickness significantly
increased from the NE to the CSME group (P<0.0001), whereas macular sensitivity
significantly decreased from the NE to the CSME group (P<0.0021). A significant
correlation coefficient was noted between retinal sensitivity and normalized
macular thickness (r=-0.37, P<0.0001). Linear regression analysis showed a
decrease of 0.83 dB (P<0.0001) for every 10% of deviation of retinal thickness
from normal values. Visual acuity and central macular sensitivity correlated
significantly in the NCSME group (r=-0.6, P=0.0008), but not in the NE (r=-0.144,
P=0.6) or in the CSME (r=-0.46, P=0.11) groups. CONCLUSIONS: Macular edema may be
better documented by adding macular sensitivity mapping by microperimetry to
macular thickness measurement by OCT and visual acuity determination because
macular sensitivity seems to be a relevant explanatory variable of visual
function, independent of macular thickness data. Moreover, microperimetry may be 
of value in predicting the outcome of diabetic macular edema, because it
incorporates a functional measure that may supplement the predictive value of OCT
and visual acuity.

Publication Types: 
    Comparative Study

PMID: 16799051 [PubMed - indexed for MEDLINE]

1408: J Diabetes Complications. 2006 Jul-Aug;20(4):246-51.

Posterior subtenon and intravitreal triamcinolone acetonide for diabetic macular 
edema.

Ozdek S, Bahçeci UA, Gürelik G, Hasanreisoğlu B.

Ophthalmology Department, School of Medicine, Gazi University, Beşevler, Ankara, 
Turkey.

AIM: To evaluate retroprospectively the clinical consequences of posterior
subtenon (PSTT) and intravitreal (IVT) triamcinolone acetonide injections in
diabetic macular edema (DME) refractory to conventional grid laser
photocoagulation. MATERIAL AND METHODS: Eyes with clinically significant DME
refractory to grid laser photocoagulation were assessed for the inclusion in the 
study. Complete ophthalmic examination with fluorescein angiography (FA) and
optic coherence tomography (OCT) were performed before and in the 1st, 3rd, and
6th months of the treatment. The IVT group received 4 mg/0.1 ml and the PSTT
group received 20 mg/0.5 ml triamcinolone injection. PSTT but not IVT injection
was repeated in case of recurrent edema. IVT was also applied to the eyes with
resistant macular edema after PSTT injection (secondary IVT group). RESULTS:
There were 85 eyes of 60 patients in the PSTT group and 41 eyes of 35 patients in
IVT group. There were 24 eyes in the primary IVT group and 17 eyes in the
secondary IVT group. Mean follow-up time was 4.1+/-1.9 and 4.6+/-2.2 months after
PSTT and IVT injections, respectively. In the PSTT group, the mean visual acuity 
increased from 0.19+/-0.18 to 0.22+/-0.19 and the mean central foveal thickness
decreased from 413.1+/-117.5 to 312.1+/-103.1 microm (P=.001 and P=.0001,
respectively) during the first 3 months. In the IVT group, the mean visual acuity
and central foveal thickness were found to be 0.15+/-0.14 and 494.5+/-141.3
microm before the treatment and 0.20+/-0.16 and 288.4+/-88.5 microm 3 months
after the treatment, respectively (P=.008 and P=.001, respectively). The effect
in central foveal thickness was significantly greater in the primary IVT group
than in the PSTT group (P=.002). There was no significant difference with respect
to the decrease in the central foveal thickness and increase in visual acuity
between the primary and secondary IVT injections (Mann-Whitney U test, P>.05).
The steroid effect started to diminish after the 3rd month. The recurrence of
macular edema was seen in 7.1% in the PSTT group starting after 3 months. Twenty 
percent of the eyes in the PSTT group did not respond to the treatment at all and
had secondary IVT injections. Significant intraocular pressure increase was found
in 8.2% of the PSTT group and in 24.3% of IVT injection. There was one case of
pseudomonas endophthalmitis in the IVT group. CONCLUSION: This study is the first
study comparing the clinical outcomes of PSTT and IVT injections for the
treatment of DME. Both PSTT and IVT injections caused a significant increase in
visual acuity and a decrease in central foveal thickness, especially in the short
term. The effect was more pronounced in the IVT group; however, PSTT injection
also seemed to be a safe and effective technique for the treatment of DME.
Further prospective studies are warranted to assess the efficacy and side effects
of IVT and PSTT injections for the treatment of DME.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 16798476 [PubMed - indexed for MEDLINE]

1409: Curr Opin Ophthalmol. 2006 Jun;17(3):278-80.

New evidence that vision rehabilitation is a key component in the management of
patients with macular degeneration.

Edmonds SA, Edmonds SE.

Wills Eye Hospital, Philadelphia, Pennsylvania 19103, USA. scottaed@aol.com

PURPOSE OF REVIEW: Vision rehabilitation has been considered as an adjunct
support option or just the dispensing of magnifiers in the management of macular 
degeneration. RECENT FINDINGS: New research suggests that vision rehabilitation
can cause physical changes in the brain that help patients adjust to permanent
vision loss. SUMMARY: Vision rehabilitation is related to physical changes that
occur in the brain. Its use in conjunction with clinical low-vision programs may 
pave the way for developing better rehabilitation techniques for patients with
macular blindness.

Publication Types: 
    Review

PMID: 16794441 [PubMed - indexed for MEDLINE]

1410: Curr Opin Ophthalmol. 2006 Jun;17(3):267-74.

Treatment of nonexudative (dry) age-related macular degeneration.

Donaldson MJ, Pulido JS.

Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota 55905, USA.

PURPOSE OF REVIEW: The purpose of this report is to review the recent literature 
and summarize currently available and potential new treatment options for
nonexudative age-related macular degeneration. RECENT FINDINGS: High-dose vitamin
supplementation may have some associated systemic toxicity. It is important to
check that the patient is taking beta-carotene and not vitamin A as retinal
acetate or palmitate, which have been associated with osteoporosis and
hepatotoxicity. High-dose vitamins E and C may be associated with cardiovascular 
disease. Decreasing inflammation by lowering systemic cardiac C-reactive protein,
fibrinogen and cholesterol may be important, especially in light of recent
epidemiologic and genetic data. The results of randomized trials of laser
treatment for drusen and rheopheresis should be available during 2006. Treatment 
with these modalities before the results of the trials are evaluated should be
avoided. SUMMARY: The holy grail of therapy for age-related macular degeneration 
is to avoid the development of choroidal neovascularization. High-dose vitamin
supplementation should be used only in those in whom it is indicated and
inflammatory parameters including highly sensitive C-reactive protein, fibrinogen
and cholesterol should be stabilized because there are data associating these
parameters with age-related macular degeneration and also with cardiovascular
disease.

Publication Types: 
    Review

PMID: 16794439 [PubMed - indexed for MEDLINE]

1411: Curr Opin Ophthalmol. 2006 Jun;17(3):257-66.

Erratum in:
    Curr Opin Ophthalmol. 2006 Jun;17(3):265.

The burden of age-related macular degeneration: a value-based analysis.

Brown MM, Brown GC, Sharma S, Stein JD, Roth Z, Campanella J, Beauchamp GR.

Center for Value-Based Medicine, Flourtown 19031, USA.
mbrown@valuebasedmedicine.com

PURPOSE OF REVIEW: The quality-of-life loss and the financial consequences
associated with age-related macular degeneration are assessed. RECENT FINDINGS:
The quality-of-life loss associated with macular degeneration is markedly
underestimated by the general public, nonophthalmic physicians, and
ophthalmologists who treat patients with this condition. Mild age-related macular
degeneration causes a 17% decrement in the quality of life of the average
patient, similar to that encountered with moderate cardiac angina or symptomatic 
human immunodeficiency virus syndrome. Moderate age-related macular degeneration 
causes a 40% decrease in the average patient's quality of life, similar to that
associated with severe cardiac angina or renal dialysis. Very severe age-related 
macular degeneration causes a large 63% decrease in the average patient's quality
of life, similar to that encountered with end-stage prostatic cancer or a
catastrophic stroke that leaves a person bedridden, incontinent and requiring
constant nursing care. The return on investment is high for both treatment with
current age-related macular degeneration therapies and the research costs
invested in the development of age-related macular degeneration treatment
modalities. SUMMARY: Age-related macular degeneration is a major public health
problem that has a devastating effect upon patients and marked adverse financial 
consequences for the economy.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 16794438 [PubMed - indexed for MEDLINE]

1412: Curr Opin Ophthalmol. 2006 Jun;17(3):223-7.

Update on utilities and cost-utility analyses.

Hollands H, Sharma S.

Cost-effective Ocular Health Policy Unit, Queens University, Kingston, Ontario,
Canada.

PURPOSE OF REVIEW: The purpose of this review is to summarize the recent and
noteworthy utility studies and cost-utility analyses in the area of
retina/vitreous during the period January 2004 to January 2006. RECENT FINDINGS: 
This review considers the cost-effectiveness of treatments for wet age-related
macular degeneration, dry age-related macular degeneration, telemedicine in
diabetic retinopathy, and utilities and patients with age-related macular
degeneration and diabetic retinopathy. SUMMARY: Utilities are being used
increasingly to measure health-related quality of life. Cost-utility analyses are
becoming more readily available for comparing the incremental cost-effectiveness 
of different ophthalmic interventions.

Publication Types: 
    Review

PMID: 16794433 [PubMed - indexed for MEDLINE]

1413: Ophthalmic Physiol Opt. 2006 Jul;26(4):431-7.

The Scotopic Sensitivity Tester-1 and the detection of early age-related macular 
degeneration.

Jackson GR, Felix T, Owsley C.

Department of Ophthalmology, School of Medicine, University of Alabama at
Birmingham, 700 S. 18th Street, Suite 609, Birmingham, AL 35294-0009, USA.

PURPOSE: Previous research shows that dark adaptation is a marker of early
age-related macular degeneration (ARMD), even when visual acuity remains good.
This study evaluates whether a commercially available, off-the-shelf device for
measuring dark adaptation, the Scotopic Sensitivity Tester-1 (SST-1), which uses 
a full-field stimulus, detects early ARMD as defined by fundus appearance. Fundus
appearance is the gold standard method for defining the presence of ARMD.
METHODS: Dark adaptation was measured using the SST-1 in 12 young adults (mean
age 23 years), 17 old adults with normal retinal health (mean age 69) and 19 old 
adults with early ARMD (mean age 74). Normal retinal health and presence of early
ARMD were defined by masked grading of dilated fundus photographs using the
Wisconsin Age-Related Maculopathy Grading System. RESULTS: Older adults in normal
retinal health exhibited slower dark adaptation as compared with young adults. No
difference in the rate of dark adaptation was found between early ARMD patients
and older adults in normal retinal health. CONCLUSIONS: Although the SST-1
differentiated between young and older adults, it failed to detect dark
adaptation abnormalities in early ARMD when referenced against older adults in
normal retinal health. This may be attributable to the full-field stimulation
used by the SST-1, which may be better suited for characterizing retinal
degenerations affecting large retinal areas than for focal macular diseases like 
ARMD.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16792744 [PubMed - indexed for MEDLINE]

1414: J Biol Chem. 2006 Aug 25;281(34):24713-20. Epub 2006 Jun 20.

His-384 allotypic variant of factor H associated with age-related macular
degeneration has different heparin binding properties from the
non-disease-associated form.

Clark SJ, Higman VA, Mulloy B, Perkins SJ, Lea SM, Sim RB, Day AJ.

Medical Research Council (MRC) Immunochemistry Unit and Laboratory of Molecular
Biophysics, Department of Biochemistry, University of Oxford, South Parks Road,
Oxford, United Kingdom.

A polymorphism in complement factor H has recently been associated with
age-related macular degeneration (AMD), the leading cause of blindness in the
elderly. A histidine rather than a tyrosine at residue position 384 in the mature
protein increases the risk of AMD. Here, using a recombinant construct, we show
that amino acid 384 is adjacent to a heparin-binding site in CCP7 of factor H and
demonstrate that the allotypic variants differentially recognize heparin. This
functional alteration may affect binding of factor H to polyanionic patterns on
host surfaces, potentially influencing complement activation, immune complex
clearance, and inflammation in the macula of AMD patients.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16787919 [PubMed - indexed for MEDLINE]

1415: Expert Opin Investig Drugs. 2006 Jul;15(7):779-93.

Promising new treatments for neovascular age-related macular degeneration.

Michels S, Schmidt-Erfurth U, Rosenfeld PJ.

Klinik für Augenheilkunde und Optometrie, Medizinische Universität Wien,
Währinger Gürtel 18-20, Allgemeines Krankenhaus 8i, 1090 Wien/Vienna, Austria.
stephan.michels@meduniwien.ac.at

Angiogenesis, the growth of new blood vessels from existing blood vessels, is
responsible for vision loss in a variety of ophthalmic diseases. In neovascular
age-related macular degeneration (AMD), the leading cause for legal blindness in 
many industrialised countries, abnormal blood vessels grow in the macula and
cause blindness. There are a number of factors important in the angiogenic
cascade but VEGF-A has been implicated in recent years as the major factor
responsible for neovascular and exudative diseases of the eye. Numerous
antiangiogenic drugs are in development but anti-VEGF drugs have shown great
promise in treating neovascular AMD and other ocular diseases, and many of these 
drugs have been adopted from oncology where antiangiogenic therapy is gaining
wide acceptance. For the first time in neovascular AMD, anti-VEGF drugs have
brought the hope of vision improvement to a significant proportion of patients.
This review provides an overview on angiogenic mechanisms, potential
antiangiogenic treatment strategies and different antiangiogenic drugs with
special focus on neovascular AMD.

Publication Types: 
    Review

PMID: 16787141 [PubMed - indexed for MEDLINE]

1416: Int Ophthalmol. 2005 Feb-Apr;26(1-2):3-8. Epub 2006 Jun 19.

Visual acuity comparison of vitrectomy with and without internal limiting
membrane removal in the treatment of diabetic macular edema.

Bahadir M, Ertan A, Mertoğlu O.

Kudret Eye Hospital, Kennedy Caddesi 71, 06660, Kavaklidere, Ankara, Turkey.

PURPOSE: To evaluate whether internal limiting membrane (ILM) peeling during
vitrectomy affects vision outcome in patients with diabetic macular edema.
MATERIAL AND METHOD: Fifty-eight eyes of 49 patients were included in the study. 
Patients with persistent diffuse clinically significant macular edema were
divided into two groups according to the surgical method used. Group I subjects
(15 patients; mean age 56.60+/-8.50 years; 17 eyes total) underwent vitrectomy
with ILM peeling. Group II subjects (34 patients; mean age 57.52+/-11.54 years;
41 eyes total) underwent vitrectomy without ILM peeling. The data recorded for
each case were type and duration of diabetes, insulin treatment (yes/no),
presence of arterial hypertension, stage of diabetic retinopathy, lens status,
history of macular laser treatment, and detection of posterior vitreous
detachment during surgery. Visual acuity was measured preoperatively and 1 year
postoperatively in decimal notation, and values were converted to logarithm of
minimal-angle-of-resolution (logMAR) scores. Mean pre- and postoperative visual
acuity were compared within each group, and the mean change in visual acuity in
Group I was compared to that in Group II. RESULTS: There were no significant
differences between the groups with respect to age; sex distribution; diabetes
type; duration of diabetes; numbers of patients on insulin treatment; frequencies
of hypertension, proliferative diabetic retinopathy, previous macular laser
treatment; or frequency of intraoperatively confirmed posterior vitreous
detachment (chi-square, P>0.05 for all). Comparison of pre- and post-operative
visual acuity revealed significant improvement in both Group I (1.15+/-0.307 vs. 
0.764+/-0.355 logMAR, respectively; Wilcoxon rank test, P<0.01) and Group II
(1.22+/-0.516 vs. 0.829+/-0.436 logMAR, respectively; Wilcoxon rank test,
P<0.001). The change in visual acuity for Group I was not significantly different
from that observed in Group II (0.391+/-0.335 vs. 0.393+/-0.273 logMAR,
respectively; Mann-Whitney U test, P>0.05). CONCLUSION: The visual acuity
outcomes in the study indicate that vitrectomy without ILM peeling is just as
effective as vitrectomy with ILM peeling in the treatment of diabetic macular
edema. Both techniques led to significant and similar degrees of improvement in
visual acuity.

Publication Types: 
    Randomized Controlled Trial

PMID: 16786177 [PubMed - indexed for MEDLINE]

1417: Int Ophthalmol. 2005 Feb-Apr;26(1-2):27-34. Epub 2006 Jun 16.

Effects of intravitreal triamcinolone injection on macular edema and visual
prognosis in central retinal vein occlusion.

Ozdek SC, Aydin B, Gürelik G, Bahçeci U, Hasanreisoğlu B.

Ophthalmology Department, Gazi University, School of Medicine, Huzur Mahallesi
2.Cadde 164/14, 06460, Dikmen, Ankara, Turkey.

AIM: To determine the effect of intravitreal triamcinolone injection on macular
edema and the visual prognosis in cases with CRVO. METHODS: Eyes with CRVO were
classified as ischemic or nonischemic according to extend of retinal capillary
nonperfusion. The patients received intravitreal triamcinolone acetonide
injection (4 mg/0.1 ml). A complete ophthalmologic evaluation together with
flourescein angiography (FA) and optical coherence tomography (OCT) were
performed for each patient at presentation and at follow-up visits. The
functional and anatomical results of both groups were assessed separately.
RESULTS: A total of 22 eyes (11 ischemic, 11 nonischemic) were included in the
study. Mean duration of symptoms before steroid injection was 4.9+/-5.5 months.
Mean follow-up time was 11.5+/-2.4. All the eyes completed at least 9 months of
examination. At least 3 lines of visual acuity increase using snellen visual
acuity chart was observed in 81.8% of the eyes in nonischemic group, while only
in 18.2% of the eyes in the ischemic group. In ischemic group, the mean foveal
thickness was 766+/-320.7 microm at presentation, which significantly decreased
to 441.7+/-166.9 microm at 9th month. In nonischemic group, the mean foveal
thickness was 667+/-223 microm at presentation, which significantly decreased to 
320+/-175.5 at 9th month. Significant IOP elevation was observed in 8 (36.4%) of 
the eyes, 75% of which could be controlled with medical treatment. CONCLUSION:
Intravitreal triamcinolone injection may be a promising and effective method for 
the treatment of macular edema associated with CRVO. Although anatomical results 
are similar in both groups, functional results are better in non-ischemic CRVO
cases.

Publication Types: 
    Comparative Study

PMID: 16783483 [PubMed - indexed for MEDLINE]

1418: Int Ophthalmol. 2005 Feb-Apr;26(1-2):21-6. Epub 2006 Jun 15.

Vitrectomy seems to be beneficial for advanced diffuse diabetic macular oedema
not responding to laser treatment.

Lövestam-Adrian M, Larsson J.

Department of Ophthalmology, University of Lund, S 221 85, Lund, Sweden.
monica.lovestam_adrian@oft.lu.se

BACKGROUND: To evaluate the surgical efficacy of vitrectomy, with optical
coherence tomography, in patients with non-ischemic and ischemic diffuse diabetic
macular oedema not responding to laser treatment. METHODS: Ten eyes from nine
patients (aged 46.0 +/- 20 years, diabetes duration 12.4 +/- 4 years) operated
with vitrectomy for diabetic macular oedema not responding to laser treatment
were evaluated before and 6 months postoperatively. Retinal thickness was
assessed with optical coherence tomography, OCT, measuring the mean values of the
centre of fovea and the second and third concentric rings from foveola. Four
patients with type 1 diabetes had ischemic and five patients (6 eyes) with type 2
diabetes had non-ischemic diffuse macular oedema diagnosed on fluorescein
angiography (FA). All eyes had an attached vitreous diagnosed on OCT. RESULTS:
Mean foveal thickness for the three concentric rings from centre and out was
significantly less 6 months postoperatively 437 +/- 125 vs. 286 +/- 67 microm; p 
= 0.027, 426 +/- 105 vs. 308 +/- 35 microm; p = 0.019 and 404 +/- 69 microm vs.
318 +/- 29 microm; p = 0.011 respectively. The decrease in foveal thickness was
similar for eyes with and without signs of ischemic maculopathy. There was a
trend toward improved visual acuity (VA) 6 months after surgery 0.4; range
0.2-0.6 compared to 0.3; range 0.1-0.5 before vitrectomy; p = 0.107). CONCLUSION:
Vitrectomy seems to be a beneficial treatment for both ischemic and non-ischemic 
advanced diffuse diabetic macular oedema not responding to laser treatment.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 16779572 [PubMed - indexed for MEDLINE]

1419: J Br Menopause Soc. 2006 Jun;12(2):64-70.

Age-related macular degeneration.

Arden GB.

Henry Wellcome Research Laboratories, Applied Vision Research Centre, Department 
of Optometry and Visual Science, City University, Northampton Square, London, UK.
g.arden@city.ac.uk

Age-related macular degeneration is a common cause of blindness. Its incidence is
increasing, partly due to the advancing age of the population in North America
and Europe, but there is no doubt that the age-adjusted rates are also
increasing, which points to some environmental influence. The condition is
characterized by the appearance of retinal deposits called drusen. These and
other changes form a barrier between the retinal pigment epithelium and the
choroidal circulation. As a result, new vessels may grow from the choroid and
penetrate the retina. These new vessels are delicate and can leak or bleed. Such 
episodes occur in the "wet" form of age-related macular degeneration and cause
the well known disciform degeneration, which in turn leads to distortion of the
image and rapid loss of vision. Even when this does not happen, areas of retina
may atrophy, probably due to anoxia: this is the "dry" form of the disease, also 
called geographic atrophy. In trials, scattered laser burns have been applied to 
the retina but the long-term benefits of this are as yet uncertain. New
micro-pulse lasers are coming into use which may be more effective. Surgical
treatments include translocation of the retina and photodynamic therapy. Medical 
therapies attracting attention are intraocular injections of anti-angiogenic
drugs, such as ranibizumab. These need further evaluation, as does the role of
diet. Within a few years blindness due to age-related macular degeneration may be
reduced by combining dietary control, screening for visual loss, and medical and 
surgical methods of treatment.

Publication Types: 
    Review

PMID: 16776857 [PubMed - indexed for MEDLINE]

1420: Br J Ophthalmol. 2006 Sep;90(9):1152-6. Epub 2006 Jun 14.

Phase I clinical trial results of verteporfin enhanced feeder vessel therapy in
subfoveal choroidal neovascularisation in age related macular degeneration.

Kozak I, Cheng L, Cochran DE, Freeman WR.

Jacobs Retina Center, University of California San Diego, La Jolla, CA 92037,
USA. ikozak@eyecenter.ucsd.edu

AIMS: To investigate the safety and effectiveness of extrafoveal photodynamic
therapy (PDT) occlusion of feeder vessels (FVs) in patients with subfoveal
choroidal neovascularisation (CNV) as a result of age related macular
degeneration. METHODS: FVs were identified using dynamic fluorescein and
indocyanine green angiography with scanning laser ophthalmoscope. The standard
doses of verteporfin and laser wavelength were used. The light dose was escalated
by increasing the duration of the light dose so the light regimen was 50 J/cm2
for patients 1 and 2; 100 J/cm2 for patients 3, 4, 5; 125 J/cm2 for patients 6
and 7; and 150 J/cm2 for patients 8 and 9. Patients were examined at weeks 1, 4, 
and 12. RESULTS: The mean improvement on EDTRS chart 3 months after treatment was
an increase of 2.1 lines (p = 0.07). Closure of the FV was achieved
angiographically in three eyes at various light doses, in three eyes the FV was
hypoperfused, and in three eyes the vessels were were neither closed nor
hypoperfused. At the last follow up all FVs were reperfused. There was no
evidence of retinal damage. CONCLUSION: Verteporfin enhanced FV therapy does not 
cause subfoveal retinal damage and may have potential to improve central vision
in subfoveal CNV caused by exudative macular degeneration. It is not recommended 
as a monotherapy for CNV.

Publication Types: 
    Clinical Trial, Phase I

PMID: 16774958 [PubMed - indexed for MEDLINE]

1421: Br J Ophthalmol. 2006 Sep;90(9):1087-90. Epub 2006 Jun 14.

Comment in:
    Br J Ophthalmol. 2006 Sep;90(9):1073-4.

Associated factors for age related maculopathy in the adult population in China: 
the Beijing eye study.

Xu L, Li Y, Zheng Y, Jonas JB.

Beijing Institute of Opthalmology, Beijing Tongren Hospital and Capital
University of Medical Science, Beijing, China.

BACKGROUND: To evaluate factors associated with the prevalence of age related
maculopathy (ARM) in the adult Chinese population. METHODS: The Beijing Eye
Study, a population based prevalence study, included 4439 out of 5324 subjects
from a rural area and an urban region of greater Beijing, aged 40+ years and
invited to participate (response rate 83.4%). Fundus photographs were graded
using the Wisconsin Age-Related Maculopathy Grading system. The following
parameters were graded: drusen size, drusen type, and the area covered by drusen;
pigmentary abnormalities; geographic atrophy; and exudative ARM. RESULTS: Fundus 
photographs were available for 8655 eyes of 4376 (98.6%) subjects. Early age
related macular degeneration (ARD), late ARD, and exudative ARD, respectively,
were present in 1.4%, 0.20%, and 0.10% of the subjects. In a binary logistic
regression analysis, early ARM was statistically associated with age (p<0.001;
95% CI: 1.04 to 1.08), hyperopic refractive error (p = 0.008; 95% CI: 1.04 to
1.28), rural region (p<0.001; 95% CI: 0.17 to 0.49), and lower level of education
(p = 0.01; 95% CI: 1.07 to 1.65). Early ARM was not significantly associated with
the optic disc size (p = 0.42), and size of beta zone of peripapillary atrophy (p
= 0.28), the self reported diagnosis of diabetes mellitus (p = 0.39; OR: 1.37;
95% CI: 0.66 to 2.85), amount of cortical cataract (p = 0.72), subcapsular
cataract (p = 0.98), nuclear cataract (p = 0.26), sex (p = 0.23), cataract
surgery (p = 1.0; OR: 0.96; 95% CI: 0.13 to 6.95), glaucomatous optic nerve
damage (p = 0.77; OR: 0.62; 95% CI: 0.15 to 2.52), and history of smoking (p =
0.66; OR: 1.14; 95% CI: 0.65 to 2.00). CONCLUSIONS: Hyperopic refractive error
besides age was the single most important risk factor for ARM in adult Chinese.
Other associated factors were rural region and lower level of education.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16774957 [PubMed - indexed for MEDLINE]

1422: Br J Ophthalmol. 2006 Sep;90(9):1142-5. Epub 2006 Jun 14.

Comment in:
    Br J Ophthalmol. 2006 Sep;90(9):1080-1.

Polymorphism p.402Y>H in the complement factor H protein is a risk factor for age
related macular degeneration in an Italian population.

Simonelli F, Frisso G, Testa F, di Fiore R, Vitale DF, Manitto MP, Brancato R,
Rinaldi E, Sacchetti L.

Dipartimento di Oftalmologia, Second University of Naples, Italy.

AIMS: To evaluate the complement factor H (CFH) p.402Y>H polymorphism as a risk
factor in age related macular degeneration (AMD) in an Italian population.
METHODS: 104 unrelated Italian AMD patients and 131 unrelated controls were
screened for the CFH polymorphism p.402Y>H (c.1277 T>C), which has been
associated with AMD. Retinography was obtained for patients and controls; the AMD
diagnosis was confirmed by fluorescein angiograms. The c.1277 T>C polymorphism
was genotyped with the TaqMan real time polymerase chain reaction single
nucleotide polymorphism assay. RESULTS: The frequency of c.1277C allele was
higher in AMD patients than in controls (57.2% v 39.3%; p<0.001). The odds ratio 
(OR; logistic regression analysis) for AMD was 3.9 (95% confidence interval (CI):
1.9 to 8.2) for CC homozygotes. The CC genotype conferred a higher risk for
sporadic (OR 4.6; CI: 2.0 to 10.5) than for familial AMD (OR 2.9; CI: 1.0 to
8.4). Genotypes were not related to either age at AMD diagnosis or to AMD
phenotype. However, geographic atrophy and choroidal neovascularisation were more
frequent in sporadic than in familial AMD (p = 0.027). Overall, the percentage of
population attributable risk for the CC genotype was 28% (95% CI:18% to 33%).
CONCLUSION: The association between the p.402Y>H (c.1277T>C) polymorphism and AMD
applies to the Italian population and the CC genotype is more frequent in
sporadic than in familial AMD cases.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16774956 [PubMed - indexed for MEDLINE]

1423: Retina. 2006 May-Jun;26(5):562-70.

Diabetic macular edema associated with glitazone use.

Ryan EH Jr, Han DP, Ramsay RC, Cantrill HL, Bennett SR, Dev S, Williams DF.

VitreoRetinal Surgery, PA, Minneapolis, Minnesota, USA.

PURPOSE: To describe diabetic macular edema (DME) in patients who developed fluid
retention as a consequence of glitazone use. METHODS: A chart review identified
30 patients who used pioglitazone or rosiglitazone and had both lower extremity
edema and macular edema. Clinical reports, photographs, and fluorescein
angiograms were reviewed. Patients followed for >3 months were analyzed
separately. RESULTS: Seventeen patients took oral pioglitazone, 11 took
rosiglitazone, and 2 took both drugs at different times. Eleven patients were
observed for >3 months after cessation of glitazones. Mean weight gain during
drug administration in this group was 30 lb, and mean weight loss after drug
discontinuation was 19 lb. Rapid reduction in macular edema off drug occurred in 
only 4 of 11 patients, but 8 of 11 had reduced edema over 2 years. Mean visual
acuity in this group at the initial visit was 20/60, and at the final visit, it
was 20/85. Four eyes of three patients had resolution of diffuse macular edema
with improved vision after cessation of glitazones without laser treatment.
CONCLUSIONS: Fluid retention occurs in 5% to 15% of patients taking glitazones.
In some of these patients, glitazone use appears to be a cause of macular edema, 
and drug cessation appears to result in rapid resolution of both peripheral and
macular edema. Fluid retention associated with glitazone use should be considered
when assessing treatment options for patients with DME, especially those with
concomitant peripheral edema.

PMID: 16770264 [PubMed - indexed for MEDLINE]

1424: Retina. 2006 May-Jun;26(5):495-511.

Short-term safety and efficacy of intravitreal bevacizumab (Avastin) for
neovascular age-related macular degeneration.

Rich RM, Rosenfeld PJ, Puliafito CA, Dubovy SR, Davis JL, Flynn HW Jr, Gonzalez
S, Feuer WJ, Lin RC, Lalwani GA, Nguyen JK, Kumar G.

Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami
School of Medicine, FL 33136, USA.

PURPOSE: To evaluate the safety and efficacy of intravitreal bevacizumab
(Avastin, Genentech Inc.) for the treatment of neovascular age-related macular
degeneration (ARMD). METHODS: A retrospective review was performed on consented
patients with neovascular ARMD receiving intravitreal bevacizumab therapy. All
patients received intravitreal bevacizumab at baseline with additional monthly
injections given at the discretion of the treating physician. At each visit, a
routine Snellen visual acuity assessment was performed followed by an ophthalmic 
examination and optical coherence tomography (OCT) imaging. RESULTS: Fifty-three 
eyes of 50 patients received an intravitreal bevacizumab injection between May
and August 2005. Including the month 3 visit, the average number of injections
was 2.3 out of a maximum of 4 injections. No serious drug-related ocular or
systemic adverse events were identified. Improvements in visual acuity and
central retinal thickness measurements were evident by week 1 and continued
through month 3. At month 3, the mean visual acuity improved from 20/160 to
20/125 (P < 0.001) and the mean central retinal thickness decreased by 99.6
microm (P < 0.001). CONCLUSION: Off-label intravitreal bevacizumab therapy for
neovascular ARMD was well tolerated over 3 months with improvements in visual
acuity and OCT central retinal thickness measurements. While the long-term safety
and efficacy of intravitreal bevacizumab remain unknown, these short-term results
suggest that intravitreal bevacizumab may be the most cost effective therapy for 
the treatment of neovascular ARMD.

Publication Types: 
    Case Reports

PMID: 16770255 [PubMed - indexed for MEDLINE]

1425: Indian J Ophthalmol. 2006 Jun;54(2):133-7.

Comment in:
    Indian J Ophthalmol. 2006 Dec;54(4):290; author reply 290-1.

Intravitreal injection of triamcinolone acetonide for diabetic macular edema:
principles and practice.

Vedantham V, Kim R.

Retina - Vitreous Service, Aravind Eye Hospital and Postgraduate Institute of
Ophthalmology, Madurai, Tamilnadu, India. drvasumathy@yahoo.com

Diabetic retinopathy is fast emerging as a leading cause of newly diagnosed legal
blindness amongst the working population. Macular edema, as it is commoner,
accounts for more vision impairment than neovascular proliferation in diabetic
patients. Laser photocoagulation, which is the standard treatment of macular
edema, is associated with significant complications and an improvement in visual 
acuity is unsatisfactory. Intravitreal injection of corticosteroids (especially
triamcinolone acetonide) is an emerging treatment modality in the management of
diabetic macular edema. This article presents an overview of the principles,
technique and complications associated with this procedure.

Publication Types: 
    Review

PMID: 16770036 [PubMed - indexed for MEDLINE]

1426: Arch Ophthalmol. 2006 Jun;124(6):887-9.

Novel de novo mutation in a patient with Best macular dystrophy.

Apushkin MA, Fishman GA, Taylor CM, Stone EM.

Department of Ophthalmology and Visual Science, University of Illinois at
Chicago, USA.

OBJECTIVE: To report a novel de novo vitelliform macular dystrophy (VMD2)
mutation in a patient with Best macular dystrophy. METHODS: Best-corrected visual
acuity, dilated fundus examination, and electro-oculography were performed in a
patient with Best macular dystrophy and his parents. Both the patient and his
parents also had blood samples drawn, and their DNA was analyzed by direct
genomic sequencing. RESULTS: A heterozygous VMD2 gene missense mutation in exon 2
(Thr6Ala [ACA>GCA]) was identified in the proband. This mutation was not present 
in his clinically unaffected parents. CONCLUSIONS: A novel de novo mutation in
the VMD2 gene was found in a patient whose phenotype and electro-oculographic
findings were characteristic of Best macular dystrophy, whereas both parents were
phenotypically and genetically unaffected. The findings in this family document
that a de novo mutation needs to be considered when an isolated family member is 
found to have a Best disease phenotype.

Publication Types: 
    Case Reports
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16769844 [PubMed - indexed for MEDLINE]

1427: Arch Ophthalmol. 2006 Jun;124(6):807-12.

Lesion morphology in age-related macular degeneration and its therapeutic
significance.

Beaumont PE, Kang HK.

Eye and Vision Research Institute, Sydney, New South Wales, Australia.

OBJECTIVES: To quantify and categorize the lesions of neovascular age-related
macular degeneration on the basis of fluorescein angiographic morphology.
METHODS: We retrospectively reviewed 3580 consecutive cases of neovascular
age-related macular degeneration. The lesions were graded in terms of the
location, size, and composition and categorized according to the lesion
components. RESULTS: A comprehensive schema for lesion description and
categorization is presented. There were 2642 subfoveal (73.8%), 658 juxtafoveal
(18.4%), and 276 extrafoveal (7.7%) lesions. After disciform lesions were
excluded, 1337 subfoveal (72.3%), 580 juxtafoveal (88.1%), and 242 extrafoveal
lesions (87.7%) consisted of at least 50% choroidal neovascularization, most of
which included a classic or an occult component but not both. Subfoveal lesions
(mean size, 2.82 Macular Photocoagulation Study disc areas) were significantly
larger than juxtafoveal (mean size, 0.89 Macular Photocoagulation Study disc
areas) or extrafoveal lesions (mean size, 1.04 Macular Photocoagulation Study
disc areas) (Kruskal-Wallis, P<.001), but overall the lesions were substantially 
smaller than those found in the major trials. It is estimated that photodynamic
therapy or photocoagulation may be offered to one half to two thirds of all
patients with nondisciform neovascular age-related macular degeneration.
CONCLUSION: The smaller lesion size and low proportion of mixed choroidal
neovascularization lesions suggest that treatment benefit and eligibility may be 
greater in the clinical setting than previously thought.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16769834 [PubMed - indexed for MEDLINE]

1428: Curr Eye Res. 2006 Jun;31(6):535-47.

An extension of the Early Treatment Diabetic Retinopathy Study (ETDRS) system for
grading of diabetic macular edema in the Astemizole Retinopathy Trial.

Gardner TW, Sander B, Larsen ML, Kunselman A, Tenhave T, Lund-Andersen H, Reimers
J, Hubbard L, Blankenship GW, Quillen DA, Brod RD, Wilmarth MH, Post-Hansen H,
Parving HH, Davis MD.

Department of Ophthalmology, Penn State College of Medicine, Hershey, PA 17033,
USA. tgardner@psu.edu

PURPOSE: To compare the effects of astemizole, an antihistamine, versus placebo
on the 1-year course of diabetic macular edema (DME) and to illustrate use of a
modified ETDRS system for grading areas of retinal thickening and hard exudates
that may be useful in clinical trials of treatments for this disorder. METHODS:
Between June 1994 and September 1997, at 2 clinics, 63 patients who had, in at
least one eye (the study eye), DME that had not previously been treated with
macular photocoagulation, and for which photocoagulation was not currently
recommended by the investigator, were enrolled and randomly assigned to
astemizole or placebo. Fifty-four of the 63 patients (86%, 26 in Clinic 1 and 28 
in Clinic 2) completed 1 year of followup and had adequate 7-field stereoscopic
film-based color fundus photographs of the study eye at the baseline and 1-year
visits. DME was > 0.33 disc diameters (DD) from the center of the macula in 48%
of study eyes and involved the center in 13%. Photographs were graded using the
ETDRS protocol modified to allow estimates of areas of retinal thickening (RT)
and hard exudate (HE) to be made on continuous scales in disc area (DA) units.
Principal outcome measures were mean change in the square root of RT area (the
average diameter of the area in DD), mean change in area of HE, and change in the
degree to which RT involved or threatened the center of the macula. Results: At
baseline, RT area in the 54 study eyes ranged from 0.09 to 4.0 DA (median 1.1).
At the 1-year visit the square root of RT area (RTdd) had decreased by > or= 0.3 
DD in 10 eyes, increased by >or = 0.3 DD in 19 and was about the same in 25. Mean
change at 1 year was +0.09 DD (SD 0.57) for astemizole versus +0.19 DD (SD 0.48) 
for placebo, for a difference of -0.10 DD (95% CI -0.38, +0.19; p = 0.51).
Adjustments for baseline and time-dependent risk factors did not change this
result appreciably, although there was a trend towards a difference in favor of
astemizole in the subgroup of patients with more severe retinopathy. Other
morphologic outcomes paralleled change in RTdd. Change in RTdd did vary by
clinic: -0.03 DD in Clinic 2, versus + 0.32 DD in Clinic 1, for a difference of
-0.35 DD (95% CI -0.62, -0.07; p = 0.014). Clinic 1 is a tertiary retinal
referral center in Pennsylvania and Clinic 2 a retinal clinic closely affiliated 
with a large diabetes clinic in Copenhagen. The unexpected clinic difference in
outcome provided an opportunity for further analyses using the modified ETDRS
system. In comparison to Clinic 1, Clinic 2 patients were more often male, were
younger at diagnosis of diabetes, and had less severe retinopathy and better
visual acuity, but these differences did not appear to explain the trend for
lesser increase in RTdd. CONCLUSION: No effect of astemizole was found, but the
confidence interval for the principal outcome, mean change in RTdd, included both
a modest beneficial effect and a small harmful effect. This outcome measure did
demonstrate a small difference in outcome by clinic, which could not be explained
by baseline characteristics but may reflect differences in access to and/or
continuity of care or other unmeasured differences associated with different
referral patterns. Although optical coherence tomography may supplant photography
as a measure of central RT, photographic assessments of change in RT and HE areas
analyzed with the methods described herein may be useful outcomes in trials
assessing treatment of early stages of DME. Application of these methods to other
data sets is needed to confirm this conclusion.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16769613 [PubMed - indexed for MEDLINE]

1429: Jpn J Ophthalmol. 2006 May-Jun;50(3):235-8.

Risk factors for elevated intraocular pressure after trans-tenon retrobulbar
injections of triamcinolone.

Hirooka K, Shiraga F, Tanaka S, Baba T, Mandai H.

Department of Ophthalmology, Kagawa University Faculty of Medicine, Miki, Kagawa,
Japan. kazuyk@med.kagawa-u.ac.jp

PURPOSE: To determine the risk factors that induce an elevation of intraocular
pressure (IOP) after trans-Tenon retrobulbar injections of triamcinolone
acetonide. METHODS: We retrospectively reviewed the medical records of 49
consecutive patients (49 eyes) with choroidal neovascularization or diffuse
diabetic macular edema who had received one trans-Tenon retrobulbar injection of 
triamcinolone acetonide (20 mg) between June 2003 and September 2004, while being
treated at Kagawa University Hospital or Okayama Saiseikai General Hospital.
Diabetes mellitus had been diagnosed in ten of the patients. Steroid responders
were defined as having a relative increase in intraocular pressure (IOP) of >6
mmHg and an absolute IOP >20 mmHg with an anatomically open anterior chamber
angle. The mean follow-up time was 4.2 +/- 0.2 months (range, 3-6 months).
RESULTS: Nine patients were responders and 40 patients were nonresponders. The
elevation of the IOP occurred 1 to 4 weeks after the injection. The only
preoperative predictive factor for the steroid responders was the presence of
diabetes mellitus (multiple logistic regression analysis, odds ratio = 32.78, P =
0.006). After topical glaucoma medication, the IOP returned to acceptable levels 
in all responders. CONCLUSIONS: Our results suggest an association between
diabetes mellitus and elevated IOP after a trans-Tenon retrobulbar triamcinolone 
acetonide injection.

Publication Types: 
    Comparative Study

PMID: 16767378 [PubMed - indexed for MEDLINE]

1430: Can J Ophthalmol. 2006 Apr;41(2):197-200.

Optical coherence tomography findings in niacin maculopathy.

Dajani HM, Lauer AK.

The School of Medicine, Oregon Health & Science University, and the Devers Eye
Institute, Legacy Hospitals, Portland, OR 97239-4197, USA.

CASE REPORT: We present the case of 54-year-old male who developed bilateral
cystoid macular thickening while taking 3 g of niacin per day, and we describe
the optical coherence tomography (OCT) features of niacin (nicotinic acid)
maculopathy. COMMENTS: Cystoid spaces were seen in both the outer plexiform and
inner nuclear layers of both eyes. The cystoid spaces were largest and central in
the outer plexiform layer, whereas a broader distribution of smaller cysts was
seen in the inner nuclear layer. With cessation of niacin, his vision improved
and the OCT features normalized.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 16767207 [PubMed - indexed for MEDLINE]

1431: Can J Ophthalmol. 2006 Jun;41(3):333-9.

Fixation stability using radial gratings in patients with age-related macular
degeneration.

González EG, Teichman J, Lillakas L, Markowitz SN, Steinbach MJ.

Centre for Vision Research, York University, Toronto, ON, Canada.
gonzalez@yorku.ca

BACKGROUND: The fixation stability of patients with macular atrophy is generally 
worse than that of people without pathology. METHODS: The effects of 2 types of
high-contrast fixation stimuli on fixation stability were compared between
patients with longstanding age-related macular degeneration (AMD) and control
subjects with normal vision. One stimulus was a 9-cycle square-wave radial
grating measuring 5 degrees in diameter and the other a white 0.5 degrees disc. A
video-based infrared eye tracker with remote optics was used to record eye
position while participants fixated the stimuli in primary position of gaze for 6
to 7 s. Fixation stability was measured with a bivariate contour ellipse area
(BCEA). RESULTS: For patients with AMD, fixation stability for the radial grating
was largely independent of visual acuity, whereas fixation stability for the disc
diminished with acuity. For the control observers, there were no differences in
fixation stability for the 2 kinds of stimuli. INTERPRETATION: In clinical and
research settings, radial gratings can be useful targets for fixation for
patients with macular disease since they provide enough visual information to
help maintain fixation stability. These findings have important implications for 
the design of clinical tests and procedures such as perimetry, multifocal
electroretinography, and optical coherence tomography for patients with macular
atrophies.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16767189 [PubMed - indexed for MEDLINE]

1432: Can J Ophthalmol. 2006 Jun;41(3):327-32.

Binocular function in patients with age-related macular degeneration: a review.

Tarita-Nistor L, González EG, Markowitz SN, Steinbach MJ.

Centre for Vision Research, York University, Toronto, ON, Canada.
lumi.tarita-nistor@rogers.com

Normally sighted observers typically benefit from binocular viewing when
monocular sensitivities are equivalent. Age-related macular degeneration (AMD)
not only destroys the foveal vision, however, but it also affects the 2 eyes
unequally, providing grounds for impairment of binocular function. The aim of the
present article is to provide a review of the current research on the effect of
AMD on binocular vision. The main findings to date reveal that a high proportion 
of patients show characteristics of binocular contrast inhibition at low and
medium spatial frequencies. Yet binocular acuity gain is not different from that 
of age-matched control participants without AMD. Additional findings show that
rivalry processes are severely disrupted in patients with AMD. The effects of the
disease on other binocular functions have yet to be explored. Knowledge of
binocular function in AMD may one day help clinicians decide on the most
appropriate management and rehabilitation techniques.

Publication Types: 
    Review

PMID: 16767188 [PubMed - indexed for MEDLINE]

1433: Can J Ophthalmol. 2006 Jun;41(3):322-6.

Identification of preferred retinal loci with the Heidelberg Retina Tomograph II 
in patients with age-related macular degeneration.

Markowitz SN, Eskander E, Markowitz M.

Low Vision Service, University Health Network, Department of Ophthalmology and
Vision Sciences, University of Toronto, Toronto, ON, Canada. snm1@rogers.com

BACKGROUND: To determine the suitability and accuracy of the Heidelberg Retina
Tomograph II (HRT II) scanning laser ophthalmoscope for identification of
preferred retinal loci (PRLs) in patients with age-related macular degeneration
(AMD). METHODS: Fixation location was assessed prospectively in 9 eyes by 3
methods: the HRT II, a retinal camera equipped with a fixation target, and grid
macular perimetry. Two testing protocols were also used: using an HRT protocol
for disc location analysis and an HRT protocol for macular fixation analysis.
RESULTS: Locations of PRLs on retinal quadrants identified by all 3 methods were 
identical in 7 of 9 (78%) cases (McNemar chi(2) test, p = 0.48, kappa = 0.78, at 
95% confidence interval) with both testing protocols. Eccentric location
coordinates for PRLs were not significantly different by testing modality when
using either the disc location protocol (R = 0.47, p = 0.20 [t7 = 1.4], y = 0.29x
+ 3.29) or the macular fixation protocol (R = 0.44, p = 0.23 [t7 = 1.3], y =
0.31x + 3.23). INTERPRETATION: Eccentric locations of the optic disc on recorded 
video frames with the HRT II correspond to eccentric locations of PRLs in
patients with AMD.

PMID: 16767187 [PubMed - indexed for MEDLINE]

1434: Can J Ophthalmol. 2006 Jun;41(3):313-8.

Image relocation with prisms in patients with age-related macular degeneration.

Al-Karmi R, Markowitz SN.

Low Vision Service, University Health Network, Department of Ophthalmology and
Vision Sciences, University of Toronto, Toronto, ON, Canada.

BACKGROUND: To determine the benefits of image relocation (IR) with prisms in
patients with age-related macular degeneration (AMD). METHODS: This was a
retrospective comparative interventional case series of 100 patients with AMD and
5 years of available follow-up records. Participants underwent complete low
vision (LV) assessments, including identification of preferred retinal locus
(PRL). Prisms were added to prescription glasses to produce IR to the presumed
PRL. Main outcome measures were best-corrected visual acuity (BCVA), location of 
the PRL preferred by the patient for rehabilitation, use of glasses prescribed,
and number of prism diopters prescribed. RESULTS: Patients wearing prescribed
glasses for distance with prisms for IR showed improved BCVA (t(63) = 9.5, p =
0.001) as did those patients wearing prescribed glasses for distance without
prisms for IR (t(14) = 2.25, p = 0.04). Patients wearing prescribed glasses for
distance with prisms for IR achieved better BCVA than those patients wearing
prescribed glasses for distance without prisms for IR (t(77) = 2.0, p = 0.05).
Patients reported using distance glasses with prisms for 3 to 48 months (mean
[SD], 8.4 [11.7] mo). Number of prism diopters used (mean [SD], 5.8 [1.9] D) was 
well tolerated by all patients. PRL preferred by patients was on the upper retina
in 98.5% of cases. INTERPRETATION: IR with prisms to PRL in patients with AMD
results in a significant and sizable improvement in BCVA. This effect is probably
created by facilitation of oculomotor functions resulting from direct reduction
of fixation instability.

Publication Types: 
    Comparative Study

PMID: 16767185 [PubMed - indexed for MEDLINE]

1435: Genome. 2006 May;49(5):505-10.

Mutant alpha-synuclein-induced degeneration is reduced by parkin in a fly model
of Parkinson's disease.

Haywood AF, Staveley BE.

Department of Biology, Memorical University of Newfoundland, St. John's, Canada.

Parkinson's disease (PD) patients show a characteristic loss of motor control
caused by the degeneration of dopaminergic neurons. Mutations in the genes that
encode alpha-synuclein and parkin have been linked to inherited forms of this
disease. The parkin protein functions as a ubiquitin ligase that targets proteins
for degradation. Expression of isoforms of human alpha-synuclein in the
Drosophila melanogaster nervous system forms the basis of an excellent genetic
model that recapitulates phenotypic and behavioural features of PD. Using this
model, we analysed the effect of parkin co-expression on the climbing ability of 
aging flies, their life span, and their retinal degeneration. We have determined 
that co-expression of parkin can suppress phenotypes caused by expression of
mutant alpha-synuclein. In the developing eye, parkin reduces retinal
degeneration. When co-expressed in the dopaminergic neurons, the ability to climb
is extended over time. If conserved in humans, we suggest that upregulation of
parkin may prove a method of suppression for PD induced by mutant forms of
alpha-synuclein.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 16767175 [PubMed - indexed for MEDLINE]

1436: Indian J Dermatol Venereol Leprol. 2006 May-Jun;72(3):227-30.

Macular degeneration in a case of Reiter's disease.

Sawhney MP, Parihar JK.

Department of Dermatology and STD, Base Hospital, Barrackpore, India.
mpssawhney@hotmail.com

Posterior uveitis is not a documented feature of Reiter's disease. We describe
here a patient of Reiter's disease, who after a bout of dysentery in January 2002
developed macular edema of the right eye with visual acuity of 6/36. In December 
2002, she was found to have phlyctenular conjunctivitis. In June 2004, when she
reported with scaly plaques over both palms, repeat ophthalmological examination 
revealed macular degeneration of the right eye. The simultaneous occurrence of
Reiter's disease and macular degeneration in this patient may be fortuitous but
the immunological basis of both diseases suggests a possible association.

Publication Types: 
    Case Reports

PMID: 16766841 [PubMed - indexed for MEDLINE]

1437: J Cataract Refract Surg. 2006 May;32(5):803-11.

Quantification of macular and optic disc hyperfluorescence after
phacoemulsification in diabetes mellitus.

Escaravage GK Jr, Cohen KL, Patel SB, Hartnett ME, Armstrong BD, Janowski CM.

Department of Ophthalmology, University of North Carolina at Chapel Hill, Chapel 
Hill, North Carolina, USA.

PURPOSE: To quantify changes in areas of hyperfluorescence of the macula,
perifovea, and optic disc after phacoemulsification in patients with diabetes
mellitus and evaluate relationships between hyperfluorescence, macular thickness,
diabetic retinopathy (DR), and logMAR best corrected visual acuity (BCVA).
SETTING: Ophthalmology Clinic and Operating Room, Ambulatory Care Center,
University of North Carolina at Chapel Hill, School of Medicine, and the
University of North Carolina Hospitals, Chapel Hill, North Carolina, USA.
METHODS: This prospective case-control study comprised 30 eyes of 24 subjects
with cataracts and diabetes mellitus with different levels of DR. Preoperatively 
and 2 months postoperatively, BCVA was recorded, digital retinal photography and 
fluorescein angiography were performed, macular thickness was measured (optical
coherence tomography), and DR and hyperfluorescence of the optic disc, macula,
and perifovea were quantified. RESULTS: Postoperatively, BCVA improved in
surgical eyes but was unchanged in nonsurgical eyes. Preoperatively, between
eyes, there was no difference in hyperfluorescence. Postoperatively,
hyperfluorescence of the optic disc, macula, and perifovea increased in surgical 
eyes and was unchanged in nonsurgical eyes. Macular thickness increased in
surgical eyes, although DR was unchanged in surgical and nonsurgical eyes.
Although there was no correlation between hyperfluorescence and macular thickness
in surgical eyes, increased hyperfluorescence of the perifovea was associated
with less improvement in BCVA. CONCLUSIONS: After phacoemulsification,
hyperfluorescence and macular thickness increased in the eyes of diabetic
subjects. These short-term changes are more likely an effect of the surgery than 
a worsening of DR.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16765799 [PubMed - indexed for MEDLINE]

1438: Am J Ophthalmol. 2006 Jun;141(6):1165-8.

Histologic correlation of in vivo optical coherence tomography images of the
human retina.

Chen TC, Cense B, Miller JW, Rubin PA, Deschler DG, Gragoudas ES, de Boer JF.

Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, 02114, USA. 
teresa_chen@meei.harvard.edu

PURPOSE: To correlate in vivo human retina optical coherence tomography (OCT)3
images with histology. DESIGN: Case series. METHODS: Linear OCT3 scans through
the macula and optic nerve were obtained in three eyes of three patients who then
underwent exenteration surgery for orbital cancers. OCT3 images were then
correlated with histology. RESULTS: On histology, two eyes were normal, and one
eye had dry macular degeneration. The plexiform layers on histology correlated
with the green/yellow areas on the OCT3 scans, and the nuclear layers correlated 
with the black areas on the OCT3 scans. CONCLUSIONS: The authors are unaware of
previous reports correlating histology to in vivo human retina OCT3 images. Our
findings using human eyes are not different from previous animal studies, in that
the plexiform layers are optically highly backscattering and the nuclear layers
are not.

Publication Types: 
    Case Reports
    Research Support, N.I.H., Extramural

PMID: 16765704 [PubMed - indexed for MEDLINE]

1439: Clin Experiment Ophthalmol. 2006 May-Jun;34(4):312-6.

Use of real-time telemedicine in the detection of diabetic macular oedema: a
pilot study.

Peter J, Piantadosi J, Piantadosi C, Cooper P, Gehling N, Kaufmann C, Goggin M.

Department of Ophthalmology, University of Adelaide, The Queen Elizabeth
Hospital, South Australia, Australia.

PURPOSE: The high prevalence of diabetic retinopathy (21-36%) and 2 yearly
reviews recommended by the National Health and Medical Research Council for
diabetics with no retinopathy creates a considerable burden for review in rural
and regional Australia. Screening for diabetic retinopathy using telemedicine has
significant implications. If effective, such a tool would have an impact on
finance and resource allocation. The purpose of the study was to establish if
telemedicine could distinguish clinically significant macular oedema (CSME) from 
eyes free of this form of disease. METHODS: A study population with
representative examples of normal fundi and the different grades of retinopathy
was chosen from existing records. The specificity and sensitivity of telemedicine
diagnosis was compared with fundus photography and examination by an experienced 
ophthalmologist as a 'gold standard', in a blinded manner. Real-time telemedicine
assessment was performed with live video and audio connections with the
transmitting and receiving units set in different areas of the ophthalmology
department. The transmission end consisted of a video camera mounted on a slit
lamp and the receiving unit consisted of a 21'' LCD monitor. A video conference
link was established using three ISDN lines capable of 128 kb per second transfer
per line allowing for a total of 348 kb per second when utilizing all three lines
for high resolution images. Fundus photographs were taken with a Zeiss FF 450
Plus Digital imaging system. RESULTS: For telemedicine, sensitivity was 38% (95% 
CI, 35-40%) and specificity was 95% (95% CI, 91-99%). For photography,
sensitivity was 75% (95% CI, 71-79%) and specificity was 95% (95% CI, 91-99%).
CONCLUSIONS: In this pilot study, sensitivity of detection of CSME by photography
was considerably better than for live-link telemedicine. This study tends to
confirm the continued superiority of examination of the patient by an experienced
ophthalmologist as the best method of screening for CSME, a sight threatening
form of diabetic retinopathy.

Publication Types: 
    Comparative Study

PMID: 16764649 [PubMed - indexed for MEDLINE]

1440: Clin Experiment Ophthalmol. 2006 May-Jun;34(4):299-304.

Comment in:
    Clin Experiment Ophthalmol. 2006 May-Jun;34(4):295-6.

Use of a cyclo-oxygenase 2 inhibitor for prophylaxis of cystoid macular oedema
following cataract surgery: a randomized placebo-controlled trial.

Riley AF, Wakely LA, Patel HY, Neveldsen B, Purdie GL, Wells AP.

Ophthalmology Unit, Department of Surgery and Anaesthesia, Wellington School of
Medicine, University of Otago, Wellington, New Zealand.

BACKGROUND: To assess the efficacy of Celecoxib, a cyclo-oxygenase 2 (COX-2)
inhibitor, as prophylaxis for cystoid macular oedema after routine cataract
surgery. METHODS: A prospective, randomized, double-blind placebo-controlled
trial of 69 hospital patients undergoing cataract surgery. Celecoxib 200 mg twice
daily or placebo was given immediately after surgery for 14 days. Optical
coherence tomography was used to quantify macular thickness before surgery and on
day 1, week 2 and week 6 after surgery. RESULTS: Sixty-nine patients were
enrolled, of which 33 received placebo and 36 received active drug. Clinically
apparent cystoid macular oedema occurred in four of the treatment group and two
of the placebo group (P = 0.68). No difference in best-corrected visual acuity
was seen at 6 weeks (P = 0.37). Covariate analysis of the results at 2 weeks and 
6 weeks showed a macular thickness of 3% less in the treatment group compared
with placebo (P = 0.050). CONCLUSION: Celecoxib may decrease macular thickening
following routine cataract surgery at 2 and 6 weeks after surgery as measured by 
Stratus OCT III. No difference in best-corrected visual acuity or clinically
apparent cystoid macular oedema was seen. Further investigation of COX-2
inhibitors in a larger prospective randomized trial is required.

Publication Types: 
    Randomized Controlled Trial

PMID: 16764647 [PubMed - indexed for MEDLINE]

1441: Eur J Ophthalmol. 2006 May-Jun;16(3):491-4.

Evolution of retinal pigment epithelium detachment after photodynamic therapy for
choroidal neovascularization in age-related macular degeneration.

Theodossiadis GP, Grigoropoulos VG, Emfietzoglou I, Nikolaidis P, Panagiotidis D,
Vergados I, Theodossiadis PG.

2nd Department of Ophthalmology, Henry Dunant Hospital, Athens, Greece.
george@hellasnet.gr

PURPOSE: To report a case of pigment epithelium detachment (PED) which appeared
after photodynamic therapy (PDT) and was followed up for 50 months. METHODS: Case
report. RESULTS: A 71-year-old woman with occult choroidal neovascular membrane
due to age-related macular degeneration (ARMD) developed PED 48 hours after PDT. 
The patient was studied with fluorescein angiography (FA) and optical coherence
tomography (OCT). Fluorescein angiographic evidence of PED remained essentially
unchanged during the follow-up period of 50 months. Although OCT initially gave
clear evidence of PED, in the last 12 months of follow-up the PED appears to have
resolved. CONCLUSIONS: Photodynamic treatment could be involved in the occurrence
of PED in occult choroidal neovascular membrane due to ARMD. In this particular
case OCT could be considered since it offers useful information in the
pretreatment and the post-treatment follow-up period.

Publication Types: 
    Case Reports

PMID: 16761259 [PubMed - indexed for MEDLINE]

1442: Eur J Ophthalmol. 2006 May-Jun;16(3):426-34.

Triamcinolone and PDT to treat exudative age-related macular degeneration and
submacular hemorrhage.

Ruiz-Moreno JM, Montero JA, Barile S.

Department of Ophthalmology, Miguel Hernandez University School of Medicine,
Alicante and Instituto Oftalmologico de Alicante, Vitreo-Retinal Unit,
Alicante--Spain. jm.ruiz@umh.es

PURPOSE. To evaluate the efficacy of photodynamic therapy (PDT) with verteporfin 
and intravitreal injection of triamcinolone to treat choroidal neovascularization
(CNV) with flat sub-macular hemorrhage in age-related macular degeneration
(ARMD). METHODS. A prospective, consecutive, noncomparative, interventional case 
series study was performed at the Instituto Oftalmologico de Alicante, Spain. Ten
consecutive eyes from 10 patients with flat submacular hemorrhage secondary to
ARMD were treated by PDT followed by intravitreal injection of 19.4+/-2.1 mg/0.1 
mL triamcinolone 5 days later. PDT was repeated if leakage from the CNV appeared 
on fluorescein angiography (FA) at 3 months follow-up intervals. Main outcome
measures were best-corrected visual acuity (BCVA) before and after treatment,
post-treatment FA, results, and complications. RESULTS. Stable or improved BCVA
was achieved in seven eyes at 6 months follow-up. Complete absence of leakage in 
FA was observed in five and in eight eyes at 3 and 6 months follow-up,
respectively. Intraocular pressure rose in seven eyes. CONCLUSIONS. PDT followed 
by intravitreal triamcinolone seems useful to treat CNV with flat submacular
hemorrhage in ARMD. However, further studies with longer follow-up and randomized
controlled trials are necessary to assess its efficacy in the management of this 
difficult clinical problem.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16761245 [PubMed - indexed for MEDLINE]

1443: Proc Natl Acad Sci U S A. 2006 Jun 13;103(24):9256-61. Epub 2006 Jun 5.

Synergic effect of polymorphisms in ERCC6 5' flanking region and complement
factor H on age-related macular degeneration predisposition.

Tuo J, Ning B, Bojanowski CM, Lin ZN, Ross RJ, Reed GF, Shen D, Jiao X, Zhou M,
Chew EY, Kadlubar FF, Chan CC.

Division of Epidemiology and Clinical Research, and Ophthalmic Genetics and
Visual Function Branch, Section on Ophthalmic Molecular Genetics, National Eye
Institute, National Institutes of Health, Bethesda, MD 20892, USA.

This study investigates age-related macular degeneration (AMD) genetic risk
factors through identification of a functional single-nucleotide polymorphism
(SNP) and its disease association. We chose ERCC6 because of its roles in the
aging process, DNA repair, and ocular degeneration from the gene disruption.
Bioinformatics indicated a putative binding-element alteration on the sequence
containing C-6530>G SNP in the 5' flanking region of ERCC6 from Sp1 on the C
allele to SP1, GATA-1, and OCT-1 on the G allele. Electrophoretic mobility shift 
assays displayed distinctive C and G allele-binding patterns to nuclear proteins.
Luciferase expression was higher in the vector construct containing the G allele 
than that containing the C allele. A cohort of 460 advanced AMD cases and 269
age-matched controls was examined along with pathologically diagnosed 57 AMD and 
18 age-matched non-AMD archived cases. ERCC6 C-6530>G was associated with AMD
susceptibility, both independently and through interaction with an SNP (rs380390)
in the complement factor H (CFH) intron reported to be highly associated with
AMD. A disease odds ratio of 23 was conferred by homozygozity for risk alleles at
both ERCC6 and CFH compared with homozygozity for nonrisk alleles. Enhanced ERCC6
expression was observed in lymphocytes from healthy donors bearing ERCC6 C-6530>G
alleles. Intense immunostaining of ERCC6 was also found in AMD eyes from ERCC6
C-6530>G carriers. The strong AMD predisposition conferred by the ERCC6 and CFH
SNPs may result from biological epistasis, because ERCC6 functions in universal
transcription as a component of RNA pol I transcription complex.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16754848 [PubMed - indexed for MEDLINE]

1444: Br J Ophthalmol. 2006 Sep;90(9):1157-62. Epub 2006 Jun 5.

Analysis of retinal flecks in fundus flavimaculatus using optical coherence
tomography.

Querques G, Leveziel N, Benhamou N, Voigt M, Soubrane G, Souied EH.

Department of Ophthalmology, Centre Hospitalier Intercommunal de Creteil, 40
Avenue de Verdun, 94000 Creteil, France.

BACKGROUND/AIM: Retinal flecks are commonly observed in both Stargardt disease
and fundus flavimaculatus (FFM). The aim was to determine the precise
localisation of these flecks within the retinal layers using Stratus optical
coherence tomography (OCT). METHODS: A prospective observational case series. A
complete ophthalmological examination, including autofluorescence, fluorescein
angiography (FA), and Stratus OCT (Carl Zeiss) was performed in 49 eyes of 26
consecutive patients with FFM. Six to 12 Stratus OCT linear scans focused on the 
retinal flecks were performed in each eye. RESULTS: The age at presentation
ranged from 23 years to 71 years and visual acuity ranged from 20/20 to 20/400.
Hyper-reflective deposits classified into two types were observed on Stratus OCT:
type 1 lesions (94% of eyes) presented as dome-shaped deposits located in the
inner part of the retinal pigment epithelium (RPE) layer and type 2 lesions (86% 
of eyes) presented as small linear deposits located at the level of the outer
nuclear layer and clearly separated from the RPE layer. CONCLUSIONS: Stratus OCT 
is a non-invasive instrument that provides new information on the location of
flecks in FFM. The location of type 2 lesions is quite unusual among macular
dystrophies; OCT may therefore be useful in the diagnosis of retinal flecks in
some cases of FFM.

PMID: 16754647 [PubMed - indexed for MEDLINE]

1445: Eye. 2007 Nov;21(11):1391-4. Epub 2006 Jun 2.

Visualization of vitreomacular tractions with en face optical coherence
tomography.

Forte R, Pascotto F, de Crecchio G.

Eye Department, University Federico II, Naples, Italy. raifor@hotmail.com

BACKGROUND: In vitreomacular traction syndrome, an incomplete vitreous detachment
with persistent vitreous traction on the macula is present. This condition may
determine formation of epiretinal membranes, macular puckering, macular oedema,
and traction macular detachment. Recently introduced en face optical coherence
tomography (OCT) provides not only longitudinal B-scan but also coronal C-scan
images of the retina. METHODS: Fifteen eyes of 11 non-diabetic patients
presenting vitreomacular traction syndrome have been evaluated with en face OCT
(OTI, Toronto, Ontario, Canada). RESULTS: In 12 eyes, cystoid macular oedema was 
detectable at fundus examination and was associated with a broad-based adherence 
of the posterior hyaloid to the macula. In three eyes, foveal detachment appeared
to be associated with focal foveal vitreoretinal traction. In all eyes, the
lateral extent of the hyaloidal tractions on the macula was clearly detectable at
coronal C-scan. They appeared as sigmoid hyper-reflective bands in the
hyporeflective vitreous chamber. Overlay of C-scans on red-free confocal images
allowed the visualization of the edges of the adherences in relation to the
structures of the posterior pole. CONCLUSIONS: The C-scan images allowed clear
visualization of the total extension of the posterior vitreomacular adherences
and their relationships with the vascular arcades, the optic disc, and the fovea.

PMID: 16751756 [PubMed - indexed for MEDLINE]

1446: Eye. 2008 Jan;22(1):8-12. Epub 2006 Jun 2.

Change of foveal and perifoveal thickness measured by OCT after
phacoemulsification and IOL implantation.

Biro Z, Balla Z, Kovacs B.

Department of Ophthalmology, University of Pecs, Faculty of Medicine, Pécs,
Baranya, Hungary. zsolt.biro@aok.pte.hu

PURPOSE: Cataract surgery is known to elicit postoperative macular oedema owing
to its traumatic effect. The aim of the study was to measure the foveal and
perifoveal thickness of the retina after uneventful phacoemulsification and
posterior chamber intraocular lens (PC-IOL) implantation. METHODS: Retinal
thickness values of the foveal and perifoveal (fovea+3.0 mm, fovea+6.0 mm)
sectors and the minimum values were measured in a prospective study using optical
coherence tomography (OCT) in 71 eyes of 71 patients (34 men, 37 women, mean age:
68.8 years) who underwent cataract surgery. Phacoemulsification and 'in the bag' 
implantation of a foldable PC-IOL was performed under topical anaesthesia. Data
were collected 1 day before the operation, and postoperatively at 1, 7, 30, and
60 days. Contralateral eyes of each patient served as controls. 'Student's
t-test' was used for statistical analysis, and P<0.05 value was considered
significant. RESULTS: No significant change of the thickness values could be
measured 1 day after surgery. However, a significant increase could be detected
on the postoperative 7, 30, and 60 days in the perifoveal 3.0 and 6.0 mm sectors 
either calculated alone or averaged together with the foveal values. The initial 
(preoperative) average value of 234.1+/-2.6 microm (mean+/-SEM, n=536) in the 6.0
mm perifoveal region increased to 242.5+/-2.6 microm (mean+/-SEM, n=488, P<0.01) 
1 week, to 247.7+/-4.6 microm (n=352, P<0.01) 1 month, and to 246.0+/-5.9 microm 
(n=208, P<0.05) 2 months after surgery, which proved to be significant. However, 
the relative change of macular thickness was moderate, 3.5, 5.6, and 5.3% at the 
above periods, respectively. In a subgroup of patients (n=34) minimum 6 months
after cataract surgery, the 6.0 mm perifoveal values were found to be elevated at
(237.8+/-3.9 microm, mean+/-SEM, n=272) as compared to the control eyes
(233.9+/-3.8 microm, mean+/-SEM, n=272). The difference was 1.7% and proved not
to be significant (P>0.05). CONCLUSIONS: Mild subclinical perifoveal oedema
following cataract surgery was detected using OCT at postoperative day 7 to 6
months. The minimal and the foveal values in itself are inadequate to describe
the phenomenon. The macular thickness values of the perifoveal 3.0 and 6.0 mm
sectors alone or averaged together with the foveal values provide more accurate
description of the postoperative macular oedema.OCT enables the detection of
minimal increases in perifoveal retinal thickness even 6 months after cataract
surgery.

PMID: 16751754 [PubMed - indexed for MEDLINE]

1447: Eye. 2007 Feb;21(2):169-76. Epub 2006 May 26.

Characteristics of progression of early age-related macular degeneration: the
cardiovascular health and age-related maculopathy study.

Tikellis G, Robman LD, Dimitrov P, Nicolas C, McCarty CA, Guymer RH.

Department of Ophthalmology, Centre for Eye Research Australia, University of
Melbourne, East Melbourne, Victoria, Australia. gtike@unimelb.edu.au

AIMS: To determine the risk of age-related macular degeneration (AMD) progression
posed by the presence of each early AMD characteristic. METHODS: A prospective
cohort study of 254 participants aged 50 years and older, all with early AMD
features at their baseline visit followed for an average of 7 years. Stereoscopic
colour fundus photographs were graded for early AMD features using the
International Classification System. AMD status was stratified into six exclusive
levels along a continuum of disease severity according to drusen type, pigmentary
abnormalities, or late AMD. Progression was assessed according to three
definitions: a change between or within a severity level, or by side by side
grading. RESULTS: The progression rate of early AMD ranged between 3.4 and 4.67% 
per annum depending upon the definition used. In total, 15 (6%) cases progressed 
from early AMD to the late complication of AMD. After controlling for age and
smoking, cases with soft indistinct drusen at baseline were at a greater risk of 
progressing from early to late AMD than were cases without this characteristic
(OR=3.72, 95%CI 1.20-11.54; P=0.02). CONCLUSION: Our proposed definitions of AMD 
progression give rates that are consistent with current knowledge of progression 
and its determinants. Each early AMD characteristic conveys its own risk of
progression to an eye, with soft indistinct drusen carrying the greater risk. An 
international consensus on what defines AMD progression would greatly help the
research community when trying to assess the importance of new risk factors and
the effectiveness of novel interventions.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16732219 [PubMed - indexed for MEDLINE]

1448: BioDrugs. 2006;20(3):167-79.

New pharmacologic approaches to therapy for age-related macular degeneration.

Eter N, Krohne TU, Holz FG.

Department of Ophthalmology, University of Bonn Medical Center, Bonn, Germany.
eter@uni-bonn.de

As a result of a better understanding of molecular mechanisms, a variety of new
pharmacologic treatments have recently been developed for patients with
age-related macular degeneration (AMD). Efficacy and tolerability have been
demonstrated for drugs targeting vascular endothelial growth factor (VEGF), a key
player in the pathogenesis of choroidal neovascularization. Both pegaptanib
(anti-VEGF aptamer) and ranibizumab (anti-VEGF antibody fragment), applied at 4- 
to 6-week intervals into the vitreous, modified the natural course of the disease
in phase III clinical studies. Corticosteroids with anti-angiogenic properties
also represent a treatment option for wet AMD. Both intravitreal triamcinolone
and anecortave acetate, administered juxtasclerally, are currently being
pursued.The combination of different treatment strategies and potential
synergistic effects offers new perspectives. While photodynamic therapy (PDT)
combined with intravitreal triamcinolone is already frequently applied, other
combinations (e.g. anti-VEGF drugs with PDT or antifibrotic agents) appear to be 
attractive alternatives. Pigment epithelium-derived factor represents another
potential target, as well as inhibitors of matrix-metallo-proteinases. With the
advent of gene therapy, the use of small interfering RNA (siRNA) is also on the
horizon.Prophylactic measures are still limited. The combination of vitamins C
and E, beta-carotene, and zinc as used in the AREDS (Age-Related Eye Disease
Study) reduces risk for conversion from early- to late-stage disease in patients 
with high-risk features, at least to some extent. Lutein and zeaxanthin dietary
supplements for improvement of macular pigment density need to be investigated in
future longitudinal trials.

Publication Types: 
    Review

PMID: 16724865 [PubMed - indexed for MEDLINE]

1449: Invest Ophthalmol Vis Sci. 2006 Jun;47(6):2739-45.

The letter contrast sensitivity test: clinical evaluation of a new design.

Haymes SA, Roberts KF, Cruess AF, Nicolela MT, LeBlanc RP, Ramsey MS, Chauhan BC,
Artes PH.

Department of Ophthalmology and Visual Sciences, Dalhousie University, Halifax,
Canada. sharon.haymes@dal.ca

PURPOSE: To compare the reliability, validity, and responsiveness of the Mars
Letter Contrast Sensitivity (CS) Test to the Pelli-Robson CS Chart. METHODS: One 
eye of 47 normal control subjects, 27 patients with open-angle glaucoma, and 17
with age-related macular degeneration (AMD) was tested twice with the Mars test
and twice with the Pelli-Robson test, in random order on separate days. In
addition, 17 patients undergoing cataract surgery were tested, once before and
once after surgery. RESULTS: The mean Mars CS was 1.62 log CS (0.06 SD) for
normal subjects aged 22 to 77 years, with significantly lower values in patients 
with glaucoma or AMD (P<0.001). Mars test-retest 95% limits of agreement (LOA)
were +/-0.13, +/-0.19, and +/-0.24 log CS for normal, glaucoma, and AMD,
respectively. In comparison, Pelli-Robson test-retest 95% LOA were +/-0.18,
+/-0.19, and +/-0.33 log CS. The Spearman correlation between the Mars and
Pelli-Robson tests was 0.83 (P<0.001). However, systematic differences were
observed, particularly at the upper-normal end of the range, where Mars CS was
lower than Pelli-Robson CS. After cataract surgery, Mars and Pelli-Robson effect 
size statistics were 0.92 and 0.88, respectively. CONCLUSIONS: The results
indicate the Mars test has test-retest reliability equal to or better than the
Pelli-Robson test and comparable responsiveness. The strong correlation between
the tests provides evidence the Mars test is valid. However, systematic
differences indicate normative values are likely to be different for each test.
The Mars Letter CS Test is a useful and practical alternative to the Pelli-Robson
CS Chart.

Publication Types: 
    Comparative Study
    Evaluation Studies
    Research Support, Non-U.S. Gov't

PMID: 16723494 [PubMed - indexed for MEDLINE]

1450: Invest Ophthalmol Vis Sci. 2006 Jun;47(6):2655-61.

Predictive value of fundus autofluorescence for development of geographic atrophy
in age-related macular degeneration.

Hwang JC, Chan JW, Chang S, Smith RT.

Department of Ophthalmology, Columbia University, New York, New York 10032, USA.

PURPOSE: It has been suggested that lipofuscin accumulation, as measured by
increased fundus autofluorescence (FAF), precedes progression or development of
junctional zone geographic atrophy (GA) in age-related macular degeneration
(AMD). The tools of biomedical image analysis were used to measure the
probabilistic relationship of GA progression to increased FAF. METHODS: Serial AF
images of eight eyes of six patients with AMD with GA were registered on
computer. The images were leveled with a 12-zone quadratic polynomial
mathematical model to minimize background variability. Semiautomated segmentation
of GA was performed on the leveled images. Increased FAF was defined as a gray
level greater than 2 standard deviations above the leveled image mean, identified
on the initial image with automated segmentation, and measured as a fraction of
the 250-microm border zone surrounding the initial GA lesion. Areas of GA lesions
were identified on the final image. The positive predictive value (PPV) of
increased FAF was determined as the probability that any pixel with increased FAF
in the initial image would become part of new GA in the final image. Relative PPV
was determined relative to the total quantity of new GA. The NPV (NPV) of
increased FAF was calculated as the probability that any pixels without increased
FAF would not become atrophic. The relative NPV was determined similarly. A
similar analysis was also conducted with a 500-microm border zone to determine
the predictive value of proximity to the original GA lesion ("proximity") for GA 
progression. RESULTS: As a fraction of the geographic atrophy border zone, the
mean new GA was 0.44+/-0.20, and the mean increased FAF was 0.06+/-0.06. The mean
PPV of increased FAF for new GA formation was 0.50+/-0.26. Compared with the
relative PPV of chance of 1.0, the mean relative PPV of increased FAF was
1.15+/-0.28. The mean NPV of increased FAF was 0.57+/-0.20. The mean relative NPV
of increased FAF was 1.00+/-0.02. In the 500-microm border zone, the mean
relative PPV of FAF and of proximity were essentially equal (1.56+/-.70 and
1.52+/-0.26, respectively), whereas the mean relative NPV of proximity was
significantly greater than that of FAF (1.26+/-0.19 and 1.01+/-0.01,
respectively, P=0.02) CONCLUSIONS: The results of digital image analysis suggest 
that although increased FAF may have a modest PPV for new GA development, the
relative PPV is generally no greater than chance. Similarly, the relative NPV
demonstrates negligible difference from chance and is also lower than the
relative NPV of proximity. This suggests that increased FAF, though a disease
manifestation, is not a strong risk factor for development or extension of GA.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16723483 [PubMed - indexed for MEDLINE]

1451: Invest Ophthalmol Vis Sci. 2006 Jun;47(6):2648-54.

Correlation between the area of increased autofluorescence surrounding geographic
atrophy and disease progression in patients with AMD.

Schmitz-Valckenberg S, Bindewald-Wittich A, Dolar-Szczasny J, Dreyhaupt J, Wolf
S, Scholl HP, Holz FG; Fundus Autofluorescence in Age-Related Macular
Degeneration Study Group.

Department of Ophthalmology, University of Bonn, Bonn, Germany, and First Eye
Hospital, University of Lublin, Poland.

PURPOSE: To test the hypothesis that the extension of areas with increased fundus
autofluorescence (FAF) outside atrophic patches correlates with the rate of
spread of geographic atrophy (GA) over time in eyes with age-related macular
degeneration (AMD). METHODS: The database of the multicenter longitudinal natural
history Fundus Autofluorescence in AMD (FAM) Study was reviewed for patients with
GA recruited through the end of August 2003, with follow-up examinations within
at least 1 year. Only eyes with sufficient image quality and with diffuse
patterns of increased FAF surrounding atrophy were chosen. In standardized
digital FAF images (excitation, 488 nm; emission, >500 nm), total size and spread
of GA was measured. The convex hull (CH) of increased FAF as the minimum polygon 
encompassing the entire area of increased FAF surrounding the central atrophic
patches was quantified at baseline. Statistical analysis was performed with the
Spearman's rank correlation coefficient (rho). RESULTS: Thirty-nine eyes of 32
patients were included (median age, 75.0 years; interquartile range [IQR],
67.8-78.9); median follow-up, 1.87 years; IQR, 1.43-3.37). At baseline, the
median total size of atrophy was 7.04 mm2 (IQR, 4.20-9.88). The median size of
the CH was 21.47 mm2 (IQR, 15.19-28.26). The median rate of GA progression was
1.72 mm2 per year (IQR, 1.10-2.83). The area of increased FAF around the atrophy 
(difference between the CH and the total GA size at baseline) showed a positive
correlation with GA enlargement over time (rho=0.60; P=0.0002). CONCLUSIONS: FAF 
characteristics that are not identified by fundus photography or fluorescein
angiography may serve as a prognostic determinant in advanced atrophic AMD. As
the FAF signal originates from lipofuscin (LF) in postmitotic RPE cells and since
increased FAF indicates excessive LF accumulation, these findings would
underscore the pathophysiological role of RPE-LF in AMD pathogenesis.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 16723482 [PubMed - indexed for MEDLINE]

1452: Invest Ophthalmol Vis Sci. 2006 Jun;47(6):2336-40.

A prospective assessment of the Y402H variant in complement factor H, genetic
variants in C-reactive protein, and risk of age-related macular degeneration.

Schaumberg DA, Christen WG, Kozlowski P, Miller DT, Ridker PM, Zee RY.

Division of Preventive Medicine, Center for Cardiovascular Disease Prevention,
Brigham and Women's Hospital, and Department of Ophthalmology, Schepens Eye
Research Institute, Harvard Medical School, Boston, MA 02215, USA.
dschaumberg@rics.bwh.harvard.edu

PURPOSE: Two biologically related factors, complement factor H (CFH) and
C-reactive protein (CRP), have been associated with AMD. The Y402H variant of CFH
is located within the binding site of CFH for CRP. Although plasma CRP levels
have been related to AMD and plasma CRP levels are partly determined by genetic
variation, there is no information on whether genetic variants in CRP are
associated with AMD. METHODS: A prospective analysis was performed of 111 men who
eventually developed AMD and 401 men who remained free of AMD, all participants
in the Physicians' Health Study. Genotypes were determined for the common T-->C
single nucleotide polymorphism (SNP) in exon 9 of CFH (rs1061170; protein Y402H),
as well as seven previously described CRP SNPs (rs3093059, rs2794521, rs3091244, 
rs1417938, rs1800947, rs1130864, and rs1205). Logistic regression analysis was
used to evaluate individual SNPs, as well as six CRP haplotypes for association
with AMD. RESULTS: The high-risk C allele of CFH was present in 45% of cases and 
34% of controls. An odds ratio (OR) of 1.46 was observed for AMD (95% confidence 
interval [CI]: 1.05-2.04) for TC heterozygotes and an OR of 2.13 (95% CI:
1.10-4.16) for CC homozygotes, assuming a multiplicative (log-additive) model and
attributable fraction of 25% (95% CI: 1% to 44%) was calculated. For CRP,
single-marker or haplotype-based analysis failed to reveal any significant
associations with a risk of AMD. CONCLUSIONS: These prospective data confirmed an
association between the Y402H variant of CFH and a risk of AMD. In contrast,
although a biologically plausible, genetic variation in CRP does not appear to be
associated with a risk of AMD. Further prospective studies of a larger number of 
subjects are needed to substantiate available information on the genetic
epidemiology of AMD.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 16723442 [PubMed - indexed for MEDLINE]

1453: Invest Ophthalmol Vis Sci. 2006 Jun;47(6):2329-35.

Plasma lutein and zeaxanthin and other carotenoids as modifiable risk factors for
age-related maculopathy and cataract: the POLA Study.

Delcourt C, Carrière I, Delage M, Barberger-Gateau P, Schalch W; POLA Study
Group.

Institut National de la Santé et de la Recherche Médicale (INSERM), Research Unit
U593 for Epidemiology, Public Health and Development, Université Victor Segalen
Bordeaux 2, Bordeaux, France. cecile.delcourt@isped.u-bordeaux2.fr

PURPOSE: To assess the associations of plasma lutein and zeaxanthin and other
carotenoids with the risk of age-related maculopathy (ARM) and cataract in the
population-based Pathologies Oculaires Liées à l'Age (POLA) Study. METHODS:
Retinal photographs were graded according to the international classification.
ARM was defined by the presence of late ARM (neovascular ARM, geographic atrophy)
and/or soft indistinct drusen (>125 microm) and/or soft distinct drusen (>125
microm) associated with pigmentary abnormalities. Cataract classification was
based on a direct standardized lens examination at the slit lamp, according to
Lens Opacities Classification System III. Plasma carotenoids were measured by
high-performance liquid chromatography (HPLC), in 899 subjects of the cohort.
RESULTS: After multivariate adjustment, the highest quintile of plasma zeaxanthin
was significantly associated with reduced risk of ARM (OR=0.07; 95% CI:
0.01-0.58; P for trend=0.005), nuclear cataract (OR=0.23; 95% CI: 0.08-0.68; P
for trend=0.003) and any cataract (OR=0.53; 95% CI: 0.31-0.89; P for trend=0.01).
ARM was significantly associated with combined plasma lutein and zeaxanthin
(OR=0.21; 95% CI: 0.05-0.79; P for trend=0.01), and tended to be associated with 
plasma lutein (OR=0.31; 95% CI: 0.09-1.07; P for trend=0.04), whereas cataract
showed no such associations. Among other carotenoids, only beta-carotene showed a
significant negative association with nuclear cataract, but not ARM. CONCLUSIONS:
These results are strongly suggestive of a protective role of the xanthophylls,
in particular zeaxanthin, for the protection against ARM and cataract.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16723441 [PubMed - indexed for MEDLINE]

1454: Invest Ophthalmol Vis Sci. 2006 Jun;47(6):2280-90.

The proteome of central and peripheral retina with progression of age-related
macular degeneration.

Ethen CM, Reilly C, Feng X, Olsen TW, Ferrington DA.

Department of Biochemistry, University of Minnesota, Minneapolis 55455, USA.

PURPOSE: A growing understanding of the molecular events in age-related macular
degeneration (AMD) has lead to targeted therapies for a select group of patients 
with advanced AMD. Development of therapies for the earlier stages requires
further elucidation of disease mechanisms. In this study, a proteomics approach
was used to identify proteins that had altered content in human donor eyes with
progression of AMD. METHODS: The early molecular events associated with AMD were 
identified by comparing the proteome of the macular and peripheral neurosensory
retina during four progressive stages of AMD. Proteins were resolved and
quantified by two-dimensional gel electrophoresis. Twenty-six proteins exhibited 
changes in content and were identified by matrix-assisted laser desorption
ionization-time of flight (MALDI-TOF) mass spectrometry. Two-dimensional (2-D)
and semiquantitative one-dimensional (1-D) Western blot analyses were used to
determine whether changes identified by proteomic analysis were specific for a
protein subpopulation or representative of the entire protein population.
RESULTS: Twenty-six proteins were identified that exhibited changes at disease
onset or with progression (indicating potential causal mechanisms) and at
end-stage disease (indicating potential secondary consequences). These proteins
are involved in key functional pathways, such as microtubule regulation and
protection from stress-induced protein unfolding. Approximately 60% of the
proteins exhibited changes specific to either the macula or periphery, with the
remaining 40% changing in both regions. These results imply that both the macula 
and periphery are affected by AMD. CONCLUSIONS: This study provides the first
direct evidence of AMD stage- and region-specific changes in retinal protein
levels and highlights potential novel, disease-related proteins and biochemical
pathways for future studies of AMD.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16723435 [PubMed - indexed for MEDLINE]

1455: Br J Ophthalmol. 2006 Sep;90(9):1107-10. Epub 2006 May 24.

Erratum in:
    Br J Ophthalmol. 2007 Aug;91(8):1097. Zambarajki, H [corrected to Zambarakji, H].

The effect of pars plana vitrectomy on cystoid macular oedema associated with
chronic uveitis: a randomised, controlled pilot study.

Tranos P, Scott R, Zambarakji H, Ayliffe W, Pavesio C, Charteris DG.

Department of Vitreoretinal Surgery, Moorfields Eye Hospital, London, EC1V 2PD,
UK.

AIM: To evaluate the efficacy of pars plana vitrectomy (PPV) in the management of
chronic uveitic cystoid macular oedema (CMO). METHODS: A prospective,
interventional, randomised, controlled, pilot study. 23 eyes of 23 patients with 
CMO secondary to chronic intermediate or posterior uveitis unresponsive to
medical treatment were randomised into a surgical (group S) or medical group
(group M). 12 patients in group S underwent PPV as opposed to 11 patients in
group M who received systemic corticosteroid and/or immunosuppressive treatment
during the study period. The primary outcome measures of the study were change in
visual acuity and angiographic appearance of CMO at 6 months. RESULTS: Mean
visual acuity in group S improved significantly from 1.0 (0.62) at baseline to
0.55 (0.29) at 6 months following vitrectomy (p = 0.011), with five (42%) eyes
reaching vision of 20/40 or better. Conversely, mean visual acuity in group M
improved only marginally by 0.03 (0.27) (p = 0.785). CMO after vitrectomy was
angiographically improved in four (33%) eyes, remained unchanged in seven (58%)
eyes, and deteriorated in one (8%) eye. In the medical group, fluorescein leakage
decreased in one eye, did not alter in four eyes, and deteriorated in two eyes.
CONCLUSION: PPV for macular oedema secondary to chronic uveitis despite
angiographic improvement in only one third of the patients, seems to have a
significant beneficial effect on visual function. This study provides enough
evidence to justify a large scale trial which would define the role of vitrectomy
in uveitic macular oedema.

Publication Types: 
    Randomized Controlled Trial

PMID: 16723360 [PubMed - indexed for MEDLINE]

1456: Br J Ophthalmol. 2006 Aug;90(8):1028-33. Epub 2006 May 24.

Erratum in:
    Br J Ophthalmol. 2007 Mar;91(3):403.

Plasma apolipoproteins and risk for age related maculopathy.

Dashti N, McGwin G, Owsley C, Curcio CA.

Department of Medicine, Division of Geriatrics and Gerontology, Atherosclerosis
Research Unit, University of Alabama School of Medicine, Birmingham AL
35294-0009, USA.

AIM: To determine if elevated plasma levels of atherogenic and/or
anti-atherogenic lipoproteins are risk factors for developing age related
maculopathy (ARM). METHODS: In a cross sectional study in a university clinic
setting, 129 patients (72 women and 57 men) underwent colour fundus photography, 
acuity and contrast sensitivity assessment, and electroimmunoassays of plasma
apolipoproteins B (apoB) and A-I (apoA-I), the principal proteins of low density 
and high density lipoproteins, respectively. Maculopathy stage was assigned using
the AREDS grading system. RESULTS: Levels of apoB in no ARM, mild, intermediate, 
and advanced ARM groups were 93.3, 91.8, 95.2, and 98.2 mg/dl, respectively.
Levels of apoA-I were 147.4, 148.6, 141.0, and 144.9 mg/dl in the same groups.
There was no significant association between these measures, typical for age, and
maculopathy stage. CONCLUSION: Although drusen associated with ARM and ageing
contain cholesterol and apoB, like the lipid rich core of an atherosclerotic
plaque, the results of this study and our previous work in toto make the
prospects of a plasma origin for these lesion constituents increasingly
untenable. This conclusion is consistent with an emerging hypothesis that a large
lipoprotein of intraocular origin is an important pathway for constituent retinal
lipid processing and the biogenesis of drusen.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Review

PMID: 16723359 [PubMed - indexed for MEDLINE]

1457: J Ocul Pharmacol Ther. 2006 Apr;22(2):139-44.

Association between topical prostaglandin analog use and development of choroidal
neovascular membranes in patients with concurrent glaucoma and age-related
macular degeneration.

Scherer WJ.

Montgomery Eye Center, Naples, FL 34103, USA. warrenscherer@hotmail.com

PURPOSE: Matrix metalloproteinases (MMPs) are a family of enzymes that act to
degrade extracellular matrix (ECM) molecules, such as collagen, elastin, and
gelatin. The glaucoma medication latanoprost, and possibly other topical
prostaglandin analogs, increase uveoscleral outflow and lower intraocular
pressure (IOP) in primary open-angle glaucoma (POAG) by activating MMPs 1, 2, 3, 
and 9 in the ciliary body. It has been reported that latanoprost may also gain
access to the posterior segment and induce cystoid macular edema, although the
mechanism is unknown. In the choroid, activation of some of the same subtypes of 
MMPs (particularly subtypes 2 and 9) has been implicated in the formation of
choroidal neovascular membranes (CNVMs) in age-related macular degeneration
(AMD). This study examined whether topical prostaglandin analog use is associated
with a greater risk of CNVM formation in patients diagnosed with both AMD and
POAG. METHODS: A retrospective record review was performed to identify patients
with a concurrent diagnosis of AMD and POAG between 1998 and 2004. Four hundred
and eighty-four (484) eyes were identified and grouped as wet (n = 65) or dry (n 
= 419) AMD. Prostaglandin usage was compared between the two groups. Usage of
other glaucoma medications was also compared. A minimum of 1 year of topical
glaucoma medication was required for inclusion in the study. Exclusion criteria
included a history of CNVM prior to starting glaucoma medications and a previous 
history of glaucoma surgery. RESULTS: Fifty-six percent (56%) of dry AMD and 62% 
of wet AMD eyes were using a topical prostaglandin (P > 0.10; not significant).
Analysis of specific topical prostaglandin analog usage in the wet versus dry AMD
groups revealed no statistically significant differences in the percentage of
eyes treated with latanoprost (37.7% versus 41.5%), bimatoprost (12.9% versus
10.8%), or travoprost (9.2% versus 5.3%), respectively. No significant
differences in the use of other glaucoma medications were observed between the
two groups. CONCLUSIONS: No association between long-term topical prostaglandin
use and CNVM development was found in patients with AMD and POAG.

PMID: 16722800 [PubMed - indexed for MEDLINE]

1458: Hum Genet. 2006 Aug;120(1):139-43. Epub 2006 May 19.

No association between complement factor H gene polymorphism and exudative
age-related macular degeneration in Japanese.

Gotoh N, Yamada R, Hiratani H, Renault V, Kuroiwa S, Monet M, Toyoda S, Chida S, 
Mandai M, Otani A, Yoshimura N, Matsuda F.

Department of Ophthalmology, Kyoto University Graduate School of Medicine, Kyoto,
Japan.

Age-related macular degeneration (ARMD) is the leading cause of blindness in the 
elderly population not only Western but also Asian industrial countries. In
Caucasian, a polymorphism of the complement factor H gene (CFH), the C allele of 
rs1061170 (Y402H), was established as the first strong genetic factor for
excursively exudative type of ARMD. In this study, we performed an extensive
sequencing of the 22 exons in the CFH gene by recruiting 146 exudative ARMD
patients and 105 normal controls of Japanese origin and identified 61
polymorphisms. We found that the frequency of the C allele of rs1061170 (Y402H)
is much lower (0.04) in Japanese controls than in Caucasians (0.45). No case
disease susceptibility to exudative ARMD was noted for rs1061170 (Y402H) (chi (2)
= 3.19, P (corr) = 0.423), or other 12 single nucleotide polymorphisms (SNPs)
whose frequency is greater than 0.05. When haplotypes were inferred for 13 SNPs
(these 12 SNPs with a frequency greater than 0.05 and rs1061170), three
haplotypes whose pattern was similar to those in Caucasians were identified but
with substantial difference in frequency. Again we failed to identify genetic
association between Japanese exudative ARMD and any of the haplotypes including
the J1 haplotype which was shown to be susceptible to ARMD in Caucasians (chi (2 
)=( )3.92, P (corr) = 0.157). CFH does not appear to be a primary hereditary
contributor to ARMD in Japanese. The absence of CFH contribution to ARMD in
Japanese may correlate with the findings in ethnic differences of ARMD
phenotypes.

PMID: 16710702 [PubMed - indexed for MEDLINE]

1459: Eye. 2007 Jun;21(6):831-4. Epub 2006 May 19.

Cystoid macular oedema following pneumatic retinopexy vs scleral buckling.

Tunc M, Lahey JM, Kearney JJ, Lewis JM, Francis R.

Department of Ophthalmology, Kaiser-Permanante Medical Center, Union City, CA,
USA. mtunc@isbank.net.tr

AIMS: To determine the incidence of angiographic cystoid macular oedema (CMO)
following pneumatic retinopexy (PR) and scleral buckling (SB) in consecutive case
series. METHODS: Patients who had successful anatomical attachment following PR
and SB were included in our study; 132 patients had PR and 121 patients had SB.
We evaluated the demographic characteristics, visual acuity, lens status, macular
status, and previous ocular history in all patients. CMO was evaluated by
fluorescein angiography (FA) in a masked pattern, 6 and 12 weeks after surgery in
all cases. We analysed the CMO incidence and its correlation with preoperative
ocular status and visual outcome. Chi2 and Fisher's exact tests were used in
statistical analysis. RESULTS: CMO was present in 15 of 132 (11%) PR, and 35 of
121 (29%) SB patients at 6 weeks (P=0.0005); the oedema was persistent in eight
of 132 (6%) PR and 21 of 121 (17%) SB patients at 12 weeks (P=0.0005). Eight of
106 (8%) phakic and seven of 26 (27%) pseudophakic patients developed CMO
following PR (P=0.02). In the SB group, 26 of 72 (36%) patients who had
preoperative macular detachment developed CMO (P=0.03). Visual improvement was
limited in patients who developed angiographic CMO despite anatomical
re-attachment of the retina. CONCLUSIONS: CMO may occur following both PR and SB 
and deteriorate the visual outcome. Previous cataract surgery and macular
detachment may increase the CMO rates following PR and SB, respectively.

Publication Types: 
    Comparative Study
    Controlled Clinical Trial

PMID: 16710429 [PubMed - indexed for MEDLINE]

1460: Br J Ophthalmol. 2006 Sep;90(9):1137-41. Epub 2006 May 17.

Comment in:
    Br J Ophthalmol. 2006 Sep;90(9):1079-80.

Decreasing efficacy of repeated intravitreal triamcinolone injections in diabetic
macular oedema.

Chan CK, Mohamed S, Shanmugam MP, Tsang CW, Lai TY, Lam DS.

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong
Kong, University Eye Center, Hong Kong Eye Hospital, 147K, Argyle Street, Hong
Kong.

BACKGROUND/AIM: Intravitreal triamcinolone (IVTA) results in transient
improvements in diabetic macular oedema (DMO), necessitating repeated injections.
The authors report a case series of 10 eyes of 10 patients with DMO, who received
a repeat injection of 4 mg IVTA, at least 26 weeks after the first injection of
the same dose. METHOD: Pre-injection and at 2, 4, 9, and 17 weeks post-injection,
best corrected visual acuity (BCVA) and central foveal thickness (CFT) on optical
coherence tomography, after the first and repeat injections, were compared using 
paired t test. Side effects were monitored. RESULTS: BCVA, CFT, intraocular
pressure (IOP), and cataract scores were not significantly different before
initial and repeat injections (given at 32.5 (SD 3.5) weeks after the first
injection). Transient improvements of BCVA and CFT were achieved after both
injections. However, after the repeat injection, the BCVA was significantly worse
at all time points (p<0.05) and so were the best achieved CFT and the CFT at 4
weeks post-injection (p = 0.034 and 0.011 respectively), compared with the
initial injection. Post-injection maximum IOPs and increase in cataract scores
were not significantly different between the two injections. CONCLUSION: A repeat
injection of 4 mg of IVTA may not be as effective as an initial injection for the
treatment of DMO.

PMID: 16707525 [PubMed - indexed for MEDLINE]

1461: Klin Monatsbl Augenheilkd. 2006 May;223(5):376-8.

Macular atrophy after combined intravitreal triamcinolone acetonide (IVTA) and
photodynamic therapy (PDT) for retinal angiomatous proliferation (RAP).

Sutter FK, Kurz-Levin MM, Fleischhauer J, Bösch MM, Barthelmes D, Helbig H.

Augenklinik, UniversitätsSpital Zürich, Zürich, Switzerland.
Florian.Sutter@usz.ch

BACKGROUND: Retinal angiomatous proliferation (RAP) is a variant of exudative AMD
that appears to respond poorly to standard PDT. This pilot study explores the
potential efficacy and safety of combined intravitreal triamcinolone acetonide
(IVTA). PATIENTS AND METHODS: In a prospective interventional case series 10 eyes
of 8 patients with RAP were treated with combined IVTA/PDT. RESULTS: After 3
months there was no evidence of significant exudative activity in 7/10 eyes
treated with IVTA/PDT, three eyes required re-treatment. After 6 months 4/10 eyes
were "dry" on fluorescein angiography, visual acuity was stable (loss of less
than 3 Snellen lines) or had improved in 5/10 eyes. 5/10 eyes had lost 3 or more 
lines, due to central macular atrophy in 4/5 eyes and secondary to a progressive 
exudative lesion in 1/5 eyes. CONCLUSIONS: Intravitreal steroids combined with
PDT appear to be a step ahead in the treatment of RAP. Our results, however,
raise the question whether combined treatment may create more atrophy leading to 
vision loss in some cases.

Publication Types: 
    Clinical Trial

PMID: 16705508 [PubMed - indexed for MEDLINE]

1462: Acta Ophthalmol Scand. 2006 Jun;84(3):333-7.

Chlamydia pneumoniae is not detectable in subretinal neovascular membranes in the
exudative stage of age-related macular degeneration.

Kessler W, Jantos CA, Dreier J, Pavlovic S.

Department of Opthalmology, University of Giessen, Giessen, Germany.
Werner.Kessler@augen.med.uni-giessen.de

PURPOSE: Age-related macular degeneration (AMD) is the most frequent cause of
severe visual impairment in western countries, but its aetiology remains unclear.
A growing body of evidence suggests that inflammation contributes to the
pathogenesis of AMD, similarly to that shown for atherosclerosis. In view of a
number of shared risk factors between the two entities and the hypothesized link 
between Chlamydia pneumoniae infection and atherosclerosis, we investigated
whether C. pneumoniae might be involved in exudative AMD. METHODS: To examine
whether C. pneumoniae contributes to the development of subretinal neovascular
(SRNV) membranes in AMD, 13 consecutive SRNV membranes surgically excised from
patients with exudative AMD were collected and assayed for the presence of C.
pneumoniae or other bacterial pathogens by means of polymerase chain reaction
(PCR). RESULTS: The age of patients ranged from 68 to 85 years (median 73.5
years). In all 13 SRNV membranes, no DNA of either C. pneumoniae or other
pathogens was found by PCR. CONCLUSIONS: These findings indicate that C.
pneumoniae is not associated with the development of SRNV membranes in exudative 
AMD.

PMID: 16704694 [PubMed - indexed for MEDLINE]

1463: Acta Ophthalmol Scand. 2006 Jun;84(3):328-32.

Transpupillary thermotherapy for the treatment of occult CNV in age-related
macular degeneration: a prospective randomized controlled pilot study.

Myint K, Armbrecht AM, Mon S, Dhillon B.

Princess Alexandra Eye Pavilion, Edinburgh, UK. kmyintuk@yahoo.co.uk

PURPOSE: To evaluate whether transpupillary thermotherapy (TTT) reduces the risk 
of moderate visual loss in patients with occult choroidal neovascularization
(CNV) secondary to age-related macular degeneration (AMD). METHODS: A group of 25
patients were recruited and randomized into TTT or placebo groups. Patients were 
included if they had a subfoveal purely or predominantly (> 50%) occult CNV
secondary to AMD with best corrected visual acuity (BCVA) of 6/60 or better and
the lesion was not larger than 4.5 mm. Treatment was carried out using an 810-nm 
Oculight diode laser with a fixed spot size covering the whole lesion according
to the standard protocol. The same procedure was used for the control group,
except that the power was set at zero. The patients were followed up at 6 weeks, 
3 months and then every 6 months for up to 2 years. A maximum of three treatments
were administered in both groups if there was evidence of persistent leakage from
CNV. RESULTS: At the 12-month follow-up, there was no significant difference in
the mean values for BCVA distance and near or contrast sensitivity between the
treatment and control groups. The Mann-Whitney test was used to assess the
differences in BCVA and contrast sensitivity between the groups, both at baseline
and at the 12-month follow-up. No statistically significant difference was found;
both groups lost on average two lines of BCVA. CONCLUSION: Transpupillary
thermotherapy appeared to have been of no benefit in preventing further visual
loss in patients with occult CNV in this pilot study.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16704693 [PubMed - indexed for MEDLINE]

1464: Acta Ophthalmol Scand. 2006 Jun;84(3):314-8.

Macular oedema in central retinal vein occlusion treated with intravitreal
triamcinolone.

Gelston CD, Olson JL, Mandava N.

Department of Ophthalmology, Rocky Mountain Lions Eye Institute, University of
Colorado School of Medicine, Denver, 80041, USA.

PURPOSE: To investigate the efficacy of intravitreal triamcinolone as treatment
for macular oedema in central retinal vein occlusion (CRVO). METHODS: We
conducted a retrospective comparative case series of nine patients with macular
oedema associated with CRVO (six non-ischaemic and three ischaemic) treated with 
an intravitreal injection of 4 mg triamcinolone acetonide, compared with 10
control (observation) patients (six non-ischaemic and four ischaemic).
Examination included visual acuity (VA) tests and complete ophthalmic
examinations at baseline, 1, 2 and 6 months postoperatively. RESULTS: The mean
baseline VA was 20/161 for CRVO treatment group patients and 20/75 for
observation group patients (p = 0.15). No significant difference in VA between
CRVO treatment group patients (20/99) and controls (20/282) was observed at the
final 6-month visit (p = 0.33). Subgroup analysis of the non-ischaemic CRVO
treatment patients compared with the non-ischaemic controls also showed no
significant difference at the 6-month visit (20/59 and 20/100, respectively; p = 
0.20). At 6 months, five of the six non-ischaemic treated patients had VA >or=
20/100, compared with five of the six non-ischaemic control patients. All
patients tolerated the procedure well, but there was a significant increase in
intraocular pressure by the 2-month visit (p = 0.015). CONCLUSIONS: Intravitreal 
injection of triamcinolone may not be effective for treatment of macular oedema
in all CRVO patients or all non-ischaemic CRVO patients. A trend towards VA
improvement was noted but was not statistically significant. Although our
treatment was not hindered by severe complications, there was a significant
increase in IOP in the 2 months following treatment.

PMID: 16704690 [PubMed - indexed for MEDLINE]

1465: Acta Ophthalmol Scand. 2006 Jun;84(3):296-300.

A 3-dimensional evaluation of the macular region: comparing digitized and
film-based media with a clinical evaluation.

Knudsen LL, Skriver K.

Department of Ophthalmology, Aarhus University Hospital, Aalborg, Denmark.
ul9204@aas.nja.dk

PURPOSE: To compare the results of stereoscopic macular evaluations using three
different types of stereoscopic photographic equipment with those of a clinical
examination when establishing the presence of possible macular oedema. METHODS:
The study involved a clinical evaluation of the macular region in 57 eyes of 30
diabetes subjects with possible macular oedema. Clinical examinations were
followed by photographic stereoscopic evaluations of the macular region using two
digital systems (low and high resolution) and one film-based system. All the
photographic recordings were classified by two consultants, who were trained in
making macular gradations and blinded to the results of previous assessments.
RESULTS: The low-resolution digital equipment was found to have relatively low
optical resolution and found a significantly lower number of eyes with macular
oedema compared with the clinical examination. The high-resolution digital
equipment and the film-based equipment were found to have relatively high optical
resolution. The number of eyes with macular oedema found by the high-resolution
digital and film-based evaluations was comparable with the number found by the
clinical examination. Low intra- and interobserver agreement was observed.
CONCLUSION: All three photographic systems have disadvantages that make them
suboptimal as tools for evaluating the presence of macular oedema. The film-based
system seems the most reliable, while low-resolution digital equipment seems
least useful. The development of new and objective measurements giving a
3-dimensional presentation of the macular region might be advantageous.

Publication Types: 
    Comparative Study

PMID: 16704686 [PubMed - indexed for MEDLINE]

1466: Eur J Ophthalmol. 2006 Mar-Apr;16(2):335-8.

Occurrence of full-thickness macular hole complicating Stargardt disease with
ABCR mutation.

Sodi A, Bini A, Passerini I, Menchini U, Torricelli F.

Department of Oto-Neuro-Ophthalmological Surgical Sciences, Eye Clinic, Firenze, 
Italy.

PURPOSE: To report an unusual episode of full-thickness macular hole complicating
Stargardt disease with an ABCR mutation. METHODS: Case report . RESULTS: Fundus
examination of a 20-year-old healthy man showed typical fundus manifestation with
yellowish-round or fish-like flecks associated with vitreous macular adhesion and
a round punched-out area in the right eye. Optical coherence tomography (OCT)
illustrated a full-thickness macular hole. Molecular genetic examination of the
ABCR gene showed two heterozygous missense mutations: R1108C (CGC-->TGC) in exon 
22 and a splicing mutation IVS6--> 1GT - described in the literature in
association with Stargardt disease. CONCLUSIONS: Macular hole was once described 
in other inherited retinal degenerations (Best disease and Bietti crystal line
retinopathy). The pathogenesis gives rise to a host of speculations: widespread
alteration of the retinal pigment epithelium; inflammatory mechanisms; a minor
trauma which might cause subretinal fibrosis. Surgical procedures were not
performed on our patient after his ophthalmologic history and findings were
considered.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 16703556 [PubMed - indexed for MEDLINE]

1467: Eur J Ophthalmol. 2006 Mar-Apr;16(2):287-94.

Preoperative factors influencing visual outcome following surgical excision of
subfoveal choroidal.

Shimada H, Fujita K, Matsumoto Y, Mori R, Yuzuwa M.

Department of Ophthalmology, Surugadai Hospital of Nihon University, Tokyo,
Japan. sshimada@med.nihon-u.ac.jp

PURPOSE: To evaluate long-term visual acuity outcomes and the influences of
various preoperative factors on visual outcome in patients undergoing surgical
removal of choroidal neovascular neovascularization (CNV) caused by age-related
macular degeneration (ARMD). METHODS: The authors studied 146 eyes of 146
patients who were followed for at least 1 year after surgical excision of CNV
associated with ARMD. Surgical indications included subfoveal active CNV
localized mainly above the retinal pigment epithelium (RPE) and a standard
Japanese decimal visual acuity of 0.3 or worse. CNV above the RPE was diagnosed
by fluorescein angiography, indocyanine green angiography, and optical coherence 
tomography. CNVs were divided into completely classic CNV or mainly classic CNV. 
The relationships of the post-operative logarithm of the minimum angle of
resolution (logMAR) visual acuity with preoperative logMAR visual acuity, the
shortest distance from the center of the foveal avascular zone to the CNV margin,
CNV size, and age were analyzed. RESULTS: Final logMAR visual acuity was improved
(defined as a logMAR visual acuity increase of 0.2 or more) in 78 eyes (54%),
stable in 47 (32%), and worsened in 21 (14%). Stepwise regression identified CNV 
size as a significant factor influencing final logMAR visual acuity (R2 = 0.213, 
p<0.0001), while preoperative logMAR visual acuity, shortest distance from the
center of the foveal avascular zone to the CNV margin, and age showed no
significant correlation with final logMAR visual acuity. Surgical complications
included retinal detachment in six eyes (4%), subretinal hematoma in four eyes
(2%), macular hole in three (2%), and proliferative vitreoretinopathy in two
(1%). CNV recurred postoperatively in 18 eyes (12%). In 92 eyes with completely
classic CNV, visual acuity was improved in 57 (62%), stable in 27 (29%), and
worsened in 8 (9%). In 54 eyes with mainly classic CNV, visual acuity was
improved in 21(39%), stable in 20 (37%), and worsened in 13 (24%). CONCLUSIONS:
Surgical excision of CNV for ARMD was effective for completely classic CNV, and
better postoperative visual acuity was achieved in cases of small CNV. Given the 
fact that photodynamic therapy (PDT) has only been used in Japan since 2004,
future study should compare PDT and surgical excision in Japanese subjects for
relative merits against surgical risk and postoperative complications, to define 
indications for PDT and surgical excision.

Publication Types: 
    Case Reports

PMID: 16703548 [PubMed - indexed for MEDLINE]

1468: Eye. 2007 Aug;21(8):1067-70. Epub 2006 May 12.

Prognostic factors for visual acuity improvement after intravitreal triamcinolone
injection.

Shulman S, Ferencz JR, Gilady G, Ton Y, Assia E.

Department of Ophthalmology, Sapir Medical Center, Meir Hospital, Kfar Saba,
Israel. shirishu@aol.com

PURPOSE: In some patients with macular oedema, intravitreal triamcinolone
acetonide injection (IVTA) fails to improve visual acuity, although oedema shows 
clinical and angiographic improvement. Side effects can include increased
intraocular pressure, cataract development, and (rarely) endophthalmitis. Our
purpose was to identify prognostic factors for visual acuity improvement after
IVTA. METHODS: Data on patients treated by IVTA for macular oedema were
retrospectively reviewed. Three months postinjection, visual acuity was rated as 
'improved' (two or more Snellen lines gained) or 'nonimproved' (unchanged or
worsened). Comparative demographic data and pre- and post-IVTA clinical and
fluorescein angiographic findings were analysed with SPSS software. RESULTS: Of
57 eyes (57 patients), 27 (47%) improved after IVTA. Initial visual acuity
('good', 'moderate', or 'poor') and aetiology of macular oedema (diabetic, venous
occlusion, or pseudophakic) did not differ between the two groups. Improvement
occurred in significantly more eyes with clinical or angiographic evidence of
cystoid macular oedema (CME) than in those with diffuse retinal thickening
(P=0.04) or diffuse leakage on fluorescein angiography (P=0.02), respectively,
and in significantly more pseudophakic than phakic eyes (P=0.046). Conclusions:
Pseudophakia and clinical or angiographic CME, but not aetiology or initial
visual acuity, were prognostic of visual acuity improvement after IVTA for
macular oedema.

Publication Types: 
    Review

PMID: 16691251 [PubMed - indexed for MEDLINE]

1469: Arch Ophthalmol. 2006 May;124(5):660-4.

Occult with no classic subfoveal choroidal neovascular lesions in age-related
macular degeneration: clinically relevant natural history information in larger
lesions with good vision from the Verteporfin in Photodynamic Therapy (VIP)
Trial: VIP Report No. 4.

Pieramici DJ, Bressler SB, Koester JM, Bressler NM.

OBJECTIVE: To determine whether data from patients with age-related macular
degeneration (AMD) assigned to the placebo group in the Verteporfin in
Photodynamic Therapy (VIP) Trial provide a rationale for continuation or
cessation of follow-up of individuals with subfoveal occult choroidal
neovascularization (CNV) with no classic lesions, presumed recent disease
progression, larger lesion size (>4 disc areas), and a higher level of visual
acuity (approximate Snellen equivalent, > or =20/50 in the affected eye) in whom 
no treatment is given at initial examination. METHODS: In a prospective,
noncomparative case series, angiograms of participants assigned to a placebo
group who had occult with no classic lesion composition at baseline were reviewed
to identify conversion to minimally classic (area of classic CNV >0% but <50% of 
the entire lesion area) or predominantly classic (area of classic CNV > or =50%
of the entire lesion area) composition. RESULTS: Of the 114 patients with AMD
assigned to the placebo group, 89 were judged to have occult with no classic
lesion composition at baseline in the study eye when fluorescein angiograms were 
reviewed in late 2001 for this report. By 24 months, 7 (8%) of the 89 patients
had lesions that converted to predominantly classic composition, and 41 (46%) had
minimally classic composition. Among the 24 patients with a baseline visual
acuity better than 20/50(-1) and lesion size greater than 4 disc areas whose
lesions did not convert to predominantly classic composition, the visual acuity
of 18 (75%) dropped below 20/50. Six of these 18 continued to have occult with no
classic CNV with a visual acuity of 20/100 or better and had a lesion size no
greater than 9 disc areas at the time that visual acuity dropped below 20/50.
CONCLUSIONS: Continued monitoring, rather than cessation of follow-up, is
recommended for patients with occult with no classic lesions, similar to those
patients enrolled in the VIP Trial who did not initially receive treatment when
they had relatively large lesions with good visual acuity. In these cases, if
visual acuity decreases or predominantly classic features develop, photodynamic
therapy with verteporfin or pegaptanib sodium injections may be considered.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16682587 [PubMed - indexed for MEDLINE]

1470: Arch Ophthalmol. 2006 May;124(5):653-8.

Macular grid photocoagulation after intravitreal triamcinolone acetonide for
diffuse diabetic macular edema.

Kang SW, Sa HS, Cho HY, Kim JI.

Department of Ophthalmology, Samsung Medical Center, Sungkyunkwan University
School of Medicine, Seoul 135-710, Korea. swkang@smc.samsung.co.kr

OBJECTIVE: To evaluate the clinical outcomes of macular laser photocoagulation
after the intravitreal injection of 4 mg of triamcinolone acetonide (IVTA) for
diffuse diabetic macular edema (DME). METHODS: Eighty-six eyes of 74 patients
with diffuse DME were randomized into 2 groups. The laser group eyes (n = 48)
were subjected to a macular grid laser photocoagulation 3 weeks after IVTA. The
control group eyes (n = 38) underwent only IVTA. Both groups were compared with
regard to the changes in visual acuity and central macular thickness at 3 weeks, 
3 months, and 6 months after IVTA. RESULTS: The mean central macular thickness
before, 3 weeks after, and 3 and 6 months after IVTA were 538, 250, 295, and 301 
mum in the laser group vs 510, 227, 302, and 437 mum in the control group,
respectively. The logMAR visual acuities were not significantly different between
the 2 groups at baseline and at 3 weeks after IVTA but were significantly better 
in the laser group at 3 (P = .02) and 6 months (P<.001) after IVTA. CONCLUSIONS: 
Macular laser coagulation effectively maintains improved visual acuity after IVTA
for diffuse DME and is believed to reduce recurrent DME after IVTA.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16682586 [PubMed - indexed for MEDLINE]

1471: Exp Eye Res. 2006 Sep;83(3):638-50. Epub 2006 May 8.

Different death stimuli evoke apoptosis via multiple pathways in retinal pigment 
epithelial cells.

Ferrington DA, Tran TN, Lew KL, Van Remmen H, Gregerson DS.

Department of Ophthalmology, University of Minnesota, 380 Lions Research
Building, 2001 6th Street SE, Minneapolis, MN 55455, USA. ferri013@umn.edu

Loss of retinal pigment epithelial (RPE) cells via apoptosis plays a prominent
role in several retinal degenerative diseases, such as age-related macular
degeneration, and with light damage. Strategies for preservation of vision that
would interrupt the apoptotic cascade require understanding the molecular events 
associated with apoptosis. This study investigated the susceptibility of RPE to
caspase-dependent and -independent apoptotic pathways when challenged with
different stimuli, including oxidants, anti-Fas antibody, and activated cytotoxic
T lymphocytes (CTLs). These experiments used novel RPE cell lines developed from 
wildtype and heterozygous mice with reduced levels of either Mn superoxide
dismutatse (SOD) or CuZnSOD. Peroxide and 4-hydroxynonenal induced apoptosis
through both caspase-independent and -dependent pathways, respectively. With both
oxidants, translocation of apoptosis inducing factor into the nucleus was
observed. Cells containing reduced levels of CuZnSOD were the most susceptible to
oxidant-induced cell death. Targeted killing by CTLs and activation of the Fas
death receptor induced caspase-dependent apoptosis. These results show
stimulus-specific activation of either the caspase-dependent or -independent
pathway. Since cultured RPE express the protein components required for different
apoptotic pathways, they provide a good model system for studying molecular
events associated with multiple signals that lead to cell death.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, Non-P.H.S.

PMID: 16682026 [PubMed - indexed for MEDLINE]

1472: Bull Soc Belge Ophtalmol. 2006;(299):57-64.

Photodynamic therapy with verteporfin in Belgian patients with subfoveal
choroidal neovascularization secondary to age-related macular degeneration.

Mori R, Kelkar A, De Laey JJ.

Department of Ophthalmology, Nihon University School of medicine, Tokyo, Japan.

This is a retrospective, uncontrolled study of 55 patients (61 eyes) treated
between January 2002 and January 2004 with Photodynamic Therapy with Verteporfin 
for subfoveal choroidal neovascularization (CNV) secondary to age-related macular
degeneration. The eyes were divided into three groups: predominantly classic CNV 
(21 eyes), minimally classic CNV (7) and occult with no classic CNV (4 eyes). For
31 patients (32 eyes) the follow-up period was at least one year. The following
parameters were studied: visual acuity, progression of the CNV, and activity of
the CNV expressed as leakage on fluorescein angiography and edema on OCT. In the 
group of predominantly classic CNV at 12 month the treatment resulted in an
inactive lesion in 43% of the eyes, however in 48% the visual acuity had
decreased. For the group of minimally classic CNV, regression of activity was
noted in 71% but vision further decreased in 57%. In the group of occult with no 
classic CNV one eye developed classic CNV, whereas the lesion regressed on 3
eyes. Two of the 4 eyes lost vision. These results suggest that although PDT is
capable of stabilizing the lesion, further visual loss is to be expected in a
large number of patients.

PMID: 16681088 [PubMed - indexed for MEDLINE]

1473: J Med Assoc Thai. 2005 Nov;88 Suppl 9:S143-50.

Sheathotomy without separation of venule overlying arteriole at occlusion site in
uncommon branch retinal vein occlusion.

Rodanant N, Thoongsuwan S.

Department of Ophthalmology, Siriraj Hospital, Faculty of Medicine, Mahidol
University, 2 Prannok Rd, Bangkoknoi, Bangkok 10700, Thailand.
rodanant@hotmail.com

Two cases of uncommon branch retinal vein occlusion (BRVO) with vein overlying
artery at occlusion site that can be found in less than 1% who underwent retinal 
venule sheathotomy without separation of retinal vessel for decompression of BRVO
were reported. Both patients had macular hemorrhage, edema, and area of macular
capillary nonperfusion. Visual acuity (VA) worsened to 6/60 in both cases. The
retinal venules were dissected around the crossing site without separation of
retinal vessels. Intraoperative dilation, pulsation and restoration of downstream
blood flow of the involved venules were observed. In the first patient, at 1 day,
2 weeks, and 6 weeks postoperatively, VA improved to 6/36, 6/9, and 6/6,
respectively, and remained unchanged at 12 months postoperatively. In the second 
patient, VA improved to 6/24 on the first day postoperatively and improved to
6/18 at 1 week follow up and continuously improved to nearly normal at 2 months
postoperatively then patient lost contact. Postoperative fundus fluorescein
angiogram showed dilated and improved perfusion with decreased macular edema in
both cases. Optical coherent tomography confirmed remarkable reduction of retinal
thickness (from 874 microns preoperatively to 420 microns at 1 week
postoperatively) in the second patient. Retinal venule sheathotomy without
separation of retinal vessel for decompression of BRVO with venule overlying
arteriole at occlusion site could be effective for improving VA and decreased
macular edema.

Publication Types: 
    Case Reports

PMID: 16681068 [PubMed - indexed for MEDLINE]

1474: J Med Assoc Thai. 2005 Nov;88 Suppl 9:S51-6.

The fundoscopic features for differentiation between polypoidal choroidal
vasculopathy and choroidal neovascularization from age-related macular
degeneration.

Ampornpruet A, Ruamviboonsuk P, Kokekhuntod S.

Department of Ophthalmology, Rajavithi Hospital, Bangkok 10400, Thailand.

OBJECTIVES: To evaluate the fundus features that can differentiate polypoidal
choroidal vasculopathy (PCV) from choroidal neovascularization (CNV) due to
age-related macular degeneration (AMD). DESIGN: Retrospective, case-control
study. MATERIAL AND METHOD: The fundoscopic features of AMD-related CNV and PCV
were compared for evaluation of relative risks for PCV. The odds ratio,
sensitivity and specificity of each feature were also calculated. RESULTS: A
total of 30 patients, 15 PCV and 15 age-matched non-PCV cases, approved by
indocyanine green angiography (ICG), were enrolled. The odds ratio is highest for
subretinal polyp-like structure and lowest in scar formation (28 and 0,
respectively) and these ratios are statistically significant differences (p =
0.001 and 0.032 respectively). The ratio for either circinate exudates, or larger
than 4-disc area of subretinal fluid, or retinal pigment epithelial detachment is
1.75. The ratio for peripapillary location is 1.63. Subretinal membrane has a
ratio of 1 while subretinal hemorrhage and subretinal fibrin have less than 1;
they are 0.31 and 0.23 respectively. All these ratios are not statistically
significant differences (p > 0.05). CONCLUSION: The orange polyp-like structures 
beneath retina are hallmarks for diagnosis of PCV. The "serosanguineous
retinopathy", described as serous retinal deatchment or retinal pigment
epithelial detachment with circinate exudates with or without subretinal
hemorrhage at the posterior pole or peripapillary region, may also suggest the
condition.

Publication Types: 
    Comparative Study

PMID: 16681052 [PubMed - indexed for MEDLINE]

1475: Eye. 2007 Jun;21(6):689-96. Epub 2006 May 5.

Functional loss in early age-related maculopathy: the ischaemia postreceptoral
hypothesis.

Feigl B, Brown B, Lovie-Kitchin J, Swann P.

Institute of Health and Biomedical Innovation, School of Optometry, Queensland
University of Technology, Brisbane, Queensland, Australia. b.feigl@qut.edu.au

We review proposed models and psychophysical and electrophysiological tests
performed in many studies for early age-related maculopathy (ARM). We suggest
that ischaemia is the trigger for impaired retinal pigment epithelium function
causing imbalance of secretion of vascular growth factors, reduced disc
degradation capability and reduced metabolic activity and possible inflammatory
response. This results in increased deposition of cell debris, such as drusen and
thickens Bruch's membrane causing even more ischaemia of the overlying
neurosensory retina. The photoreceptors are more resistant to ischaemia given
their proximity to the choroid. Furthermore, being 'upstream' from the inner
retinal layers, they act as an oxygen sink depriving retinal layers further from 
the choroid. Postreceptoral cell layers and especially parts of the inner nuclear
layer that are located in the watershed zone between two sources of blood supply 
are preferentially vulnerable to ischaemia. Based on psychophysical and
electrophysiological findings we propose that most of the function impairment in 
early ARM starts postreceptorally.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 16680100 [PubMed - indexed for MEDLINE]

1476: Ophthalmologica. 2006;220(3):147-52.

Long-term outcome after vitrectomy for diabetic macular edema.

Kralinger MT, Pedri M, Kralinger F, Troger J, Kieselbach GF.

Department of Ophthalmology, University of Innsbruck, Medical School, Innsbruck, 
Austria. martina.kralinger@uibk.ac.at

BACKGROUND: To determine the benefit of vitrectomy on eyes with diabetic macular 
edema. METHODS: A retrospective institutional case series was used including 66
patients (69 eyes) who had undergone pars plana vitrectomy for diabetic macular
edema between 1992 and 2000. Prior to surgery, the patients had been treated with
laser coagulation as recommended by the Early Treatment Diabetic Retinopathy
Study. In the case of persistent macular edema, vitrectomy with removal of the
posterior hyaloid in all cases and the inner limiting mem brane in 51 (74%) of
all cases was performed. RESULTS: The mean preoperative best-corrected visual
acuity improved from 20/320 to 20/80 at the time of best postoperative
best-corrected visual acuity (p < 0.0001). The mean increase in Snellen lines was
2.7 +/- 7.9. In 90% of eyes, the macular edema improved. A persistence of the
edema was observed in 10%. All eyes had at least 12 months of follow-up with a
mean of 55 months and a maximum of 120 months. CONCLUSIONS: Our findings confirm 
that vitrectomy might represent a therapeutic alternative in the case of
persisting diabetic macular edema after laser photocoagulation.

Publication Types: 
    Comparative Study

PMID: 16679787 [PubMed - indexed for MEDLINE]

1477: Am J Ophthalmol. 2006 May;141(5):976-8.

Indocyanine green angiography abnormality of the periphery in vitelliform macular
dystrophy.

Maruko I, Iida T, Spaide RF, Kishi S.

Department of Ophthalmology, Fukushima Medical University School of Medicine, 1
Hikarigaoka, Fukushima, Japan.

PURPOSE: To report the peripheral abnormalities seen only with indocyanine green 
angiography in patients with vitelliform macular dystrophy (Best disease, caused 
by a mutation in the bestrophin gene). DESIGN: Observational case report series. 
METHODS: Eight eyes of four patients, two with only a central macular lesion and 
two with multifocal lesions, were studied. Results of indocyanine green
angiography were compared with findings from ophthalmoscopy and fluorescein
angiography. RESULTS: Throughout the fundus periphery, indocyanine green
angiography demonstrated a number of hyperfluorescent spots in all eight eyes.
The spots were observed in the midperiphery and the periphery in areas with no
abnormality visible by ophthalmoscopy or fluorescein angiography. CONCLUSIONS:
Although Best disease generally causes lesions visible in the posterior pole, the
extensive distribution of the hyperfluorescent spots is consistent with the
wide-ranging abnormalities of the retinal pigment epithelium, Bruch membrane, and
the choroid as seen histopathologically.

Publication Types: 
    Case Reports

PMID: 16678528 [PubMed - indexed for MEDLINE]

1478: Exp Eye Res. 2006 Sep;83(3):615-9. Epub 2006 May 4.

Pegaptanib for the treatment of age-related macular degeneration.

Zhou B, Wang B.

Department of Pharmacology, Nanjing Medical University, 140 Hanzhong Road,
Nanjing 210029, Jiangsu Province, China.

Although neovascular (wet) age-related macular degeneration (AMD) only accounts
for 10-20% of all AMD, the majority (about 90%) of severe vision loss associated 
with AMD is due to this form. Results from recent studies have implied that
vascular endothelial growth factor (VEGF), particularly VEGF(165), plays a
predominant role in the development of ocular neovascularization and vascular
leakage secondary to AMD. Thus VEGF is an important therapeutic target in
neovascular AMD. Pegaptanib, an anti-VEGF aptamer, can selectively bind with
VEGF(165) and inhibit both the growth of blood vessels and vascular leakage, and 
was approved by the Food and Drug Administration in the United States as the
therapy for the treatment of all subtypes of neovascular AMD in December 2004.
This review summaries the mechanism, preclinical and clinical studies, and
adverse events of pegaptanib treatment.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 16678158 [PubMed - indexed for MEDLINE]

1479: Graefes Arch Clin Exp Ophthalmol. 2007 Apr;245(4):490-501. Epub 2006 May 4.

The end of submacular surgery for age-related macular degeneration? A
meta-analysis.

Falkner CI, Leitich H, Frommlet F, Bauer P, Binder S.

Department of Ophthalmology, Rudolf Foundation Clinic, The Ludwig Boltzmann
Institute of Retinology and Biomicroscopic Lasersurgery, Juchgasse 25, 1030,
Vienna, Austria. christiane.falkner@chello.at

BACKGROUND: The aim of this meta-analysis was to summarize and to discuss the
results of the four main submacular surgical procedures for age-related macular
degeneration (AMD) as reported in the literature through 2004 and to compare them
to the Submacular Surgery Trials (SST) data. METHODS: The existing data in the
literature on submacular surgery for AMD from 1992 to 2004 were evaluated. The
main outcomes were proportion of patients with two or more lines of improvement
in visual acuity (VA) and proportion with two or more lines of deterioration in
VA after surgery. RESULTS: Eighty-eight studies including 1,915 cases met the
inclusion criteria. Estimates for the treatment outcome within the four groups of
treatment based on a logistic regression model gave comparable results for
removal of choroidal neovascularization (CNV) (improvement of VA 28%,
deterioration of VA 25%), macular translocation (improvement of VA 31%,
deterioration of VA 27%), and for transplantation of pigment epithelium
(improvement of VA 22%, deterioration of VA 21%). Estimates for removal of
subretinal hemorrhage were significantly different (improvement of VA 62%,
deterioration of VA 13%). CONCLUSIONS: Selected case series showed superior
results of VA compared to the SST. The question of whether this is due to
selection bias that seems inevitable when dealing with medium-sized nonrandomized
case series or due to better results in single centers cannot be answered. In our
opinion there still seem to be indications for submacular surgery such as in
patients with AMD with low preoperative VA due to large hemorrhagic or fibrotic
membranes or nonresponders to photodynamic therapy (PDT).

Publication Types: 
    Meta-Analysis

PMID: 16673139 [PubMed - indexed for MEDLINE]

1480: Clin Experiment Ophthalmol. 2006 Apr;34(3):282-3.

Correlation study between optical coherence tomography and fluorescein
angiography in post-membrane peeling recalcitrant macular oedema.

Liu DT, Lee VY, Kwok MK, Chan WM, Lam DS.

Correlation between optical coherence tomography and fluorescein angiography in a
post-membrane peeling patient indicated a surgically disturbed retinal vessel as 
the cause of recalcitrant macular oedema.

Publication Types: 
    Case Reports
    Letter

PMID: 16671913 [PubMed - indexed for MEDLINE]

1481: Clin Experiment Ophthalmol. 2006 Apr;34(3):226-32.

Visual function following transpupillary thermotherapy with adjusted laser
parameters for the treatment of exudative age-related macular degeneration: a
pilot study.

Tranos P, Peter NM, Nath R, Singh MV, Wren S, Dimitrakos S, Rassam S, Kon C.

Worthing General Hospital, Worthing, UK.

PURPOSE: To evaluate the efficacy of transpupillary thermotherapy (TTT) using
adjusted laser parameters for the treatment of choroidal neovascularization (CNV)
secondary to age-related macular degeneration. METHODS: TTT was performed on
patients with CNV using a diode laser (810 nm) for 60 s in a subthreshold manner.
Power settings were varied between 460 and 1200 mW, depending on lesion size,
presence of pigment epithelial detachment and the amount of fundal pigmentation
and subretinal fluid. LogMAR visual acuity, contrast sensitivity (Pelli-Robson)
and metamorphopsia (Amsler chart) were assessed prior to and 6 months following
treatment. Subjects also self-administered the National Eye Institute 25-Item
Visual Function Questionnaire. RESULTS: Thirty occult/minimally classic and eight
predominantly classic membranes were treated with TTT. At 6 months, absence or
significant reduction of fluorescein leakage was observed in 20 (53%) patients.
Stabilization of vision (loss of less than 15 letters) was observed in 25/30
(83%) eyes with occult/minimally classic CNV and 5/8 (63%) eyes with
predominantly classic CNV. Improvement of contrast sensitivity was noted in 15
(35%) eyes, in 10 (26%) eyes it remained unchanged and in 13 (34%) eyes it
deteriorated. There was no statistically significant effect of TTT on the
National Eye Institute 25-Item Visual Function Questionnaire composite or
subscale scores. CONCLUSIONS: TTT using adjusted parameters depending on fundal
characteristics appears to be effective in stabilizing subjective and objective
visual ability in a considerable number of patients with subfoveal CNV due to
age-related macular degeneration. Larger-scale studies are required to confirm
the benefit of this technique as opposed to the natural history of occult CNV.

Publication Types: 
    Clinical Trial

PMID: 16671902 [PubMed - indexed for MEDLINE]

1482: Med Res Rev. 2006 Jul;26(4):483-530.

Anti-angiogenic drugs: from bench to clinical trials.

Quesada AR, Muñoz-Chápuli R, Medina MA.

Department of Molecular Biology and Biochemistry, Faculty of Science, University 
of Málaga, 29071 Málaga, Spain. quesada@uma.es

Angiogenesis, the generation of new capillaries through a process of pre-existing
microvessel sprouting, is under stringent control and normally occurs only during
embryonic and post-embryonic development, reproductive cycle, and wound repair.
However, in many pathological conditions (solid tumor progression, metastasis,
diabetic retinopathy, hemangioma, arthritis, psoriasis and atherosclerosis among 
others), the disease appears to be associated with persistent upregulated
angiogenesis. The development of specific anti-angiogenic agents arises as an
attractive therapeutic approach for the treatment of cancer and other
angiogenesis-dependent diseases. The formation of new blood vessels is a complex 
multi-step process. Endothelial cells resting in the parent vessels are activated
by an angiogenic signal and stimulated to synthesize and release degradative
enzymes allowing endothelial cells to migrate, proliferate and finally
differentiate to give rise to capillary tubules. Any of these steps may be a
potential target for pharmacological intervention. In spite of the disappointing 
results obtained initially in clinical trials with anti-angiogenic drugs, recent 
reports with positive results in phases II and III trials encourage expectations 
in their therapeutic potential. This review discusses the current approaches for 
the discovery of new compounds that inhibit angiogenesis, with emphasis on the
clinical developmental status of anti-angiogenic drugs. Copyright 2006 Wiley
Periodicals, Inc.

Publication Types: 
    Review

PMID: 16652370 [PubMed - indexed for MEDLINE]

1483: Hum Mutat. 2006 Jun;27(6):568-74.

Reduced secretion of fibulin 5 in age-related macular degeneration and cutis
laxa.

Lotery AJ, Baas D, Ridley C, Jones RP, Klaver CC, Stone E, Nakamura T, Luff A,
Griffiths H, Wang T, Bergen AA, Trump D.

Human Genetics Division, University of Southampton, Southampton, Hampshire,
United Kingdom. a.j.lotery@soton.ac.uk

Age-related macular degeneration (ARMD) is the leading cause of irreversible
visual loss in the Western world, affecting approximately 25 million people
worldwide. The pathogenesis is complex and missense mutations in FBLN5 have been 
reported in association with ARMD. We have investigated the role of fibulin 5 in 
ARMD by completing the first European study of the gene FBLN5 in ARMD (using 2
European cohorts of 805 ARMD patients and 279 controls) and by determining the
functional effects of the missense mutations on fibulin 5 expression. We also
correlated the FBLN5 genotype with the ARMD phenotype. We found two novel
sequence changes in ARMD patients that were absent in controls and expressed
these and the other nine reported FBLN5 mutations associated with ARMD and two
associated with the autosomal recessive disease cutis laxa. Fibulin 5 secretion
was significantly reduced (P<0.001) for four ARMD (p.G412E, p.G267S, p.I169 T,
and p.Q124P) and two cutis laxa (p.S227P, p.C217R) mutations. These results
suggest that some missense mutations associated with ARMD lead to decreased
fibulin 5 secretion with a possible corresponding reduction in elastinogenesis.
This study confirms the previous work identifying an association between FBLN5
mutations and ARMD and for the first time suggests a functional mechanism by
which these mutations can lead to ARMD. It further demonstrates that FBLN5
mutations can be associated with different phenotypes of ARMD (not limited to the
previously described cuticular drusen type). Such knowledge may ultimately lead
to the development of novel therapies for this common disease. Copyright 2006
Wiley-Liss, Inc.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16652333 [PubMed - indexed for MEDLINE]

1484: Ophthalmology. 2006 May;113(5):841-7.e3.

Hypotrichosis with juvenile macular dystrophy: clinical and electrophysiological 
assessment of visual function.

Leibu R, Jermans A, Hatim G, Miller B, Sprecher E, Perlman I.

Department of Ophthalmology, Rambam Medical Center, Haifa, Israel.

PURPOSE: To evaluate retinal function in subjects suffering from hypotrichosis
with juvenile macular dystrophy (HJMD). DESIGN: Retrospective case-control study.
PARTICIPANTS: Sixteen HJMD patients belonging to 2 genetic groups and 20 control 
subjects. METHODS: The HJMD patients underwent clinical ophthalmological
examination and electrophysiological testing for a period of as many as 14 years.
The electroretinogram (ERG), electro-oculogram (EOG), and visual evoked potential
(VEP) were recorded serially to assess visual function and to follow possible
progression of the disease. MAIN OUTCOME MEASURES: Amplitudes and implicit times 
of ERG and VEP, and Arden ratio of EOG. RESULTS: Fundus examination revealed
pigmentary abnormalities with atrophic changes at the posterior pole extending to
regions beyond the macular area. A slow and time-dependent decline in visual
acuity was noted. The ERG responses were subnormal in amplitude. The ERG deficit 
was similar for light- and dark-adapted responses. There was a gradual but
consistent decrease in the ERGs with time. The EOG measurements were within the
normal range. Pattern reversal VEPs were very subnormal, even in patients with
mild deterioration of visual acuity. The flash VEPs were of slightly subnormal
amplitudes and implicit times in the upper limit of the normal range.
CONCLUSIONS: The fundus pictures and electrophysiological tests were consistent
with retinal involvement extending beyond the macular region. Follow-up of visual
acuity and ERG testing indicated a slowly progressing retinal disorder affecting 
cone-mediated vision as well as rod-mediated vision. Therefore, we suggest that a
more appropriate name for this syndrome is hypotrichosis with cone-rod dystrophy.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16650681 [PubMed - indexed for MEDLINE]

1485: Ophthalmology. 2006 Jun;113(6):992-1001.e6. Epub 2006 Apr 27.

Pegaptanib sodium for neovascular age-related macular degeneration: two-year
safety results of the two prospective, multicenter, controlled clinical trials.

VEGF Inhibition Study in Ocular Neovascularization (V.I.S.I.O.N.) Clinical Trial 
Group, D'Amico DJ, Masonson HN, Patel M, Adamis AP, Cunningham ET Jr, Guyer DR,
Katz B.

Department of Ophthalmology, Harvard Medical School, Retina Service,
Massachusetts Eye and Ear Infirmary, 243 Charles Street, Boston, MA 02114, USA.
djdamico@meei.harvard.edu

OBJECTIVE: To evaluate the safety of pegaptanib sodium injection, a specific
vascular endothelial growth factor (VEGF) antagonist, in the treatment of
neovascular age-related macular degeneration (AMD) during 2 years of therapy.
DESIGN: Two concurrent, prospective, randomized, multicenter, double-masked,
sham-controlled studies. METHODS: Patients with all angiographic choroidal
neovascularization lesion compositions of AMD received either intravitreous
pegaptanib sodium (0.3 mg, 1 mg, 3 mg) or sham injections every 6 weeks for 54
weeks. Those initially assigned to pegaptanib were re-randomized (1:1) to
continue or discontinue therapy for 48 more weeks; sham-treated patients were
re-randomized (1:1:1:1:1) to continue sham, discontinue, or receive one of the
pegaptanib doses. MAIN OUTCOME MEASURES: All reported adverse events, serious
adverse events, and deaths. PARTICIPANTS: In year 1, 1190 subjects received at
least one study treatment (0.3 mg, n = 295; 1 mg, n = 301; 3 mg, n = 296; sham, n
= 298); 7545 intravitreous injections of pegaptanib were administered. In year 2,
425 subjects (0.3 mg, n = 128; 1 mg, n = 126; 3 mg, n = 120; sham, n = 51)
continued the same masked treatment as in year 1 and received at least one study 
treatment in year 2; 2663 intravitreous injections of pegaptanib were
administered in these subjects. RESULTS: All doses of pegaptanib were well
tolerated. The most common ocular adverse events were transient, mild to moderate
in intensity, and attributed to the injection preparation and procedure. There
was no evidence of an increase in deaths, in events associated with systemic VEGF
inhibition (e.g., hypertension, thromboembolic events, serious hemorrhagic
events), or in severe ocular inflammation, cataract progression, or glaucoma in
pegaptanib-treated patients relative to sham-treated patients. In year 1, serious
injection-related complications included endophthalmitis (12 events,
0.16%/injection), retinal detachment (RD) (6 events [4 rhegmatogenous, 2
exudative], 0.08%/injection), and traumatic cataract (5 events, 0.07%/injection).
Most cases of endophthalmitis followed violations of the injection preparation
protocol. In patients receiving pegaptanib for >1 year, there were no reports of 
endophthalmitis or traumatic cataract in year 2; RD was reported in 4 patients
(all rhegmatogenous, 0.15%/injection). CONCLUSION: The 2-year safety profile of
pegaptanib sodium is favorable in patients with exudative AMD.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16647134 [PubMed - indexed for MEDLINE]

1486: Ophthalmology. 2006 Jul;113(7):1187.e1-12. Epub 2006 May 2.

Automated detection of clinically significant macular edema by grid scanning
optical coherence tomography.

Sadda SR, Tan O, Walsh AC, Schuman JS, Varma R, Huang D.

Doheny Eye Institute, University of Southern California Keck School of Medicine, 
Los Angeles, California 90033, USA.

OBJECTIVE: To compare the detection of clinically significant diabetic macular
edema (DME) by an optical coherence tomography (OCT) grid scanning protocol and
biomicroscopic examination. DESIGN: Retrospective case series. PARTICIPANTS:
Outpatients at the Doheny Eye Institute. METHODS: The clinical and imaging
records of a consecutive series of 71 eyes of 40 patients referred for DME who
underwent OCT using the both the Macular Grid 5 (MG5) scanning protocol (to allow
a more evenly distributed sampling of points in the macula) and the standard Fast
Macular Thickness Map (FMTM) pattern were reviewed. An automated algorithm was
developed to generate a retinal thickness map using the MG5 data, which was then 
compared with a normative database to identify presumed areas of retinal edema.
Clinically significant macular edema (CSME) was also identified by clinical
examination and stereoscopic fundus photographs for comparison with the results
of the OCT protocols. MAIN OUTCOME MEASURES: Sensitivity and specificity of
scanning protocols. RESULTS: Optical coherence tomograms were inspected visually,
and automatically detected retinal boundaries were found to be correct in 69 of
71 MG5 scans and in 65 of 71 FMTM scans. Macular Grid 5 scanning was performed
twice in each eye, and the repeatability (pooled standard deviation) of the total
area of edema was 0.48 mm2 (coefficient of variation, 6.8%). Sensitivity and
specificity of the MG5 for detection of CSME relative to the clinical examination
were 89% and 86%, respectively, with kappa being 0.74. Macular Grid 5 and FMTM
assessment of foveal CSME also showed good agreement, with kappa being 0.68.
CONCLUSIONS: The analysis algorithm for the OCT MG5 grid scan seems to be
accurate and repeatable. Automated detection of CSME by the MG5 analysis
correlated well with the clinical grading and standard OCT analysis (FMTM).
Macular Grid 5 provides more information regarding the perifoveal macula than
FMTM and may be of value to clinicians in planning treatment and in future
studies of macular edema.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16647123 [PubMed - indexed for MEDLINE]

1487: Med J Aust. 2006 May 1;184(9):455-8.

Modifiable risk factors for age-related macular degeneration.

Guymer RH, Chong EW.

Department of Ophthalmology, Centre for Eye Research Australia, University of
Melbourne, Melbourne, VIC, Australia.

Age-related macular degeneration (AMD) is the leading cause of irreversible
blindness in Australia and other Western countries. As there is no cure for AMD, 
and treatments to stop its progression have met with limited success, there is an
interest in identifying modifiable risk factors to prevent or slow disease
progression. To date, smoking is the only proven modifiable risk factor for AMD. 
Other factors under study include (i) cardiovascular risk factors such as
hypertension, body mass index, and atherosclerosis; and (ii) dietary risk factors
including fat and antioxidant intake, but so far these studies have produced
conflicting results. Dietary fat in relation to AMD has recently attracted media 
attention. Despite very limited work supporting an association between vegetable 
fat and AMD, widespread publicity advocating margarine as a cause of AMD and
encouraging use of butter instead has caused confusion and anxiety among
sufferers of AMD and the general public, as well as concern among health
professionals. The antioxidant carotenoids--lutein and zeaxanthin--found in dark 
green or yellow vegetables exist in high concentrations in the macula and are
hypothesised to play a protective role. Of nine controlled trials of
supplementation with carotenoids and other antioxidants, three suggested that
various combinations of antioxidants and carotenoids were protective. While a
low-fat diet rich in dark green and yellow vegetables is advocated in general,
any specific recommendations regarding certain fats or antioxidant
supplementation and AMD are not based on consistent findings at this stage.

PMID: 16646746 [PubMed - indexed for MEDLINE]

1488: Am J Hum Genet. 2006 May;78(5):852-64. Epub 2006 Mar 20.

Cigarette smoking strongly modifies the association of LOC387715 and age-related 
macular degeneration.

Schmidt S, Hauser MA, Scott WK, Postel EA, Agarwal A, Gallins P, Wong F, Chen YS,
Spencer K, Schnetz-Boutaud N, Haines JL, Pericak-Vance MA.

Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA.
silke.schmidt@duke.edu

We used iterative association mapping to identify a susceptibility gene for
age-related macular degeneration (AMD) on chromosome 10q26, which is one of the
most consistently implicated linkage regions for this disorder. We employed
linkage analysis methods, followed by family-based and case-control association
analyses, using two independent data sets. To identify statistically the most
likely AMD-susceptibility allele, we used the Genotype-IBD Sharing Test (GIST)
and conditional haplotype analysis. To incorporate the two most important known
AMD risk factors--smoking and the Y402H variant of the complement factor H gene
(CFH)--we used logistic regression modeling to test for gene-gene and
gene-environment interactions in the case-control data set and used the
ordered-subset analysis to account for genetic linkage heterogeneity in the
family-based data set. Our results strongly implicate a coding change (Ala69Ser) 
in the LOC387715 gene as the second major identified AMD-susceptibility allele,
confirming earlier suggestions. This variant's effect on AMD is statistically
independent of CFH and is of similar magnitude to the effect of Y402H. The
overall effect is driven primarily by a strong association in smokers, since we
observed significant evidence for a statistical interaction between the LOC387715
variant and a history of cigarette smoking. This gene-environment interaction is 
supported by statistically independent family-based and case-control analysis
methods. We estimate that CFH, LOC387715, and cigarette smoking together explain 
61% of the population-attributable risk (PAR) of AMD. The adjusted PAR percentage
estimates are 20% for smoking, 36% for LOC387715, and 43% for CFH. We
demonstrate, for the first time, that a genetic susceptibility coupled with a
modifiable lifestyle factor such as cigarette smoking confers a significantly
higher risk of AMD than either factor alone.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 16642439 [PubMed - indexed for MEDLINE]

1489: Graefes Arch Clin Exp Ophthalmol. 2006 Dec;244(12):1565-74.

Comment in:
    Graefes Arch Clin Exp Ophthalmol. 2006 Dec;244(12):1562-4.

Macular pigment optical density measurement in autofluorescence imaging:
comparison of one- and two-wavelength methods.

Trieschmann M, Heimes B, Hense HW, Pauleikhoff D.

Department of Ophthalmology, St. Franziskus Hospital Münster, Münster, Germany.
meiketri@aol.com

BACKGROUND: Measurement of macular pigment (MP) can be performed by analysis of
autofluorescence (AF) images. These can be obtained by standard 488-nm
argon-imaging alone (one wavelength, 1-Lambda) or with additional digital
subtraction of a second image at 514 nm (two wavelengths, 2-Lambda). The analyses
are easy to perform, and we present a comparison of both methods and investigate 
their reliability and repeatability. METHODS: Inter-individual variability of MP 
optical density (MPOD) measurements was assessed in single eyes of 120 subjects
with a modified Heidelberg retina angiograph (HRA). MPOD values obtained with one
(488 nm) Lambda (MPOD(1Lambda)) were compared with those obtained with two (488
nm and 514 nm) Lambda (MPOD(2Lambda)). To test the repeatability of the two
methods, 20 subjects were subjected to five repeated measurements. RESULTS: Among
120 individuals, mean MPOD(1Lambda) at 0.5 degrees eccentricity was 0.59 (range
0.06-1.32), mean MPOD(2Lambda) was 0.5 (range 0.01-1.21). Apart from this
systematic difference, 1-Lambda and 2-Lambda measurements at 0.5 degrees agreed
well across the range of MPOD values (beta=0.964, around the fovea, a systematic 
difference (0.11) was accompanied by declining agreement at higher MPOD values
(beta=0.669, 95% CI 0.519-0.844; R=0.48). Among 20 subjects with five repeated
measurements, the reliability ratio was 0.97 for 1-Lambda and 0.94 for 2-Lambda
at 0.5 degrees and 0.93 and 0.94, respectively, at a distance of 2 degrees.
CONCLUSIONS: Both methods showed a high repeatability with little influence of
measurement error. They agree well at the fovea centre in terms of ranking
individuals according to their MPOD, but provide increasingly deviating results
at a distance of 2 degrees around the fovea, probably because the 1-Lambda
method, in contrast to the 2-Lambda method, cannot compensate for disruptive
influences and for heterogeneous distributions of the lipofuscin fluorophores.
The 1-Lambda method can be performed by standard HRA and could therefore be used 
for screening in multicentre studies, but only approaches the actual amounts of
MP. The 2-Lambda method remains the more precise method for MPOD measurement in
autofluorescence imaging.

Publication Types: 
    Comparative Study

PMID: 16642363 [PubMed - indexed for MEDLINE]

1490: Invest Ophthalmol Vis Sci. 2006 May;47(5):2135-40.

The iron carrier transferrin is upregulated in retinas from patients with
age-related macular degeneration.

Chowers I, Wong R, Dentchev T, Farkas RH, Iacovelli J, Gunatilaka TL, Medeiros
NE, Presley JB, Campochiaro PA, Curcio CA, Dunaief JL, Zack DJ.

Department of Ophthalmology, Hadassah-Hebrew University Medical Center,
Jerusalem, Israel.

PURPOSE: Iron can cause oxidative stress, and elevated iron levels have been
associated with several neurodegenerative diseases including age-related macular 
degeneration (AMD). Transferrin, an iron transport protein, is expressed at high 
levels in the retina. The purpose of this study was to assess transferrin
involvement in AMD by determining the expression profile of transferrin in
retinas with AMD compared with retinas without evidence of disease. METHODS:
Postmortem retinas were obtained from AMD and non-AMD eyes. Expression of
transferrin was assessed in a microarray dataset from 33 retinas of unaffected
donors and 12 retinas of patients with AMD (six with neovascular AMD and six with
non-neovascular AMD). Quantitative real-time RT-PCR (QPCR) was used to confirm
the microarray results. Transferrin protein expression was assessed by
semiquantitative Western blot analysis and immunohistochemistry. RESULTS: In
comparison to unaffected retinas, mean transferrin mRNA levels, as measured by
microarray analysis were elevated 3.5- and 2.1-fold in non-neovascular and
neovascular AMD retinas, respectively. Semiquantitative Western blot analysis
demonstrated a 2.1-fold increase in transferrin protein in AMD eyes.
Immunohistochemistry showed more intense and widespread transferrin label in AMD 
maculas, particularly in large drusen, Müller cells, and photoreceptors.
CONCLUSIONS: These data demonstrate that transferrin expression is increased in
the retinas of patients with AMD relative to those of healthy control patients of
comparable age. Along with previous studies that have demonstrated elevated iron 
levels in AMD retinas, early onset drusen formation in a patient with retinal
iron overload resulting from aceruloplasminemia, and retinal degeneration with
some features of macular degeneration in the iron-overloaded retinas of
ceruloplasmin/hephestin knockout mice, the present study suggests that altered
iron homeostasis is associated with AMD.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16639025 [PubMed - indexed for MEDLINE]

1491: Exp Eye Res. 2007 Jun;84(6):1135-9. Epub 2006 Apr 25.

A dual Golgi- and mitochondria-localised Ala25Ser precursor cystatin C: an
additional tool for characterising intracellular mis-localisation leading to
increased AMD susceptibility.

Ratnayaka A, Paraoan L, Spiller DG, Hiscott P, Nelson G, White MR, Grierson I.

An artificial mutant Ala25Ser precursor cystatin C was created to help elucidate 
the cause of intracellular mis-localisation of the biochemically related variant 
B (Ala25Thr) precursor cystatin C to the mitochondria. Homozygotes of variant B
precursor cystatin C were reported to carry an increased susceptibility to
developing the exudative form of AMD. Ala25Ser precursor cystatin C shows a dual 
distribution to the Golgi apparatus and to the mitochondria. This localisation is
thus intermediary between that of wild-type cystatin C (targeted to ER/Golgi
compartment) and that of variant B precursor cystatin C. Furthermore, the level
of secretion of Ala25Ser cystatin C by RPE cells is intermediary between wild
type and variant B cystatin C. Ala25Ser precursor cystatin C thus represents a
biochemical intermediate between the wild type and the AMD-associated cystatin C 
and as such, is a novel tool for the investigation of the mechanism of
intracellular mis-localisation of variant B cystatin C. Our findings further
support the hypothesis that substitution of the alanine residue in the
penultimate position of precursor cystatin C signal sequence with a less
hydrophobic amino acid residue, such as threonine (as in variant B cystatin C) or
serine is sufficient to impair the intracellular trafficking and processing of
the protein.

Publication Types: 
    Letter
    Research Support, Non-U.S. Gov't

PMID: 16635487 [PubMed - indexed for MEDLINE]

1492: J Cataract Refract Surg. 2006 Mar;32(3):468-74.

Single perioperative triamcinolone injection versus standard postoperative
steroid drops after uneventful phacoemulsification surgery: Randomized controlled
trial.

Negi AK, Browning AC, Vernon SA.

Ophthalmology Department, Eye and ENT Centre, Queen's Medical Centre University
Hospital, Nottingham, United Kingdom. negianil@doctors.org.uk

PURPOSE: To evaluate the safety and efficacy of a single perioperative
sub-Tenon's injection of triamcinolone following cataract surgery and its effect 
on the incidence of early pseudophakic cystoid macular edema (CME). SETTING:
Ophthalmology Department, Queen's Medical Centre University Hospital, Nottingham.
United Kingdom. METHODS: This prospective randomized controlled trial included 54
eyes (54 patients) having routine cataract surgery. Twenty-seven eyes received
the conventional postoperative care with steroid drops (drops group), whereas the
other 27 were given a perioperative sub-Tenon's injection of triamcinolone
(injection group); 10 of these received 20 mg, and the remaining 17 eyes had 30
mg triamcinolone. All patients were evaluated preoperatively and at days 1, 8,
30, and 90. The outcome measures evaluated were logMAR best corrected visual
acuity (BCVA), anterior chamber flare (Kowa-500 flare meter), intraocular
pressure, and slitlamp biomicroscopy. Oral fluorescein angiograms were performed 
at 30 and 90 days to detect angiographic CME. RESULTS: The mean logMAR BCVA
improved from a baseline of 0.38 +/- 0.38 (SD) and 0.44 +/- 0.26 to 0.02 +/- 0.14
and 0.0 +/- 0.07 at 90 days in the steroid drops and injection groups,
respectively. (P = .59). The mean flare increased from a baseline of 8.9 +/- 3.2 
photons/ms and 8.3 +/- 3.7 photons/ms in the steroid drops and injection groups, 
respectively, to a maximum of +/-14.1 photons/ms and 25.8 +/- 7.5 photons/ms at
day 8. Mean flare decreased to 15.8 +/- 9.7 photons/ms and 13.8 +/- 10.1
photons/ms at 30 days (P = .48, difference between groups) and 10.4 +/- 3.6
photons/ms and 9.8 +/- 3.1 photons/ms at 90 days, respectively, in the 2 groups. 
Subanalysis revealed lowest peak flare (17.9 +/- 7.9 photons/ms) at 8 days in the
group that received 30 mg triamcinolone. CONCLUSIONS: A single sub-Tenon's
injection of 30 mg triamcinolone seem to be safe and effective as a route of
steroid delivery after uneventful phacoemulsification surgery. Larger numbers in 
patients at high risk are required to assess its effectiveness in reducing the
risk for pseudophakic CME.

Publication Types: 
    Randomized Controlled Trial

PMID: 16631060 [PubMed - indexed for MEDLINE]

1493: Clin Experiment Ophthalmol. 2006 Mar;34(2):124-9; quiz 194.

Comment in:
    Clin Experiment Ophthalmol. 2007 Jan-Feb;35(1):105; author reply 105-6.

Correlations between optical coherence tomography measurement of macular
thickness and visual acuity after cataract extraction.

Nicholas S, Riley A, Patel H, Neveldson B, Purdie G, Wells AP.

Ophthalmology Department, Wellington Hospital, Wellington, New Zealand.
simonandkerry@hotmail.com

PURPOSE: To investigate correlations between optical coherence tomography macular
thickness measurements and visual acuity after cataract surgery. METHODS:
Sixty-two patients underwent routine cataract surgery as part of a randomized
clinical trial of oral Cox-2 inhibitor prophylaxis of cystoid macular oedema.
Optical coherence tomography was used to quantify several parameters of macular
thickness. Optical coherence tomography measurements were obtained before
surgery, day one, week two and week six after surgery. These measurements were
then correlated with logMAR best-corrected visual acuity. RESULTS: Optical
coherence tomography macular thickness parameters increased after surgery by up
to 20%. A significant correlation was identified between foveal minimum macular
thickness and best-corrected visual acuity at day one and week six after surgery.
Other macular parameters failed to show any significant correlation. At day one
and week six, the 10 patients with greatest macular thickness had significantly
lower visual acuity than the other patients. CONCLUSION: In this study routine
cataract surgery caused an increase in macular thickness. Some significant
positive correlations between macular thickness and best-corrected visual acuity 
were found, although not for all parameters or time points. There may be a
threshold relationship between degree of foveal anatomic change and significant
loss of visual acuity.

Publication Types: 
    Randomized Controlled Trial

PMID: 16626425 [PubMed - indexed for MEDLINE]

1494: Cochrane Database Syst Rev. 2006 Apr 19;(2):CD000254.

Update of:
    Cochrane Database Syst Rev. 2002;(2):CD000254.

Antioxidant vitamin and mineral supplements for slowing the progression of
age-related macular degeneration.

Evans JR.

London School of Hygiene & Tropical Medicine, International Centre for Eye
Health, Keppel Street, London, UK, WC1E 7HT. jennifer.evans@lshtm.ac.uk

BACKGROUND: It has been proposed that antioxidants may prevent cellular damage in
the retina by reacting with free radicals that are produced in the process of
light absorption. OBJECTIVES: The objective of this review was to assess the
effects of antioxidant vitamin or mineral supplementation, or both, on the
progression of age-related macular degeneration (AMD). SEARCH STRATEGY: We
searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The
Cochrane Library (2005, Issue 4); MEDLINE (1966 to January 2006); SIGLE (1980 to 
March 2005); EMBASE (1980 to January 2005); NRR (2005, Issue 4); AMED (1985 to
January 2006); and PubMed (24 January 2006 covering last 60 days), reference
lists of identified reports and the Science Citation Index. We contacted
investigators and experts in the field for details of unpublished studies.
SELECTION CRITERIA: We included randomised trials comparing antioxidant vitamin
or mineral supplemention (alone or in combination) to a control intervention in
people with AMD. DATA COLLECTION AND ANALYSIS: The author extracted data and
assessed trial quality. Where appropriate, data were pooled using a
random-effects model unless three or fewer trials were available in which case a 
fixed-effects model was used. MAIN RESULTS: Eight trials were included in this
review. The majority of people were randomised in one trial (AREDS in the USA)
that found a beneficial effect of antioxidant (beta-carotene, vitamin C and
vitamin E) and zinc supplementation on progression to advanced AMD (adjusted odds
ratio 0.68, 99% confidence interval 0.49 to 0.93). People taking supplements were
less likely to lose 15 or more letters of visual acuity (adjusted odds ratio
0.77, 99% confidence interval 0.58 to 1.03). Hospitalisation for genito-urinary
problems was more common in people taking zinc and yellowing of skin was more
common in people taking antioxidants. The other trials were, in general, small
and the results were inconsistent. AUTHORS' CONCLUSIONS: The evidence as to the
effectiveness of antioxidant vitamin and mineral supplementation in halting the
progression of AMD comes mainly from one large trial in the USA. The
generalisability of these findings to other populations with different
nutritional status is not known. Further large, well-conducted randomised
controlled trials in other populations are required. Long-term harm from
supplementation cannot be ruled out. Beta-carotene has been found to increase the
risk of lung cancer in smokers; vitamin E has been associated with an increased
risk of heart failure in people with vascular disease or diabetes.

Publication Types: 
    Meta-Analysis
    Review

PMID: 16625532 [PubMed - indexed for MEDLINE]

1495: Ann Acad Med Singapore. 2006 Mar;35(3):145-50.

The natural history of occult choroidal neovascularisation associated with
age-related macular degeneration. A systematic review.

Polito A, Isola M, Lanzetta P, Gregori D, Bandello F.

Department of Ophthalmology, University of Udine, Udine, Italy.

INTRODUCTION: The purpose of this review is to combine the results of existing
literature on the natural history of occult choroidal neovascularisation (CNV)
associated with age-related macular degeneration (AMD). MATERIALS AND METHODS:
Published reports evaluating eyes with occult CNV in AMD patients were selected
for meta-analysis based on a computerised MEDLINE search. Pooled estimates of the
proportions of eyes with a vision loss greater than 2 to 3 (moderate vision loss)
or 6 lines (severe vision loss) at 1 year and 2 to 3 years, respectively, or
developing a classic component on fluorescein angiography at 1 year were
measured. RESULTS: There is no significant heterogeneity among published rates of
visual loss and development of classic CNV. The overall pooled estimates (95%
confidence limits) of the proportions of eyes with at least moderate or severe
vision loss, respectively, were 59% (53% to 64.5%) and 34% (25% to 43%) at 1 year
and 70% (64% to 76%) and 47% (40% to 54%) at 2 to 3 years; the overall pooled
estimate of the percentage of eyes developing classic CNV at 1 year was 46% (39% 
to 54%). CONCLUSION: A substantial number of patients with occult CNV from AMD
will develop at least moderate visual loss at 1 year and severe visual loss
within 3 years. However, visual acuity may remain stable in up to 30% of
patients. These results may help us to understand the exact role of new therapies
and in planning future trials.

Publication Types: 
    Meta-Analysis
    Review

PMID: 16625262 [PubMed - indexed for MEDLINE]

1496: Ann Acad Med Singapore. 2006 Mar;35(3):137-44.

Retinal prostheses for the blind.

Javaheri M, Hahn DS, Lakhanpal RR, Weiland JD, Humayun MS.

Doheny Retina Institute, Doheny Eye Institute, Department of Ophthalmology, Keck 
School of Medicine, University of Southern California, 1450 San Pablo Street
(Room 3600), Los Angeles, CA 90033, USA.

INTRODUCTION: Using artificial means to treat extreme vision impairment has come 
closer to reality during the past few decades. The goal of this research has been
to create an implantable medical device that provides useful vision for those
patients who are left with no alternatives. Analogous to the cochlear implants
for some forms of hearing loss, these devices could restore useful vision by
converting visual information into patterns of electrical stimulation that excite
the remaining viable inner retinal neurons in patients with retinitis pigmentosa 
or age-related macular degeneration. METHODS: Data for this review were selected 
through a comprehensive literature search. RESULTS: Advances in microtechnology
have facilitated the development of a variety of prostheses that can be implanted
in the visual cortex, around the optic nerve, or in the eye. Some of these
approaches have shown the promise of providing useful visual input to patients
with visual impairments. CONCLUSION: While the development of various retinal
prostheses have shown promise in limited clinical trials, there are distinct
advantages and disadvantages for each type of prosthesis. This review will focus 
primarily on the Epiretinal Intraocular Retinal Prosthesis, studied by our group,
but will also briefly review other modalities: the subretinal prosthesis,
cortical prosthesis, and optic nerve prosthesis.

Publication Types: 
    Review

PMID: 16625261 [PubMed - indexed for MEDLINE]

1497: Br J Ophthalmol. 2006 May;90(5):593-6.

Comment in:
    Br J Ophthalmol. 2007 Jul;91(7):986.

Impact of age related macular degeneration on quality of life.

Hassell JB, Lamoureux EL, Keeffe JE.

Centre for Eye Research Australia, University of Melbourne.
hassell@unimelb.edu.au

AIMS: To describe the impact of age related macular degeneration (AMD) on quality
of life and explore the association with vision, health, and demographic
variables. METHODS: Adult participants diagnosed with AMD and with impaired
vision (visual acuity <6/12) were assessed with the Impact of Vision Impairment
(IVI) questionnaire. Participants rated the extent that vision restricted
participation in activities affecting quality of life and completed the Short
Form General Health Survey (SF-12) and a sociodemographic questionnaire. RESULTS:
The mean age of the 106 participants (66% female) was 83.6 years (range 64-98).
One quarter had mild vision impairment, (VA<6/12-6/18) and 75% had moderate or
severely impaired vision. Participants reported from at least "a little" concern 
on 23 of the 32 IVI items including reading, emotional health, mobility, and
participation in relevant activities. Those with mild and moderate vision
impairment were similarly affected but significantly different from those with
severe vision loss (p<0.05). Distance vision was associated with IVI scores but
not age, sex, or duration of vision loss. CONCLUSION: AMD affects many quality of
life related activities and not just those related to reading. Referral to low
vision care services should be considered for people with mild vision loss and
worse.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16622089 [PubMed - indexed for MEDLINE]

1498: Br J Ophthalmol. 2006 May;90(5):546-50.

Comment in:
    Br J Ophthalmol. 2006 May;90(5):524.    Br J Ophthalmol. 2006 May;90(5):525-6.

Visual outcomes for high myopic patients with or without myopic maculopathy: a 10
year follow up study.

Shih YF, Ho TC, Hsiao CK, Lin LL.

Department of Ophthalmology, College of Medicine, National Taiwan University
Hospital, Taipei. yfshih@ha.mc.ntu.edu.tw

AIM: To evaluate the visual outcomes for high myopic patients aged 40 years and
older with or without myopic maculopathy. METHODS: 552 high myopic (spherical
equivalent < or =-6.0D or axial length > or =26.5 mm) patients were enrolled in
the study, 230 cases with myopic maculopathy (at least lacquer cracks were
identified) and 322 cases without maculopathy. The initial and final visual
acuity (VA) (after 10 years) was compared between two groups. Additionally, the
relation between sex, age, refraction, and axial length was analysed to find out 
the possible risk factors associated with visual outcome in myopic maculopathy.
RESULTS: In 92% of patients aged 40-49, final VA was better than 20/40 after 10
years of follow up. However, it was less than 40% in those older than 60 years.
For more than 50% of patients older than 40 years of age with maculopathy, their 
vision had decreased more than two lines in Snellen VA after 10 years of follow
up, compared to only 4.3% of analogues without myopic maculopathy. Patchy atrophy
and choroidal neovascularisation in myopic macular degeneration groups showed
poorer visual outcome than lacquer cracks in the macular lesion group. Other
prognostic factors of visual outcomes were myopic refraction, axial length, and
ageing. CONCLUSIONS: Clearly, prognosis for patients with maculopathy is poorer
than for those without maculopathy. Refractive status, axial length, and ageing
are the main factors involved in determining the visual outcomes. The macular
grading also affects the visual outcome for high myopic patients.

Publication Types: 
    Comparative Study

PMID: 16622083 [PubMed - indexed for MEDLINE]

1499: Lasers Surg Med. 2006 Jul;38(6):643-6.

Absorption of diode 810 nm used for transpupillary thermotherapy by blood. An in 
vitro study.

Morales AM, Lapuente CR, Peyman GA, Kivilcim M.

Department of Ophthalmology, Virgen del Rocío Hospital, Seville, Spain.

BACKGROUND AND OBJECTIVES: To evaluate the in vitro energy attenuation by
transpupillary thermotherapy (TTT) using an 810-nm diode laser after the
treatment of exudative age-related macular degeneration. STUDY DESIGN/MATERIALS
AND METHODS: In this experiment, an 810-nm diode laser was coupled to a slit lamp
to deliver laser energy to a laser-power sensor adjusted in the track of the
laser light. The spotlight was 0.5 mm in diameter; duration of exposure, 3
seconds. Citrated Pasteur pipettes were filled with blood diluted in saline in
several concentrations and placed in the path of the laser light. The absorption 
of the light measured by the power sensor was tested for various delivered
irradiances between 50.92 and 509.29 W/cm2. The differences were analyzed
statistically. RESULTS: There were significant differences in laser blockage
comparing various conditions for all power levels (P<0.05). Increasing the
proportion of blood resulted in more laser blockage with all irradiances
(P<0.05). CONCLUSIONS: Blood significantly blocks the transmission of the 810-nm 
diode TTT laser. (c) 2006 Wiley-Liss, Inc.

PMID: 16615134 [PubMed - indexed for MEDLINE]

1500: Graefes Arch Clin Exp Ophthalmol. 2006 Nov;244(11):1453-66. Epub 2006 Apr
13.

Genotype-phenotype correlation and longitudinal course in ten families with Best 
vitelliform macular dystrophy.

Wabbels B, Preising MN, Kretschmann U, Demmler A, Lorenz B.

Department of Paediatric Ophthalmology, Strabismology and Ophthalmogenetics,
University of Regensburg, Klinikum, Franz Josef Strauss Allee 11, 93053
Regensburg, Germany.

AIM: Longitudinal course and genotype-phenotype correlation in patients and
carriers with heterozygous mutations in hBEST1 (bestrophin). METHODS: Thirteen
patients and seven possible carriers were characterised by mutation analysis with
SSCPA and direct sequencing, clinical examination and fundus autofluorescence
(AF). Electrophysiology (EOG and mfERG) and optical coherence tomography (OCT)
were additionally performed whenever possible. RESULTS: We identified seven
different heterozygous mutations in ten unrelated families with Best disease.
I296del was the most frequent mutation. Five of nine individuals with I295del and
two of three with N99K were asymptomatic carriers. One patient with I295del
mutation had funduscopically unilateral Best disease. In three children (all with
I295del), EOG initially showed a clearly present light peak that deteriorated
during 5 years of follow-up in two of them. Increased AF corresponded well to
funduscopically visible lesions. During 3-6 years of follow-up, the lesion area
did not change significantly, but there were obvious changes in the inner
structure of the lesion. CONCLUSION: In the present series I295del, the most
frequent mutation in our study, and N99K showed reduced penetrance. EOG was
normal in young patients even if prime signs were visible. The lesion area did
not depend on the mutation and did not correlate with VA. Lower VA was associated
with a more irregular AF pattern due to scarring or haemorrhage. Our results
indicate a disease causing effect that is cumulative over time.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16612637 [PubMed - indexed for MEDLINE]

1501: Drugs Aging. 2006;23(3):217-25.

Economic cost of age-related macular degeneration: a review of recent research.

Ke KM, Chakravarthy U, O'Neill C.

School of Economics and Politics, University of Ulster, Newtownabbey, UK.

As the population of most developed countries ages so the prevalence of diseases 
such as age-related macular degeneration (AMD) are likely to increase. To
facilitate planning and informed debate regarding making provisions for this
disease it is important that we have a clear understanding of the economic impact
of visual impairment associated with AMD. In this paper we assess the state of
current knowledge based on a review of published evidence in scientific journals.
Based on our assessment of the evidence we argue that the paucity of research
studies on the subject and wide variation in estimates produced from the few
studies available make it difficult to assess with confidence the likely average 
direct cost-of-illness associated with AMD. We further argue that significant
gaps in our understanding of the costs of AMD (particularly in respect of
indirect costs) also exist. Current research should be augmented by more
comprehensive studies.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 16608377 [PubMed - indexed for MEDLINE]

1502: Arch Ophthalmol. 2006 Apr;124(4):537-43.

Cognitive impairment in the Age-Related Eye Disease Study: AREDS report no. 16.

Clemons TE, Rankin MW, McBee WL; Age-Related Eye Disease Study Research Group.

OBJECTIVE: To investigate potential associations between cognitive function
and/or impairment and age-related macular degeneration (AMD) and visual
impairment in the Age-Related Eye Disease Study (AREDS). METHODS: The AREDS is an
11-center natural history study of AMD and age-related cataract. The AREDS
Cognitive Function Battery was administered to 2946 participants. The battery
consists of 6 neuropsychological tests measuring performance in several cognitive
domains. The Dunnett multiple comparison test was used to identify differences by
AMD and visual acuity severity. The relationship with cognitive impairment was
also assessed using logistic regression. RESULTS: Mean scores of instruments in
the AREDS Cognitive Function Battery declined with increased macular
abnormalities and reduced visual acuity. After adjustment for age, sex, race,
education, smoking status, diabetes mellitus, hypertension, and depression,
increased macular abnormalities (trend P value <.05) reduced mean cognitive
function scores as measured by the Modified Mini-Mental State Examination and the
Wechsler Logical Memory Scale. Reduced vision was found to be associated with
reduced mean cognitive function scores as measured by the Modified Mini-Mental
State Examination and letter and verbal fluency tasks. Persons with vision worse 
than 20/40 OU were more likely to be cognitively impaired (Modified Mini-Mental
State Examination score <80) (odds ratio, 2.88 [95% confidence interval,
1.75-4.76]) compared with persons with visual acuity of 20/40 or better OU.
CONCLUSION: These data suggest a possible association of advanced AMD and visual 
acuity with cognitive impairment in older persons.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 16606880 [PubMed - indexed for MEDLINE]

1503: Arch Ophthalmol. 2006 Apr;124(4):529-35.

Prevalence of age-related maculopathy in older Europeans: the European Eye Study 
(EUREYE).

Augood CA, Vingerling JR, de Jong PT, Chakravarthy U, Seland J, Soubrane G,
Tomazzoli L, Topouzis F, Bentham G, Rahu M, Vioque J, Young IS, Fletcher AE.

Department of Epidemiology and Population Health, London School of Hygiene and
Tropical Medicine, London, England.

OBJECTIVE: To estimate the prevalence of age-related maculopathy in an older
population from 7 European countries. METHODS: Randomly sampled people 65 years
and older were invited to an eye examination in centers across 7 European
countries (Norway, Estonia, United Kingdom, France, Italy, Greece, and Spain).
Fundus images of each eye were graded at a single reading center. Prevalence
rates were calculated for stage of age-related maculopathy with 95% confidence
intervals (CIs) estimated for clustered data. RESULTS: Of 5040 participants (45% 
response rate), 4753 (2128 men and 2625 women) had gradable fundus images. The
prevalences were grade 0, 47.59% (95% CI, 43.53%-51.65%); grade 1, 36.48% (95%
CI, 32.66%-40.30%); grade 2, 10.14% (95% CI, 8.92% to 11.37%); grade 3, 2.46%
(95% CI, 1.79%-3.13%); and grade 4 (age-related macular degeneration [AMD]),
3.32% (95% CI, 2.52%-4.13%) and large drusen only (> or = 125 microm), 15.41%
(95% CI, 13.61%-17.21%). The prevalence of geographic atrophic AMD was 1.2% (95% 
CI, 0.8%-1.7%) and of neovascular AMD, 2.3% (95% CI, 1.7%-2.9%). The prevalence
of bilateral AMD was 1.4% (95% CI, 1.0%-1.8%). CONCLUSION: Age-specific
prevalences of age-related maculopathy in the European Eye Study (EUREYE) are
similar to other population-based studies in Western populations.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 16606879 [PubMed - indexed for MEDLINE]

1504: Pharmacoeconomics. 2006;24(4):319-34.

The burden of age-related macular degeneration.

Schmier JK, Jones ML, Halpern MT.

Exponent, Alexandria, Virginia, USA.

As age-related macular degeneration (AMD) becomes more prevalent as a result of
longer life expectancy and the number of elderly people worldwide, it will become
increasingly important to understand its potential health and economic impact for
appropriate healthcare planning. This review identified published literature on
costs and resource use associated with AMD. Despite the increasing prevalence of 
AMD, the worldwide burden of illness is unknown. Several studies of direct
medical costs, both those associated with ophthalmic care and those associated
with other care, have been conducted and have identified increased medical care
associated with AMD. Direct non-medical costs include the cost for vision aids;
while these costs may be substantial, they are difficult to quantify as no
comprehensive sources track the distribution or use of vision aids. Because AMD
is uncommon among people of working age, there is less concern regarding the
impact of indirect (workplace) costs among AMD patients. However, indirect costs 
are incurred by caregivers who leave the workforce early or change their work
patterns in order to provide assistance to AMD patients; the magnitude of
caregiver-related costs is unknown. The cost effectiveness of some interventions 
for AMD has been explored. Supplementation with zinc and antioxidants for
non-exudative (dry) AMD has been shown to result in an acceptable cost per QALY
and is considered cost effective. Studies suggest that laser photocoagulation is 
cost effective but that photodynamic therapy with verteporfin appears to be cost 
effective only among patients with good visual acuity at baseline or when models 
extend longer than 5 years. Further research is needed to integrate the
information on various components of AMD-related costs into a comprehensive
burden of illness estimate and to evaluate basic utility assumptions in existing 
models.

Publication Types: 
    Review

PMID: 16605279 [PubMed - indexed for MEDLINE]

1505: Retina. 2006 Apr;26(4):383-90.

Intravitreal bevacizumab treatment of choroidal neovascularization secondary to
age-related macular degeneration.

Spaide RF, Laud K, Fine HF, Klancnik JM Jr, Meyerle CB, Yannuzzi LA, Sorenson J, 
Slakter J, Fisher YL, Cooney MJ.

Vitreous Retina Macula Consultants of New York and the LuEsther T. Mertz Retinal 
Research Center at Manhattan Eye, Ear & Throat Hospital, 460 Park Avenue, New
York, NY 10022, USA. vrmny@aol.com

PURPOSE: To describe the short-term anatomical and visual acuity responses after 
intravitreal injection of bevacizumab (Avastin, Genentech) in patients with
choroidal neovascularization (CNV) secondary to age-related macular degeneration 
(AMD). METHODS: We conducted a retrospective study of patients with CNV secondary
to AMD who were treated with intravitreal injection of bevacizumab (1.25 mg)
during a 3-month period. Patients underwent best-corrected Snellen visual acuity 
testing, optical coherence tomography, and ophthalmoscopic examination at
baseline and follow-up visits. RESULTS: There were 266 consecutive eyes of 266
patients who received injections, and follow-up information was available for 251
(94.4%). The mean age of the patients was 80.3 years, the mean baseline visual
acuity was 20/184, and 175 (69.7%) had inadequate response to alternate methods
of treatment. At the 1-month follow-up (data available for 244 patients), the
mean visual acuity was 20/137 (P < 0.001 as compared with baseline), and 74
(30.3%) of patients had improvement in visual acuity as defined by a halving of
the visual angle. At the 2-month follow-up (data available for 222 patients), the
mean visual acuity was 20/122 (P < 0.001), and 78 (31.1%) of patients had visual 
improvement. At the 3-month follow-up (data available for 141 patients), the mean
visual acuity was 20/109 (P < 0.001), and 54 (38.3%) of patients had visual
acuity improvement. The mean central macular thickness at baseline was 340 mum
and decreased to a mean of 247 microm at month 1 (P < 0.001) and 213 microm at
month 3 (P < 0.001). At 1 month, two patients had mild vitritis, as did one
patient at 2 months, who had a history of recurrent uveitis. No endophthalmitis, 
increased intraocular pressure, retinal tear, or retinal detachment occurred. The
risk for thromboembolic disorders did not seem to be different than reported
previously in studies concerning macular degeneration. CONCLUSION: There were no 
apparent short-term safety concerns for intravitreal bevacizumab injection for
CNV. Treated eyes had a significant decrease in macular thickness and improvement
in visual acuity. The follow-up was too short to make any specific treatment
recommendations, but the favorable short-term results suggest further study is
needed.

PMID: 16603955 [PubMed - indexed for MEDLINE]

1506: Graefes Arch Clin Exp Ophthalmol. 2006 Nov;244(11):1446-52. Epub 2006 Apr
7.

Effect of grid laser photocoagulation in diffuse diabetic macular edema in
correlation to glycosylated haemoglobin (HbA1c).

Schmid KE, Neumaier-Ammerer B, Stolba U, Binder S.

Department of Ophthalmology, The Ludwig Boltzmann Institute of Retinology and
Biomicroscopic Lasersurgery, Rudolf Foundation Clinic Vienna, Vienna, Austria.
katharina.schmid@wienkav.at

BACKGROUND: Glycosylated haemoglobin (HbA1c) correlates with the amount of
hyperglycemia in diabetic patients. High HbA1c levels often predict clinically
significant macular edema (CSME), which then needs to be treated with grid laser 
photocoagulation. The question asked in this study was whether there is a
correlation between the effect grid laser photocoagulation in diffuse diabetic
macular edema and HbA1c, using an optical coherence tomography (OCT) for the
evaluation of the retinal thickness. METHODS: A prospective, non-comparative case
series was performed to find a correlation between the effect of grid laser
photocoagulation in diffuse diabetic macular edema and HbA1c. Thirty eyes with
CSME of diabetic patients were included in the study. Complete ophthalmic
examinations and OCT were performed at baseline, 1 month, 3, and 6 months after
grid laser photocoagulation therapy. HbA1c was measured at the end of study.
RESULTS: Significance level was set at P<0.05. A significant difference in the
foveal (P=0.02) and superior (P=0.021) retinal thickness 6 months after laser
therapy, no correlation between HbA1c and retinal thickness after
photocoagulation, and an insignificant decrease in visual acuity (P=0.9) were
found. The correlation between foveal retinal thickness and visual acuity was
P=0.24 6 months after treatment. CONCLUSION: There was no significant correlation
between HbA1c and the effect of grid laser photocoagulation therapy in diffuse
diabetic macular edema. The retinal thickness decreased significantly in the
foveal and superior area 6 months after therapy. No correlation between the
foveal retinal thickness and the visual acuity was found. The visual acuity did
not increase after treatment. There are many factors influencing the retinal
thickness, such as the blood pressure and the attached posterior hyaloid.

PMID: 16601980 [PubMed - indexed for MEDLINE]

1507: Hum Mol Genet. 2006 May 15;15(10):1680-9. Epub 2006 Apr 6.

Disease mechanisms in late-onset retinal macular degeneration associated with
mutation in C1QTNF5.

Shu X, Tulloch B, Lennon A, Vlachantoni D, Zhou X, Hayward C, Wright AF.

MRC Human Genetics Unit, Western General Hospital, Edinburgh EH4 2XU, UK.
xinhua.shu@hgu.mrc.ac.uk

Late-onset retinal macular degeneration (L-ORMD) is an autosomal dominant
condition resembling age-related macular degeneration (AMD) in which a key
pathological feature is a thick extracellular sub-retinal pigment epithelial
(RPE) deposit. L-ORMD is caused by mutation in the C1QTNF5 (CTRP5) short-chain
collagen gene, but the disease mechanism is unknown. Here, we first show that
wild-type C1QTNF5 is secreted, whereas mutant C1QTNF5 is misfolded and retained
within the endoplasmic reticulum (ER). Secondly, the ER retained mutant protein
has a shorter half-life than wild-type C1QTNF5 and is preferentially degraded by 
proteasomes. Thirdly, C1QTNF5 is shown to interact with the membrane-type
frizzled related protein (MFRP), on the basis of yeast two-hybrid, protein
pull-down and co-immunoprecipitation assays and RPE co-localization. These data
suggest that L-ORMD is due to insufficient levels of secreted C1QTNF5,
compromised RPE cell function resulting from ER retention of the mutant protein
or both mechanisms.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16600989 [PubMed - indexed for MEDLINE]

1508: Am J Clin Nutr. 2006 Apr;83(4):880-6.

Comment in:
    Am J Clin Nutr. 2006 Apr;83(4):733-4.

Dietary glycemic index and carbohydrate in relation to early age-related macular 
degeneration.

Chiu CJ, Hubbard LD, Armstrong J, Rogers G, Jacques PF, Chylack LT Jr, Hankinson 
SE, Willett WC, Taylor A.

Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging 
at Tufts University, 711 Washington Street, Boston, MA 02111, USA.

BACKGROUND: Several dietary factors have been linked to age-related maculopathy
(ARM), the early form of age-related macular degeneration, and there is reason to
think that dietary carbohydrate may play a role in the development of ARM.
OBJECTIVE: The purpose of the present study was to examine the relation between
dietary carbohydrate quality, as measured by dietary glycemic index (GI) or total
carbohydrate intake, and ARM. DESIGN: From the Nurses' Health Study, 1036 eyes
from 526 Boston-area participants without a previous ARM diagnosis were included 
in the present study. The presence and degree of ARM were classified by the
Age-Related Eye Diseases Study system. Long-term dietary information was based on
data from an average of 4 food-frequency questionnaires collected over a 10-y
period before the assessment of ARM. With eyes as the unit of analysis, we used a
generalized estimating approach to logistic regression to estimate the odds
ratios for ARM in a manner that accounted for the lack of independence between
the 2 eyes from the same subject. RESULTS: After multivariate adjustment, dietary
GI was related to ARM (specifically to retinal pigmentary abnormalities), whereas
total carbohydrate intake was not. The odds ratio for ARM being in the highest
tertile of dietary GI (> or =77.0) versus the lowest (<74.6) was 2.71 (95% CI:
1.24, 5.93; P for trend = 0.01). Neither dietary GI nor total carbohydrate intake
was related to drusen. CONCLUSION: Our results suggest that dietary GI may be an 
independent risk factor for ARM.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, Non-P.H.S.

PMID: 16600942 [PubMed - indexed for MEDLINE]

1509: Br J Ophthalmol. 2006 Jun;90(6):724-7. Epub 2006 Apr 5.

Does smoking influence the type of age related macular degeneration causing
visual impairment?

Dandekar SS, Jenkins SA, Peto T, Bird AC, Webster AR.

Professorial Unit, Moorfields Eye Hospital, 162 City Road, London EC1V 2PD, UK.
sam@hitbits.co.uk

AIMS: To assess the influence of smoking on the type of age related macular
degeneration (AMD) lesion causing visual impairment in a large cohort of patients
with AMD at a tertiary referral UK centre. METHODS: Prospective, observational,
cross sectional study to analyse smoking data on 711 subjects, of western
European origin, in relation to the type of AMD lesion present. Colour fundus
photographs were graded according to a modified version of the international
classification. Multiple logistic regression analysis was performed, adjusting
for age and sex using the statistical package SPSS ver 9.0 for Windows. chi(2)
tests were also used to assess pack year and ex-smoker data. RESULTS: 578
subjects were graded with neovascular AMD and 133 with non-neovascular AMD. There
was no statistically significant association found between smoking status or
increasing number of pack years and type of AMD lesion. The odds of "current
smokers" compared to "non-smokers" developing neovascular rather than
non-neovascular AMD when adjusted for age and sex was 1.88 (95% CI: 0.91 to 3.89;
p = 0.09). CONCLUSIONS: Smoking is known to be a risk factor for AMD and this
study suggests that smokers are at no more risk of developing neovascular than
atrophic lesions.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16597668 [PubMed - indexed for MEDLINE]

1510: Br J Ophthalmol. 2006 Jul;90(7):906-10. Epub 2006 Apr 5.

Localisation of SDF-1 and its receptor CXCR4 in retina and choroid of aged human 
eyes and in eyes with age related macular degeneration.

Bhutto IA, McLeod DS, Merges C, Hasegawa T, Lutty GA.

Wilmer Ophthalmological Institute, Johns Hopkins Hospital, Baltimore, MD,
21287-9115, USA.

AIM: To examine the immunolocalisation of stromal cell derived factor 1 (SDF-1)
and its receptor CXCR4 in aged control human donor eyes and eyes with age related
macular degeneration (AMD). METHODS: Postmortem eyes from eight aged control
donors (mean age 79.8 years) and from 12 donors with AMD (mean age 83.9 years)
were cryopreserved and sectioned through the macular region. SDF-1 and CXCR4 were
localised using streptavidin alkaline phosphatase immunohistochemistry and then
sections were bleached. Three independent masked observers scored the
immunohistochemical reaction product. RESULTS: In aged control retinas, SDF-1
immunoreactivity was most intense in inner photoreceptor matrix (IPM). CXCR4
showed a similar pattern of immunostaining, but was more prominent in inner
segments of photoreceptors. In aged control and AMD choroid, SDF-1 and CXCR4
localisations were most prominent in retinal pigment epithelial (RPE) cells and
choroidal stroma. However, the intensity for SDF-1 was significantly reduced in
RPE (p < 0.0001) and choroidal stroma (p < 0.05) in late AMD eyes. SDF-1 and
CXCR4 immunoreactivities were weak or nearly absent in disciform scars with
choroidal neovascularisation (CNV). Circulating cells, presumably leucocytes,
were most intensely positive for CXCR4. CONCLUSIONS: These results show that
changes in distribution and relative levels of SDF-1/CXCR4 were not evident in
early AMD. This suggests that SDF-1/CXCR4 may not contribute to the formation of 
CNV in AMD, in that CXCR4+ cells were not incorporated into neovascularisation.
However, the examples of CNV studied were within disciform scars, so the authors 
cannot comment on the role of SDF-1/CXCR4 in the early stages of CNV formation.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16597663 [PubMed - indexed for MEDLINE]

1511: Ocul Immunol Inflamm. 2006 Apr;14(2):73-85.

The pros and cons of intravitreal triamcinolone injections for uveitis and
inflammatory cystoid macular edema.

van Kooij B, Rothova A, de Vries P.

F.C. Donders Institute of Ophthalmology, University Medical Center Utrecht,
Utrecht, The Netherlands. b.vankooij@oogh.azu.nl

Intravitreal triamcinolone acetonide (IVTA) injections are gaining in popularity 
and are regularly administered nowadays for various ocular diseases. This paper
presents a literature review on the use, efficacy, and complications of IVTA
application in non-infectious uveitis and inflammatory cystoid macular edema
(CME). In addition, we describe the experiences of our own institute. IVTA
applications brought about a quick improvement in vision in the majority of
cases. Drawbacks included the temporary duration of the effect with the need for 
repeated injections which re-exposed patients to the risk of complications. The
risk of bacterial endophthalmitis was 0.5% and was further influenced by the
specific IVTA preparation. Based on the literature review, we chose ready-for-use
IVTA injections prepared by our pharmacy department, in which 90% of the toxic
additives were removed and the dispensed dose of triamcinolone acetonide was
validated to diminish the risk of endophthalmitis. Elevated intraocular pressure 
(IOP) was seen in 30-43% of the eyes and cataract developed in 29% of the eyes of
patients, who were usually of advanced age. In conclusion, the rapid effect of
IVTA might be of value in severe presentations of non-infectious uveitis and CME 
and might shorten the time interval needed for the improvement.

Publication Types: 
    Review

PMID: 16597536 [PubMed - indexed for MEDLINE]

1512: BMC Ophthalmol. 2006 Apr 4;6:15.

The effect of posterior subtenon methylprednisolone acetate in the refractory
diabetic macular edema: a prospective nonrandomized interventional case series.

Javadzadeh A.

Retina service, Department of Ophthalmology, Nikookari Hospital--Drug of applied 
research center, Tabriz University of Medical Sciences, Tabriz, Iran.
javadzadehalireza@yahoo.com

BACKGROUND: To investigate the efficacy of posterior subtenon methylprednisolone 
acetate injection in treatment of refractory diffuse clinically significant
diabetic macular edema (CSME). METHODS: In a prospective, nonrandomized,
interventional case series, 52 eyes were diagnosed with CSME and treated with at 
least two sessions of laser photocoagulation according to Early Treatment
Diabetic Retinopathy Study guidelines. At least 3 months after laser therapy,
eyes with a residual central macular thickness were offered posterior subtenon
injection of 40 mg methylprednisolone acetate. Main outcome measures were visual 
acuity, macular thickness and intraocular pressure. Potential complications were 
monitored, including intraocular pressure response, cataract progression and
scleral perforation. RESULTS: Mean baseline visual acuity (in logMAR) improved
significantly (p = 0.003) from 0.8 +/- 0.36 to 0.6 +/- 0.41 at 3 months. Mean
foveal thickness decreased from 388 +/- 78 mum at baseline to 231 +/- 40 mum
after 3 months (p < 0.0001). Visual acuity improvement in eyes with CSME with
extrafoveal hard exudates was significant (p = 0.0001), but not significant in
eyes with CSME with subfoveal hard exudates (p = 0.32). Intraocular pressure
increased from 14.7 +/- 2.0 mmHg (range, 12-18 mmHg) to a maximum value of 15.9
+/- 2.1 mmHg (range, 12-20 mmHg) during the follow-up period. Complications in
two eyes developed focal conjunctival necrosis at the site of injection.
CONCLUSION: Posterior subtenon methylprednisolone acetate may improve early
visual outcome in diffuse diabetic macular edema that fails to respond to
conventional laser photocoagulation. Visual acuity improvement in eyes with CSME 
with extrafoveal hard exudates was significant; and this improvement is depends
on location of hard exudates. Further study is needed to assess the long-term
efficacy, safety, and retreatment.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 16595011 [PubMed - indexed for MEDLINE]

1513: Exp Eye Res. 2006 Aug;83(2):329-38. Epub 2006 Apr 11.

Expression of endostatin in human choroidal neovascular membranes secondary to
age-related macular degeneration.

Tatar O, Shinoda K, Adam A, Rohrbach JM, Lucke K, Henke-Fahle S, Bartz-Schmidt
KU, Grisanti S.

University Eye Clinic at the Centre for Ophthalmology of the
Eberhard-Karls-University Tübingen, Schleichstrasse 12-15, 72076 Tuebingen,
Germany.

Endostatin is an endogenous angiogenesis inhibitor which requires E-selectin for 
its antiangiogenic activity. The aim of this study was to investigate the
expression of endostatin in human choroidal neovascular membranes (CNV) secondary
to age-related macular degeneration (AMD) with regard to vascularization and
proliferative activity. An interventional case series of 36 patients who
underwent removal of CNV were retrospectively investigated. Thirty-six CNV were
analyzed by light microscopic immunohistochemistry for the expression of CD34
(endothelial cells, EC), CD105 (activated EC), Ki-67 (cell proliferation),
Cytokeratin 18 (epithelial cells), VEGF (vascular endothelial growth factor),
E-selectin and endostatin. Donor eyes (n=7) including one with AMD were used as
controls. Endostatin immunoreactivity was present in choroidal vessels of five as
well as in the retinal pigment epithelium (RPE)-Bruch's membrane complex of two
donor eyes without AMD. In one eye with AMD, endostatin was detected in RPE,
Bruch's membrane and choroidal vessels. Ninety-two percent (33/36) of CNV
disclosed endostatin staining. RPE-Bruch's membrane complex, choroidal vessels
and stroma were positive in 50% (18/36), 72% (26/36), and 78% (28/36) of the
membranes, respectively. Both control eyes and CNV expressed all the investigated
markers except E-selectin being positive only in membranes. Endostatin, an
endogenous angiogenesis inhibitor, is expressed in CNV and its therapeutic
up-regulation may be a new strategy in the treatment of neovascular AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16584730 [PubMed - indexed for MEDLINE]

1514: Ophthalmic Epidemiol. 2006 Apr;13(2):137-43.

Validation of the Daily Living Tasks Dependent on Vision (DLTV) questionnaire in 
a U.S. population with age-related macular degeneration.

Schmier JK, Halpern MT, Covert D.

Exponent, Inc., Alexandria, VA 22314, USA. jschmier@exponent.com

PURPOSE: The Daily Living Tasks Dependent on Vision questionnaire (DLTV) has been
used to assess functional impairment among patients with age-related macular
degeneration (AMD). This study evaluated the psychometric properties of the DLTV 
using patient-reported rates of use of services and devices in an outpatient
population. METHODS: The DLTV was included in a survey mailed to members of an
AMD advocacy organization. Included in the survey were questions about
demographic and clinical characteristics as well as questions about use of low
vision aids and care-giving. Respondents provided informed consent. Data were
analyzed in SAS. RESULTS: Four respondents of 803 did not complete the DLTV;
missing data were uncommon. Most (56%) respondents were male; the mean age was 73
years. Internal consistency reliability of the DLTV was 0.9699. Construct
validity was demonstrated with moderate to high correlations between the DLTV and
use of services and devices. The DLTV demonstrated discriminant validity and
could distinguish between respondents with different levels of impairment, i.e., 
those who reported regular care-giving compared to those without regular
care-giving. CONCLUSIONS: In this outpatient population, the DLTV demonstrated
reliability and validity. This analysis complements existing research and
supports the use of the DLTV in AMD patients.

Publication Types: 
    Comparative Study
    Validation Studies

PMID: 16581618 [PubMed - indexed for MEDLINE]

1515: Ophthalmology. 2006 Apr;113(4):623.e1.

Tolerability and efficacy of multiple escalating doses of ranibizumab (Lucentis) 
for neovascular age-related macular degeneration.

Rosenfeld PJ, Heier JS, Hantsbarger G, Shams N.

Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami,
Miami, Florida 33136, USA. prosenfeld@med.miami.edu

PURPOSE: To investigate whether multiple intravitreal doses of up to 2 mg of an
antigen-binding fragment known as ranibizumab, derived from a humanized
anti-vascular endothelial growth factor antibody, can be tolerated and are
biologically active when injected using a dose-escalating strategy in eyes of
patients with neovascular age-related macular degeneration (AMD). DESIGN:
Open-label, 2-center, uncontrolled, randomized clinical study of 3 different
dose-escalating regimens of ranibizumab. PARTICIPANTS: Thirty-two patients with
primary or recurrent subfoveal choroidal neovascularization secondary to AMD were
enrolled. Baseline best-corrected visual acuity (VA) in the study eye was from
20/40 to 20/640 (Snellen equivalent). METHODS: Treatment regimens consisted of 5,
7, or 9 intravitreal injections of ranibizumab at 2- or 4-week intervals for 16
weeks, with escalating doses ranging from 0.3 to 2.0 mg. Patients were evaluated 
through day 140, 4 weeks after their last injection. MAIN OUTCOME MEASURES:
Safety was assessed based on ocular and nonocular adverse events, changes in VA, 
changes in intraocular pressure (IOP), slit-lamp ocular examination, changes in
lesion characteristics based on fluorescein angiography and color fundus
photography, and the presence of anti-ranibizumab antibodies. RESULTS:
Twenty-nine patients received an injection at baseline, and 27 patients completed
the study through day 140. Results were similar across the 3 treatment groups.
All patients experienced ocular adverse events, most of which were mild. The most
common ocular adverse events were iridocyclitis (83%) and injection-site
reactions (72%). Inflammation did not increase with repeated injections, despite 
the increasing ranibizumab doses. Transient mild IOP elevations were common after
ranibizumab injection. No serum anti-ranibizumab antibodies were detected.
Overall, median and mean VAs in the study eyes improved by day 140 in all 3
groups. Only 3 of the 27 patients lost significant vision. There was no
significant lesion growth, and a decrease in area of leakage from choroidal
neovascularization was detected through day 140. CONCLUSIONS: Multiple
intravitreal injections of ranibizumab at escalating doses ranging from 0.3 to
2.0 mg were well tolerated and biologically active in eyes with neovascular AMD
through 20 weeks. Mild transient ocular inflammation was the most common
postinjection adverse event.

Publication Types: 
    Clinical Trial, Phase I
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16581423 [PubMed - indexed for MEDLINE]

1516: Ophthalmology. 2006 Apr;113(4):622.e1.

Prophylactic treatment of age-related macular degeneration report number 1:
810-nanometer laser to eyes with drusen. Unilaterally eligible patients.

Friberg TR, Musch DC, Lim JI, Morse L, Freeman W, Sinclair S; PTAMD Study Group.

Department of Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania
15213, USA.

OBJECTIVE: To determine the effects of subthreshold 810-nm-diode laser treatment 
on the rate of development of choroidal neovascularization (primary end point)
and the effect on visual acuity (VA) in participants with multiple large drusen
in one eye and a preexisting neovascular age-related macular degeneration (AMD)
lesion in the other. DESIGN: Multicenter, prospective, randomized controlled
trial. PARTICIPANTS: Two hundred forty-four patients > or =50 years of age and
with a neovascular or advanced AMD lesion in one eye and, in the fellow "study"
eye, (1) at least 5 drusen > or = 63 mum in diameter, (2) Early Treatment
Diabetic Retinopathy Study best-corrected VA (BCVA) of 20/63 or better, and (3)
no evidence of neovascularization at baseline. METHODS: Patients were randomized 
to treatment or observation of their study eye at each of 22 centers. At each
visit, the protocol specified that BCVA, a complete retinal examination, and
fluorescein angiography be documented. Treated eyes had a grid of 48 extrafoveal,
subthreshold diode (810 nm) laser spots, 125 mum in diameter, placed in an
annulus outside of the foveola. Patients were seen at baseline and at 3, 6, 12,
18, 24, 30, and 36 months after randomization. No retreatments were allowed. MAIN
OUTCOME MEASURES: Development of choroidal neovascularization (as confirmed by
fluorescein angiography) and change in BCVA. RESULTS: Throughout follow-up, the
rate of choroidal neovascularization events in treated eyes consistently exceeded
that in observed eyes. At 1 year, the difference was 15.8% versus 1.4% (P =
0.05). Most of the intergroup differences in choroidal neovascularization events 
occurred during the first 2 years of follow-up. Treated eyes showed a higher rate
of VA loss (> or =3 lines) at 3- and 6-month follow-ups relative to observed eyes
(8.3% vs. 1% and 11.4% vs. 4%, respectively; Ps = 0.02, 0.07). After 6 months, no
significant differences were observed in VA loss between groups. CONCLUSION:
Prophylactic subthreshold 810-nm-diode laser treatment to an eye with multiple
large drusen in a patient whose fellow eye has already suffered a neovascular
event places the treated eye at higher risk of developing choroidal
neovascularization. We advise against using prophylactic subthreshold diode laser
treatment in these eyes.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16581422 [PubMed - indexed for MEDLINE]

1517: Prog Retin Eye Res. 2006 May;25(3):249-76. Epub 2006 Mar 31.

Visual function and dysfunction in early and late age-related maculopathy.

Hogg RE, Chakravarthy U.

Ophthalmology and Vision Science, Queen's University and Royal Victoria
Hospitals, Belfast BT12 6BA, UK.

Late age-related maculopathy (ARM) is responsible for the majority of blind
registrations in the Western world among persons over 50 years of age. It has
devastating effects on quality of life and independence and is becoming a major
public health concern. Current treatment options are limited and most aim to slow
progression rather than restore vision; therefore, early detection to identify
those patients most suitable for these interventions is essential. In this work, 
we review the literature encompassing the investigation of visual function in ARM
in order to highlight those visual function parameters which are affected very
early in the disease process. We pay particular attention to measures of acuity, 
contrast sensitivity (CS), cone function, electrophysiology, visual adaptation,
central visual field sensitivity and metamorphopsia. We also consider the impact 
of bilateral late ARM on visual function as well as the relationship between
measures of vision function and self-reported visual functioning. Much interest
has centred on the identification of functional changes which may predict
progression to neovascular disease; therefore, we outline the longitudinal
studies, which to date have reported dark-adaptation time, short-wavelength cone 
sensitivity, colour-match area effect, dark-adapted foveal sensitivity, foveal
flicker sensitivity, slow recovery from glare and slower foveal electroretinogram
implicit time as functional risk factors for the development of neovascular
disease. Despite progress in this area, we emphasise the need for longitudinal
studies designed in light of developments in disease classification and retinal
imaging, which would ensure the correct classification of cases and controls, and
provide increased understanding of the natural course and progression of the
disease and further elucidate the structure-function relationships in this
devastating disorder.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 16580242 [PubMed - indexed for MEDLINE]

1518: Optometry. 2006 Apr;77(4):156-66.

Adult-onset foveomacular vitelliform dystrophy.

Do P, Ferrucci S.

VA Greater Los Angeles Healthcare System, Sepulveda Ambulatory Care Center and
Nursing Home, California 91343, USA.

BACKGROUND: Adult-onset foveomacular vitelliform dystrophy (AOFVD) is a condition
that presents classically as bilateral, symmetrical, grayish-yellow, round or
oval-shaped lesions within the macular area. These lesions are mildly elevated
and are typically one third to one half disc diameter in size. The onset of the
disease is usually between 30 and 50 years of age with variable genetic
inheritance, although some have suggested an autosomal dominance inheritance
pattern. Patients with AOFVD typically present with symptoms of blurred vision or
mild metamorphopsia. Results of diagnostic testing show a normal or mildly
subnormal electro-oculogram (EOG). Fluorescein angiography results (FA) typically
show hypofluorescence in the area corresponding to the vitelliform lesion and a
surrounding ring of hyperfluorescence. Results of optical coherence tomography
(OCT) show the vitelliform lesion as being located in the retinal pigment
epithelium (RPE) layer or between the RPE and photoreceptor layer. CASE REPORTS: 
Two cases of AOFVD are presented with each patient having different macular
appearances owing to the different stage of the disease process. In case 1, a
76-year-old white man presented with stage II AOFVD characterized by typical
vitelliform lesions. His best-corrected acuities were 20/70+ in the right eye
(O.D.) and 20/80- in the left eye (O.S.). In case 2, a 54-year-old white man
presented with stage V AOFVD with bilateral atrophic maculae with best-corrected 
acuities of 10/60- O.D. and 10/160- O.S. CONCLUSION: Patients with adult-onset
foveomacular vitelliform dystrophy typically have slow progressive vision loss.
However, patients can develop dramatically decreased vision owing to subfoveal
choroidal neovascularization (CNV). Thus, it is important to establish the
correct diagnosis and monitor this condition. Furthermore, because there are
reports of AOFVD having an autosomal dominance inheritance pattern with variable 
penetrance, it is recommended that the patient's family members have a
comprehensive eye examination to rule out any early signs of this rare eye
condition.

Publication Types: 
    Case Reports

PMID: 16567277 [PubMed - indexed for MEDLINE]

1519: Ann Acad Med Singapore. 2006 Feb;35(2):112-4.

Intravitreal triamcinolone acetonide for the treatment of diffuse diabetic
macular oedema--a case report.

Wang C, Katz BJ, Turner MJ, Hu J, Zhang K.

Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center,
University of Utah Health Sciences Center, Salt Lake City, Utah 84132, USA.

INTRODUCTION: Although laser photocoagulation is the primary treatment for
diabetic macular oedema, treatment of eyes with diffuse macular oedema has been
disappointing. Intravitreal injection of steroids is being investigated for the
treatment of diabetic macular oedema. Preliminary results indicate that steroid
injections do improve macular oedema, but it is not clear if they improve visual 
acuity. CLINICAL PICTURE, TREATMENT, AND OUTCOME: In this report, we describe a
patient with a form of diffuse diabetic macular oedema that responded favourably 
to intravitreal steroid injections, with improvements in both foveal thickness
and visual acuity. CONCLUSION: Intravitreal steroids can be useful for the
treatment of diffuse diabetic macular oedema.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 16565766 [PubMed - indexed for MEDLINE]

1520: Invest Ophthalmol Vis Sci. 2006 Apr;47(4):1703-9.

Perifoveal function in patients with North Carolina macular dystrophy: the
importance of accounting for fixation locus.

Seiple W, Szlyk JP, Paliga J, Rabb MF.

Department of Ophthalmology, New York University School of Medicine, New York,
New York 10016, USA. whs4@nyu.edu

PURPOSE: To quantify the extent of visual function losses in patients with North 
Carolina Macular Dystrophy (NCMD) and to demonstrate the importance of accounting
for eccentric fixation when making comparisons with normal data. METHODS: Five
patients with NCMD who were from a single family were examined. Multifocal
electroretinograms (mfERGs) and psychophysical assessments of acuity and
luminance visual field sensitivities were measured throughout the central retina.
Comparisons of responses from equivalent retinal areas were accomplished by
shifting normal templates to be centered at the locus of fixation for each
patient. RESULTS: Losses of psychophysically measured visual function in patients
with NCMD extend to areas adjacent to the locations of visible lesions. The
multifocal ERG amplitude was reduced only within the area of visible lesion.
Multifocal ERG implicit times were delayed throughout the entire central retinal 
area assessed. CONCLUSIONS: ERG timing is a sensitive assay of retinal function, 
and our results indicate that NCMD has a widespread effect at the level of the
mid and outer retina. The findings also demonstrated that it is necessary to
account for fixation locus and to ensure that equivalent retinal areas are
compared when testing patients with macular disease who have eccentric fixation.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, Non-P.H.S.

PMID: 16565412 [PubMed - indexed for MEDLINE]

1521: Invest Ophthalmol Vis Sci. 2006 Apr;47(4):1581-6.

Regulation of subfoveal choroidal blood flow in age-related macular degeneration.

Pournaras CJ, Logean E, Riva CE, Petrig BL, Chamot SR, Coscas G, Soubrane G.

Department of Ophthalmology, University of Geneva, Geneva, Switzerland.
constantin.pournaras@hcuge.ch

PURPOSE: To assess the capability of the subfoveal choroidal circulation to
regulate its blood flow in response to an acute increase in ocular perfusion
pressure in the eyes of healthy elderly persons or of subjects with neovascular
age-related macular degeneration (AMD). METHODS: Changes of subfoveal choroidal
blood velocity (ChBVel), volume (ChBVol), and flow (ChBF) induced by isometric
exercise were determined using laser Doppler flowmetry (LDF) in 19 young healthy 
volunteers (group 1), 24 elderly healthy volunteers with mild macular pigment
distribution changes (group 2), and 23 subjects with subfoveal classic
neovascularization caused by AMD (group 3). RESULTS: Isometric exercise induced
significant increases in mean ocular perfusion pressure (PPm) of 19.5% +/- 4.9%, 
20.2% +/- 3.8%, and 23.2% +/- 4.2%, for groups 1, 2, and 3, respectively (mean
+/- 95% confidence interval). In groups 1 and 2, the increase in PPm did not
induce significant changes in the mean values of the different LDF parameters. In
group 3, however, ChBF increased significantly by 12.4% +/- 5.0%. No significant 
correlations were found between age and the changes of each of the LDF parameters
and of PPm at the end of squatting for the young and elderly healthy groups.
CONCLUSIONS: In response to an acute, moderate increase in PPm induced by
isometric exercise, subfoveal choroidal blood flow behaves similarly in young and
elderly healthy persons and is not significantly different from its value at
rest. In contrast, in patients with neovascular AMD, this flow increases,
indicating altered regulation in response to the increase in PPm.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16565395 [PubMed - indexed for MEDLINE]

1522: Invest Ophthalmol Vis Sci. 2006 Apr;47(4):1310-8.

Effect of short-term, high-dose retinol on dark adaptation in aging and early
age-related maculopathy.

Owsley C, McGwin G, Jackson GR, Heimburger DC, Piyathilake CJ, Klein R, White MF,
Kallies K.

Department of Ophthalmology, School of Medicine, University of Alabama at
Birmingham, 35294-0009, USA. owsley@uab.edu

PURPOSE: To examine the effect of a short course of high-dose retinol (preformed 
vitamin A) on dark adaptation in older adults with normal retinal health or early
age-related maculopathy (ARM). METHODS: The study design was a randomized,
double-masked, placebo-controlled experiment. Adults > or = 50 years of age whose
fundus photographs for the eye to be tested psychophysically fell within steps 1 
to 9 of the Age-Related Eye Disease Study (AREDS) Grading System were randomly
assigned to a 30-day course of 50,000 IU oral retinol or a placebo. At baseline
and 30-day follow-up, dark adaptation was tested and the Low Luminance
Questionnaire (LLQ), an instrument for assessing difficulty with vision in
reduced lighting, was administered. Primary outcomes of interest were rod- and
cone-mediated parameters of dark adaptation, with scores on the LLQ's six
subscales as secondary outcomes. RESULTS: The sample consisted of 104
participants with 52 each in the intervention and placebo groups. There were no
group differences in baseline variables. At 30-days, the dark-adaptation
parameters of cone time-constant, cone threshold, rod-cone break, and rod
threshold did not differ. The retinol intervention group had significantly larger
(i.e., steeper) rod slopes, indicating faster sensitivity recovery, than did the 
placebo group (P = 0.0419). There were no group differences in scores on the LLQ 
subscales driving, extreme lighting, emotional distress, general lighting, or
peripheral vision. The retinol group had a higher score by five points on the
mobility subscale compared with the placebo group (P = 0.0141). Those who had the
most self-reported change on the mobility subscale at day 30 were more likely to 
have greater change in the speed of dark adaptation, as indicated by the rod
slope parameter (r = 0.24, P = 0.0141). CONCLUSIONS: A short-term, high-dose
course of retinol increased the rate of rod-mediated dark adaptation in older
adults who were in the early phases of ARM or were exhibiting normal retinal
aging. These results are consistent with the hypothesis that depositions and
other structural changes in the retinal pigment epithelium and Bruch's membrane
in aging and early ARM cause a localized retinoid deficiency.

Publication Types: 
    Randomized Controlled Trial
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16565362 [PubMed - indexed for MEDLINE]

1523: Am J Ophthalmol. 2006 Apr;141(4):646-51.

A randomized, masked, cross-over trial of lisinopril for inflammatory macular
edema.

van Kooij B, Fijnheer R, de Boer J, ten Dam-van Loon N, Bartelink I, Roest M,
Rothova A.

F.C. Donders Institute of Ophthalmology, Department of Hematology, University
Medical Center, Utrecht, The Netherlands. b.vankooij@oogh.azu.nl

PURPOSE: To analyze the effect of angiotensin-converting enzyme (ACE) inhibitor
lisinopril on inflammatory cystoid macular edema and visual acuity. DESIGN:
Randomized, double-blind, placebo-controlled cross-over trial. METHODS: setting: 
Outpatient clinic of the Department of Ophthalmology at the University Medical
Center of Utrecht. patients: Forty patients with inflammatory cystoid macular
edema were included. intervention: Each patient received lisinopril (10 mg daily)
or placebo for three months. After two months of a lisinopril/placebo free
wash-out period, the groups received the reverse study medication for three
months. Fluorescein angiography was performed to evaluate the retina. main
outcome measures: Cystoid macular edema, best-corrected visual acuity and
contrast sensitivity. RESULTS: Lisinopril had no effect on cystoid macular edema,
visual acuity, papillary leakage, retinal vasculitis, and choroidal leakage. In a
subgroup analysis, we observed a decrease in blood pressure (lisinopril, 14 of 36
patients; placebo, 5 of 36 patients; P = .02) and a decrease in morning urinary
albumin excretion (lisinopril, 23 of 35 patients; placebo 10 of 34 patients, P = 
.003) was observed. CONCLUSIONS: Although lisinopril had no effect on
inflammatory cystoid macular edema and visual acuity, we found a positive effect 
on the vascular system.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16564798 [PubMed - indexed for MEDLINE]

1524: Am J Ophthalmol. 2006 Apr;141(4):638-45.

Verteporfin and intravitreal triamcinolone acetonide combination therapy for
occult choroidal neovascularization in age-related macular degeneration.

Augustin AJ, Schmidt-Erfurth U.

Department of Ophthalmology, Klinikum Karlsruhe, Karlsruhe, Germany.

PURPOSE: To evaluate the efficacy and safety of photodynamic therapy (PDT) with
verteporfin combined with intravitreal triamcinolone (IVTA) in occult choroidal
neovascularization (CNV) secondary to age-related macular degeneration (AMD).
DESIGN: Single center, nonrandomized interventional case series. METHODS: A
prospective, noncomparative, interventional case series of 41 eyes of 41 patients
with a two-year follow-up period. Verteporfin PDT was performed using the
recommended standard procedure for approved forms of AMD. A solution containing
25 mg of crystalline triamcinolone acetonide was injected intravitreally 16 hours
post PDT. The procedure was repeated after three months in case of persistent CNV
leakage. RESULTS: The mean number of treatments needed was 1.8. Thirty-four eyes 
(82.9%) required one retreatment at three months. No additional retreatments were
necessary. Visual acuity improved gradually in most of the patients with mean
values of 20/133 and 20/115 at baseline and three months; 20/101 and 20/84 at six
and twelve months; and 20/83 and 20/81 at eighteen and twenty-four months. Eleven
of 41 treated study eyes (26.8%) underwent cataract surgery between six and
fifteen months after the first treatment. Nine patients required local or
systemic glaucoma therapy because of a transient steroid induced intraocular
pressure increase. CONCLUSIONS: Verteporfin PDT combined with intravitreal
triamcinolone may improve the outcome of standard verteporfin PDT in the
treatment of occult CNV secondary to AMD. An improvement in visual acuity was
observed in most of the treated patients and was maintained during a two-year
follow-up period. Retreatment numbers were lower than expected from monotherapy
trials.

PMID: 16564797 [PubMed - indexed for MEDLINE]

1525: Am J Ophthalmol. 2006 Apr;141(4):629-37.

Cataract formation and other complications of intravitreal triamcinolone for
macular edema.

Thompson JT.

Greater Baltimore Medical Center, Baltimore, Maryland, USA.
JThompson@retinaspec.com

PURPOSE: To evaluate complications and results of intravitreal triamcinolone
acetonide for treatment of macular edema. DESIGN: Interventional, consecutive,
retrospective case series. METHODS: Ninety-three eyes with macular edema arising 
from retinovascular etiologies were treated with 4 mg intravitreal triamcinolone.
Eyes were monitored after injection for visual acuity changes and complications, 
including cataract formation and increase in intraocular pressure (IOP). Cataract
progression was analyzed by linear regression analysis of lens scores from lens
opacity standards. RESULTS: The mean visual acuity improved from 20/125 to -1 to 
20/100 + 2 by one to two months after injection (P < .001) and was 20/100 at the 
final examination (P = .006) at a mean of 1.2 years after injection.
Complications included a severe, culture-negative inflammatory reaction in one
eye (1.1%). IOP increased to 30 mm Hg or more in nine (9.7%) of 93 eyes between 1
and 140 days after injection and was more frequent in eyes receiving one or more 
preinjection glaucoma drops (two of 13 eyes, 15.4%, vs seven of 80 eyes, 8.75%,
without preinjection glaucoma drops). Nuclear sclerosis increased at a rate of
0.175 U per year, posterior subcapsular cataracts at 0.423 U per year, and
cortical cataracts at 0.045 U per year. Posterior subcapsular cataract increased 
by > or = 1 U or required cataract surgery in 45.2% of eyes followed at least one
year. CONCLUSIONS: Intravitreal triamcinolone improves visual acuity in most eyes
but eyes must be monitored carefully for increase in IOP. Posterior subcapsular
cataract formation becomes visually significant in almost half of eyes by one
year after injection.

PMID: 16564796 [PubMed - indexed for MEDLINE]

1526: Am J Ophthalmol. 2006 Apr;141(4):611-5.

Comment in:
    Am J Ophthalmol. 2006 Apr;141(4):731-2.    Am J Ophthalmol. 2006 Oct;142(4):706-7; author reply 707.

Ocular rigidity in patients with age-related macular degeneration.

Pallikaris IG, Kymionis GD, Ginis HS, Kounis GA, Christodoulakis E, Tsilimbaris
MK.

Department of Ophthalmology, Institute of Vision and Optics, University of Crete,
Crete, Greece.

PURPOSE: To compare the ocular rigidity in vivo measurements of patients with
age-related macular degeneration (AMD) and control subjects. DESIGN: Prospective 
comparative clinical study. METHODS: The pressure-volume relation and the ocular 
rigidity coefficient were compared among 32 patients with AMD (AMD group: 16 with
neovascular and 16 with nonneovascular AMD) and 44 age-matched control patients
(control group) who underwent operation for cataract. This was achieved by an
injection of 200 microl of a balanced salt solution (in steps of 4.5 microl)
through the limbus in the anterior chamber, while the intraocular pressure was
monitored continually with a transducer, up to the limit of 30 mm Hg. RESULTS:
The mean age (AMD group: 69.89 +/- 15.92 years vs control group: 65.28 +/- 12.34 
years; P = .195), gender (AMD group: 13 female vs control group: 17 female; P =
.513), eye's axial length (AMD group: 23.14 +/- 0.75 mm vs control group: 23.04
+/- 1.16 mm; P = .725) of patients with AMD and the healthy control subjects were
comparable. No statistically significant difference in ocular rigidity
measurements between patients with AMD and control subjects (AMD group: 0.0142
+/- 0.0077 microl(-1) vs control group: 0.0125 +/- 0.0049 microl(-1); P = .255)
was found. When we examined separately the two subgroups of patients with AMD
(neovascular and nonneovascular AMD), the average ocular rigidity measurements
were higher in patients with neovascular AMD vs both control subjects and
patients with nonneovascular AMD (neovascular AMD group: 0.0186 +/- 0.0078
microl(-1) vs control group: 0.0125 +/- 0.0048 microl(-1) [P = .014] vs
nonneovascular AMD group: 0.0104 +/- 0.0053 microl(-1) [P = .004]). CONCLUSIONS: 
Despite the limitations placed by the small sample of the examined cases,
patients with neovascular AMD who are treated (with photodynamic therapy) have
increased ocular rigidity measurements compared with patients with nonneovascular
AMD and control patients.

Publication Types: 
    Comparative Study

PMID: 16564793 [PubMed - indexed for MEDLINE]

1527: Drug Ther Bull. 2006 Feb;44(2):9-11.

Nutritional supplements for macular degeneration.

[No authors listed]

Age-related macular degeneration is the commonest cause of blindness in developed
countries and the third most common worldwide. Each year in the UK, around 17,000
people become blind or partially sighted as a result of this condition, and its
prevalence is likely to increase with an ageing population. Laser therapy and
rarely surgery, can slow disease progression in a minority of patients but is
unlikely to restore lost vision. A wide range of nutritional supplements are now 
on sale with promotional claims that they improve eye health. While some
specialists recommend their use to patients with advanced disease, these
supplements are also increasingly promoted to people with early or no signs of
disease. Consequently, GPs come under pressure from patients to recommend, or
even prescribe, a nutritional supplement. Here we examine the evidence for
nutritional supplements in the management of age-related macular degeneration and
consider which, if any, can be recommended.

Publication Types: 
    Review

PMID: 16550811 [PubMed - indexed for MEDLINE]

1528: Br J Ophthalmol. 2006 Apr;90(4):442-6.

Comment in:
    Br J Ophthalmol. 2006 Apr;90(4):396-7.    Br J Ophthalmol. 2006 Apr;90(4):398-9.

Development of atrophy of the retinal pigment epithelium around disciform scars.

Sarks J, Tang K, Killingsworth M, Arnold J, Sarks S.

Prince of Wales Medical Research Institute, Randwick, Sydney, NSW, Australia.
jssarks@bigpond.net.au

BACKGROUND/AIMS: Eyes with burnt out disciform scars secondary to age related
macular degeneration (AMD) are regarded as visually stable. The aim of this study
is to report the subsequent development of atrophy of the retinal pigment
epithelium (RPE) around the scars and discuss the possible basis. METHODS: 20
eyes from 18 patients were observed to develop atrophy around choroidal
neovascularisation (CNV). A method of measuring expansion of the atrophy over
time is described using the Topcon Imagenet 2000 system. An additional 10
clinicopathological examples were reviewed. RESULTS: Clinically CNV became
surrounded initially by a ring of pallor that progressed to an expanding band of 
atrophy of the RPE. It developed most rapidly in the first 3 years after CNV
became quiescent but then continued to expand slowly to more than three times the
size of the scar. Histopathological specimens showed large choroidal vessels
entering the scars directly and a reduced number of small choroidal vessels
beneath and around the scar CONCLUSIONS: Disciform scars may become surrounded by
an expanding band of atrophy of the RPE, postulated to result from remodelling of
the choroidal circulation. The ongoing enlargement of the resulting scotoma may
need to be considered when planning management and assessing treatment outcomes.

Publication Types: 
    Case Reports

PMID: 16547324 [PubMed - indexed for MEDLINE]

1529: Br J Ophthalmol. 2006 Apr;90(4):432-4.

Effect of age related macular degeneration on the Eger macular stressometer
photostress recovery time.

Wolffsohn JS, Anderson SJ, Mitchell J, Woodcock A, Rubinstein M, Ffytche T,
Browning A, Willbond K, Amoaku WM, Bradley C.

School of Life and Health Sciences, Aston University, Birmingham B4 7ET, UK.
j.s.w.wolffsohn@aston.ac.uk

AIM: To assess the repeatability of Eger macular stressometer (EMS) measures of
photostress recovery and determine their association with other measures of
visual function. METHODS: EMS photostress recovery time was measured in 90
patients with bilateral exudative age related macular degeneration (AMD), 19 with
bilateral atrophic AMD and 47 with both forms of the condition (mean age 79 (SD
13) years). Measurements were made on two occasions separated by 1 year.
Intrasession repeatability was assessed by repeating the measures after a 10
minute recovery period at the first visit. Distance visual acuity was measured
with a logMAR chart, near visual acuity with a MNRead chart at 25 cm, contrast
sensitivity with a Pelli-Robson chart, and the presence of central visual
disturbance assessed with an Amsler grid. A questionnaire was used to assess self
reported difficulties with glare recovery. RESULTS: The average EMS recovery time
was 11.0 (SD 8.9) seconds, decreasing by 1.6 (5.2) seconds on repeated
measurement (p<0.05). EMS photostress recovery was not correlated with visual
function measures or subjective difficulties with lights (p>0.05). EMS
photostress recovery time did not predict those whose vision decreased over the
following year compared with those among whom it remained stable. CONCLUSIONS:
The EMS test is not a useful tool in determining the severity or progression of
AMD.

Publication Types: 
    Evaluation Studies

PMID: 16547321 [PubMed - indexed for MEDLINE]

1530: Am J Ophthalmol. 2006 May;141(5):850-8. Epub 2006 Mar 20.

Comment in:
    Am J Ophthalmol. 2006 Oct;142(4):707; author reply 707-8.

Topical dorzolamide for the treatment of cystoid macular edema in patients with
retinitis pigmentosa.

Grover S, Apushkin MA, Fishman GA.

Department of Ophthalmology and Visual Sciences, University of Illinois at
Chicago, 1855 West Taylor Street, Chicago, IL 60612, USA.

PURPOSE: To determine if topical dorzolamide, as observed with the use of
systemic acetazolamide and methazolamide, would be effective in treating cystoid 
macular edema (CME) in patients with retinitis pigmentosa (RP). DESIGN:
Prospective, nonrandomized clinical trial. METHODS: setting: Institutional.
patients: Fifteen patients with CME and RP. intervention: A baseline visual
acuity and optical coherence tomography (OCT) measurements were obtained in all
patients. Each one of them was then treated with topical dorzolamide, three times
a day, for at least four weeks in both eyes. main outcome measures: Significant
decrease in "foveal thickness" (more than 16%) and "foveal zone thickness" (more 
than 11%), as measured by OCT. RESULTS: Thirteen (87%) of 15 patients showed a
significant decrease in retinal thickness in at least one eye after use of
topical dorzolamide for at least four weeks. Five patients (33%) demonstrated
improvement in both eyes. All patients, except one, who responded showed the
effect within four weeks, but were monitored for a period of two to nine months
(average 4.5 months). Four patients (31%) who showed an initial improvement in
macular edema showed worsening with continued treatment. CONCLUSIONS: The present
study documents the potential efficacy of topical dorzolamide for treating CME in
patients with RP. We observed that some patients may show a "rebound phenomenon" 
with continued use of the medication; hence, there is a need for careful
follow-up in patients being treated.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 16546110 [PubMed - indexed for MEDLINE]

1531: Vision Res. 2006 Aug;46(16):2487-98. Epub 2006 Mar 20.

Binocular interactions in patients with age-related macular degeneration: acuity 
summation and rivalry.

Tarita-Nistor L, González EG, Markowitz SN, Steinbach MJ.

Centre for Vision Research, York University, Toronto, Canada.

This study examined two aspects of binocular function in patients with
age-related macular degeneration (AMD): summation/inhibition of visual acuity and
rivalry. The performance of 17 patients with AMD was compared with that of 17
elderly controls and 21 young people. Monocular and binocular acuities were
measured using a multiple-E optotype test. Binocular ratios, defined as the
better-eye acuity divided by the binocular acuity, were calculated. We also
measured eye dominance during rivalry (proportion of time the participants
reported perceiving the input to each eye) and rivalry rates (number of
alternations per minute). The results showed that while overall binocular ratios 
were similar for the three groups, the frequency distributions of people who
experienced inhibition, equality or summation were different for the young and
AMD groups. In the rivalry test, patients experienced more piecemeal perception
than the elderly and young controls, but time dominance from the better-seeing
eye was comparable for the three groups. Rivalry rates decreased with age and
further with pathology. Moreover, rivalry time dominance of the worse-seeing eye 
was negatively correlated with interocular acuity differences for the AMD group.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16545856 [PubMed - indexed for MEDLINE]

1532: Isr Med Assoc J. 2006 Feb;8(2):83-7.

Comment in:
    Isr Med Assoc J. 2006 Feb;8(2):127-8.

Intravitreal triamcinolone injection for diffuse diabetic macular edema with
foveal cystoid changes.

Barak A, Regenbogen M, Goldstein M, Loewenstein A.

Department of Ophthalmology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. 
omadb@post.tau.ac.il

BACKGROUND: Diabetic macular edema causes visual loss in almost one-third of
diabetic patients. There is currently no treatment for the accompanying cystoid
foveal changes. OBJECTIVES: To assess the clinical outcome, i.e., change in
visual acuity, in patients treated with steroids for long-standing diabetic
macular edema with foveal cystoid changes. METHODS: In the ophthalmology
department of a tertiary care university-affiliated medical center and the
ophthalmology service of a health management organization, 46 diabetic subjects
(56 eyes) who had diabetic macular edema with cystoid foveal changes received one
intravitreal injection of 4 mg triamcinolone acetonide. RESULTS: The mean
baseline (pre-injection) visual acuity of 0.21 increased to 0.31 and 0.48 at 1
and 3 months, respectively, after which it decreased to 0.33 at 6 months. The
mean intraocular pressure was 15.07 mmHg at baseline, 15.83 at day 1, gradually
rising to 17.16, 18.38 and 18.57 mmHg at 1, 3 and 6 months respectively. Three
patients suffered immediate visual decline after the injection. CONCLUSIONS:
Intravitreal triamcinolone acetonide may be a therapeutic option for
long-standing diabetic macular edema with foveal cystoid changes.

PMID: 16544727 [PubMed - indexed for MEDLINE]

1533: Issues Emerg Health Technol. 2005 Dec;(76):1-4.

Pegaptanib for neovascular age-related macular degeneration.

Maberley D.

(1) Neovascular (wet) age-related macular degeneration (AMD) results from the
growth of abnormal blood vessels under the retina (choroidal neovascularization).
Sudden and permanent vision loss occurs as these vessels grow, leak, bleed, and
scar. (2) A human protein, vascular endothelial growth factor (VEGF), is
implicated in the development of wet AMD. Pegaptanib attaches to VEGF and blocks 
its action. (3) In two concurrent, high quality studies using identical research 
methods, pegaptanib demonstrated a therapeutic advantage over placebo for the
prevention of vision loss due to neovascular AMD. (4) Pegaptanib is injected into
the eye every six weeks. This carries the risk of endophthalmitis (intraocular
infection), lens damage (if accidentally penetrated), and retinal detachment.
Systemic side-effects have not been associated with pegaptanib.

PMID: 16544440 [PubMed - indexed for MEDLINE]

1534: Eye. 2007 Mar;21(3):321-3. Epub 2006 Mar 17.

Intravitreal triamcinolone will cause posterior subcapsular cataract in most eyes
with diabetic maculopathy within 2 years.

Islam MS, Vernon SA, Negi A.

Directorate of Ophthalmology, Queen's Medical Centre, University Hospital NHS
Trust, Nottingham, UK. msislam@doctors.org.uk

PURPOSE: To determine the incidence of cataract following intravitreal
triamcinolone (IVTA) for diabetic macular oedema. METHODS: Prospective,
non-randomised, interventional cohort case series. A total of 27 eyes of 27
patients with diabetic macular oedema received an intravitreal injection of 4 mg 
(0.1 ml) of triamcinolone acetonide inferotemporally through the pars plana under
direct vision. In 20 patients the fellow eye served as control, whereas seven
patients had both eyes injected (not simultaneously). Seven patients had a repeat
(second) injection in the same eye. The main outcome measures were cataract and
intraocular pressure (IOP) rise of at least 5 mmHg (IOP responder). RESULTS: The 
mean follow-up time was 18.9 months (range 13-29 months). A total of 22 (81%) of 
27 eyes developed cataract during the follow-up period, of which 20 (74%) were
posterior subcapsular in nature. None of the 20 uninjected fellow eyes developed 
posterior subcapsular cataract. Mean time to cataract formation was 16.2 months. 
In the seven patients who had both eyes injected, mean time to cataract formation
was 16.5 and 17.1 months in the first and second eye, respectively. Mean time to 
cataract formation in seven eyes receiving a repeat second injection was 17.9
months. There was no significant difference in cataract formation between IOP
responders (85%) and non-responders (79%) (P=1.00, Fisher's exact test).
Uneventful cataract surgery was performed in six eyes of five patients.
CONCLUSION: This study demonstrates that given appropriate long-term follow-up,
the majority of patients, even after a single IVTA injection, will go on to
develop cataract, of which posterior subcapsular will be by far the most common.

PMID: 16543927 [PubMed - indexed for MEDLINE]

1535: Eye. 2007 Jun;21(6):721-6. Epub 2006 Mar 17.

Transpupillary thermotherapy for the treatment of choroidal neovascularization in
age-related macular degeneration in Taiwan.

Tsai TH, Yang CM, Yang CH, Ho TC, Huang JS, Chen MS.

Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan.

PURPOSE: To evaluate the therapeutic outcome and the recurrence of choroidal
neovascularization (CNV) secondary to age-related macular degeneration (AMD)
after transpupillary thermotherapy (TTT) in light-brown retinas. METHODS: A
retrospective, non-randomized study of 58 eyes in 55 patients with subfoveal CNV 
treated with TTT was conducted. Power settings were set about half the value for 
Caucasian eyes. The outcome was assessed with best-corrected visual acuity,
fluorescein angiography, indocyanine green angiography, and fundoscopic
examination. RESULTS: Forty-four membranes were occult, six classic, and eight
mixed. Mean follow-up was 16.6+/-10.7 months (range: 6-48 months). Membranes
closed in 46 eyes. Iatrogenic complications included three subretinal
haemorrhage, two retinal pigment epithelium tears, and two macular area cystic
changes. In eyes with occult CNV, visual acuity improved in six (13.6%), 14
(31.8%) remained unchanged, and 24 (54.6%) deteriorated. For various CNV, average
logMAR changes from baseline at last follow-up were 0.30 in occult, -0.08 in
classic, and 0.59 in mixed (P<0.01). Thirty eyes experienced recurrence within
9.2+/-6.2 months (range: 2-22 months). Cumulative recurrence rate was 45% at 12
months and 71% at 22 months, with no significant difference between occult and
non-occult type CNV. CONCLUSIONS: Transpupillary thermotherapy does not cure CNV 
secondary to AMD. High recurrence was found independent of CNV type. Most
improved vision was found mostly in classic CNV. Complications associated with
high energy level should be considered in light-brown retinas.

Publication Types: 
    Evaluation Studies

PMID: 16543926 [PubMed - indexed for MEDLINE]

1536: Mol Vis. 2006 Mar 6;12:156-8.

Complement factor H polymorphisms in Japanese population with age-related macular
degeneration.

Okamoto H, Umeda S, Obazawa M, Minami M, Noda T, Mizota A, Honda M, Tanaka M,
Koyama R, Takagi I, Sakamoto Y, Saito Y, Miyake Y, Iwata T.

National Institute of Sensory Organs, National Hospital Organization Tokyo
Medical Center, Tokyo, Japan. okamotoharu@kankakuki.go.jp

PURPOSE: To study the frequency of five haplotypes previously reported in the
complement factor H (CFH) gene for Japanese patients with age-related macular
degeneration (AMD). METHODS: Genomic DNA was isolated from peripheral blood
samples taken from 96 Japanese AMD patients and 89 age-matched controls. All
patients were diagnosed as having exudative (wet-type) AMD. The amplified
polymerase chain reaction (PCR) products of CFH exons 2, 9, and 13, and intron 6 
were analyzed by temperature gradient capillary electrophoresis (TGCE) and by
direct sequencing. The haplotypes were identified, and their frequencies were
calculated and compared with reported results. RESULTS: Five haplotypes were
identified in the Japanese population including four already reported in the
American population. The frequencies of these haplotypes were significantly
different between Japanese and American in both control and case groups. The
haplotype containing Y402H, which was previously reported to be associated with
AMD, was only 4% in the control and case population, with a p value of 0.802.
However, two other haplotypes were found as risk factors, which gave an increased
likelihood of AMD of 1.9 and 2.5 fold (95% CI 1.12-3.69 and 1.42-6.38). One
protective haplotype that decreased the likelihood of AMD by 1.6 fold (95% CI
0.26-0.67) was identified. CONCLUSIONS: The frequencies for five haplotypes
previously identified were analyzed in a Japanese population with AMD. Four
previously found haplotypes were identified and one additional haplotype was
found. The frequencies of each haplotype were significantly different from that
in found Americans affected with AMD. Two of the haplotypes were identified as
risk factors and one was considered protective.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16541016 [PubMed - indexed for MEDLINE]

1537: Graefes Arch Clin Exp Ophthalmol. 2006 Sep;244(9):1132-42. Epub 2006 Mar
15.

Verteporfin therapy of subfoveal choroidal neovascularization in age-related
macular degeneration: 5-year results of two randomized clinical trials with an
open-label extension: TAP report no. 8.

Kaiser PK; Treatment of Age-Related Macular Degeneration with Photodynamic
Therapy (TAP) Study Group.

Cole Eye Institute, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
pkkaiser@aol.com

PURPOSE: To report vision and safety outcomes up to 5 years from an extension of 
the Treatment of Age-related Macular Degeneration with Photodynamic Therapy (TAP)
Investigation evaluating verteporfin therapy in patients with subfoveal choroidal
neovascularization (CNV) in age-related macular degeneration. METHODS: Patients
who completed the 2-year randomized, placebo-controlled portion of the TAP
Investigation could participate in the open-label extension study for an
additional 3 years. Patients in the study extension received open-label
verteporfin therapy in the study eye, fellow eye or both eyes, irrespective of
original treatment assignment to placebo or verteporfin, if leakage from CNV was 
evident on fluorescein angiography. Follow-up visits occurred at 3-month
intervals through to month 48, with a final follow-up visit at month 60. RESULTS:
Of the 402 verteporfin-treated patients in the randomized trials, 320 (80%)
enrolled in the extension study; 193 (60%) of these completed the extension study
up to 5 years. Patients received an average of approximately two treatments
during the 3 years of the extension study. Seventy-seven (62%) of the 124
verteporfin-treated patients with predominantly classic lesions at baseline who
enrolled in the extension completed the month 60 examination. Twenty-six (34%) of
these 77 patients had lost 3 or more lines of visual acuity by month 24 and 27
(35%) had lost this amount of vision by month 60; the mean change in visual
acuity from baseline was also similar at the month 24 and month 60 examinations
(-1.5 and -1.6 lines, respectively). When visual acuity results were examined for
all extension patients who received verteporfin at baseline, regardless of
baseline lesion composition and extension study completion status, a similar
pattern of visual acuity stabilization was evident. Few additional instances of
infusion-related back pain or photosensitivity reactions were reported from month
24 to month 60. No additional safety issues were noted after bilateral treatment.
CONCLUSIONS: Vision outcomes remained relatively stable from month 24 to month 60
even though the treatment rate was low during this period. The TAP Study Group
identified no new safety concerns to preclude repeating verteporfin therapy as
described in this study through 5 years.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16538452 [PubMed - indexed for MEDLINE]

1538: Graefes Arch Clin Exp Ophthalmol. 2006 Oct;244(10):1255-61. Epub 2006 Mar
15.

The blood pressure-induced diameter response of retinal arterioles decreases with
increasing diabetic maculopathy.

Frederiksen CA, Jeppesen P, Knudsen ST, Poulsen PL, Mogensen CE, Bek T.

Department of Ophthalmology, Aarhus University Hospital, Aarhus, Denmark.
chr.frederiksen@teliamail.dk

BACKGROUND: The aim of the study was to compare the diameter response of retinal 
arterioles and retinal thickness in patients with different stages of diabetic
maculopathy during an increase in the arterial blood pressure. METHODS: Four
groups each consisting of 19 individuals were studied. Group A consisted of
normal individuals and groups B-D consisted of type 2 diabetic patients matched
for diabetes duration, age, and gender, and characterized by: Group B no
retinopathy, Group C mild retinopathy, Group D maculopathy not requiring laser
treatment. The diameter changes of a large retinal arteriole were measured using 
the Retinal Vessel Analyzer (RVA, Imedos, Germany) before, during, and after an
increase in the blood pressure induced by isometric exercise. Additionally, the
retinal thickness was measured using optical coherence tomography scanning.
RESULTS: The arterioles contracted during isometric exercise in normal persons
(diameter response: -0.70+/-0.48%) and in patients with no retinopathy
(-1.15+/-0.44%), but dilated in patients with mild retinopathy (0.41+/-0.49%) and
diabetic maculopathy (0.54+/-0.44%), p=0.01. Retinal thickness was normal in
Group A (260+/-5.0 microm), Group B (257+/-4.5 microm), and Group C (253+/-4.4
microm), but was significantly (p=0.006) increased in Group D (279+/-5.3 microm).
CONCLUSIONS: The diameter response was reduced in type 2 diabetic patients with
retinopathy, whereas retinal thickness was increased in patients with diabetic
maculopathy. This suggests that impairment of diameter response in retinal
arterioles precedes the development of diabetic macular edema.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16538448 [PubMed - indexed for MEDLINE]

1539: Optom Vis Sci. 2006 Mar;83(3):178-89.

Visual function in patients with choroidal neovascularization resulting from
age-related macular degeneration: the importance of looking beyond visual acuity.

Fletcher DC, Schuchard RA.

Department of Ophthalmology, Smith Kettlewell Eye Research Institute, San
Francisco, California, USA. floridafletch@msn.com

PURPOSE: A detailed understanding of overall quality of vision may help primary
care physicians, optometrists, and general ophthalmologists to improve the care
of patients with choroidal neovascularization (CNV) resulting from age-related
macular degeneration (AMD). METHODS: Published literature was reviewed using
Medline searches and the authors' knowledge of the field. RESULTS: Both visual
acuity and contrast sensitivity are strongly associated with the ability to
perform vision-related activities of daily living. CNV resulting from AMD often
leads to scotoma, which is also strongly associated with the ability to perform
everyday activities such as reading and driving. Contrast sensitivity and visual 
field extent may be better predictors of many abilities than visual acuity. Laser
photocoagulation, verteporfin therapy, and pegaptanib sodium have been proven to 
reduce the risk of visual acuity loss in patients with CNV resulting from AMD.
Laser photocoagulation frequently causes scotoma, but data on its effects on
other aspects of overall quality of vision are scarce. Verteporfin therapy has
been shown to also reduce the risk of contrast sensitivity loss and has been
associated with stabilization or reduction of scotoma size. Treatment effects
beyond visual acuity have not been investigated for pegaptanib. Detailed
assessment of overall quality of vision also aids the design of vision
rehabilitation programs tailored to the needs of individual patients.
CONCLUSIONS: Understanding the impact of vision loss on patients with CNV
resulting from AMD and assessing treatment benefits requires assessment of
overall quality of vision. Primary care physicians and optometrists have an
important role in ensuring that patients receive the best possible care, which
can be aided by prompt referral to an ophthalmologist or retina specialist and
collaboration with low-vision specialists and optometrists who together can make 
detailed assessments of overall quality of vision, implement appropriate
treatment, and design effective rehabilitation strategies.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 16534460 [PubMed - indexed for MEDLINE]

1540: Arch Ophthalmol. 2006 Mar;124(3):345-52.

Cone-mediated multifocal electroretinogram in age-related macular degeneration:
progression over a long-term follow-up.

Gerth C, Delahunt PB, Alam S, Morse LS, Werner JS.

Department of Ophthalmology and Vision Sciences and Section of Neurobiology,
Physiology, and Behavior, University of California, Davis, USA. chgerth@web.de

OBJECTIVE: To evaluate the progression of change in the cone-driven multifocal
electroretinogram (mfERG) responses in patients previously identified as having
high-risk, soft drusen 63 mum or greater. METHODS: Seventeen eyes of 14 patients 
were reevaluated after 28 to 41 months. Fundus changes were graded depending on
drusen size and extent. Each of the 103 mfERG responses was analyzed and compared
with age-matched normal controls and with the baseline measurement. RESULTS:
Stable visual acuity was found in 12 of the 17 eyes. Drusen size or extent was
increased, decreased, and unchanged in 6, 3, and 8 eyes, respectively. The mfERG 
responses demonstrated a significant progression in the response density loss and
in N1 and P1 implicit time delay compared with the baseline evaluation regardless
of drusen change. The extent of response deterioration occurred over the entire
retinal area tested. Eyes having decreased drusen at follow-up were typically
associated with higher response delays at baseline and follow-up than eyes with
stable or increased drusen. CONCLUSIONS: Early age-related macular degeneration
is associated with a progressive loss in the cone-driven mfERG response despite
stable visual acuity. The response deterioration extended beyond the visible
drusen area. Implicit times seem to be an important predictor of drusen
regression.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16534054 [PubMed - indexed for MEDLINE]

1541: Arch Ophthalmol. 2006 Mar;124(3):337-42.

Agreement of the Heidelberg Retina Tomograph II macula edema module with fundus
biomicroscopy in diabetic maculopathy.

Kisilevsky M, Hudson C, Flanagan JG, Nrusimhadevara RK, Guan K, Wong T,
Mandelcorn M, Lam WC, Devenyi RG.

Multi-Disciplinary Laboratory for the Research of Sight-Threatening Diabetic
Retinopathy, Department of Ophthalmology and Vision Science, University of
Toronto, Ontario.

OBJECTIVES: To estimate the agreement between the macular edema maps (MEMs) of
the Retina Module of the Heidelberg Retina Tomograph II (Heidelberg Engineering, 
Heidelberg, Germany) and contact lens fundus biomicroscopy (FB) and to assess the
influence of combining MEM data with the results of short-wavelength automated
perimetry (SWAP) and fluorescein angiography (FA) on diagnostic test performance.
DESIGN: Prospective, observational case series. METHODS: Twenty patients (20
eyes) with diabetic retinopathy with or without clinically manifest macular edema
(11 and 9 eyes, respectively) were enrolled. All patients underwent full
ophthalmologic examination and also MEM assessment, SWAP, and FA. RESULTS: Using 
FB as the "gold standard," the agreement between the MEMs and FB was very good
(Kendall coefficient of concordance, 0.80). Macular edema maps showed good
agreement with FA and SWAP (Kendall coefficient, 0.64 and 0.65). Virtually all of
the edematous areas detected with MEM but not seen clinically had decreased
sensitivity on SWAP and/or fluorescein leakage. CONCLUSIONS: Macular edema maps
demonstrated very good agreement with FB. Combining the results of FA and SWAP
with those of the MEMs provided supporting evidence of concomitant blood-retinal 
barrier leakage and visual dysfunction, respectively, in areas of early retinal
thickening. Prospective studies are ongoing to fully assess the diagnostic test
performance of MEMs in the detection of early and progressive diabetic macular
edema.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 16534053 [PubMed - indexed for MEDLINE]

1542: Ophthalmology. 2006 May;113(5):800-4. Epub 2006 Mar 13.

Repeated intravitreal high-dosage injections of triamcinolone acetonide for
diffuse diabetic macular edema.

Jonas JB, Spandau UH, Kamppeter BA, Vossmerbaeumer U, Harder B, Sauder G.

Department of Ophthalmology, Faculty of Clinical Medicine Mannheim of the
University Heidelberg, Mannheim, Germany. Jost.Jonas@ma.augen.uni-heidelberg.de

OBJECTIVE: To report the results of repeated intravitreal injections of
triamcinolone acetonide for treatment of diffuse diabetic macular edema. DESIGN: 
Retrospective interventional comparative study. PARTICIPANTS: The investigation
included a study group (the responders) of 19 patients (22 eyes) with diffuse
diabetic macular edema, who showed an improvement in visual acuity after an
intravitreal injection of approximately 20 mg triamcinolone acetonide, and who
received a second intravitreal injection 10.0+/-3.8 months after the first
injection. A control group consisted of 31 patients with diffuse diabetic macular
edema without treatment during follow-up. METHODS: Intravitreal injection of
approximately 20 mg triamcinolone acetonide. MAIN OUTCOME MEASURES: Visual acuity
and intraocular pressure. RESULTS: Follow-up after the second injection was
9.1+/-4.9 months. Four patients received a third injection at 9.7+/-3.7 months
after the second injection, with a follow-up after the third injection that was
at 7.9+/-11.5 months. After the second and third injections, visual acuity
increased significantly (P = 0.002 and P = 0.068, respectively) by 1.8+/-2.1 and 
4.0+/-2.6 Snellen lines, respectively. Eleven eyes (50%) showed an improvement in
visual acuity by at least 2 Snellen lines after the second injection, and 3
patients (75%) experienced a gain in visual acuity by at least 2 Snellen lines
after the third injection. Intraocular pressure increased significantly (P<0.01) 
after each injection, and returned to baseline values before each reinjection.
Visual acuity improvement (P>0.05) and intraocular pressure rise did not differ
significantly (P>0.55) between the various injections. Improvement in visual
acuity and rise of intraocular pressure lasted approximately 6 to 8 months after 
each injection. CONCLUSIONS: Intravitreal injection of approximately 20 mg
triamcinolone acetonide may repeatedly lead to an improvement in visual acuity
and a rise of intraocular pressure in patients with diffuse diabetic macular
edema. The duration of the effect after each injection is approximately 6 to 8
months. Tachyphylaxis in visual acuity or intraocular pressure outcomes were not 
observed.

Publication Types: 
    Comparative Study

PMID: 16530840 [PubMed - indexed for MEDLINE]

1543: Exp Eye Res. 2006 Jul;83(1):128-32. Epub 2006 Mar 10.

Effect of viagra on retinal vein diameter in AMD patients.

Metelitsina TI, Grunwald JE, DuPont JC, Ying GS, Liu C.

Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania, 51
North 39th Street, Philadelphia, PA 19104, USA. tanya.metelisina@uphs.upenn.edu

The aim of the present study was to investigate the effect of sildenafil citrate 
(viagra) on retinal venous diameter in patients with age-related macular
degeneration (AMD). We investigated 14 male patients in a double-masked,
randomized, placebo-controlled, crossover study. In each subject, one eye with
typical non-exudative AMD fundus features was studied. Each of the subjects
received 100 mg dose of sildenafil or matching placebo on two separate study
visits. Monochromatic fundus photographs were obtained in the study eye before
dosing and then 30, 90, 180 and 300 min later. Measurements of the diameter of
the major retinal veins from digitized negatives were carried out using "Vessel
map" static vessel analysis program (IMEDOS GmbH, Weimar, Germany). Statistical
analysis of the data comparing the effect of sildenafil and placebo on venous
diameters was performed using analysis of variance (ANOVA) for repeated measures.
An analysis of variance (ANOVA) comparing the effects of sildenafil citrate and
placebo on retinal vein diameters showed a significant interaction between time
and treatment (P = 0.03). In comparison to placebo, sildenafil citrate produced a
statistically significant vasodilatation of major retinal veins of 4.7% at 90 min
(P = 0.004), 5.5% at 180 min (P < 0.0001) and 5.8% at 300 min (P < 0.0001). At 30
min there was a 2.2% difference, which was not statistically significant
(P=0.14). Our results suggest that in patients with age-related macular
degeneration, sildenafil citrate (viagra) produces a statistically significant
vasodilatation of major retinal veins that is similar to what has been reported
in normal subjects. Whether this vasodilatation is associated with changes in
retinal blood flow needs to be further investigated.

Publication Types: 
    Randomized Controlled Trial

PMID: 16530757 [PubMed - indexed for MEDLINE]

1544: Nutrition. 2006 Apr;22(4):441-3.

C-reactive protein and homocysteine are associated with dietary and behavioral
risk factors for age-related macular degeneration.

Seddon JM, Gensler G, Klein ML, Milton RC.

Epidemiology Unit, Massachusetts Eye and Ear Infirmary, Department of
Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA.
jseddon@earthlink.net

OBJECTIVE: We investigated whether age-related macular degeneration risk factors 
are associated with high-sensitivity C-reactive protein (CRP) and homocysteine
(HCY), systemic biomarkers for cardiovascular disease. METHODS: Subjects with a
range of age-related macular maculopathies or no maculopathy at two centers in
the United States were evaluated. Risk factors and biomarkers were assessed by
questionnaire, direct measurement, or analyses of blood specimens. RESULTS:
Higher levels of serum antioxidants vitamin C and lutein/zeaxanthin and higher
fish intake were associated with lower serum CRP levels, whereas serum vitamin E,
smoking, and increased body mass index were associated with increased CRP. Serum 
vitamin E, serum alpha-carotene, and dietary intake of antioxidants and vitamin
B6 were associated with lower levels of plasma HCY, whereas hypertension was
associated with increased HCY. CONCLUSIONS: C-reactive protein and HCY levels are
related to traditional dietary and behavioral factors associated with age-related
macular degeneration.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16530626 [PubMed - indexed for MEDLINE]

1545: Am J Ophthalmol. 2006 May;141(5):863-7. Epub 2006 Mar 9.

Long-term effect of laser treatment for dry age-related macular degeneration on
choroidal hemodynamics.

Figueroa M, Schocket LS, DuPont J, Metelitsina TI, Grunwald JE.

Department of Ophthalmology, Scheie Eye Institute, School of Medicine, University
of Pennsylvania, 51 North 39th Street, Philadelphia, PA 19104, USA.

PURPOSE: To determine whether laser treatment applied according to the
complications of age-related macular degeneration prevention trial (CAPT) has an 
effect on the choroidal circulation. DESIGN: Randomized controlled trial.
METHODS: This study included 30 CAPT patients with bilateral drusen. Laser
Doppler flowmetry was used to measure relative choroidal blood flow (Ch(flow)) in
the fovea. Measurements were obtained through dilated pupils in both eyes of each
patient before photocoagulation was applied in one eye. Measurements were
repeated at three months (30 patients) and 28 months (23 patients). RESULTS:
Average Ch(flow) at baseline, three months, and 28 months was 7.2 +/- 2.1 (+/-1
SD), 7.3 +/- 2.5, and 6.8 +/- 2.7 arbitrary units (AU) in the control eyes and
6.6 +/- 1.6, 7.0 +/- 2.3, and 7.8 +/- 3.0 AU in the treated eyes. In comparison
to control eyes, there was no significant change in Ch(flow) in the treated eyes 
at three months after treatment. At 28 months, however, there was a 5.6% drop in 
Ch(flow) in control eyes and an 18.2% increase in Ch(flow) in treated eyes from
baseline. The average difference of 23.8% between the percentage changes in
Ch(flow) observed in the control and treated eyes was statistically significant
(paired two-tailed Student t test; P = .05). CONCLUSIONS: Our results suggest an 
increase in choroidal blood flow 28 months after laser treatment according to the
CAPT protocol. This increase may play a role in the mechanism leading to the
disappearance of drusen after photocoagulation. Whether removal of drusen after
photocoagulation is beneficial to the patients is not known at this time.

Publication Types: 
    Randomized Controlled Trial
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16527229 [PubMed - indexed for MEDLINE]

1546: Am J Ophthalmol. 2006 May;141(5):876-883. Epub 2006 Mar 9.

Comment in:
    Am J Ophthalmol. 2006 Oct;142(4):710; author reply 710.

Intravitreal triamcinolone for the treatment of ischemic macular edema associated
with branch retinal vein occlusion.

Chen SD, Sundaram V, Lochhead J, Patel CK.

Oxford Eye Hospital, Woodstock Road, Oxford, United Kingdom.

PURPOSE: To evaluate the safety and efficacy of intravitreal triamcinolone
acetonide (IVTA) for ischemic macular edema associated with branch retinal vein
occlusion (BRVO) and foveal ischemia. DESIGN: Prospective interventional case
series. METHODS: setting: Clinical practice. study population: Eighteen eyes of
18 patients with macular edema associated with BRVO and foveal ischemia.
intervention: Four mg IVTA. main outcome measures: Visual acuity (VA), optical
coherence tomography, macular thickness measurements, and treatment-related
complications. RESULTS: The mean duration of BRVO before treatment was 14 months.
All patients were followed for a minimum of nine months, and 12 patients
completed 12 months follow-up. The mean logarithm of the minimum angle of
resolution (logMAR) VA improved significantly from 0.81 +/- 0.36 at baseline to
0.65 +/- 0.30 at one month (P = .03) but did not vary significantly from baseline
at three, six, nine, and 12 months. Macular thickness improved significantly in
all eyes from a mean of 400 +/- 134 mum preinjection, to 228 +/- 58 mum at one
month (P < .01) and 256 +/- 121 mum at three months (P < .01) but did not vary
significantly from baseline at six, nine, and 12 months. Eight eyes developed
posterior subcapsular cataract, intraocular pressure (IOP) exceeded 21 mm Hg in
four eyes, and two eyes developed vitreomacular traction during follow-up.
CONCLUSIONS: IVTA is effective in reducing ischemic macular edema associated with
BRVO and foveal capillary nonperfusion. This reduction is often associated with a
temporary improvement in VA. Raised IOP and development of posterior subcapsular 
cataract are disadvantages of this treatment.

PMID: 16527226 [PubMed - indexed for MEDLINE]

1547: Graefes Arch Clin Exp Ophthalmol. 2006 Oct;244(10):1224-32. Epub 2006 Mar
9.

Photodynamic therapy with verteporfin for retinal angiomatous proliferation.

Boscia F, Parodi MB, Furino C, Reibaldi M, Sborgia C.

Dipartimento di Oftalmologia ed Otorinolaringoiatria, Università di Bari, Piazza 
Giulio Cesare 11, Bari, Italy. francescoboscia@hotmail.com

PURPOSE: The aim of this study was to evaluate the results of photodynamic
therapy (PDT), using verteporfin, for subfoveal neovascular age-related macular
degeneration (ARMD) with retinal angiomatous proliferation (RAP) with pigment
epithelial detachment (PED) and/or choroidal neovascularization (CNV). METHODS:
In this non-comparative, consecutive, interventional, case series, the data on 21
eyes (19 with stage 2 and two with stage 3 RAP) of 20 patients were reviewed.
Serous PED occupied more than 50% of the lesion in 19 eyes. PDT was performed as 
per TAP protocol. Biomicroscopy and fluorescein and indocyanine-green angiography
were performed to evaluate anatomical results and need for retreatment. Changes
from baseline in best-corrected visual acuity (BCVA), and complications, were
assessed. RESULTS: A mean of 3.5+/-0.9 treatments was performed. After 13.7+/-2.2
months, mean BCVA decreased from 20/80 to 20/174 (P=0.0063). In six eyes (28.6%) 
BCVA remained stable, whereas in 15 eyes (71.5%) it decreased. Occlusion of RAP
and flattening of PED was observed in three (14.2%) eyes, conversion to disciform
lesion in one (4.7%), and persistence of PED in 11 eyes (52.3%). One eye (4.7%)
evolved to haemorrhagic PED, and one (4.7%) toward stage 3 RAP. A tear in the
retinal pigment epithelium (RPE) was observed in four eyes (19%). Eleven (52.3%) 
showed progression of leakage, six moderate leakage (28.6%), and three (14.2%)
absence of leakage. CONCLUSIONS: Timely PDT with verteporfin in the early stages 
in eyes with smaller lesions has the potential for a beneficial effect on vision,
whereas it might worsen the natural course of larger lesions, with most eyes
undergoing enlargement, disciform transformation or RPE tear.

PMID: 16525824 [PubMed - indexed for MEDLINE]

1548: Drug Saf. 2006;29(3):189-99.

A preliminary benefit-risk assessment of verteporfin in age-related macular
degeneration.

Wickens J, Blinder KJ.

Barnes Retina Institute, Department of Ophthalmology, Washington University
School of Medicine, St Louis, Missouri 63144, USA.

The prevalence of neovascular age-related macular degeneration (AMD) is expected 
to increase significantly during the next 20 years. New treatment alternatives to
laser photocoagulation are on the horizon - the first of these, photodynamic
therapy (PDT) with verteporfin, was approved by the US FDA in 2000. In this
article we present a preliminary risk-benefit assessment of verteporfin in AMD,
focusing on the landmark randomised, double-blind, placebo-controlled studies.
The TAP (Treatment of Age-related macular degeneration with Photodynamic therapy)
trial established the efficacy of PDT for classic subfoveal neovascularisation in
AMD at 2 years follow-up. The VIP (Verteporfin in Photodynamic therapy) study
concentrated on subfoveal occult-only lesions not included in the TAP study.
After 2 years, treated eyes were less likely to experience visual loss.
Exploratory analyses of TAP and VIP suggest that lesion size is a more
significant predictor of the treatment benefit than either lesion composition or 
visual activity. The VIM (Visudyne in Minimally classic) trial altered the
standard PDT light fluence rate in the treatment of subfoveal minimally classic
lesions. This trial again demonstrated a beneficial effect for those receiving
treatment with PDT. The VIO (Visudyne in Occult) trial, evaluating PDT in
occult-only lesions as a confirmatory study of the VIP trial, did not achieve its
primary end-point at 2 years. Further analyses are pending.PDT with verteporfin
has an excellent safety profile that has been established with >1 million
treatment applications. Cost-effectiveness data are limited but suggest that PDT 
may be a cost-effective treatment modality. Other FDA-approved treatments
(pegaptanib, ranibizumab and bevacizumab) for neovascular AMD are discussed, as
well as investigational substances such as anecortave acetate.

Publication Types: 
    Review

PMID: 16524319 [PubMed - indexed for MEDLINE]

1549: Graefes Arch Clin Exp Ophthalmol. 2006 Sep;244(9):1119-23. Epub 2006 Mar 8.

Added value of OCT in evaluating the presence of leakage in patients with
age-related macular degeneration treated with PDT.

van Velthoven ME, de Smet MD, Schlingemann RO, Magnani M, Verbraak FD.

Department of Ophthalmology, Academic Medical Centre, Amsterdam, The Netherlands.

BACKGROUND: Evaluating the presence of leakage on fluorescein angiography (FA) in
patients with age-related macular degeneration (AMD) retreated with photodynamic 
therapy (PDT) can be difficult. New diagnostic tools such as optical coherence
tomography (OCT) might help to optimize PDT management. METHODS: Thirty AMD
patients scheduled for regular follow-up FA in conjunction with PDT treatment
were also scanned with OCT. Follow-up data at 9 months were retrieved from the
patients' medical records. Inter-observer agreement [kappa coefficient] for the
presence of leakage on FA, for OCT parameters for leakage, and agreement between 
FA and OCT evaluations were calculated. The indication for retreatment was
evaluated using the leakage analysis based on FA alone, OCT alone, and both
examinations combined, and compared to the actual follow-up of the patients at 9 
months. RESULTS: Agreement between the two observers for the presence of leakage 
on FA was moderate (kappa=0.51). OCT agreement between the two observers for the 
presence of leakage was good (kappa=0.85). Agreement between FA and OCT for the
presence of leakage was poor (kappa=0.16). Follow-up data at 9 months on all
patients were analyzed. Seven out of 30 patients were not retreated at the time
of examination, and four of these patients (57%) remained stable without further 
treatment. Twenty-three patients did receive a PDT treatment at the time of
examination; and eight of these patients did not show leakage on OCT, and five of
these patients (62%) remained stable without additional treatment. In contrast,
only three out of 15 patients (20%) with leakage on both FA and OCT remained
stable during this 9 month follow-up period. CONCLUSIONS: Inter-observer
agreement for the presence of leakage was moderate for FA and good for OCT. There
was considerable disagreement between leakage as judged by OCT and by FA. OCT
could be of help in the decision regarding PDT retreatment. Assuming that 57% of 
the patients without leakage either on FA or OCT would remain stable without
retreatment, the rate of probable ineffective retreatment could be reduced from
35% to 20%.

PMID: 16523305 [PubMed - indexed for MEDLINE]

1550: Doc Ophthalmol. 2005 Nov;111(3):135-48. Epub 2006 Mar 6.

Dynamics of retinal function after multiple photodynamic therapies in age-related
macular degeneration: a report of cases.

Feigl B, Brown B, Lovie-Kitchin J, Lee L.

Centre for Health Research, School of Optometry, Queensland University of
Technology, Brisbane, Australia. b.feigi@qut.edu.au

PURPOSE: To monitor retinal function after multiple laser treatments by
photodynamic therapy (PDT) with the multifocal electroretinogram (mfERG) in
age-related macular degeneration (AMD). METHODS: Five eyes of five subjects with 
AMD were investigated before the first and 1 month after each of three PDT
treatments. Function was assessed using the cone- and rod-mediated mfERG,
high-contrast distance visual acuity, central visual fields and contrast
sensitivity. For each subject the local first-order mfERG results before
treatment were used as a template and fitted against the local post-treatment
results (Matlab, Mathworks). RESULTS: We found transient reduction of the cone-
and rod-mediated amplitudes between the first and second treatments but stable or
improved mfERG function in four of five eyes for the cone-mediated mfERG and in
all eyes for the rod-mediated mfERG after three treatments. Visual acuities and
contrast sensitivities remained stable between treatments in four and two eyes
respectively, whereas visual fields showed substantially higher mean defects in
two subjects after all treatments. CONCLUSION: As found in previous studies of
the cone-mediated mfERG after one PDT treatment, objective function was
stabilized after multiple treatments in this case report. Similarly, although
poor at baseline, rod-mediated function was not further compromised. Transiently 
reduced amplitudes after 1 month possibly reflected choroidal hypoperfusion. A
larger sample size is needed to confirm if additional evaluation using
electrophysiological criteria might be helpful in re-treatment decisions during
PDT.

Publication Types: 
    Comparative Study

PMID: 16523231 [PubMed - indexed for MEDLINE]

1551: Nat Genet. 2006 Apr;38(4):458-62. Epub 2006 Mar 5.

Variation in factor B (BF) and complement component 2 (C2) genes is associated
with age-related macular degeneration.

Gold B, Merriam JE, Zernant J, Hancox LS, Taiber AJ, Gehrs K, Cramer K, Neel J,
Bergeron J, Barile GR, Smith RT; AMD Genetics Clinical Study Group, Hageman GS,
Dean M, Allikmets R.

Laboratory of Genomic Diversity, National Cancer Institute, Frederick, Maryland
21702, USA.

Age-related macular degeneration (AMD) is the most common form of irreversible
blindness in developed countries. Variants in the factor H gene (CFH, also known 
as HF1), which encodes a major inhibitor of the alternative complement pathway,
are associated with the risk for developing AMD. Here we test the hypothesis that
variation in genes encoding other regulatory proteins of the same pathway is
associated with AMD. We screened factor B (BF) and complement component 2 (C2)
genes, located in the major histocompatibility complex class III region, for
genetic variation in two independent cohorts comprising approximately 900
individuals with AMD and approximately 400 matched controls. Haplotype analyses
identify a statistically significant common risk haplotype (H1) and two
protective haplotypes. The L9H variant of BF and the E318D variant of C2 (H10),
as well as a variant in intron 10 of C2 and the R32Q variant of BF (H7), confer a
significantly reduced risk of AMD (odds ratio = 0.45 and 0.36, respectively).
Combined analysis of the C2 and BF haplotypes and CFH variants shows that
variation in the two loci can predict the clinical outcome in 74% of the affected
individuals and 56% of the controls. These data expand and refine our
understanding of the genetic risk for AMD.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, N.I.H., Intramural
    Research Support, Non-U.S. Gov't

PMID: 16518403 [PubMed - indexed for MEDLINE]

1552: Chang Gung Med J. 2005 Dec;28(12):852-9.

Pneumatic displacement of a dense submacular hemorrhage with or without tissue
plasminogen activator.

Yang PM, Kuo HK, Kao ML, Chen YJ, Tsai HH.

Department of Ophthalmology, Chang Gung Memorial Hospital, Kaohsiung.

BACKGROUND: To evaluate the efficacy of treating a dense submacular hemorrhage
with pneumatic displacement with or without tissue plasminogen activator (tPA).
METHODS: Twenty-four patients with a dense submacular hemorrhage were treated
with intravitreal expansile gas, with or without an intravitreal injection of
tPA, in order to displace the submacular blood. The main outcome measurements
include preoperative and postoperative visual acuity, postoperative fluorescein
angiography (FAG) results and additional postoperative treatments. RESULTS: Total
or subtotal subfoveal blood displacement was achieved in all 24 eyes. After a
mean follow-up of 15.5 months (range 6-50 months), final visual acuity had
improved two or more lines in 11 (45.8%) of the 24 eyes, and measured 20/100 or
better in 10 (41.7%) of the 11 eyes. Based on the FAG results for 14 cases, nine 
eyes (64.3%) received additional postoperative laser treatment. Final visual
acuity of 20/100 or better was achieved in four (40%) of the 10 eyes, with a
choroidal neovascular membrane (CNVM) detected on FAG, and dye leakage not
detected in three (75%) of the four eyes. CONCLUSIONS: Pneumatic displacement,
with or without intravitreal injection of tPA, seems useful in displacing dense
submacular hemorrhage and facilitating visual improvement, although the visual
result is often limited by the progression of the underlying macular disease. In 
patients with age-related macular degeneration, more treatable CNVM may be
detected on postoperative FAG.

PMID: 16515019 [PubMed - indexed for MEDLINE]

1553: Doc Ophthalmol. 2005 Sep;111(2):107-12. Epub 2006 Mar 2.

The changes of pattern electroretinography at the early stage of photodynamic
therapy.

Oner A, Karakucuk S, Mirza E, Erkilic K.

Department of Ophthalmology, Erciyes University Medical Faculty, Kayseri, Turkey.
aoner@erciyes.edu.tr

PURPOSE: To evaluate the short-term changes in pattern electroretinography (PERG)
after photodynamic therapy (PDT). METHODS: Thirty eyes of 30 patients (17 males, 
13 females) with choroidal neovascularization secondary to age related macular
degeneration were included in this study. Standard PDT with verteporfin was
performed on each patient. Serial PERG recordings were performed before, 1 week, 
and 1 month after PDT. RESULTS: Mean age of the patients was 69.6+/-8.4 years
(range 56 and 90 years). One month after PDT, the visual acuity improved in 16
eyes, remained unchanged in 12 eyes and deteriorated in two eyes. New hemorrhages
were seen in two eyes in the first week after PDT and visual acuity was decreased
in those patients. No other patient complained of ocular and systemic adverse
events. There was a statistically significant reduction in the amplitudes of P50 
and N95 waves at the first week recordings after PDT. At 1 month after PDT, no
significant differences in the P50 and N95 amplitudes were observed compared with
pre-PDT PERG recordings. There were no significant changes in the latencies of
P50 and N95 at the first week and first month recordings when compared with
pre-treatment PERG values. CONCLUSIONS: Reduction in P50 and N95 amplitudes
suggests that transient impairments in macular function occur at the first week
after PDT.

Publication Types: 
    Comparative Study

PMID: 16514492 [PubMed - indexed for MEDLINE]

1554: Doc Ophthalmol. 2005 Sep;111(2):83-6. Epub 2006 Mar 2.

Electrooculography after photodynamic therapy.

Oner A, Karakucuk S, Mirza E, Erkilic K.

Department of Ophthalmology, Erciyes University Medical Faculty, Kayseri, Turkey.
aoner@erciyes.edu.tr

PURPOSE: To evaluate the changes in electrooculography (EOG) after photodynamic
therapy (PDT). METHODS: Thirty-eight eyes of 38 patients (21 males, 17 females)
with choroidal neovascularization secondary to age related macular degeneration
were included in this study. Standart PDT with verteporfin was performed on each 
patient. Serial EOG recordings were performed before, 1 week, and 1 month after
PDT. RESULTS: Mean age of the patients was 69.8+/-9.7 years (range 56 and 90
years). Seven days after PDT the visual acuity improved in 17 eyes, remained
unchanged in 16 eyes and deteriorated in 5 eyes. One month after PDT the visual
acuity findings were the same as the first week. New hemorrhages were seen in
three eyes in the first week after PDT and visual acuity was decreased in those
patients. No other patient complained of ocular and systemic adverse events.
There was a statistically significant reduction in the Arden ratio of the EOG 1
week after PDT and the reduction persisted in the first month recordings.
CONCLUSIONS: The reduction in Arden ratio of EOG findings may indicate that
retina pigment epithelium function could be affected after PDT.

Publication Types: 
    Comparative Study

PMID: 16514489 [PubMed - indexed for MEDLINE]

1555: Ophthalmology. 2006 Mar;113(3):373-80.

Prevalence of age-related macular degeneration in 4 racial/ethnic groups in the
multi-ethnic study of atherosclerosis.

Klein R, Klein BE, Knudtson MD, Wong TY, Cotch MF, Liu K, Burke G, Saad MF,
Jacobs DR Jr.

Department of Ophthalmology and Visual Sciences, University of Wisconsin,
Madison, Wisconsin 53726-2336, USA. kleinr@epi.ophth.wisc.edu

OBJECTIVE: To describe the prevalence of age-related macular degeneration (AMD)
in 4 racial/ethnic groups (white, black, Hispanic, and Chinese) that participated
in the second examination of the Multi-ethnic Study of Atherosclerosis (MESA).
DESIGN: Prospective cohort study. PARTICIPANTS: Six thousand one hundred
seventy-six 45- to 85-year-old subjects selected from 6 United States
communities. METHODS: Fundus images were taken using a 45 degrees digital camera 
through dark-adapted pupils and were graded for drusen size, type, area,
increased retinal pigment, retinal pigment epithelial depigmentation, neovascular
lesions, and geographic atrophy using the modified Wisconsin Age-Related
Maculopathy Grading System. MAIN OUTCOME MEASURE: Age-related macular
degeneration. RESULTS: Prevalences of AMD were 2.4% (black), 4.2% (Hispanic),
4.6% (Chinese), to 5.4% (white) (P<0.001 for any differences among groups). The
highest prevalence of any AMD occurred in those 75 to 84 years old, varying from 
7.4% in blacks to 15.8% in whites and Chinese (P = 0.03). Estimated prevalences
of late AMD were 0.3% (black), 0.2% (Hispanic), 0.6% (white), and 1.0% (Chinese).
These differences were marginally significant (age and gender adjusted, P =
0.08). The frequency of exudative AMD was highest in Chinese (age- and
gender-adjusted odds ratio, 4.30; 95% confidence interval, 1.30-14.27) compared
with whites. Differences in age, gender, pupil size, body mass index, smoking,
alcohol drinking history, diabetes, and hypertension status did not explain the
variability among the 4 racial/ethnic groups. CONCLUSIONS: Low prevalences of AMD
were found in the MESA cohort in all groups. A lower prevalence of AMD was found 
in blacks compared with whites. The higher prevalence of exudative AMD in Chinese
needs further study.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16513455 [PubMed - indexed for MEDLINE]

1556: Retina. 2006 Mar;26(3):314-21.

One-year results of a pilot study using oral 13-cis retinoic acid as a treatment 
for subfoveal predominantly occult choroidal neovascularization in patients with 
age-related macular degeneration.

Lim JI, Walonker AF, Levin L, Mahmoud M, Sadda S, Flaxel CJ, Humayun M, deJuan E,
Labree L.

Doheny Retina Institute of the Doheny Eye Institute, Los Angeles, CA, USA.
jennifil@usc.edu

PURPOSE: To evaluate the safety and evidence of efficacy for oral 13-cis retinoic
acid as a treatment for patients with subfoveal occult choroidal
neovascularization (CNV) due to age-related macular degeneration (ARMD). METHODS:
Patients with active, subfoveal occult CNV with no prior treatment of the
subfoveal component were eligible for inclusion. Patients received 40 mg of
13-cis retinoic acid twice daily for 5 months, stopped treatment for 2 months,
and then resumed treatment for 5 months. Patients were observed monthly with
Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA), clinical
examination, fluorescein angiography, and laboratory testing. RESULTS: Eleven
patients, aged 64 to 88 years, were enrolled and followed for 1 year. Initial VA 
ranged from 55 (20/40) to 5 (20/400) ETDRS letters (median 48 letters). Mild
drug-related side effects (dry skin, chapped lips) occurred in all 11 patients.
Three patients experienced more severe side effects (muscle aches, mood swings)
and did not resume treatment after the drug holiday. Moderate VA loss occurred in
36% at both 6 and 12 months. CONCLUSIONS: Oral 13-cis retinoic acid is too toxic 
to be useful in patients with ARMD. Oral 13-cis retinoic acid did not improve
vision although it may have slowed visual acuity loss in patients with ARMD with 
occult subfoveal CNV.

Publication Types: 
    Clinical Trial
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16508432 [PubMed - indexed for MEDLINE]

1557: Retina. 2006 Mar;26(3):279-84.

Intravitreal bevacizumab (Avastin) treatment of macular edema in central retinal 
vein occlusion: a short-term study.

Iturralde D, Spaide RF, Meyerle CB, Klancnik JM, Yannuzzi LA, Fisher YL, Sorenson
J, Slakter JS, Freund KB, Cooney M, Fine HF.

Vitreous, Retina, Macula Consultants of New York, NY, USA. vrmny@aol.com

PURPOSE: To report the short term anatomic and visual acuity response after
intravitreal injection of bevacizumab (Avastin, Genentech) in patients with
macular edema due to central retinal vein occlusion (CRVO). METHODS: The authors 
conducted a retrospective study of patients with macular edema due to CRVO who
were treated with at least one intravitreal injection of bevacizumab 1.25 mg in
0.05 mL. Patients underwent Snellen visual acuity testing, optical coherence
tomography (OCT) imaging, and ophthalmoscopic examination at baseline and
follow-up visits. RESULTS: There were 16 eyes of 15 consecutive patients with a
mean age of 76.1 years (SD 9.8 years). Intravitreal triamcinolone had been
previously administered to 9 patients, but all of these patients either had no
improvement or had excessive intraocular pressure caused by the triamcinolone.
The patients received a mean of 2.8 injections of bevacizumab per eye. No adverse
events were observed, including endophthalmitis, clinically evident inflammation,
increased intraocular pressure, retinal tears, retinal detachment, or
thromboembolic events in any patient. The mean central macular thickness at
baseline was 887 microm and decreased to a mean of 372 microm at month 1 (P <
0.001). The mean baseline acuity was 20/600 (logMAR = 1.48) and the mean acuity
at month 1 was 20/200 (logMAR = 1.05), a difference that was highly significant
(P = 0.001). At last follow-up, a mean of 3 months after the first injection, the
mean visual acuity was 20/138 (logMAR = 0.84), which was significantly better
than baseline (P < 0.001). Visual acuity improvement, defined as a halving of the
visual angle, was seen in 14 of the 16 eyes. CONCLUSION: Initial treatment
results of patients with macular edema secondary to CRVO did not reveal any
short-term safety concerns. Intravitreal bevacizumab resulted in a significant
decrease in macular edema and improvement in visual acuity. The number of
patients in this pilot study was limited and the follow-up is too short to make
any specific treatment recommendations, but the favorable short-term results
suggest further study is needed.

PMID: 16508427 [PubMed - indexed for MEDLINE]

1558: Retina. 2006 Mar;26(3):270-4.

Electrophysiologic findings after intravitreal bevacizumab (Avastin) treatment.

Maturi RK, Bleau LA, Wilson DL.

Vitreo-retinal Service, Midwest Eye Institute, Indianapolis, Indiana 46280, USA. 
rmaturi@indyretina.com

PURPOSE: To evaluate the short-term electrophysiologic effects of intravitreal
bevacizumab in the treatment of exudative age-related macular degeneration (AMD).
METHODS: Nine subjects with AMD who received treatment with intravitreal
bevacizumab for exudative AMD underwent pretreatment testing with multifocal
electroretinography (mf-ERG) or Ganzfeld electroretinography (G-ERG). All five
G-ERG subjects underwent repeated testing at 1 week after intravitreal
bevacizumab. All four mf-ERG subjects and four of the five G-ERG subjects
underwent repeated testing with the same pretreatment protocol at 1 month after
treatment. One G-ERG subject also received a second intravitreal injection of
bevacizumab at 6 weeks after initial treatment and underwent repeated testing at 
1 month after the second dose (3 months after initial treatment). RESULTS: All
four subjects undergoing mf-ERG had improvement of the macular response at 1
month of after treatment. The average improvement in response density of the
central 15 degrees of macular response was 35% (range, 11-65%). Subjects
undergoing G-ERG testing had no significant changes in electrophysiologic
response, although some variation in amplitude and implicit time was noted at
different testing times. Optical coherence tomography central subfield thickness 
decreased from 298 microm at baseline to 274 microm at 1 month after treatment.
Visual acuity improved in a majority of subjects. CONCLUSION: In this study, the 
intravitreal use of bevacizumab resulted in improvement of mf-ERG macular
function responses and relatively stable G-ERG responses. The macular
electrophysiologic response suggests that macular function improves with
treatment. G-ERG suggests that there is no significant measurable photoreceptor
toxicity with the use of intravitreal bevacizumab over the short term.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 16508425 [PubMed - indexed for MEDLINE]

1559: Diabetes. 2006 Mar;55(3):813-8.

Retinal hemodynamics in early diabetic macular edema.

Guan K, Hudson C, Wong T, Kisilevsky M, Nrusimhadevara RK, Lam WC, Mandelcorn M, 
Devenyi RG, Flanagan JG.

Department of Ophthalmology and Vision Science, University of Toronto, Toronto,
Ontario M5T 2S8, Canada.

The objective of this study was to establish the baseline retinal hemodynamic
characteristics of stratified groups of diabetic patients at increasing risk for 
the development of diabetic macular edema (DME). Group 1 had 50 control subjects,
group 2 had 56 diabetic patients without clinically visible retinopathy, group 3 
had 54 diabetic patients with microaneurysms and/or hard exudates within two disc
diameters of the fovea in the absence of clinically manifest DME, and group 4 had
40 patients with clinically manifest DME. Retinal hemodynamics (diameter,
velocity, maximum-to-minimum velocity ratio, and flow) were assessed. Intraocular
pressure, blood pressure, and relevant systemic markers of diabetes control and
complications were also undertaken. The maximum-to-minimum velocity ratio was
elevated with increasing risk of clinically significant DME (P < 0.0001). No
significant differences were found between the groups with respect to diameter,
velocity, or flow. The maximum-to-minimum velocity ratio was correlated to age,
duration of diabetes, blood pressure, pulse rate, intraocular pressure, and serum
potassium levels. In conclusion, the maximum-to-minimum velocity ratio was
significantly increased with increasing risk of development of DME. Retinal
arteriolar hemodynamics were positively correlated to age, duration of diabetes, 
and blood pressure. These findings suggest a reduction in the compliance (i.e.,
an increase of vascular rigidity) of the arteriolar circulation with increasing
risk of DME.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16505248 [PubMed - indexed for MEDLINE]

1560: Invest Ophthalmol Vis Sci. 2006 Mar;47(3):815-22.

Proteomics of the retinal pigment epithelium reveals altered protein expression
at progressive stages of age-related macular degeneration.

Nordgaard CL, Berg KM, Kapphahn RJ, Reilly C, Feng X, Olsen TW, Ferrington DA.

Department of Ophthalmology, University of Minnesota, Minneapolis, USA.

PURPOSE: Age-related macular degeneration (AMD) is characterized clinically by
changes in the retinal pigment epithelium (RPE), formation of drusen between the 
RPE and the underlying vasculature, geographic atrophy, and choroidal
neovascularization. Later clinical stages are accompanied by impaired central
vision. A limited understanding of the molecular events responsible for AMD has
constrained the development of effective treatments. A proteomics approach was
used to investigate the underlying mechanisms of AMD and to identify proteins
exhibiting significant changes in expression with disease onset and progression. 
METHODS: Human donor eyes were categorized into one of four progressive stages of
AMD. Proteins from the RPE were resolved and quantified by two-dimensional (2-D) 
gel electrophoresis. Proteins exhibiting significant expression changes at
different disease stages were identified by matrix-assisted laser desorption
ionization time-of-flight (MALDI-TOF) mass spectrometry. 2-D and semiquantitative
one dimensional (1-D) Western blot analyses were used to determine whether
changes identified by the proteomic analysis were specific for a protein
subpopulation or representative of the entire protein population. RESULTS:
Proteins were identified from several critical pathways that changed at early and
late disease stages, indicating potential causal mechanisms and secondary
consequences of AMD, respectively. Proteins involved in protecting from
stress-induced protein unfolding and aggregation, mitochondrial trafficking and
refolding, and regulating apoptosis changed early in the disease process.
Late-stage changes occurred in proteins that regulate retinoic acid and
regeneration of the rhodopsin chromophore. CONCLUSIONS: These results provide the
first direct evidence of AMD stage-specific changes in human RPE protein
expression and provide a basis for functional investigation of AMD that may
ultimately suggest new therapeutic strategies.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16505012 [PubMed - indexed for MEDLINE]

1561: Doc Ophthalmol. 2005 Jul;111(1):49-56. Epub 2006 Feb 25.

Non-familial occult macular dystrophy.

Lyons JS.

jslami@aol.com

PURPOSE: To present a series of patients who have poor central vision with normal
funduscopic examination, fluorescein angiograms, and full field
electroretinograms but significantly reduced multifocal electroretinographic
responses most of whom are unaware of a family member similarly affected.
METHODS: Patients were evaluated clinically and with the use of visual field
testing, fluorescein angiography, full field electroretinography, VERIS
Multifocal Electroretinographic testing (MFERG), which along with focal
electroretinography is currently the only objective method of detecting these
localized retinal dysfunctions, and Optical Coherence Tomography (OCT) where
possible. RESULTS: Nine patients (18 eyes) referred for evaluation of undiagnosed
poor central vision were found to have abnormal multifocal ERG findings affecting
all or part of the central portion of the test field. Funduscopic examination,
fluorescein angiography, and full field electroretinography were all normal.
These patients each reported a long history of poor vision with little if any
clinical progression. There were no family members reported to have the same
condition although a few were reported to have poor vision and only one of the
patients had a sibling with decreased vision. At the time of their first
examination patients ages ranged from 13 to 53. CONCLUSION: Although there is
little evidence that the condition observed in these patients is inherited, all
reported early onset often in childhood. Previous reports by Miyake and
co-workers have described Occult Macular Dystrophy condition as an inherited
macular dystrophy characterized by progressive macular dysfunction. In the
present series there is little historical evidence of progression or of
inheritance. Based on this data, Occult Macular Dystrophy may in fact represent
more than one condition with multiple etiologies. Several etiologies are
considered.

Publication Types: 
    Case Reports
    Comparative Study

PMID: 16502307 [PubMed - indexed for MEDLINE]

1562: Surv Ophthalmol. 2006 Mar-Apr;51(2):137-52.

Comment in:
    Surv Ophthalmol. 2006 Sep-Oct;51(5):532; author reply 532.

The role of inflammation in the pathogenesis of age-related macular degeneration.

Donoso LA, Kim D, Frost A, Callahan A, Hageman G.

The Henry and Corinne Bower Laboratory, the Eye Research Institute, Wills Eye
Hospital, Philadelphia, Pennsylvania 19105, USA.

Age-related macular degeneration (AMD), the leading cause of blindness in the
elderly, is a complex disease to study because of the potential role of
demographic, environmental, and other systemic risk factors, such as age, sex,
race, light exposure, diet, smoking, and underlying cardiovascular disease which 
may contribute to the pathogenesis of this disease. Recently, single nucleotide
polymorphisms, DNA sequence variations found within the complement Factor H gene,
have been found to be strongly associated with the development of AMD in
Caucasians. One single nucleotide polymorphism, Tyr402His, was associated with
approximately 50% of AMD cases. We review recent developments in the molecular
biology of AMD, including single nucleotide polymorphisms within the Factor H
gene, which may predispose individuals to the susceptibility of AMD as well as
single nucleotide polymorphisms that may confer a protective effect. Taken
together these findings help to provide new insights into the central issues
surrounding the pathogenesis of AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 16500214 [PubMed - indexed for MEDLINE]

1563: Eur J Ophthalmol. 2006 Jan-Feb;16(1):138-40.

Use of autologous plasmin during vitrectomy for diabetic maculopathy.

Sakuma T, Tanaka M, Inoue J, Mizota A, Souri M, Ichinose A.

Department of Ophthalmology, Juntendo University, Urayasu Hospital, Urayasu,
Chiba, Japan.

PURPOSE: To evaluate the efficacy of autologous plasmin enzyme as an adjunct to
vitrectomy in diabetic macular edema. METHODS: Plasmin derived from autologous
blood was injected intravitreally into seven eyes 15 min before vitreous surgery.
The development and progression of a posterior vitreous detachment (PVD) was
followed, and the time required for vitreous removal was measured. Both pre- and 
postoperative visual acuities and optical coherence tomography (OCT)-determined
macular thickness were measured. RESULTS: In the seven eyes in which plasmin was 
used, a PVD developed approximately 5 min after the injection and was confirmed
to extend to the far periphery. In all cases, the removal of the vitreous was
completed in a shorter time and no complications were observed. A restoration of 
the shape of the macula was observed in all cases. The visual acuity improved by 
two or more lines in four eyes, and remained unchanged in the remaining three
eyes. CONCLUSIONS: Autologous plasmin alone will create a full PVD, and
eliminates the need for a mechanical creation of a PVD. Thus, plasmin is a safe
and effective adjunct to vitreous surgery for the treatment of diabetic
maculopathy.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16496258 [PubMed - indexed for MEDLINE]

1564: Eur J Ophthalmol. 2006 Jan-Feb;16(1):134-7.

Anomalous vitreoretinal adhesions in patients with exudative age-related macular 
degeneration: an OCT study.

Quaranta-El Maftouhi M, Mauget-Faÿsse M.

Centre Ophtalmologique Rabelais, Lyon, France.

PURPOSE: To analyze the relationship between the retina and the vitreous in
patients with exudative age-related macular degeneration (ARMD). METHODS:
Consecutive patients with exudative ARMD, proven by fluorescein angiography, were
recruited. Fundus biomicroscopic examination, color and re d - f ree fundus
photographs, and serial scans of the macular region using optical coherence
tomography (OCT3, Carl Zeiss) were performed before and after photodynamic
therapy (PDT) with verteporfin (Visudyne, Novartis Ophthalmics). Vitreoretinal
relationships have been described and compared with fundus photographs and data
of fundus biomicroscopy examination. RESULTS: Sixty-six eyes of 52 consecutive
patients (33 women, 19 men; mean age 75 years, range 64 to 89 years) with
exudative ARMD were studied. Analysis of serial OCT scans showed that 13 eyes
(20%) did not present any visible vitreous structures. Two eyes (3%) had the
appearance of a complete posterior vitreous detachment (PVD). Fifty-one eyes
(77%) exhibited some abnormalities of the vitre o retinal interface including 12 
eyes with epiretinal membrane and retinal thickening and distortion. Among the 39
eyes examined before and after PDT with Visudyne, only 3 eyes developed a partial
vitreous detachment and 1 eye progressed to a complete PVD. CONCLUSIONS: Eyes
with exudative ARMD exhibit a high prevalence of abnormalities of the
vitreoretinal interface similar to that observed in many chronic inflammatory
diseases. PDT with verteporfin does not modify the observed vitre o retinal
adhesions.

PMID: 16496257 [PubMed - indexed for MEDLINE]

1565: Eur J Ophthalmol. 2006 Jan-Feb;16(1):129-33.

Intravitreal triamcinolone acetonide as primary treatment for diffuse diabetic
macular edema: a prospective noncomparative interventional case series.

Nicolò M, Nasciuti F, Lai S, Ghiglione D, Borgia L, Calabria G.

Dipartimento di Neurologia, Oftalmologia e Genetica (Di.N.O.G.), Sezione di
Clinica Oculistica, Università di Genova, Italy.
massimonicolo@occhioallaretina.it

PURPOSE: To evaluate the efficacy and safety of one intravitreal injection of 25 
mg of triamcinolone acetonide as primary treatment for diffuse diabetic macular
edema. METHODS: Intravitreal triamcinolone acetonide injection was performed in
30 eyes with previously untreated diabetic macular edema. The main outcome
measures were logMAR visual acuity (VA) and central macular thickness (CMT) at 1,
3, and 6 months. A secondary outcome was intraocular pressure progression.
RESULTS: Visual acuity results for 30 eyes that had a follow-up of at least 6
months are presented. Twenty of them were followed up to 10.1+/-2.38 months.
Preoperatively, VA was 0.54+/-0.27. At 1, 3, and 6 months follow-up, VA was
0.44+/-0.29 (p=0.001), 0.43+/-0.28 (p=0.001), and 0.45+/-0.29 (p=0.006),
respectively. Preoperatively, CMT was 417.3+/-143.5 microm. At 1, 3, and 6 months
follow-up, CMT was 277.3 +74.0 microm (p<0.0001), 279.6+/-94.4 microm (p<0.0001),
and 297.07+/-114.87 microm (p=0.002), respectively. For the 20 eyes with a
follow-up of 10.1+/-2.38 months, VA was 0.5+/-0.25 and 0.50+/-0.32 at baseline
and at the last follow-up visit, respectively (p>0.05). Preoperatively,
intraocular pressure (IOP) was 15.13+/-1.48 mmHg. IOP was 18.26+/-2.71 mmHg,
20.07+/-4.27 mmHg, and 20.4+/-6.18 mmHg, at 1, 3, and 6 months, respectively
(p<0.0001). Four eyes underwent uncomplicated filtrating surgery for intractable 
glaucoma. CONCLUSIONS: Intravitreal triamcinolone as primary treatment
effectively increases VA and reduces CMT due to diffuse diabetic macular edema.
Longer follow-up and randomized clinical trial are warranted. Safety results
highlight the need to further study the relationship between triamcinolone and
intraocular pressure.

Publication Types: 
    Clinical Trial

PMID: 16496256 [PubMed - indexed for MEDLINE]

1566: Eur J Ophthalmol. 2006 Jan-Feb;16(1):119-28.

Hypericin-enhanced argon laser photocoagulation for subfoveal choroidal
neovascular membrane in age-related macular degeneration: a pilot study.

Sobaci G, Bayraktar MZ, Karslioğlu Y, Durukan AH, Hürmeriç V, Aykaş S.

Department of Ophthalmology, Gülhane Military Medical Academy and Medical School 
(GMMA-MS), Ankara, Turkey. gsobaci@gata.edu.tr

PURPOSE: To evaluate the efficacy and safety of hypericin-enhanced argon laser
photocoagulation (H-ALP) in the treatment of subfoveal choroidal neovascular
membrane (CNM) secondary to age-related macular degeneration (ARMD). METHODS:
After preliminary studies for definition of parameters, argon-green laser was
administered 4 hours after single dose of oral 1800 mg hypericin (Saint-John's
wort tablets, 0.3%, 300 mg) with a subthreshold light fluence, 24 J/cm2 in 34
eyes (20 with subfoveal classical and 14 with subfoveal occult CNM).
Additionally, histopathologic examination was done in two eyes destined for
enucleation and exenteration. Maintenance therapy (one tablet, twice a day) was
performed for the following 6 months. Anatomic (complete closure of CNM) and
functional success (improvement of final visual acuity in three or more Snellen
lines) were analyzed with minimum 6-month follow-ups. RESULTS: Histopathologic
examinations revealed photothrombosed choriocapillaries together with minimal
retinal pigment epithelial disruption in H-ALP exposed areas. One to four (mean
1.88+/-0.91) treatment sessions were applied in 6 to 29 months (mean 12.2+/-5.1
months) follow-up period. Twenty-three (67.6%) eyes had 12 months follow-up. Two 
eyes in each group had functional success (20% in subfoveal classical and 14.3%
in subfoveal occult CNM), which had a minimum 12-month follow-up. Anatomic
success was achieved in 16 of 20 (80%) eyes with subfoveal classical and 10 of 14
(71.4%) eyes with subfoveal occult CNM. Severe gastric irritation was noted in 1 
(2.9%) and pigment epithelial rupture in 2 (5.9%) patients. CONCLUSIONS: H-ALP is
a novel and low-cost treatment for subfoveal CNM secondary to ARMD. It seems its 
efficacy depends on the photodynamic and antiproliferative properties of
hypericin. Comparative studies are required to apply this new technique in
ophthalmic practice.

Publication Types: 
    Clinical Trial

PMID: 16496255 [PubMed - indexed for MEDLINE]

1567: Eur J Ophthalmol. 2006 Jan-Feb;16(1):105-10.

Glutathione S-transferase M1, T1, and P1 gene polymorphism in exudative
age-related macular degeneration: a preliminary report.

Oz O, Aras Ates N, Tamer L, Yildirim O, Adigüzel U.

Department of Ophthalmology, Faculty of Medicine, Mersin University, Mersin,
Turkey.

PURPOSE: To elucidate whether the gene polymorphisms of glutathione S-transferase
(GST) M1, T1, and P1 are associated with the development of exudative age-related
macular degeneration. METHODS: The authors genotyped 35 white patients with
exudative age-related macular degeneration and 159 healthy controls. Genomic DNA 
from peripheral blood was examined using polymerase chain reaction and defined
for the genetic polymorphisms of GST. RESULTS: No association was observed
between GSTM1, GSTT1, and GSTP1 polymorphisms and age-related macular
degeneration risk (p>0.05). The frequencies of the combination of the GSTM1
(null) and GSTP1 (mutant), GSTM1 (null), and GSTT1 (null) genotype polymorphisms 
in patients with exudative age-related macular degeneration differed greatly from
those of the control group (p=0.001 OR [95% CI]: 7.70 [2.28-25.98] and p=0.007 OR
[95% CI]: 3.88 [1.51-10.02], respectively). CONCLUSIONS: The present study
suggests that the GSTM1 (null) and GSTT1 (null), GSTM1 (null), and GSTP1 (mutant)
combinations may be a genetic risk factor for the development of exudative
age-related macular degeneration. However, the potential role of GST
polymorphisms as a marker of susceptibility to age-related macular degeneration
needs further studies in a larger number of patients.

PMID: 16496253 [PubMed - indexed for MEDLINE]

1568: Ophthalmologica. 2006;220(2):118-24.

Intravitreal triamcinolone acetonide for exudative age-related macular
degeneration among Japanese patients.

Ito M, Okubo A, Sonoda Y, Yamakiri K, Sakamoto T.

Department of Ophthalmology, Faculty of Medicine, Kagoshima University Graduate
School of Medicine and Dental Sciences, Kagoshima, Japan.

AIM: To study the results of intravitreal triamcinolone acetonide (TA) for
exudative age-related macular degeneration (AMD) among Japanese patients.
METHODS: 13 eyes of 12 Japanese patients (9 males and 3 females) with subfoveal
choroidal neovascularization (CNV) of exudative AMD received intravitreal TA (8
mg). Visual acuity, size of CNV and serous retinal detachment, and complications 
related to treatment were evaluated for 6 months or longer. RESULTS:
Postoperative maximum visual acuity significantly improved (p < 0.05).
Postoperative eyes had a greater probability of a reduced size of CNV and/or
retinal detachment compared to preoperative eyes. Seven eyes showed increased
intraocular pressure (21 mm Hg or over), which was controlled well by medication.
Cataract development and advancement were observed in 90% of phakic eyes. No
other serious complications were found. CONCLUSIONS: Intravitreal TA might be an 
effective treatment for subfoveal CNV of exudative AMD among Japanese as well as 
Caucasian patients for a comparatively short period.

Publication Types: 
    Comparative Study

PMID: 16491035 [PubMed - indexed for MEDLINE]

1569: Clin Ther. 2006 Jan;28(1):36-44.

Pegaptanib sodium for the treatment of neovascular age-related macular
degeneration: a review.

Kourlas H, Schiller DS.

Division of Pharmacy Practice, Arnold and Marie Schwartz College of Pharmacy and 
Health Sciences, Long Island University, Brooklyn, New York 11201-5497, USA.
helen.kourlas@liu.edu

OBJECTIVE: This article reviews available information on the new selective
vascular endothelial growth factor aptamer pegaptanib in the treatment of
neovascular age-related macular degeneration (ARMD). The pharmacology,
pharmacokinetics, pharmacodynamics, contraindications, and drug-interaction
potential of pegaptanib are discussed, and the results of clinical trials
evaluating its efficacy and tolerability are summarized. METHODS: Relevant
articles were identified through searches of MEDLINE (1966-June 2005) and
International Pharmaceutical Abstracts (1970-June 2005). The search terms
included pegaptanib sodium, Macugen, age-related macular degeneration, and
choroidal neovascularization. The reference lists of identified articles were
reviewed for additional publications, and further information was obtained from
the manufacturer of pegaptanib. Included studies were review articles and Phase
II, III, and IV clinical trials, with preference given to available Phase III
studies. RESULTS: Only 1 research group has evaluated the tolerability and
efficacy of pegaptanib in patients with neovascular ARMD. The VEGF Inhibition
Study in Ocular Neovascularization involved 2 concurrent randomized trials of
intravitreous injections of pegaptanib 0.3 mg (n = 294), 1 mg (n = 300), and 3 mg
(n = 296) compared with sham injections (n = 296) every 6 weeks for 54 weeks in
patients with neovascular ARMD. Assessments were conducted at 6, 12, 18, 24, 30, 
42, 48, and 54 weeks. The primary end point was the proportion of patients losing
<15 letters on the study eye chart at 54 weeks. This end point was achieved in
70%, 71%, and 65% of patients who received pegaptanib 0.3 (P < 0.001), 1 (P <
0.001), and 3 mg (P = 0.03), respectively, compared with 55% of those receiving
the sham injections. Significant improvements in visual acuity with pegaptanib
compared with the sham-injection group were seen at all time points (0.3 and 1
mg: P < 0.002; 3 mg: P < 0.05). The sham-injection group was twice as likely to
have severe vision loss (loss of > or =30 letters or 6 lines on the eye chart)
compared with those receiving pegaptanib 0.3 or 1 mg (P < 0.001). Adverse events 
reported significantly more often in the pegaptanib group compared with the
sham-injection group included vitreous floaters (33% vs 28%, respectively; P <
0.001), vitreous opacities (18% vs 10%; P < 0.001), and anterior-chamber
inflammation (14% vs 6%; P = 0.001). Injection-related adverse events during the 
first year of pegaptanib treatment included endophthalmitis in 12 (1.3%)
patients, retinal detachment in 6 (0.7%) patients, and traumatic injury to the
lens in 5 (0.6%) patients. CONCLUSIONS: There are few published clinical data on 
pegaptanib. In 2 clinical comparisons with sham injections, pegaptanib was well
tolerated and effective in slowing the decline in visual acuity in patients with 
neovascular ARMD. This agent may be considered an option for the treatment of
neovascular ARMD.

Publication Types: 
    Review

PMID: 16490578 [PubMed - indexed for MEDLINE]

1570: Am J Ophthalmol. 2006 Mar;141(3):574-6.

Early optical coherence tomography changes after photodynamic therapy in patients
with age-related macular degeneration.

Ozdemir H, Karacorlu SA, Karacorlu M.

Istanbul Retina Institute Inc, Hakki Yeten Caddesi No. 8, K.7, 34349
Sisli-Istanbul, Turkey.

PURPOSE: To evaluate early changes after photodynamic therapy (PDT) in patients
with age-related macular degeneration (AMD) by optical coherence tomography
(OCT). DESIGN: Prospective interventional case series. METHODS: PDT was performed
on 20 eyes of 20 patients who presented with subfoveal choroidal
neovascularization (CNV) attributable to AMD. OCT was used to evaluate changes at
2, 12, and 24 hours and at 3, 7, 15, and 30 days after therapy. RESULTS: In the
first 24 hours, OCT showed an increase in the subretinal fluid (SF) in all eyes
and an increase in intraretinal fluid (IF) in 13 eyes. On the 15th day and the
30th day after therapy, reduction of SF and IF was observed in almost all eyes.
CONCLUSIONS: Serial OCT evaluation of patients with subfoveal CNV attributable to
AMD suggests that the initial response after PDT is an increase in SF and IF.

PMID: 16490515 [PubMed - indexed for MEDLINE]

1571: Am J Ophthalmol. 2006 Mar;141(3):494-7.

Age-related macular degeneration and optic disk cupping: the Beaver Dam Eye
Study.

Hall ER, Klein BE, Knudtson MD, Meuer SM, Klein R.

Department of Ophthalmology and Visual Sciences, School of Medicine and Public
Health, University of Wisconsin-Madison, 610 North Walnut Street, Madison, WI
53726, USA. hall@epi.ophth.wisc.edu

PURPOSE: To examine the association between presence, severity, and extent of
lesions of age-related macular degeneration (AMD) and optic disk and cup
diameters in a general population. DESIGN: Cross-sectional study. METHODS:
setting: Population-based. study population: Adults aged 43 to 86 years
participating in the Beaver Dam Eye Study. observation procedures: Fundus
photographs were graded for lesions of AMD using standard protocols. The
photographs were obtained during the baseline examination of the Beaver Dam Eye
Study. main outcome measure: Optic disk cupping as related to presence, severity,
and extent of lesions of AMD. RESULTS: There were no significant differences in
the vertical optic disk and cup measurements or in the vertical cup to disk
ratios by severity of lesions of AMD (P values all greater than .10). In those
eyes with late lesions of AMD, there was no association of the size of the
lesions or their distribution in the fundus and the extent of cupping.
CONCLUSIONS: From a population perspective, there is no relationship of the
presence or severity of AMD and optic disk cupping.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16490495 [PubMed - indexed for MEDLINE]

1572: Br J Ophthalmol. 2006 Mar;90(3):342-6.

Effect of systemic hypertension on foveolar choroidal blood flow in age related
macular degeneration.

Metelitsina TI, Grunwald JE, DuPont JC, Ying GS.

Department of Opthalmology, Scheie Eye Institute, School of Medicine, University 
of Pennsylvania, Philadelphia, PA 19104, USA.

AIM: To investigate the effect of systemic hypertension (SH) on the foveolar
choroidal circulation in patients with age related macular degeneration (AMD).
METHODS: This study included 163 study eyes with early AMD characteristics of 124
AMD patients. Study eyes had visual acuity of 20/40 or better, drusen > or =63
microm, and/or RPE hypertrophy. 56 of the AMD patients had a history of SH and 47
of these patients were receiving antihypertensive medications. Laser Doppler
flowmetry (Oculix) was used to assess relative choroidal blood velocity (ChBVel),
volume (ChBVol), and flow (ChBFlow) in the centre of the fovea of the study eyes.
Differences in the mean haemodynamic parameters between groups of eyes were
assessed using analysis of variance (ANOVA) and a test of linear trend, with
adjustment for the correlation between eyes of the same patient. RESULTS: AMD
patients with SH showed decreased ChBFlow in comparison with those without SH
(ANOVA, p = 0.02). This association was maintained after adjustments for multiple
factors (p = 0.04). CONCLUSIONS: AMD patients with SH have lower ChBFlow than
those without SH. This decrease in choroidal blood circulation may help explain
the mechanism by which systemic hypertension may contribute to the progression of
AMD and the development of choroidal neovascularisation.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16488959 [PubMed - indexed for MEDLINE]

1573: Br J Ophthalmol. 2006 Mar;90(3):337-41.

Combined photodynamic therapy and intravitreal triamcinolone injection for the
treatment of subfoveal choroidal neovascularisation in age related macular
degeneration: a comparative study.

Chan WM, Lai TY, Wong AL, Tong JP, Liu DT, Lam DS.

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong
Kong, Hong Kong Eye Hospital, 147K Argyle Street, Hong Kong.
cwm6373@netvigator.com

AIM: To evaluate the outcomes of combined intravitreal triamcinolone (IVTA) and
photodynamic therapy (PDT) with verteporfin in the treatment of subfoveal
choroidal neovascularisation (CNV) caused by age related macular degeneration
(AMD). METHODS: 48 eyes from 48 patients with subfoveal CNV caused by AMD were
prospective recruited, with 24 eyes treated with combined PDT with IVTA and
compared with a control group of 24 eyes which received PDT monotherapy. In the
combined treatment group, IVTA was performed immediately after PDT as an
outpatient procedure. The mean number of treatments, mean logMAR best corrected
visual acuity (BCVA), mean line of visual acuity changes, and proportion of
patients without moderate visual loss at 1 year were compared between the
combined and monotherapy groups. RESULTS: At 1 year the logMAR BCVA for the PDT
with IVTA group changed from 0.88 to 0.95 (p = 0.32 compared with baseline),
whereas the logMAR BCVA for the monotherapy group reduced from 0.74 to 1.09
(p<0.001 compared with baseline). A significantly higher proportion of patients
who had PDT with IVTA did not develop moderate visual loss at 1 year compared
with the monotherapy group (70.8% and 33.3% respectively, p = 0.009). Eyes which 
had combined treatment had significantly fewer lines lost compared with
monotherapy alone (0.7 and 3.5 lines respectively, p = 0.015). Subgroup analysis 
showed that PDT with IVTA is effective in preventing visual loss in both
predominately classic and occult CNV groups. The mean number of treatments for
the combined and monotherapy groups was 1.5 and 1.96 respectively (p = 0.076).
CONCLUSIONS: Combined PDT with IVTA appeared more effective statistically at 12
months for stabilisation of vision (<3 logMAR lines change) compared with PDT
monotherapy. Further randomised control trials might be justified to conclude the
efficacy of PDT with IVTA.

Publication Types: 
    Controlled Clinical Trial
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 16488958 [PubMed - indexed for MEDLINE]

1574: Br J Ophthalmol. 2006 Mar;90(3):296-300.

Indocyanine green angiography features of Malattia leventinese.

Souied EH, Leveziel N, Querques G, Darmon J, Coscas G, Soubrane G.

Clinique Ophtamologique Universitaire de Créteil, 40 Avenue de Verdun, 94010
Créteil, France. eric.souied@chicreteil.fr

BACKGROUND/AIM: Malattia leventinese (ML) is an inherited macular degeneration
characterised by the presence of small radial drusen. Despite extensive
descriptions of this study of the fundus, angiographic features of ML have been
inadequately described. The aim is to describe the indocyanine green angiography 
(ICG) features observed in ML. METHODS: 10 eyes from five consecutive ML patients
(aged 27-44 years) were prospectively included. A complete ophthalmological
examination including colour fundus photographs, autofluorescence, fluorescein
angiography (FA), and ICG was performed. RESULTS: ICG differentiated two types of
drusen. Large round aggregated drusen were consistently hypofluorescent in the
early phases and presented as hyperfluorescent spots surrounded by halos of
hypofluorescence in the late phases. Conversely, small radial drusen were mostly 
hyperfluorescent in the early phases with decreased fluorescence in the late
phases of the ICG sequence. FA also showed differences in staining between the
two types of drusen. CONCLUSIONS: ICG angiography revealed marked differences
between the large round and small radial drusen observed in ML. The large central
drusen presented with an unusual pustuliform feature on the late phases of the
ICG sequence. This distinct feature may be useful in the diagnosis of late stage 
disease when drusen consolidation could obscure the radial drusen.

PMID: 16488948 [PubMed - indexed for MEDLINE]

1575: Aging Clin Exp Res. 2005 Dec;17(6):435-44.

Age-related macular disease: how to assess the retina using scanning laser
techniques?

Bellmann C, Kabanarou SA, Sahel JA, Rubin GS, Fitzke FW.

Institute of Ophthalmology, University College London, UK.
bellmann@quinze-vingts.fr

Age-related macular disease (AMD) is the leading cause of legal blindness among
the elderly in Western nations. The magnitude of the problem will undoubtedly
grow, as age is a significant risk factor and the number of people aged 65 and
over is projected to increase. The most frequent cause of severe visual loss
associated with AMD is irreversible degeneration of the overlying neurosensory
retina, caused by the growth of choroidal neovascularization or, alternatively,
the development of geographic atrophy of the retinal pigment epithelium. Today,
we are able to image the human retina in vivo. Recently developed imaging
techniques provide better assessment of retinal pathology than conventional
ophthalmoscopy alone. This overview presents the most recent devices available
for retinal imaging, which mainly exploit laser technology such as scanning laser
ophthalmoscopy. Its basic principles, as well as its characteristics for imaging 
and functional assessment of the retina, are described. Lastly, potential
benefits for clinical routine, rehabilitation strategies in AMD, and future
research aspects are discussed.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 16485860 [PubMed - indexed for MEDLINE]

1576: Ophthalmology. 2006 Apr;113(4):633.e1-4. Epub 2006 Feb 14.

Ranibizumab for treatment of neovascular age-related macular degeneration: a
phase I/II multicenter, controlled, multidose study.

Heier JS, Antoszyk AN, Pavan PR, Leff SR, Rosenfeld PJ, Ciulla TA, Dreyer RF,
Gentile RC, Sy JP, Hantsbarger G, Shams N.

Ophthalmic Consultants of Boston, Boston, Massachusetts 02114, USA.

OBJECTIVE: To assess safety of repeated intravitreal injections of ranibizumab in
treating neovascular age-related macular degeneration (AMD), and to assess
changes in visual acuity (VA) and AMD lesion characteristics. DESIGN:
Multicenter, controlled, open-label, clinical trial. PARTICIPANTS: Sixty-four
patients with subfoveal predominantly or minimally classic AMD-related choroidal 
neovascularization. METHODS: In part 1, subjects were randomized to monthly
intravitreal ranibizumab for 3 months (4 injections of 0.3 mg or 1 injection of
0.3 mg followed by 3 injections of 0.5 mg; n = 53) or usual care (UC; n = 11). In
part 2, subjects could continue their regimen for 3 additional months or cross
over to the alternative treatment. MAIN OUTCOME MEASURES: Adverse events (AEs),
intraocular pressure (IOP), VA, and lesion characteristics assessed by
fluorescein angiography and fundus photography. RESULTS: Of the 64 randomized
subjects, 62 completed the 6-month study. Twenty of 25 subjects (80%) randomized 
to 0.3 mg, and 22 of 28 subjects (79%) randomized to 0.5-mg ranibizumab in part 1
continued on that treatment in part 2; 9 of 11 (82%) subjects randomized to UC in
part 1 crossed over to ranibizumab treatment in part 2. The most common AEs with 
ranibizumab were reversible inflammation and minor injection-site hemorrhages.
Serious AEs were iridocyclitis, endophthalmitis, and central retinal vein
occlusion (1 subject each). Postinjection, IOP increased transiently in 22.6% of 
ranibizumab-treated eyes in parts 1 and 2. After 4 ranibizumab injections (day
98), mean (+/- standard deviation) VA had increased 9.4+/-13.3 and 9.1+/-17.2
letters in the 0.3- and 0.5-mg groups, respectively, but had decreased 5.1+/-9.6 
letters with UC. In part 2 (day 210), VA increased from baseline 12.8+/-14.7 and 
15.0+/-14.2 letters in subjects continuing on 0.3 and 0.5 mg, respectively.
Visual acuity improved from baseline > or =15 letters in 26% (day 98) and 45%
(day 210) of subjects initially randomized to and continuing on ranibizumab,
respectively, and areas of leakage and subretinal fluid decreased. No UC subject 
had a > or =15-letter improvement at day 98. CONCLUSIONS: Repeated intravitreal
injections of ranibizumab had a good safety profile and were associated with
improved VA and decreased leakage from choroidal neovascularization in subjects
with neovascular AMD.

Publication Types: 
    Clinical Trial, Phase I
    Clinical Trial, Phase II
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16483659 [PubMed - indexed for MEDLINE]

1577: Med Hypotheses. 2006;66(6):1137-9. Epub 2006 Feb 14.

Induction of posterior vitreous separation using LASIK suction ring may have a
potential role in the management of diabetic macular edema.

Venkatesh P, Vajpayee RB, Garg S.

Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of
Medical Sciences, Ansari Nagar, New Delhi. venkyprao@yahoo.com

A significant percentage of patients with diabetic macular edema respond poorly
to conventional laser photocoagulation. One associated factor in such patients
with refractory diabetic macular edema is the absence of posterior vitreous
detachment (PVD). Several invasive methods, such as surgical induction of PVD
result in resolution of macular edema and improvement in visual acuity. Being
invasive such modalities may have important surgical risks, such as retinal
detachment and endophthalmitis. Recently, laser in situ keratomeilusis (LASIK), a
well-accepted refractive procedure, has been reported to produce posterior
vitreous detachment in patients with myopia. We herein hypothesize that
application of LASIK suction ring, an external procedure, may be useful in the
induction of PVD in patients with refractory diabetic macular edema and may have 
a better safety profile.

PMID: 16481121 [PubMed - indexed for MEDLINE]

1578: Arch Ophthalmol. 2006 Feb;124(2):257-63.

Association of adipose and red blood cell lipids with severity of dominant
Stargardt macular dystrophy (STGD3) secondary to an ELOVL4 mutation.

Hubbard AF, Askew EW, Singh N, Leppert M, Bernstein PS.

Department of Foods and Nutrition, University of Utah, Salt Lake City, USA.

OBJECTIVE: To determine whether adipose and red blood cell membrane lipids,
particularly long-chain polyunsaturated fatty acids such as docosahexaenoic acid 
and eicosapentaenoic acid, are significantly correlated with phenotype in a
family with autosomal dominant Stargardt macular dystrophy (gene locus STGD3). A 
mutation in the ELOVL4 gene is responsible for the macular dystrophy in this
family, and its disease-causing mechanism may be its possible involvement in
fatty acid elongation in the retina. METHODS: The subjects in this study included
18 adult family members known to have a 2-base pair deletion in the ELOVL4 gene. 
Control subjects included 26 family members without the mutation. Each subject
received a complete eye examination including fundus photographs, the results of 
which were used to grade the severity of macular dystrophy on a 3-tier scale. Red
blood cell membrane and adipose tissue lipids were analyzed as an indication of
short-term and long-term dietary fatty acid intake. RESULTS: When adipose lipids 
were analyzed, there was a significant inverse relationship between phenotypic
severity and the level of eicosapentaenoic acid (r = -0.54; P = .04). When red
blood cell lipids were analyzed, there were significant inverse relationships
between phenotypic severity and levels of eicosapentaenoic acid (r = -0.55; P =
.02) and docosahexaenoic acid (r = -0.48; P = .04). CONCLUSIONS: These results
indicate that the phenotypic diversity in this family may be related to
differences in dietary fat intake as reflected by adipose and red blood cell
lipids. CLINICAL RELEVANCE: This study demonstrates that dietary factors can
influence the severity of an inherited human macular dystrophy.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16476896 [PubMed - indexed for MEDLINE]

1579: Arch Ophthalmol. 2006 Feb;124(2):183-8.

Iris pigment epithelial translocation in the treatment of exudative macular
degeneration: a 3-year follow-up.

Aisenbrey S, Lafaut BA, Szurman P, Hilgers RD, Esser P, Walter P, Bartz-Schmidt
KU, Thumann G.

Center of Ophthalmology, Department of Vitreoretinal Surgery, Eberhard-Karls
University Tuebingen, Tuebingen, Germany.

OBJECTIVE: To report the functional and anatomical outcome of 20 patients who
underwent surgical removal of choroidal neovascularization combined with
transplantation of autologous iris pigment epithelial cells to the subretinal
space 3 years after treatment. METHODS: Freshly isolated autologous iris pigment 
epithelial cells were translocated to the subretinal space in 20 patients after
membrane extraction. Patients were followed up by funduscopy, angiography,
microperimetry, and visual acuity testing. RESULTS: After a follow-up of 3 years,
1 patient showed improved visual acuity, 13 patients retained stable visual
acuity, and 3 patients had reduced visual acuity. No macular edema or recurrent
choroidal neovascularization was apparent at any time during the follow-up.
CONCLUSIONS: Transplanted autologous iris pigment epithelial cells were well
tolerated for 3 years and stabilization of visual acuity was achieved in most
patients. These results suggest that iris pigment epithelial cells may serve as a
substitute for retinal pigment epithelial cells after choroidal
neovascularization removal in patients with exudative macular degeneration;
however, whether these cells will be of any value for the restoration of vision
and possible protection against choroidal neovascularization recurrence awaits
further clinical observation and additional research.

PMID: 16476887 [PubMed - indexed for MEDLINE]

1580: Clin Chim Acta. 2006 Jul 15;369(1):52-60. Epub 2006 Feb 13.

Evaluation of essential and toxic metals by ultrasound-assisted acid leaching
from scalp hair samples of children with macular degeneration patients.

Kazi TG, Afridi HI, Kazi GH, Jamali MK, Arain MB, Jalbani N.

Center of Excellence in Analytical Chemistry, University of Sindh, Jamshoro
76080, Pakistan. tgkazi@yahoo.com

BACKGROUND: The causes of night blindness in children are multifactorial and
particular consideration has been given to childhood nutritional deficiency,
which is the most common problem found in underdeveloped countries. Such
deficiency can result in physiological and pathological processes that in turn
influence hair composition. METHOD: An ultrasonic-assisted acid leaching
procedure was developed as a sample pretreatment for the determination of Zn, Cu,
Cd, As and Pb in human scalp hair samples of night blindness male children with
age between 5 to 15 y and compared with the children without vision anomalies
that lived in the same localities. The effects of different factors on acid
leaching of metals, such as preintensification time (without ultrasonic stirring)
after treatment of acid mixture, exposure time to ultrasound and temperature of
the ultrasonic bath have been investigated. The proposed method was validated by 
certified reference samples of scalp hair CRM 397. The wet acid digestion method 
was used to obtain the total metal concentration in both scalp hair and CRM
samples. Cu and Zn in leachates and digests were measured by flame atomic
absorption spectrometry (FAAS) using a conventional air/acetylene flame, while Cd
and Pb were determined by electrothermal atomic absorption spectrometry (ETAAS)
under optimized conditions. RESULTS: It was observed that at optimal conditions, 
the recovery for Zn, Cd, Pb, As and Cu were 98%, 98.5%, 96%, 97.2% and 94%
respectively. The mean values of Zn and Cu in scalp hair samples of children
having night blindness were significantly lower as compared to normal healthy
children (p for Zn<0.001 and Cu<0.003), while the level of toxic metals As, Cd
and Pb were significantly higher in children having ocular problems as related to
normal children (p As<0.0074, Cd<0.001 and lead<0.004). CONCLUSION: These data
present guidance to clinicians and other professional investigating deficiency of
essential trace metals and excessive level of toxic metals in biological samples.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16473343 [PubMed - indexed for MEDLINE]

1581: J Cataract Refract Surg. 2005 Dec;31(12):2427-8.

Imatinib as a cause of cystoid macular edema following uneventful
phacoemulsification surgery.

Masood I, Negi A, Dua HS.

Division of Ophthalmology, Queens Medical Centre, Nottingham, United Kingdom.
imranmasood777@gmail.com

Cystoid macular edema (CME) is an important cause of visual impairment following 
phacoemulsification surgery. Imatinib is a new drug that is being used as
adjunctive therapy in the management of various malignancies. A reported ocular
side effect of this drug is spontaneous retinal edema. We report the case of a
patient on imatinib who developed significant premature CME following uneventful 
phacoemulsification surgery. This resolved soon after cessation of imatinib
therapy, and there was an improvement in visual acuity.

Publication Types: 
    Case Reports

PMID: 16473243 [PubMed - indexed for MEDLINE]

1582: Ophthalmic Surg Lasers Imaging. 2006 Jan-Feb;37(1):20-4.

Posterior capsule opacity and choroidal neovascularization in patients with
age-related macular degeneration.

Rumelt S, Pollack A.

Department of Ophthalmology, Western Galilee-Nahariya Medical Center and Leumit
Health Care System, Jerusalem, Israel.

BACKGROUND AND OBJECTIVE: To present a series of 3 patients with the dry form of 
age-related macular degeneration (AMD) in whom choroidal neovascularization (CNV)
was observed following neodymium: yttrium-aluminum-garnet (Nd:YAG) capsulotomy.
PATIENTS AND METHODS: Three consecutive patients aged 80 to 87 years (average =
83.7 years) with hard drusen or retinal pigment epithelial changes underwent
uneventful cataract extraction between 6 months and 20 years before undergoing
Nd:YAG capsulotomy for posterior capsule opacity. The patients were examined for 
retinal changes before laser treatment and at regular intervals after treatment. 
RESULTS: All patients developed CNV between 12 days and 1 month after capsulotomy
that caused a decrease in the visual acuity from 20/20-20/40 to 20/200--counting 
fingers at 4 feet. The fellow eye did not show a substantial change in AMD over a
year of follow-up. Two of the fellow eyes had disciform scar due to CNV before
the cataract surgery, and these patients remained legally blind. CONCLUSIONS: The
development of CNV after Nd:YAG capsulotomy suggests a temporal association
between the two and calls for further study. Because posterior capsule opacity
may mask CNV, patients with dry AMD and posterior capsule opacity who experience 
decreased visual acuity or glare may undergo indocyanine green angiography before
it is decided to perform Nd:YAG capsulotomy.

Publication Types: 
    Case Reports

PMID: 16468547 [PubMed - indexed for MEDLINE]

1583: Retina. 2006 Feb;26(2):153-8.

Stereoscopic fluorescein angiography in diabetic maculopathy.

Jensen DB, Knudsen LL.

Department of Ophthalmology, Arhus University Hospital, Aalborg Sygehus Syd,
Hobrovej 18-22, DK-9000 Aalborg Sygehus, Denmark.

PURPOSE: To explore the possible differences in the depth location of
microaneurysms in focal as well as diffuse diabetic macular edema. METHODS: The
density of superficial and deep retinal microaneurysms was assessed using a
stereoscopic fluorescein angiographic method. RESULTS: The density of deep
retinal microaneurysms was nearly identical in the group with diffuse macular
edema (89.9 +/- 28.5 microaneurysms/test grid) and the group with focal macular
edema (90 +/- 65.4 microaneurysms/test grid). The density of superficial retinal 
microaneurysms was significantly lower in the group with diffuse macular edema
(22.8 +/- 12.5) than in the group with focal macular edema (47.9 +/- 30.6). The
density fraction of superficial retinal microaneurysms was lower in the group
with diffuse macular edema (0.19 +/- 0.07) than in the group with focal macular
edema (0.36 +/- 0.14). In the group with focal macular edema, areas without edema
had a significantly lower density of superficial (6.1 +/- 2.8) and deep (15.6 +/-
7.8) retinal microaneurysms than did areas with edema (superficial: 47.9 +/-
30.6; deep: 90.0 +/- 65.4). In the group with focal macular edema, the density
fraction of superficial retinal microaneurysms was nearly identical in areas with
(0.36 +/- 0.14) and areas without (0.30 +/- 0.10) edema. CONCLUSION: The
development of focal macular edema might be linked to the density of
microaneurysms. Diffuse macular edema might be a result of some unknown effect on
the deeper retina and/or the choroid.

Publication Types: 
    Comparative Study

PMID: 16467670 [PubMed - indexed for MEDLINE]

1584: Retina. 2006 Feb;26(2):143-8.

Evaluating adjunctive surgical procedures during vitrectomy for diabetic macular 
edema.

Mochizuki Y, Hata Y, Enaida H, Yoshiyama K, Miyazaki M, Ueno A, Murata T,
Sakamoto T, Kubota T, Ishibashi T.

Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu
University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.

PURPOSE: To evaluate the long-term outcomes of adjunctive surgical procedures
during pars plana vitrectomy (PPV) for the treatment of diabetic macular edema
(DME). METHODS: In this nonrandomized study, we retrospectively analyzed 57 eyes 
of 54 patients who had DME and had undergone PPV. We performed PPV using three
different surgical procedures: conventional PPV (group PVD; 13 eyes),
triamcinolone acetonide (TA)-assisted PPV (group TA; 22 eyes), and TA-assisted
PPV combined with internal limiting membrane (ILM) peeling (group ILM; 22 eyes). 
We also evaluated the preoperative and postoperative best-corrected visual acuity
(BCVA) results. RESULTS: The overall mean preoperative BCVA was 0.86 logarithm of
the minimal angle of resolution unit. In groups PVD, TA, and ILM, BCVAs were
0.99, 0.90, and 0.74 (P = 0.310), respectively. The mean postoperative BCVA for
all patients improved to 0.68 (P = 0.005). The postoperative BCVA improved in 47%
of the treated eyes, it remained unchanged in 37% of the treated eyes, and it
deteriorated in 16% of the treated eyes. However, we observed no significant
difference in the mean postoperative BCVAs between the three groups. Furthermore,
we found that there was no significant difference in postoperative BCVA
improvements between any of the groups (P = 0.450). CONCLUSION: The present study
suggests that these 3 PPV approaches do not significantly affect postoperative
BCVAs after 18 months of DME treatment.

Publication Types: 
    Comparative Study

PMID: 16467668 [PubMed - indexed for MEDLINE]

1585: Retina. 2006 Feb;26(2):137-42.

Panretinal photocoagulation and intravitreal triamcinolone acetonide for the
management of proliferative diabetic retinopathy with macular edema.

Zein WM, Noureddin BN, Jurdi FA, Schakal A, Bashshur ZF.

Department of Ophthalmology, American University of Beirut, Medical Center,
Beirut, Lebanon.

PURPOSE: To investigate intravitreal triamcinolone acetonide (IVTA) as an
adjunctive therapy to panretinal photocoagulation (PRP) in patients with both
high-risk proliferative diabetic retinopathy (PDR) and clinically significant
macular edema (CSME). METHODS: Thirty-five eyes diagnosed with both high-risk PDR
and CSME underwent PRP and a single injection of 4 mg of IVTA (IVTA group).
Visual, anatomic, and fluorescein angiographic changes were documented. Any
complications resulting from the combined procedure were noted. These data were
compared retrospectively to 35 eyes that underwent grid laser treatment to the
macula followed 2 weeks later by PRP (laser group). Main outcome measures
included change in best-corrected visual acuity, improvement in macular edema
(clinical or angiographic), and control of the neovascular disease. RESULTS: Mean
follow-up was 9.6 months for the IVTA group and 11.9 months for the laser group. 
Mean pretreatment best-corrected visual acuity was 20/286 in the IVTA group and
20/282 in the laser group (P = 0.80). After 9 months of follow-up, visual acuity 
was 20/80 in the IVTA group versus 20/156 in the laser group (P = 0.007).
Thirty-four percent of eyes in the IVTA group had final vision of 20/40 or better
versus 11% in the laser group (P = 0.044). At 9 months follow-up, 84% of IVTA
eyes had complete resolution of macular edema versus 46% of laser eyes (P =
0.002). Three eyes in the IVTA group had recurrence of macular edema after 6
months and required reinjection of IVTA. Elevation in intraocular pressure
occurred in eight eyes in the IVTA group and responded to topical therapy.
Cataract progression was observed in nine eyes in the IVTA group. CONCLUSIONS:
The addition of intravitreal triamcinolone acetonide to PRP in the management of 
patients with both PDR and CSME seems promising. Further study is needed to
assess the effect of this combined treatment.

PMID: 16467667 [PubMed - indexed for MEDLINE]

1586: Int Psychogeriatr. 2006 Sep;18(3):415-28. Epub 2006 Feb 8.

Psychosocial effects of age-related macular degeneration.

Berman K, Brodaty H.

Academic Department for Old Age Psychiatry, Prince of Wales Hospital, Randwick,
NSW, Australia.

BACKGROUND: Age-related macular degeneration (AMD) affects approximately 10% of
persons aged 65-74 years and 30% of those aged 75 and older and is the major
cause of blindness in old age. AMD is progressive and irreversible. AIM: To
review the psychosocial effects of AMD. METHOD: OVID data bases (MEDLINE,
psycINFO and CINAHL) from 1966 to 2004 were reviewed. RESULTS: AMD is associated 
with functional impairment, high rates of depression, anxiety and emotional
distress and increased mortality. Risk factors for depression are not
well-defined, except for the degree of functional impairment and impending or
actual loss of vision in the second eye. Behavioral and self-management programs 
may be effective in managing depression associated with AMD, but few studies have
been performed, and none using drugs or multimodal therapy. CONCLUSION: AMD will 
become even more prevalent as the population ages. Identification of risk factors
for psychological consequences and of effective interventions remain to be
recognized.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 16466594 [PubMed - indexed for MEDLINE]

1587: Ophthalmic Physiol Opt. 2006 Mar;26(2):169-79.

Effects of task lighting on visual function in age-related macular degeneration.

Haymes SA, Lee J.

Department of Optometry and Vision Sciences, The University of Melbourne,
Victoria, Australia. haymesdomain@eastlink.ca

The purpose was to investigate the effects of the spectral power distribution
(SPD) and illuminance of task lighting on visual function in age-related macular 
degeneration (ARMD) compared to normal healthy eyes. Twenty-eight subjects with
ARMD and 18 age-matched normal subjects were studied. The effects on visual
function were determined for four common task light sources: standard pearl coat 
incandescent (SP), daylight blue incandescent (DL), warm white fluorescent (WW)
and cool white fluorescent (CW). Apart from a small, statistically significant
improvement in contrast sensitivity with DL compared to SP lighting (0.5 dB, p = 
0.01), there were no significant effects of SPD on other visual functions and no 
differences in the effects for subjects with ARMD and those with normal vision.
Thus, for task lighting typically used in low vision rehabilitation, the SPD
would seem to be of minimal clinical importance to visual function. However,
increasing the task illuminance had a greater effect on visual function, in
particular for subjects with ARMD (p < 0.01). For an increase in illuminance from
300 to 3000 lux, the mean increase in contrast sensitivity and near visual acuity
was 1.5 dB and 0.13 log MAR, respectively. Although this effect is not large, we 
suggest that it is clinically relevant and supports the provision of additional
task illuminance as an important part of low vision rehabilitation for patients
with ARMD.

Publication Types: 
    Comparative Study
    Multicenter Study

PMID: 16460317 [PubMed - indexed for MEDLINE]

1588: Ophthalmology. 2006 Mar;113(3):363-372.e5. Epub 2006 Feb 3.

Comment in:
    Ophthalmology. 2007 Feb;114(2):400; author reply 400-1.

Intravitreal bevacizumab (Avastin) for neovascular age-related macular
degeneration.

Avery RL, Pieramici DJ, Rabena MD, Castellarin AA, Nasir MA, Giust MJ.

California Retina Consultants, Santa Barbara, California 93103, USA.

PURPOSE: To report the short-term safety, biologic effect, and a possible
mechanism of action of intravitreal bevacizumab in patients with neovascular
age-related macular degeneration (AMD). DESIGN: Interventional, consecutive,
retrospective case series. PARTICIPANTS: Eighty-one eyes of 79 patients with
subfoveal neovascular AMD. METHODS: Patients received intravitreal bevacizumab
(1.25 mg) on a monthly basis until macular edema, subretinal fluid (SRF), and/or 
pigment epithelial detachment (PED) resolved. Ophthalmic evaluations included
nonstandardized Snellen visual acuity (VA), complete ophthalmic examination,
fluorescein angiography, and optical coherence tomography (OCT). MAIN OUTCOME
MEASURES: Assessments of safety, changes in Snellen VA, OCT retinal thickness,
and angiographic lesion characteristics were performed. RESULTS: No significant
ocular or systemic side effects were observed. Most patients (55%) had a
reduction of >10% of baseline retinal thickness at 1 week after the injection. At
4 weeks after injection, 30 of 81 eyes demonstrated complete resolution of
retinal edema, SRF, and PEDs. Of the 51 eyes with 8 weeks' follow-up, 25 had
complete resolution of retinal thickening, SRF, and PEDs. At 1, 4, 8,and 12
weeks, the mean retinal thickness of the central 1 mm was decreased by 61, 92,
89, and 67 mum, respectively (P<0.0001 for 1, 4, and 8 weeks and P<0.01 for 12
weeks). At 4 and 8 weeks, mean VA improved from 20/200 to 20/125 (P<0.0001).
Median vision improved from 20/200 to 20/80(-) at 4 weeks and from 20/200 to
20/80 at 8 weeks. CONCLUSIONS: Short-term results suggest that intravitreal
bevacizumab (1.25 mg) is well tolerated and associated with improvement in VA,
decreased retinal thickness by OCT, and reduction in angiographic leakage in most
patients, the majority of whom had previous treatment with photodynamic therapy
and/or pegaptanib. Further evaluation of intravitreal bevacizumab for the
treatment of choroidal neovascularization is warranted.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 16458968 [PubMed - indexed for MEDLINE]

1589: Am J Ophthalmol. 2006 Feb;141(2):404-7.

Optical coherent tomography features of malattia leventinese.

Souied EH, Leveziel N, Letien V, Darmon J, Coscas G, Soubrane G.

Clinique Ophthamologique Universitaire de Créteil, Höpital Intercommunal,
Créteil, France. eric.souied@chicreteil.fr

PURPOSE: Malattia leventinese (ML) is an inherited macular degeneration
characterized by the presence of large paracentral and small radial drusen. Our
purpose was to describe optical coherent tomography (OCT) features observed in
ML. DESIGN: Prospective observational case series. METHODS: Ten eyes from five
patients with ML aged 27 to 44 years were prospectively included. Best-corrected 
visual acuity, fundus color photography of the retina, and OCT were performed in 
each patient. RESULTS: OCT revealed a hyperreflective thickening of the retinal
pigment epithelium-Bruch membrane complex, associated with localized dome-shaped 
elevations. Retinal thickness above the drusen ranged from 221 to 292 microm
(mean 260 microm). Foveal thickness ranged from 72 to 200 microm (mean 144
microm) CONCLUSIONS: The large paracentral drusen presented either as a
thickening of the retinal pigment epithelium-Bruch complex or as local limited
elevation of retinal pigment epithelium-Bruch complex, both associated with
preservation of the neurosensory retina.

PMID: 16458713 [PubMed - indexed for MEDLINE]

1590: Am J Ophthalmol. 2006 Feb;141(2):276-81.

Comment in:
    Am J Ophthalmol. 2006 Feb;141(2):354-5.

Prophylactic laser treatment hastens choroidal neovascularization in unilateral
age-related maculopathy: final results of the drusen laser study.

Owens SL, Bunce C, Brannon AJ, Xing W, Chisholm IH, Gross M, Guymer RH, Holz FG, 
Bird AC; Drusen Laser Study Group.

Moorfields Eye Hospital, London, United Kingdom, and the Universitätsklinikum
Benjamin Franklin, Berlin, Germany. Sarah.Owens@moorfields.nhs.uk

PURPOSE: The Drusen Laser Study evaluated macular laser to prevent choroidal
neovascularization (CNV) and vision loss in high-risk age-related maculopathy
(ARM). DESIGN: Prospective, interventional, randomized, controlled clinical trial
in five hospital centers. METHODS: Patients in the unilateral group had
neovascular ARM and drusen in the study eye. Study eyes were randomized to
laser-treated or no-laser groups. For patients in the bilateral drusen group,
eyes were randomized to right eye, laser or no laser; and left eye, alternative. 
Laser treatment comprised 12 argon spots. Outcome was best-corrected visual
acuity and CNV signs, which were monitored for 3 years. RESULTS: In the
unilateral group, vision loss occurred in 21 (28.8%) of 73 patients in laser vs
13 (19.7%) of 66 no-laser patients (P=.214). Incidence of CNV was 27 (29.7%) of
91 in laser vs 15 (17.65%) of 85 no-laser patients (P=.061). CNV onset was
approximately 6 months earlier in laser-treated compared with no-laser patients
(P=.05). In the bilateral group, vision loss occurred in six (8.3%) of 72
laser-treated vs 10 (13.9%) of 72 fellow eyes (P=.3877). CNV incidence was 12
(11.6%) of 103 in laser-treated vs seven (6.8%) of 103 fellow eyes (P=.225).
There was no difference in onset of CNV. CONCLUSIONS: Results do not support
prophylactic laser of the fellow eye of patients with neovascular ARM. Its role
in patients with bilateral drusen remains unclear.

Publication Types: 
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16458680 [PubMed - indexed for MEDLINE]

1591: Ophthalmology. 2006 Feb;113(2):260-6.

Evaluation of the clinical age-related maculopathy staging system.

Seddon JM, Sharma S, Adelman RA.

Epidemiology Unit, Department of Ophthalmology, Massachusetts Eye and Ear
Infirmary, Harvard Medical School, Boston, Massachusetts 02114, USA.

OBJECTIVE: To evaluate a clinical classification system, the Clinical Age-Related
Maculopathy Staging (CARMS) system, for age-related maculopathy (ARM) using a
simple grading scale designed for clinical practice and clinical research
protocols. PARTICIPANTS: Two hundred forty-six male and female participants with 
various stages of ARM who were enrolled during the first 4 years of a
longitudinal study were selected for the evaluation of the CARMS system. DESIGN: 
Cross-sectional comparison study. METHODS: The CARMS system divides patients into
5 mutually exclusive categories based on slit-lamp assessment of drusen, retinal 
pigment epithelial irregularities, geographic atrophy, retinal pigment epithelial
detachment, and choroidal neovascularization. Fundus photographs and clinical
data of the subjects were used to evaluate this scale. Clinical grades assigned
for 492 eyes of 246 patients with varying stages of ARM were compared with grades
obtained from photographs evaluated by a reading center. To compare grades
obtained from an inexperienced grader with those of an experienced grader,
observations based on photographs from 50 randomly selected patients were
reviewed. To quantify intraobserver agreement for photographic grades,
observations from one observer were compared with those made at a later date by
the same observer. MAIN OUTCOME MEASURES: Reliability and validity of the CARMS
system in grading various stages of ARM based on clinical examination and
photography. RESULTS: The degree of overall agreement between the clinically
assigned grade and photographic assessment for 492 eyes was substantial (exact
overall agreement, 75%; unweighted kappa, 0.63; weighted kappa, 0.78). For
advanced age-related macular degeneration, the sensitivity was 0.83, and
specificity was 0.97. When assessing photographic grades, the degree of agreement
between an inexperienced and an experienced grader was very high (unweighted
kappa, 0.79; weighted kappa, 0.86), and the degree of intraobserver agreement was
excellent (unweighted kappa, 0.92; weighted kappa, 0.97). CONCLUSIONS: The CARMS 
system, a 5-level clinical scale, is a valid and reliable staging system that can
be used in both clinical practice and in clinical research protocols involving
patients with all stages of ARM.

Publication Types: 
    Comparative Study
    Evaluation Studies
    Research Support, Non-U.S. Gov't

PMID: 16458093 [PubMed - indexed for MEDLINE]

1592: Eye. 2007 Apr;21(4):506-11. Epub 2006 Feb 3.

Pulsatile ocular blood flow in asymmetric age-related macular degeneration.

Sandhu R, Sivaprasad S, Shah SP, Adewoyin T, Chong NV.

Retinal Research Unit, Department of Ophthalmology, King's College Hospital,
Denmark Hill, London, UK.

PURPOSE: Ocular perfusion abnormalities have been proposed in the pathogenesis of
age-related macular degeneration (AMD) with differences in pulsatile ocular blood
flow (POBF) in eyes with asymmetric AMD in Japanese and Taiwanese patients. The
purpose of our study was to observe POBF difference in the fellow eyes of
Caucasians with asymmetric AMD. METHODS: This was a cross-sectional study
comparing POBF in three groups of patients with asymmetric AMD in the fellow
eyes: Group 1 (n=21) with drusen and active choroidal neovascularisation (CNV);
Group 2 (n=18) with drusen and disciform scar; Group 3 (n=8) with CNV and
disciform scar. The POBF was adjusted for intraocular pressure (IOP), pulse rate 
(PR), and axial length using multiple regression analysis. Generalised estimation
equation model was used to include both eyes in each group. RESULTS: The
geometric mean (95% confidence interval) POBF values were as follows: Group 1
with drusen 1097.9 microl/min (957.0, 1259.7) in one eye and the fellow eye with 
CNV 1090.1 microl/min (932.3, 1274.7); Group 2 with drusen 946.0 microl/min
(794.2, 1126.7) and disciform scar 966.2 microll/min (780.3, 1196.4); Group 3
with CNV 877.1 microl/min (628.3, 1224.6) and disciform scar 767.2 microl/min
(530.5, 1109.7). Adjusting for differences in axial length, pulse rate and
intraocular pressure, no statistically significant difference in POBF was found
between fellow eyes in the same subject. CONCLUSIONS: POBF is not different
between fellow eyes of Caucasian patients with asymmetric AMD.

PMID: 16456596 [PubMed - indexed for MEDLINE]

1593: Hum Gene Ther. 2006 Feb;17(2):167-76.

Comment in:
    Hum Gene Ther. 2006 Feb;17(2):177-9.

Adenoviral vector-delivered pigment epithelium-derived factor for neovascular
age-related macular degeneration: results of a phase I clinical trial.

Campochiaro PA, Nguyen QD, Shah SM, Klein ML, Holz E, Frank RN, Saperstein DA,
Gupta A, Stout JT, Macko J, DiBartolomeo R, Wei LL.

Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 
21287, USA. pcampo@jhmi.edu

Twenty-eight patients with advanced neovascular age-related macular degeneration 
(AMD) were given a single intravitreous injection of an E1-, partial E3-,
E4-deleted adenoviral vector expressing human pigment epithelium- derived factor 
(AdPEDF.11). Doses ranging from 10(6) to 10(9.5) particle units (PU) were
investigated. There were no serious adverse events related to AdPEDF.11 and no
dose-limiting toxicities. Signs of mild, transient intraocular inflammation
occurred in 25% of patients, but there was no severe inflammation. Six patients
experienced increased intraocular pressure that was easily controlled by topical 
medication. All adenoviral cultures were negative. At 3 and 6 months after
injection, 55 and 50%, respectively, of patients treated with 10(6)-10(7.5) PU
and 94 and 71% of patients treated with 10(8)-10(9.5) PU had no change or
improvement in lesion size from baseline. The median increase in lesion size at 6
and 12 months was 0.5 and 1.0 disk areas in the low-dose group compared with 0
and 0 disk areas in the high-dose group. These data suggest the possibility of
antiangiogenic activity that may last for several months after a single
intravitreous injection of doses greater than 10(8) PU of AdPEDF.11. This study
provides evidence that adenoviral vector-mediated ocular gene transfer is a
viable approach for the treatment of ocular disorders and that further studies
investigating the efficacy of AdPEDF.11 in patients with neovascular AMD should
be performed.

Publication Types: 
    Clinical Trial, Phase I
    Multicenter Study

PMID: 16454650 [PubMed - indexed for MEDLINE]

1594: Hum Mutat. 2006 Apr;27(4):337-42.

Apolipoprotein (APOE) gene is associated with progression of age-related macular 
degeneration (AMD).

Baird PN, Richardson AJ, Robman LD, Dimitrov PN, Tikellis G, McCarty CA, Guymer
RH.

Centre for Eye Research Australia, University of Melbourne, East Melbourne,
Australia. pnb@unimelb.edu.au

Progression of age-related macular degeneration (AMD), the leading cause of
blindness in the elderly, was followed in a cohort of 238 individuals from a
single center. Individuals with an epsilon (epsilon)2 genotype (c.526C>T of
reference sequence NM_000041.2) of the apolipoprotein (APOE) gene were found to
be strongly associated with disease with a significant 4.8-fold increased
relative risk compared to individuals with an epsilon4 genotype (c.388T>C of
reference sequence NM_000041.2) (odds ratio [OR], 4.8; 95% confidence interval
[CI], 1.19-19.09) and a nearly significant three-fold increased relative risk
compared to individuals with an epsilon3 genotype (reference sequence
NM_000041.2) (OR, 2.8; 95% CI, 0.96-19.09). This finding was present only in
females who progressed with AMD, which suggests that there may be a
gender-specific role in progression of AMD in individuals with an epsilon2
allele. A gender-related factor is therefore implicated either directly or
indirectly in the AMD disease process. (c) 2006 Wiley-Liss, Inc.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16453339 [PubMed - indexed for MEDLINE]

1595: Jpn J Ophthalmol. 2006 Jan-Feb;50(1):25-32.

Tracing method in the assessment of retinal capillary blood flow velocity by
fluorescein angiography with scanning laser ophthalmoscope.

Funatsu H, Sakata K, Harino S, Okuzawa Y, Noma H, Hori S.

Department of Ophthalmology, Diabetes Center, Tokyo Women's Medical University,
Tokyo, Japan. tfunatsu@nifty.com

PURPOSE: To evaluate the feasibility of a new method (the tracing method) for
measuring perifoveal capillary blood flow velocity (BFV). METHODS: The BFV in the
perifoveal capillaries was measured in 12 eyes of healthy subjects and 12 eyes of
patients with clinically significant macular edema (CSME) by fluorescein
angiography using a scanning laser ophthalmoscope by either the tracing method or
the conventional method. A randomized crossover design was employed to assign the
subjects to each method. RESULTS: The number of capillaries recognized by the
tracing method in healthy subjects and in patients with CSME was significantly
higher than that recognized with the conventional method (P = 0.0134 and P =
0.0108, respectively). The number of fluorescent dots detected by the tracing
method in healthy subjects and in patients with CSME was also significantly
higher than that detected with the conventional method (P = 0.0002 and P =
0.0137, respectively). Accurate detection of the movement of fluorescent dots and
analysis of BFV were possible with the tracing method. The BFV varied within each
perifoveal capillary, and the mean BFV also varied according to capillary
location in the macula. CONCLUSION: The new tracing method is useful for
analyzing the retinal capillary BFV in healthy subjects and in patients with
CSME. Copyright Japanese Ophthalmological Society 2006.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16453184 [PubMed - indexed for MEDLINE]

1596: J Clin Invest. 2006 Feb;116(2):378-85.

Drusen deposits associated with aging and age-related macular degeneration
contain nonfibrillar amyloid oligomers.

Luibl V, Isas JM, Kayed R, Glabe CG, Langen R, Chen J.

Beckman Macular Research Center, Doheny Eye Institute and Zilkha Neurogenetic
Institute, University of Southern California Keck School of Medicine, Los
Angeles, California 90033, USA.

Protein misfolding and aggregation are thought to underlie the pathogenesis of
many amyloid diseases, such as Alzheimer and Parkinson diseases, whereby a
stepwise protein misfolding process begins with the conversion of soluble protein
monomers to prefibrillar oligomers and progresses to the formation of insoluble
amyloid fibrils. Drusen are extracellular deposits found in aging eyes and in
eyes afflicted with age-related macular degeneration (AMD). Recent
characterizations of drusen have revealed protein components that are shared with
amyloid deposits. However, characteristic amyloid fibrils have thus far not been 
identified in drusen. In this study, we tested the hypothesis that nonfibrillar
oligomers may be a common link in amyloid diseases. Oligomers consisting of
distinct amyloidogenic proteins and peptides can be detected by a recently
developed antibody that is thought to recognize a common structure. Notably,
oligomers exhibit cellular toxicity, which suggests that they play a role in the 
pathogenesis of neurodegenerative diseases. Through use of the anti-oligomer
antibody, we came to observe the presence of nonfibrillar, toxic oligomers in
drusen. Conversely, no reactivity was observed in age-matched control eyes
without drusen. These results suggest that amyloid oligomers may be involved in
drusen biogenesis and that similar protein misfolding processes may occur in AMD 
and amyloid diseases.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16453022 [PubMed - indexed for MEDLINE]

1597: Proc Natl Acad Sci U S A. 2006 Feb 14;103(7):2328-33. Epub 2006 Feb 1.

Drusen complement components C3a and C5a promote choroidal neovascularization.

Nozaki M, Raisler BJ, Sakurai E, Sarma JV, Barnum SR, Lambris JD, Chen Y, Zhang
K, Ambati BK, Baffi JZ, Ambati J.

Department of Ophthalmology and Visual Sciences, University of Kentucky,
Lexington, KY 40536, USA.

Age-related macular degeneration (AMD) is the leading cause of irreversible
blindness in industrialized nations, affecting 30-50 million people worldwide.
The earliest clinical hallmark of AMD is the presence of drusen, extracellular
deposits that accumulate beneath the retinal pigmented epithelium. Although
drusen nearly always precede and increase the risk of choroidal
neovascularization (CNV), the late vision-threatening stage of AMD, it is unknown
whether drusen contribute to the development of CNV. Both in patients with AMD
and in a recently described mouse model of AMD, early subretinal pigmented
epithelium deposition of complement components C3 and C5 occurs, suggesting a
contributing role for these inflammatory proteins in the development of AMD. Here
we provide evidence that bioactive fragments of these complement components (C3a 
and C5a) are present in drusen of patients with AMD, and that C3a and C5a induce 
VEGF expression in vitro and in vivo. Further, we demonstrate that C3a and C5a
are generated early in the course of laser-induced CNV, an accelerated model of
neovascular AMD driven by VEGF and recruitment of leukocytes into the choroid. We
also show that genetic ablation of receptors for C3a or C5a reduces VEGF
expression, leukocyte recruitment, and CNV formation after laser injury, and that
antibody-mediated neutralization of C3a or C5a or pharmacological blockade of
their receptors also reduces CNV. Collectively, these findings establish a
mechanistic basis for the clinical observation that drusen predispose to CNV,
revealing a role for immunological phenomena in angiogenesis and providing
therapeutic targets for AMD.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, Non-P.H.S.

PMID: 16452172 [PubMed - indexed for MEDLINE]

1598: Clin Experiment Ophthalmol. 2006 Jan-Feb;34(1):27-32.

Intravitreal triamcinolone injection for chronic diffuse diabetic macular oedema.

Avci R, Kaderli B, Akalp FD.

Department of Ophthalmology, Uludag University Hospital, 16059 Gorukle, Bursa,
Turkey. ravci@uludag.edu.tr

PURPOSE: To determine the efficacy and safety of intravitreal triamcinolone in
chronic diffuse diabetic macular oedema. METHODS: This prospective,
interventional consecutive case series study consisted of 59 eyes (36 patients)
with chronic diffuse diabetic macular oedema, which received an intravitreal
injection of 4 mg triamcinolone acetonide. The results were evaluated by clinical
examination and fluorescein angiography. Potential complications such as a rise
in intraocular pressure, cataract progression and endophthalmitis were recorded. 
RESULTS: All patients completed at least 6 months follow up. The mean visual
acuity improved significantly from 0.17 +/- 3.4 to a maximum of 0.30 +/- 3.3 at
the third postinjection month (P < 0.01). Mean improvements in visual acuity
measured were 2.15 +/- 1.66, 2.42 +/- 2.66, 1.13 +/- 2.74, 0.96 +/- 2.01 and 0.08
+/- 2.34 lines at the 1, 3, 6, 9 and 12 months follow-up intervals, respectively.
In all eyes in fluorescein angiography, macular oedema was resolved (63%) or
decreased (37%) during the follow up. However, the macular oedema reached the
pretreatment level in 29 (49%) of the eyes at 6 months and 15 of 21 eyes (71%) at
9 months after injection. Intraocular pressure exceeded 21 mmHg in 10 eyes, which
were controlled by topical medication. Four eyes showed cataract progression.
Endophthalmitis was not observed in any of the eyes. CONCLUSIONS: Intravitreal
injection of 4 mg triamcinolone acetonide appears to be an effective and
relatively safe therapeutic method for diffuse diabetic macular oedema. Further
studies are warranted to assess the long-term efficacy, safety and the need for
reinjection.

Publication Types: 
    Clinical Trial

PMID: 16451255 [PubMed - indexed for MEDLINE]

1599: Clin Experiment Ophthalmol. 2006 Jan-Feb;34(1):9-14.

Awareness of and compliance with recommended dietary supplement among age-related
macular degeneration patients.

Ng WT, Goggin M.

Department of Ophthalmology, University of Adelaide, The Queen Elizabeth
Hospital, Woodville South, South Australia, Australia. wengt@yahoo.com

BACKGROUND: The age-related eye disease study suggested that taking zinc and
anti-oxidants supplements could reduce the progression of age-related macular
degeneration (AMD). In Australia, the available supplement is Macu-Vision. The
study aimed to assess the awareness of and compliance with taking this supplement
and the public health implication. METHODS: The fundus photograph database of
patients aged 55 years and older at the ophthalmology department of a public
teaching hospital in Adelaide, Australia was reviewed. In total, 125 patients
with category 3 and 4 AMD were identified. A total of 100 patients participated
in this cross-sectional study. RESULTS: In total, 53% of participants were aware 
of the availability of the formulae available in Australia, 38% were taking the
supplement and only 1% were taking the correct dose. Of those taking the
supplement 95% (36/38) were taking half the recommended dosage. Among those who
were aware of the supplement but not taking it, cost was the most common reason
(31%). Another 31% were not taking it because of actual side-effects experienced,
fear of potential side-effect and/or fear of interaction with other medications. 
There was no predictive factor for failing to take the formulae available in
Australia among age, sex, smoking status, living arrangement and category of AMD.
CONCLUSIONS: Clinicians need to emphasize that the recommended dosage is twice
that on the supplement label. If the trend demonstrated here of underutilizing
the formulae available in Australia among public hospital patients continues, it 
is unlikely to have any major public health impact in similar settings in
Australia.

PMID: 16451252 [PubMed - indexed for MEDLINE]

1600: Acta Ophthalmol Scand. 2006 Feb;84(1):27-35.

Retinal function following transpupillary thermotherapy for occult choroidal
neovascularization in age-related macular degeneration: a short-term study by
focal electroretinography.

Pirozzi E, Manganelli C, Piccardi M, Minnella A, Fadda A, Ziccardi L, Coccimiglio
F, Falsini B.

Institute of Ophthalmology, Catholic University of Sacred Heart, Rome, Italy.

PURPOSE: To assess short-term changes in macular function after transpupillary
thermotherapy (TTT) in patients with occult subfoveal choroidal
neovascularization (CNV) secondary to age-related macular degeneration (AMD),
using focal electroretinography (FERG). METHODS: Twenty-five patients with occult
subfoveal CNV due to AMD were treated with TTT delivered using an infrared (810
nm) diode laser (spot size 3.0 mm, laser power 400-600 mW, duration 60 seconds). 
All patients were clinically evaluated before, 1 and 6 weeks after treatment.
Snellen visual acuity (VA) was measured at each visit. Fluorescein angiography
(FA) was performed at baseline and 6 weeks after TTT. Focal ERGs were recorded in
all patients immediately before and 1 week after TTT in response to an 18-degree 
diameter, 41 Hz flickering spot (630 nm) centred on the fovea, presented on a
steady background in Maxwellian view. A subgroup of 12 patients was also
re-tested by FERG at 6-weeks post-TTT. RESULTS: No significant changes in mean
FERG amplitude and phase were observed across the different recording sessions
before and after TTT. One week after TTT, four patients had significant (> 2 SD
from baseline variability) increases in FERG amplitude and/or phase advances, one
had a decrease in amplitude and four had phase delays, compared to baseline. The 
remaining 15 patients had stable FERGs. Six weeks after TTT, four patients had
significant increases in FERG amplitude and/or phase advances, four had decreases
in amplitude and/or phase delays, and four had stable FERGs, compared to
baseline. Improvement in FERG parameters after TTT was always associated with an 
improvement in VA and a decrease in exudation. Patients with post-TTT FERG
deterioration had stable or deteriorated clinical pictures. At either 1 or 6
weeks post-TTT, the FERG amplitude increase was inversely correlated (p < 0.05)
with the baseline FERG amplitude and VA. CONCLUSIONS: Three major conclusions can
be drawn: in a short-term follow-up, TTT was not found to be associated with
significant changes in macular function; FERG improvement was associated with VA 
improvement, and the increase in FERG amplitude was greatest in patients with the
worst baseline acuity.

PMID: 16445436 [PubMed - indexed for MEDLINE]

1601: Acta Ophthalmol Scand. 2006 Feb;84(1):4-15.

Age-related maculopathy and the impact of blue light hazard.

Algvere PV, Marshall J, Seregard S.

Karolinska Institute, St Erik's Eye Hospital, Stockholm, Sweden.
peep.algvere@sankterik.se

The pathogenesis of age-related maculopathy (ARM), the most common cause of
visual loss after the age of 60 years, is indeed a complicated scenario that
involves a variety of hereditary and environmental factors. The pathological
cellular and molecular events underlying retinal photochemical light damage,
including photoreceptor apoptosis, have been analysed in experimental animal
models. Studies of age-related alterations of the retina and photoreceptors, the 
accumulation of lipofuscin in retinal pigment epithelium (RPE) cells, and the
formation of drusen have greatly contributed to our knowledge. A new concept of
an inflammatory response to drusen has emerged, suggesting immunogenic and
systemic reactions in Bruch's membrane and the subretinal space. Oxidative stress
and free radical damage also impact on the photoreceptors and RPE cells in the
ageing eye. Based on the photoelectric effect, a fundamental concept in quantum
physics, the consequences of high-energy irradiation have been analysed in animal
models and cell culture. Short-wavelength radiation (rhodopsin spectrum), and the
blue light hazard (excitation peak 440 nm), have been shown to have a major
impact on photoreceptor and RPE function, inducing photochemical damage and
apoptotic cell death. Following cataract surgery, there is a dramatic change in
ocular transmittance. In aphakic or pseudophakic eyes (with clear intraocular
lenses), high-energy (blue) and ultraviolet-A radiation strikes the retina.
Epidemiological data indicate a significantly increased 5-year incidence of late 
ARM in non-phakic eyes compared with phakic eyes. In recent years, putative
prophylactic measures against ARM have emerged. The implantation of 'yellow'
intraocular lenses (IOLs) that absorb high-energy blue radiation is, from a
theoretical point of view, the most rational approach, and, from a practical
point of view, is easy to accomplish. With increasing age, RPE cells accumulate
lipofuscin (chromophore A2E). It is noteworthy that the yellow IOL not only
protects A2E-laden human RPE cells from blue light (peak 430 nm) damage, but also
alleviates the detrimental effects of green (peak 550 nm) and white light. A
prophylactic treatment using antioxidants is aimed at counteracting oxidative
stress and free radical cellular damage. The Age-Related Eye Disease Study
(AREDS), a randomized clinical trial, showed a significantly lower incidence of
late ARM in a cohort of patients with drusen maculopathy treated with high doses 
of antioxidants than in a placebo group. In recent years, considerable progress
in retinal research has been achieved, creating a platform for the search for new
prophylactic and therapeutic measures to alleviate or prevent photoreceptor and
RPE degeneration in ARM.

Publication Types: 
    Review

PMID: 16445433 [PubMed - indexed for MEDLINE]

1602: Eye. 2007 Apr;21(4):512-7. Epub 2006 Jan 27.

Early age-related maculopathy in eyes after cataract surgery.

Pham TQ, Cugati S, Rochtchina E, Mitchell P, Maloof A, Wang JJ.

Department of Ophthalmology (Centre for Vision Research, Westmead Millennium
Institute), Westmead Hospital, University of Sydney, Westmead, NSW, Australia.

PURPOSE: To assess age-related maculopathy (ARM) in eyes of patients who had
undergone cataract surgery for at least a year. METHODS: Consecutive patients
aged 60+ years who had undergone cataract surgery at Westmead Hospital, Sydney,
Australia, during 2001-2003 were examined in 2004. Interview using standardized
questionnaires and stereo retinal photography was performed. Retinal photographs 
were graded using the Wisconsin ARM grading system. The proportions with ARM were
compared between surgical and nonsurgical eyes, and between this surgical cohort 
and the Blue Mountains Eye Study (BMES) population. RESULTS: Of the 622 eligible 
patients, 454 (73%) were re-examined, with a mean follow-period of 2.8 years.
Surgical eyes had a higher proportion of early ARM compared to nonsurgical eyes
(15.2 vs10.3%, P=0.07) and to the early ARM prevalence found in BMES participants
of similar age (14.5 vs6.9%, P<0.01), which persisted after age standardization
to the BMES population (9.7 vs6.9%, P<0.05). CONCLUSIONS: We found an increased
prevalence of early ARM in surgical eyes of patients 1-3 years after cataract
surgery. Whether this increased early ARM prevalence leads to an increased
prevalence of late ARM in the long-term warrants further investigation.

PMID: 16440007 [PubMed - indexed for MEDLINE]

1603: Cochrane Database Syst Rev. 2006 Jan 25;(1):CD005138.

Antiangiogenic therapy with interferon alfa for neovascular age-related macular
degeneration.

Reddy U, Kryzstolik M.

Brown Medical School, Box G-8064, 593 Eddy Street, Providence, Rhode Island
02903, USA. Usha_Reddy@brown.edu

BACKGROUND: Antiangiogenic therapy is a new approach to the treatment of
neovascular age-related macular degeneration. Interferon alfa is one
antiangiogenic agent thought to function by inhibiting the migration and
proliferation of vascular endothelial cells. It has been used in the treatment of
hepatitis, solid tumors and hematologic malignancies. OBJECTIVES: The aim of this
review was to investigate interferon alfa as a treatment modality for neovascular
age-related macular degeneration. SEARCH STRATEGY: We searched and identified
trials from the Cochrane Central Register of Controlled Trials (CENTRAL), which
contains the Cochrane Eyes and Vision Group Trials Register, in The Cochrane
Library (Issue 2, 2005), MEDLINE (1966 to 2005/06 week 1), EMBASE (1980 to
2005/week 23), LILACS (Latin American and Caribbean Health Science Literature
Database) (June 2005) and the reference lists of included studies. SELECTION
CRITERIA: This review included randomized controlled trials evaluating interferon
alfa therapy in people with neovascular age-related macular degeneration who were
followed for at least one year. DATA COLLECTION AND ANALYSIS: Both review authors
independently extracted data and assessed trial quality. No data synthesis was
conducted as only one trial met the inclusion criteria. MAIN RESULTS: The one
included trial enrolled and randomized 481 participants from 45 centers worldwide
into four groups. The study allowed for analysis of the number of participants
who had lost three or more lines of vision at 52 weeks in three interferon
alfa-2a groups versus placebo. The results show an odds ratio of 1.60 (95%
Confidence Interval 1.01 to 2.53) indicating that interferon is associated with a
60% increased odds of losing three or more lines at 52 weeks. This finding is
marginally statistical with a P value of 0.04 and indicates that the treatment
has the potential for harm rather than benefit. AUTHORS' CONCLUSIONS: At present 
there is not enough evidence to recommend the use of interferon alfa-2a for the
treatment of age-related macular degeneration.

Publication Types: 
    Review

PMID: 16437522 [PubMed - indexed for MEDLINE]

1604: Curr Opin Ophthalmol. 2006 Feb;17(1):94-8.

The Implantable Miniature Telescope for macular degeneration.

Lane SS, Kuppermann BD.

Department of Ophthalmology, University of Minnesota, Stillwater, USA.
sslane@associatedeyecare.com

PURPOSE OF REVIEW: The function is described of the Implantable Miniature
Telescope, which is completing clinical development for bilateral end-stage
macular degeneration, and 6-month results of the Phase II/III IMT002 prospective,
multicenter study are presented. Multispecialty patient management and
implications of the study's findings are discussed. RECENT FINDINGS: No medical
treatments are currently available for bilateral end-stage age-related macular
degeneration (atrophic or disciform scar age-related macular degeneration). The
visual prosthetic device discussed in this update is implanted in the posterior
chamber to reduce the impact of the scotomata on the patient's central vision.
The goal of treatment is to improve the patient's ability to perform everyday
activities and participate in roles and hobbies that impact their quality of
life. Patients implanted with the device experienced clinically significant gains
in visual acuity and quality of life at 6 months. In total, 89% gained two or
more lines of best-corrected near or distance visual acuity. The device was
generally safe and well tolerated. The surgical technique is important to
minimize surgically related reduction in endothelial cell density. SUMMARY: This 
age-related macular degeneration visual prosthesis has been shown to improve
visual acuity and quality of life for the bilateral end-stage age-related macular
degeneration patient population that at present has no other acceptable options. 
Endothelial cell density from baseline to 6 and 12 months after device
implantation was reduced due to trauma from the surgical procedure, but was
compatible with a healthy cornea. Meticulous surgical technique and a
comprehensive, multispecialty approach to preoperative and postoperative patient 
management are essential for successful outcomes.

Publication Types: 
    Review

PMID: 16436930 [PubMed - indexed for MEDLINE]

1605: Expert Opin Investig Drugs. 2006 Feb;15(2):163-9.

Erratum in:
    Expert Opin Investig Drugs. 2006 May;15(5):573.

Anecortave acetate.

Bakri SJ, Kaiser PK.

Cole Eye Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Desk i3,
Cleveland, OH 44195, USA.

This manuscript reviews the pharmacotherapeutics of the novel, angiostatic
cortisene, anecortave acetate suspension, for the treatment of age-related
macular degeneration. The chemistry, pharmacokinetics and pharmacodynamics of
anecortave acetate are discussed, and the results of the multi-centre,
randomised, controlled clinical trials for the treatment of subfoveal choroidal
neovascularisation in age-related macular degeneration summarised. It also
discusses ongoing clinical trials involving anecortave acetate for dry and wet
age-related macular degeneration.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 16433595 [PubMed - indexed for MEDLINE]

1606: Invest Ophthalmol Vis Sci. 2006 Feb;47(2):729-37.

Cigarette smoke-related oxidants and the development of sub-RPE deposits in an
experimental animal model of dry AMD.

Espinosa-Heidmann DG, Suner IJ, Catanuto P, Hernandez EP, Marin-Castano ME,
Cousins SW.

Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami
School of Medicine, Miami, Florida, USA.

PURPOSE: Oxidative injury to the retinal pigment epithelium (RPE) has been
proposed to be an important injury stimulus relevant to the accumulation of
subretinal deposits in age-related macular degeneration (AMD). Cigarette smoking 
is a major risk factor for AMD, and cigarette smoke-related tar contains high
concentrations of a potent oxidant, hydroquinone (HQ). This study was an
investigation of the effects of cigarette smoke (CS) and HQ in the development of
sub-RPE deposits in an experimental mouse model. METHODS: Sixteen-month-old
C57BL/6 female mice were fed a high-fat diet (HFD) for 4.5 months. Mice were
divided into two major experimental groups, one to examine the effects of
cigarette smoke and one to study the effects of a defined cigarette smoke
component such as HQ. In the first group, mice eyes were exposed to blue-green
light (positive controls) or to whole cigarette smoke. A third group with no
intervention served as the negative control. In the second experimental group,
animals received a purified diet with HQ (0.8%) with low or high fat content for 
4.5 months. Mice in both groups were euthanatized at 4.5 months and eyes
processed for transmission electron microscopy. RESULTS: As previously
demonstrated by our laboratory and others, most mice fed an HFD without other
oxidant exposure demonstrated normal morphology or, in a few cases, small nodular
basal laminar deposits. Eyes of mice exposed to whole cigarette smoke or to HQ in
the food demonstrated a variable degree of basal laminar deposits and diffusely
thickened Bruch's membrane. The choriocapillaris endothelium was variably
hypertrophic. CONCLUSIONS: Exposure to cigarette smoke or the smoke-related redox
molecule, HQ, results in the formation of sub-RPE deposits, thickening of Bruch's
membrane, and accumulation of deposits within Bruch's membrane. Smoke-related
oxidants may be another oxidative injury stimulus to the choriocapillaris and
RPE, and may explain the association between cigarette smoking and early AMD.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16431974 [PubMed - indexed for MEDLINE]

1607: Invest Ophthalmol Vis Sci. 2006 Feb;47(2):536-40.

Complement factor H variant Y402H is a major risk determinant for geographic
atrophy and choroidal neovascularization in smokers and nonsmokers.

Sepp T, Khan JC, Thurlby DA, Shahid H, Clayton DG, Moore AT, Bird AC, Yates JR.

Department of Medical Genetics, University of Cambridge, Cambridge, United
Kingdom.

PURPOSE: The complement factor H (CFH) gene polymorphism Y402H (1277T-->C) has
been associated with susceptibility to age-related macular degeneration (AMD).
The purpose of this study was to confirm this association in a U.K. population,
to determine whether the association holds for both geographic atrophy (GA) and
choroidal neovascularization (CNV), and to investigate interactions with smoking.
METHODS: A case-control study was undertaken in 443 cases of AMD, with 262
spouses as control subjects. All subjects completed a health and lifestyle
questionnaire, had an ophthalmic assessment with fundus photography, and were
genotyped. RESULTS: The frequencies of the C allele and CC genotype were
significantly higher in cases than in controls. In comparison to the TT genotype,
the odds ratios for AMD associated with the CT and CC genotypes were 3.1 (CI
2.0-4.6) and 6.3 (CI 3.8-10.4), respectively. The results were similar in
subgroup analyses confined to cases with GA or CNV. The findings were also
similar for subgroup analyses restricted to subjects who had never smoked,
moderate smokers, or heavier smokers (>20 pack years of smoking). Heavier smokers
with the CC genotype may be particularly at risk. The frequency of the CC
genotype did not differ significantly between cases with and without a family
history of AMD. There was no evidence that genotype had any influence on age at
onset of disease. CONCLUSIONS: The CFH Y402H variant is strongly associated with 
both GA and CNV in the U.K. population. This association is similar in smokers
and nonsmokers. Heavier smokers with the CC genotype may be at particular risk.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16431947 [PubMed - indexed for MEDLINE]

1608: Invest Ophthalmol Vis Sci. 2006 Feb;47(2):528-35.

Development of a questionnaire to assess vision problems under low luminance in
age-related maculopathy.

Owsley C, McGwin G Jr, Scilley K, Kallies K.

Department of Ophthalmology, School of Medicine, University of Alabama at
Birmingham, AL 35294-0009, USA. owsley@uab.edu

PURPOSE: To develop a questionnaire for assessing self-reported visual problems
under low luminance and at night for use in studies on age-related maculopathy
(ARM). METHODS: The questionnaire was developed in three steps: (1) Content for
questionnaire items was identified through focus groups of older adults with ARM 
and those exhibiting normal retinal aging. The topic for discussion was "vision
at night and under low lighting." Discussion was audiotaped, transcribed, and
subjected to content analysis to identify problem categories expressed by
patients. (2) This content was used to develop a preliminary questionnaire
administered by telephone to persons with ARM or normal retinal aging.
Principal-components analysis identified groups of items that formed the
questionnaire's subscales that were evaluated for internal consistency, and an
item-reduction strategy was implemented to generate a briefer questionnaire. (3) 
Psychometric properties of the shortened Low-Luminance Questionnaire (LLQ) were
determined, including construct validity, criterion validity, and test-retest
reliability. RESULTS: The 32-item LLQ has six subscales (driving, extreme
lighting, mobility, emotional distress, general dim lighting, and peripheral
vision), all with good internal consistency (Cronbach alpha > or = 0.82). Scores 
on LLQ subscales correlated moderately with nearly all National Eye Institute
Visual Function Questionnaire (NEI VFQ)-25 subscales and decreased in value
(indicating more disability) for patients with increasing ARM disease severity.
Whereas rod-mediated parameters of dark adaptation were significantly associated 
with LLQ subscale scores (r = 0.19-0.43, all P < 0.03), cone-mediated parameters 
were not. Test-retest reliability ranged from 0.74 to 0.88 for all subscales (P <
0.0001), except for peripheral vision (0.46; P = 0.0003), which also exhibited a 
ceiling effect in almost half of the respondents. CONCLUSIONS: The 32-item LLQ,
derived from the content of focus group comments by persons with ARM, has good
construct validity, subscale scores related to rod-mediated visual function, and 
good test-retest reliability for five of six subscales. The LLQ may ultimately be
useful in patient-centered evaluation of the outcome of interventions to prevent 
ARM or to arrest progression of early disease.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16431946 [PubMed - indexed for MEDLINE]

1609: Br J Ophthalmol. 2006 Feb;90(2):198-201.

Impaired retinal autoregulation in small retinal arterioles before and after
focal laser treatment for diabetic maculopathy.

Jeppesen P, Bek T.

Department of Ophthalmology, Arhus University Hospital, Denmark. pj@dadlnet.dk

AIMS: To study the effect of an acute increase in the arterial blood pressure on 
the diameter response of retinal arterioles supplying areas with focal diabetic
macular oedema before and after laser photocoagulation, and control arterioles
supplying areas without oedema. METHODS: In 17 diabetic patients the diameter
response of arterioles after an increase in the arterial blood pressure induced
by isometric exercise was studied using the retinal vessel analyser (RVA). In
each patient a study arteriole supplying a focal area of macular oedema as well
as a control arteriole supplying a retinal area without retinopathy lesions was
selected, and the diameter response of these vessels was performed immediately
before, and 1 hour and 3 months after focal laser photocoagulation of the focal
oedema area. RESULTS: The diameter response was impaired in both study arterioles
and control arterioles before focal laser photocoagulation. The treatment induced
regression of the focal retinal oedema, but did not affect the diameter response 
in the arteriole supplying this area (p = 0.85). CONCLUSION: Impairment of the
diameter response in small arterioles from diabetic patients does not parallel
the regional distribution of retinopathy lesions. Other factors than disturbed
autoregulation are probably involved in generating flow disturbances and oedema
in diabetic maculopathy.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16424533 [PubMed - indexed for MEDLINE]

1610: Br J Ophthalmol. 2006 Feb;90(2):191-7.

Ultrahigh resolution optical coherence tomography in non-exudative age related
macular degeneration.

Pieroni CG, Witkin AJ, Ko TH, Fujimoto JG, Chan A, Schuman JS, Ishikawa H,
Reichel E, Duker JS.

New England Eye Center, Tufts-New England Medical Center, Tufts University, 750
Washington Street, Box 450, Boston, MA 02111, USA.

AIM: To describe the appearance of the non-exudative forms of age related macular
degeneration (AMD) as imaged by ultrahigh resolution optical coherence tomography
(UHR-OCT). METHODS: A UHR-OCT ophthalmic imaging system, which utilises a
femtosecond laser light source capable of approximately 3 mum axial resolution,
was employed to obtain retinal cross sectional images of patients with
non-exudative AMD. Observational studies of the resulting retinal images were
performed. RESULTS: 52 eyes of 42 patients with the clinical diagnosis of
non-exudative AMD were imaged using the UHR-OCT system. 47 of the 52 (90%) eyes
had the clinical diagnosis of drusen and/or retinal pigment epithelial (RPE)
changes. In these patients, three patterns of drusen were apparent on UHR-OCT:
(1) distinct RPE excrescences, (2) a saw toothed pattern of the RPE, and (3)
nodular drusen. On UHR-OCT, three eyes (6%) with a clinical diagnosis of
non-exudative AMD had evidence of fluid under the retina or RPE. Two of these
three patients had findings suspicious for subclinical choroidal
neovascularisation on UHR-OCT. CONCLUSION: With the increased resolution of
UHR-OCT compared to standard OCT, the involvement of the outer retinal layers are
more clearly defined. UHR-OCT may allow for the detection of early exudative
changes not visible clinically or by angiography.

Publication Types: 
    Case Reports
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, Non-P.H.S.

PMID: 16424532 [PubMed - indexed for MEDLINE]

1611: Br J Ophthalmol. 2006 Feb;90(2):158-61.

Long term results after transpupillary thermotherapy in eyes with occult
choroidal neovascularisation associated with age related macular degeneration: a 
prospective trial.

Stolba U, Krebs I, Lamar PD, Aggermann T, Gruber D, Binder S.

Department of Ophthalmology, Rudolf Foundation Hospital, Juchgasse 25, 1030
Vienna, Austria. ulrike.stolba@wienkav.at

AIM: To evaluate long term results after transpupillary thermotherapy (TTT) in
eyes with exudative age related macular degeneration. METHODS: In a prospective
clinical study eyes with occult or predominantly occult choroidal
neovascularisation and no pretreatment were scheduled to have a TTT with a power 
of 630 mW. Visual acuity for far and near distances as well as contrast
sensitivity were evaluated 6, 12, and 24 months postoperatively and statistically
analysed. RESULTS: 47 eyes fulfilled the inclusion criteria. Overall, 70% of the 
patients showed an improved (14%) or had unchanged (56%) ETDRS vision after 24
months. Reading vision was stabilised (51%) or better (5%) in 56% of the eyes at 
this time. However, the increasing number of eyes with severe deterioration
resulted in a significant decrease of both parameters over time (p = 0.0002 and p
= 0.0003, respectively). Contrast sensitivity could be maintained (70%) or
improved (9%) in 79%. Statistical analyses indicated a trend but no significant
decrease over time (p = 0.056). CONCLUSION: Although in the majority of patients 
far and near distance acuity could be stabilised on average a significant
decrease over time after TTT was observed. Statistical comparison of months 12
and 24 showed no further deterioration.

Publication Types: 
    Clinical Trial

PMID: 16424525 [PubMed - indexed for MEDLINE]

1612: J Cataract Refract Surg. 2005 Nov;31(11):2111-9.

Discriminative power of reading tests to differentiate visual impairment caused
by cataract and age-related macular degeneration.

Stifter E, Weghaupt H, Benesch T, Thaler A, Radner W.

Department of Ophthalmology, Medical University of Vienna, Vienna, Austria.

PURPOSE: To determine whether preoperative reading tests can be used for
differentiating visual impairments with regard to the diagnosis of cataract and
age-related macular degeneration (ARMD). SETTING: Department of Ophthalmology,
Medical University of Vienna, Vienna, Austria. METHODS: Reading performance of
patients with nuclear cataract, posterior subcapsular cataract, and ARMD were
evaluated with respect to reading acuity, maximum reading speed, and critical
print size; normal-sighted participants were tested as controls. A multivariate
discriminant analysis of the 4 groups (100 eyes of 100 participants) was
performed to evaluate how many patients could be correctly diagnosed by
significant differences in the tested reading parameters. Subsequently, the
nuclear cataract and posterior subcapsular cataract patients were compared with
cataract patients with coexisting ARMD. RESULTS: Distance visual acuity was
comparable in the nuclear cataract, posterior subcapsular cataract, and ARMD
groups (P>.05). Reading acuity was significantly reduced in posterior subcapsular
cataract and ARMD patients compared with nuclear cataract patients and controls
(P<.0001). No significant difference in maximum reading speed was found between
the nuclear cataract patients and the controls (P = .07), whereas the maximum
reading speed of the posterior subcapsular cataract and ARMD patients was
significantly reduced (P<.0001). In the discriminant analysis, it was possible to
assign the correct diagnosis to 72% of the nuclear cataract patients, 76% of the 
posterior subcapsular cataract patients, 72% of the ARMD patients, and 92% of the
controls. Comparing the reading performance of nuclear cataract and posterior
subcapsular cataract patients and cataract patients with coexisting ARMD showed
that reading performance was significantly impaired in the comorbid patients
(nuclear cataract and ARMD, P<.001; posterior subcapsular cataract and ARMD,
P<.05). CONCLUSION: The high discriminant accuracy shows that this standardized
reading test system is a valuable diagnostic tool for evaluating functional
visual impairments when distance visual acuity alone cannot elucidate the origin 
of functional impairment. Considering the significant discrepancies in reading
performance among patients with nuclear cataract, posterior subcapsular cataract,
and ARMD, reading tests may relevantly improve the clinical evaluation of
patients with visual loss, even of patients with ocular comorbidity.

Publication Types: 
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 16412924 [PubMed - indexed for MEDLINE]

1613: Graefes Arch Clin Exp Ophthalmol. 2006 Aug;244(8):963-71. Epub 2006 Jan 13.

Association between systemic arterial stiffness and age-related macular
degeneration.

Sato E, Feke GT, Appelbaum EY, Menke MN, Trempe CL, McMeel JW.

Schepens Retina Associates Foundation, 6th Floor, 1 Autumn Street, Boston, MA
02215, USA.

BACKGROUND: A number of epidemiological studies suggest that age-related macular 
degeneration (AMD) and cardiovascular disease share the same risk factors.
Systemic arterial stiffness is a clear indicator of cardiovascular disease. We
investigated whether there is an association between directly measured systemic
arterial stiffness and the presence of AMD. METHODS: We used a SphygmoCor 2000
system to noninvasively measure two indicators of the systemic arterial
stiffness, the arterial pulse wave velocity (PWV) and the central aortic blood
pressure waveform, from which the augmentation pressure is determined. We studied
50 patients with AMD (12 men, 38 women, aged 60 to 91 years, mean 77 years) and
11 age-matched control subjects (3 men, 8 women, aged 66 to 92 years, mean 75
years). All study subjects received a complete ophthalmic examination including
digital fundus photography. All of the patients with AMD were classified as stage
3 or worse in at least one eye according to the AREDS system. RESULTS: Pulse wave
velocity was significantly higher in the patients with AMD (8.2+/-1.1 m/s, mean
+/- SD) compared with controls (7.1+/-0.8 m/s, p=0.0025), indicating increased
arterial stiffness. There was no significant difference in PWV in AMD patients
with and without choroidal neovascularization. There was no association between
PWV and the presence of hypertension in either the patients or the controls. The 
central aortic augmentation pressure was significantly higher in the AMD patients
than in the controls (p=0.040), also indicating increased arterial stiffness.
CONCLUSIONS: Patients with AMD have increased systemic arterial stiffness
compared with age-matched controls. Treatments aimed at preventing or reversing
systemic arterial stiffness may also be effective in preventing the onset or
slowing the progression of AMD.

PMID: 16411106 [PubMed - indexed for MEDLINE]

1614: Graefes Arch Clin Exp Ophthalmol. 2006 Aug;244(8):972-7. Epub 2006 Jan 13.

Influence of photodynamic therapy for age related macular degeneration upon
subjective vision related quality of life.

Hewitt AW, Jeganathan VS, Kidd JE, Pesudovs K, Verma N.

Department of Ophthalmology, Royal Hobart Hospital, 7000, Tasmania, Australia.
hewitt.alex@gmail.com

BACKGROUND: Photodynamic therapy (PDT) has been used in the treatment of
choroidal neovascularisation secondary to age-related macular degeneration (AMD).
This study prospectively investigated patients' subjective change in visual
function following PDT as treatment for AMD. METHODS: Eighty-two consecutive
patients receiving PDT in Tasmania, Australia, between May and November 2003 were
recruited. In conjunction with a comprehensive clinical examination, the Visual
Function-14 (VF-14) questionnaire was administered. Final follow-up occurred
between February and March 2005. The VF-14 was scored by traditional summary
scoring and by Rasch analysis. RESULTS: Five of the 82 (6.1%) subjects recruited 
were excluded from analysis. PDT was performed on average 5.7+/-2.6 times per
patient. Raw VF-14 scores tended towards being significantly lower at follow-up
than at baseline (67.6+/-27.2 against 64.5+/-27.7; P=0.052), and did
significantly deteriorate using a collapsed Rasch analysis (P=0.0102). Following 
treatment, 38 (47.5%) eyes had lost three or more Snellen lines of best-corrected
visual acuity. CONCLUSION: Patients undergoing PDT typically report reasonable
visual function. In parallel with visual acuity, self-reported visual function
may deteriorate slightly after PDT for AMD, but not as much as reported in
untreated AMD.

PMID: 16411103 [PubMed - indexed for MEDLINE]

1615: Eye. 2006 Aug;20(8):867-72. Epub 2006 Jan 13.

The complement system and age-related macular degeneration.

Sivaprasad S, Chong NV.

Laser and Retinal Research Unit, King's College Hospital, Denmark Hill, London,
UK.

PURPOSE: Age-related macular degeneration (AMD) is the leading cause of blindness
in the developed world. There are increasing evidences to suggest the complement 
system may play a significant role on the pathogenesis of AMD. In this review, we
summarise the current research in this area. METHODS: Review of literature.
RESULTS: The complement system is a complex system with several activation
pathways. Complement factor H (CFH) polymorphisms has been associated with
increase risk of AMD. CFH is an inhibitor protein; the polymorphisms might cause 
uncontrolled activation by initiation events. CONCLUSION: Further studies on the 
molecular basis of the complement-mediated pathogenesis of AMD may offer novel
therapy to AMD.

PMID: 16410816 [PubMed - indexed for MEDLINE]

1616: Eye. 2007 Mar;21(3):387-94. Epub 2006 Jan 13.

Follow-up after intravitreal triamcinolone acetonide for exudative age-related
macular degeneration.

Jonas JB, Spandau UH, Kamppeter BA, Harder B.

Department of Ophthalmology, Faculty of Clinical Medicine Mannheim of the
University Heidelberg, Mannheim, Germany. Jost.Jonas@augen.ma.uni-heidelberg.de

PURPOSE: To report on the follow-up of patients who received an intravitreal
triamcinolone acetonide injection (IVTA) as treatment of exudative age-related
macular degeneration. METHODS: The clinical interventional case-series study
included 205 patients (222 eyes) with progressive exudative age-related macular
degeneration with subfoveal neovascularization who consecutively received an IVTA
of about 20 mg as only therapeutic procedure and for whom follow-up was at least 
3 months. Mean follow-up was 10.4+/-7.1 months (range, 3-35.7 months). RESULTS:
Visual acuity improved significantly (P<0.001) from baseline (0.90+/-0.45
logarithm of the minimum angle of resolution (LogMar)) to a mean minimum of
0.79+/-0.42 LogMar during follow-up. In 86 (38.7%) eyes and in 55 (24.8%) eyes,
best visual acuity increased by at least two and three Snellen lines,
respectively. Comparing the measurements at specific postinjection examination
dates showed that visual acuity measurements taken at 1, 2, and 3 months after
injection were not significantly different from the baseline value. Measurements 
taken at 6, 9, and 12 months after the injection were significantly (P<0.001)
lower than the measurements at baseline. Mean loss at 6 months was 1.4+/-3.8
Snellen lines, at 9 months, 2.5+/-4.6 lines, and at 12 months after the
injection, 2.6+/-4.0 lines. Intraocular pressure increased significantly
(P<0.001) during the first 6 months, and returned to baseline at 9 months after
injection. CONCLUSIONS: Single injection high-dosage IVTA did not show an
apparent benefit at 12 months after injection in patients with neovascular
age-related macular degeneration.

PMID: 16410809 [PubMed - indexed for MEDLINE]

1617: Ophthalmology. 2006 Feb;113(2):255-9. Epub 2006 Jan 10.

Comment in:
    Ophthalmology. 2006 Oct;113(10):1888-9; author reply 1889.

Apolipoprotein E gene and early age-related maculopathy: the Atherosclerosis Risk
in Communities Study.

Wong TY, Shankar A, Klein R, Bray MS, Couper DJ, Klein BE, Sharrett AR, Folsom
AR.

Centre for Eye Research Australia, University of Melbourne, Melbourne, Victoria, 
Australia. twong@unimelb.edu.au

OBJECTIVE: To examine the association between the apolipoprotein E (APOE) gene
and early age-related maculopathy (ARM) in middle-aged persons. DESIGN:
Population-based cross-sectional study. PARTICIPANTS: Participants from the
Atherosclerosis Risk in Communities Study (n = 10139; age range, 49-73 years).
METHODS: Retinal photography was performed on 1 randomly selected eye, and
grading for presence of ARM was carried out using a modification of the Wisconsin
ARM Grading System. Early ARM was defined as the presence of either soft drusen
alone, retinal pigment epithelial depigmentation alone, or a combination of soft 
drusen with increased retinal pigment and/or depigmentation. DNA extracted from
blood samples of participants were analyzed for common allelic variants of the
APOE gene (epsilon2, epsilon3, and epsilon4). MAIN OUTCOME MEASURES: Presence of 
early ARM on retinal photographs. RESULTS: The prevalence of early ARM was
similar in participants with different APOE genotypes: epsilon2/epsilon2 (5.9%), 
epsilon2/epsilon3 (5.2%), epsilon2/epsilon4 (3.2%), epsilon3/epsilon3 (5.2%),
epsilon3/epsilon4 (4.9%), and epsilon4/epsilon4 (4.1%). After controlling for
age, gender, race, cigarette smoking, and other factors, early ARM was not
associated with APOE genotypes, with an odds ratio (OR) of 1.35 (95% confidence
interval [CI], 0.54-3.38) for epsilon2/epsilon2 genotype, an OR of 1.06 (95% CI, 
0.80-1.40) for epsilon2/epsilon3 genotype, an OR of 0.63 (95% CI, 0.32-1.24) for 
epsilon2/epsilon4 genotype, an OR of 0.99 (95% CI, 0.80-1.24) for
epsilon3/epsilon4 genotype, and an OR of 0.88 (95% CI, 0.47-1.63) for
epsilon4/epsilon4 genotype, as compared with epsilon3/epsilon3 genotype
(reference). No associations were found for specific early ARM signs or in
analyses stratified by age, gender, race, or cigarette smoking status.
CONCLUSIONS: These data provide no evidence of a strong association between the
APOE gene and early ARM in middle-aged persons. This suggests that APOE is not
likely a major determinant of the early stages of ARM in younger people. However,
our study does not exclude the possibility of a weaker association or that APOE
may influence only the development of late ARM in older populations, as reported 
in other studies.

Publication Types: 
    Multicenter Study
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16406547 [PubMed - indexed for MEDLINE]

1618: Ophthalmology. 2006 Feb;113(2):294-301. Epub 2006 Jan 10.

Vitreous levels of pigment epithelium-derived factor and vascular endothelial
growth factor are related to diabetic macular edema.

Funatsu H, Yamashita H, Nakamura S, Mimura T, Eguchi S, Noma H, Hori S.

Department of Ophthalmology, Diabetes Center, Tokyo Women's Medical University,
Tokyo, Japan. tfunatsu@nifty.com

PURPOSE: To investigate whether vitreous levels of vascular endothelial growth
factor (VEGF) and pigment epithelium-derived factor (PEDF) are related to
diabetic macular edema (DME). DESIGN: Retrospective case-control study.
PARTICIPANTS: Thirty-six patients with DME, 6 diabetic patients without
retinopathy, and 13 patients with nondiabetic ocular disease. METHODS: After
vitreous fluid samples were obtained at vitreoretinal surgery, VEGF and PEDF
levels in the vitreous fluid were measured by enzyme-linked immunosorbent assay. 
MAIN OUTCOME MEASURES: Correlations between vascular permeability and the
vitreous fluid levels of VEGF and PEDF. RESULTS: The vitreous level of VEGF was
significantly higher in patients with DME than in nondiabetic patients and
diabetic patients without retinopathy (P<0.0001 and P<0.0001, respectively).
Conversely, the vitreous level of PEDF was significantly lower in patients with
DME than in nondiabetic patients and diabetic patients without retinopathy
(P<0.0001 and P<0.0001, respectively). The vitreous level of PEDF did not
correlate significantly with that of VEGF (P = 0.1806). The vitreous level of
VEGF was significantly higher in patients with hyperfluorescent DME than in those
with minimally fluorescent DME (P = 0.0022). Conversely, the vitreous PEDF level 
was significantly lower in patients with hyperfluorescent DME than in those with 
minimally fluorescent DME (P = 0.0172). Vitreous levels of VEGF and PEDF were
related to the retinal thickness at the central fovea (P<0.0001 and P = 0.0469,
respectively). CONCLUSIONS: Our retrospective study suggests that VEGF and PEDF
have an independent association with vascular permeability in the eye and on the 
DME, and we recommend that prospective validation of our findings be undertaken
to confirm these observations.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16406543 [PubMed - indexed for MEDLINE]

1619: Arch Ophthalmol. 2006 Jan;124(1):33-7.

3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitors and the presence of
age-related macular degeneration in the Cardiovascular Health Study.

McGwin G Jr, Modjarrad K, Hall TA, Xie A, Owsley C.

Department of Ophthalmology, School of Medicine, University of Alabama at
Birmingham, Suite 609, 700 S. 18th Street, Birmingham, AL 35294-0009, USA.
mcgwin@uab.edu

OBJECTIVE: To evaluate both the use of cholesterol-lowering medications as a
group and the use of statins specifically with regard to the risk of age-related 
macular degeneration (AMD). METHODS: A case-control study was conducted using
data from the Cardiovascular Health Study, a population-based prospective study
of adults enrolled from 4 communities in the United States in 1989 and 1990.
Individuals with AMD (cases) and those without AMD (controls) were compared with 
regard to their use of cholesterol-lowering medications and statins. RESULTS:
Nearly equal proportions of cases and controls used cholesterol-lowering
medications, both before adjustment (odds ratio, 0.92; 95% confidence interval,
0.70-1.21) and after adjustment for selected confounding variables (age, sex, and
race) (odds ratio, 1.35; 95% confidence interval, 0.98-1.87). Statin use was also
found to be similar among cases and controls (odds ratio, 0.98; 95% confidence
interval, 0.73-1.30). After controlling for the aforementioned 3 confounders
(odds ratio, 1.40; 95% confidence interval, 0.99-1.98), we noted a modest trend
for statin users to have an increased risk of AMD. CONCLUSION: The results
suggest that no association exists between having used cholesterol-lowering
medications and AMD. However, there was a suggestion that statin use might
increase the risk of AMD.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16401782 [PubMed - indexed for MEDLINE]

1620: Ann N Y Acad Sci. 2005 Dec;1057:384-92.

Effects of melatonin in age-related macular degeneration.

Yi C, Pan X, Yan H, Guo M, Pierpaoli W.

Department of Fundus Diseases, Zhongshan Ophthalmic Center, Sun Yat-Sen
University, 510060 Guangzhou, China. yichang@public.guangzhou.gd.cn

Age-related macular degeneration (AMD) is the leading cause of severe visual loss
in aged people. Melatonin has been shown to have the capacity to control eye
pigmentation and thereby regulate the amount of light reaching the
photoreceptors, to scavenge hydroxyradicals and to protect retinal pigment
epithelium (RPE) cells from oxidative damage. Therefore, it is reasonable to
think that the physiological decrease of melatonin in aged people may be an
important factor in RPE dysfunction, which is a well known cause for initiation
of AMD. Our purpose is to explore a new approach to prevent or treat AMD. We
began case control study with a follow-up of 6 to 24 months. One hundred patients
with AMD were diagnosed and 3 mg melatonin was given orally each night at bedtime
for at least 3 months. Both dry and wet forms of AMD were included. Fifty-five
patients were followed for more than 6 months. At 6 months of treatment, the
visual acuity had been kept stable in general. Though the follow up time is not
long, this result is already better than the otherwise estimated natural
course.1,2 The change of the fundus picture was remarkable. Only 8 eyes showed
more retinal bleeding and 6 eyes more retinal exudates. The majority had reduced 
pathologic macular changes. We conclude that the daily use of 3 mg melatonin
seems to protect the retina and to delay macular degeneration. No significant
side effects were observed.

Publication Types: 
    Clinical Trial

PMID: 16399908 [PubMed - indexed for MEDLINE]

1621: Eye. 2007 Mar;21(3):353-61. Epub 2006 Jan 6.

Relationship between foveal birefringence and visual acuity in neovascular
age-related macular degeneration.

Weber A, Elsner AE, Miura M, Kompa S, Cheney MC.

The Schepens Eye Research Institute and Harvard Medical School, Boston 47405,
USA.

PURPOSE: To investigate the relationship between visual acuity and foveal
birefringence in patients with neovascular age-related macular degeneration.
METHODS: In total, 40 patients with choroidal neovascularization underwent
macular imaging with scanning laser polarimetry. Bowtie patterns, typically seen 
in birefringence images of the macula, were evaluated and classified into three
categories: (1) regular bowtie present; (2) bowtie present, but disrupted; and
(3) no bowtie present. The relation of the bowtie appearance to the
best-corrected logMAR visual acuities was tested (ANOVA). RESULTS: Mean visual
acuity was best for the group that had regular bowties (mean logMAR=0.34) and
differed statistically significantly from the disrupted bowtie group and no
bowtie group (P=0.01 and 0.0007). Ages for the three groups did not differ
(P=0.31). CONCLUSIONS: Appearance of a regular bowtie indicates a substantially
intact Henle fibre layer with the potential for good visual function, despite the
presence of underlying pathology. Conversely, disruption or absence of a bowtie
may indicate severe damage to the photoreceptors, consistent with the finding of 
poorer visual acuity.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 16397620 [PubMed - indexed for MEDLINE]

1622: Acta Ophthalmol Scand. 2005 Dec;83(6):645-63.

Intravitreal triamcinolone acetonide for treatment of intraocular oedematous and 
neovascular diseases.

Jonas JB.

Department of Ophthalmology, Faculty of Clinical Medicine Mannheim,
Ruprecht-Karls-University of Heidelberg, Germany.
Jost.Jonas@augen.ma.uni-heidelberg.de

Intravitreal triamcinolone acetonide (IVTA) has increasingly been applied as
treatment for various intraocular neovascular and oedematous diseases. Comparing 
the various diseases with respect to effect and side-effects of the treatment,
the best response in terms of gain in visual acuity (VA) has been achieved for
intraretinal oedematous diseases such as diffuse diabetic macular oedema, branch 
retinal vein occlusion, central retinal vein occlusion and pseudophakic cystoid
macular oedema. In eyes with various types of non-infectious uveitis, including
acute or chronic sympathetic ophthalmia and Adamantiadis-Behcet's disease, VA
increased and the degree of intraocular inflammation decreased. Some studies have
suggested that intravitreal triamcinolone may be useful as angiostatic therapy in
eyes with iris neovascularization and proliferative ischaemic retinopathies.
Intravitreal triamcinolone may possibly be helpful as adjunct therapy for
exudative age-related macular degeneration (AMD), particularly in combination
with photodynamic therapy. In eyes with chronic, therapy-resistant ocular
hypotony, intravitreal triamcinolone can induce an increase in intraocular
pressure (IOP) and may stabilize the eye. The complications of intravitreal
triamcinolone therapy include: secondary ocular hypertension in about 40% of the 
eyes injected; medically uncontrollable high IOP leading to antiglaucomatous
surgery in about 1-2% of the eyes; posterior subcapsular cataract and nuclear
cataract leading to cataract surgery in about 15-20% of elderly patients within 1
year of injection; postoperative infectious endophthalmitis occurring at a rate
of about one per 1000; non-infectious endophthalmitis, perhaps due to a reaction 
to the solvent agent, and pseudo-endophthalmitis with triamcinolone acetonide
crystals appearing in the anterior chamber. Intravitreal triamcinolone injection 
can be combined with other intraocular surgeries, including cataract surgery,
particularly in eyes with iris neovascularization. Cataract surgery performed
some months after the injection does not show a markedly elevated complication
rate. The injection may be repeated if the resultant benefits decrease after the 
initial IVTA injection. In non-vitrectomized eyes, the duration of the effect and
side-effects of a single intravitreal injection of triamcinolone is about 6-9
months for a dosage of about 20 mg, and about 2-4 months for a dosage of 4 mg. So
far, it has remained unclear whether the solvent agent should be removed, and if 
so, how.

Publication Types: 
    Review

PMID: 16396641 [PubMed - indexed for MEDLINE]

1623: Drugs Today (Barc). 2005 Nov;41(11):703-9.

Pegaptanib for wet macular degeneration.

Fraunfelder FW.

National Registry of Drug-Induced Ocular Side Effects, Casey Eye Institute,
Oregon Health & Science University, Portland, Oregon 97239-4197, USA.
fraunfer@ohsu.edu

Pegaptanib sodium injection (Macugen, Eyetech Pharmaceuticals, Pfizer, New York, 
NY, USA) is a relatively new medication intended to treat the so-called wet
(neovascular ) form of age-related macular degeneration (AMD). This form of AMD
is characterized by the growth of unwanted new blood vessels into the macula
(angiogenesis). The aqueous solution containing pegaptanib is injected into the
vitreous of the eye, where it binds to the 165 amino acid isoform of vascular
endothelial growth factor (VEGF), a secreted protein that is thought to play a
major role in the pathologic angiogenesis that occurs in wet AMD. Neovascular AMD
is the leading cause of severe vision loss in people over age 60 in the United
States and other industrialized countries (1). Pegaptanib acts as a selective
VEGF antagonist through its molecular structure as an aptamer, a pegylated
modified oligonucleotide that adopts a three-dimensional configuration, enabling 
it to bind to extracellular VEGF (Fig. 1). Aptamers are macromolecules composed
of chemically synthesized single-stranded nucleic acids (either RNA or DNA) that 
bind with a high degree of selectivity and affinity when exposed to target
proteins. Pegaptanib binds VEGF165, and bound VEGF165 is not able to bind to the 
VEGF receptor, thereby negating its ability to cause angiogenesis and vascular
permeability. Other aptamers exist, as do other forms of treatment for AMD. To
date, however, no treatment for AMD has allowed for better vision after
treatment, with most surgical treatments leading to almost immediate loss of some
vision in the expectation of preventing more severe loss. Research in the field
of macular degeneration is advancing rapidly, and treatment with an aptamer such 
as pegaptanib is a viable option despite the possibility of adverse events.
Copyright (c) 2005 Prous Science. All rights reserved.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16395411 [PubMed - indexed for MEDLINE]

1624: Retina. 2006 Jan;26(1):58-64.

Comment in:
    Retina. 2006 Jul-Aug;26(6):714; author reply 715.

Occult with no classic choroidal neovascularization secondary to age-related
macular degeneration treated by intravitreal triamcinolone and photodynamic
therapy with verteporfin.

Nicolò M, Ghiglione D, Lai S, Nasciuti F, Cicinelli S, Calabria G.

Dipartimento di Neuroscienze, Oftalmologia e Genetica, Sezione di Clinica
Oculistica, Università di Genova, Italy. massimo.nicolo@hsanmartino.it

PURPOSE: To examine combined treatment with intravitreal triamcinolone acetonide 
(IVT) and photodynamic therapy (PDT) for occult with no classic choroidal
neovascularization (CNV) secondary to age-related macular degeneration. METHODS: 
In this prospective, interventional case series, 11 eyes of 10 consecutive
patients with occult with no classic CNV underwent a single injection (25 mg) of 
IVT followed 1 month later by PDT. Best-corrected visual acuity was measured by
Early Treatment Diabetic Retinopathy Study (ETDRS) protocol refraction. RESULTS: 
Median best-corrected visual acuity was 20/160, 20/80, 20/80, 20/50, and 20/80 at
baseline and 1, 3, 6, and 12 months, respectively. Best-corrected visual acuity
at baseline was statistically different (P < 0.05) than best-corrected visual
acuity at 1, 3, and 6 months. Of 11 eyes, 5 (45.5%), 7 (63.6%), 7 (63.6%), and 4 
(36.3%) had improved best-corrected visual acuity of at least 3 ETDRS lines at 1,
3, 6, and 12 months, respectively, while 6 (54.5%), 9 (81.8%), 10 (91%), and 8
(73%) had improved best-corrected visual acuity of at least 2 ETDRS lines at 1,
3, 6, and 12 months, respectively. Two eyes (18%) lost >3 lines at 12 months. One
eye had intraocular hypertension at 3 months and was treated with a combination
of topical antiglaucomatous drugs. One eye developed a dense cataract at the last
follow-up visit. No endophthalmitis, retinal detachment, or vitreous hemorrhage
developed. Fluorescein leakage and retinal thickness reduced significantly after 
treatment. CONCLUSIONS: Improvement of best-corrected visual acuity and lack of
fluorescein leakage suggest combination treatment with IVT and PDT for occult
with no classic CNV merits further investigation.

PMID: 16395140 [PubMed - indexed for MEDLINE]

1625: Retina. 2006 Jan;26(1):44-8.

Macular thickness mapping in exudative age-related macular degeneration.

Shakoor A, Shahidi M, Blair NP, Gieser JP, Zelkha R.

Department of Ophthalmology and Visual Sciences, University of Illinois at
Chicago, 60612, USA.

PURPOSE: To report the feasibility of retinal thickness mapping for evaluating
thickness differences in retinal areas with and without leakage shown by
fluorescein angiography for patients who have age-related macular degeneration
with choroidal neovascularization. METHODS: A custom-built version of the retinal
thickness analyzer was used for thickness mapping. Retinal thickness was defined 
as the separation between vitreoretinal and pigment epithelium-choroid
interfaces. Imaging was performed in 1 eye of 10 patients with the clinical
diagnoses of age-related macular degeneration and choroidal neovascularization.
Patients either had never undergone photodynamic therapy at the time of
measurement (untreated) or had received one or more photodynamic therapy
treatments (treated). Average retinal thicknesses in selected areas with and
without the presence of leakage shown by fluorescein angiography were calculated 
and compared statistically. RESULTS: Retinal thickness (mean +/- SD) in areas
with leakage (315 +/- 54 microm) was significantly greater than that in areas
without leakage (280 +/- 28 microm) (P = 0.03). In untreated patients, areas with
leakage (345 +/- 45 microm) were significantly thicker than areas without leakage
(289 +/- 23 microm) (P = 0.02). In treated patients, retinal thickness in areas
with leakage (271 +/- 33 microm) and without leakage (267 +/- 34 microm) was
similar. CONCLUSION: Retinal thickness mapping may prove to be useful as an
adjunct to fluorescein angiography to monitor choroidal neovascularization and
its treatment.

Publication Types: 
    Research Support, U.S. Gov't, Non-P.H.S.
    Research Support, U.S. Gov't, P.H.S.

PMID: 16395138 [PubMed - indexed for MEDLINE]

1626: Retina. 2006 Jan;26(1):14-20.

Diurnal variation in clinically significant diabetic macular edema measured by
the Stratus OCT.

Polito A, Del Borrello M, Polini G, Furlan F, Isola M, Bandello F.

Department of Ophthalmology, University of Udine, Italy.

PURPOSE: To investigate diurnal variation in clinically significant macular edema
(CSME) using the Stratus OCT (Carl Zeiss Meditec). METHODS: Fifteen eyes of 15
diabetic patients with CSME and 10 healthy subjects (controls) underwent four
optical coherence tomography (OCT) measurements of macular thickness with the
fast macular thickness mapping protocol of the Stratus OCT at 9 am, 12 pm, 3 pm, 
and 6 pm. Early Treatment Diabetic Retinopathy Study visual acuity and refraction
data were also collected at each time. Retinal thickness measurements from each
of the nine macular Early Treatment Diabetic Retinopathy Study areas of the
retina map, visual acuity, and refraction were plotted over time. RESULTS: Mean
retinal thickness remained unchanged in all retinal sectors over the course of
the day for the controls and the 6 diabetic patients with a baseline foveal
thickness of <300 mum, and it significantly decreased in 7 of the 9 retinal
sectors for the 9 diabetic patients with a baseline foveal thickness of > or =300
microm (ANOVA model for repeated measures). In these patients, the mean initial
foveal thickening +/- SD of 211 +/- 104 microm was reduced by an average of 6.1%,
15.2%, and 21.2% at 12 pm, 3 pm, and 6 pm, respectively. Two of these nine
patients also had an increase in visual acuity without change in refraction.
There were no changes in refractive errors over the course of the study in the
two groups. A positive correlation between initial central thickening and
decrease in thickness was found (r = 0.732; P = 0.002). CONCLUSION: This study
suggests that macular thickening, as measured by the Stratus OCT, may
spontaneously decrease in some patients with more severe CSME over the course of 
the day, and it confirms previous findings. However, in our study, the entity of 
this decline was relatively small and not relevant from a clinical standpoint.

PMID: 16395133 [PubMed - indexed for MEDLINE]

1627: Retina. 2006 Jan;26(1):5-13.

Comment in:
    Retina. 2008 Jan;28(1):187-8; author reply 188-9.

Pars plana vitrectomy with and without peeling of the inner limiting membrane for
diabetic macular edema.

Patel JI, Hykin PG, Schadt M, Luong V, Fitzke F, Gregor ZJ.

Moorfields Eye Hospital, London, UK.

PURPOSE: A prospective, comparative, nonrandomized study to evaluate the efficacy
of pars plana vitrectomy (PPV) with and without inner limiting membrane (ILM)
peeling for persistent diffuse clinically significant macular edema. METHODS:
Eighteen patients with persistent diffuse clinically significant macular edema
despite laser photocoagulation were recruited for the study. Clinical assessment 
included determination of best-corrected visual acuity, fundus fluorescein
angiography, optical coherence tomography, and perifoveal cone function testing. 
Eight patients underwent PPV with elevation and removal of the posterior hyaloid 
alone, and 10 patients underwent vitrectomy and ILM peeling. The follow-up was 12
months. RESULTS: Patients with ILM peeling had improvement in foveal thickness (P
= 0.07) and significant improvement in the macular volume (P = 0.039) 12 months
after surgery but did not have significant improvement in Early Treatment
Diabetic Retinopathy Study vision or perifoveal cone function. There was no
significant difference in outcome parameters between the no peeling group and the
ILM peeling group. CONCLUSIONS: In this prospective, comparative study of PPV
with and without ILM peeling for diffuse clinically significant macular edema,
structural improvement was seen but with limited visual improvement after ILM
peeling.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 16395132 [PubMed - indexed for MEDLINE]

1628: Retina. 2006 Jan;26(1):1-4.

Could blue light-blocking lenses decrease the risk of age-related macular
degeneration?

Glazer-Hockstein C, Dunaief JL.

Epidemiologic and experimental evidence suggests that blue light-blocking lenses 
could theoretically benefit patients with age-related macular degeneration.
Clinical trials are needed to determine the effect of yellow lenses in preventing
the progression of age-related macular degeneration.

Publication Types: 
    Editorial

PMID: 16395131 [PubMed - indexed for MEDLINE]

1629: Can J Ophthalmol. 2005 Oct;40(5):573-84.

The use of subretinal triamcinolone acetonide in the management of neovascular
age-related macular degeneration: a pilot study.

Kertes PJ, Coupland SG.

University of Ottawa Eye Institute, Ottawa, Ont. peter.kertes@sw.ca

BACKGROUND: We conducted this study to investigate the toxicity and efficacy of
pars plana vitrectomy combined with a single dose of sub-retinally administered
triamcinolone acetonide (4 mg) in patients with subfoveal choroidal neovascular
membranes secondary to age-related macular degeneration (AMD). METHODS: The
important eligibility criteria included eyes with recent and progressive onset of
decreased vision (<or= 20/400) secondary to active subfoveal choroidal
neovascularization secondary to AMD demonstrable on fluorescein angiography, in
which subretinal hemorrhage accounted for < 25% of the area of the choroidal
neovascular complex. Eligible patients were offered vitrectomy surgery combined
with subretinal injection of 0.1 mL of triamcinolone acetonide (40 mg/mL)
followed by air-fluid exchange. Two eyes of 2 patients were enrolled and followed
for 28 and 35 months with regular and serial complete ophthalmologic
examinations, fluorescein and indocyanine green videoangiography, and multifocal 
electro-retinography. The primary outcome measures were best-corrected visual
acuity, changes in the fluorescein angiographic area and in the greatest linear
dimension of leakage of the choroidal neovascular complex, and changes in
amplitude and latency of the multifocal electroretinogram (ERG). RESULTS: Patient
1 sustained a limited subretinal hemorrhage intraoperatively that cleared
spontaneously over approximately 3 months, as well as a rise in intraocular
pressure that required the use of 2 topical medications to control. Patient 2
demonstrated progression of his nuclear sclerosis and posterior subcapsular lens 
changes over the 35 months of follow-up. Best-corrected visual acuity improved
from 20/400 to 20/200 in patient 1 and improved from counting fingers to 20/320
in patient 2. For patient 1, the area of the neovascular complex increased from
4.5 mm2 at baseline to 7.2 mm2 at the 6-month follow-up; for patient 2, this
increase was from 6.2 mm2 to 8.4 mm2. Over the same interval, the greatest linear
dimension increased from 3.8 mm to 4.8 mm for patient 1 and from 4.1 mm to 4.8 mm
for patient 2. With respect to the multifocal ERG, the response density increased
in the first 4 months for patient 1 and declined marginally thereafter. For
patient 2, the electro-retinal response density function was stabilized for a
5-month period but declined and stabilized thereafter. INTERPRETATION: Our
results from this pilot study suggest that vitrectomy combined with subretinal
injections of 0.1 mL of triamcinolone acetonide (40 mg/mL) and air-fluid exchange
is easily accomplished. Although some complications were encountered, these did
not appear to be prohibitive. A salutary effect was clearly demonstrated, not
unlike the course seen with photodynamic therapy. Further study, perhaps in
combination with other antiangiogenic agents, is warranted.

Publication Types: 
    Clinical Trial

PMID: 16391620 [PubMed - indexed for MEDLINE]

1630: Scand J Occup Ther. 2005 Mar;12(1):10-7.

Assistive devices in activities of daily living used by persons with age-related 
macular degeneration: a population study of 85-year-olds living at home.

Dahlin Ivanoff S, Sonn U.

Institute of Occupational Therapy and Physiotherapy, Sahlgrenska Academy at
Göteborg University, Göteborg, Sweden. sydi@fhs.gu.se

The purpose of this study was to investigate the overall use of assistive devices
among persons with age-related macular degeneration (ARMD) and how it is related 
to dependence in daily activities. This was a retrospective, descriptive,
cross-sectional population study of 85-year-olds. The most common category of
assistive devices was bathing devices followed by mobility devices. The overall
use of assistive devices was 82%, and around 80% of the device users were
independent in activities of daily living. They were multiple device users (57%) 
and used more mobility devices and personal assistance in mobility. In
conclusion, the ARMD group comprises very frequent users of assistive devices and
uses assistive devices to remain independent. This implies that health services
should provide assistive devices at an early stage in the disablement process to 
avoid the development of dependence and should consider the likelihood of
multiple health problems when assessing the needs of assistive devices among
persons with ARMD.

PMID: 16389994 [PubMed - indexed for MEDLINE]

1631: Am J Ophthalmol. 2006 Jan;141(1):201-3.

Evaluation of plasma homocysteine and risk of age-related macular degeneration.

Seddon JM, Gensler G, Klein ML, Milton RC.

Epidemiology Unit, Massachusetts Eye and Ear Infirmary, 243 Charles Street,
Boston, MA 02114, USA. Johanna_Seddon@meei.harvard.edu

PURPOSE: To assess the relationship between plasma levels of homocysteine and
age-related macular degeneration (AMD). DESIGN: Cross-sectional, case-control
study. METHODS: Fasting plasma homocysteine levels were measured at two centers
in 934 individuals who were participating in an ancillary study of the
Age-Related Eye Disease Study. There were 547 cases and 387 control subjects, who
were determined by fundus photography. Conditional logistic regression analyses
were conducted to assess the association of homocysteine with AMD. RESULTS:
Median values of homocysteine were higher among advanced AMD cases (9.51 mmol/l) 
compared with persons with no AMD (8.81 mmol/l; P = .01). Values of >12 mmol/l vs
< or =12 mmol/l were also associated with an increased risk of AMD (P = .023),
when controlled for other covariates. CONCLUSION: Results are consistent with a
possible small, independent association between higher homocysteine levels and
AMD. Homocysteine may be a modifiable risk factor for AMD.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16387004 [PubMed - indexed for MEDLINE]

1632: Am J Ophthalmol. 2006 Jan;141(1):200-1.

Short-term intraocular pressure trends following intravitreal pegaptanib
(Macugen) injection.

Hariprasad SM, Shah GK, Blinder KJ.

Department of Ophthalmology and Visual Science, University of Chicago, Chicago,
Illinois, USA.

PURPOSE: To report the changes and trends in intraocular pressures (IOP)
following intravitreal injection of Pegaptanib (Macugen) for the treatment of
exudative age-related macular degeneration. DESIGN: Retrospective chart review.
METHODS: Review of 79 patients who underwent 122 consecutive Pegaptanib
injections. Analysis of the short-term effect of Pegaptanib injections on IOP was
performed. RESULTS: Baseline mean IOP was 15.73 +/- 3.41 mm Hg (mean +/- standard
deviation) with a range of 9 to 27 mm Hg. Postinjection mean IOP was 24.47 +/-
6.29 mm Hg with a range of 8 to 36 mm Hg. Mean IOP change from baseline to
roughly 30 minutes after Pegaptanib injection was 8.74 +/- 7.23 mm Hg. At the 5- 
to 7-day follow-up visit, IOP had normalized. CONCLUSIONS: Pegaptanib injection
in this limited series seems to be safe from an IOP standpoint in the short-term.
IOP monitoring postinjection may not be necessary.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16387003 [PubMed - indexed for MEDLINE]

1633: Am J Ophthalmol. 2006 Jan;141(1):193-4.

Vitamin E in the treatment of uveitis-associated macular edema.

Nussenblatt RB, Kim J, Thompson DJ, Davis MD, Chew E, Ferris FL, Buggage R.

Laboratory of Immunology, National Eye Institute, National Institutes of Health, 
Building 10, Rm. 10S219, 10 Center Drive, Bethesda, MD 20892, USA.
drbob@nei.nih.gov

PURPOSE: To investigate whether high-dose alpha-tocopherol (vitamin E) could
reduce vision loss and retinal thickening associated with uveitis-associated
cystoid macular edema. DESIGN: A double-masked, randomized study. METHODS:
Uveitis patients with macular edema seen at the NIH were randomized and received 
either 1600 IU/day of vitamin E or placebo for 4 months. Visual acuity and
retinal thickening were collected for the efficacy and the safety of the high
dose of vitamin E. RESULTS: Changes in visual acuity and retinal thickening.
CONCLUSIONS: Four-month oral supplementation with 1600 IU/d of vitamin E had no
apparent effect on uveitis-associated macular edema or visual acuity in this
small study.

Publication Types: 
    Randomized Controlled Trial
    Research Support, N.I.H., Intramural

PMID: 16386999 [PubMed - indexed for MEDLINE]

1634: Am J Ophthalmol. 2006 Jan;141(1):93-104.

Clinicopathologic studies of eyes that were obtained postmortem from four
patients who were enrolled in the submacular surgery trials: SST Report No. 16.

Grossniklaus HE, Wilson DJ, Bressler SB, Bressler NM, Toth CA, Green WR, Miskala 
P.

Department of Ophthalmology, Emory University School of Medicine, 428 Emory Eye
Center, 1365 Clifton Road, Atlanta, GA 30322, USA. ophtheg@emory.edu

PURPOSE: To compare the fundus photographic and fluorescein angiographic features
with the histologic findings in eyes from patients enrolled in the Submacular
Surgery Trials (SST). DESIGN: Clinical trials with clinicopathologic correlation.
METHODS: Eyes that were obtained postmortem from patients who participated in the
donor program were processed at the SST Pathology Center and examined
histologically; the macular regions were reconstructed topographically with
two-dimensional cartography. Fundus photographic and fluorescein angiographic
features were correlated with the histopathologic and two-dimensional
cartographic findings. RESULTS: The eyes from two patients each from the SST
Group N and B Trials were studied. The study eye of one patient that had been
assigned randomly to observation contained a subretinal fibrovascular scar that
corresponded to a histologic growth pattern of a thick, collagenized subretinal
component combined with a subretinal pigment epithelium (subRPE) fibrovascular
component. The study eye of the other patient who was assigned randomly to
observation showed angiographic occult without classic choroidal
neovascularization (CNV) that corresponded to subRPE CNV. The study eye of one
patient who was assigned randomly to surgery showed an angiographic surgical
defect without CNV and histologic retinal pigment epithelium (RPE)/photoreceptor 
atrophy that was associated with a thin layer of subRPE CNV. The study eye of the
other patient who was assigned randomly to surgery showed an angiographic
surgical defect with classic CNV that corresponded to histologic
RPE/photoreceptor atrophy that was associated with subRPE fibrovascular tissue
and subretinal CNV. Both surgical eyes contained linear breaks in Bruch's
membrane that included chevron-shaped breaks. CONCLUSION: Four SST study eyes
that were examined postmortem contained CNV. The angiographic patterns and
histologic features of the CNV support previous correlations of surgically
excised CNV.

Publication Types: 
    Case Reports
    Research Support, N.I.H., Extramural

PMID: 16386982 [PubMed - indexed for MEDLINE]

1635: Am J Ophthalmol. 2006 Jan;141(1):79-87.

Smoking, alcohol intake, estrogen use, and age-related macular degeneration in
Latinos: the Los Angeles Latino Eye Study.

Fraser-Bell S, Wu J, Klein R, Azen SP, Varma R.

Department of Preventive Medicine, Keck School of Medicine, University of
Southern California, 1450 San Pablo Street, Los Angeles, CA 90033, USA.

PURPOSE: To assess the association between smoking, alcohol intake, estrogen use,
and both early age-related macular degeneration (AMD) (soft indistinct drusen,
retinal pigment abnormalities) and advanced AMD (exudative AMD, geographic
atrophy) in the Latino community. DESIGN: Population-based, cross-sectional
study. METHODS: Complete ophthalmic examination included stereoscopic macular
photographs graded with a modified Wisconsin Age-related Maculopathy Grading
System. A history of smoking, alcohol intake, and exogenous estrogen use was
obtained by interview. Logistic regression was performed, and odds ratios (OR)
were calculated with each AMD lesion as a dependent variable. RESULTS: There were
5875 participants (92.4%) with gradable photographs. Having ever smoked was
associated with a higher risk of having advanced AMD (OR, 2.4). Heavy consumption
of alcohol (>5 drinks per session) was significantly associated with a greater
risk of having exudative AMD (OR, 5.8) and geographic atrophy (OR, 12.7) Beer
drinking was associated with a higher risk of having advanced AMD (OR, 2.9),
whereas wine drinking appeared to be protective for increased retinal pigment
(OR, 0.7). Exogenous estrogen use also appeared to be protective from soft
indistinct drusen (OR, 0.5) and increased retinal pigment (OR, 0.6), but power
was limited in the assessment of its association with advanced AMD. CONCLUSION:
Smoking and heavy alcohol consumption, particularly beer, was associated with a
greater risk of having advanced AMD; exogenous estrogen use appeared to have a
weak protective effect in Latino participants. Similar modifiable risk factors
have been identified previously in non-Hispanic white patients, which suggests
that common pathogenic mechanisms may be associated with AMD in persons of
different ethnicities.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16386980 [PubMed - indexed for MEDLINE]

1636: Am J Ophthalmol. 2006 Jan;141(1):31-34.

Comment in:
    Am J Ophthalmol. 2006 Jan;141(1):145-6.    Am J Ophthalmol. 2006 Oct;142(4):710; author reply 710-1.

Retinal blood flow and macular edema after radial optic neurotomy for central
retinal vein occlusion.

Horio N, Horiguchi M.

Department of Ophthalmology, Fujita Health University School of Medicine, 1-98
Toyoake, Aichi 470-1192, Japan. naoichi@fujita-hu.ac.jp

PURPOSE: To determine the effect of radial optic neurotomy (RON) on retinal blood
flow (RBF) and macular edema in eyes with a central retinal vein occlusion.
DESIGN: Prospective interventional study. METHODS: Seven eyes of seven patients
with central retinal vein occlusion underwent RON and vitrectomy and were
followed for at least 6 months. The RBF was calculated from dye dilution curves
of video fluorescein angiograms. The foveal thickness was determined by optical
coherence tomography. RESULTS: At 1 week after surgery, the RBF was significantly
reduced from 28.5 +/- 5.4 to 21.1 +/- 6.6 pixel(2)/s (P < .01). At 6 months after
surgery, the RBF (26.0 +/- 7.7 pixel(2)/s) was not significantly different from
the preoperative RBF, although chorioretinal anastomoses were found in all seven 
eyes. The foveal thickness was significantly decreased from 711 +/- 271 to 488
+/- 182 mum (P = .03). The postoperative visual acuity was better than the
preoperative visual acuity by two or more lines in three out of seven eyes, and
was worse in two eyes. CONCLUSIONS: Neither RON nor chorioretinal anastomoses
improved the RBF but macular edema was improved. These findings suggest that
removal of the vitreous could reduce macular edema as in diabetic macular edema. 
However, we cannot exclude the possibility that the changes represent the natural
course of this disease.

PMID: 16386973 [PubMed - indexed for MEDLINE]

1637: Invest Ophthalmol Vis Sci. 2006 Jan;47(1):377-85.

Ocular changes after photodynamic therapy.

Tzekov R, Lin T, Zhang KM, Jackson B, Oyejide A, Orilla W, Kulkarni AD,
Kuppermann BD, Wheeler L, Burke J.

Department of Biological Sciences, Allergan Inc., Irvine, California 92612, USA. 
tzekov_radouil@allergan.com

PURPOSE: The aim of this study was to identify the changes in the primate visual 
system after a single session of photodynamic therapy (PDT) in an intact nonhuman
primate retina. METHODS: As part of a larger study, PDT (wavelength 689 nm, 50
J/cm2, 600 mW/cm2, 83 seconds, 4-mm spot size) with verteporfin (6 mg/m2
intravenous infusion) was performed in one eye each of two cynomolgus monkeys.
Fundus photography, fluorescein angiography (FA), indocyanine green angiography
(ICG), optical coherence tomography (OCT), and multifocal electroretinography
(mfERG) were performed at baseline and 12 time points (1-283 days) after PDT. In 
addition, retinal histopathologic findings were evaluated at 9 months. RESULTS:
Various morphologic changes, including whitening of the treated area, RPE
proliferation, closure of the choroidal vasculature, and subretinal edema
(followed by foveolar thinning) were observed. Most of the changes persisted and 
were detectable in histopathologic evaluation at 9 months. Reductions of the
mfERG amplitude, followed by varying degrees of recovery from the treated and the
border regions, were observed. This was accompanied by progressive delay of P1
peak time up to 3 months after treatment, followed by complete recovery at 9
months. In addition, the nontreated area showed amplitude and timing mfERG
deficits, which underwent gradual (but not complete) recovery. CONCLUSIONS: In a 
primate model, under standard clinical parameters, a single PDT treatment
resulted in various dynamic morphologic and functional retinal changes detectable
for up to 9 months after treatment. The significance of the observed changes and 
possible ways of pharmacologic interference with PDT adverse effects are
discussed.

PMID: 16384988 [PubMed - indexed for MEDLINE]

1638: Invest Ophthalmol Vis Sci. 2006 Jan;47(1):371-6.

Influence of treatment parameters on selectivity of verteporfin therapy.

Michels S, Hansmann F, Geitzenauer W, Schmidt-Erfurth U.

University Eye Hospital Vienna, Vienna, Austria. stephan.michels@meduniwien.ac.at

PURPOSE: To improve selectivity of verteporfin therapy (PDT) in neovascular
age-related macular degeneration (AMD) using modified treatment parameters.
METHODS: Nineteen consecutive patients with predominantly classic choroidal
neovascularization (CNV) in AMD were treated with 6 mg/m2 verteporfin given as
bolus infusion. Patients received PDT with a fluence of either 25 or 50 J/cm2.
Choroidal perfusion changes were evaluated by indocyanine green angiography
(ICGA) at baseline, day 1, week 1, week 4, and month 3. Secondary outcomes were
CNV closure rate and therapy-induced leakage documented by fluorescein
angiography (FA). The safety of the treatment was assessed with ETDRS visual
acuity. RESULTS: Complete CNV closure was achieved in all patients at day 1.
Choroidal hypoperfusion was minimal in eyes treated with a reduced fluence of 25 
J/cm2. Most patients treated with 50 J/cm2 showed significant choriocapillary
nonperfusion at week 1, lasting as long as 3 months. A transient PDT-induced
increase in leakage area in FA at day 1 was found to be more extensive in the
50-J/cm2 group. CONCLUSIONS: Bolus administration of verteporfin combined with a 
reduced light dose achieved improved selectivity of photodynamic effects,
avoiding collateral alteration of the physiologic choroid while obtaining
complete CNV closure. An increased selectivity with decreased effect on the
surrounding choroid should be of advantage in verteporfin monotherapy as well as 
in combination strategies.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16384987 [PubMed - indexed for MEDLINE]

1639: Invest Ophthalmol Vis Sci. 2006 Jan;47(1):329-35.

Functional candidate genes in age-related macular degeneration: significant
association with VEGF, VLDLR, and LRP6.

Haines JL, Schnetz-Boutaud N, Schmidt S, Scott WK, Agarwal A, Postel EA, Olson L,
Kenealy SJ, Hauser M, Gilbert JR, Pericak-Vance MA.

Center for Human Genetics Research, Vanderbilt University Medical Center,
Nashville, TN 37232, USA. jonathan@chgr.mc.vanderbilt.edu

PURPOSE: Age-related macular degeneration (AMD) is a retinal degenerative disease
that is the leading cause of blindness worldwide for individuals over the age of 
60. Although the etiology of AMD remains largely unknown, numerous studies have
suggested that both genes and environmental risk factors significantly influence 
the risk of developing AMD. Identification of the underlying genes has been
difficult, with both genomic screen (locational) and candidate gene (functional) 
approaches being used. The present study tested candidate genes for association
with AMD. METHODS: Eight genes (alpha-2-macroglobulin [A2M], creatine kinase
[CKB], angiotensin-converting enzyme [DCP1], interleukin-1alpha [IL1A],
low-density lipoprotein receptor-related protein 6 [LRP6], microsomal
glutathione-S-transferase 1 [MGST1], vascular entothelial growth factor [VEGF],
and very low density lipoprotein receptor [VLDLR]) were tested for genetic
linkage and allelic association, using two independent datasets: a family-based
association dataset including 162 families and an independent case-control
dataset with 399 cases and 159 fully evaluated controls. RESULTS: Test results
suggested that genetic variation in five of these genes (IL1A, CKB, A2M, MGST1,
and DCP1) is unlikely to explain a significant fraction of the risk of developing
AMD in this population. LRP6 showed evidence both for linkage (heterogeneity lod 
[HLOD] = 1.14) in the family-based dataset and for association (P = 0.004) in the
case-control dataset. VEGF showed evidence of linkage (HLOD = 1.32) and
demonstrated significant independent allelic association in both the family-based
(P = 0.001) and case-control (P = 0.02) datasets. VLDLR showed evidence of
association in both the family based (P = 0.03) and case-control (P = 0.01)
datasets. CONCLUSIONS: These data suggest that LRP6, VEGF, and VLDLR may play a
role in the risk of developing AMD.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 16384981 [PubMed - indexed for MEDLINE]

1640: Invest Ophthalmol Vis Sci. 2006 Jan;47(1):48-54.

H244R VSX1 is associated with selective cone ON bipolar cell dysfunction and
macular degeneration in a PPCD family.

Valleix S, Nedelec B, Rigaudiere F, Dighiero P, Pouliquen Y, Renard G, Le
Gargasson JF, Delpech M.

Laboratoire de Biochimie et Génétique Moléculaire, Hôpital Cochin, Paris, France.
sophie.valleix@cch.ap-hop-paris.fr

PURPOSE: To elucidate the retinal dysfunction and the molecular basis of
posterior polymorphous corneal dystrophy (PPCD) associated with macular
dystrophy, both inherited in a dominant manner through a three-generation family.
METHODS: Ophthalmologic examinations including slit lamp examination, visual
acuity tests, fundus visualization by scanning laser ophthalmoscopy, fluorescein 
angiography, color vision tests, electro-oculography, photopic and scotopic
electroretinography (ERG) according to the International Society for Clinical
Electrophysiology of Vision (ISCEV) protocols, and oscillatory potential (OP)
recordings were conducted on affected family members. Corneal button from one
affected patient was examined by transmission electron microscopy. All exons and 
intron-exon boundaries of the VSX1 and the COL8A2 genes were amplified by
polymerase chain reaction and sequenced. RESULTS: The presence of endothelial
cells that have epithelial-like features with multiple layers, desmosomal
junctions, and microvillous projections supports the diagnosis of PPCD. Sequence 
analysis indicated that the H244R variant in the VSX1 segregated with corneal and
macular disease phenotypes in this family. Electrophysiologic studies indicated
normal scotopic ERG findings, decreased amplitude of the photopic b-wave,
photopic OP2 and OP3 barely recordable with a preserved OP4 amplitude, and
variably decreased 30-Hz flicker amplitude. CONCLUSIONS: The human VSX1 is
required for cone ON bipolar cell function but not for rod and cone OFF bipolar
cells, giving a unique example of such a selective heritable retinal defect in
humans. Furthermore, the authors provide the first clinical support for a new
alternative role of VSX1 in cone biology, probably similar to that proposed for
its goldfish ortholog during retinal differentiation.

PMID: 16384943 [PubMed - indexed for MEDLINE]

1641: JAMA. 2005 Dec 28;294(24):3101-7.

Dietary intake of antioxidants and risk of age-related macular degeneration.

van Leeuwen R, Boekhoorn S, Vingerling JR, Witteman JC, Klaver CC, Hofman A, de
Jong PT.

Department of Epidemiology, Erasmus Medical Centre, Rotterdam, The Netherlands;

CONTEXT: Age-related macular degeneration (AMD) is the most prevalent cause of
irreversible blindness in developed countries. Recently, high-dose
supplementation with beta carotene, vitamins C and E, and zinc was shown to slow 
the progression of AMD. OBJECTIVE: To investigate whether regular dietary intake 
of antioxidants is associated with a lower risk of incident AMD. DESIGN: Dietary 
intake was assessed at baseline in the Rotterdam Study (1990-1993) using a
semiquantitative food frequency questionnaire. Incident AMD until final follow-up
in 2004 was determined by grading fundus color transparencies in a masked way
according to the International Classification and Grading System. SETTING:
Population-based cohort of all inhabitants aged 55 years or older in a
middle-class suburb of Rotterdam, the Netherlands. PARTICIPANTS: Of 5836 persons 
at risk of AMD at baseline, 4765 had reliable dietary data and 4170 participated 
in the follow-up. MAIN OUTCOME MEASURE: Incident AMD, defined as soft distinct
drusen with pigment alterations, indistinct or reticular drusen, geographic
atrophy, or choroidal neovascularization. RESULTS: Incident AMD occurred in 560
participants after a mean follow-up of 8.0 years (range, 0.3-13.9 years). Dietary
intake of both vitamin E and zinc was inversely associated with incident AMD. The
hazard ratio (HR) per standard deviation increase of intake for vitamin E was
0.92 (95% confidence interval [CI], 0.84-1.00) and for zinc was 0.91 (95% CI,
0.83-0.98). An above-median intake of all 4 nutrients, beta carotene, vitamin C, 
vitamin E, and zinc, was associated with a 35% reduced risk (HR, 0.65; 95% CI,
0.46-0.92) of AMD. Exclusion of supplement users did not affect the results.
CONCLUSION: In this study, a high dietary intake of beta carotene, vitamins C and
E, and zinc was associated with a substantially reduced risk of AMD in elderly
persons.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16380590 [PubMed - indexed for MEDLINE]

1642: Mol Vis. 2005 Dec 19;11:1141-50.

Disease-associated mutations in CNGB3 produce gain of function alterations in
cone cyclic nucleotide-gated channels.

Bright SR, Brown TE, Varnum MD.

Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology,
Washington State University, Pullman, WA 99164, USA.

PURPOSE: To characterize the functional consequences of disease-associated
mutations in the CNGB3 (B3) subunit of human cone photoreceptor cyclic
nucleotide-gated channels in order to gain insight into disease mechanisms.
METHODS: Three separate disease-associated mutations were generated in CNGB3:
F525N, R403Q, and T383fsX. These mutant subunits were then heterologously
expressed in Xenopus oocytes in combination with wild type CNGA3 (A3) subunits,
and characterized by patch-clamp recording in the inside-out configuration.
RESULTS: Co-expression of A3 and B3F525N, A3 and B3R403Q, or A3 and B3R403Q and
B3T383fsX subunits resulted in channels that exhibited an increase in ligand
sensitivity without a reduction in current density compared to wild-type
heteromeric channels. Each simulated disease state produced channels that
exhibited greater sensitivity to block by L-cis-diltiazem than homomeric CNGA3
channels, confirming that the mutant CNGB3 subunits were competent to form
functional heteromeric channels. Each combination of subunits displayed an
increase in apparent affinity for cGMP relative to wild-type heteromeric
channels. However, F525N enhanced cGMP apparent affinity to a significantly
greater extent than the other two modeled disease states. CONCLUSIONS: We have
examined the gating effects of two previously uncharacterized disease-associated 
mutations in the CNGB3 subunit and found that in each case, the mutations
resulted in a gain of function molecular phenotype. Furthermore, the magnitude of
the effect on channel function correlated with the severity of the associated
disease. The complete achromatopsia-associated F525N mutation resulted in more
pronounced alterations in channel function than the mutation combinations linked 
to macular degeneration or progressive cone dystrophy.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16379026 [PubMed - indexed for MEDLINE]

1643: Mol Vis. 2005 Dec 19;11:1135-40.

Y402H complement factor H polymorphism associated with exudative age-related
macular degeneration in the French population.

Souied EH, Leveziel N, Richard F, Dragon-Durey MA, Coscas G, Soubrane G, Benlian 
P, Fremeaux-Bacchi V.

Creteil University Eye Clinic, Faculte de Medecine Henri Mondor, Creteil, France.
eric.souied@chicreteil.fr

PURPOSE: Identification of genetic factors for age-related macular degeneration
(AMD) is of crucial importance in this common cause of blindness. A positive
association between Y402H polymorphism of the complement factor H (CFH) gene and 
AMD has been recently reported in North American populations but not yet in
European populations. The exudative form of AMD is rapidly progressive and
usually associated with a severe prognosis. Our purpose was to investigate this
association in a French population specifically affected with exudative AMD, in a
case-control study. METHODS: Two series of unrelated exudative AMD patients,
sporadic cases (n=60, mean age 74.9+/-5.7) and familial cases (n=81, mean age
74.0+/-9.4) were compared with healthy controls (n=91, mean age 74.6+/-6.3). The 
coding region of exon 9 of CFH was examined for the Y402H polymorphism by
PCR-direct sequencing. RESULTS: The 1,279-C allele frequencies were significantly
higher in exudative AMD patients than controls (0.564 compared to 0.302;
p<0.0001). Genotypic distribution of the Y402H polymorphism was significantly
different between sporadic cases compared to controls (chi2=14.48 with 2 df,
p<0.0007) and between familial cases compared to controls (chi2=23.78 with 2 df, 
p<0.0001). The odds ratio (OR) for exudative AMD was 3.00 CI95% (1.60-5.62) for
heterozygotes (CT) and 6.93 CI95% (3.11-15.46) for homozygotes (CC). CONCLUSIONS:
These results suggest the contribution of the Y402H polymorphism of the CFH gene 
to exudative AMD susceptibility also in the French population. This relationship 
with the CFH may lead to early detection and new strategies for prevention and
treatment of AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16379025 [PubMed - indexed for MEDLINE]

1644: Am J Ophthalmol. 2005 Dec;140(6):1163-5.

Fundus autofluorescence imaging in serous and drusenoid pigment epithelial
detachments associated with age-related macular degeneration.

Karadimas P, Bouzas EA.

Medical Retina Unit, 1st Department of Ophthalmology, Henry Dunant Hospital, 107 
Mesogion Avenue, 11526 Athens, Greece. t_karadimas@yahoo.com

PURPOSE: To investigate the fundus autofluorescence (FAF) imaging findings in
patients with serous and drusenoid pigment epithelial detachment (PED) associated
with age-related macular degeneration (AMD). DESIGN: Observational case series.
METHODS: Fourteen eyes of 13 consecutive patients with serous (n = 10) and
drusenoid (n = 4) PED were prospectively included. RESULTS: In all cases of
serous vascularized (n = 7) and avascular (n = 3) PED, the FAF signal was
increased, corresponding to the area of detachment. In drusenoid PED, the FAF was
either increased or decreased. The decreased signal was recorded in cases
associated with pigmented clumping. CONCLUSIONS: These findings are useful for a 
more detailed phenotyping of patients with PED associated with AMD. FAF may
derive not only from lipofuscin, but also from other sources, such as sub-retinal
pigment epithelium fluid.

PMID: 16376680 [PubMed - indexed for MEDLINE]

1645: Am J Ophthalmol. 2005 Dec;140(6):1159-61.

Ankle-brachial index and the prevalence of age-related maculopathy.

Moss SE, Klein R, Klein BE.

Department of Ophthalmology and Visual Sciences, University of Wisconsin Medical 
School, 610 N. Walnut Street, 4th Floor WARF, Madison, WI 53726, USA.
moss@epi.ophth.wisc.edu

PURPOSE: To examine the association of ankle-brachial blood pressure index (ABI) 
with prevalence of age-related maculopathy (ARM). DESIGN: A cross-sectional
cohort study. METHODS: ABI was measured in 2447 subjects aged 53 to 97 years. ARM
was determined from 30-degree color stereoscopic fundus photographs. RESULTS: Low
ABI (< or =0.9) was present in 5.4% of subjects. Early ARM was present in 22.1%
of subjects with and 18.8% without low ABI. Late ARM was present in 5.3% of
subjects with and 1.7% without low ABI. This result was not statistically
significant. CONCLUSIONS: Low ABI does not appear to be a risk factor for ARM.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 16376678 [PubMed - indexed for MEDLINE]

1646: Am J Ophthalmol. 2005 Dec;140(6):1096-105.

Vitrectomy in the treatment of uveitis.

Becker M, Davis J.

Bascom Palmer Eye Institute, University of Miami School of Medicine, 900 NW 17th 
Street, Miami, FL 33136, USA.

PURPOSE: To assess the evidence that pars plana vitrectomy (PPV) is useful in
improving vision, reducing disease activity, or ameliorating cystoid macular
edema (CME) in patients with uveitis. DESIGN: Review of the literature. METHODS: 
A Medline search was conducted for relevant articles published in English,
German, or French. Articles were analyzed for content and evidence level.
RESULTS: A total of 44 interventional case series published between 1981 and 2005
were identified that included 1575 patients (1762 eyes). Evidence level was grade
CII-3 indicating possibly improved clinical outcomes with fair or poor evidence. 
The average age of patients was 36 years with a median duration of uveitis before
surgery of 48 months and a median follow-up of 1.9 years. Intermediate uveitis
was present in 841 eyes. Cystoid macular edema and cataract were common
co-morbidities, and there were large numbers of additional surgical procedures.
Visual outcomes in 39 articles were stated as improved in 708 eyes (68%),
unchanged in 202 eyes (20%), and worsened in 124 eyes (12%). Reduction in
systemic medication following PPV was reported in 25 studies. The median reported
percentage of patients per study with CME was 36% preoperatively and 18%
postoperatively. CONCLUSIONS: Based on the evidence in the literature, PPV is
possibly relevant to the outcomes of improving vision and reducing inflammation
and CME. Randomized, controlled, collaborative trials or hypothesis-based case
series with precise outcome measures that incorporate control groups would
improve the quality of evidence supporting PPV as an adjunct to the medical
treatment of uveitis.

Publication Types: 
    Meta-Analysis

PMID: 16376658 [PubMed - indexed for MEDLINE]

1647: Am J Ophthalmol. 2005 Dec;140(6):1085-93.

Long-term follow-up of fixation patterns in eyes with central scotomas from
geographic atrophy that is associated with age-related macular degeneration.

Sunness JS, Applegate CA.

Greater Baltimore Medical Center, The Johns Hopkins University School of
Medicine, Baltimore, MD 21204, USA. jsunness@gbmc.org

PURPOSE: To study whether fixation patterns changed over time in patients with
central scotomas from geographic atrophy from age-related macular degeneration.
DESIGN: Prospective cohort study. METHODS: setting: Institutional. patient or
study population: Prospective natural history study of geographic atrophy
included 34 eyes of 25 patients with baseline acuity between 20/80 and 20/200 and
with subsequent follow-up. observation procedures: Baseline and annual follow-up 
visits included best-corrected visual acuity, scanning laser ophthalmoscope
macular perimetry, reading rate, and clinical evaluation. main outcome measures: 
Location of eccentric preferred retinal locus for fixation (PRL). RESULTS: At
baseline, 77% of study eyes had a PRL. At the final visit (median follow-up, 5.3 
years), 91% of study eyes had a PRL, with 81% of the eyes retaining the baseline 
PRL location. Fixation with the scotoma to the right and fixation with the
scotoma superior were the first and second most common fixation patterns,
respectively. Reading rates of <50 words/min were present in 54% of eyes. Eyes
fixating with the scotoma to the left tended to have lower reading rates than
eyes fixating with right or superior patterns. CONCLUSION: Fixation with right
pattern remained the most common fixation pattern, both in patients with a PRL at
baseline and in patients who had a PRL during follow-up. Eyes with a PRL at
baseline generally retained this pattern. The reading rate data suggest an
advantage of fixation with right or superior pattern, rather than left. Reading
rate declined further during follow-up in most patients.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16376656 [PubMed - indexed for MEDLINE]

1648: Am J Ophthalmol. 2005 Dec;140(6):1020-6.

Antioxidant supplements prevent oxidation of cysteine/cystine redox in patients
with age-related macular degeneration.

Moriarty-Craige SE, Adkison J, Lynn M, Gensler G, Bressler S, Jones DP, Sternberg
P Jr.

Department of Ophthalmology, Biochemistry, and Medicine, Emory University,
Atlanta, Georgia, USA.

PURPOSE: Determine whether antioxidant supplements alter the plasma glutathione
and/or cysteine redox potential in age-related macular degeneration (AMD)
patients. DESIGN: This was an ancillary study to the Age-Related Eye Disease
Study (AREDS), where subset of AREDS subjects at two sites were studied at two
time points, an average of 1.7 and 6.7 years after enrollment. METHODS: Plasma
glutathione (GSH), glutathione disulfide (GSSG), cysteine (Cys), and cystine
(CySS) were measured by high-performance liquid chromatography, and redox
potentials of GSH/GSSG (E(h) GSH) and Cys/CySS (E(h) Cys) were calculated. The
means of the metabolites and redox potentials were compared by repeated-measures 
analysis of variance for subjects receiving antioxidants and those not receiving 
antioxidants. RESULTS: At the first blood draw, the means for the antioxidant
group (n = 153) and no antioxidant group (n = 159) were not significantly
different for any of the metabolites or redox potentials. At the second draw, the
GSH parameters were not significantly different between the antioxidant (n = 37) 
and no antioxidant (n = 45) groups; however, mean Cys was significantly higher in
the antioxidant group (9.5 vs 7.2 micromol/l, P = .008). Also, mean E(h) Cys was 
significantly more reduced in the antioxidant group (-74 vs -67.3 mV, P = .03).
CONCLUSIONS: The AREDS antioxidant supplements reduced oxidation of E(h) Cys but 
had no effect on GSH. Because Cys is important for cell growth, apoptosis, and
immune function, the beneficial effect of antioxidant supplementation on
progression to advanced AMD may be partially explained by its effect on E(h) Cys 
and/or its effect on Cys availability.

Publication Types: 
    Multicenter Study
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16376645 [PubMed - indexed for MEDLINE]

1649: Am J Ophthalmol. 2005 Dec;140(6):976-983.

Ultrahigh resolution optical coherence tomography in macular dystrophy.

Wirtitsch MG, Ergun E, Hermann B, Unterhuber A, Stur M, Scholda C, Sattmann H, Ko
TH, Fujimoto JG, Drexler W.

Department of Ophthalmology, Medical University of Vienna, Währinger Strasse 13, 
1090 Vienna, Austria.

PURPOSE: To visualize and investigate intraretinal changes in macular dystrophies
with ultrahigh resolution optical coherence tomography (UHR OCT). DESIGN:
Prospective observational case series. METHODS: setting: Department of
Ophthalmology and Center for Biomedical Engineering and Physics, Christian
Doppler Laboratory, Medical University of Vienna, Vienna, Austria. patients:
Thirteen patients (23 eyes) with adult-onset foveomacular vitelliform dystrophy
(AOFVD) and 14 patients (27 eyes) with Stargardt's disease (SD) or fundus
flavimaculatus (FF). OBSERVATIONS: Imaging using a compact, new generation UHR
OCT system, achieving considerably improved visualization of intraretinal layers,
especially the photoreceptor layer. main outcome measures: UHR OCT tomograms
visualizing intraretinal differences in morphology of AOFVD and SD/FF as location
and extension of deposits and loss of photoreceptors. Central foveal thickness
defined as distance between internal limiting membrane and photoreceptors/retinal
pigment epithelium interface. RESULTS: Patients with AOFVD had a mostly intact
photoreceptor layer, a central foveal thickness of 142 +/- 23 microm as well as
subretinal deposits. Patients with SD generally had a diffuse degenerative change
with a visible reduction in thickness of all intraretinal layers, resulting in a 
corresponding reduction of central foveal thickness (94 +/- 38 microm) and
central loss of photoreceptors (PRs). Comparative central foveal thickness of
patients with AOFVD and SD/FF was significantly different (P < .001). Patients
with FF had pigment epithelial deposits and paracentral focal photoreceptor loss.
CONCLUSIONS: UHR OCT is a clinically feasible tool for examining intraretinal
changes, in particular photoreceptor atrophy in macular dystrophies and,
therefore, has the potential to be an adequate imaging system for monitoring the 
course of disease.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16376639 [PubMed - indexed for MEDLINE]

1650: Ophthalmologica. 2006;220(1):12-6.

Serum paraoxonase 1 activity and lipid peroxidation levels in patients with
age-related macular degeneration.

Baskol G, Karakucuk S, Oner AO, Baskol M, Kocer D, Mirza E, Saraymen R, Ustdal M.

Department of Biochemistry and Clinical Biochemistry, Medical Faculty, Erciyes
University, Kayseri, Turkey. gbaskol@yahoo.com

Our objective was to investigate antioxidant paraoxonase 1 (PON1) activity
together with malondialdehyde (MDA) levels to evaluate oxidative stress in
patients with age-related macular degeneration (AMD), an important cause of
blindness in the elderly population. Serum PON1 activity and MDA levels were
analyzed in 37 patients with AMD and compared with 29 healthy controls using a
spectrophotometric method. Serum MDA levels were significantly higher in the
patient group (2.76 +/- 1.28 nmol/ml) than controls (1.00 +/- 0.36 nmol/ml; p <
0.001), whereas PON1 activity was lower in the patient group (132.27 +/- 63.39
U/l) than controls (312.13 +/- 136.23 U/l; p < 0.001). There was a negative
correlation between MDA and PON1 levels (r = -0.470, p < 0.001). We conclude that
the observed increase in MDA levels may be related to decreased PON1 activity;
the present data also demonstrated that an obvious negative correlation between
PON1 activity and MDA levels exists in patients with AMD. PON1 is also an
antioxidant agent, therefore effective antioxidant therapy to inhibit lipid
peroxidation is necessary and agents to increase PON1 activity may be a
therapeutic option in AMD. 2006 S. Karger AG, Basel

Publication Types: 
    Comparative Study

PMID: 16374043 [PubMed - indexed for MEDLINE]

1651: Cornea. 2006 Feb;25(2):240-1.

Intravitreal triamcinolone acetonide for persisting cystoid macular edema after
penetrating keratoplasty.

Jonas JB, Kamppeter B.

Department of Ophthalmology, Faculty of Clinical Medicine Mannheim,
Ruprecht-Karls-University of Heidelberg, Germany.
Jost.Jonas@augen.ma.uni-heidelberg.de

PURPOSE: The intravitreal application of triamcinolone acetonide as treatment of 
long-standing, therapy-resistant cystoid macular edema after penetrating
keratoplasty is reported. METHODS: A 44-year-old patient showed therapy-resistant
cystoid macular edema for 2 years after repeated penetrating keratoplasty was
performed as treatment of keratoconus. The crystalline lens was clear. The
patient received an intravitreal injection of approximately 20 mg of
triamcinolone acetonide. Preinjection visual acuity measured 20/80. RESULTS:
Within the first 4 weeks after the injection, dense cataract developed
necessitating cataract surgery. After phakoemulsification, visual acuity improved
to 20/50. Optical coherent tomography and fluorescein angiography showed an
almost complete resolution of cystoid macular edema. Ten months after the
injection, visual acuity remained at 20/50, and intraocular pressure measured 15 
mm Hg without antiglaucomatous therapy taken. CONCLUSIONS: Intravitreal injection
of triamcinolone acetonide may be an additional tool in the treatment of
therapy-resistant cystoid macular edema after penetrating keratoplasty. After
intravitreal injection of triamcinolone acetonide, cataract may rapidly develop
in eyes that have been intensively treated, topically and systemically, by
corticosteroids for several years.

Publication Types: 
    Case Reports

PMID: 16371793 [PubMed - indexed for MEDLINE]

1652: Ophthalmology. 2006 Jan;113(1):3-13. Epub 2005 Dec 20.

Comment in:
    Ophthalmology. 2006 Dec;113(12):2372; author reply 2372-3.

Anecortave acetate (15 milligrams) versus photodynamic therapy for treatment of
subfoveal neovascularization in age-related macular degeneration.

Slakter JS, Bochow TW, D'Amico DJ, Marks B, Jerdan J, Sullivan EK, Robertson SM, 
Slakter JS, Sullins G, Zilliox P; Anecortave Acetate Clinical Study Group.

Vitreous-Retina-Macula Consultants of New York, New York, New York, USA.

PURPOSE: To compare 1-year safety and efficacy of anecortave acetate 15 mg with
photodynamic therapy (PDT) with verteporfin in patients eligible for initial PDT 
treatment. DESIGN: Prospective, masked, randomized, multicenter, parallel group, 
active control, noninferiority clinical trial. PARTICIPANTS: Five hundred thirty 
patients with predominantly classic subfoveal choroidal neovascularization
secondary to age-related macular degeneration were randomized to treatment with
either anecortave acetate 15 mg or PDT. METHODS: In the anecortave acetate group,
the drug was administered under the Tenon's capsule as a periocular posterior
juxtascleral depot (PJD) at the beginning of the study and at month 6. Before the
first administration of anecortave acetate, patients in this treatment group
received a sham PDT treatment, and sham PDT treatments were repeated every 3
months if there was evidence of leakage on fluorescein angiography (FA). Patients
assigned to PDT received up to 4 PDT treatments at 3-month intervals, as needed
based upon FA, and a sham PJD procedure at the beginning of the study and at
month 6. Best-corrected visual acuity was determined at baseline and all
follow-up visits. Safety data were regularly reviewed by an independent safety
committee. MAIN OUTCOME MEASURE: Percent responders (patients losing <3 lines of 
vision) at month 12. RESULTS: Percent responders in the anecortave acetate and
PDT groups were 45% and 49%, respectively (not statistically different, P =
0.43). The confidence interval (CI) for the difference ranged from -13.2%
favoring PDT to +5.6% favoring anecortave acetate. The month 12 clinical outcome 
for anecortave acetate was improved in patients for whom reflux was controlled
and who were treated within the 6-month treatment window (57% vs. 49%; 95% CI,
-4.3% favoring PDT to +21.7% favoring anecortave acetate). No serious adverse
events related to the study drug were reported in either treatment group.
CONCLUSIONS: The safety and efficacy outcomes in this study demonstrate that the 
benefits of anecortave acetate for the treatment of choroidal neovascularization 
outweigh the risks associated with either the drug or the PJD administration
procedure.

Publication Types: 
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial

PMID: 16368146 [PubMed - indexed for MEDLINE]

1653: Jpn J Ophthalmol. 2005 Nov-Dec;49(6):509-15.

Trans-Tenon's retrobulbar injection of triamcinolone acetonide for diffuse
diabetic macular edema.

Wada M, Ogata N, Minamino K, Koriyama M, Higuchi A, Matsumura M.

Department of Ophthalmology, Kansai Medical University, Moriguchi, Japan.

PURPOSE: To determine whether a trans-Tenon's retrobulbar injection of
triamcinolone acetonide (TA) is a safe and effective treatment for diffuse
diabetic macular edema. METHODS: Thirty-nine eyes of 30 diabetic patients with
persistent macular edema were treated with 20 mg of TA injection. Central macular
thickness (CMT) determined by optical coherence tomography (OCT) and visual
acuity were evaluated before the injection and at 1, 2, 3, and 6 months, and up
to 1 year in some eyes, after the injection. RESULTS: The CMT decreased
significantly from 478 +/- 129 microm (mean +/- SD) before injection to 316 +/-
102 microm at 1 month, 307 +/- 104 microm at 2 months, and 275 +/- 89 microm at 3
months after a single injection of TA. A 20% reduction of CMT from the initial
value was maintained by a single injection of TA in 27 of 39 eyes (69.2%) at 3
months, in 14 of 22 eyes (63.6%) at 6 months, and in 5 of 7 eyes at 12 months. A 
recurrence of macular edema was observed in 10% of the eyes at 3 months, and in
22.7% at 6 months. The 17 eyes in which vitrectomy had been carried out had a
more significant improvement in CMT than the eyes without vitrectomy. CONCLUSION:
A 20-mg trans-Tenon's retrobulbar TA injection is a safe and effective treatment 
for diabetic macular edema.

Publication Types: 
    Comparative Study

PMID: 16365798 [PubMed - indexed for MEDLINE]

1654: Jpn J Ophthalmol. 2005 Nov-Dec;49(6):462-8.

How spatial orientation of Japanese text affects fixation points in patients with
bilateral macular atrophy.

Matsumoto Y, Yuzawa M, Oda K.

Department of Ophthalmology, Surugadai Nihon University Hospital, Tokyo, Japan.

PURPOSE: To ascertain the retinal area used by patients with bilateral macular
atrophy when reading Japanese text of different character sizes written
horizontally or vertically. In addition, to determine fixation points as part of 
the first of a series of studies designed ultimately to enhance the quality of
life of these patients through the improvement of reading acuity. METHODS:
Seventeen patients (34 eyes) with bilateral macular atrophy were tested to
determine the retinal area employed for reading (R fixation point). Sentences
were arranged either horizontally or vertically and projected onto the retina
using a scanning laser ophthalmoscope. We also determined the fixation point
using microperimetry (M fixation point). The positional relationships between
these two fixation points and the scotoma were examined. RESULTS: The R and M
fixation points were the same in 20 of the 34 eyes. Multiple R fixation points
were found in 11 eyes. The R fixation point was frequently positioned above the
lesion when reading horizontally (nine eyes), while it was often positioned in
the area nasal to (eight eyes) or temporal to (six eyes) the lesion when reading 
vertically. CONCLUSIONS: Fixation points changed frequently in these patients
with bilateral macular atrophy depending on the spatial orientation of the text. 
These data should be used in the future to help patients learn how to use the
preferred retinal locus to improve their reading skills and enhance their quality
of life.

Publication Types: 
    Case Reports
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 16365791 [PubMed - indexed for MEDLINE]

1655: Exp Eye Res. 2006 May;82(5):840-8. Epub 2005 Dec 20.

The expression of advanced glycation endproduct receptors in rpe cells associated
with basal deposits in human maculas.

Yamada Y, Ishibashi K, Ishibashi K, Bhutto IA, Tian J, Lutty GA, Handa JT.

Michael Panitch Macular Degeneration Research Laboratory, Johns Hopkins Medical
Institutes, Baltimore, MD, USA.

Basal deposits within Bruch's membrane are associated with aging and age-related 
macular degeneration (AMD) although the factors causing their formation are
incompletely understood. Advanced glycation endproducts (AGEs) accumulate in
Bruch's membrane including basal deposits and drusen with aging. One mechanism by
which AGEs alter a cell's phenotype is via AGE receptors. The purpose of this
study was to immunolocalize and quantify the expression of AGE receptors by RPE
cells associated with basal deposits or normal Bruch's membrane that were
microdissected from human maculas. Postmortem eyes from 14 aged control donors
and five donors with non-neovascular AMD were cryopreserved. RPE cells associated
with normal Bruch's membrane or basal deposits were laser capture microdissected.
The RNA was extracted and used for RT-qPCR to quantify the expression of RAGE,
AGE R1, AGE R2, and AGE R3. Streptavidin alkaline phosphatase
immunohistochemistry for these receptors was also performed and sections were
bleached from 14 normal and nine AMD donors. RT-qPCR showed significant
upregulation of RAGE, AGE R1, and AGE R3 in RPE cells overlying basal deposits
compared to cells attached to morphologically normal Bruch's membrane.
Immunohistochemical analysis for RAGE, AGER1, R2, and R3 showed diffuse, light
staining of RPE cells and strong choriocapillaris staining in areas of normal
Bruch's membrane. In areas of basal deposits, the RPE had more intense staining
for RAGE and AGER1 compared to regions of normal Bruch's membrane. These results 
suggest that AGE receptors could influence the formation of basal deposits during
aging and AMD.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16364296 [PubMed - indexed for MEDLINE]

1656: Br J Ophthalmol. 2006 Jan;90(1):75-80.

Smoking and age related macular degeneration: the number of pack years of
cigarette smoking is a major determinant of risk for both geographic atrophy and 
choroidal neovascularisation.

Khan JC, Thurlby DA, Shahid H, Clayton DG, Yates JR, Bradley M, Moore AT, Bird
AC; Genetic Factors in AMD Study.

Department of Medical Genetics, University of Cambridge, Cambridge CB2 2QQ, UK.

BACKGROUND/AIMS: There is evidence that smoking is a risk factor for age related 
macular degeneration (AMD). However, not all studies have demonstrated this
association and several key questions about the role of smoking in AMD have still
to be determined. The aim of this study was to further investigate this relation 
for both choroidal neovascularisation (CNV) and geographic atrophy (GA). METHODS:
To investigate the relation between smoking and the risk of developing age
related macular degeneration (AMD) in white people, 435 cases with end stage AMD 
were compared with 280 controls. All subjects had graded stereoscopic colour
fundus photography and AMD was defined as the presence of GA or CNV. Smoking
history was assessed using multiple parameters in a detailed questionnaire.
RESULTS: Comparison of current and former smokers with non-smokers was consistent
with smoking being a risk factor for AMD but did not reach statistical
significance. There was a strong association between AMD and pack years of
cigarette smoking (p = 0.002), the odds ratio increasing with the amount smoked; 
for subjects with more than 40 pack years of smoking the odds ratio was 2.75 (95%
CI 1.22 to 6.20) compared with non-smokers. Both types of AMD showed a similar
relation; smoking more than 40 pack years of cigarettes was associated with an
odds ratio of 3.43 (95% CI 1.28 to 9.20) for GA and 2.49 (95% CI 1.06 to 5.82)
for CNV. Stopping smoking was associated with reduced odds of AMD and the risk in
those who had not smoked for over 20 years was comparable to non-smokers. The
risk profile was similar for males and females. Passive smoking exposure was
associated with an increased risk of AMD (OR 1.87; 95% CI 1.03 to 3.40) in
non-smokers. CONCLUSIONS: The authors have demonstrated a strong association
between the risk of both GA and CNV and pack years of cigarette smoking. This
provides support for a causal relation between smoking and AMD. They also show an
increased risk for AMD in non-smokers exposed to passive smoking. Stopping
smoking appears to reduce the risk of developing AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16361672 [PubMed - indexed for MEDLINE]

1657: Br J Ophthalmol. 2006 Jan;90(1):48-54.

Comment in:
    Br J Ophthalmol. 2006 Jan;90(1):5-6.

Impaired expression of thrombospondin-1 in eyes with age related macular
degeneration.

Uno K, Bhutto IA, McLeod DS, Merges C, Lutty GA.

Ophthalmological Institute, Johns Hopkins Hospital, Baltimore, MD 21287-9115,
USA.

AIMS: This study investigated the expression and localisation of thrombospondin-1
(TSP-1), a known anti-angiogenic extracellular matrix protein, in normal aged
control human eyes and eyes with age related macular degeneration (AMD). METHODS:
Immunohistochemical analysis with mouse anti-human TSP-1 antibody and mouse
anti-human CD 34 antibody, as a blood vessel marker, was performed on frozen
sections from macular and peripheral blocks of aged control donor eyes (n = 12;
mean age 78.8 years), and eyes with AMD (n = 12; mean age 83.9 years). Pigment in
retinal pigment epithelium (RPE) and choroidal melanocytes was bleached. Three
independent observers scored the immunohistochemical reaction product. RESULTS:
In the macular region, TSP-1 expression was observed intensely in Bruch's
membrane and weakly in RPE basement membrane, choriocapillaris, and the wall of
large choroidal blood vessels in the aged control eyes. In eyes with AMD, TSP-1
immunoreactivity was significantly lower in all structures except RPE basement
membrane (p<0.01). There was significantly lower TSP-1 in the far periphery than 
the equator and submacular regions in all eyes. TSP-1 immunoreactivity was low in
choroidal neovascularisation (CNV), but it was high and diffuse in adjacent scar 
tissue. CONCLUSION: These findings suggest that decreased TSP-1 in Bruch's
membrane and choroidal vessels during AMD may permit the formation of CNV.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16361667 [PubMed - indexed for MEDLINE]

1658: Br J Ophthalmol. 2006 Jan;90(1):37-9.

Cystoid macular oedema in paediatric aphakia and pseudophakia.

Kirwan C, O'Keeffe M.

The Children's Hospital, Dublin 7, Republic of Ireland.

AIM: To assess the incidence of cystoid macular oedema (CMO), following
lensectomy, anterior vitrectomy (limbal and pars plicata), and primary posterior 
capsulorhexis following surgery for congenital and developmental cataract.
METHODS: A prospective study was carried out involving 30 eyes (20 children) with
cataract. Lensectomy, primary posterior capsulorhexis, and anterior vitrectomy
were performed on all eyes. Vitrectomy was performed using either a limbal or
pars plicata approach. Fluorescein angiography was carried out 4-7 weeks after
surgery. Fluorescein was administered intravenously and visualised using the
Retcam. RESULTS: Anterior vitrectomy was carried out via the limbal approach in
12 eyes and, of these, six were implanted with an intraocular lens. The pars
plicata approach was carried out in 18 eyes and 10 received an implant. CMO was
not detected in any eye. CONCLUSION: CMO was not detected in the early
postoperative period irrespective of approach to anterior vitrectomy or presence 
of an intraocular lens. Intravenous fluorescein angiography was performed without
complication.

PMID: 16361664 [PubMed - indexed for MEDLINE]

1659: Br J Ophthalmol. 2006 Jan;90(1):33-6.

Factors predicting outcome of vitrectomy for diabetic macular oedema: results of 
a prospective study.

Shah SP, Patel M, Thomas D, Aldington S, Laidlaw DA.

London School of Hygiene and Tropical Medicine, UK.

AIM: To determine preoperative demographic, clinical, and optical coherence
tomography (OCT) factors which might predict the visual and anatomical outcome at
1 year in patients undergoing vitrectomy and inner limiting membrane peel for
diabetic macular oedema (DMO). METHODS: A prospective, interventional case series
of 33 patients who completed 1 year follow up. Measurements were taken
preoperatively and at 1 year. Outcome measures were logMAR visual acuity (VA) and
OCT macular thickness. A priori explanatory variables included baseline presence 
of clinical and/or OCT signs suggesting macular traction, grade of diabetic
maculopathy, posterior vitreous detachment, fluorescein leakage and ischaemia on 
angiography, presence of subretinal fluid, and peroperative indocyanine green
(ICG) use. RESULTS: 33 patients completed 1 year follow up. On average VA
deteriorated by 0.035 logMAR (p = 0.40). Macular thickness significantly improved
by a mean of 139 microm (95% CI; 211 to 67, p<0.001). Patients with evidence of
clinical and/or OCT macular traction significantly improved logMAR acuity (logMAR
improvement = 0.08) compared with patients without traction (logMAR deterioration
0.11, p = 0.01). Presence of subretinal fluid significantly predicted worse
postoperative result (p = 0.01) CONCLUSION: On average, patients showed a
statistically significant improvement in central macular thickness following
treatment but a marginal acuity worsening. Presence of subretinal fluid on OCT is
hypothesised to be exudative rather than tractional in nature. The visual benefit
of vitrectomy for DMO in this study was limited to patients who exhibit signs of 
macular traction either clinically and/or on OCT.

PMID: 16361663 [PubMed - indexed for MEDLINE]

1660: Br J Ophthalmol. 2006 Jan;90(1):29-32.

Age related macular degeneration and sun exposure, iris colour, and skin
sensitivity to sunlight.

Khan JC, Shahid H, Thurlby DA, Bradley M, Clayton DG, Moore AT, Bird AC, Yates
JR; Genetic Factors in AMD Study.

Department of Medical Genetics, University of Cambridge, Cambridge CB2 2QQ, UK.

BACKGROUND/AIM: It has been suggested that sun exposure may be a risk factor for 
age related macular degeneration (AMD) and that skin sensitivity to sunlight and 
iris colour could be confounding factors. The aim was to investigate this further
in the white population. METHODS: 446 cases with end stage AMD were compared with
283 spouse controls. Data on sun exposure, places of residence, iris colour,
subjective assessment of change in iris colour, hair colour at age 20, and skin
sensitivity were obtained using a questionnaire. Iris colour was graded
clinically by comparison with standard photographs. AMD was graded using
stereoscopic colour fundus photographs as well as clinical examination and was
defined as the presence of geographic atrophy or choroidal neovascularisation.
All variables were included in a multiple logistic regression model including
age, sex, and smoking. RESULTS: There was no association between AMD and sun
exposure or related factors except for the suggestion of an association between
sunburn prone skin type and geographic atrophy which reached borderline
significance. CONCLUSIONS: No significant association between AMD and sun
exposure, iris colour, change in iris colour, or hair colour was demonstrated.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 16361662 [PubMed - indexed for MEDLINE]

1661: Ophthalmology. 2006 Jan;113(1):14-22. Epub 2005 Dec 19.

Comment in:
    Ophthalmology. 2006 Aug;113(8):1470-1.    Ophthalmology. 2006 Nov;113(11):2109-10.

Verteporfin therapy combined with intravitreal triamcinolone in all types of
choroidal neovascularization due to age-related macular degeneration.

Augustin AJ, Schmidt-Erfurth U.

Department of Ophthalmology, Klinikum Karlsruhe, Karlsruhe, Germany.
106020.560@compuserve.com

OBJECTIVE: To evaluate the efficacy and safety of photodynamic therapy with
verteporfin combined with intravitreal triamcinolone in choroidal
neovascularization secondary to age-related macular degeneration (AMD). DESIGN:
Prospective, noncomparative, interventional case series. PARTICIPANTS: One
hundred eighty-four patients undergoing treatment for neovascular AMD at one
retinal referral center. METHODS: One hundred eighty-four eyes of 184 consecutive
patients (63.6% female, 36.4% male) with a mean age of 76.5 years and a follow-up
of a median of 38.8 weeks (range, 12-103) were included in a case series. One
hundred forty-eight (80.4%) patients had subfoveal choroidal neovascularization, 
19 patients (10.3%) had juxtafoveal choroidal neovascularization, and 17 patients
(9.2%) had extrafoveal choroidal neovascularization. Verteporfin photodynamic
therapy was performed using the recommended standard procedure. A solution
containing 25 mg of triamcinolone was injected intravitreally 16 hours after
photodynamic therapy in 184 patients. The combined therapy procedure was repeated
at the 3-month follow-up visits whenever persistent choroidal neovascularization 
leakage was documented angiographically. MAIN OUTCOME MEASURES: Mean change in
best-refracted visual acuity (VA) between baseline and the last visit, and number
of treatments necessary to achieve absence of leakage. RESULTS: Visual acuity
improved in the majority of patients (baseline VA, mean 20/125) by a mean
increase of 1.22 Snellen lines and 1.43 lines using laser interferometry
(P<0.01). The mean number of required treatments was 1.21. Twenty-three eyes
(12.5%) required 2 treatments, 6 eyes (3.26%) required 3 treatments, and 1 eye
(0.5%) required 4 treatments. The combination treatment including laser and
intravitreal steroid administration was well tolerated. Forty-six patients (25%) 
required glaucoma therapy due to a transient steroid-induced intraocular pressure
(IOP) increase. Twelve patients (6.5%) were on topical medication for preexisting
glaucoma. Two patients (1%) whose IOP increase could not be controlled with
topical therapy required surgery. CONCLUSIONS: Verteporfin photodynamic therapy
combined with intravitreal triamcinolone may improve the outcome of standard
verteporfin photodynamic therapy in the treatment of choroidal neovascularization
secondary to AMD. A significant improvement in VA was observed in a majority of
treated patients and was maintained during the maximum follow-up. In addition,
retreatment rates were lower than anticipated.

PMID: 16360209 [PubMed - indexed for MEDLINE]

1662: Arch Ophthalmol. 2005 Dec;123(12):1651-6.

Comment in:
    Arch Ophthalmol. 2007 Jun;125(6):855; author reply 855-6.

Analysis of the macula with optical coherence tomography after successful surgery
for proliferative vitreoretinopathy.

Benson SE, Grigoropoulos V, Schlottmann PG, Bunce C, Charteris DG.

Vitreoretinal Research Unit, Moorfields Eye Hospital, London, England.

OBJECTIVE: To use optical coherence tomography to assess the in vivo pathologic
findings associated with incomplete visual recovery in patients who have
undergone anatomically successful surgery to treat proliferative
vitreoretinopathy. METHODS: Eligible patients were recruited in vitreoretinal
outpatient clinics between April 1, 2002, and July 31, 2003. Patients were
included who had undergone anatomically successful vitreoretinal surgery to treat
proliferative vitreoretinopathy and, at least 3 months after surgery, had
postoperative vision worse than expected (< or =6/12) with no identifiable cause 
at clinical examination. Patients underwent optical coherence tomography, stereo 
fundus fluorescein angiography was performed in a cohort of patients, and
angiographic findings were compared with those on the optical coherence
tomograms. Relevant clinical data were collected retrospectively from patient
case notes. RESULTS: A total of 35 patients were recruited. Optical coherence
tomograms revealed cystoid macular edema in 23 patients (66%) but did not
identify any other specific intraretinal disease. Location of edema (outer or
inner retina), determined with stereo fundus fluorescein angiography and optical 
coherence tomography, correlated well. CONCLUSIONS: Optical coherence tomography 
is a useful diagnostic tool for assessing poor postoperative visual acuity and
can reveal disease undetected at clinical examination. Cystoid macular edema is a
common finding on optical coherence tomograms in eyes with incomplete visual
recovery after anatomically successful surgery to treat proliferative
vitreoretinopathy.

PMID: 16344435 [PubMed - indexed for MEDLINE]

1663: Arch Ophthalmol. 2005 Dec;123(12):1644-50.

Comment in:
    Arch Ophthalmol. 2005 Dec;123(12):1741-3.

Treatment of retinal angiomatous proliferation in age-related macular
degeneration: a series of 104 cases of retinal angiomatous proliferation.

Bottoni F, Massacesi A, Cigada M, Viola F, Musicco I, Staurenghi G.

Department of Ophthalmology, San Giuseppe Hospital, Milan, Italy.
ferdinando.bottoni@fastwebnet.it

OBJECTIVE: To report the management of retinal angiomatous proliferation (RAP), a
recently described intraretinal neovascular lesion occurring in age-related
macular degeneration. METHODS: This was a retrospective review of consecutive
patients with age-related macular degeneration who underwent treatment of RAP
from January 1, 2000, through January 31, 2003. Inclusion criteria were age 55
years or older, signs of age-related macular degeneration, and diagnosis of RAP
based on dynamic indocyanine green angiography. Baseline angiograms were reviewed
and RAP was classified into the following 3 stages: stage 1, intraretinal
neovascularization, early stage; stage 2, subretinal neovascularization, middle
stage; and stage 3, choroidal neovascularization, late stage. Treatment and
concomitant treatment results were assessed separately for each RAP stage. The
clinical data were statistically analyzed (chi2 test and analysis of variance)
for 2 main outcome measures--complete obliteration of the lesion and final visual
acuity. RESULTS: Eighty-one patients (99 eyes) with 104 RAPs were identified.
Forty-two lesions were at stage 1, 42 at stage 2, and 20 at stage 3. The
following 5 treatments were performed: direct laser photocoagulation of the
vascular lesion, laser photocoagulation of the feeder retinal arteriole, scatter 
"gridlike" laser photocoagulation, photodynamic therapy, and transpupillary
thermotherapy. Complete obliteration of RAP was achieved in about 24 (57.1%) of
the stage 1 lesions (direct laser photocoagulation of the vascular lesion, 73%
success rate; photodynamic therapy, 45%), 11 (26.2%) of the stage 2 lesions
(scatter gridlike laser photocoagulation, 38% success rate; direct laser
photocoagulation of the vascular lesion, 17%), and only 3 (15.0%) of stage 3
lesions (P = .001). Predictive factors with a significant effect on final visual 
acuity were initial visual acuity (P = .003) and early lesion stage (P = .04).
Best final visual acuity was 0.41 (mean, direct laser photocoagulation of the
vascular lesion in stage 1) and 0.39 (mean, photodynamic therapy in stage 1),
with a mean decrease of 2.5 and 3 lines from baseline, respectively. CONCLUSIONS:
Treatment of RAP remains difficult. Early detection of the lesion and subsequent 
direct conventional laser photocoagulation seems to be associated with better
anatomical and functional outcome. Once the vascular complex is well established,
anatomical closure is rarely achieved. Further study is warranted to assess the
long-term efficacy and the need for re-treatment.

Publication Types: 
    Multicenter Study

PMID: 16344434 [PubMed - indexed for MEDLINE]

1664: Ophthalmology. 2006 Jan;113(1):23-8. Epub 2005 Dec 15.

Comment in:
    Ophthalmology. 2007 Mar;114(3):615-6.

Changes in retinal neovascularization after pegaptanib (Macugen) therapy in
diabetic individuals.

Adamis AP, Altaweel M, Bressler NM, Cunningham ET Jr, Davis MD, Goldbaum M,
Gonzales C, Guyer DR, Barrett K, Patel M; Macugen Diabetic Retinopathy Study
Group.

OBJECTIVE: To study effects of intravitreal pegaptanib (Macugen) on retinal
neovascularization. DESIGN: Retrospective analysis of a randomized clinical
trial. PARTICIPANTS, INTERVENTION, AND MAIN OUTCOME MEASURES: Individuals with
retinal neovascularization identified from a multicenter, randomized, controlled 
trial evaluating pegaptanib for treatment of diabetic macular edema, with a
best-corrected visual acuity letter score between 68 and 25 (approximate Snellen 
equivalent between 20/50 and 20/320) and receiving a sham injection or
intravitreal pegaptanib (0.3 mg, 1 mg, 3 mg) administered at study entry, week 6,
and week 12, with additional injections and/or focal photocoagulation as needed
during the ensuing 18 weeks, up to a maximum of 6 pegaptanib/sham therapies, were
evaluated. Scatter panretinal photocoagulation before study enrollment was
permitted, but not within 6 months of randomization and study entry. Changes in
retinal neovascularization were assessed on fundus photographs and fluorescein
angiograms graded at a reading center in a masked fashion. RESULTS: Of 172
participants, 19 had retinal neovascularization in the study eye at baseline.
Excluding 1 who had scatter photocoagulation 13 days before randomization and 2
with no follow-up photographs, 1 of the remaining 16 subjects had panretinal
photocoagulation during study follow-up. Of these 16 subjects, 8 of 13 (62%) in a
pegaptanib treatment group (including the one receiving panretinal
photocoagulation), 0 of 3 in the sham group, and 0 of 4 fellow (nonstudy) eyes
showed either regression of neovascularization on fundus photographs or
regression or absence of fluorescein leakage from neovascularization (or both) at
36 weeks. In 3 of 8 with regression, neovascularization progressed at week 52
after cessation of pegaptanib at week 30. CONCLUSIONS: Most subjects with retinal
neovascularization at baseline assigned to pegaptanib showed regression of
neovascularization by week 36. These findings suggest a direct effect of
pegaptanib upon retinal neovascularization in patients with diabetes mellitus.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16343627 [PubMed - indexed for MEDLINE]

1665: Diabetologia. 2006 Jan;49(1):200-6. Epub 2005 Dec 10.

Visual acuity and perimetry as measures of visual function in diabetic macular
oedema.

Agardh E, Stjernquist H, Heijl A, Bengtsson B.

Department of Ophthalmology, Malmö University Hospital, SE 205 02, Malmö, Sweden.
elisabet.agardh@med.lu.se

AIMS/HYPOTHESIS: We examined to what extent visual acuity and perimetric
sensitivity as measures of central and paracentral visual function would be
useful for evaluating the presence and severity of diabetic macular oedema.
MATERIALS AND METHODS: We evaluated 59 eyes of 59 diabetic patients by
identifying the presence (n=20) or absence (n=39) of macular oedema on stereo
fundus photographs. The area of oedema and its distance to the centre of the
macula were measured. Ischaemic macular damage was quantified by measuring the
foveal avascular zone and adjacent perifoveolar intercapillary areas on
fluorescein angiograms. Visual function was assessed by visual acuity charts and 
by short-wavelength perimetry and standard white-on-white perimetry of the
central 10 degrees field. RESULTS: Visual acuity did not differ between eyes with
and without macular oedema. In eyes with oedema, visual acuity was correlated to 
the distance of the oedema from the centre of the macula (log of minimum angle of
resolution {LogMar} score decreased by 0.15/mm; p=0.006) and to the thickness of 
the retina when the centre was affected (LogMar score decreased by 0.003/mum of
thickness; p=0.0002). Multivariate analyses confirmed the results (R (2)=0.46 and
0.77, respectively). Short-wavelength perimetry sensitivity was more depressed in
eyes with oedema (p=0.033) but was not significantly associated with the presence
of oedema after correction for macular ischaemic damage. There was no correlation
between these field defects and the severity of oedema.
CONCLUSIONS/INTERPRETATION: Visual acuity was a useful measure of visual function
in diabetic macular oedema involving the centre. Visual field defects were more
common in eyes with macular oedema but reflected ischaemic damage of the macula
rather than macular oedema itself.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16341838 [PubMed - indexed for MEDLINE]

1666: Graefes Arch Clin Exp Ophthalmol. 2006 Jul;244(7):829-35. Epub 2005 Dec 9.

Arterio-venous dissection after isovolaemic haemodilution in branch retinal vein 
occlusion: a non-randomised prospective study.

Feltgen N, Herrmann J, Agostini H, Sammain A, Hansen LL.

Department of Ophthalmology, University of Freiburg, Killianstrasse 5, 79106
Freiburg, Germany. nicolas.feltgen@uniklinik-freiburg.de

PURPOSE: The rationale for this pilot study was to add arterio-venous dissection 
(AVD) after unsuccessful medical treatment in a well-defined group of patients
with branch retinal vein occlusion (BRVO). METHODS: In this prospective,
interventional case series 35 consecutive patients with a visual acuity (VA) of
0.4 (logMar) or worse were scheduled for surgery within the first 3 months of the
onset of BRVO. The study endpoint was VA 1 year after AVD. Secondary study
endpoints were: correlation of VA and successful vessel dissection; complication 
rate; and number of additional surgical procedures within the first year of AVD. 
RESULTS: Preoperative VA (logMar) was 0.82+/-0.05 (range 0.2-1.6). VA 6 weeks
postoperatively was 0.54+/-0.06 (range 0-1.6), 3 months postoperatively
0.61+/-0.07 (0-1.56), 6 months postoperatively 0.74+/-0.08 (range 0-2) and 12
months postoperatively 0.55+/-0.07 (range 0.1-1.5). VA improved 1 year after AVD 
(p=0.0004). An improvement in VA did not depend on successful separation of the
artery and the vein. Four patients had a retinal detachment, 19 patients needed
cataract surgery within the first year of AVD. A total of 24 additional surgical 
procedures were needed. CONCLUSIONS: Patients with BRVO may profit from AVD
compared with a historical control group. Visual improvement was found
irrespective of the successful dissection of vessels. The cataract formation rate
and additional surgery was a shortcoming of the AVD procedure.

PMID: 16341702 [PubMed - indexed for MEDLINE]

1667: Graefes Arch Clin Exp Ophthalmol. 2006 Aug;244(8):1026-8. Epub 2005 Dec 8.

One-year outcomes after photodynamic therapy in patients with age-related macular
degeneration with poor baseline visual acuity.

Potter MJ, Szabo SM.

Department of Ophthalmology and Visual Sciences, University of British Columbia, 
Vancouver, British Columbia, Canada. mpotter@interchange.ubc.ca

BACKGROUND: Photodynamic therapy with verteporfin (PDT) has been demonstrated in 
randomized controlled trials to be a safe and effective therapy for choroidal
neovascular membranes (CNV) secondary to age-related macular degeneration (AMD). 
Limited information is available on the prognosis with PDT for patients who fell 
outside the inclusion criteria for the clinical trials, however. The purpose of
this study is to describe the clinical course of patients with CNV lesions in AMD
treated with PDT, with baseline visual acuities sufficiently poor to warrant
exclusion from previous randomized trials. METHODS: Retrospective case series.
Ten consecutive patients with CNV secondary to exudative AMD treated with PDT
with baseline visual acuity less than 34 ETDRS letters were followed for 1 year. 
The main outcome was median change in visual acuity on the ETDRS chart. RESULTS: 
The median change in acuity over 12 months was + 13 letters. All patients lost <3
lines of ETDRS acuity, and eight of ten patients (80%) gained at least one line
of vision, over 12 months. CONCLUSIONS: In our series, patients with low visual
acuity at baseline appeared to respond to PDT on both visual acuity and
fluorescein angiographic measurements. PDT treatment may be considered for
selected patients with these baseline characteristics.

PMID: 16341540 [PubMed - indexed for MEDLINE]

1668: Retina. 2005 Dec;25(8):1065-84.

neovascular age-related macular degeneration: Natural History and Treatment
Outcomes.

Pauleikhoff D.

Department of Ophthalmology, St. Franziskus Hospital, Muenster, Germany.
dapauleikhoff@muenster.de

BACKGROUND: This review summarizes the data reported in peer-reviewed literature 
and presents current knowledge on differentiation, natural history, and
therapeutic outcomes of neovascular age-related macular degeneration (AMD).
METHODS: The MEDLINE database was searched to review natural history of
neovascular AMD and therapeutic effects of available treatments. RESULTS: The
search produced>7,000 articles. Research suggests that fluorescein angiographic
characterization of location, composition, and size of neovascular lesions may be
important in prognosis and should be considered for evaluation of treatment
benefits in conjunction with evidence of recent disease progression for lesions
not composed of predominantly classic choroidal neovascularization (CNV). Laser
photocoagulation, photodynamic therapy with verteporfin, and administration of
pegaptanib sodium reduce the risk of vision loss in selected cases of neovascular
AMD, while submacular surgery can reduce the risk of severe visual acuity loss in
selected cases of predominantly hemorrhagic CNV; further approaches are under
investigation. CONCLUSION: Visual prognosis of neovascular AMD is variable
according to lesion location, composition, and size. Often, lesions have a poor
prognosis, resulting in rapid and progressive loss of visual acuity and contrast 
sensitivity. Such losses have a profound effect on patients' quality of life and 
ability to perform everyday tasks. Reducing the risk of further loss of visual
acuity and contrast sensitivity might enable patients with neovascular AMD to
maintain better functional abilities.

Publication Types: 
    Review

PMID: 16340538 [PubMed - indexed for MEDLINE]

1669: Retina. 2005 Dec;25(8):981-8.

Effect of subthreshold infrared laser treatment for drusen regression on macular 
autofluorescence in patients with age-related macular degeneration.

Bessho K, Rodanant N, Bartsch DU, Cheng L, Koh HJ, Freeman WR.

Department of Ophthalmology, University of California at San Diego, Jacobs Retina
Center/Shiley Eye Center, La Jolla, California 92093-0946, USA.

BACKGROUND: Subthreshold laser therapy has been shown to cause drusen reduction. 
Using this method, visible laser burns are not created in the retina; presumably,
the energy is absorbed by the retinal pigment epithelium (RPE) and stimulates
reabsorption of drusen material, sparing photoreceptors from destruction. We
hypothesized that autofluorescence (AF) changes would be visible after such
treatment and might be sensitive to quantify RPE changes. METHODS: Twenty eyes of
13 patients with non-exudative age-related macular degeneration were studied.
Forty-eight subthreshold infrared diode laser spots were applied as treatment to 
cause drusen regression. Before, immediately after, and 3 months after treatment,
color fundus photography, fluorescein angiography (FA), and autofluorescence (AF)
imaging were performed. Treated lesions were identified on overlay images of all 
three imaging methods. RESULTS:: The averaged sensitivity of AF imaging compared 
with FA was 29.6+/-28.7% versus 10.2+/-12.2% (P=0.008) at the immediate
posttreatment time point and 43.5+/-28.7% versus 33.8+/-26.5% (P=0.043) at the
3-month posttreatment time point, respectively. Reduction of drusen at 3 months
correlated with the detection sensitivity of AF imaging at the immediate
posttreatment time point (P=0.022). CONCLUSION: Immediately after subthreshold
laser treatment, AF imaging was more sensitive to detect RPE changes than FA.
This suggests that noninvasive AF imaging may allow prediction of the effect of
subthreshold laser treatment and might be used to titrate treatment dose.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16340527 [PubMed - indexed for MEDLINE]

1670: Graefes Arch Clin Exp Ophthalmol. 2006 Jul;244(7):863-7. Epub 2005 Dec 6.

A new treatment regimen in combined intravitreal injection of triamcinolone
acetonide and photodynamic therapy.

Krebs I, Binder S, Stolba U.

Department of Ophthalmology, Rudolf Foundation Clinic, Juchgasse 25, 1030 Vienna,
Austria. Ilse.Krebs@wienkav.at

BACKGROUND: Combined photodynamic therapy (PDT) and intravitreal injection of
triamcinolone acetonide is a new option in the treatment of the neovascular form 
of age-related macular degeneration. With the aim of increasing safety and
efficacy we examined whether it is possible to administer the intravitreal
injection prior to PDT. METHODS: Patients with retinal angiomatous proliferation,
who have an unfavourable prognosis when treated with PDT alone, were recruited to
this study. Intravitreal injection of triamcinolone acetonide was applied 1 day
before PDT. Distance acuity testing, retinal thickness measurement and
fluorescein angiography were performed before treatment and 6 weeks and 3 months 
thereafter. RESULTS: Twenty-five patients were included: 18 were female, 7 male. 
Their mean age was 79 years. The distance acuity was 68 letters before treatment 
and at the follow-up examinations. The retinal thickness decreased significantly 
from mean 470.8 microm to 335.4 microm at week 6 and 360.8 microm at month 3. At 
month 3, 48% showed signs of activity in the fluorescein angiography needing
retreatment. Visualisation of the fundus was not reduced by the triamcinolone
crystals. DISCUSSION: PDT was possible without difficulty after intravitreal
injection of triamcinolone acetonide. Stabilisation of the visual acuity was
possible, although only eyes with retinal angiomatous proliferation were
included.

PMID: 16331486 [PubMed - indexed for MEDLINE]

1671: Eur J Ophthalmol. 2005 Nov-Dec;15(6):774-81.

Topographic angiography and optical coherence tomography: a correlation of
imaging characteristics.

Ahlers C, Michels S, Elsner H, Birngruber R, Pruente C, Schmidt-Erfurth U.

University Eye Hospital Vienna, Vienna, Austria.

PURPOSE: Topographic angiography (TAG) using confocal scanning laser angiography 
and optical coherence tomography (OCT) are new imaging modalities that have been 
introduced during recent years. OCT and TAG imaging were compared to specify the 
characteristics of each imaging modality. METHODS: TAG using fluorescein
angiography (FA) provides a three-dimensional profile of the vascular structures 
based on the analysis of a set of 32 confocal images over a depth of 4 mm. OCT
provides cross-sectional images of the neurosensory retina and the retinal
pigment epithelium-choriocapillary complex (RPE-CC). The authors compared and
evaluated both modalities in 10 patients with predominantly classic choroidal
neovascularization (CNV), 10 patients with serous pigment epithelial detachment
(PED), and 10 patients with geographic RPE atrophy, all secondary to age-related 
macular degeneration (ARMD). RESULTS: In patients with classic CNV, TAG detected 
neovascular structures and delineated their configuration. In PEDs pooling of
extravascular fluid is demonstrated, and in geographic RPE atrophy TAG showed
reduced choroidal perfusion. Classic CNV was demonstrated by OCT as a
hyperreflective band at the level of the RPE-CC, and PED showed a dome-shaped RPE
detachment. In geographic RPE atrophy, OCT imaged loss of the RPE band and had an
increased depth resolution. CONCLUSIONS: TAG and OCT are useful imaging
modalities in the evaluation of ARMD cases. TAG visualizes the vascular
configuration and dynamic perfusion and leakage changes. OCT is able to document 
intra-, subretinal, and sub-RPE fluid accumulation secondary to CNV. Both
modalities may provide further valuable insight into ARMD pathogenesis, enhance
diagnostic quality, and improve the assessment of therapeutic effects.

Publication Types: 
    Case Reports
    Comparative Study

PMID: 16329065 [PubMed - indexed for MEDLINE]

1672: Eur J Ophthalmol. 2005 Nov-Dec;15(6):768-73.

Magnification requirement after photodynamic therapy with verteporfin for
subfoveal predominantly classic choroidal neovascularization due to age-related
macular degeneration.

Thoelen AM, Bernasconi PP, Buser F, Fierz AB, Messmer EP.

Augenklinik Stadtspital Triemli Zurich, Switzerland.
heidy.thoelen@triemli.stzh.ch

PURPOSE: To prospectively assess the magnification requirement after repeat
photodynamic therapy (PDT) with verteporfin in patients with predominantly
classic subfoveal choroidal neovascularization (CNV) due to age-related macular
degeneration (AMD). METHODS: A total of 103 patients were treated for the first
time with PDT between November 1999 and September 2002. These patients were
followed up at 3-month intervals for a minimum of 12 months. In addition to the
usual investigations undertaken during PDT therapy, the magnification requirement
was determined, under standardized conditions, using the SZB test developed by
the Swiss Central Association for Blindness. RESULTS: A stable lesion with a
stable magnification requirement was achieved in 86 (83.5%) patients; these
patients were followed up for 24.8 months (range 12 to 36 months). At the time of
the last follow-up examination, the magnification requirement compared with
baseline was < 3 log units higher in 46 patients (53.5%) and > or = 3 log units
higher in the remaining 40 patients (46.5%). Seventy-four (86%) of these 86
patients had a magnification requirement of < or = 8x. Stability was not achieved
in 17 (16.5%) patients; up to the last examination these patients had been
followed up for 12 to 30 months (mean 20.8). At the time of the most recent
examination, 7 (41.2%) patients had a higher magnification requirement of < 3 log
units while 10 (58.8%) had changed by > or = 3 log units. Sixteen patients (94%) 
had a magnification requirement of < or = 8x. CONCLUSIONS: PDT with verteporfin
helps achieve stability without severe impairment in reading ability in most
patients with predominantly classic subfoveal CNV due to AMD.

PMID: 16329064 [PubMed - indexed for MEDLINE]

1673: Eur J Ophthalmol. 2005 Nov-Dec;15(6):764-7.

Homocysteine, vitamin B12, and folic acid in age-related macular degeneration.

Nowak M, Swietochowska E, Wielkoszyński T, Marek B, Kos-Kudła B, Szapska B,
Kajdaniuk D, Głogowska-Szelág J, Siemińska L, Ostrowska Z, Kozioł H, Klimek J.

Pathophysiology Division, Department of Pathophysiology and Endocrinology,
Medical University of Silesia, Zabrze, Poland. nowak-mar@wp.pl

PURPOSE: Hyperhomocysteinemia is considered an independent risk factor for
atherosclerosis and thrombosis. The purpose of this study was to evaluate plasma 
homocysteine, red blood cell folate, plasma folate, and plasma vitamin B12
concentration in patients with exudative age-related macular degeneration (ARMD).
METHODS: The participants of this study included 30 patients aged 60 to 71 years 
(mean age 66.2+/-3.6) with exudative ARMD. Plasma homocysteine levels were
determined by high performance liquid chromatography (HPLC). Red blood cell
folate, plasma folate, and plasma vitamin B12 concentration were determined using
a standard kit (Dualcount Solid Phase No Boill radioassay kit for B12/folic acid,
DPC Diagnostic, USA) by radioassay method. RESULTS: The plasma concentration of
Hcy (14.88+/-6.23 micromol/L) in ARMD patients was significantly increased
(p<0.0001) compared with the control group (8.72+/-3.34 micromol/L). We found not
a significant decrease of the plasma vitamin B12 concentration in the ARMD group 
(476.88+/-220.91 pg/mL) compared with the control group (527.08+/-208.97 pg/mL). 
Red blood cell folate (158.44+/-56.30 ng/mL) and plasma folate (6.5+/-3.4 ng/mL) 
in ARMD patients were also not significantly decreased when compared with the
control group (183.86+/-59.33 ng/mL and 7.93+/-5.05 ng/mL). CONCLUSIONS:
Hyperhomocysteinemia might be one of the risk factors for the exudative form of
ARMD.

PMID: 16329063 [PubMed - indexed for MEDLINE]

1674: Eur J Ophthalmol. 2005 Nov-Dec;15(6):759-63.

Fluorescein angiography and indocyanine green angiography for identifying occult 
choroidal neovascularization in age-related macular degeneration.

Pece A, Sannace C, Menchini U, Virgili G, Galli L, Isola V, Brancato R.

Department of Ophthalmology, Hospital of Melegnano, Predabissi (MI), Italy.
pece.retina@mclink.it

PURPOSE: To assess whether fluorescein angiography (FA) alone without indocyanine
green angiography (ICGA) can identify and localize occult choroidal
neovascularization (CNV) in age-related macular degeneration (ARMD). METHODS:
Seventy-nine eyes of 77 consecutive patients with occult CNV were evaluated
independently by two skilled physicians at first with FA alone and then with FA
combined with ICGA by fundus camera. RESULTS: The agreement between FA and ICGA
was 73% and 68% for the two physicians (K=0.585 and 0.512, respectively). The
first operator correctly identified 20/27 as plaque CNV; six had different sizes 
and locations. The second operator identified 25/30, with one mistaken for size
and location. For focal CNV the first operator identified 34/39, and the second
one 23/35. CONCLUSIONS: Comparing the FA results with ICGA, CNV was correctly
identified in about 60% of cases. Therefore, ICGA should be considered an
indispensable diagnostic test to identify the presence, the type, and the
location of occult CNV.

Publication Types: 
    Comparative Study

PMID: 16329062 [PubMed - indexed for MEDLINE]

1675: Eur J Ophthalmol. 2005 Nov-Dec;15(6):746-50.

Posterior sub-tenon triamcinolone for refractory diabetic macular edema: a
randomized clinical trial.

Entezari M, Ahmadieh H, Dehghan MH, Ramezani A, Bassirnia N, Anissian A.

Department of Ophthalmology, Emam Hossein Medical Center, Tehran, Iran.
entezari@negah-eye-center.com

PURPOSE: To evaluate the effect of posterior sub-tenon triamcinolone acetonide
(TA) injection on clinical, angiographic, and optical coherence tomographic (OCT)
parameters in refractory diabetic macular edema (DME). METHODS: In a
double-masked placebo-controlled clinical trial, 64 eyes were randomly assigned
to two groups. The treatment group (32 eyes) received 40 mg posterior sub-tenon
injection of TA and the placebo group (32 eyes) received subconjunctival
injection of a placebo. The injections were repeated after 2 months in both
groups. Complete ophthalmologic examination, fluorescein angiography, and OCT
were performed before intervention and after 4 months. Quantitative measurement
of angiographic variables such as the amount of hard exudates (HE), size of
foveal avascular zone (FAZ), and leakage severity was performed by computer,
using Photoshop software. RESULTS: Initial best-corrected visual acuity (VA) was 
0.93+/-0.39 logMAR in the placebo group and 0.75+/-0.38 logMAR in the treatment
group. At 4 months, corrected VA was 0.88+/-0.48 logMAR in the controls versus
0.71+/-0.42 logMAR in the cases. Mean central macular thickness measured by OCT
before and 4 months after injection was 392 and 377 microns in the treatment
group and 388 and 357 microns in the placebo group, respectively. No
statistically significant difference was detected between the two groups. The
difference was also not significant in HE, FAZ, and leakage in the angiograms.
CONCLUSIONS: Two injections of posterior sub-tenon TA had no therapeutic effect
on refractory DME.

Publication Types: 
    Randomized Controlled Trial

PMID: 16329060 [PubMed - indexed for MEDLINE]

1676: Doc Ophthalmol. 2005 Mar-May;110(2-3):271-5.

Pattern visual evoked potentials in eyes with disc swelling due to cat scratch
disease-associated neuroretinitis.

Chai Y, Yamamoto S, Hirayama A, Yotsukura J, Yamazaki H.

Department of Ophthalmology and Visual Science, Chiba University Graduate School 
of Medicine, Chiba, Japan.

PURPOSE: To evaluate optic nerve function by pattern visual evoked potentials
(VEPs) in eyes with optic disc swelling due to neuroretinitis associated with cat
scratch disease (CSD). METHODS: Four eyes of four patients with marked optic disc
swelling resembling optic neuritis but diagnosed serologically as CSD received
systemic steroid treatment. VEPs elicited by black and white checkerboard stimuli
created on a TV monitor were recorded before the treatment. RESULTS: The visual
acuity (VA) in the affected eyes was decreased to 20/50 in two eyes and finger
counting in two eyes at their initial visits. Ophthalmoscopic examination
revealed neuroretinitis characterized by severe optic disc swelling,
chorioretinal exudates, and macular edema in all eyes. Anti-Bartonella henselae
serum antibody was markedly elevated in all patients confirming the diagnosis of 
CSD. The P100 of the transient VEPs was only mildly reduced without a delay in
the implicit times in three eyes and only slightly delayed in the other eye. The 
steady-state VEPs were mildly reduced in two eyes and phase-reversed in other two
eyes. The VA fully recovered after systemic steroid treatment in all patients.
CONCLUSIONS: Although all examined patients showed marked swelling of the optic
disc and visual decrease, the pattern VEPs were not affected as severely as in
idiopathic optic neuritis. However, the degree of change of the pattern VEPs
varied among patients.

Publication Types: 
    Comparative Study

PMID: 16328936 [PubMed - indexed for MEDLINE]

1677: Doc Ophthalmol. 2005 Mar-May;110(2-3):237-46.

Alcohol- and light-induced electro-oculographic responses in age-related macular 
degeneration & central serous chorioretinopathy. alcohol- and light-induced EOG
responses in ARMD & CSC.

Wu KH, Marmor MF.

Department of Ophthalmology, Stanford University Medical Center, CA 94305-5308,
USA.

The non-photic electro-oculographic (EOG) response induced by alcohol has been
proposed as an indicator of retinal pigment epithelial (RPE) integrity, and
reported to be abnormal in age-related macular degeneration (ARMD). To evaluate
this proposal, we have measured the alcohol-EOG as well as the ISCEV-standard EOG
in patients with ARMD (n=11 patients, 4 eyes with drusen, 8 eyes with 'dry' and 7
eyes with 'wet' lesions) and central serous chorioretinopathy (CSC, n=11
patients, 7 eyes with active and 6 eyes with inactive lesions), compared with 29 
normal controls. We recorded the alcohol-induced EOG response after a single oral
administration of ethanol at 160 mg/kg, followed by an ISCEV-standard EOG. Blood 
alcohol levels were monitored with a breath analyzer. We found that neither the
alcohol-EOG nor the light-induced EOG response showed any difference between
either ARMD or CSC patients and normal controls. Nor was there difference among
eyes of different ARMD or CSC subgroups. In addition, blood alcohol
concentrations near the time of the alcohol-EOG peak showed no obvious
relationship with peak/baseline ratios. These data suggest that neither the
alcohol- nor the light-induced EOG is a sensitive indicator of these diseases.

Publication Types: 
    Comparative Study

PMID: 16328932 [PubMed - indexed for MEDLINE]

1678: Gerontologist. 2005 Dec;45(6):747-53.

Psychosocial adaptation to visual impairment and its relationship to depressive
affect in older adults with age-related macular degeneration.

Tolman J, Hill RD, Kleinschmidt JJ, Gregg CH.

Department of Educational Psychology, University of Utah, Salt Lake City,
84112-9255, USA. jennifer.tolman@hsc.utah.edu

PURPOSE: In this study we examined psychosocial adaptation to vision loss and its
relationship to depressive symptomatology in legally blind older adults with
age-related macular degeneration (ARMD). DESIGN AND METHODS: The 144 study
participants were outpatients of a large regional vision clinic that specializes 
in the diagnosis and treatment of ARMD in older adults. They were administered a 
battery of cognitive and psychological screening instruments including the
Adaptation to Vision Loss Scale, the Short Portable Mental Status Questionnaire, 
and the short form of the Geriatric Depression Scale. RESULTS: A principal
components analysis of the Adaptation to Vision Loss Scale identified three
distinct adaptation factors, namely, acceptance of vision loss, negative impact
on relationships, and attitudes toward compensation. Of these, acceptance of
vision loss and attitudes toward compensation were positively associated with
depressive affect. In addition, self-reported use of outpatient rehabilitative
services was less frequent in those reporting greater depressive symptomatology. 
IMPLICATIONS: These findings support the contention that depressive
symptomatology as measured by self-report in older adults with ARMD is mediated
by one's perceived sense of individual control as it relates to intrapersonal
factors underlying adaptation to profound vision loss in old age caused by ARMD.

PMID: 16326656 [PubMed - indexed for MEDLINE]

1679: Med Hypotheses. 2006;66(4):793-5. Epub 2005 Dec 2.

Potential role of uric acid in the molecular pathogenesis of age-related macular 
degeneration.

Mehryar M, Farvardin M, Hosseini H, Aslani M.

Ophthalmology Department, Shiraz University of Medical Sciences, Khalili
Hospital, Shiraz, Iran.

Age-related macular degeneration (ARMD) is the foremost cause of blindness among 
the elderly population in industrialised countries. Currently, there is no
effective treatment for the majority of patients. To develop new and effective
modes of therapy, understanding of the molecular basis of the disease is
mandatory. Many age-related pathologies have been attributed to cumulative
oxidative damage caused by reactive oxygen intermediates. There is growing
evidence that uric acid has antioxidant properties and it is a naturally
occurring antioxidant. Based on antioxidant role in pathogenesis of ARMD and
antioxidant properties of uric acid we conclude that altered uric acid metabolism
could play a role in ARMD damage and pathogenesis. Future research needs to
evaluate uric acid metabolism in ARMD patients.

PMID: 16326027 [PubMed - indexed for MEDLINE]

1680: Ophthalmology. 2005 Dec;112(12):2081-7.

Comment in:
    Ophthalmology. 2006 Aug;113(8):1471.e1-2; author reply 1471-2.

Long-term results of submacular surgery combined with macular translocation of
the retinal pigment epithelium in neovascular age-related macular degeneration.

MacLaren RE, Bird AC, Sathia PJ, Aylward GW.

Moorfields Eye Hospital, London, United Kingdom.

PURPOSE: To provide long-term (> or =5 years) follow-up data on patients who had 
previously undergone macular retinal pigment epithelium (RPE) translocation
surgery for choroidal new vessels (CNVs) associated with age-related macular
degeneration. DESIGN: Retrospective interventional case series. PARTICIPANTS:
Four of 9 patients who originally underwent surgery and whose results were
reported after 2 years of follow-up were reviewed again 5 to 6 years after
surgery. METHODS: All surviving patients from the original trial were contacted, 
and those who consented to full ocular examination were called in for review.
Examination included best-corrected visual acuity (VA), optical coherence
tomography (OCT), fundus autofluorescence, fluorescein angiography (FA), and
indocyanine green angiography. MAIN OUTCOME MEASURES: Long-term success of RPE
translocation was assessed by VA, imaging, angiography, and maintenance of
overlying foveal fixation. Comparisons were made to the original 2-year follow-up
data previously published. RESULTS: Over the long term, VA had declined further
in 3 patients and improved slightly in 1 patient. Significantly, all 4 patients
had lost foveal fixation and autofluorescence of translocated RPE, which had been
present at the original 2-year follow-up assessment. The RPE graft, however,
seemed viable when assessed by OCT, FA, and indocyanine green angiography, and no
patient had suffered a recurrence of CNVs. CONCLUSIONS: In these 4 patients, RPE 
choroidal grafts had survived in the subfoveal space for at least 5 to 6 years,
but rescue of visual function had been transient. The long-term loss of foveal
fixation and graft autofluorescence might be explained by chronic photoreceptor
apoptosis, initiated by either surgery or the disease process itself. Caution
should be applied when drawing firm conclusions from similar studies that provide
data after only 2 years' follow-up.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16325706 [PubMed - indexed for MEDLINE]

1681: Ophthalmology. 2005 Dec;112(12):2061-9.

Time course and morphology of vascular effects associated with photodynamic
therapy.

Schmidt-Erfurth U, Niemeyer M, Geitzenauer W, Michels S.

Department of Ophthalmology, Medical University of Vienna, Vienna, Austria.

PURPOSE: To evaluate the time course and morphologic features of verteporfin
therapy-induced vascular effects using 3-dimensional topographic angiography
(TAG) in patients with choroidal neovascularization (CNV). DESIGN: Prospective
observational case series. PARTICIPANTS: Fifty-three eyes of 53 patients with
neovascular age-related macular degeneration and Treatment of Age-Related Macular
Degeneration with Photodynamic Therapy/Verteporfin in Photodynamic Therapy
characteristics were treated with verteporfin therapy using standard parameters. 
METHODS: Treatment effects were evaluated before and at 5 hours, 1 day, 1 week,
and 3 months after treatment by serial confocal fluorescein angiography (FA) and 
indocyanine green angiography (ICGA). The axial distribution of fluorescence at
each x-position and y-position within a tomographic scan of 32 images over a
depth of 4 mm was analyzed, and a 3-dimensional profile was generated. Changes at
the level of the CNV lesion and the collateral choroid were documented over time 
with respect to vascular closure, leakage resulting from vascular barrier
breakdown, and alteration of physiologic perfusion. MAIN OUTCOME MEASURES:
Three-dimensional imaging of exudation and nonperfusion. RESULTS: At baseline,
3-dimensional FA and ICGA imaging demonstrated a well-defined prominent CNV
complex. At 5 hours after verteporfin therapy, 3-dimensional FA identified an
extensive increase in hyperfluorescent prominence as well as lesion extension in 
most verteporfin-treated eyes (65%), resulting from increased permeability and
leakage due to a vascular barrier breakdown in the collateral choroid. Massive
exudation throughout the entire light-exposed area was still noted in most eyes 1
day after treatment. At 1 week, the exudative response, seen in 3-dimensional
imaging, had diminished substantially. Simultaneously, documented best by
3-dimensional ICGA, TAG demonstrated perfusion defects within the adjacent
choroid, which started as early as 1 day after verteporfin therapy and persisted 
during extended follow-up. Three-dimensional angiography identified the
morphologic features of hyperfluorescence and hypofluorescence more realistically
than conventional angiography. CONCLUSIONS: Three-dimensional angiography
demonstrates a characteristic sequence of changes in the vascular architecture of
the CNV lesion and the collateral choroid after verteporfin therapy. Choroidal
neovascularization occlusion is associated with immediate massive exudation and
is followed by occlusive effects within the collateral choroid. Knowledge of the 
time course and mechanisms of phototoxic events should help to develop
appropriate combination treatment strategies.

PMID: 16325705 [PubMed - indexed for MEDLINE]

1682: Exp Eye Res. 2006 May;82(5):741-52. Epub 2005 Dec 1.

Mouse models of age-related macular degeneration.

Elizabeth Rakoczy P, Yu MJ, Nusinowitz S, Chang B, Heckenlively JR.

Lions Eye Institute, Centre for Ophthalmology and Visual Science, Department of
Molecular Opthalmology, The University of Western Australia, 2 Verdun Street,
Nedland Western Australia 6009, Australia. rakoczy@cyllene.uwa.edu.au

Recent advances in genetic technologies have greatly accelerated our ability to
find disease-related genes and to generate animal models. The availability of
ocular tissues with known genetic diseases are greatly contributing to our
understanding of retinal disease processes including age-related macular
degeneration (AMD), and panretinal and cone degenerations. While the macula is a 
highly specialised area of the retina not present in many mammals, the use of
animal models such as mouse strains will give basic physiology and visual
processing genetics relevant to human AMD. This review aims to provide a
framework for better understanding some of the existing animal models and the
knowledge that has been derived from their evaluations.

Publication Types: 
    Research Support, N.I.H., Extramural
    Review

PMID: 16325179 [PubMed - indexed for MEDLINE]

1683: Exp Eye Res. 2006 May;82(5):798-806. Epub 2005 Dec 1.

Vitreous and aqueous concentrations of proangiogenic, antiangiogenic factors and 
other cytokines in diabetic retinopathy patients with macular edema: Implications
for structural differences in macular profiles.

Patel JI, Tombran-Tink J, Hykin PG, Gregor ZJ, Cree IA.

Institute of Ophthalmology, London, UK. jigs37@hotmail.com

The aim of the study was to determine anatomical and growth factor profiles in
patients with clinically significant macular oedema (CSMO) undergoing pars plana 
vitrectomy (PPV). Twenty patients with moderate nonproliferative diabetic
retinopathy (NPDR) with persistent CSMO underwent PPV. Patients had baseline and 
postoperative clinical assessment including Ocular Coherence Tomography (OCT).
Baseline vitreous and aqueous and serial postoperative aqueous samples were
analysed for vascular endothelial growth factor-A (VEGF-A), pigment epithelium
derived Factor (PEDF) and other factors (pg/ml) including hepatocyte growth
factor, MMP 9, soluble flt-1 Receptor, and TGF beta1 by ELISA. Vitreous from
patients with full thickness macular holes (8) and proliferative diabetic
retinopathy (22) were collected for comparison as controls. Vitreous VEGF-A
concentration in the NPDR group was 957 pg/ml compared to 239 pg/ml in the macula
hole (FTMH) control (p < 0.0001) and 596 pg/ml compared to PDR (p = 0.006). The
median diabetic vitreous PEDF concentration was 1.36 microg/ml (FTMH 2.6
microg/ml p = 0.05). In NPDR, it was higher (1.59 microg/ml) than PDR (1.27
microg/ml) p = 0.02. There were changes to the HGF, soluble flt-1 Receptor and
TGF b1 concentrations in the NPDR compared to either PDR or the normal state. In 
CSMO, two OCT profiles were identified: dome-shaped macular elevation (Group 1)
(n = 4) and diffuse-low elevation profile (Group 2) (n = 16) which also showed
differences in the postoperative median aqueous VEGF concentrations despite
macular volume decreasing for both. The results suggest that there is an
up-regulation of VEGF in the vitreous of the diabetic eye with a reciprocal
decrease in PEDF. The structural and molecular differences between the two OCT
macular profiles may explain the varying response to PPV in patients with diffuse
CSMO.

PMID: 16324700 [PubMed - indexed for MEDLINE]

1684: Ocul Immunol Inflamm. 2005 Dec;13(6):469-70.

Somatostatin for Uveitic Cystoid Macular Edema (CME).

Papadaki T, Zacharopoulos I, Iaccheri B, Fiore T, Foster CS.

Ocular Immunology and Uveitis Service, Massachusetts Eye and Ear Infirmary,
Harvard Medical School, Boston, MA, USA.

PURPOSE: To report the favorable response of bilateral recalcitrant uveitic
cystoid macular edema (CME) to treatment with a somatostatin analog. METHODS:
Medical ophthalmic history and the results of ophthalmic examinations were
recorded. Fluorescein angiography (FA) studies were reviewed. RESULTS: A
52-year-old white female with intermediate uveitis developed bilateral
recalcitrant CME. Treatment with subcutaneous injections of the somatostatin
analog octreotide resulted in partial resolution of the CME and improvement of
visual acuity. CONCLUSIONS: Somatostatin may play a role in the treatment of CME 
secondary to uveitis.

Publication Types: 
    Case Reports

PMID: 16321893 [PubMed - indexed for MEDLINE]

1685: J Rehabil Res Dev. 2005 Jul-Aug;42(4):459-70.

Comparison of low-vision reading with spectacle-mounted magnifiers.

Watson GR, Maino J, De l'aune W.

Atlanta Department of Veterans Affairs (VA) Medical Center, Rehabilitation
Research and Development, Center on Aging and Vision Loss, Atlanta, GA 30033,
USA. Gale.Watson@med.va.gov

Reading is the most common goal among persons with age-related macular
degeneration and other retinal diseases that lead to macular loss, as well as the
functional task most affected by the resulting central scotomas. This project
determined whether reading ability is different when persons with macular loss
read with a new hybrid-diffractive spectacle magnifier versus a
refractive-aspheric spectacle magnifier and an aplanatic spectacle magnifier.
After subjects completed a low-vision examination, we assigned them to groups
that compared different types of spectacle magnifiers and assessed their reading 
acuity, speed, critical print size (print size large enough to provide a
subject's best fluent reading), accuracy, and comprehension. Subjects completed
visual analog scales to indicate their perceptions of satisfaction with reading, 
comfort with reading, and cosmesis (comfort with allowing others to see them
read) and were asked which of the compared spectacle magnifiers they preferred
for prescription. We subjected the data to paired t-tests to ascertain whether
differences existed in subjects' reading ability and perceptions between the
types of reading devices. Subjects' reading comprehension, perception of
satisfaction, and perception of cosmesis were significantly better with the
hybrid-diffractive lens than with the refractive-aspheric lens. Although
subjects' critical print size was significantly better with the aplanatic lens
than with the hybrid-diffractive lens, functional reading ability was not
significantly different. More subjects preferred the hybrid-diffractive lenses
for prescription. The hybrid-diffractive spectacle magnifiers are an important
addition to the optical-device armamentarium for reading with low vision.

Publication Types: 
    Comparative Study
    Evaluation Studies
    Research Support, U.S. Gov't, Non-P.H.S.

PMID: 16320142 [PubMed - indexed for MEDLINE]

1686: Adv Drug Deliv Rev. 2005 Dec 13;57(14):2092-8. Epub 2005 Nov 28.

Regulatory aspects of drug approval for macular degeneration.

Gryziewicz L.

Global Regulatory Affairs, Allergan, Inc., 2525 Dupont Drive, Irvine, CA
92612-1599, USA. Gryziewicz_Lewis@allegran.com

Age-related macular degeneration (AMD) is the leading cause of blindness in
developed countries with approximately 15 million people with the disease in the 
United States. AMD is characterized as a progressive degenerative disease of the 
macula. There are two forms of AMD: neovascular and non-neovascular. The
non-neovascular form of AMD is more common and leads to a slow deterioration of
the macula with a gradual loss of vision over a period of years. The neovascular 
form of the disease is responsible for the majority of cases of severe vision
loss and is due to proliferation of abnormal blood vessels behind the retina.
These blood vessels leak blood and fluid into the retina, which results in visual
abnormalities. The development of these abnormal blood vessels is due in part to 
the activity of VEGF (vascular endothelial growth factor) and its inhibition is
expected to impact on the onset and/or severity of vision loss associated with
the proliferation of abnormal blood vessels. Age-related macular degeneration is 
an underserved treatment population. Visudyne (verteporfin for injection),
Novartis Ophthalmics, is FDA approved for the treatment of patients with
predominantly classic subfoveal choroidal neovascularization due to age-related
macular degeneration, pathologic myopia or presumed ocular histoplasmosis.
Pegaptanib sodium (Macugen, Eyetech Pharmaceuticals, Inc. and Pfizer, Inc.) is
indicated for the treatment of neovascular (wet) age-related macular
degeneration. This article will review the approval pathway for these two
products and that required of future products indicated for macular degeneration.

Publication Types: 
    Review

PMID: 16316706 [PubMed - indexed for MEDLINE]

1687: Nurs Times. 2005 Nov 15-21;101(46):30-3.

Using light to treat age-related macular degeneration.

Nosek J.

Wolverhampton Eye Infirmary.

Age-related macular degeneration (AMD) is a potentially blinding disease that can
be treated by verteporfin photodynamic therapy. This article discusses the
specialist ophthalmic nurse's role in the assessment, treatment and support of
patients with AMD, highlighting key elements in the care pathway and the benefit 
of prompt triage in safeguarding remaining vision.

PMID: 16315801 [PubMed - indexed for MEDLINE]

1688: Ophthalmol Clin North Am. 2005 Dec;18(4):561-7.

Anti-macular degeneration agents.

Rothen M, Jablon E, Monares G, Fontal MR, Alfaro DV 3rd.

Carolina Foundation for Macula Research and Education, Charleston, SC 29414, USA.

Anti-VEGF therapy is a promising new avenue for the treatment of ocular
neovascular diseases. Early preclinical data and recent clinical data support the
efficacy and safety of several novel anti-VEGF for NVAMD. Whether these novel
biologics are used on their own, in combination with previously available
therapies, or with newly developing therapies, they represent a new avenue in
treatment. These agents are highly selective in their targeted approaches, and
when administered appropriately , offer treatment with minimal damage to retinal 
tissue. In the future, biotherapeutic agents will certainly play a powerful role 
in the treatment of human choroidal neovascular membrane formation.

Publication Types: 
    Review

PMID: 16314219 [PubMed - indexed for MEDLINE]

1689: Curr Opin Investig Drugs. 2005 Nov;6(11):1159-67.

Retisert (Bausch & Lomb/Control Delivery Systems).

Lim LL, Smith JR, Rosenbaum JT.

Casey Eye Institute, Oregon Health & Science University, Portland, OR 97201, USA.
liml@ohsu.edu

Retisert (Envision TD), a sustained release intraocular implant containing
fluocinolone acetonide, has been developed and launched in the US by Bausch &
Lomb and Control Delivery Systems for the treatment of chronic non-infectious
uveitis affecting the posterior segment of the eye.

PMID: 16312138 [PubMed - indexed for MEDLINE]

1690: Am J Ophthalmol. 2005 Nov;140(5):948-9.

The effect of subtenon triamcinolone acetonide injection for diabetic macular
edema on retinal and choroidal circulation.

Mawatari Y, Koga T, Inumaru J, Hirata A, Fukushima M, Tanihara H.

Department of Ophthalmology and Visual Science, Graduate School of Medical
Sciences, Kumamoto University, Kumamoto, Japan.

PURPOSE: To evaluate changes in retinal and choroidal circulation after subtenon 
triamcinolone acetonide (TA) injection for diabetic macular edema. DESIGN:
Prospective interventional case series. METHODS: Thirteen eyes of 13 patients
with diabetic macular edema were studied. Fluorescein and indocyanine green
angiograms were performed at three periods: before the injection and 1 week and 6
months after subtenon injection of TA (40 mg). Retinal arteriovenous passage time
(as an indicator of retinal circulation) and choroidal tau (as an indicator of
early filling velocity of choroid) were obtained with image analysis software.
RESULTS: Choroidal tau values before and 1 week after subtenon TA injection were,
respectively, 3.2 +/- 0.4 and 4.0 +/- 0.7 seconds, which showed a significant
delay (P = .01, Wilcoxon signed-rank test). The delayed choroidal tau values
returned to pretreatment level at 6 months after TA injection. In contrast, the
arteriovenous passage time remained unchanged. CONCLUSION: Subtenon TA injection 
transiently influences choroidal blood flow.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16310489 [PubMed - indexed for MEDLINE]

1691: Am J Ophthalmol. 2005 Nov;140(5):924-6.

The three-year incidence of age-related macular degeneration: the "Pathologies
Oculaires Liées à l'Age" (POLA) prospective study.

Delcourt C, Lacroux A, Carrière I; POLA Study Group.

Institut National de la Santé et de la Recherche Médicale, Research Unit U593 for
Epidemiology, Public Health and Development, Université Victor Segalen Bordeaux
2, Bordeaux, France. delcourt@montp.inserm.fr

PURPOSE: To assess the 3-year incidence of age-related macular degeneration (AMD)
in a French population. DESIGN: The "Pathologies Oculaires Liées à l'Age" (POLA) 
Study, a population-based prospective cohort study. METHODS: Retinal photographs 
were graded according to the international classification. Early age-related
maculopathy (ARM) was defined by the presence of (1) soft indistinct drusen (>125
microm) and/or (2) soft distinct drusen (>125 microm) associated with pigmentary 
abnormalities. RESULTS: The 3-year incidence of AMD was 0.49% (95% confidence
interval [CI]: 0.13 to 0.85) and increased significantly with age, reaching 3.41%
(95% CI: 0 to 7.2) in participants aged 80 years or more. After adjustment for
age, eyes with early ARM at baseline were 78 times more at risk of developing AMD
than eyes without early ARM (OR = 78.4, 95% CI: 14.6 to 420.1). CONCLUSIONS: This
study confirms that AMD develops mainly in subjects aged 80 years or older, and
in subjects with early ARM.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16310477 [PubMed - indexed for MEDLINE]

1692: Adv Drug Deliv Rev. 2005 Dec 13;57(14):1994-2009. Epub 2005 Nov 23.

Wet age-related macular degeneration.

Kulkarni AD, Kuppermann BD.

Department of Ophthalmology, University of California, Irvine, 118 Med Surge I,
Irvine, CA 92697, USA.

Age-related macular degeneration (AMD) is the leading cause of irreversible
visual loss in industrialized nations for those age 65 and above. The majority of
patients with severe visual loss suffer from the wet form of AMD wherein there is
choroidal neovascularization (CNV) and associated manifestations such as retinal 
pigment epithelial detachment, subretinal hemorrhages, and fibrovascular
disciform scarring. The main focus on understanding the pathogenesis of CNV has
been on the hypothesis that the diffuse thickening of Bruch's membrane
predisposes it to develop cracks and in-growth of new vessels from
choriocapillaries with associated low-grade inflammatory response. Currently,
three types of treatments (laser photocoagulation, photodynamic therapy, and
anti-Vascular Endothelial Growth Factor (VEGF) therapy) have been demonstrated to
limit or delay loss of vision in patients. Only a minority of cases show
stabilization of vision and a small proportion of cases show significant
improvement in vision. This highlights the need for more and better pharmacologic
or other interventions, with the goal of lowering recurrence rates and preventing
the development of CNV in order to achieve better functional outcomes.

Publication Types: 
    Review

PMID: 16309781 [PubMed - indexed for MEDLINE]

1693: BMC Ophthalmol. 2005 Nov 25;5:27.

Intravitreal triamcinolone with transpupillary therapy for subfoveal choroidal
neovascularization in age related macular degeneration. A randomized controlled
pilot study [ISRCTN74123635].

Agurto-Rivera R, Diaz-Rubio J, Torres-Bernal L, Macky TA, Colina-Luquez J,
Papa-Oliva G, Jager RD, Martinez-Jardon S, Fromow-Guerra J, Quiroz-Mercado H.

Retina Service, Asociación Para Evitar la Ceguera, Mexico City, Mexico.
ricardo_agurto@yahoo.com

BACKGROUND: To assess the effect of intravitreal triamcinolone acetonide (iTA) as
an adjunctive treatment to transpupillary therapy (TTT) for new subfoveal
choroidal neovascular membranes (CNV) in age-related macular degeneration (AMD). 
METHODS: This prospective randomized controlled pilot study comprised 26 patients
scheduled to receive TTT, due to either absent indications for photodynamic
therapy or financial issues. Patients were assigned into; Group A (n = 14)
received TTT alone and Group B (n = 12) received iTA (4 mg) followed by TTT
within one week. Follow ups were at 2 weeks, and 1, 3 and 6 months for;
best-corrected visual acuity (BCVA) by ETDRS chart at 4 meters, intraocular
pressures (IOP), fluorescein angiography (FAG), and central foveal thickness by
optical coherence tomography (OCT). RESULTS: All 26 patients completed 6 months
of follow ups. The average age for both groups was 74 years. Occult CNV formed
64% and 41%; classis/predominately classic 21% and 16.6%; and minimally classic
15% and 42.4% of group A and B respectively. At baseline; the mean BCVA was 0.045
for group A and 0.04 for group B; mean CNV size was 6.15 disc diameter (DD) and
2.44 DD; mean OCT foveal thickness was 513 um and 411 um for group A and B
respectively with no statistical differences (P = 0.8, 0.07, and 0.19). At six
months the proportion of patients gained > or = 1 lines was 14% and 25% (P =
0.136) and stabilization was 86% and 66% (P = 0.336); the mean size of the CNV
was 5.63 DD and 2.67 DD (P = 0.162); rate of CNV closure was 64% and 83% (P =
0.275); and the mean OCT central foveal thickness was 516.36 um and 453.67 um (P 
= 0.341), for group A and B respectively. CONCLUSION: The use of iTA as an
adjunctive to TTT for new subfoveal CNV in AMD showed a tendency towards better
functional results. However due to the small sample size of the study a
statistically significant results could not be reached.

Publication Types: 
    Randomized Controlled Trial

PMID: 16309554 [PubMed - indexed for MEDLINE]

1694: Invest Ophthalmol Vis Sci. 2005 Dec;46(12):4788-95.

Synaptic pathology, altered gene expression, and degeneration in photoreceptors
impacted by drusen.

Johnson PT, Brown MN, Pulliam BC, Anderson DH, Johnson LV.

Center for the Study of Macular Degeneration, Neuroscience Research Institute,
University of California, Santa Barbara, California 93106-5060, USA.
p_johnso@lifesci.ucsb.edu

PURPOSE: Drusen are risk factors for age-related macular degeneration and have
been shown to negatively impact cells of the RPE and retina. In this study, the
effects of drusen on the synaptic machinery of retinal photoreceptors are
investigated. METHODS: Human donor eye tissue containing retina, RPE, and choroid
was processed for confocal immunofluorescence microscopy, laser capture
microdissection, and light and electron microscopy. Tissue sections were
immunostained with a panel of antibodies to synapse-associated proteins.
Populations of photoreceptors over drusen and normal populations of
photoreceptors were microdissected from fresh frozen tissue, RNA was purified,
and quantitative PCR was performed to compare relative levels of gene expression.
RESULTS: The number of photoreceptor synaptic terminals is reduced in regions of 
the outer plexiform layer over drusen, synaptic proteins are mislocalized in
photoreceptor cells, and synaptic terminals are often observed within the outer
nuclear layer. Photoreceptors over drusen also increase expression of the stress 
response proteins apolipoprotein E and alphaB-crystallin. Abnormal immunolabeling
patterns are not restricted to photoreceptors directly over drusen but are also
observed in cells flanking drusen. Gene expression analysis confirms reductions
in the expression of genes coding for synapse-associated proteins and signal
transduction proteins and increases in the expression of apolipoprotein E and
alphaB-crystallingene transcripts. Ultrastructural analysis of photoreceptor
synaptic terminals over drusen reveals significant abnormalities, and cell counts
show a reduction in photoreceptor density directly over, and lateral to, drusen
of all sizes. CONCLUSIONS: Photoreceptors overlying and flanking drusen exhibit
morphologic and biochemical signs of degeneration. The expression of
synapse-associated proteins decreases in photoreceptor synaptic terminals,
whereas the expression of stress-response proteins increases. Reductions in
photoreceptor cell densities over, and flanking, drusen suggest that these
degenerative effects eventually result in the death of photoreceptors.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16303980 [PubMed - indexed for MEDLINE]

1695: Invest Ophthalmol Vis Sci. 2005 Dec;46(12):4722-7.

Adaptation responses in early age-related maculopathy.

Feigl B, Brown B, Lovie-Kitchin J, Swann P.

Centre for Health Research, School of Optometry, Queensland University of
Technology, Brisbane, Australia. b.feigl@qut.edu.au

PURPOSE: To investigate the global-flash multifocal electroretinogram (mfERG) in 
early age-related maculopathy (ARM). METHODS: Thirty-two eyes from 20 healthy
control subjects and 12 age-matched subjects with early ARM were investigated
with the conventional and the global-flash mfERG. Early ARM subjects were graded 
according to an international grading system. The conventional mfERG consisted of
103 hexagons flickering according to a pseudorandom m-sequence. The global-flash 
mfERG paradigm used four frames starting with the conventional m-sequence
stimulation, followed by a dark frame, a global flash, and another dark frame.
The responses include a direct response (DR) and a later induced component (IC). 
The first-order kernel peak-to-trough response densities of the conventional
mfERG (N1P1), the global-flash DR and IC, and the implicit times of the
conventional P1, global-flash DR, and IC peak were analyzed after averaging the
results into five groups according to five field locations: a central area and
four quadrants. RESULTS: There was a significant reduction of the global-flash
mfERG DR response density (P < or = 0.05) in the early ARM group compared with
the control group. Neither the IC response density nor DR and IC implicit times
were significantly impaired. However, the superior retina showed longer implicit 
times than did the inferior retina for the DR in the early ARM group. There was
no significant correlation between funduscopic features and the central averaged 
responses of the global-flash mfERG (for the DR response density: r = -0.19, P = 
0.3, or for the DR implicit time: r = -0.18, P = 0.3). None of the conventional
mfERG parameters was significantly different between the two groups. CONCLUSIONS:
The global-flash mfERG detects deficits in early ARM before the conventional
mfERG. Retinal ischemia may play a role in producing function impairment in ARM.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16303971 [PubMed - indexed for MEDLINE]

1696: Invest Ophthalmol Vis Sci. 2005 Dec;46(12):4707-11.

Circadian fluctuations of macular edema in patients with morning vision blurring:
correlation with arterial pressure and effect of light deprivation.

Paques M, Massin P, Sahel JA, Gaudric A, Bergmann JF, Azancot S, Lévy BI, Vicaut 
E.

Ophthalmology Departments of the Fondation Ophtalmologique Rothschild, Paris,
France. michel.paques@laposte.net

PURPOSE: This study explored the causes of vision fluctuations in patients with
chronic macular edema. METHODS: Fifteen patients (16 eyes) with vision blurring
at awakening due to post-central retinal vein occlusion (CRVO) macular edema
underwent three examination sessions over 24 hours (at 7 PM, immediately after
awakening at 7 AM, and at 7 PM), which comprised assessment of Early Treatment
Diabetic Retinopathy Study score and measurement of macular thickness (MT) by
optical coherence tomography. Ocular perfusion pressure was calculated from
ambulatory arterial pressure measurement. In addition, after the 7 AM
measurements, the patients were randomly selected for monocular light deprivation
during the day to evaluate the role of retinal illumination in these
fluctuations. RESULTS: Circadian fluctuation of MT was documented in all
patients. At 7 AM, mean visual acuity (VA) was worse (mean +/- SD of the
difference: 6.5 +/- 7.2 points; P < 0.002) and mean MT was higher (57.4 +/- 34
microm; P < 0.001) than at 7 PM. Fluctuations of MT were correlated to
fluctuation of arterial pressure (P = 0.05), but were not influenced by monocular
light deprivation. CONCLUSIONS: In most patients complaining of visual
fluctuations due to macular edema secondary to CRVO, MT and VA were found to
undergo a circadian cycle. These short-term anatomic and functional variations
were associated with arterial pressure variations (that is, macular thickening
was inversely correlated to the arterial pressure drop during the night), but
were not due to light deprivation.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16303968 [PubMed - indexed for MEDLINE]

1697: Invest Ophthalmol Vis Sci. 2005 Dec;46(12):4442-9.

Risk factors for age-related macular degeneration: findings from the Andhra
Pradesh eye disease study in South India.

Krishnaiah S, Das T, Nirmalan PK, Nutheti R, Shamanna BR, Rao GN, Thomas R.

L. V. Prasad Eye Institute, Banjara Hills, Hyderabad, India. krishnaiah@lvpei.org

PURPOSE: To assess prevalence, potential risk factors, and population
attributable risk percentage (PAR%) for age-related macular degeneration (AMD) in
the Indian state of Andhra Pradesh. METHODS: A population-based study, using a
stratified, random, cluster, systematic sampling strategy, was conducted in the
state of Andhra Pradesh in India from 1996 to 2000. Participants from 94 clusters
in one urban and three rural areas representative of the population of Andhra
Pradesh underwent a detailed interview and a detailed dilated ocular evaluation
by trained professionals. In this report, the authors present the prevalence
estimates of AMD and examine the association of AMD with potential risk factors
in persons aged 40 to 102 years (n = 3723). AMD was defined according to the
international classification and grading system. Standard bivariate and
multivariate analyses were performed to identify the potential risk factors for
AMD. PAR% was calculated by Levin's formula. RESULTS: AMD was present in 71
subjects--an age-gender-area-adjusted prevalence of 1.82% (95% confidence
interval [CI], 1.39%-2.25%). Risk factors that were significant in bivariate
analyses were considered for multivariate logistic regression analysis.
Multivariate analysis showed that the adjusted prevalence of AMD was
significantly higher in those 60 years of age or older (odds ratio [OR], 3.55;
95% CI, 1.61-7.82) and history of prior cigar smoking (OR, 3.29; 95%CI,
1.42-7.57). Presence of cortical cataract and prior cataract surgery were
significantly associated with increased prevalence of AMD (adjusted OR, 2.87; 95%
CI, 1.57-5.26 and 3.79; 95% CI, 2.1-6.78), respectively. The prevalence of AMD
was significantly lower in light alcohol drinkers (adjusted OR, 0.38; 95% CI,
0.19-0.76) compared with nondrinkers. The PAR% for hypertension and heavy cigar
smoking was 10% and 14%, respectively, in this population. CONCLUSIONS: The
prevalence of AMD in this south Indian population is similar to those reported in
other developed countries. Abstinence from smoking may reduce the risk of AMD in 
this population.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16303932 [PubMed - indexed for MEDLINE]

1698: Invest Ophthalmol Vis Sci. 2005 Dec;46(12):4402-8.

Correlation of clinical and genetic findings in Hungarian patients with Stargardt
disease.

Hargitai J, Zernant J, Somfai GM, Vamos R, Farkas A, Salacz G, Allikmets R.

2nd Department of Ophthalmology, Semmelweis University, Budapest, Hungary.

PURPOSE: Autosomal recessive Stargardt disease (arSTGD) presents with substantial
clinical and genetic heterogeneity. This study was conducted to correlate
foveolar thickness (FT) and total macular volume (TMV), measured by optical
coherence tomography (OCT), with other clinical characteristics and with specific
genetic variation in Hungarian patients with arSTGD. METHODS: After a standard
ophthalmic workup, both eyes of 35 patients with STGD from Hungary and of 25
age-matched healthy control subjects were tested with OCT. FT and TMV were
measured automatically with the OCT mapping software in the nine Early Treatment 
Diabetic Retinopathy Study areas of 3500 microm in diameter. All patients were
screened for mutations by a combination of the ABCR400 microarray and direct
sequencing. RESULTS: The patients with STGD presented with markedly thinned
retina in the foveola and decreased macular volume, 72 microm and 1.69 mm3,
respectively, compared with 169 microm and 2.48 mm3 in the normal subjects,
respectively. Statistically significant correlation was observed between visual
acuity (VA) and TMV and between VA and FT. Disease-associated mutations were
detected in 23 (65.7%) of 35 patients, including 48.5% with both alleles and
17.2% with one allele. The most frequent ABCA4 alleles in Hungarian patients with
STGD were L541P/A1038V (in 28% of all patients), G1961E (20%) and IVS40+5G-->A
(17%). Specific genotypes correlated with some phenotypic features and allowed
for predictions of the disease progression. CONCLUSIONS: Hungarian patients with 
STGD presented with extensive foveolar thinning and macular volume loss. Genetic 
analysis detected several ABCA4 alleles at high frequency in the cohort of
patients, suggesting founder effect(s). Unusually homogeneous distribution of
disease-associated mutations aided genotype-phenotype correlation analyses in
this population.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16303926 [PubMed - indexed for MEDLINE]

1699: PLoS Med. 2006 Jan;3(1):e5. Epub 2005 Nov 29.

CFH Y402H confers similar risk of soft drusen and both forms of advanced AMD.

Magnusson KP, Duan S, Sigurdsson H, Petursson H, Yang Z, Zhao Y, Bernstein PS, Ge
J, Jonasson F, Stefansson E, Helgadottir G, Zabriskie NA, Jonsson T, Björnsson A,
Thorlacius T, Jonsson PV, Thorleifsson G, Kong A, Stefansson H, Zhang K,
Stefansson K, Gulcher JR.

DeCODE Genetics, Reykjavik, Iceland. kristinn.p.magnusson@decode.is

BACKGROUND: Age-related macular degeneration (AMD) is the most common cause of
irreversible visual impairment in the developed world. The two forms of advanced 
AMD, geographic atrophy and neovascular AMD, represent different pathological
processes in the macula that lead to loss of central vision. Soft drusen,
characterized by deposits in the macula without visual loss, are considered to be
a precursor of advanced AMD. Recently, it has been proposed that a common
missense variant, Y402H, in the Complement Factor H (CFH) gene increases the risk
for advanced AMD. However, its impact on soft drusen, GA, or neovascular AMD--or 
the relationship between them--is unclear. METHODS AND FINDINGS: We genotyped 581
Icelandic patients with advanced AMD (278 neovascular AMD, 203 GA, and 100 with
mixed neovascular AMD/GA), and 435 with early AMD (of whom 220 had soft drusen). 
A second cohort of 431 US patients from Utah, 322 with advanced AMD (244
neovascular AMD and 78 GA) and 109 early-AMD cases with soft drusen, were
analyzed. We confirmed that the CFH Y402H variant shows significant association
to advanced AMD, with odds ratio of 2.39 in Icelandic patients (p = 5.9 x
10(-12)) and odds ratio of 2.14 in US patients from Utah (p = 2.0 x 10(-9)) with 
advanced AMD. Furthermore, we show that the Y402H variant confers similar risk of
soft drusen and both forms of advanced AMD (GA or neovascular AMD). CONCLUSION:
Soft drusen occur prior to progression to advanced AMD and represent a
histological feature shared by neovascular AMD and GA. Our results suggest that
CFH is a major risk factor of soft drusen, and additional genetic factors and/or 
environmental factors may be required for progression to advanced AMD.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16300415 [PubMed - indexed for MEDLINE]

1700: Br J Ophthalmol. 2005 Dec;89(12):1627-30.

Comment in:
    Br J Ophthalmol. 2005 Dec;89(12):1549-51.

Increased expression of vascular endothelial growth factor associated with
accumulation of lipids in Bruch's membrane of LDL receptor knockout mice.

Rudolf M, Winkler B, Aherrahou Z, Doehring LC, Kaczmarek P, Schmidt-Erfurth U.

University of Schleswig-Holstein, Campus Kiel, Department of Ophthalmology,
Hegewisch-Strasse 2, 24105 Kiel, Germany. mirudolf@aol.com

AIM: To investigate the pathogenesis of age related macular degeneration (ARM)
with respect to lipid accumulation within Bruch's membrane (BrM) in a knockout
model with low density lipoprotein (LDL) receptor deficiency. METHODS: LDL
receptor deficient mice and C57BL/6 controls were fed a standard diet or a high
fat (HF) diet. Plasma total cholesterol (pTC) was determined. Eyes were examined 
by transmission electron microscopy. Immunohistochemical staining for VEGF was
performed. RESULTS: pTC were highest in LDL receptor deficient mice after HF diet
and elevated after standard diet compared to controls with and without HF diet.
While BrM of controls did not exhibit any visible changes, membrane bound
translucent particles were seen in all BrM of knockout mice. The amount of these 
particles was substantially increased and membranes were thickened after HF diet.
VEGF staining was positive in knockout mice only and was located in retinal
pigment epithelial cells, the outer plexiform layer, and photoreceptor inner
segments. Most intensive VEGF expression was documented after HF diet.
CONCLUSION: LDL receptor deficient mice exhibit an accumulation of lipid
particles in BrM which is further increased after fat intake. VEGF expression is 
found in the outer retinal layers of LDL receptor deficient mice and appears to
correlate with the amount of lipid particles present in BrM.

PMID: 16299144 [PubMed - indexed for MEDLINE]

1701: Br J Ophthalmol. 2005 Dec;89(12):1609-15.

Lower limits of fluorescein and indocyanine green dye for digital cSLO
fluorescence angiography.

Bindewald A, Stuhrmann O, Roth F, Schmitz-Valckenberg S, Helb HM, Wegener A, Eter
N, Holz FG.

Department of Ophthalmology, University of Bonn, Ernst-Abbe-Strasse 2, D-53127
Bonn, Germany.

BACKGROUND: With the advent of digital confocal scanning laser ophthalmoscopy it 
is possible to detect low levels of fluorescence. Here we used a novel confocal
scanning laser ophthalmoscope (cSLO) to determine lower limits of dye required
for fluorescein (FL) and indocyanine green (ICG) angiography. METHODS: A cSLO
(Heidelberg retina angiograph 2, Heidelberg Engineering, Dossenheim, Germany)
with an optically pumped solid state laser (488 nm) for FL and a diode laser (790
nm) for ICG angiography (FL/ICG-A) was used. 62 FL-As were performed in 53
patients and 45 ICG-As were performed in 39 patients with neovascular age related
macular degeneration. The volume and overall dye content of bolus injections was 
gradually tapered (FL: 500 mg, 250 mg, 200 mg, 166 mg, 100 mg; ICG: 25 mg, 20 mg,
15 mg, 10 mg, 5 mg, 2.5 mg), while dye concentrations were kept constant at 100
mg/ml for FL and at 5 mg/ml for ICG. Images were obtained 1, 5, 15, and 30
minutes after dye injection. Image quality was evaluated by two independent
readers using standardised criteria. RESULTS: For amounts down to 166 mg for FL
and to 5 mg for ICG, sufficient image quality was achieved during all phases
following injection. Only late phase images showed less contrast compared to
typically used dye amounts, which was irrelevant for interpretation and clinical 
management. CONCLUSIONS: With the increased sensitivity of this novel cSLO
system, amounts of injected dye during FL-A can be reduced to one third for FL
and to one fifth for ICG without relevant loss of image quality or information
compared to conventionally used dye levels. These amounts can be used for routine
angiography and allow relevant savings for units performing FL-A.

Publication Types: 
    Evaluation Studies

PMID: 16299141 [PubMed - indexed for MEDLINE]

1702: Br J Ophthalmol. 2005 Dec;89(12):1581-5.

Comparison of optical coherence tomography models OCT1 and Stratus OCT for
macular retinal thickness measurement.

Pierre-Kahn V, Tadayoni R, Haouchine B, Massin P, Gaudric A.

Service d'Ophtalmologie, Hôpital Lariboisière 2, rue Ambroise Paré, 75475 Paris
Cedex 10, France.

AIMS: To compare the values measured for retinal macular thickness with the first
and last generations of the optical coherence tomograph (OCT1 and Stratus OCT,
Zeiss, Humphrey Division). METHODS: This was a cohort study. 59 eyes were
examined: 17 had a normal macula and 42 had a diabetic macular oedema. In each
eye, mean retinal thickness (RT) was measured automatically in the nine macular
Early Treatment Diabetic Retinopathy Study areas and at the foveal centre, using 
OCT1 and Stratus OCT. The paired mean RT values for each area and the type and
proportion of artefacts were compared. RESULTS: Of the 590 automatic
measurements, 505 had no artefact, either with OCT1 or Stratus OCT. The mean
difference between the OCT1 and Stratus OCT measurements was 25 (SD 26.2) microm 
(p<0.0001). With Stratus OCT, RT values were significantly higher, by 8.1%
(7.8%), than with OCT1. Artefacts were only observed in cases of diabetic macular
oedema and were significantly more frequent with OCT1 than Stratus OCT (10.5%
versus 4.4, p<0.0001). CONCLUSION: The macular retinal thickness values measured 
with Stratus OCT were significantly higher than those measured with OCT1. Stratus
OCT has the advantage of producing fewer artefacts than OCT1 in pathological
cases.

Publication Types: 
    Comparative Study

PMID: 16299134 [PubMed - indexed for MEDLINE]

1703: Disabil Rehabil. 2005 Oct 30;27(20):1203-12.

A cost-effectiveness analysis of a health education programme for elderly persons
with age-related macular degeneration: a longitudinal study.

Eklund K, Sonn U, Nystedt P, Dahlin-Ivanoff S.

Institute of Occupational Therapy and Physiotherapy, Sahlgrenska Academy at
Göteborg University, Göteborg, Sweden. kajsa.eklund@fhs.gu.se

PURPOSE: To analyse the cost-effectiveness of the activity-based Health Education
Programme 'Discovering New Ways' versus a standard Individual Programme. METHOD: 
Two-hundred and twenty-nine persons were randomized to either the Health
Education Programme or an Individual Programme. The present study is based on 131
persons who participated in the 28-month follow-up. Costs for the low vision
clinic were documented prospectively along with external costs. A
cost-effectiveness analysis was done using cases with an improved level of
perceived security in daily activities as the effectiveness measure. RESULTS: The
Health Education Programme led to significantly more cases with an improved level
of perceived security (45 vs. 10%, CI 95%: 21-49, p value < 0.001) and the total 
social cost per treatment was lower (28,004 vs. 36,341 SEK). Taken separately the
low vision clinic costs were slightly higher due to a higher prescription of
assistive devices, but external costs were lower for the Health Education
Programme compared to the Individual Programme, though neither of these
differences was statistically significant. CONCLUSION: The results suggest that
replacing the standard Individual Programme with the Health Education Programme
'Discovering New Ways' is cost-effective as more persons experience increased
security to a lesser total cost.

Publication Types: 
    Randomized Controlled Trial

PMID: 16298922 [PubMed - indexed for MEDLINE]

1704: Adv Drug Deliv Rev. 2005 Dec 13;57(14):2047-52. Epub 2005 Nov 17.

Micro- and nanoparticulates.

Moshfeghi AA, Peyman GA.

Bascom Palmer Eye Institute, 900 NW 17th St Miami, FL 33136, USA.
amoshfeghi@med.miami.edu

OBJECTIVES: Pharmacotherapeutics has begun to play an increasingly important role
in the management of patients with neovascular age-related macular degeneration
(AMD). Because micro- and nano-particulates are currently being evaluated as a
potential drug-delivery option for AMD patients, the purpose of this analysis was
to describe how micro- and nano-particulates have been used experimentally and
what their potential clinical applications may be. FINDINGS: Micro- and
nano-particulates have been used primarily on a pre-clinical basis as new
drug-delivery devices in experimental models of neovascular AMD. CONCLUSIONS: It 
is likely that micro- and nano-particulates will become an important component of
targeted clinical pharmacotherapeutics in patients with neovascular AMD.

Publication Types: 
    Review

PMID: 16298454 [PubMed - indexed for MEDLINE]

1705: Eye. 2006 Dec;20(12):1357-9. Epub 2005 Nov 18.

Comparison of ICG-assisted ILM peeling and triamcinolone-assisted posterior
vitreous removal in diffuse diabetic macular oedema.

Bardak Y, Cekiç O, Tiğ SU.

Department of Ophthalmology, Süleyman Demirel University Medical School, Isparta,
Turkey. yavuzbardak@hotmail.com

AIM: To compare the effect of indocyanine green (ICG)-assisted internal limiting 
membrane (ILM) peeling and triamcinolone acetonide-assisted posterior vitreous
removal on visual acuity in patients with diffuse diabetic macular oedema (DMO). 
METHODS: In total, 24 patients with diffuse DMO who underwent pars plana
vitrectomy were included in this study. In all, 11 patients (mean age 57 years)
were performed ICG-assisted ILM peeling; while 13 patients (mean age 54 years)
underwent triamcinolone-assisted posterior vitreous removal. Patients from two
different treatment regimens were compared in terms of best-corrected visual
acuity (BCVA) at postoperative sixth months. RESULTS: In ICG-assisted ILM peeling
group, preoperative BCVA (1.3+/-0.4, mean+/-SD, logMAR) improved postoperatively 
to 0.9+/-0.5 (P=0.011). In eyes underwent triamcinolone-assisted posterior
vitreous removal, baseline BCVA of 1.4+/-0.4 improved to 1.0+/-0.5 (P=0.007).
There was no difference between baseline as well as postoperative sixth-month
BCVA results of both groups (P=0.59 and P=0.57, respectively). CONCLUSIONS:
Triamcinolone-assisted posterior vitreous removal and ICG-assisted ILM peeling
have the same effect in terms of postoperative BCVA in patients with diffuse DMO.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial

PMID: 16294204 [PubMed - indexed for MEDLINE]

1706: Expert Rev Med Devices. 2005 Nov;2(6):657-65.

Visual prosthetic device for bilateral end-stage macular degeneration.

Chun DW, Heier JS, Raizman MB.

Ophthalmic Consultants of Boston, Tufts -- New England Eye Center, 50 Staniford
Street, Suite 600, Boston, MA 02114, USA. chundal@yahoo.com

Age-related macular degeneration is the leading cause of blindness in the USA.
For the 1.8 million patients in the most advanced stages, there are currently no 
available treatments to improve vision. A visual prosthetic device that provides 
one eye with an enlarged retinal image of the central visual field has been
developed with the goal of improving central vision in patients with bilateral
end-stage macular degeneration. The other eye is left unimplanted to provide
peripheral vision. This device is designed for implantation in the posterior
chamber of the eye during an outpatient surgical procedure. In US Food and Drug
Administration clinical trials, 72% of patients experienced an improvement in
their level of visual impairment (profound or severe, to severe or moderate).
This was accompanied by a clinically significant improvement in quality of life.

PMID: 16293092 [PubMed - indexed for MEDLINE]

1707: Ophthalmology. 2006 Jan;113(1):29-35. Epub 2005 Nov 10.

Nine-year incidence of age-related macular degeneration in the Barbados Eye
Studies.

Leske MC, Wu SY, Hennis A, Nemesure B, Yang L, Hyman L, Schachat AP; Barbados Eye
Studies Group.

Department of Preventive Medicine, Stony Brook University, Stony Brook, New York 
11794-8036, USA. cleske@notes.cc.sunysb.edu

OBJECTIVE: To provide 9-year incidence estimates of age-related macular
degeneration (AMD) in a population of African descent. DESIGN: Population-based
cohort study. PARTICIPANTS: Two thousand seven hundred ninety-three participants 
(81% of eligible) after 9 years' follow-up. MAIN OUTCOME MEASURES: Nine-year
incidence of AMD-related features, based on fundus photographic gradings and/or
clinical examinations. RESULTS: The overall incidence rate of early AMD was 12.6%
(95% confidence interval [CI], 11.0%-14.1%), and that of late AMD was 0.7% (95%
CI, 0.4%-1.1%). Both increased with age (P<0.05). For early AMD, incidence ranged
from 10.7% at 40 to 49 years of age to 16.8% at > or =70 years. For late AMD,
incidence increased from 0.1% to 2.3% in the same age groups. Late AMD was more
likely to develop in eyes with pigment changes (risk ratio [RR], 5.8; 95% CI,
2.0-16.8) and retinal pigment epithelial atrophy (RR, 5.4; 95% CI, 1.9-15.8) at
baseline. Crude RRs indicated significant associations of late AMD to elevated
systolic blood pressure and diabetes history, but only the diabetes relationship 
was suggested after adjusting for age, with borderline statistical significance
(age-adjusted RR, 2.7; P = 0.054). CONCLUSIONS: Nine-year data on natural history
indicate that early AMD is common in this population of African origin, although 
late AMD is infrequent. These long-term observations provide further evidence for
the lower AMD risk in black populations compared with white populations.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 16290049 [PubMed - indexed for MEDLINE]

1708: Mol Vis. 2005 Nov 4;11:941-9.

Joint effects of smoking history and APOE genotypes in age-related macular
degeneration.

Schmidt S, Haines JL, Postel EA, Agarwal A, Kwan SY, Gilbert JR, Pericak-Vance
MA, Scott WK.

Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA.
silke.schmidt@duke.edu

PURPOSE: Age-related macular degeneration (AMD) is a leading cause of severe
visual impairment in older adults worldwide. Cigarette smoking is one of the most
consistently identified environmental risk factors for the disease. Several
studies have implicated the apolipoprotein E (APOE) gene as modulating AMD risk. 
The purpose of this study was to investigate whether APOE genotypes modify the
smoking-associated risk of AMD. METHODS: Patients with early- and late-stage AMD 
(n=377) and a group of unrelated ethnically matched controls of similar age
(n=198) were ascertained at two sites in the southeastern United States. Smoking 
history and APOE genotype distribution in cases and controls were compared by
multivariable logistic regression. RESULTS: All measures of smoking history
showed a highly significant association with AMD, and odds ratio estimates were
consistently higher when only patients with exudative AMD were compared to
controls. Main effects of APOE genotypes in the overall analysis did not reach
statistical significance. The analysis of exudative AMD patients suggested that
the risk increase due to smoking was greatest in carriers of the APOE-2 allele,
with genotype-specific odds ratios increasing from 1.9 for APOE-4 carriers
(p=0.11) to 2.2 for APOE-3/3 homozygotes (p=0.007) to 4.6 (p=0.001) for APOE-2
carriers, compared to nonsmoking APOE-3/3 individuals. Measures of statistical
interaction indicated more than additive, and possibly more than multiplicative, 
joint effects of APOE and smoking history, however, the interaction was not
statistically significant on either scale. CONCLUSIONS: We hypothesize that a
history of smoking is a stronger risk factor for exudative AMD in carriers of the
APOE-2 allele, compared to carriers of APOE-4 and the most common APOE-3/3
genotype. To further clarify the association of AMD with APOE and smoking
history, future studies should consider both factors simultaneously.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 16288198 [PubMed - indexed for MEDLINE]

1709: Ophthalmologica. 2005 Nov-Dec;219(6):394-400.

Comment in:
    Ophthalmologica. 2006;220(5):349-50; author reply 350.

Intravitreal cortisone injection for refractory diffuse diabetic macular edema.

Er H, Yilmaz H.

Department of Ophthalmology, Inonu University Turgut Ozal Medical Center,
Malatya, Turkey. hamdier@inonu.edu.tr

PURPOSE: The purpose of this study was to evaluate the safety and efficacy of
intravitreal triamcinolone acetonide injection in patients with diffuse diabetic 
macular edema. We also compared the effect of intravitreal triamcinolone with
macular grid laser photocoagulation in macular edema. PATIENTS AND METHODS:
Thirty patients with diabetic diffuse macular edema unresponsive to grid laser
photocoagulation for at least 4 months received 0.1 ml (4 mg/ml) intravitreal
triamcinolone acetonide (Kenakort-A) injection as treatment. This study group was
compared with a control group of 30 patients (30 eyes) who had undergone grid
laser macular coagulation. Mean follow-up time was 17 months (range 14-24 months)
in the study group and 19 months (range 16-24 months) in the control group.
RESULTS: In the study group, mean improvement in visual acuity measured 3.8, 3.4,
0.9 and 0.2 Snellen lines at the follow-up intervals of 1, 3, 6 and 12 months,
respectively. Improvement in visual acuity was statistically significant only at 
1 month (p = 0.002) and 3 months (p = 0.003) after injection. Visual acuity was
significantly (p < 0.05) better in the study group than the control group at 1
and 3 months. Overall, 6 of 30 eyes (20%) required a second injection and 3 eyes 
(10%) a third due to regression in visual acuity. Towards the end of the
follow-up period, the visual acuity decreased to almost baseline levels.
Elevation of intraocular pressure was found in 4 patients and controlled with
topical antiglaucomatosis treatment. Sterile endophthalmitis was detected in only
one eye. No eye exhibited cataract progression during the follow-up period.
CONCLUSION: Intravitreal injection of triamcinolone may be beneficial for
temporarily increasing visual acuity in patients with diabetic diffuse macular
edema who are unresponsive even to grid laser photocoagulation. But the
regression of visual acuity looks inevitable in the long term after injection.
Therefore, repeated injections with/without increasing doses might be required
for the stabilization of visual acuity. Copyright 2005 S. Karger AG, Basel.

Publication Types: 
    Comparative Study

PMID: 16286802 [PubMed - indexed for MEDLINE]

1710: Arch Ophthalmol. 2005 Nov;123(11):1588-94.

Late development of vitelliform lesions and flecks in a patient with best
disease: clinicopathologic correlation.

Mullins RF, Oh KT, Heffron E, Hageman GS, Stone EM.

Center for Macular Degeneration, Department of Ophthalmology and Visual Sciences,
University of Iowa Hospitals and Clinics, Iowa City 52242, USA.

OBJECTIVE: To provide the clinicopathologic findings of a patient who developed
the clinical characteristics of Best disease (typically considered a juvenile
macular degeneration) at the age of 75 years after being documented to be
ophthalmoscopically normal at the age of 51 years. DESIGN: A member of a large
family with Best disease, possessing a Y227N mutation in the VMD2 gene (the gene 
responsible for the disease, which encodes the bestrophin protein), developed
small vitelliform lesions in both eyes at the age of 75 years and later developed
yellow flecklike depositions at the level of the retinal pigment epithelium
(RPE), which were also identified in fundus photographs of family members. The
patient died at the age of 93 years, and the histological features of the macular
lesion and peripheral flecks were examined. RESULTS: Histopathologically, the
retinal outer nuclear layer was attenuated, particularly in the macula. This
attenuation was frequently associated with normal RPE. A large area of
photoreceptor degeneration was present in the central macula, with loss of the
underlying RPE cells. Outside of this region, the RPE density was within normal
limits. The peripheral flecks were clusters of basal laminar deposits and drusen.
Bestrophin immunohistochemistry revealed labeling along both the basolateral and 
apical membranes of the RPE. CONCLUSIONS: Findings characteristic of Best disease
may not manifest in a molecularly affected individual until late in life.
Mutations in bestrophin appear to lead to extracellular deposit formation outside
the macula in some families. The distribution of bestrophin in the RPE suggests
that the protein may be mistargeted in those with Best disease who have the Y227N
mutation, and that this may be a cause of the associated RPE and photoreceptor
dysfunction.

Publication Types: 
    Case Reports
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 16286623 [PubMed - indexed for MEDLINE]

1711: Arch Ophthalmol. 2005 Nov;123(11):1575-80.

Prevalence of age-related macular degeneration in a population-based sample of
Hispanic people in Arizona: Proyecto VER.

Muñoz B, Klein R, Rodriguez J, Snyder R, West SK.

Dana Center for Preventive Ophthalmology, Wilmer Eye Institute, Johns Hopkins
University, Baltimore, MD 21287, USA. bmunoz@jhmi.edu

OBJECTIVE: To report the prevalence of age-related macular degeneration (AMD) in 
a population-based sample of Hispanic individuals aged 50 years and older.
METHODS: Proyecto VER (Vision and Eye Research) is a population-based study of
blindness and visual impairment of Hispanic people in Arizona. Participants
underwent complete ophthalmic evaluation, including stereoscopic fundus
photography of fields 1, 2, and 4. All photographs for participants aged 50 years
and older were graded using the Wisconsin Age-Related Maculopathy Grading system.
The following signs were graded: drusen size, drusen type, and the area covered
by drusen; pigmentary abnormalities; geographic atrophy; and exudative AMD.
RESULTS: Sixty-seven percent (3178) of the original 4774 participants were 50
years of age or older. Of those, 92% (2928) had fundus photographs in at least 1 
eye, and 95% (2780) of the photographs were of sufficient quality to grade early 
and late AMD. OUTCOME MEASURES: The overall prevalence of late AMD was 0.5%. The 
prevalence increased from 0.1% in the 50- to 59-year age group to 4.3% in the
group aged 80 years and older. Likewise, early AMD was strongly associated with
age with a prevalence of 20% in the 50- to 59-year age group, increasing to 54%
in the group aged 80 years and older. The prevalence of early AMD in Hispanic
people was significantly higher than the reported prevalence in the white
population. However, the prevalence of late AMD was lower than the estimates for 
the white population of the United States. CONCLUSIONS: Although early macular
changes were very common among Hispanic people, the prevalence of late AMD was
infrequent. Further work is necessary to understand the underlying reasons for
the different patterns of presentation of early and late signs of AMD among
racial/ethnic groups and to characterize early AMD based on predictive value for 
severe disease in different populations.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, U.S. Gov't, P.H.S.

PMID: 16286621 [PubMed - indexed for MEDLINE]

1712: Arch Ophthalmol. 2005 Nov;123(11):1570-4.

Comment in:
    Arch Ophthalmol. 2005 Nov;123(11):1484-98.    Arch Ophthalmol. 2005 Nov;123(11):1598-9.

A simplified severity scale for age-related macular degeneration: AREDS Report
No. 18.

Ferris FL, Davis MD, Clemons TE, Lee LY, Chew EY, Lindblad AS, Milton RC,
Bressler SB, Klein R; Age-Related Eye Disease Study (AREDS) Research Group.

AREDS Coordinating Center, The EMMES Corporation, Rockville, MD 20850-1707, USA.

OBJECTIVE: To develop a simplified clinical scale defining risk categories for
development of advanced age-related macular degeneration (AMD). METHODS:
Following development of a detailed scale for individual eyes based on gradings
of fundus photographs in the Age-Related Eye Disease Study, rates of progression 
to advanced AMD were assessed in cross-tabulations of presence or absence in each
eye of 2 easily identified retinal abnormalities, drusen and pigment
abnormalities. Large drusen and any pigment changes were particularly predictive 
of developing advanced AMD. RESULTS: The scoring system developed for patients
assigns to each eye 1 risk factor for the presence of 1 or more large (> or = 125
microm, width of a large vein at disc margin) drusen and 1 risk factor for the
presence of any pigment abnormality. Risk factors are summed across both eyes,
yielding a 5-step scale (0-4) on which the approximate 5-year risk of developing 
advanced AMD in at least one eye increases in this easily remembered sequence: 0 
factors, 0.5%; 1 factor, 3%; 2 factors, 12%; 3 factors, 25%; and 4 factors, 50%. 
For persons with no large drusen, presence of intermediate drusen in both eyes is
counted as 1 risk factor. CONCLUSION: This simplified scale provides convenient
risk categories for development of advanced AMD that can be determined by
clinical examination or by less demanding photographic procedures than used in
the Age-Related Eye Disease Study.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 16286620 [PubMed - indexed for MEDLINE]

1713: Arch Ophthalmol. 2005 Nov;123(11):1507-13.

Autofluorescence imaging of choroidal neovascularization due to age-related
macular degeneration.

Dandekar SS, Jenkins SA, Peto T, Scholl HP, Sehmi KS, Fitzke FW, Bird AC, Webster
AR.

Moorfields Eye Hospital and Institute of Ophthalmology, London, England.
sam@hitbits.co.uk

OBJECTIVE: To describe the autofluorescence (AF) characteristics of choroidal
neovascularization (CNV) in patients with age-related macular degeneration.
METHODS: Autofluorescence images of 65 consecutive eyes with CNV at various
stages of evolution were analyzed. Twenty images were of recent-onset CNV (group 
1), 8 were of eyes 1 to 6 months after CNV diagnosis (group 2), and 37 were
late-stage CNV (group 3). Autofluorescence images from groups 1 and 2 were
compared with fundus fluorescein angiographic images. RESULTS: Group 1 showed
areas of hyperfluorescence on fundus fluorescein angiography corresponding to
areas of normal AF in 16 of 20 cases, with adjacent areas of increased AF in 13
cases. The main areas of abnormal AF were larger than the main areas of abnormal 
fluorescence on fundus fluorescein angiography in 18 of the 20 cases. Groups 2
and 3 showed areas of decreased AF corresponding to areas of previous leakage on 
fundus fluorescein angiography (in group 2) or atrophy. CONCLUSIONS: Preserved AF
in group 1 indicates viable retinal pigment epithelium initially, which has
implications for visual prognosis. Decreased AF in groups 2 and 3 indicates loss 
of retinal pigment epithelium and photoreceptors. Autofluorescence imaging may
increase our understanding of CNV in age-related macular degeneration.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16286612 [PubMed - indexed for MEDLINE]

1714: Arch Ophthalmol. 2005 Nov;123(11):1501-6.

Inflammatory markers in age-related maculopathy: cross-sectional analysis from
the Muenster Aging and Retina Study.

Dasch B, Fuhs A, Behrens T, Meister A, Wellmann J, Fobker M, Pauleikhoff D, Hense
HW.

Institute of Epidemiology and Social Medicine, University of Muenster, Germany.

OBJECTIVE: To evaluate recent reports indicating that plasma levels of fibrinogen
and high-sensitivity C-reactive protein (CRP) are associated with age-related
maculopathy (ARM). METHODS: From the baseline examinations of the Muenster Aging 
and Retina Study, a cohort of 1060 subjects aged 59 to 82 years was assembled. Of
these, 873 persons (82%) with bilateral gradable fundus photographs and complete 
data on fibrinogen, CRP, and potential confounders were included in a
cross-sectional analysis. The main outcome measure was the association among
fibrinogen, CRP, and ARM as assessed by multivariate logistic regression
analysis. RESULTS: Fibrinogen and CRP levels were higher among participants with 
early and late ARM than among those without ARM. The crude odds ratios for ARM
between the highest vs the lowest quartile were 1.90 (95% confidence interval
[CI], 1.29-2.80) for fibrinogen and 1.43 (95% CI, 0.97-2.10) for CRP. After
adjustment for cardiovascular risk factors, these odds ratios were 1.37 for
fibrinogen (95% CI, 0.91-2.06) and 1.12 (95% CI, 0.73-1.73) for CRP. CONCLUSIONS:
After adjustment for cardiovascular risk factors, we found no statistically
significant association between fibrogen, CRP, and ARM. Therefore, our results do
not indicate a role of systemic inflammation in ARM beyond what is already
present owing to concurrent cardiovascular disease.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16286611 [PubMed - indexed for MEDLINE]

1715: Arch Ophthalmol. 2005 Nov;123(11):1484-98.

Erratum in:
    Arch Ophthalmol. 2006 Feb;124(2):289-90.

Comment in:
    Arch Ophthalmol. 2005 Nov;123(11):1598-9.

Comment on:
    Arch Ophthalmol. 2005 Nov;123(11):1570-4.

The Age-Related Eye Disease Study severity scale for age-related macular
degeneration: AREDS Report No. 17.

Davis MD, Gangnon RE, Lee LY, Hubbard LD, Klein BE, Klein R, Ferris FL, Bressler 
SB, Milton RC; Age-Related Eye Disease Study Group.

AREDS Coordinating Center, EMMES Corp, Rockville, MD 20850-1707, USA.

OBJECTIVE: To develop a fundus photographic severity scale for age-related
macular degeneration (AMD). METHODS: In the Age-Related Eye Disease Study,
stereoscopic color fundus photographs were taken at baseline, at the 2-year
follow-up visit, and annually thereafter. Photographs were graded for drusen
characteristics (size, type, area), pigmentary abnormalities (increased pigment, 
depigmentation, geographic atrophy), and presence of abnormalities characteristic
of neovascular AMD (retinal pigment epithelial detachment, serous or hemorrhagic 
sensory retinal detachment, subretinal or sub-retinal pigment epithelial
hemorrhage, subretinal fibrous tissue). Advanced AMD was defined as presence of 1
or more neovascular AMD abnormalities, photocoagulation for AMD, or geographic
atrophy involving the center of the macula. We explored associations among right 
eyes of 3212 participants between severity of drusen characteristics and
pigmentary abnormalities at baseline and development of advanced AMD within 5
years of follow-up. RESULTS: A 9-step severity scale that combines a 6-step
drusen area scale with a 5-step pigmentary abnormality scale was developed, on
which the 5-year risk of advanced AMD increased progressively from less than 1%
in step 1 to about 50% in step 9. Among the 334 eyes that had at least a 3-step
progression on the scale between the baseline and 5-year visits, almost half
showed stepwise progression through intervening severity levels at intervening
visits. Replicate gradings showed agreement within 1 step on the scale in 87% of 
eyes. CONCLUSIONS: The scale provides convenient risk categories and has
acceptable reproducibility. Progression along it may prove to be useful as a
surrogate for progression to advanced AMD.

Publication Types: 
    Comment
    Research Support, N.I.H., Extramural
    Research Support, U.S. Gov't, P.H.S.

PMID: 16286610 [PubMed - indexed for MEDLINE]

1716: Eye. 2007 Mar;21(3):324-30. Epub 2005 Nov 11.

Age-related maculopathy and cataract surgery outcomes: visual acuity and
health-related quality of life.

Pham TQ, Cugati S, Rochtchina E, Mitchell P, Maloof A, Wang JJ.

Department of Ophthalmology, Centre for Vision Research, Westmead Millennium
Institute, University of Sydney, Westmead Hospital, Westmead, NSW, Australia.

PURPOSE: To assess visual acuity (VA) and health-related quality of life (HRQoL) 
outcomes in patients with and without age-related maculopathy (ARM) after
cataract surgery. METHODS: Patients aged 60+ years who had undergone cataract
surgery at the Westmead Hospital during 2001-2003 were re-examined 1-3 years
after surgery. Tests included VA and assessment of visual- and HRQoL using
standardised questionnaires (VF-14, SF-12). Preoperative comorbidity data were
collected from medical records. Poor surgical outcomes (VA<6/12; no VA
improvement; lowest quintile of VF-14, SF-12 scores) were compared in patients
with and without ARM, adjusting for age, sex, preoperative systemic
comorbidities, ocular comorbidities and surgical or postoperative complications. 
RESULTS: Of 622 surviving patients, 454 (73%) were followed up for a mean period 
of 2.8 years. Similar proportions with VA>or=6/12 were observed in patients with 
(80.2%) and without (88.8%) pre-existing ARM. Preoperative early ARM was only
associated with slightly lower mean VF-14 scores (87.64 with vs 92.58 without
ARM, P=0.01). Increasing age and preoperative ocular comorbidities were
associated with all poor outcomes measured. Low SF-12 scores were associated with
preoperative systemic comorbidities. CONCLUSION: Our study documents favourable
cataract surgical outcomes 1-3 years after cataract surgery in patients with
preoperative ARM.

PMID: 16284600 [PubMed - indexed for MEDLINE]

1717: Ophthalmic Epidemiol. 2005 Dec;12(6):353-62.

Modelling the natural history of geographic atrophy in patients with age-related 
macular degeneration.

Dreyhaupt J, Mansmann U, Pritsch M, Dolar-Szczasny J, Bindewald A, Holz FG.

Department of Medical Biometry and Informatics, University of Heidelberg,
Germany. dreyhaupt@imbi.uni-heidelberg.de

PURPOSE: To model the natural course of geographic atrophy (GA) in patients with 
age-related macular degeneration (AMD). METHODS: Data on the natural course of GA
were collected in the multi-center, longitudinal, prospective observational FAM
study. The size of GA was measured by autofluorescence scanning laser
ophthalmoscopy. The natural course of GA is modelled by two different mixed
effect models (MEM). Both models are compared with respect to the correctness of 
the model assumptions, goodness of fit, and predictive behavior. RESULTS: The
linear model results in better prediction, the non-linear model is more in
agreement with the model assumptions. The non-linear model fits the data for
small and large areas of GA better, while the linear model seems to be more
adequate for the medial areas. More data will be needed to study the interplay of
both models in more detail. CONCLUSIONS: The natural course of GA varies
extremely between individuals. However, reliable factors for the explanation of
this variability have so far not been established. MEM are useful for describing 
"inter-individual" as well as "intra-individual" influences without the need for 
precise knowledge of the influencing factors. Using MEM to evaluate data on the
natural history of GA allows one to derive parameter estimates, which could be
used to design interventional trials for modes of therapy with a potential to
reduce or stop the progression of GA in patients with AMD.

Publication Types: 
    Comparative Study
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 16283987 [PubMed - indexed for MEDLINE]

1718: Clin Trials. 2004 Feb;1(1):91-107.

The Complications of Age-Related Macular Degeneration Prevention Trial (CAPT):
rationale, design and methodology.

Complications of Age-Related Macular Degeneration Prevention Trial Study Group.

BACKGROUND: The Complications of Age-Related Macular Degeneration Prevention
Trial (CAPT) is a randomized clinical trial to evaluate whether prophylactic
laser treatment to the retina can prevent the complications of the advanced stage
of Age-Related Macular Degeneration (AMD), the leading cause of irreversible
blindness. METHODS: CAPT is conducted in 23 clinical centers and in three central
resource centers. The primary outcome measure is change in visual acuity;
secondary outcomes include the incidence of complications of AMD, changes in
other measures of visual functioning and vision-related quality of life. In
total, 1052 patients with two high-risk eyes were enrolled. One eye was
randomized to receive laser treatment and the other eye to observation. All
patients were treated immediately after randomization and again at 12 months,
dependent on clinical status. All patients are followed via study visits and
telephone calls for a minimum of five years. Study visit procedures include
established tests of visual function conducted by examiners masked to the
treatment assignment of each eye, a biomicroscopic examination by
CAPTophthalmologists, and photographs of each eye taken according to protocol and
assessed by masked graders in a centralized Photograph Reading Center. RESULTS:
This paper describes the CAPT study, including study rationale, operational
structure, and measures implemented to ensure standardization of assessments,
adherence to protocol, quality assurance, and maintaining follow-up. Several
features related to study design and procedures that are specific to CAPT are
highlighted, including clinic selection and judgements regarding patient
eligibility. CONCLUSIONS: An intervention that can reduce the risk of advanced
AMD by 30% in the eyes of people with two high-risk eyes may halve the rate of
bilateral blindness from AMD. It would also yield substantial savings in
expenditures devoted to treating advanced AMD and the disability it causes, and
enhance the quality of life for people at risk.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, U.S. Gov't, P.H.S.

PMID: 16281465 [PubMed - indexed for MEDLINE]

1719: Mol Vis. 2005 Nov 2;11:922-8.

Sequence variations in the retinal fascin FSCN2 gene in a Spanish population with
autosomal dominant retinitis pigmentosa or macular degeneration.

Gamundi MJ, Hernan I, Maseras M, Baiget M, Ayuso C, Borrego S, Antiñolo G, Millán
JM, Valverde D, Carballo M.

Laboratori de Biologia i Genetica Molecular, Hospital de Terrassa, Ctra.
Torrebonica, Terrassa, Spain.

PURPOSE: Only one mutation in the retinal fascin gene (FSCN2) has so far been
associated with autosomal dominant retinitis pigmentosa (adRP) and macular
dystrophy (adMD), in a Japanese population. Our study was designed to identify
mutations in the FSCN2 gene among Spanish persons with adRP or adMD. METHODS:
Denaturing gradient gel electrophoresis and direct genomic sequencing were used
to evaluate the complete coding region and flanking intronic sequences of the
FSCN2 gene for mutations in 150 unrelated adRP and 15 adMD index patients, and in
50 sporadic cases of retinitis pigmentosa, together with 50 controls. Ophthalmic 
and electrophysiological examination of retinitis pigmentosa patients and their
relatives was carried out according to pre-existing protocols. RESULTS: Sixteen
nucleotide substitutions were detected in the coding sequence of the index
patients. Nine of these, His7Tyr, Ala122Thr, Ser126Phe, His138Tyr, Arg149Gln,
Ala240Thr, Ala323Thr, Asn331His, and Phe367Leu are missense mutations, one is a
nonsense mutation (Lys302Stop), and six are silent mutations. Co-segregation of
the mutations in the families showed no direct relation between mutation and
disease. CONCLUSIONS: The photoreceptor-specific FSCN2 gene showed a relatively
high number of sequence variations. The mutation 208delG in FSCN2, the only
mutation so far associated with adRP or adMD, and which presumably causes a null 
allele, was not detected in these Spanish families. The nonsense mutation,
Lys302Stop, detected in one adRP Spanish family is not the cause of the disease. 
These findings support the fact that the kind and frequency of the mutations
depend on the ethnic population.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16280978 [PubMed - indexed for MEDLINE]

1720: Mol Ther. 2006 Mar;13(3):609-16. Epub 2005 Nov 2.

Choroidal neovascularization in transgenic mice expressing prokineticin 1: an
animal model for age-related macular degeneration.

Tanaka N, Ikawa M, Mata NL, Verma IM.

Laboratory of Genetics, The Salk Institute, La Jolla, CA, USA.

The prognosis of choroidal neovascularization (CNV) in age-related macular
degeneration (AMD) is poor and existing treatments are limited in retarding the
progression of disease. The development of an animal model for AMD will be
beneficial for finding potential treatments, including gene therapy. Recently
prokineticin 1 (hPK1) was identified as a mitogen of fenestrated endothelium. We 
hypothesized that hPK1 could induce CNV, a hallmark of the exudative or wet form 
of AMD, since the endothelium of the choriocapillaris, but not retinal
endothelium, has fenestration. We generated transgenic mice expressing hPK1 in
the retina using the rhodopsin promoter. In these transgenic mice, an enlarged
vascular bed of choroid resembling CNV was observed without any morphological
changes in the retinal vasculature. In addition, the major fluorophore of
lipofuscin, N-retinylidene-N-retinylethanolamine, which has several potential
cytotoxic effects on the RPE, was accumulated approximately twice as much in the 
transgenic mouse eyes compared to controls. hPK1 could be one of the causative
factors of AMD and the transgenic mouse exhibiting CNV may be useful to establish
treatments for the wet form of AMD.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16263331 [PubMed - indexed for MEDLINE]

1721: Adv Drug Deliv Rev. 2005 Dec 13;57(14):2033-46. Epub 2005 Nov 2.

Intraocular sustained drug delivery using implantable polymeric devices.

Yasukawa T, Ogura Y, Sakurai E, Tabata Y, Kimura H.

Kurashiki Central Hospital, Kurashiki 710-8602, Japan; Department of
Ophthalmology, Nagoya City University Medical School, Aichi 467-8601, Japan.

Vitreoretinal diseases involving age-related macular degeneration (AMD) are
refractory to most topical or systemic drugs. The retina and the vitreous cavity 
have a unique position regarding pharmacokinetics in that the inner and outer
blood retinal barriers separate the retina and vitreous from the systemic
circulation. Eye drops achieve minimal therapeutic concentrations in the
vitreoretinal tissue. Drug delivery systems are a strategy to address this.
Intraocular sustained drug release using implantable devices has been
investigated to treat vitreoretinal diseases. Possible targeted diseases include 
those in which repeated intraocular injections are effective (cytomegalovirus
retinitis, uveitis), diseases requiring surgery (proliferative
vitreoretinopathy), and chronic diseases (AMD, macular edema, retinitis
pigmentosa). Hydrophobic or hydrophilic polymers shaped into a sheet, disc, rod, 
plug, or a larger device can be implanted into the subretinal space, intrascleral
space, vitreous space, peribulbar space, or at the pars plana. Many researchers
suggest the feasibility of these implants to treat AMD.

Publication Types: 
    Review

PMID: 16263193 [PubMed - indexed for MEDLINE]

1722: Expert Rev Mol Med. 2005 Oct 31;7(24):1-15.

TIMP3 mutation in Sorsby's fundus dystrophy: molecular insights.

Li Z, Clarke MP, Barker MD, McKie N.

Henry Wellcome Laboratory for Biogerontology Research, Newcastle General
Hospital, Newcastle, NE4 6BH, UK. zheng.li@ncl.ac.uk

Sorsby's fundus dystrophy (SFD) is a rare autosomal dominant disorder that
results in degeneration of the macular region of the retina, with onset usually
in the fourth to fifth decade of life. It leads to the rapid loss of central
vision, often followed by further loss of peripheral vision. SFD shares several
pathological features commonly found in the 'wet' or exudative form of
age-related macular degeneration (AMD), the most common cause of blindness in the
elderly in developed countries. These phenotypic similarities have led to SFD
being proposed as an acceptable genetic model for AMD. Whereas AMD appears to
have a complex aetiology, with both genetic and environmental factors playing a
role, SFD has been shown to be a single-gene disorder, linked to mutations in
exon 5 of the tissue inhibitor of metalloproteinases 3 (TIMP3) gene on chromosome
22q12-q13. This review confines itself to a discussion of the known biochemical
properties of the wild-type and SFD TIMP3 proteins and attempts to relate these
to the pathology encountered in SFD patients. We also discuss briefly how,
despite the lack of inherited mutations in the structural gene, the TIMP3 protein
might play a role in the onset and progression of AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 16259644 [PubMed - indexed for MEDLINE]

1723: Clin Exp Optom. 2005 Sep;88(5):322-34.

Treatment of age-related macular degeneration.

Bylsma GW, Guymer RH.

Centre for Eye Research Australia, Locked Bag 8, East Melbourne, VIC, 8002,
Australia.

Age-related macular degeneration (AMD) is the greatest cause of legal blindness
in the western world. Established treatments include argon laser photocoagulation
of extrafoveal choroidal neovascularisation (CNV) and photodynamic therapy of
selected sub-foveal CNV. Newer approaches are targeting the angiogenic pathway in
CNV development. Currently, other treatment modalities, such as radiotherapy and 
transpupillary thermotherapy do not have a clear role to play. Surgical options
are experimental and only available in some centres for selected patients.
Prevention of AMD remains elusive. Dietary supplements may have a role, while
statins and prophylactic laser photocoagulation of drusen remain experimental.
This paper explains the principles behind these approaches.

Publication Types: 
    Review

PMID: 16255691 [PubMed - indexed for MEDLINE]

1724: Clin Exp Optom. 2005 Sep;88(5):313-21.

Visual function: the problem with eccentricity.

Battista J, Kalloniatis M, Metha A.

Department of Optometry and Vision Sciences, The University of Melbourne,
Parkville, VIC, 3010, Australia.

Age-related macular degeneration (AMD) is the leading cause of blindness in
developed countries. With an ageing population, the prevalence of such a
condition has resulted in a large proportion of the population relying on
peripheral vision to undertake activities of daily living. Peripheral vision is
not a scaled-down version of the fovea, simply requiring larger print or
increased contrast for detection of objects or reading text. Even when print size
is scaled and eye movements are minimised, the peripheral retina cannot perform
at the level of the foveal region. Understanding how and why reading performance 
is limited as a function of eccentricity has important implications for how we
approach rehabilitation of patients with central visual loss. This brief review
of the extensive literature on reading with peripheral vision and the research
aimed at better reading rehabilitation for low vision patients focuses on why
many of the problems associated with the reduced reading capability of peripheral
vision cannot be completely solved with magnification, reducing eye movements or 
modifying print.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 16255690 [PubMed - indexed for MEDLINE]

1725: Clin Exp Optom. 2005 Sep;88(5):304-12.

Objective functional assessment of age-related maculopathy: a special application
for the multifocal electroretinogram.

Feigl B, Lovie-Kitchin J, Brown B.

Queensland University of Technology, Victoria Park Road, Kelvin Grove, QLD, 4059,
Australia. b.feigi@qut.edu.au

This paper gives a brief review of methods that assess objectively function in
age-related maculopathy (ARM) with emphasis on a newer method, the multifocal
electroretinogram (mfERG). In contrast to other electrophysiological tests, such 
as the full-field and focal electroretinogram (ERG) or the electro-oculogram
(EOG), which measure summed responses from various cells from larger areas of the
retina, the multifocal electroretinogram maps function locally with a resolution 
as small as four degrees within the central 30 degrees. By using different
paradigms it can measure local cone- and rod-mediated functional impairment at
early and late stages of ARM. This improved mapping and higher resolution of the 
posterior pole compared to other objective methods might lead to earlier
detection of ARM. Its usefulness has been demonstrated in documenting the effects
of treatment after established laser treatments, such as photodynamic therapy
(PDT) and in documenting function after retinal pigment epithelial
transplantation, a possible future treatment in late neovascular ARM.

Publication Types: 
    Review

PMID: 16255689 [PubMed - indexed for MEDLINE]

1726: Clin Exp Optom. 2005 Sep;88(5):292-303.

Assessment of age-related maculopathy using subjective vision tests.

Lovie-Kitchin J, Feigl B.

Queensland University of Technology, Faculty of Health, Victoria Park Road,
Kelvin Grove, QLD, 4059, Australia. j.lovie-kitchin@qut.edu.au

This paper reviews non-standard, clinical vision tests that may be used to detect
the earliest visual loss in age-related maculopathy (ARM), before fundus changes 
are detected. We recommend a clinical test battery for all patients aged 60 years
and older, comprising low luminance/low contrast (SKILL) VA or low contrast VA,
desaturated D-15 colour vision assessment, flicker perimetry, glare recovery and 
dark adaptation if possible, together with conventional assessments of case
history, ophthalmoscopy and high contrast visual acuity (VA) for the detection
and diagnosis of ARM. Reading rate is also discussed as a potential indicator of 
early visual loss. For monitoring the progressive visual loss in age-related
macular degeneration (AMD) and determining the requirements for optometric vision
rehabilitation, we recommend more conventional clinical vision tests of distance 
and near visual acuity, reading rate, the effects of varying illumination and a
functional central visual field assessment.

Publication Types: 
    Review

PMID: 16255688 [PubMed - indexed for MEDLINE]

1727: Clin Exp Optom. 2005 Sep;88(5):269-81.

Anatomy and development of the macula: specialisation and the vulnerability to
macular degeneration.

Provis JM, Penfold PL, Cornish EE, Sandercoe TM, Madigan MC.

Research School of Biological Sciences, The Australian National University, GPO
Box 475, Canberra, ACT, 2601, Australia. Jan.Provis@anu.edu.au

The central retina in primates is adapted for high acuity vision. The most
significant adaptations to neural retina in this respect are: 1. The very high
density of cone photoreceptors on the visual axis; 2. The dominance of Midget
pathways arising from these cones and 3. The diminishment of retinal blood supply
in the macula, and its absence on the visual axis. Restricted blood supply to the
part of the retina that has the highest density of neural elements is
paradoxical. Inhibition of vascular growth and proliferation is evident during
foetal life and results in metabolic stress in ganglion cells and Muller cells,
which is resolved during formation of the foveal depression. In this review we
argue that at the macula stressed retinal neurons adapt during development to a
limited blood supply from the choriocapillaris, which supplies little in excess
of metabolic demand of the neural retina under normal conditions. We argue also
that while adaptation of the choriocapillaris underlying the foveal region may
initially augment the local supply of oxygen and nutrients by diffusion, in the
long term these adaptations make the region more vulnerable to age-related
changes, including the accumulation of insoluble material in Bruch's membrane and
beneath the retinal pigment epithelium. These changes eventually impact on
delivery of oxygen and nutrients to the RPE and outer neural retina because of
reduced flow in the choriocapillaris and the increasing barriers to effective
diffusion. Both the inflammatory response and the sequelae of oxidative stress
are predictable outcomes in this scenario.

Publication Types: 
    Review

PMID: 16255686 [PubMed - indexed for MEDLINE]

1728: Invest Ophthalmol Vis Sci. 2005 Nov;46(11):4016-23.

The impact of age-related macular degeneration on health status utility values.

Espallargues M, Czoski-Murray CJ, Bansback NJ, Carlton J, Lewis GM, Hughes LA,
Brand CS, Brazier JE.

Health Economics and Decision Science, University of Sheffield, UK.

PURPOSE: To estimate health status utility values in patients with age-related
macular degeneration (ARMD) associated with visual impairments, by using
preference-based measures of health. METHOD: This was a cross-sectional study
involving patients with unilateral or bilateral ARMD who attended a large
teaching hospital. Patients underwent visual tests (near and distant visual
acuity [VA] and contrast sensitivity [CS]) and completed health status
questionnaires including the Index of Visual Function (VF)-14 and three
preference-based measures (the Health Utilities Index Mark III [HUI-3], the
EuroQoL Health Questionnaire [EQ-5D], and the Short Form 6D Health Status
Questionnaire [SF-6D]) and the time tradeoff (TTO). The mean health status is
presented for five groups, defined according to the VA in the better-seeing eye
and for four CS groups. RESULTS: Two hundred nine patients were recruited with
substantial loss of visual function as obtained by visual tests (mean decimal VA 
in the better-seeing eye: 0.2) and self-report (mean VF-14 score: 41.5). The mean
(+/-SD) utilities were 0.34 +/- 0.28 for HUI-3, 0.66 +/- 0.14 for SF-6D, 0.72 +/-
0.22 for EQ-5D, and 0.64 +/- 0.31 for TTO. The HUI-3 had the highest correlation 
with VA and CS (0.40 and -0.34), followed by TTO (0.25 and -0.21). Across the VA 
and CS groups, only HUI3 and TTO had a significant linear trend (P < 0.05). In a 
regression model with CS and VA as explanatory variables, only the coefficient on
CS was statistically significant. CONCLUSIONS: ARMD is associated with a
substantial impact on patients' health status, but this was not reflected in two 
of the generic preference-based measures used. The HUI-3 seems to be the
instrument of choice for use in economic evaluations in which community data are 
needed. It may be more appropriate to base economic models on CS or some
combination of CS and VA rather than on VA alone.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 16249475 [PubMed - indexed for MEDLINE]

1729: Health Qual Life Outcomes. 2005 Oct 26;3:65.

Psychometric properties of the 25-item National Eye Institute Visual Function
Questionnaire (NEI VFQ-25), Japanese version.

Suzukamo Y, Oshika T, Yuzawa M, Tokuda Y, Tomidokoro A, Oki K, Mangione CM, Green
J, Fukuhara S.

Department of Epidemiology and Healthcare Research, Kyoto University, Kyoto,
Japan. suzukamo@pbh.med.kyoto-u.ac.jp

BACKGROUND: The importance of evaluating the outcomes of health care from the
standpoint of the patient is now widely recognized. The purpose of this study is 
to develop and test a Japanese version of the National Eye Institute Visual
Function Questionnaire (NEI VFQ-25). METHODS: A Japanese version was developed
with a previously standardized method. The questionnaire and optional items were 
completed by 245 patients with cataracts, glaucoma, or age-related macular
degeneration, by 110 others before and after cataract surgery, and by a reference
group (n = 31). We computed rates of missing data, measured reproducibility and
internal consistency reliability, and tested for convergent and discriminant
validity, concurrent validity, known-groups validity, factor structure, and
responsiveness to change. RESULTS: Based on information from the participants,
some items were changed to 2-step items (asking if an activity was done, and if
it was done, then asking how difficult it was). The near-vision and
distance-vision subscales each had 1 item that was endorsed by very few
participants, so these items were replaced with items that were optional in the
English version. For example, more than 60% of participants did not drive, so the
driving question was excluded. Reliability and validity were adequate for all
subscales except driving, ocular pain, color vision, and peripheral vision. With 
cataract surgery, most scores improved by at least 20 points. CONCLUSION: With
minor modifications from the English version, the Japanese NEI VFQ-25 can give
reliable, valid, responsive data on vision-related quality of life, for
group-level comparisons or for tracking therapeutic outcomes.

Publication Types: 
    Validation Studies

PMID: 16248900 [PubMed - indexed for MEDLINE]

1730: Eye. 2006 Jun;20(6):674-80. Epub 2005 Oct 21.

Pars plana vitrectomy for diabetic macular oedema: OCT and functional
correlations.

Patel JI, Hykin PG, Schadt M, Luong V, Fitzke F, Gregor ZJ.

Moorfields Eye Hospital, London, UK. jigs37@hotmail.com

PURPOSE: A prospective study to evaluate the macular structural and functional
effects of pars plana vitrectomy (PPV) for persistent diffuse clinically
significant macular oedema (CSMO). METHOD: A total of 12 patients with persistent
diffuse CSMO were recruited and underwent assessment including best-corrected
visual acuity, fundus fluorescein angiography, optical coherence tomography (OCT)
and fine matrix mapping (FMM) at baseline and over a period of a year
poststandard three-port PPV. RESULTS: The median baseline ETDRS letters score for
all 12 patients was 52 (range 41-63) while at 12 months it had increased to 65
(range of 27-68), an improvement of two complete ETDRS lines (P=0.037).
Similarly, there was an improvement in the perifoveal cone thresholds (P=0.02).
The foveal thickening for all 12 patients ranged from a median of 183 to 751
microm (normal range 126-180 microm) and the macular volume ranged from a median 
of 2.13 to 6.42 mm(3) (normal <1.66 mm(3)). After surgery, both the median foveal
thickness (from 334 to 280 microm) and median macular volume (from 3.24 to 2.61
mm(3)) demonstrated decreases over 12 months (P=0.01). On baseline OCT, the
patients fell into two anatomically distinct groups: Group 1 (n=4) had a
dome-shaped thickened macula with a partial posterior hyaloid separation and a
significantly higher foveal thickness and macular volume than Group 2 (n=8) which
had a diffuse low-elevation profile of the thickened macula (P=0.007).
CONCLUSIONS: In this prospective study of PPV for persistent fovea-involving CSMO
there was structural and functional improvement.

Publication Types: 
    Evaluation Studies

PMID: 16244647 [PubMed - indexed for MEDLINE]

1731: Vision Res. 2006 Apr;46(8-9):1422-31. Epub 2005 Oct 20.

Impact of aging and age-related maculopathy on inactivation of the a-wave of the 
rod-mediated electroretinogram.

Jackson GR, McGwin G Jr, Phillips JM, Klein R, Owsley C.

Department of Ophthalmology, School of Medicine, University of Alabama at
Birmingham, USA.

This study examined the impact of aging and age-related maculopathy (ARM) on the 
inactivation of phototransduction in rod photoreceptors by measuring the recovery
of the a-wave using a paired flash electroretinogram technique. Measurements were
made on 32 older adults in normal retinal health, 25 with early ARM, 7 with late 
ARM, and 20 young adults for comparison purposes. ARM presence and severity were 
defined by the Wisconsin Age-Related Maculopathy Grading System based on grading 
of fundus photographs. The inactivation of rod phototransduction exhibited an
aging-related slowing. Those with early ARM did not exhibit inactivation slowing 
over and above what would be expected based on normal retinal aging. Persons in
the late stages of ARM exhibited dramatic slowing in inactivation kinetics.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16242751 [PubMed - indexed for MEDLINE]

1732: Ophthalmic Surg Lasers Imaging. 2005 Sep-Oct;36(5):358-64.

Surgical removal of peripapillary choroidal neovascularization associated with
age-related macular degeneration.

Blinder KJ, Shah GK, Thomas MA, Holekamp NM, Joseph DP, Grand MG, Sharma S.

Barnes Retina Institute, Washington University School of Medicine, St Louis,
Missouri, USA.

BACKGROUND AND OBJECTIVE: To describe the results of surgical treatment of
peripapillary choroidal neovascularization in age-related macular degeneration as
an option to both laser photocoagulation and photodynamic therapy. PATIENTS AND
METHODS: Retrospective review of patients with peripapillary choroidal
neovascularization secondary to age-related macular degeneration who were not
eligible for or refused laser photocoagulation. Patients without the diagnosis of
age-related macular degeneration and those who had extension of their
neovascularization subfoveally were excluded from the review. RESULTS: Eleven
patients total were identified who met the specified inclusion criteria. The male
to female ratio was 4:7, with an age range of 63 to 94 years (mean = 78 years).
The mean area of involved retina temporal to the optic disc was 5 clock hours,
with the distance of the temporal edge of the lesion from the fovea ranging from 
100 to 2,000 microm. The mean duration of follow-up was 23 months, with 27% (3 of
11) experiencing recurrent choroidal neovascularization. The preoperative and
postoperative visual acuity ranges were both 20/25 to counting fingers.
Sixty-four percent (7 of 11) of patients had stable or improved visual acuity
postoperatively, with a mean visual acuity change of 1 line visual improvement.
CONCLUSION: In cases where photodynamic therapy and laser photocoagulation are
not indicated, the surgical treatment of peripapillary choroidal
neovascularization secondary to age-related macular degeneration may prove
beneficial.

Publication Types: 
    Case Reports

PMID: 16238033 [PubMed - indexed for MEDLINE]

1733: Cochrane Database Syst Rev. 2005 Oct 19;(4):CD002030.

Update in:
    Cochrane Database Syst Rev. 2007;(3):CD002030.

Update of:
    Cochrane Database Syst Rev. 2003;(2):CD002030.

Photodynamic therapy for neovascular age-related macular degeneration.

Wormald R, Evans J, Smeeth L, Henshaw K.

Moorfields Eye Hospital and London School of Hygiene & Tropical Medicine,
Research and Development Department, City Road, London, UK EC1V 2PD.
r.wormald@ucl.ac.uk

BACKGROUND: In neovascular age-related macular degeneration (AMD) new vessels
grow under the retina distorting vision and leading to scarring. This is
exacerbated if the blood vessels leak. Photodynamic therapy (PDT) has been
investigated as a way to treat the neovascular membranes without affecting the
retina. OBJECTIVES: The aim of this review was to examine the effects of PDT in
the treatment of neovascular AMD. SEARCH STRATEGY: We searched the Cochrane
Central Register of Controlled Trials (CENTRAL) (which includes the Cochrane Eyes
and Vision Group Trials Register) on The Cochrane Library (Issue 1, 2005),
MEDLINE (1966 to January 2005), EMBASE (1980 to January 2005). We used the
Science Citation Index to search for reports that cited relevant studies. We
contacted experts in the field and searched the reference lists of relevant
studies. SELECTION CRITERIA: We included randomised trials of PDT in people with 
choroidal neovascularisation due to AMD. DATA COLLECTION AND ANALYSIS: Two
authors independently extracted the data. Relative risks were combined using a
fixed-effect model after testing for heterogeneity. MAIN RESULTS: Two published
trials were identified that randomised 948 participants to verteporfin therapy
compared to 5% dextrose in water. Both trials were performed by the same
investigators using largely the same clinical centres and funded by manufacturers
of verteporfin. Outcome data were available at 12 and 24 months after the first
treatment. Participants received on average five treatments over two years. The
relative risk of losing three or more lines of visual acuity at 24 months
comparing the intervention with the control group was 0.77 (95% confidence
interval 0.69 to 0.87). The relative risk of losing six or more lines of visual
acuity at 24 months comparing the intervention with the control group was 0.62
(95% confidence interval 0.50 to 0.76). The results at 12 months were similar to 
those at 24 months. The most serious adverse outcome, acute (within 7 days of
treatment) severe visual acuity decrease, occurs in about one in 50 patients.
AUTHORS' CONCLUSIONS: Photodynamic therapy in people with choroidal
neovascularisation due to AMD is probably effective in preventing visual loss
though there is doubt about the size of the effect. Outcomes and potential
adverse effects of this treatment should be monitored closely. Further
independent trials of verteporfin are required to establish that the effects seen
in this study are consistent and to examine important issues not yet addressed,
particularly relating to quality of life and cost.

Publication Types: 
    Meta-Analysis
    Review

PMID: 16235294 [PubMed - indexed for MEDLINE]

1734: Br J Ophthalmol. 2005 Nov;89(11):1420-2.

Non-steroidal anti-inflammatory agents for cystoid macular oedema following
cataract surgery: a systematic review.

Sivaprasad S, Bunce C, Wormald R.

Moorfields Eye Hospital, 162 City Road, London EC1V 2PD, UK.

AIM: To examine the effectiveness of non-steroidal anti-inflammatory drugs
(NSAIDs) in the treatment of cystoid macular oedema (CMO) following cataract
surgery. METHODS: Systematic literature review of randomised controlled trials
(RCTs) that evaluated the effects of NSAIDs in the treatment of CMO following
cataract surgery was done according to the Cochrane Collaboration methodology.
RESULTS: Seven trials involving a total of 266 participants were included. Four
trials studied the effects of NSAIDs in chronic CMO while the other three trials 
examined the effect of NSAIDs in acute CMO. Little evidence of effectiveness was 
found for oral indomethacin and topical fenoprofen for chronic CMO in two small
trials. Treatment with topical 0.5% ketorolac for chronic CMO was found to be
effective in two trials. Three trials examined the effect of topical NSAIDs on
acute CMO. The comparisons among these studies were of a NSAID to placebo,
prednisolone or another NSAID. Because of considerable heterogeneity between
these study designs, their results were not combined in a meta-analysis.
CONCLUSION: A positive effect of topical NSAID (0.5% ketorolac tromethamine
ophthalmic solution) on chronic CMO was noted. However, there is not enough
evidence to show the effectiveness of NSAIDs in acute CMO following cataract
surgery.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 16234444 [PubMed - indexed for MEDLINE]

1735: Cornea. 2005 Nov;24(8):1027-8.

Conjunctival necrosis following intravitreal injection of triamcinolone
acetonide.

Srinivasan S, Prasad S.

Department of Ophthalmology, Arrowe Park Hospital, Wirral, UK.
sathish@tiscali.co.uk

PURPOSE: To report a case of localized conjunctival necrosis following
intravitreal injection of triamcinolone acetonide (TA). DESIGN: Single
observational case report. METHODS: A 63-year- old man presented with
inferotemporal branch retinal vein occlusion and macular edema in his left eye
(OS). He underwent pars plana vitrectomy combined with arteriovenous sheathotomy.
Postoperatively, as the macular edema persisted, he underwent an uneventful
intravitreal injection of TA. RESULTS: Ten days following the intravitreal
injection, he presented with an area of localized conjunctival necrosis overlying
the scleral entry site. Gram stain showed a few white blood cells and no
organisms. The conjunctival swab showed no growth on culture. The area of
conjunctival necrosis responded well to intense topical antibiotic therapy.
CONCLUSIONS: Conjunctival necrosis is a rare anterior segment complication of
intravitreal injection of TA. With the increased usage of intravitreal TA for
various posterior segment disorders, the treating physician should be aware of
this complication.

PMID: 16227858 [PubMed - indexed for MEDLINE]

1736: Am J Ophthalmol. 2005 Oct;140(4):695-702.

Comment in:
    Am J Ophthalmol. 2006 Apr;141(4):785-6; author reply 786.    Am J Ophthalmol. 2006 Apr;141(4):786-7; author reply 787-8.    Am J Ophthalmol. 2006 Jul;142(1):197; author reply 197-8.    Am J Ophthalmol. 2006 May;141(5):985-6; author reply 986.    Am J Ophthalmol. 2006 Sep;142(3):531; author reply 531-2.

Intravitreal triamcinolone compared with macular laser grid photocoagulation for 
the treatment of cystoid macular edema.

Avitabile T, Longo A, Reibaldi A.

Sezione di Oftalmologia, Dipartimento di Specialità Medico-Chirurgiche,
Università di Catania, Catania, Italy. Clinica.Oculistica@mbox.unict.it

PURPOSE: To evaluate the outcome of cystoid macular edema (CME) treated with
intravitreal injections of triamcinolone acetonide (TA), macular laser grid
photocoagulation (MLG), or both (TA+MLG). DESIGN: Prospective, randomized,
interventional, parallel, three-arm clinical trial. METHODS: SETTING:
Institutional clinical study. PATIENTS: Fifty-six patients (63 eyes) affected by 
diabetic or retinal vein occlusion CME. PROCEDURES: Twenty-two eyes received
intravitreal injections of 4 mg TA; 21 eyes underwent MLG; and 20 eyes received
intravitreal injection of 4 mg TA, and after 3 months, MLG. MAIN OUTCOME
MEASURES: Best-corrected visual acuity (VA), central macular thickness (CMT) (by 
optical coherence tomography), and postoperative complications. RESULTS: Mean
follow-up was 9 +/- 2 months (range 6 to 12 months). Baseline VA (logarithm of
minimal angle of resolution [logMAR]) and CMT were, respectively, 0.82 +/- 0.19
and 556 +/- 139 microm microns for the TA group, 0.84 +/- 0.15 and 601 +/- 102
microm microns for the MLG group, and 0.83 +/- 0.22 and 573 +/- 106 microm
microns for the TA+MLG group (no statistically significant difference among the
groups). After the treatment, at 45 days, 3, 6, and 9 months in the TA group, VA 
had improved (P = .004) by 0.26, 0.25, 0.22, and 0.23 logMAR and CMT had
decreased by 37%, 33%, 29%, and 31% (P = < .001). In the MLG group, VA was
unchanged although CMT had decreased by 5%, 13%, 14%, and 16% (P = .021). In the 
TA+MLG group, VA had improved (P = .003) by 0.26, 0.24, 0.19, and 0.20 logMAR,
and CMT had decreased by 36%, 34%, 28%, and 29% (P = < .001). The groups
receiving triamcinolone had better VA and lower CMT values at all time points (P 
< .05). A reinjection was performed in eight eyes; intraocular pressure increased
in nine eyes (treated with medical therapy), and cataract progressed in one eye. 
No injection-related complications occurred. CONCLUSIONS: TA intravitreal
injection improves VA and reduces CMT more than MLG, which in
triamcinolone-treated eyes does not offer further advantages. Intravitreal TA
injection could be used as primary treatment in patients with CME.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 16226521 [PubMed - indexed for MEDLINE]

1737: Am J Ophthalmol. 2005 Oct;140(4):679-87.

The cost-utility of photodynamic therapy in eyes with neovascular macular
degeneration--a value-based reappraisal with 5-year data.

Brown GC, Brown MM, Campanella J, Beauchamp GR.

Center for Value-Based Medicine, Flourtown, Pennsylvania 19031, USA.
gbrown@valuebasedmedicine.com

PURPOSE: To assess the value conferred by photodynamic therapy (PDT) and the
cost-utility of PDT for the treatment of classic, subfoveal choroidal
neovascularization associated with age-related macular degeneration (ARMD).
DESIGN: Average cost-utility analysis utilizing clinical trial data,
patient-based time tradeoff utility preferences, and a third party insurer cost
perspective. METHODS: Five-year visual acuity data from the TAP (Treatment of
Age-related Macular Degeneration With Photodynamic Therapy) Investigation were
modeled into a 12-year, value-based, reference case, cost-utility model utilizing
year 2004 Medicare costs and an outcome of dollar/QALY (dollars/quality-adjusted 
life-year). Discounting of outcomes and costs using net present value analysis
with a 3% annual rate was performed as recommended by the Panel for
Cost-Effectiveness in Health and Medicine. RESULTS: PDT with verteporfin
(Visudyne) dye for classic subfoveal choroidal neovascularization confers an 8.1%
quality of life (value) improvement over the 12-year life expectancy of the
reference case, while during the last 8 years the value improvement is 9.5%. The 
average cost-utility of the intervention is dollar 31,103/QALY (quality-adjusted 
life-year). Extensive one-way sensitivity analysis values range from dollar
20,736/QALY if treatment efficacy is increased by 50% to dollar 62,207 if
treatment efficacy is decreased by 50%, indicating robustness of the model.
CONCLUSIONS: PDT using verteporfin dye to treat classic subfoveal choroidal
neovascularization is a very cost-effective treatment by conventional standards. 
The marked improvement in cost-effectiveness compared with a previous report
results from the facts that the treatment benefit increasingly accrues during 5
years of follow-up while the number of yearly treatments diminishes markedly
during that time.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16226519 [PubMed - indexed for MEDLINE]

1738: Ophthalmology. 2005 Dec;112(12):2070-5. Epub 2005 Oct 12.

Comparison of early retreatment with the standard regimen in verteporfin therapy 
of neovascular age-related macular degeneration.

Michels S, Wachtlin J, Gamulescu MA, Heimann H, Prünte C, Inhoffen W, Krebs I,
Schmidt-Erfurth U.

Klinik für Augenheilkunde und Optometrie, Medizinische Universität Wien, Vienna, 
Austria.

PURPOSE: To compare the efficacy and safety of early retreatment with verteporfin
therapy with that of approved standard verteporfin therapy in neovascular
age-related macular degeneration. DESIGN: Prospective, randomized, multicenter
clinical trial. PARTICIPANTS: Two hundred three patients with predominantly
classic choroidal neovascularization secondary to age-related macular
degeneration. METHODS: Throughout the first 6 months of follow-up, patients
received retreatment with verteporfin therapy either every 2 months (group A) or 
3 months (group B). From 6 to 12 months, both groups received retreatment at
3-month intervals. MAIN OUTCOME MEASURES: The primary outcome of the study was
best-corrected mean visual acuity as measured using the Early Treatment Diabetic 
Retinopathy Study protocol. The secondary outcomes were percentage of patients
losing at least 3 lines of vision, percentage of patients gaining at least 1 line
of vision, and lesion size based on the greatest linear dimension (GLD)
documented by fluorescein angiography, impact of initial lesion size, and
retreatment rate as well as safety. RESULTS: Visual acuity was similar in both
groups at baseline with a mean visual acuity of 20/100(-1). During the 12 months 
of follow-up, mean visual acuity was better in the early retreatment group at all
intervals; however, no statistically significant benefit was seen in the overall 
population at any time (P>0.1). At month 12, mean visual acuity was 20/160(+1) in
group A and 20/160(-1) in group B. There was a trend for better outcomes in the
early retreatment group with regard to loss of less than 3 lines of vision at 12 
months (61% vs. 51.7%). No statistically significant difference was seen with
regard to lesion size for either group throughout follow-up with a final GLD of
the lesion of 2790 microm (group A) and 2996 microm (group B). However, subgroup 
analysis indicated a statistically relevant benefit (P< or =0.004) for patients
with small lesions (GLD<2000 microm) at baseline receiving early retreatment.
CONCLUSIONS: Early retreatment in 2-month intervals did not show a significant
overall benefit at 1 year of follow-up compared with the standard regimen.
However, smaller lesions seemed to benefit from early retreatment with
verteporfin therapy in contrast to larger lesions.

Publication Types: 
    Clinical Trial, Phase III
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16225928 [PubMed - indexed for MEDLINE]

1739: Ophthalmology. 2005 Dec;112(12):2076-80. Epub 2005 Oct 12.

Biomarkers of cardiovascular disease as risk factors for age-related macular
degeneration.

Vine AK, Stader J, Branham K, Musch DC, Swaroop A.

Department of Ophthalmology, University of Michigan, Kellogg Eye Center, Ann
Arbor, Michigan 48105, USA. akv@umich.edu

PURPOSE: To measure and contrast 2 biomarkers of cardiovascular disease,
C-reactive protein (CRP) and plasma homocysteine, in individuals with age-related
macular degeneration (AMD) and control individuals without AMD. DESIGN:
Case-control study. PARTICIPANTS: Seventy-nine affected individuals and 77
unaffected individuals from the AMD Genetic Study Group returned to obtain CRP
and homocysteine levels. METHODS: Both affected and unaffected individuals
underwent testing for CRP and homocysteine. A detailed cardiovascular history was
taken. MAIN OUTCOME MEASURES: Mean CRP and homocysteine levels in affected and
unaffected individuals. RESULTS: Mean CRP levels for affected and unaffected
individuals were 3.42 and 2.30 mg/l, respectively (P = 0.03). Mean homocysteine
levels for affected and unaffected individuals were 11.72 and 8.88 micromol/l,
respectively (P<0.0001). In logistic regression models, older age, higher CRP,
and higher homocysteine were risk factors for AMD. There were no significant
differences between cases and controls in terms of gender, diabetes,
hypertension, use of statin drugs, and smoking. The control group was
significantly younger and had a lower rate of vitamin usage than the affected
group. CONCLUSIONS: Elevated CRP and homocysteine levels are associated with AMD 
and implicate the role of chronic inflammation and atherosclerosis.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16225921 [PubMed - indexed for MEDLINE]

1740: Graefes Arch Clin Exp Ophthalmol. 2006 Apr;244(4):425-32. Epub 2005 Oct 12.

Disclosing disease mechanisms with a spatio-temporal summation paradigm.

Zele AJ, O'Loughlin RK, Guymer RH, Vingrys AJ.

Department of Optometry and Vision Sciences, The University of Melbourne,
Melbourne, Victoria, Australia.

BACKGROUND: We develop the logic for a stimulus that can evaluate cone-dependent 
spatial summation and detail the modelling and interpretation of thresholds
obtained with this stimulus. METHODS: Fifteen observers participated, including
two young normals tested extensively in control experiments, and a clinical trial
based on four observers with age-related macular degeneration (AMD), four
age-similar controls and five young observers. Monocular spatial summation
functions were measured with contrast-modulated Gabor targets that approximated
the optimal visual contrast detector. Thresholds were returned from a yes/no
adaptive psychophysical algorithm. By fine titration along the size domain it was
demonstrated that the spatial summation of normal observers can be adequately
described by a two-component model. A reduced set of variables are proposed for
clinical applications and the model was applied to data derived using these
variables in persons with AMD and age-similar controls. RESULTS: We do not find a
significant age-related loss of contrast sensitivity in our normal group. On the 
other hand, persons with early AMD exhibited a 0.41 log unit loss of sensitivity 
(P=0.04) from age-similar controls, without any change in their maximum summation
area (A(max)). CONCLUSIONS: The nature of the spatial summation is consistent
with the interpretation that early AMD produces a decrease in cone input to
post-receptoral mechanisms in the absence of neural remodelling.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 16220278 [PubMed - indexed for MEDLINE]

1741: Arch Ophthalmol. 2005 Oct;123(10):1338-43.

Comment in:
    Arch Ophthalmol. 2006 Oct;124(10):1506-7; author reply 1507.

Predictive factors for visual acuity after intravitreal triamcinolone treatment
for diabetic macular edema.

Jonas JB, Martus P, Degenring RF, Kreissig I, Akkoyun I.

Department of Ophthalmology, Faculty of Clinical Medicine Mannheim of the
University Heidelberg, Mannheim. Jost.Jonas@augen.ma.uni-heidelberg.de

OBJECTIVE: To evaluate which factors influence maximum gain in best-corrected
visual acuity after intravitreal injection of triamcinolone acetonide as
treatment for diffuse diabetic macular edema. METHODS: This prospective clinical 
interventional study included 53 eyes with diffuse diabetic macular edema
receiving an intravitreal injection of about 20 mg of triamcinolone. The mean +/-
SD follow-up was 10.2 +/- 7.6 months. RESULTS: In a multiple linear regression
analysis, maximum gain in best-corrected visual acuity after the intravitreal
injection of triamcinolone was significantly (P < .001) and negatively correlated
with an increased degree of macular ischemia and a higher preoperative visual
acuity. Improvement in best-corrected visual acuity was significantly and
positively correlated with increased degree of macular edema (P = .001). Change
in best-corrected visual acuity after the intravitreal triamcinolone injection
was statistically independent (P > .15) of age, sex, pseudophakia, and macula
grid laser treatment before inclusion into the study. The results were comparable
for gain in visual acuity at 6 months after the injection. CONCLUSION: Pronounced
macular edema may have a positive impact, and marked macular ischemia and a high 
preoperative best-corrected visual acuity may have a negative impact, on an
increase in best-corrected visual acuity after intravitreal triamcinolone
injection in patients with diabetic macular edema.

PMID: 16219724 [PubMed - indexed for MEDLINE]

1742: Arch Ophthalmol. 2005 Oct;123(10):1330-7.

Repeatability and reproducibility of fast macular thickness mapping with stratus 
optical coherence tomography.

Polito A, Del Borrello M, Isola M, Zemella N, Bandello F.

Author Affiliations: Departments of Ophthalmology and Medical and Morphological
Research, University of Udine, Udine, Italy.

OBJECTIVE: To determine the repeatability and reproducibility of retinal
thickness measurements with the fast macular thickness mapping protocol of
Stratus optical coherence tomography. METHODS: Ten eyes of 10 healthy subjects
and 15 eyes of 15 diabetic patients with clinically significant macular edema
(CSME) underwent 2 scanning sessions before and after pupil dilation during the
same visit by 2 experienced examiners. Healthy subjects also received a third
scanning session during a second visit. Repeatability and reproducibility for the
foveolar center and for each of 9 Early Treatment of Diabetic Retinopathy Study
(ETDRS)-like regions were calculated by their repeatability and reproducibility
coefficients and intraclass correlation coefficients. RESULTS: The coefficients
of repeatability were less than 8% in healthy subjects and less than 9% in
patients with diabetes and CSME. The reproducibility coefficients were less than 
10% and 11% in healthy subjects and diabetic patients with CSME, respectively.
There was no significant difference between scans acquired by different observers
or during different visits. The intraclass correlation coefficients were always
greater than 0.80 and 0.98 in healthy subjects and diabetic patients with CSME,
respectively. Average +/- SD thickness was found to be 223 +/- 14 and 404 +/- 108
mum for the central ETDRS-like region in healthy subjects and diabetic patients
with CSME, respectively. CONCLUSION: With the fast macular thickness mapping
protocol of Stratus ocular coherence tomography, our results indicate that
retinal thickness measurements in dilated and undilated eyes of healthy subjects 
and diabetic patients with CSME are repeatable and reproducible.

PMID: 16219723 [PubMed - indexed for MEDLINE]

1743: Retina. 2005 Oct-Nov;25(7 Suppl):S1-S22.

Neovascular age-related macular degeneration: roundtable.

Singerman LJ, Brucker AJ, Jampol LM, Lim JI, Rosenfeld P, Schachat AP, Spaide RF.

Retina Associates of Cleveland, Cleveland, OH, USA.

Several recent developments may provide an opportunity to improve outcome in
individuals who develop neovascular age-related maculopathy (age-related macular 
degeneration [ARMD]). Concurrent with progress in isolating clinically relevant
subtypes of neovascular ARMD, several therapies have been introduced that show
promise for halting progression of this disorder. However, data from controlled
clinical trials to test the relative efficacy of different management strategies 
across these subtypes of disease presentation remain limited. In addition,
strategies to control ARMD may evolve quickly as more is learned about how
specific molecular events, such as cell-mediated inflammation and angiogenesis,
contribute to disease expression. A roundtable of investigators was convened to
discuss and summarize recent progress in the treatment of ARMD. Case studies were
then presented to provide an opportunity for experts to reveal their specific
thought processes in the approach to neovascular ARMD based on their own
interpretation of current clinical data and empirical experience.

Publication Types: 
    Case Reports
    Congresses
    Research Support, Non-U.S. Gov't

PMID: 16208185 [PubMed - indexed for MEDLINE]

1744: Retina. 2005 Oct-Nov;25(7):883-8.

Frequency and associations of a taut thickened posterior hyaloid, partial
vitreomacular separation, and subretinal fluid in patients with diabetic macular 
edema.

Thomas D, Bunce C, Moorman C, Laidlaw AH.

Department of Ophthalmology, St. Thomas' Hospital, London, United Kingdom.

PURPOSE: To determine prospectively among patients with diabetic macular edema
(DME) the frequency of a clinically evident taut thickened posterior hyaloid
(TTPH), optical coherence tomography (OCT) signs suggestive of partial
vitreomacular separation (PVMS), and OCT evidence of subretinal fluid (SRF) and
to investigate for associations between these findings. METHODS: In a prospective
case series, patients with DME despite previous laser treatment were examined for
the presence of a TTPH. OCT was performed to investigate for PVMS and SRF.
RESULTS: One hundred forty patients and eyes were included in the study. A TTPH
was present in six patients (4%). PVMS was present in 14 (10%) of 140 patients
with DME, of whom 5 also had a TTPH. SRF was present in 15 (11%) of 140 patients,
of whom 4 had TTPH. OCT showed that 66% of patients with SRF and DME had neither 
a clinical TTPH nor partial posterior hyaloid separation. CONCLUSION: A TTPH was 
found in 4% of subjects with DME. Partial posterior hyaloid separation and SRF
may be found in patients who do not have a TTPH. SRF in patients with DME may not
be tractional.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16205568 [PubMed - indexed for MEDLINE]

1745: Retina. 2005 Oct-Nov;25(7):861-7.

Triamcinolone acetonide with vitrectomy for treatment of macular edema associated
with branch retinal vein occlusion.

Tsujikawa A, Fujihara M, Iwawaki T, Yamamoto K, Kurimoto Y.

Department of Ophthalmology, Kobe City General Hospital, Kobe, Japan.
tujikawa@kuhp.kyoto-u.ac.jp

PURPOSE: To review the efficacy of a combination of triamcinolone acetonide (TA) 
injection and pars plana vitrectomy (PPV) for the treatment of macular edema
associated with branch retinal vein occlusion (BRVO). METHODS: Seventeen eyes
with macular edema associated with BRVO underwent PPV with an intraoperative
injection of TA (10 mg) into the vitreous cavity. Residual or recurrent macular
edema was treated with postoperative sub-Tenon capsule injections of TA (20 mg). 
RESULTS: With PPV and an intraoperative injection of TA, 82% of eyes showed rapid
reduction of macular edema; foveal thickness decreased from 507 +/- 115 microm
preoperatively to 261 +/- 123 microm 2 months after surgery (P = 0.0041).
However, 59% of eyes showed recurrence of macular edema during the follow-up
period. Twelve eyes with residual or recurrent macular edema received sub-Tenon
capsule injections of TA; of these eyes, 9 showed substantial reduction of
macular edema. Foveal thickness decreased from 381 +/- 102 microm to 256 +/- 56
microm (P = 0.0076) 2 weeks after postoperative injections of TA. At the final
visit, visual acuity (logMAR) improved from 0.74 +/- 0.40 preoperatively to 0.40 
+/- 0.34 (P = 0.010). CONCLUSION: An intraoperative injection of TA in
combination with PPV has the potential to facilitate the absorption of macular
edema associated with BRVO. In addition, residual or recurrent macular edema can 
be treated with additional sub-Tenon capsule injections of TA.

PMID: 16205565 [PubMed - indexed for MEDLINE]

1746: Retina. 2005 Oct-Nov;25(7):851-5.

Intravitreal triamcinolone injection for treatment of macular edema secondary to 
branch retinal vein occlusion.

Cekiç O, Chang S, Tseng JJ, Barile GR, Del Priore LV, Weissman H, Schiff WM, Ober
MD.

From the Department of Ophthalmology, College of Surgeons and Physicians of
Columbia University, New York, New York 10032, USA. ocekic@hotmail.com

PURPOSE: To evaluate the efficacy of intravitreal triamcinolone injection in eyes
with macular edema due to branch retinal vein occlusion (BRVO) over a 2-year
period. METHODS: The authors performed a retrospective chart review of 13 eyes of
13 patients (mean age 68 years) who underwent intravitreal injections with 4 mg
triamcinolone acetonide for macular edema due to BRVO. Six eyes received a single
injection. Repeated injections were performed in one eye twice, four eyes three
times, and two eyes four times. Mean follow-up was 13 months (range, 4 to 24).
The time between the onset of symptoms and the injection averaged 7.4 months
(range, 2 to 24). RESULTS: Mean postinjection central foveal thickness decreased 
to 56% of preinjection values (529 mum versus 295 mum, P < 0 .001). Final visual 
acuity improved in seven eyes (range 2 to 6 Snellen lines), remained the same in 
four eyes (range 0 to 1 Snellen lines), and worsened in two eyes (range -1 to -4 
Snellen lines) compared to baseline. The retinal thickness decreased in all
cases; vision improved in most cases. As the number of injections increased
cataractous changes increased. Visual acuity improvement was significantly
correlated with patient age (P = 0.026). Eight patients developed steroid induced
ocular hypertension controlled by topical medication. Cataract extraction was
judged to aggravate macular edema in three of the five eyes undergoing surgery,
based upon optical coherence tomography or fluorescein angiography. Median best
postinjection visual acuity (20/50) was significantly better than that of
baseline (20/100) (P = 0.028) as well as last follow-up (20/70) (P = 0.003).
CONCLUSIONS: Intravitreal triamcinolone should be further evaluated as a
treatment option for macular edema associated with BRVO.

PMID: 16205563 [PubMed - indexed for MEDLINE]

1747: Retina. 2005 Oct-Nov;25(7):846-50.

Intravitreal triamcinolone treatment for macular edema associated with central
retinal vein occlusion and hemiretinal vein occlusion.

Cekiç O, Chang S, Tseng JJ, Barile GR, Weissman H, Del Priore LV, Schiff WM,
Weiss M, Klancnik JM Jr.

Department of Ophthalmology, College of Surgeons and Physicians of Columbia
University, Harkness Eye Institute, New York, New York 10032, USA.
ocekic@hotmail.com

PURPOSE: To assess the efficacy of intravitreal triamcinolone treatment for
macular edema from central retinal vein occlusion (CRVO) and hemiretinal vein
occlusion (HRVO). METHODS: This study was a retrospective medical records review 
of 24 eyes of 24 patients (mean age, 71 years) that were injected with 4 mg of
intravitreal triamcinolone acetonide for treatment of macular edema due to CRVO
(n = 21) and HRVO (n = 3). Of the 24 eyes, 14 were injected once, 6 were injected
twice, 3 were injected 3 times, and 1 received 4 injections. Mean follow-up time 
was 10 months (range, 3-24 months). The average time between onset of symptoms
and first injection was 5.4 months (range, 2-48 months). Available documents on
pre- and postinjection optical coherence tomography central foveal thickness in
23 of 39 total injections were evaluated. RESULTS: All injections resulted in
reduction in central foveal thickness as determined by optical coherence
tomography. The mean central foveal thickness decreased to 55% of preinjection
values ([n = 23] 635 vs. 352 mum, respectively; P < 0.001). The average gain in
visual acuity was 1.3 Snellen lines (range, -3-7) over the course of the study
period. Ten eyes gained > or =2 lines of visual acuity, 3 eyes improved 1 line, 7
eyes remained the same, and 4 eyes worsened. There was no correlation between
improvement in foveal thickness and corresponding visual gain (P = 0.24). None of
the eyes of diabetic patients (n = 6) or patients with ischemic CRVO (n = 2)
improved in visual acuity. The difference in mean baseline (20/167) and mean
final visual acuity (20/91) was statistically significant (P = 0.015). The mean
best postinjection visual acuity (20/67) was also significantly higher than the
mean final visual acuity (P = 0.019). When diabetic and ischemic CRVO patients
were excluded, the difference between mean baseline visual acuity and mean final 
visual acuity was found to be highly significant ([n = 16] 20/133 vs. 20/67,
respectively; P < 0.001), while mean final and best postinjection visual acuities
(20/50) did not differ (P = 0.085). Eight of 16 phakic eyes showed progression of
cataract, 2 of which underwent cataract extraction. Nine of 18 patients without a
history of glaucoma developed ocular hypertension and required glaucoma
medication during postinjection follow-up. Trabeculectomy was performed on two
eyes with glaucoma. Two other eyes developed epiretinal membranes, one of which
underwent vitrectomy. CONCLUSIONS: Intravitreal triamcinolone may be effective in
treating macular edema from CRVO and HRVO. Subjects with concurrent diabetes or
ischemic central retinal vein were less likely to have visual improvement.

PMID: 16205562 [PubMed - indexed for MEDLINE]

1748: Retina. 2005 Oct-Nov;25(7):840-5.

Time course of changes in retinal thickness and visual acuity after intravitreal 
triamcinolone acetonide for diffuse diabetic macular edema with and without
previous macular laser treatment.

Patelli F, Fasolino G, Radice P, Russo S, Zumbo G, DI Tizio FM, Frisone G, Marchi
S.

Department of Ophthalmology, "Villa Tiberia" Clinic, Rome, Italy.
f.patelli@tiscali.it

PURPOSE: To describe the changes in retinal thickness (RT) and visual acuity over
time in patients with clinically significant diffuse diabetic macular edema (DME)
after intravitreal injection of triamcinolone acetonide (IVTA) and to compare
patients with and without previous laser treatment. METHODS: A total of 23 eyes
with clinically significant DME received a 4-mg IVTA injection. Twelve eyes were 
refractory to macular laser treatment (group 1), and 11 eyes received IVTA as
primary therapy (group 2). Visual acuity and changes in macular thickening shown 
by optical coherence tomography were evaluated 48 hours after injection, every 7 
days for 1 month, and at 3 months and 6 months of follow-up. RESULTS: RT
decreased in all eyes in both groups. The reduction of edema was maximal in the
first 7 days after IVTA and tended to remain stable for 3 months. The decrease in
RT over time was significant in both groups (P < 0.001). At 6 months, RT had
increased in almost all eyes. Visual acuity improved quickly, to a maximum at 2
weeks in both groups, after which it remained stable for 3 months and then
decreased. Improvement in visual acuity over time was significant in both groups 
(P < 0.001). The temporal characteristics of the changes in RT and visual acuity 
were similar in the two groups (P < 0.05). CONCLUSIONS: IVTA was effective in
reducing clinically significant DME and improving visual acuity in eyes with and 
without previous laser treatment. Its action was maximal in the first week and
lasted approximately 3 months in this study.

Publication Types: 
    Comparative Study

PMID: 16205561 [PubMed - indexed for MEDLINE]

1749: Retina. 2005 Oct-Nov;25(7):835-9.

Primary intravitreal triamcinolone acetonide for diabetic massive macular hard
exudates.

Khairallah M, Zeghidi H, Ladjimi A, Yahia SB, Attia S, Zaouali S, Messaoud R.

Department of Ophthalmology, Fattouma Bourguiba University Hospital, Monastir,
Tunisia. moncef.khairallah@rns.tn

PURPOSE: To evaluate the efficacy of intravitreal triamcinolone acetonide as
treatment for massive macular hard exudates in diabetic patients. METHODS: The
study was a prospective, noncomparative, interventional case series of 12 eyes
(12 patients) with massive hard exudates involving the fovea that had no previous
focal laser treatment. A single intravitreal injection of 4 mg of triamcinolone
acetonide in 0.1 mL was performed. Visual acuity and evolution of hard exudates
and fluorescein leakage were assessed. Potential complications were monitored,
including ocular hypertension and endophthalmitis. RESULTS: The follow-up period 
ranged from 6 to 12 months (mean, 8.25 months). Visual acuity improved
significantly at examinations performed 7 days (P = 0.036), 1 month (P = 0.008), 
3 months (P = 0.008), and 6 months (P = 0.003) after the injection. Visual acuity
improved by at least 2 Snellen lines in 4 patients (33%). However, no eyes with
initial visual acuity worse than 20/100 improved to better than 20/100. Foveal
hard exudates resolved completely in 6 eyes (50%) and partially in 6 eyes (50%). 
Fluorescein leakage decreased and a variable proportion of microaneurysms
disappeared in all cases. Intraocular pressure elevation occurred in 3 eyes (25%)
and was successfully treated by topical medication. No other complications, such 
as endophthalmitis, were recorded. CONCLUSION: Intravitreal injection of
triamcinolone acetonide appears to be beneficial for reducing hard exudates,
decreasing fluorescein leakage, and significantly improving visual acuity in
patients with diabetic massive hard exudates. Visual improvement may not be
important due to profound anatomical impairment caused by hard exudate
deposition. Further studies with a larger number of patients are required to
assess the long-term efficacy and safety and the need for retreatment.

PMID: 16205560 [PubMed - indexed for MEDLINE]

1750: Retina. 2005 Oct-Nov;25(7):828-34.

Intravitreal triamcinolone acetonide for diabetic macular edema.

Chieh JJ, Roth DB, Liu M, Belmont J, Nelson M, Regillo C, Martidis A.

Retina-Vitreous Center, University of Medicine and Dentistry of New
Jersey--Robert Wood Johnson Medical School, New Brunswick, New Jersey 08903, USA.

PURPOSE: Intravitreal injection of triamcinolone acetonide has been advocated to 
treat exudative diabetic macular edema. The purpose of the study was to evaluate 
the clinical outcome of an intravitreal injection of triamcinolone acetonide as
treatment for diffuse diabetic macular edema. METHODS: This study was a
retrospective, interventional, clinical case series examining 210 eyes of 174
patients who received an intravitreal injection of 1 or 4 mg of triamcinolone
acetonide for treatment of diffuse diabetic macular edema. Inclusion criteria
were clinically significant macular edema, visual acuity loss, and leakage shown 
by fluorescein angiography. Main outcome measures were visual acuity and
intraocular pressure. Mean follow-up time +/- SD was 6.6 +/- 3.1 months. RESULTS:
In the study group, visual acuity improved significantly (P < 0.001) from a
median of 20/200 (mean logMAR, 0.92) at baseline to 20/80 (mean logMAR, 0.82) at 
6 months. Mean intraocular pressure +/- SD increased from 15.4 +/- 3.4 mmHg
(median, 16 mmHg; range, 6-26 mmHg) to a maximal value of 20.4 +/- 6.2 mmHg
(median, 19 mmHg; range, 12-51 mmHg) during the follow-up period. Complications
included culture-negative sterile endophthalmitis in six cases and cataract
extraction in five eyes. CONCLUSIONS: Intravitreal injection of 1 to 4 mg of
triamcinolone acetonide may benefit patients by improving visual acuity in eyes
with clinically significant diabetic macular edema. This study did not provide
significant evidence to justify its routine use in clinical practice for all
patients with diabetic macular edema. A randomized clinical trial on this issue
would provide more conclusive evidence and help identify those patients most
likely to benefit from intravitreal triamcinolone acetonide.

PMID: 16205559 [PubMed - indexed for MEDLINE]

1751: Retina. 2005 Oct-Nov;25(7):815-27.

Enhanced efficacy associated with early treatment of neovascular age-related
macular degeneration with pegaptanib sodium: an exploratory analysis.

Gonzales CR; VEGF Inhibition Study in Ocular Neovascularization (V.I.S.I.O.N.)
Clinical Trial Group.

Jules Stein Eye Institute and Department of Ophthalmology, David Geffen School of
Medicine, UCLA, 200 Stein Plaza, Los Angeles, CA 90095, USA.
gonzales@jsei.ucla.edu

PURPOSE: To assess the vision benefit of treating early subfoveal choroidal
neovascularization secondary to age-related macular degeneration (AMD) with
pegaptanib sodium. METHODS: Exploratory analyses of week 54 vision outcomes (VEGF
Inhibition Study in Ocular Neovascularization study) of subject subgroups with
early disease who received 0.3 mg of pegaptanib (Groups 1 [n = 34] and 2 [n =
30]) or sham injections (usual care). Two sets of clinical characteristics
typical of early disease defined the subgroups. RESULTS: Baseline characteristics
were generally well balanced between treatment arms. Pegaptanib responder rates
(loss of <15 letters of visual acuity) were 76% and 80% in treatment Groups 1 and
2 versus 50% and 57% for usual care Groups 1 and 2 (P = 0.03 and P = 0.05),
respectively. Compared with subjects assigned to pegaptanib, those in Groups 1
and 2 receiving usual care on average lost 11.1 letters and 12.7 letters more of 
visual acuity (P < 0.01 and P < 0.006), respectively. Subjects assigned to usual 
care were approximately 10 times more likely to have severe vision loss than were
those treated with pegaptanib (Group 1, 29% vs. 3%, respectively; P < 0.01). In
Group 1, 12% of pegaptanib-treated subjects gained > or =15 letters of visual
acuity versus 4% receiving usual care; 20% of Group 2 pegaptanib-treated subjects
gained > or =15 letters of visual acuity versus none of the usual care subjects. 
CONCLUSION: Early detection and treatment with pegaptanib may result in superior 
vision outcomes in patients with neovascular AMD.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16205558 [PubMed - indexed for MEDLINE]

1752: Biomaterials. 2006 Mar;27(8):1670-8. Epub 2005 Sep 30.

Determination of human lens capsule permeability and its feasibility as a
replacement for Bruch's membrane.

Lee CJ, Vroom JA, Fishman HA, Bent SF.

Department of Chemical Engineering, Stanford University, Stanford, California
94305-5025, USA.

We have investigated human anterior lens capsule as a potential replacement for
Bruch's membrane as a treatment for age-related macular degeneration. Any
substrate to replace Bruch's membrane should possess certain characteristics to
maintain proper function of the overlying retina. One of the important properties
of Bruch's membrane is allowing the flow of nutrients and waste between the
retinal pigment epithelium and the choriocapillaris. Here, we measured the
permeability of the lens capsule by studying the diffusion of various molecular
weight FITC-dextran molecules. Expressions for extraction of diffusion
coefficients from concentration vs. time data from a blind-well chamber apparatus
were derived for both a single and double membrane experiments. The diffusion
coefficients in the lens capsule were found to be in the range of 10(-6) to
10(-10)cm2/s. We demonstrated a power law relationship, with the diffusion
coefficient possessing a -0.6 order dependence on molecular weight. The molecular
weight exclusion limit was determined to be 150+/-40 kDa. We have compared this
value with reported values of Bruch's membrane molecular weight exclusion limit
and find that the lens capsule has the potential to act as a substitute Bruch's
membrane.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 16199085 [PubMed - indexed for MEDLINE]

1753: Expert Opin Biol Ther. 2005 Oct;5(10):1373-85.

Emerging biological therapies for age-related macula degeneration.

Constable I, Shen WY, Rakoczy E.

Lions Eye Institute, Centre for Ophthalmology and Visual Science, University of
Western Australia, Nedlands, WA 6009, Australia. ijc@cyllene.uwa.edu.au

Age-related macular degeneration (AMD) has emerged as the dominant cause of
irretrievable visual loss in most developed countries achieving increasing
longevity. The major cause of rapid and severe visual loss is the development of 
choroidal neovascularisation under the macula (exudative or wet AMD). Physical
treatments, especially thermal laser and photodynamic therapy following
intravenous verteporfin, have made statistically significant but modest progress 
in limiting visual loss, whereas surgical translocation of the macula and even
light or electrically sensitive retinal implants are spectacular, but likely to
only ever benefit a few. Intravitreal fine needle injections and slow release
implants of steroid derivatives have opened new areas for investigation. The
blocking of endothelial receptors for vascular endothelial growth factor by
RNA-based aptamer or immune-protected antibody fragments has been the subject of 
intensive scientific development and large scale clinical trials. This approach
may expand the range of AMD patients amenable to treatment. Additional
therapeutic gains await measures to modify photoreceptor cell loss and subretinal
fibrosis involving the retinal pigment epithelium as well as prevention or
treatment for pigment epithelial detachment. Epidemiological associations with
smoking and diet, and antioxidant dietary supplements offer important strategies 
for prevention.

Publication Types: 
    Review

PMID: 16197342 [PubMed - indexed for MEDLINE]

1754: Coll Antropol. 2005;29 Suppl 1:103-5.

Treatment of pseudophakic cystoid macular oedema.

Curković T, Vukojević N, Bućan K.

University Department of Ophthalmology, Clinical Hospital Center, Rebro, Zagreb, 
Croatia.

Cystoid oedema of macula is the most frequent problem following non-complicated
cataract surgery, which leads to weakening of visual acutity. We have studied the
treatment outcomes of the topical therapy with corticosteroids and nonsteroid
antirheumatics during prospective randomized study in comparison with orally
applied acethazolamide. However, 8 weeks later in treatment was observed a
positive effect in both groups, on the eyes of patients, treated with
acetazolamide, resorption of the oedema was faster, more intensive and ultimate
visual acutity was statistically significantly better. Results demonstrated a
benefit of combined therapy with antiinflamative drugs and orally prescribed
acetazolamide in pseudophakic macular oedema.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 16193688 [PubMed - indexed for MEDLINE]

1755: Acta Ophthalmol Scand. 2005 Oct;83(5):600-4.

Intravitreal triamcinolone acetonide in patients with macular oedema due to
branch retinal vein occlusion: a pilot study.

Krepler K, Ergun E, Sacu S, Richter-Müksch S, Wagner J, Stur M, Wedrich A.

Department of Ophthalmology, Medical University of Vienna, Vienna, Austria.
katharina.krepler@meduniwien.ac.at

PURPOSE: To evaluate treatment of macular oedema due to branch retinal vein
occlusion (BRVO) with intravitreal triamcinolone acetonide. METHODS: In a
prospective case series, nine patients with macular oedema due to BRVO received
an intravitreal injection of 4 mg triamcinolone acetonide. Examination included
best-corrected visual acuity (BCVA) for distance and reading, intraocular
pressure (IOP) measurement, fluorescein angiography and high resolution imaging
by optical coherence tomography, preoperatively and at 1 week, 1 month, 3 and 6
months postoperatively. RESULTS: Preoperative mean BCVAs were 1.3 +/- 0.8 for
distance vision, and 1.1 +/- 0.3 for reading acuity, respectively. A significant 
improvement in reading acuity was observed until 1 month (0.7 +/- 0.4, p = 0.02).
No significant reduction in mean macular thickness was observed. CONCLUSIONS:
Intravitreal injection of triamcinolone acetonide led to a significant
improvement in mean VA in patients with macular oedema due to BRVO. However, the 
significant effect was not permanent and persisted for only 1 month.

PMID: 16188000 [PubMed - indexed for MEDLINE]

1756: Acta Ophthalmol Scand. 2005 Oct;83(5):595-9.

Intravitreal triamcinalone acetonide for refractory uveitic cystoid macular
oedema: longterm management and outcome.

Angunawela RI, Heatley CJ, Williamson TH, Spalton DJ, Graham EM, Antcliffe RJ,
Stanford MR.

GKT Department of Ophthalmology, Rayne Institute, St Thomas' Hospital, London,
UK.

PURPOSE: To establish the role of intravitreal triamcinalone acetonide (TA) in
the long term management of refractory uveitic cystoid macular oedema (CMO) and
to determine the long term visual outcome in these patients. METHOD: This is a
retrospective observational case series. All patients had resistant CMO and
active inflammation. The primary outcome measure was complete resolution of CMO
on ocular coherence tomography. Visual acuity and intraocular pressure were also 
monitored. Twelve eyes of twelve patients received 2 (n = 10) to 4 (n = 2) mg of 
intravitreal TA. All had previously been unresponsive to orbital floor steroids. 
Fluorescein angiography was performed where indicated. RESULTS: There was
complete resolution of CMO in all patients. Nine patients had improvement in
acuity at there final follow up (mean follow up 40.5 months). Seven had improved 
by 2 lines (58%). In 3 patients there was no visual improvement. These 3 failed
to respond to re-treatment. Five other patients were re-treated because of
recurring CMO and deteriorating VA (median time to re-treatment 4 mths). The mean
number of re-treatments for this group with orbital floor TA was three. 41.6% of 
patients developed ocular hypertension (33.8 mhg mean). One required a
trabeculectomy. CONCLUSIONS: 2 mg of intravitreal TA is effective even in cases
of resistant uveitic CMO. Although re-treatment is often required, the initial
response to treatment can be maintained by subsequent orbital floor steroid
injections.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16187999 [PubMed - indexed for MEDLINE]

1757: Acta Ophthalmol Scand. 2005 Oct;83(5):419-23.

Corrected and republished from:
    Acta Ophthalmol Scand. 2005 Aug;83(4):419-23.

Refraction, axial length and age-related maculopathy.

Ulvik SO, Seland JH, Wentzel-Larsen T.

Department of Ophthalmology, Haukeland University Hospital, Bergen, Norway.

PURPOSE: To study the relationship between age-related maculopathy
(ARM)/age-related macular degeneration (AMD) and phakic refraction and between
ARM/AMD and axial length. METHODS: The study was a point prevalence study that
included 663 randomly selected persons aged over 65 years. We measured axial
length and refraction. Fundus images were graded for ARM according to a modified 
Wisconsin Age-related Maculopathy Grading System standard. Data from both eyes
were available from most participants. We analysed the results for both
individual eyes and pairs. RESULTS: The mean axial length was 23.22 mm for right 
eyes and 23.21 mm for left eyes. Women had a 0.57-mm shorter mean axial length
than men. The mean refraction was +1.0 dioptres (D) for right eyes and +0.9 D for
left eyes. At 70 years of age women were more hypermetropic than men by 0.66 D.
There was no significant difference in refraction or axial length among the
groups with different ARM stages. CONCLUSION: We found no statistically
significant relationship between axial length/refraction and AMD/ARM. There was a
statistically significant sex difference in axial length and refraction, where
women had shorter axial lengths and were more hypermetropic than men.

Publication Types: 
    Corrected and Republished Article
    Research Support, Non-U.S. Gov't

PMID: 16187985 [PubMed - indexed for MEDLINE]

1758: J Chin Med Assoc. 2005 Sep;68(9):419-24.

Photodynamic therapy for subfoveal choroidal neovascularization secondary to
age-related macular degeneration.

Shyong MP, Lee FL, Chen SJ, Tung TH, Tsai DC, Hsu WM.

Su-Ao Veterans Hospital, I-Lan, Taiwan.

BACKGROUND: To evaluate the safety and efficacy of verteporfin photodynamic
therapy (PDT) in patients with subfoveal choroidal neovascularization (CNV)
secondary to age-related macular degeneration (AMD). METHODS: We retrospectively 
reviewed the chart records and fluorescein angiography of patients with subfoveal
CNV who were treated with verteporfin PDT between September 2001 and March 2003
and who completed at least 1 year of follow-up. The primary efficacy outcomes
were the proportions of patients whose Snellen visual acuities had more than 1
line increase, no change or more than 1 line decrease 1 year after study entry
compared with their baseline examinations. The secondary efficacy outcome was the
changes in the logarithm of the minimum angle of resolution visual acuities at
1-year follow-up. Complications were monitored and tabulated. RESULTS:
Forty-eight eyes of 48 patients with subfoveal CNV secondary to AMD were enrolled
in this study. The mean follow-up was 12.56 +/- 1.37 months. At their last visit,
10.4% of eyes had more than 1 line improvement in Snellen visual acuity, 72.9% of
eyes had no change, and 16.7% experienced more than 1 line of visual acuity loss 
(7 eyes lost < 3 lines of Snellen visual acuity, 1 eye lost between 3 and 6
lines). None experienced more than 6 lines of visual loss. There was no
statistically significant difference between baseline and final visual acuity for
eyes with predominantly classic CNV, minimally classic CNV and occult without
classic CNV (Wilcoxon Signed Rank test, p = 0.59 ). There was a positive
correlation between baseline visual acuity and final visual outcome
(Kruskal-Wallis test, p = 0.002). No severe systemic and ocular adverse events
were encountered. CONCLUSION: Of our patients with subfoveal CNV secondary to
AMD, 83.3% could maintain or improve their visual acuity 1 year after verteporfin
PDT. The risk of deterioration in visual acuity due to subfoveal CNV could be
reduced by verteporfin PDT. Baseline visual acuity is significantly correlated
with the final proportion of visual outcome.

PMID: 16187598 [PubMed - indexed for MEDLINE]

1759: Invest Ophthalmol Vis Sci. 2005 Oct;46(10):3855-8.

Effect of ruboxistaurin on blood-retinal barrier permeability in relation to
severity of leakage in diabetic macular edema.

Strøm C, Sander B, Klemp K, Aiello LP, Lund-Andersen H, Larsen M.

Department of Ophthalmology, Herlev Hospital, University of Copenhagen, Denmark.

PURPOSE: The purpose of the study was to investigate the effect of orally
administered ruboxistaurin (RBX, LY333531), a selective protein kinase C beta
inhibitor, on the permeability of the blood-retinal barrier in patients with
diabetic macular edema. METHODS: Forty-one patients with diabetic macular edema
were randomly assigned to an 18-month randomized, placebo-controlled,
double-masked trial including four study arms (4, 16, or 32 mg/d RBX, or
placebo). The RBX group comprised 30 patients (42 eyes) and the placebo group 11 
patients (13 eyes). Retinal vascular leakage was assessed using vitreous
fluorometry at baseline and after 3, 12, and 18 months. Statistical analysis of
the effect of treatment accounted for repeated measurements and tested potential 
interaction with baseline permeability, HbA(1c), and arterial blood pressure.
RESULTS: Statistical analysis and modeling demonstrated a significant interaction
between RBX treatment at any dosage and baseline permeability (P = 0.032, mixed
models). A threefold or higher increase in retinal vascular leakage at baseline
was associated with a significant reduction (30%) in retinal vascular leakage
after RBX treatment compared with placebo. Visual acuity was normal at baseline
and remained unchanged throughout the study. CONCLUSIONS: RBX treatment was
associated with a reduction of retinal vascular leakage in eyes that had diabetic
macular edema and markedly elevated leakage at baseline. These data suggest that 
clinical benefit from RBX treatment may be most prominent in patients with severe
macular edema at baseline, and trials investigating this therapy may benefit from
stratification according to baseline leakage.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16186374 [PubMed - indexed for MEDLINE]

1760: Invest Ophthalmol Vis Sci. 2005 Oct;46(10):3845-9.

Intravitreal injection versus sub-Tenon's infusion of triamcinolone acetonide for
refractory diabetic macular edema: a randomized clinical trial.

Bonini-Filho MA, Jorge R, Barbosa JC, Calucci D, Cardillo JA, Costa RA.

Department of Ophthalmology, School of Medicine of Ribeirão Preto, Brazil.

PURPOSE: To compare the effectiveness of posterior sub-Tenon's infusion (STi) and
intravitreal injection (IVI) of triamcinolone acetonide (TA) for treatment of
refractory diffuse diabetic macular edema. METHODS: Thirty-six phakic diabetic
patients with refractory diffuse diabetic macular edema were prospectively
enrolled. Patients randomly received either 40 mg STi or 4 mg IVI of TA.
Comprehensive ophthalmic evaluation was performed at baseline and 1, 2, 4, 8 +/- 
1, 12 +/- 2 and 24 +/- 2 weeks after treatment. Macular morphologic changes
detected by optical coherence tomography and visual acuity, intraocular pressure,
and lens status were evaluated. RESULTS: Twenty-eight patients (28 eyes)
completed the 24-week study. Central macular thickness was significantly reduced 
in the IVI group when compared with the STi group at 2, 4, 8, 12, and 24 weeks
after treatment (P < 0.01). Mean visual acuities (in logarithm of the minimum
angle of resolution [logMAR]) at week-4, -8, and -12 follow-up examinations were 
significantly higher in the IVI group (0.74, 0.75, and 0.82, respectively) when
compared with the STi group (0.88, 0.88, and 0.90, respectively; P < 0.01). A
significant change from baseline in mean intraocular pressure (mm Hg) was seen at
weeks 4 (+/-3.21) and 8 (+/-3.35) in STi the group (P < 0.01), and at week 8
(+/-2.78) in the IVI group (P < 0.05). No patient had cataract progression during
the study. CONCLUSIONS: Although the number of patients and length of follow-up
in this preliminary study were limited, the changes in central macular thickness 
and visual acuity observed after treatment suggest that IVI TA may be more
effective than STi for the management of refractory diffuse diabetic macular
edema. Further studies are needed to confirm these preliminary findings.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16186372 [PubMed - indexed for MEDLINE]

1761: Clin Experiment Ophthalmol. 2005 Oct;33(5):544-5.

Severe loss of vision after removal of cataract caused by intravitreal
triamcinolone in combination with photodynamic therapy for exudative age-related 
macular degeneration.

Larsson J, Gillies MC.

Intravitreal triamcinolone has been suggested as an adjunctive to photodynamic
therapy in the treatment of exudative macular degeneration. One of the
side-effects of intravitreal triamcinolone is the development of cataract, and it
is known that cataract extraction can exacerbate macular degeneration. A case is 
presented where combined intravitreal triamcinolone and photodynamic therapy
stopped the progression of the exudative macular degeneration. Subsequent
progression of cataract required cataract extraction, which resulted in a very
rapid progression of the exudative macular degeneration and loss of vision.

Publication Types: 
    Case Reports
    Letter

PMID: 16181292 [PubMed - indexed for MEDLINE]

1762: Clin Experiment Ophthalmol. 2005 Oct;33(5):518-23.

Bruch's membrane and the vascular intima: is there a common basis for age-related
changes and disease?

Sivaprasad S, Bailey TA, Chong VN.

King's College Hospital, London, UK. senswathi@aol.com

Several clinical and epidemiological studies have concurrently illuminated
established cardiovascular risk factors in age-related macular degeneration
(AMD), raising the possibility that cardiovascular disease and AMD may share a
similar pathogenic process. The vascular intima and the Bruch's membrane share
several age-related changes and are the seat of many common molecules. Diseases
of these structures may represent parallel responses to the tissue injury induced
by multiple intercalated factors such as genetic variations, oxidative stress,
inappropriately directed immune response or inflammatory disease complex.
However, there are marked differences in the age-related changes in these two
structures. The strategic location of the Bruch's membrane between the retinal
pigment epithelium and the choriocapillaris can at least partially explain the
differential susceptibility of AMD to cardiovascular risk factors. Unlike the
vascular wall that is exposed to changes from the endothelium, the Bruch's
membrane is subject to changes from both the endothelium (choriocapillaris) and
epithelium (retinal pigment epithelium). Moreover, although both the vascular
wall and Bruch's membrane become lipid laden with age, the lipid composition is
characteristically different. This review examines the morphological and
biochemical alterations in the senescent Bruch's membrane and its analogy to the 
vascular wall to evaluate the concurrence of atherosclerosis and AMD.

Publication Types: 
    Review

PMID: 16181282 [PubMed - indexed for MEDLINE]

1763: Hum Mol Genet. 2005 Nov 1;14(21):3227-36. Epub 2005 Sep 20.

Hypothetical LOC387715 is a second major susceptibility gene for age-related
macular degeneration, contributing independently of complement factor H to
disease risk.

Rivera A, Fisher SA, Fritsche LG, Keilhauer CN, Lichtner P, Meitinger T, Weber
BH.

Institute of Human Genetics, University of Regensburg, Germany.

Age-related macular degeneration (AMD) is a multifactorial disease and a
prevalent cause of visual impairment in developed countries. Risk factors include
environmental components and genetic determinants. The complement factor H (CFH) 
has been the first major susceptibility gene for AMD identified within 1q32.
Here, we focused on a second region of interest in 10q26 where a recent
meta-analysis revealed strongest evidence for linkage to AMD at a genome-wide
significance level. Within an interval of 22 Mb, we have analyzed 93 single
nucleotide polymorphisms for allelic association with AMD in two independent
case-control cohorts of German origin (AMD(combined) n=1166; controls(combined)
n=945). Significant association was found across a 60 kb region of high linkage
disequilibrium harboring two genes PLEKHA1 and hypothetical LOC387715. The
strongest association (P=10(-34)) centered over a frequent coding polymorphism,
Ala69Ser, at LOC387715, strongly implicating this gene in the pathogenesis of
AMD. Besides abundant expression in placenta, we demonstrate weak expression of
LOC387715 in the human retina. At present, however, there is no functional
information on this gene, which appears to have evolved recently within the
primate lineage. The joint contribution of the common risk allele at LOC387715,
Ala69Ser, and at CFH, Tyr402His, was assessed in our case-control population,
which suggests an additive model indicating an independent contribution of the
two gene loci to disease risk. Our data show a disease odds ratio of 57.6 (95%
CI: 37.2, 89.0) conferred by homozygosity for risk alleles at both CFH and
LOC387715 when compared with the baseline non-risk genotype.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 16174643 [PubMed - indexed for MEDLINE]

1764: Ophthalmology. 2005 Nov;112(11):1916.e1-7. Epub 2005 Sep 19.

Outcome of intravitreal triamcinolone in uveitis.

Kok H, Lau C, Maycock N, McCluskey P, Lightman S.

Department of Clinical Ophthalmology, Institute of Ophthalmology, Moorfields Eye 
Hospital, London, United Kingdom.

PURPOSE: To report the short-term outcome of intravitreal triamcinolone acetate
(TA) in the treatment of uveitic cystoid macular edema (CME). DESIGN:
Retrospective noncomparative (nonrandomized, uncontrolled) interventional case
series. PARTICIPANTS: Sixty-five eyes of 54 patients with uveitis-related CME
inadequately responsive to treatment combinations of oral corticosteroid,
periocular orbital floor corticosteroid injections, and second-line
immunosuppressive agents. INTERVENTION: Intravitreal injection of 4 mg/0.1 ml of 
TA. MAIN OUTCOME MEASURES: Visual acuity (VA), intraocular pressure (IOP), levels
of inflammation, and immunosuppressive therapy were assessed. Other potential
complications, including cataract progression, vitreous hemorrhage,
endophthalmitis, and retinal detachment (RD), were looked for. RESULTS: The mean 
follow-up was 8.0 months (range, 3-51), and the mean improvement of VA after
intravitreal TA was 0.26 (from 0.65 to 0.39 logarithm of the minimum angle of
resolution; Snellen, 6/24-6/12, approximately). This occurred at a mean of 4
weeks (range, 1-30). The improvement in VA was more significant if the duration
of CME before intravitreal TA was < or =12 months (P = 0.006) and if patients
were < or =60 years old (P = 0.005). Patients with the worst vision before
treatment also improved the least. The most important side effect was raised IOP 
(mean rise, 10.3 mmHg), with 28 eyes (43.1%) experiencing an IOP rise of >10
mmHg. Patients younger than 40 years were more likely to experience this IOP rise
than those older than 40. Thirty-three eyes (51%) were treated with antiglaucoma 
medications, with a mean duration of treatment of 17.4+/-13.3 weeks, and no
patient required trabeculectomy or lost vision. The dosage of oral
corticosteroids and/or second-line immunosuppressive medication was reduced or
stopped altogether in 18 of 33 eyes (54.5%) during the study period. There were
no cases of injection-related vitreous hemorrhage, endophthalmitis, or RD.
CONCLUSIONS: In patients with uveitic CME, intravitreal TA can effectively reduce
CME and improve VA and, in some eyes, allows the cessation and/or reduction of
immunosuppressive therapy. The period of effectivity varies in different patients
and, in some eyes, is limited. Treatment was associated in 43.1% with a rise in
IOP, which was transient and treatable medically.

PMID: 16171868 [PubMed - indexed for MEDLINE]

1765: Vision Res. 2005 Dec;45(28):3496-503. Epub 2005 Sep 19.

Imaging maculopathy in post-mortem human eyes.

Curcio CA.

Department of Ophthalmology, University of Alabama School of Medicine,
Birmingham, USA. curcio@uab.edu

Age-related maculopathy (ARM) remains a poorly understood degeneration. To
discover new pathways using contemporary genomics, proteomics, and
immunohistochemistry, validate emerging animal models, and validate new imaging
modalities, human tissues obtained from donor eyes will be essential to ARM
research for the foreseeable future. Because fundus appearance is the clinical
diagnostic lingua franca, laboratory investigators adapted these standards to the
distinctive appearance of post-mortem tissues in order to identify and stage ARM 
in donor eyes. Post-mortem tissues offer unique advantages and limitations
relative to pre-mortem tissues for imaging studies. One fellow eye can be used
for imaging and the other for correlative laboratory studies, if some degree of
disease stage asymmetry between eyes is acceptable. Histological verification is 
a necessary, albeit challenging, step in validating a grading system.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Review

PMID: 16171840 [PubMed - indexed for MEDLINE]

1766: Eur J Ophthalmol. 2005 Sep-Oct;15(5):619-26.

Prospective evaluation of intravitreal triamcinolone acetonide injection in
macular edema associated with retinal vascular disorders.

Tewari HK, Sony P, Chawla R, Garg SP, Venkatesh P.

Retina Services, Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India
Institute of Medical Sciences, New Delhi, India.

PURPOSE: To evaluate the effect of intravitreal triamcinolone acetonide on visual
acuity and macular thickness using optical coherence tomography (OCT) in macular 
edema associated with various retinal vascular disorders. METHODS: This
prospective nonrandomized clinical interventional study included 81 eyes (76
patients) comprised of Group I, 57 eyes (51 patients) with diabetic macular
edema; Group II, 10 eyes (10 patients) with branch retinal vein occlusion; and
Group III, 13 eyes (13 patients) with central retinal vein occlusion. All eyes
received an intravitreal injection of 4 mg triamcinolone acetonide (with the
solvent) in the operation theater under sterile conditions. RESULTS: Mean
preinjection central macular thickness was 531.84+/-132 microm in Group I,
458.4+/-149 microm in Group II, and 750.81+/-148 microm in Group III. All groups 
showed a statistically significant decrease in mean central macular thickness at 
1 month (300.7+/-119 microm in Group I, 218.2+/-99 microm in Group II, and 210.5 
+/-56 microm in Group III) and 3 months (253.19+/-109 microm in Group I, 187+/-47
microm in Group II, and 182+/-50 microm in Group III) after injection (p < 0.05).
Mean follow-up was 22+/-2.4 weeks. Mean visual acuity increased in all three
groups (preoperative visual acuity in Group I, 1.2+/-0.4 logMAR units; Group II, 
1.24+/-0.5 logMAR units; Group III, 1.1+/-0.4 logMAR units; 1 month postinjection
in Group I, 0.88+/-0.3 logMAR units; Group II, 0.67+/-0.3 logMAR units; Group
III, 0.86+/-0.4 logMAR units; 3 months postinjection in Group I, 0.84+/-0.4
logMAR units; Group II, 0.59+/-0.3 logMAR units; Group III, 0.82+/-0.5 logMAR
units) (p < 0.05). Forty-one eyes completed 6 months and 20 eyes completed 9
months follow-up. Twelve of 20 (41%) eyes in Group I, 2/6 (33%) eyes in Group II,
3/6 (50%) eyes in Group III, and 8/15 (53%) eyes in Group I, 1/3 (33%) eyes in
Group II, and 2/2 (100%) eyes in Group III developed recurrence of macular edema 
with worsening of visual acuity at 6 and 9 months, respectively. Thirty-three
(40.7%) eyes developed IOP elevation (at least one reading > 24 mmHg). One eye
developed infective endophthalmitis. CONCLUSIONS: Intravitreal injection of
triamcinolone acetonide may be considered as an effective treatment for reducing 
macular thickening due to diffuse diabetic macular edema, venous occlusion
associated macular edema, and may result in increase in visual acuity at least in
the short term. Further follow-up and analysis is required to demonstrate its
long-term efficacy.

PMID: 16167293 [PubMed - indexed for MEDLINE]

1767: J Clin Invest. 2005 Oct;115(10):2793-800. Epub 2005 Sep 15.

The potential role of amyloid beta in the pathogenesis of age-related macular
degeneration.

Yoshida T, Ohno-Matsui K, Ichinose S, Sato T, Iwata N, Saido TC, Hisatomi T,
Mochizuki M, Morita I.

Department of Ophthalmology and Visual Science and Instrumental Analysis Research
Center, Tokyo Medical and Dental University, Tokyo, Japan.

Drusen are extracellular deposits that lie beneath the retinal pigment epithelium
(RPE) and are the earliest signs of age-related macular degeneration (AMD).
Recent proteome analysis demonstrated that amyloid beta (Abeta) deposition was
specific to drusen from eyes with AMD. To work toward a molecular understanding
of the development of AMD from drusen, we investigated the effect of Abeta on
cultured human RPE cells as well as ocular findings in neprilysin gene-disrupted 
mice, which leads to an increased deposition Abeta. The results showed that Abeta
treatment induced a marked increase in VEGF as well as a marked decrease in
pigment epithelium-derived factor (PEDF). Conditioned media from Abeta-exposed
RPE cells caused a dramatic increase in tubular formation by human umbilical vein
endothelial cells. Light microscopy of senescent neprilysin gene-disrupted mice
showed an increased number of degenerated RPE cells with vacuoles. Electron
microscopy revealed basal laminar and linear deposits beneath the RPE layer, but 
we did not observe choroidal neovascularization (CNV). The present study
demonstrates that Abeta accumulation affects the balance between VEGF and PEDF in
the RPE, and an accumulation of Abeta reproduces features characteristic of human
AMD, such as RPE atrophy and basal deposit formation. Some other factors, such as
breakdown of integrity of Bruch membrane, might be necessary to induce CNV of
AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16167083 [PubMed - indexed for MEDLINE]

1768: Graefes Arch Clin Exp Ophthalmol. 2006 May;244(5):565-9. Epub 2005 Sep 15.

Plasma homocysteine, vitamin B12 and folate levels in age-related macular
degeneration.

Kamburoglu G, Gumus K, Kadayifcilar S, Eldem B.

Department of Ophthalmology, Hacettepe University Hospital, 06100, Sihhiye,
Ankara, Turkey.

PURPOSE: The purpose of this study was to investigate the association of
age-related macular degeneration (AMD) with plasma homocysteine, vitamin B12, and
folate levels. METHODS: Sixty patients diagnosed with AMD at our clinic between
March 2004 and September 2004 were assessed in a prospective cross-sectional
study. Plasma homocysteine, vitamin B12, and folate levels taken after 8 h of
fasting from 30 patients with exudative AMD and 30 patients with dry AMD were
compared with the results of 30 age- and sex-matched healthy participants.
RESULTS: Patients with both exudative and dry types of AMD had significantly
higher plasma homocysteine levels (mean 14.19+/-3.11 micromol/l; 13.07+/-2.90
micromol/l respectively) compared with the controls (mean 10.79+/-2.56
micromol/l; (p=0.000 and p=0.008 respectively). Homocysteine levels were higher
in the exudative AMD group compared with the dry AMD group, but the difference
was not statistically significant (p=0.290). Plasma vitamin B12 levels were found
to be significantly lower in the exudative AMD group (289.14+/-113.44 pg/l)
compared with the controls (436.17+/-204.12 pg/l) and dry AMD group
(443.47+/-190.83 pg/l; (p=0.000). Plasma folate levels were comparable among
groups (p=0.106). CONCLUSION: This study suggests an association between elevated
plasma homocysteine and AMD regardless of the subtype. Further controlled
prospective studies are needed to investigate the possible role of homocysteine
in AMD and the effect of vitamin B12 and folate supplementation in this process.

PMID: 16163497 [PubMed - indexed for MEDLINE]

1769: Graefes Arch Clin Exp Ophthalmol. 2006 May;244(5):570-6. Epub 2005 Sep 15.

The relationship between word length and threshold character size in patients
with central scotoma and eccentric fixation.

Déruaz A, Goldschmidt M, Mermoud C, Whatham AR, Safran AB.

Clinique d'Ophtalmologie, Hôpitaux Universitaires de Genève, 22, Alcide-Jentzer, 
1211, Genève 14, Switzerland. anouk.deruaz@hcuge.ch

BACKGROUND: Understanding limitations on text reading with eccentric fixation is 
of major concern in low vision research. Our objective was to determine, in
patients with a central scotoma, whether threshold character size is similar for 
different word lengths and paragraphed texts. METHODS: In 19 patients, we
retrospectively analyzed the relationship between minimum readable character size
for isolated words and text. Isolated letters, two, five, and ten-letter words
and a paragraphed text were presented randomly through a scanning laser
ophthalmoscope in eight different character sizes. RESULTS: Threshold character
size varied according to the text stimulus (p<0.05). Threshold character sizes
for single letters and two-letter words were matched (p>0.99), as were those for 
five-letter words, ten-letter words, and paragraphed text (p>0.99). Threshold
character size for single letters and two-letter words was significantly lower
than that measured with other text stimuli. DISCUSSION: Reading performance is
influenced by a variety of factors such as crowding, contextual effects, visual
span, degree of oculomotor adaptation needed, and frequency of a defined word.
Globally, when reading with a central scotoma, it appears that within word
characteristics have more impact than inter-word parameters on threshold
character size.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16163495 [PubMed - indexed for MEDLINE]

1770: Arch Ophthalmol. 2005 Sep;123(9):1207-14.

Responsiveness of the National Eye Institute Visual Function Questionnaire to
progression to advanced age-related macular degeneration, vision loss, and lens
opacity: AREDS Report no. 14.

Lindblad AS, Clemons TE.

AREDA Coordinating Center, The EMMES Corporation, 401 N. Washington Street, Ste. 
700, Rockville, MD 20850-1707, USA. aredspub@emmes.com

OBJECTIVE: To describe the ability of the National Eye Institute Visual Function 
Questionnaire (NEI-VFQ) to detect meaningful change over time (responsiveness) to
the primary Age-Related Eye Disease Study outcomes. METHODS: The 25-item NEI-VFQ 
plus appendix was administered at 2 visits at 1- to 4-year intervals to 4119
participants in the Age-Related Eye Disease Study. Events evaluated were
progression to advanced age-related macular degeneration (AMD), visual acuity
(VA) loss of at least 15 letters, and lens opacity progression. Responsiveness
was measured by the t statistic, effect size (ES), responsiveness statistic, and 
area under the receiver operating characteristic curve. Variance components were 
used to estimate the contributions of events to variability of the NEI-VFQ score.
RESULTS: Overall NEI-VFQ score was responsive to AMD progression (t = 14.0; P<
.001; ES = 0.81) and VA (t = 16.2; P< .001; ES = 0.74). Mean changes ranged from 
11 to 25 points for the subscales of general vision, near and distance
activities, social functioning, mental health, role difficulties, dependency, and
driving. The NEI-VFQ was unresponsive to lens opacity progression, although when 
the event occurred in the eye with the best vision at the first administration,
the lens opacity ES was moderate for the color vision (ES = 0.62) and driving
subscales (ES = 0.66). Progression to advanced AMD and VA loss contributed
significantly to the variation in the mean difference in overall VFQ score.
CONCLUSIONS: Changes in the NEI-VFQ overall and subscale scores of 10 points or
more are associated with clinically significant changes in vision and AMD. This
finding may assist the design of interventional studies of AMD and VA loss that
include the NEI-VFQ as an outcome measure.

Publication Types: 
    Multicenter Study
    Research Support, N.I.H., Extramural
    Research Support, U.S. Gov't, P.H.S.

PMID: 16157800 [PubMed - indexed for MEDLINE]

1771: Ophthalmic Surg Lasers Imaging. 2005 Jul-Aug;36(4):336-9.

Comment in:
    Ophthalmic Surg Lasers Imaging. 2005 Jul-Aug;36(4):270-1.

Optical coherence tomography findings after an intravitreal injection of
bevacizumab (avastin) for macular edema from central retinal vein occlusion.

Rosenfeld PJ, Fung AE, Puliafito CA.

Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami
School of Medicine, Miami, Florida, USA.

To determine whether bevacizumab could improve visual acuity and optical
coherence tomography outcomes in a patient with macular edema from central
retinal vein occlusion, an intravitreal injection of bevacizumab (1.0 mg) was
given. Prior intravitreal injections of triamcinolone acetonide resulted in
vision improvement but worsening cataract and borderline glaucoma. Within 1 week 
of the bevacizumab injection, visual acuity improved from 20/200 to 20/50 and
optical coherence tomography revealed resolution of the cystic maculopathy. The
improvements were maintained for at least 4 weeks. Intravitreal injections of
bevacizumab may provide another treatment option for patients with macular edema 
from vein occlusions.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 16156153 [PubMed - indexed for MEDLINE]

1772: Ophthalmic Surg Lasers Imaging. 2005 Jul-Aug;36(4):331-5.

Comment in:
    Ophthalmic Surg Lasers Imaging. 2005 Jul-Aug;36(4):270-1.

Optical coherence tomography findings after an intravitreal injection of
bevacizumab (avastin) for neovascular age-related macular degeneration.

Rosenfeld PJ, Moshfeghi AA, Puliafito CA.

Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami
School of Medicine, Miami, Florida, USA.

To determine whether intravitreal bevacizumab could improve optical coherence
tomography and visual acuity outcomes in a patient with neovascular age-related
macular degeneration who was responding poorly to pegaptanib therapy, an
intravitreal injection of bevacizumab (1.0 mg) was given. Within 1 week, optical 
coherence tomography revealed resolution of the subretinal fluid, resulting in a 
normal-appearing macular contour. The improved macular appearance was maintained 
for at least 4 weeks, and visual acuity remained stable. No inflammation was
observed. An intravitreal injection of bevacizumab may provide an effective,
safe, and inexpensive option for patients with age-related macular degeneration
who are losing vision secondary to macular neovascularization.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 16156152 [PubMed - indexed for MEDLINE]

1773: Ophthalmic Surg Lasers Imaging. 2005 Jul-Aug;36(4):310-4.

Assessment of the effects of morphological changes related to age-related macular
degeneration on optical coherence tomography retinal thickness measurements.

Menke MN, Feke GT.

Schepens Retina Associates Foundation, Boston, Massachusetts, USA.

BACKGROUND AND OBJECTIVE: Age-related macular degeneration (AMD) leads to
morphological changes that can interfere with optical coherence tomography
retinal thickness measurements. The effects of AMD on two available retinal
thickness scan modes were tested. PATIENTS AND METHODS: Ninety-four scans,
equally divided into Radial Line Scans (RLS) and Fast Macula Scans (FMS), of 42
patients with AMD were reviewed. Patients were graded into 4 categories regarding
AMD severity. Each scan mode was evaluated for each AMD category. RESULTS: In dry
moderate AMD, 2% of the RLS and 5% of the FMS thickness measurements failed. In
dry progressed AMD, the RLS mode performed better (26% failure rate) than the FMS
mode (42% failure rate). However, in exudative AMD the FMS mode performed better 
(6% failure rate) than the RLS mode (28% failure rate). The difference between
the RLS and FMS performance in dry progressed AMD compared with exudative AMD was
significant (P < .0001). CONCLUSION: The optical coherence tomography retinal
thickness scan modes perform differently, depending on AMD severity. Retinal
thickness algorithms with better performance are needed to facilitate
measurements in patients with AMD.

PMID: 16156148 [PubMed - indexed for MEDLINE]

1774: Ophthalmology. 2005 Oct;112(10):1758-65.

Preferential Hyperacuity Perimeter (PreView PHP) for detecting choroidal
neovascularization study.

Alster Y, Bressler NM, Bressler SB, Brimacombe JA, Crompton RM, Duh YJ, Gabel VP,
Heier JS, Ip MS, Loewenstein A, Packo KH, Stur M, Toaff T; Preferential
Hyperacuity Perimetry Research Group.

Clin Reg Consulting Services Inc., Irvine, California, USA.

PURPOSE: To assess the ability of the Preferential Hyperacuity Perimeter (PreView
PHP; Carl Zeiss Meditec, Dublin, CA) to detect recent-onset choroidal
neovascularization (CNV) resulting from age-related macular degeneration (AMD)
and to differentiate it from an intermediate stage of AMD. DESIGN: Prospective,
comparative, concurrent, nonrandomized, multicenter study. PARTICIPANTS: Eligible
participants' study eyes had a corrected visual acuity of 20/160 or better and
either untreated CNV from AMD diagnosed within the last 60 days or an
intermediate stage of AMD. METHODS: After obtaining consent, visual acuity with
habitual correction, masked PHP testing, stereoscopic color fundus photography,
and fluorescein angiography were performed. Photographs and angiograms were
evaluated by graders masked to diagnosis and PHP results. The reading center's
diagnosis determined if the patient was categorized as having intermediate AMD or
neovascular AMD. MAIN OUTCOME MEASURES: A successful study outcome was defined a 
priori as a sensitivity of at least 80% and a specificity of at least 80%.
RESULTS: Of 185 patients who gave consent to be enrolled, 11 (6%) had PHP results
judged to be unreliable. An additional 52 were not included because they did not 
meet all eligibility criteria. Of the remaining 122 patients, 57 had an
intermediate stage of AMD and 65 had neovascular AMD. The sensitivity to detect
newly diagnosed CNV using PHP testing was 82% (95% confidence interval [CI],
70%-90%). The specificity to differentiate newly diagnosed CNV from the
intermediate stage of AMD using PHP testing was 88% (95% CI, 76%-95%).
CONCLUSIONS: Preferential Hyperacuity Perimeter testing can detect recent-onset
CNV resulting from AMD and can differentiate it from an intermediate stage of AMD
with high sensitivity and specificity. These data suggest that monitoring with
PHP should detect most cases of CNV of recent onset with few false-positive
results at a stage when treatment usually would be beneficial. Thus, this
monitoring should be considered in the management of the intermediate stage of
AMD.

Publication Types: 
    Comparative Study
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 16154198 [PubMed - indexed for MEDLINE]

1775: Ophthalmology. 2005 Oct;112(10):1747-57.

A phase II randomized double-masked trial of pegaptanib, an anti-vascular
endothelial growth factor aptamer, for diabetic macular edema.

Cunningham ET Jr, Adamis AP, Altaweel M, Aiello LP, Bressler NM, D'Amico DJ,
Goldbaum M, Guyer DR, Katz B, Patel M, Schwartz SD; Macugen Diabetic Retinopathy 
Study Group.

Stanford University, USA.

OBJECTIVE: To evaluate the safety and efficacy of pegaptanib sodium injection
(pegaptanib) in the treatment of diabetic macular edema (DME). DESIGN:
Randomized, double-masked, multicenter, dose-ranging, controlled trial.
PARTICIPANTS: Individuals with a best-corrected visual acuity (VA) between 20/50 
and 20/320 in the study eye and DME involving the center of the macula for whom
the investigator judged photocoagulation could be safely withheld for 16 weeks.
INTERVENTION: Intravitreous pegaptanib (0.3 mg, 1 mg, 3 mg) or sham injections at
study entry, week 6, and week 12 with additional injections and/or focal
photocoagulation as needed for another 18 weeks. Final assessments were conducted
at week 36. MAIN OUTCOME MEASURES: Best-corrected VA, central retinal thickness
at the center point of the central subfield as assessed by optical coherence
tomography measurement, and additional therapy with photocoagulation between
weeks 12 and 36. RESULTS: One hundred seventy-two patients appeared balanced for 
baseline demographic and ocular characteristics. Median VA was better at week 36 
with 0.3 mg (20/50), as compared with sham (20/63) (P = 0.04). A larger
proportion of those receiving 0.3 mg gained VAs of > or =10 letters
(approximately 2 lines) (34% vs. 10%, P = 0.003) and > or =15 letters (18% vs.
7%, P = 0.12). Mean central retinal thickness decreased by 68 microm with 0.3 mg,
versus an increase of 4 microm with sham (P = 0.02). Larger proportions of those 
receiving 0.3 mg had an absolute decrease of both > or =100 microm (42% vs. 16%, 
P = 0.02) and > or =75 microm (49% vs. 19%, P = 0.008). Photocoagulation was
deemed necessary in fewer subjects in each pegaptanib arm (0.3 mg vs. sham, 25%
vs. 48%; P = 0.04). All pegaptanib doses were well tolerated. Endophthalmitis
occurred in 1 of 652 injections (0.15%/injection; i.e., 1/130 [0.8%] pegaptanib
subjects) and was not associated with severe visual loss. CONCLUSIONS: In this
phase II trial, subjects assigned to pegaptanib had better VA outcomes, were more
likely to show reduction in central retinal thickness, and were deemed less
likely to need additional therapy with photocoagulation at follow-up.

Publication Types: 
    Clinical Trial
    Clinical Trial, Phase II
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16154196 [PubMed - indexed for MEDLINE]

1776: Eye. 2005 Sep;19(9):935-44.

Smoking and age-related macular degeneration: a review of association.

Thornton J, Edwards R, Mitchell P, Harrison RA, Buchan I, Kelly SP.

Evidence for Population Health Unit, Division of Epidemiology and Health
Sciences, University of Manchester, Manchester, UK.

PURPOSE: Age-related macular degeneration (AMD) is the leading cause of severe
and irreversible vision loss in the Western world. As there is no effective
treatment for all types of AMD, identifying modifiable risk factors is of great
importance. This review evaluates the epidemiological evidence associating
smoking with AMD. METHODS: Systematic review of published epidemiological studies
evaluated against established criteria for evidence of a causal relationship.
RESULTS: In total, 17 studies (cross-sectional studies, prospective cohort
studies, and case-control studies) were included in the review. A total of 13
studies found a statistically significant association between smoking and AMD
with increased risk of AMD of two- to three-fold in current-smokers compared with
never-smokers. Five studies found no association between smoking and AMD. There
was also evidence of dose-response, a temporal relationship and reversibility of 
effect. CONCLUSION: The literature review confirmed a strong association between 
current smoking and AMD, which fulfilled established causality criteria.
Cigarette smoking is likely to have toxic effects on the retina. In spite of the 
strength of this evidence, there appears to be a lack of awareness about the
risks of developing eye disease from smoking among both healthcare professionals 
and the general public.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 16151432 [PubMed - indexed for MEDLINE]

1777: Mol Vis. 2005 Aug 30;11:657-64.

Loss of ER retention and sequestration of the wild-type ELOVL4 by Stargardt
disease dominant negative mutants.

Karan G, Yang Z, Howes K, Zhao Y, Chen Y, Cameron DJ, Lin Y, Pearson E, Zhang K.

Department of Ophthalmology and Visual Sciences, Eccles Institute of Human
Genetics, University of Utah Health Sciences Center, Salt Lake City, UT, USA.
gkaran@hmbg.utah.edu

PURPOSE: Mutations in ELOVL4, a member of the fatty acid elongase (ELO) family,
are responsible for autosomal dominant Stargardt-like macular degeneration. The
specific role of ELOVL4 in photoreceptors and the degenerative events induced by 
dominant ELOVL4 mutations are not well understood. As a first step to identifying
possible mechanisms contributing to cellular dysfunction, we transfected HEK293
and COS cells with fluorescent-labeled wild-type and mutant ELOVL4 constructs.
Effects of mutant ELOVL4 on interaction with wild-type protein were examined in
this in vitro model. METHODS: Wild-type and mutant ELOVL4 proteins including
ELOVL4 truncation (270X, a truncated ELOVL4 protein at amino acid position 270)
and ELOVL4 5 bp deletion (5bp-del) and ELOVL4 (5A, substituting the ER retention 
signal, KAKGD, with a five alanine amino acid tract) were expressed as EGFP or
DsRed fusion proteins. Cellular localization of these proteins was examined by
fluorescence microscopy. ELOVL4 protein aggregates were measured by
co-immunoprecipitation and by sucrose gradient centrifugation followed by
immunodetection with western blots. To study cellular status of cells expressing 
mutant ELOVL4 proteins, transfected cells were examined for upregulation of Bip
and CHOP, markers for the unfolded protein response (UPR) by western blotting.
RESULTS: ELOVL4 mutants were not retained within the ER but were rather
mislocalized and formed aggregates. Importantly, when cotransfected with
wild-type ELOVL4, the mutants bound to and sequestered the wild-type protein into
the aggregates. Expression of ELOVL4 mutants also induced UPR as evidenced by Bip
and CHOP expression. CONCLUSIONS: Using this in vitro cell system, we have
identified alterations in wild-type ELOVL4 protein localization, aggregate
formation, and the induction of cellular stress by the ELOVL4 mutants. We propose
that "inactivation" of the wild-type ELOVL4 protein through sequestration to a
non-ER compartment by ELOVL4 mutants may play a role in cellular dysfunction.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 16145543 [PubMed - indexed for MEDLINE]

1778: Retina. 2005 Sep;25(6):719-26.

Indocyanine green-mediated photothrombosis with and without intravitreal
triamcinolone acetonide for subfoveal choroidal neovascularization in age-related
macular degeneration: a pilot study.

Arevalo JF, Mendoza AJ, Fernández CF.

Retina and Vitreous Service, Clinica Oftalmologica Centro Caracas, Venezuela.
areval1@telcel.net.ve

PURPOSE: To determine the feasibility, safety, and clinical effect of treating
patients with subfoveal choroidal neovascularization (CNV) in age-related macular
degeneration (AMD) with indocyanine green (ICG)-mediated photothrombosis (IMP)
with and without intravitreal triamcinolone acetonide (TA). METHODS: Fifteen
patients (19 eyes) participated in the study. Nine eyes of seven patients were
treated with IMP immediately followed by an intravitreal injection of 4 mg of TA 
(Group A), and 10 eyes of 8 patients were treated with IMP only (Group B).
Patients had a mean follow-up of 6.9 months (range: 3 to 12 months). Patients
underwent single or two sessions of IMP. RESULTS: In Group A, visual acuity (VA) 
showed stability in 6 eyes (66.7%), improvement of VA in 2 eyes (22.2%), and
worsening of VA in 1 eye (11.1%). Group B presented VA stability in 9 eyes (90%),
and improvement in 1 eye (10%). In total, of the 15 patients (19 eyes) with IMP
with or without intravitreal TA, 3 eyes (15.8%) showed improvement, 15 eyes
(78.9%) stability, and 1 eye (5.3%) showed worsening of VA. A significant
regression of the CNV and diminishing of subretinal fluid was demonstrated with
fluorescein angiography and optical coherence tomography in both groups. No
patient in Group A required retreatment. Four of 10 eyes (40%) in Group B
required one retreatment during the study period. CONCLUSIONS: ICG-mediated
photothrombosis with and without intravitreal TA may provide stability or
improvement in visual acuity and fundus findings in subfoveal CNV in AMD. Further
evaluation in a multicenter, randomized, placebo-controlled clinical trial with
longer follow-up is needed to accurately assess the safety and efficacy of this
new treatment modality.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 16141859 [PubMed - indexed for MEDLINE]

1779: Retina. 2005 Sep;25(6):713-8.

Nature and risk of neovascularization in the fellow eye of patients with
unilateral retinal angiomatous proliferation.

Gross NE, Aizman A, Brucker A, Klancnik JM Jr, Yannuzzi LA.

LuEsther T. Mertz Retinal Research Center, Manhattan Eye, Ear & Throat Hospital, 
New York, New York 10021, USA.

PURPOSE: To determine the nature and risk of neovascularization in the fellow
eyes of patients with unilateral retinal angiomatous proliferation (RAP), a
neovascular form of age-related macular degeneration (AMD). METHODS: A
consecutive series of 52 patients diagnosed with unilateral RAP were studied
retrospectively. Clinical biomicroscopic examination, fluorescein angiography,
and indocyanine green angiography were used to evaluate all patients for the
development of neovascular manifestations in the fellow eye. RESULTS:
Neovascularization developed in the fellow eye in 52 patients over the follow-up 
period (range, 2-36 months). All patients developed neovascular manifestations of
RAP in the fellow eye. Twenty-one patients (40%) developed a RAP lesion within 1 
year; 29 (56%), within 2 years; and 52 (100%), within 3 years. At the time of
diagnosis of neovascularization in the fellow eye, 8 patients (15%) had a stage I
RAP lesion, 36 (70%) had a stage II RAP lesion, and 8 (15%) had a stage III RAP
lesion. Other characteristic findings in these patients included the presence of 
preretinal, intraretinal, and subretinal hemorrhages in 49 patients (94%) and
pigment epithelial detachments in 41 patients (79%). CONCLUSIONS: In patients
diagnosed with unilateral RAP lesions, the form of neovascularization that
develops in the fellow eye is virtually always RAP. The annual and accumulative
risk of neovascularization in the fellow eye is higher in patients with RAP than 
in those with other forms of neovascular AMD. These new findings enhance our
understanding of the clinical spectrum of RAP in terms of its natural course and 
visual prognosis and may possibly offer useful information to establish future
treatment options.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16141858 [PubMed - indexed for MEDLINE]

1780: Am J Ophthalmol. 2005 Sep;140(3):563-4.

The effect of non-steroidal anti-inflammatory drugs on inflammatory cystoid
macular edema.

van Kooij B, De Boer J, Ten Dam N, Fijnheer R, Rothova A.

Department of Ophthalmology, F.C. Donders Institute of Ophthalmology, University 
Medical Center Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands.
h.vankooij@oogh.azu.nl

PURPOSE: To assess the role of systemic non-steroidal anti-inflammatory drugs
(NSAIDs) in the treatment of inflammatory cystoid macular edema (iCME). DESIGN:
Pilot study. METHODS: We included 66 patients with iCME and treated them with
naproxen (2 x 250 mg daily; n = 28) or rofecoxib (1 x 25 mg daily; n = 38). After
4 months of therapy, visual acuity and inflammation activity were measured. We
evaluated the grade of CME, retinal vasculitis, and papillary leakage with
fluorescein angiography. RESULTS: No clear effect of NSAIDs on iCME, visual
acuity, and intraocular inflammation was observed. A beneficial effect was noted 
in less than 8% of the affected eyes. The drop-out rate after 4 months of
treatment was 52%, because of adverse effects or inefficacy of the treatment.
Improvement of visual acuity was slightly better in patients who were treated
with naproxen compared with rofecoxib (P < or = .05). CONCLUSION: Systemic NSAIDs
have a limited role (if any) in the treatment of iCME.

Publication Types: 
    Clinical Trial

PMID: 16139022 [PubMed - indexed for MEDLINE]

1781: Am J Ophthalmol. 2005 Sep;140(3):540-2.

Trans-tenon retrobulbar triamcinolone injection for macular edema associated with
branch retinal vein occlusion remaining after vitrectomy.

Kawaji T, Hirata A, Awai N, Takano A, Inomata Y, Fukushima M, Tanihara H.

Department of Ophthalmology and Visual Science, Graduate School of Medical
Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan.

PURPOSE: To evaluate the effectiveness and safety of trans-Tenon retrobulbar
triamcinolone injection for macular edema associated with branch retinal vein
occlusion (BRVO) after vitrectomy. DESIGN: Prospective interventional case
series. METHODS: The study included 20 eyes of 20 patients with BRVO,
characterized by macular edema lasting more than 3 months after vitrectomy.
Trans-Tenon retrobulbar injection of 40 mg triamcinolone was performed, and
visual and anatomic responses were evaluated. RESULTS: Mean foveal thickness was 
499.4 +/- 209.1 microm preoperatively, 281.8 +/- 110.1 microm at 2-week
follow-up, and 196.9 +/- 92.1 microm at 6-month follow-up (P < .0001, at 2 weeks 
and 6 months, paired t test). Improvement of visual acuity by at least 0.2 logMAR
(logarithm of the minimum angle of resolution) was seen in 14 (70%) of the 20
eyes. CONCLUSIONS: Trans-Tenon retrobulbar injection of triamcinolone may be an
alternative for additional treatment of eyes with BRVO that remains after
vitrectomy.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16139011 [PubMed - indexed for MEDLINE]

1782: Graefes Arch Clin Exp Ophthalmol. 2006 Mar;244(3):342-51. Epub 2005 Aug 18.

Mapping of the retinal pigment epithelium in exudative age related macular
degeneration.

Neubauer AS, Thiel M, Priglinger S, Chryssafis C, Alge C, Welge-Lüssen U, Kampik 
A.

Department of Ophthalmology, Ludwig-Maximilians-University, Mathildenstr. 8,
80336, Muenchen, Germany. aljoscha.neubauer@med.uni-muenchen.de

PURPOSE: To evaluate a novel technique for three-dimensional mapping of the
retinal pigment epithelium (RPE) layer in patients with subfoveal choroidal
neovascularization (CNV) due to age-related macular degeneration. METHODS:
Scanning with a recent generation retinal thickness analyzer (RTA) was performed 
in consecutive patients undergoing fluorescein angiography. From a 3 x 3 mm area 
centered on the fovea, three-dimensional area maps of the RPE level were
calculated by external spreadsheet software. Included were 18 eyes with classic
CNV, 18 eyes with occult CNV and 18 eyes from age-matched normal subjects.
Repeatability was assessed by measuring 17 eyes with CNV 3 times. In ten
additional patients, RTA imaging results were compared with cross-sections
obtained by optical coherence tomography. RESULTS: By both methods, distinctive
changes in RPE level maps were observed in classic and occult CNV. In classic CNV
with the lesion extending over the RPE, only focal irregularities in the
anteriorly displaced RPE surface were observed. In contrast, mapping of occult
CNV showed a more irregular displacement of the RPE layer. The RPE map standard
deviation indicating surface irregularity differed statistically significantly
between the groups, with coefficients of variance of 5.9% for controls, 6.1% for 
classic and 8.8% for occult CNV (P < 0.001). Regarding repeatability, RPE level
maps showed 1.2% coefficient of variance and an intra-class correlation
coefficient of 0.87 for triplicate measurements in CNV patients. CONCLUSIONS:
Topographic mapping of CNV lesions offers a fast, reproducible method for
obtaining three-dimensional morphometric information on the RPE level and to
quantify changes.

PMID: 16133030 [PubMed - indexed for MEDLINE]

1783: Graefes Arch Clin Exp Ophthalmol. 2006 Mar;244(3):309-15. Epub 2005 Aug 13.

Intravitreal levels of vascular endothelial growth factor and interleukin-6 are
correlated with macular edema in branch retinal vein occlusion.

Noma H, Minamoto A, Funatsu H, Tsukamoto H, Nakano K, Yamashita H, Mishima HK.

Department of Ophthalmology and Visual Science, Graduate School of Biomedical
Sciences, Hiroshima University, 1-2-3, Kasumi-cho, Minami-ku, Hiroshima,
734-8551, Japan.

BACKGROUND: To investigate whether vascular endothelial growth factor (VEGF) or
interleukin-6 (IL-6) contributes to the pathogenesis of macular edema in eyes
with branch retinal vein occlusion (BRVO), the correlations between these factors
were investigated. METHODS: We studied 25 patients suffering from macular edema
with BRVO and 14 patients with nonischemic ocular disease (control group). The
degree of retinal ischemia was evaluated in terms of the area of capillary
nonperfusion using Scion Images, and the severity of macular edema was examined
using optical coherence tomography. Vitreous fluid samples were obtained at the
time of vitreoretinal surgery, and VEGF and IL-6 levels in the vitreous fluid and
plasma were determined by means of enzyme-linked immunosorbent assays. RESULTS:
Vitreous fluid levels of VEGF and IL-6 were significantly elevated in patients
with BRVO compared with control patients (P = 0.0011 and P < 0.0001,
respectively). Also, the vitreous level of VEGF was significantly correlated with
that of IL-6 (P = 0.0012), and vitreous levels of VEGF and IL-6 were correlated
with the size of the BRVO nonperfusion area (P < 0.0001 and P = 0.0033,
respectively). Furthermore, vitreous levels of VEGF and IL-6 were correlated with
the severity of macular edema (P = 0.0008 and P = 0.0191, respectively) and the
severity of macular edema of BRVO was significantly correlated with the size of
the BRVO nonperfusion area (P=0.0044). CONCLUSIONS: The levels of VEGF and IL-6
are increased in patients with macular edema with BRVO and are significantly
correlated with the size of the nonperfusion area and the severity of macular
edema. Therefore, they may play a role in macular edema with BRVO.

PMID: 16133018 [PubMed - indexed for MEDLINE]

1784: Graefes Arch Clin Exp Ophthalmol. 2006 Apr;244(4):498-501. Epub 2005 Aug
13.

Relationship between the retinal thickness of the macula and the difference in
axial length.

Ueda T, Nawa Y, Hara Y.

Department of Ophthalmology, Nara Medical University, 840, Kashihara-Shi, Nara,
Japan. tueda@naramed-u.ac.jp

PURPOSE: The purpose of this study was to evaluate the relationship between the
retinal thickness of the macula and the difference in axial length with A-scan
ultrasonography (UD-6000) and partial coherence interferometry (IOLMaster).
METHODS: In 38 eyes of 26 patients with macular edema (ME), we measured axial
length using both instruments and the retinal thickness of the macula using
optical coherence tomography (OCT). To compare the difference in axial length
between both methods, the Wilcoxon signed-ranks test was used. In addition, the
relationship between macula thickness and axial length difference was analyzed by
Spearman's correlation coefficient. RESULTS: There was a significant difference
between axial-length measurements (p<0.001). In addition, the retinal thickness
of the macula and the difference in axial-length measurements were positively
correlated (correlation coefficient = 0.55, p=0.003). CONCLUSIONS: The difference
in axial length obtained by both methods was considered to be the difference in
optical and acoustic reflection site. This study may suggest that IOLMaster is
sufficient for measuring axial length in eyes with macular edema and reducing
postoperative refractive errors.

Publication Types: 
    Comparative Study

PMID: 16133015 [PubMed - indexed for MEDLINE]

1785: Eye. 2006 Aug;20(8):923-6. Epub 2005 Aug 26.

Second eye of patients with unilateral neovascular age-related macular
degeneration: Caucasians vs Chinese.

Sivaprasad S, Membrey WL, Sivagnanavel V, Gonzalez JG, Liu DT, Chan WM, Lam DS,
Jackson H, Chong NV.

Retinal Research Unit, King's College Hospital, Denmark Hill, London, UK.

PURPOSE: To investigate the correlation between morphological features of
choroidal neovascularisation (CNV) secondary to age-related macular degeneration 
(AMD) in the first eye and the severity of age-related maculopathy (ARM) in the
fellow eyes in two racial groups: Caucasians and Chinese. PARTICIPANTS: A total
of 135, fluorescein angiograms of patients with unilateral neovascular AMD and
ARM in the fellow eyes were included in the study: 38 Caucasians from King's
College Hospital, UK; 45 Caucasians from West Kent Eye Centre, UK; 52 Chinese
from Hong Kong Eye Hospital, Hong Kong. MAIN OUTCOME MEASURES: CNV subtype in the
affected eye and ARM severity in the second eyes. RESULTS: Although the
proportion of CNV subtypes in the three groups were similar, the Chinese cohort
showed significantly less ARM severity compared to the Caucasian cohorts (P <
0.05). CONCLUSION: Although drusen and retinal pigmentary changes may be
prognostic indicators of CNV, this study suggest that other factors contribute
significantly to the pathogenesis of CNV in AMD.

Publication Types: 
    Multicenter Study

PMID: 16123783 [PubMed - indexed for MEDLINE]

1786: Ophthalmologica. 2005 Sep-Oct;219(5):303-8.

Pigment epithelial detachments with retinal vascular anomalous complex in
age-related macular degeneration.

Schneider U, Gelisken F, Inhoffen W, Bartz-Schmidt KU.

University Eye Clinic Tübingen, Tübingen, Germany.
ulrike.schneider@med.uni-tuebingen.de

PURPOSE: To analyze and compare the angiographic features of retinal vascular
anomalous complex (RVAC) in patients with a vascularized pigment epithelial
detachment (PED) secondary to age-related macular degeneration. METHODS:
Retrospective evaluation of fluorescein and indocyanine green angiographies of
180 patients with occult choroidal neovascularization and PED. RESULTS: On
indocyanine green angiography (ICGA), RVAC demonstrated as a focal
hyperfluorescence in connection with retinal choroidal anastomosis was identified
in 12 of the 180 eyes (6.7%) with a vascularized PED. In comparison, fluorescein 
angiography revealed RVAC in 6 of the 12 eyes. Associated clinical and
angiographic features were intraretinal hemorrhage in all 12 eyes, cystoid
macular edema in 6 eyes and preretinal hemorrhage in 4 eyes. CONCLUSIONS: RVAC is
better delineated on ICGA than on fluorescein angiography. In clinically
suspected cases with a vascularized PED in connection with intraretinal
hemorrhage and/or cystoid macular edema, ICGA should be performed to enhance
management considerations. Copyright 2005 S. Karger AG, Basel.

Publication Types: 
    Comparative Study

PMID: 16123558 [PubMed - indexed for MEDLINE]

1787: Invest Ophthalmol Vis Sci. 2005 Sep;46(9):3426-34.

SOD2 protects against oxidation-induced apoptosis in mouse retinal pigment
epithelium: implications for age-related macular degeneration.

Kasahara E, Lin LR, Ho YS, Reddy VN.

Kellogg Eye Center, Department of Ophthalmology and Visual Sciences, University
of Michigan, 1000 Wall Street, Ann Arbor, MI 48105, USA.

PURPOSE: Oxidative stress from reactive oxygen species (ROS) has been implicated 
in many diseases, including age-related macular degeneration (AMD), in which the 
retinal pigment epithelium (RPE) is considered a primary target. Because
manganese superoxide dismutase (SOD2), localized in mitochondria, is known to be 
a key enzyme that protects the cells against oxidative stress, this study was
undertaken to examine oxidation-induced apoptosis in cultured RPE cells with
various levels of SOD2. METHODS: Primary cultures of RPE cells were established
from wild-type (WT), heterozygous Sod2-knockout mouse (HET) and hemizygous Sod2
mice with overexpression of the enzyme (HEMI). Purity of the RPE cell cultures
was verified by immunostaining with antibody to RPE65 and quantified by flow
cytometry. Oxidative stress was induced in RPE cells by exposing them to H(2)O(2)
(0-500 muM) for 1 hour and reculturing them in normal medium for various times
(0-24 hours). Apoptosis in the RPE was examined by TUNEL staining and quantified 
by cell-death-detection ELISA. Mitochondrial transmembrane potential (MTP) was
measured by a cationic dye, and cytochrome c leakage from mitochondria was
analyzed by Western blot analysis. RESULTS: More than 95% of the cells in each
culture were RPE65 positive, and the relative SOD2 levels in HET, WT, and HEMI
cells were 0.6, 1.0, and 3.4, respectively. H(2)O(2)-induced apoptotic cell death
was both dose and time dependent, and apoptosis in these cells was related to the
cellular SOD2 level. Disruption of MTP and release of cytochrome c were observed 
to occur before apoptotic cell death, and they correlated with cellular SOD2.
CONCLUSIONS: The results demonstrate a critical role of SOD2 in protection
against oxidative challenge. Cells from HET mice showed greater apoptotic cell
death, whereas in those from HEMI mice, cell death induced by oxidative injury
was suppressed.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, U.S. Gov't, P.H.S.

PMID: 16123448 [PubMed - indexed for MEDLINE]

1788: Invest Ophthalmol Vis Sci. 2005 Sep;46(9):3363-71.

Late-onset macular degeneration and long anterior lens zonules result from a
CTRP5 gene mutation.

Ayyagari R, Mandal MN, Karoukis AJ, Chen L, McLaren NC, Lichter M, Wong DT,
Hitchcock PF, Caruso RC, Moroi SE, Maumenee IH, Sieving PA.

Department of Ophthalmology and Visual Sciences, University of Michigan, 1000
Wall Street, Ann Arbor, MI 48105, USA. ayyagari@umich.edu

PURPOSE: To identify the gene responsible for a complex ocular phenotype of
late-onset macular degeneration, long anterior zonules (LAZ), and elevated
intraocular pressure (IOP) and to study its expression. METHODS: Ocular
examination, visual field, fluorescein angiography, and electrophysiology testing
were performed. One affected individual was treated with vitamin A. DNA from 55
family members (UM:H389) was used for linkage, mapping, and mutation analysis.
Linkage analysis of macular degeneration and LAZ phenotypes was performed
independently. Mutations in candidate genes were screened by sequencing. mRNA
expression of CTRP5 and MFRP, which are bicistronic genes, was studied by
semiquantitative RT-PCR (qRT-PCR) in various human tissues. CTRP5 expression was 
also evaluated by in situ hybridization. RESULTS: Affected members had LAZ
detectable by the third decade and/or macular degeneration by the fourth to fifth
decade. A six-month treatment with vitamin A shortened dark adaptation
considerably in one affected member. Both conditions mapped independently with
zero recombination to 11q23, with maximum lod scores of 3.31 for macular
degeneration and 5.41 for LAZ. The same CTRP5 missense mutation was identified in
all affected individuals. Retinal pigment epithelium (RPE) and ciliary epithelium
(CE) showed highest CTRP5 transcript expression, which was also true for MFRP.
CTRP5 tissue expression was confirmed by in situ hybridization. CONCLUSIONS: A
single locus at 11q23 is implicated in a complex ocular phenotype involving RPE
and CE, tissues of neuroectodermal origin. All individuals with either LAZ and/or
macular degeneration carry the same CTRP5 S163R mutation, which is transmitted in
autosomal dominant manner.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 16123441 [PubMed - indexed for MEDLINE]

1789: Invest Ophthalmol Vis Sci. 2005 Sep;46(9):3309-14.

Classification of fundus autofluorescence patterns in early age-related macular
disease.

Bindewald A, Bird AC, Dandekar SS, Dolar-Szczasny J, Dreyhaupt J, Fitzke FW,
Einbock W, Holz FG, Jorzik JJ, Keilhauer C, Lois N, Mlynski J, Pauleikhoff D,
Staurenghi G, Wolf S.

Department of Ophthalmology, University of Bonn, Ernst-Abbe-Strasse 2, 53127
Bonn, Germany.

PURPOSE: To describe and classify patterns of abnormal fundus autofluorescence
(FAF) in eyes with early nonexudative age-related macular disease (AMD). METHODS:
FAF images were recorded in eyes with early AMD by confocal scanning laser
ophthalmoscopy (cSLO) with excitation at 488 nm (argon or OPSL laser) and
emission above 500 or 521 nm (barrier filter). A standardized protocol for image 
acquisition and generation of mean images after automated alignment was applied, 
and routine fundus photographs were obtained. FAF images were classified by two
independent observers. The kappa statistic was applied to assess intra- and
interobserver variability. RESULTS: Alterations in FAF were classified into eight
phenotypic patterns including normal, minimal change, focal increased, patchy,
linear, lacelike, reticular, and speckled. Areas with abnormal increased or
decreased FAF signals may or may not have corresponded to funduscopically visible
alterations. For intraobserver variability, kappa of observer I was 0.80 (95%
confidence interval [CI]0.71-0.89) and of observer II, 0.74. (95% CI, 0.64-0.84).
For interobserver variability, kappa was 0.77 (95% CI, 0.67-0.87). CONCLUSIONS:
Various phenotypic patterns of abnormal FAF can be identified with cSLO imaging. 
Distinct patterns may reflect heterogeneity at a cellular and molecular level in 
contrast to a nonspecific aging process. The results indicate that the
classification system yields a relatively high degree of intra- and interobserver
agreement. It may be applicable for determination of novel prognostic
determinants in longitudinal natural history studies, for identification of
genetic risk factors, and for monitoring of future therapeutic interventions to
slow the progression of early AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16123434 [PubMed - indexed for MEDLINE]

1790: Invest Ophthalmol Vis Sci. 2005 Sep;46(9):3046-51.

Serum elastin-derived peptides in age-related macular degeneration.

Sivaprasad S, Chong NV, Bailey TA.

Laser and Retinal Research Unit, King's College Hospital, University of London,
Denmark Hill, London SE5 9RS, UK. senswathi@aol.com

PURPOSE: Dysregulation of the extracellular matrix (ECM) plays an important role 
in the pathogenesis of age-related macular degeneration (AMD). Elastin is a
fibrous protein constituent of the ECM, degradation of which may be detected by
the presence of serum elastin-derived peptides (S-EDPs) in circulation. This
study was undertaken to estimate levels of S-EDPs in patients with AMD compared
with age-matched control subjects. METHODS: Fifty-six patients with AMD were
classified into two groups: early age-related maculopathy (ARM) and neovascular
AMD. The control group consisted of 15 age-matched subjects with no AMD. S-EDP
levels in the serum of these subjects was estimated by competitive ELISA, using
solubilized alpha-elastin from human aorta and polyclonal antibodies to this
antigen. RESULTS: S-EDPs were significantly higher in patients with AMD than in
control subjects. In addition, subjects with neovascular AMD had higher levels of
S-EDPs than did those with early disease. CONCLUSIONS: The cause of this
association between S-EDPs and AMD is unknown, but it suggests that systemic
elastin degradation may increase the risk of conversion from early ARM to
neovascular AMD. Further studies are needed to confirm whether the serum level of
S-EDPs is a useful predictor of conversion from early ARM to neovascular AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16123400 [PubMed - indexed for MEDLINE]

1791: Invest Ophthalmol Vis Sci. 2005 Sep;46(9):3031-8.

Correlation between inactive cathepsin D expression and retinal changes in
mcd2/mcd2 transgenic mice.

Zhang D, Brankov M, Makhija MT, Robertson T, Helmerhorst E, Papadimitriou JM,
Rakoczy PE.

Department of Molecular Ophthalmology, Lions Eye Institute, Perth, Australia.

PURPOSE: To investigate the correlation between the presence of the inactive
cathepsin D (CatD) and retinal changes in mcd2/mcd2 transgenic mice. METHODS:
Computational modeling was used to examine whether CatD mutants maintain
competitive substrate binding. D407 cells were transfected with pcDNACatDM1 or
pcDNACatDM2, containing procathepsin D (pro-CatD) with 6-bp (CatDM1) or 12-bp
(CatDM2) deletions, respectively, flanking the pro-CatD cleavage site, and the
aspartic protease activity of the transfected cells was measured. Subsequently,
transgenic mice (mcd2/mcd2) containing CatDM2 were generated. Relative transgene 
copy number and transcript levels in the previously produced mcd/mcd (carrying
CatDM1) and mcd2/mcd2 mice were measured by quantitative real-time PCR. Western
blot analysis and aspartic protease activity were used to characterize the
mutated proteins. Retinal changes were described by using color fundus
photography and fluorescein angiography, histology, immunohistochemistry, and
electron microscopy. RESULTS: Computational modeling of the CatDM1 and CatDM2
structures indicated that the substrate binding site was not altered. There was
limited or no aspartic protease activity associated with CatDM1 and CatDM2
proteins, respectively. Mcd2/mcd2 animals contained a higher amount of inactive
CatD than mcd/mcd or wild-type mice. Retinal abnormalities in mcd2/mcd2 mice
developed at 3 months of age, earlier than in mcd/mcd mice. These changes
included hypopigmentation, hyperfluorescence, retinal pigment epithelial (RPE)
cell depigmentation or clumping, cell proliferation, and pleomorphism.
Proliferating cells were identified as being of RPE origin. CONCLUSIONS: This
study demonstrated a correlation between the presence of the inactive CatD in RPE
cells and the development of ophthalmoscopic, cellular, and histologic changes in
the retina.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16123398 [PubMed - indexed for MEDLINE]

1792: Br J Dermatol. 2005 Sep;153(3):635-8.

Molecular basis of hypotrichosis with juvenile macular dystrophy in two siblings.

Indelman M, Leibu R, Jammal A, Bergman R, Sprecher E.

Department of Dermatology and Laboratory of Molecular Dermatology, Rambam Medical
Center, Haifa, Israel.

BACKGROUND: Hypotrichosis with juvenile macular dystrophy (HJMD) is a rare
autosomal recessive disorder characterized by sparse and short scalp hair from
birth, followed within a few years by progressive macular degeneration leading to
blindness. HJMD was shown to result from mutations in CDH3 encoding P-cadherin.
OBJECTIVES: In the present study, we attempted to identify the molecular basis of
abnormal hair growth in two siblings of Arab Muslim origin with hypotrichosis but
no visual symptoms. METHODS: Mutation analysis was performed using direct
sequencing and polymerase chain reaction-restriction fragment length polymorphism
analysis. RESULTS: Patients displayed sparse and short hair since birth.
Significant macular degenerative pigmentary changes were noticed in the face of
normal visual acuity. Despite the fact that a single CDH3 mutation had previously
been described in several families of Israeli Arab Muslim origin, the two
affected patients were found to be homozygous carriers of a novel nonsense
mutation (Y615X) predicted to result in premature termination of P-cadherin
translation. CONCLUSIONS: The present results indicate that all patients with
congenital hypotrichosis should undergo thorough fundus examination, which, when 
revealing pigmentary macular changes, can be considered as indicative of an
underlying CDH3 causative mutation.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 16120155 [PubMed - indexed for MEDLINE]

1793: Br J Ophthalmol. 2005 Sep;89(9):1171-5.

A case control study of age related macular degeneration and use of statins.

Smeeth L, Cook C, Chakravarthy U, Hubbard R, Fletcher AE.

Department of Epidemiology and Population Health, London School of Hygiene and
Tropical Medicine, Keppel Street, London WC1E 7HT, UK. liam.smeeth@lshtm.ac.uk

AIMS: Age related macular degeneration (AMD) is the leading cause of blindness in
industrialised countries. Previous studies have suggested that statins may have a
protective effect against the disease; however, existing studies have had limited
power to reliably detect or exclude an effect and have produced conflicting
results. The authors assessed the risk of AMD associated with the use of statins.
METHODS: Population based case control study using the United Kingdom General
Practice Research Database. 18 007 people with diagnosed AMD were compared with
86 169 controls matched on age, sex, and general practice. The primary outcome
was the odds ratio for the association between exposure to statins and AMD.
RESULTS: The crude odds ratio for the association between any recorded exposure
to statins and AMD was 1.32 (95% CI 1.17 to 1.48), but this reduced to 0.93 (95% 
CI 0.81 to 1.07, p=0.33) after adjustment for consultation rate, smoking, alcohol
intake, body mass index, atherosclerotic disease, hyperlipidaemia, heart failure,
diabetes mellitus, hypertension, use of other cardiovascular drugs, and use of
fibrates. There was no evidence that the risk varied by dose of statin, duration 
of use, or that the risk varied for individual statins. CONCLUSION: In the short 
and medium term statin use is not associated with a decreased risk of AMD.
Whether subgroups of patients with specific forms of AMD (particularly choroidal 
neovascularisation) benefit from statin therapy remains a possibility.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16113375 [PubMed - indexed for MEDLINE]

1794: Br J Ophthalmol. 2005 Sep;89(9):1166-70.

The relation between C reactive protein and age related macular degeneration in
the Cardiovascular Health Study.

McGwin G, Hall TA, Xie A, Owsley C.

Department of Ophthalmology, School of Medicine, University of Alabama at
Birmingham, 700 S 18th Street, Suite 609, Birmingham, AL 35294-0009, USA.
mcgwin@uab.edu

AIM: To test the hypothesis that individuals with age related macular
degeneration (AMD) have increased C reactive protein (CRP) levels. METHODS: A
cross sectional study design using data from the Cardiovascular Health Study
(CHS), a longitudinal study that enrolled older adults from four communities in
the United States from 1989 to 1990, was employed to investigate the existence of
an association between AMD and CRP levels in this population. Fundus photographs 
from 1997 and 1998 were used to identify individuals with (n=390) and without AMD
(n=2365). The association between AMD and CRP levels (measured at baseline) was
compared, adjusting for the potentially confounding effect of demographic,
lifestyle, and health related characteristics. RESULTS: Among the 2755 CHS
participants with gradable fundus photographs, 390 were identified as having AMD.
Overall, median CRP levels among those with AMD (1.76 mg/l) were similar to those
without AMD (1.77 mg/l). CRP levels were categorised into quartiles and compared 
between those with and without AMD. Relative to those in the lowest quartile
(0.07-0.93 mg/l), the odds ratios (OR) in the higher quartiles, adjusted for
demographic, lifestyle, and health related characteristics were increased but not
statistically significant (0.94-1.77 mg/l: OR=1.14, 95% CI 0.82 to 1.60;
1.78-3.04 mg/l: OR=1.24, 95% CI 0.88 to 1.75; >3.04 mg/l: OR=1.24, 95% CI 0.87 to
1.78). CONCLUSIONS: In the CHS, there is no evidence that CRP levels are
associated with AMD. These data do not support the theory alleging non-specific
systemic inflammation in the aetiology and natural history of this disease.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 16113374 [PubMed - indexed for MEDLINE]

1795: Br J Ophthalmol. 2005 Sep;89(9):1127-30.

Further validation of the Daily Living Tasks Dependent on Vision: identification 
of domains.

Hart PM, Stevenson MR, Montgomery AM, Muldrew KA, Chakravarthy U.

Department of Ophthalmology and Vision Science, The Queen's University of Belfast
and Royal Group of Hospitals, Grosvenor Road, Belfast BT12 6BA, UK.
pat.hart@royalhospitals.n-i.nhs.uk

AIM: To examine the Daily Living Tasks Dependent on Vision (DLTV), a visual
function questionnaire for domain structure, and redundancy. METHOD: 235 subjects
underwent full ophthalmic assessment and completed the DLTV questionnaire by
interview. Principal component analysis with varimax rotation and item response
theory (IRT) were used to assign the items to domains. The internal consistency
of each domain was examined using Cronbach's alpha. Redundancy was assessed by
regressing each item in a domain against the remainder of items in that domain.
RESULTS: Four domains were identified. Domain 1 was formed by nine items, which
after applying IRT were seen to be among the most difficult questions in the
instrument. Domain 2 contained eight items, all of which fell in the easier half 
of the instrument on applying IRT. Domain 3 contained only three items, all of
which were among the easier questions and appear to deal with peripheral vision
function. Domain 4 consisted of two items dealing with adaptation to light and
dark conditions. Cronbach's alpha for each domain was 0.96, 0.93, 0.73, 0.66.
Redundancy was found to be present in domain 1, which was therefore reduced by
two items, with little effect on internal consistency. CONCLUSIONS: The authors
believe using the domains identified in this report will optimise the information
provided by patients on their ability to function on visually demanding tasks.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Validation Studies

PMID: 16113365 [PubMed - indexed for MEDLINE]

1796: Br J Radiol. 2005 Sep;78(933):827-31.

A phase I trial of stereotactic external beam radiation for subfoveal choroidal
neovascular membranes in age-related macular degeneration.

Barak A, Hauser D, Yipp P, Morse L, Leigh B, Kubo D, Goldberg Z, Earle J, Handa
JT.

Department of Ophthalmology, UC Davis, Sacramento, CA, USA.

Effective treatment for neovascular age-related macular degeneration (AMD) is
currently limited. Radiation therapy, a therapeutic approach with known
antiangiogenic properties, has been investigated as a modality to prevent severe 
visual loss in AMD. Most of the studies using external beam radiation employed
<25 Gy to the whole eye, which is below the dose of radiation that is toxic to
the retina and optic nerve ( approximately 50 Gy and approximately 59 Gy,
respectively). Stereotactic fractionated external beam radiation (St-EBR) is a
method that allows radiation to be delivered to a small, defined area. We
investigated the effects of St-EBR in incremental doses up to 40 Gy on
neovascular AMD. Patients with clinical signs and fluorescein angiography
demonstrating neovascular AMD, visual acuity (VA) better than 20/400 and
ineligible for laser treatment (MPS criteria) or who refused to have laser
photocoagulation were enrolled in the study. Each patient was treated with
radiation at incremental dosages from 20 Gy to 40 Gy. After completion of the
radiation course, all patients were followed-up at 3 and 7 weeks and 3, 6, and 12
months. Best-corrected VA (ETDRS), slit-lamp and fluorescein angiographic
evaluations were performed at each visit. 94 eyes of 89 patients were treated
from October 1997 to April 2000. The VA was 0.82+/-0.35 before treatment,
0.83+/-0.36 at 6 months, and 0.89+/-0.33 at 12 months. No patients suffered any
significant acute side effects. No significant benefits in either VA or in
membrane size were derived from increasing the doses of radiation. Our results
are consistent with trends of a palliative benefit of radiotherapy in neovascular
AMD and support further investigation of radiotherapy. Since there is no evidence
that therapeutic effectiveness is dose dependent, our data provide no
justification for potentially dangerous escalations in radiation dosage for
treating neovascular AMD.

Publication Types: 
    Clinical Trial
    Clinical Trial, Phase I
    Research Support, Non-U.S. Gov't

PMID: 16110105 [PubMed - indexed for MEDLINE]

1797: Free Radic Biol Med. 2005 Sep 15;39(6):781-96.

Differences in gene expression profiles in dermal fibroblasts from control and
patients with age-related macular degeneration elicited by oxidative injury.

Strunnikova N, Hilmer S, Flippin J, Robinson M, Hoffman E, Csaky KG.

National Eye Institute, Bethesda, MD 20892-1857, USA.

The pathogenesis of age-related macular degeneration (AMD) is still unknown but
there is growing evidence that a combination of both oxidative injury and genetic
factors may play a role. One particle hypothesis proposes that dysregulation of
multiple genes in response to an oxidative injury could contribute to the
development of AMD. While direct examination of ocular cells from AMD patients is
difficult, AMD also appears to have a systemic component. Therefore, as is the
case with other central nervous diseases, peripheral sites may also manifest any 
underlying genetic abnormalities. For the present study, biopsy-derived
fibroblasts from 4 patients with the early form and 4 patients with the late form
of AMD and 3 age-matched control patients were grown in culture and treated with 
a nonlethal dose of the oxidative stimulus menadione. Gene expression patterns
were quantitatively and qualitatively examined using Human Genome U95A GeneChips 
(Affymetrix) and verified by real-time PCR analysis. In response to the oxidative
injury 755 genes were found to be upregulated at least twofold in one of the
patients groups. Cluster analysis of expression profiles detected six patterns of
dysregulation initiated by oxidative injury specific for the disease groups (98
genes total). Clusters of genes dysregulated by the sublethal oxidative injury in
either early and/or late AMD groups were further categorized by
overrepresentation of GO "biological process" categories using Expression
Analysis Systematic Explorer (EASE) software. This approach demonstrated that
four major functional gene groups including inflammatory/innate immune response, 
transcriptional regulation, cell cycle, and proliferation were significantly
overrepresented (Fisher test ranging from 0.0393 to 0.00018) in both AMD patients
groups in response to the oxidative injury. Despite the small number of patients 
in the study, specific biological and statistical differences in gene expression 
profiles between control and AMD patients were identified but only in the
presence of an environmental stimulus.

PMID: 16109308 [PubMed - indexed for MEDLINE]

1798: J Cataract Refract Surg. 2005 Jul;31(7):1437-40.

Cyclooxygenase-2 inhibitors: a new therapeutic option in the treatment of macular
edema after cataract surgery.

Reis A, Birnbaum F, Hansen LL, Reinhard T.

Reis Medical Institution, Principality of Liechtenstein, Germany.
reis@augenwerk.li

Two patients had uneventful phacoemulsification. After initial improvement,
vision deteriorated because of cystoid macular edema (CME). In 1 patient,
treatment with systemic nonsteroidal antiinflammatory drugs showed significant
improvement in visual acuity but had to be discontinued because of side effects
and a relapse of the disease. In the other patient, this therapy was not
sufficient. Both patients were given valdecoxib, a cyclooxygenase-2 inhibitor.
The new therapy was tolerated well and led to significant and stable improvement 
in visual acuity in both patients. To our knowledge, this is the first report of 
using a cyclooxygenase-2 inhibitor in the treatment of clinically significant
CME.

Publication Types: 
    Case Reports

PMID: 16105620 [PubMed - indexed for MEDLINE]

1799: FASEB J. 2005 Oct;19(12):1683-5. Epub 2005 Aug 12.

Erratum in:
    FASEB J. 2005 Dec;19(14):2088.

Molecular composition of drusen and possible involvement of anti-retinal
autoimmunity in two different forms of macular degeneration in cynomolgus monkey 
(Macaca fascicularis).

Umeda S, Suzuki MT, Okamoto H, Ono F, Mizota A, Terao K, Yoshikawa Y, Tanaka Y,
Iwata T.

National Institute of Sensory Organs, National Hospital Organization Tokyo
Medical Center, Meguro-ku, Tokyo, Japan.

We have previously reported a cynomolgus monkey (Macaca fascicularis) pedigree
with early onset macular degeneration that develops drusen at 2 yr after birth.
In this study, the molecular composition of drusen in monkeys affected with late 
onset and early onset macular degeneration was both characterized. Involvement of
anti-retinalautoimmunity in the deposition of drusen and the pathogenesis of the 
disease was also evaluated. Funduscopic and histological examinations were
performed on 278 adult monkeys (mean age=16.94 yr) for late onset macular
degeneration. The molecular composition of drusen was analyzed by
immunohistochemistry and/or direct proteome analysis using liquid chromatography 
tandem mass spectroscopy (LC-MS/MS). Anti-retinal autoantibodies in sera were
screened in 20 affected and 10 age-matched control monkeys by Western blot
techniques. Immunogenic molecules were identified by 2D electrophoresis and
LC-MS/MS. Relative antibody titer against each antigen was determined by ELISA in
sera from 42 affected (late onset) and 41 normal monkeys. Yellowish-white spots
in the macular region were observed in 90 (32%) of the late onset monkeys that
were examined. Histological examination demonstrated that drusen or degenerative 
retinal pigment epithelium (RPE) cells were associated with the pigmentary
abnormalities. Drusen in both late and early onset monkeys showed
immunoreactivities for apolipoprotein E, amyloid P component, complement
component C5, the terminal C5b-9 complement complex, vitronectin, and membrane
cofactor protein. LC-MS/MS analyses identified 60 proteins as constituents of
drusen, including a number of common components in drusen of human age-related
macular degeneration (AMD), such as annexins, crystallins, immunoglobulins, and
complement components. Half of the affected monkeys had single or multiple
autoantibodies against 38, 40, 50, and 60 kDa retinal proteins. The reacting
antigens of 38 and 40 kDa were identified as annexin II and mu-crystallin,
respectively. Relative antibody titer against annexin II in affected monkeys was 
significantly higher than control animals (P<0.01). Significant difference was
not observed in antibody titer against mu-crystallin; however, several affected
monkeys showed considerably elevated titer (360-610%) compared with the mean for 
unaffected animals. Monkey drusen both in late and early onset forms of macular
degeneration had common components with drusen in human AMD patients, indicating 
that chronic inflammation mediated by complement activation might also be
involved in the formation of drusen in these affected monkeys. The high
prevalence of anti-retinalautoantibodies in sera from affected monkeys
demonstrated an autoimmune aspect of the pathogenesis of the disease. Although
further analyses are required to determine whether and how autoantibodies against
annexin II or mu-crystallin relate to the pathogenesis of the disease, it could
be hypothesized that immune responses directed against these antigens might
trigger chronic activation of the complement cascade at the site of drusen
formation.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16099945 [PubMed - indexed for MEDLINE]

1800: Eye. 2006 Aug;20(8):934-7. Epub 2005 Aug 12.

Low-dose intraocular triamcinolone injection for intractable macular oedema and
inflammation in patients with uveitis.

Das-Bhaumik RG, Jones NP.

The Royal Eye Hospital, Manchester, UK.

AIMS: To evaluate the efficacy and safety of low-dose (2 mg in 0.05 ml)
intraocular triamcinolone injection for patients with uveitis-related cystoid
macular oedema and/or intractable intraocular inflammation. PATIENTS AND METHODS:
Retrospective clinical case series. RESULTS: Cystoid macular oedema was
eliminated in 24/30 eyes (80%). Intractable intraocular inflammation was
eliminated in 4/8 eyes (50%). Snellen visual acuity was improved by two lines or 
more after 14/36 injections (38.9%). Intraocular pressure rose to above 21 mmHg
after 8/36 injections (22%). There were no major complications. CONCLUSIONS:
Low-dose (2 mg in 0.05 ml) intraocular triamcinolone acetonide injection is safe 
and effective for the management of refractory uveitic macular oedema. Its
usefulness in controlling inflammation alone is questionable.

PMID: 16096656 [PubMed - indexed for MEDLINE]

1801: BMC Ophthalmol. 2005 Aug 10;5:18.

The macular mapping test: a reliability study.

Bartlett H, Davies LN, Eperjesi F.

Ophthalmic and Physiological Optics Research Group, Aston University, Birmingham,
UK. bartlehe@aston.ac.uk

BACKGROUND: Age-related macular degeneration (ARMD) is the leading cause of
visual disability in people over 60 years of age in the developed world. The
success of treatment deteriorates with increased latency of diagnosis. The
purpose of this study was to determine the reliability of the macular mapping
test (MMT), and to investigate its potential as a screening tool. METHODS: The
study population comprised of 31 healthy eyes of 31 participants. To assess
reliability, four macular mapping test (MMT) measurements were taken in two
sessions separated by one hour by two practitioners, with reversal of order in
the second session. MMT readings were also taken from 17 age-related maculopathy 
(ARM), and 12 AMD affected eyes. RESULTS: For the normal cohort, average MMT
scores ranged from 85.5 to 100.0 MMT points. Scores ranged from 79.0 to 99.0 for 
the ARM group and from 9.0 to 92.0 for the AMD group. MMT scores were reliable to
within +/- 7.0 points. The difference between AMD affected eyes and controls (z =
3.761, p = < 0.001) was significant. The difference between ARM affected eyes and
controls was not significant (z = -0.216, p = 0.829). CONCLUSION: The reliability
data shows that a change of 14 points or more is required to indicate a
clinically significant change. This value is required for use of the MMT as an
outcome measure in clinical trials. Although there was no difference between MMT 
scores from ARM affected eyes and controls, the MMT has the advantage over the
Amsler grid in that it uses a letter target, has a peripheral fixation aid, and
it provides a numerical score. This score could be beneficial in office and home 
monitoring of AMD progression, as well as an outcome measure in clinical
research.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16092954 [PubMed - indexed for MEDLINE]

1802: IEEE Trans Med Imaging. 2005 Aug;24(8):929-45.

Delineating fluid-filled region boundaries in optical coherence tomography images
of the retina.

Fernández DC.

Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami
Miller School of Medicine, Miami, FL 33136, USA. dcabrera2@med.miami.edu

We evaluate the ability of a deformable model to yield accurate shape
descriptions of fluid-filled regions associated with age-related macular
degeneration. Calculation of retinal thickness and volume by the current optical 
coherence tomography (OCT) system includes fluid-filled regions or lesions along 
with actual retinal tissue. In order to quantify these lesions independently from
the retinal tissue, they must be outlined. A deformable model was applied to OCT 
images of retinas demonstrating cystoids and subretinal fluid spaces. Several
implementation issues were addressed in order to choose appropriate parameters.
The use of a nonlinear anisotropic diffusion filter to suppress speckle noise
while at the same time preserving the edges of the original image was explored.
Once the contours of the lesions were outlined, quantitative analysis of the
surface area and volume of the lesions was performed. The deformable model could 
accurately outline fluid-filled regions within the retina. The detection method
tested proved effective in capturing the complexity of fluid-filled regions in
OCT images. Deformable models combined with nonlinear anisotropic diffusion
filtering show promise in the detection of retinal features of interest for
diagnosis in clinical OCT images. Thus, fluid-filled region detection may
significantly aid in analysis of treatments and diagnosis.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, U.S. Gov't, P.H.S.

PMID: 16092326 [PubMed - indexed for MEDLINE]

1803: Ophthalmologica. 2005 Jul-Aug;219(4):214-21.

Activated STAT 3 in choroidal neovascular membranes of patients with age-related 
macular degeneration.

Fasler-Kan E, Wunderlich K, Hildebrand P, Flammer J, Meyer P.

Department of Research, University of Basel, Basel, Switzerland.

PURPOSE: The Jak/STAT (Janus tyrosine kinase/signal transducers and activators of
transcription) pathway is critical for growth control, developmental regulation
and homeostasis. Here we studied the expression of STAT proteins in the
proliferative disease of age-related macular degeneration (AMD) with choroidal
neovascular membranes (CNVM). The STAT family are of cytoplasmic proteins with
roles as signal messengers and transcription factors that participate in normal
cellular responses to cytokines and growth factors. Abnormal activity of certain 
STAT family members, particularly STAT 3 and STAT 5, is associated with a wide
variety of human malignancies and other diseases. Here were studied STAT
activation in CNVM of patients with AMD. METHODS: Sections of formalin-fixed,
paraffin-embedded samples from 8 eyes with AMD and 5 controls were included in
this study. Immunohistochemical staining was performed using antibodies against
activated STAT 1, STAT 3 and STAT 5 proteins, and tenascin. RESULTS: In CNVM, we 
observed a strong positive staining for tenascin and STAT 3 in retinal pigmented 
epithelial (RPE) cells restricted to areas of developing scars. In contrast, STAT
3 immunoreactivity failed in areas completely composed of fibrovascular disciform
scar material. In addition, no immunoreactivity for both STAT 1 and STAT 5 was
detected in all CNVM and in all control samples. CONCLUSION: In CNVM, activation 
of STAT 3 appears in RPE cells simultaneously with the formation of scars.
Copyright (c) 2005 S. Karger AG, Basel.

PMID: 16088240 [PubMed - indexed for MEDLINE]

1804: Ophthalmologica. 2005 Jul-Aug;219(4):206-13.

Comment in:
    Ophthalmologica. 2006;220(3):206; author reply 206-7.

Vitrectomy for diabetic macular edema with and without internal limiting membrane
removal.

Yamamoto T, Hitani K, Sato Y, Yamashita H, Takeuchi S.

Department of Ocular Cellular Engineering, Yamagata University Hospital,
Yamagata, Japan. teiko-y@med.id.yamagata-u.ac.jp

PURPOSE: To compare the efficacy of surgically removing or not removing the
internal limiting membrane (ILM) during pars plana vitrectomy on the visual
acuity and retinal thickness in eyes with diabetic macular edema. METHODS: A
prospective, case-control study was carried out on 30 eyes of 29 patients
undergoing pars plana vitrectomy for diabetic macular edema. Fifteen eyes
underwent pars plana vitrectomy with ILM removal and 15 eyes without ILM removal.
RESULTS: In 7 of 15 eyes (47%) in the ILM-removed group, the visual acuity
improved by 0.2 or more log of the minimum angle of resolution (log MAR) units
and remained unchanged in 8 eyes (53%). In the ILM-preserved group, the final
visual acuity improved in 9 of 15 eyes (60%) and remained unchanged in 6 eyes
(40%). The difference in visual acuity between the two groups after 11 months the
surgery was not significant (Fisher's exact test, p=0.4938). In the ILM-removed
group, the final retinal thickness decreased by more than 20% of the preoperative
retinal thickness in 12 of 15 eyes (80%), remained unchanged in 2 of 15 eyes
(13%), and increased in 1 of 15 eyes (7%). In the ILM-preserved group, the final 
retinal thickness decreased in 13 of 15 eyes (87%) and remained unchanged in 2 of
15 eyes (23%). The differences in the changes in the retinal thickness between
the two groups were not statistically significant (Fisher's exact test,
p=0.5945). CONCLUSION: Vitrectomy in eyes with diabetic macular edema without ILM
removal was as effective in reducing the retinal thickness and improving the
visual acuity as eyes with ILM removal. We conclude that ILM need not be removed 
to treat eyes with diabetic macular edema. Copyright (c) 2005 S. Karger AG,
Basel.

PMID: 16088239 [PubMed - indexed for MEDLINE]

1805: Arch Ophthalmol. 2005 Aug;123(8):1042-50.

A randomized controlled trial to determine the effectiveness of prism spectacles 
for patients with age-related macular degeneration.

Smith HJ, Dickinson CM, Cacho I, Reeves BC, Harper RA.

Department of Optometry and Neuroscience, University of Manchester Institute of
Science and Technology, Manchester, England. heatherj.smith@rjah.nhs.uk

OBJECTIVE: To determine the effectiveness of prism spectacles in people with
age-related macular degeneration by relocating the retinal image. METHODS: We
implemented a randomized, placebo-controlled, double-masked trial. Participants
with age-related macular degeneration received a standard low-vision assessment
and the prescription of conventional low-vision aids 6 weeks before the study
intervention. Participants were randomized to receive 1 of the following,
including the optimal refractive correction: (1) custom, incorporating bilateral 
prisms to match participants' preferred power and base direction; (2) standard,
incorporating standard bilateral prisms (6 prism diopters [Delta] base up for
logMAR [logarithm of the minimum angle of resolution] visual acuity (VA) of
0.48-1.00 and 10Delta base up for logMAR VA of 1.02-1.68); or (3) placebo,
consisting of spectacles matched in weight and thickness to prism spectacles but 
without prism. MAIN OUTCOME MEASURES: Outcomes measured binocularly at baseline
and 3-month follow-up included distance logMAR VA, reading speed, critical print 
size, visual functioning questionnaires, and observed visual task performance.
Scores on the 25-item National Eye Institute Visual Functioning Questionnaire and
the Melbourne Low-Vision ADL (Activities of Daily Living) Index were converted to
linear estimates using Rasch analysis. The Manchester Low Vision Questionnaire
was used to collect descriptive data. RESULTS: A total of 225 participants
completed the trial (median age, 81 years). We found no significant effect of
treatment group on any of the outcome measures, including VA, the primary outcome
(adjusted for baseline) (P = .63). Participants' responses to the Manchester Low 
Vision Questionnaire suggested that the prism spectacles added to their problems.
CONCLUSIONS: Prism spectacles are no more effective than conventional spectacles 
for people with age-related macular degeneration.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16087836 [PubMed - indexed for MEDLINE]

1806: Ophthalmology. 2005 Sep;112(9):1579-85.

Preferred retinal locus development in patients with macular disease.

Crossland MD, Culham LE, Kabanarou SA, Rubin GS.

Institute of Ophthalmology, University College London, London, United Kingdom.
m.crossland@ucl.ac.uk

OBJECTIVE: To observe the development of the preferred retinal locus (PRL) in a
group of patients with central scotomas caused by recent onset macular disease
(MD). DESIGN: Prospective observational case series. PARTICIPANTS: Twenty-five
individuals with bilateral central scotomas caused by MD. All patients had
experienced visual loss in their better eye in the 2 weeks before recruitment.
METHODS: Patients were assessed at baseline and at 4 further visits for up to 12 
months. At each visit, the retinal area used for fixation was assessed using a
scanning laser ophthalmoscope, the infrared Gazetracker was used to determine the
number of discrete retinal areas used for fixation in 5 positions of gaze, and
reading speed was measured using MN-Read-style sentences. RESULTS: All 25
patients developed a PRL within 6 months. Sixteen patients (64%) made an
adaptation whereby they were unaware of using an eccentric retinal area for
fixation. Multiple fixation loci were exhibited by 11 patients at the end of the 
study. Nineteen patients used a consistent number of PRLs under all positions of 
gaze. Reading speed was not associated with PRL location or the presence of
multiple PRLs. CONCLUSIONS: All of the patients in this study developed a
repeatable preferred retinal locus within 6 months of visual loss in their second
affected eye. Reading performance was better in patients who were not aware of
using eccentric viewing strategies and who used a repeatable number of PRLs under
all positions of gaze. These findings are relevant for counseling patients with
MD and for the design of rehabilitation programs for patients with central vision
loss.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16087239 [PubMed - indexed for MEDLINE]

1807: Am J Ophthalmol. 2005 Aug;140(2):316-8.

Spontaneous rip of the retinal pigment epithelium with a macular hole in
neovascular age-related macular degeneration.

Emerson GG, Ghazi NG.

Wilmer Eye Institute, General Eye Service, Baltimore, Maryland 21287-5001, USA.
gemerso1@jhmi.edu

PURPOSE: To report a case of retinal pigment epithelial tear associated with a
macular hole in a patient with neovascular age-related macular degeneration
(AMD). DESIGN: Observational case report. METHODS: An 87-year-old woman with
AMD-related fibrovascular pigment epithelial detachment associated with vision
loss was followed with sequential fundus photography, fluorescein angiography,
and optical coherence tomography for 8 months. RESULTS: The detachment developed 
into a retinal pigment epithelium tear with macular hole formation. The temporal 
evolution of the lesion and optical coherence tomography findings suggested that 
the retinal pigment epithelium tear led to stretching forces along the posterior 
surface of the neurosensory retina with secondary foveal dehiscence. CONCLUSION: 
Macular hole formation is one mechanism by which retinal pigment epithelium tears
may cause vision loss in AMD.

Publication Types: 
    Case Reports

PMID: 16086957 [PubMed - indexed for MEDLINE]

1808: Am J Ophthalmol. 2005 Aug;140(2):256-61.

Pathogenesis of macular edema with branch retinal vein occlusion and intraocular 
levels of vascular endothelial growth factor and interleukin-6.

Noma H, Funatsu H, Yamasaki M, Tsukamoto H, Mimura T, Sone T, Jian K, Sakamoto I,
Nakano K, Yamashita H, Minamoto A, Mishima HK.

Department of Ophthalmology and Visual Science, Graduate School of Biomedical
Sciences, Hiroshima University, Hiroshima, Japan. noma@hiroshima-u.ac.jp

PURPOSE: To determine whether correlations between vascular endothelial growth
factor (VEGF) or interleukin-6 (IL-6) contribute to the pathogenesis of macular
edema in eyes of patients with branch retinal vein occlusion (BRVO). DESIGN:
Retrospective case-control study. METHODS: Nineteen patients with macular edema
with BRVO and seven patients with non-ischemic ocular disease (control group)
were studied. The degree of retinal ischemia was evaluated in terms of the area
of capillary non-perfusion, and the severity of macular edema was examined by
optical coherence tomography. Aqueous humor samples were obtained at the time of 
combined vitrectomy and cataract surgery, and VEGF and IL-6 levels in aqueous
humor and plasma were determined by enzyme-linked immunosorbent assay. RESULTS:
Aqueous levels of VEGF (351 +/- 273 pg/ml) and IL-6 (7.10 +/- 6.51 pg/ml) were
significantly elevated in patients with BRVO compared with the control patients
(119 +/- 38.7 pg/ml and 2.27 +/- 1.11 pg/ml, respectively) (P = .0017 and P =
.0052, respectively). Aqueous level of VEGF was significantly correlated with
that of IL-6 (P = .0396), and aqueous levels of VEGF and IL-6 were correlated
with the size of the BRVO non-perfused area (P < .0001 and P = .0331,
respectively). Aqueous level of VEGF was correlated with the severity of macular 
edema (P = .0306). CONCLUSIONS: VEGF and IL-6 may be involved in the pathogenesis
of macular edema with BRVO. The increase in these cytokines might be used as a
unique index of BRVO, through which we can determine the severity of the ischemic
condition as being in a quiescent state or an exacerbation of macular edema.

PMID: 16086947 [PubMed - indexed for MEDLINE]

1809: Am J Ophthalmol. 2005 Aug;140(2):184-92.

Tractional cystoid macular edema: a subtle variant of the vitreomacular traction 
syndrome.

Johnson MW.

Department of Ophthalmology and Visual Sciences, University of Michigan, W. K.
Kellogg Eye Center, 1000 Wall Street, Ann Arbor 48105, USA. markwj@umich.edu

PURPOSE: To describe clinical characteristics and treatment outcomes in a series 
of patients with tractional cystoid macular edema, a subtle variant of the
vitreomacular traction syndrome. DESIGN: Retrospective, uncontrolled,
observational, and interventional case series. METHODS: Patient population: Ten
consecutive patients (11 eyes) with multicystoid foveolar thickening caused by
localized perifoveal vitreous detachment. EXPERIMENTAL PROCEDURES: Slit-lamp
biomicroscopy and fluorescein angiography; confirmation of vitreomacular
relationship with B-scan ultrasonography, optical coherence tomography (OCT), or 
both. Vitrectomy with peeling of posterior hyaloid in 8 eyes with pretreatment
visual acuity <or=20/60. MAIN OUTCOME MEASURES: Visual acuity and resolution of
cystoid macular edema at final follow-up. RESULTS: The median age of symptom
onset was 71 years (range 48-81 years). Shallow perifoveal vitreous detachment
was detectable on biomicroscopy in 8 of 11 eyes (73%) and with ultrasound and OCT
in all eyes. Fluorescein angiography revealed no leakage from perifoveal
capillaries in 8 eyes (73%). After a mean postoperative follow-up of 26.0 months 
(range 3-84 months), the final visual acuity had improved by 2 or more Snellen
lines and measured 20/40 or better in 8 (100%) of 8 operated eyes. Cystoid foveal
thickening resolved in all operated eyes. CONCLUSION: Subtle, localized
perifoveal vitreous detachment may cause anterior traction on the foveola,
resulting in multicystoid foveal thickening without macular hole formation or
capillary leakage. OCT and ultrasound imaging are useful in detecting the
detached posterior hyaloid when clinically invisible. Foveal thickening resolves 
and visual acuity typically improves after the relief of vitreofoveolar traction.

PMID: 16086944 [PubMed - indexed for MEDLINE]

1810: J Med Assoc Thai. 2004 Sep;87 Suppl 2:S78-82.

Treatment of subfoveal choroidal neovascularization secondary to age related
macular degeneration with single treatment of verteporfin photodynamic therapy: a
safety and short-term outcome.

Tayanithi P, Pisankosakul P, Laksakapuk P.

Department of Ophthalmology, Faculty of Medicine, Chulalongkorn University,
Bangkok 10330, Thailand.

OBJECTIVE: To evaluate the short-term efficacy on visual outcome and safety of a 
single treatment of photodynamic therapy with verteporfin using the standard
dosage regimen in patients with predominantly classic subfoveal choroidal
neovascularization (CNV) from age related macular degeneration. DESIGN:
Prospective, noncomparative, consecutive, interventional case series. SETTING:
Department of Ophthalmology, Chulalongkorn University and Hospital, Bangkok,
Thailand. PARTICIPANTS: Patients with subfoveal CNV caused by age related macular
degeneration. METHOD: Standardized protocol refraction, visual acuity testing,
complete ophthalmic examination, color photography, and fluorescein angiography
were used to evaluate the effects of a single treatment of photodynamic therapy
with verteporfin. Follow-up was planned through 3 months in all patients.
RESULTS: A total of 39 eyes from 35 patients enrolled into the present study and 
have completed 3 months follow-up. The mean +/- SD logMAR BCVA at baseline was
0.76 +/- 0.48, equivalent to the Snellen BCVA of 20/114 (range, 20/40 to
20/1000). The mean +/- SD logMAR BCVA at the final 3-month visit was 0.55 +/-
0.37, which was a Snellen equivalent of 20/70 (range, 20/30 to 20/1000). The mean
line of BCVA improvement was 2.1 lines. The improvement in BCVA at the 3-month
follow-up was statistically significant (Wilcoxon signed-rank test, P = .043). No
patient suffered moderate loss of vision or a loss of vision in 2 or more lines. 
None of the patients suffered severe visual threatening adverse events at the
time of treatment and during the study period. CONCLUSIONS: The results of
short-term visual outcome is encouraging; PDT is the least invasive treatment
method currently available to achieve a stable or improved vision in AMD
patients. PDT with verteporfin can lead to cessation of fluorescein leakage from 
CNV for up to 3 months, with stabilization or improvement of vision for 12 weeks.
A randomized, controlled study in the near future would be beneficial to
demonstrate the long-term results and efficacy in the treatment of CNV associated
with AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16083167 [PubMed - indexed for MEDLINE]

1811: Eye. 2006 May;20(5):523-6.

Review of first year result of photodynamic therapy on age-related macular
degeneration in Chinese population.

Yang N, Fan CM, Ho CK.

Department of Ophthalmology, Tuen Mun Hospital, HKSAR, Tuen Mun, NT, Hong Kong.
nyang8@hotmail.com

PURPOSE: To evaluate the effect of verteporfin therapy (Visudyne) on age-related 
macular degeneration (AMD) in Chinese patients. The baseline characteristic and
the visual outcome will be compared with the treatment of AMD with photodynamic
therapy study (TAP) and verteporfin in photodynamic therapy study (VIP). DESIGN: 
Retrospective comparative case series. METHOD: We recruited patients >50 years
old, with best-corrected visual acuity >20/200 and fluorescein angiography
documenting subfoveal either predominantly classic with greatest linear dimension
<5400 mum or pure occult choroidal neovascularization (CNV) secondary to AMD. We 
applied non-thermal laser to the lesion 15 min after visudyne infusion as
described in TAP study. Patients were followed up with fluorescein angiography
every 3 months. Additional treatment would be offered if there was evidence of
recurrence of CNV. OUTCOME MEASURE: Baseline characteristic and visual outcome.
RESULT: In all, 46 eyes of 42 patients were enrolled at our centre from July 2002
to June 2003. They comprised 11 eyes with predominantly classic lesions and 35
eyes with pure occult lesion. The mean number of treatment sessions given was 2.9
in the first year. At the 12-month examination, there were 63 and 29% of patients
showing visual improvement in predominantly classic and occult groups,
respectively, while there were only 16% of patients in the TAP study and 12% of
patients in the VIP study showing visual improvement in the same period.
CONCLUSION: Verteporfin therapy for subfoveal CNV is beneficial to Chinese
patients with AMD at first year. The visual result seems to be better than that
observed in Caucasian patients.

Publication Types: 
    Evaluation Studies

PMID: 16082401 [PubMed - indexed for MEDLINE]

1812: Eye. 2006 Jun;20(6):649-54. Epub 2005 Aug 5.

Comment in:
    Eye. 2007 Apr;21(4):554-5.

Low power vs standard power transpupillary thermotherapy in patients with
age-related macular degeneration and subfoveal choroidal neovascularization
ineligible for photodynamic therapy.

Hogan AC, Kilmartin DJ.

Research Foundation, Royal Victoria Eye & Ear Hospital, Dublin, Ireland.

AIM: To assess the effect of standard power vs low power transpupillary
thermotherapy (TTT) in patients with active subfoveal choroidal
neovascularization secondary to age-related macular degeneration ineligible for
photodynamic therapy (PDT) by original treatment of age-related macular
degeneration with photodynamic therapy (TAP) study group recommendations.
METHODS: Retrospective review of 79 patients with active predominantly occult
subfoveal choroidal neovascularization or predominantly classic subfoveal
choroidal neovascularization but Snellen visual acuity <20/200. All patients were
treated with TTT administered via a Mainster wide field fundus contact lens with 
a retinal power/diameter coefficient of 248 mW/mm in the standard power (n=27)
and 181 mW/mm in the low power group (n=52). The primary outcome was
stabilization (<1 Snellen line change) or improvement (two or more Snellen lines)
in visual acuity. Clinical and fluorescein angiographic resolution of overlying
exudation was documented. RESULTS: At 24 month follow-up, 17 patients (63%) in
the standard power and 36 patients (69%) in the low power group achieved stable
or improved vision. Improved vision (mean three lines) was observed in 22% of the
standard power and 23% of the low power group. Overlying exudation was reduced
clinically with minimal or no leakage on fluorescein angiogram in 85% of standard
power and 90% of low power group. Subgroup analysis in the low power group
demonstrated a visual benefit in patients with subfoveal lesions, which had any
classic component. CONCLUSIONS: Low power TTT is as effective as standard power
in stabilizing or improving vision and reducing overlying exudation in patients
with active subfoveal choroidal neovascularization ineligible for PDT.

Publication Types: 
    Comparative Study
    Evaluation Studies

PMID: 16082398 [PubMed - indexed for MEDLINE]

1813: Exp Eye Res. 2005 Aug;81(2):176-82.

Proteomic analysis of vitreous from diabetic macular edema.

Ouchi M, West K, Crabb JW, Kinoshita S, Kamei M.

Department of Ophthalmology, Kyoto Prefectural University of Medicine, 465
Kawaramachi Hirokoji Kamigyo-ku, Kyoto 602-0841, Kyoto, Japan.

To identify and analyze diabetic macular edema (DME)-related proteins in the
vitreous, en masse, using two-dimensional gel (2D gel) electrophoresis and
mass-spectrometry (MS). Vitreous samples were corrected from 20 eyes with
pre-proliferative diabetic retinopathy associated with DME (DME group) and
without DME (non-DME group). They were subjected to 2D gel electrophoresis, and
the spot intensities were compared between the groups. Apparently visible spots
were excised from the gel, and the proteins were identified by liquid
chromatography tandem MS (LC MS/MS) sequence analysis. We identified 14 proteins 
from the DME group, and 15 proteins from the non-DME group. The intensity of
eight spots was markedly higher in DME than non-DME samples and one spot was
detected only in non-DME samples. From the eight spots, six proteins were
identified, including PEDF, ApoA-4, ApoA-1, Trip-11, PRBP, and VDBP. On the other
hand, Apo H was expressed only in non-DME. Certain vitreous proteins expressed
exclusively in DME and lacked in DME. These chemical mediators in the posterior
vitreous may play a role in the pathogenesis of DME.

PMID: 16080911 [PubMed - indexed for MEDLINE]

1814: Exp Eye Res. 2005 Aug;81(2):159-64.

Effect of Viagra on the foveolar choroidal circulation of AMD patients.

Metelitsina TI, Grunwald JE, DuPont JC, Ying GS.

Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, 51
North 39th Street, Philadelphia, PA 19104, USA.

To investigate the effects of sildenafil citrate (Viagra) on foveolar choroidal
circulation in patients with age related macular degeneration (AMD).
Double-blinded, randomized, placebo-controlled, crossover study. Fifteen male AMD
patients received a dose of 100 mg of sildenafil or matching placebo on two
separate days. Laser Doppler flowmetry was performed to assess relative choroidal
blood velocity (ChB(Vel)), volume (ChB(Vol)) and flow (ChB(Flow)) in the study
eye prior to administration of the drug at baseline and 30, 90, 180, 300 min
after dosing. Best corrected visual acuity (BCVA), contrast sensitivity (CS),
mean arterial blood pressure (BPm), heart rate (HR), intraocular pressure (IOP)
and ocular perfusion pressure (PP) were determined. In comparison to placebo,
sildenafil did not cause any statistically significant changes in mean ChB(Vel)
(ANOVA, P=0.12), ChB(Vol) (ANOVA, P=0.24) or ChB(Flow) (ANOVA, P=0.46). There
were no statistically significant changes in CS (ANOVA, P=0.59), BCVA (P=0.58),
IOP (P=0.81) or HR (P=0.07) throughout the study. Significant decreases in BPm
(P=0.006) and PP (P=0.006) were observed at 30 min after sildenafil.
Administration of sildenafil citrate didn't cause any statistically significant
changes in the foveolar choroidal circulation of AMD patients.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 16080909 [PubMed - indexed for MEDLINE]

1815: Am J Hum Genet. 2005 Sep;77(3):389-407. Epub 2005 Jul 26.

Susceptibility genes for age-related maculopathy on chromosome 10q26.

Jakobsdottir J, Conley YP, Weeks DE, Mah TS, Ferrell RE, Gorin MB.

Department of Biostatistics, Graduate School of Public Health, University of
Pittsburgh, Pittsburgh, PA 15213, USA.

On the basis of genomewide linkage studies of families affected with age-related 
maculopathy (ARM), we previously identified a significant linkage peak on 10q26, 
which has been independently replicated by several groups. We performed a focused
SNP genotyping study of our families and an additional control cohort. We
identified a strong association signal overlying three genes, PLEKHA1, LOC387715,
and PRSS11. All nonsynonymous SNPs in this critical region were genotyped,
yielding a highly significant association (P < .00001) between PLEKHA1/LOC387715 
and ARM. Although it is difficult to determine statistically which of these two
genes is most important, SNPs in PLEKHA1 are more likely to account for the
linkage signal in this region than are SNPs in LOC387715; thus, this gene and its
alleles are implicated as an important risk factor for ARM. We also found weaker 
evidence supporting the possible involvement of the GRK5/RGS10 locus in ARM.
These associations appear to be independent of the association of ARM with the
Y402H allele of complement factor H, which has previously been reported as a
major susceptibility factor for ARM. The combination of our analyses strongly
implicates PLEKHA1/LOC387715 as primarily responsible for the evidence of linkage
of ARM to the 10q26 locus and as a major contributor to ARM susceptibility. The
association of either a single or a double copy of the high-risk allele within
the PLEKHA1/LOC387715 locus accounts for an odds ratio of 5.0 (95% confidence
interval 3.2-7.9) for ARM and a population attributable risk as high as 57%.

Publication Types: 
    Comparative Study
    Research Support, N.I.H., Extramural
    Research Support, U.S. Gov't, P.H.S.

PMID: 16080115 [PubMed - indexed for MEDLINE]

1816: Retina. 2005 Jul-Aug;25(5):597-607.

Impact of fluorescein angiographic characteristics of macular lesions on outcomes
after macular translocation 360 degree surgery in eyes with age-related macular
degeneration.

Mruthyunjaya P, Stinnett SS, Toth CA.

Department of Ophthalmology, Duke University Medical Center, Durham, North
Carolina 27710, USA.

PURPOSE: To evaluate the relationship between preoperative lesion size and
composition and visual outcomes at 1 year after macular translocation surgery
with 360 degree peripheral retinectomy (MT360) for neovascular age-related
macular degeneration (AMD). METHODS: A prospective, interventional, consecutive, 
noncomparative case series of 64 patients with bilateral neovascular AMD treated 
with MT360 in the eye with more recent vision loss. Masked reviewers graded
preoperative fluorescein angiograms for lesion size in Macular Photocoagulation
Study disk areas (MPS DAs) and predominant lesion composition (classic or occult 
choroidal neovascularization or subretinal hemorrhage). Median changes in
distance and near visual acuities and reading speed at 12 months after surgery
were analyzed with respect to lesion size and composition. RESULTS: There was no 
significant difference between the outcomes for small-, medium- or large-sized
preoperative lesions. Patients in each predominant lesion composition group had
median improvement in visual outcomes with significant improvement in near visual
acuity and reading speed for predominantly classic and occult lesions.
CONCLUSION: MT360 stabilizes or improves visual function in patients with
neovascular AMD irrespective of lesion size categories and with a variety of
lesion compositions. Removal of the subretinal lesion and repositioning of the
fovea over a healthier retinal pigment epithelial bed may account for these
improvements.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 16077357 [PubMed - indexed for MEDLINE]

1817: Retina. 2005 Jul-Aug;25(5):551-5.

Intravitreal triamcinolone as primary treatment of cystoid macular edema
secondary to branch retinal vein occlusion.

Lee H, Shah GK.

Barnes Retina Institute and Department of Ophthalmology and Visual Sciences,
Washington University School of Medicine, St. Louis, Missouri 63144, USA.

PURPOSE: To describe six patients treated with intravitreal triamcinolone (IVT)
as primary therapy for cystoid macular edema (CME) secondary to branch retinal
vein occlusion (BRVO). METHODS: Retrospective case series. RESULTS: The age of
the patients ranged from 53 years to 87 years (mean, 66 years). The time between 
BRVO and treatment with IVT ranged from 2.0 months to 4.7 months (mean, 3.5
months). Pretreatment visual acuity ranged from 20/40 to 6/200 (mean, 20/166).
Length of follow-up ranged from 107 days to 175 days (mean, 149.5 days). Final
visual acuity ranged from 20/40 to 3/200 (mean, 20/137). Three of six eyes showed
improvement in vision. All three patients who did not have vision improvement
were treated with a second injection. At the final follow-up visit, all six eyes 
had improved vision from baseline. Five (83.3%) of six eyes showed an improvement
of > or = 2 lines of vision. One patient had a postoperative rise in intraocular 
pressure requiring a trabeculectomy. Final visual acuity in the 6 eyes ranged
from 20/200 to 20/30 (mean, 20/106). CONCLUSION: IVT may be of potential use in
treating CME due to BRVO, as either a primary or an adjunctive treatment
modality. A prospective, randomized trial to clarify this role is warranted.

Publication Types: 
    Case Reports

PMID: 16077348 [PubMed - indexed for MEDLINE]

1818: Jpn J Ophthalmol. 2005 Jul-Aug;49(4):324-6.

Surgical excision of type 1 + 2 choroidal neovascularization in age-related
macular degeneration.

Shimada H, Fujita K, Matsumoto Y, Mori R, Yuzawa M.

Department of Ophthalmology, Surugadai Hospital of Nihon University, 1-8-13
Surugadai, Kanda, Chioyoda-ku, Tokyo 101-8309, Japan. sshimada@olive.ocn.ne.jp

PURPOSE: To evaluate the visual acuity outcome and the various factors
influencing visual outcome in patients undergoing surgical removal of type 1 + 2 
choroidal neovascularization (CNV) caused by age-related macular degeneration
(AMD). METHODS: We studied the records of 54 patients (54 eyes) followed for at
least 1 year after surgical excision of CNV associated with AMD. RESULTS: The
final visual acuity was 0.4 or better in 4%, 0.1 to 0.3 in 46%, and worse than
0.1 in 50% of the patients. Final visual acuity was improved in 39%, stable in
37%, and worse in 24%. Stepwise regression showed that the distance between the
center of the foveal avascular zone and the CNV margin had the greatest effect on
final visual acuity. CONCLUSIONS: Surgical excision of type1 + 2 CNV due to AMD
may be indicated for preserving preoperative visual acuity. The distance between 
the center of the foveal avascular zone and the CNV margin is the most important 
factor affecting final visual acuity. (c) Japanese Ophthalmological Society 2005.

PMID: 16075336 [PubMed - indexed for MEDLINE]

1819: Jpn J Ophthalmol. 2005 Jul-Aug;49(4):321-3.

Surgical excision of type 2 choroidal neovascularization in age-related macular
degeneration.

Shimada H, Fujita K, Matsumoto Y, Mori R, Yuzawa M.

Department of Ophthalmology, Surugadai Hospital of Nihon University, 1-8-13
Surugadai, Kanda, Chioyoda-ku, Tokyo 101-8309, Japan. sshimada@olive.ocn.ne.jp

PURPOSE: To evaluate the visual acuity outcome and the influence of various
factors on visual outcome in patients undergoing surgical removal of type 2
choroidal neovascular neovascularization (CNV) caused by age-related macular
degeneration (AMD). METHODS: We studied the records of 92 patients (92 eyes) who 
were followed for at least 1 year after surgical excision of CNV associated with 
AMD. RESULTS: The final visual acuity was 0.4 or better in 21%, 0.1 to 0.3 in
66%, and worse than 0.1 in 13% of the patients. Final visual acuity was improved 
in 62%, stable in 29%, and worse in 9%. Stepwise regression identified CNV size
as a significant factor influencing final visual acuity (R = 0.287, P = 0.0045). 
CONCLUSIONS: Surgical excision of CNV for AMD is indicated for patients with
subfoveal active type 2 CNV with a visual acuity of 0.3 or worse. To achieve
better postoperative visual acuity it is important to operate on AMD patients in 
the early stage of CNV. (c) Japanese Ophthalmological Society 2005.

PMID: 16075335 [PubMed - indexed for MEDLINE]

1820: Jpn J Ophthalmol. 2005 Jul-Aug;49(4):297-300.

Effects of internal limiting membrane peeling in vitrectomy on diabetic cystoid
macular edema patients.

Kamura Y, Sato Y, Isomae T, Shimada H.

Department of Ophthalmology, Nihon University School of Medicine, 30-1 Ohyaguchi 
Kamimachi, Itabashi-ku, Tokyo 173-8610, Japan. ykamura@med.nihon-u.ac.jp

PURPOSE: We evaluated the effects of the peeling of the internal limiting
membrane (ILM) during vitrectomy in diabetic cystoid macular edema (CME)
patients. METHODS: Visual outcome and intraoperative and postoperative
complications were evaluated retrospectively in 84 CME patients (100 eyes), all
of whom had been followed for at least 1 year postoperatively. Before January
2001, we did not perform ILM peeling at our hospitals; 57 patients (66 eyes)
treated before 2001 were included in this retrospective study as the non-peeling 
group. After January 2001, ILM peeling was performed in 27 (34 eyes) CME
patients, who were included in this study as the peeling group. In the peeling
group, indocyanine green (ICG) staining was performed at the time of ILM peeling.
RESULTS: Visual acuity improved significantly after vitrectomy regardless of ILM 
peeling. Visual acuity improved gradually from 6 months to 1 year after the
operation, and improved further at the final observation point in both groups.
Visual acuity did not differ significantly between the two groups at any time
point. There was no difference in the incidence of intraoperative and
postoperative complications between the two groups. There were no adverse events 
associated with ICG-assisted ILM peeling. CONCLUSIONS: Visual acuity improved
with vitrectomy for diabetic cystoid macular edema in both groups. ILM peeling
was not found to improve visual acuity postoperatively. (c) Japanese
Ophthalmological Society 2005.

PMID: 16075329 [PubMed - indexed for MEDLINE]

1821: Appl Spectrosc. 2005 Jul;59(7):861-7.

Comment in:
    Appl Spectrosc. 2006 Nov;60(11):1348-9; author reply 1350-1.

Simple Raman instrument for in vivo detection of macular pigments.

Ermakov IV, Ermakova MR, Gellermann W.

Department of Physics, University of Utah, Salt Lake City, Utah 84112, USA.

Raman spectroscopy holds promise as a novel noninvasive technology for the
quantification of the macular pigments (MP) lutein and zeaxanthin. These
compounds, which are members of the carotenoid family, are thought to prevent or 
delay the onset of age-related macular degeneration, the leading cause of
irreversible blindness in the elderly. It is highly likely that they achieve this
protection through their function as optical filters and/or antioxidants. Using
resonant excitation in the visible region, we measure and quantify the Raman
signals that originate from the carbon double bond (C=C) stretch vibrations of
the pi-conjugated molecule backbone. In this manuscript we describe the
construction and performance of a novel compact MP Raman instrument utilizing
dielectric angle-tuned band-pass filters for wavelength selection and a
single-channel photo-multiplier for the detection of MP Raman responses. MP
concentration measurements are fast and accurate, as seen in our experiments with
model eyes and living human eyes. The ease and rapidity of Raman MP measurements,
the simplicity of the instrumentation, the high accuracy of the measurements, and
the lack of significant systematic errors should make this technology attractive 
for widespread clinical research.

Publication Types: 
    Comparative Study
    Evaluation Studies
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.
    Validation Studies

PMID: 16053555 [PubMed - indexed for MEDLINE]

1822: Eye. 2006 Aug;20(8):873-81. Epub 2005 Jul 29.

Diabetic macular oedema: pilot randomised trial of pars plana vitrectomy vs
macular argon photocoagulation.

Patel JI, Hykin PG, Schadt M, Luong V, Bunce C, Fitzke F, Gregor ZJ.

Moorfields Eye Hospital, London, UK. jigs37@hotmail.com

INTRODUCTION: Focal macular photocoagulation for clinically significant macular
oedema (CSME) is the proven method for treatment of this condition, but with
little chance of visual improvement. Pars plana vitrectomy (PPV) may produce
resolution of macular oedema and improvement in visual acuity. However, there
have been no randomised trials to ascertain role of vitrectomy in the management 
of persistent CSME. METHODS: Patients with persistent CSME despite previous
macular photocoagulation and Snellen visual acuity 6/15 to 6/60 were recruited.
Dilated fundoscopy, best-corrected visual acuity including Early Treatment
Diabetic Retinopathy Study (ETDRS) vision, ocular coherence tomography and fundus
fluorescein angiography (FFA) at baseline and up to 12 months post-treatment was 
performed. Exclusion criteria were signs of posterior vitreous detachment,
macular traction or the taut posterior hyaloid face syndrome, or macular
ischaemia on FFA. In all, 20 patients were randomised (10 in each arm) to either 
standard macular photocoagulation or PPV and removal of the posterior hyaloid
face. RESULTS: Of the 20 patients recruited, seven patients completed the
protocol in the vitrectomy and eight in the laser arms, respectively. There was
little evidence of any difference in the foveal thickness at 12 months between
the two treatment arms despite a gradual improvement. Only one patient, from the 
vitrectomy arm, suffered moderate visual loss (defined as loss of 15 ETDRS
letters) (our primary outcome). DISCUSSION: In this pilot RCT, standard PPV
provides little visual benefit compared to macular photocoagulation, but a larger
definitive study is required to confirm this early appraisal.

Publication Types: 
    Randomized Controlled Trial

PMID: 16052254 [PubMed - indexed for MEDLINE]

1823: Mol Vis. 2005 Jul 14;11:509-17.

Glycoconjugates of choroidal neovascular membranes in age-related macular
degeneration.

Mullins RF, Grassi MA, Skeie JM.

Center for Macular Degeneration, Department of Ophthalmology and Visual Science, 
The University of Iowa Carver College of Medicine, Iowa City, IA, USA.
robert-mullins@uiowa.edu

PURPOSE: Choroidal neovascularization (CNV) is a complication of multiple eye
diseases, including age-related macular degeneration, that usually results in
irreversible vision loss. It is characterized by proliferation and growth of
choroidal blood vessels through Bruch's membrane into the subpigment epithelial
and/or subretinal space. The purpose of this study was to characterize the
carbohydrate groups associated with CNV by lectin histochemistry. METHODS: Frozen
sections from three human eyes with CNV (two fixed eyes and one unfixed eye) were
prepared. Sections containing choroidal neovascular membranes were incubated with
a battery of biotinylated lectins directed against a number of distinct
oligosaccharide moieties. Lectin labeling of the vessels in CNV was visualized
with avidin-Texas red. RESULTS: Several carbohydrate groups were preferentially
associated with the vascular elements in CNV. Glycoconjugates that react with
lectins derived from wheat germ, soybean, and hairy vetch seed (sWGA, SBA, and
VVA, respectively) all showed reactivity with CNV vessels that was higher than
the labeling of the surrounding matrix. SBA and sWGA also reacted with CNV
vessels at low concentrations at which normal retinal and choroidal vessels were 
largely unlabeled. CONCLUSIONS: Choroidal neovascular membranes possess a
distinct set of carbohydrate moieties. These data may be valuable in
understanding endothelial cell biology in CNV.

Publication Types: 
    Case Reports
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 16052166 [PubMed - indexed for MEDLINE]

1824: Ophthalmology. 2005 Sep;112(9):1586-91.

Rapid recurrence of geographic atrophy after full macular translocation for
nonexudative age-related macular degeneration.

Khurana RN, Fujii GY, Walsh AC, Humayun MS, de Juan E Jr, Sadda SR.

Doheny Retina Institute, Doheny Eye Institute, Department of Ophthalmology, Keck 
School of Medicine, University of Southern California, Los Angeles, California,
USA.

OBJECTIVE: To report the recurrence of geographic atrophy (GA) in a patient with 
nonexudative age-related macular degeneration (AMD) after full macular
translocation. DESIGN: Observational case report. METHODS: Review of the
clinical, photographic, and angiographic records of a patient with GA who
underwent full macular translocation. MAIN OUTCOME MEASURES: Progression of GA.
RESULTS: A 73-year-old man with GA secondary to nonexudative AMD underwent a
macular translocation with 360 peripheral retinectomy (MT 360) in his left eye.
On postoperative month 4, fundus photography showed subtle alterations of the
pigment underneath the translocated foveal region. On postoperative month 9, the 
visual acuity worsened to preoperative levels and there was frank retinal pigment
epithelium atrophy involving the new macular region. CONCLUSIONS: The rapid
recurrence and development of GA in the translocated fovea after MT 360 raise new
questions regarding the pathogenesis of GA. They also raise concerns regarding
the use of MT 360 in the management of nonexudative AMD.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 16051364 [PubMed - indexed for MEDLINE]

1825: Bull Soc Belge Ophtalmol. 2005;(296):15-23.

Vitrectomy with peeling of the inner limiting membrane for treating diabetic
macular edema.

Kolacny D, Parys-Vanginderdeuren R, Van Lommel A, Stalmans P.

Dept. Ophthalmology UZLeuven, Leuven, Belgium.

PURPOSE: to evaluate the results of pars plana vitrectomy with peeling of the
inner limiting membrane (ILM stained with infracyanine green (IfCG) in 26
patients with diabetic macular edema, and to identify which factors are
associated with a better postoperative visual outcome. PATIENTS AND METHODS: 26
patients with diabetic macular edema were included in the study. A pars plana
vitrectomy with ILM peeling stained with IfCG was performed, in some cases
combined with cataract surgery. In 22 patients the ILM was retained, examined
with electron microscopy and compared with normal ILM's. Visual acuity and fundus
examination were recorded several months after surgery. To determine which
factors lead to the best postoperative results, patients were divided into
different groups and compared. RESULTS: during surgery, a taut posterior hyaloid 
was found in 26 patients, which was successfully detached in all cases. ILM
peeling within the vessel arcade succeeded in all patients. Postoperative
examination showed improved visual acuity and decreased macular edema in 19
patients, unaltered visual acuity in 3 patients and decreased visual acuity in 4 
patients. Comparison between different groups of patients revealed that young
patients with recent vision loss and without previous macular laser treatment,
had better postoperative results. Electron microscopical examination showed a
more condensed ILM in diabetic patients, consisting of a layer of fine curled
fibers. CONCLUSION: pars plana vitrectomy with peeling of the ILM stained with
IfCG leads to good postoperative results in young diabetic patients with recent
vision loss due to macular edema and without previous macular laser treatment.

Publication Types: 
    Clinical Trial

PMID: 16050416 [PubMed - indexed for MEDLINE]

1826: Invest Ophthalmol Vis Sci. 2005 Aug;46(8):2886-96.

Eye-movement training for reading in patients with age-related macular
degeneration.

Seiple W, Szlyk JP, McMahon T, Pulido J, Fishman GA.

Department of Ophthalmology, New York University School of Medicine, New York, NY
10016, USA. whs4@nyu.edu

PURPOSE: To determine whether training oculomotor control, without direct
practice in reading sentences, could increase reading speed in patients with
age-related macular degeneration (AMD). METHODS: Sixteen patients with AMD
participated in the study (age range, 65-87 years; mean, 77). The training
program consisted of a series of exercises that were designed to allow the
patients to practice eye movements. At the beginning of training, the subjects
practiced small horizontal saccades in response to cognitively easy stimuli
(e.g., dots). The training then progressed to practicing larger eye movements and
then to practicing saccades with single letters, pairs of letters, and
three-letter words. Reading of sentences was practiced in only one exercise,
during the last session of the 8-week training. RESULTS: The difference between
average reading speeds before and after training was 24.7 wpm (difference between
medians, 17.9 wpm). The increase in speed was statistically significant (Wilcoxon
signed rank test = 124.0, P < 0.001). There was no significant relationship
between change in maximum reading speed and ETDRS (Early Treatment Diabetic
Retinopathy Study) acuity (r = -0.14, P = 0.76) or between change in maximum
reading speed and age (r = 0.25, P = 0.45). CONCLUSIONS: The results indicate
that a training curriculum that concentrates on eye-movement control can increase
reading speed in patients with AMD. This finding is especially interesting,
because the training involved little direct practice in reading sentences but
instead concentrated on having subjects practice control of eye positions and eye
movements.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, Non-P.H.S.

PMID: 16043863 [PubMed - indexed for MEDLINE]

1827: Am J Ophthalmol. 2005 Jul;140(1):147-9.

Cystoid macular edema in gyrate atrophy of the choroid and retina: a fluorescein 
angiography and optical coherence tomography evaluation.

Oliveira TL, Andrade RE, Muccioli C, Sallum J, Belfort R Jr.

Vision Institute-IPEPO, Department of Ophthalmology, Federal University of São
Paulo, Brazil.

PURPOSE: To analyze the importance f optical coherence tomography (OCT) to
diagnose the cystoid macular edema in a case of gyrate atrophy. DESIGN:
Observational case report. METHODS: A 12-year-old boy presenting with gyrate
atrophy of the choroid and retina underwent ophthalmologic, clinical, and
laboratory tests. RESULTS: Plasma ornithine level was 735 mumol/l. Fluorescein
angiography showed bilateral hyperfluorescence involving the central region of
the macula. Optical coherence tomography (OCT) disclosed bilateral intraretinal
cysts areas of low reflectivity with occasional high-signal elements bridging the
retinal layers and intraretinal thickening. CONCLUSIONS: Both fluorescein
angiography and OCT were helpful to confirm the diagnosis of macular involvement 
as a complication of gyrate atrophy of the choroid and retina in a patient who
presented without any clinical evidence of cystoid macular edema, except a
decrease in visual acuity.

Publication Types: 
    Case Reports

PMID: 16038665 [PubMed - indexed for MEDLINE]

1828: Am J Ophthalmol. 2005 Jul;140(1):144-6.

Displacement of rectus muscle pulleys by torsional muscle surgery for treatment
of full macular translocation-induced incyclotropia.

Kono R, Ohtsuki H, Okanobu H, Kinugasa K.

Department of Ophthalmology, Okayama University Graduate School of Medicine and
Dentistry, Japan. opth@cc.okayama-u.ac.jp

PURPOSE: To elucidate the coronal plane locations of extraocular muscle (EOM)
pulleys following torsional muscle surgery. DESIGN: Case report. METHODS: A
76-year-old man underwent advancement of the anterior part of the inferior
oblique muscle to treat full macular translocation-induced incyclotropia.
Postoperatively, magnetic resonance imaging was used to obtain contiguous,
2-mm-thick coronal orbital images. On each MRI image, the cross-sectional area
and center of the EOM was computed, and all rectus EOM positions were translated 
to the coordinate origin at the area centroid of the globe at the level of
pulleys. RESULTS: The superior rectus pulley was displaced temporally, and the
lateral rectus pulley was displaced inferiorly more than 2 SD from normal
subjects. Coronal plane locations of EOM pulleys of the ipsilateral eye showed
extorsion compared with that of the contralesional eye. CONCLUSIONS: Torsional
muscle surgery causes an extorsional shift of the superior and lateral rectus
pulleys.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 16038663 [PubMed - indexed for MEDLINE]

1829: Am J Ophthalmol. 2005 Jul;140(1):129-31.

Frailty and age-related macular degeneration: the Beaver Dam Eye Study.

Klein R, Klein BE, Knudtson MD.

Department of Ophthalmology and Visual Sciences, University of Wisconsin Medical 
School, Madison, 53726, USA. kleinr@epi.ophth.wisc.edu

PURPOSE: To investigate the associations of measures of frailty to prevalent
age-related maculopathy (ARM). DESIGN: Cross-sectional population-based study.
METHODS: Time to walk a measured course (gait-time), handgrip strength, peak
expiratory flow rate, ability to stand from a sitting position without using
arms, self-reported co-morbidities, and ARM were assessed at the third
examination of the Beaver Dam Eye Study (n = 2,962). ARM was determined by
grading stereoscopic color fundus photographs. RESULTS: While controlling for
age, smoking, and the number of co-morbid conditions, weaker handgrip strength
was associated with early ARM (odds ratio [OR]/10 kg decrease 1.28, confidence
interval [CI] 1.08, 1.52, P = .004) and late ARM (OR 1.55, 95% CI 1.02, 2.36) in 
men but not women. Other measures of frailty were not related to ARM.
CONCLUSIONS: A weak cross-sectional association of handgrip strength with ARM (in
men) was found after controlling for co-morbid conditions. These data suggest
that ARM is due to a specific disease process, albeit age-related, rather than to
biologic aging, as reflected by measures of frailty.

PMID: 16038655 [PubMed - indexed for MEDLINE]

1830: Am J Ophthalmol. 2005 Jul;140(1):45-51.

Birdshot retinochoroidopathy: ocular complications and visual impairment.

Thorne JE, Jabs DA, Peters GB, Hair D, Dunn JP, Kempen JH.

Department of Ophthalmology, the Johns Hopkins University School of Medicine,
Baltimore, MD 21250, USA. jthorne@jhmi.edu

PURPOSE: To describe the incidence of vision loss and of ocular complications
attributable to birdshot retinochoroidopathy and to describe the association
between therapy and the incidence thereof. DESIGN: Retrospective cohort study.
METHODS: SETTING: Single-center, academic practice. STUDY POPULATION: Forty
patients with birdshot retinochoroidopathy were evaluated from January 1984
through March 2004. OBSERVATION PROCEDURE: Demographic and clinical information
on patients diagnosed with birdshot retinochoroidopathy was collected. MAIN
OUTCOME MEASURES: Visual acuity and visual field loss; ocular complications
including cystoid macular edema (CME). RESULTS: In affected eyes, the frequencies
of vision loss to 20/50 or worse and to 20/200 or worse and of CME at
presentation were 33%, 13%, and 20%, respectively. Patients who presented with a 
duration of disease of > or = 30 months had higher frequencies of visual
impairment to 20/50 or worse (68% vs 32%; P = .004) and to 20/200 or worse (32%
vs 9%; P = .01), and had a higher frequency of CME (38% vs 14%; P = .02) than
patients who presented with a duration of disease <30 months. The incidence rates
on follow-up for vision loss to 20/50 or worse and to 20/200 or worse were 13%
and 4% per eye-year (EY), respectively. The incidence of CME was 10%/EY. Use of
immunosuppressive drug therapy was associated with a reduced risk of developing
CME (relative risk = 0.17; 95% confidence interval: 0.05, 0.64; P = .009).
CONCLUSIONS: Birdshot retinochoroidopathy is a progressive disease with the
potential for visual impairment. Patients who present at a later date after the
onset of disease were more likely to have vision impairment and CME. Use of
long-term immunosuppressive therapy may reduce the risk of CME.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 16038650 [PubMed - indexed for MEDLINE]

1831: J Biol Chem. 2005 Sep 16;280(37):32521-30. Epub 2005 Jul 21.

Dominant negative mechanism underlies autosomal dominant Stargardt-like macular
dystrophy linked to mutations in ELOVL4.

Grayson C, Molday RS.

Department of Biochemistry and Molecular Biology, Centre for Macular Research,
University of British Columbia, Vancouver, Canada.

ELOVL4 (elongation of very long chain fatty acids 4) is a member of the ELO
family of proteins involved in the biosynthesis of very long chain fatty acids.
Protein truncation mutations in ELOVL4 have been identified in patients with
autosomal dominant Stargardt-like macular degeneration. To determine whether a
dominant negative mechanism is responsible for the autosomal dominant inheritance
pattern of this disease, we studied the subcellular localization and interaction 
of wild type and mutant ELOVL4 in COS-7 and HEK 293T cultured cells by
immunofluorescence and co-immunoprecipitation. Wild type ELOVL4 containing an
endoplasmic reticulum retention sequence was localized to the endoplasmic
reticulum as expected. In contrast, disease-associated C-terminal truncation
ELOVL4 mutants accumulated as large inclusions exhibiting aggresome-like
characteristics in a juxtanuclear position within COS-7 cells. When the wild type
and mutant proteins were co-expressed incultured cells, wild type ELOVL4
co-purified with mutant ELOVL4 on an immunoaffinity column and co-localized with 
the mutant protein in aggresome-like inclusions adjacent to the nucleus. These
results indicate that wild type and mutant ELOVL4 form a complex that exhibits an
abnormal subcellular localization found for individually expressed mutant ELOVL4.
From these studies, we conclude that disease-linked C-terminal truncation mutants
of ELOVL4 exert a dominant negative effect on wild type ELOVL4, altering its
subcellular localization. This dominant negative mechanism contributes to the
autosomal dominant inheritance of Stargardt-like macular dystrophy.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 16036915 [PubMed - indexed for MEDLINE]

1832: Graefes Arch Clin Exp Ophthalmol. 2006 Jan;244(1):28-35. Epub 2005 Jul 21.

Intravitreal triamcinolone injection for chronic diabetic macular oedema with
severe hard exudates.

Avci R, Kaderli B.

Department of Ophthalmology, Uludag University Hospital, 16059 Gorukle, Bursa,
Turkey. ravci@uludag.edu.tr

BACKGROUND: The purpose of the study was to determine the efficacy and safety of 
intravitreal triamcinolone acetonide (TA) in chronic diabetic macular oedema with
severe hard exudates. METHODS: This prospective, interventional consecutive case 
series study consisted of 33 eyes of 28 patients with chronic diabetic macular
oedema and severe foveal hard exudates who received an intravitreal injection of 
4 mg of TA. The patients were divided into two groups according to the type of
foveal hard exudates: group I, plaque-like (17 eyes) and group II, dot-like
scattered hard exudates (16 eyes). The results of both groups, evaluated by
colour fundus photography and fluorescein angiography, were compared and
complications were recorded. RESULTS: All patients completed at least 6 months of
follow-up. In all eyes, the hard exudates were completely resolved (24% in group 
I and 50% in group II) or decreased (76% in group I and 50% in group II). In
group I, the mean diameter of the exudates plaques significantly decreased from
5.5+/-3.8 mm(2) in the pre-treatment period to 2.2+/-2.7 mm(2) at the end of the 
follow-up period. There was no recurrence of the hard exudates in either of the
groups. The mean +/- SD visual acuity (VA) improved from 0.07+/-2.5 at the
baseline to a maximum of 0.09+/-2.1 lines in group I (P<0.01) and from 0.13+/-3.9
to a maximum of 0.27+/-2.7 lines in group II (P<0.01). The mean VA improvement in
group II was better than group I (3.2+/-2.5 vs. 1.4+/-1.0 lines, P<0.05).
Intraocular pressure exceeded 21 mmHg in 10 eyes (30%), which was then controlled
by topical medication. Three eyes (9%) exhibited signs of subcapsular cataract
progression. CONCLUSIONS: Intravitreal TA appears to be a valuable treatment in
chronic diabetic macular oedema with severe foveal hard exudates. In all eyes in 
this study the hard exudates were completely resolved or decreased, and the mean 
VA improved significantly in both groups. However, the VA improvement was
significantly worse in eyes with plaque-like exudates suggesting the possible
value of earlier treatment. Further studies would enable the assessment of the
universal effectiveness of this treatment.

PMID: 16034605 [PubMed - indexed for MEDLINE]

1833: Clin Experiment Ophthalmol. 2005 Aug;33(4):442-4.

Use of intravitreal triamcinolone in the management of birdshot
retinochoroidopathy associated with cystoid macular oedema: a case study over a
three-year period.

Shah A, Branley M.

North Shore Eye Centre, North Shore Private Hospital, Sydney, New South Wales,
Australia.

Birdshot retinochoroidopathy is a bilateral, chronic posterior uveitis of likely 
autoimmune aetiology characterized by multiple depigmented choroidal lesions
scattered throughout the post-equatorial retina. It has been managed with
variable results using systemic immunosuppression. Herein, a case is described in
which the patient, aware of the side-effects of systemic immunosuppression,
refused this form of treatment and was successfully managed over a 3-year period 
with intravitreal triamcinolone. She developed the ocular complications of
cataract and increased intraocular pressures, but maintained good vision while
avoiding any systemic side-effects.

Publication Types: 
    Case Reports

PMID: 16033372 [PubMed - indexed for MEDLINE]

1834: Clin Experiment Ophthalmol. 2005 Aug;33(4):360-3.

Cataract surgery in patients with age-related maculopathy: preoperative diagnosis
and postoperative visual acuity.

Pham TQ, Wang JJ, Maloof A, Mitchell P.

Centre for Vision Research, Department of Ophthalmology, University of Sydney,
Westmead, NSW, Australia.

PURPOSE: To report the reliability in detecting age-related maculopathy (ARM)
lesions before cataract surgery and postoperative visual acuity (VA) in cataract 
surgery patients with ARM. METHODS: Medical records of surgical patients in a
large public hospital, west of Sydney, were reviewed retrospectively. Detection
of ARM lesions was compared before and after surgery to determine sensitivity and
specificity of preoperative diagnoses. Postoperative VA was assessed 4 weeks
after surgery. RESULTS: Data were available for 721/784 eyes (92.0%) of 656
patients aged 60 years or older. ARM lesions were detected in 98 eyes (13.6%)
before and 92 eyes (12.8%) after surgery. Sensitivities for detecting late ARM
lesions, soft drusen and retinal pigment epithelium abnormalities preoperatively 
were 100%, 94% and 69%, respectively. Corresponding specificities were 100%, 100%
and 77%, respectively. Postoperative VA achieved or remained 6/12 or better in
81.6% of eyes. CONCLUSION: A high sensitivity and specificity in detecting late
ARM lesions and soft drusen preoperatively, and a good postoperative VA outcome
is achievable in patients with preoperative early ARM lesions.

PMID: 16033346 [PubMed - indexed for MEDLINE]

1835: Drugs. 2005;65(11):1571-7; discussion 1578-9.

Pegaptanib: in exudative age-related macular degeneration.

Siddiqui MA, Keating GM.

Adis International Limited, Auckland, New Zealand. demail@adis.co.nz

Pegaptanib, an aptamer, is an antagonist of vascular endothelial growth factor
that has shown efficacy in the treatment of patients with exudative age-related
macular degeneration (AMD). In two randomised, double-masked trials in patients
with exudative AMD (n=1208), the proportion of responders (those losing <15
letters of visual acuity) at 54 weeks was significantly higher in intravitreous
pegaptanib 0.3 mg recipients than in those receiving sham injections (70% vs 55%;
p<0.001). These trials were conducted concurrently and analysed as a single
study; the treatments were given every 6 weeks for 48 weeks. The improvement in
visual acuity with pegaptanib was maintained in a 1-year extension of these
trials. Similar favourable results with pegaptanib 0.3 mg were seen in terms of
the secondary efficacy endpoints (e.g. proportion of patients experiencing severe
loss of visual acuity or legal blindness in the study eye). These
vision-improving effects of pegaptanib were associated with beneficial
angiographic effects. Intravitreous pegaptanib 0.3-3 mg was well tolerated with
most ocular adverse events being mild-to-moderate and transient. Serious
injection-related adverse events occurred in <or=1.3% of patients treated with
pegaptanib. There were no systemic adverse events that could be definitely
attributed to pegaptanib.

Publication Types: 
    Review

PMID: 16033295 [PubMed - indexed for MEDLINE]

1836: Mol Vis. 2005 Jul 7;11:482-90.

Melanization and phagocytosis: implications for age related macular degeneration.

Sarangarajan R, Apte SP.

Department of Pharmaceutical Sciences, Massachusetts College of Pharmacy and
Health Sciences, Worcester, MA, USA. ranga.sarangarajan@wor.mcphs.edu

Signaling pathways that upregulate melanization in the retinal pigment epithelium
(RPE) may also be implicated in the downregulation of rod outer segment (ROS)
phagocytosis by the RPE. Melanization activating pathways may also modulate
oxygen consumption by the photoreceptors, apolipoprotein E4 levels, and the rate 
of photoisomerization events such that the net effect may be a reduction in
drusen and/or lipofuscin accumulation. An increase in melanin at the apical
microvilli of the RPE may shield ROS from light thereby contributing in part to
the decrease in the rate of ROS phagocytosis. This decrease in ROS phagocytosis
by the RPE may serve to maintain a balance between ingestion and
degradation/recycling thereby avoiding an increase to its already substantial
metabolic load. Several experimental drugs for age related macular degeneration
(ARMD) coincidentally are also capable of decreasing the rate of ROS
phagocytosis. This review attempts to identify the signaling pathways that may
link the upregulation of melanization to the downregulation of ROS phagocytosis. 
Phagocytic pathways that are modulated by melanization need to be studied in
isolation to determine what role, if any, they possess in ameliorating the onset 
and progression of ARMD. Many more empirical studies are needed to unravel
specific pathways and mechanisms that seem to link melanization with ARMD.

Publication Types: 
    Review

PMID: 16030499 [PubMed - indexed for MEDLINE]

1837: Acta Ophthalmol Scand. 2005 Aug;83(4):428-35.

Unilateral macular oedema secondary to retinal venous congestion without
occlusion in patients with diabetes mellitus.

Larsen M.

Department of Ophthalmology, Herlev Hospital, University of Copenhagen, Herlev,
Denmark. mla@dadlnet.dk

OBJECTIVE: To identify fundus characteristics associated with intraocular and
intra-individual variations in the distribution of macular oedema in patients
with diabetes. METHODS: A review was carried out of fundus photographs and
fluorescein angiograms from 226 diabetes patients who received photocoagulation
treatment for macular oedema. Cases with strictly unilateral clinically
significant macular oedema were identified. RESULTS: Strictly unilateral macular 
oedema was identified in five patients with non-proliferative diabetic
retinopathy, three of whom demonstrated angiographic leakage confined to a single
venous drainage unit, and two of whom demonstrated leakage confined to two
adjacent venous drainage units opposing one another on either side of the
temporal circulatory watershed. Involved drainage units were delimited by
arteriovenous crossings displaying signs of venous compression. Affected eyes had
more frequent and more severe crossing signs involving macular drainage than
fellow eyes. Although all patients had been examined regularly, no patient had
had branch retinal vein occlusion and no patient developed such occlusion during 
5 years of follow-up. CONCLUSION: In the present study, unilateral macular oedema
in patients with diabetes was associated with angiographic leakage from venous
drainage units where compression signs indicated a higher than normal likelihood 
of upstream congestion being present. Presumably, a modest increase in venous
pressure induced macular oedema because of an underlying abnormal vascular
vulnerability induced by diabetes.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 16029265 [PubMed - indexed for MEDLINE]

1838: Acta Ophthalmol Scand. 2005 Aug;83(4):419-23.

Erratum in:
    Acta Ophthalmol Scand. 2005 Oct;83(5):637.

Corrected and republished in:
    Acta Ophthalmol Scand. 2005 Oct;83(5):419-23.

Refraction, axial length and age-related maculopathy.

Ulvik SO, Seland JH, Wentzel-Larsen T.

Department of Ophthalmology, Haukeland University Hospital, Bergen, Norway.

PURPOSE: To study the relationship between age-related maculopathy
(ARM)/age-related macular degeneration (AMD) and phakic refraction and between
ARM/AMD and axial length. METHODS: The study was a point prevalence study that
included 663 randomly selected persons aged over 65 years. We measured axial
length and refraction. Fundus images were graded for ARM according to a modified 
Wisconsin Age-related Maculopathy Grading System standard. Data from both eyes
were available from most participants. We analysed the results for both
individual eyes and pairs. RESULTS: The mean axial length was 23.22 mm for right 
eyes and 23.21 mm for left eyes. Women had a 0.57-mm shorter mean axial length
than men. The mean refraction was +1.0 dioptres (D) for right eyes and +0.9 D for
left eyes. At 70 years of age women were more hypermetropic than men by 0.66 D.
There was no significant difference in refraction or axial length among the
groups with different ARM stages. CONCLUSION: We found no statistically
significant relationship between axial length/refraction and AMD/ARM. There was a
statistically significant sex difference in axial length and refraction, where
women had shorter axial lengths and were more hypermetropic than men.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16029263 [PubMed - indexed for MEDLINE]

1839: Acta Ophthalmol Scand. 2005 Aug;83(4):409-18.

Risk factors for age-related maculopathy in a 14-year follow-up study: the
Copenhagen City Eye Study.

Buch H, Vinding T, la Cour M, Jensen GB, Prause JU, Nielsen NV.

Department of Ophthalmology, Rigshospitalet, National University Hospital,
Copenhagen, Denmark. hbh@dadlnet.dk

PURPOSE: To examine the association between potential risk factors and the
14-year incidence of age-related maculopathy (ARM). DESIGN: Population-based
cohort study. PARTICIPANTS: At baseline, 946 volunteers participated in the study
during 1986--88. These subjects were between 60 and 80 years of age and lived in 
the Østerbro district of Copenhagen. Excluding participants who had died since
baseline, 359 subjects (97.3% of survivors) were re-examined 14 years later,
during 2000--2002. A total of 31.8% (301/946) of the original material was
included in the risk factor analyses. METHODS: Participants underwent an
ophthalmological examination at Rigshospitalet, the National University Hospital 
of Copenhagen. Similar standardized protocols for physical examination were used 
at the baseline and follow-up examinations. Age-related maculopathy lesions were 
determined by the same grader grading colour fundus photographs from both
examinations using a modification of the Wisconsin Age-related Maculopathy
Grading System protocol. RESULTS: Of the 359 participants, 94 had incident early 
ARM and 52 had incident late ARM at follow-up in either eye. In logistic
regression, the risk factors for early ARM or worse were as follows: cataract
(odds ratio [OR] 2.8, 95% confidence interval [CI] 1.2-6.2); family history of
ARM (OR 4.5, 95% CI 1.3--15.5), and alcohol consumption >250 g/week (OR 4.6, 95% 
CI 1.1-19.2). High levels of apolipoprotein B (>100 mg/l) decreased the risk of
development of early ARM or worse (OR 0.4, 95% CI 0.2-0.8), while high levels of 
apolipoprotein A1 (>or= 150 mg/l) increased the risk of late ARM (OR 2.5, 95% CI 
1.2-5.3). Advanced age at baseline was also associated with the incidence of late
ARM (OR 2.0, 95% CI 1.4-2.9). CONCLUSIONS: These findings indicate a direct
correlation between age, cataract, family history, alcohol consumption, the
apolipoproteins A1 and B and the 14-year incidence of ARM.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16029262 [PubMed - indexed for MEDLINE]

1840: Mol Immunol. 2006 Jan;43(1-2):97-106.

Complement and diseases: defective alternative pathway control results in kidney 
and eye diseases.

Zipfel PF, Heinen S, Józsi M, Skerka C.

Department of Infection Biology, Leibniz Institute for Natural Products Research 
and Infection Biology, Hans Knoell Institute, Beutenbergstr. 11a, 07745 Jena,
Germany. peter.zipfel@hki-jena.de

The complement system is a central part of innate immunity and in its normal
setting aimed to recognize and eliminate microbes. For elimination toxic
activation products are generated locally and are reported directly of the
surface of the invading microbe. A deregulation of the alternative pathway
results in defective recognition and toxic activation products can be formed on
the surface of host tissues and structures. Recent studies have shown that
mutated or defective regulators of the alternative pathway of complement are
associated with auto immune diseases of the kidney, including the atypical form
of hemolytic uremic syndrome (HUS), membranoproliferative glomerulonephritis
(MPGN) and also of the eye, such as age-related macular degeneration (ARMD).
Current research provides clues how mutations occurring in genes coding for
single complement components or the inactivation of single regulators lead to
defective alternative pathway amplification, via the convertase C3bBb. These
scenarios explain how defects of a single regulator lead to local, organ specific
damage.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 16026839 [PubMed - indexed for MEDLINE]

1841: Br J Ophthalmol. 2005 Aug;89(8):1045-51.

Visual functioning and quality of life in the SubFoveal Radiotherapy Study
(SFRADS): SFRADS report 2.

Stevenson MR, Hart PM, Chakravarthy U, Mackenzie G, Bird AC, Owens SL, Chisholm
IH, Hall V, Houston RF, McCulloch DW, Plowman N.

Ophthalmology and Vision Science, Royal Hospitals, Belfast BT12 6BA, UK.

AIMS: To determine whether or not self reported visual functioning and quality of
life in patients with choroidal neovascularisation caused by age related macular 
degeneration (AMD) is better in those treated with 12 Gy external beam
radiotherapy in comparison with untreated subjects. METHODS: A multicentre single
masked randomised controlled trial of 12 Gy of external beam radiation therapy
(EBRT) delivered as 6 x 2 Gy fractions to the macula of an affected eye versus
observation. Patients with AMD, aged 60 years or over, in three UK hospital
units, who had subfoveal CNV and a visual acuity equal to or better than 6/60
(logMAR 1.0). METHODS: Data from 199 eligible participants who were randomly
assigned to 12 Gy teletherapy or observation were available for analysis. Visual 
function assessment, ophthalmic examination, and fundus fluorescein angiography
were undertaken at baseline and at 3, 6, 12, and 24 months after study entry. To 
assess patient centred outcomes, subjects were asked to complete the Daily Living
Tasks Dependent on Vision (DLTV) and the SF-36 questionnaires at baseline, 6, 12,
and 24 months after enrolment to the study. Cross sectional and longitudinal
analyses were conducted using arm of study as grouping variable. Regression
analysis was employed to adjust for the effect of baseline co-variates on outcome
at 12 months and 24 months. RESULTS: Both control and treated subjects had
significant losses in visual functioning as seen by a progressive decline in mean
scores in the four dimensions of the DLTV. There were no statistically
significant differences between treatment and control subjects in any of
dimensions of the DLTV at 12 months or 24 months after study entry. Regression
analysis confirmed that treatment status had no effect on the change in DLTV
dimensional scores. CONCLUSIONS: The small benefits noted in clinical measures of
vision in treated eyes did not translate into better self reported visual
functioning in patients who received treatment when compared with the control
arm. These findings have implications for the design of future clinical trials
and studies.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16024863 [PubMed - indexed for MEDLINE]

1842: Br J Ophthalmol. 2005 Aug;89(8):1026-30.

Improved visualisation of choroidal neovascularisation by scanning laser
ophthalmoscope using image averaging.

Bartsch DU, El-Bradey MH, El-Musharaf A, Freeman WR.

Jacobs Retina Center, Department of Ophthalmology, University of California San
Diego, 9415 Campus Point Drive, La Jolla, CA 92093-0946, USA. dbartsch@ucsd.edu

AIMS: To improve visualisation of angiographic features in patients with age
related macular degeneration associated with choroidal neovascularisation (CNV)
and related complications. To evaluate if image averaging can achieve this goal. 
METHODS: 27 eyes of 20 sequential patients with age related macular degeneration 
over a 3 month period were studied. Indocyanine green angiograms (ICGA),
fluorescein angiograms (FA), and oral fluorescein angiograms were recorded with a
confocal scanning laser ophthalmoscope. Software was used to average multiple
images from a 10-20 image series (over 0.5-1.0 seconds). Image quality was
assessed by two masked observers and graded on a scale of 0-3. A more
quantifiable grading method was devised by adding a variable amount of Gaussian
noise to the improved image until the original and image averaged image appeared 
equal. RESULTS: Masked review showed mild to strong improvement of visualisation 
of structures including borders of CNV. Improvement varied depending on the type 
and phase of the angiogram. Improvement was highest in late phase FA, mid and
late phase ICGA, and all phases of oral FA. CONCLUSION: Image averaging using
software based algorithms improves the quality of angiographic images,
particularly late ICGA images and oral FAs. This method may assist in the
visualisation of choroidal neovascularisation in age related macular
degeneration.

Publication Types: 
    Evaluation Studies
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 16024859 [PubMed - indexed for MEDLINE]

1843: Br J Ophthalmol. 2005 Aug;89(8):999-1003.

Dosage dependency of intravitreal triamcinolone acetonide as treatment for
diabetic macular oedema.

Spandau UH, Derse M, Schmitz-Valckenberg P, Papoulis C, Jonas JB.

Department of Opthamology, Evangelisches Stift, Koblenz, Germany.
ulrich.spandau@augen.ma.uni-heidelberg.de

AIM: To evaluate the effect of different doses of intravitreal triamcinolone
acetonide on diffuse diabetic macular oedema. METHODS: The prospective,
randomised, double masked, clinical interventional study included 27 eyes (27
patients) with diffuse diabetic macular oedema. They were randomly divided into
three study groups receiving an intravitreal injection of filtered triamcinolone 
acetonide of about 2 mg (n = 8 eyes), 5 mg (n = 10), or 13 mg (n = 9),
respectively. Dosage measurement was performed before filtration. Mean follow up 
was 6.6 (SD 2.4) months (3-12 months). Main outcome measures were visual acuity
and intraocular pressure. RESULTS: Maximal increase in visual acuity was
significantly (p = 0.046; 95% CI: 0.032 to 2.99; r = 0.38) correlated with the
dosage of intravitreal triamcinolone acetonide. Additionally, the duration of the
effect of intravitreal triamcinolone acetonide increased significantly with the
dosage of intravitreal triamcinolone acetonide (r = 0.45; p = 0.014). Increase in
intraocular pressure during follow up was statistically not significantly
associated with the dosage used (p = 0.77). CONCLUSIONS: In patients with diffuse
diabetic macular oedema receiving intravitreal triamcinolone acetonide, treatment
response may last longer and be more pronounced with a dosage of 13 mg than in
lower doses of 5 mg or 2 mg. Triamcinolone acetonide induced increase in
intraocular pressure may not be markedly associated with the dosage used.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 16024853 [PubMed - indexed for MEDLINE]

1844: Br J Ophthalmol. 2005 Aug;89(8):967-70.

Correlation of optical coherence tomography, with or without additional colour
fundus photography, with stereo fundus fluorescein angiography in diagnosing
choroidal neovascular membranes.

Sandhu SS, Talks SJ.

Department of Ophthalmology, Royal Victoria Infirmary, Queen Victoria Road,
Newcastle upon Tyne NE1 4LP, UK.

AIMS: To assess the diagnostic accuracy of optical coherence tomography (OCT),
with/without colour fundus photographs, in predicting fundus fluorescein
angiography (FFA) findings in patients suspected of having choroidal
neovascularisation (CNV). METHODS: A consecutive series of patients suspected of 
having CNV underwent OCT and stereo FFA images, which were assigned a diagnosis
by two masked observers, one examining OCT alone and then OCT plus stereo colour 
photographs, and one examining FFA alone. The main outcome measures were the
diagnostic accuracy of OCT (with/without colour photos) in predicting the
presence of CNV and secondly the characteristics of the CNV compared to the FFA
findings. RESULTS: 131 eyes of 118 patients were analysed. The sensitivity and
specificity of OCT for detecting new potentially treatable CNV lesions compared
to FFA was 96.4%, and 66.0%, respectively. For OCT with stereo images the
sensitivity was 94.0% and specificity 89.4%. For detecting CNV with a classic
component the sensitivity and specificity of OCT alone was 78.6% and 82.7%. With 
stereo colour images the sensitivity was 82.1% and specificity 89.3%. CONCLUSION:
OCT is good at detecting the presence of CNV in patients suspected of having new 
CNV. However, it is less accurate at identifying the exact components of CNV. OCT
cannot at present replace FFA in accurately diagnosing CNV components. However,
this imaging method may have a role as a screening tool to help prioritise FFA
requests.

Publication Types: 
    Evaluation Studies

PMID: 16024845 [PubMed - indexed for MEDLINE]

1845: Br J Ophthalmol. 2005 Aug;89(8):964-6.

A study of the relation between body mass index and the incidence of age related 
macular degeneration.

Moeini HA, Masoudpour H, Ghanbari H.

Feiz Hospital, Opthamology Department, Isfahan, University of Medical Sciences,
Islamic Republic of Iran.

BACKGROUND: Age related macular degeneration (ARMD) is the most frequent cause of
blindness among the elderly. Obesity may be one of the risk factors of ARMD as
suggested, yet not proved, by several studies. This study assesses the relation
between body mass index (BMI) and the incidence of ARMD METHODS: This
case-control study included 50 patients with ARMD and 80 subjects who were
adjusted for age, sex, cigarette smoking, blood pressure, and diabetes. Data
analysis was performed by SPSS V9.0 using Student's t and chi2 tests. RESULTS:
42% of the subjects in the case group and 35% of those in the control group were 
men. Mean age of subjects in the case and control groups was 69.9 years (62-77
years) and 64.08 years (56-71 years), respectively. Mean BMI measured 25.38
(range 21-29) and 30.24 (26-34) in the case and control groups, respectively
(p>0.05). 12% of subjects in the case group were obese, 42% were overweight, and 
14% were lean. 22.5% of subjects in the control group were obese, 45% were
overweight, and 7.5% were lean (p>0.05). CONCLUSION: 43% of patients in this
study were aged 70 years or older, which is similar to other studies. There was
no significant difference in BMI between the case and control groups. Recent
studies indicate that obesity is a probable risk factor for progression of ARMD, 
but there is no significant relation with the presence of ARMD. With
multifactorial analysis, the authors could identify no significant relation
between the presence of ARMD and the studied risk factors.

PMID: 16024844 [PubMed - indexed for MEDLINE]

1846: Am J Ophthalmol. 2005 Aug;140(2):295-301.

Vitrectomy for persistent diffuse diabetic macular edema.

Stolba U, Binder S, Gruber D, Krebs I, Aggermann T, Neumaier B.

Department of Ophthalmology, Rudolf Foundation Clinic, Vienna, Austria.
ulrike.stolba@wienkav.at

PURPOSE: To evaluate the potential benefit of vitrectomy in eyes with persistent 
diffuse macular edema. DESIGN: Prospective randomized comparative clinical trial.
METHODS: Eyes with diffuse diabetic macular edema for 6 to 18 months, an attached
posterior hyaloid, and grid laser photocoagulation performed at least 4 months
before were included. Patients were randomized either to a vitrectomy group or to
a control group. MAIN OUTCOME MEASURES: Evaluations of Early Treatment Diabetic
Retinopathy Study (ETDRS) visual acuity, reading vision, and retinal thickness
were carried out at baseline and 1, 3, and 6 months after enrollment. RESULTS:
Fifty-six eyes (100%) were enrolled in this study. Twenty-five eyes (44.6%) were 
randomized into Gr I (vitrectomy group) and 31 eyes (55.4%) into Gr II
(controls). Both groups were comparable in mean age (62.7 years and 63.9 years)
and distribution of gender (one third male, two thirds female). ETDRS visual
acuity showed a statistical significance in favor of Gr I at all time points (P =
.035 to .005 Fisher's exact test). With Jaeger charts a significance for Gr I was
found only at the 6-month examination (P = .01). With optical coherence
tomography, the different behavior of retinal thickness changes in both groups
during follow-up was statistically significant; P values were <.0001 for month 1,
3, and 6, preferring Gr I. CONCLUSIONS: We provide evidence that vitrectomy with 
internal limiting membrane peeling is superior to observation alone in eyes with 
persistent diffuse diabetic macular edema for 6 to 18 months. Longer follow-up
periods and larger series might be needed to confirm these results and gain
additional information.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 16023067 [PubMed - indexed for MEDLINE]

1847: Graefes Arch Clin Exp Ophthalmol. 2005 Dec;243(12):1247-52. Epub 2005 Jul
15.

Trans-Tenon's retrobulbar triamcinolone acetonide infusion for refractory
diabetic macular edema after vitrectomy.

Koga T, Mawatari Y, Inumaru J, Fukushima M, Tanihara H.

Department of Ophthalmology and Visual Science, Kumamoto University Graduate
School of Medical Sciences, Japan.

PURPOSE: To evaluate the efficacy and safety of trans-Tenon's retrobulbar
triamcinolone acetonide (TA) infusion for the treatment of refractory diabetic
macular edema (DME) after vitrectomy. METHODS: After topical anesthesia, 20 eyes 
from 20 patients with persistent DME after pars plana vitrectomy were treated
with trans-Tenon's retrobulbar infusion of 40 mg TA through an inferotemporal
approach. The mean duration (+/-SD) between vitrectomy and trans-Tenon's
retrobulbar TA infusion was 11.4+/-7.9 months. The mean follow-up period (+/-SD) 
after trans-Tenon's retrobulbar TA infusion was 13.3+/-2.8 months. RESULTS: At 1 
week after trans-Tenon's retrobulbar TA infusion, the mean central retinal
thickness (+/-SD) measured by optical coherence tomography was 381+/-99 mum,
which was a statistically significant decrease in comparison with the
preoperative thickness (555+/-112 mum) (P<0.001). Additional trans-Tenon's
retrobulbar TA infusions were performed in ten eyes (50%), due to the recurrence 
of DME at 6.6+/-3.0 months after the first TA infusion. At the final examination,
macular edema resolved in 13 (65%), improved in four (20%), and remained
unchanged in three (15%) of the 20 eyes. At 1 month after trans-Tenon's
retrobulbar TA infusion, the mean laser flare value (+/-SD) was 9.6+/-3.0
photon/ms, which was a statistically significant decrease in comparison with the 
preoperative value (15.5+/-5.9 photon/ms) (P<0.01). Furthermore, in ten eyes
(50%) with recurrent DME, re-elevated laser flare values were observed prior to
the recurrence of DME. The final best-corrected Snellen visual acuity improved by
two or more lines in nine eyes (45%), and remained unchanged in 11 eyes (55.0%). 
IOP elevation equal to or higher than 21 mmHg was observed in three (15%) of the 
20 eyes with TA infusion, and was controlled by topical medications. No other
injection-related complications were observed. CONCLUSION: Trans-Tenon's
retrobulbar TA infusion is an effective and safe method for the treatment of
refractory DME, which is present even after vitrectomy.

Publication Types: 
    Case Reports
    Comparative Study

PMID: 16021497 [PubMed - indexed for MEDLINE]

1848: Int Arch Occup Environ Health. 2005 Sep;78(8):681-5. Epub 2005 Oct 12.

Welder's maculopathy?

Maier R, Heilig P, Winker R, Neudorfer B, Hoeranter R, Ruediger H.

Clinical Department of Occupational Medicine, Medical University of Vienna,
Waehringer Guertel 18-20, 1090, Vienna, Austria. richardmaier@chello.at

OBJECTIVE: The aim of this study was to verify or to disprove whether the term
'Welder's maculopathy' or 'Welding arc maculopathy' has to be considered being a 
justifiable occupational hazard and is to be annexed to the list of occupational 
diseases. METHODS: Multifocal electroretinography (MERG) and thorough
ophthalmologic examinations were performed in a group of 89 welders. The matched 
control group comprised 81 subjects who had never been exposed to welding. All
participants of this study were examined by a specialist of occupational medicine
prior to the MERG. RESULTS: Multifocal electroretinography as well as
ophthalmological tests did not reveal a significant morphological or functional
differences between the welders and the control group. On an average, the
welders' visual acuity appeared to be better than that of the control group. This
phenomenon could be attributed to the so-called healthy worker effect.
CONCLUSION: Welding arc maculopathy seems to be rather a sequel of occupational
accidents and negligence of safety regulations. The results of this study
indicate that the usual protective measures in professional welding appears to be
sufficient in order to prevent an occupational risk of welding arc maculopathy.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 16021465 [PubMed - indexed for MEDLINE]

1849: Eye. 2006 Jun;20(6):720-4. Epub 2005 Jul 8.

Intravitreal triamcinolone for diffuse diabetic macular oedema.

Gibran SK, Cullinane A, Jungkim S, Cleary PE.

Department of Ophthalmology, Cork University Hospital, Cork, Ireland.
syedgibran@yahoo.com

AIM: To evaluate the efficacy of intravitreal triamcinolone (IVTA) for the
treatment of diffuse diabetic macular oedema (DME) refractory to conventional
argon macular laser therapy. METHODS: A prospective, consecutive, and
noncomparative case series was undertaken involving 38 eyes of 38 patients with
refractory DME. Triamcinolone acetonide (4 mg) in 0.1 ml was injected
intravitreally. LogMar visual acuity (VA) and macular thickness measured by
ocular coherence tomography (OCT) were assessed preoperatively and
postoperatively at 1, 3, and 6 months. RESULTS: All patients completed 6 months
of follow up. VA (mean+/-SD) improved from 0.905+/-0.23 to 0.605+/-0.28,
0.555+/-0.29, and 0.730+/-0.30 at 1, 3, and 6 months, respectively. Macular
thickness baseline (mean+/-SD) on OCT was 418.7+/-104.2 microm and this decreased
to 276.9+/-72.6 microm, 250.6+/-53.1 microm, and 308.8+/-87.3 microm at 1, 3, and
6 months, respectively. CONCLUSIONS: IVTA may be a potential temporary treatment 
for refractory DME. It is effective in decreasing macular thickness and improving
VA but the effect lasts approximately for 6 months in the majority of patients.
Further investigations are required to establish the safety of IVTA for the
treatment of DME.

Publication Types: 
    Clinical Trial

PMID: 16021193 [PubMed - indexed for MEDLINE]

1850: Eye. 2006 Jul;20(7):805-9. Epub 2005 Jul 15.

Comment in:
    Eye. 2006 Nov;20(11):1307-8.

Correlation of retinal sensitivity measured with fundus-related microperimetry to
visual acuity and retinal thickness in eyes with diabetic macular edema.

Okada K, Yamamoto S, Mizunoya S, Hoshino A, Arai M, Takatsuna Y.

Department of Ophthalmology and Visual Science, Chiba University Graduate School 
of Medicine, Inohana, Chuo-ku, Chiba, Japan.

AIM: To determine whether significant correlations exist between retinal
sensitivity measured by fundus-related microperimetry and the visual acuity and
the foveal thickness measured by optical coherence tomography (OCT) in eyes with 
diabetic macular edema (DME). METHODS: A retrospective chart review of 32 eyes
with DME and 17 normal healthy eyes that had undergone fundus-related
microperimetry and OCT. The macular sensitivity was measured using the recently
introduced fundus-related microperimeter, Micro Perimeter 1. The mean retinal
sensitivities within the central 2 degrees and 10 degrees were correlated with
the best-corrected visual acuity and OCT-measured foveal retinal thickness.
RESULTS: The mean sensitivities in the central 2 degrees and 10 degrees were
significantly lower in patients with DME than in normal subjects (P<0.0001). The 
mean retinal sensitivities in the central 2 degrees and 10 degrees were inversely
correlated with visual acuity (r(2)=0.623, P<0.0001; r(2)=0.581, P<0.0001) and
foveal thickness (r(2)=0.581, P<0.0001; r(2)=0.551, P<0.0001). CONCLUSIONS: The
mean retinal sensitivities measured with fundus-related microperimetry were
significantly lower in eyes with DME than in normal eyes. Because a significant
correlation of the microperimeter-determined retinal sensitivity to visual acuity
and foveal thickness was observed, the retinal sensitivities obtained by
fundus-related microperimetry may be another measure that can be used to assess
the effects of DME.

PMID: 16021181 [PubMed - indexed for MEDLINE]

1851: Ophthalmic Genet. 2005 Jun;26(2):101-5.

HEMICENTIN-1 (FIBULIN-6) and the 1q31 AMD locus in the context of complex
disease: review and perspective.

Schultz DW, Weleber RG, Lawrence G, Barral S, Majewski J, Acott TS, Klein ML.

Macular Degeneration Center, Casey Eye Institute, Oregon Health & Science
University, 3375 SW Terwilliger Boulevard, Portland, OR 97239-4197, U.S.A.
schultzd@ohsu.edu

Age-related macular degeneration (AMD) is the most common blinding disorder in
the Western world. Similar to other common diseases in which age is a risk factor
(e.g., type II diabetes or Alzheimer's disease), AMD is thought to have a complex
etiology. Previously, a Gln5345Arg mutation in HEMICENTIN-1 was found to
segregate with AMD in a large family. However, the population frequency of this
allele is inconsistent with the large proportion of families shown by linkage
studies to map near this gene at 1q31. This review summarizes current knowledge
regarding the role of HEMICENTIN-1 in AMD, the results of association studies for
the Gln5345Arg mutation, and the linkage evidence for an AMD locus on 1q31. The
data can be reconciled through proposing both additional variants in HEMICENTIN-1
and a second genetic risk factor for AMD in the region.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.
    Review

PMID: 16020313 [PubMed - indexed for MEDLINE]

1852: Ophthalmic Genet. 2005 Jun;26(2):61-7.

Comment in:
    Ophthalmic Genet. 2005 Jun;26(2):57-9.

A discordant sib-pair linkage analysis of age-related macular degeneration.

Santangelo SL, Yen CH, Haddad S, Fagerness J, Huang C, Seddon JM.

Psychiatric & Neurodevelopmental Genetics Unit, Center for Human Genetic
Research, Massachusetts General Hospital, 149 13th Street, Charlestown, MA, USA. 
ssantang@psych.mgh.harvard.edu

BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of visual
impairment and blindness among older adults in the United States and throughout
the developed world. Etiological research implicates both genetic and
environmental components. Our prior genome scan in 511 affected sib-pairs and
other relative pairs identified significant or suggestive linkage signals on
chromosomes 1, 2, 3, 6, 8, 10, 12, 16, and 22. PURPOSE: To search for genetic
loci for AMD using the extremely discordant sib-pair (EDSP) method of linkage
analysis, which until now has never been applied to the study of AMD. METHODS:
The EDSP method is a more powerful approach than standard methods which rely on
relative pairs selected at random or pairs concordant for the phenotype. The EDSP
approach has also been characterized as the only design that is uniformly
powerful in nearly all genetic situations. Thus, substantial reductions in sample
size can be achieved. STUDY POPULATION: The study sample for analysis included
110 EDSPs from 40 families that comprise a subset of the 158 families studied in 
a prior genome-wide scan using affected relative pairs. RESULTS: Evidence for
linkage was found on chromosomes 1q, 2q, 6q, 19p, and 20q. The regions identified
on chromosomes 1q and 2q were the same regions identified in our prior analysis, 
whereas the identified region on 6q was approximately 80 cM distal to our
previous signal. DISCUSSION: Within this study population, we have narrowed the
focus to chromosomes 1q, 2q, 6q, 19p, and 20q in our search for AMD loci.
However, given the fact that a gene was recently identified on chromosome 1q,
future family- and population-based analyses should concentrate on testing for
associations with candidate gene variants in the other identified chromosomal
regions in searches for additional AMD loci.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 16020308 [PubMed - indexed for MEDLINE]

1853: Ocul Immunol Inflamm. 2005 Apr-Jun;13(2-3):245-7.

Steroid hypopyon following intravitreal triamcinolone acetonide injection in a
pseudophakic patient.

Amato JE, Lee DH, Santos BA, Akduman L.

Saint Louis University Eye Institute, MO 63104, USA.

PURPOSE: A 64-year-old woman presenting with the complaint of 'white stuff' in
her left eye one day after intravitreal triamcinolone injection for chronic
pseudophakic cystoid macular edema after cataract extraction and anterior chamber
intraocular lens implant is presented. METHODS: Differential diagnosis included
post-injection endophthalmitis versus 'steroid hypopyon.' RESULTS: The patient
was observed closely and the hypopyon cleared in four days. Three weeks after the
injection, her visual acuity had improved from 20/200 to 20/70 with complete
resolution of the macular edema. CONCLUSION: Patients having no capsular barrier 
presenting with hypopyon one day after IVTA may be observed closely for a few
days for resolution of hypopyon prior to being treated as endophthalmitis.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 16019686 [PubMed - indexed for MEDLINE]

1854: Ocul Immunol Inflamm. 2005 Apr-Jun;13(2-3):205-12.

Safety and efficacy of intravitreal triamcinolone acetonide for uveitic macular
edema.

Androudi S, Letko E, Meniconi M, Papadaki T, Ahmed M, Foster CS.

Ocular Immunology and Uveitis Service, Department of Ophthalmology, Massachusetts
Eye and Ear Infirmary, Harvard Medical School, and the Massachusetts Eye Research
and Surgery Institute (MERSI), Boston, 02114, USA.

BACKGROUND: To evaluate the safety and efficacy of intravitreal triamcinolone
acetonide (TA) for treating macular edema secondary to non-infectious uveitis.
METHODS: Retrospective review of sixteen patients (20 eyes) with chronic cystoid 
macular edema (CME) as a consequence of controlled intermediate uveitis,
posterior uveitis, or panuveitis who received at least one intravitreal injection
of TA. Main outcome measures were visual acuity (VA), intraocular pressure (IOP),
formation or progression of an existing cataract, and CME resolution during the
follow-up period. RESULTS: At last follow-up, VA showed improvement (compared to 
baseline) in 11 eyes (55%), deterioration in three eyes (15%), remained
completely unchanged in one eye (5%), and showed improvement initially but
returned to baseline levels in five eyes (25%). At last follow-up, CME had
relapsed or was still present in 10 of the eyes (50%). The remaining eyes showed 
complete resolution of the CME, without evidence of recurrence during the
follow-up time. Mean VA at last follow-up showed statistically significant
improvement (p = 0.02) in nonvitrectomized eyes (mean baseline VA: 1.14 +/- 0.58;
mean final VA: 0.96 +/- 0.66) compared to the almost unaltered mean visual acuity
for vitrectomized eyes (mean baseline VA: 0.76 +/- 0.41; mean final VA: 0.71 +/- 
0.48)(p = 0.40, paired samples t-test). Elevation of IOP was transient in all
cases and responded well to topical medications, except for one patient who
required placement of an Ahmed valve. Preexisting cataract progressed in three of
the 15 phakic eyes (20%). One patient developed a retinal detachment and required
additional surgery to reattach it. Patients were followed for a mean of 34 weeks 
(median: 32 weeks; range: 19-56 weeks). CONCLUSIONS: Intravitreal TA may play a
role in the treatment of uveitis-related CME. Further controlled studies are
necessary to test this hypothesis.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 16019680 [PubMed - indexed for MEDLINE]

1855: Ophthalmology. 2005 Sep;112(9):1557-63.

Comparison of intravitreal versus posterior sub-Tenon's capsule injection of
triamcinolone acetonide for diffuse diabetic macular edema.

Cardillo JA, Melo LA Jr, Costa RA, Skaf M, Belfort R Jr, Souza-Filho AA, Farah
ME, Kuppermann BD.

Hospital de Olhos de Araraquara, Araraquara, São Paulo, Brazil.
hospitaldeolhos@uol.com.br

PURPOSE: To compare the safety and efficacy of intravitreal versus posterior
Sub-Tenon's capsule injection of triamcinolone acetonide for diffuse diabetic
macular edema. DESIGN: Prospective, double-masked, randomized controlled trial.
PARTICIPANTS: Twelve patients (24 eyes) with bilateral diffuse diabetic macular
edema. INTERVENTION: One eye of each patient was randomly assigned to receive a
single 4-mg triamcinolone acetonide intravitreal injection and the fellow eye to 
receive a 40-mg triamcinolone acetonide posterior Sub-Tenon's capsule injection. 
MAIN OUTCOME MEASURES: Changes in visual acuity and central macular thickness
obtained using optical coherence tomography were measured during a 6-month
follow-up. Potential treatment complications were monitored, including increases 
in intraocular pressure (IOP) and cataract progression. RESULTS: Both
intravitreal and Sub-Tenon's capsule injections of triamcinolone acetonide
resulted in significant but transient improvements in central macular thickness. 
The mean (+/-standard deviation [SD]) central macular thickness in eyes with
intravitreal injection was significantly thinner than in the Sub-Tenon's
capsule-injected eyes at 1 month (226.8+/-41.7 microm and 431.5+/-165.8 microm,
respectively; P = 0.002) and 3 months (242.3 +/- 93.9 microm and 364.7+/-78.2
microm, respectively; P = 0.005) after triamcinolone acetonide injection. The
mean visual acuity (logarithm of the minimum angle of resolution) in the
intravitreally injected eyes was significantly better than in the Sub-Tenon's
capsule-injected eyes at 3 months post injection (0.832+/-0.293 and
1.107+/-0.339, respectively; P = 0.004). Intraocular pressure did not show any
significant difference between the 2 forms of triamcinolone acetonide delivery at
any follow-up visit, and no eyes had IOPs >25 mmHg. CONCLUSIONS: The findings
from our study neither advocate nor support the use of corticosteroids for the
treatment of diabetic macular edema, but do imply that both intravitreal and
Sub-Tenon's capsule injections of triamcinolone acetonide may be equally
tolerated, with short-term performance clearly favoring the intravitreal (4 mg)
more than the SBT capsule (40 mg) route for the anatomic and functional aspects
of improvement tested in this investigation.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16019075 [PubMed - indexed for MEDLINE]

1856: Exp Eye Res. 2006 Jan;82(1):99-110. Epub 2005 Jul 12.

Pigment epithelium-derived factor (PEDF) and vascular endothelial growth factor
(VEGF) in aged human choroid and eyes with age-related macular degeneration.

Bhutto IA, McLeod DS, Hasegawa T, Kim SY, Merges C, Tong P, Lutty GA.

Department of Ophthalmology, The Wilmer Ophthalmological Institute, Johns Hopkins
Hospital, Johns Hopkins University School of Medicine, 600 North Wolfe Street,
Baltimore, MD 21287-9115, USA.

The purpose of this study was to examine the localization and relative levels of 
vascular endothelial growth factor (VEGF; an angiogenic factor) and pigment
epithelium-derived factor (PEDF; an antiangiogenic factor) in aged human choroid 
and to determine if the localization or their relative levels changed in
age-related macular degeneration (AMD). Ocular tissues were obtained from eight
aged control donors (age range, 75-86 years; mean age, 79.8 years) with no
evidence or history of chorioretinal disease and from 12 donors diagnosed with
AMD (age range, 61-105 years; mean age, 83.9 years). Tissues were cryopreserved
and streptavidin alkaline phosphatase immunohistochemistry was performed with
rabbit polyclonal anti-human VEGF and rabbit polyclonal anti-human PEDF
antibodies. Binding of the antibodies was blocked by preincubation of the
antibody with an excess of recombinant human PEDF or VEGF peptide. Choroidal
blood vessels were identified with mouse anti-human CD-34 antibody in adjacent
tissue sections. Three independent observers graded the immunohistochemical
reaction product. The most prominent sites of VEGF and PEDF localization in aged 
control choroid were RPE-Bruch's membrane-choriocapillaris complex including RPE 
basal lamina, intercapillary septa, and choroidal stroma. There was no
significant difference in immunostaining intensity and localization of VEGF and
PEDF in aged control choroids. The most intense VEGF immunoreactivity was
observed in leukocytes within blood vessels. AMD choroid had a similar pattern
and intensity of VEGF immunostaining to that observed in aged controls. However, 
PEDF immunoreactivity was significantly lower in RPE cells (p=0.0073), RPE basal 
lamina (p=0.0141), Bruch's membrane (p<0.0001), and choroidal stroma (p=0.0161)
of AMD choroids. The most intense PEDF immunoreactivity was observed in disciform
scars. Drusen and basal laminar deposits (BLDs) were positive for VEGF and PEDF. 
In aged control subjects, VEGF and PEDF immunostaining was the most intense in
RPE-Bruch's membrane-choriocapillaris complex. In AMD, PEDF was significantly
lower in RPE cells, RPE basal lamina, Bruch's membrane and choroidal stroma.
These data suggest that a critical balance exists between PEDF and VEGF, and PEDF
may counteract the angiogenic potential of VEGF. The decrease in PEDF may disrupt
the balance and be permissive for the formation of choroidal neovascularization
(CNV) in AMD.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16019000 [PubMed - indexed for MEDLINE]

1857: Proc Natl Acad Sci U S A. 2005 Jul 26;102(30):10433-8. Epub 2005 Jul 13.

Altered retinoid homeostasis catalyzed by a nicotine metabolite: implications in 
macular degeneration and normal development.

Brogan AP, Dickerson TJ, Boldt GE, Janda KD.

The Skaggs Institute for Chemical Biology and Department of Chemistry, The
Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037,
USA.

Retinoids (vitamin A) serve two distinct functions in higher animals: light
absorption for vision and gene regulation for growth and development. Cigarette
smoking is a contributing factor for diseases that affect vision such as
age-related macular degeneration and increases the risk of birth defects;
however, altered retinoid homeostasis has received little attention as a
potential mechanism for smoking-associated toxicities. Herein, we demonstrate
that nornicotine, a nicotine metabolite and component of cigarette smoke,
catalyzes the Z-to-E alkene isomerization of unsaturated aldehydes and ketones,
including retinals. Despite the recent explosion in the use of organic compounds 
as chemical catalysts, minimal effort has been devoted to biologically relevant
organocatalysis. Our study demonstrates a system in which a lowest unoccupied
molecular orbital-lowering intermediate similar to the endogenous protein
rhodopsin effectively catalyzes isomerization under biologically relevant
conditions. The product of retinal isomerization is all-E-retinal, which in the
eye is a biosynthetic precursor to N-retinylidene-N-retinylethanolamine, a
hallmark of age-related macular degeneration. Furthermore, 9-Z- and all-E-retinal
isomers are biosynthetic precursors to 9-Z- and all-E-retinoic acids, ligands
that mediate specific cellular responses by binding to transcriptional regulatory
proteins critical in growth and development. Strict maintenance of retinal isomer
composition is essential for proper transcriptional regulation.
Nornicotine-catalyzed retinal isomerization implies an underlying molecular
mechanism for age-related macular degeneration, the birth defects associated with
smoking, and other smoking-associated abnormalities that stem from disruption of 
retinoid metabolism.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 16014706 [PubMed - indexed for MEDLINE]

1858: Expert Opin Pharmacother. 2005 Jul;6(8):1421-3.

Pegaptanib: the first antiangiogenic agent approved for neovascular macular
degeneration.

Doggrell SA.

Auckland University of Technology-Akoranga Campus, School of Nursing Northcote,
Auckland, New Zealand. s_doggrell@yahoo.com

Age-related macular degeneration is the leading cause of irreversible visual loss
in the industrialised world. Angiogenesis underlies the neovascularisation, and
vascular endothelial growth factor (VEGF) is an angiogenesis growth factor. In
the VEGF Inhibition Study in Ocular Neovascularisation-1 (VISION-1) trial,
pegaptanib (an aptamer inhibitor of VEGF) was tested in neovascular age-related
macular degeneration. The 1186 patients received a sham injection or
intravitreous injection of pegaptanib (0.3, 1.0 or 3.0 mg) every 6 weeks over a
period of 48 weeks. The primary end point was the proportion of patients who lost
< 15 letters of visual acuity between baseline and 54 weeks, and this occurred in
164/296 patients (55%) who received the sham injection. A higher percentage of
patients maintained this visual acuity if they were treated with pegaptanib 0.3
mg (54/206 patients, 70%). There was no evidence that pegaptanib 1 or 3 mg was
more effective than 0.3 mg. There was no excess of systemic adverse effects with 
pegaptanib, but ocular adverse effects occurred more commonly with pegaptanib
than with sham injection; vitreous floaters (33 versus 8%), vitreous opacities
(18 versus 10%) and anterior chamber inflammation (14 versus 6%). Although these 
results represent a new, beneficial and relatively safe approach to age-related
macular degeneration, the progression was not halted or reversed, and further
improvement to treatment for this condition should be sought.

Publication Types: 
    Review

PMID: 16013991 [PubMed - indexed for MEDLINE]

1859: Graefes Arch Clin Exp Ophthalmol. 2005 Dec;243(12):1241-6. Epub 2005 Jul
12.

Verteporfin photodynamic therapy for extrafoveal choroidal neovascularisation
secondary to age-related macular degeneration.

Voelker M, Gelisken F, Ziemssen F, Wachtlin J, Grisanti S.

Department of Ophthalmology I, University of Tübingen, Germany.

PURPOSE: To report the results of verteporfin photodynamic therapy (PDT) of
extrafoveal predominantly classic choroidal neovascularisation (CNV) secondary to
age-related macular degeneration (AMD). METHODS: In this retrospective study 20
consecutive patients (20 eyes) undergoing verteporfin PDT for extrafoveal
predominantly classic CNV in AMD were examined. Colour photography of the fundus,
fluorescein angiography and complete ophthalmic examination, including visual
acuity assessment with ETDRS charts, were performed before treatment and at
3-month intervals thereafter. The primary outcome criterion was the change in
visual acuity. The secondary outcome criterion was the extension of the CNV
beneath the centre of the fovea during the follow-up period. RESULTS: Mean
follow-up time of the patients was 24.2 months (range 12 to 58 months). Visual
acuity at baseline varied from 20/200 to 20/20 (mean 20/50+/-2.3 lines). Final
visual acuity ranged from 20/1000 to 20/20 (mean 20/200+/-5.1 lines) (P<0.001).
In 85% (17/20) of the eyes visual acuity worsened. Visual acuity improved in 15% 
(3/20) of the eyes. During the course of the follow-up period, subfoveal
extension of the CNV was detected in 80% (16/20) of the eyes. CONCLUSION: In 85% 
of the eyes with extrafoveal predominantly classic CNV secondary to AMD, visual
acuity worsened after verteporfin PDT in an average follow-up time of 24 months. 
Subfoveal CNV was found in 80% of the eyes during follow-up. Even though
verteporfin PDT can preserve visual acuity in selected cases, deterioration was
seen in the majority of the patients.

Publication Types: 
    Comparative Study

PMID: 16010552 [PubMed - indexed for MEDLINE]

1860: Arch Ophthalmol. 2005 Jul;123(7):944-9.

Quantitative phenotyping of chromatic dysfunction in best macular dystrophy.

Campos SH, Forjaz V, Kozak LR, Silva E, Castelo-Branco M.

Center for Ophthalmology, Institute of Biomedical Research in Light and Image,
Faculty of Medicine, University of Coimbra, Az. de Sta Comba, Celas 3000-354,
Coimbra, Portugal.

OBJECTIVES: To quantify chromatic dysfunction in Best disease to reassess the
classic categorization of macular chromatic damage and to investigate
psychophysical and clinical correlations. METHODS: Color-contrast discrimination 
was measured using 2 different psychophysical strategies in age-matched control
(n = 41) and patient (n = 34) eyes. The first strategy measured performance along
3 main confusion lines (testing cone function), and the second evaluated
discrimination ellipses (modified Cambridge Color Test). The main outcome
measures were chromatic discrimination variables (confusion line length, ellipse 
length, angle, and axis ratio) and visual acuity (VA). RESULTS: Significant loss 
of performance was seen in all color axes in our patients, and it increased
monotonically with staging, becoming significant in Fishman stages 2 and 3. The
classically assumed preferential type I red-green deficit was true only for stage
4. Substantial chromatic dysfunction occurred even with relatively preserved VA
despite that negative correlations between all test variables and VA reached
statistical significance. Partial correlation analysis showed that protan/deutan 
loss was related to VA independent of tritan loss. Statistically significant
positive correlations were also found between lesion size and chromatic
dysfunction. CONCLUSIONS: Chromatic discrimination is often impaired in Best
disease, even when VA is still spared. Our quantitative psychophysical approach
shows that the classic categorization as a type I red-green deficit is valid only
for disease stage 4.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16009836 [PubMed - indexed for MEDLINE]

1861: Arch Ophthalmol. 2005 Jul;123(7):939-43.

A standardized method for reporting changes in macular thickening using optical
coherence tomography.

Chan A, Duker JS.

New England Eye Center, Tufts-New England Medical Center, Tufts University School
of Medicine, 750 Washington Street, Boston, MA 02111-1533, USA.

OBJECTIVE: To describe a standardized method for reporting quantitative changes
in macular thickening using optical coherence tomography (OCT). METHODS: The
proposed method consists of calculating the actual change in central foveal
thickening (the initial pretreatment thickness minus the posttreatment thickness)
using OCT and dividing that value by the potential change (the initial
pretreatment thickness minus the normal thickness based on normative data) to
provide the total improvement in macular edema as a percentage. We refer to this 
method as the standardized change in macular thickening (SCMT). To illustrate the
effectiveness of this method, we performed a retrospective review of 2 studies
that evaluated different strategies for treating refractory macular edema.
RESULTS: Patients treated with intravitreal triamcinolone acetonide for
refractory diabetic macular edema had an overall SCMT of approximately 75%, 78%, 
and 55% at the 1-, 3-, and 6-month follow-up visits, respectively. More than half
of the patients in the study cohort (9 of 16 patients) experienced greater than
80% SCMT at the last follow-up visit. Patients who underwent vitrectomy for a
taut, thickened posterior hyaloid on OCT responded with an SCMT of approximately 
78% at the 3-month follow-up visit and 87% at the final follow-up visit (mean, 19
months). Patients who underwent vitrectomy for diabetic macular edema
unresponsive to laser photocoagulation but with no evidence of vitreomacular
traction experienced an SCMT of 37% at the 3-month follow-up visit and 20% at the
final follow-up visit (mean, 17 months). CONCLUSION: The proposed method offers
an objective and intuitive basis for evaluating and comparing the efficacy of
different therapeutic modalities.

Publication Types: 
    Comparative Study

PMID: 16009835 [PubMed - indexed for MEDLINE]

1862: Vision Res. 2006 Feb;46(4):590-7. Epub 2005 Jul 11.

Eye movements and reading in macular disease: further support for the shrinking
perceptual span hypothesis.

Crossland MD, Rubin GS.

Institute of Ophthalmology, University College London, UK. m.crossland@ucl.ac.uk

Reduced perceptual span is one factor which limits reading speed in patients with
macular disease. This study measured the perceptual span and the number of
saccades to locate a target in 18 patients with macular disease and seven control
subjects on two occasions separated by up to 12 months. Perceptual span changed
by up to two letters. Changes in perceptual span were significantly related to
changes in reading speed (r2 = 0.43, p < 0.005), and were independent of changes 
in the number of saccades used to observe a target (r2 = 0.003, p = 0.62). These 
findings have important implications for the development of training programmes
for patients with macular disease.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16005930 [PubMed - indexed for MEDLINE]

1863: Exp Eye Res. 2005 Dec;81(6):731-41. Epub 2005 Jul 11.

Esterified and unesterified cholesterol in drusen and basal deposits of eyes with
age-related maculopathy.

Curcio CA, Presley JB, Malek G, Medeiros NE, Avery DV, Kruth HS.

Department of Ophthalmology, Callahan Eye Foundation Hospital, University of
Alabama School of Medicine, 700 South 18th Street, Room H020, Birmingham AL
35294-0009, USA. curcio@uab.edu

To address the potential for an outer segment (OS) contribution to the
sub-retinal pigment epithelium (RPE) lesions of age-related maculopathy (ARM), we
quantified esterified and unesterified cholesterol (EC, UC) with the
sterol-specific fluorescent probe filipin in cryosections of ARM eyes. Twenty six
eyes from 20 donors were preserved <5 hr after death in 4% paraformaldehyde (n = 
16) or 2.5% glutaraldehyde/1% paraformaldehyde (n = 10). Eyes had exudative late 
ARM (n = 6), geographic atrophy (n = 15), and drusen > or =125 microm (n = 11).
Sections were stained with filipin for UC or were extracted and hydrolysed with
cholesterol esterase before filipin staining for EC. Drusen varied in cholesterol
content, with a rough correlation between EC and UC. Dome-shaped drusen contained
distinctive, loosely packed UC-rich loops. In basal deposits, EC and UC were more
prominent near Bruch's membrane than near the RPE. A UC-rich material was
localized within the subretinal space (n = 4). Maximum filipin fluorescence due
to UC was quantified in 47 lesions (19 drusen, 24 basal deposits, and 4
sub-retinal) from 12 ARM eyes and compared to OS and inner plexiform layer (IPL) 
of uninvolved retina in the same sections. Relative to IPL, UC fluorescence was
higher in lesions (mean+/-s.d: 1.63+/-0.69) and lower in OS (0.64+/-0.18). If
only the packing of membranes explained fluorescence intensity, then one would
expect much higher intensities in membrane-rich OS than in lesions. Because the
converse is true, the membranous material in lesions must be more highly enriched
in cholesterol on a per unit area basis. UC in sub-RPE deposits cannot be derived
directly from OS without considerable intracellular processing within RPE,
additional cholesterol sources, or both.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16005869 [PubMed - indexed for MEDLINE]

1864: Curr Med Res Opin. 2005 Jul;21(7):1131-7.

Erratum in:
    Curr Med Res Opin. 2005 Sep;21(9):1431-2.

Emerging guidelines for use of NSAID therapy to optimize cataract surgery patient
care.

O'Brien TP.

The Wilmer Ophthalmology Institute, The Johns Hopkins Hospital, Baltimore, MD
21287-0682, USA. tobrien@jhmi.edu

This analysis provides guidelines for the proper use of topical ophthalmic
nonsteroidal anti-inflammatory drugs (NSAIDs), discusses their effect on
inflammation, and their role in the prevention of cystoid macular edema (CME). A 
novel treatment strategy is presented for recommended topical ophthalmic NSAID
dosing in patient populations based on risk factors for CME. The article reviews 
current topical ophthalmic NSAIDs, as well as a newest generation of pro-drug
NSAIDs. In addition, combination therapy of NSAIDs and corticosteroids are
discussed, along with a general review of therapeutic guidelines for dosing
regimens, and benefits and risks of therapy. The goal of this analysis is to
provide a suggested therapeutic regimen with topical NSAIDs to assist in
achieving optimal clinical and functional outcomes.

Publication Types: 
    Guideline
    Practice Guideline
    Research Support, Non-U.S. Gov't
    Review

PMID: 16004683 [PubMed - indexed for MEDLINE]

1865: Eur J Ophthalmol. 2005 Jul-Aug;15(4):513-6.

Combined surgical ablation and intravitreal triamcinolone acetonide for retinal
angiomatous proliferation.

Boscia F, Furino C, Prascina F, Delle Noci N, Sborgia L, Sborgia C.

Department of Ophthalmology and Otolaryngology, University of Bari, Bari - Italy.
francescoboscia@hotmail.com

PURPOSE: Neovascular age-related macular degeneration (ARMD) with retinal
angiomatous proliferation (RAP) has a poor natural history and the efficacy of
any treatment has not yet been established. The authors describe a combined
surgical treatment. METHODS: A 76-year-old woman presented with a best-corrected 
visual acuity (BCVA) of 20/600 in the right eye and macula with stage 3 RAP as
identified by fluorescein angiography (FA), indocyanine green angiography (ICGA),
and optical coherence tomography (OCT). After a standard three-port pars plana
core vitrectomy (PPV), endodiathermy of the arteriolar and venous feeder vessels 
of each lesion was performed, intraretinal RAP feeder vessels were cut with
manual vertical intraocular scissors, and 0.1 mL of triamcinolone acetonide
(TAAC) was injected intravitreally. At 1 and 4 weeks and at the sixth month, the 
patient underwent a complete eye examination, FA, ICGA, and OCT to assess
outcomes and complications. RESULTS: Six months later, BCVA was stable at 20/300,
intraocular pressure was 15 mmHg, anterior segment and vitreous cavity were clear
without evidence of TAAC granules, and retina was attached. FA and ICGA showed a 
complete occlusion of the RAP and absence of leakage or ischemia and OCT
demonstrated decreased macular thickness with resolution of both intraretinal
edema and pigment epithelium detachment, and the restoration of the normal
macular profile. At the end of follow-up, the authors did not observe any ocular 
or systemic complication. CONCLUSIONS: Surgical approach to RAP stage 3 with
intravitreal injection of 4 mg of TAAC was safe and anatomically effective.

Publication Types: 
    Case Reports

PMID: 16001389 [PubMed - indexed for MEDLINE]

1866: Eur J Ophthalmol. 2005 Jul-Aug;15(4):482-5.

Anecortave acetate for the treatment of subfoveal choroidal neovascularization
secondary to age-related macular degeneration.

Schmidt-Erfurth U, Michels S, Michels R, Aue A.

Department of Ophthalmology, University of Vienna, Vienna - Austria.

PURPOSE: Anecortave acetate is a novel angiostatic cortisene being evaluated
clinically for treatment of exudative age-related macular degeneration (ARMD). A 
randomized, placebo-controlled, efficacy and safety dose duration study of
anecortave acetate for depot suspension (3 mg, 15 mg, 30 mg) in this patient
population was completed in June 2003. As part of this trial, 128 patients with
subfoveal choroidal neovascularization (CNV) secondary to ARMD were enrolled and 
treated for up to 2 years by 18 clinical sites in the United States and European 
Union. METHODS: Study patients were evaluated clinically with detailed ophthalmic
examinations, general physical examinations, assessments of best-corrected logMAR
visual acuity, and angiographic evaluations. The Digital Angiography Reading
Center (New York City, NY) assessed lesion eligibility while the clinical
investigators assessed overall patient eligibility prior to treatment. As part of
this study, study medication was delivered as a posterior juxtascleral depot
using a specially designed curved cannula at 6-month intervals if in the masked
investigator's opinion the patient's lesion could benefit from additional
treatment. RESULTS: The 2-year efficacy results of this placebo-controlled study 
demonstrated that RETAANE 15 mg (anecortave acetate for depot suspension) was
statistically superior to placebo for stabilization of vision (<3 logMAR line
change from baseline) and for inhibition of neovascular lesion growth. There were
no serious treatment-related safety issues associated with either the study
medication or the procedure for administration. CONCLUSIONS: Anecortave acetate
15 mg for depot suspension is clinically efficacious compared to placebo for
treatment of subfoveal exudative ARMD lesions when administered at 6-month
intervals as a posterior juxtascleral depot.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16001382 [PubMed - indexed for MEDLINE]

1867: Auton Neurosci. 2005 Jun 15;120(1-2):46-51. Epub 2005 Apr 18.

Cervical sympathectomy causes photoreceptor-specific cell death in the rat
retina.

Steinle JJ, Lindsay NL, Lashbrook BL.

Department of Physiology, Southern Illinois University School of Medicine,
Carbondale, IL 62901, United States. jsteinle@siumed.edu

Changes in the regulation of the vasculature of the eye may be related to some
age-related ocular diseases. We have previously shown that loss of sympathetic
innervation, as can normally occur with age, resulted in substantial vascular
growth of the choroid. The current study was designed to determine whether
changes induced by sympathetic denervation causes significant loss of
photoreceptors and increased glial cell reactivity in the retina. Sympathetic
denervation was performed followed by immunohistochemistry, TUNEL staining, and
protein expression analysis to investigate photoreceptor loss. There was a
significant reduction (30%) in photoreceptor numbers in the sympathectomized eye.
This loss was due to apoptosis, as there was over a doubling in apoptotic cell
numbers after sympathectomy. This loss of photoreceptors in the sympathectomized 
eye resulted in a significantly reduced width of the outer nuclear layer of the
retina when compared to the contralateral eye. Increased glial fibrillary acidic 
protein (GFAP) staining was also noted after sympathectomy in the ganglion cell
layer with streaking toward the bipolar cell layer. These results suggest that
loss of sympathetic innervation may cause significant changes to the physiology
of the choroid.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15996624 [PubMed - indexed for MEDLINE]

1868: Biochem Biophys Res Commun. 2005 Aug 19;334(1):245-53.

Erratum in:
    Biochem Biophys Res Commun. 2005 Dec 2;337(4):1353.

Protection from oxidative stress by methionine sulfoxide reductases in RPE cells.

Sreekumar PG, Kannan R, Yaung J, Spee CK, Ryan SJ, Hinton DR.

Arnold and Mabel Beckman Macular Research Center, Doheny Eye Institute, Keck
School of Medicine of the University of Southern California, Los Angeles, CA
90033, USA.

We investigated the role of methionine sulfoxide reductases (Msrs) in
oxidant-stress-induced cell death in retinal pigmented epithelial (RPE) cells. In
RPE cells exposed to varying doses of H(2)O(2), gene expression of MsrA and
hCBS-1 (the human analog of MsrB2) increased in a dose-dependent and
time-dependent manner with maximal increase with 150 microM H(2)O(2) in 24h.
H(2)O(2) treatment resulted in the generation of reactive oxygen species and
activation of caspase 3. Confocal microscopic and protein analysis showed an
increase in MsrA expression in cytosol and mitochondria. Silencing of MsrA
resulted in caspase 3 induction and accentuated cell death from H(2)O(2). Focal, 
strong immunoreactivity for MsrA was observed in sub-RPE macular drusen from
patients with age-related macular degeneration. In summary, our data show that
MsrA and hCBS-1 are up-regulated in oxidative stress to counteract injury to RPE.

Publication Types: 
    Comparative Study
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15993845 [PubMed - indexed for MEDLINE]

1869: Am J Ophthalmol. 2005 Aug;140(2):251-5.

Regression of serous macular detachment after intravitreal triamcinolone
acetonide in patients with diabetic macular edema.

Ozdemir H, Karacorlu M, Karacorlu SA.

Istanbul Retina Institute Inc, Istanbul, Turkey.

PURPOSE: To evaluate the effect of intravitreal triamcinolone acetonide on serous
macular detachment in eyes with diabetic macular edema. DESIGN: Interventional
case series. METHODS: The study population comprised twenty eyes of 20 patients
with diabetic macular edema (12 men, eight women), aged 48 to 76 years. The
eligibility criteria for this study included clinically detectable macular edema 
in which the presence of serous macular detachment was documented by optical
coherence tomography. After intravitreal injection of 0.1 ml (4 mg) triamcinolone
acetonide, visual and anatomic responses were observed. RESULTS: In all eyes,
after an injection of triamcinolone acetonide, macular edema and serous macular
detachment regressed. At 3 and 6 months, macular edema and serous macular
detachment had recurred in eight (40%) and nine eyes (45%), respectively.
Patients with recurrence were re-treated. No eyes lost vision at 1 month, and all
eyes showed improvement. At 3 months, no eyes had lost vision from baseline, and 
17 eyes (85%) showed improvement. At 6 months, again no eyes had lost vision from
baseline, and 16 eyes (80%) maintained improved visual acuity. CONCLUSION:
Intravitreal triamcinolone acetonide is an effective treatment for serous macular
detachment in patients with diabetic macular edema.

Publication Types: 
    Clinical Trial

PMID: 15992756 [PubMed - indexed for MEDLINE]

1870: Am J Ophthalmol. 2005 Aug;140(2):200-6.

Characterization of macular edema from various etiologies by optical coherence
tomography.

Catier A, Tadayoni R, Paques M, Erginay A, Haouchine B, Gaudric A, Massin P.

Department of Ophthalmology, Hôpital Lariboisière, Assistance publique-Hôpitaux
de Paris, Université Paris 7, Paris, France.

PURPOSE: To use optical coherence tomography (OCT) to characterize the
intraretinal changes associated with macular edema (ME) according to its
etiology. DESIGN: Observational case series. METHODS: Seventy-eight eyes of 78
patients with ME were examined retrospectively by OCT, using the Humphrey 2000
OCT system (Humphrey Co., San Leandro, California). ME etiologies were diabetic
retinopathy (27 cases), central retinal vein occlusion (18 cases), pseudophakia
(15 cases), posterior uveitis (10 cases), and retinitis pigmentosa (eight cases).
Macular thickness was measured using OCT mapping software. It was correlated with
logarithmic visual acuity. RESULTS: In 72 of 78 cases (92%), ME was located in
the outer retinal layers. Serous retinal detachment was present in 29 of 78 cases
(37%). It was most frequent in central retinal vein occlusion (10 of 18 cases,
56%). There were no significant differences in visual acuity (P = .26) or macular
thickness (P = .95) whether or not serous retinal detachment was combined with
ME. The posterior hyaloid was partially detached in 17 of 78 cases (22%) of
overall cases. Serous retinal detachment did not correlate with partial posterior
hyaloid detachment (P = .6). Mean macular thickness ranged from 506 microm in
central retinal vein occlusion to 373 microm in retinitis pigmentosa. Visual
acuity correlated with macular thickness in diabetic retinopathy (R = 0.55; P =
.0027) and pseudophakia cases (R = 0.66; P = .016). CONCLUSIONS: OCT
characterized the retinal morphologic changes associated with ME, especially the 
vitreomacular relationship and sub-clinical serous macular detachment. This
detachment did not correlate with poor visual acuity. Macular thickening only
correlated with visual loss in diabetic retinopathy and pseudophakia.

PMID: 15992752 [PubMed - indexed for MEDLINE]

1871: Appl Nurs Res. 2005 May;18(2):110-6.

Driving strategies used by older adults with macular degeneration: assessing the 
risks.

Moore LW, Miller M.

Department of Nursing, Xavier University, Cincinnati, OH 45207-7351, USA.
moore@xavier.edu

Older adults with macular degeneration use multiple driving strategies. A
secondary analysis focused on driving strategies was conducted on data from two
studies that had explored the experience of visual impairment in older adults
diagnosed with macular degeneration. Findings revealed 24 driving strategies.
Twelve categories emerged, reflecting two themes: (1) strategies used while
performing the task of driving and (2) strategies used to continue driving. By
understanding these strategies, nurses can assess the conditions under which
these older adults drive and the risks taken. Findings guide nurses to counsel
and educate older adults regarding driving.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15991110 [PubMed - indexed for MEDLINE]

1872: Korean J Ophthalmol. 2005 Jun;19(2):122-7.

Intraocular pressure elevation after intravitreal triamcinolone acetonide
injection.

Park HY, Yi K, Kim HK.

Department of Ophthalmology, Kangnam Sacred Heart Hospital, College of Medicine, 
Hallym University, Seoul, Korea.

PURPOSE: This study investigated firstly the change of intraocular pressure (IOP)
after injection of intravitreal triamcinolone acetonide (IVTA) for the treatment 
of macular edema and secondly the factors that influence these changes. METHODS: 
A prospective, non-comparative study was performed in 60 patients at Kangnam
Sacred Heart Hospital from October 2003 to September 2004. All the patients
received 4-mg IVTA injection. RESULTS: Mean IOP was elevated from the day after
injection and peaked at 20.5 mmHg after 2 months (p=0.000). Twenty-six eyes
(43.3%) showed significant IOP elevation. IOP was not controlled despite full
glaucoma medication in 7 (11.7%) eyes. Two eyes underwent filtering surgery.
Younger age was a statistically significant predictive factor for IOP elevation
(p=0.009). CONCLUSIONS: In this study, patients who needed filtering surgery
developed an IOP spike within one week after the injection. Therefore, clinicians
should consider checking IOP at the end of the first week. Furthermore, greater
cautions is mandatory with relatively younger patients.

PMID: 15988928 [PubMed - indexed for MEDLINE]

1873: Hum Mol Genet. 2005 Aug 1;14(15):2257-64. Epub 2005 Jun 29.

Meta-analysis of genome scans of age-related macular degeneration.

Fisher SA, Abecasis GR, Yashar BM, Zareparsi S, Swaroop A, Iyengar SK, Klein BE, 
Klein R, Lee KE, Majewski J, Schultz DW, Klein ML, Seddon JM, Santangelo SL,
Weeks DE, Conley YP, Mah TS, Schmidt S, Haines JL, Pericak-Vance MA, Gorin MB,
Schulz HL, Pardi F, Lewis CM, Weber BH.

Department of Medical and Molecular Genetics, Guy's, King's and St Thomas' School
of Medicine, King's College London, London SE1 9RT, UK.
sheila.fisher@genetics.kcl.ac.uk

A genetic contribution to the development of age-related macular degeneration
(AMD) is well established. Several genome-wide linkage studies have identified a 
number of putative susceptibility loci for AMD but only a few of these regions
have been replicated in independent studies. Here, we perform a meta-analysis of 
six AMD genome screens using the genome-scan meta-analysis method, which allows
linkage results from several studies to be combined, providing greater power to
identify regions that show only weak evidence for linkage in individual studies. 
Results from non-parametric analysis for a broad AMD clinical phenotype
(including two studies with quantitative traits) were extracted. For each study, 
120 genomic bins of approximately 30 cM were defined and ranked according to
maximum evidence for linkage within each bin. Bin ranks were weighted according
to study size and summed across all studies; the summed rank (SR) for each bin
was assessed empirically for significance using permutation methods. A high SR
indicates a region with consistent evidence for linkage across studies. The
strongest evidence for an AMD susceptibility locus was found on chromosome 10q26 
where genome-wide significant linkage was observed (P=0.00025). Several other
regions met the empirical significance criteria for bins likely to contain linked
loci including adjacent pairs of bins on chromosomes 1q, 2p, 3p and 16. Several
of the regions identified here showed only weak evidence for linkage in the
individual studies. These results will help prioritize regions for future
positional and functional candidate gene studies in AMD.

Publication Types: 
    Meta-Analysis
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15987700 [PubMed - indexed for MEDLINE]

1874: Invest Ophthalmol Vis Sci. 2005 Jul;46(7):2561-6.

Thrombin inhibitor reduces leukocyte-endothelial cell interactions and vascular
leakage after scatter laser photocoagulation.

Musashi K, Kiryu J, Miyamoto K, Miyahara S, Katsuta H, Tamura H, Hirose F,
Yoshimura N.

Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School
of Medicine, Kyoto, Japan.

PURPOSE: Macular edema is one of the most serious adverse effects after retinal
scatter laser photocoagulation. It has been suggested that the inflammatory
reaction after photocoagulation may be involved in the pathogenesis of macular
edema. This study was designed to evaluate quantitatively the inhibitory effects 
of argatroban, a direct thrombin inhibitor, on leukocyte-endothelial cell
interactions and vascular permeability after scatter laser photocoagulation.
METHODS: Argon laser photocoagulation was performed in one half of the retina in 
pigmented male rats (n = 114). Argatroban was administered just before scatter
laser photocoagulation. In the other half of the retina, AO leukocyte
fluorography was used to evaluate in vivo leukocyte rolling along the retinal
vein and accumulation in the retinal capillary bed. The expressions of P-selectin
and intercellular adhesion molecule (ICAM)-1 were evaluated by reverse
transcription-polymerase chain reaction. Retinal vessel permeability was
quantified by using fluorescein isothiocyanate (FITC)-conjugated dextran.
RESULTS: Scatter laser photocoagulation caused significant inflammatory
leukocyte-endothelial cell interactions in the nonphotocoagulated half of the
retina. Treatment with argatroban suppressed leukocyte-endothelial cell
interactions. The maximum number of rolling and accumulating leukocytes was
reduced by 46.6% (P < 0.01) and 51.4% (P < 0.01), respectively. The expression of
P-selectin and ICAM-1 mRNA was suppressed significantly in the argatroban-treated
retinas (P < 0.05). Retinal vascular permeability was also suppressed
significantly (P < 0.05). CONCLUSIONS: Argatroban suppressed
leukocyte-endothelial cell interactions and blood-retinal barrier breakdown after
scatter laser photocoagulation, suggesting that argatroban prevents postlaser
macular edema.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15980248 [PubMed - indexed for MEDLINE]

1875: Invest Ophthalmol Vis Sci. 2005 Jul;46(7):2313-6.

Overnight thickness variation in diabetic macular edema.

Larsen M, Wang M, Sander B.

Department of Ophthalmology, Herlev Hospital, University of Copenhagen, Denmark. 
mla@dadlnet.dk

PURPOSE: To study the evening-to-morning variation in retinal thickness in
patients with fovea-involving diabetic macular edema. METHODS: Twelve eyes in 12 
patients aged 39 to 78 years (mean, 57) with fovea-involving diabetic macular
edema and 14 eyes in 7 healthy volunteers aged 30 to 70 years (mean, 57) were
examined by optical coherence tomography, in the evening and in the morning after
> or =6 hours of sleep in the recumbent position in darkness followed by 0.5 hour
wakefulness in the same position in room light with both eyes open. RESULTS: In
patients with diabetic macular edema, macular thickness increased overnight, from
316 +/- 72 microm in the evening to 336 +/- 81 microm in the morning (P = 0.003).
Visual acuity decreased from a mean of 41 ETDRS letters (Early Treatment of
Diabetic Retinopathy Study; range, 4-61) in the evening, to a mean of 36 letters 
(range, 2-60) in the morning (P = 0.03). No overall change was found in mean
arterial blood pressure (MABP; P = 0.48), blood glucose (P = 0.25), or corneal
thickness (P = 0.26). The overnight change in macular thickness correlated
directly with the change in MABP (r = 0.65, P = 0.03) but not with baseline MABP 
or blood glucose. The overnight increase in retinal thickness remained
significant after statistical adjustment for the effect of arterial blood
pressure (P = 0.002). Healthy subjects demonstrated no significant change in any 
parameter. CONCLUSIONS: In fovea-involving diabetic macular edema, a reduction in
visual acuity accompanies overnight retinal thickening, the magnitude being
related to the nocturnal change in blood pressure. The results indicate that
deficient regulation of retinal capillary filling pressure promotes edema, but
the bulk of the overnight increase in macular edema is caused by other
mechanisms, of which postural variation in venous blood pressure and increased
retinal metabolism in the dark merit further study.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15980216 [PubMed - indexed for MEDLINE]

1876: Neurobiol Aging. 2006 Jul;27(7):983-93. Epub 2005 Jun 23.

Mitochondrial alterations of retinal pigment epithelium in age-related macular
degeneration.

Feher J, Kovacs I, Artico M, Cavallotti C, Papale A, Balacco Gabrieli C.

Opthalmic Neuroscience Program, Department of Ophthalmology, University of Rome
La Sapienza, Via Lombardia, 23/c, 00187 Rome, Italy. j.feher@libero.it

Mitochondrial dysfunctions have been implicated in the pathophysiology of several
age-related diseases including age-related macular degeneration (AMD), a
progressive neurodegenerative disease affecting primarily the retinal pigment
epithelium (RPE). The aims of our electron microscopic and morphometric studies
were to reveal qualitative and quantitative alterations of mitochondria in human 
RPE from AMD and from age- and sex-matched controls. With increasing age a
significant decrease in number and area of mitochondria, as well as loss of
cristae and matrix density were found in both AMD and control specimens. These
decreases were significantly greater in AMD than in normal aging. Alterations of 
mitochondria were accompanied by proliferation of peroxisomes and lipofuscin
granules in both AMD and control specimens, although the difference between
groups was significant only for peroxisomes. Unexpectedly, morphometric data
showed that the RPE alterations seen in AMD may also develop in normal aging,
10-15 years after appearing in AMD patients. These findings suggest that (i) the 
severity of mitochondrial and peroxisomal alterations are different between AMD
and normal aging, and (ii) the timing of damage to RPE may be critical for the
development of AMD. We conclude that besides the well-documented age-related
changes in mitochondrial DNA, alterations of mitochondrial membranes may also
play a role in the pathogenesis of AMD. These membranes could be a new target for
treatment of AMD and other age-related diseases.

PMID: 15979212 [PubMed - indexed for MEDLINE]

1877: Exp Eye Res. 2005 Jul;81(1):97-102.

Dynamic contrast enhanced MRI in patients with diabetic macular edema: initial
results.

Trick GL, Liggett J, Levy J, Adamsons I, Edwards P, Desai U, Tofts PS, Berkowitz 
BA.

Department of Ophthalmology, Henry Ford Hospital, Detroit, MI 48201, USA.
gltrick1@aol.com

To assess the ability of dynamic contrast enhanced magnetic resonance imaging
(DCE-MRI) to detect blood retinal barrier (BRB) damage in patients with diabetic 
macular edema (DME). DCE-MRI with 0.1 mmol Gd-DTPA was used to measure BRB
permeability in 10 healthy and visually normal subjects and eight patients with
DME, including five patients with non-clinically significant (NCS) DME and three 
patients with clinically significant (CS) DME. For each subject, the enhancement 
of the MRI signal intensity in the pre-macular vitreous was measured as a
function of time following contrast injection. A linear regression analysis was
performed on each subject and the slopes of the contrast enhancement functions
were compared. The DCE-MRI procedure was well tolerated by all 18 subjects.
However, in four subjects, excessive eye movements resulted in spurious results. 
Consequently, 78% (14/18) of the subjects provided usable data. The mean slope of
the control group was not significantly (p>0.05) different from zero (i.e. signal
intensity in the pre-macular vitreous space was constant as a function of time
post-contrast injection). For the diabetic patients, the average slope of the
contrast enhancement function was significantly greater than in the control group
(p<0.01). Furthermore, for both diabetic sub-groups, the average slopes were
greater (p<0.05) than that for the control group but not significantly (p>0.05)
different from each other. This 'proof of concept' study demonstrated that
DCE-MRI detects passive leakage through the BRB in diabetic patients with either 
NCS or CS macular edema. In future studies, DCE-MRI may be useful for early
quantitative evaluation of drug treatment effects in patients with DME.

Publication Types: 
    Evaluation Studies

PMID: 15978260 [PubMed - indexed for MEDLINE]

1878: Exp Eye Res. 2005 Jul;81(1):38-47.

Blood-derived macrophages infiltrate the retina and activate Muller glial cells
under experimental choroidal neovascularization.

Caicedo A, Espinosa-Heidmann DG, Piña Y, Hernandez EP, Cousins SW.

Bascom Palmer Eye Institute, University of Miami School of Medicine, 1638 NW 10th
Avenue, Miami, FL 33136, USA.

Inflammation is a major mechanism in the pathogenesis of age-related macular
degeneration, the most important cause of blindness in the elderly. Previous
studies have focused on the role of macrophages in regulating the growth of
pathological new vessels over the retina, called choroidal neovascularization
(CNV). However, no research has been done to evaluate the role of inflammation as
a mechanism of vision loss and retinal degeneration in the retina underlying CNV.
In other neuropathological conditions, hematogenous macrophages and/or resident
microglia contribute to neurodegeneration. We have combined laser-induced CNV in 
mice and bone marrow transplantation with GFP-labeled bone marrow to determine
the relative role of recruited blood-derived macrophages versus resident
microglia in the retina associated with CNV. Using these chimeric mice, we have
found that many GFP-labeled cells infiltrated the retina underlying CNV but not
the retina unaffected by CNV. Immunostaining for the cell adhesion molecules VCAM
1, ICAM 1, and PECAM was strongly upregulated in retinal blood vessels under CNV.
All GFP-labeled cells were immunoreactive for the macrophage marker F4/80. Most
(70%) of the F4/80 immunoreactive cells were GFP-labeled under CNV. The density
of resident microglia did not increase. Most GFP-labeled cells were found in
close proximity to activated Muller cells. Depleting circulating macrophages with
clodronic acid diminished the density of F4/80 immunoreactive cells as well as
the density of pERK immunoreactive Muller cells in the retina under CNV. Thus,
recruitment of blood-derived macrophages more than resident microglia seems to be
associated with CNV.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15978253 [PubMed - indexed for MEDLINE]

1879: BMC Ophthalmol. 2005 Jun 22;5:15.

The combination of intravitreal triamcinolone and phacoemulsification surgery in 
patients with diabeticfoveal oedema and cataract.

Habib MS, Cannon PS, Steel DH.

Sunderland Eye Infirmary, Queen Alexandra Road, SR2 9HP, UK.
Maged.Habib@chs.northy.nhs.uk

BACKGROUND: The management of diabetic patients with refractory macular oedema or
patients with no adequate pre-operative view to administer laser treatment
provide a challenge to the ophthalmologist. We wished to assess the use, safety
and effect of intravitreal triamcinolone injection at the time of cataract
surgery in patients with diabetic foveal oedema and sight limiting lens
opacities. METHOD: This was a longitudinal non-randomised prospective pilot study
in 18 eyes (12 patients). All patients had visually significant lens opacities
and either persistent diabetic foveal oedema unresponsive to laser
treatment-group A, or foveal oedema with no adequate pre-operative view for laser
treatment- group B. The cataract surgery was carried out under full aseptic
technique using a self-sealing temporal incision and a foldable acrylic lens.
Intravitreal triamcinolone was given infratemporally pars plana at the completion
of the cataract surgery. The patients were reviewed at day 5, 2 weeks, 2 months
and then every 3 months as required. The Wilcoxin matched-pairs test was used to 
assess the significance of the improvement in visual acuity at 2 months. RESULTS:
Twelve patients with a total of 18 eyes were included in the study. There were 10
patients (15 eyes) in group A and 3 patients (3 eyes) in group B. Preoperatively 
16 of the 18 eyes had a visual acuity of 6/24 or worse. Postoperatively 83% of
patients had completely dry foveae at 2 weeks. Best-corrected visual acuities at 
two months review ranged from 6/6 to CF with 9 eyes (50%) achieving 6/12 or
better (7 eyes (47%) in group A and 2 eyes (67%) in group B). Three eyes had no
recorded improvement in visual acuity, but no eyes had deterioration in acuity.
The improvement in visual acuity was significant at p = 0.001. There were no
significant sight threatening complications. CONCLUSION: Intravitreal
triamcinolone has been shown to lead to an improvement in macular oedema and
visual improvement in diabetic patients not undergoing cataract surgery but has
not, to our knowledge, been previously used in a study like this one.We suggest
that intravitreal injection at the time of cataract surgery could be carried out 
safely with encouraging visual outcomes in patients with diabetic foveal oedema
and cataract.

PMID: 15972106 [PubMed - indexed for MEDLINE]

1880: Curr Med Res Opin. 2005 May;21(5):705-13.

Verteporfin therapy in combination with triamcinolone: published studies
investigating a potential synergistic effect.

Kaiser PK.

Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
pkkaiser@mac.com

Evidence from randomized, placebo-controlled, double-masked studies has
demonstrated that verteporfin (Visudyne) therapy is effective in reducing the
risk of visual acuity loss in selected groups of patients with choroidal
neovascularization (CNV) due to age-related macular degeneration (AMD). Pilot
studies of intravitreal triamcinolone acetonide monotherapy revealed promising
results in patients with CNV due to AMD, but the visual acuity outcomes in a
randomized, controlled study were lower than anticipated. Recently, however,
there has been growing interest in the adjunctive use of triamcinolone to improve
visual acuity and reduce regrowth of CNV in patients receiving verteporfin
therapy. This review article surveys the currently available evidence, based on a
Medline search covering the years 1980-2005 and abstracts from recent scientific 
meetings. A number of small-scale, uncontrolled pilot studies have indicated that
the combination of triamcinolone acetonide with verteporfin therapy may be
beneficial. Evidence is now needed from randomized, controlled studies to
determine whether the potential benefits of combination therapy outweigh the
possible risks of increased intraocular pressure, endophthalmitis, and
progression of cataract that have been observed in trials of triamcinolone
monotherapy.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 15969870 [PubMed - indexed for MEDLINE]

1881: Br J Ophthalmol. 2005 Jul;89(7):874-8.

Classification of abnormal fundus autofluorescence patterns in the junctional
zone of geographic atrophy in patients with age related macular degeneration.

Bindewald A, Schmitz-Valckenberg S, Jorzik JJ, Dolar-Szczasny J, Sieber H,
Keilhauer C, Weinberger AW, Dithmar S, Pauleikhoff D, Mansmann U, Wolf S, Holz
FG.

Department of Ophthalmology, University of Bonn, Ernst-Abbe-Strasse 2, D-53127
Bonn, Germany.

AIM: To describe and classify patterns of abnormal fundus autofluorescence (FAF) 
in the junctional zone of geographic atrophy (GA) in patients with age related
macular degeneration. METHODS: Digital FAF images were recorded in 164 eyes of
107 patients using a confocal scanning laser ophthalmoscope (cSLO; excitation 488
nm, detection above 500 nm) as part of a prospective multicentre natural history 
study (FAM Study). FAF images were obtained in accordance with a standardised
protocol for digital image acquisition and generation of mean images after
automated alignment. RESULTS: Image quality was sufficient for classification of 
FAF patterns in 149 eyes (90.9%) with lens opacities being the most common reason
for insufficient image quality. Abnormal FAF outside GA in 149 eyes was
classified into four patterns: focal (12.1%), banded (12.8%), patchy (2.0%), and 
diffuse (57.0%), whereby 12.1% had normal background FAF in the junctional zone. 
In 4% there was no predominant pattern. The diffuse pattern was subdivided into
four groups including reticular (4.7%), branching (27.5%), fine granular (18.1%),
and fine granular with peripheral punctate spots (6.7%). CONCLUSIONS: Different
phenotypic patterns of abnormal FAF in the junctional zone of GA can be
identified with cSLO FAF imaging. These distinct patterns may reflect
heterogeneity at a cellular and molecular level in contrast with a non-specific
ageing process. A refined phenotypic classification may be helpful to identify
prognostic determinants for the spread of atrophy and visual loss, for
identification of genetic risk factors as well as for the design of future
interventional trials.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 15965170 [PubMed - indexed for MEDLINE]

1882: Br J Ophthalmol. 2005 Jul;89(7):864-70.

"Light" versus "classic" laser treatment for clinically significant diabetic
macular oedema.

Bandello F, Polito A, Del Borrello M, Zemella N, Isola M.

Department of Ophthalmology, University of Udine, P le S Maria della
Misericordia, 33100 Udine, Italy. francesco.bandello@uniud.it

AIM: To compare the effectiveness of "light" versus "classic" laser
photocoagulation in diabetic patients with clinically significant macular oedema 
(CSMO). METHODS: A prospective randomised pilot clinical trial in which 29 eyes
of 24 diabetic patients with mild to moderate non-proliferative diabetic
retinopathy (NPDR) and CSMO were randomised to either "classic" or "light" Nd:YAG
532 nm (frequency doubled) green laser. "Light" laser treatment differed from
conventional ("classic") photocoagulation in that the energy employed was the
lowest capable to produce barely visible burns at the level of the retinal
pigment epithelium. Primary outcome measure was the change in foveal retinal
thickness as measured by optical coherence tomography (OCT); secondary outcomes
were the reduction/elimination of macular oedema on contact lens biomicroscopy
and fluorescein angiography, change in visual acuity, contrast sensitivity, and
mean deviation in the central 10 degrees visual field. Examiners were masked to
patients' treatment. RESULTS: 14 eyes were assigned to "classic" and 15 were
assigned to "light" laser treatment. At 12 months, seven (50%) of 14 eyes treated
with "classic" and six (43%) of 14 eyes treated with "light" laser had a decrease
of foveal retinal thickness on OCT (p = 0.79). A comparison of
reduction/elimination of oedema, visual improvement, visual loss, change in
contrast sensitivity, and mean deviation in the central 10 degrees showed no
statistical difference between the groups at 12 months (p>0.05 for all groups).
CONCLUSIONS: This study suggests that "light" photocoagulation for CSMO may be as
effective as "classic" laser treatment, thus supporting the rationale for a
larger equivalence trial.

Publication Types: 
    Case Reports
    Clinical Trial
    Randomized Controlled Trial

PMID: 15965168 [PubMed - indexed for MEDLINE]

1883: Am J Ophthalmol. 2005 Jul;140(1):107-16.

Occult chorioretinal anastomosis in age-related macular degeneration: a
prospective study by optical coherence tomography.

Costa RA, Calucci D, Paccola L, Jorge R, Cardillo JA, Castro JC, Scott IU.

Unidade de Diagnóstico Avançado e Tratamento (U.D.A.T.), Retina Diagnostic and
Treatment Division, Hospital de Olhos de Araraquara, Araraquara-SP, Brazil.
roger.retina@globo.com

PURPOSE: To investigate macular optical coherence tomography (OCT) features in
patients with chorioretinal anastomosis (CRA) and drusen, as well as their
correlation with the Gass occult-CRA hypothesis. DESIGN: Prospective
observational case series. METHODS: setting: Tertiary ophthalmic referral center.
study population: All patients with biomicroscopic evidence of CRA and drusen
consecutively evaluated between February 2003 and March 2004. observation
procedures: Third-generation OCT evaluation and stereoscopic angiographic
studies. main outcome measures: Macular morphologic features at baseline and at
12 weeks. RESULTS: Twenty eyes with CRA and drusen were identified in 11
patients, seven women (63.6%) and four men (36.4%) ranging in age from 69 to 82
years (median, 79 years). Focal elevation of the retinal pigment epithelium was
seen in eyes with stage 1 (pre-clinical) CRA. Small hyperreflective signals at
the level of the elevated retinal pigment epithelium were seen in stage 2 CRA. In
stage 3 CRA, a hyperreflective "mound" at the level of the elevated retinal
pigment epithelium was seen in association with a thickened retina. In stage 4
CRA sub-retinal pigment epithelium fluid accumulation was present, and complete
disorganization of the macular region was observed in stage 5 CRA. Macular
changes were observed in eight eyes (40%) at follow-up, with all but one CRA
lesion progressing one stage. CONCLUSION: Morphologic features and changes
demonstrated by OCT suggest that fibrovascular detachment of the retinal pigment 
epithelium followed by development of occult CRA are the initial events occurring
in eyes with CRA in age-related macular degeneration. Our findings may support
the evolutionary CRA staging system proposed by Gass.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15963937 [PubMed - indexed for MEDLINE]

1884: Clin Chim Acta. 2005 Jul 1;357(1):34-42.

Lycopene but not lutein nor zeaxanthin decreases in serum and lipoproteins in
age-related macular degeneration patients.

Cardinault N, Abalain JH, Sairafi B, Coudray C, Grolier P, Rambeau M, Carré JL,
Mazur A, Rock E.

Unité des Maladies Métaboliques et Micronutriments, INRA Clermont-Ferrand/Theix, 
63122 St Genes Champanelle, France. Nicolas.Cardinault@clermont.inra.fr

BACKGROUND: Epidemiological studies have established that a low serum
concentration of carotenoids was associated with risk of Age-Related Macular
Degeneration (ARMD). The aim of this study was to determine carotenoid levels in 
serum and in different lipoprotein fractions in patients diagnosed for ARMD and
in matched control group. METHOD: Thirty-four ARMD patients and 21 control
subjects from Brest area (France) have been included to this study. Lipoproteins 
have been separated from serum by gradient density ultracentrifugation. We
measured concentration of carotenoids and tocopherols in serum and in different
lipoprotein fractions by HPLC. RESULTS: No difference was observed between ARMD
patients and control subjects in total serum carotenoids. Individual carotenoid
levels showed that only lycopene was decreased significantly in serum, LDL and
HDL fractions in patients (P<0.05). Concentrations in serum and lipoparticle
fractions of lutein and zeaxanthin, the major pigments present in macula were not
modified between both groups. CONCLUSIONS: Lycopene, as liposoluble antioxidant
nutrient, is the only carotenoid altered in ARMD patients. It cannot be excluded 
that this effect is related to different dietary habits, but we hypothesise that 
lower lycopene status could result also from specific antioxidant protection of
lutein and zeaxanthin by lycopene.

PMID: 15963792 [PubMed - indexed for MEDLINE]

1885: Biochem Biophys Res Commun. 2005 Aug 5;333(3):679-85.

Functional VEGF C-634G polymorphism is associated with development of diabetic
macular edema and correlated with macular retinal thickness in type 2 diabetes.

Awata T, Kurihara S, Takata N, Neda T, Iizuka H, Ohkubo T, Osaki M, Watanabe M,
Nakashima Y, Inukai K, Inoue I, Kawasaki I, Mori K, Yoneya S, Katayama S.

Division of Endocrinology and Diabetes, Department of Medicine, Saitama Medical
School, Saitama, Japan. awata@saitama-med.ac.jp

Since vascular endothelial growth factor (VEGF) has a strong effect on induction 
of vascular permeability, VEGF is an attractive candidate gene for development of
diabetic macular edema (ME). Among the 378 patients with type 2 diabetes studied,
203 patients had no retinopathy, 93 had non-proliferative diabetic retinopathy
(NPDR), and 82 had proliferative diabetic retinopathy (PDR). ME was present in 16
patients with NPDR and 47 patients with PDR. We genotyped three VEGF
polymorphisms: C-2,578A, G-1,154A, and C-634G. Genotype and allele distribution
of C-634G, but not C-2,578A or G-1,154A, were significantly different between
patients with and without diabetic retinopathy. Logistic regression analysis
revealed that the C-634G genotype was a risk factor for DR (p = 0.002), and
furthermore for ME (p = 0.047), independently from severity of DR, with the -634C
allele increasing the risk. Macular thickness measured by optical coherence
tomography was correlated with the C-634G genotype, with the trend increasing
with the presence of more -634C alleles (p = 0.006). Stepwise regression analysis
showed that duration of diabetes and presence of the C-634G genotype were
independent predictors of macular thickness. In addition, basic transcriptional
activity levels associated with the -634C allele were greater compared to those
seen with the -634G allele in human glioma and lymphoblastic T-lymphocyte cells. 
These results demonstrate that the VEGF C-634G polymorphism is a genetic risk
factor for ME as well as DR.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15963467 [PubMed - indexed for MEDLINE]

1886: Doc Ophthalmol. 2004 Nov;109(3):249-53.

Morphological and functional changes of the macula after vitrectomy and creation 
of posterior vitreous detachment in eyes with diabetic macular edema.

Yamamoto S, Yamamoto T, Ogata K, Hoshino A, Sato E, Mizunoya S.

Department of Ophthalmology and Visual Science, Chiba University Graduate School 
of Medicine, Chiba, Japan. shuyama@faculty.chiba-u.jp

The purpose of this study was to determine the morphological and functional
changes in the macula after pars plana vitrectomy with the creation of a
posterior vitreous detachment in eyes with diabetic macular edema (DME). A simple
posterior vitreous detachment was created during pars plana vitrectomy
accompanied by simultaneous cataract surgery in 19 eyes of 17 patients with DME. 
The visual acuity (log MAR units), multifocal electroretinograms (mfERGs), and
optical coherence tomographically (OCT)-determined foveal thickness were
determined preoperatively and at 6 months postoperatively. The median
preoperative log MAR visual acuity was 0.7 (20/100; range, 0.3-1.1), and it
improved significantly to 0.4 (20/50; range, 0.15-1.0) postoperatively (p =
0.016). The median foveal thickness was 510 (range, 194-800) microm
preoperatively and was significantly reduced to 201 (range, 60-631) microm
postoperatively (p =0.0002). The median of response density of the mfERGs in the 
macular area was 6.3 nV/ deg2 (range, 2.8-14.8) preoperatively, and 6.1 nV/deg2
(range, 2.4-14.3) postoperatively, a non-significant change (p = 0.27). The
median of peak latency of the macular response was 30.0 ms (range, 25.0-44.2)
preoperatively and it decreased significantly to 28.3 ms (range, 26.7-35.0)
postoperatively (p = 0.003). In conclusion, vitrectomy with the creation of a PVD
in eyes with DME improved the visual acuity and foveal thickness significantly.
In addition, a decrease of the peak latency of the macular mfERGs suggested an
improvement of the physiological function of the macula although the amplitude of
the mfERGs was not changed significantly.

PMID: 15957610 [PubMed - indexed for MEDLINE]

1887: Ophthalmic Surg Lasers Imaging. 2005 May-Jun;36(3):258-60.

Treatment of juxtafoveal choroidal neovascularization with photodynamic therapy
using verteporfin in eyes with age-related macular degeneration.

Hariprasad SM, Shah GK.

Barnes Retina Institute, 1600 South Brentwood Blvd., 8th Floor, St. Louis, MO
63144, USA.

To report the results of treating juxtafoveal choroidal neovascularization with
photodynamic therapy using verteporfin in eyes with age-related macular
degeneration. Seven patients with predominantly classic juxtafoveal choroidal
neovascularization were treated by photodynamic therapy using verteporfin. Three 
of the 7 patients had a gain in visual acuity and 2 had a stabilization of
vision. The remaining 2 patients had a decrease in visual acuity. Subfoveal
extension of the choroidal neovascularization was not observed in any patient and
all choroidal neovascularization lesions after treatment were found to be
nonperfused on fluorescein angiography. The encouraging results based on this
small pilot study suggest that photodynamic therapy should be considered for
treatment of select juxtafoveal choroidal neovascularization due to age-related
macular degeneration.

PMID: 15957487 [PubMed - indexed for MEDLINE]

1888: Ophthalmic Surg Lasers Imaging. 2005 May-Jun;36(3):237-9.

Resolution of advanced cystoid macular edema following photodynamic therapy for
choroidal hemangioma.

Shields CL, Materin MA, Marr BP, Mashayekhi A, Shields JA.

Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University,
Philadelphia, Pennsylvania 19107, USA.

A 45-year-old man was referred for 2 months of decreasing vision in his left eye.
His visual acuity was 20/200 secondary to a subtle juxtapapillary choroidal
hemangioma producing profound cystoid macular edema, with the affected retina
measuring 330 microns thick by optical coherence tomography. Due to the severe
cystoid macular edema, visual prognosis was judged to be poor. One month
following photodynamic therapy to the tumor using verteporfin, the cystoid
macular edema completely resolved, foveal anatomy returned to normal, optical
coherence tomography thickness was 179 microns, and visual acuity recovered to
20/25. Photodynamic therapy of choroidal hemangioma may be effective in resolving
associated cystoid macular edema and improving visual acuity.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 15957481 [PubMed - indexed for MEDLINE]

1889: Ophthalmic Surg Lasers Imaging. 2005 May-Jun;36(3):228-36.

Feasibility of screening for high-risk age-related macular degeneration with an
Internet-based automated fundus camera.

Zimmer-Galler IE, Zeimer R.

Johns Hopkins University School of Medicine, Wilmer Eye Institute, Baltimore,
Maryland 21287-9131, USA.

BACKGROUND AND OBJECTIVE: The objective of this pilot study was to determine
whether a new screening system, the DigiScope (EyeTel Imaging, Inc., Columbia,
MD), can detect the presence of age-related macular degeneration (AMD) at a level
requiring referral to an ophthalmologist for further evaluation and possible
treatment. PATIENTS AND METHODS: The DigiScope is an Internet-based
semi-automated digital imaging system designed to be in primary care physicians' 
offices. Forty-two eyes of 21 patients with different categories of AMD were
imaged with both the DigiScope and a standard color fundus camera. The imaging
capability of the two modalities was compared for identification of lesions
associated with AMD and classification into stages. RESULTS: There was good
agreement for low-risk lesions and excellent agreement for high-risk lesions.
Thirty-five of 36 eyes with intermediate or advanced disease were correctly
identified with DigiScope images. Choroidal neovascularization was identified in 
all cases with the DigiScope due to the presence of subretinal hemorrhage or
subretinal fibrosis. The DigiScope was found less capable of detecting subretinal
fluid than standard stereo fundus photographs. CONCLUSIONS: This pilot study
suggests that the DigiScope may be a useful screening tool for AMD.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15957480 [PubMed - indexed for MEDLINE]

1890: Arch Ophthalmol. 2005 Jun;123(6):774-82.

Progression of age-related macular degeneration: prospective assessment of
C-reactive protein, interleukin 6, and other cardiovascular biomarkers.

Seddon JM, George S, Rosner B, Rifai N.

Epidemiology Unit, Massachusetts Eye and Ear Infirmary, Boston, MA 02114, USA.

BACKGROUND: Age-related macular degeneration (AMD) and cardiovascular disease
share common risk factors. Inflammatory biomarkers, including C-reactive protein 
(CRP), interleukin 6 (IL-6), soluble tumor necrosis factor alpha receptor 2,
soluble intercellular and vascular adhesion molecules (intercellular adhesion
molecule 1 and vascular cell adhesion molecule 1), and lipid biomarkers,
including lipoprotein(a) and apolipoprotein B, have all been associated with
cardiovascular disease. We previously found an association between AMD and CRP in
a cross-sectional analysis, but the prospective relationships between AMD, CRP,
and the other cardiovascular disease markers are unknown. OBJECTIVE: To test the 
hypothesis that baseline cardiovascular disease biomarkers are associated with
subsequent increased risk for progression of AMD.Design, Setting, and
PARTICIPANTS: This prospective cohort study involved 251 participants aged 60
years and older who had some sign of nonexudative AMD and visual acuity of 20/200
or better in at least one eye at baseline. The AMD status was assessed by
standardized grading of fundus photographs, and stored fasting blood specimens
obtained at baseline were analyzed for levels of the various biomarkers. The
average follow-up time was 4.6 years. MAIN OUTCOME MEASURES: Relationship between
biomarkers and incidence rates of progression of AMD. RESULTS: Comparing the
highest quartile with the lowest quartile, CRP was associated with progression of
AMD, with a multivariate adjusted relative risk (RR) of 2.10 (95% confidence
interval [CI], 1.06-4.18; P for trend, .046) controlling for body mass index,
smoking, and other cardiovascular variables and a multivariate adjusted RR of
2.02 (95% CI, 1.00-4.04; P for trend, .06) controlling additionally for
antioxidant nutrients. Interleukin 6 was also related to progression of AMD, with
a multivariate adjusted RR of 1.81 (95% CI, 0.97-3.36; P for trend, .03).
Comparing the highest quartile with the lowest quartile, the effect estimates for
vascular cell adhesion molecule 1 (multivariate adjusted RR, 1.94) and
apolipoprotein B (adjusted RR, 1.39) were in the positive direction but were not 
statistically significant (P for trend, .08 and .24, respectively). The CRP and
IL-6 levels were both significantly related to higher body mass index and current
smoking. CONCLUSIONS: Higher levels of the systemic inflammatory markers CRP and 
IL-6 are independently associated with progression of AMD.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15955978 [PubMed - indexed for MEDLINE]

1891: Am J Ophthalmol. 2005 Jul;140(1):117-24.

Regional patterns of sight-threatening diabetic macular edema.

Browning DJ, Fraser CM.

Charlotte Eye, Ear, Nose, and Throat Associates, North Carolina, USA.
djbrowning@carolina.rr.com

PURPOSE: To define regional patterns of macular thickening in diabetic macular
edema (DME). DESIGN: Retrospective case series. METHODS: SETTING: Retina
practice. PATIENT POPULATION: Fifty-two normal eyes of 48 patients and 100 eyes
of 80 patients with DME. EXPERIMENTAL PROCEDURE: We measured retinal thickness
for nine zones and total macular volume using the 3.5-mm display of an optical
coherence tomograph (OCT). We determined the normal ranges of values for zones,
and then normal ranges of values for the difference in thickness between each
pair of zones, termed comparisons. main outcome measures: Frequencies of
increased zonal thickness, increased total macular volume, and abnormalities in
zonal comparisons. RESULTS: We found the following abnormalities: increased total
macular volume 49% (49/100), increased foveal zone thickness 46% (46/100),
increased inner parafoveal zone thickness (average 42.2% for the four zones), and
increased outer zone thickness (average 34.3% for the four zones). Abnormal
two-zone comparisons were found in 1027 of the 7200 possible comparisons (14.3%).
Of these abnormal comparisons, the fovea was thicker relative to another zone in 
26%; the four inner parafoveal zones were thicker relative to other zones in 8.7%
to 15.2% (average 13.0%); and the four outer zones were thicker relative to other
zones in 3.9% to 7.6% (average 6%). Eighty-eight percent (88/100) of the eyes
chosen on clinical grounds as needing focal laser photocoagulation were detected.
CONCLUSION: A broader concept of OCT abnormality, which includes abnormalities in
zonal relationships, may improve automated detection of DME compared with
clinical judgment.

PMID: 15953575 [PubMed - indexed for MEDLINE]

1892: Am J Ophthalmol. 2005 Jun;139(6):1073-9.

Comment in:
    Am J Ophthalmol. 2006 Jan;141(1):228; author reply 228-9.

Intereye difference in exudative age-related macular degeneration with minimally 
classic or occult subfoveal neovascularization after unilateral intravitreal
injection of triamcinolone acetonide.

Jonas JB, Spandau UH, Harder B, Vossmerbaeumer U, Kamppeter BA.

Department of Ophthalmology, Faculty of Clinical Medicine Mannheim, University
Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
Jost.Jonas@augen.ma.uni-heidelberg.de

PURPOSE: To report on visual outcome after intravitreal injection of
triamcinolone acetonide for exudative age-related macular degeneration. DESIGN:
Interventional comparative non-randomized clinical trial. METHODS: SETTING:
Institutional. PATIENTS: Twenty consecutive patients with bilateral exudative
age-related macular degeneration with minimally classic or occult subfoveal
neovascularisation. INTERVENTIONS: Unilateral intravitreal injection of about 20 
mg triamcinolone acetonide into the eye (study group) more severely affected or
showing more pronounced progression of the disease. Mean follow-up was 13.5 +/-
4.1 months. MAIN OUTCOME MEASURES: Visual acuity. RESULTS: In the study group,
visual acuity increased significantly (P < 0.001) from 0.96 +/- 0.32 logMar to a 
mean maximum of 0.76 +/- 0.30 logMar during follow-up. An increase in best visual
acuity during follow-up was found in 18 (90%) eyes. In 11 (55%) eyes and 7 (35%) 
eyes, respectively, best visual acuity increased by at least two Snellen lines
and three Snellen lines, respectively. In the control group, visual acuity at
baseline and the highest visual acuity measurements during follow-up did not vary
significantly (P = 0.90). Comparing study group and control group, visual acuity 
gain was significantly (P = 0.003) higher in the study group. Correspondingly,
the number of eyes with an increase in visual acuity (P = 0.002) and with an
increase in visual acuity higher > or = 3 lines compared to a loss of > or = 3
lines was significantly (P = 0.027) higher in the study group. CONCLUSIONS:
Intravitreal triamcinolone acetonide may temporarily increase visual acuity in
eyes with exudative age-related macular degeneration.

Publication Types: 
    Clinical Trial

PMID: 15953439 [PubMed - indexed for MEDLINE]

1893: Am J Ophthalmol. 2005 Jun;139(6):972-82.

Comment in:
    Am J Ophthalmol. 2005 Jun;139(6):1095-6.    Am J Ophthalmol. 2006 Jan;141(1):226; author reply 226-7.

Intravitreal versus retrobulbar injections of triamcinolone for macular edema
associated with branch retinal vein occlusion.

Hayashi K, Hayashi H.

Hayashi Eye Hospital, 4-7-13 Hakataekimae, Hakata-ku, Fukuoka 812-0011, Japan.
hayashi-ken@hayashi.or.jp

PURPOSE: To compare the short-term effect of intravitreal versus retrobulbar
injection of triamcinolone acetonide for the treatment of macular edema caused by
branch retinal vein occlusion. DESIGN: Randomized clinical trial. METHODS: Sixty 
eyes of 60 patients who had macular edema associated with branch retinal vein
occlusion were randomly assigned to receive a single intravitreal injection (4
mg) or repeated retrobulbar injections (40 mg, three times) of triamcinolone.
These injections (first injection in the retrobulbar group) were given
approximately 1 week after focal laser photocoagulation. Using optical coherence 
tomography, the central retinal (foveal) thickness and total macular volume were 
measured before and at 1 and 3 months after injection. Visual acuity, intraocular
pressure, and the incidence of reinjection were also examined. Fifty-two patients
(86.7%) completed the 3-month follow-up. RESULTS: The mean foveal thickness and
total macular volume decreased significantly after either intravitreal or
repeated retrobulbar triamcinolone injections. Foveal thickness and macular
volume were significantly less after intravitreal injection than after repeated
retrobulbar injections, although there had been no significant differences at
baseline. The percent reductions in foveal thickness and macular volume were also
greater after intravitreal injection than after retrobulbar injections.
Improvement in visual acuity was significantly better after intravitreal
injection than after the retrobulbar injections. The incidence of intraocular
pressure rise (to > or =20 mm Hg) was greater in the intravitreal group than in
the retrobulbar group, but this was readily controlled by the use of antiglaucoma
medications. After completion of the 3-month follow-up, 24 patients (46.2%)
underwent reinjection. The need for reinjections was significantly greater in the
retrobulbar group than in the intravitreal group (P = .0001). CONCLUSIONS: A
single intravitreal injection of triamcinolone is significantly more effective
than are repeated retrobulbar injections in reducing macular edema associated
with branch retinal vein occlusion, and leads to greater improvement in visual
acuity.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 15953425 [PubMed - indexed for MEDLINE]

1894: Eye. 2006 Jun;20(6):688-96. Epub 2005 Jun 10.

Mapping of central visual function by microperimetry and autofluorescence in
patients with Best's vitelliform dystrophy.

Jarc-Vidmar M, Popovic P, Hawlina M.

University Eye Clinic, Medical Centre, Ljubljana, Slovenia.
jarc-vidmar@MF.UNI-LJ.SI

PURPOSE: To evaluate retinal sensitivity and fixation patterns in patients with
Best's dystrophy by microperimetry (MP) and to correlate the results with static 
perimetry and retinal morphology seen by autofluorescence (AF). METHODS: Central 
10 degrees visual fields in 11 patients with Best's dystrophy (VA: 0.5+/-0.38)
were recorded by the Octopus M2 TOP program and by MP (MP1, Nidek Technologies). 
AF was recorded by HRA (Heidelberg Engineering). RESULTS: High correlation
(R=0.75, -0.76, -0.48) was found between static perimetry (MS, MD and CLV
indices) and MP. Based on MP and AF results, three groups of patients were
formed. Patients in the first two groups fixated inside the central nonuniform
hypo- and hyperfluorescent AF ring area, next to relative (Group 1) or absolute
scotoma (Group 2). Inner parts of the retina close to the fovea were most
affected, whereas regions closer to the periphery of the 10 degrees visual field 
showed near normal function. As the disease progressed, there was an evident
shift of fixation to preferential retinal locus (PRL) in eight eyes with visual
acuity 0.2 or less (Group 3). Fixation shift was superior in four eyes, temporal 
in two eyes, and nasal in two eyes. CONCLUSION: MP enabled a highly sensitive
topographic monitoring of retinal function, showing central or pericentral
fixation in the early stages, until loss of central function, in eyes with VA 0.2
or less, caused evident shift of fixation to PRL. PRL was never situated inside
the central uniform hypofluorescent area, but corresponded with the
hyperfluorescent ring seen with AF imaging.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15951755 [PubMed - indexed for MEDLINE]

1895: Acta Ophthalmol Scand. 2005 Jun;83(3):333-6.

The time pattern of bilateral exudative age-related macular degeneration.

Gudnadottir GS, Magnusson KP, Stefansson E, Jonasson F, Helgadottir G, Sigurdsson
H.

Department of Ophthalmology, University of Iceland, Landspitali, Reykjavik,
Iceland.

PURPOSE: To study time patterns in bilateral exudative age-related macular
degeneration (AMD) and the pattern of drusen before and after the onset of
exudative AMD. MATERIAL AND METHODS: Out of 2220 individuals in the Icelandic
genetic study of AMD, 151 had bilateral exudative AMD. We searched for previous
records in the Icelandic University Retina Unit. For the 65 patients with a
fluorescein angiography record of both eyes, we established the time between the 
onset of disease in each eye. For the 53 patients with colour fundus photographs 
of the latter eye taken prior to the occurrence of exudative disease, we graded
the drusen before and after the onset of exudative AMD in the second eye.
RESULTS: The time interval between the onset of exudative AMD in the first and
second eyes was 2.5 years (95% CI: 1.8-3.2; n = 65) and the median was 1.8 years.
In 82% of cases the second eye was affected within 4 years. Soft drusen in the
macula were found in 95% of eyes that later developed exudative disease (n = 53).
Soft and hard drusen decreased in number in the central macula following the
development of exudative disease. CONCLUSIONS: Bilateral exudative AMD develops
within a few years in both eyes. Drusen are less visible following the onset of
exudative AMD in the second eye.

PMID: 15948787 [PubMed - indexed for MEDLINE]

1896: Can J Ophthalmol. 2005 Jun;40(3):389-91.

Age-related macular degeneration: treating the whole patient.

Tasman W, Rovner B.

Department of Ophthalmology, Jefferson Medical College, and Wills Eye Hospital,
Philadelphia, PA 19107, USA. wst1@ureach.com

Ophthalmologists can help to improve the quality of life for patients with
age-related macular degeneration (AMD) by treating the whole patient. Patients
should be encouraged to seek psychiatric care for depression, especially if
symptoms are persistent. They may also cope better with their vision loss by
participating in AMD support groups. For earlier diagnosis of AMD, patients at
high risk should be screened; if large drusen are present, nutritional
suggestions can be made. Until treatments to prevent vision loss or to restore
vision are available, these approaches provide optimal care.

Publication Types: 
    Comparative Study

PMID: 15947809 [PubMed - indexed for MEDLINE]

1897: Can J Ophthalmol. 2005 Jun;40(3):384-8.

Socioeconomic status and clinical features of patients undergoing photodynamic
therapy or transpupillary thermotherapy for subfoveal choroidal
neovascularization due to age-related macular degeneration.

Chew H, Maberley DA, Ma P, Chang A, Maberley A.

Department of Ophthalmology, University of Toronto, Ontario, Canada.

BACKGROUND: The purpose of this study was to compare baseline clinical and
socioeconomic features of patients undergoing self-funded photodynamic therapy
(PDT) or government-funded subthreshold transpupillary thermotherapy (TTT) with a
diode laser for subfoveal choroidal neovascularization secondary to age-related
macular degeneration (AMD). METHODS: Between July 2000 and August 2001, 115
patients with subfoveal choroidal neovascularization secondary to AMD were
offered PDT as an initial intervention. If individuals believed that they could
not afford or did not want PDT, then TTT was offered. In masked fashion, leakage 
pattern and lesion size were determined retrospectively from pretreatment
angiograms. Baseline visual acuity was determined with autorefraction and
subsequent Snellen testing. The mean income of each treatment group was estimated
from the average sex-specific income for each subject's postal code, based on the
1996 Canadian census data. The average education level for each subject's postal 
code was also determined. RESULTS: The patients who were not willing to pay for
PDT had significantly worse macular disease before treatment (larger lesions and 
poorer visual acuity) and a significantly lower mean income than the patients who
were willing to pay for PDT. INTERPRETATION: The severity of exudative choroidal 
neovascularization appears to be associated with lower socioeconomic status.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15947808 [PubMed - indexed for MEDLINE]

1898: Can J Ophthalmol. 2005 Jun;40(3):378-83.

Comparison of photodynamic therapy and transpupillary thermotherapy for subfoveal
choroidal neovascularization due to age-related macular degeneration.

Maberley DA, Chew H, Ma P, Chang A, Hollands H, Maberley A.

Department of Ophthalmology, University of British Columbia, Vancouver, BC,
Canada. crtg_vancouver@hotmail.com

BACKGROUND: The purpose of this study was to compare photodynamic therapy (PDT)
against subthreshold transpupillary thermotherapy (TTT) with a diode laser for
subfoveal choroidal neovascularization secondary to age-related macular
degeneration (AMD). METHODS: Patients with subfoveal choroidal neovascularization
secondary to AMD were offered PDT as an initial intervention. If they declined
PDT, then TTT was offered. RESULTS: We evaluated and followed 115 consecutive
patients for an average of 1 year. The primary outcome measure was visual acuity,
but the interventions were also compared on the basis of lesion size and
angiographically determined lesion activity. Baseline comparisons between the 2
treatment groups showed significant differences in pretreatment visual acuity,
lesion size, and lesion composition. Univariate analysis of outcomes demonstrated
equivalence between the treatment groups in final lesion size, angiographic
activity, and visual acuity. Multivariate analysis also demonstrated equivalence 
between the treatment groups in final visual acuity while controlling for age,
pretreatment visual acuity, and lesion category. Predominantly classic lesions
were associated with poorer visual outcomes. INTERPRETATION: The PDT and TTT
groups were equivalent in terms of all outcome parameters evaluated.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15947807 [PubMed - indexed for MEDLINE]

1899: Can J Ophthalmol. 2005 Jun;40(3):369-77.

Drug pricing for a novel treatment for wet macular degeneration: using
incremental cost-effectiveness ratios to ensure societal value.

Sharma S, Bakal J, Sharma SM, Covert D, Shah GK.

Cost-Effective Ocular Health Policy Unit, Department of Ophthalmology & Community
Health and Epidemiology, Queen's University, Hotel Dieu Hospital, Kingston,
Ontario, Canada.

OBJECTIVE: Health economic models can assist policy-makers in determining the
value of novel treatments from the viewpoint of society. In this context, value
is defined as the benefit of treatment, given its cost. A new treatment for wet
age-related macular degeneration (AMD), juxtascleral administration of anecortave
acetate, 15 mg for depot suspension (Retaane), is now in a late-phase clinical
trial. In a theoretical analysis, we sought to determine the cost at which this
treatment might offer economic value to society, using incremental
cost-effectiveness ratios (ICERs). METHODS: A series of 1-year cost-utility
models was created for the investigational treatment and standard treatment
(photodynamic therapy [PDT] with verteporfin [Visudyne]). Value to society was
defined in terms of theoretical associated ICERs (in US dollars): $100,000 per
quality-adjusted life-year (QALY), $50,000/QALY, $20,000/QALY and $0/QALY, the
point of economic indifference. Models were created from the societal perspective
and included a patient-derived utility assessment involving regression equations 
to estimate time trade-off preferences, event probabilities derived from a
randomized clinical trial comparing the safety and efficacy of anecortave
administration and PDT with verteporfin, decision analysis and relevant costing
information. RESULTS: An ICER of $100,000/QALY would be associated with an
anecortave cost of $3022/vial, an ICER of $50,000/QALY with an anecortave cost of
$2986/vial and an ICER of $20,000/QALY with an anecortave cost of $2964/vial. The
point of economic indifference between anecortave administration and standard
therapy would occur with an anecortave cost of $2950/vial. INTERPRETATION: In
theory, an anecortave cost of $2986/vial is associated with an ICER of
$50,000/QALY, the threshold used by many health technology assessment and
reimbursement agencies.

Publication Types: 
    Comparative Study

PMID: 15947806 [PubMed - indexed for MEDLINE]

1900: Can J Ophthalmol. 2005 Jun;40(3):352-68.

Targeting angiogenesis, the underlying disorder in neovascular age-related
macular degeneration.

Ng EW, Adamis AP.

Eyetech Pharmaceuticals, Inc., New York, NY 10036, USA.

Angiogenesis has a causal role in many diseases, including neovascular
age-related macular degeneration (AMD). Identification of key regulators of
angiogenesis, including vascular endothelial growth factor (VEGF), fibroblast
growth factor 2, pigment epithelium-derived growth factor, angiopoietins and
extracellular matrix molecules, has facilitated the development of novel
therapeutic agents that target the underlying pathological angiogenic process.
Among these, VEGF serves as a "master switch" for many ocular neovascular
conditions through its promotion of endothelial cell proliferation and survival, 
vascular permeability and ocular inflammation. Two anti-VEGF agents are now
clinically available: bevacizumab, an antibody for metastatic colorectal cancer, 
and pegaptanib sodium, an aptamer for neovascular AMD. Unlike bevacizumab, which 
binds all VEGF isoforms, pegaptanib targets only VEGF165, the isoform responsible
for pathological ocular neovascularization and thus an ideal target for treatment
of AMD. Although other therapies targeting angiogenesis in AMD are in clinical
development, to date, pegaptanib is the only therapy approved by the Food and
Drug Administration of the United States for the treatment of all neovascular AMD
and represents a valuable addition to the hitherto limited options available for 
patients.

Publication Types: 
    Review

PMID: 15947805 [PubMed - indexed for MEDLINE]

1901: Can J Ophthalmol. 2005 Jun;40(3):341-51.

Surgical management of age-related macular degeneration.

Conti SM, Kertes PJ.

University of Toronto, Sunnybrook and Women's College Health Sciences Centre,
Ontario, Canada.

The development of increasingly refined vitreoretinal surgical techniques has
resulted in a variety of surgical procedures for age-related macular degeneration
(AMD). These have included submacular surgery with removal of choroidal
neovascular membranes and subretinal blood, intraoperative lysis of feeder
vessels, pneumatic displacement of subretinal blood and macular translocation
surgery. The goals of these procedures have been to improve upon the poor natural
history of exudative AMD and restore useful central vision. This article reviews 
the varied approaches, results and complications of the surgical management of
AMD.

Publication Types: 
    Review

PMID: 15947804 [PubMed - indexed for MEDLINE]

1902: Can J Ophthalmol. 2005 Jun;40(3):332-40.

Rheopheresis for age-related macular degeneration: clinical results and putative 
mechanism of action.

Pulido JS, Sanders D, Klingel R.

Department of Ophthalmology, Mayo Clinic, Rochester, MN 55905, and Department of 
Ophthalmology, University of Illinois, College of Medicine, Chicago, USA.
pulido.jose@mayo.edu

BACKGROUND: Rheopheresis is being evaluated in a clinical trial. The rationale
and available results are presented. METHODS: We reviewed the literature about
the pathophysiology of age-related macular degeneration (AMD) that might support 
the use of rheopheresis. In addition, we reviewed the previously published
results of the use of rheopheresis for AMD. RESULTS: There appears to be a
diffusion barrier caused by accumulation of cross-linked proteins known as
advanced macular oxidation products (AMOPS) in AMD. Rheopheresis allows removal
of uncross-linked proteins and facilitates antioxidant entry into Bruch's
membrane, preventing further accumulation of AMOPS. The Multicenter Investigation
of Rheopheresis for AMD (MIRA-1), an ongoing double-masked randomized trial,
should determine the efficacy of rheopheresis in preventing the progression of
AMD. The interim results, from an analysis of visual acuity data for 43 patients,
are encouraging, confirming the potential of rheopheresis as a therapeutic option
for dry AMD. The benefit was evident immediately after treatment and remained
essentially stable throughout the 12-month period of evaluation. Eyes with
late-stage, high-risk, dry AMD appeared to be at significant risk for substantial
vision loss over the 12 months if not treated. Subgroup analysis demonstrated
that the timing of rheopheresis in the course of a patient's disease may have a
pronounced effect on outcome. INTERPRETATION: There appears to be a rationale for
the use of rheopheresis in AMD. Further results of the clinical trial are
awaited.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 15947803 [PubMed - indexed for MEDLINE]

1903: Can J Ophthalmol. 2005 Jun;40(3):320-31.

Laser prophylaxis for age-related macular degeneration.

Hsu J, Maguire MG, Fine SL.

Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania,
Philadelphia 19104, USA.

BACKGROUND: Age-related macular degeneration (AMD) is the most common cause of
severe and irreversible vision loss among people 50 years of age or older in many
Western countries. Most of the available treatments for AMD are intended for the 
late stage, specifically for choroidal neovascularization (CNV). Effective
preventive treatments could have an even greater impact on the vision of the
millions of people at risk for vision loss from AMD. Drusen are typically the
earliest lesions seen in patients with AMD and precede the development of CNV. In
1973, Gass noted the disappearance of drusen in eyes that received laser
photocoagulation, which led to the hypothesis that laser-induced drusen reduction
could alter the natural course of AMD. METHODS: We reviewed relevant articles
found through a search of MEDLINE through February 2005 by means of the following
key words, alone or in combination: drusen, laser, photocoagulation, age-related 
macular degeneration, macula and choroidal neovascularization. RESULTS: Reports
ranging from individual cases and case series to randomized controlled pilot
studies have described various laser treatment protocols and their effects on
eyes with high-risk drusen but no neovascular changes. These reports provide
evidence that laser photocoagulation can induce drusen reduction. Although some
investigators have reported a corresponding improvement in visual function,
others have found no change or even worsening. The results in several of the
larger randomized controlled studies suggest that CNV may occur at an increased
rate in laser-treated eyes with high-risk drusen in patients who have neovascular
AMD in the other eye. The long-term effects of laser treatment in patients with
high-risk drusen in both eyes and no neovascular changes have yet to be
determined. INTERPRETATION: The outcome of clinical trials such as the
Prophylactic Treatment of Age-Related Macular Degeneration and the Complications 
of Age-Related Macular Degeneration Prevention Trial will help to determine the
role of laser prophylaxis in patients with AMD.

Publication Types: 
    Review

PMID: 15947802 [PubMed - indexed for MEDLINE]

1904: Can J Ophthalmol. 2005 Jun;40(3):313-9.

Progression of visual loss and time between initial assessment and treatment of
wet age-related macular degeneration.

Oliver-Fernandez A, Bakal J, Segal S, Shah GK, Dugar A, Sharma S.

Department of Ophthalmology, Indiana University, Indianapolis, USA, and
Cost-Effective Ocular Health Policy Unit, Queen's University, Hotel Dieu
Hospital, Kingston, Ontario, Canada.

PURPOSE: To determine whether the time elapsed from initial (referral) diagnosis 
of neovascular (wet) age-related macular degeneration (AMD) to assessment and
treatment by a retinal specialist is associated with visual deterioration in the 
intervening period. METHODS: A prospective pilot study of 38 consecutive AMD
patients who presented with newly diagnosed subfoveal choroidal
neovascularization was conducted in a tertiary care retinal practice. All
eligible subjects underwent clinical examination and digital fluorescein
angiography at the time of assessment by a retinal specialist. Correlations were 
performed to assess the association between continuous independent variables and 
any visual deterioration since initial diagnosis. Multivariate linear regression 
models with stepwise techniques were used to evaluate any association between
visual progression and time elapsed, while controlling for potential clinical
covariates. RESULTS: Of the 38 patients, 32 (84%) met the inclusion and exclusion
criteria; no differences in important variables were noted between those included
and those excluded. The median time between initial diagnosis and referral
assessment and treatment was 28 days (interquartile range=36.5 days); some degree
of visual loss developed in 14 (44%) of the subjects. The elapsed time was
correlated with progression of visual loss (r=0.50, p=0.003). Multivariate linear
regression demonstrated that only time elapsed and lesion type based on
fluorescein angiography were associated with progression of visual loss
(R2=0.491, F(4,28)=6.744, p=0.001); lesion size, age and sex were not
significantly associated with progression of visual loss. INTERPRETATION: Delay
in assessment and treatment of new-onset wet AMD by a retinal specialist is
associated with a higher risk of visual loss.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15947801 [PubMed - indexed for MEDLINE]

1905: Can J Ophthalmol. 2005 Jun;40(3):303-12.

Preferred retinal loci and macular scotoma characteristics in patients with
age-related macular degeneration.

Schuchard RA.

Department of Veterans Affairs, Atlanta VA Rehabilitation Research & Development,
Center of Excellence of Aging with Vision Loss, Decatur, GA 30033-4004, USA.
rschuch@emory.edu

Many patients with macular scotomas due to age-related macular degeneration do
not perceive black spots in the visual field where the scotomas are located.
Rather, they describe objects as "vanishing," "jumping out of nowhere" or "having
blurry parts," or a combination of features. In addition, when the macular
scotoma affects the fovea, the visual system uses 1 or more preferred retinal
loci (PRLs) as a "pseudofovea" to perform visual tasks. Visual function testing
with the scanning laser ophthalmoscope has provided a wealth of information
regarding how patients perceive the visual world and how the oculomotor system
directs eye movements. This article describes 2 specific functions of the
oculomotor system, fixation stability and refixation precision, with data
collected from normally sighted people and patients with visual field loss. The
implications of the characteristics of PRLs and macular scotomas for clinical
testing are discussed.

Publication Types: 
    Review

PMID: 15947800 [PubMed - indexed for MEDLINE]

1906: Can J Ophthalmol. 2005 Jun;40(3):293-302.

Comparison of stereoscopic digital imaging and slide film photography in the
identification of macular degeneration.

Somani R, Tennant M, Rudnisky C, Weis E, Ting A, Eppler J, Greve M, Hinz B, de
Leon A.

Department of Ophthalmology, Royal Alexandra Hospital, University of Alberta,
Edmonton, Canada.

BACKGROUND: This study compared the sensitivity and specificity of stereoscopic
digital photography of the retina through a dilated pupil with a 45 degrees
nonmydriatic camera and Joint Photographic Experts Group (JPEG) compression of
the images with the sensitivity and specificity of 35-mm slide film photography
in the identification of age-related macular degeneration (AMD). METHODS:
Consecutive patients with a diagnosis of AMD were enrolled. Stereoscopic retinal 
images of the disc, macula and temporal macula were captured with a digital 45
degrees nonmydriatic camera (then compressed into JPEG format) and with a
standard fundus camera and slide film. A single retinal specialist graded both
image formats in masked fashion, at least 1 month apart, using a modified
Age-Related Eye Disease Study (AREDS) severity scale. The digital images were
displayed on a monitor and viewed with the use of liquid crystal display shutter 
glasses and stereo imaging software. The film images were mounted on a light box 
and graded with the use of a stereoviewer. Primary outcome measures included the 
presence or absence of AMD pathological features. Positive and negative
predictive values (PPVs and NPVs), sensitivity, specificity and weighted kappaw
statistics were calculated. RESULTS: We photographed 203 eyes (of 103 patients)
with both digital and slide film cameras. Correlation of the 2 image formats was 
substantial in identifying AREDS level 3a or greater (kappaw=0.64, standard
error=0.08, PPV=0.95, NPV=0.66, sensitivity=0.93, specificity=0.74) and excellent
in identifying level 4b or greater (kappaw=0.83, standard error=0.05, PPV=0.81,
NPV=0.98, sensitivity=0.94, specificity=0.94). INTERPRETATION: High-resolution
stereoscopic, mydriatic, 45 degrees digital images captured with a nonmydriatic
camera and JPEG compressed correlate well with stereoscopic slide film
photographs in the identification of moderate to advanced AMD (AREDS level 3a or 
greater).

Publication Types: 
    Comparative Study

PMID: 15947799 [PubMed - indexed for MEDLINE]

1907: Can J Ophthalmol. 2005 Jun;40(3):288-92.

Genetic aspects of age-related macular degeneration.

MacDonald IM.

Department of Ophthalmology, University of Alberta, Royal Alexandra Hospital,
Edmonton, Canada. macdonal@ualberta.ca

Age-related macular degeneration (AMD) is a complex phenotype that has multiple
causes, including genetic.This paper reviews pertinent single-gene disorders,
polymorphisms in the human genome that modify disease severity, and maculopathies
that provide insight into the pathogenesis of AMD and the function of the normal 
macula. The availability of DNA-based analysis for certain genes will likely
increase the demand for genetic counselling of patients and families with AMD.
Better knowledge of risks should help prevent blindness in these families.

Publication Types: 
    Review

PMID: 15947798 [PubMed - indexed for MEDLINE]

1908: Can J Ophthalmol. 2005 Jun;40(3):277-87.

Age-related macular degeneration: economic burden and value-based medicine
analysis.

Brown MM, Brown GC, Stein JD, Roth Z, Campanella J, Beauchamp GR.

Center for Value-Based Medicine, Flourtown 19031, and the Department of
Ophthalmology, University of Pennsylvania School of Medicine, Philadelphia, USA. 
mbrown@valuebasedmedicine.com

It can be estimated that 17,100 new cases of neovascular (wet) AMD and 180,000
new cases of geographic-atrophy (dry) AMD occur in Canada annually. In addition
to having a devastating effect on patients' lives, the condition causes
significant adverse consequences for the economy. The deleterious effect of AMD
on quality of life is markedly underestimated by ophthalmologists who treat
patients with AMD, by non-ophthalmic physicians and by the public. In fact,
patients with different degrees of severity of AMD have a perceived impairment of
their quality of life that is 96% to 750% greater than the impairment estimated
by treating ophthalmologists. Mild AMD causes a 17% decrease in the quality of
life of the average patient, a decrease similar to that encountered with
symptomatic human immunodeficiency virus infection or moderate cardiac angina.
Moderate AMD produces a 40% decrease in quality of life, a decrease similar to
that associated with permanent renal dialysis or severe cardiac angina. Very
severe AMD causes a 63% decrement in quality of life, a decrease similar to that 
encountered with advanced prostatic cancer with uncontrollable pain or a severe
stroke that leaves a person bedridden, incontinent and requiring constant nursing
care. The adverse economic consequences of AMD include an annual $2.6 billion
negative impact on Canada's gross domestic product. The return on investment is
high for both current AMD therapies and research into new treatment modalities.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 15947797 [PubMed - indexed for MEDLINE]

1909: Ophthalmologica. 2005 May-Jun;219(3):154-66.

Improvement of visual functions and fundus alterations in early age-related
macular degeneration treated with a combination of acetyl-L-carnitine, n-3 fatty 
acids, and coenzyme Q10.

Feher J, Kovacs B, Kovacs I, Schveoller M, Papale A, Balacco Gabrieli C.

Ophthalmic Neuroscience Program, Department of Ophthalmology, University of Rome 
'La Sapienza', Rome, Italy. j.feher@libero.it

The aim of this randomized, double-blind, placebo-controlled clinical trial was
to determine the efficacy of a combination of acetyl-L-carnitine, n-3 fatty
acids, and coenzyme Q10 (Phototrop) on the visual functions and fundus
alterations in early age-related macular degeneration (AMD). One hundred and six 
patients with a clinical diagnosis of early AMD were randomized to the treated or
control groups. The primary efficacy variable was the change in the visual field 
mean defect (VFMD) from baseline to 12 months of treatment, with secondary
efficacy parameters: visual acuity (Snellen chart and ETDRS chart), foveal
sensitivity as measured by perimetry, and fundus alterations as evaluated
according to the criteria of the International Classification and Grading System 
for AMD. The mean change in all four parameters of visual functions showed
significant improvement in the treated group by the end of the study period. In
addition, in the treated group only 1 out of 48 cases (2%) while in the placebo
group 9 out of 53 (17%) showed clinically significant (>2.0 dB) worsening in VFMD
(p = 0.006, odds ratio: 10.93). Decrease in drusen-covered area of treated eyes
was also statistically significant as compared to placebo when either the most
affected eyes (p = 0.045) or the less affected eyes (p = 0.017) were considered. 
These findings strongly suggested that an appropriate combination of compounds
which affect mitochondrial lipid metabolism, may improve and subsequently
stabilize visual functions, and it may also improve fundus alterations in
patients affected by early AMD.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 15947501 [PubMed - indexed for MEDLINE]

1910: Immunology. 2005 Jul;115(3):422-30.

Circulating anti-retinal antibodies as immune markers in age-related macular
degeneration.

Patel N, Ohbayashi M, Nugent AK, Ramchand K, Toda M, Chau KY, Bunce C, Webster A,
Bird AC, Ono SJ, Chong V.

Ocular Immunology, Institute of Ophthalmology, University College of London, Bath
Street, London WC1V 9EL, UK.

Age-related macular maculopathy (ARM) and age-related macular degeneration (AMD) 
are the leading causes of blindness in the Western world. Despite the magnitude
of this clinical problem, very little is known about the pathogenesis of the
disease. In this study, we analysed the sera (using indirect immunohistochemistry
and Western blot analysis) from a very large cohort of such patients and normal
age-matched controls to detect circulating anti-retinal antibodies. Patients with
bilateral drusen (n = 64) and with chorioretinal neovascularization (CNV) (n =
51) were recruited in addition to age-matched control subjects (n = 39). The sera
were analysed for anti-retinal immunoglobulins on retinal sections. The data were
then correlated with the clinical features graded according to the International 
Classification and Grading System of ARM and AMD. The sera of patients with
drusen (93.75%) and CNV (82.27%) were found to have a significantly (P = 0.02)
higher titre of autoantibodies to the retina in comparison with controls (8.69%),
indicating significant evidence of involvement of the immune process in early
stages of AMD. Subsequent statistical analysis of the drusen group showed
significant progressive staining (P = 0.0009) in the nuclei layers from early to 
late stages of ARM. Western blotting confirmed the presence of anti-retinal
immunoglobulins to retinal antigens. As anti-retinal immunoglobulins are present 
in patients with bilateral drusen and exudative AMD, these antibodies could play 
a significant role in the pathogenesis of AMD. Whilst we do not have evidence
that these antibodies precede disease onset, the possibility that their presence 
might contribute to disease progression needs to be investigated. Finally, the
eventual identification of the target antigens detected by these antibodies may
permit the future development of new diagnostic methods for ARM and AMD.

PMID: 15946260 [PubMed - indexed for MEDLINE]

1911: Eur J Ophthalmol. 2005 May-Jun;15(3):415-9.

Intravitreal triamcinolone in the treatment of serous pigment epithelial
detachment and occult choroidal neovascularization secondary to age-related
macular degeneration.

Nicolò M, Ghiglione D, Lai S, Calabria G.

University Eye Clinic of Genova, Genova, Italy. massimo.nicolo@hsanmartino.it

PURPOSE: To report two cases of occult choroidal neovascularization (CNV) and
serous pigment epithelial detachment (PED) treated with intravitreal
triamcinolone (IVT) injections. METHODS: Interventional case reports. RESULTS:
Both patients showed an increase in visual acuity and a complete flattening of
the PED at 10 months (Case 1) and 4 months (Case 2) after IVT injections. No
complications or adverse effects are reported. CONCLUSIONS: Future studies should
be designed to investigate if IVT can effectively influence the clinical and
functional outcome of eyes with serous PED and occult CNV secondary to
age-related macular degeneration, for which at the moment no treatment has been
shown to be effective.

Publication Types: 
    Case Reports

PMID: 15945015 [PubMed - indexed for MEDLINE]

1912: Eur J Ophthalmol. 2005 May-Jun;15(3):329-35.

Cataract surgery combined with intravitreal injection of triamcinolone acetonide.

Jonas JB, Kreissig I, Budde WM, Degenring RF.

Department of Ophthalmology, Faculty of Clinical Medicine Mannheim of the
University Heidelberg, Mannheim, Germany. Jost.Jonas@ma.augen.uni-heidelberg.de

PURPOSE: To evaluate whether the addition of cataract surgery to an intravitreal 
injection of triamcinolone acetonide markedly increases frequency and spectrum of
complications. METHODS: The comparative nonrandomized clinical interventional
investigation included a study group of 60 eyes (56 patients) undergoing cataract
surgery and additionally receiving an intravitreal injection of about 20 mg of
triamcinolone acetonide and a triamcinolone control group of 290 eyes (262
patients) that consecutively received an intravitreal injection of about 20 mg
triamcinolone acetonide without cataract surgery. Reasons for intravitreal
injection of triamcinolone acetonide were exudative age-related macular
degeneration (n=228; 65%), diffuse diabetic macular edema (n=94; 27%), central
retinal vein occlusion (n=17; 5%), and branch retinal vein occlusion (n=11; 3%). 
Mean follow-up was 8.6+/-6.8 months. A second control group included 1068
patients (1068 eyes) who consecutively underwent routine cataract surgery without
intravitreal injection. RESULTS: Study group and triamcinolone control group did 
not vary significantly in best visual acuity during follow-up (p=0.08), final
visual acuity at the end of follow-up (p=0.30), maximal intraocular pressure
during follow-up (p=0.99), frequency of an intraocular pressure higher than 21
mmHg (p=0.66), and intraocular pressure at the end of follow-up (p=0.06).
Postoperative infectious endophthalmitis, wound leakage or other corneal wound
healing problems, persisting corneal endothelial decompensation, rhegmatogenous
retinal detachment, marked postoperative pain, or a clinically significant
decentration of the intraocular lens were not observed. Study group and the
non-triamcinolone control group did not vary significantly in the rate of
posterior lens capsule rupture (p=0.11), postoperative infectious
endophthalmitis, and persisting postoperative corneal endothelial decompensation.
CONCLUSIONS: The addition of cataract surgery to an intravitreal injection of
triamcinolone acetonide may not markedly increase amount and frequency of side
effects and complications of intravitreal triamcinolone acetonide. No safe
conclusions can be reached regarding differences in frequency of postoperative
infectious endophthalmitis.

Publication Types: 
    Clinical Trial
    Comparative Study

PMID: 15945000 [PubMed - indexed for MEDLINE]

1913: Histol Histopathol. 2005 Jul;20(3):857-63.

Detection of CX3CR1 single nucleotide polymorphism and expression on archived
eyes with age-related macular degeneration.

Chan CC, Tuo J, Bojanowski CM, Csaky KG, Green WR.

National Eye Institute, National Institutes of Health, Bldg. 10, 10 Center Drive,
Bethesda, MD 20895, USA. chanc@nei.nih.gov

There is a significant genetic component in age-related macular degeneration
(AMD). CX3CR1, which encodes the fractalkine (chemokine, CX3CL1) receptor, has
two single nucleotide polymorphisms (SNPs): V249I and T280M. These SNPs are
correlated with other aged-related diseases such as atherosclerosis. We have
reported an association of CX3CR1 SNP and AMD. In this study we examined CX3CR1
SNP frequencies and protein expression on archived sections of AMD and normal
eyes. We microdissected non-retinal, peripheral retinal and macular cells from
archived slides of eyes of AMD patients and normal subjects. CX3CR1 SNP typing
was conducted by PCR and restriction fragment length polymorphism analysis.
CX3CR1 transcripts from retinal cells were also measured using RT-PCR. CX3CR1
protein expression was evaluated using avidin-biotin complex
immunohistochemistry. We successfully extracted DNA from 32/40 AMD cases and 2/2 
normal eyes. Among the 32 AMD cases, 18 had neovascular AMD and 14 had
non-neovascular AMD. The M280 allele was detected in 19/64 (32 cases x2) with a
frequency of 29.7%, which was significantly higher as compared to the frequency
in the normal population (11.2%). We detected CX3CR1 expression in the various
retinal cells. CX3CR1 transcript and protein levels were diminished in the
macular lesions. This study successfully analyzed CX3CR1 SNP and transcript
expression in microdissected cells from archived paraffin fixed slides. Our data 
suggest that the M280 allele, a SNP resulting in aberrant CX3CR1 and CX3CL1
interaction, as well as lowered expression of macular CX3CR1, may contribute to
the development of AMD.

PMID: 15944936 [PubMed - indexed for MEDLINE]

1914: Jpn J Ophthalmol. 2005 May-Jun;49(3):231-4.

Clinical course of macular edema in two cases of interferon-associated
retinopathy observed by optical coherence tomography.

Shimura M, Saito T, Yasuda K, Tamai M.

Department of Ophthalmology and Medical Sciences, Tohoku University Graduate
School of Medicine, Sendai, Japan. masahiko@oph.med.tohoku.ac.jp

BACKGROUND: Interferon (IFN)-associated retinopathy is typically characterized by
retinal hemorrhages and cotton wool spots at the posterior fundus, but visual
function is usually maintained. With the use of optical coherence tomography
(OCT), two patients with IFN-associated retinopathy who had developed macular
edema and reduced visual acuity during the clinical course of IFN therapy were
observed. CASES: A 37-year-old man with chronic hepatitis C and a 59-year-old man
with chronic myeloid leukemia, both of whom had received IFN therapy, were
referred to our outpatient clinic. The former patient had complained once that
his visual acuity had decreased after the termination of IFN therapy, and the
latter patient complained twice during IFN therapy that his visual acuity had
decreased. OBSERVATIONS: In both patients, at the time of the visual
disturbances, macular edema was clearly observed by OCT. Hypoalbuminemia and
thrombocytopenia were observed at this time also. After the remission of the
hypoalbuminemia and thrombocytopenia, the macular edema observed by OCT
disappeared and visual acuity returned to normal. CONCLUSION: During and after
IFN therapy, OCT is a useful examination technique for revealing macular edema in
patients who have decreased vision. Ophthalmologists should be aware of the
ocular side effects of IFN therapy and carefully monitor patients for the
possible occurrence of hypoalbuminemia and thrombocytopenia. Jpn J Ophthalmol
2005;49:231-234 (c) Japanese Ophthalmological Society 2005.

Publication Types: 
    Case Reports

PMID: 15944830 [PubMed - indexed for MEDLINE]

1915: Ophthalmic Res. 2005 May-Jun;37(3):159-67. Epub 2005 May 7.

Genotype-phenotype correlation in Italian families with Stargardt disease.

Simonelli F, Testa F, Zernant J, Nesti A, Rossi S, Allikmets R, Rinaldi E.

Department of Ophthalmology, Second University of Naples, Naples, Italy.
franctes@tin.it

Autosomal recessive Stargardt disease (STGD) has been associated with substantial
genetic and phenotypic heterogeneity. By systematic clinical analyses of STGD
patients with complete genetic data (i.e. identified mutations on both alleles of
the ABCA4 gene), we set out to determine phenotypic subtypes and to correlate
these with specific ABCA4 alleles. Twenty-eight patients from 18 families with
STGD/fundus flavimaculatus were investigated. All patients were submitted to
complete ophthalmologic examination, electrophysiology, fluorescein angiography
and ABCA4 gene chip analysis. Two main clinical phenotypes were observed among
the examined patients. The severe phenotype was characterized by the onset of the
disease <20 years and reduced ERG response, whereas the mild phenotype presented 
with later onset of the disease and a normal ERG response. Genetic analysis of
the ABCA4 gene revealed, in the severe group, more frequently deletions, stop
codons and insertions as compared to the mild phenotype group (p=0.0113 by
Fisher's exact test). Moreover, the compound heterozygous mutations
G1961E/5018+2T-->C found in 7 patients from 3 unrelated STGD families were
associated with a mild phenotype in all subjects, except 1. This study documented
variability of the clinical expression of STGD in relation to the age of onset of
the disease, fundus appearance and the ERG response and allowed to subdivide
patients into a severe and a mild phenotype group. These findings suggest that an
extensive and comprehensive genetic analysis of STGD patients combined with
thorough clinical evaluation, including the careful recording of the age of onset
of the disease, would allow a more precise prognostic evaluation. Copyright (c)
2005 S. Karger AG, Basel.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15942264 [PubMed - indexed for MEDLINE]

1916: Am J Ophthalmol. 2005 Jul;140(1):35-44.

Systemic markers of inflammation, endothelial dysfunction, and age-related
maculopathy.

Klein R, Klein BE, Knudtson MD, Wong TY, Shankar A, Tsai MY.

Department of Ophthalmology and Visual Sciences, University of Wisconsin Medical 
School Madison, 53726, USA. kleinr@epi.ophth.wisc.edu

PURPOSE: To examine the association of systemic markers of inflammatory disease
and endothelial dysfunction with age-related maculopathy (ARM). DESIGN: (1)
Nested case-control analysis of prevalent ARM and (2) prospective analyses of
incident ARM in a random sample of a population-based cohort. METHODS:
Standardized protocols for blood collection, measurement of markers,
administration of a questionnaire, and gradings of stereoscopic color fundus
photography to determine ARM were used. Standard univariate and multivariate
analyses were performed. participants: Included in the nested case-control study 
were 188 cases with moderate to advanced ARM and 195 controls matched for age,
gender, and current smoking status at a baseline examination from 1988 to 1990,
and living in Beaver Dam, Wisconsin. Included in the prospective analyses as a
random sample of 321 persons were those who participated in a 5-year and/or
10-year follow-up. main outcome measures: Prevalent and incident ARM. RESULTS:
Serum C-reactive protein, amyloid A, interleukin-6, tumor necrosis factor-alpha, 
intracellular adhesion molecule, E-selectin, folate, and Chlamydia pneumoniae IgG
antibody were not associated with either prevalent or incident ARM. CONCLUSION:
Contrary to other reports, we cannot confirm a strong or consistent relationship 
of markers of inflammation and endothelial dysfunction with ARM.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, U.S. Gov't, P.H.S.

PMID: 15939388 [PubMed - indexed for MEDLINE]

1917: Exp Eye Res. 2005 Jun;80(6):821-6.

Crystallin distribution in Bruch's membrane-choroid complex from AMD and
age-matched donor eyes.

Nakata K, Crabb JW, Hollyfield JG.

Department of Ophthalmic Research, Cole Eye Institute, i-31, The Cleveland Clinic
Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.

Crystallins were consistently found in a recent proteomic analysis of drusen from
age-related macular degeneration (AMD) donor eyes. Here we compare the
distribution of several crystallins in drusen, Bruch's membrane and choroid from 
AMD and non-AMD age-matched control eyes. Immunohistochemistry and Western blots 
of tissue samples were performed using antibodies to alphaA- and
alphaB-crystallins. Bruch's membrane, drusen and the subjacent choroidal
connective tissue from AMD tissues showed greater immunoreactivity for alphaA-
and alphaB-crystallins than were observed in normal age-matched control tissues. 
Western blots also demonstrated more intense alphaA- and alphaB-crystallin
signals from AMD tissues than were present in age-matched controls. These data
indicate that alphaA- and alphaB-crystallins accumulate in Bruch's membrane and
choroidal connective tissues to a greater degree in AMD than in normal aging.
These findings suggest that the accumulation of these small heat shock proteins
at this critical interface below the RPE reflects a disease-related stress
response manifested during the progression of AMD.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15939038 [PubMed - indexed for MEDLINE]

1918: Exp Eye Res. 2005 Jun;80(6):761-75.

Basal deposits and drusen in eyes with age-related maculopathy: evidence for
solid lipid particles.

Curcio CA, Presley JB, Millican CL, Medeiros NE.

Department of Ophthalmology, University of Alabama School of Medicine, 700 South 
18th Street, Birmingham, AL 35294-0009, USA.

Neutral lipid, including esterified cholesterol, and apolipoproteins B and E are 
abundant in basal deposits and drusen of aged and age-related maculopathy (ARM)
eyes. The principal component of basal linear deposit (BlinD), a specific ARM
lesion, is membranous debris, which if actually derived from membranes cannot
account for extracellular neutral lipid. We therefore used a lipid-preserving
ultrastructural method to obtain improved images of membranous debris. Maculas
from 44 human donors (71-96 yr) were preserved <7.5 hr after death. Blocks were
post-fixed in 2% osmium or osmium-tannic acid-paraphenylenediamine (OTAP) to
preserve neutral lipid for thin-section transmission electron microscopic (TEM)
examination. Solid particles identified by OTAP were considered closest to the in
vivo state of extracellular lipids. Micrographs were examined for intermediate
forms, with greatest weight given to comparable images from different
preparations of same or fellow eyes. Twenty eyes of older adults (12 with ARM
including fellows treated with photodynamic and radiation therapies) had
adequately preserved extracellular lipid. The exterior surface of membranous
debris was thicker and more electron-dense than basal infoldings of retinal
pigment epithelium (RPE) cells. By OTAP, individual membranous debris profiles
were solid (diameters, 80-200 nm) and formed tracks across or aggregations within
basal laminar deposits. Solid particles and/or pools of neutral lipid were
visible in BlinD and drusen. When processed to preserve lipid, membranous debris 
resembles neither membranes of surrounding cells nor vesicles possessing aqueous 
interiors but rather solid particles. These results are consistent with recent
evidence implicating lipoprotein particles of intra-ocular origin as a potential 
source of neutral lipids, including esterified cholesterol, in the specific
lesions of ARM.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15939032 [PubMed - indexed for MEDLINE]

1919: Ophthalmology. 2005 Jun;112(6):1035-47.

Systemic bevacizumab (Avastin) therapy for neovascular age-related macular
degeneration twelve-week results of an uncontrolled open-label clinical study.

Michels S, Rosenfeld PJ, Puliafito CA, Marcus EN, Venkatraman AS.

Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami
School of Medicine, Miami, Florida 33136, USA.

PURPOSE: To evaluate the short-term safety of systemic bevacizumab (Avastin,
Genentech, Inc., South San Francisco, CA) and its effects on visual acuity (VA)
and subfoveal choroidal neovascularization (CNV) in patients with neovascular
age-related macular degeneration (AMD). DESIGN: Open-label, single-center,
uncontrolled clinical study. PARTICIPANTS: Age-related macular degeneration
patients with subfoveal CNV (N = 9) and best-corrected VA letter scores of 70 to 
20 (approximate Snellen equivalent, 20/40-20/400). METHODS: Patients were treated
at baseline with an infusion of bevacizumab (5 mg/kg), followed by 1 or 2
additional doses given at 2-week intervals. Safety assessments were performed at 
all visits. Ophthalmologic evaluations included protocol VA measurements and
ocular examinations, along with optical coherence tomography (OCT) imaging,
fluorescein angiography, and indocyanine green angiography. MAIN OUTCOME
MEASUREMENTS: Safety assessments were performed, along with assessments of
changes from baseline in VA scores, OCT measurements, and angiographic lesion
characteristics. RESULTS: There were no serious ocular or systemic adverse events
identified. By 6 weeks, the only adverse event identified was a mild elevation of
systolic blood pressure (BP) (+12 mmHg; P = 0.035), and this elevation was
controlled by either changing or initiating antihypertensive medication. By 12
weeks, the elevation of systolic BP was no longer significant (P = 0.51). In the 
study eyes, significant increases in VA were evident within 1 week of treatment, 
and by 12 weeks, the median and mean VA letter scores increased by 8 letters (P =
0.011) and 12 letters (P = 0.008), respectively. The median and mean central
retinal thickness measurements decreased by 157 microm (P = 0.008) and 177 microm
(P = 0.001), respectively. In the fellow eyes at 12 weeks, the median and mean VA
letter scores increased by 27 letters (P = 0.018) and 16 letters (P = 0.012), and
the median and mean central retinal thickness measurements decreased by 59 mum (P
= 0.028) and 92 microm (P = 0.06). In all study eyes, angiography revealed a
marked reduction or an absence of leakage from CNV. CONCLUSION: Overall,
bevacizumab therapy was well tolerated, with an improvement in VA, OCT, and
angiographic outcomes. Although these preliminary results are promising, a
randomized controlled clinical trial is necessary before concluding that systemic
bevacizumab therapy is safe and effective for patients with neovascular AMD.

Publication Types: 
    Case Reports
    Clinical Trial
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15936441 [PubMed - indexed for MEDLINE]

1920: Vis Neurosci. 2005 Mar-Apr;22(2):187-201.

Functional and cortical adaptations to central vision loss.

Cheung SH, Legge GE.

Department of Psychology, University of Minnesota, Minneapolis, MN 55455, USA.
sing@umn.edu

Age-related macular degeneration (AMD), affecting the retina, afflicts one out of
ten people aged 80 years or older in the United States. AMD often results in
vision loss to the central 15-20 deg of the visual field (i.e. central scotoma), 
and frequently afflicts both eyes. In most cases, when the central scotoma
includes the fovea, patients will adopt an eccentric preferred retinal locus
(PRL) for fixation. The onset of a central scotoma results in the absence of
retinal inputs to corresponding regions of retinotopically mapped visual cortex. 
Animal studies have shown evidence for reorganization in adult mammals for such
cortical areas following experimentally induced central scotomata. However, it is
still unknown whether reorganization occurs in primary visual cortex (V1) of AMD 
patients. Nor is it known whether the adoption of a PRL corresponds to changes to
the retinotopic mapping of V1. Two recent advances hold out the promise for
addressing these issues and for contributing to the rehabilitation of AMD
patients: improved methods for assessing visual function across the fields of AMD
patients using the scanning laser ophthalmoscope, and the advent of brain-imaging
methods for studying retinotopic mapping in humans. For the most part,
specialists in these two areas come from different disciplines and communities,
with few opportunities to interact. The purpose of this review is to summarize
key findings on both the clinical and neuroscience issues related to questions
about visual adaptation in AMD patients.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.
    Review

PMID: 15935111 [PubMed - indexed for MEDLINE]

1921: Eye. 2006 Jun;20(6):697-702. Epub 2005 Jun 3.

Retinal haemodynamics in patients with age-related macular degeneration.

Sato E, Feke GT, Menke MN, Wallace McMeel J.

Schepens Retina Associates Foundation, Boston, MA 02115, USA.

OBJECTIVE: To investigate whether there is an association between the magnitude
of retinal haemodynamic abnormalities in patients with age-related macular
degeneration (AMD) and the degree of severity of the AMD. METHODS: A retinal
laser Doppler system (Canon CLBF 100) was used to measure retinal arterial
haemodynamic parameters in 25 eyes of 25 patients with AMD and nine eyes of nine 
age-matched control subjects. Severity of AMD was classified into Mild (n=11),
Moderate (n=7), or Severe (n=7). The pulsatility ratio (PR), the pulsatility
index (PI), and the resistivity index (RI) were determined. RESULTS: PR, PI, and 
RI in the patients with AMD were each significantly higher than in the control
group, and increased monotonically with increasing severity of AMD. However,
there were no differences in mean blood velocity, arterial diameter, or blood
flow rate among the groups. This suggests that the increased blood flow
pulsatility in the retinal arteries of the eyes with AMD is not due to increased 
distal vascular resistance, but instead is likely due to a loss of compliance in 
the arterial vasculature leading to the eye. CONCLUSION: Our results suggest that
an increasing vascular rigidity in the systemic arterial circulation is directly 
associated with an increasing severity of AMD.

PMID: 15933745 [PubMed - indexed for MEDLINE]

1922: Retina. 2005 Jun;25(4):489-97.

Comprehensive functional vision assessment of patients with North Carolina
macular dystrophy (MCDR1).

Szlyk JP, Paliga J, Seiple W, Rabb MF.

Research and Development Service, Veterans Administration Chicago Health Care
System, West Side Division, Chicago, Illinois, USA. janeszly@uic.edu

PURPOSE: Previous studies indicated abnormal development of fixation toward the
optic nerve head in patients with the inherited retinal disease North Carolina
macular dystrophy (NCMD). The implication of this development on functional
vision and structural characteristics has not been described. METHODS: The
anatomical characteristics of five NCMD-affected individuals were assessed by
measuring the retinal thickness of the macula using optical coherence tomography.
The underlying physiologic health of the retina was assessed using the multifocal
ERG. Psychophysical assessment of remaining vision in the affected areas was done
with a new microperimetry system that measures functional visual acuity at 27
discrete locations and the Humphrey visual field analyzer. RESULTS: All patients 
had better areas of visual sensitivity toward the nasal macula. Follow-up
examination showed no changes in the clinical appearance of the retina. Visual
acuities ranged from -0.10 logMAR (Snellen equivalent, approximately 20/16) to
0.50 logMAR (Snellen equivalent, approximately 20/63) in the better eye. No
significant changes in visual acuity were found over time. Local multifocal
electroretinogram deficits were found in all patients. Patients with grade 2 or 3
disease had large patches of decreased amplitudes and delayed implicit times.
Results of the anatomical, electrophysiological, and psychophysical tests were
consistent. CONCLUSION: The electrophysiological and psychophysical deficits
found in patients with more severe disease were consistent with an abnormal
development of fixation from the anatomical fovea toward the optic nerve head
with the placement of the lesion temporal to fixation (into the nasal visual
field).

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, Non-P.H.S.
    Research Support, U.S. Gov't, P.H.S.

PMID: 15933597 [PubMed - indexed for MEDLINE]

1923: Retina. 2005 Jun;25(4):454-61.

Comment in:
    Retina. 2006 Apr;26(4):485-6; author reply 486-7.

Efficacy of surgical removal of the internal limiting membrane in diabetic
cystoid macular edema.

Kimura T, Kiryu J, Nishiwaki H, Oh H, Suzuma K, Watanabe D, Kurimoto M, Takagi H.

Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School
of Medicine, Kyoto, Japan.

PURPOSE: To evaluate the efficacy of surgical removal of the internal limiting
membrane (ILM) in diabetic cystoid macular edema (CME). METHODS: Prospective,
noncomparative, interventional case series including 21 eyes of 18 consecutive
patients with diabetic CME. Vitrectomy with separation of the posterior hyaloid
and induction of posterior vitreous detachment had been performed previously on
nine eyes. Pars plana vitrectomy for removal of the ILM was performed. RESULTS:
CME resolved in eyes that underwent initial vitrectomy and in those with
long-standing (>1 year) CME after previous vitrectomy. Postoperative
best-corrected visual acuity improved by >/=2 lines of a Snellen equivalent in 14
eyes (67%) (P < 0.01). The mean foveal thickness (distance between the inner
retinal surface and the retinal pigment epithelium) decreased from 553 microm to 
221 microm at 4 weeks (P < 0.001). No recurrences or deterioration of CME was
observed during the entire follow-up period (mean, 17.8 months; range, 8-34
months). CONCLUSION: Surgical removal of the ILM might be an effective procedure 
for reducing CME in patients with diabetes. A prospective, randomized, controlled
study is necessary to further evaluate the efficacy of the procedure.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15933592 [PubMed - indexed for MEDLINE]

1924: Retina. 2005 Jun;25(4):446-53.

Scotomas of age-related macular degeneration detected and characterized by means 
of a novel three-dimensional computer-automated visual field test.

Nazemi PP, Fink W, Lim JI, Sadun AA.

Doheny Eye Institute and Keck School of Medicine at the University of Southern
California, Los Angeles, California 90033-4671, USA.

PURPOSE: We used the recently devised three-dimensional computer-based threshold 
Amsler grid test to acquire and identify typical patterns of visual field defects
(scotomas) caused by age-related macular degeneration (AMD). METHODS: Patients
with AMD traced on a computer touch screen the borders of those areas on an
Amsler grid that were missing from their field of vision. Scotomas were
repeatedly outlined and recorded at different grid contrast levels. The resulting
three-dimensional "hole" in the central 25 degrees of the visual field was
further characterized by its slope, location, shape, and depth. The results were 
compared with fundus photographs and fluorescein angiograms. RESULTS: Twenty-five
patients and 41 eyes were examined. The three-dimensional depictions consistently
demonstrated central scotomas with "scallop"-shaped borders and steplike
patterns, with either steep slopes or a combination of steep and shallow slopes. 
The steep slopes corresponded to nonexudative AMD, while the shallow slopes
indicated exudative AMD. CONCLUSION: The three-dimensional computer-automated
threshold Amsler grid test may demonstrate characteristic scotoma patterns in
patients with AMD that conform to the respective fluorescein angiograms. The test
shows promise as an effective tool in accurately evaluating, characterizing, and 
monitoring scotomas in patients with AMD. It may have the potential as a
screening tool for the early diagnosis of AMD.

PMID: 15933591 [PubMed - indexed for MEDLINE]

1925: Retina. 2005 Jun;25(4):443-5.

Comparison of the original Amsler grid with the modified Amsler grid: result for 
patients with age-related macular degeneration.

Augustin AJ, Offermann I, Lutz J, Schmidt-Erfurth U, Tornambe P.

Department of Ophthalmology, Karlsruhe, Germany. 106020.560@compuserve.com

PURPOSE: To compare the sensitivity of the original Amsler grid presenting white 
lines on a black background with that of the modified standard version of the
grid presenting black lines on a white background in the detection of visual
disturbances. PATIENTS AND METHODS: One hundred eighty-two patients (182 eyes)
with dry and exudative age-related macular degeneration and a history of
metamorphopsia were instructed to use an Amsler grid. None of the patients were
familiar with an Amsler grid or had used it previously. If the disease was
present in both eyes, one eye was chosen as the study eye by randomization. Both 
grid types were presented and used for documentation of central visual field
changes. The sequence of presentation of the respective grid was also chosen by
randomization. Original Amsler grid questions were used for grading
("metamorphomas" and "scotomas"). Visual acuity of patients ranged from 0.1 to
0.7. Subgroup analysis was performed based on the visual acuity levels. RESULTS: 
For the overall study population, the original Amsler grid provided significantly
better results than the modified version. Evaluation of data for the different
subgroups showed no significant difference between patients with visual acuity
ranging from 0.1 to 0.3. For patients with visual acuity of 0.5 or better, the
original Amsler grid was significantly more informative and reliable than the
modified version. CONCLUSION: For patients with macular diseases, use of the
original Amsler grid (white lines on a black background) should be recommended.
This is particularly important for patients with visual acuity of 0.5 or better.

Publication Types: 
    Comparative Study

PMID: 15933590 [PubMed - indexed for MEDLINE]

1926: Retina. 2005 Jun;25(4):430-7.

Decreased arterial dye-filling and venous dilation in the macular choroid
associated with age-related macular degeneration.

Mori K, Gehlbach PL, Ito YN, Yoneya S.

Department of Ophthalmology, Saitama Medical School, Iruma, Saitama, Japan.
keisuke@saitama-med.ac.jp

PURPOSE: To compare the angioarchitecture of choroidal arteries and veins in
patients with age-related macular degeneration (AMD) to the angioarchitecture of 
age-matched normal subjects using indocyanine green (ICG) angiography. METHODS:
ICG angiography was performed in 35 consecutive AMD patients and 18 normal
age-matched volunteers with a fundus ICG camera. ICG video images, including the 
arterial and venous phases, were quantitatively analyzed using image analyzing
software. RESULTS: In patients with AMD, the choroidal arterioles are dilated,
fewer, run a straighter course, and possess fewer bifurcations. The number of
choroidal arteries and the macular fluorescent intensity in the arterial phase of
choroidal filling was significantly less in patients with AMD as compared to
age-matched normal controls (P = 0.008). The mean and maximum caliber of
choroidal veins in the macula was dilated in AMD eyes than in age-matched normal 
control eyes (P < 0.001). There was no statistically significant difference in
arterial dye filling or venous caliber observed in AMD eyes, with or without
choroidal neovascular membrane (CNV). CONCLUSION: Choroidal arterial perfusion in
the macula was significant decreased in eyes with AMD with and without CNV, and
was associated with choroidal venous dilation. These observations implicate poor 
choroidal perfusion of the macula in the pathogenesis of AMD.

Publication Types: 
    Comparative Study

PMID: 15933588 [PubMed - indexed for MEDLINE]

1927: Clin Experiment Ophthalmol. 2005 Jun;33(3):240-5.

Comparison of mean macular thickness using optical coherence tomography and
visual acuity in diabetic retinopathy.

Hussain A, Hussain N, Nutheti R.

Smt Kanuri Santhamma Retina Vitreous Center, LV Prasad Eye Institute, Hyderabad, 
India. anjli@lvpei.org

BACKGROUND: The purpose of the present study was to quantitatively assess the
mean macular thickness in diabetic patients using optical coherence tomography
and its correlation with visual acuity. METHODS: A prospective case series study 
was undertaken of consecutive diabetic patients referred to a tertiary eye care
centre for an eye check up from January 2003 to June 2003. One hundred and five
eyes from 55 patients with varying degree of diabetes underwent optical coherence
tomography examination. The study patients were divided into four groups: group
I, non-proliferative diabetic retinopathy (NPDR); group II, NPDR with clinically 
significant macular oedema (CSME); group III, proliferative diabetic retinopathy 
(PDR); and group IV, PDR with CSME. RESULTS: The mean macular thickness of the
entire group was 256.0 +/- 129.7 microm. A positive correlation (r = 0.424, P <
0.0001) was evident between mean macular thickness and visual acuity. CONCLUSION:
Optical coherence tomography is a useful tool for objectively monitoring macular 
thickness in patients with diabetic retinopathy. Mean macular thickness
correlates with visual acuity.

Publication Types: 
    Comparative Study

PMID: 15932526 [PubMed - indexed for MEDLINE]

1928: Graefes Arch Clin Exp Ophthalmol. 2005 May;243(5):493-6. Epub 2004 Dec 17.

Retinal angiomatous proliferation with a cilioretinal artery anastomosis: an
unusual presentation.

Ghazi NG, Conway BP.

Department of Ophthalmology, University of Virginia Health System,
Charlottesville, Virginia 22903, USA. nghazi@eyeweb.org

PURPOSE: To report an unusual phenotype of retinal angiomatous proliferation
(RAP) in age-related macular degeneration (AMD) and its short-term response to
laser photocoagulation. METHODS: Case report. RESULTS: An 85-year-old woman was
found to have an unusual RAP with a major feeder vessel originating from a
cilioretinal artery and associated with a cilioretinal-retinal anastomosis
(C-RRA). Diffuse cystoid macular edema (CME), intraretinal hard exudates in a
circinate pattern, and a fibrovascular pigment epithelial detachment (PED) were
present. Laser photocoagulation was performed and led to occlusion of the
cilioretinal feeder vessel and angiomatous lesion, with less CME. The other
(retinal) arm of the C-RRA became more engorged and a new cilioretinal feeder
developed, and both were associated with intraretinal hemorrhages. Visual acuity 
was stable and the PED persisted throughout follow-up. CONCLUSIONS: We report an 
unusual phenotype of RAP that is associated with a major cilioretinal feeder
vessel and comment on the possible effect of such an association on the response 
to laser treatment.

Publication Types: 
    Case Reports

PMID: 15931547 [PubMed - indexed for MEDLINE]

1929: Hum Mol Genet. 2005 Jul 15;14(14):1991-2002. Epub 2005 Jun 1.

Candidate gene analysis suggests a role for fatty acid biosynthesis and
regulation of the complement system in the etiology of age-related maculopathy.

Conley YP, Thalamuthu A, Jakobsdottir J, Weeks DE, Mah T, Ferrell RE, Gorin MB.

Department of Health Promotion and Development, School of Nursing, University of 
Pittsburgh, PA, USA.

Age-related maculopathy (ARM) is a leading cause of visual impairment in elderly 
Americans and is a complex genetic disorder. Hypothesized pathways for the
etiology of ARM include cholesterol and lipoprotein metabolism and transport,
extracellular matrix integrity, oxidative stress and inflammatory/immunologic
processes. This study investigates 21 polymorphisms within 15 candidate genes
whose products function within these pathways by performing family and
case-control genetic association studies using clearly affected familial cases
(n=338 families, 796 individuals), clearly affected, unrelated sporadic cases
(n=196) and clearly unaffected, unrelated controls (n=120). Two genes
demonstrated significant association with ARM status. A Met299Val variant in the 
elongation of very long chain fatty acids-like 4 (ELOVL4) gene was significantly 
associated with ARM in the case-control allele (P=0.001), case-control genotype
(P=0.001) and case-control family (P<0.0001) tests. A Tyr402His variant in exon 9
in the complement factor H (CFH) gene was also significantly associated with ARM 
in the case-control allele (P<0.0001), case-control genotype (P<0.0001) and
case-control family (P<0.0001) tests. All of these results remain significant
after adjusting for false discovery rates to control for the impact of multiple
testing. In addition, the CFH variant appears to play a role in exudative and
atrophic disease, whereas the ELOVL4 variant may play a greater role in exudative
disease in our population. These results support a potential role for multiple
pathways in the etiology of ARM, including pathways involved with fatty acid
biosynthesis and the complement system.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15930014 [PubMed - indexed for MEDLINE]

1930: Expert Opin Investig Drugs. 2005 May;14(5):671-82.

Pegaptanib sodium for the treatment of neovascular age-related macular
degeneration.

Moshfeghi AA, Puliafito CA.

Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami
Miller School of Medicine, 900 NW 17th Street, Miami, FL 33136, USA.

This article reviews pegaptanib sodium, a compound developed by Eyetech
Pharmaceuticals Inc. and Pfizer Inc., for the treatment of neovascular
age-related macular degeneration (AMD). Traditional treatment approaches to
neovascular AMD have included destructive therapies such as thermal laser
photocoagulation and photodynamic therapy; the use of pegaptanib sodium heralds a
new treatment approach that is a non-destructive therapy based on the inhibition 
of vascular endothelial growth factor activity in the eye. This diminishes the
neovascular drive in the pathologically hyperpermeable state of the diseased eye.
Pegaptanib sodium is one of the first therapeutics belonging to the class of
compounds known as aptamers. The chemistry, mechanism of action, pharmacokinetics
and rationale for the clinical use of the drug are reviewed. The article
highlights and summarises the results of the multi-centre, randomised,
sham-controlled clinical trials with pegaptanib sodium to treat subfoveal
choroidal neovascularisation in AMD. In addition, the safety profile is reviewed.

Publication Types: 
    Review

PMID: 15926872 [PubMed - indexed for MEDLINE]

1931: Am J Ophthalmol. 2005 Jul;140(1):23-8.

Using optical coherence tomography to monitor photodynamic therapy in age related
macular degeneration.

Salinas-Alamán A, García-Layana A, Maldonado MJ, Sainz-Gómez C, Alvárez-Vidal A.

Department of Ophthalmology, University Clinic, University of Navarra, Pamplona, 
Spain. asalinas@unav.es

PURPOSE: To evaluate the role of optical coherence tomography (OCT) in
determining choroidal neovascularization (CNV) activity before and after
photodynamic therapy (PDT) in patients with age-related macular degeneration
(ARMD). DESIGN: Prospective observational case series. METHODS: SETTING:
Institutional study. patient population: Fifty-three patients (62 eyes) with
ARMD. OBSERVATION PROCEDURE: Prospective observational case study. MAIN OUTCOME
MEASURES: Presence or absence of leakage on fluorescein angiography, presence of 
intraretinal or sub-retinal fluid on OCT, and macular and choroidal neovascular
complex thickness on OCT. RESULTS: The macular thickness decreased significantly 
after PDT (P = .001). However, no significant changes in CNV thickness were
measured after PDT (P = .567). Once the diagnosis of ARMD was established before 
treatment, OCT had a sensitivity of 96.77% for detecting CNV activity. After
treatment, OCT had a good sensitivity (95.65%) and a moderate specificity
(59.01%) in determining CNV activity, which resulted in a diagnostic efficiency
(proportion of correct results) of 82.95%. CONCLUSIONS: OCT appears to be useful 
for indicating CNV activity. Therefore, it may serve as a complementary technique
for deciding the need for PDT and re-treatment in patients with ARMD.

PMID: 15922284 [PubMed - indexed for MEDLINE]

1932: Neurobiol Aging. 2005 Aug-Sep;26(8):1199-203. Epub 2005 Apr 19.

Comment in:
    Neurobiol Aging. 2006 Oct;27(10):1531-2; discussion 1533-4.

Sparing of age-related macular degeneration in rheumatoid arthritis.

McGeer PL, Sibley J.

Kinsmen Laboratory of Neurological Research, University of British Columbia,
Vancouver, Canada. mcgeerp1@interchange.ubc.ca

Age-related macular degeneration (AMD), for which inflammatory changes have been 
demonstrated, is the commonest cause of blindness in the elderly. We compared the
prevalence of AMD in a prospectively followed cohort of rheumatoid arthritic (RA)
patients from Saskatchewan with published data from four racially similar general
populations. For individuals 65 years or older, only three cases of AMD were
identified in the Saskatchewan cohort of 993 RA patients (0.2% prevalence). This 
compares with 67 out of 1955 subjects in the Beaver Dam survey (prevalence
3.43%); 101 out of 4071 in the Rotterdam survey (prevalence 2.48%); and 63 out of
1950 in the Blue Mountains survey (prevalence 3.23%). For individuals 75 years or
older, only two cases out of 497 were identified in the RA cohort (prevalence
0.40%), compared with 516 cases out of 13,900 in the United Kingdom survey
(prevalence 3.72%). Patients with RA appear to be relatively spared from AMD. We 
hypothesize that this results from long term antiinflammatory treatment. Genetic 
or environmental factors could also be responsible.

Publication Types: 
    Comparative Study
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15917104 [PubMed - indexed for MEDLINE]

1933: Exp Eye Res. 2005 Nov;81(5):513-29.

Nutritional manipulation of primate retinas. IV. Effects of n--3 fatty acids,
lutein, and zeaxanthin on S-cones and rods in the foveal region.

Leung IY, Sandstrom MM, Zucker CL, Neuringer M, Max Snodderly D.

The Schepens Eye Research Institute, 20 Staniford Street, Boston, MA 02114, USA. 
ivanleung@jhu.edu

Lutein and zeaxanthin are xanthophylls selectively accumulated by primate retinas
that may protect the macula from age-related macular degeneration. In this
project, we manipulated n-3 fatty acids, lutein and/or zeaxanthin levels in the
diet and studied their possible outcome on S-cone and rod cell density in the
foveal region. Rhesus monkeys (7-16 year, n=17) were fed from birth
xanthophyll-free semipurified diets with either adequate or low n-3 fatty acids. 
Five monkeys were supplemented with lutein and six with zeaxanthin for 6-24
months, while six remained xanthophyll-free until sacrifice. Retinas were
embedded in methacrylate and serial 2 microm sections were cut along the vertical
meridian. Rod nuclei, and immuno-labelled outer segments of S-cones and rods,
were reconstructed and counted in an 8 microm strip. The density profiles were
compared with data from control monkeys (n=7) fed a standard laboratory diet.
S-cone density profiles were symmetrical along the vertical meridian and the
densities decreased rapidly with retinal eccentricity. Rod densities were higher 
in the superior region than the inferior region in most of the control and
experimental animals. Unlike the significant effects observed for retinal pigment
epithelial cells of these same monkeys (Leung, I.Y-F., Sandstrom, M.M., Zucker,
C.L., Neuringer, M., Snodderly, D.M., 2004. Nutritional manipulation of primate
retinas. II. Effects of age, n-3 fatty acids, lutein, and zeaxanthin on retinal
pigment epithelium. Invest. Ophthalmol. Vis. Sci. 45, 3244-3256), neither
xanthophyll supplementation nor low dietary n-3 fatty acids produced consistent
effects on S-cone or rod density profiles of the experimental animals. However,
monkeys low in n-3 fatty acids had increased variability of S-cone density in the
fovea and low density of foveal rod outer segments. The high variability suggests
that the photoreceptors of some animals were resistant to the nutritional
manipulations, while others may have been affected. Thus, the photoreceptors
appear less sensitive than the retinal pigment epithelium to these nutritional
manipulations. However, it is possible that more consistent effects would emerge 
at a later age or after exposure to stressors such as high light levels.

Publication Types: 
    Comparative Study
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 15916761 [PubMed - indexed for MEDLINE]

1934: Invest Ophthalmol Vis Sci. 2005 Jun;46(6):1907-10.

The 5-year incidence and risk factors for age-related maculopathy in a general
Japanese population: the Hisayama study.

Miyazaki M, Kiyohara Y, Yoshida A, Iida M, Nose Y, Ishibashi T.

Departments of Ophthalmology, Kyushu University, Fukuoka, Japan.
miho-m@info.med.kyushu-u.ac.jp

PURPOSE: To estimate the 5-year incidence and risk factors for age-related
maculopathy (ARM) in a representative older Japanese population. METHODS: A
population-based cohort study was conducted in 1998 on 1482 Hisayama residents
aged 50 years or older, and 961 of these subjects attended the 5-year follow-up
examinations in 2003. At both time points, the characteristics of ARM were
determined by grading color fundus photographs according to the Wisconsin
Age-Related Maculopathy Grading System. Using these cohort data, logistic
regression analyses were performed to determine the risk factors for ARM. Nine
possible risk factors were examined: age, sex, hypertension, diabetes,
hyperlipidemia, smoking, alcohol intake, body mass index, and white blood cell
count. RESULTS: The 5-year incidence of early ARM was 8.5%, and that of late ARM 
was 0.8%. Men were found to have a significantly higher incidence of late ARM
than did women. The incidence of both early and late ARM increased significantly 
with age. Multiple logistic regression analysis showed that age and smoking were 
significantly associated with early and late ARM. CONCLUSIONS: The results
suggest that the overall 5-year incidence of early ARM is 8.0% and that of late
ARM is 0.8% in the general Japanese population and that higher age and smoking
are relevant risk factors for early and late ARM in the Japanese.

PMID: 15914602 [PubMed - indexed for MEDLINE]

1935: Graefes Arch Clin Exp Ophthalmol. 2005 Nov;243(11):1080-90. Epub 2005 May
21.

Identification of Chlamydia pneumoniae within human choroidal neovascular
membranes secondary to age-related macular degeneration.

Kalayoglu MV, Bula D, Arroyo J, Gragoudas ES, D'Amico D, Miller JW.

Angiogenesis Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear
Infirmary, Harvard Medical School, Boston, MA 02114, USA.

Age-related macular degeneration (AMD) is a leading cause of blindness in the
United States, and increasing evidence suggests that it is an inflammatory
disease. The prokaryotic obligate intracellular pathogen Chlamydia pneumoniae is 
emerging as a novel risk factor in cardiovascular disease, and recent
sero-epidemiological data suggest that C. pneumoniae infection is also associated
with AMD. In this study, we examined choroidal neovascular membrane (CNV) tissue 
from patients with neovascular AMD for the presence of C. pneumoniae and
determined whether the pathogen can dysregulate the function of key cell types in
ways that can cause neovascular AMD. Nine CNV removed from patients with
neovascular AMD were examined for the presence of C. pneumoniae by
immunohistochemistry (IHC) and polymerase chain reaction (PCR); in addition, we
performed PCR on nine non-AMD eyes, and IHC on five non-AMD CNV, seven non-AMD
eyes, and one internal limiting membrane specimen. Finally, human
monocyte-derived macrophages and retinal pigment epithelial (RPE) cells were
exposed to C. pneumoniae and assayed in vitro for the production of
pro-angiogenic immunomodulators (VEGF, IL-8, and MCP-1). C. pneumoniae was
detected in four of nine AMD CNV by IHC and two of nine AMD CNV by PCR, induced
VEGF production by human macrophages, and increased production of IL-8 and MCP-1 
by RPE cells. In contrast, none of the 22 non-AMD specimens showed evidence for
C. pneumoniae. These data indicate that a pathogen capable of inducing chronic
inflammation and pro-angiogenic cytokines can be detected in some AMD CNV, and
suggest that infection may contribute to the pathogenesis of AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15909160 [PubMed - indexed for MEDLINE]

1936: Graefes Arch Clin Exp Ophthalmol. 2005 Oct;243(10):1028-35. Epub 2005 Oct
20.

Serum levels of macular carotenoids in relation to age-related maculopathy: the
Muenster Aging and Retina Study (MARS).

Dasch B, Fuhs A, Schmidt J, Behrens T, Meister A, Wellmann J, Fobker M,
Pauleikhoff D, Hense HW.

Institute of Epidemiology and Social Medicine, University of Muenster,
Domagkstrasse 3, 48149, Muenster, Germany.

BACKGROUND: It has been hypothesized that the macular carotenoids, lutein and
zeaxanthin, may protect against age-related maculopathy. We evaluated the
association between blood concentrations of lutein (L) and zeaxanthin (Z) and
age-related maculopathy (ARM) in a case-control analysis of the baseline
examination of the Muenster Ageing and Retina Study (MARS). METHODS: Of the 1060 
participants aged 59-82 years at baseline, 910 (85.9%) with bilateral gradable
fundus photographs and complete data for the carotenoids and potential
confounders were included. The Rotterdam classification system was used for
definition of ARM stages. Multivariate linear regression methods were applied to 
model the relationship between macular carotenoids and the presence of ARM.
RESULTS: The participants' mean age was 70.9+5.5 years, 59.9% were female, 20.8% 
had a normal bilateral fundus, and 48.5% showed signs of early ARM (uni- or
bilateral) and 30.7% of late ARM (in at least one eye). In study participants
with L and/or Z supplementation (15.6%), the median serum levels for L (Z) were
approximately 2 times (1.5 times) higher than in subjects with no
supplementation. After exclusion of subjects with L and/or Z supplementation, no 
statistically significant bivariate relationship was observed between the serum
levels of L or Z and the presence of ARM. Multivariate regression models,
adjusting for age, gender, smoking, body-mass index, and HDL-cholesterol blood
levels, produced adjusted mean serum levels of 0.124, 0.112, and 0.131 microg/ml 
for L and 0.019, 0.020, and 0.022 microg/ml for Z in subjects with normal fundus,
early ARM, and late ARM, respectively. CONCLUSION: In this large study, the serum
concentrations of L and Z were not related to the prevalence of ARM. However, the
large proportion of study participants taking L and/or Z supplementation may have
affected these results.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15909159 [PubMed - indexed for MEDLINE]

1937: J Submicrosc Cytol Pathol. 2004 Jul-Oct;36(3-4):295-303.

Contrast enhancement of the retinal image and image distortion associated with
macular degeneration.

Sjöstrand FS.

Department of Biology, University of California, Los Angeles, CA, USA.
fsjostra@ucla.edu

An analysis of image distortion in connection with macular degeneration revealed 
that seeing objects requires brightness contrast enhancement. Thus macular
degeneration changes neural interaction controlling bipolar cell responses to
light stimulating photoreceptors to reverse spatial brightness contrast
enhancement with the consequence that objects cannot be seen. This shows that the
contrast of the retinal images is too low for vision without enhancement. However
images consisting of randomly arranged small spots of different brightness are
seen because of cones enhancing bipolar cell responses to rod input and rods
enhancing bipolar cell responses to cone input. This residual vision and the
observation that image distortion disappears at low light intensities reveal that
macular degeneration is a functional disorder with intact photoreceptor function.
The affection may therefore be caused by a reduction of blood flow through the
choriocapillaries associated with ageing. The analysis of image distortion
associated with the affection led to a simple way to determine the size of the
affected retinal area, making it possible to follow the progression of the
affection in a direct and simple way. Basic aspects are described of synaptic
interaction within the information processing unit that determines the responses 
of the bipolar cells to photoreceptor input. This unit is the first information
processing unit that has been revealed thanks to the extension of the analysis of
the nervous system to the nanometer level at which information is processed. The 
minute size of the information processing unit, the special conditions for
synaptic transmission combined with the short distances separating the synapses
create special conditions for neural interaction at the nanometer level,
establishing conditions for high speed neural communication.

PMID: 15906604 [PubMed - indexed for MEDLINE]

1938: Graefes Arch Clin Exp Ophthalmol. 2005 Nov;243(11):1180-5. Epub 2005 May
20.

Indocyanine green-mediated photothrombosis with intravitreal triamcinolone
acetonide for subfoveal choroidal neovascularization in age-related macular
degeneration.

Arevalo JF, Garcia RA, Mendoza AJ.

Retina and Vitreous Service, Clinica Oftalmologica Centro Caracas, Caracas,
Venezuela. areval1@telcel.net.ve

BACKGROUND: There is a need for alternative treatments for the management of
exudative age-related macular degeneration (AMD). The purpose of this paper is to
determine the feasibility, safety, and clinical effect of indocyanine green
(ICG)-mediated photothrombosis (IMP) combined with intravitreal triamcinolone
acetonide (TA) in patients with subfoveal choroidal neovascularization (CNV) in
AMD. METHODS: Thirty-one eyes of 26 patients who were treated with IMP
immediately followed by an intravitreal injection of 4 mg of TA were investigated
in the study. The patients had a mean follow-up of 9 months (range 3 months to 26
months). Patients underwent one to four sessions of IMP combined with
intravitreal TA. RESULTS: Visual acuity showed stability in 19 eyes (61.3%),
improvement of visual acuity (VA) in seven eyes (22.6%), and worsening of VA in
five eyes (16.1%). A significant regression of the CNV, and diminishing of
subretinal fluid, was demonstrated with fluorescein angiography and optical
coherence tomography. We found no complications associated with the intravitreal 
injection procedure or IMP. Five (16.1%) eyes developed an increase in
intraocular pressure related to the presence of TA in the vitreous cavity.
However, it was medically controlled with topical anti-glaucoma medications.
Nineteen of 31 eyes (61.2%) required at least one re-treatment (mean 1.7; range
1-4) during the study period. CONCLUSIONS: Combined IMP and intravitreal TA may
provide stability or improvement in visual acuity and fundus findings in
choroidal neovascularization. Further evaluation in a multicenter, randomized,
placebo-controlled clinical trial with longer follow-up is needed to accurately
assess the safety and efficacy of this new treatment modality.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 15906068 [PubMed - indexed for MEDLINE]

1939: Am J Epidemiol. 2005 Jun 1;161(11):1013-9.

Exposure to Chlamydia pneumoniae infection and progression of age-related macular
degeneration.

Robman L, Mahdi O, McCarty C, Dimitrov P, Tikellis G, McNeil J, Byrne G, Taylor
H, Guymer R.

Centre for Eye Research Australia, University of Melbourne, Melbourne, Australia.
liubov@unimelb.edu.au

Recent studies have found an association between exposure to Chlamydia pneumoniae
infection and risk of age-related macular degeneration (AMD). To assess a
potential risk of AMD progression posed by exposure to C. pneumoniae, the authors
reexamined Australian residents in 2001-2002 who were aged 51-89 years with early
AMD at baseline (1992-1995). Examination included macular photography and an
enzyme-linked immunosorbent assay to determine antibody titers to the elementary 
bodies from C. pneumoniae AR39. AMD progression was assessed quantitatively,
using both coarse and fine progression steps following an international
classification for AMD grading, and also qualitatively, by side-by-side
comparison of baseline and follow-up macular photographs. Serologic data were
available for 246 of 254 (97%) subjects. AMD progression was associated with a
higher antibody titer. After adjustment for age, smoking, family history of AMD, 
history of cardiovascular diseases, and source study, the subjects in the upper
tertiles of antibody titers were 2.1 (95% confidence interval: 0.92, 4.69), 2.6
(95% confidence interval: 1.24, 5.41), and 3.0 (95% confidence interval: 1.46,
6.37) times more at risk of progression than those in the lowest tertile, using
three definitions of progression, respectively. The fact that seroreactivity to
C. pneumoniae was independently associated with the risk of AMD progression
suggests that C. pneumoniae infection may be an additional risk factor for AMD
progression.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15901621 [PubMed - indexed for MEDLINE]

1940: Am J Hum Genet. 2005 Jul;77(1):149-53. Epub 2005 May 13.

Strong association of the Y402H variant in complement factor H at 1q32 with
susceptibility to age-related macular degeneration.

Zareparsi S, Branham KE, Li M, Shah S, Klein RJ, Ott J, Hoh J, Abecasis GR,
Swaroop A.

Department of Ophthalmology and Visual Sciences, University of Michigan, Ann
Arbor, MI, USA.

Using a large sample of cases and controls from a single center, we show that a
T-->C substitution in exon 9 (Y402H) of the complement factor H gene is strongly 
associated with susceptibility to age-related macular degeneration, the most
common cause of blindness in the elderly. Frequency of the C allele was 0.61 in
cases, versus 0.34 in age-matched controls (P<1x10(-24)). Genotype frequencies
also differ markedly between cases and controls (chi2=112.68 [2 degrees of
freedom]; P<1x10(-24)). A multiplicative model fits the data well, and we
estimate the population frequency of the high-risk C allele to be 0.39 (95%
confidence interval 0.36-0.42) and the genotype relative risk to be 2.44 (95%
confidence interval 2.08-2.83) for TC heterozygotes and 5.93 (95% confidence
interval 4.33-8.02) for CC homozygotes.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15895326 [PubMed - indexed for MEDLINE]

1941: Eye. 2006 Apr;20(4):471-5.

Comment in:
    Eye. 2007 Feb;21(2):253; author reply 253-4.    Eye. 2007 Feb;21(2):302-3.

Screening for age-related macular degeneration using nonstereo digital fundus
photographs.

Jain S, Hamada S, Membrey WL, Chong V.

Retinal Research Unit, Kings College Hospital, Denmark Hill, London, UK.
drsaurabhjain@hotmail.com

Age-related macular degeneration (AMD) is a disease with significant visual
morbidity and accounts for the majority of blind registrations in the developed
world including the UK. Certain forms of neovascular AMD are amenable to
treatment but require expeditious referral to a retinal specialist. AIM: To
evaluate the possibility of using nonstereo fundus photographs as a low-cost
screening tool for neovascular AMD. DESIGN: Retrospective review of patients
referred to the macular clinic of a teaching hospital in London. METHODS: A total
of 198 randomised digital fundus photographs, without any other clinical
information, were presented to two independent ophthalmic interns who graded them
into one of the three categories: normal, age-related maculopathy (ARM), or
neovascular age-related macular degeneration (AMD) to determine the urgency of
referral to clinic. The results were compared with the known diagnosis for each
patient and sensitivities and specificities for each diagnostic category
calculated. RESULTS: The intraobserver Kappa statistic was 0.75 and 0.91 for
grader 1 and 2, respectively. The interobserver Kappa was 0.54. The mean
sensitivity and specificity for the identification of ARM was 60.5 and 76.3%,
respectively The mean sensitivity and specificity for the identification of AMD
was 85.7 and 78.8%, respectively. CONCLUSION: Nonstereo digital fundus photograph
is a reasonable screening tool for CNV and may aid in decreasing the visual
morbidity it causes by enabling timely referrals and treatment.

Publication Types: 
    Evaluation Studies

PMID: 15895024 [PubMed - indexed for MEDLINE]

1942: J Clin Apher. 2005 Oct;20(3):185-94.

Comment in:
    J Clin Apher. 2005 Oct;20(3):166-7.

Clinical outcomes and mechanism of action for rheopheresis treatment of
age-related macular degeneration (AMD).

Pulido J, Sanders D, Winters JL, Klingel R.

Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota 55905, USA.
Pulido.Jose@mayo.edu

The primary goals are to provide a comprehensive explanation of the potential
role of therapeutic apheresis in the treatment of Age-Related Macular
Degeneration (AMD). Initial clinical results with this technique and a summary of
current literature that addresses the mechanism of action for the Rheopheresis
approach are presented. Rheopheresis has been found to be a safe and effective
application of double filtration plasmapheresis (DFPP) for extracorporeal
hemorheotherapy. In this report, it is proposed that Rheopheresis results in an
immediate decrease in the proportion of high molecular weight proteins that could
combine with the TIMP-3 fibulin complex allowing for the barely functioning
retinal pigment epithelial (RPE) cells to function better and diminish the
release of vascular endothelial growth factor (VEGF). Interim results from the
randomized, double-masked MIRA-1 clinical trial include (1) improved vision
restoration; 28.0% of Treated Primary Eyes increased by > or = 2 lines of best
corrected visual acuity (BCVA) compared to 18.2% of Placebo Eyes; (2) a decline
in progressive vision loss; 0.0% of treated eyes progressing to worse than 20/200
vision over the 12-month study compared to 18.2% of Placebo Eyes; (3) 57.9% of
Treatment Eyes obtained improvement in their BCVA to 20/40 or better (driver's
license qualification), compared to only 14.3% of Placebo Eyes 12-month
post-treatment. Rheopheresis treatment shows strong promise as a viable clinical 
option for patients suffering from the dry form of AMD in terms of minimizing
vision loss, vision restoration, and overall quality of life factors. Expanded
clinical outcomes from the ongoing MIRA-1 clinical study will be valuable in the 
assessment of this new clinical tool for ophthalmic applications. Copyright 2005 
Wiley-Liss, Inc

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 15892078 [PubMed - indexed for MEDLINE]

1943: Ophthalmology. 2005 Jun;112(6):1086-91.

Comment in:
    Ophthalmology. 2006 May;113(5):885; author reply 885-6.

Posterior sub-Tenon's capsule triamcinolone injection combined with focal laser
photocoagulation for diabetic macular edema.

Tunc M, Onder HI, Kaya M.

Department of Ophthalmology, Abant Izzet Baysal University Düzce Medical School, 
Düzce, Turkey. mtunc@isbank.net.tr

PURPOSE: To investigate the efficacy of posterior sub-Tenon's capsule
triamcinolone injection (PSTI) combined with focal laser (FL) photocoagulation in
treatment of diffuse clinically significant diabetic macular edema (CSME).
DESIGN: Prospective randomized clinical study. PARTICIPANTS: Sixty patients with 
diffuse CSME. METHODS: We randomized the patients who had CSME into 2 treatment
groups. A total of 30 eyes received macular focal and grid laser photocoagulation
(MP), and the second group of 30 eyes received FL photocoagulation combined with 
PSTI (FL + PSTI). Clinical and visual evaluations were performed at baseline and 
12 and 18 weeks after treatment, and the results were compared by statistical
methods. MEAN OUTCOME MEASURES: Early Treatment Diabetic Retinopathy Study
(ETDRS) visual acuity (VA) scores and clinical changes in macular edema. RESULTS:
Before treatment, mean ETDRS VA scores were 45.9+/-12.7 (mean +/- standard
deviation [SD]; range, 24-66) in MP (focal + grid laser) and 44.5+/-12.6 (range, 
22-66) in the FL + PSTI group. Early Treatment Diabetic Retinopathy Study scores 
at 18 weeks were 46.4+/-14.2 (range, 20-70) after MP and 52.5+/-17.5 (range,
22-82) after FL + PSTI. Early Treatment Diabetic Retinopathy Study scores
significantly improved in eyes that received FL + PSTI (P = 0.0001, paired t
test). The FL + PSTI group had an increase of 12.4+/-7.1 (range, 5-26) ETDRS
letters, and the MP group had an increase of 7.8+/-3.1 (range, 5-15) letters (P =
0.04, unpaired t test). Twelve of 30 (40%) cases in the MP group and 24 of 30
(80%) cases in the FL + PSTI group showed clinical improvement in macular edema
according to the stereoscopic evaluation of fundus and fluorescein angiography (P
= 0.003). CONCLUSION: Posterior sub-Tenon's capsule application of triamcinolone 
may improve early visual outcome in diffuse diabetic macular edema when combined 
with FL photocoagulation.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 15885789 [PubMed - indexed for MEDLINE]

1944: Ophthalmology. 2005 Jun;112(6):1048-53.

Maximum tolerated dose of a humanized anti-vascular endothelial growth factor
antibody fragment for treating neovascular age-related macular degeneration.

Rosenfeld PJ, Schwartz SD, Blumenkranz MS, Miller JW, Haller JA, Reimann JD,
Greene WL, Shams N.

Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami,
Miami, Florida 33136, USA. prosenfeld@med.miami.edu

PURPOSE: To investigate the maximum tolerated dose of ranibizumab administered as
a single intravitreal injection. DESIGN: Open-label, 5-center, uncontrolled,
prospective, dose-ranging, interventional case series. PARTICIPANTS: Twenty-seven
patients with subfoveal choroidal neovascularization (CNV) secondary to
age-related macular degeneration (AMD) with best-corrected Snellen equivalent
visual acuity (VA) of 20/100 or worse and considered ineligible for laser
photocoagulation or photodynamic therapy. METHODS: A single intravitreal
injection of ranibizumab was to be administered at 1 of 6 escalating doses (50,
150, 300, 500, 1000, and 2000 microg), with escalation to the next dose level
occurring only after the safety and tolerability of the lower dose level was
established through postinjection day 14. Follow-up examinations were performed
on postinjection days 1, 3, 7, 14, 42, and 90. Enrollment was stopped if > or =2 
patients experienced dose-limiting toxicity. MAIN OUTCOME MEASURES: The primary
safety measures were changes from baseline in VA, intraocular pressure (IOP),
intraocular inflammation, and production of antiranibizumab antibody.
Dose-limiting toxicity was defined by intraocular inflammation, elevated IOP,
reduced VA, or hemorrhage within 90 days after injection. RESULTS: All patients
completed this single intravitreal injection study, and 500 microg of ranibizumab
was the maximum tolerated dose. At the higher dose of 1000 microg, significant
intraocular inflammation was noted. All adverse events were self-limited, and no 
infectious endophthalmitis occurred. Aqueous or vitreous ocular inflammation
occurred in 12 subjects, with complete resolution within 42 days. In 9 of the
subjects, the inflammation was graded as trace to 1+ and required no treatment;
in 3 of the subjects, the inflammation was graded as 2+ or 3+, and 2 of the 3
were treated with topical 1% prednisolone acetate. No serum antiranibizumab
antibodies were detected. All patients had VA similar or improved compared with
baseline values. CONCLUSION: The maximum tolerated single dose of ranibizumab in 
neovascular AMD patients was 500 microg. Single intravitreal injections of
ranibizumab up to a dose of 500 microg were safe and well tolerated in this small
group of patients.

Publication Types: 
    Clinical Trial
    Clinical Trial, Phase I
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 15885778 [PubMed - indexed for MEDLINE]

1945: BMC Health Serv Res. 2005 May 10;5:34.

Trends in provision of photodynamic therapy and clinician attitudes: a tracker
survey of a new health technology.

Foy RC, Foot B, Francis J, Chakravarthy U, Wormald RP.

The Centre for Health Services Research, University of Newcastle upon Tyne, UK.
R.C.Foy@newcastle.ac.uk

BACKGROUND: There has been debate about the cost-effectiveness of photodynamic
therapy (PDT), a treatment for neovascular age-related macular degeneration. We
have been monitoring trends for the provision of PDT in the UK National Health
Service. The fourth annual 'tracker' survey took place as definitive National
Institute for Clinical Excellence (NICE) guidance was issued. We assessed trends 
in PDT provision up to the point of release of the NICE guidance and identified
likely sources of pressure on ophthalmologists to provide PDT. METHODS: National 
postal questionnaire survey of clinicians with potential responsibility for PDT
provision. The survey explored reported local provision, beliefs about the
effectiveness of PDT and what sources of opinion might influence attitudes
towards providing PDT. RESULTS: The response rate was 73% (111/150). Almost half 
of the surveyed ophthalmology units routinely provided PDT, as part of a trend of
steady growth in provision. The proportion of respondents who believed that
further proof of effectiveness was required has also declined despite the absence
of any new substantial evidence. Attitudes towards providing PDT were positive,
on average, and were more strongly associated with perceived social pressure from
local colleagues than from other sources. Local colleagues were seen as being
most approving of PDT. CONCLUSION: Those responsible for implementing the NICE
guidance need to address ophthalmologists' beliefs about the evidence of
effectiveness for PDT and draw upon supportive local individuals or networks to
enhance the credibility of the guidance.

PMID: 15885142 [PubMed - indexed for MEDLINE]

1946: Ophthalmology. 2005 Jun;112(6):1062-5.

Macular degeneration in a patient with aceruloplasminemia, a disease associated
with retinal iron overload.

Dunaief JL, Richa C, Franks EP, Schultze RL, Aleman TS, Schenck JF, Zimmerman EA,
Brooks DG.

F. M. Kirby Center for Molecular Ophthalmology, Philadelphia, Pennsylvania, USA. 
jdunaief@mail.med.upenn.edu

PURPOSE: To provide the first ophthalmic case report of a Caucasian patient with 
the rare autosomal recessive disease aceruloplasminemia, which results in iron
overload in the retina, brain, and pancreas. DESIGN: Single observational case
report. METHODS: Perls' staining of a conjunctival biopsy was used to detect
elevated iron levels in the conjunctival epithelium. Fundus photography,
fluorescein angiography, and electroretinography were used to document retinal
appearance and function. RESULTS: Unlike a report of a Japanese patient with
aceruloplasminemia, who had midperipheral retinal pigment epithelium (RPE) cell
atrophy and yellowish discoloration of the fundus, our Caucasian patient had a
maculopathy. Beginning at age 47, he had development and progression of multiple 
subretinal yellowish-white lesions and RPE cell atrophy. To confirm tissue iron
overload in our patient, we took the novel approach of a conjunctival biopsy,
which showed Perls' Prussian blue-positive epithelial cells. CONCLUSIONS: Given
our recent finding of elevated iron levels in the RPE of patients with
age-related macular degeneration (AMD), it is interesting that retinal iron
overload in aceruloplasminemia is associated with a maculopathy that clinically
resembles AMD. This finding supports the hypothesis that retinal iron homeostasis
is essential for normal retinal function. Disruption of iron homeostasis could
contribute to the pathogenesis of AMD.

Publication Types: 
    Case Reports
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15882908 [PubMed - indexed for MEDLINE]

1947: Ophthalmology. 2005 Jun;112(6):1079-85.

Redefining the limit of the outer retina in optical coherence tomography scans.

Pons ME, Garcia-Valenzuela E.

The New York Eye and Ear Infirmary, New York, New York, USA.

OBJECTIVE: A highly reflective layer seen in retinal optical coherence tomography
(OCT) has been believed to correspond to the choriocapillaris (CHC) and retinal
pigment epithelium (RPE). On gray-scale scans of OCT-2000, and on Stratus OCT,
this layer by the outer retinal limit can be resolved into 2 distinct laminae. We
analyzed these 2 laminae in normal and abnormal maculae to infer their anatomic
correlate. DESIGN: Retrospective study. METHODS: Analysis of macular OCT scans
was performed in 44 patients using OCT-2000, and in 39 patients using Stratus
OCT. Thirty of these patients had no ocular disease, and their OCT was normal.
The other 53 patients had several macular diseases of different etiologies. Both 
color and gray-scale images were analyzed. RESULTS: Macular OCT scans showed a
double laminae at the level where the retina interfaces the RPE in normal
subjects using both OCT-2000 and Stratus OCT. In 2-dimensional scans, this
laminar structure appears as a double line. It is best distinguished on the
Stratus OCT and gray-scale images of OCT-2000. This double line consisted of a
thin inner line and a thicker outer line. Similar analysis in patients with
macular pathology showed a discernible double line at the retina/RPE interface in
at least part of the scan. However, in patients with macular hole, the area
corresponding to the absent retina showed only a single line. The inner line
component appeared to follow the contour of the retina. This phenomenon was also 
seen in eyes with neurosensory detachment secondary to central serous
chorioretinopathy and other etiologies. In contrast, in macular pathologies where
the outer retina did not lose contiguity with the RPE, such as in lamellar
macular hole and in cystoid macular edema, the double line persisted. Software
for retinal thickness measurements regularly place the outer limit of the retina 
at the internal aspect of the inner line, probably underestimating the retinal
thickness by about 24 to 34 mum. CONCLUSIONS: A double laminar structure at the
outer retina/RPE/CHC interface can be consistently distinguished on commercially 
available OCT of normal eyes. In eyes with macular pathology, OCT analysis of the
inner lamina leads us to conclude it is most likely part of the neurosensory
retina and not part of the RPE/CHC complex as previously thought.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15882904 [PubMed - indexed for MEDLINE]

1948: Ophthalmology. 2005 Jun;112(6):1054-61.

Ocular conditions associated with peripapillary subretinal neovascularization,
their relative frequencies, and associated outcomes.

Browning DJ, Fraser CM.

Charlotte Eye, Ear, Nose, and Throat Associates, Charlotte, North Carolina, USA. 
djbrowning@carolina.rr.com

OBJECTIVE: To determine frequency and outcomes of conditions with peripapillary
subretinal neovascular membranes (PSRNVMs). DESIGN: Retrospective observational
case series. PARTICIPANTS: All patients from a private community-based retina
practice diagnosed with a PSRNVM. METHODS: Review of clinical charts,
photographs, and fluorescein angiograms of 115 eyes of 96 patients, accrued over 
18 years. MAIN OUTCOME MEASURES: Demographics, visual acuity (VA), laterality,
neovascular membrane type and recurrence status over treatment course, and
associated ocular conditions. RESULTS: Prevalences of reported associations were 
52 (45.2%), age-related maculopathy (ARM); 45 (39.1%), idiopathic; 5 (4.3%),
multifocal choroiditis; 3 (2.6%), angioid streaks; 2 (1.7%), histoplasmosis; 2
(1.7%), choroidal osteoma; 1 (0.9%), optic disc drusen; and 1 (0.9%), congenital 
disc anomaly. Newly recognized associations include pattern dystrophy (3 [2.6%]) 
and peripapillary pseudopodal pigment epithelial and choroidal atrophy (1
[0.9%]). Second-eye involvement was observed in 19.8% of patients over a median
follow-up of 2 years. Median initial VAs were 20/40 for ARM-associated eyes and
20/30 for idiopathic eyes (P = 0.0230). Median final VAs were 20/70 for
ARM-associated eyes and 20/32 for idiopathic eyes (P = 0.0261). The VA changes in
the ARM-associated and idiopathic groups did not differ significantly (P =
0.1453). Recurrence of PSRNVMs after laser ablation was seen in 14 of 73 eyes
(19.2%). A case of a PSRNVM as a cause of pseudopapilledema leading to
unnecessary neurological imaging is reported. CONCLUSIONS: Close inspection of
fellow eyes at the time of first eye diagnosis and regular follow-up afterward
are indicated, given the high rate of eventual bilateral involvement regardless
of associated condition. Laser ablation of PSRNVMs with broad treatment margins
reduces recurrence rates relative to earlier series. The differential diagnosis
of disc edema should include PSRNVMs. Pattern dystrophy can be associated with
PSRNVMs.

Publication Types: 
    Case Reports

PMID: 15882903 [PubMed - indexed for MEDLINE]

1949: Doc Ophthalmol. 2004 Sep;109(2):139-45.

Pattern electroretinogram for monitoring the efficacy of intravitreal
triamcinolone injection in diabetic macular edema.

Ozkiris A, Evereklioglu C, Oner A, Erkiliç K.

Erciyes University Medical Faculty, Kayseri, Turkey. aozkiris@erciyes.edu.tr

PURPOSE: To investigate the efficacy of intravitreal triamcinolone (IVT) by
evaluation of pattern electroretinogram (PERG) in diabetic patients with
clinically significant macular edema (CSME). METHODS: Forty eyes of 40 diabetic
patients were treated with 8 mg of IVT injection as primary therapy for CSME. The
main outcome measures included best-corrected visual acuity, fundus fluorescein
angiography, P50 amplitudes of pattern electroretinogram (PERG) and intraocular
pressures before and after injection. RESULTS: The mean follow-up time was 6.1
months. Mean visual acuity improved significantly from a mean LogMAR value of
1.14 +/- 0.16 at baseline to a maximum of 0.73 +/- 0.30. The mean baseline P50
amplitude of PERG before intravitreal injection was 1.5 +/- 0.9 microV. After the
treatment, it was 2.1 +/- 1.1 microV at 1-month, 2.4 +/- 1.0 microV at 3-month
and 2.1 +/- 0.9 microV at last visit and the differences were significant when
compared with baseline values (for each, p < 0.001). Temporary increases in
intraocular pressures were controlled with topical antiglaucomatous medications, 
if required. CONCLUSION: IVT injection provides rapid improvement in visual
acuity of diabetic patients with CSME that has been supported by P50 amplitudes
of PERG. P50 amplitudes of PERG may he used as novel predictive value in the
evaluation of the effectiveness of IVT injection.

Publication Types: 
    Comparative Study

PMID: 15881259 [PubMed - indexed for MEDLINE]

1950: Doc Ophthalmol. 2004 Sep;109(2):131-7.

Assessment of macular function by multifocal electroretinogram in diabetic
macular edema before and after vitrectomy.

Ma J, Yao K, Jiang J, Wu D, Gao R, Yin J, Fang X.

Eye Center of Affiliated Second Hospital School of Medicine Zhejiang University, 
Hangzhou, 310009, P.R. China. zhang691231@yahoo.com.cn

The purpose of this study was to assess the effects of vitrectomy on retinal
function in macular and paramacular areas in patients with diabetic macular edema
(DME). Ten eyes of 9 patients with successful vitrectomy for DME were evaluated
by multifocal electroretinogram (mfERG), optical coherence tomography (OCT), and 
visual acuity preoperatively and 1, 2, 3, 4, 5 and 6 months postoperatively.
Compared with pretreatment values, the response of the positive wave (P1) in
macular and paramacular areas tended to decrease in latency from the second
postoperative month, and increase in amplitude at the third postoperative month. 
There was no significant change in response of the negative wave (N1). The
tendency in the change of macular function is coincident with that of macular
morphology. Therefore, The multifocal ERG may provide objective criteria for the 
functional evaluation of DME before and after vitrectomy.

Publication Types: 
    Comparative Study

PMID: 15881258 [PubMed - indexed for MEDLINE]

1951: Ophthalmology. 2005 May;112(5):806-16.

Vitreous levels of vascular endothelial growth factor and intercellular adhesion 
molecule 1 are related to diabetic macular edema.

Funatsu H, Yamashita H, Sakata K, Noma H, Mimura T, Suzuki M, Eguchi S, Hori S.

Department of Ophthalmology, Diabetes Center, Tokyo Women's Medical University,
Tokyo, Japan. tfunatsu@nifty.com

PURPOSE: To investigate whether vascular endothelial growth factor (VEGF) or
soluble intercellular adhesion molecule 1 (sICAM-1) is related to diabetic
macular edema (DME). DESIGN: Retrospective case-control study. PARTICIPANTS:
Thirty-three patients who had DME and 13 patients with nondiabetic ocular disease
(control group). METHODS: Vitreous fluid samples were obtained at the time of
vitreoretinal surgery, and the VEGF and sICAM-1 levels in vitreous fluid and
plasma were measured by enzyme-linked immunosorbent assay. MAIN OUTCOME MEASURES:
Relationship between vitreous levels of VEGF or sICAM-1 and DME. RESULTS:
Vitreous levels of VEGF and sICAM-1 were significantly higher in DME patients
than in control patients (P < 0.0001 and P = 0.0004, respectively). The vitreous 
level of VEGF was significantly correlated with that of sICAM-1 (P < 0.0001).
Vitreous levels of both VEGF and sICAM-1 were significantly higher in patients
with hyperfluorescent DME than in those with minimally fluorescent DME (P =
0.0027 and P = 0.0005, respectively). The vitreous levels of both VEGF and
sICAM-1 were significantly correlated with retinal thickness at the central fovea
(P < 0.0001 and P = 0.0005, respectively) CONCLUSIONS: We found that both VEGF
and sICAM-1 were elevated in the vitreous fluid of patients with hyperfluorescent
DME. These results suggest that VEGF and ICAM-1 are related to the increase of
vascular permeability in DME patients.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15878060 [PubMed - indexed for MEDLINE]

1952: Ophthalmology. 2005 May;112(5):787-98.

14-year incidence, progression, and visual morbidity of age-related maculopathy: 
the Copenhagen City Eye Study.

Buch H, Nielsen NV, Vinding T, Jensen GB, Prause JU, la Cour M.

Department of Ophthalmology, National University Hospital (Rigshospitalet),
Copenhagen, Denmark. hbh@dadlnet.dk

PURPOSE: To describe the 14-year incidence of age-related maculopathy (ARM)
lesions and the related visual loss. DESIGN: Population-based cohort study.
PARTICIPANTS: Nine hundred forty-six residents (age range, 60-80 years) of
Copenhagen participated in the study from 1986 through 1988. Excluding
participants who had died since baseline, 359 persons (97.3% of survivors) were
reexamined from 2000 through 2002. METHODS: Participants underwent extensive
ophthalmologic examinations. Age-related maculopathy lesions were determined by
grading color fundus photographs from the examinations using a modified Wisconsin
Age-Related Maculopathy Grading System. MAIN OUTCOME MEASURES: Incidence of
drusen type and size, pigmentary abnormalities, pure geographic atrophy,
exudative ARM, visual impairment, and blindness. RESULTS: The 14-year incidences 
of early and late ARM were 31.5% and 14.8%, respectively. Individuals 75 to 80
years of age at baseline had significantly (P< or =0.05) higher 14-year
incidences of the following lesions than those aged 60 to 64 years: medium or
large drusen (> or =125 microm; 34.2% vs. 12.8%, respectively), soft drusen
(45.2% vs. 21.4%), pigmentary abnormalities (31.4% vs. 17.0%), pure geographic
atrophy (17.4% vs. 1.0%), and exudative ARM (23.3% vs. 5.7%). Severe drusen type,
large drusen, and retinal pigmentary abnormalities at baseline were important
predictors of incident late ARM. The 14-year incidences of visual impairment
(<20/40 but >20/200) or legal blindness from late ARM were 6.0% and 3.4%,
respectively. Late ARM caused 35.7% of all visual impairment and 66.7% of all
blindness. CONCLUSIONS: There is a high incidence of ARM lesions in this elderly 
white population. Severe drusen type and size or a combination of drusen and
pigmentary abnormalities significantly increases the risk of developing late ARM,
the most frequent cause of legal blindness in this population.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15878058 [PubMed - indexed for MEDLINE]

1953: Curr Opin Ophthalmol. 2005 Jun;16(3):179-83.

Self-reported visual functioning and quality of life in age-related macular
degeneration.

Chakravarthy U, Stevenson M.

Centre for Ophthalmology and Vision Science, Queen's University, Institute for
Clinical Science, Royal Group of Hospitals Trust, Belfast, UK.
u.chakravarthy@qub.ac.uk

PURPOSE OF REVIEW: To review the current literature on the impact of age-related 
macular degeneration on self-reported visual functioning, quality of life, and
independent living. RECENT FINDINGS: The quantitative relationships between
visual acuity, an objective clinical measure of vision, and self-reported visual 
functioning have been explored and described within prospective longitudinal
clinical trials. When age-related macular degeneration is bilateral, the severe
and irreversible loss of central vision experienced by affected persons has been 
shown to result in despondency, inability to care for self or others, and a state
of disutility, which is equivalent to that experienced in coronary heart disease 
and stroke. SUMMARY: Quality-of-life indicators and self-reported visual
functioning have gained acceptance as key outcome measure in studies designed to 
test therapeutic interventions and rehabilitation strategies in age-related
macular degeneration. Vision loss from age-related macular degeneration engenders
a profound sense of loss and the resultant handicap has been likened to that of
the most severe medical conditions.

Publication Types: 
    Review

PMID: 15870576 [PubMed - indexed for MEDLINE]

1954: Curr Opin Ophthalmol. 2005 Jun;16(3):166-9.

Light energy, cataract surgery, and progression of age-related macular
degeneration.

Smith BT, Belani S, Ho AC.

Wills Eye Hospital, Philadelphia, PA 19107, USA. acho@att.net

PURPOSE OF REVIEW: Some studies suggest an association between light exposure and
increased risk of advanced age-related macular degeneration. The natural lens
serves as a barrier to some of the higher energy light rays. There is some
concern that cataract surgery may be contributing to the increase in prevalence
of age-related macular degeneration. RECENT FINDINGS: It has been shown that blue
light absorption by retinal pigment epithelium results in free radical formation,
leading to cellular injury, and that blue filters can reduce this rate of cell
death. Other studies have shown a tendency for pseudophakic eyes to progress to
the wet form of age-related macular degeneration more so than their fellow eyes. 
SUMMARY: Currently there is no conclusive evidence to support a relation between 
progression of age-related macular degeneration and cataract surgery. Given that 
nearly two million cataract extractions are performed yearly, a large randomized 
controlled study is required to prove or disprove the ability of tinted
intraocular lenses to aid in preventing the progression of age-related macular
degeneration.

Publication Types: 
    Review

PMID: 15870573 [PubMed - indexed for MEDLINE]

1955: Proc Natl Acad Sci U S A. 2005 May 17;102(20):7227-32. Epub 2005 May 3.

Comment in:
    Proc Natl Acad Sci U S A. 2005 May 17;102(20):7053-4.

A common haplotype in the complement regulatory gene factor H (HF1/CFH)
predisposes individuals to age-related macular degeneration.

Hageman GS, Anderson DH, Johnson LV, Hancox LS, Taiber AJ, Hardisty LI, Hageman
JL, Stockman HA, Borchardt JD, Gehrs KM, Smith RJ, Silvestri G, Russell SR,
Klaver CC, Barbazetto I, Chang S, Yannuzzi LA, Barile GR, Merriam JC, Smith RT,
Olsh AK, Bergeron J, Zernant J, Merriam JE, Gold B, Dean M, Allikmets R.

Department of Ophthalmology and Visual Sciences, Cell Biology and Functional
Genomics Laboratory, University of Iowa, Iowa City, IA 52240, USA.
gregory-hageman@uiowa.edu

Age-related macular degeneration (AMD) is the most frequent cause of irreversible
blindness in the elderly in developed countries. Our previous studies implicated 
activation of complement in the formation of drusen, the hallmark lesion of AMD. 
Here, we show that factor H (HF1), the major inhibitor of the alternative
complement pathway, accumulates within drusen and is synthesized by the retinal
pigmented epithelium. Because previous linkage analyses identified chromosome
1q25-32, which harbors the factor H gene (HF1/CFH), as an AMD susceptibility
locus, we analyzed HF1 for genetic variation in two independent cohorts comprised
of approximately 900 AMD cases and 400 matched controls. We found association of 
eight common HF1 SNPs with AMD; two common missense variants exhibit highly
significant associations (I62V, chi2 = 26.1 and P = 3.2 x 10(-7) and Y402H, chi2 
= 54.4 and P = 1.6 x 10(-13)). Haplotype analysis reveals that multiple HF1
variants confer elevated or reduced risk of AMD. One common at-risk haplotype is 
present at a frequency of 50% in AMD cases and 29% in controls [odds ratio (OR) =
2.46, 95% confidence interval (1.95-3.11)]. Homozygotes for this haplotype
account for 24% of cases and 8% of controls [OR = 3.51, 95% confidence interval
(2.13-5.78)]. Several protective haplotypes are also identified (OR = 0.44-0.55),
further implicating HF1 function in the pathogenetic mechanisms underlying AMD.
We propose that genetic variation in a regulator of the alternative complement
pathway, when combined with a triggering event, such as infection, underlie a
major proportion of AMD in the human population.

Publication Types: 
    Comparative Study
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15870199 [PubMed - indexed for MEDLINE]

1956: Ophthalmic Res. 2005 May-Jun;37(3):136-41. Epub 2005 May 3.

Melanin aggregation and polymerization: possible implications in age-related
macular degeneration.

Sarangarajan R, Apte SP.

Department of Phamaceutical Sciences, Massachusetts College of Pharmacy and
Health Sciences, Worcester, MA, USA.

The state of aggregation of the polymer melanin may determine its propensity to
act either as an antioxidant or as a pro-oxidant. Age-related alterations in its 
state of aggregation are suggested to alter the degree of polymerization so as to
confer increased pro-oxidant propensity to the melanin polymer. Degradative
processes in/of melanosomes and lysosomes in the retinal pigment epithelium (RPE)
appear to be intimately connected so that they may involve exchange of contents
between these two organelles. An increased pro-oxidant environment inside
lysosomes has been associated with preventing the digestion of cellular
components including photoreceptor outer rod segments partly by altering function
of lysosomal hydrolases. It is speculated that age-related accumulation of
low-molecular-weight phototoxic pro-oxidant melanin oligomers within lysosomes in
the RPE may be partly responsible for decreasing the digestive rate of
incorporated cellular components (including photoreceptor outer rod segments)
which may lead to lipofuscin formation. More work is required to definitively
refute or support such a hypothesis. Copyright (c) 2005 S. Karger AG, Basel.

PMID: 15867475 [PubMed - indexed for MEDLINE]

1957: Graefes Arch Clin Exp Ophthalmol. 2005 Apr;243(4):300-5. Epub 2004 Oct 13.

Changes in fundus autofluorescence in patients with age-related maculopathy.
Correlation to visual function: a prospective study.

Einbock W, Moessner A, Schnurrbusch UE, Holz FG, Wolf S; FAM Study Group.

Department of Ophthalmology, University of Leipzig, Liebigstrasse 10-14, 04103,
Leipzig, Germany.

BACKGROUND: As members of the Fundus Autofluorescence in Age-related Macular
Degeneration Study Group (FAM Study Group), we report changes of fundus
autofluorescence (AF) in patients with multiple soft drusen in correlation to
visual function. METHODS: Inclusion criteria were age >50 years, the presence of 
soft drusen, visual acuity of 20/100 or better, and no previous laser treatment
in the study eye. All patients underwent a detailed ophthalmological examination 
including ETDRS visual acuity, binocular funduscopy, and color fundus
photography. AF imaging was performed with a confocal scanning laser
ophthalmoscope following a standard protocol. We used the classification of the
International Fundus Autofluorescence Classification Group (IFAG) for the
description of the AF patterns. RESULTS: One hundred and twenty-five patients (81
women, 44 men) aged from 55 to 86 years (mean 70+/-7 years) were included in this
prospective study. During follow-up (mean 18+/-6 months), 6 of 35 eyes with
patchy AF pattern developed exudative changes, as well as 2 eyes with
focal-plaque-like AF pattern and 1 eye with reticular pattern at baseline.
Geographic atrophy was seen in two eyes with focal AF pattern and one eye with
focal-plaque-like pattern at baseline. A total of 11 eyes presented with severe
visual loss (> or = 6 ETDRS lines). Ten (91%) of these had patchy AF pattern.
CONCLUSION: Imaging of fundus AF in patients with age-related maculopathy allows 
identification of different patterns of fundus AF. Our preliminary data suggest
that a patchy pattern of AF indicates a relatively high risk of progression to
age-related macular degeneration with visual loss.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 15864618 [PubMed - indexed for MEDLINE]

1958: Am J Ophthalmol. 2005 May;139(5):923-5.

Anatomical and functional characteristics in atrophic maculopathy associated with
spinocerebellar ataxia type 7.

Ahn JK, Seo JM, Chung H, Yu HG.

Department of Ophthalmology, Seoul National University College of Medicine, 28
Yongon-dong, Chongno-gu, Seoul 110-744, Republic of Korea.

PURPOSE: To assess the anatomic and functional characteristics in a Korean family
with spinocerebellar ataxia type 7-associated atrophic maculopathy. DESIGN:
Observational case report. METHODS: Three patients in a family underwent
funduscopic examination, fluorescein angiogram, full-field electroretinogram
(ERG), electro-oculogram, and optical coherence tomography (OCT). Macular
functions were assessed using multifocal ERG and scanning laser ophthalmoscope
(SLO) microperimetry. RESULTS: Both eyes showed bull's eye configuration and
cone-rod dystrophy phenotype. OCT revealed that retinal thinning extended outside
the visibly atrophic lesions. Multifocal ERG demonstrated that amplitudes from
the six ring segments were reduced in a centrifugal pattern. SLO microperimetry
showed that fixations were unstable and shifted superior to the atrophic lesions.
The areas of functional deficits were greater than those of anatomic deficits.
CONCLUSIONS: Macular functions were severely depressed in atrophic maculopathy
associated with spinocerebellar ataxia type 7 in both the visibly atrophic areas 
and the areas without visible atrophy in a centrifugal pattern.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 15860307 [PubMed - indexed for MEDLINE]

1959: Am J Ophthalmol. 2005 May;139(5):860-6.

Intravitreal triamcinolone acetonide for cystoid macular edema in nonischemic
central retinal vein occlusion.

Williamson TH, O'Donnell A.

Department of Ophthalmology, St Thomas' Hospital, Lambeth Palace Road, London SE1
7EH, United Kingdom. tom@retinasurgery.co.uk

PURPOSE: The effectiveness of intravitreal triamcinolone acetonide in the
treatment of cystoid macular edema from central retinal vein occlusion (CRVO) was
investigated. DESIGN: A noncomparative, prospective, interventional case series. 
METHODS: In a clinical practice, 18 patients were enrolled with nonischemic CRVO 
and cystoid macular edema. Two milligrams of triamcinolone acetonide were
injected into the vitreous of only one eye from each patient. The outcome
measures were 1-mm mean central retinal thickness on optical coherence tomography
and visual acuity. RESULTS: Mean duration of symptoms before surgery was 2 months
(SD, 1.3 months). Ten patients required repeated injections for recurrent cystoid
macular edema (mean, 1.8 injections). Mean visual acuity significantly improved
from 20/300 to 20/166 (P = .007) at 1 month, 20/100 (P = .0005) at 2 months,
20/130 (P = .007) at 3 months, and 20/150 (P = .02) at 6 months but deteriorated 
again to 20/270 (not significant) at 12 months. There was a significant
improvement in retinal thickness from presentation 518 microm, to 363 microm (P =
.03) at 1 month, 304 microm (P = .04) at 2 months, and 353 microm (P = .01) at 3 
months but not from presentation at 6 months (mean, 383 microm) and 12 months
(mean, 406 microm). Eleven patients suffered intraocular pressure rises requiring
intervention. Intravitreal triamcinolone acetonide did not prevent collateral
circulation formation, which was seen in 10 patients. CONCLUSION: Intravitreal
corticosteroid injection is very effective in reversing cystoid macular edema and
improving visual acuity in recent-onset nonischemic CRVO in the first 6 months,
but this is unfortunately not sustained at 1 year.

PMID: 15860292 [PubMed - indexed for MEDLINE]

1960: Am J Ophthalmol. 2005 May;139(5):820-5.

Comment in:
    Am J Ophthalmol. 2005 May;139(5):908-11.

Comparing age-related macular degeneration phenotype in probands from singleton
and multiplex families.

Postel EA, Agarwal A, Schmidt S, Fan YT, Scott WK, Gilbert JR, Haines JL,
Pericak-Vance MA.

Duke University Eye Center, Box 3802, Durham, NC 27710, USA. poste002@mc.duke.edu

PURPOSE: To compare age-related macular degeneration (AMD) phenotype between
probands in singleton and multiplex families to determine whether data from these
two groups may be combined for consolidated genetic analyses. DESIGN:
Retrospective case-control study. METHODS: Individuals 55 years of age or older
with AMD were identified. Complete histories and examinations were recorded,
35-mm fundus photographs obtained, and macular findings graded. Detailed
information was recorded, including the presence of extramacular and peripheral
drusen, peripheral reticular pigmentary change, posterior vitreous detachment,
and iris color. Comparisons were performed between probands from singleton and
multiplex families. RESULTS: There was no statistically significant difference in
grade between the 411 singleton and 125 multiplex probands (P = .52), and the
distribution of grades was similar between the two groups. No statistically
significant difference was found between proband groups with respect to the
presence or extent of small (P = .48), intermediate (P = .72), and large drusen
(P = .74) and retinal pigment epithelium hyper- (P = .76) and hypopigmentation (P
= .55); in the presence or grade of peripheral reticular pigment change; the
presence of geographic atrophy in exudative disease, extramacular drusen, or
posterior vitreous detachment; lens status; iris color; visual acuity;
intraocular pressure; optic nerve cupping; and body mass index. A statistically
significant difference between the two groups was noted in the presence of
peripheral drusen (P = .0001). CONCLUSIONS: Singleton and multiplex AMD probands 
share a similar phenotype. This suggests that multiplex and singleton data can be
combined for consolidated genetic analyses.

Publication Types: 
    Comparative Study
    Research Support, N.I.H., Extramural
    Research Support, U.S. Gov't, P.H.S.

PMID: 15860286 [PubMed - indexed for MEDLINE]

1961: Am J Ophthalmol. 2005 May;139(5):807-13.

Comment in:
    Am J Ophthalmol. 2006 Jan;141(1):234-5; author reply 235.

Optical coherence tomography assessment of the vitreoretinal relationship in
diabetic macular edema.

Gaucher D, Tadayoni R, Erginay A, Haouchine B, Gaudric A, Massin P.

Department of Ophthalmology, Hôpital Lariboisière, Université Paris 7, and
Assistance Publique-Hôpitaux de Paris, 2 rue Ambroise Paré, 75010 Paris, France.

PURPOSE: To study the vitreoretinal relationship in diabetic patients with and
without diabetic macular edema (DME) using optical coherence tomography. DESIGN: 
Retrospective case-control study. METHODS: setting: Institutional practice.
patients: Thirty-five consecutive diabetic patients (49 eyes) with DME and 35
sex- and age-matched diabetic control patients without DME (49 eyes). observation
procedure: All patients had Early Treatment Diabetic Retinopathy Study visual
acuity measurement and biomicroscopic examination of the vitreoretinal interface.
OCT was performed to obtain cross-sectional images of the vitreoretinal interface
of the macular region. Posterior vitreous detachment (PVD) was staged from 0 to 3
as follows: stage 0: absence of PVD; stage 1: perifoveolar PVD with foveolar
attachment; stage 2: incomplete PVD with residual attachment to the optic nerve; 
and stage 3: complete PVD. Retinal thickness was measured using OCT mapping
software in all cases. main outcome measures: Prevalence of the different PVD
stages in both groups of eyes. RESULTS: The mean age of the patients was 60 years
in both groups. Of the eyes with macular edema, 19 (38.8%) were stage 0, 26
(53.0%) stage 1, 1 (2.0%) was stage 2, and 3 (6.2%) were stage 3. In eyes without
DME, the corresponding figures were, respectively, 34 (69.4%), 11 (22.4%), 1
(2.0%), and 3 (6.2%). The prevalence of perifoveolar PVD with foveolar attachment
was significantly higher in the group of eyes with DME (P =.006). CONCLUSIONS:
These results show the high prevalence of perifoveolar PVD with foveolar
attachment in diabetic patients with macular edema. Even though PVD is not the
main factor involved in the pathogenesis of DME, perifoveolar PVD may have a role
in the development of this complication.

PMID: 15860284 [PubMed - indexed for MEDLINE]

1962: Am J Ophthalmol. 2005 May;139(5):802-6.

Relation between reduction of foveal thickness and visual acuity in diabetic
macular edema treated with intravitreal triamcinolone.

Larsson J, Zhu M, Sutter F, Gillies MC.

Department of Clinical Ophthalmology, Save Sight Institute, University of Sydney,
GPO Box 4337, Sydney, NSW 2001, Australia. jorgen@eye.usyd.edu.au

PURPOSE: To evaluate the correlation between improvement in visual acuity and the
reduction of foveal thickness after a single intravitreal injection of 4 mg of
triamcinolone in diabetic macular edema. DESIGN: Prospective, interventional,
nonrandomized clinical trial. METHOD: Patients: In a prospective study 24 eyes
with diabetic macular edema were treated with an intravitreal injection of 4 mg
of triamcinolone acetonide. Main Outcome Measures: Best-corrected logMAR visual
acuity and optical coherence tomography were performed at baseline and 3 months
after the treatment. RESULTS: At baseline the average foveal thickness was 462
+/- 154 microm (95% confidence interval, 397-527 microm) and at 3 months 257
+/-114 microm (95% confidence interval, 209-305 microm) (P < .0001). The
best-corrected logMAR average visual acuity was 60.5 +/- 10.5 (95% confidence
interval, 56.0-65.0) ETDRS letters at baseline compared with 65.5 +/- 11.1 (95%
confidence interval, 60.8-70.1) 3 months after the injection (P = .0001). There
was no correlation between the improvement in visual acuity and the reduction of 
foveal thickness (r = 0.054, P = .8), but there was a correlation between
reduction in foveal thickness and the age of the patients (r = 0.53, P = .008).
CONCLUSION: A single injection of 4 mg of intravitreal triamcinolone acetonide
effectively reduces the foveal thickness in diabetic macular edema and improves
visual acuity, but there does not appear to be a strong correlation between the
reduction of foveal thickness and the improvement in visual acuity.

Publication Types: 
    Clinical Trial

PMID: 15860283 [PubMed - indexed for MEDLINE]

1963: Am J Ophthalmol. 2005 May;139(5):795-801.

Comment in:
    Am J Ophthalmol. 2005 Nov;140(5):964; author reply 965.

Modified grid laser photocoagulation versus pars plana vitrectomy with internal
limiting membrane removal in diabetic macular edema.

Yanyali A, Nohutcu AF, Horozoglu F, Celik E.

Department of Ophthalmology, Haydarpasa Numune Education and Research Hospital,
Istanbul, Turkey. ayanyali@hotmail.com

PURPOSE: To compare the effectiveness of pars plana vitrectomy (PPV) and removal 
of the internal limiting membrane (ILM) with modified grid laser photocoagulation
in diabetic macular edema. DESIGN: Randomized, comparative, interventional study.
METHODS: In this prospective study, 24 eyes of 12 patients with bilateral
diabetic macular edema were evaluated. PPV with removal of the ILM was performed 
at random in one eye of 12 patients (ILM group), and a single session of modified
grid laser photocoagulation was performed in the fellow eyes (grid group). Main
outcome measures were the foveal thickness measured with optical coherence
tomography, preoperative, and postoperative visual acuities. Mann-Whitney U and
Wilcoxon tests were used in statistical analysis. RESULTS: All patients were
followed up for 6 months. In the ILM group, mean foveal thickness was 439.2 +/-
106.5 microm preoperatively and 219.8 +/- 63.2 mum postoperatively (P = .002). In
the grid group, mean foveal thickness was 407 +/- 100.2 microm preoperatively and
378.5 +/- 141.6 microm postoperatively (P = .433). A mean decrease in foveal
thickness was found to be 219.4 +/- 127.6 microm in the ILM group and 28.5 +/-
90.5 microm in the grid group (P = .001). In the ILM group, best-corrected logMAR
visual acuity was 0.75 +/- 0.41 preoperatively and 0.53 +/- 0.41 postoperatively 
(P = .006). In the grid group, best-corrected logMAR visual acuity was 0.59 +/-
0.27 preoperatively and 0.49 +/- 0.27 postoperatively (P = .058). Visual acuity
improved by 2 or more lines in six eyes (50%) in the ILM group and in three eyes 
(25%) in the grid group. Visual acuity remained stable in six eyes (50%) in the
ILM group and in nine eyes (75%) in the grid group. CONCLUSIONS: PPV with ILM
removal appears to be more effective than a single session of modified grid laser
photocoagulation in the treatment of diabetic macular edema. Further studies with
a large number of patients are required for a more reliable conclusion.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 15860282 [PubMed - indexed for MEDLINE]

1964: Invest Ophthalmol Vis Sci. 2005 May;46(5):1765-73.

Nuclear gene expression changes due to mitochondrial dysfunction in ARPE-19
cells: implications for age-related macular degeneration.

Miceli MV, Jazwinski SM.

Department of Biochemistry and Molecular Biology, Louisiana State University
Health Sciences Center, 1901 Perdido Street, New Orleans, LA 70112, USA.

PURPOSE: To measure changes in nuclear gene expression resulting from
mitochondrial dysfunction in retinal pigment epithelial cells. METHODS: ARPE-19
retinal pigment epithelial cells were depleted of their mitochondrial (mt)DNA by 
passaging in a low concentration of ethidium bromide. Loss of mitochondrial DNA
was determined by uridine auxotrophy and quantitative real-time polymerase chain 
reaction of isolated DNA. Loss of mitochondrial membrane potential was estimated 
by uptake of JC-1. Changes in nuclear gene expression were determined by
quantitative real-time reverse transcription-polymerase chain reaction of
isolated total RNA from ethidium-bromide-treated and untreated cells. Morphologic
and phenotypic changes were determined by phase-contrast microscopy, sensitivity 
to the oxidant tert-butyl hydroperoxide (tBH), and invasion assay. RESULTS:
ARPE-19 cells became auxotrophic for growth on uridine after eight passages in 50
ng/mL ethidium bromide. Quantitative PCR revealed almost complete loss of
mitochondrial DNA (rho(0) cells). Uptake of JC-1 was reduced in the rho(0) cells,
indicating reduction of mitochondrial membrane potential. Quantitative RT-PCR
measured increased expression of genes coding for drusen components, lipid
transport, extracellular matrix components, and responses to inflammation in the 
rho(0) cells. The rho(0) cells also exhibited an increased sensitivity to killing
by tBH and increased migration and invasion through solubulized basement
membrane-coated tissue culture inserts. CONCLUSIONS: ARPE-19 cells respond to
loss of mitochondrial function by changes in nuclear gene expression that
resemble changes observed in age-related macular degeneration. The results lead
to the hypothesis that loss of mitochondrial function with age and resultant
changes in nuclear gene expression may explain some of the changes in the macula 
that are associated with the known clinical manifestations of age-related macular
degeneration.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, U.S. Gov't, P.H.S.

PMID: 15851580 [PubMed - indexed for MEDLINE]

1965: Invest Ophthalmol Vis Sci. 2005 May;46(5):1726-34.

Association of HLA class I and class II polymorphisms with age-related macular
degeneration.

Goverdhan SV, Howell MW, Mullins RF, Osmond C, Hodgkins PR, Self J, Avery K,
Lotery AJ.

Human Genetics Division, University of Southampton, Duthie Building, Southampton 
General Hospital, Tremona Road, Southampton SO16 6YD, UK.

PURPOSE: To evaluate whether HLA genotypes are associated with age-related
macular degeneration (AMD). METHODS: HLA class I-A, -B, and -Cw and class II DRB1
and DQB1 principal allele groups were genotyped in two stages: initially for
principal allele groups in a cohort of 100 AMD cases and 92 control subjects, and
then, in the next 100 cases and controls from the same cohort, for alleles or
allele groups with P < 0.1 on initial typing. Genotype frequencies were compared 
by 2 x 2 contingency tables. The strongest associations for individual HLA
alleles were calculated with two-locus stratification analysis and logistic
regression for all possible pair-wise HLA combinations. Bonferroni corrections
were applied for multiple measurements (P(c)). Each HLA allele was subjected to
logistic regression for known AMD covariates. HLA immunohistochemistry for class 
I antigens was performed on elderly donor eyes. RESULTS: Allele Cw*0701 (P =
0.004, P(c) = 0.036) correlated positively with AMD, whereas alleles B*4001 (P = 
0.003, P(c) = 0.027) and DRB1*1301(P = 0.001, P(c) = 0.009) were negatively
associated. These HLA associations were independent of any linkage
disequilibrium. Immunohistochemistry demonstrated differential HLA class I
expression in choriocapillary endothelial cells. CONCLUSIONS: Significant
positive and negative associations exist between HLA alleles and AMD. HLA
polymorphisms influence the development of AMD, possibly via modulating choroidal
immune function.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15851575 [PubMed - indexed for MEDLINE]

1966: Surv Ophthalmol. 2005 May-Jun;50(3):263-73.

Quality of life in patients with age-related macular degeneration: impact of the 
condition and benefits of treatment.

Slakter JS, Stur M.

Vitreous-Retina-Macula Consultants of New York, New York, USA.

Age-related macular degeneration (AMD) is a chronic, progressive, degenerative
disease of the macula and is the leading cause of central vision loss among
elderly people in the western world. Traditionally, clinical studies of AMD have 
described the impact of AMD, and treatments for AMD, in terms of the patient's
visual acuity. However, visual acuity alone does not provide information about a 
patient's perception of his or her quality of life. Researchers have used a
variety of instruments to measure quality of life. Several studies have shown
that AMD can severely impair quality of life and that increasing vision loss is
associated with increasing impairment of quality of life and frequently causes
depression. Interestingly, patients with only one eye affected may become more
depressed than those with both eyes affected, possibly because of uncertainty
surrounding future vision loss in patients with one eye affected and a greater
acceptance of the condition in those with both eyes affected. Studies also have
provided some information on the possible quality of life benefits of therapy for
AMD. By incorporating measurements of quality of life into the design of future
prospective studies, clinical researchers may be able to obtain more
comprehensive data on the impact of AMD on patients and the relative benefits of 
different therapies.

Publication Types: 
    Review

PMID: 15850815 [PubMed - indexed for MEDLINE]

1967: Ophthalmic Epidemiol. 2005 Feb;12(1):37-45.

Hormone replacement therapy, reproductive factors, and age-related macular
degeneration: the Salisbury Eye Evaluation Project.

Freeman EE, Muñoz B, Bressler SB, West SK.

Dana Center for Preventive Ophthalmology, Wilmer Eye Institute, Johns Hopkins
Hospital, Baltimore, MD 21287, USA. efreeman@jhsph.edu

PURPOSE: To evaluate a potential relationship between hormone replacement therapy
(HRT), reproductive factors and age-related macular degeneration (AMD). METHODS: 
1,458 female participants (age 65-84) from the Salisbury Eye Evaluation study
were available for this cross-sectional analysis. AMD outcomes were identified by
reading center assessment of fundus photographs. RESULTS: Women who currently
used HRT had a lower adjusted odds of large drusen (> 125 microm) (OR = 0.5, 95% 
CI 0.2-1.0). Use of HRT was not statistically significantly associated with the
prevalence of early AMD or advanced AMD, although the odds ratios were all much
less than 1. Women who had had an increased number of births had a greater
prevalence of large drusen (test of linear trend, p = 0.03). CONCLUSIONS: Current
use of HRT was associated with a lower odds of large drusen, which may be
predictive of advanced AMD. No statistically significant correlations were found 
between HRT or reproductive factors and early or advanced AMD.

Publication Types: 
    Comparative Study

PMID: 15848919 [PubMed - indexed for MEDLINE]

1968: Int Ophthalmol. 2004 May;25(3):143-6.

Comment in:
    Int Ophthalmol. 2005 Jun;26(3):119-20.

Vitreoretinal surgery for optic pit associated serous macular detachment: a
discussion of two cases.

Bakri SJ, Beer PM.

Lions Eye Institute, Albany Medical College, 35 Hackett Boulevard, Albany, NY
12208, USA.

PURPOSE: To report the successful surgical outcome of two patients with a serous 
macular detachment and cystoid macular edema associated with a congenital optic
nerve pit. METHOD: Case reports. Two patients with a serous macular detachment
associated with a congenital optic nerve pit were treated with 360 degrees
peripapillary endophotocoagulation during vitrectomy, attempted internal
subretinal fluid drainage, and fluid-gas exchange. RESULTS: In both cases, the
retina remained attached during a follow-up period of 6 months, and the patient's
vision improved dramatically. One patient improved from the counting finger level
to 20/70, and the other improved from 20/200 to 20/70. CONCLUSION: The use of 360
degrees peripapillary endophotocoagulation after pars plana vitrectomy for the
treatment of optic nerve pit associated retinal detachment resulted in excellent 
visual acuity and anatomic reattachment. Attempted internal subretinal fluid
drainage was unsuccessful and did not contribute to the success of the case.

Publication Types: 
    Case Reports

PMID: 15847312 [PubMed - indexed for MEDLINE]

1969: Graefes Arch Clin Exp Ophthalmol. 2005 Oct;243(10):1036-42. Epub 2005 Oct
20.

Neuroprotective effects of cardiotrophin-like cytokine on retinal ganglion cells.

Schuettauf F, Zurakowski D, Quinto K, Varde MA, Besch D, Laties A, Anderson R,
Wen R.

Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania,
Philadelphia, Pennsylvania, USA. fschuettauf@uni-tuebingen.de

BACKGROUND: Premature neuronal cell death is a feature of numerous central
nervous system and eye diseases, including glaucoma. Neurons (including retinal
ganglion cells, RGCs) are protected by several neurotrophic factors, among those 
the IL-6 family of cytokines. Lately, a novel member of the IL-6 family of
cytokines has been identified and cloned. This cytokine is known as novel
neurotrophin-1/B-cell-stimulating factor-3 (NNT-1/BSF-3) or cardiotrophin-like
cytokine (CLC). It shows neurotrophic as well as B-cell stimulatory effects.
METHODS: In this study, the neuroprotective properties of CLC on RGC loss in vivo
were investigated. RESULTS: CLC significantly protected RGCs from degeneration in
both chosen models of retinal neuronal damage: optic nerve crush (P<0.01) and
N-methyl-D-aspartate (NMDA) injection (P<0.001). CONCLUSIONS: CLC shows
neuroprotective effects on RGCs in vivo and might be a treatment option for
chronic neurodegenerative eye diseases such as glaucoma. Clinical feasibility for
the substance requires further investigation since the immunomodulatory and
possible adverse effects have not yet been thoroughly characterized.

Publication Types: 
    Comparative Study
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 15838664 [PubMed - indexed for MEDLINE]

1970: Graefes Arch Clin Exp Ophthalmol. 2005 Sep;243(9):903-10. Epub 2005 Apr 15.

Binocular fixation topography in patients with diabetic macular oedema: possible 
implications for photocoagulation therapy (3rd revision).

Møller F, Laursen ML, Sjølie AK.

Department of Ophthalmology, Odense University Hospital, Sdr. Boulevard, 5000
Odense C, Denmark. f.moeller@dadlnet.dk

BACKGROUND: During retinal photocoagulation for diabetic maculopathy, there is a 
potential risk of foveal burns, and laser scars may later enlarge to be
sight-threatening when involving retinal areas previously used during fixation.
Since the retinal area used during binocular steady fixation has been found to
vary considerably in the normal test person and central fixation may be even
further compromised in patients with diabetic maculopathy, the sight-threatening 
side effects could possibly be reduced by taking into account the fixation area
individually. However, no study has described and quantified the retinal area of 
fixation binocularly in patients with clinically significant macular oedema
(CSME). METHODS: Sixteen diabetic patients with CSME in one or both eyes were
examined. Each examination included visual acuity testing (ETDRS charts), a
standard eye examination, central retinal thickness assessment by optical
coherent tomography, fluorescein angiography and binocular quantification of
fixational eye movements using an infrared recording technique. RESULTS: A
negative correlation was found between visual acuity and mean microsaccadic
amplitude (R=0.48, p=0.009). The maximal retinal extension of the fixation area
ranged between 1.0 degrees and 3.0 degrees , and in two eyes with CSME, this area
was estimated to exceed 800 mum on the retinal plane. No correlation was found
between retinal thickness and visual acuity, retinal area of fixation, maximal
extension of the fixation area or mean microsaccadic amplitude. CONCLUSION: Large
interindividual differences in quantitative measures of binocular fixational eye 
movements were found. The mean amplitude of fixational eye movements was not
correlated to central retinal thickness, and fixation area could only partly be
predicted by visual acuity. Two eyes with CSME had an estimated maximal extension
of the fixation area exceeding the central 800 mum on the retinal plane; thus,
the possible benefit of individualising central photocoagulation according to
precise measures of fixation area needs to be investigated on a larger
population.

PMID: 15834607 [PubMed - indexed for MEDLINE]

1971: Graefes Arch Clin Exp Ophthalmol. 2005 Sep;243(9):947-50. Epub 2005 Apr 15.

Visual acuity and structural findings in old age-related macular degeneration.

Riusala A, Sarna S, Immonen I.

Department of Ophthalmology, Helsinki University Hospital, Haartmaninkatu 4 C,
FIN-00029 JP 220 Helsinki, Finland.

BACKGROUND: Although exudative age-related macular degeneration (AMD) leads to a 
substantial visual loss in most patients there is still significant variation in 
the end- stage visual acuity level. We analysed lesions in eyes with
long-standing AMD in order to find contributing factors for this variation.
METHODS: Sixty-one out of 121 patients examined for exudative AMD and still alive
4.8-9.2 (mean 6.8) years after the acute phase were re-examined. The lesion size,
area of subretinal fibrosis, geographic atrophy, presence of a persistent
exudative process, and shortest distance to normal looking retina were measured
from digital fundus photographs taken at the re-examination and correlated with
visual acuity. RESULTS: Lesion size, the presence of a continuing exudative
process, or subretinal fibrosis were independent predictors for poor vision.
Better vision in the other eye was connected with poor vision in the affected
study eye. CONCLUSIONS: In addition to lesion size, the presence of a continuing 
exudative process and subretinal fibrosis also have deleterious effects on
long-term visual acuity after exudative AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15834599 [PubMed - indexed for MEDLINE]

1972: Genet Med. 2005 Apr;7(4):272-7.

MMP-9 microsatellite polymorphism and susceptibility to exudative form of
age-related macular degeneration.

Fiotti N, Pedio M, Battaglia Parodi M, Altamura N, Uxa L, Guarnieri G, Giansante 
C, Ravalico G.

Department of Clinical, Morphological and Technological Sciences, University of
Trieste, Trieste, Italy. fiotti@units.it

PURPOSE: To assess if a polymorphism (PM) of the microsatellite (CA(13-27)) in
the promoter region of Matrix Metalloproteinase 9 (MMP-9) was associated with the
exudative form of age-related macular degeneration (AMD) and to its risk factors.
METHODS: In 107 patients with AMD (AMD Group) and 223 age- and gender-matched
controls (Control Group) with cataract, demographic, clinical data, and MMP-9 PM 
have been compared. RESULTS: The comparison of allelic frequencies showed a
different pattern of CA repeats between AMD and Control Group (P < 0.00005), in
particular the prevalence of longer microsatellites (> or = 22 CA repeats) was
higher in AMD than in Control Group (O.R. 2.49, 95% CI 1.71-3.37, P < 0.001).
Analyses of genetic frequencies gave similar results. Logistic regression
confirmed that 22 or more CA repeats are associated to AMD. The only association 
between MMP-9 PM and other risk factors for AMD was with BMI (Spearman's R =
0.298, P < 0.00005): all patients with both microsatellites > or = 22 CA repeats 
were overweight or obese (chi2 test P < 0.0005, compared to other genotypes).
CONCLUSIONS: Longer microsatellites in the promoter of MMP-9 are associated to
the exudative form of AMD and to body mass index, a well-known risk factor for
the disease.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15834245 [PubMed - indexed for MEDLINE]

1973: Br J Ophthalmol. 2005 May;89(5):554-7.

An interinstitutional comparative study and validation of computer aided drusen
quantification.

Sivagnanavel V, Smith RT, Lau GB, Chan J, Donaldson C, Chong NV.

Retinal Research Unit, King's College Hospital, University of London, UK.
vasuki_siva1@yahoo.co.uk

AIMS: To assess the portability and clinical applicability of a software program 
based on Photoshop (Adobe Systems Inc, San Jose, CA, USA) for digital drusen
quantification. METHODS: Independent graders from the Digital Fundus Photo
Reading Center of Columbia University and King's College Hospital used macular
background levelling software to quantify the percentage of drusen in the central
and middle Wisconsin subfields. 100 images of consecutive patients with choroidal
neovascularisation in one eye and significant drusen in the other eye were
analysed to determine suitability, and 10 were chosen for assessment by this
software. RESULTS: Of the 10 images used in the interinstitutional validation,
the random effects ANOVA for the central and middle subfields showed a high
degree of interobserver agreement. The ICC for interobserver reliability was 0.83
(95% CI: 67 to 95) for the central subfield and 0.84 (95% CI: 69 to 99) for the
middle subfield. Overall agreement with the manual grading results was good and
the within patient coefficient of variation was about 20% for all the pairwise
comparisons between observers and the manual stereo gradings. Of the 100 images
used to assess practical applicability of the software, 79 were suitable for
semiautomated analysis. 13 had extensive mixed retinal pigment epithelial (RPE)
changes limiting drusen identification, five had a significant number of
reticular drusen, which are poorly identified by the software, and three had
multiple small areas of RPE atrophy, which are difficult to distinguish from
drusen. CONCLUSIONS: The software was successfully used by two institutions
demonstrating portability, with good correlation between graders and to the
manual stereo grading. Digital drusen quantification was possible in 79% of the
images analysed.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't
    Validation Studies

PMID: 15834083 [PubMed - indexed for MEDLINE]

1974: Br J Ophthalmol. 2005 May;89(5):550-3.

28,000 Cases of age related macular degeneration causing visual loss in people
aged 75 years and above in the United Kingdom may be attributable to smoking.

Evans JR, Fletcher AE, Wormald RP.

International Centre for Eye Health, London School of Hygiene and Tropical
Medicine, Keppel Street, London WC1E 7HT, UK. Jennifer.evans@lshtm.ac.uk

BACKGROUND: Age related macular degeneration (AMD) causing visual impairment is
common in older people. Previous studies have identified smoking as a risk factor
for AMD. However, there is limited information for the older population in
Britain. METHODS: Population based cross sectional analytical study based in 49
practices selected to be representative of the population of Britain. Cases were 
people aged 75 years and above who were visually impaired (binocular acuity
<6/18) as a result of AMD. Controls were people with normal vision (6/6 or
better). Smoking history was ascertained using an interviewer administered
questionnaire. RESULTS: After controlling for potentially confounding factors,
current smokers were twice as likely to have AMD compared to non-smokers (odds
ratio 2.15, 95% CI 1.42 to 3.26). Ex-smokers were at intermediate risk (odds
ratio 1.13, 0.86 to 1.47). People who stopped smoking more than 20 years
previously were not at increased risk of AMD causing visual loss. Approximately
28,000 cases of AMD in older people in the United Kingdom may be attributable to 
smoking. CONCLUSION: This is the largest study of the association of smoking and 
AMD in the British population. Smoking is associated with a twofold increased
risk of developing AMD. An increased risk of AMD, which is the most commonly
occurring cause of blindness in the United Kingdom, is yet another reason for
people to stop smoking and governments to develop public health campaigns against
this hazard.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 15834082 [PubMed - indexed for MEDLINE]

1975: Eye. 2006 Jan;20(1):43-5.

Does lesion size determine the success rate of photodynamic therapy for
age-related macular degeneration?

Sivaprasad S, Saleh GM, Jackson H.

West Kent Eye Centre, Princess Royal University Hospital, Orpington, Kent BR6
8ND, UK. Senswathi@aol.com

Photodynamic therapy (PDT) is a new evidence-based treatment modality available
for choroidal neovascularisation (CNV) secondary to age-related macular
degeneration (AMD). Eligibility for PDT is based on the morphological
classification of the neovascular complex, the benefit being greater in classic
with no occult lesions. Lesion size is also shown to be a predictive factor for
treatment benefit. This retrospective case series looked at effect of initial and
final lesion size on the visual outcome of patients with subfoveal classic with
no occult CNV and found that increasing initial and final lesion size is
associated with poorer visual outcome.

PMID: 15832188 [PubMed - indexed for MEDLINE]

1976: Health Qual Life Outcomes. 2005 Apr 14;3:25.

+Psychometric evaluation of the MacDQoL individualised measure of the impact of
macular degeneration on quality of life.

Mitchell J, Wolffsohn JS, Woodcock A, Anderson SJ, McMillan CV, Ffytche T,
Rubinstein M, Amoaku W, Bradley C.

Department of Psychology, Royal Holloway, University of London, Egham, Surrey,
TW20 0EX, UK. j.mitchell@rhul.ac.uk

BACKGROUND: The MacDQoL is an individualised measure of the impact of macular
degeneration (MD) on quality of life (QoL). There is preliminary evidence of its 
psychometric properties and sensitivity to severity of MD. The aim of this study 
was to carry out further psychometric evaluation with a larger sample and
investigate the measure's sensitivity to MD severity. METHODS: Patients with MD
(n = 156: 99 women, 57 men, mean age 79 +/- 13 years), recruited from eye clinics
(one NHS, one private) completed the MacDQoL by telephone interview and later
underwent a clinic vision assessment including near and distance visual acuity
(VA), comfortable near VA, contrast sensitivity, colour recognition, recovery
from glare and presence or absence of distortion or scotoma in the central 10
degrees of the visual field. RESULTS: The completion rate for the MacDQoL items
was 99.8%. Of the 26 items, three were dropped from the measure due to
redundancy. A fourth was retained in the questionnaire but excluded when
computing the scale score. Principal components analysis and Cronbach's alpha
(0.944) supported combining the remaining 22 items in a single scale. Lower
MacDQoL scores, indicating more negative impact of MD on QoL, were associated
with poorer distance VA (better eye r = -0.431 p < 0.001; worse eye r = -0.350 p 
< 0.001; binocular vision r = -0.419 p < 0.001) and near VA (better eye r =
-0.326 p < 0.001; worse eye r = -0.226 p < 0.001; binocular vision r = -0.326 p <
0.001). Poorer MacDQoL scores were associated with poorer contrast sensitivity
(better eye r = 0.392 p < 0.001; binocular vision r = 0.423 p < 0.001), poorer
colour recognition (r = 0.417 p < 0.001) and poorer comfortable near VA (r =
-0.283, p < 0.001). The MacDQoL differentiated between those with and without
binocular scotoma (U = 1244 p < 0.001). CONCLUSION: The MacDQoL 22-item scale has
excellent internal consistency reliability and a single-factor structure. The
measure is acceptable to respondents and the generic QoL item, MD-specific QoL
item and average weighted impact score are related to several measures of vision.
The MacDQoL demonstrates that MD has considerable negative impact on many aspects
of QoL, particularly independence, leisure activities, dealing with personal
affairs and mobility. The measure may be valuable for use in clinical trials and 
routine clinical care.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Validation Studies

PMID: 15831093 [PubMed - indexed for MEDLINE]

1977: Hum Mol Genet. 2005 Jun 1;14(11):1449-55. Epub 2005 Apr 13.

Toll-like receptor 4 variant D299G is associated with susceptibility to
age-related macular degeneration.

Zareparsi S, Buraczynska M, Branham KE, Shah S, Eng D, Li M, Pawar H, Yashar BM, 
Moroi SE, Lichter PR, Petty HR, Richards JE, Abecasis GR, Elner VM, Swaroop A.

Department of Ophthalmology and Visual Sciences, University of Michigan, Ann
Arbor, MI 48105, USA.

Age-related macular degeneration (AMD) is a genetically heterogeneous disease
that leads to progressive and irreversible vision loss among the elderly.
Inflammation, oxidative damage, cholesterol metabolism and/or impaired function
of retinal pigment epithelium (RPE) have been implicated in AMD pathogenesis. We 
examined toll-like receptor 4 (TLR4) as a candidate gene for AMD susceptibility
because: (i) the TLR4 gene is located on chromosome 9q32-33, a region exhibiting 
evidence of linkage to AMD in three independent reports; (ii) the TLR4-D299G
variant is associated with reduced risk of atherosclerosis, a chronic
inflammatory disease with subendothelial accumulation; (iii) the TLR4 is not only
a key mediator of proinflammatory signaling pathways but also linked to
regulation of cholesterol efflux and (iv) the TLR4 participates in phagocytosis
of photoreceptor outer segments by the RPE. We examined D299G and T399I variants 
of TLR4 in a sample of 667 unrelated AMD patients and 439 unrelated controls, all
of Caucasian ancestry. Multiple logistic regression demonstrated an increased
risk of AMD in carriers of the G allele at TLR4 residue 299 (odds ratio=2.65,
P=0.025), but lack of an independent effect by T399I variant. TLR4-D299G showed
an additive effect on AMD risk (odds ratio=4.13, P=0.002) with allelic variants
of apolipoprotein E (APOE) and ATP-binding cassette transporter-1 (ABCA1), two
genes involved in cholesterol efflux. Interestingly, the effect of TLR4, APOE and
ABCA1 variants on AMD susceptibility was opposite to that of association with
atherosclerosis risk. Our data provide evidence of a link between multiple
diverse mechanisms underlying AMD pathogenesis.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15829498 [PubMed - indexed for MEDLINE]

1978: Arch Ophthalmol. 2005 Apr;123(4):448-57.

Verteporfin therapy of subfoveal minimally classic choroidal neovascularization
in age-related macular degeneration: 2-year results of a randomized clinical
trial.

Azab M, Boyer DS, Bressler NM, Bressler SB, Cihelkova I, Hao Y, Immonen I, Lim
JI, Menchini U, Naor J, Potter MJ, Reaves A, Rosenfeld PJ, Slakter JS, Soucek P, 
Strong HA, Wenkstern A, Su XY, Yang YC; Visudyne in Minimally Classic Choroidal
Neovascularization Study Group.

OBJECTIVE: To compare the treatment effect and safety of photodynamic therapy
with verteporfin using a standard (SF) or reduced (RF) light fluence rate with
that of placebo therapy in patients with subfoveal minimally classic choroidal
neovascularization (CNV) with age-related macular degeneration. DESIGN: Phase 2, 
multicenter, double-masked, placebo-controlled, randomized clinical trial.
SETTING: Nineteen ophthalmology practices in North America and Europe.
PARTICIPANTS: Patients with initial best-corrected visual acuity of at least
20/250 and a lesion size of no greater than 6 Macular Photocoagulation Study
(MPS) disc areas. METHODS: We randomly assigned 117 patients (1:1:1) to
verteporfin infusion (6 mg/m(2)) and light application with an RF rate (300
mW/cm(2)) for 83 seconds (light dose of 25 J/cm(2)) or an SF rate (600 mW/cm(2)) 
for 83 seconds (light dose of 50 J/cm(2)) or to placebo infusion with RF or SF.
Treatment was repeated every 3 months if the treating physician noted fluorescein
leakage from CNV on angiography. Patients in whom a predominantly classic lesion 
developed could receive open-label standard verteporfin treatment. Best-corrected
visual acuity was measured every 3 months, and angiographic changes were assessed
by the Photograph Reading Center through the 3-month examination unless an ocular
adverse event or conversion to a predominantly classic lesion was identified by
an investigator. Safety was assessed throughout the study. All outcomes were on
an intent-to-treat basis. RESULTS: One hundred three (88%) of 117 patients
completed the 24-month examination. Twelve (30%) of 40 patients assigned to
placebo received open-label standard verteporfin treatment after confirmation of 
presence of predominantly classic CNV. At month 12, a loss of at least 3 lines of
visual acuity occurred in 5 (14%) of 36 eyes assigned to RF and 10 (28%) of 36
eyes assigned to SF, compared with 18 (47%) of 38 eyes assigned to placebo (RF, P
= .002; SF, P = .08; RF + SF, P = .004). At month 24, this loss occurred in 9
(26%) of 34 eyes assigned to RF and 17 (53%) of 32 assigned to SF, compared with 
23 (62%) of 37 eyes assigned to placebo (RF, P = .003; SF, P = .45; RF + SF, P = 
.03). Progression to predominantly classic CNV by 24 months was more common in
the placebo group (11 [28%] of 39 patients compared with 2 [5%] of 38 in the RF
group [P = .007] and 1 [3%] of 37 in the SF group [P = .002]). No unexpected
ocular or systemic adverse events were identified. Treatment-related, usually
transient visual disturbances were 13% with SF, 10% with placebo, and 5% with RF.
CONCLUSIONS: Verteporfin therapy safely reduced the risks of losing at least 15
letters (> or =3 lines) of visual acuity and progression to predominantly classic
CNV for at least 2 years in individuals with subfoveal minimally classic lesions 
due to age-related macular degeneration measuring 6 MPS disc areas or less. Based
on the overall evidence available on verteporfin therapy for these lesions, the
VIM Study Group would consider recommending verteporfin therapy for relatively
small minimally classic lesions similar to those enrolled in the VIM Trial.

Publication Types: 
    Clinical Trial
    Clinical Trial, Phase II
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15824216 [PubMed - indexed for MEDLINE]

1979: Med Hypotheses. 2005;64(6):1202-4.

Met72Thr polymorphism of pigment epithelium-derived factor gene and
susceptibility to age-related macular degeneration.

Yamagishi S, Nakamura K, Inoue H, Takeuchi M.

Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi,
Kurume 830-0011, Japan. shoichi@med.kurume-u.ac.jp

Age-related macular degeneration (ARMD) is the most common cause of acquired
blindness among the people of occupational age. Although the pathogenesis of ARMD
is not fully understood, several studies suggest a possible contribution of a
genetic factor in the development and progression of ARMD. Pigment
epithelium-derived factor (PEDF), a glycoprotein that belongs to the superfamily 
of serine protease inhibitors, was first purified from the conditioned media of
human retinal pigment epithelial cells as a factor with potent neuronal
differentiating activity in human retinoblastoma cells. Recently, PEDF has been
shown to be a highly effective inhibitor of angiogenesis in cell culture and
animal models. In addition, PEDF has been found in the vitreous, and its levels
were decreased in angiogenic eye diseases, thus suggesting that a loss of PEDF in
the eye is functionally important in the pathogenesis of ARMD. A functional amino
acid change, a methionine to threonine polymorphism (Met72Thr polymorphism) at
codon 72 in exon 3 (T/C polymorphism) of the PEDF gene, that results in the
formation of BsstSI restriction site, has recently been identified. Since it is
well known that a single nucleotide polymorphism and resultant amino acid change 
often alters the activity or expression level of the target protein, we would
like to propose here a novel hypothesis that the Met72Thr polymorphism (T/C
polymorphism) of PEDF gene may be a genetic marker for ARMD. Are genotype and
allele frequencies of the Met72Thr polymorphism (T/C polymorphism) different
between the patients with or without ARMD? Is this polymorphism associated with
disease severity and progression? If the answer is yes, does this Met72Thr
polymorphism regulate the vitreous levels of PEDF? These clinical studies could
provide us with information whether this genetic variant of the PEDF gene could
present an attractive candidate susceptibility gene for ARMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15823717 [PubMed - indexed for MEDLINE]

1980: Eye. 2006 Mar;20(3):297-303.

Cystoid macular oedema and changes in retinal thickness after phacoemulsification
with optical coherence tomography.

Ching HY, Wong AC, Wong CC, Woo DC, Chan CW.

Department of Ophthalmology, Tung Wah Eastern Hospital, Hong Kong, China.

AIMS: To study the incidence of cystoid macular oedema and changes in retinal
thickness after phacoemulsification with optical coherence tomography (OCT).
METHODS: In all, 131 eyes of 131 patients were studied at the ophthalmology
clinic at Tung Wah Eastern Hospital from September 2001 to October 2002. All the 
patients had clinical assessment and OCT preoperatively and at weeks 2, 4, and 8 
postoperatively. The incidence of postoperative cystoid macular oedema (CMO) was 
evaluated. The foveal thickness (FT) and central 1 mm retinal thickness (CT) at
different time intervals were analysed. RESULTS: Four (3.05%) patients developed 
CMO after phacoemulsification, which was evident clinically and tomographically. 
Fluorescein angiogram confirmed leakage in all cases. For other patients, the
mean preoperative FT was 189.36 +/- 26.83 microm. The mean FT, were 175.74 +/-
26.79 microm, 180.25 +/- 27.13 microm, 176.58 +/- 26.45 microm at 2 weeks, 4
weeks, and 8 weeks postoperatively, respectively. The preoperative FT was
significantly thicker than those in the postoperative period. The same trend was 
noted for CT. CONCLUSION: OCT is useful for detecting and confirming clinical CMO
after cataract surgery; however, its use in detecting subtle changes in retinal
thickness is limited by the normal variation in retinal thickness. The
measurement of retinal thickness with OCT may also be affected by the status of
the lens.

PMID: 15818389 [PubMed - indexed for MEDLINE]

1981: BMC Ophthalmol. 2005 Apr 6;5:8.

Automated analysis of digital fundus autofluorescence images of geographic
atrophy in advanced age-related macular degeneration using confocal scanning
laser ophthalmoscopy (cSLO).

Deckert A, Schmitz-Valckenberg S, Jorzik J, Bindewald A, Holz FG, Mansmann U.

Institute of Medical Biometry and Informatics, University of Heidelberg, Im
Neuenheimer Feld 305, 69120 Heidelberg, Germany. deckert@imbi.uni-heidelberg.de

BACKGROUND: Fundus autofluorescence (AF) imaging using confocal scanning laser
ophthalmoscopy (cSLO) provides an accurate delineation of areas of geographic
atrophy (GA). Automated computer-assisted methods for detecting and removing
interfering vessels are needed to support the GA quantification process in
longitudinal studies and in reading centres. METHODS: A test tool was implemented
that uses region-growing techniques to segment GA areas. An algorithm for
illuminating shadows can be used to process low-quality images. Agreement between
observers and between three different methods was evaluated by two independent
readers in a pilot study. Agreement and objectivity were assessed using the
Bland-Altman approach. RESULTS: The new method (C) identifies vascular structures
that interfere with the delineation of GA. Results are comparable to those of two
commonly used procedures (A, B), with a mean difference between C and A of -0.67 
mm2 (95% CI [-0.99, -0.36]), between B and A of -0.81 mm2, (95% CI [-1.08,
-0.53]), and between C and B of 0.15 mm2 (95% CI [-0.12, 0.41]). Objectivity of a
method is quantified by the mean difference between observers: A 0.30 mm2 (95% CI
[0.02, 0.57]), B -0.11 mm2 (95% CI [-0.28, 0.10]), and C 0.12 mm2 (95% CI [0.02, 
0.22]). CONCLUSION: The novel procedure is comparable with regard to objectivity 
and inter-reader agreement to established methods of quantifying GA. It
considerably speeds up the lengthy measurement process in AF with well defined GA
zones.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15813972 [PubMed - indexed for MEDLINE]

1982: Eur J Ophthalmol. 2005 Mar-Apr;15(2):289-91.

Macular edema and visual loss after macular pucker surgery with ICG-assisted
internal limiting membrane peeling.

Tognetto D, Haritoglou C, Kampik A, Ravalico G.

Clinica Oculistica Università di Trieste, Ospedale Maggiore--Italy.
tognetto@univ.trieste.it

PURPOSE: To describe the occurrence of massive macular edema and visual loss
after indocyanine green-assisted (ICG) macular pucker surgery. METHODS/RESULTS: A
74 years old female presented with a macular pucker and a hypertrophy of the
retinal pigment epithelium (RPE) in her left eye. The preoperative visual acuity 
(VA) was 20/100. Surgery consisted of cataract extraction, lens implantation and 
standard pars plana vitrectomy with peeling of epiretinal tissue followed by the 
removal of the internal limiting membrane (ILM) remnants stained using a 0.05%
ICG solution. One day after surgery, VA was counting fingers. There was an
extensive macular edema and retinal thickening with hyperfluorescence during
fluorescein angiography and pronounced autofluorescence using ICG filters. During
follow up, the macular edema resolved completely, but VA decreased to 20/800 at
six months postoperatively. There was a central scotoma and unstable fixation
seen during microperimetry. DISCUSSION: This case report indicates that ICG might
come into contact with bare retina if injected following removal of epiretinal
membranes. Whether the observed RPE hypertrophy might have contributed to the
pathogenesis of the adverse effect described remains hypothetical.

Publication Types: 
    Case Reports

PMID: 15812777 [PubMed - indexed for MEDLINE]

1983: Eur J Ophthalmol. 2005 Mar-Apr;15(2):255-62.

Early age-related maculopathy and risk factors of cardiovascular disease in
middle-aged Lithuanian urban population.

Paunksnis A, Cimbalas A, Cerniauskiene LR, Luksiene DI, Margeviciene L,
Domarkiene S, Tamosiunas A, Norkus A.

Institute for Biomedical Research, University of Medicine, Kaunas, Lithuania.
apaun@medi.it

PURPOSE: To assess the prevalence of age-related maculopathy (ARM) in a
middle-aged urban population and the relationship between ARM and the main risk
factors of cardiovascular disease (CVD). METHODS: The survey according to the WHO
MONICA study protocol was carried out in Kaunas city, Lithuania, from 2001 to
2002. A total of 1403 persons aged 35 to 64 years were screened (626 men and 777 
women: response rate 62.4%). Ophthalmologic investigation was performed for 1337 
respondents (594 men and 743 women). Analysis of the relationship between ARM and
risk factors of CVD was performed in case-control subdivision matching for sex,
age, and education level. RESULTS: Early ARM was diagnosed in 7.4% of men and
5.4% of women. Rate of current smoking in case and control groups did not differ 
in men but in case group of women it was greater than in control group. Mean
systolic and diastolic blood pressure and body mass index (BMI) in male case
group and mean fasting blood glucose concentration in female case group were
higher than in corresponding control groups. Frequency of diastolic hypertension 
(diastolic blood pressure > or = 90 mmHg) and obesity (BMI > or = 30 kg/m2) in
male case group was higher than in control group. ARM was not associated with
cholesterol and triglyceride levels in men and women. CONCLUSIONS: Early ARM in
middle-aged Lithuanian urban population was associated with current smoking in
women but not in men; it was associated with diastolic blood pressure and BMI in 
men and with fasting glucose level in women.

PMID: 15812769 [PubMed - indexed for MEDLINE]

1984: Ophthalmology. 2005 Apr;112(4):586-92.

Late onset is common in best macular dystrophy associated with VMD2 gene
mutations.

Renner AB, Tillack H, Kraus H, Krämer F, Mohr N, Weber BH, Foerster MH, Kellner
U.

Augenklinik, Charité Campus Benjamin Franklin, Universitätsmedizin Berlin,
Berlin, Germany. a.renner@berlin.de

PURPOSE: To perform a detailed morphologic and functional evaluation of Best
macular dystrophy (BMD) associated with mutations in the VMD2 gene. DESIGN:
Retrospective study. PARTICIPANTS: The records of 16 patients with BMD and
heterozygous VMD2 mutations (group 1) and 5 patients with Best-like lesions with 
no detectable disease-associated alterations in the VMD2 gene (group 2) were
evaluated retrospectively. METHODS: The data were reviewed regarding visual
acuity (VA), color vision, perimetry, autofluorescence of the retinal pigment
epithelium (RPE), fluorescein angiography, electro-oculography (EOG), and
full-field electroretinography (ERG) and multifocal ERG (mfERG). MAIN OUTCOME
MEASURES: VMD2 mutations, age at onset of BMD, RPE autofluorescence, EOG, ERG,
and mfERG. RESULTS: The mean age of the patients in group 1 was 47.1 years
(range, 16.7-86.5), and age at onset varied between 5 and 58 years (median,
42.0). Visual acuity ranged between 20/16 and 20/400 (median, 20/40). No
association existed between the specific nature of the VMD2 mutation and disease 
onset or expressivity. Retinal pigment epithelium autofluorescence was increased 
corresponding to ophthalmoscopically visible yellow material, whereas it was
decreased in the atrophic stage of BMD. Electro-oculography light rise was
reduced in 18 of 19 eyes. Electroretinography amplitudes were normal in 3
patients and reduced in 6 patients. Multifocal ERG revealed in 10 of 20 eyes a
central amplitude reduction and in 7 eyes a generalized one. There were no marked
differences in clinical and functional findings between the patients in groups 1 
and 2, except that the mean age of the patients in group 2 was higher (64.0 years
[range, 45.7-80.6]) and the median VA lower (20/50 [range, 20/32-20/320]).
CONCLUSIONS: The onset of BMD is highly variable and occurred in the majority of 
patients after the second decade of life. Best-like lesions may develop in older 
patients without associated VMD2 mutations. Those manifestations may be related
to a specific form of age-related macular degeneration. This article contains
additional online-only material available at .

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15808248 [PubMed - indexed for MEDLINE]

1985: Ophthalmology. 2005 Apr;112(4):567-73.

Strontium plaque brachytherapy for exudative age-related macular degeneration:
three-year results of a randomized study.

Jaakkola A, Heikkonen J, Tommila P, Laatikainen L, Immonen I.

Department of Ophthalmology, Helsinki University Central Hospital, Helsinki,
Finland.

OBJECTIVE: To determine the efficacy of strontium plaque (Sr90) brachytherapy for
age-related macular degeneration (AMD) with subfoveal choroidal
neovascularization (CNV). DESIGN: Randomized clinical trial. PARTICIPANTS:
Eighty-eight eyes of 86 patients with subfoveal CNV secondary to AMD were
randomized either to plaque radiotherapy or to observation. INTERVENTION:
Radiotherapy was given as episcleral brachytherapy using Sr90 plaques. Two
different plaque types were used. Plaque I had a diameter of 8 mm and delivered a
dose of 15 Gy at a depth of 1.75 mm in 54 minutes. With plaque II, the
corresponding values were 4 mm, 12.6 Gy, and 11 minutes. The control group was
observed without any treatment. MAIN OUTCOME MEASURES: The primary outcome
measure was visual acuity at 6, 12, 24, and 36 months. Other outcome variables
were contrast sensitivity, fluorescein angiographic, and clinically evaluated
changes in the macula. RESULTS: Eighty-two patients (84 eyes [95%]) completed the
1-year follow-up, and 80 (93%) and 74 (86%) patients completed the 2- and 3-year 
follow-ups, respectively. At 6 months, visual loss of > or =3 lines occurred in
20% of treated patients and 42% of control patients (P = 0.031). At 12 months, a 
visual loss of > or =3 lines occurred in 45% (treated) and 56% (controls) (P =
0.325); at 24 months, in 73% and 71% (P = 0.914); and at 36 months, in 80% and
84% of patients (P = 0.591), respectively. Patients irradiated with plaque I had 
better results: a visual loss of > or =3 lines occurred in 6% at 6 months (P =
0.008, relative to controls), in 18% at 12 months (P = 0.007), in 59% at 24
months (P = 0.348), and in 71% at 36 months (P = 0.212). In patients treated with
plaque II, the corresponding values were 29% (P = 0.032), 65% (P = 0.459), 83% (P
= 0.317), and 80% (P = 0.687) at 6, 12, 24, and 36 months, respectively.
CONCLUSIONS: The short-term clinical course of exudative AMD is affected by Sr90 
brachytherapy, but by 12 months, there was no treatment benefit. This article
contains additional online-only material available at
http://www.ophsource.org/periodicals/ophtha.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15808245 [PubMed - indexed for MEDLINE]

1986: Ophthalmology. 2005 Apr;112(4):548-52.

Retinal vessel diameters and the risk of incident age-related macular disease:
the Rotterdam Study.

Ikram MK, van Leeuwen R, Vingerling JR, Hofman A, de Jong PT.

Department of Epidemiology and Biostatistics, Erasmus Medical Center, Rotterdam, 
The Netherlands.

PURPOSE: To study the relationship between retinal vessel diameters and incident 
age-related macular disease (iAMD). DESIGN: Prospective population-based cohort
study. PARTICIPANTS: Persons (55 years and older) from the Rotterdam Study, who
participated at the baseline (1990-1993) and 1 of 2 follow-up examinations
(1993-1994 and 1997-1999). METHODS: In the current analysis, 4345 participants
who were free of AMD at baseline and had gradable macular transparencies at both 
baseline and follow-up examination were included. Also, arteriolar and venular
diameters were measured on digitized baseline images. Stereoscopic transparencies
of the macular region were graded according to the International Classification
and Grading System for AMD. Incidence of AMD was defined as the development of
soft distinct drusen with pigmentary changes or indistinct or reticular drusen
with or without pigmentary changes (early iAMD) or atrophic or neovascular AMD
(late iAMD). Logistic regression models were used to assess these associations,
adjusting for age, gender, and follow-up time and, additionally, for smoking,
body mass index, intima-media thickness, systolic blood pressure, and total and
high-density lipoprotein cholesterol levels. MAIN OUTCOME MEASURE: Incidence of
AMD. RESULTS: After a mean follow-up time of 5.2 years, a total of 374 persons
developed early and late iAMD. Neither arteriolar nor venular diameters were
related to the risk of iAMD. The odds ratio (OR) per standard deviation (SD)
decrease in arteriolar diameter was 1.03 (95% confidence interval [CI],
0.93-1.15), and the OR per SD increase in venular diameter was 1.04 (95% CI,
0.93-1.16). After categorizing the retinal vessel diameters into quintiles, there
was no trend. After stratifying on age, only persons 75 years and older with
smaller arteriolar diameters were at a borderline significant increased risk of
iAMD: OR/SD decrease in arteriolar diameters adjusted for age, gender, follow-up 
time, and other cardiovascular risk factors, 1.24 (95% CI, 0.94-1.63).
CONCLUSION: Overall retinal vessel diameters were not related to the risk of iAMD
in this general elderly population.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15808242 [PubMed - indexed for MEDLINE]

1987: Ophthalmology. 2005 Apr;112(4):533-9.

Risk factors for the incidence of Advanced Age-Related Macular Degeneration in
the Age-Related Eye Disease Study (AREDS) AREDS report no. 19.

Clemons TE, Milton RC, Klein R, Seddon JM, Ferris FL 3rd; Age-Related Eye Disease
Study Research Group.

The EMMES Corporation, Rockville, Maryland 20850-1707, USA.

PURPOSE: To describe the association of demographic, behavioral, medical, and
nonretinal ocular factors with the incidence of neovascular age-related macular
degeneration (AMD) and central geographic atrophy (CGA) in the Age-Related Eye
Disease Study (AREDS), a randomized trial of antioxidants and zinc
supplementation prophylaxis for development of advanced AMD. DESIGN: Clinic-based
prospective cohort study. PARTICIPANTS: Of individuals with early or intermediate
AMD at baseline with a median follow-up of 6.3 years, 788 were at risk of
developing advanced AMD in one eye (the fellow eye had advanced AMD), and 2506
were at risk in both eyes. METHODS: The incidence of neovascular AMD and CGA was 
assessed from stereoscopic color fundus photographs taken at baseline and at
annual visits beginning at year 2. MAIN OUTCOME MEASURES: Neovascular AMD was
defined as photocoagulation for choroidal neovascularization, or photographic
documentation at the reading center of any of the following: nondrusenoid retinal
pigment epithelial detachment, serous or hemorrhagic retinal detachment,
hemorrhage under the retina or the retinal pigment epithelium, and subretinal
fibrosis. Central geographic atrophy was defined as geographic atrophy involving 
the center of the macula. RESULTS: In multivariable models, in persons at risk of
advanced AMD in both eyes, while controlling for age, gender, and AREDS treatment
group, the following variables were statistically significantly associated with
the incidence of neovascular AMD: race (odds ratio [OR], white vs. black, 6.77;
95% confidence interval [CI], 1.24-36.9) and larger amount smoked (OR, >10 vs. < 
or =10 pack-years [a pack-year is an average of 1 pack of cigarette smoked per
day for a year], 1.55; 95% CI, 1.15-2.09). The following were statistically
significantly associated with the incidence of CGA: less education (OR, high
school graduate or less vs. college graduate, 1.75; 95% CI, 1.10-2.78), greater
body mass index (BMI) (OR, obese vs. nonobese, 1.93; 95% CI, 1.25-2.65), larger
amount smoked (OR, >10 pack-years vs. < or =10 pack-years, 1.82; 95% CI,
1.25-2.65), and antacid use (OR, 0.29; 95% CI, 0.09-0.91). In persons at risk of 
developing advanced AMD in one eye, the incidence of neovascular AMD was
associated with diabetes (OR, 1.88; 95% CI, 1.07-3.31), and the incidence of CGA 
was associated with use of antiinflammatory medications (OR, 0.22; 95% CI,
0.08-0.59). CONCLUSIONS: Results suggest that, among persons with early or
intermediate AMD, smoking and BMI are modifiable factors associated with
progression to advanced AMD, and suggest other associations (e.g., use of
antacids and antiinflammatory medications) that warrant further study. This
article contains additional online-only material available at
http://www.ophsource.org/periodicals/ophtha. .

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, U.S. Gov't, P.H.S.

PMID: 15808240 [PubMed - indexed for MEDLINE]

1988: Am J Ophthalmol. 2005 Apr;139(4):739-40.

Effect of arteriovenous sheathotomy on retinal blood flow and macular edema in
patients with branch retinal vein occlusion.

Horio N, Horiguchi M.

Department of Ophthalmology, Fujita Health University, School of Medicine, Aichi,
Japan. naoichi@fujita-hu.ac.jp

PURPOSE: To determine the effect of arteriovenous sheathotomy on retinal blood
flow (RBF) in eyes with branch retinal vein occlusion (BRVO). DESIGN:
Interventional case series. METHODS: Seven eyes of 7 patients with BRVO underwent
sheathotomy and were followed for more than 6 months. RESULTS: At 1 week
postoperatively, the RBF in the affected vessels was significantly improved from 
14.1 +/- 5.7 to 27.3 +/- 11.3 pixel(2)/sec (P < 0.01), and the foveal thickness
(FT) was significantly reduced from 536 +/- 84 to 366 +/- 134 microm (P = 0.03). 
However, the RBF was reduced again to 11.7 +/- 7.7 pixel(2)/sec at 1 month
postoperatively, and the FT was increased to 424 +/- 184 microm. CONCLUSIONS:
Arteriovenous sheathotomy led to a transient improvement of the RBF and was
effective in reducing macular edema. It is not clear whether the transient effect
of sheathotomy affects the long-term visual acuity and macular edema.

PMID: 15808186 [PubMed - indexed for MEDLINE]

1989: Am J Ophthalmol. 2005 Apr;139(4):653-7.

Multiple laser treatments for macular edema attributable to branch retinal vein
occlusion.

Esrick E, Subramanian ML, Heier JS, Devaiah AK, Topping TM, Frederick AR, Morley 
MG.

Ophthalmic Consultants of Boston, Boston, Massachusetts 02114, USA.

PURPOSE: To report the visual outcome of multiple laser treatments for macular
edema attributable to branch retinal vein occlusions (BRVO) and to determine if
any prognostic factors exist for improvement. DESIGN: Retrospective chart review.
METHODS: A private practice with four vitreoretinal surgeons performed laser
treatments on 88 eyes of 88 patients with macular edema secondary to BRVO from
1984 to 2003. Mean preoperative and postoperative visual acuities were collected 
after each laser treatment. Final visual acuities were also documented. RESULTS: 
All 88 patients received at least one laser treatment, and 46 patients of the
initial 88 underwent multiple treatments. Overall, forty-one (46.6%) of the total
88 patients improved by 2 or more lines, whereas 33 patients (37.5%) were within 
1 line of the preoperative vision, and 14 patients (15.9%) worsened by 2 or more 
lines. The mean final visual improvement was 0.92 lines for all 88 patients. The 
group of patients that responded favorably to the first laser treatment (n = 37) 
showed an overall improvement of 3.5 lines. However, patients who responded
poorly to the first laser treatment resulted in an overall worsening of vision by
0.96 lines. CONCLUSIONS: Our study found that multiple laser treatments can
improve visual acuity and resolve macular edema and that each additional laser
treatment gives a patient a modest chance of visual improvement. A positive or
stable visual response to first laser treatment portends a favorable prognosis
with subsequent laser treatments.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15808160 [PubMed - indexed for MEDLINE]

1990: Am J Ophthalmol. 2005 Apr;139(4):638-52.

Epiretinal pathology of diffuse diabetic macular edema associated with
vitreomacular traction.

Gandorfer A, Rohleder M, Grosselfinger S, Haritoglou C, Ulbig M, Kampik A.

Department of Ophthalmology, University Eye Hospital Munich,
Ludwig-Maximilians-University, München, Germany.
arnd.gandorfer@med.uni-muenchen.de

PURPOSE: To investigate the ultrastructure of the vitreomacular interface in
patients with diffuse diabetic macular edema (DDME) associated with vitreomacular
traction. DESIGN: Laboratory investigation. METHODS: Fifty-five consecutive
patients with DDME underwent vitrectomy with en-bloc removal of the inner
limiting membrane (ILM) and epimacular tissue. Six patients were operated on both
eyes. Sixty-one specimens harvested during vitrectomy were analyzed by electron
microscopy. RESULTS: Preoperatively, a thickened premacular cortical vitreous was
present in 47 eyes. Native vitreous collagen with single cells interspersed
within the collagenous layer or a cellular monolayer were the ultrastructural
features in these eyes. Twenty-three eyes showed an epimacular membrane. In eyes 
with obvious signs of tangential vitreomacular traction, multilayered membranes
situated on a layer of native vitreous collagen were found. Fibroblasts and
fibrous astrocytes were the predominant cell types; myofibroblasts and
macrophages were also present. Sixty of 61 specimens showed native vitreous
collagen covering the ILM. Macular edema resolved in 58 eyes and persisted in 3
eyes. No recurrent fibrocellular proliferation was observed during the follow-up 
period of 18 months (mean, 3 to 56 months). CONCLUSIONS: The vitreomacular
interface in eyes with DDME is characterized by a layer of native vitreous
collagen and a varying cellular component. Tangential vitreomacular traction is
associated with multilayered membranes situated on a layer of vitreous collagen. 
Resolution of macular edema does not depend on the presence and removal of
contractile membranes. In eyes without tangential traction, complete removal of
epimacular tissue also leads to fluid resorption.

PMID: 15808159 [PubMed - indexed for MEDLINE]

1991: Am J Ophthalmol. 2005 Apr;139(4):624-30.

Intraobserver repeatability of macula measurements by confocal scanning laser
tomography.

Pallikaris A, Skondra D, Tsilimbaris M.

VEIC, Department of Ophthalmology, School of Medicine, University of Crete,
Heraklion, Greece. apallik@med.uoc.gr

PURPOSE: To assess the repeatability of macula measurements provided by the
Heidelberg Retina Tomograph II (HRT II) in normal subjects, patients with
diabetic macular edema (DME), and patients with choroidal neovascularization
(CNV). DESIGN: Prospective, observational case. METHODS: Setting:
Institutional-based study. Patient population: Ten normal eyes, 14 eyes with DME,
and 14 eyes with CNV. Observational procedure: Three scans within a single day.
An additional three scans of each of the 10 normal eyes on a different day. Main 
outcome measures: Bland and Altman analysis for a 0.25 mm, 0.50 mm, and 0.75 mm
radius circle. RESULTS: Variability and repeatability of the measurements were
not related to circle size for either group of patients. Coefficient of
variability values of the normal group and a 0.50-mm radius circle were 17%,
5.7%, and 6.1% for mean surface height, signal width, and edema index,
respectively. The corresponding values were 15.6%, 10%, and 10% for the DME
group, and 10.5%, 7.4%, and 8.5% for the CNV group. The 95% confidence interval
of the difference between single observations across days of the normal group was
+/-106 microm, +/-80 microm, and +/-0.10 for mean surface height, signal width,
and edema index, respectively. When three scans were combined, the corresponding 
values were +/-61.5 microm, +/-46.7 microm, and +/-0.06. CONCLUSIONS: The
repeatability and variability of measurements of normal subjects, patients with
DME, and patients with CNV were determined. Differences between the three groups 
exist and are important for diagnosing a pathologic condition or measuring the
effect of various treatments.

Publication Types: 
    Comparative Study

PMID: 15808157 [PubMed - indexed for MEDLINE]

1992: Am J Ophthalmol. 2005 Apr;139(4):620-3.

Comment in:
    Am J Ophthalmol. 2005 Nov;140(5):960-1; author reply 961.

Persistent diabetic macular edema is associated with elevated hemoglobin A1c.

Do DV, Shah SM, Sung JU, Haller JA, Nguyen QD.

Vitreoretinal Service, Wilmer Eye Institute, Johns Hopkins University School of
Medicine, Baltimore, Maryland 21287, USA.

PURPOSE: To assess the correlation between persistent diabetic macular edema and 
hemoglobin A1c (HbA1C). DESIGN: Retrospective study. METHODS: Records of type 2
diabetic patients who received eye care for persistent clinically significant
macular edema (CSME) from January 2002 to January 2004 were reviewed. Subjects
who met one of two criteria were identified: 1) persistent CSME, detected by
contact lens biomicroscopy and fluorescein angiography, despite at least two
focal laser photocoagulations (FLP) performed at least 3 months before the
current diagnosis, or 2) a history of CSME with resolution of macular edema at
the time of examination. Patients also needed to have had their HbA1C measured at
the Johns Hopkins Hospitals within 3 months of meeting these criteria. RESULTS:
The study identified 92 patients (152) eyes with persistent CSME and 32 patients 
(56 eyes) with resolved CSME. HbA1C values ranged from 5.3% to 15.6% (mean, 8.9%;
median, 8.7%) and 5.3% to 9.7% (mean, 6.7%; median, 6.6%) among patients with
persistent and resolved edema (P = .0005). Among the 32 patients with persistent 
unilateral CSME, mean HbA1C was 8.6% (median 8.5%), and among the 60 patients
with bilateral CSME, mean HbA1C was 9.1% (median, 8.9%). Of patients with
persistent CSME, 74% had HbA1C greater than 7.5% compared with 12.5% of the
patients with resolved CSME (P = .0005). CONCLUSIONS: Persons with type 2
diabetes and persistent CSME have higher HbA1C at time of their disease than
patients with resolved CSME. Patients with bilateral disease have more elevated
HbA1C than those with unilateral disease.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15808156 [PubMed - indexed for MEDLINE]

1993: Am J Ophthalmol. 2005 Apr;139(4):589-96.

Comment in:
    Am J Ophthalmol. 2005 Apr;139(4):710-1.

Expression of VEGF and angiopoietins in subfoveal membranes from patients with
age-related macular degeneration.

Hera R, Keramidas M, Peoc'h M, Mouillon M, Romanet JP, Feige JJ.

Department of Opthalmology, University Hospital of Grenoble, La Tronche, France.

PURPOSE: Vascular endothelial growth factor (VEGF) and angiopoietins are key
regulators of angiogenesis. The purpose of this study was to measure mRNA levels 
of these factors and of their receptors in surgically excised subfoveal membranes
from patients with age-related macular degeneration (AMD) and to evaluate their
relevance as prognostic markers of postsurgical recurrence of choroidal
neovascularization (CNV). DESIGN: Prospective observational case series. METHODS:
setting: Institutional. study population: In a prospective series of 24 patients 
(aged 51 to 91 years) with classic CNV of AMD diagnosed less than 6 months
previously, 24 subfoveal membranes (one eye per patient) were surgically removed 
and collected. Thirteen patients underwent treatment for recurrence of CNV within
6 months of surgery. main outcome measures: Four 8-mu sections were prepared from
each membrane for immunohistochemical determination of vascular density (CD31
immunostaining). The remaining tissue was used for preparation of total RNA. The 
levels of VEGF-A, VEGF-R1, VEGF-R2, neuropilin-1, angiopoietin-1, angiopoietin-2,
Tie-2, and hypoxanthine phosphoribosyltransferase mRNAs were determined by
real-time reverse-transcriptase polymerase chain reaction. RESULTS: Vascular
endothelial growth factor, angiopoietin-1, and angiopoietin-2 appeared to be
expressed to variable levels in most samples, whereas Tie-2, VEGF-R1, and VEGF-R2
were undetectable. Low levels of VEGF expression correlated with postsurgical
recurrence of CNV (P = .07). Angiopoietin-1 and angiopoietin-2 levels did not
predict recurrence (P > .1). CONCLUSION: The results indicate that at the time of
surgical excision, subfoveal membranes express angiopoietin-1, VEGF, and, to a
lesser degree, angiopoietin-2. Because CNV appears to recur less often in
membranes expressing high levels of VEGF, we hypothesize that VEGF acts as a
stabilizer of neovessels at this stage of the disease.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15808152 [PubMed - indexed for MEDLINE]

1994: Graefes Arch Clin Exp Ophthalmol. 2005 Mar;243(3):222-7. Epub 2004 Oct 2.

Macular pigment density in age-related maculopathy.

Jahn C, Wüstemeyer H, Brinkmann C, Trautmann S, Mössner A, Wolf S.

Klinik und Poliklinik für Augenheilkunde, Universität Leipzig, Germany.

PURPOSE: Macular pigment (MP) is believed to have a protective role in the
development and progression of age-related maculopathy (ARM). We present results 
of measurements of macular pigment density (MPD) in patients with ARM at
different stages with a modified confocal scanning laser ophthalmoscope (HRA,
Heidelberg Engineering, Heidelberg, Germany). METHOD: ARM patients were
categorized into four groups. Staging depended upon the size of drusen,
geographic atrophy, and loss of visual acuity due to ARMD in the fellow eye; 1:
drusen size <125 microm, 2: drusen size >125 microm, 3: drusen size <125 microm +
ARMD in fellow eye, and 4: drusen size >125 microm + ARMD in fellow eye. We took 
autofluorescence images at 488 nm and 514 nm with a modified HRA. MP density was 
evaluated within 2 degrees around the center of the fovea. In this study, we
included 146 patients with ARM: 26 in group 1, 19 in group 2, 80 in group 3, and 
21 in group 4. RESULTS: The mean MPD of the different stages of ARM was: in group
1, 0.233 +/- 0.091 DU; group 2, 0.218 +/- 0.102 density units (DU); group 3,
0.252 +/- 0.085 DU; and group 4, 0.208 +/- 0.100 DU. Statistical analysis
(Kruskal-Wallis test) showed no differences between groups. CONCLUSIONS: Recent
studies in ARM did not result in significant differences of MPD between the
various stages of ARM. Further longitudinal studies are requested to compare the 
incidence of ARMD in eyes with high and low MPD in order to provide definite
evidence of the influence of MPD on the progression of ARMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15806375 [PubMed - indexed for MEDLINE]

1995: Retina. 2005 Apr-May;25(3):324-31.

Prevalence of patients presenting with neovascular age-related macular
degeneration in an urban population.

Zawinka C, Ergun E, Stur M.

Department of Ophthalmology, University of Basel, Basel, Switzerland.

PURPOSE: To determine the number and type of new cases of neovascular age-related
macular degeneration (AMD) present in a defined urban population and to establish
the proportion that would be recommended for treatment with verteporfin or laser 
photocoagulation. METHODS: Patients referred to an ophthalmic center in Vienna
during a 10-week period because of recent deterioration in vision caused by newly
diagnosed neovascular AMD were included. RESULTS: Neovascular AMD was diagnosed
in 168 eyes in 153 patients. One hundred one eyes (60.1%) had lesions that were
occult with no classic choroidal neovascularization (CNV); of these, 70 were
subfoveal, 19 were juxtafoveal, and 12 were extrafoveal. Thirty-five eyes (20.8%)
had predominantly classic lesions; of these, 27 were subfoveal, 6 were
juxtafoveal, and 2 were extrafoveal. Thirty-two eyes (19.0%) had minimally
classic lesions, of which 31 were subfoveal and 1 was extrafoveal. In accordance 
with consensus guidelines from a panel of experts and with American Academy of
Ophthalmology's Preferred Practice Pattern guidelines, 33 lesions (17%) would be 
considered for treatment with verteporfin therapy. A further 37 subfoveal lesions
with occult with no classic CNV and 7 juxtafoveal lesions with occult with no
classic CNV might also benefit from verteporfin therapy if there is evidence of
presumed recent disease progression. Five lesions (3.0%) could have been treated 
with laser photocoagulation according to Macular Photocoagulation Study criteria.
CONCLUSIONS: These results suggest that verteporfin therapy substantially
increases the number of patients with treatable neovascular AMD.

PMID: 15805910 [PubMed - indexed for MEDLINE]

1996: Retina. 2005 Apr-May;25(3):311-6.

Comment in:
    Retina. 2006 Jan;26(1):122-3; author reply 123.

Histopathologic evaluation of the internal limiting membrane surgically excised
from eyes with diabetic maculopathy.

Matsunaga N, Ozeki H, Hirabayashi Y, Shimada S, Ogura Y.

Department of Ophthalmology and Visual Science, Nagoya City University Graduate
School of Medical Sciences, Japan. matsunaga@hakuaikai.jp

PURPOSE: To histopathologically evaluate the internal limiting membrane (ILM) in 
diabetic eyes with macular edema as compared to nondiabetic controls. METHODS:
The authors ultrastructurally and immunohistochemically studied ILM specimens
that were intentionally peeled from five eyes with diabetic maculopathy,
comprising four with diffuse diabetic macular edema and one with macular hole
accompanying diabetic retinopathy (DM group), and five with nondiabetic
idiopathic macular hole (MH group). They compared ultrastructural and
immunohistochemical findings between the two groups. RESULTS: A larger amount of 
cellular elements was observed on the vitreous side of the ILM in the DM group.
The thickness of the ILM in the DM group was significantly increased (mean 4.8
+/- 1.6 microm) compared with that in the MH group (1.8 +/- 0.6 microm) (P <
0.0001). Immunoreactions for heparan sulfate proteoglycan in the ILM were more
abundant in the DM group than in the MH group. CONCLUSION: The ILM thickening and
cell abundance on the vitreous surface might contribute to the course and the
pathogenesis of diabetic maculopathy.

PMID: 15805908 [PubMed - indexed for MEDLINE]

1997: Retina. 2005 Apr-May;25(3):296-303.

Results of a multicenter clinical trial to evaluate the preferential hyperacuity 
perimeter for detection of age-related macular degeneration.

Goldstein M, Loewenstein A, Barak A, Pollack A, Bukelman A, Katz H, Springer A,
Schachat AP, Bressler NM, Bressler SB, Cooney MJ, Alster Y, Rafaeli O, Malach R; 
Preferential Hyperacuity Perimeter Research Group.

Department of Ophthalmology, Tel-Aviv Medical Center, Israel.

PURPOSE: To compare the preferential hyperacuity perimeter (PHP) with an Amsler
grid in detection of age-related macular degeneration (AMD). METHODS: Patients
underwent refraction, visual acuity examination, PHP, Amsler grid examination,
and macular photography. RESULTS: One hundred fifty patients participated in the 
trial. Of 19 eyes with neovascular AMD, 19 (100%) were positive on the PHP, and
10 (53%), on the Amsler grid. Of 27 eyes with geographic atrophy, 26 (96%) were
positive on the PHP, and 12 (44%), on the Amsler grid. Of 20 eyes with
intermediate AMD, 14 (70%) were positive on the PHP, and 4 (20%), on the Amsler
grid. Of 51 eyes with early AMD, 21 (41%) were positive on the PHP, and 4 (8%),
on the Amsler grid. Of 33 eyes with no AMD, 6 (18%) were positive on the PHP, and
none, on the Amsler grid. Thus, 80 (68%) of 117 patients with AMD had a positive 
PHP, while 30 (26%) had positive results of Amsler grid examination (P < 0.001,
McNemar test). CONCLUSION: The PHP had greater sensitivity, although with a
relatively high rate of false-positive results for healthy individuals, than the 
Amsler grid in detecting AMD-related lesions.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 15805906 [PubMed - indexed for MEDLINE]

1998: Ocul Immunol Inflamm. 2005 Feb;13(1):3-11.

Immunological factors in the pathogenesis and treatment of age-related macular
degeneration.

Kijlstra A, La Heij E, Hendrikse F.

Eye Research Institute Maastricht, Department of Ophthalmology, University of
Maastricht Maastricht The Netherlands. aize.kijlstra@wur.nl

Recent findings indicate that immunological factors are involved not only in the 
pathogenesis of age-related macular degeneration (AMD), but also in its
treatment. Earlier data showing the presence of inflammatory cells in affected
areas of AMD retinas support this statement. Although a possible role for
autoimmunity was initially suggested, it has never reached general acceptance.
Microorganisms have also been implied in the pathogenesis of AMD. Both serum
antibacterial antibody levels and positive DNA tests from neovascular membranes
have pointed to a possible role for Chlamydia pneumoniae in the pathogenesis of
AMD. New data is providing evidence for the hypothesis that deposits between
Bruch's membrane and the retinal pigment epithelium (RPE) cell layer may act as a
stimulus for the local activation of the complement system. This may lead to a
further growth of the deposits due to the strong chemotactic activity of certain 
complement activation products (such as C5a) with an influx of inflammatory
cells. The buildup of cells and extracellular deposits may lead to local ischemia
resulting in the activation of RPE cells. These activated RPE cells are thought
to release angiogenic stimuli leading to choroidal neovascularization, which is
the most serious complication of AMD. The fact that immunosuppressive drugs such 
as triamcinolone acetonide and anecortave acetate are capable of inhibiting
choroidal neovascularization is consistent with an inflammatory component in the 
pathogenesis of AMD. Specific immunotherapy directed at certain cytokines or
growth factors is now being investigated at both the animal and patient levels.
Various clinical trials involving engineered antibodies are now being applied to 
block angiogenic factors such as the vascular endothelial growth factor (VEGF).
An approach using gene therapy to influence angiogenesis by inducing the
production of the pigment epithelium-derived factor (PEDF) was able to block
neovascularization in an experimental murine model. Besides trying to block
ongoing processes in AMD, retinal transplantation is now also being investigated 
as a treatment option. The fact that the retina is possibly an immunoprivileged
tissue in combination with experimental data showing that the subretinal space is
an immunoprivileged site is an indication that transplantation would not suffer
from the rejection process. A larger obstacle is the question whether
transplanted retinal tissue will regain its functional properties.

Publication Types: 
    Review

PMID: 15804763 [PubMed - indexed for MEDLINE]

1999: Eye. 2005 Dec;19(12):1315-24.

Retinal pigment epithelial tear following photodynamic therapy for choroidal
neovascularization secondary to AMD.

Goldstein M, Heilweil G, Barak A, Loewenstein A.

Department of Ophthalmolgy, Tel-Aviv Medical center, Sackler School of medicine, 
Tel-Aviv, Israel. michgold@netvision.net.il

PURPOSE: To describe retinal pigment epithelial tear following photodynamic
therapy (PDT) for subfoveal choroidal neovascularization (CNV) secondary to
age-related macular degeneration (AMD). DESIGN: Retrospective interventional case
series. METHODS: A retrospective study in an institutional practice. We describe 
seven cases of retinal pigment epithelial (RPE) tear, which developed in seven
eyes of seven patients following PDT. All eyes had subfoveal CNV secondary to
AMD. RESULTS: Six eyes had occult subfoveal CNV, and one eye had recurrent
classic subfoveal CNV. In five patients, the eye that developed the tear was the 
second eye, whereas the first eye had a disciform scar. In four eyes, the RPE
tear developed after one PDT, in one eye the RPE tear developed after the second 
PDT, and in two eyes the RPE tear developed after the third PDT. In five of seven
cases, there was a significant visual deterioration following the RPE tear.
CONCLUSIONS: RPE tear is a complication that may occur following PDT in
particular when the PDT is applied to an occult subfoveal CNV.

Publication Types: 
    Case Reports

PMID: 15803179 [PubMed - indexed for MEDLINE]

2000: Eye. 2006 Feb;20(2):203-7.

Plasma homocysteine and total thiol content in patients with exudative
age-related macular degeneration.

Coral K, Raman R, Rathi S, Rajesh M, Sulochana KN, Angayarkanni N, Paul PG,
Ramakrishnan S.

Biochemistry Research Department, Vision Research Foundation, Sankara Nethralaya,
Chennai, India.

PURPOSE: Exudative age-related macular degeneration (ARMD) is one of the
debilitating ocular complications, which results in permanent blindness. Elevated
homocysteine (Hcys) levels have been associated in the development of several
vascular diseases. Vascular and oxidative stress theories have been implicated
for the development of choroidal neovascularization in exudative ARMD. The aim of
the present study was to investigate the possible role of plasma Hcys and thiol
content (tSH) as a risk factor for the development of exudative ARMD. METHOD: A
total of 16 patients with exudative ARMD and 20 age-matched controls were
recruited for the study. Plasma Hcys levels were analysed using Reverse Phase
High Performance Liquid Chromatography. Plasma glutathione (GSH) content was
determined using o-phthalaldehyde (OPA) derivatization and subsequent detection
by fluorimeter. Plasma tSH levels were determined by using thiol-specific reagent
dithionitrobenzoic acid (DTNB) spectrophotometrically. RESULTS: Plasma Hcys
levels in exudative ARMD were elevated three-fold (18+/-5.0 microM) when compared
to healthy controls (6.7+/-1.8 microM). There was a two-fold decrease in the GSH 
and tSH in exudative ARMD when compared with controls. Negative correlation was
observed between diminished tSH and Hcys levels (r=-0.4837, P=0.05). Similarly
plasma Hcys levels negatively correlated with GSH content (r=-0.6620, P<0.05).
CONCLUSION: Results from our present study revealed that there is an elevated
Hcys level and diminished thiol pool content in exudative ARMD that are
significant.

PMID: 15803172 [PubMed - indexed for MEDLINE]

2001: Ophthalmologica. 2005 Mar-Apr;219(2):86-92.

Optical coherence tomographic assessment of diabetic macular edema: comparison
with fluorescein angiographic and clinical findings.

Ozdek SC, Erdinç MA, Gürelik G, Aydin B, Bahçeci U, Hasanreisoğlu B.

Department of Ophthalmology, Gazi University, School of Medicine, Ankara, Turkey.

PURPOSE: To compare the optical coherence tomographic (OCT) features with
clinical and fluorescein angiographic (FA) findings in patients with diabetic
retinopathy. METHODS: In a retrospective study ophthalmologic examination
together with FA and OCT images were obtained from 195 eyes of 110 patients with 
different stages of diabetic retinopathy and OCT images were obtained from 40
eyes of 20 control subjects. Fluorescein leakage characteristics were organized
into five groups: no leakage (1), focal (2), diffuse (3), combined focal+diffuse 
leakage (4) and cystoid (5). The Pearson correlation test was used to test the
correlation between visual acuity and central foveal thickness and ANOVA was used
for the statistical comparison between the groups. RESULTS: The OCT images
demonstrated retinal swelling in 66.1% of eyes, cystoid macular edema (CME) in
11.8% of eyes, serous foveal detachment + swelling in 6.2% of eyes, serous foveal
detachment+swelling+CME in 3.6% of eyes and normal foveal structure in 12.3% of
eyes. The best-corrected visual acuity was significantly correlated with central 
foveal thickness (r:-0.528, p<0.01). There was 77% agreement between clinical
examination and OCT results. CME was detected with OCT in 15.4% of eyes in our
study, 40% of which was not detected with slit-lamp biomicroscopy and 63.3% of
which was not evident in FA. None of the serous foveal detachments could be
detected during slit-lamp biomicroscopy or FA. CONCLUSIONS: OCT-3 provided
objective documentation of foveal structural changes in eyes with diabetic
retinopathy. Best-corrected visual acuity provided a significant correlation with
the retinal thickness at the central fovea. These results indicate that OCT can
facilitate deciding on the treatment protocol (surgical or medical) and follow-up
of diabetic patients, which is especially important in the early stages of
diabetic maculopathy when the structural changes are not yet evident with
slit-lamp biomicroscopy or angiographically. Copyright (c) 2005 S. Karger AG,
Basel.

Publication Types: 
    Comparative Study

PMID: 15802932 [PubMed - indexed for MEDLINE]

2002: Acta Ophthalmol Scand. 2005 Apr;83(2):248-51.

Intravitreal triamcinolone acetonide for treatment of cystoid macular oedema in
patients with retinitis pigmentosa.

Ozdemir H, Karacorlu M, Karacorlu S.

Istanbul Retina Institute Inc., Istanbul, Turkey.

PURPOSE: To evaluate the anatomic and visual outcomes of intravitreal
triamcinolone acetonide injection in patients with cystoid macular oedema (CMO)
secondary to retinitis pigmentosa (RP). METHODS: Five eyes of five patients with 
CMO secondary to RP, aged 25-41 years (mean 33.2 years) made up the study
population. All eyes had persistent CMO despite medical treatment with 250 mg of 
oral acetazolamide twice daily for 1 month. Intravitreal injection of 4 mg (0.1
ml) triamcinolone acetonide was offered to treat macular oedema. The visual and
anatomic responses were observed, as well as complications related to the
injection procedure and corticosteroid medication. RESULTS: Follow-up periods
varied between 6 and 8 months (mean 6.8 months); all patients completed 6 months 
of follow-up. After intravitreal triamcinolone acetonide injection all patients
showed good anatomic response. The baseline median central macular thickness was 
418 microm (range 376-626 microm). At 1 month, the median central macular
thickness had decreased to 224 microm (range 214-326 microm). At 3 and 6 months, 
the median central macular thicknesses were 275 microm (range 215-584 microm) and
312 microm (range 239-521 microm), respectively. Recurrent CMO was found in one
patient at the 3-month follow-up and in two patients at the 6-month follow-up.
Retreatment was performed in these patients. At the 1-month follow-up, no patient
was found to have lost vision and two patients showed improvement. At the 3- and 
6-month follow-ups, no patient had lost vision from baseline but no patient had
maintained their improved visual acuity (VA). CONCLUSIONS: In our small series,
all patients showed an anatomic improvement in CMO after intravitreal injection
of triamcinolone acetonide. However, in three out of five patients, despite good 
anatomic results, no improvement in VA was achieved. Because of the limitations
of this pilot study, it is difficult to explain why no improvement in VA was
achieved despite good anatomic results in some patients. Further study with
longer follow-up periods and larger series is warranted to assess the efficacy of
the treatment.

Publication Types: 
    Case Reports

PMID: 15799743 [PubMed - indexed for MEDLINE]

2003: Acta Ophthalmol Scand. 2005 Apr;83(2):154-60.

Topical dorzolamide increases pericentral visual function in age-related
maculopathy: pilot study findings with short-wavelength automated perimetry.

Remky A, Weber A, Arend O, Sponsel WE.

Department of Ophthalmology, Medical School of the Technical University of
Aachen, Germany. andreas.remky@post.rwth-aachen.de

PURPOSE: Numerous studies have confirmed the enhancement of ocular circulation by
carbonic anhydrase inhibitors (CAIs). Topical CAI treatment with dorzolamide
averts the significant pericentral visual function loss accompanying retinal and 
choroidal vasoconstriction during acute hyperventilation-induced hypocapnia. This
study was designed to discern whether dorzolamide might similarly enhance macular
function in patients with age-related maculopathy (ARM). METHODS: In a masked,
placebo-controlled study, 40 patients with ARM and acuity > 20/50 were randomized
to receive either dorzolamide or placebo for 12 weeks, thrice daily. After
pre-study perimetric training, pericentral function (mean sensitivity) was
quantified using Humphrey 10-2 short-wavelength automated perimetry (SWAP),
before and after 12 weeks of topical therapy. RESULTS: Dorzolamide-treated eyes
demonstrated a significant increase in mean sensitivity of + 1.55 dB (p = 0.04); 
placebo-treated eyes showed no significant change (+ 0.58 dB; p = 0.10). Given
the non-significant increase of mean sensitivity in the placebo-treated group,
fewer than 100 subjects per group would be required to afford > 70% power to
yield a significant direct comparative difference between treatment and placebo
in a prospective, randomized study of equally short duration. CONCLUSIONS: This
study demonstrated a significant increase in short-wavelength sensitivity in ARM 
with dorzolamide and the lack thereof with placebo. These encouraging pilot study
data suggest a potential role for topical CAIs in ARM patients, and establish
objective parameters for prospective studies to further evaluate the effects of
dorzolamide in ARM.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 15799725 [PubMed - indexed for MEDLINE]

2004: Acta Ophthalmol Scand. 2005 Apr;83(2):141-7.

Natural course of occult choroidal neovascularization in age-related macular
degeneration: development of classic lesions in fluorescein angiography.

Schneider U, Gelisken F, Inhoffen W.

University Eye Clinic Tübingen, Tübingen, Germany.
ulrike.schneider@uni-tuebingen.de

PURPOSE: To analyse the frequency of conversion from occult with no classic
choroidal neovascularization (CNV) and occult with minimally classic CNV into
predominantly classic CNV secondary to age-related macular degeneration. METHODS:
Retrospective evaluation of baseline and repeat angiograms of 54 eyes with a
follow-up of 6-12 months. RESULTS: In the group with initially occult with no
classic CNV, nine of 40 eyes (23%) progressed to a predominantly classic lesion, 
whereas in the group of occult with a minimally classic CNV, 10 of 14 eyes (71%) 
eyes developed a predominantly classic CNV. CONCLUSIONS: The proportion of eyes
that develop predominantly classic CNV is much higher in eyes with initially
occult and minimally classic CNV, compared with eyes with initially occult and no
classic CNV. Our data suggest that the natural course of CNV secondary to AMD
begins as occult and progresses to classic CNV.

PMID: 15799723 [PubMed - indexed for MEDLINE]

2005: Ophthalmic Surg Lasers Imaging. 2005 Mar-Apr;36(2):94-102.

Results 28 months following transpupillary thermotherapy for classic and occult
choroidal neovascularization in patients with age-related macular degeneration.

Newsom RS, McAlister JC, Saeed M, El-Ghonemy K, McHugh JD.

King's College Hospital, London, United Kingdom.

BACKGROUND AND OBJECTIVE: To report the outcome of patients 28 months following
treatment with transpupillary thermotherapy (TTT) for classic and occult
choroidal neovascularization (CNV) secondary to age-related macular degeneration.
PATIENTS AND METHODS: A nonrandomized pilot trial of 36 eyes of 33 patients was
performed. Eyes with angiographically defined CNV, 11 predominantly classical and
25 predominantly occult, were treated with large spot diode laser (810 nm) TTT
for 1 minute, the end point being no or minimal visible change. Outcome was
assessed with best-corrected LogMAR visual acuity, clinical examination, and
fluorescein angiography. RESULTS: Patients were observed for a mean of 28.7
months (range, 18 to 40 months). The mean change in LogMAR visual acuity for
predominantly classic membranes was -1.91 (standard deviation [SD] = 4.3) and 5
of 11 (45.5%) eyes had a loss of 3 or more LogMAR lines. Predominantly classic
membranes were closed in 9 of 11 eyes and stabilized in 2 of 11 eyes. The mean
change in LogMAR visual acuity for predominantly occult membranes was -1.48 (SD =
6.3) and 10 of 25 (40%) patients had a loss of 3 lines or more. Predominantly
occult CNV was stabilized in 25 of 25 cases, and recurrence developed in 2 of 25 
cases; one of the latter developed classic CNV. CONCLUSIONS: The medium-term
results for patients treated with TTT for both occult and classic CNV show good
stability, with little visual loss and few recurrences. These data confirm the
original findings of this study.

Publication Types: 
    Clinical Trial
    Comparative Study

PMID: 15792308 [PubMed - indexed for MEDLINE]

2006: Invest Ophthalmol Vis Sci. 2005 Apr;46(4):1440-4.

Intravitreal injection of corticosteroid attenuates leukostasis and vascular
leakage in experimental diabetic retina.

Tamura H, Miyamoto K, Kiryu J, Miyahara S, Katsuta H, Hirose F, Musashi K,
Yoshimura N.

Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School
of Medicine, Kyoto, Japan.

PURPOSE: Recently, intravitreal injection of corticosteroids has been in wide use
as a treatment for diabetic macular edema, and the outcomes have been favorable. 
However, the exact mechanism remains unclear. The hypothesis for the current
study was that intravitreal corticosteroids may improve diabetic retinal edema by
amelioration of blood-retinal barrier (BRB) breakdown, by inhibiting leukocyte
stasis (leukostasis). METHODS: Diabetes was induced in 6-week-old male Long-Evans
rats by intraperitoneal injection of streptozotocin (75 mg/kg). Three weeks after
induction of diabetes, intravitreal injection of dexamethasone (40 microg/10
microL) was performed. At 2 days after intravitreal injection, accumulated
leukocytes were counted in vivo by acridine orange leukocyte fluorography, and
BRB breakdown was evaluated by measurement of retinal vascular permeability. The 
mRNA expression and protein levels of intercellular adhesion molecule (ICAM)-1 in
the retina were also studied. RESULTS: The number of leukocytes accumulated in
the retina, once increased in the diabetic group, was decreased by 31.6% (P =
0.0001) after dexamethasone injection. The level of BRB breakdown, also elevated 
in the diabetic group, was suppressed by 61.1% (P = 0.0046) after dexamethasone
injection. The level of ICAM-1 mRNA expression and its protein, upregulated in
the diabetic group, were downregulated by dexamethasone treatment by 70.0% (P <
0.0001) and 56.4% (P = 0.0003). CONCLUSIONS: Intravitreal injection of
corticosteroids improves diabetic retinal edema through inhibiting leukocyte
recruitment in the diabetic retina.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15790913 [PubMed - indexed for MEDLINE]

2007: Klin Monatsbl Augenheilkd. 2005 Mar;222(3):202-5.

Simultaneous fluorescein and indocyanine green angiography for exudative macular 
degeneration.

Helbig H, Niederberger H, Valmaggia C, Bischoff P.

Klinik für Augenkrankheiten, Kantonsspital St. Gallen, St. Gallen, Switzerland.
horst.helbig@usz.ch

BACKGROUND: The present study investigates how often a simultaneous fluorescein
and indocyanine green (ICG) angiography had therapeutic consequences and if it is
useful as a clinical routine diagnostic tool. PATIENTS AND METHODS: 502
consecutive simultaneous angiographies in eyes with exudative macular
degeneration were retrospectively studied. RESULTS: A classic extra- or
juxtafoveolar choroidal neovascularisation (CNV) was found in 3.5 % of the eyes. 
A subfoveal predominantly classic CNV was present in 19 % of the angiographies.
ICG angiography showed a vascular network in 3 % of the eyes with occult CNV in
fluorescein angiography. A neovascularisation supplied by retinal vessels
(retinal angiomatous proliferation) was found in 9 % and a polypoidal choroidal
vasculopathy (PCV) in 6 %. Other plaques or hot spots were visible in 4 %. In 11 
eyes with progressive exudation from PCV and threatening of the fovea, laser
treatment was successfully performed. CONCLUSIONS: Combined angiography
identifies treatable PCV. Advantages of a combined procedure (easier logistics,
no missing of treatable cases) and arguments for a two step procedure with ICG
angiography only in selected cases (lower costs, lower rate of adverse reactions)
must be weighed against each other.

PMID: 15785980 [PubMed - indexed for MEDLINE]

2008: Br J Ophthalmol. 2005 Apr;89(4):470-4.

Association study of detoxification genes in age related macular degeneration.

Esfandiary H, Chakravarthy U, Patterson C, Young I, Hughes AE.

Centre for Vision Sciences, Queen's University Belfast, Belfast BT12 6BA, UK.

BACKGROUND/AIMS: Age related macular degeneration (AMD) is a complex disorder
leading to loss of central vision, and identification of risk factors associated 
with susceptibility to AMD has been a key objective for ophthalmic genetics
research for almost a decade. This association study has examined genetic
polymorphisms in 12 candidate genes as possible risk factors for predisposition
to the development of the exudative variant of AMD in a Northern Irish
population. The choice of genes was based on their function in the breakdown of
industrial pollutants, cigarette smoke, defence against oxidative stress, or
involvement in the general ageing process. METHODS: Up to five single nucleotide 
polymorphisms (SNPs) were typed for CYP1A1, CYP1A2, CYP2E1, CYP2D6, EPHX1, MnSOD,
AhR, NAT2, CAT, GPX1, PON1, and ADPRT1 by multiplex snapshot single base primer
extension method. Genes showing high linkage disequilibrium (LD) between SNPs
were analysed by haplotype analysis. Genes showing low LD were assessed using
individual SNPs based on genotypes. RESULTS: After correction for number of
genes/SNPs tested, no significant association with AMD was found although several
genes merit further investigation. This study suggests that a coding SNP in EPHX1
(Y113H) may be important in AMD and supports a previous observation of an
association with exudative AMD. In addition, haplotype analysis highlighted
ADPRT1, CYP2D6, and AhR as worthy of further study. CONCLUSION: This study has
identified a number of genes requiring further investigation including EPHX1,
ADPRT1, CYP2D6, and AhR.

PMID: 15774926 [PubMed - indexed for MEDLINE]

2009: Br J Ophthalmol. 2005 Apr;89(4):464-9.

Blue on yellow perimetry with scanning laser ophthalmoscopy in patients with age 
related macular disease.

Remky A, Elsner AE.

Schepens Eye Research Institute, Harvard Medical School, Boston, MA 02114, USA.
andreas.remky@post.rwth-aachen.de

BACKGROUND/AIM: The loss of short wavelength sensitive (SWS) cone mechanism
sensitivity is related to severe vision loss in patients with age related
maculopathy (ARM). A case-control study of patients with ARM and age matched
controls was performed, using blue on yellow static perimetry. METHODS: A bright 
yellow background at 594 nm isolated the responses of short wavelength cone
mechanisms to 458 nm targets. A scanning laser ophthalmoscope produced stimuli
and provided real time, simultaneous fundus illumination. The macula was probed
with 16 Goldmann IV targets, 1-10 degrees from fixation, using a staircase
method. RESULTS: 24 patients with non-exudative ARM were matched to 24 subjects
with normal fundus appearance. SWS cone pathway sensitivity for macular targets
was significantly reduced in the patients with ARM compared to normals--15.45 (SD
4.56) dB v 17.22 (0.28) dB, respectively (p<0.0005). There was not only a diffuse
loss of sensitivity in ARM patients, but also a localised loss of sensitivity
over drusen (p<0.025). Neither the mean age, 69 (8) years, nor the mean visual
acuity differed between groups, logMAR 0.09 (0.10) v 0.05 (0.06) for ARM patients
v normals, respectively. Patients with soft drusen had lower sensitivity than
those with hard drusen (p<0.05). CONCLUSION: A loss of SWS cone pathway
sensitivity occurred in most patients with early ARM, despite good visual acuity,
demonstrating a loss of visual function that cannot be attributed to ageing
changes. The loss of sensitivity, despite good visual acuity, included both a
diffuse loss and localised losses.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15774925 [PubMed - indexed for MEDLINE]

2010: Arch Ophthalmol. 2005 Mar;123(3):321-7.

The US twin study of age-related macular degeneration: relative roles of genetic 
and environmental influences.

Seddon JM, Cote J, Page WF, Aggen SH, Neale MC.

Epidemiology Unit, Massachusetts Eye and Ear Infirmary, Department of
Opthalmology, Harvaed Medical School, Boston, MA 02114, USA.
Johanna_Seddon@meei.harvard.edu

CONTEXT: Age-related macular degeneration (AMD) is the leading cause of
irreversible blindness among older individuals in many parts of the world. The
relative importance of genes and environment in the etiology of this major public
health problem is not well understood. OBJECTIVE: To investigate the impact of
genetic and environmental factors. PARTICIPANTS: Living twins in the National
Academy of Sciences-National Research Council World War II Veteran Twin Registry 
born between 1917 and 1927. METHODS: Twins were surveyed for the known presence
of macular degeneration. Enrolled twins underwent a standardized examination and 
fundus photography. Age-related macular degeneration evaluation was completed for
840 elderly male twins, 210 monozygotic and 181 dizygotic complete twin pairs,
both concordant and discordant for presence or absence of AMD, and 58 singletons.
A bivariate twin model incorporating initial screening ascertainment and age
effects was employed to partition variation in liability to AMD and signs of
maculopathy into additive genetic, common environment, and unique environment
components. MAIN OUTCOME MEASURE: Heritability of AMD grade and signs of
maculopathy based on clinical examination and fundus photographs. RESULTS: Of the
840 twins, 331 had no signs of maculopathy and 241 had early signs, while 162 had
intermediate AMD and 106 had advanced AMD. Heritability (additive genetic)
estimates were significant for overall AMD grade (0.46) and for intermediate
(0.67) and advanced (0.71) AMD. Significant unique environmental proportions of
variance were also observed for these AMD variables (0.37, 0.19, and 0.24,
respectively). Shared or common environmental contributions were not significant 
(0.05-0.17). For specific macular drusen and retinal pigment epithelial
characteristics, significant genetic (0.26-0.71) and unique environmental
(0.28-0.64) proportions of variance were detected. CONCLUSIONS: Genetic factors
play a substantial role in the etiology of AMD and associated macular
characteristics, explaining 46% to 71% of the variation in the overall severity
of the disease. Environmental factors unique to each twin also contribute to the 
occurrence of this disease. This quantification of relative genetic and
environmental contributions to the development of AMD should guide future
research on this important cause of blindness.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.
    Twin Study

PMID: 15767473 [PubMed - indexed for MEDLINE]

2011: Am J Ophthalmol. 2005 Mar;139(3):563-6.

A case of POEMS syndrome with cystoid macular edema.

Imai H, Kusuhara S, Nakanishi Y, Teraoka Escaño MF, Yamamoto H, Tsukahara Y, Negi
A.

Department of Organ Therapeutics, Division of Ophthalmology, Kobe University
Graduate School of Medicine, Kobe, Japan.

PURPOSE: To introduce a case of POEMS (polyneuropathy, organomegaly,
endocrinopathy, monoclonal gammopathy, and skin changes) syndrome with bilateral 
cystoid macular edema (CME). DESIGN: Interventional case report. METHODS:
Temporal changes of serum vascular endothelial growth factor (VEGF) levels and
macular thickness were evaluated. RESULTS: A 53-year-old woman with POEMS
syndrome was referred complaining of long-standing impaired vision. Typical CME
demonstrating petal-like dye pooling was observed in both eyes. After subtenon
administrations of triamcinolone acetonide (TA), pars plana vitrectomy, and
intraocular TA injection in the right eye, macular thickness decreased.
Intraocular VEGF levels were <31 pg/ml at the vitrectomy and intraocular TA
injection, whereas serum the VEGF level was >2000 pg/ml throughout the follow-up 
periods. In the untreated left eye, macular thickness altered related to serum
VEGF level. CONCLUSIONS: Based on the low intraocular VEGF level and serum
VEGF-related change of macular thickness, elevated serum VEGF might be a cause of
CME in POEMS syndrome.

Publication Types: 
    Case Reports

PMID: 15767082 [PubMed - indexed for MEDLINE]

2012: Am J Ophthalmol. 2005 Mar;139(3):537-40.

Regression of neovascular age-related macular degeneration following infliximab
therapy.

Markomichelakis NN, Theodossiadis PG, Sfikakis PP.

Ocular Inflammation and Immunology Service, Gennimatas Hospital, Athens
University Medical School, Athens, Greece.

PURPOSE: To describe the effects of the antitumor necrosis factor (TNF)
monoclonal antibody Infliximab systemic therapy on choroidal neovacularisation
(CNV) secondary to age-related macular degeneration (AMD). DESIGN: Prospective,
noncomparative series of three patients. METHODS: A subretinal membrane secondary
to AMD was documented by fluoroangiography at baseline in three elderly patients 
scheduled to receive Infliximab therapy for inflammatory arthritis (infusions of 
5 mg/kg at weeks 0, 2, 6, and every 8 weeks thereafter). Follow-up was performed 
at three months post-baseline, as well as during 18 months of continuing
treatment in the first patient. RESULTS: CNV regressed partially at three months 
and resolved at six months in the first patient. Best-corrected visual acuity
(BCVA) increased from 0.05 to 0.2; this effect was sustained at 18 months.
Regression of subretinal membrane and increase of BCVA was also documented in the
other patients. No ocular or extra-ocular side effects were noted. CONCLUSIONS:
These findings suggest a plausible pathogenetic role of TNF in CNV secondary to
AMD. Additional patients should be studied to confirm the promising clinical
results.

Publication Types: 
    Case Reports

PMID: 15767068 [PubMed - indexed for MEDLINE]

2013: Am J Ophthalmol. 2005 Mar;139(3):536-7.

Pterygium/pinguecula and the five-year incidence of age-related maculopathy.

Pham TQ, Wang JJ, Rochtchina E, Mitchell P.

Center for Vision Research, Department of Ophthalmology, University of Sydney,
NSW, Australia.

PURPOSE: To assess the relationship between baseline pterygium and pinguecula and
the five-year incidence of age-related maculopathy (ARM). DESIGN:
Population-based longitudinal study. METHODS: The Blue Mountains Eye Study
examined 3654 residents aged 49+ years during 1992 to 1994 and then re-examined
2335 (75.1% of survivors) after five years. Retinal photographs were graded using
the Wisconsin Age-Related Maculopathy Grading System. Slit-lamp examination
recorded pterygium and pinguecula. Eye-specific data were analyzed using
generalized estimating equation models. RESULTS: After adjusting for age, gender,
and smoking, eyes with pterygium or previous pterygium surgery had a higher risk 
of incident late ARM, odds ratio (OR) 3.3, 95% confidence interval (CI) 1.1 to
10.3, early ARM (OR 1.8, CI 1.1 to 2.9) and soft drusen (OR 2.0, CI 1.9 to 3.4), 
than eyes without pterygium. We found no association between pinguecula and
incident ARM. CONCLUSIONS: This study found that pterygium was associated with a 
two- to threefold increased risk of incident late and early ARM.

PMID: 15767067 [PubMed - indexed for MEDLINE]

2014: Am J Ophthalmol. 2005 Mar;139(3):455-61.

Prospective evaluation of digital non-stereo color fundus photography as a
screening tool in age-related macular degeneration.

Pirbhai A, Sheidow T, Hooper P.

Department of Ophthalmology, University of Western Ontario, London, Canada.

PURPOSE: To evaluate mydriatic, non-stereo digital color fundus photographs as a 
screening tool for identifying and classifying exudative age-related macular
degeneration (AMD). DESIGN: Prospective case series. METHODS: Digital color
fundus photographs were obtained from patients seen in the AMD screening clinic
over a 9-month period at the Ivey Eye Institute in London, Ontario. Photographs
for eligible patients were separated by eye, cataloged, blinded, and randomly
labeled before interpretation by an experienced vitreoretinal surgeon. Exact
agreement, sensitivity, specificity, positive predictive value, and negative
predictive value of the fundus photographs in diagnosing, classifying, and
managing cases of suspected exudative AMD were then calculated against gold
standard clinical examination and fluorescein angiography. RESULTS: A total of
223 images were used from 118 eligible patients. Exact agreement between
photographic evaluation and gold standard ranged from 89.2% (presence of pigment 
epithelial detachment (PED)) to 82.5% (evidence of retinal pigment epithelium
geographic atrophy). Sensitivities ranged from 89.2% (presence of choroidal
neovascular membrane (CNVM)) to 40.0% (presence of PED). Specificities ranged
from 94.1% (presence of PED) to 86.8% (presence of retinal pigment epithelium
geographic atrophy). Positive predictive value ranged from 86.1% (presence of
CNVM) to 40.0% (presence of PED). Negative predictive value ranged from 94.1%
(presence of PED) to 88.9% (presence of CNVM). As a screening tool for high-risk 
dry changes and active exudative changes, overall sensitivity specificity,
positive predictive value, and negative predictive value were 82.1%, 79.1%,
70.4%, and 88.0%, respectively. CONCLUSIONS: Digital, non-stereo color fundus
photographs are highly sensitive and have high negative predictive value as a
screening tool. Very few treatable lesions are missed using telemedicine in
age-related macular degeneration.

Publication Types: 
    Comparative Study
    Evaluation Studies

PMID: 15767053 [PubMed - indexed for MEDLINE]

2015: Am J Ophthalmol. 2005 Mar;139(3):447-54.

Comment in:
    Am J Ophthalmol. 2006 Jan;141(1):225; author reply 225.    Am J Ophthalmol. 2006 May;141(5):984; author reply 984-5.

Pars plana vitrectomy with removal of the internal limiting membrane in the
treatment of persistent diabetic macular edema.

Recchia FM, Ruby AJ, Carvalho Recchia CA.

Associated Retinal Consultants, P.C., William Beaumont Hospital, Royal Oak,
Michigan 48073, USA.

PURPOSE: To evaluate the benefit of pars plana vitrectomy (PPV) and removal of
the internal limiting membrane (ILM) in eyes with diffuse diabetic macular edema 
refractory to laser photocoagulation. DESIGN: Prospective, consecutive,
interventional case series. METHODS: Diabetic patients with biomicroscopic,
angiographic, and tomographic evidence of diabetic macular edema persisting for
at least 3 months after numerous sessions of macular photocoagulation were
evaluated for inclusion. Patients with biomicroscopic evidence of epiretinal
membrane or taut posterior hyaloid, previous vitreoretinal surgery, or active
proliferative diabetic retinopathy were excluded. The main outcome measures were 
macular thickness, as measured by optical coherence tomography (OCT) and visual
acuity (VA). RESULTS: PPV with ILM removal was performed in 11 eyes of 10
patients (four men, six women; mean age = 58.2 years). Six-month follow-up data
were available for 10 eyes (91%). At 6 months postoperatively, central macular
thickness had improved by at least 20% in eight of 11 eyes (mean preoperative
thickness of 421 mum compared with mean postoperative thickness of 188 mum; P =
.007). Mean VA improved from 20/352 to 20/94 at 6 months (P = .002). By the most 
recent visit (range = 6-20 months postoperatively), VA had improved by at least 2
Snellen lines in 6 of 10 eyes treated with surgery alone. CONCLUSIONS: The early 
results of this ongoing study suggest that PPV with ILM removal may provide
anatomic and visual benefit in some eyes with chronic diabetic macular edema
unresponsive or unamenable to additional laser photocoagulation.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15767052 [PubMed - indexed for MEDLINE]

2016: Am J Ophthalmol. 2005 Mar;139(3):405-20.

Age-related macular degeneration 1969-2004: a 35-year personal perspective.

Fine SL.

Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania,
Philadelphia, Pennsylvania 19104, USA. stuart.fine@uphs.upenn.edu

PURPOSE: To provide a personal perspective concerning diagnosis, treatment, and
evaluation of treatment for early and late stages of age-related macular
degeneration (AMD) over a 35 year period, 1969-2004. DESIGN: Literature review,
personal recollections, and conversations with investigators who participated in 
trials to evaluate treatments for AMD. METHODS: The author reviewed the
literature pertaining to evaluation and treatment of patients with AMD and
conversed with investigators who, over the past 35 years, designed, conducted and
participated in trials to assess new and existing treatments for AMD. RESULTS: In
1969, patients with AMD constituted a small part of a typical ophthalmic
practice. From 1969 to 2004, the prevalence of AMD has increased, and the methods
of evaluation and treatment have changed dramatically. The emergence of
fluorescein angiography and the development of laser photocoagulation and
photodynamic therapy have substantially altered clinical practice. Several
promising pharmacologic interventions are now being assessed in clinical trials. 
Nevertheless, AMD remains the leading cause of severe and irreversible vision
loss in the United States because there are no highly effective treatments
available for most patients. CONCLUSIONS: Because of an aging population and the 
lack of highly effective treatments, late AMD remains a major unsolved problem.
However, there is extensive research being conducted with support from the
National Eye Institute and from industry. There is also great interest in
prevention trials. Accordingly, the author is optimistic that over the next 35
years there will be significant improvements in our ability to prevent severe
vision loss from late AMD.

Publication Types: 
    Lectures
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15767048 [PubMed - indexed for MEDLINE]

2017: Curr Eye Res. 2004 Dec;29(6):387-401.

AMD and micronutrient antioxidants.

Hogg R, Chakravarthy U.

Ophthalmology & Vision Science, Institute of Clinical Science, The Royal Victoria
Hospital, Belfast, Northern Ireland.

Age-related maculopathy (ARM) is a common clinical entity. The late-stage
manifestations of ARM, which are known as age-related macular degeneration (AMD),
have devastating consequences for vision. Various risk factors have been
identified in the development of the condition, which are consistent with the
premise that oxidative stress plays an important role in its pathogenesis. Thus, 
the possibility that antioxidant balance can be manipulated through diet or
supplementation has created much interest. Associations between diet and
nutrition and the clinical features of ARM have been described. Scrutiny of the
literature shows consistency in the report of notable reductions in serum
micronutrients in wet AMD, however, the evidence for causation is still
circumstantial. In this comprehensive review of the clinical literature, we have 
assessed the evidence for a link between diet and nutrition as risk factors for
the development of ARM and AMD. All published case control, population-based, and
interventional studies on ARM were examined. Although initial support appeared to
be moderate and somewhat contradictory, the evidence that lifetime oxidative
stress plays an important role in the development of ARM is now compelling. The
positive outcomes in the Age-Related Eye Diseases Study, a major controlled
clinical trial, have given hope that modulation of the antioxidant balance
through supplementation can help prevent progression of ARM to AMD.

Publication Types: 
    Review

PMID: 15764083 [PubMed - indexed for MEDLINE]

2018: Prostaglandins Leukot Essent Fatty Acids. 2005 Apr;72(4):251-6.

Prostaglandin E1 infusion therapy in dry age-related macular degeneration.

Ladewig MS, Ladewig K, Güner M, Heidrich H.

Charité Ophthalmological Clinic, Campus Benjamin Franklin, Free University of
Berlin, Berlin, Germany.

OBJECTIVE: The pilot study is intended to show whether prostaglandin E1 (PGE1)
infusions are able to stop the gradual vision loss in dry age-related macular
degeneration (AMD) and, further, to stabilize or improve visual acuity. METHODS: 
With PGE1 infusions 11 patients with different forms of dry AMD were treated and 
compared with a control group of 10 untreated patients with dry AMD. The target
parameter was the visual acuity, as determined with the ETDRS logMAR charts.
Other examinations performed during the study were tests of contrast vision,
colour vision and central visual fields, as well as autofluorescence and
fluorescein angiography and multifocal electroretinography. RESULTS: On
termination of the infusions, six patients showed an increase in visual acuity by
at least one line, an improvement that was seen in eight patients 2 months after 
the end of the infusion therapy. After 6 months, one patient exhibited an
improvement of visual acuity by three lines and three patients an improvement by 
one line. Five patients were found to show no change of their baseline acuity
values after 6 months, while two patients exhibited an impairment by one line.
The visual acuity in the dry AMD control group without PGE1 treatment had
decreased by 0.8 lines on the average after 6 months. Contrast vision, central
visual fields and the multifocal electroretinogram showed improvements on the
termination of infusions and up to 2 months later; no substantial change of these
parameters, as compared with the baseline findings, was seen 6 months after the
termination of infusions. SUMMARY: This pilot study suggests that PGE1 infusions 
have a stabilizing or improving effect on the visual acuity of patients with dry 
AMD. Owing to the limitations of a pilot study, these results should, however, be
validated in a larger, randomized and blinded study.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial

PMID: 15763436 [PubMed - indexed for MEDLINE]

2019: Science. 2005 Apr 15;308(5720):385-9. Epub 2005 Mar 10.

Comment in:
    Science. 2005 Apr 15;308(5720):362-4.

Complement factor H polymorphism in age-related macular degeneration.

Klein RJ, Zeiss C, Chew EY, Tsai JY, Sackler RS, Haynes C, Henning AK,
SanGiovanni JP, Mane SM, Mayne ST, Bracken MB, Ferris FL, Ott J, Barnstable C,
Hoh J.

Laboratory of Statistical Genetics, Rockefeller University, 1230 York Avenue, New
York, NY 10021, USA.

Age-related macular degeneration (AMD) is a major cause of blindness in the
elderly. We report a genome-wide screen of 96 cases and 50 controls for
polymorphisms associated with AMD. Among 116,204 single-nucleotide polymorphisms 
genotyped, an intronic and common variant in the complement factor H gene (CFH)
is strongly associated with AMD (nominal P value <10(-7)). In individuals
homozygous for the risk allele, the likelihood of AMD is increased by a factor of
7.4 (95% confidence interval 2.9 to 19). Resequencing revealed a polymorphism in 
linkage disequilibrium with the risk allele representing a tyrosine-histidine
change at amino acid 402. This polymorphism is in a region of CFH that binds
heparin and C-reactive protein. The CFH gene is located on chromosome 1 in a
region repeatedly linked to AMD in family-based studies.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15761122 [PubMed - indexed for MEDLINE]

2020: Science. 2005 Apr 15;308(5720):421-4. Epub 2005 Mar 10.

Comment in:
    Science. 2005 Apr 15;308(5720):362-4.

Complement factor H polymorphism and age-related macular degeneration.

Edwards AO, Ritter R 3rd, Abel KJ, Manning A, Panhuysen C, Farrer LA.

Department of Ophthalmology and McDermott Center for Human Growth and
Development, University of Texas Southwestern Medical Center (UTSWMC), 5323 Harry
Hines Boulevard, Dallas, TX 75390, USA. albert-edwards@swbell.net

Age-related macular degeneration (AMD) is a common, late-onset, and complex trait
with multiple risk factors. Concentrating on a region harboring a locus for AMD
on 1q25-31, the ARMD1 locus, we tested single-nucleotide polymorphisms for
association with AMD in two independent case-control populations. Significant
association (P = 4.95 x 10(-10)) was identified within the regulation of
complement activation locus and was centered over a tyrosine-402 -->
histidine-402 protein polymorphism in the gene encoding complement factor H.
Possession of at least one histidine at amino acid position 402 increased the
risk of AMD 2.7-fold and may account for 50% of the attributable risk of AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15761121 [PubMed - indexed for MEDLINE]

2021: Science. 2005 Apr 15;308(5720):419-21. Epub 2005 Mar 10.

Comment in:
    Science. 2005 Apr 15;308(5720):362-4.

Complement factor H variant increases the risk of age-related macular
degeneration.

Haines JL, Hauser MA, Schmidt S, Scott WK, Olson LM, Gallins P, Spencer KL, Kwan 
SY, Noureddine M, Gilbert JR, Schnetz-Boutaud N, Agarwal A, Postel EA,
Pericak-Vance MA.

Center for Human Genetics Research, Vanderbilt University Medical Center,
Nashville, TN 37232, USA.

Age-related macular degeneration (AMD) is a leading cause of visual impairment
and blindness in the elderly whose etiology remains largely unknown. Previous
studies identified chromosome 1q32 as harboring a susceptibility locus for AMD.
We used single-nucleotide polymorphisms to interrogate this region and identified
a strongly associated haplotype in two independent data sets. DNA resequencing of
the complement factor H gene within this haplotype revealed a common coding
variant, Y402H, that significantly increases the risk for AMD with odds ratios
between 2.45 and 5.57. This common variant likely explains approximately 43% of
AMD in older adults.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15761120 [PubMed - indexed for MEDLINE]

2022: Expert Opin Emerg Drugs. 2005 Feb;10(1):119-35.

Future pharmacological treatment options for nonexudative and exudative
age-related macular degeneration.

Comer GM, Ciulla TA, Heier JS, Criswell MH.

Indiana University School of Medicine, Department of Ophthalmology, 702 Rotary
Circle, Indianapolis, IN 46202, USA. gcomer@iupui.edu

Age-related macular degeneration (AMD) is the leading cause of irreversible
vision loss in the industrialised world. Within the past decade, researchers have
introduced many promising prevention and treatment options in an attempt to
minimise the central vision loss imparted from AMD. Based on large-scale,
randomised, prospective, placebo-controlled trials, a specially formulated
combination of the antioxidants vitamin C, vitamin E, beta-carotene, copper and
zinc is the only proven means of AMD prophylaxis. Thermal laser photocoagulation 
and photodynamic therapy with verteporfin are the only standard treatment
options. However, efficacy is limited and treatment is only applicable to a
minority of AMD patients. Thus, alternative pharmacological interventions are in 
all phases of clinical development. Researchers are guardedly optimistic that
these advances may change the entire approach to AMD management in the near
future. This review article will detail the currently accepted treatment options,
as well as describe several of the more promising investigational pharmacological
approaches to AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 15757408 [PubMed - indexed for MEDLINE]

2023: Mo Med. 2005 Jan-Feb;102(1):63-6.

Ophthalmic topics for the non-ophthalmologist.

Lederer CM.

University of Missouri-Kansas City School of Medicine, USA.

This article provides information for the medical practitioner who deals with
patients receiving care for eye disease. It is written for the
non-ophthalmologist physician. The goal is to update the practitioner by
discussing common ophthalmic issues that are encountered in everyday interactions
with patients. Glaucoma, age-related macular degeneration, and treatment of
refractive errors are emphasized in this summary article.

Publication Types: 
    Review

PMID: 15754621 [PubMed - indexed for MEDLINE]

2024: Eur J Ophthalmol. 2005 Jan-Feb;15(1):170-2.

Delayed atrophy of the retinal pigment epithelium after submacular surgery.

MacLaren RE, Aylward GW.

Moorfields Eye Hospital, London - UK. maclaren@herald.ox.ac.uk

PURPOSE: We report a case of delayed atrophy of the retinal pigment epithelium
(RPE) eighteen months after apparently successful excision of submacular
choroidal new vessels (CNV) in a patient with age-related macular degeneration
(AMD). METHODS: Case report. RESULTS: Submacular surgery for CNV was achieved
without visible disturbance of the underlying RPE in an 83 year old man diagnosed
with AMD. At the time of surgery the CNV displayed clinical features consistent
with lying internal to Bruch's membrane (Type 2 configuration). There was no
visible RPE defect at the fovea and vision improved during the subsequent 12
months follow-up. Eighteen months later, however, an atrophic central RPE defect 
appeared, with a similar shape to the CNV originally excised. CONCLUSIONS: This
case demonstrates that submacular CNV with Type 2 configuration can occur in AMD 
and lead to an initially favourable outcome following submacular surgery. Atrophy
of the RPE nevertheless did eventually occur and in a pattern consistent with
damage during the original operation. It is important to consider results of
longer term follow-up when interpreting success rates for surgery in AMD.

Publication Types: 
    Case Reports

PMID: 15751262 [PubMed - indexed for MEDLINE]

2025: Eur J Ophthalmol. 2005 Jan-Feb;15(1):158-61.

Cystoid macular edema associated with latanoprost after uncomplicated cataract
surgery.

Altintaş O, Yüksel N, Karabaş VL, Demirci G.

Department of Ophthalmology, Medical Faculty, Kocaeli University, Kocaeli -
Turkey. ozgulaltintas@yahoo.com

PURPOSE: To report clinically symptomatic and angiographically documented cystoid
macular edema (CME) associated with the use of latanoprost in two pseudophakic
eyes after uncomplicated cataract surgery. METHODS: Retrospective review of two
patients who had history of latanoprost use and uncomplicated cataract surgery
and described blurred vision in the first postoperative month. RESULTS: Ocular
examination revealed CME, which was confirmed by fluorescein angiography. The
visual acuities of patients improved and the CME was angiographically resolved
after discontinuation of latanoprost and the initiation of nonsteroidal
anti-inflammatory eye-drops and oral acetazolamide. CONCLUSIONS: Until a causal
relationship between CME and latanoprost is proved or disproved, caution in its
use in pseudophakic patients would be prudent.

Publication Types: 
    Case Reports

PMID: 15751259 [PubMed - indexed for MEDLINE]

2026: Eur J Ophthalmol. 2005 Jan-Feb;15(1):96-101.

The efficacy of intravitreal triamcinolone acetonide on macular edema in branch
retinal vein occlusion.

Ozkiris A, Evereklioglu C, Erkiliç K, Ilhan O.

Erciyes University Medical Faculty, Kayseri - Turkey. aozkiris@erciyes.edu.tr

PURPOSE: To evaluate the effectiveness of intravitreal triamcinolone acetonide as
primary treatment of macular edema in branch retinal vein occlusion. METHODS:
Fifteen eyes of 15 patients with macular edema due to branch retinal vein
occlusion (Group 1) who received 8 mg/0.2 ml of intravitreal triamcinolone
injection as primary treatment were retrospectively evaluated. The control group 
(Group 2) consisted of 19 eyes of 19 patients who had received laser treatment
for macular edema. The main outcome measures included best-corrected visual
acuity, intraocular pressure, and macular edema map values of Heidelberg Retinal 
Tomograph II. RESULTS: In Group 1, mean visual acuity improved significantly from
a mean logMAR (logarithm of minimal angle of resolution) value of 0.98+/-0.19 at 
baseline to a maximum of 0.24+/-0.24 during a mean follow-up time of 6.3 months. 
In the control group, the mean baseline log-MAR visual acuity before laser
treatment was 1.02+/-0.22, and it was 0.50+/-0.28 at 6-month examinations. Mean
improvement in visual acuity at 1-, 3-, and 6-month examinations was
significantly higher in Group 1 when compared with the control group (for each,
p<0.001). The mean edema map value of Group 1 significantly decreased by 40% at
6-month examinations when compared with preinjection value (p<0.001). In Group 1,
mean increase in intraocular pressure elevation was 19.8% at the 1-month, 26.9%
at 3-month, and 5.7% at 6-month visits, but intraocular pressures were under
control with topical antiglaucomatous medications. CONCLUSIONS: Intravitreal
triamcinolone acetonide injection may be a new and promising approach as initial 
therapy for macular edema due to branch retinal vein occlusion.

PMID: 15751246 [PubMed - indexed for MEDLINE]

2027: Eur J Ophthalmol. 2005 Jan-Feb;15(1):89-95.

Intravitreal triamcinolone acetonide in refractory pseudophakic cystoid macular
edema: functional and anatomic results.

Boscia F, Furino C, Dammacco R, Ferreri P, Sborgia L, Sborgia C.

Department of Ophthalmology and Otorhinolaryngology, University of Bari, Bari -
Italy. francescoboscia@hotmail.com

PURPOSE: To evaluate safety and efficacy of intravitreal triamcinolone acetonide 
(TAAC) injections in the treatment of refractory pseudophakic cystoid macular
edema (CME). METHODS: Seven eyes of six patients (age range: 50-74) with
pseudophakic CME resistant to standard treatment received intravitreal injections
of 4 mg of TAAC with all vehicle. Mean preinjection duration of CME was 18.3
months. A mean of 2.1+/-1.2 (range 1 to 4) treatments were performed in four eyes
(57.1 %) when visual acuity deteriorated towards baseline levels. Visual acuity
assessment, optical coherence tomography (OCT), and fluorescein angiography (FFA)
were performed pre- and postoperatively to evaluate results of TAAC injections.
Intraocular pressure (IOP) and complications related to treatment were assessed. 
RESULTS: After 11.1+/-3.9 months, mean best-corrected visual acuity (BCVA)
increased (p =0.019) from 20/132 to a best value of 20/38. Mean macular thickness
decreased from 517.29+/-146.98 mm to a best value of 263.71+/-83.13 mm
(p=0.0018). Area of fluorescein leakage decreased (p<0.0001) from 11.84+/-0.93
mm2 at baseline to a minimal value of 3.86+/-0.98 mm2. The anatomic and
functional improvement appeared after 1 month from the intravitreal injection and
persisted through at least 3 months of follow-up. At the end of follow-up BCVA,
macular thickness, and area of fluorescein leakage did not differ from baseline. 
Four eyes (57.1 %) developed IOP values higher than 21 mmHg, controlled by
topical treatment. Two patients developed an endophthalmitis-like reaction.
CONCLUSIONS: Intravitreal TAAC was relatively safe and effective in resistant
cases of pseudophakic CME with a temporary beneficial effect on visual acuity and
macular edema.

PMID: 15751245 [PubMed - indexed for MEDLINE]

2028: Eur J Ophthalmol. 2005 Jan-Feb;15(1):74-80.

Clinical outcome and subjective quality of life after photodynamic therapy in
patients with age-related macular degeneration.

Krummenauer F, Braun M, Dick HB.

Department of Medical Biometry, Epidemiology and Informatics, Universität of
Mainz, Mainz, Germany. Frank.Krummenauer@uniklinikum-dresden.de

PURPOSE: Whereas the efficacy of photodynamic therapy (PDT) in preventing the
progression of age-related macular degeneration (ARMD) is established, its effect
on quality of life is under discussion. METHODS: All patients who underwent PDT
during 2000 and 2001 at the University Eye Hospital of Mainz were interviewed
using a standardized 82-item questionnaire on quality of life and patient
satisfaction in ophthalmologic patients. Information was assessed in terms of 82 
questions; global scores ranging from 1.0 (optimum self-estimated quality of
life) to 4.0 (worst) were derived. Cataract patients' scores were used to
characterize the ARMD patients' subjective outcome; the latter were then related 
to clinical outcome parameters via logistic regressions. RESULTS: A total of 84
patients (50% female, median age 77 years) were interviewed, who underwent a
median of three PDT interventions. During the period of PDT treatment, their
median decrease in visual acuity was 3 lines from 0.125 to 0.063. Patients who
reported a subjective increase in visual function during this period showed a
median private flexibility score of 1.86; patients with the subjective impression
of visual function decrease, a median score of 2.71; the median scores for
mobility were 2.00 versus 3.00, for flexibility in reading 1.91 versus 3.64, for 
psychological stress 1.56 versus 2.25, and for communicational flexibility 1.72
versus 2.25. The difference in reading flexibility was statistically significant 
(p=0.001) after correction for clinical cofactors. CONCLUSIONS: The established
clinical benefit of PDT treatment concerning its efficacy in ARMD progression
prevention coincides with an at least slight subjective benefit in quality of
life and patient satisfaction. However, the latter is associated with the
patients' subjective impression of visual acuity progression rather than with
clinically validated outcome after PDT treatment.

PMID: 15751243 [PubMed - indexed for MEDLINE]

2029: Proc Natl Acad Sci U S A. 2005 Mar 15;102(11):4164-9. Epub 2005 Mar 4.

Lipofuscin accumulation, abnormal electrophysiology, and photoreceptor
degeneration in mutant ELOVL4 transgenic mice: a model for macular degeneration.

Karan G, Lillo C, Yang Z, Cameron DJ, Locke KG, Zhao Y, Thirumalaichary S, Li C, 
Birch DG, Vollmer-Snarr HR, Williams DS, Zhang K.

Department of Ophthalmology and Visual Science, University of Utah, Salt Lake
City, UT 84132, USA.

Macular degeneration is a heterogeneous group of disorders characterized by
photoreceptor degeneration and atrophy of the retinal pigment epithelium (RPE) in
the central retina. An autosomal dominant form of Stargardt macular degeneration 
(STGD) is caused by mutations in ELOVL4, which is predicted to encode an enzyme
involved in the elongation of long-chain fatty acids. We generated transgenic
mice expressing a mutant form of human ELOVL4 that causes STGD. In these mice, we
show that accumulation by the RPE of undigested phagosomes and lipofuscin,
including the fluorophore,
2-[2,6-dimethyl-8-(2,6,6-trimethyl-1-cyclohexen-1-yl)-1E,3E,5E,7E-octatetraenyl]-
1-(2-hyydroxyethyl)-4-[4-methyl-6-(2,6,6,-trimethyl-1-cyclohexen-1-yl)-1E,3E,5E-h
exatrienyl]-pyridinium (A2E) is followed by RPE atrophy. Subsequently,
photoreceptor degeneration occurs in the central retina in a pattern closely
resembling that of human STGD and age-related macular degeneration. The ELOVL4
transgenic mice thus provide a good model for both STGD and dry age-related
macular degeneration, and represent a valuable tool for studies on therapeutic
intervention in these forms of blindness.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15749821 [PubMed - indexed for MEDLINE]

2030: Surv Ophthalmol. 2005 Mar-Apr;50(2):194-206.

HMG CoA reductase inhibitors (statins): do they have a role in age-related
macular degeneration?

Guymer RH, Chiu AW, Lim L, Baird PN.

Centre for Eye Research Australia, Department of Ophthalmology, University of
Melbourne, East Melbourne, Australia.

Age-related macular degeneration is a progressive late onset disease affecting
central vision. It is the leading cause of irreversible blindness in developed
countries, and with the aging population the problem is increasing. Current
treatment options are limited to the late stage of the disease when central
vision is already under great threat, and even new treatments make little impact 
on the rate of blindness. Intervention earlier in the disease may prove more
rewarding, but to date little progress has been made with this approach.
Epidemiologic, genetic, and pathological evidence continues to accumulate,
suggesting a possible link between risk factors for cardiovascular diseases and
age-related macular degeneration. This article reviews the evidence and discusses
the rationale behind the recent suggestions that cholesterol-lowering agents may 
be useful in the treatment of early age-related macular degeneration. The
cholesterol-lowering family of drugs called statins are
3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) inhibitors with pleiotropic
actions. Their therapeutic effects in cardiovascular disease and dyslipidaemia
have been well proven. In this review we will outline the known actions of
statins and discuss possible ways that they may impact on age-related macular
degeneration.

Publication Types: 
    Review

PMID: 15749309 [PubMed - indexed for MEDLINE]

2031: Trans Am Ophthalmol Soc. 2004;102:83-93; discussion 93-5.

A model of spectral filtering to reduce photochemical damage in age-related
macular degeneration.

Meyers SM, Ostrovsky MA, Bonner RF.

Retina Consultants, Des Plaines, Illinois, USA.

BACKGROUND/PURPOSE: Cumulative sunlight exposure and cataract surgery are
reported risk factors for advanced age-related macular degeneration (AMD).
Laboratory studies suggest that accumulation and photochemical reactions of A2E
(N-retinylidene-N-retinylethanolamine) and its epoxides, components of
lipofuscin, are important in AMD. To relate this data to the clinical setting, we
modeled the effects of macular irradiance and spectral filtering on production of
A2E and reactive oxygen intermediates (ROIs) in pseudophakic eyes with a clear or
"yellow" intraocular lens (IOL) and in phakic eyes. METHODS: We calculated
relative changes of macular irradiance as a function of light (390 to 700 nm)
intensity, pupil size, age, and lens status, and modeled resulting
all-trans-retinal concentration and rates of production of A2E-related
photochemicals and photon-induced ROIs in rods and retinal pigment epithelium
(RPE). We compared these photoproducts following cataract surgery and IOL
implantation with and without spectral sunglasses to normal age-related nuclear
sclerotic lens changes. RESULTS: Following cataract and IOL surgery,
all-trans-retinal and lipofuscin photochemistry would theoretically increase
average generation of 1) A2E-related photochemicals, 2) ROI in rods and 3) ROI in
RPE, respectively, 2.6-, 15- and 6.6-fold with a clear IOL, and 2.1-, 4.1- and
2.6 fold with a yellow IOL, but decrease approximately 30-, approximately 20- and
4-fold with a vermillion filter sunglass and clear IOL compared to an average 70 
year old phakic eye. CONCLUSION: Sunglasses that strongly decrease both deep blue
light and rod photobleaching, while preserving photopic sensitivity and color
perception, would provide upstream protection from potential photochemical damage
in subjects at risk for AMD progression after cataract surgery.

PMID: 15747748 [PubMed - indexed for MEDLINE]

2032: Eye. 2006 Feb;20(2):199-202.

Drusen classification in bilateral drusen and fellow eye of exudative age-related
macular degeneration.

Hamada S, Jain S, Sivagnanavel V, Patel N, Chong NV.

Retinal Research Unit, King's College Hospital, University of London, UK.

AIM: To assess the value of the modified international classification system in
screening high-risk patients with bilateral age-related maculopathy (ARM) from
those with lower risk characteristics. METHODS: In total, 164 digital images of
106 patients with either bilateral ARM (group A) or the fellow eyes of unilateral
exudative age-related macular degeneration (AMD) (Group B) were included.
Patients with no signs of ARM in both eyes or those with bilateral late AMD were 
excluded. The images were randomised and then graded by two masked
ophthalmologists based on the modified International Classification of ARM.
RESULTS: The interobserver consistency between the two graders was high with a
Kappa value of 0.82 (SE 0.34, P<0.0001). There were no significant differences in
the distribution of the stages of ARM between the two subgroups. Stage 3 was the 
most common stage in each group for both graders followed by stage 2a in the
bilateral drusen group. Stages 1a, 2a and 2b were equally the next common stage
in the fellow eye of chordial neovascularisation group. CONCLUSION: A screening
system based on clinical characteristics would be of value in risk prediction in 
a clinical setting. Type of Drusen alone, as identified by the modified
International grading system, may not be reliably predictive in screening for
patients who are at high risk of developing choroidal neovascularisation.

PMID: 15746948 [PubMed - indexed for MEDLINE]

2033: Ophthalmology. 2005 Mar;112(3):488-94.

The use of cholesterol-lowering medications and age-related macular degeneration.

McGwin G Jr, Xie A, Owsley C.

Department of Epidemiology and International Health, School of Public Health,
University of Alabama at Birmingham, Birmingham, Alabama 35294-0009, USA.
mcgwin@uab.edu

PURPOSE: To evaluate the association between cholesterol-lowering medications and
age-related macular degeneration (AMD). DESIGN: Case-control study. PARTICIPANTS:
The Atherosclerosis Risk in Communities study is a prospective, population-based,
cohort study conducted in 4 communities across the United States. A total of
15792 individuals aged 45 to 65 years were enrolled between 1987 and 1989; fundus
photographs were added to the study protocol at the 6-year follow-up (1993-1995).
Cases were subjects who were identified as having AMD after applying a standard
definition to their fundus photographs; controls did not have AMD. METHODS: The
use of cholesterol-lowering medications at any time during the study was
determined and compared between cases and controls, adjusting for the potentially
confounding effect of demographic, behavioral, and medical characteristics. MAIN 
OUTCOME MEASURES: Presence of AMD and the use of cholesterol-lowering
medications. RESULTS: A total of 871 AMD cases and 11,717 controls were
identified. Of the AMD cases, 11% made use of cholesterol-lowering medications,
as compared with 12.3% of controls (odds ratio [OR], 0.89; 95% confidence
interval [CI], 0.71-1.11). Adjusting for the confounding influence of age,
gender, and race revealed a statistically significant relationship between AMD
and use of cholesterol-lowering medications (OR, 0.79; 95% CI, 0.63-0.99).
CONCLUSIONS: The results of this study add to the growing body of evidence that
cholesterol-lowering medications may reduce the risk of developing AMD.
Additional research is needed to document the mechanism responsible for this
association. A clinical trial of the impact of statins on AMD deserves
consideration.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15745779 [PubMed - indexed for MEDLINE]

2034: Ophthalmology. 2005 Mar;112(3):482-7.

Heterogeneity of the genetic risk in age-related macular disease: a
population-based familial risk study.

Assink JJ, Klaver CC, Houwing-Duistermaat JJ, Wolfs RC, van Duijn CM, Hofman A,
de Jong PT.

Department of Ophthalmogenetics, The Netherlands Ophthalmic Research Institute,
Amsterdam, The Netherlands.

OBJECTIVE: To assess the extent of heterogeneity of the genetic risk of
age-related macular disease (AMD) among families. DESIGN: Case-controlled
population-based familial aggregation study. PARTICIPANTS: Participants comprised
190 first-degree relatives of 65 case probands and 347 relatives of 100 control
probands. All probands had been identified from the baseline phase of the
Rotterdam Study in The Netherlands. METHODS: A family score was computed for each
family based on the presence and type of macular disease, the expected risk of
disease, and the number, extent of kinship, and age of all family members. MAIN
OUTCOME MEASURES: Presence and stage of AMD as diagnosed on fundus photographs,
family score, and logistic regression coefficient. RESULTS: The family score of
case families showed a peak of approximately 0 with a skewed tail (14% of
families) of higher than expected risks of disease toward a maximum of 2.9. The
family score of control families centered on 0, apart from 1 outlier. The risk of
AMD increased significantly with higher family scores (beta = 1.34; P<0.001).
CONCLUSIONS: The heterogeneity of genetic risk among AMD families is
considerable, and the proportion of high-risk families is relatively small. The
family score method is relevant for genetic counseling as well as for
implementation in studies of genetic dissection of AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15745778 [PubMed - indexed for MEDLINE]

2035: Int J Circumpolar Health. 2004;63 Suppl 2:320-3.

Age-related macular degeneration among the Inuit in Greenland.

Andersen N.

Department of Ophthalmology, Rigshospitalet, The University Hospital of
Copenhagen, Denmark. nis_andersen@yahoo.dk

OBJECTIVES: To investigate the clinical appearance and prevalence of Age-related 
Macular Degeneration (AMD) among the Inuit in Greenland, to investigate risk
factors and to initiate the search for possible genetic markers. STUDY DESIGN: A 
cross-sectional population study including all individuals older than 60 years of
age, born in Greenland and living in the communities of Nuuk and Sisimiut, was
performed in 2000 and 2001. METHODS: All participants underwent an ophthalmologic
examination, which was complemented by fundus photography and a questionnaire.
RESULTS: 689 individuals, or more than 70%, participated in the study. Data are
currently being processed. The preliminary data suggest that AMD among the Inuit 
is characterised by a rather uniform morphology and poor visual outcome. The
detection of more cases of AMD in the early and late stages in relation to
intermediate stages furthermore indicates a rapid development of AMD among the
Inuit. CONCLUSION: The relative homogeneity of the Inuit population of Greenland 
may represent an opportunity for identifying the aetiological factors responsible
for the development of AMD. The future results of this research project will
hopefully also contribute towards an increased focus on the growing number of
individuals with visual impairment due to AMD among the Inuit.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15736677 [PubMed - indexed for MEDLINE]

2036: Am J Ophthalmol. 2005 Feb;139(2):351-3.

Optical coherence tomography in Best's disease: an observational case report.

Vedantham V, Ramasamy K.

Retina-Vitreous Service, Aravind Eye Hospital and Postgraduate Institute of
Ophthalmology, Madurai 625 020, Tamilnadu, India. drvasumathy@yahoo.com

PURPOSE: To report the optical coherence tomographic (OCT) findings in a case of 
Best's disease. DESIGN: Observational case report. METHODS: Optical coherence
tomography was carried out to understand the pathogenesis of Best's disease in a 
13-year-old girl. RESULTS: Optical coherence tomography demonstrated that the
lipofuscin accumulated in a cystic space underneath the retinal pigment
epithelium in the "pseudohypopyon stage" of Best's disease. It also demonstrated 
the disruption of the photoreceptors in the "scrambled egg" stage. CONCLUSIONS:
These new OCT findings could explain the retention of good visual acuity in the
"pseudohypopyon stage" and the loss of visual acuity in the "scrambled egg" stage
of Best's disease.

Publication Types: 
    Case Reports

PMID: 15734003 [PubMed - indexed for MEDLINE]

2037: Am J Ophthalmol. 2005 Feb;139(2):290-4.

Comment in:
    Am J Ophthalmol. 2005 Nov;140(5):958; author reply 958-9.

Posterior subtenon triamcinolone acetonide for refractory diabetic macular edema.

Bakri SJ, Kaiser PK.

Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, Ohio 4195, USA.

PURPOSE: To evaluate posterior subtenon injection of triamcinolone acetonide for 
refractory diabetic macular edema (DME). DESIGN: Retrospective, interventional,
case series. METHODS: SETTING: Clinical practice. PATIENT POPULATION: Patients
with persistent clinically significant DME involving the center of the fovea 3 or
more months after one or more treatments of focal macular photocoagulation were
included. Exclusion criteria were a history of corticosteroid-responsive
intraocular pressure (IOP) rise, intraocular surgery within 3 months, and any
laser treatment within 1 month. PROCEDURE: All patients received an ophthalmic
history and examination including best-corrected Snellen visual acuity, IOP
measurement, anterior segment examination including evaluation of lens status
with LOCS II criteria, dilated fundus examination, and a posterior subtenon
injection of 40 mg triamcinolone acetonide at baseline. Patients were reevaluated
at 1, 3, 6, and 12 months after injection. RESULTS: Seventy-three injections were
performed in 63 eyes of 50 patients. The mean baseline visual acuity was 20/80.
Mean visual acuity significantly improved to 20/50 at 1 month, then stabilized to
20/65 at 3 months, 20/68 at 6 months, and 20/63 at 12 months. Complications were 
rare, with a transient significant rise in intraocular pressure at the 3-month
evaluation and ptosis in two patients. CONCLUSIONS: Visual acuities remained
stable or improved over a 12-month period after posterior subtenon triamcinolone 
injections for refractory DME. There was a statistically significant improvement 
in visual acuity at 1 month.

PMID: 15733990 [PubMed - indexed for MEDLINE]

2038: Am J Ophthalmol. 2005 Feb;139(2):271-9.

Vision-related quality of life in patients suffering from age-related macular
degeneration.

Berdeaux GH, Nordmann JP, Colin E, Arnould B.

Alcon Research Ltd, 92563 Rueil-Malmaison, France. Gilles.Berdeaux@AlconLabs.com

PURPOSE: To evaluate the relative impact of best and worst eye on vision-related 
quality of life in patients suffering from age-related macular degeneration
(AMD). DESIGN: Quality of life and visual acuity data were collected at baseline 
during a randomized clinical trial. METHODS: SETTING: Multicenter (11 centers),
international study. PATIENTS: One hundred fourteen patients with a diagnosis of 
exudative AMD and primary or recurrent subfoveal neovascular membrane (greatest
linear dimension of lesion < or =5400 microm; > or =50% of the total lesion was
choroidal neovascularization (CNV); classic component of the total CNV > or = 1.0
mm(2)). All patients were over age 50 years, of any race, either sex.
INTERVENTION OR OBSERVATION PROCEDURE: NEI-VFQ-39 questionnaire administered to
patients at home by trained telephone interviewers. MAIN OUTCOME MEASURES: ETDRS 
visual acuity (VA) was measured in both eyes separately. Vision-related quality
of life (QoL) was assessed using the NEI-VFQ-39. An analysis of variance was
performed on the NEI-VFQ scores, including best eye VA (VA > 20/40 vs VA < or =
20/40), worst eye VA (VA > 20/200 vs VA < or = 20/200), and the interaction
between the two as independent variables. RESULTS: Best eye VA was 0.34 on
average, with VA > 20/40 in 43.0% of patients. Worst eye VA was 0.85 on average, 
with VA > 20/200 in 32.5% of patients. VA was not linked to general health and
ocular pain scores. General Vision, Near Activities, Distance Vision, Driving,
Mental Health, Role Difficulties, Dependency, Peripheral Vision, and the Global
NEI-VFQ scores were affected by both best eye VA and worst eye VA. CONCLUSION: In
the study sample, worst eye VA (< or =20/200) and best eye VA (< or =20/40)
contributed independently to vision-related QoL. These results suggest that
preserving a minimal visual acuity in the worst eye may contribute to
vision-related quality of life.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 15733988 [PubMed - indexed for MEDLINE]

2039: Nutr Rev. 2005 Jan;63(1):9-15.

Obesity, lutein metabolism, and age-related macular degeneration: a web of
connections.

Johnson EJ.

Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging,
Tufts University, 711 Washington St., Boston, MA 02111, USA.
elizabeth.johnson@tufts.edu

Age-related macular degeneration (AMD) is a major cause of visual impairment in
the United States. Currently there is no effective cure for this disease. Risk
factors include decreased lutein and zeaxanthin status and obesity. Obesity is
also an increasing public health concern. The alarming increase in the prevalence
of obesity further exacerbates the public health concern of AMD. The mechanism by
which obesity increases the risk of AMD may be related to the physiologic changes
that occur with this condition. These include increased oxidative stress, changes
in the lipoprotein profile, and increased inflammation. These changes would also 
result in an increased destruction and a decreased circulatory delivery of lutein
and zeaxanthin to the macula of the eye. Therefore, the mechanism by which
obesity is related to AMD risk may be through indirect effects on changes in
lutein and zeaxanthin status and metabolism.

Publication Types: 
    Review

PMID: 15730230 [PubMed - indexed for MEDLINE]

2040: Invest Ophthalmol Vis Sci. 2005 Mar;46(3):1033-8.

Reduced foveolar choroidal blood flow in eyes with increasing AMD severity.

Grunwald JE, Metelitsina TI, Dupont JC, Ying GS, Maguire MG.

Department of Ophthalmology, Scheie Eye Institute, School of Medicine, University
of Pennsylvania, 51 North 39th Street, Philadelphia, PA 19104, USA.
juangrun@mail.med.upenn.edu

PURPOSE: In an earlier study, the authors reported that foveolar choroidal blood 
flow (ChBFlow) decreases in patients with AMD and drusen. To explore further the 
choroidal circulatory changes in patients with AMD, the relationship between
ChBFlow and fundus features associated with increased risk of choroidal
neovascularization (CNV) were investigated. METHODS: The study included 26
control eyes of 17 normal subjects and 163 eyes with early AMD characteristics of
123 patients with AMD. The AMD study eyes were divided into three groups
according to increasing risk for development of CNV: (1) drusen > or =63 microm, 
no RPE hyperpigmentary changes in the study eye, and no CNV in the fellow eye;
(2) drusen > or =63 microm, RPE hyperpigmentary changes in the study eye, and no 
CNV in the fellow eye; and (3) eyes with CNV in the fellow eye. Laser Doppler
flowmetry was used to assess relative foveolar choroidal blood velocity (ChBVel),
volume (ChBVol), and flow (ChBFlow). Differences in the mean circulatory
parameters were assessed by analysis of variance (ANOVA) and test of linear
trend. RESULTS: Mean ChBVel, ChBVol, and ChBFlow decreased with increased risk
for CNV (linear trend, P < 0.05). The lowest circulatory parameters were observed
in the eyes with the highest risk for CNV development. Trends for ChBVel and
ChBFlow were still significant after adjustment for multiple factors.
CONCLUSIONS: There is a systematic decrease in choroidal circulatory parameters
with an increase in the severity of AMD features associated with risk for the
development of CNV, suggesting a role for ischemia in the development of CNV.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15728562 [PubMed - indexed for MEDLINE]

2041: Invest Ophthalmol Vis Sci. 2005 Mar;46(3):769-75.

Declines in arrestin and rhodopsin in the macula with progression of age-related 
macular degeneration.

Ethen CM, Feng X, Olsen TW, Ferrington DA.

Department of Biochemistry, University of Minnesota, Minneapolis, MN 55455, USA.

PURPOSE: Biochemical analysis of age-related macular degeneration (AMD) at
distinct stages of the disease will help further understanding of the molecular
events associated with disease progression. This study was conducted to determine
the ability of a new grading system for eye bank eyes, the Minnesota Grading
System (MGS), to discern distinct stages of AMD so that retinal region-specific
changes in rod photoreceptor protein expression from donors could be determined. 
METHODS: Donor eyes were assigned to a specific level of AMD by using the MGS.
Expression of the rod photoreceptor proteins rhodopsin and arrestin was evaluated
by Western immunoblot analysis in the macular and peripheral regions of the
neurosensory retina from donors at different stages of AMD. RESULTS: A
significant linear decline in both arrestin and rhodopsin content correlated with
progressive MGS levels in the macula. In contrast, the peripheral region showed
no significant correlation between MGS level and the content of either protein.
CONCLUSIONS: The statistically significant relationship between decreasing
macular rod photoreceptor proteins and progressive MGS levels of AMD demonstrates
the utility of the clinically based MGS to correspond with specific protein
changes found at known, progressive stages of degeneration. Future biochemical
analysis of clinically characterized donor eyes will further understanding of the
pathobiochemistry of AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15728529 [PubMed - indexed for MEDLINE]

2042: Cornea. 2005 Mar;24(2):221-3.

Macular edema and iridocorneal endothelial syndrome: a case report.

Kocaoğlan H, Unlü N, Kanpolat A, Yalvaç IS, Acar MA, Duman S.

Department of Ophthalmology, Ankara Training and Research Hospital, Ankara,
Turkey. unlunurten@yahoo.com

PURPOSE: To report a case of cystoid macular edema (CME) in iridocorneal
endothelial syndrome. METHODS: Case report. RESULTS: The authors describe the
clinical history and ocular examination of a 38-year-old woman with iridocorneal 
endothelial syndrome and CME. This association has never been reported before.
The mechanism of CME is unknown. CONCLUSION: CME may cause visual deterioration
in iridocorneal endothelial syndrome. We emphasize the importance of posterior
segment examination in these cases.

Publication Types: 
    Case Reports

PMID: 15725892 [PubMed - indexed for MEDLINE]

2043: Eye. 2006 Jan;20(1):13-7.

Comment in:
    Eye. 2006 Jan;20(1):1-2.    Eye. 2007 Feb;21(2):254-5.    Eye. 2007 Feb;21(2):255-6.

Intravitreal triamcinolone acetonide for treatment of persistent macular oedema
in branch retinal vein occlusion.

Ozkiris A, Evereklioglu C, Erkilic K, Dogan H.

Ophthalmology, Erciyes University Medical Faculty, Kayseri, Turkey.
aozkiris@erciyes.edu.tr

BACKGROUND: To evaluate the efficacy of intravitreal triamcinolone acetonide
injection on persistent macular oedema in branch retinal vein occlusion that
fails to respond to previous laser photocoagulation. MATERIAL AND METHODS: A
total of 19 eyes of 19 patients with persistent macular oedema due to branch
retinal vein occlusion were treated with 8 mg/0.2 ml of intravitreal
triamcinolone acetonide injection. The main outcome measures included
best-corrected visual acuity, intraocular pressure, and macular oedema map values
of Heidelberg Retinal Tomograph II (HRT II) before and after intravitreal
triamcinolone injection. RESULTS: The mean follow-up time was 6.2+/-1.0 months.
The mean baseline best-corrected logarithm of minimal angle of resolution
(LogMAR) value for visual acuities of the patients before intravitreal
triamcinolone injection was 1.01+/-0.16. After treatment, it was 0.55+/-0.22 at
the 1-month, 0.56+/-0.22 at 3-month, and 0.62+/-0.22 at the last visits and the
differences were statistically significant when compared with baseline values
(for each, P<0.001). The mean oedema map values on HRT II significantly decreased
by 28.5% at 1-month, 23.8% at 3-month, and 23.8% at the last visit when compared 
with preinjection values (for each, P<0.001). Intraocular pressure elevation
exceeding 21 mmHg was observed in 26.3% of eyes at 1-month, 15.7% at 3-month, and
5.2% at the last visit, but was controlled with topical anti-glaucomatous
medications in all eyes. CONCLUSION: Intravitreal triamcinolone acetonide
application is a promising approach in the treatment of persistent macular oedema
due to branch retinal vein occlusion non-respondent to laser photocoagulation.

Publication Types: 
    Clinical Trial

PMID: 15723039 [PubMed - indexed for MEDLINE]

2044: Eye. 2006 Feb;20(2):163-5.

Resolution of severe macular oedema in adult Coat's syndrome with high-dose
intravitreal triamcinolone acetonide.

Jarin RR, Teoh SC, Lim TH.

The Eye Institute, Tan Tock Seng Hospital, Singapore, Republic of Singapore.

OBJECTIVE: To report the clinical outcome of a patient who received high-dose
intravitreal triamcinolone acetonide as treatment for severe macular oedema
secondary to adult Coat's syndrome. METHOD: Case report. RESULTS: A 74-year-old
Indian man complaining of chronic gradual blurring of vision in the left eye was 
found to have adult Coat's syndrome with severe macular oedema. He received 25 mg
of intravitreal triamcinolone acetonide following unsuccessful resolution with
grid laser. Optical coherence tomography (OCT) demonstrated up to 75% decrease in
macular oedema that was evident even after 9 months follow-up. However, there was
no significant improvement in visual acuity. CONCLUSION: Intravitreal
triamcinolone is a reasonable option in reducing severe macular oedema in cases
of adult Coat's syndrome.

Publication Types: 
    Case Reports

PMID: 15723038 [PubMed - indexed for MEDLINE]

2045: Br J Ophthalmol. 2005 Mar;89(3):321-6.

Diffuse diabetic macular oedema treated by intravitreal triamcinolone acetonide: 
a comparative, non-randomised study.

Jonas JB, Akkoyun I, Kreissig I, Degenring RF.

Department of Ophthalmology, Faculty of Clinical Medicine Mannheim of the
University of Heidelberg, Heidelberg, Germany.
Jost.Jonas@ma.augen.uni-heidelberg.de

AIM: To report on visual outcome of patients receiving an intravitreal injection 
of triamcinolone acetonide for treatment of diffuse diabetic macular oedema.
METHODS: Prospective, comparative, non-randomised clinical interventional study
included 136 patients with diffuse diabetic macular oedema. Patients of the study
group (97 eyes) received an intravitreal injection of 20-25 mg of triamcinolone
acetonide and no other retinal treatment. Patients of the control group (69 eyes)
received focal or panretinal laser treatment if indicated. Mean (standard
deviation) follow up was 8.4 (SD 6.0) months (range 1.03-25.2 months). RESULTS:
Visual acuity (VA) increased significantly (p<0.001) in the study group with 66
(68%) eyes gaining in VA by at least two Snellen lines. In the control group, VA 
did not change significantly during the first 4 months of follow up, and
decreased significantly (p<0.001) towards the end of the follow up. Difference in
change of best VA was significant (p<0.001) between both groups. Correspondingly,
the number of patients with VA improvement of two or more Snellen lines and
visual loss of two or more Snellen lines, respectively, was significantly
(p<0.001) higher and lower, respectively, in the study group. CONCLUSIONS:
Intravitreal triamcinolone acetonide can temporarily increase VA in some patients
with diffuse diabetic macular oedema.

Publication Types: 
    Clinical Trial
    Comparative Study
    Controlled Clinical Trial

PMID: 15722313 [PubMed - indexed for MEDLINE]

2046: Br J Ophthalmol. 2005 Mar;89(3):316-20.

Comment in:
    Br J Ophthalmol. 2005 Jul;89(7):928-9.    Br J Ophthalmol. 2005 Jul;89(7):929; author reply 929.

Optical coherence tomography in photodynamic therapy for subfoveal choroidal
neovascularisation secondary to age related macular degeneration: a cross
sectional study.

Sahni J, Stanga P, Wong D, Harding S.

St Paul's Eye Unit, Royal Liverpool University Hospital, Liverpool L7 8XP, UK.
jayashree2001@hotmail.com

AIMS: To introduce new terminology and validate its reliability for the analysis 
of optical coherence tomography (OCT) scans, compare clinical detection of
cystoid macular oedema (CMO) and subretinal fluid (SRF) with OCT findings, and to
study the effect of photodynamic therapy (PDT) on the foveal morphology. METHODS:
Patients with subfoveal, predominantly classic choroidal neovascularisation (CNV)
secondary to age related macular degeneration (AMD) undergoing PDT were evaluated
with refraction protocol best corrected logMAR visual acuity (VA), slit lamp
biomicroscopy, stereoscopic fluorescein angiography (FFA), and OCT. New
terminologies introduced to interpret the OCT scans were: neuroretinal foveal
thickness (NFT), bilaminar foveal thickness (BFT), outer high reflectivity band
thickness (OHRBT), intraretinal fluid (IRF), subretinal fluid (oSRF), and
vitreomacular hyaloid attachment (VMHA). RESULTS: Fifty six eyes of 53 patients
were studied. VA was better in eyes with a thinner outer high reflectivity band
(OHRBT) (p = 0.02) and BFT (p = 0.05). BFT was less in eyes that had undergone a 
greater number of PDT treatments (p = 0.04). There was poor agreement between OCT
and clinical examination in the detection of CMO and subretinal fluid (kappa =
0.289 and kappa = 0.165 respectively). To validate the interpretation and
measurements on OCT, two groups of 20 scans were analysed by two independent
observers. There was good agreement between the observers in the detection of
IRF, oSRF, and VMHA (p<0.001). Measurements of NFT and BFT had a high
reproducibility, and of OHRBT reproducibility was low. CONCLUSIONS: New
terminology has been introduced and tested. OCT appears to be superior to
clinical examination and FFA in the detection of CMO. In this study, better
vision was associated with a thinner OHRBT and/or the absence of SRF giving
insight into the biological effect of PDT.

Publication Types: 
    Validation Studies

PMID: 15722312 [PubMed - indexed for MEDLINE]

2047: Br J Ophthalmol. 2005 Mar;89(3):312-5.

Impact of lesion size on photodynamic therapy with verteporfin of predominantly
classic lesions in age related macular degeneration.

Arias L, Pujol O, Berniell J, Rubio M, Roca G, Castillo L, Acebes E.

Department of Ophthalmology, Bellvitge University Hospital, L'Hospitalet de
Llobregat, Barcelona, Spain. luisarias@telefonica.net

AIM: To determine if photodynamic therapy (PDT) outcomes are related to lesion
size in patients with subfoveal predominantly classic choroidal
neovascularisation (CNV) secondary to age related macular degeneration (AMD).
METHODS: According to greatest linear dimension (GLD) of the entire lesion
determined with fluorescein angiography (FA) patients were divided into two
groups. In the first group GLD was <3000 microm and in the second one GLD was
3000-5000 microm. All eyes were treated with standard PDT with the verteporfin
protocol. The primary outcome was the proportion of eyes in both groups that did 
not show significant leakage in FA at the end of follow up. Secondary outcomes
were changes in GLD and in best corrected visual acuity (BCVA). RESULTS: 64
patients (mean (SD) age, 76.7 (7.7) years; range 58-95 years) were recruited to
participate in the study. All participants in the study completed the follow up
time (mean 16.6 months). 24 patients (75%) in the group of smaller lesions (n =
32) compared with 15 patients (46.8%) in the group of larger lesions (n = 32) did
not show significant leakage in FA at the end of follow up (p = 0.02). A GLD
increase >1000 microm was recorded in nine eyes (28.1%) in the group of smaller
lesions and in 16 eyes (50%) in the group of larger lesions (p = 0.07). 22 eyes
(68.7%) in the group of smaller lesions compared with 19 eyes (59.3%) in the
group of larger lesions lost less than three lines of vision (p = 0.06). Relevant
side effects related to verteporfin therapy were not recorded, except for four
patients (6.2%) with infusion related back pain. CONCLUSIONS: These results
suggest that lesion size at baseline may be a prognosis factor in PDT in patients
with subfoveal predominantly classic CNV secondary to AMD. There are no relevant 
side effects or safety concerns derived from verteporfin therapy.

PMID: 15722311 [PubMed - indexed for MEDLINE]

2048: Acta Ophthalmol Scand. 2005 Feb;83(1):71-5.

Intravitreal triamcinolone acetonide in patients with macular oedema due to
central retinal vein occlusion.

Krepler K, Ergun E, Sacu S, Richter-Müksch S, Wagner J, Stur M, Wedrich A.

Department of Ophthalmology, Medical University of Vienna, Waehringer Guertel
18-20, A-1090 Vienna, Austria. katharina.krepler@meduniwien.ac.at

PURPOSE: To evaluate treatment of macular oedema due to central retinal vein
occlusion (CRVO) with intravitreal triamcinolone acetonide. METHODS: In a
prospective case series, 13 patients with macular oedema due to non-ischaemic
CRVO received an intravitreal injection of 4 mg triamcinolone acetonide.
Examination included assessment of best corrected visual acuity (BCVA) for
distance and reading, measurement of intraocular pressure (IOP), fluorescein
angiography and high resolution imaging by optical coherence tomography,
preoperatively and 1 week, 1 month, 3, 6 and 9 months postoperatively. RESULTS:
Preoperative mean BCVA was 0.9 +/- 0.4 for distance vision and 1.0 +/- 0.3 for
reading acuity, respectively. A significant improvement in distance VA (0.5 +/-
0.3, p < 0.001) and reading acuity (0.7 +/- 0.3, p = 0.03) was observed until 3
months and 6 months, respectively. Mean macular thickness was significantly
reduced until 9 months postoperatively. CONCLUSION: Intravitreal injection of
triamcinolone acetonide led to a significant improvement in mean VA in patients
with macular oedema due to CRVO. However, the significant effect was not
permanent and persisted for a maximum of 6 months.

PMID: 15715561 [PubMed - indexed for MEDLINE]

2049: Acta Ophthalmol Scand. 2005 Feb;83(1):67-70.

Intravitreal triamcinolone for macular oedema: efficacy in relation to aetiology.

Sørensen TL, Haamann P, Villumsen J, Larsen M.

Department of Ophthalmology, University of Copenhagen, Herlev Hospital, Herlev
Ringvej 75, 2730 Herlev, Denmark. torbenls@dadlnet.dk

PURPOSE: To evaluate the efficacy and safety of intravitreal triamcinolone in
patients with macular oedema of varying aetiology. METHODS: Two milligrams of
intravitreal triamcinolone acetonide was injected into 34 eyes with persistent
macular oedema (17 eyes with macula oedema secondary to posterior uveitis, 13
eyes with diabetic retinopathy, and four with pseudophakic macular oedema). Best 
corrected visual acuity was determined and transfoveal optical coherence
tomography performed after 1 week, 1 month, 3 months and 6 months. RESULTS:
Treatment improved visual acuity and subjective visual quality, and reduced
foveal thickness in eyes with posterior uveitis and eyes with macular oedema
secondary to diabetic retinopathy. Eyes treated for pseudophakic cystoid macular 
oedema demonstrated no improvement. A total of 32% of patients experienced a
significant post-injection increase in intraocular pressure. Endophthalmitis,
rhegmatogenous retinal detachment and cataract were absent. CONCLUSION:
Intravitreal triamcinolone appears to induce marked a improvement in macular
oedema secondary to non-infectious uveitis and diabetic retinopathy.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15715560 [PubMed - indexed for MEDLINE]

2050: Acta Ophthalmol Scand. 2005 Feb;83(1):63-6.

Serous macular detachment in diabetic cystoid macular oedema.

Ozdemir H, Karacorlu M, Karacorlu S.

Istanbul Retina Institute Inc., Hakki Yeten Cad. No: 8/7, Fulya, Istanbul,
Turkey. retina@pobox.com

PURPOSE: To define serous macular detachment in patients with diabetic cystoid
macular oedema (CME). METHODS: This study involved 78 eyes of 58 patients with
diabetic CME. The patients underwent complete ophthalmic examination, fluorescein
angiography and optical coherence tomography (OCT). Eyes with epiretinal membrane
or vitreo-macular traction were not included in the study. Optical coherence
tomography-3 was used in all patients and fundi were scanned on the horizontal,
vertical and four oblique planes through the centre of the fovea. RESULTS: In all
cases the increased thickness of the retina was related primarily to the
hyporeflective intraretinal cavities. With OCT, 24 of 78 eyes (31%) had serous
macular detachment as shown by retinal elevation over a non-reflective cavity
with minimal shadowing of the underlying tissues. Fluorescein angiography did not
show serous macular detachment in any patient. CONCLUSIONS: Our data showed that 
the incidence of serous macular detachment in diabetic CME was much higher than
previously reported. Optical coherence tomography-3 allows an in vivo
cross-sectional observation of very subtle serous macular detachment that is
difficult to diagnose at the slit-lamp or by fluorescein angiography in patients 
with diabetic CME.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15715559 [PubMed - indexed for MEDLINE]

2051: Hum Mutat. 2005 Mar;25(3):248-58.

Cone cGMP-gated channel mutations and clinical findings in patients with
achromatopsia, macular degeneration, and other hereditary cone diseases.

Nishiguchi KM, Sandberg MA, Gorji N, Berson EL, Dryja TP.

Ocular Molecular Genetics Institute and the Berman-Gund Laboratory for the Study 
of Retinal Degenerations, Harvard Medical School, Massachusetts Eye and Ear
Infirmary, Boston, Massachusetts 02114, USA.

Unrelated patients with achromatopsia, macular degeneration with onset under age 
50 years, cone degeneration or dysfunction, cone-rod degeneration, or macular
malfunction were screened for mutations in the three genes known to be associated
with achromatopsia: the GNAT2 gene encoding the alpha subunit of cone transducin 
and the CNGA3 and CNGB3 genes encoding the alpha and beta subunits of the cone
cGMP-gated cation channel. We found no examples of patients with GNAT2 mutations.
Out of 36 achromats, 12 (33%) had mutations in CNGA3 (13 different mutations
including five novel mutations) and 12 (33%) had mutations in CNGB3 (six
different mutations including four novel mutations). All achromats with CNG
mutations had residual, presumably cone function as determined by
computer-averaged 30-Hz electroretinograms (ERGs). There was considerable
variability in acuity and color vision, with most patients having acuities of
20/200-20/400 and complete absence of color perception, and others having
acuities of 20/25-20/40 and some color vision. Two pseudodominant achromatopsia
cases were uncovered, both with CNGA3 mutations, including one family in which
some compound heterozygotes with achromatopsia mutations were clinically
unaffected. We found two novel CNGB3 changes in three patients with juvenile
macular degeneration, a phenotype not previously associated with mutations in the
cone channel subunits. These patients had subnormal acuity (20/30-20/60), normal 
to subnormal color vision, and normal to subnormal full-field cone ERG
amplitudes. Our results indicate that some patients with channel protein
mutations retain residual foveal cone function. Based on our findings, CNGB3
should be considered as a candidate gene to be evaluated in patients with forms
of cone dysfunction, including macular degeneration. (c) 2005 Wiley-Liss, Inc.

Publication Types: 
    Comparative Study
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15712225 [PubMed - indexed for MEDLINE]

2052: Optom Vis Sci. 2005 Feb;82(2):114-27.

Short-term in-office practice improves reading performance with stand magnifiers 
for people with AMD.

Cheong AM, Lovie-Kitchin JE, Bowers AR, Brown B.

Centre for Health Research, School of Optometry, Queensland University of
Technology, Australia. cheon015@umn.edu

PURPOSE: People with low vision often use optical low vision aids to assist
reading. There have been numerous training programs recommended to train people
using magnifiers for reading. However, most of the programs are time consuming
and labor intensive. In this study, we investigated the effects of home-based
large print reading practice on reading performance when stand magnifiers (STM's)
are first prescribed. METHODS: Thirty-two subjects with age-related macular
degeneration (AMD) and with minimal experience in using magnifiers for reading
were recruited. They were divided into three groups: control, practice 1 (P1),
and practice 2 (P2). Before the prescription of STM's, all the subjects were
given the same amount of in-office practice with the STM (weeks 0 to 2). In
addition, in these 2 weeks, P1 and P2 subjects were given large print books to
read daily at home. P2 subjects were required to read the large print books
through a reduced field of view. The control group subjects received no
additional reading practice. Reading rates with and without STM's on passages of 
text were assessed for all the subjects regularly for 20 weeks. RESULTS: There
were no significant differences between the control, P1, and P2 groups in the
increase in reading rate with STM (p = 0.29). At week 0, reading rate for small
print with STM was significantly slower than reading rate on the equivalent-sized
large print (p = 0.004); however, as time went on, reading rate with STM's
increased significantly (p = 0.02). After 2 weeks of in-office magnifier practice
and repeated measures of reading rate with STM, reading rate with STM had
improved such that it was not significantly different from reading rate on large 
print (p = 0.11). CONCLUSION: Supervised, short-term, in-office practice with the
magnifier was effective in improving magnifier reading performance to achieve
maximum reading rate. Additional large print reading practice did not result in
any greater improvement in reading rate than in-office magnifier practice alone.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15711458 [PubMed - indexed for MEDLINE]

2053: Arch Ophthalmol. 2005 Feb;123(2):200-6.

Automated detection of macular drusen using geometric background leveling and
threshold selection.

Smith RT, Chan JK, Nagasaki T, Ahmad UF, Barbazetto I, Sparrow J, Figueroa M,
Merriam J.

Edward S. Harkness Eye Institute, New York Presbyterian Medical Center, New York,
NY 10032, USA. rts1@columbia.edu

BACKGROUND: Age-related macular degeneration (ARMD) is the most prevalent cause
of visual loss in patients older than 60 years in the United States. Observation 
of drusen is the hallmark finding in the clinical evaluation of ARMD. OBJECTIVES:
To segment and quantify drusen found in patients with ARMD using image analysis
and to compare the efficacy of image analysis segmentation with that of
stereoscopic manual grading of drusen. DESIGN: Retrospective study. SETTING:
University referral center.Patients Photographs were randomly selected from an
available database of patients with known ARMD in the ongoing Columbia University
Macular Genetics Study. All patients were white and older than 60 years.
INTERVENTIONS: Twenty images from 17 patients were selected as representative of 
common manifestations of drusen. Image preprocessing included automated color
balancing and, where necessary, manual segmentation of confounding lesions such
as geographic atrophy (3 images). The operator then chose among 3 automated
processing options suggested by predominant drusen type. Automated processing
consisted of elimination of background variability by a mathematical model and
subsequent histogram-based threshold selection. A retinal specialist using a
graphic tablet while viewing stereo pairs constructed digital drusen drawings for
each image. MAIN OUTCOME MEASURES: The sensitivity and specificity of drusen
segmentation using the automated method with respect to manual stereoscopic
drusen drawings were calculated on a rigorous pixel-by-pixel basis. RESULTS: The 
median sensitivity and specificity of automated segmentation were 70% and 81%,
respectively. After preprocessing and option choice, reproducibility of automated
drusen segmentation was necessarily 100%. CONCLUSIONS: Automated drusen
segmentation can be reliably performed on digital fundus photographs and result
in successful quantification of drusen in a more precise manner than is
traditionally possible with manual stereoscopic grading of drusen. With only
minor preprocessing requirements, this automated detection technique may
dramatically improve our ability to monitor drusen in ARMD.

PMID: 15710816 [PubMed - indexed for MEDLINE]

2054: Can J Ophthalmol. 2004 Dec;39(7):755-60.

Intravitreal triamcinolone injection for diabetic macular edema: a clinical and
fluorescein angiographic case series.

Bakri SJ, Beer PM.

Lions Eye Institute, Albany Medical College, Albany, NY 12208, USA.

BACKGROUND: A significant number of eyes with diabetic macular edema remain
refractory to treatment despite numerous attempts at photocoagulation.
Triamcinolone acetonide, a minimally water soluble steroid injected in suspension
form, has been reported to be a well-tolerated agent for intravitreal injection, 
prompting a decrease in diabetic macular edema on optical coherence tomography.
We report our experience with this treatment in 19 eyes with persistent diabetic 
macular edema. METHODS: We reviewed the charts of 16 patients (19 eyes) from a
clinical practice with diabetic macular edema persistent after focal or grid
laser photocoagulation. All eyes had received 4 mg of triamcinolone, injected
into the vitreous cavity 3.5 mm posterior to the limbus. Fluorescein angiography 
was performed before and about 2 weeks after the injection. Snellen visual acuity
and intraocular pressure (as determined with Goldmann applanation tonometry) were
also measured before and after the injection. RESULTS: Fluorescein angiography
showed marked improvement of macular edema in 4 eyes (21.0%), mild improvement in
10 eyes (52.6%) and no change in 5 eyes (26.3%); no patient had worsening of
macular edema. Visual acuity improved by at least 1 line in 13 eyes (68.4%), by 2
or more lines in 5 eyes (26.3%), by 3 or more lines in 2 eyes (10.5%) and by 4
lines in 1 eye (5.3%); visual acuity remained unchanged in 5 eyes (26.3%) and
deteriorated by 1 line in 1 eye (5.3%). Intraocular pressure elevation of 10 mm
Hg or greater occurred in two eyes (10.5%) and was successfully treated with
topical administration of 0.15% brimonidine.The triamcinolone was well tolerated,
and there were no other ocular complications. INTERPRETATION: Intravitreal
injection of triamcinolone has potential in the treatment of diabetic macular
edema and warrants investigation in a randomized prospective clinical trial.

PMID: 15696765 [PubMed - indexed for MEDLINE]

2055: Ophthalmology. 2005 Feb;112(2):305-12.

Age-related maculopathy: a risk indicator for poorer survival in women: the
Copenhagen City Eye Study.

Buch H, Vinding T, la Cour M, Jensen GB, Prause JU, Nielsen NV.

Department of Ophthalmology, National University Hospital, Rigshospitalet,
Copenhagen, Denmark. hbh@dadlnet.dk

PURPOSE: To examine patient survival in age-related maculopathy in a 14-year
follow-up study. DESIGN: Population-based 14-year cohort study. PARTICIPANTS:
Nine hundred forty-six residents, aged 60 to 80 years, living in the Osterbro
district of Copenhagen, Denmark, participated in the first examination conducted 
from 1986 to 1988. These participants were followed until death or until May 1,
2002, whichever came first. METHODS: Participants underwent an extensive
ophthalmologic examination at Rigshospitalet, the National University Hospital of
Copenhagen. Standardized protocols for physical examination, blood samples, and
data from the National Central Person Register, the National Death Register, and 
the National Patient Register were used. MAIN OUTCOME MEASURES: Mortality and
age-related maculopathy. RESULTS: By May 1, 2002, 60.9% (577 of 946) of the
participants of the baseline study cohort had died. The adjusted 14-year
cumulative mortality hazard ratio for subjects with early and late age-related
maculopathy at baseline was 1.26 (95% confidence interval [CI], 1.06-1.51). We
identified a strong correlation between mortality and age-related maculopathy
among women (relative risk, 1.59; 95% CI, 1.23-2.07) but not among men.
CONCLUSIONS: When adjusting for survival-related factors, age-related maculopathy
is a significant risk indicator for poorer survival in women and may be a marker 
of underlying serious systemic factors or aging processes specific to women.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15691568 [PubMed - indexed for MEDLINE]

2056: Retina. 2005 Feb-Mar;25(2):182-8.

Long-term effect of acetazolamide treatment of patients with uveitic chronic
cystoid macular edema is limited by persisting inflammation.

Schilling H, Heiligenhaus A, Laube T, Bornfeld N, Jurklies B.

University Eye Hospital Essen, Essen, Germany. harald.schilling@uni-essen.de

PURPOSE: To assess the long-term effect of acetazolamide treatment on patients
with cystoid macular edema (CME) in the course of intermediate or posterior
chronic uveitis and to define those patients who may particularly benefit from
the drug. METHODS: Fifty-two eyes (45 patients) with chronic uveitic CME were
treated with acetazolamide at an initial dosage of 500 mg/d. The effect of
treatment was assessed by fluorescein angiography, ophthalmoscopy, visual acuity,
and Amsler testing. Therapy was withdrawn when CME did not improve at 3 weeks. In
cases with CME improvement, the dosage was gradually tapered. RESULTS: The mean
follow-up was 3.1 years (minimum, 1.5 years). Two subgroups were identified:
group 1, quiescence of uveitis with acetazolamide as the single therapeutic agent
(33 eyes); and group 2, chronically active uveitis requiring additional systemic 
antiinflammatory drugs (19 eyes). In both groups, visual acuity improvement was
statistically significant (group 1, P = 0.012; group 2, P = 0.025). In 12
patients with a stable visual acuity gain, the medication dose could be tapered
off completely without any recurrent edema shown by fluorescein angiography after
a minimum follow-up of 1 year. Sixteen patients required a maintenance dosage,
ranging from 125 to 500 mg daily. No major adverse effects of the medication were
observed. CONCLUSIONS: During long-term follow-up, low-dose acetazolamide can be 
a useful therapeutic option for chronic CME in uveitis. The effect was better in 
patients with quiescence of uveitis than in those with chronically active
uveitis. Permanent therapy is not imperative in every case.

PMID: 15689809 [PubMed - indexed for MEDLINE]

2057: Retina. 2005 Feb-Mar;25(2):135-40.

Comment in:
    Retina. 2005 Jul-Aug;25(5):675; author reply 675-6.

Combined intravitreal injection of triamcinolone acetonide and panretinal
photocoagulation for concomitant diabetic macular edema and proliferative
diabetic retinopathy.

Zacks DN, Johnson MW.

The Retina Service, Kellogg Eye Center, University of Michigan Medical School,
Ann Arbor, Michigan 48105, USA. davzacks@umich.edu

PURPOSE: To present our results of intravitreal injection of triamcinolone
acetonide (IVTA) combined with panretinal photocoagulation (PRP) for patients
with concomitant clinically significant diabetic macular edema and proliferative 
diabetic retinopathy. METHODS: Charts of patients undergoing combined IVTA and
PRP were reviewed. Outcome measures included visual acuity, presence of macular
edema, and response of proliferative disease to laser photocoagulation. RESULTS: 
Four patients were included in this study. All patients maintained stable visual 
acuity during the treatment period. All patients had improvement in the amount of
macular edema, despite the application of PRP, as well as complete regression of 
their proliferative disease. There were no short-term complications associated
with IVTA or PRP. CONCLUSION: Combination treatment with IVTA and PRP may provide
benefit in patients with diffuse diabetic macular edema who require urgent PRP
for proliferative diabetic retinopathy by preventing exacerbation of macular
edema.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 15689801 [PubMed - indexed for MEDLINE]

2058: Retina. 2005 Feb-Mar;25(2):119-34.

Guidelines for using verteporfin (Visudyne) in photodynamic therapy for choroidal
neovascularization due to age-related macular degeneration and other causes:
update.

Verteporfin Roundtable Participants.

Guidelines originally were published in 2002 based on best available scientific
data as well as consensus of expert opinion in the absence of controlled clinical
trial data to assist ophthalmologists with selection of patients for whom
photodynamic therapy with verteporfin (Visudyne, Novartis AG, Basel,
Switzerland), termed "verteporfin therapy," should be considered, and to offer
suggestions regarding initial treatment, follow-up, and additional courses of
treatment at follow-up. Consensus was based on results of clinical trials and
expert opinion. Additional input and advice were received from representatives on
behalf of the American Society of Retina Specialists, the Macula Society, and the
Retina Society, as well as principal investigators of randomized clinical trials 
evaluating verteporfin therapy. Since 2002, additional information relevant to
clinical care was published in the peer-reviewed literature; therefore, revisions
to the originally published guidelines judged warranted are provided here.
Patient selection criteria include the following: (1) in cases due to age-related
macular degeneration (AMD), lesion composition of (a) predominantly classic
choroidal neovascularization (CNV), (b) occult with no classic CNV with presumed 
recent disease progression, or (c) relatively small minimally classic lesions;
(2) CNV location subfoveal or so close to the foveal center that conventional
laser photocoagulation treatment almost certainly would extend under the center; 
(3) etiology of CNV from AMD, pathologic myopia, or other causes in which the
outcome without treatment is likely to be worse than with treatment; and (4)
vision at a level where further loss would be recognized as detrimental to the
quality of life of the patient. Criteria include lesion size for AMD patients
with either a minimally classic lesion composition (where treatment usually
should be considered only for relatively smaller lesions) or occult with no
classic lesions (where treatment usually should be considered for relatively
smaller lesions or those >4 Macular Photocoagulation Study disc areas with a
relatively lower or poorer best-corrected visual acuity) but not patient age,
history of systemic arterial hypertension, or prior laser photocoagulation.
Therapy should be initiated ideally within 1 week of the initial fluorescein
angiogram on which the clinical decision to treat is based. Patients should
return for follow-up at least as often as every 3 months (+/-2 weeks) after any
initial or subsequent treatment to determine if there is fluorescein leakage from
CNV. Additional courses of treatment should be considered as often as every 3
months (+/-2 weeks) if fluorescein leakage from CNV is noted at that time.
Additional courses of treatment could be deferred if the biomicroscopic and
fluorescein angiographic appearances of the lesion are unchanged and show minimal
fluorescein leakage, especially when there is no subretinal fluid or fluorescein 
leakage from CNV underlying the center of the foveal avascular zone. Patients
should avoid exposure of skin or eyes to direct sunlight or bright indoor light
for 48 hours after treatment or until resolution of any swelling or discoloration
from extravasation. Follow-up of relatively larger minimally classic lesions and 
occult with no classic lesions that initially do not undergo therapy appears
indicated so therapy can be considered if a predominantly classic lesion develops
or, in the case of occult with no classic lesions, if visual acuity declines
slightly to a lower (poorer) level without a marked increase in lesion size.
Additional revisions of these guidelines may be required as new data become
available.

Publication Types: 
    Consensus Development Conference
    Guideline
    Practice Guideline
    Review

PMID: 15689800 [PubMed - indexed for MEDLINE]

2059: Ophthalmic Surg Lasers Imaging. 2005 Jan-Feb;36(1):30-6.

Early treatment of cystoid macular edema secondary to branch retinal vein
occlusion with intravitreal triamcinolone acetonide.

Yepremyan M, Wertz FD, Tivnan T, Eversman L, Marx JL.

Tufts-New England Eye Center, Boston, Massachusetts, USA.

BACKGROUND AND OBJECTIVE: To determine the efficacy of intravitreal triamcinolone
acetonide (IVTA) in the early treatment of severe cystoid macular edema (CME)
related to acute branch retinal vein occlusion. PATIENTS AND METHODS:
Retrospective, non-comparative case series. Twelve eyes with severe CME (foveal
thickness > 450 microm) secondary to acute branch retinal vein occlusion received
IVTA. RESULTS: Average follow-up was 15.3 months. Mean visual acuity was 0.88
LogMar units (20/160) initially, 0.55 LogMar units (20/70) at 1 week, 0.46 LogMar
units (20/60) at 1 month, and 0.49 LogMar units (20/60) at last follow-up. Visual
acuity improved by 3 lines or greater in 42% of patients at 1 week, 50% at 1
month, and 42% at last follow-up. Average foveal thickness was 589 microm (range,
460 to 840 microm) at baseline, 237 microm at 1 week, 196 microm at 1 month, and 
235 microm at last follow-up. All eyes showed reduction of foveal thickness as
measured by optical coherence tomography. Eight eyes developed recurrent CME at
an average of 5.5 months after initial IVTA injection. Ten eyes required
additional intervention during the follow-up period. CONCLUSIONS: Early treatment
of severe CME secondary to branch retinal vein occlusion with IVTA is effective
in reducing foveal thickness as measured by optical coherence tomography and
improving visual acuity. However, monotherapy with IVTA can be associated with a 
significant rate of recurrent CME.

PMID: 15688969 [PubMed - indexed for MEDLINE]

2060: Doc Ophthalmol. 2004 Jul;109(1):1-8.

The local cone and rod system function in early age-related macular degeneration.

Chen C, Wu L, Wu D, Huang S, Wen F, Luo G, Long S.

Renmin Hospital, Wuhan University, Wuhan 430060, P.R. China. antony7127@sina.com

To compare cone and rod system function in patients with early age- related
macular degeneration (ARMD) and control group using multifocal electroretinogram 
(MERG) and perimetry, to investigate whether there is rod system dysfunction in
the central retina in ARMD. Cone-mediated MERG, photopic sensitivity,
rod-mediated MERG, and scotopic sensitivity in 16 eyes of control subjects and 24
eyes of early dry-form ARMD were measured with VERIS Science 4.0 and Octopus 101 
perimetry. The latencies and average response densities of the summed responses
and five ring retinal regions, average sensitivity of all locus and eight ring
retinal regions in control eyes were compared with those in ARMD. Mean scotopic
and photopic sensitivity of ARMD patients were significantly lower than that of
normal controls. Sotopic sensitivity reduced more than photopic sensitivity and
the greatest deficit was 2.5-5.0 degrees. The amplitudes of N1 and P1 wave in one
ring (5.0 degrees) of rod MERG were significantly lower of ARMD patients than
that of normal subjects. Our results suggest that rod function decreased and the 
parafoveal rod cells were predominantly damaged in ARMD. The rod function testing
in macula may be a useful tool to diagnose and measure the fundus dysfunction of 
ARMD.

PMID: 15675195 [PubMed - indexed for MEDLINE]

2061: Cochrane Database Syst Rev. 2005 Jan 25;(1):CD004239.

Non-steroidal anti-inflammatory agents for treating cystoid macular oedema
following cataract surgery.

Sivaprasad S, Bunce C, Patel N.

West Kent Eye Centre, Farnborough Hospital, Orpington, UK, BR6 8ND.
senswathi@aol.com

BACKGROUND: Cystoid macular oedema (CMO) is the accumulation of fluid in the
central retina (the macula) due to leakage from dilated capillaries. It is the
most common cause of poor visual outcome following cataract surgery. The exact
cause is unclear. Acute CMO, defined as oedema of less than four months duration,
often resolve spontaneously. CMO that persists for four months or more is termed 
chronic CMO. Different types of non-steroidal anti-inflammatory agents (NSAIDs)
are used in the treatment of CMO which may be delivered topically or
systemically. OBJECTIVES: To examine the effectiveness of NSAIDs in the treatment
of CMO following cataract surgery. SEARCH STRATEGY: We searched the Cochrane
Central Register of Controlled Trials - CENTRAL (which contains the Cochrane Eyes
and Vision Group Trials Register) on The Cochrane Library (Issue 2 2004), MEDLINE
(1966 to April 2004), EMBASE (1980 to May 2004), LILACS (April 2004) and the
reference lists of identified trials. We searched conference abstracts (sessions 
related to cataract) in ARVO 1975 to 2003. We contacted experts in the field and 
NSAIDs manufacturers for details on published and unpublished trials. SELECTION
CRITERIA: Randomised controlled trials evaluating the effects of NSAIDs in the
treatment of CMO following cataract surgery. DATA COLLECTION AND ANALYSIS: Two
reviewers independently extracted data. Since considerable heterogeneity was
observed between studies we did not conduct meta-analyses. MAIN RESULTS: Seven
trials involving a total of 266 participants were included. Four trials studied
the effects of NSAIDs in chronic CMO while the other three examined the effect of
NSAIDs in acute CMO. Of the studies examining chronic CMO, one study enrolled 120
participants, but the remainder had 34 or fewer participants. Four different
NSAIDs were used and administered in different ways. Indomethacin was used orally
and was found to be ineffective for chronic CMO in one trial. Topical fenoprofen 
was also found to be ineffective for chronic CMO in another small trial.
Treatment with topical 0.5% ketorolac for chronic CMO was found to be effective
in two trials.Three trials examined the effect of topical NSAIDs on acute CMO.
The comparisons among these studies were of an NSAID to placebo, prednisolone or 
another NSAID. The study design differed between the studies in other important
aspects thus they could not be combined in a meta-analysis. AUTHORS' CONCLUSIONS:
This review found two trials which showed that topical NSAID (0.5% ketorolac
tromethamine ophthalmic solution) has a positive effect on chronic CMO. However, 
the effects of NSAIDs in acute CMO remains unclear and needs further
investigation.

Publication Types: 
    Review

PMID: 15674935 [PubMed - indexed for MEDLINE]

2062: Invest Ophthalmol Vis Sci. 2005 Feb;46(2):683-91.

Early-onset macular degeneration with drusen in a cynomolgus monkey (Macaca
fascicularis) pedigree: exclusion of 13 candidate genes and loci.

Umeda S, Ayyagari R, Allikmets R, Suzuki MT, Karoukis AJ, Ambasudhan R, Zernant
J, Okamoto H, Ono F, Terao K, Mizota A, Yoshikawa Y, Tanaka Y, Iwata T.

National Institute of Sensory Organs, National Hospital Organization Tokyo
Medical Center, Tokyo 152-8902, Japan.

PURPOSE: To describe hereditary macular degeneration observed in the cynomolgus
monkey (Macaca fascicularis), which shares phenotypic features with age-related
macular degeneration in humans, and to test the involvement of candidate gene
loci by mutation screening and linkage analysis. METHODS: Ophthalmic examinations
with fundus photography, fluorescein angiography (FA), indocyanine green
angiography (IA), electroretinography (ERG), and histologic studies were
performed on both affected and unaffected monkeys in the pedigree. The monkey
orthologues of the human ABCA4, VMD2, EFEMP1, TIMP3, and ELOVL4 genes were cloned
and screened for mutations by single-strand conformation polymorphism (SSCP)
analysis or denaturing high-performance liquid chromatography (DHPLC) and direct 
sequencing in six affected and five unaffected monkeys from the pedigree and in
six unrelated, unaffected monkeys. Subsequently, 13 human macular degeneration
loci including these five genes were analyzed to test for linkage with the
disease. Nineteen affected and seven unaffected monkeys in the pedigree were
analyzed by using human microsatellite markers linked to the 13 loci. RESULTS:
Yellowish white spots were observed in the macula and fovea centralis, and in
some cases the spots scattered to the peripheral retina along the blood vessels. 
FA showed hyperfluorescence corresponding to the dots except in the foveola. No
anomalies were found by IA and ERG. Histologic studies demonstrated that the
spots were drusen. Mutation analysis of the ABCA4, VMD2, EFEMP1, TIMP3, and
ELOVL4 genes identified a few sequence variants, but none of them segregated with
the disease. Linkage analysis with markers linked to these five genes and an
additional eight human macular degeneration loci failed to establish linkage.
Haplotype analysis excluded the involvement of the 13 candidate loci for
harboring the gene associated with macular degeneration in the monkeys.
CONCLUSIONS: Significant homology was identified between monkey and human
orthologues of the five macular degeneration genes. Thirteen loci associated with
macular degeneration in humans or harboring macular degeneration genes were
excluded as causal of early-onset macular degeneration in the monkeys. It is
likely that none of these loci, but rather a novel gene, is involved in causing
the observed phenotype in this monkey pedigree.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15671300 [PubMed - indexed for MEDLINE]

2063: Exp Eye Res. 2005 Feb;80(2):249-58.

Corticosteroids inhibit VEGF-induced vascular leakage in a rabbit model of
blood-retinal and blood-aqueous barrier breakdown.

Edelman JL, Lutz D, Castro MR.

Department of Biological Sciences, Allergan Inc., 2525 Dupont Drive, Irvine, CA
92612, USA. edelman_jeffrey@allergan.com

PURPOSE: Recent clinical studies show that a single intravitreal injection of the
corticosteroid triamcinolone acetonide (TAA) may reduce edematous retinal
swelling and improve visual acuity in patients with diabetic macular edema (DME).
In addition, clinical and experimental studies strongly suggest that
blood-retinal barrier breakdown in diabetes is induced by vascular endothelial
growth factor (VEGF). These results suggest that corticosteroids may modulate
VEGF-mediated responses in vivo. To test this hypothesis directly, the current
study evaluated the effects of TAA and dexamethasone (DEX) in a newly developed
rabbit model of VEGF-induced blood-retinal barrier and blood-aqueous (iris)
barrier breakdown. METHODS: VEGF165 or vehicle was injected intravitreally in
female Dutch Belt rabbits, and scanning ocular fluorophotometry was used to
non-invasively measure fluorescein leakage from retinal and iris vasculature.
VEGF-induced retinal vasculopathy was further assessed with fundus imaging,
fluorescein angiography, and ocular coherence tomography. For pharmacologic
studies, rabbits were treated with either DEX (2 mg kg(-1) daily, s.c.), TAA (2
or 4 mg, intravitreal), indomethacin (20 mg kg(-1) daily, s.c.), or vehicle (s.c.
or intravitreal). Human umbilical vein endothelial cells (HUVEC) were loaded with
the fluorescent Ca2+ indicator dye fluo-4 and treated with dexamethasone (0.1-10 
microM) or vehicle for either 2 or 24 hr prior to stimulation with 10 ng ml(-1)
VEGF165. RESULTS: VEGF injected intravitreally induced a time and dose-dependent 
breakdown of the blood-retinal and blood-aqueous barriers. Maximal vascular
leakage was measured at 48 hr after intravitreal injection with a dose of 500 ng 
VEGF. Other effects of VEGF included prominent retinal vasodilation, vessel
tortuousity, fluorescein leakage from retinal vessels, and inner retinal edema.
These VEGF-mediated responses are transient and approach baseline by 1 week.
VEGF-induced blood-retinal and blood-aqueous barrier breakdown was completely
blocked by the corticosteroid DEX administered systemically for 3 days. In
contrast, the non-steroidal anti-inflammatory drug, indomethacin, had no effect. 
In a separate study with VEGF injected intravitreally at six different time
points over 5 months, a single intravitreal 2 mg dose of TAA completely blocked
VEGF-induced retinal and iris leakage for 45 days. VEGF/VEGF receptor-2-mediated 
Ca2+ mobilization in endothelial cells was not affected by 2 or 24 hr
pretreatment with dexamethasone. CONCLUSION: These results indicate that one
mechanism by which corticosteroids block blood-ocular barrier breakdown and edema
is via their modulation of signaling or effector proteins downstream of the VEGF 
receptor.

PMID: 15670803 [PubMed - indexed for MEDLINE]

2064: Exp Eye Res. 2005 Feb;80(2):235-48.

Impaired RPE survival on aged submacular human Bruch's membrane.

Gullapalli VK, Sugino IK, Van Patten Y, Shah S, Zarbin MA.

Institute of Ophthalmology and Visual Science, University of Medicine and
Dentistry of New Jersey-New Jersey Medical School, Newark, NJ, USA.

Resurfacing of diseased or iatrogenically damaged Bruch's membrane with healthy
retinal pigment epithelium (RPE) has been proposed as adjunctive treatment for
age-related macular degeneration (AMD). The purpose of this study was to
determine whether cultured fetal human RPE cells can attach and differentiate on 
aged submacular human Bruch's membrane. Bruch's membrane was debrided to expose
native RPE basement membrane, the superficial inner collagenous layer directly
below the RPE basement membrane, or the deep inner collagenous layer. These are
three surfaces that transplanted RPE cells will encounter in situ. Approximately 
3146 cultured fetal RPE cells mm(-2) were seeded onto these three surfaces and
grown in organ culture for 1, 7, or 14 days. Explants were bisected and examined 
histologically or analyzed with a scanning electron microscope. RPE nuclear
density was measured on stained sections. Morphology and cell density were
compared to cells seeded onto bovine corneal endothelial cell-extracellular
matrix (BCE-ECM). In situ submacular RPE nuclear density was also measured in
tissue sections of donor eyes ranging from 18 weeks gestation to 88 years of age 
to determine the effect of age on RPE density. Compared to cells seeded onto
BCE-ECM at similar density, RPE cell coverage and cellular morphology on aged
submacular human Bruch's membrane was poor at all time points. In contrast to
cells on BCE-ECM, RPE cell density on Bruch's membrane decreased with time. In
general, cell morphology on all three Bruch's membrane surfaces worsened by day-7
compared to day-1. Although some cells were more pigmented on RPE basement
membrane and the deep inner collagenous layer at day-7, poor cellular morphology 
indicated the remaining cells were not well differentiated. At day-14, the cells 
were uniform and cuboidal on BCE-ECM, with cell density similar to that at day-7 
and similar to in situ density of young donors (<age 30 years). The morphology of
cells on Bruch's membrane was variable, and the nuclear density declined over
time. A Bruch's membrane explant from a donor with large soft drusen showed the
poorest resurfacing at day-7 in organ culture. These data indicate that aged
submacular human Bruch's membrane does not support transplanted RPE survival and 
differentiation readily. The formation of localized RPE defects, cell death, and 
worsening cellular morphology on aged Bruch's membrane indicates that
modification of Bruch's membrane may be necessary to prevent graft failure in AMD
patients receiving RPE transplants.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15670802 [PubMed - indexed for MEDLINE]

2065: Br J Ophthalmol. 2005 Feb;89(2):142-6.

Exaggerated relative nasal-temporal asymmetry of macular capillary blood flow in 
patients with clinically significant diabetic macular oedema.

Hudson C, Flanagan JG, Turner GS, Chen HC, Rawji MH, McLeod D.

University Department of Ophthalmology, Royal Eye Hospital, Manchester M13 9WH,
UK. chudson@sciborg.uwaterloo.ca

AIMS: To compare the macular capillary blood flow of patients with clinically
significant diabetic macular oedema (DMO) with that of non-diabetic subjects and 
to determine the relation between blood flow and capillary leakage in patients
with DMO. METHODS: The sample comprised 45 non-diabetic subjects (mean age 59
years) and 18 type 2 patients with clinically significant DMO (mean age 60
years). Macular capillary blood flow measurements were acquired using the
Heidelberg retina flowmeter (HRF) and a 10 degrees x2.5 degrees scan field
centred on the fovea. Fluorescein angiography was undertaken on each of the
diabetic patients after the completion of HRF measurements. RESULTS: Temporal
macular capillary blood flow was significantly lower for the patients with
clinically significant DMO compared with age matched non-diabetic subjects
(ANCOVA, p = 0.0011) while relative nasal-temporal asymmetry of macular capillary
blood flow was significantly higher (p = 0.0125). Nasal-temporal asymmetry of
macular capillary blood flow was significantly higher for the patients with DMO
and capillary leakage within the scan area (two tailed t test, p = 0.0071).
Macular capillary blood flow was always lower in areas of DMO and capillary
leakage. CONCLUSION: Capillary blood flow was reduced in areas of DMO and
capillary leakage, suggesting the presence of a localised perturbation of
capillary blood flow regulation.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15665341 [PubMed - indexed for MEDLINE]

2066: J Neurosurg. 2005 Jan;102 Suppl:200-3.

Gamma knife surgery for choroidal neovascularization in age-related macular
degeneration. Technical note.

Hayashi M, Chernov M, Usukura M, Abe K, Ono Y, Izawa M, Hori S, Hori T, Takakura 
K.

Departments of Neurosurgery, Neuroradiology, and Ophthalmology, Tokyo Women's
Medical University, Tokyo, Japan. GKRmoto@aol.com

The authors conducted a study to determine a way of overcoming the poor-quality
demonstration of choroidal neovascularization (CNV) associated with age-related
macular degeneration (AMD) on conventional magnetic resonance (MR) imaging
studies. The poor MR imaging demonstration of CNV in patients with AMD makes the 
use of gamma knife surgery more difficult. This difficulty, however, can be
overcome by use of a modified time-of-flight MR imaging,sequence with Gd
enhancement and coronal reconstruction.

Publication Types: 
    Case Reports

PMID: 15662810 [PubMed - indexed for MEDLINE]

2067: J Neurosci. 2005 Jan 19;25(3):614-8.

Reorganization of visual processing in macular degeneration.

Baker CI, Peli E, Knouf N, Kanwisher NG.

McGovern Institute for Brain Research and Department of Brain and Cognitive
Sciences, Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts
02139, USA. cibaker@mit.edu

Macular degeneration (MD), the leading cause of visual impairment in the
developed world, damages the central retina, often obliterating foveal vision and
severely disrupting everyday tasks such as reading, driving, and face
recognition. In such cases, the macular damage eliminates the normal retinal
input to a large region of visual cortex, comprising tens of square centimeters
of surface area in each hemisphere, which is normally responsive only to foveal
stimuli. Using functional magnetic resonance imaging, we asked whether this
deprived cortex simply becomes inactive in subjects with MD, or whether it takes 
on new functional properties. In two adult MD subjects with extensive bilateral
central retinal lesions, we found that parts of visual cortex (including primary 
visual cortex) that normally respond only to central visual stimuli are strongly 
activated by peripheral stimuli. Such activation was not observed (1) with visual
stimuli presented to the position of the former fovea and (2) in control subjects
with visual stimuli presented to corresponding parts of peripheral retina. These 
results demonstrate large-scale reorganization of visual processing in MD and
will likely prove important in any effort to develop new strategies for
rehabilitation of MD subjects.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, Non-P.H.S.
    Research Support, U.S. Gov't, P.H.S.

PMID: 15659597 [PubMed - indexed for MEDLINE]

2068: Semin Ophthalmol. 2004 Mar-Jun;19(1-2):13-20.

Diabetic macular edema: an OCT-based classification.

Panozzo G, Parolini B, Gusson E, Mercanti A, Pinackatt S, Bertoldo G, Pignatto S.

Teclo, Vitreoretinal Service, Verona, Italy. g.panozzo@iol.it

PURPOSE: More than ten years after ETDRS, Optical Coherence Tomography (OCT)
greatly enhanced our ability to detect macular thickening and has brought new
insights on the morphology of edema and on the presence of vitreal traction. In
this study we propose a new classification of macular edema based on OCT findings
to better catalogue and follow this complex clinical entity. METHODS: Since
January 2000 we analysed with OCT 2 (Zeiss Inc.) more than one thousand and two
hundred eyes with DME. RESULTS: The classification takes into account five
parameters: retinal thickness, diffusion, volume, morphology and presence of
vitreous traction. Standard figures and numerical values for every parameter are 
given. CONCLUSION: Although ETDRS guidelines for laser treatment of DME still
remain the only proven therapy for this condition, many other strategies are now 
on trial, and the vast majority of authors use OCT as the best indicator of
therapeutic benefit. The amount of information given by OCT demonstrates that
macular edema is a complex clinical entity with various morphology and gravity,
and disclaimed the limitations of a simple "clinical" definition. As in many
other examples such as macular holes and choroidal neovascularization, a uniform 
and precise definition of macular edema would increase the possibility to compare
and judge the result of different therapeutic strategies. Aim of this
classification is to implement the ETDRS clinical definition of DME with the
precise and useful data given by OCT to better diagnose, catalogue and follow
macular edema.

PMID: 15658007 [PubMed - indexed for MEDLINE]

2069: Semin Ophthalmol. 2004 Mar-Jun;19(1-2):1-12.

Diode laser, vitrectomy and intravitreal triamcinolone. A comparative study for
the treatment of diffuse non tractional diabetic macular edema.

Parolini B, Panozzo G, Gusson E, Pinackatt S, Bertoldo G, Rottini S, Pignatto S.

Teclo Vitreo-Retinal Service, Verona, Italy.

PURPOSE: To determine the effectiveness and safety of diode laser, pars plana
vitrectomy (PPV) with gas tamponade, and intravitreal triamcinolone (IVT) as
possible treatments for diffuse diabetic macular edema (dDME). To determine
whether the new macular edema Classification previously proposed by some of the
authors may help as a guide in the choice of treatment. METHODS: A retrospective,
comparative study of 169 eyes with dDME that underwent treatment. The eyes
divided into 3 groups: in the PPV Group, 59 eyes received PPV with gas tamponade;
in the DIODE Group, 53 eyes received a laser grid; in the IVT Group, 57 eyes
received an intravitreal injection of 4 mg of triamcinolone acetonide. The follow
up ranged from 6 to 24 months. The eyes were classified according to the new DME 
Classification based on OCT. MAIN OUTCOMES: Change in foveal thickness as
determined by Optical Coherence Tomography (OCT); change in visual acuity; intra 
and postoperative complications. RESULTS: Mean visual acuity (VA) improved at 3
months with every treatment. At one year only eyes which underwent PPV still had 
better VA than the pre-op value, while eyes which underwent IVT and laser
treatment showed regression. PPV show the greater percentage of eyes which gain 3
or more lines of VA at one year (17%). Mean foveal thickness improved at 3 months
with every treatment. Only the eyes into the PPV Group showed relatively low
foveal thickness at one year. Better final VA and foveal thickness were obtained 
if preop VA is > or = 0.3 and if earlier stages of DME were treated according to 
the new DME Classification. PPV was the treatment which offered the most stable
results with at one year or longer. Similar results were observed into the PPV
Groups as a whole and into a subgroup of eyes with preoperative PVD. No
complications were encountered with laser diode treatment. Long term
complications into the IVT Group were elevated IOP (8%), retinal detachment
(3.5%) and posterior cataract (15%). Long term complications into the PPV Group
were retinal detachment (3.4%) and cataract (90%). CONCLUSIONS: Diode laser, PPV 
with gas tamponade and IVT are effective alternative treatments to decrease
foveal thickness and improve visual acuity in eyes with DME. However while the
results of PPV are stable in the long term follow-up, diode laser and IVT do not 
offer stable results. Complications may be severe with PPV and IVT. It is
necessary to carefully select cases which would benefit from these types of
treatments. The authors think that the OCT Classification may serve as a guide
for the choice of treatment.

Publication Types: 
    Comparative Study

PMID: 15658006 [PubMed - indexed for MEDLINE]

2070: J Lipid Res. 2005 Apr;46(4):628-40. Epub 2005 Jan 16.

Retina expresses microsomal triglyceride transfer protein: implications for
age-related maculopathy.

Li CM, Presley JB, Zhang X, Dashti N, Chung BH, Medeiros NE, Guidry C, Curcio CA.

Department of Ophthalmology, University of Alabama School of Medicine,
Birmingham, AL, USA.

The principal extracellular lesions of age-related maculopathy (ARM), the leading
cause of vision loss in the elderly, involve Bruch's membrane (BrM), a thin
vascular intima between the retinal pigment epithelium (RPE) and its blood
supply. With age, 80-100 nm solid particles containing esterified cholesterol
(EC) accumulate in normal BrM, and apolipoprotein B (apoB) immunoreactivity is
detectable in BrM- and ARM-associated lesions. Yet little evidence indicates that
increased plasma cholesterol is a risk factor for ARM. To determine if RPE is
capable of assembling its own apoB-containing lipoprotein, we examined RPE for
the expression of microsomal triglyceride transfer protein (MTP), which is
required for this process. Consistent with previous evidence for apoB expression,
MTP is expressed in RPE, the ARPE-19 cell line, and, unexpectedly, retinal
ganglion cells, which are neurons of the central nervous system. De novo
synthesis and secretion of neutral lipid by ARPE-19 was supported by high levels 
of radiolabeled EC and triglyceride in medium after supplementation with oleate. 
Lipoprotein assembly and secretion is implicated as a constitutive retinal
function and a plausible candidate mechanism involved in forming extracellular
cholesterol-containing lesions in ARM. The pigmentary retinopathy and neuropathy 
of abetalipoproteinemia (Mendelian Inheritance of Man 200100; Bassen-Kornzwieg
disease), which is caused by mutations in the MTP gene, may involve loss of
function at the retina.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15654125 [PubMed - indexed for MEDLINE]

2071: Am J Ophthalmol. 2005 Jan;139(1):214-5.

Functional changes after photodynamic therapy with verteporfin.

Meyer CH, Lapolice DJ, Fekrat S.

Department of Ophthalmology, Duke University Medical Center, Durham, North
Carolina 27710-3802, USA.

OBJECTIVE: To investigate image preferences after photodynamic therapy (PDT).
DESIGN: Prospective, cross-sectional study. METHODS: Seventeen patients with
neovascular age-related macular degeneration were tested by color vision,
contrast sensitivity, and near visual acuity (VA) with positive images and
negative images before, 1 week after, and 3 months after PDT. RESULTS: Before
PDT, 13 patients (76%) preferred positive images; the difference was not
significant (P < .04). One week after PDT, 16 patients (94%) preferred negative
images. The average near VA improved to 27 letters on positive images and to 32
letters on negative images (P < .00001). Three months after PDT, near VA declined
to 19 letters on positive images and to 26 letters on negative images (P <
.000001). Color vision and contrast sensitivity remained constant during all
examinations. CONCLUSION: Although PDT may not alter the neurosensory retina, it 
may affect intraretinal function by changing image preference.

PMID: 15652863 [PubMed - indexed for MEDLINE]

2072: Am J Ophthalmol. 2005 Jan;139(1):188-90.

Adenoma arising from nonpigmented ciliary epithelium concomitant with
neovascularization of the optic disk and cystoid macular edema.

Suzuki J, Goto H, Usui M.

Department of Ophthalmology, Tokyo Medical University Hospital, Tokyo, Japan.
jun-s@qc4.so-net.ne.jp

PURPOSE: To report a case of adenoma of the nonpigmented ciliary epithelium
concomitant with marked neovascularization of the optic disk and cystoid macular 
edema (CME). DESIGN: Observational case report. METHODS: A 34-year-old woman
presented with a nonpigmented, vascularized tumor behind the iris and
neovascularization of the optic disk (NVD). Visual acuity decreased gradually as 
a result of the development of CME. RESULTS: Iridocyclectomy to excise the tumor 
was performed 8 months after initial examination. Histopathologic study revealed 
an adenoma arising from the NPCE. The levels of vascular endothelial growth
factor were significantly elevated in both aqueous and vitreous humor obtained at
surgery. The NVD and CME regressed after surgery, and the postoperative visual
acuity improved to 20/40. CONCLUSIONS: NVD and CME may develop secondary to
adenoma of the nonpigmented ciliary epithelium. Increased levels of vascular
endothelial growth factor in intraocular fluids may play a role in NVD and CME
development.

Publication Types: 
    Case Reports

PMID: 15652849 [PubMed - indexed for MEDLINE]

2073: Am J Ophthalmol. 2005 Jan;139(1):30-8.

Sociodemographic factors and age-related macular degeneration in Latinos: the Los
Angeles Latino Eye Study.

Fraser-Bell S, Donofrio J, Wu J, Klein R, Azen SP, Varma R; Los Angeles Latino
Eye Study Group.

Department of Preventive Medicine, Keck School of Medicine, University of
Southern California, Los Angeles, USA.

PURPOSE: To assess the association of various sociodemographic factors and early 
and advanced (geographic atrophy, exudative) age-related macular degeneration
(AMD) in Latinos. DESIGN: Population-based, cross-sectional study METHODS: The
study population included Latinos (primarily Mexican-American) aged 40 years and 
older living in La Puente, California. Sociodemographic factors, obtained from an
interviewer-administered questionnaire, included age, sex, Native American
ancestry, acculturation, country of birth, employment, income, marital status,
health insurance, and education level. All participants underwent complete
ophthalmic examination. AMD was diagnosed from stereoscopic macular photographs. 
Univariate and multivariable logistic regression was used to assess associations 
between sociodemographic factors and AMD. RESULTS: Gradable retinal photographs
from 5875 participants were included. Mean participant age was 54.9 years, 42%
were male, and 5% had Native American ancestry. Stepwise logistic regression
analyses indicated that age, sex, and being born in the United States were
associated with early AMD (odds ratio [OR] = 1.8, 1.8, and 0.80, respectively).
Native American ancestry was the associated with any advanced AMD and geographic 
atrophy (OR = 3.8 and 16.4, respectively). Family history of AMD was also
associated with geographic atrophy (OR = 28.1). Acculturation was not associated 
with AMD. CONCLUSION: Independent risk indicators for the various types of AMD
include older age, male sex, being born outside of the United States, Native
American ancestry, and a family history of AMD. These risk factors were
independent of other possible behavioral factors such as smoking and alcohol
consumption.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15652825 [PubMed - indexed for MEDLINE]

2074: Radiat Med. 2004 Nov-Dec;22(6):398-404.

External-beam radiation therapy for age-related macular degeneration: two years' 
follow-up results at a total dose of 20 Gy in 10 fractions.

Churei H, Ohkubo K, Nakajo M, Hokotate H, Baba Y, Ideue J, Miyagawa K, Nakayama
H, Hiraki Y, Kitasato T, Yabe N.

Department of Radiology, Kagoshima University Hospital, Kagoshima University
Hospital, Sakuragaoka, Kagoshimashi, Kagoshima, Japan.

PURPOSE: The efficacy of external-beam radiation therapy (RT) was evaluated in
the treatment of eyes with subfoveal or juxtafoveal choroidal neovascularization 
in age-related macular degeneration (ARMD). MATERIALS AND METHODS: Twenty-one
eyes of 18 patients with occult or mixed-type ARMD received a total dose of 20 Gy
of 6 MV X-rays in 10 fractions. The follow-up time was 24 months. Fifteen
non-treated eyes of 13 patients who had been followed served as a control.
RESULTS: In the RT group, visual acuity was improved in three eyes, maintained in
14 eyes, and worsened in four eyes. In the control group, it was not improved in 
any eyes, was maintained in six eyes, and worsened in nine eyes. The improved or 
maintained rate in visual acuity was 81% in the RT group and 40% in the control
group (p=0.0342). In the RT group, fundoscopic and angiographic findings were
improved in five eyes, unchanged in seven eyes, and worsened in nine eyes, while 
they were not improved in any eyes, unchanged in two eyes, and worsened in 13
eyes in the control group(p=0.0342). CONCLUSION: RT at a total dose of 20 Gy in
10 fractions is effective for ARMD for at least two years. RT may be effective
treatment for occult or mixed-type ARMD compared with the classic type.

Publication Types: 
    Comparative Study

PMID: 15648455 [PubMed - indexed for MEDLINE]

2075: Arch Ophthalmol. 2005 Jan;123(1):58-63.

Erratum in:
    Arch Ophthalmol. 2005 Apr;123(4):582.

Photodynamic therapy with verteporfin: observations on the introduction of a new 
treatment into clinical practice.

Schein OD, Bressler NM, Price P.

Department of Ophthalmology, Wilmer Eye Institute, The Johns Hopkins University
School of Medicine, Baltimore, MD 21287-9019, USA. oschein@jhmi.edu

OBJECTIVE: To assess adherence to Food and Drug Administration-approved
indications and Centers for Medicare & Medicaid Services policy through June 2001
regarding the use of photodynamic therapy in Medicare beneficiaries. DESIGN:
Systematic review of pretreatment fluorescein angiograms of 1245 consecutive
Medicare patients who received photodynamic therapy from physicians in 3
contiguous Medicare coverage areas (fee-for-service arrangement) and in 136
consecutive patients in a Medicare health maintenance organization. RESULTS: In
the 3 Medicare fee-for-service regions, payment denial due to nonconforming
fluorescein angiograms ranged from 17% to 29% by region in 1245 beneficiaries. In
the health maintenance organization setting, 60 (44%) of 136 submitted angiograms
were nonconforming, including 8 in which the photographic quality was too poor to
grade the lesion size, composition, or both. CONCLUSIONS: A substantial
proportion of the actual or intended clinical application of photodynamic therapy
with verteporfin was directed to patients who did not meet concurrent published
clinical criteria associated with treatment benefit or national coverage policy. 
Although this policy has evolved, it still depends on fluorescein angiographic
interpretation, suggesting that there is an opportunity to improve the
cost-effectiveness of delivery of photodynamic therapy with verteporfin to
Medicare beneficiaries.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15642813 [PubMed - indexed for MEDLINE]

2076: Arch Ophthalmol. 2005 Jan;123(1):46-53.

Self-management of age-related macular degeneration at the 6-month follow-up: a
randomized controlled trial.

Brody BL, Roch-Levecq AC, Thomas RG, Kaplan RM, Brown SI.

Department of Ophthalmology, University of California, San Diego, La Jolla
92093-0946, USA.

OBJECTIVE: To assess the effectiveness at the 6-month follow-up of an age-related
macular degeneration (AMD) self-management program consisting of health education
and enhancement of problem-solving skills in improving quality of life as shown
by measures of mood and function. METHODS: Six-month follow-up data were analyzed
from 214 of 252 older adult volunteers (mean age, 80.8 years) with advanced AMD
who had been randomly assigned to a 12-hour self-management program (n = 82), a
series of 12 hours of tape-recorded health lectures (n = 66), or a waiting list
(n = 66). The primary outcome measure was emotional distress (Profile of Mood
States). Secondary outcome measures included function (National Eye Institute
Visual Function Questionnaire), self-confidence to handle AMD-specific challenges
in daily life (AMD Self-efficacy Questionnaire), and depression status on the
Structured Clinical Interview for Diagnostic and Statistical Manual of Mental
Disorders, Fourth Edition. RESULTS: At the 6-month follow-up, participants in the
self-management program reported significantly less emotional distress (P=.008), 
better function (P=.05), and increased self-efficacy (P=.006) compared with
control subjects. The latter effects were more pronounced in the depressed than
in the nondepressed subjects. Finally, the incidence of clinical depression at
the 6-month follow-up was significantly lower in the self-management group
(P=.05) than in the control group. CONCLUSION: The sustained positive effects at 
the 6-month follow-up provide support for the effectiveness of the AMD
self-management program in reducing distress and disability, improving
self-efficacy, and preventing depression in poorly sighted elderly patients with 
AMD.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, U.S. Gov't, P.H.S.

PMID: 15642811 [PubMed - indexed for MEDLINE]

2077: Exp Eye Res. 2004 Dec;79(6):753-9.

Transmission of light to the aging human retina: possible implications for age
related macular degeneration.

Dillon J, Zheng L, Merriam JC, Gaillard ER.

Department of Ophthalmology, College of Physicians and Surgeons, Columbia
University, 630 West 168th Street, New York, NY 10032, USA. jpd1@columbia.edu

The purpose of this study is to determine the transmission properties of the
anterior segment of the human eye as a function of age and relate those changes
to possible consequences for retinal disorders. For this a new method has been
developed. This consists of a probe which is inserted into the posterior sclera
and detects light passing through the anterior segment. The probe is connected to
a CCD spectrophotometer via a fibre optic bundle. Using this, the transmission
properties of human cadaver eyes were determined. A young primate anterior
segment has a maximum absorption of 365 nm due to the O-beta-glucoside of
3-hydroxykynurenine (3-HKG) in the lens. There is a steep increase in
transmission of the human anterior segment at wavelengths longer than 400 nm.
With aging there is an increase in absorption throughout the visible such that by
the sixth decade only 20% of blue light is transmitted to the retina compared to 
the young primate eye. The rate of decrease of blue light was similar to the age 
related change of the ratio of absorbance at 365/320 nm of the lens. (IOVS
41:1454;1999). The age related rate of decrease in the transmission of blue light
to the retina was similar to the rate of increase of lipofuscin formation in the 
retina, and the amount of light absorbed by A2E in the RPE is constant from the
second to seventh decade. Although this yellowing is thought to be detrimental to
the lens, it would appear to be beneficial to the retina. It was determined that 
the implantation of a standard IOL after cataract surgery increased the amount of
light absorbed by A2-E by approximately a factor of five.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15642312 [PubMed - indexed for MEDLINE]

2078: Eur J Ophthalmol. 2004 Nov-Dec;14(6):581-3.

Intravitreal triamcinolone in cystoid macular edema due to uveitis and repeated
surgery after a penetrating trauma.

Marullo M, Perilli R, Balestrazzi E.

Department of Ophthalmology, Ospedale Civile dello Spirito Santo, Pescara -
Italy. ro.perilli@tiscali.it

PURPOSE: To test the effectiveness of intravitreal triamcinolone acetonide in
treating macular edema due to multiple vitreoretinal surgical procedures and
uveitis after a penetrating trauma with metallic foreign body retention in a
37-year-old man. METHODS: The patient received two intravitreal injections of
triamcinolone acetonide-2 mg/0.05 mL and 4 mg/0.1 ml(-1) month apart. The 6-month
follow-up included best-corrected visual acuity (BCVA) measurement and optical
coherence tomography evaluation. RESULTS: After the first injection (2 mg) the
foveal thickness (685 microm, as compared to a normal value of <165 microm) and
the BCVA (20/200) remained unchanged with respect to the preinjection values; 1
week after the second injection (4 mg), the foveal thickness went down to 130
microm and the BCVA improved (20/80). Such results were unchanged at the 6-month 
control. No complications occurred. CONCLUSIONS: A 2 mg dose of triamcinolone
acetonide did not improve the anatomic and functional status of the macula. A 4
mg dose markedly improved BCVA and reduced the macular thickness in this case of 
macular edema.

Publication Types: 
    Case Reports

PMID: 15638114 [PubMed - indexed for MEDLINE]

2079: Eur J Ophthalmol. 2004 Nov-Dec;14(6):543-9.

Intravitreal triamcinolone acetonide injection as primary treatment for diabetic 
macular edema.

Ozkiris A, Evereklioglu C, Erkiliç K, Tamçelik N, Mirza E.

Department of Ophthalmology, Erciyes University Medical Faculty, Kayseri -
Turkey. aozkiris@erciyes.edu.tr

PURPOSE: To evaluate the effectiveness of intravitreal triamcinolone injection on
the course of diabetic macular edema. METHODS: Forty-eight eyes of 48 diabetic
patients were treated with 8 mg of intravitreal triamcinolone injection as the
primary therapy for diabetic macular edema. The main outcome measures included
best-corrected visual acuity, fundus fluorescein angio- graphy, macular edema map
values of Heidelberg Retinal Tomograph II (HRT II), and intraocular pressures
before and after intravitreal injection. RESULTS: The visual acuity increased in 
41 of 48 eyes (85.4%) during a mean follow-up time of 7.5 months. The mean
baseline best-corrected logMAR (logarithm of minimal angle of resolution) value
for visual acuities of the patients before intravitreal triamcinolone injection
was 1.17+/-0.20. After treatment, it was 0.85+/-0.29 at 1 month, 0.73+/-0.30 at 3
months, and 0.74+/-0.31 at 6 months, and the differences were significant when
compared with baseline values (for each, p<0.001). The mean edema map values
significantly decreased by 36% at the 6-month examinations when compared with
preinjection values (p<0.001). Average intraocular pressure rose 24.3%, 29.1%,
and 11.8% from baseline at the 1-, 3-, and 6-month follow-up intervals.
Intraocular pressure elevation exceeding 21 mmHg was observed in 8 of 48 eyes
(16.6%), but was controlled with topical antiglaucomatous medications in all
eyes. CONCLUSIONS: Intravitreal triamcinolone application provides significant
improvement in visual acuity of diabetic patients and clinical course of macular 
edema, and may therefore be a promising approach in the primary treatment of
diabetic macular edema.

PMID: 15638105 [PubMed - indexed for MEDLINE]

2080: Ophthalmic Res. 2005 Jan-Feb;37(1):34-42. Epub 2004 Dec 30.

Changes in foveal thickness and macular function after transpupillary
thermotherapy for age-related macular degeneration.

Ishikawa K, Terasaki H, Kobayashi C, Niwa Y, Piao CH, Ito Y, Kondo M, Miyake Y.

Department of Ophthalmology, Nagoya University School of Medicine, Nagoya, Japan.

PURPOSE: To evaluate the effect of transpupillary thermotherapy (TTT) on foveal
thickness and macular function in eyes with choroidal neovascularization (CNV)
associated with age-related macular degeneration. METHODS: Sixteen eyes with
occult CNV and 6 eyes with classic CNV were treated with TTT. Optical coherence
tomography and focal macular electroretinograms (FMERGs) elicited by a 15-degree 
stimulus were performed before, 3 months after TTT in 22 eyes and 6 months after 
TTT in 18 eyes. RESULTS: Before TTT, the fovea in 20 of the 22 eyes with CNV was 
significantly thicker than that of normal subjects. The foveal thickness was
reduced after TTT in 11 of 14 eyes with occult CNV and remained unchanged in 2
eyes. One eye with occult CNV before TTT developed a classic CNV with significant
macular edema and increased foveal thickness 3 months after TTT. The amplitudes
of the FMERGs were reduced in all eyes before TTT. In eyes with occult CNV, the
mean b-wave amplitude increased significantly after TTT (p = 0.0260 at 3 months, 
p = 0.0142 at 6 months). When the change of foveal thickness was less than 20%
after TTT, all eyes with occult CNV had a 30% or more increase in the b-wave
amplitude. In eyes with classic CNV, the mean amplitude of the a- and b-waves did
not change significantly after TTT. CONCLUSIONS: TTT improves macular function in
eyes with occult CNV associated with age-related macular degeneration more when
the change of foveal thickness is slight. Copyright 2005 S. Karger AG, Basel

PMID: 15637420 [PubMed - indexed for MEDLINE]

2081: Am J Pathol. 2005 Jan;166(1):241-51.

Decreased thickness and integrity of the macular elastic layer of Bruch's
membrane correspond to the distribution of lesions associated with age-related
macular degeneration.

Chong NH, Keonin J, Luthert PJ, Frennesson CI, Weingeist DM, Wolf RL, Mullins RF,
Hageman GS.

Department of Ophthalmology and Visual Sciences, Center for Macular Degeneration,
The University of Iowa, 11190E PFP, 200 Hawkins Dr., Iowa City, IA 52240, USA.

Age-related macular degeneration (AMD) is a leading cause of blindness in the
elderly. In its severest form, choroidal neovessels breach the macular Bruch's
membrane, an extracellular matrix compartment comprised of elastin and collagen
laminae, and grow into the retina. We sought to determine whether structural
properties of the elastic lamina (EL) correspond to the region of the macula that
is predilected toward degeneration in AMD. Morphometric assessment of the macular
and extramacular regions of 121 human donor eyes, with and without AMD, revealed 
a statistically significant difference in both the integrity (P < 0.0001) and
thickness (P < 0.0001) of the EL between the macular and extramacular regions in 
donors of all ages. The EL was three to six times thinner and two to five times
less abundant in the macula than in the periphery. The integrity of the macular
EL was significantly lower in donors with early-stage AMD (P = 0.028), active
choroidal neovascularization (P = 0.020), and disciform scars (P = 0.003), as
compared to unaffected, age-matched controls. EL thickness was significantly
lower only in individuals with disciform scars (P = 0.008). The largest gaps in
macular EL integrity were significantly larger in all categories of AMD (each P <
0.0001), as compared to controls. EL integrity, thickness, and gap length in
donors with geographic atrophy did not differ from those of controls. These
structural properties of the macular EL correspond spatially to the distribution 
of macular lesions associated with AMD and may help to explain why the macula is 
more susceptible to degenerative events that occur in this disease.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15632016 [PubMed - indexed for MEDLINE]

2082: Drugs Aging. 2004;21(15):967-92.

Current and future treatment options for nonexudative and exudative age-related
macular degeneration.

Comer GM, Ciulla TA, Criswell MH, Tolentino M.

Department of Ophthalmology, Indiana University School of Medicine, Indianapolis,
Indiana, USA.

Age-related macular degeneration (AMD) is the leading cause of irreversible
visual loss in the industrialised world. Although relatively simple to diagnose
through direct visualisation augmented with rapid sequence fluorescein
angiography, treatment has presented a far greater challenge because the true
aetiology of AMD is largely unknown. Within the past decade, researchers have
introduced many new, potentially promising treatment and prevention options in an
attempt to minimise the damage imparted from AMD. They capitalise on many of the 
theoretical and known factors contributing to AMD progression. A high-dose of an 
orally administered combination of the antioxidants ascorbic acid (vitamin C),
tocopherol (vitamin E) and beta-carotene, in addition to copper and zinc, is the 
only widely accepted preventive therapy. Thermal laser photocoagulation and
verteporfin photodynamic therapy are the only standard treatment options
available based on large scale, randomised, prospective, placebo-controlled
trials; however, efficacy is limited and only a minority of patients who present 
with AMD are eligible for these treatments. Many other preventive and treatment
options are in all phases of clinical studies and expected to change the entire
approach to AMD management in the near future. For example, alternative
antioxidants, drusen ablation, apheresis and HMG-CoA reductase inhibitors have
shown promise in some studies by preventing or slowing the progression of certain
forms of AMD. In addition, alternative photodynamic therapies, low-intensity
laser, antiangiogenic medications, radiation treatment and surgery have
demonstrated the ability, albeit to differing degrees, to inhibit or possibly
even reverse the severe vision loss often associated with AMD characterised by
choroidal neovascularisation.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.
    Review

PMID: 15631528 [PubMed - indexed for MEDLINE]

2083: Optom Vis Sci. 2005 Jan;82(1):11-7.

Predicting reading fluency in patients with macular disease.

Crossland MD, Culham LE, Rubin GS.

Division of Vision Rehabilitation Research, Institute of Ophthalmology,
University College London, United Kingdom. m.crossland@ucl.ac.uk

PURPOSE: Difficulty in reading is the most frequent complaint of patients with
macular disease (MD). This article assesses whether clinical variables measured
at the onset of MD can be used to predict patients' future reading ability.
METHODS: Twenty-five patients with MD were recruited within 4 weeks of the onset 
of symptoms in their second affected eye. Clinical and demographic features were 
recorded at baseline and at the exit point of the study 3 to 12 months later.
Odds ratios (OR's) were constructed to assess the predictive value of these
variables in terms of reading fluency and any change in reading speed at the exit
point of the study. RESULTS: Baseline contrast sensitivity was associated with
future fluent reading (OR, 2.40; interval size, 0.15; 95% confidence interval,
1.13 to 5.07). Age, sex, scotoma size, disease type, visual acuity, and reading
speed were not statistically significant predictors of future fluent reading. It 
was not possible to predict fully in which patients reading speed improved or
deteriorated. CONCLUSIONS: Contrast sensitivity can predict the likelihood of
future fluent reading in patients with MD. Baseline reading speed, visual acuity,
age, disease type, and scotoma size are poor predictors of future reading
performance.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15630399 [PubMed - indexed for MEDLINE]

2084: Ophthalmology. 2005 Jan;112(1):152-8.

Vision-related quality of life in patients with bilateral severe age-related
macular degeneration.

Cahill MT, Banks AD, Stinnett SS, Toth CA.

Duke University Eye Center, Durham, North Carolina 27710, USA.

PURPOSE: To determine the quality of life (QOL) of patients with bilateral severe
age-related macular degeneration (AMD) before macular translocation with 360
degrees peripheral retinectomy. DESIGN: Prospective, consecutive, noncomparative 
case series. METHODS: An observational study assessed vision-related and general 
health QOL using the 25-item National Eye Institute Visual Function Questionnaire
(NEI VFQ-25) and the Medical Outcomes Study 12-item short form (SF-12) surveys,
respectively. Mean QOL scores were correlated with patient age, duration of
vision loss, and visual function. Mean QOL scores in study patients were compared
with mean QOL scores in groups of patients with low vision, patients with AMD of 
varying severity, and reference populations. MAIN OUTCOME MEASURES: National Eye 
Institute VFQ-25 and SF-12 QOL scores. RESULTS: Seventy patients with a mean age 
of 76.4 years were studied. Mean distance visual acuity (VA) was 62.4 (Early
Treatment Diabetic Retinopathy Study letters), mean near VA was 0.81 (logarithm
of the minimum angle of resolution), and mean reading speed was 74.9 words per
minute. Important NEI VFQ-25 quality of vision subscales (general vision,
difficulty with distance tasks, difficulty with near tasks) and vision-specific
subscales (dependency, role difficulties, mental health, social function
limitations) tended to correlate negatively with increasing patient age and
duration of vision loss, but correlated positively with better VA and reading
speed. The mean QOL scores for these important quality of vision and
vision-specific subscales were significantly worse than or similar to mean scores
in patients with low vision, and significantly worse than scores in patients with
AMD of varying severity and a reference population. The mean SF-12 physical
composite score in study patients was similar to that seen in patients with AMD
of varying severity, but significantly higher than that in patients with low
vision and a reference population. The SF-12 mental composite score in study
patients was similar to those of all 3 comparison groups. CONCLUSIONS: Patients
with bilateral severe AMD have vision-related QOL similar to that of patients
with low vision but significantly worse than those of patients with AMD of
varying severity and persons without eye disease. This inability to perform
vision-related daily tasks is not related to general health problems.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15629836 [PubMed - indexed for MEDLINE]

2085: Ophthalmology. 2005 Jan;112(1):144-51.

Quality of life after macular translocation with 360 degrees peripheral
retinectomy for age-related macular degeneration.

Cahill MT, Stinnett SS, Banks AD, Freedman SF, Toth CA.

Duke University Eye Center, Durham, North Carolina 27710, USA.

PURPOSE: To determine patients' quality of life (QOL) after macular translocation
with 360 degrees peripheral retinectomy (MT360) for age-related macular
degeneration. DESIGN: Prospective, interventional, consecutive, noncomparative
case series. METHODS: A prospective study assessed QOL 1 year after MT360 and its
relation to postoperative visual function. The 25-item National Eye Institute
Visual Function Questionnaire (NEI VFQ-25) and the Medical Outcomes Study 12-item
short form (SF-12) health survey were used to assess vision-related QOL and
general health, respectively. Surveys were administered preoperatively and
postoperatively. Postoperative NEI VFQ-25 QOL and SF-12 subscale scores for all
patients were compared with the preoperative scores. Preoperative and
postoperative distance and near visual acuities (VAs) and reading speed were
assessed. Changes in NEI VFQ-25 QOL subscale scores were compared in patients
with and without improved visual function. Postoperative NEI VFQ-25 QOL subscale 
scores in patients with distance VA of >or=69 Early Treatment Diabetic
Retinopathy Study letters, near VA of >or=20/70, and reading speed of >or=90
words per minute were compared with subscale scores in patients with worse
postoperative visual function. MAIN OUTCOME MEASURES: National Eye Institute
VFQ-25 and SF-12 QOL scores and their association with distance VA, near VA, and 
reading speed. RESULTS: In total, 50 patients with a mean age of 76.9 years were 
studied. Postoperative mean NEI VFQ-25 QOL scores were higher than the
preoperative mean scores, and this difference was significant for important
vision-specific subscales. Patients with improved visual function had greater
mean changes in NEI VFQ-25 QOL scores than those with no improvement. Patients
with the outlined higher levels of visual function had greater mean NEI VFQ-25
QOL scores than those who had worse visual function. Preoperative and
postoperative mean SF-12 QOL scores were similar. CONCLUSIONS: Macular
translocation with 360 degrees peripheral retinectomy was associated with
improvement in vision-related QOL. The amount of improvement was greatest in
patients with postoperative improvement in visual function, and the best
postoperative vision-related QOL was seen in patients with better postoperative
visual function. This was not associated with a change in patients' general
health.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15629835 [PubMed - indexed for MEDLINE]

2086: Ophthalmology. 2005 Jan;112(1):132-8.

5-year incidence of age-related maculopathy in the Reykjavik Eye Study.

Jonasson F, Arnarsson A, Peto T, Sasaki H, Sasaki K, Bird AC.

Department of Ophthalmology, University of Iceland, Reykjavik, Iceland.
fridbert@landspitali.is <fridbert@landspitali.is>

PURPOSE: To examine the age- and gender-specific 5-year incidence of age-related 
maculopathy (ARM) and age-related macular degeneration (AMD) in citizens of
Reykjavik. DESIGN: Population-based, prospective cohort study. PARTICIPANTS: The 
cohort was a population-based random sample of citizens 50 years and older. Of
1379 eligible subjects, 1045 had a baseline examination in 1996; 846 of the 958
survivors (88.2%) had a 5-year follow-up examination in 2001. METHODS: The
incidence of various characteristics of drusen and pigmentary changes that are
typical of ARM were determined using the international classification and grading
system for ARM and AMD. MAIN OUTCOME MEASURES: Early ARM and AMD were assessed by
masked grading of stereo fundus photographs. RESULTS: Hypopigmentation developed 
at 5 years in 10.7% of people 50 to 59 years of age (95% confidence interval
[CI], 6.9-14.4) and in 25.7% those 70 to 79 years of age (95% CI, 18.4-33.0) at
baseline. Age-related macular degeneration developed in no one who was 50 to 59
years of age at baseline. Geographic atrophy (GA) developed in 4.6% (95% CI,
1.2-7.9) and exudative AMD in none of those who were 70 years and older at
baseline. CONCLUSIONS: Geographic atrophy is the predominant type of AMD in
Iceland, and the ratio of GA to neovascular AMD is higher than in racially
similar populations.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15629833 [PubMed - indexed for MEDLINE]

2087: Am J Ophthalmol. 2004 Dec;138(6):1051-3.

MELAS A3243G mitochondrial DNA mutation and age related maculopathy.

Jones M, Mitchell P, Wang JJ, Sue C.

Kolling Institute, Department of Neurogenetics, University of Sydney, Australia.

PURPOSE: To determine whether mitochondrial DNA mutations play a role in the
development of age related maculopathy (ARM). DESIGN: Case report. METHODS: Hair 
follicles were collected from 3557 persons aged 49 years or older during the Blue
Mountains Eye Study. General health measures were assessed and a detailed eye
examination was performed, including stereo retinal photography of the macula,
and other retinal fields. ARM was graded according to international
classification. Polymerase chain reaction and restriction fragment length
polymorphism analysis was performed to detect the MELAS A3243G mutation in 570
subjects identified to have signs of Early or Late ARM, as well as in age- and
gender-matched controls. RESULTS: Only one participant with Early ARM, mild
hearing loss, hypertension, ischemic heart disease, and asthma was found to have 
the MELAS A3243G mutation. CONCLUSIONS: The MELAS A3243G mutation appears to be a
very rare cause of typical ARM in the general population.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 15629304 [PubMed - indexed for MEDLINE]

2088: Am J Ophthalmol. 2004 Dec;138(6):1048-9.

Macular edema as the only ocular finding of tuberculosis.

Torres RM, Calonge M.

Ocular Immunology Unit, Instituto Universitario Oftalmobiología Aplicada,
University of Valladolid, Valladolid, Spain.

PURPOSE: To describe an infrequent presentation of ocular tuberculosis. DESIGN:
Retrospective observational case report. METHODS: A 61-year-old woman presented
with decreased vision in her right eye and cystoid macular edema resistant to
periocular corticosteroid treatment. There were no other findings. RESULTS:
Diagnosis of probable underlying tuberculosis uveitis with macular edema as the
only ocular manifestation was established based on a clinical history of possible
tuberculosis during her infancy. Additionally, there were residual findings in
the patient's chest x-ray, a positive Mantoux reaction, and Mycobacterium
tuberculosis in sputum. Specific treatment was implemented for nine months.
Cystoid macular edema resolved completely, visual acuity improved (20/20), and no
remission occurred during two years of follow-up. CONCLUSIONS: In cases of
idiopathic cystoid macular edema, tuberculosis should be considered as a
potential cause. When treated, both are curable.

Publication Types: 
    Case Reports

PMID: 15629302 [PubMed - indexed for MEDLINE]

2089: Am J Ophthalmol. 2004 Dec;138(6):1010-5.

Trace microalbuminuria in inflammatory cystoid macular edema.

van Kooij B, Fijnheer R, Roest M, Rothova A.

F.C. Donders Institute of Ophthalmology, University Medical Center, Utrecht, The 
Netherlands. b.vankooij@oogh.azu.nl

PURPOSE: To assess the role of cardiovascular morbidity, its risk factors, and
microalbuminuria in the development of inflammatory cystoid macular edema (CME). 
DESIGN: A matched case-control study. METHODS: study population: We included 24
consecutive patients with uveitis and CME. Twenty four uveitis patients without
CME, matched for age and duration of uveitis served as controls. intervention and
observation procedures: Patients and controls were interviewed for the presence
of cardiovascular risk factors and cardiovascular morbidity. All medications were
registered. Morning urinary albumin concentration was measured, as well as blood 
pressure, C-reactive protein, and creatinine in blood. Patients suffering from
diabetes mellitus were excluded from this study. main outcome measures: The
presence of cardiovascular morbidity and its risk factors and microalbuminuria in
uveitis patients with and without CME. RESULTS: We found a positive association
between trace- and/or microalbuminuria and inflammatory CME (P = .001; odds ratio
13.0, 95% CI 2.5 to 68.1 and P = .015; odds ratio 5.9, 95% CI 1.6 to 22.6), but
no relation between CME and cardiovascular morbidity or its risk factors. No
additional association between trace- and/or any microalbuminuria and general
characteristics of patients, specific factors related to general disease as a
cause of ocular inflammation, location of uveitis, duration of uveitis, and
medication was found. CONCLUSIONS: The presence of trace- and/or microalbuminuria
in inflammatory CME might indicate the presence of early systemic vascular
disease and carry the risk of developing CME. This finding brings new insight
into the pathogenesis of CME and could open up new avenues for the treatment of
CME.

PMID: 15629293 [PubMed - indexed for MEDLINE]

2090: Am J Ophthalmol. 2004 Dec;138(6):970-7.

Inter-eye difference in diabetic macular edema after unilateral intravitreal
injection of triamcinolone acetonide.

Jonas JB, Harder B, Kamppeter BA.

Department of Ophthalmology, Faculty of Clinical Medicine, Mannheim of the
Ruprecht-Varls University, Heidelberg, Germany.
Jost.Jonas@ma.augen.uni-heidelberg.de

PURPOSE: To report on visual outcome of patients receiving intravitreal
triamcinolone acetonide for treatment of diffuse diabetic macular edema. DESIGN: 
Prospective, comparative clinical interventional study. METHODS: Setting:
Institutional. patient population: The study included 25 consecutive patients (50
eyes) with bilateral diabetic macular edema. Intervention procedure: Unilateral
intravitreal injection of about 20 mg triamcinolone acetonide into the eye (study
group) more severely affected by diabetic maculopathy. The contralateral eyes
served as control group. Mean follow-up was 7.1 +/- 4.1 months. MAIN OUTCOME
MEASURE: Visual acuity, intraocular pressure. RESULTS: In the study group, visual
acuity increased significantly (P < or = .001) by 3.0 +/- 2.6 Snellen lines to a 
peak at two to six months after the injection, and decreased significantly (P =
.001) towards the end of follow up. At the end of follow-up, visual acuity was
higher, not significantly (P = .18) higher, than at baseline. An increase in
visual acuity was found in 23 eyes (92%). In the control group, differences
between visual acuity at baseline and at any of the re-examinations during
follow-up were not significant (P > .10). In an intra-individual inter-eye
comparison, gain in visual acuity was significantly (P < .05) higher in the
injected eyes, for the measurements obtained up to four months after injection.
CONCLUSIONS: Intravitreal triamcinolone acetonide may temporarily increase visual
acuity in eyes with diabetic macular edema.

Publication Types: 
    Clinical Trial
    Comparative Study

PMID: 15629288 [PubMed - indexed for MEDLINE]

2091: Am J Ophthalmol. 2004 Dec;138(6):907-14.

Comment in:
    Am J Ophthalmol. 2004 Dec;138(6):1037-8.    Am J Ophthalmol. 2005 Jun;139(6):1146; author reply 1146-7.

Vitrectomy with or without arteriovenous adventitial sheathotomy for macular
edema associated with branch retinal vein occlusion.

Yamamoto S, Saito W, Yagi F, Takeuchi S, Sato E, Mizunoya S.

Department of Ophthalmology and Visual Science, Chiba University Graduate School 
of Medicine, Chiba. shuyama@faculty.chiba-u.jp

PURPOSE: compare the results of vitrectomy with or without arteriovenous (AV)
crossing sheathotomy for macular edema associated with branch retinal vein
occlusion (BRVO). DESIGN: Interventional case series. METHODS: A retrospective
study of 36 eyes with BRVO-associated macular edema. Twenty eyes underwent AV
sheathotomy (AS group), and 16 eyes underwent posterior vitreous detachment (PVD 
group). Best-corrected visual acuity (BCVA), fluorescein angiography (FA), and
optical coherence tomography to determine foveal thickness were conducted
preoperatively and at 12 months postoperatively. RESULTS: The mean postoperative 
BCVAs were significantly better in both the AS and the PVD group (P = .008 and P 
= .001, respectively). Foveal thickness decreased significantly 1 month after
surgery in both groups (P = .002 and P = .007) and continued to decrease up to 12
months. The postoperative mean BCVA and improvement of BCVA and foveal thickness 
were not significantly different for the two groups at any postoperative period. 
Postoperative FA showed reperfusion of the occluded vein in 10 eyes in the AS
group and 2 eyes in the PVD group, and formation of shunt vessels at the AV
crossing site or around the macular region in all of the other eyes of both
groups. CONCLUSIONS: Both AV sheathotomy and simple PVD significantly reduced
macular edema associated with BRVO. However, there was no significant difference 
in the improvement of macular function following either procedure. Postoperative 
improvement of retinal circulation by either reperfusion of the occluded vein or 
collateral vessel formation was found. This accounted for functional and
morphologic improvements.

Publication Types: 
    Comparative Study

PMID: 15629280 [PubMed - indexed for MEDLINE]

2092: Wien Klin Wochenschr. 2004 Nov 30;116(21-22):737-43.

Incidence of patients presenting with exudative maculopathy and neovascular
retinal disease in an urban population.

Ergun E, Abramov A, Zawinka C, Stur M.

Department of Ophthalmology, University Vienna Medical School, Vienna, Austria.
erdem.ergun@meduniwien.ac.at

PURPOSE: To determine the incidence of exudative macular and neovascular retinal 
disease presenting within a defined urban population. STUDY DESIGN: prospective, 
observational, consecutive case series. PATIENTS AND METHODS: Patients referred
to ten ophthalmic centers within a defined 10-week period with a newly diagnosed 
exudative macular and/or neovascular retinal disease were examined
fundoscopically, angiographically and quantified according to age and underlying 
disease. RESULTS: A total of 527 eyes of 426 patients were referred. The most
frequent disease was neovascular age-related macular degeneration (AMD, 199/527, 
37.8%, 184 patients), followed by diabetic maculopathy and/or proliferative
diabetic retinopathy (199/527, 37.8%, 128 patients) and venous occlusive disease 
(67/527, 12.7%, 67 patients). The majority of neovascular AMD consisted of occult
without classic choroidal neovascularization (CNV, 115/ 199, 57.8%);
predominantly classic CNV was seen more often than minimally classic CNV (43/199,
21.6% vs. 27/ 199, 13.6%). The overwhelming majority of the diabetic cases had
diabetic macular edema (179/199, 89.9%); only 10.1% had vasoproliferative
disease. All other causes of CNV, macular edema/exudation, and retinal
neovascularization were observed in < 5% of all patients. CONCLUSION: The main
causes of exudative maculopathy are CNV due to neovascular AMD and diabetic
macular edema. Proliferative diabetic retinopathy is the main cause of retinal
neovascularization. The number of patients with neovascular AMD presents a future
challenge for ophthalmologists.

Publication Types: 
    Multicenter Study

PMID: 15628644 [PubMed - indexed for MEDLINE]

2093: N Engl J Med. 2004 Dec 30;351(27):2805-16.

Comment in:
    ACP J Club. 2005 Jul-Aug;143(1):18.    N Engl J Med. 2004 Dec 30;351(27):2863-5.    N Engl J Med. 2005 Apr 21;352(16):1720-1; author reply 1720-1.

Pegaptanib for neovascular age-related macular degeneration.

Gragoudas ES, Adamis AP, Cunningham ET Jr, Feinsod M, Guyer DR; VEGF Inhibition
Study in Ocular Neovascularization Clinical Trial Group.

Retina Service, Massachusetts Eye and Ear Infirmary and Harvard Medical School,
243 Charles St., Boston, MA 02114, USA. evangelos_gragoudas@meei.harvard.edu

BACKGROUND: Pegaptanib, an anti-vascular endothelial growth factor therapy, was
evaluated in the treatment of neovascular age-related macular degeneration.
METHODS: We conducted two concurrent, prospective, randomized, double-blind,
multicenter, dose-ranging, controlled clinical trials using broad entry criteria.
Intravitreous injection into one eye per patient of pegaptanib (at a dose of 0.3 
mg, 1.0 mg, or 3.0 mg) or sham injections were administered every 6 weeks over a 
period of 48 weeks. The primary end point was the proportion of patients who had 
lost fewer than 15 letters of visual acuity at 54 weeks. RESULTS: In the combined
analysis of the primary end point (for a total of 1186 patients), efficacy was
demonstrated, without a dose-response relationship, for all three doses of
pegaptanib (P<0.001 for the comparison of 0.3 mg with sham injection; P<0.001 for
the comparison of 1.0 mg with sham injection; and P=0.03 for the comparison of
3.0 mg with sham injection). In the group given pegaptanib at 0.3 mg, 70 percent 
of patients lost fewer than 15 letters of visual acuity, as compared with 55
percent among the controls (P<0.001). The risk of severe loss of visual acuity
(loss of 30 letters or more) was reduced from 22 percent in the sham-injection
group to 10 percent in the group receiving 0.3 mg of pegaptanib (P<0.001). More
patients receiving pegaptanib (0.3 mg), as compared with sham injection,
maintained their visual acuity or gained acuity (33 percent vs. 23 percent;
P=0.003). As early as six weeks after beginning therapy with the study drug, and 
at all subsequent points, the mean visual acuity among patients receiving 0.3 mg 
of pegaptanib was better than in those receiving sham injections (P<0.002). Among
the adverse events that occurred, endophthalmitis (in 1.3 percent of patients),
traumatic injury to the lens (in 0.7 percent), and retinal detachment (in 0.6
percent) were the most serious and required vigilance. These events were
associated with a severe loss of visual acuity in 0.1 percent of patients.
CONCLUSIONS: Pegaptanib appears to be an effective therapy for neovascular
age-related macular degeneration. Its long-term safety is not known. Copyright
2004 Massachusetts Medical Society.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15625332 [PubMed - indexed for MEDLINE]

2094: Am J Public Health. 2005 Jan;95(1):75-7.

Geographic variation in the prevalence of macular disease among elderly medicare 
beneficiaries in Kansas.

Holcomb CA, Lin MC.

Department of Human Nutrition, Kansas State University, 210 Justin Hall,
Manhattan, KS 66506-1407, USA. carolann@ksu.edu

This study used Medicare Part B claims and enrollment data to estimate the
prevalence of macular disease in Kansas at county and area levels. Spatial
analysis by aggregated county clusters was assessed with standardized prevalence 
ratios and 95% confidence intervals, and a thematic map was produced to
illustrate geographic distribution. A total of 17888 unduplicated claims were
identified among 335132 beneficiaries older than age 64 years. Compared with the 
state prevalence of 5.34%, the central agricultural area showed a
disproportionately high macular disease prevalence.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15623863 [PubMed - indexed for MEDLINE]

2095: Br J Ophthalmol. 2005 Jan;89(1):87-91.

A method of drusen measurement based on reconstruction of fundus background
reflectance.

Smith RT, Chan JK, Nagasaki T, Sparrow JR, Barbazetto I.

Harkness Eye Institute, Columbia University College of Pysicians and Surgeons,
New York, NY 10032, USA. rts1@columbia.edu

BACKGROUND: The hallmarks of age related macular degeneration (AMD) are the
subretinal deposits known as drusen. Current manual methods of drusen
segmentation and quantification are laborious and subjective. The authors
introduced a digital method and tested it for accuracy and reliability. METHODS: 
Fourteen eyes with drusen were selected. The authors digitally reconstructed the 
macular background using normal background areas ("dots") fitted to quadratic
polynomials in two zones. The model was used to level the reflectance for the
purpose of segmenting drusen by a global threshold. Measurements of drusen areas 
were compared with those of a semi-automated background levelling technique and
manual drawings from stereo pairs. RESULTS: Intraobserver reproducibility had
standard deviations from 0.1% to 4.1%. Interobserver reproducibility yielded 95% 
limits of agreement of -2.7% to 6.3%. The dots method compared with manual
drawings and with the semi-automated method had 95% limits of agreement of -8.3% 
to 2.8% and -7.1% to 4.8%, respectively. CONCLUSIONS: The dots method was
reproducible and accurate with respect to validated methods. It provided less
total operating time and greater precision than that of standard fundus photo
grading. With implementation of commercial software, this technique for macular
image analysis has potential for use in clinical research.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15615753 [PubMed - indexed for MEDLINE]

2096: Br J Ophthalmol. 2005 Jan;89(1):81-6.

A randomised controlled feasibility trial of vitrectomy versus laser for diabetic
macular oedema.

Thomas D, Bunce C, Moorman C, Laidlaw DA.

Department of Ophthalmology, St Thomas' Hospital, Lambeth Palace Road, London SE1
7EH, UK.

AIM: (1) To evaluate whether vitrectomy is preferable to further macular laser in
improving visual acuity and resolving retinal thickening in patients with
diabetic macular oedema (DMO) despite previous laser and no macular traction. (2)
To determine the feasibility of further trials in this population in terms of
magnitude of comparative clinical effect, rate of recruitment, and loss to follow
up. METHODS: A randomised controlled feasibility study. Patients with DMO and a
visual acuity of 0.3 logMAR (6/12) or worse after one or more macular laser
treatments were randomised on a 1:1 basis to either pars plana vitrectomy (PPV)
with internal limiting membrane (ILM) peeling or further macular laser. Patients 
with a posterior vitreous detachment, biomicroscopic evidence of retinal
traction, or a taut thickened posterior hyaloid (TTPH) were excluded. Primary
outcome measures were (1) best corrected logMAR visual acuity, (2) mean central
macular thickness on optical coherence tomography, and (3) rate of recruitment
and loss to follow up. Analysis was on an intention to treat basis. RESULTS: 19
patients were randomised to PPV and 21 to further macular laser. The mean
baseline logMAR visual acuity was 0.65 (SD 0.28) for the group randomised to PPV 
and 0.60 (0.23) for the group randomised to laser. The mean change in best
corrected visual acuity of the vitrectomy group was deterioration by 0.05 logMAR,
while in the control group the mean change was an improvement of 0.03 logMAR. The
median (interquartile range) baseline central macular thickness was 403 (337,
492) for the group randomised to PPV and 387 (298, 491) for the controls
randomised to laser. The median change in central macular thickness from baseline
to review in the vitrectomy group was a thinning by 73 mum (20%) and by 29 mum
(10.7%) in the control laser group. This single centre was able to recruit 40
patients in 18 months with follow up of 82% at 1 year. CONCLUSION: A randomised
controlled trial was found to be potentially feasible in this population, the
rate of recruitment was however slow and one in five patients were lost to follow
up because of death and ill health. These data provide little evidence in terms
of visual acuity and macular thickness of any benefit of vitrectomy over further 
macular laser in patients with an attached hyaloid, DMO despite previous laser,
and no clinically evident macular traction or TTPH.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15615752 [PubMed - indexed for MEDLINE]

2097: Br J Ophthalmol. 2005 Jan;89(1):74-80.

Subthreshold diode micropulse photocoagulation for the treatment of clinically
significant diabetic macular oedema.

Luttrull JK, Musch DC, Mainster MA.

Private Practice, 3160 Telegraph Road, Suite 230, Ventura, CA, 93003, USA.
jkluttrull@aol.com

AIM: To report the visual and clinical outcomes of a pilot study of subthreshold 
diode micropulse (SDM) laser photocoagulation for clinically significant diabetic
macular oedema (CSMO). METHODS: The results of infrared (810 nm) SDM laser
photocoagulation for CSMO were retrospectively reviewed in 95 eyes of 69
consecutive patients with mild to moderate non-proliferative diabetic
retinopathy. The same laser parameters were used for each patient. Only the
number of laser applications varied between patients, depending on their macular 
findings. Primary outcome measures were Snellen visual acuity, fluorescein
angiographic leakage, and CSMO status. RESULTS: Visual acuity was stable or
improved in 85% of treated eyes, with a mean follow up of 12.2 months (range 3-29
months). CSMO decreased in 96% and resolved in 79% of treated eyes. No adverse
laser events occurred. No laser lesions were detectable ophthalmoscopically or
angiographically after treatment, consistent with calculations based on ANSI
Z136.1 laser safety standards suggestive of only histologically detectable tissue
effects at the laser exposure levels. No laser scarring was observed during the
follow up period. CONCLUSION: Subthreshold diode micropulse laser
photocoagulation minimises chorioretinal damage in the management of CSMO and
demonstrates a beneficial effect on visual acuity and CSMO resolution.
Prospective studies are needed to fully evaluate this technique.

PMID: 15615751 [PubMed - indexed for MEDLINE]

2098: Epidemiology. 2005 Jan;16(1):114-20.

Comment in:
    Epidemiology. 2005 Jul;16(4):592.    Epidemiology. 2005 Sep;16(5):710.

The mediation proportion: a structural equation approach for estimating the
proportion of exposure effect on outcome explained by an intermediate variable.

Ditlevsen S, Christensen U, Lynch J, Damsgaard MT, Keiding N.

Department of Biostatistics, Institute of Public Health, University of
Copenhagen, Denmark. S.Ditlevsen@pubhealth.ku.dk

It is often of interest to assess how much of the effect of an exposure on a
response is mediated through an intermediate variable. However, systematic
approaches are lacking, other than assessment of a surrogate marker for the
endpoint of a clinical trial. We review a measure of "proportion explained" in
the context of observational epidemiologic studies. The measure has been much
debated; we show how several of the drawbacks are alleviated when exposures,
mediators, and responses are continuous and are embedded in a structural equation
framework. These conditions also allow for consideration of several intermediate 
variables. Binary or categorical variables can be included directly through
threshold models. We call this measure the mediation proportion, that is, the
part of an exposure effect on outcome explained by a third, intermediate
variable. Two examples illustrate the approach. The first example is a randomized
clinical trial of the effects of interferon-alpha on visual acuity in patients
with age-related macular degeneration. In this example, the exposure, mediator
and response are all binary. The second example is a common problem in social
epidemiology-to find the proportion of a social class effect on a health outcome 
that is mediated by psychologic variables. Both the mediator and the response are
composed of several ordered categorical variables, with confounders present.
Finally, we extend the example to more than one mediator.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15613954 [PubMed - indexed for MEDLINE]

2099: Gerontologist. 2004 Dec;44(6):836-43.

Development and pilot evaluation of a psychosocial intervention program for
patients with age-related macular degeneration.

Birk T, Hickl S, Wahl HW, Miller D, Kämmerer A, Holz F, Becker S, Völcker HE.

German Center for Research on Aging at the University of Heidelberg, Bergheimer
Strausse 20, Heidelberg, D-69115, Germany. wahl@dzfa.uni-heidelberg.de.

PURPOSE: The psychosocial needs of patients suffering from severe visual loss
associated with advanced age-related macular degeneration (ARMD) are generally
ignored in the clinical routine. The aim of this study was to develop and
evaluate a psychosocial intervention program for ARMD patients. This intervention
program was based on six modules carried out in five weekly group sessions. These
modules included (a) progressive muscle relaxation; (b) exchange of
disease-related experiences; (c) understanding the connections among thought,
emotion, and behavior; (d) description of and emphasis on the use of available
resources; (e) improvement of general problem-solving skills, and (f) information
exchange on ARMD-related treatment and rehabilitation options. DESIGN AND
METHODS: A preliminary evaluation of this intervention program was performed with
the aid of a preintervention-postintervention comparison-group research design,
which included 14 individuals (mean age of 73.1 years) in the interventional
group and 8 participants (mean age of 72.6 years) in the comparison group. The
preintervention-postintervention assessment addressed a set of emotional (e.g.,
positive and negative affect) as well as behavioral (e.g., limitations to
activities and instrumental activities of daily living) outcome measures.
RESULTS: Although the sample size of the pilot evaluation test was small, our
results demonstrate the usefulness of this pilot program. A statistical analysis 
comparing the interventional group with the comparison group revealed that the
intervention group benefited from the program in five out of six outcome
measures. IMPLICATIONS: Psychosocial group intervention is a promising approach
to improve the quality of life in patients suffering from ARMD.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial

PMID: 15611220 [PubMed - indexed for MEDLINE]

2100: Vision Res. 2005 Feb;45(4):461-8.

An application of threshold-versus-intensity functions in automated static
perimetry.

Herse P.

School of Optometry and Vision Science, University of New South Wales, Sydney,
NSW 2053, Australia. p.herse@unsw.edu.au

Increment thresholds were measured over a range of adapting illuminances using a 
modified automated static perimeter. The data were fitted to a threshold versus
intensity model (logT - logT(0) + log((A + A(0))/A(0))n) and the values logT(0)
and logA(0) estimated. The effect of eccentricity and age on logT(0) and logA(0) 
was examined in normal subjects. A small group of patients with ocular disease
were then assessed. Macular degeneration appeared to act as disease processes
acting near the photoreceptor (d1 model). Glaucoma seemed to act near the site of
retinal gain (d3 model). This analysis method may be of value in developing light
adaptation strategies in people with ocular disease.

PMID: 15610750 [PubMed - indexed for MEDLINE]

2101: Acta Ophthalmol Scand. 2004 Dec;82(6):695-700.

The effects of coloured light filter overlays on reading rates in age-related
macular degeneration.

Eperjesi F, Fowler CW, Evans BJ.

Neurosciences Research Institute, School of Life and Health Sciences, Aston
University, Birmingham, UK. f.eperjesi@aston.ac.uk

PURPOSE: To determine the effect of coloured light filter overlays on reading
rates for people with age-related macular degeneration (AMD). METHOD: Using a
prospective clinical trial design, we examined the null hypothesis that coloured 
light filter overlays do not improve reading rates in AMD when compared to a
clear filter. Reading rates for 12 subjects with non-exudative AMD, associated
with a relative scotoma and central fixation (mean age 81 years, SD 5.07 years)
were determined using the Rate of Reading Test (printed, nonsense, lower case
sans serif, stationary text) with 10 different, coloured light filter overlays
(Intuitive Overlays); figures in brackets are percentage transmission values);
rose (78%), pink (78%), purple (67%), aqua (81%), blue (74%), lime-green (86%),
mint-green (85%), yellow (93%), orange (83%) and grey (71%). A clear overlay
(Roscolene # 00) (360 cdm-2) with 100% transmittance was used as a control.
RESULTS: Anova indicated that there was no statistically significant difference
in reading rates with the coloured light filter overlays compared to the clear
filter. Furthermore, chi-squared analysis indicated that the rose, purple and
blue filters had a significantly poorer overall ranking in terms of reading rates
compared to the other coloured and clear light filters. CONCLUSION: Coloured
light filter overlays are unlikely to provide a clinically significant
improvement in reading rates for people with non-exudative AMD associated with a 
relative scotoma and central fixation.

Publication Types: 
    Clinical Trial

PMID: 15606466 [PubMed - indexed for MEDLINE]

2102: Acta Ophthalmol Scand. 2004 Dec;82(6):686-90.

Comment in:
    Acta Ophthalmol Scand. 2005 Oct;83(5):622.

Longterm results in surgical removal of subfoveal choroidal neovascularization in
age-related macular degeneration.

Guthoff R, Schrader W.

Department of Ophthalmology, Julius Maximilians University, Würzburg, Germany.
r.guthoff@mail.uni-wuerzburg.de

PURPOSE: This study aimed to analyse visual outcome, surgical complications and
recurrence rates 3 years after removal of subretinal choroidal neovascularization
(CNV) in patients with age-related macular degeneration (AMD). METHODS: The study
involved a retrospective analysis of 50 eyes of 50 patients who underwent
surgical removal of CNV in AMD between February 1996 and June 1998. The minimum
follow-up period was 36 months. Improvement or worsening of visual acuity (VA)
was defined as a change of more than two lines. RESULTS: The mean reduction in VA
was 2.2 +/- 6.9 lines. Visual acuity improved in 12 eyes, remained stable in 16
eyes and worsened in 22 eyes. Recurrence of CNV occurred in three eyes.
CONCLUSION: After surgical excision of age-related subfoveal CNV, VA improved or 
stabilized in a large group of patients. Considering the development of VA and
the low recurrence rate, surgical treatment seems to be beneficial compared to
the natural course of CNV over a longterm follow-up of more than 3 years.

PMID: 15606464 [PubMed - indexed for MEDLINE]

2103: Acta Ophthalmol Scand. 2004 Dec;82(6):651-5.

Photodynamic therapy with verteporfin in patients with age-related macular
degeneration and juxtafoveal choroidal neovascularization.

Frennesson CI.

Department of Ophthalmology, Linköping University, Linköping, Sweden.
Christina.Frennesson@lio.se

PURPOSE: To investigate the effects of photodynamic therapy (PDT) on juxtafoveal 
choroidal neovascularization (CNV) in age-related macular degeneration (AMD) in a
clinical patient material. METHODS: Thirty eyes in 30 consecutive patients with
AMD and a juxtafoveal CNV underwent PDT with verteporfin with standard
parameters. The patients were followed up for 12 months and retreated every 12
weeks in the event of leakage from CNV. Nineteen patients (63.3%) had a
predominantly classic CNV, eight (26.7%) had a 100% occult CNV and three (10%)
had a minimally classic lesion. In 27 patients (90%) the lesion was < or = 3 MPS 
(Macular Photocoagulation Study) disc diameters and < or = 3 MPS disc areas.
RESULTS: There was a positive correlation between duration of symptoms and loss
of visual acuity at 12 months (p < 0.02). For predominantly classic lesions,
there was a positive correlation between duration of symptoms and lesion size (p 
< 0.005). At 12 months, leakage had stopped after 3.3 +/- 0.9 treatments in 80%
of the patients. Visual acuity remained stable in 63.3% of the patients.
CONCLUSION: Photodynamic therapy appears to be beneficial in patients with AMD
and juxtafoveal CNV.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15606459 [PubMed - indexed for MEDLINE]

2104: Acta Ophthalmol Scand. 2004 Dec;82(6):645-50.

Encouraging results of photodynamic therapy with Visudyne in a clinical patient
material of age-related macular degeneration.

Frennesson CI, Nilsson SE.

Department of Ophthalmology, Linköping University, Linköping, Sweden.
Christina.Frennesson@lio.se

PURPOSE: To investigate the effects of photodynamic therapy (PDT) on subfoveal
choroidal neovascularization (CNV) in age-related macular degeneration (AMD) in a
Swedish patient material with smaller lesions than those investigated in the TAP 
(Treatment of Age-related Macular Degeneration with Photodynamic Therapy) and VIP
(Verteporfin in Photodynamic Therapy) Studies. METHODS: Photodynamic therapy with
verteporfin was performed according to the results and recommendations of the TAP
and VIP Studies. The patients were followed up for 12 months and retreatment was 
performed every 12 weeks when leakage from CNV was present. Of the 100 eyes in
the first 100 patients with a follow-up period of 12 months, 59% had a
predominantly classic lesion, 36% had an occult-only lesion and 5% had a
minimally classic lesion. The greatest linear dimension (GLD) was < or =3 MPS
(Macular Photocoagulation Study) disc diameters (DD) in 73%, 39% and 20% of
lesions, respectively, for the three groups. The actual lesion area was < or =3
MPS disc areas (DA) in 85%, 50% and 40% of lesions, respectively. There was a
positive correlation (p < 0.05) between the duration of symptoms and GLD, as well
as between the duration of symptoms and the lesion area (p < 0.02). RESULTS: At
12 months, visual acuity had remained stable or increased by > or =3 lines
(ETDRS) in 61% of patients with predominantly classic lesions, in 61% of patients
with occult-only lesions and in 60% of patients with minimally classic lesions.
Leakage had stopped after 2.9 +/- 0.9 treatments in 77% of the total group of
patients. CONCLUSION: The visual outcome was comparable to those of the TAP and
VIP Studies (p > 0.3). Regarding the effect on leakage, however, our results are 
far better than those of the TAP and VIP Studies. The proportion of patients in
which leakage had stopped was almost three times that of the TAP (27%) and VIP
(26%) Studies. It seems likely that this difference was caused by the fact that
the lesions in our study were much smaller, on average, than those in the TAP and
VIP Studies.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15606458 [PubMed - indexed for MEDLINE]

2105: Arch Ophthalmol. 2004 Dec;122(12):1801-7.

Vitreous levels of vascular endothelial growth factor and stromal-derived factor 
1 in patients with diabetic retinopathy and cystoid macular edema before and
after intraocular injection of triamcinolone.

Brooks HL Jr, Caballero S Jr, Newell CK, Steinmetz RL, Watson D, Segal MS,
Harrison JK, Scott EW, Grant MB.

Southern Vitreoretinal Association, Tallahassee, Fla, USA.

BACKGROUND: Diffuse macular edema (DME) and/or aberrant neovascularization (NV)
can cause vision loss in diabetic retinopathy (DR) and may be modulated by growth
factors and chemokines. The chemokine stromal-derived factor 1 (SDF-1) is a
potent stimulator of vascular endothelial growth factor (VEGF) expression, the
main effector of NV, and the key inducer of vascular permeability associated with
DME. Circulating endothelial cell precursors migrating in response to SDF-1
participate in NV. OBJECTIVE: To investigate the relationship between SDF-1 and
(VEGF) in vitreous of patients with varying degrees of DR and DME before and
after intraocular injection of triamcinolone acetonide, used to treat refractory 
DME. METHODS: In this prospective study, 36 patients were included and observed
for 6 months. Vitreous VEGF and SDF-1 levels were measured by enzyme-linked
immunosorbent assay in samples obtained immediately before and 1 month after
injection of triamcinolone. RESULTS: Both VEGF and SDF-1 were significantly
higher (P<.01) in patients with proliferative DR than in patients with
nonproliferative DR. Levels of SDF-1 were markedly increased in patients with DME
compared with those without DME. Vascular endothelial growth factor correlated
with SDF-1 levels and disease severity (r(2) = 0.88). CONCLUSIONS: Triamcinolone 
administration resulted in dramatic reductions of VEGF and SDF-1 to nearly
undetectable levels, eliminated DME, and caused regression of active NV. Our
results support a role for SDF-1 and VEGF in the pathogenesis of the adverse
visual consequences of DR and suggest that the elimination of DME with regression
and/or initiation of fibrosis of NV after triamcinolone injection may be due to
the suppression of VEGF and SDF-1.

PMID: 15596583 [PubMed - indexed for MEDLINE]

2106: Graefes Arch Clin Exp Ophthalmol. 2004 Dec;242(12):995-9. Epub 2004 Jul 17.

Optic nerve atrophy after vitrectomy with indocyanine green-assisted internal
limiting membrane peeling in diffuse diabetic macular edema. Adverse effect of
ICG-assisted ILM peeling.

Ando F, Yasui O, Hirose H, Ohba N.

EyeCare Nagoya, Nagoya Dia Building 3, Meieki 3-13-15, Nakamura-ku, 450-0002
Nagoya, Japan.

PURPOSE: To report anatomic and visual outcomes of vitrectomy and indocyanine
green (ICG)-assisted peeling of the retinal internal limiting membrane (ILM) in
the treatment of diffuse diabetic macular edema. METHODS: In a retrospective
interventional case series, 15 eyes of 11 patients with refractory diffuse
diabetic macular edema underwent pars plana vitrectomy with removal of the ILM,
which was stained by intravitreal injection of ICG (0.1-0.2 ml of 0.5% ICG),
performed by a single surgeon. The patients were followed up for 14-28 months
(mean 20.5 months). The main outcome measures were assessment of macular edema by
optical coherence tomography and determination of visual acuity and visual field.
RESULTS: Intravitreal ICG visualized the ILM to facilitate complete removal of
the structure. Qualitative assessment of optical coherence tomography images at
the end of follow-up revealed that retinal thickness in the macula appeared
nearly normal with or without reappearance of foveal pit in 11 of the 15 eyes
(73.3%), decreased in 3 eyes (20.0%), and did not change in 1 eye (6.6%).
Best-corrected visual acuity at the end of follow-up improved by 2 lines or more 
in 4 eyes (26.7%), virtually unchanged in 6 eyes (40.0%), and deteriorated by 2
lines or more in 5 eyes (26.7%). The mean logMAR visual acuity was 0.680
(approximately 12/60) preoperatively and 0.812 (approximately 9/60)
postoperatively, the difference being not statistically significant (paired
t-test, P=0.445). Seven (46.7%) of the 15 eyes developed optic nerve atrophy that
occurred gradually within 6 months after surgery and caused irreversible
peripheral visual field defect predominantly affecting the nasal field.
CONCLUSION: Intravitreal application of ICG is beneficial in uneventful ILM
peeling to help resolution of diffuse diabetic macular edema, but it may
potentially damage the optic nerve fibers and lead to unfavorable visual
outcomes.

PMID: 15592868 [PubMed - indexed for MEDLINE]

2107: Ophthalmic Epidemiol. 2004 Dec;11(5):359-67.

Visual acuity and its decrease in classic neovascular age-related macular
degeneration.

Behrendt C.

Epidemiology, Pfizer Global Research and Development, La Jolla, California, USA. 
carolynbehrendt@yahoo.com

PURPOSE: To identify factors affecting visual acuity and its decrease in eyes
with subfoveal choroidal neovascularization (CNV) associated with age-related
macular degeneration (AMD). METHODS: Distance visual acuity was recorded at
screening and up to five follow-up visits during the first year of a randomized, 
double-blind, placebo-controlled trial of oral prinomastat. Subjects had AMD in
both eyes and neovascular AMD in at least one eye. Analysis employed a
generalized linear mixed model. RESULTS: Of 158 eligible subjects (age 56-90),
125 (79.1%) received prinomastat. Visual acuity was independently affected by
relative acuity of the fellow eye, whether the study eye had been the first or
second to develop CNV, age, current smoking, leakage area, and prior
photocoagulation. Decrease in visual acuity score, unaffected by prinomastat, was
less steep in eyes that had been second to develop CNV. Such eyes had a
comparable time since CNV onset to other study eyes. CONCLUSION: Fellow eye
features independently affect visual acuity and its decrease in eyes with classic
neovascular AMD.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15590583 [PubMed - indexed for MEDLINE]

2108: Ophthalmic Epidemiol. 2004 Dec;11(5):337-46.

Model study of AREDS antioxidant supplementation of AMD compared to Visudyne: a
dominant strategy?

Trevithick J, Massel D, Robertson JM, Tomany S, Wall R.

Department of Biochemistry, Faculty of Medicine, University of Western Ontario,
London, Ontario, Canada. trevjohn@uwo.ca

OBJECTIVES: In Ontario, Canada, in a cohort of all people initially aged 50-54
years, modeling whether the Age-Related Eye Disease Study (AREDS) antioxidant
supplementation for stage 3 and 4 AMD would decrease the costs of photodynamic
treatment with Visudyne. PERSPECTIVE: Third party payer, the Ontario Health
Insurance Plan. METHODS: Using reported risk reductions, prevalence data by age
and sex from the Beaver Dam studies, and yearly costs: AREDS 182.50 Canadian
dollars, potential savings were calculated as the difference or incremental cost 
between the estimated medical costs for the untreated cohort of 17,000 Canadian
dollars for Visudyne treatment of individuals with neovascularization and the
same cohort if stage 3 and 4 AMD patients were treated with antioxidants,
decreasing progression to neovascularization. Different scenarios were explored
for sensitivity analysis of direct cost savings. RESULTS: For the Ontario cohort 
of approximately 788,000 aged 51-55 years in 2001, for photodynamic therapy of
the untreated cohort, modeled costs were 1.7 billion Canadian dollars. AREDS
treatment costs would be 513 million Canadian dollars. AREDS would reduce
photodynamic therapy costs, a net saving of 431 million Canadian dollars, a
saving of 547 Canadian dollars per person in the total cohort, or 6,753 Canadian 
dollars per stage 3 and 4 patient treated. To explore the sensitivity of this
model to AMD incidence rather than prevalence data, Framingham incidence data
were incorporated in the model: net savings of 70.3 million Canadian dollars were
modeled using Framingham incidence data. CONCLUSION: Under reasonable
assumptions, if the case progresses to wet AMD (1) AREDS with Visudyne is less
expensive than Visudyne alone in every five-year time period for the cohort that 
is age 50-54 right now until they become 75-79; thus, the lifetime cost is lower;
(2) AREDS with Visudyne yields more QALYs than Visudyne alone in every five-year 
interval; (3) under all but the most extreme assumptions, the conclusions reached
are robust. Even when AREDS costs a little more, it yields more QALYs at a
reasonable cost per QALY. Thus, AREDS antioxidant supplementation appears to be a
dominant strategy for macular degeneration. Applied to the whole Canadian
population, the potential medical cost savings for Visudyne treatment of
neovascular AMD are 5.6 billion Canadian dollars in direct costs. These values
would be tenfold higher for the USA, because of the currency and population size 
differences.

Publication Types: 
    Comparative Study

PMID: 15590581 [PubMed - indexed for MEDLINE]

2109: Semin Ophthalmol. 2004 Mar-Jun;19(1-2):55-61.

Fixation pattern and macular sensitivity in eyes with subfoveal choroidal
neovascularization secondary to age-related macular degeneration. A
microperimetry study.

Midena E, Radin PP, Pilotto E, Ghirlando A, Convento E, Varano M.

Department of Ophthalmology, University of Padova, Padova, Italy.
edoardo.midena@unipd.it

PURPOSE: To investigate the effects of subfoveal choroidal neovascularizzation
(CNV) secondary to age-related macular degeneration (AMD) on macular functional
parameters quantified with an automatic fundus perimeter. METHODS: 118 eyes of 98
consecutive patients with subfoveal CNV secondary to AMD were evaluated. Best
corrected visual acuity (ETDRS charts), fundus photography, and fluorescein
angiography were performed. Microperimetry (fundus-related perimetry) was used to
quantify macular sensitivity and fixation pattern (location and stability).
RESULTS: Of 118 eyes: 26 (21.9%) had central, 18 (15.1%) poor central and 74
(63.0%) eccentric fixation; 31 (26.0%) had stable, 42 (35.6%) relatively unstable
and 45 (38.4%) unstable fixation. In 75 eyes (63.4%) a dense central scotoma was 
found. Angiographic classification of subfoveal CNV (occult versus classic) was
not significantly related to fixation pattern (location: P = 0.274; stability: P 
= 0.385), and presence of dense scotoma (P = 0.41). CONCLUSION: Microperimetric
quantification of macular sensitivity and fixation pattern in eyes with subfoveal
CNV secondary to AMD offers new data about the impact of visual impairment in
these eyes. Moreover, microperimetry improves the functional evaluation of
subfoveal CNV in AMD.

Publication Types: 
    Comparative Study

PMID: 15590535 [PubMed - indexed for MEDLINE]

2110: Semin Ophthalmol. 2004 Mar-Jun;19(1-2):25-8.

Subthreshold transpupillary thermotherapy for subfoveal occult choroidal
neovascularization secondary to age-related macular degeneration.

Midena E, Pilotto E, Radin PP, Convento E.

Department of Ophthalmology, University of Padova, Padova, Italy.
edoardo.midena@unipd.it

PURPOSE: To describe the long term outcome of patients with subfoveal, occult
choroidal neovascularization (CNV) secondary to age-related macular degeneration 
(AMD) treated with subthreshold transpupillary thermotherapy. METHODS: 82 eyes of
82 consecutive patients with subfoveal occult CNV secondary to AMD were treated
with subthreshold transpupillary thermotherapy. Best corrected visual acuity,
fundus photography, fluorescein and indocyanine green angiography were performed.
RESULTS: All patients have been followed for at least 24 months. At the final
follow-up visit, 75.6% of patients had stable or improved visual acuity and 24.4%
had worsened visual acuity. No overtreatment side effects were found. CONCLUSION:
Subthreshold transpupillary thermotherapy seems effective in stabilizing visual
acuity in patients affected by occult, subfoveal CNV even on a long-term basis.

Publication Types: 
    Clinical Trial
    Comparative Study

PMID: 15590531 [PubMed - indexed for MEDLINE]

2111: Semin Ophthalmol. 2004 Mar-Jun;19(1-2):21-4.

Optical coherence tomography evaluation of macular edema after radial optic
neurotomy in patients affected by central retinal vein occlusion.

Patelli F, Radice P, Zumbo G, Fasolino G, Marchi S.

Department of Ophthalmology, Villa Tiberia Hospital, Via Emilio Praga, Rome,
Italy. f.patelli@tiscali.it

PURPOSE: To evaluate the characteristics of macular edema (ME) before and after
radial optic neurotomy (RON) detected by optical coherence tomography (OCT), in
patients with central retinal vein occlusion (CRVO). DESIGN: Interventional case 
series. METHODS: Five eyes of 5 patients affected by CRVO underwent RON. Complete
ocular examination including best corrected snellen visual acuity (VA),
fluorescein angiography (FA) and OCT were performed before RON and at 1, 3 and 6 
months of follow-up. RESULTS: The OCT characteristics of macular edema are
similar in all the eyes affected by CRVO. Mean retinal thickness (RT) before RON 
was 858 microns, mean VA was 20/640. By FA 3 eyes were evaluated as being
perfused and 2 as indeterminate. No complications occurred during and after
surgery. At 6 months of follow-up the RT decreased in all the patients (100%)
with a mean value of 289 microns. The VA increased in 3 patients and remained
stable in 2. CONCLUSIONS: OCT demonstrated resolution of the macular edema in all
the eyes. This resolution is not always accompanied with an improvement in VA.
Further studies are needed to better understand the efficacy of this procedure.

Publication Types: 
    Comparative Study

PMID: 15590530 [PubMed - indexed for MEDLINE]

2112: Curr Eye Res. 2004 Oct-Nov;29(4-5):327-36.

Cone-mediated multifocal electroretinogram in early age-related maculopathy and
its relationships with subjective macular function tests.

Feigl B, Brown B, Lovie-Kitchin J, Swann P.

Department of Ophthalmology, University of Graz, Austria. b.feigi@qut.edu.au

PURPOSE: To investigate the multifocal electroretinogram (mfERG) and subjective
function in early age-related maculopathy (ARM). METHODS: Seventeen subjects with
early ARM with visual acuity (VA) of 6/12 or better and 20 age-matched control
subjects were examined. We assessed mfERGs, high and low contrast distance VA,
near VA, low luminance VA, contrast sensitivity, saturated and desaturated Panel 
D-15 and visual fields (mean sensitivity). The mfERG responses were analysed by
comparing central-overall (method 1) and superior-inferior (method 2) ratios.
RESULTS: The mfERG did not discriminate between the groups whereas colour vision 
(tritan deficiency), contrast sensitivity, and high contrast and low contrast VA 
showed significantly reduced responses for the early ARM group compared with the 
control group (p < or = 0.01). The mfERG first-order kernel responses correlated 
significantly with the desaturated D-15 in both methods (r = -0.5, p < or =
0.05). Fundus grading was not correlated with the mfERG measures. CONCLUSIONS:
Although the mfERG correlated significantly with the desaturated D-15 in early
ARM, suggesting it operates at a sensitive level, it failed to discriminate
between the control and ARM groups. In our sample, the subjective function
measures were more sensitive than the mfERG measures.

PMID: 15590480 [PubMed - indexed for MEDLINE]

2113: Int J Radiat Oncol Biol Phys. 2004 Dec 1;60(5):1564-71.

Effect of irradiation on neovascularization in rat skinfold chambers:
implications for clinical trials of low-dose radiotherapy for wet-type
age-related macular degeneration.

Hori K, Saito S, Tamai M.

Department of Vascular Biology, Division of Cancer Control, Institute of
Development, Aging and Cancer, Tohoku University, Sendai, Japan.
k-hori@idac.tohoku.ac.jp

PURPOSE: Wet-type age-related macular degeneration is a refractory eye disease
that involves choroidal neovascularization. Randomized controlled trials of
low-dose radiotherapy for this disease performed in Japan showed that, at 12
months of follow-up, visual acuity was significantly well preserved and the
neovascular membrane size decreased. Because understanding the effect of
irradiation on new vascular networks is an important prerequisite for clinical
trials, we used a rat skinfold chamber technique to investigate X-ray-induced
changes in neovasculature microcirculation. METHODS AND MATERIALS:
Neovascularization was induced in rat skinfold chambers via polyvinyl chloride
resin plates. Neovessels were irradiated in a single 10-Gy dose, after which,
changes in vascular density, blood velocity, tissue blood flow, and interstitial 
fluid pressure (IFP), were measured. RESULTS: Vascular density, tissue blood
flow, and IFP measurements in resin-induced inflammatory tissue were much higher 
than those measurements in normal tissue. Although overall blood velocity was low
and sluggish or blood-flow stasis occurred in the neovascular network, after a
single 10-Gy dose of radiation, the velocity increased, stasis improved markedly,
and many dilated vessels narrowed. Thereafter, vascular density, blood flow, and 
IFP significantly decreased and approached normal values. CONCLUSION: These
findings may help explain clinical results related to radiotherapy-induced
changes in neovascular membranes in age-related macular degeneration. Both
vascular morphology and vascular function in inflammatory tissue returned to
normal, without vessel destruction, after an appropriate radiation dose.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15590188 [PubMed - indexed for MEDLINE]

2114: Biochimie. 2004 Nov;86(11):825-31.

Lipids and lipid peroxidation products in the pathogenesis of age-related macular
degeneration.

Kopitz J, Holz FG, Kaemmerer E, Schutt F.

Institute of Molecular Pathology, University of Heidelberg, Im Neuenheimer Feld
220, 69120 Heidelberg, Germany. juergen_kopitz@med.uni-heidelberg.de
<juergen_kopitz@med.uni-heidelberg.de>

In people over 50, age-related macular degeneration (ARMD) has become the most
common cause for severe visual loss and legal blindness in all industrialized
nations. Currently, there is no effective treatment for the majority of patients.
To develop new and effective modes of therapy, understanding of the molecular
basis of the disease in mandatory. However, the pathogenesis of ARMD is still
poorly understood. Several lines of evidence suggest that aging changes of the
retinal pigment epithelium (RPE), in particular the accumulation of
autofluorescent lipofuscin granules in the lysosomal compartment of postmitotic
RPE cells, play a key role in the pathogenesis of the disease. Recent studies
indicate that lipidic compounds of lipofuscin, represented by the retinoid A2-E, 
and protein damage by lipid peroxidation products, in particular malondialdehyde 
and 4-hydroxynonenal, induce lysosomal dysfunction and lipofuscinogenesis in the 
RPE. The possible mechanisms underlying this lysosomal dysfunction and the
resulting adverse effects on overall RPE function are discussed.

Publication Types: 
    Review

PMID: 15589692 [PubMed - indexed for MEDLINE]

2115: Graefes Arch Clin Exp Ophthalmol. 2005 May;243(5):478-81. Epub 2004 Dec 7.

The effect of intravitreal triamcinolone on diabetic macular oedema.

Krepler K, Wagner J, Sacu S, Wedrich A.

Department of Ophthalmology, Medical University of Vienna, Waehringer Guertel
18-20, 1090 Vienna, Austria. katharina.krepler@meduniwien.ac.at

BACKGROUND: Diabetic macular oedema is a frequent cause of visual loss in
patients with diabetic retinopathy. The purpose of this study was to assess the
efficacy of intravitreal triamcinolone acetonide in reducing diabetic macular
oedema and improving visual acuity. METHODS: In this prospective study 12 eyes of
12 patients with diabetic macular oedema unresponsive to prior laser treatment
received an intravitreal injection of 4 mg triamcinolone acetonide. Examinations 
were performed 1 day preoperatively and at 1 week and 1, 3, 6, and 9 months after
surgery and included slit-lamp examination, measurement of IOP, assessment of
distance as well as reading visual acuity and assessment of macular thickness
using optical coherence tomography (OCT). RESULTS: Mean age of the patients
(mean+/-SD) was 66.6+/-8.6 years. Mean best-corrected visual acuity (BCVA) for
distance (LogMAR using ETDRS charts) improved from 1.0+/-0.4 preoperatively to
0.9+/-0.4 (p=0.01) 1 week and to 0.9+/-0.4 (p=0.02) 1 month postoperatively. Mean
BCVA for reading vision (LogRAD using Radner Reading Charts) improved from
1.1+/-0.4 preoperatively to 0.9+/-0.4 (p=0.002) 1 month postoperatively. Mean
macular thickness decreased from 450+/-190 (microm) preoperatively to 305+/-153
(p=0.02) 1 month postoperatively. No significant improvement in VA and no
significant reduction of macular thickness could be observed 3, 6, and 9 months
postoperatively. Mean intraocular pressure significantly increased from
14.7+/-2.7 mmHg preoperatively to 16.9+/-3.0 mmHg at 1 month (p=0.02).
CONCLUSION: A single intravitreal injection of triamcinolone acetonide led to a
significant improvement in mean VA in patients with diabetic macular oedema.
However, the significant effect was not permanent and persisted for only 1 month.

PMID: 15586288 [PubMed - indexed for MEDLINE]

2116: Ophthalmic Res. 2004 Sep-Oct;36(5):241-9.

Pathomechanisms of cystoid macular edema.

Bringmann A, Reichenbach A, Wiedemann P.

Department of Ophthalmology, Eye Clinic, University of Leipzig, Germany.
bria@medizin.uni-leipzig.de

Cystoid macular edema (CME) is a well-known endpoint of various ocular diseases, 
but the relative pathogenic impact of extra- and intracellular fluid accumulation
within the retinal tissue still remains uncertain. While most authors favor an
extracellular fluid accumulation as the main causative factor of cyst formation, 
there are indications that Müller cell swelling may also contribute to CME
development (particularly in cases without significant angiographic vascular
leakage). Vascular leakage occurs after a breakdown of the blood-retinal barrier 
during traumatic, vascular, and inflammatory ocular diseases, and allows the
serum to get into the retinal interstitium. Since intraretinal fluid distribution
is restricted by two diffusion barriers, the inner and outer plexiform layers,
serum leakage from intraretinal vessels causes cysts mainly in the inner nuclear 
layer while leakage from choroid/pigment epithelium generates (in addition to
subretinal fluid accumulation) cyst formation in the Henle fiber layer. In the
normal healthy retina, the transretinal water fluxes are mediated by glial and
pigment epithelial cells. These water fluxes are inevitably coupled to fluxes of 
osmolytes; in the case of glial (Müller) cells, to K(+) clearance currents. For
this purpose, the cells express a complex, microtopographically optimized pattern
of transporters and channels for osmolytes and water in their plasma membrane.
Ischemic/hypoxic alterations of the retinal microvasculature result in gliotic
responses which involve down-regulation of K(+) channels in the perivascular
Müller cell end-feet. This means a closure of the main pathway which normally
generates the osmotic drive for the redistribution of water from the inner retina
into the blood. The result is an intracellular K(+) accumulation which, then,
osmotically drives water from the blood into the glial cells (i.e., in the
opposite direction) and causes glial cell swelling, edema, and cyst formation.
While the underlying mechanisms await further research, it is expected that their
improved knowledge will stimulate the development of novel therapeutic approaches
to resolve edema in retinal tissue. Copyright (c) 2004 S Karger AG, Basel.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 15583429 [PubMed - indexed for MEDLINE]

2117: Ophthalmology. 2004 Dec;111(12):2265-70.

Fixation stability using central and pericentral fixation targets in patients
with age-related macular degeneration.

Bellmann C, Feely M, Crossland MD, Kabanarou SA, Rubin GS.

Institute of Ophthalmology, London, United Kingdom.

PURPOSE: To determine fixation stability for central and pericentral fixation
targets in patients with age-related macular degeneration (AMD). DESIGN:
Comparative study. PARTICIPANTS: Twelve patients having late-stage AMD involving 
the fovea and 10 age-matched controls having no other eye diseases and visual
acuity better than 20/25. METHODS: Six different fixation targets (1 degrees
cross; 1 degrees filled circle; 1 degrees letter x; small 4-point diamond; large 
4-point diamond using dimensions as in a field analyzer; large-crossover
whole-image diagonal with open 1 degrees center) were presented on a
high-resolution monitor. Before examination, subjects were given verbal
instructions to move their eye to see the center of the target best. Fixation
stability was measured for the preferred eye, with the fellow eye occluded, using
a gaze tracker. Fixation stability was quantified by calculating the bivariate
contour ellipse area (BCEA) over 30 seconds for each target. For statistical
analysis, BCEA values (minutes of arc2) were converted into their logarithms. The
absolute retinal scotoma for the study eye was determined using a scanning laser 
ophthalmoscope. MAIN OUTCOME MEASURE: Bivariate contour ellipse area. RESULTS:
Visual acuity in patients (age range, 57-87 years) ranged from 20/32 to 20/600.
The lowest BCEA values were found for the 1 degrees letter x in patients (mean,
12052.2%+/-254.0%) and for the 1 degrees cross in normal subjects (mean,
1286.9%+/-47.8%); the highest BCEA values were found for the small 4-point
diamond in patients (mean, 23109.5%+/-298.3%) and for the large 4-point diamond
in normals (age range, 62-79 years) (mean, 3229.2%+/-105.4%). The difference
between the targets was significant for normal subjects (analysis of variance
[ANOVA], P<0.01) but not for patients (ANOVA, P>0.05). In normals, BCEA values
were significantly lower for central fixation targets than for pericentral
fixation targets (P<0.01). CONCLUSION: Fixation is significantly less stable for 
pericentral fixation targets in normal subjects, indicating an advantage for
central fixation targets. These results are particularly significant for any
clinical and experimental testing method that requires the patient to maintain
stable fixation.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15582084 [PubMed - indexed for MEDLINE]

2118: Retina. 2004 Dec;24(6):929-39.

Morphology and functional characteristics in adult vitelliform macular dystrophy.

Renner AB, Tillack H, Kraus H, Kohl S, Wissinger B, Mohr N, Weber BH, Kellner U, 
Foerster MH.

Augenklinik, Campus Benjamin Franklin, Charité Universitätsmedizin Berlin,
Berlin, Germany.

PURPOSE: Detailed morphologic and functional evaluation of adult vitelliform
macular dystrophy (AVMD). METHODS: The records of 61 consecutive AVMD patients
(inclusion criterion: vitelliform lesion smaller than one disk diameter at least 
in one eye) were evaluated retrospectively regarding visual acuity, color vision,
perimetry, retinal pigment epithelium (RPE) autofluorescence, fluorescein
angiography, electro-oculography, full-field and multifocal electroretinography, 
and molecular genetic evaluation of the VMD2 and RDS/peripherin genes. RESULTS:
The mean age of subjects was 54.6 years. Visual loss was variable (median, 0.6;
range, 1.25-0.05). Color vision and visual field were normal in about half of the
patients but presented defects with high variability in the remaining patients.
Autofluorescence findings showed increased fluorescence within the foveal yellow 
lesion in 76%. In the majority of eyes, the amplitude of the 30 Hz flicker
response of the full-field electroretinogram (72%) and the central P1 amplitude
of the multifocal electroretinogram (63%) were reduced. Mutational analyses
revealed a potentially disease-associated mutation in the RDS/peripherin gene in 
one patient. CONCLUSION: AVMD is characterized by late onset, slow progression,
good prognosis, and high variability of morphologic and functional abnormalities 
resulting frequently in misdiagnosis. Autofluorescence findings indicate
lipofuscin accumulation in the yellow lesion. Electroretinography revealed a
generalized cone system dysfunction with increasing severity toward the fovea.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15579992 [PubMed - indexed for MEDLINE]

2119: Retina. 2004 Dec;24(6):920-8.

Electroretinographic findings in patients with Stargardt disease and fundus
flavimaculatus.

Oh KT, Weleber RG, Stone EM, Oh DM, Rosenow J, Billingslea AM.

Department of Ophthalmology, University of North Carolina, Chapel Hill, North
Carolina, USA.

PURPOSE: To characterize the clinical and electroretinogram (ERG) features of our
cohort of patients with Stargardt disease (STGD) exhibiting coding sequence
variations in the ABCA4 gene. METHODS: Review of 76 patients with the clinical
diagnosis of Stargardt disease/fundus flavimaculatus (STGD/FF) from the
University of Iowa Department of Ophthalmology and Visual Sciences (41 patients) 
and the Casey Eye Institute (35 patients). Clinical examination, Goldmann
perimetry, and electroretinography were performed on all 76 patients. Patients
were divided into three groups on the basis of their funduscopic and
electroretinographic features: (1) a normal ERG by the standards of the
laboratory; (2) minimal rod or cone abnormalities; (3) severe ERG dysfunction.
The latter category was further subdivided on the basis of a cone-dominated loss 
of function (C > R or "cone-rod dystrophy") or diffuse depression of rods and
cones (C = R). Mutational analysis of the coding sequence of the ABCA4 gene was
performed by single strand conformation polymorphism analysis followed by
automated DNA sequencing. Each electroretinographic group was analyzed for the
presence of disease causing changes using exact tests of binomial proportions
corrected for multiple comparisons by Bonferroni method. Quantitative polymerase 
chain reaction (QPCR) was performed on patients who were homozygous for disease
causing changes in the ABCA4 gene to rule out the possibility of deletions.
RESULTS: Overall, 56 of 76 patients (and 77 of 152 alleles) exhibited coding
sequence variations that were compatible with high-penetrance disease-causing
mutations. The most common of these were His423Arg (9), frameshift mutations (7),
Ala1038Val (7), and Pro1380Leu (6). Although no patients with His423Arg presented
with normal ERGs, no significant correlation was observed between specific
sequence variations and the electroretinographic characteristics or fundus
appearance. However, a significantly greater fraction of patients with normal ERG
studies failed to exhibit detectable disease-causing coding sequence variations
in the ABCA4 gene identified on either allele (P = 0.0006). CONCLUSION: STGD/FF
patients in our cohort exhibit a wide range of electroretinographic
abnormalities, some of which are more prevalent than previously suspected. No
direct correlation between clinical appearance, electrophysiologic
characteristics and specific ABCA4 alleles could be identified, although a
significantly lower number of our cohort with a normal ERG exhibited detectable
coding sequence variations in the ABCA4 gene. However, four patients with ERG
dysfunction were homozygous for a His423Arg change proven by QPCR not to be an
artifact of a deletion. The presence of electrophysiologic dysfunction is not
uncommon in our cohort of patients with STGD. Thus, the ERG provides clinically
important information of retinal function for STGD/FF and, as such, is still
indicated as part of the evaluation of these patients.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15579991 [PubMed - indexed for MEDLINE]

2120: Retina. 2004 Dec;24(6):910-4.

Comment in:
    Retina. 2007 Nov-Dec;27(9):1316-8; author reply 1318-9.

Correlation of optical coherence tomography with angiography in retinal pigment
epithelial detachment associated with age-related macular degeneration.

Sato T, Iida T, Hagimura N, Kishi S.

Department of Ophthalmology, Gunma University School of Medicine, Maebashi,
Gunma, Japan. takusato@showa.gunma-u.ac.jp

PURPOSE: To correlate optical coherence tomography (OCT) with angiographic signs 
of choroidal neovascularization (CNV) in retinal pigment epithelial detachment
(PED) associated with age-related macular degeneration (ARMD). METHODS:
Prospectively, the authors performed OCT in 35 eyes of 35 patients (30 men and 5 
women with a mean age of 71.6 years [range, 56-76 years]) with ARMD. All 35 eyes 
had CNV in the area of PED or adjacent to it, which was shown by fluorescein or
indocyanine green angiography. Cross-sectional images were obtained by the OCT
scanning line through the CNV and PED. RESULTS: In 10 (56%) of 18 eyes in which
the CNV was at the margin of the PED, a small PED was adjacent to the central,
dome-shaped PED. There was a notch between the central and small mounds of PED.
In 13 (76%) of 17 eyes in which the CNV was within the PED, a notch was seen in
the dome-shaped PED, resulting in a contour with 2 mounds. One of the 2 mounds
contained a highly reflective mass immediately beneath the detached retinal
pigment epithelium in 8 (62%) of the 13 eyes. CONCLUSION: A tomographic notch in 
the PED may be diagnostically important as an indication of CNV beneath the
detached retinal pigment epithelium in eyes with ARMD.

Publication Types: 
    Comparative Study

PMID: 15579989 [PubMed - indexed for MEDLINE]

2121: Retina. 2004 Dec;24(6):905-9.

Retrobulbar injection of methylprednisolone in diffuse diabetic macular edema.

Knudsen LL.

Department of Ophthalmology, Aalborg University Hospital, Aalborg, Denmark.
u19204@aas.nja.dk

PURPOSE: To study some aspects of locally and extraocularly administered
methylprednisolone on diffuse diabetic macular edema. METHODS: The investigation 
included 13 eyes of 13 diabetic subjects. One eye received treatment, and the
other eye served as control. Standardized visual acuity as well as the presence
of clinically significant macular edema was recorded before and several times
after retrobulbar injection of methylprednisolone. The follow-up period was at
least 6 months. RESULTS: One month after retrobulbar injection of
methylprednisolone, visual acuity increased significantly (before, 0.19; after,
0.30). Visual acuity was also significantly increased 3 and 6 months after this
treatment (before, 0.19; 3 months after, 0.26; 6 months after, 0.28). The
proportion of eyes with diffuse clinically significant macular edema was
gradually reduced from 100% before treatment to 15% 6 months after treatment.
CONCLUSION: Retrobulbar injection of methylprednisolone increased visual acuity
significantly in diabetic subjects with diffuse macular edema. A significant
reduction in the number of eyes with clinically significant macular edema was
also observed.

PMID: 15579988 [PubMed - indexed for MEDLINE]

2122: Eye. 2005 Dec;19(12):1325-7.

Improved visual acuity and macular thickness 1 week after intravitreal
triamcinolone for diabetic macular oedema.

Islam MS, Negi A, Vernon SA.

Ophthalmology, Queen's Medical Centre, Nottingham, UK. msislam@doctors.org.uk

PURPOSE: To evaluate the clinical and volumetric improvement 1 week after an
injection of intravitreal triamcinolone acetonide in eyes with diabetic macular
oedema. METHODS: Seven phakic eyes of seven diabetic patients diagnosed with
clinically significant macular oedema were treated with a single 4-mg
intravitreal injection of triamcinolone acetonide (0.1 ml). LogMAR best corrected
visual acuity (logMAR BCVA), best corrected reading ability (RA), and central
macular thickness (CMT) with optical coherence tomography (OCT) were assessed
prior and 1 week subsequent to treatment. RESULTS: Mean improvement in logMAR
BCVA was 0.146 (P=0.03). Mean reduction in CMT was 150.9 mum (P=0.02, Wilcoxon
signed-rank test). Mean improvement in RA was 3 lines. CONCLUSION: Reduction in
macular oedema was demonstrated on OCT at 1 week, in most cases associated with
improvement in central visual function, in particular, reading ability. Total
resolution of diabetic macular oedema may occur at 1 week following intravitreal 
steroid injection.

PMID: 15578081 [PubMed - indexed for MEDLINE]

2123: Clin Experiment Ophthalmol. 2004 Dec;32(6):569-72.

Intravitreal triamcinolone for diabetic macular oedema in Chinese patients:
six-month prospective longitudinal pilot study.

Lam DS, Chan CK, Tang EW, Li KK, Fan DS, Chan WM.

Department of Ophthalmology and Visual Sciences, Chinese University of Hong Kong,
Hong Kong Eye Hospital, Hong Kong. dennislam@cuhk.edu.hk

AIM: To evaluate the safety and efficacy of intravitreal triamcinolone (IVTA) in 
Chinese patients with diabetic clinical significant macular oedema (CSMO).
METHODS: Eighteen eyes of 17 consecutive patients with CSMO were prospectively
recruited and treated with a 4 mg injection of IVTA. Best-corrected visual acuity
(BCVA) on the ETDRS chart and central macular thickness (CMT) on optical
coherence tomography were measured at baseline weeks 1, 2, 3, and months 1, 2, 3,
4, 5 and 6. Side-effects were monitored. RESULTS: All patients completed 6 months
of follow up. The mean baseline BCVA and CMT were 1.20 +/- 0.31 logMAR units and 
552 +/- 179 microm, respectively. Improvements in CMT and BCVA were observed as
early as at 1 and 2 weeks, respectively (P < 0.05). Mean BCVA peaked at 2 months 
(0.97 +/- 0.38 logMAR units) while mean CMT was maximally reduced at 3 months
(326 +/- 145 microm). Improvements in BCVA and CMT were less afterwards but still
statistically significant at 6 months; the final mean BCVA and CMT were 0.99 +/- 
0.36 logMAR units and 427 +/- 145 microm, respectively. A total of 5/18 (28%)
eyes developed a transient increase in intraocular pressure. Cataract progression
was noted in 2/12 (17%) of the phakic eyes. CONCLUSIONS: Intravitreal
triamcinolone appeared generally safe and effective in Chinese patients with
CSMO. Although the improvements in BCVA and CMT were transient, there were
residual benefits at 6 months. Due to the transient nature of IVTA, re-treatment 
seems necessary but the optimal timing and dosage will require further
investigations.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15575825 [PubMed - indexed for MEDLINE]

2124: Clin Rehabil. 2004 Nov;18(7):828-32.

Prismatic correction in patients affected by age-related macular degeneration.

Parodi MB, Toto L, Mastropasqua L, Depollo M, Ravalico G.

Eye Clinic, University of Trieste, Italy. maubp@yahoo.it

OBJECTIVE: To evaluate by means of a controlled clinical trial the effectiveness 
and the tolerance of prismatic correction in improving visual function in
patients affected by advanced bilateral age-related macular degeneration.
SETTING: Department of Ophthalmology, Eye Clinic, University of Trieste. SUBJECTS
AND INTERVENTIONS: Each patient underwent an ophthalmologic examination, complete
with distance visual acuity measurement using the Standard Early Treatment
Diabetic Retinopathy Study chart. Patients were then randomly assigned to the
treatment or control group. The treatment group received spectacles lenses with a
prismatic correction of low power (5-7 prismatic dioptres) in the better eye.
MAIN MEASURES: Visual acuity was measured at baseline and 1, 90, 180 and 360 days
after prescription in both groups. RESULTS: The treatment group consisted of 14
patients, while the control group was of 14 patients. The prismatic correction
was well tolerated in 85.7% of cases. Visual acuity in the treatment group
improved mostly at three-month follow-up, with a slight further improvement at
the six- and 12-month follow-ups, showing a statistically significant difference 
in comparison with the control group. No visual acuity improvement was registered
in the control group. CONCLUSION: Monolateral prismatic correction may be
considered a viable means to improve visual function in patients affected by
bilateral age-related macular degeneration at an advanced stage.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 15573840 [PubMed - indexed for MEDLINE]

2125: J Biomed Opt. 2004 Nov-Dec;9(6):1214-22.

In vivo measurement of time-resolved autofluorescence at the human fundus.

Schweitzer D, Hammer M, Schweitzer F, Anders R, Doebbecke T, Schenke S, Gaillard 
ER, Gaillard ER.

University of Jena, Department of Experimental Ophthalmology, Bachstr. 18, 07740 
Jena, Germany. Dietrich.Schweitzer@med.uni-jena.de

An experimental setup for measurement of time-resolved autofluorescence of the
human eye fundus is demonstrated. The method combines laser scanning technique
and time-correlated single photon counting. The light source is a laser diode,
delivering pulses of about 100 ps duration at a repetition rate of 40 MHz. The
excitation wavelength is 446 nm and the cutoff wavelength of fluorescence
detection is at 475 nm. The autofluorescence can be determined with a spatial
resolution of 80 x 80 microm2 and 25 ps time resolution. The fluorescence decay
is optimally approximated by a biexponential model. The dominating lifetime tau1 
is shortest in the macula (320 to 380 ps) and reaches 1500 ps in the optic disk. 
The lifetime tau2 varies between 2 ns and 5 ns, but the spatial distribution is
more homogeneous. Respiration of 100% oxygen for 6 min leads to changes in the
fluorescence lifetime pointing to detection of coenzymes. Diagrams of lifetime
tau2 versus tau1 are well suited for comparison of substances. Such lifetime
clusters of a 20 deg macular field of a young healthy subject and of a patient
suffering from dry age-related macular degeneration overlap only partially with
tau2-tau1 clusters of lipofuscin. Copyright 2004 Society of Photo-Optical
Instrumentation Engineers.

Publication Types: 
    Clinical Trial
    Comparative Study
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 15568942 [PubMed - indexed for MEDLINE]

2126: Ophthalmologica. 2004 Nov-Dec;218(6):378-84.

Comment in:
    Ophthalmologica. 2005 May-Jun;219(3):189.

Improvement of visual acuity in eyes with diabetic macular edema after treatment 
with pars plana vitrectomy.

Jahn CE, Töpfner von Schutz K, Richter J, Boller J, Kron M.

Augenpraxisklinik Dr. Jahn, Kempten, Deutschland. Praxisdr.Jahn@t-online.de

BACKGROUND: Diabetic macular edema (DME) is the leading cause of severe visual
loss in patients with diabetic retinopathy. This is so despite the fact that
argon laser photocoagulation of the macula (M-ALC) has been shown to be
beneficial. Recently, it has been suggested that pars plana vitrectomy (PPV) can 
lead to the resolution of DME and stop the deterioration of central visual
acuity. PURPOSE: To explore the potential benefit of PPV for the treatment of
DME. PATIENTS AND METHODS: PPV was carried out in 30 eyes of 21 consecutive
patients (median age 71 years, range 61-88 years) with type II diabetes mellitus 
suffering from DME. 23 eyes had non-proliferative diabetic retinopathy (NPDR) and
7 eyes had proliferative diabetic retinopathy (PDR) in addition to DME. Posterior
vitreous detachment had to be carried out in all cases. If epiretinal membranes
were present (23 eyes), they were removed. In 13 eyes (initially 11 eyes) the
internal limiting membrane (ILM) was also removed. Prior to PPV 8 eyes had
received M-ALC. Three eyes had M-ALC after PPV. One eye developed a retinal
detachment 6 weeks after PPV and was excluded form the analysis. After an initial
treatment failure two eyes underwent repeat PPV with peeling of the ILM. Both
eyes of another patient had 2 repeat PPVs because of recurrent vitreous
hemorrhage. Median follow-up was 16 months (range 1-62 months). RESULTS:
Following PPV the macula flattened or became attached in 20/27 (74%) eyes. 15/18 
(83%) eyes showed reduction or disappearance of leakage during
fluorescein-angiography. Central visual acuity increased by two to six lines in
15/27 (56%) for the whole group at 6 months after PPV. For the subgroup (18 eyes)
for which the evolution of visual acuity prior to PPV could be documented mean
and median visual acuity had decreased markedly from 0.26 +/- 0.19 resp. 0.2
(range 0.03-0.6) to 0.12 +/- 0.09 resp. 0.1 (range 0.02-0.4) during the 12 months
preceding PPV and increased to 0.28 +/- 0.23 resp. 0.2 (range 0.03-0.8) during
the 12 months following PPV. CONCLUSION: PPV almost always results in a reduction
and often complete disappearance of DME as evidenced by ophthalmoscopy and
fluorescein-angiography. Most importantly, central visual acuity often increases,
sometimes to a very large extent with dramatic improvement in quality of life of 
the patients. Copyright (c) 2004 S. Karger AG, Basel.

PMID: 15564755 [PubMed - indexed for MEDLINE]

2127: J Fr Ophtalmol. 2004 Nov;27(9 Pt 1):1001-6.

Assessment of macular function by multifocal electroretinogram in age-related
macular degeneration before and after photodynamic therapy.

Moschos MM, Panayotidis D, Theodossiadis G, Moschos M.

Jules Gonin Eye Hospital, University of Lausanne, Avenue de France 15, 1004
Lausanne, Switzerland. moschosmarilita@yahoo.fr

PURPOSE: To evaluate macular function, before and after photodynamic therapy
(PDT) using multifocal electroretinogram (MF-ERG), in eyes suffering from classic
subfoveal choroidal neovascularization (CNV) resulting from age-related macular
degeneration (ARMD). METHODS: Twenty eyes of 20 patients (10 male, 10 female)
with classic subfoveal CNV resulting from ARMD were studied. All received PDT
with verteporfin. Fluorescein angiography and mF-ERG were performed in each
patient 1 day before and 1 week, 3 months and 6 months after photodynamic
therapy. RESULTS: Before treatment, visual acuity (VA) and electrical retinal
response densities (RRD) in the foveal and parafoveal areas were low in all
patients. The mean VA (ETDRS chart) before PDT was 24.35 (SD, 15). The mean RRD
before PDT in area 1 was 4.39 nV/deg(2) (SD, 2.59) and in area 2 it was 2.11 (SD,
1.86). Six months after treatment, the mean VA was stable in 70% of the patients.
However, the mean RRD after PDT was 2.24 nV/deg(2) in area 1 (SD, 2.59) and 1.07 
nV/deg(2) in area 2 (SD, 1.59). CONCLUSION: Multifocal ERG objectively evaluates 
the macular function in eyes with CNV attributable to ARMD. In this study, the
stability of VA coincided with a clear impairment of electrical activity of the
foveal and parafoveal areas. This finding suggests that MF-ERG should be adopted 
to assess the efficacy of PDT objectively in the treatment of ARMD.

Publication Types: 
    Comparative Study

PMID: 15557861 [PubMed - indexed for MEDLINE]

2128: Invest Ophthalmol Vis Sci. 2004 Dec;45(12):4484-90.

The Minnesota Grading System of eye bank eyes for age-related macular
degeneration.

Olsen TW, Feng X.

University of Minnesota, Department of Ophthalmology, MMC Box 493, 420 Delaware
Street SE, Minneapolis, MN 55455-0501, USA. olsen010@umn.edu

PURPOSE: The Minnesota Grading System (MGS) is a method to evaluate human eye
bank eyes and determine the level of age-related macular degeneration (AMD), by
using criteria and definitions from the Age-Related Eye Disease Study (AREDS).
METHODS: Donor eyes (108 pairs) from the Minnesota Lions Eye Bank were cut
circumferentially at the pars plana to remove the anterior segment. A 1000 +/-
2.5-microm ruby sphere was placed on the optic nerve as a size reference. A
digital, high-resolution, color macular photograph was taken through a dissecting
microscope. The neurosensory retina was removed from one globe of the pair. The
underlying retinal pigment epithelium was rephotographed, localizing the fovea
with a proportional triangle. A grid was superimposed in the macular photographs 
and images were graded according to AREDS criteria. Twenty pairs were dissected
bilaterally and graded for symmetry. RESULTS: Eighty-eight globes were graded
into one of four MGS categories. Nineteen (95%) of 20 globes had symmetric
grades. CONCLUSIONS: The MGS provides a methodology to grade donor tissue from
eye bank eyes to correspond to the AREDS classification system. Donor tissue may 
be used for subsequent molecular analysis, including genomics and proteomics.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15557458 [PubMed - indexed for MEDLINE]

2129: Invest Ophthalmol Vis Sci. 2004 Dec;45(12):4470-6.

Erratum in:
    Invest Ophthalmol Vis Sci. 2005 Jan;46(1):7.

Fundus autofluorescence and fundus perimetry in the junctional zone of geographic
atrophy in patients with age-related macular degeneration.

Schmitz-Valckenberg S, Bültmann S, Dreyhaupt J, Bindewald A, Holz FG,
Rohrschneider K.

Department of Ophthalmology, University of Bonn, Abbe-Strasse 2, D-53127 Bonn,
Germany. frank.holz@ukb.uni-bonn.de

PURPOSE: To investigate retinal sensitivity in the junctional zone of geographic 
atrophy (GA), with variations in fundus autofluorescence (FAF) in patients with
advanced age-related macular degeneration (AMD). METHODS: The spatial
distribution and intensity of FAF were recorded with a confocal scanning laser
ophthalmoscope (SLO). Eyes had normal background FAF (group 1) or increased FAF
(group 2) surrounding the atrophic patches. Retinal sensitivity was assessed by
applying light stimuli with static automated full-threshold fundus perimetry with
a modified SLO. Threshold sensitivities were compared with age-matched normal
sensitivities. RESULTS: Thirty-nine eyes of 39 patients with GA were included.
Group 2 had a higher percentage of all test points outside the GA area, with
decreased retinal sensitivity (44.9% +/- 28.7%) compared with group 1 (20.7% +/- 
12.7%; P = 0.0063; multiple regression model; outcome variable is retinal
sensitivity; covariates are group affiliation and GA area). Within group 2, the
average percentage of stimuli in areas of normal FAF with reduced sensitivity was
38.0% +/- 33.0%, whereas the average percentage of stimuli in areas of elevated
FAF with reduced sensitivity was 52.6% +/- 29.7% (P = 0.023, Wilcoxon signed rank
test). CONCLUSIONS: Areas of increased FAF outside GA may be associated with
variable degrees of loss of retinal sensitivity and suggest a functional
correlate of excessive accumulation of retinal pigment epithelium lipofuscin in
AMD. Combining in vivo recording of FAF and retinal sensitivity, using SLO
technology, may give important clues in the understanding of mechanisms of
disease.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15557456 [PubMed - indexed for MEDLINE]

2130: Invest Ophthalmol Vis Sci. 2004 Dec;45(12):4263-7.

A novel mutation in the ELOVL4 gene causes autosomal dominant Stargardt-like
macular dystrophy.

Maugeri A, Meire F, Hoyng CB, Vink C, Van Regemorter N, Karan G, Yang Z, Cremers 
FP, Zhang K.

Department of Human Genetics, Radboud University Nijmegen Medical Centre, Geert
Grooteplein 10, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
a.maugeri@antrg.umcn.nl

PURPOSE: To conduct clinical and genetic studies in a European family with
autosomal dominant Stargardt-like macular dystrophy (adSTGD-like MD) and to
investigate the functional consequences of a novel ELOVL4 mutation. METHODS:
Ophthalmic examination and mutation screening by direct sequencing of the ELOVL4 
gene was performed in two affected individuals. Wild-type and mutant ELOVL4 genes
were expressed as enhanced green fluorescent protein (EGFP) fusion proteins in
transient transfection in NIH-3T3 and HEK293 cells. To determine the subcellular 
localization of ELOVL4, an endoplasmic-reticulum (ER)-specific marker for
pDsRed2-ER was cotransfected with ELOVL4 constructs. Transfected cells were
viewed by confocal microscopy. Western blot analysis was performed to assess
protein expression using an anti-GFP antibody. RESULTS: Affected patients
exhibited macular atrophy with surrounding flecks characteristic of adSTGD-like
MD. A novel ELOVL4 p.Tyr270X mutation was detected in affected individuals. In
cell-transfection studies, wild-type ELOVL4 localized preferentially to the ER.
In contrast, the mutant protein appeared to be mislocalized within transfected
cells. CONCLUSIONS: In a European family with adSTGD-like MD, a novel ELOVL4
mutation was found to underlie the disorder. Transfection studies indicated that,
unlike wild-type ELOVL4, the mutant protein does not localize to the ER but
rather appears to be sequestered elsewhere in an aggregated pattern in the
cytoplasm. Further analysis of the function of normal and mutant ELOVL4 will
provide insight into the mechanism of macular degeneration.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15557430 [PubMed - indexed for MEDLINE]

2131: Br J Ophthalmol. 2004 Dec;88(12):1573-6.

Acute orbital effects of retrobulbar injection on optic nerve head topography.

Akar Y, Apaydin KC, Ozel A.

Akdeniz University, School of Medicine, Department of Ophthalmology,
Antalya-07070, Turkey. yakar@akdeniz.edu.tr

AIM: To assess the effects of acute orbital volume changes after retrobulbar
injection on optic nerve head topography. METHODS: The study population consisted
of 95 patients with type 2 diabetes mellitus with clinically significant macular 
oedema who required focal pattern laser photocoagulation therapy in one eye.
Before each laser treatment, 49 patients required a retrobulbar injection
(approximately 7 ml of a mix of lidocaine 2% with epinephrine and bupivacaine
0.75% in equal volumes) to provide ocular akinesia. Both eyes of all patients
underwent optic nerve head topographic analysis once before laser treatment
(within 30 minutes), and repeated within 1 hour, 1 day, 1 week, 2 weeks, and 4
weeks after treatment, respectively. Topographic analyses were performed using a 
confocal scanning laser ophthalmoscope, HRT-II. The disc area, topography
standard deviation, and a total of 12 topographic parameters were calculated by
HRT-II. RESULTS: The mean age of the patients was 37.9 (SD 3.2) years. The mean
disc area of the subjects was 2.12 (0.44) mm(2). Fellow eyes which were not
treated with laser, and those treated eyes which did not receive retrobulbar
injection before therapy were found not to reveal significant changes in disc
topography in any of the examinations (all p values >0.05). In the topographic
examinations in the first hour, first day, and first week, laser treated eyes
which underwent retrobulbar injection demonstrated significant increase in the
disc area, rim area, rim volume, rim area/disc area, and cup shape measure
parameters while optic cup parameters significantly decreased (all p values
<0.05). In the second week examinations, they did not show significant difference
in disc area measurements (p>0.05). By the fourth week, all of the optic nerve
head topographic variables were not significantly different from the
pre-injection values (all p values >0.05). Colour stereoscopic photographs did
not reveal any differences in optic disc appearance. CONCLUSION: Acute orbital
volume change following retrobulbar injection may cause significant topographic
evidence of optic disc oedema lasting approximately 1 week. Significant changes
in optic rim and cup area may last for 2 weeks after injection, with all
topographic changes returning to baseline by 1 month after injection. The present
findings could be a model to reflect the pathological processes that occur in
cases of acute orbital volume changes such as retrobulbar haemorrhage.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15548815 [PubMed - indexed for MEDLINE]

2132: Br J Ophthalmol. 2004 Dec;88(12):1568-72.

Effect of niacin on the choroidal circulation of patients with age related
macular degeneration.

Metelitsina TI, Grunwald JE, DuPont JC, Ying GS.

Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania, 51
North 39th Street, Philadelphia, PA 19104, USA.

AIM: To investigate the effects of niacin on choroidal blood flow in age related 
macular degeneration (AMD). METHODS: 12 AMD patients with bilateral drusen and
visual acuity of 20/40 or better in the study eye received a single oral dose of 
niacin (six subjects received 500 mg and six received 250 mg) or matching placebo
on two separate occasions. Laser Doppler flowmetry was used to assess relative
choroidal blood velocity (ChB(Vel)), volume (ChB(Vol)), and flow (ChB(Flow)) in
the foveola of the study eye at baseline, 30, and 90 minutes after dosing.
RESULTS: In comparison with placebo, a statistically significant 24% increase in 
ChB(Vol) was observed 30 minutes after niacin administration (ANOVA, p = 0.01).
In comparison with placebo, a significant decrease in ChB(Vel) of 23% was
observed in the 500 mg group (p = 0.04) and no significant change in ChB(Vel) was
seen in the 250 mg group at 30 minutes. No significant changes in ChB(Flow) were 
detected at 30 or 90 minutes. Also, there were no statistically significant
changes in ChB(Vol) or ChB(Vel) at 90 minutes. CONCLUSION: In comparison with
placebo, a significant 24% increase in ChB(Vol) was observed 30 minutes after
niacin administration. Owing to simultaneous decrease in ChB(Vel), however, no
significant change in ChB(Flow) was detected.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15548814 [PubMed - indexed for MEDLINE]

2133: Br J Ophthalmol. 2004 Dec;88(12):1557-62.

Factors influencing visual acuity after intravitreal triamcinolone acetonide as
treatment of exudative age related macular degeneration.

Jonas JB, Kreissig I, Degenring RF.

Universitäts-Augenklinik, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
Jost.Jonas@ma.augen.uni-heidelberg.de

AIM: To evaluate factors influencing change in visual acuity (VA) after
intravitreal injection of triamcinolone acetonide as treatment of exudative age
related macular degeneration (AMD). METHODS: This prospective, interventional,
comparative non-randomised clinical case series study included 94 patients (99
eyes) showing progressive exudative AMD with occult (n = 61 eyes), minimally
classic (n = 18), predominantly classic (n = 1), or totally classic (n = 8)
subfoveal neovascularisation. Mean follow up was 8.5 (SD 4.7) months (median, 7.3
months; range 3.1-24.5 months). All patients received an intravitreal injection
of 20-25 mg of triamcinolone acetonide. RESULTS: An increase in best VA of at
least one line on the Snellen charts was found in 63 (63.1%) eyes.
Correspondingly, mean VA increased significantly (p<0.001) from 0.17 (SD 0.13) to
0.22 (SD 0.17) after the injection. Postoperative increase in VA was
significantly (p<0.001) and negatively correlated with preoperative VA
(correlation coefficient, -0.49). Gain in visual acuity was significantly (p =
0.009) higher if preoperative visual acuity was less than 0.08 (gain: 3.2 (SD
2.9) Snellen lines) than if preoperative VA ranged between 0.08 and 0.20 (gain:
1.2 (SD 2.2) Snellen lines). Change in VA was significantly (p = 0.016) less if
preoperative VA was higher than 0.20 (change: -0.8 (SD 3.4) Snellen lines).
Maximal gain in VA was significantly (p = 0.035) larger in eyes with retinal
pigment epithelium detachment than in eyes with minimally classic subfoveal
neovascularisation. This was statistically independent of age (p = 0.99),
refractive error (p = 0.88), sex (p = 0.92), and duration of follow up (p =
0.46). CONCLUSIONS: Gain in VA after intravitreal injection of 20-25 mg of
triamcinolone acetonide is significantly and negatively correlated with
preoperative VA. It is significantly larger in eyes with retinal pigment
epithelium detachment than in eyes with minimally classic subfoveal
neovascularisation.

PMID: 15548812 [PubMed - indexed for MEDLINE]

2134: Eye. 2005 Nov;19(11):1151-6.

Comment in:
    Eye. 2005 Nov;19(11):1137-41.

Results of radiotherapy of subfoveal neovascularization with 16 and 20 Gy.

Hoeller U, Fuisting B, Schwartz R, Roeper B, Richard G, Alberti W.

Department of Radiotherapy and Radiooncology, University Hospital,
Hamburg-Eppendorf, Germany. ulrike.hoeller@vivantes.de

PURPOSE: In a nonrandomized, prospective study the efficacy of radiotherapy with 
16 and 20 Gray (Gy) for subfoveal neovascularization in age-related macular
degeneration (ARMD) was analysed. MATERIAL AND METHODS: From 1996 to 1998, 63
eyes were irradiated with 16 Gy and 38 eyes with 20 Gy for exudative ARMD. A
total of 12 eyes had classic ARMD, 89 eyes occult ARMD, median baseline visual
acuity (VA) was 6/30 (range: 3/60-6/9.5), median age was 78 years. Risk factors
(type of ARMD, baseline VA) were evenly distributed in both groups. Median
follow-up was 1.3 years (range: 4 months-4.7 years). VA of +/-1 line or better
and unchanged size and activity of the membrane in fluorescein angiography were
defined as stable. Actuarial methods were used. RESULTS: Median loss of VA was -3
lines (range: -14 to +5), neovascularization remained unchanged or decreased in
size and activity in 35 eyes. At 18 months, the probability of stabilized VA was 
0.4 (95% confidence interval (CI): 0.3-0.5), at 24 months 0.3 (95% CI: 0.2-0.4). 
Radiation dose, type of ARMD or baseline VA had no significant impact on outcome 
of VA and membrane size and activity (P>0.05). Side effects were mild and
transient increased tearing. CONCLUSION: In this study, the results after
radiotherapy were comparable to the natural course of the disease. An impact of
radiation dose (16 vs 20 Gy) on stabilizing visual acuity and subfoveal
neovascularization could not be shown. The results of studies on dose escalation 
using very small fields and high radiation doses should be awaited.

Publication Types: 
    Clinical Trial

PMID: 15543182 [PubMed - indexed for MEDLINE]

2135: Diabetes Res Clin Pract. 2004 Dec;66(3):219-27.

Quantitative measurement of retinal thickness in patients with diabetic macular
edema is useful for evaluation of therapeutic agents.

Funatsu H, Yamashita H, Shimizu E, Mimura T, Nakamura S, Hori S.

Department of Ophthalmology, Diabetes Center, Tokyo Women's Medical University,
8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan. tfunatsu@nifty.com

The effect of lisinopril (an angiotensin-converting enzyme inhibitor) on diabetic
macular edema (DME) was investigated by quantitative measurement of macular
thickness. In a nonrandomized clinical trial, 19 normotensive type 2 diabetic
patients with DME prospectively received oral lisinopril therapy for 2 months.
Another 10 normotensive type 2 diabetic patients with similar DME were
prospectively followed for two months without treatment. Central macular
thickness was measured with a retinal thickness analyzer (RTA). In the lisinopril
group, visual acuity improved by two lines or more in two out of 19 eyes (11%),
was unchanged in 15 eyes (78%), and deteriorated by two lines or more in two eyes
(11%). The mean central macular thickness was significantly reduced after 2
months of treatment (381.3 +/- 121.1 microm) compared with that before
administration (475.2 +/- 171.0 microm, P = 0.0093). In the control group,
central macular thickness was not significantly decreased after 2 months (458.5
+/- 113.7 microm, P = 0.2178) compared with the baseline value (464.7 +/- 152.2).
Fluorescein angiography showed that macular leakage was decreased in 10 patients 
from the lisinopril group (53%) and was unchanged in nine patients (47%). There
was a significant difference of central macular thickness between the patients
with and without improvement of macular leakage (P = 0.0040). Lisinopril therapy 
may reduce macular thickness in patients with DME, as shown by this quantitative 
study. In addition, quantitative measurement of retinal thickness is useful when 
evaluating therapeutic agents for DME.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 15536018 [PubMed - indexed for MEDLINE]

2136: Arch Ophthalmol. 2004 Nov;122(11):1647-51.

Scanning laser entoptic perimetry for the detection of age-related macular
degeneration.

Freeman WR, El-Bradey M, Plummer DJ.

The Jacobs Retina Center, Department of Ophthalmology, University of California, 
San Diego, Shiley Eye Center, La Jolla, CA 92093-0946, USA.
freeman@eyecenter.ucsd.edu

OBJECTIVE: To determine the sensitivity and specificity of scanning laser
entoptic perimetry for detecting visual function damage due to age-related
macular degeneration (ARMD). METHODS: We measured the presence or absence of
visual field disturbances by entoptic perimetry and determined the severity of
ARMD based on masked readings of fundus photographs. A prospective masked study
comparing the findings of entoptic perimetry with fundus photographs was
performed. We recruited 91 patients with ARMD and 24 patients without ARMD during
ophthalmologic visits. An appropriate institutional review board approval was
obtained for the project. The main outcome measure was the detection of visual
scotomata. RESULTS: Scanning laser entoptic perimetry had an overall sensitivity 
of 82% and a specificity of 100% for the detection of ARMD. The sensitivity for
early stages of the disease is greater than 70%, and increases to above 90% for
moderate to late stages. CONCLUSION: Scanning laser entoptic perimetry is a
specific and sensitive test for detecting ARMD, even at the earliest stages when 
patients are typically asymptomatic.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15534125 [PubMed - indexed for MEDLINE]

2137: Arch Ophthalmol. 2004 Nov;122(11):1642-6.

Comment in:
    Arch Ophthalmol. 2005 Aug;123(8):1157; author reply 1157-8.    Arch Ophthalmol. 2005 Nov;123(11):1615.

Detection of age-related macular degeneration using a nonmydriatic digital camera
and a standard film fundus camera.

Klein R, Meuer SM, Moss SE, Klein BE, Neider MW, Reinke J.

Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison
53726, USA. klienr@epi.ophth.wisc.edu

OBJECTIVE: To compare gradings of lesions associated with age-related macular
degeneration (AMD) from digital and stereoscopic film images. DESIGN: Instrument 
validation study. PARTICIPANTS: Sixty-two subjects (124 eyes) with varying
degrees of AMD, including no AMD. METHODS: Images of the optic disc and macula
were taken using a 45 degrees digital camera (6.3 megapixels) through
dark-adapted pupils and pharmacologically dilated pupils. In addition, 30 degrees
stereoscopic retinal film images were taken through pharmacologically dilated
pupils of the same eyes. All images were graded for drusen size, type, and area; 
pigmentary abnormalities; geographic atrophy; and neovascular lesions using the
modified Wisconsin Age-Related Maculopathy Grading System. Exact agreement and
unweighted kappa scores were calculated for paired gradings resulting from
digital and film images. MAIN OUTCOME MEASURE: Agreement between gradings
obtained from stereoscopic slide transparencies and digital nonstereoscopic
images. RESULTS: Exact agreement between gradings of digital and stereoscopic
film images taken through pharmacologically dilated pupils was 91% (kappa = 0.85)
for the categories of none, early AMD, and late AMD. Exact agreement for gradings
of digital images taken through dark-adapted pupils compared with gradings of
film images was 80% (kappa = 0.69). Exact agreement for gradings of digital
images captured through dark-adapted and pharmacologically dilated pupils was 86%
(kappa = 0.78). In addition, kappa scores for agreement between different
approaches for individual lesions were moderate to almost perfect. CONCLUSIONS:
Gradings resulting from high-resolution digital images, especially when the pupil
is pharmacologically dilated, are comparable with those resulting from film-based
images. We conclude that digital imaging of the retina is useful for
epidemiological studies of AMD.

Publication Types: 
    Comparative Study
    Research Support, U.S. Gov't, P.H.S.
    Validation Studies

PMID: 15534124 [PubMed - indexed for MEDLINE]

2138: Am J Ophthalmol. 2004 Nov;138(5):879-81.

Optic atrophy and macular degeneration as initial presentations of subacute
sclerosing panencephalitis.

Berker N, Batman C, Guven A, Ozalp S, Aslan O, Zilelioglu O.

Department of Ophthalmology, Ankara Social Insurance Hospital, Turkey.

PURPOSE: To report a case of subacute sclerosing panencephalitis in which the
initial clinical presentations were optic atrophy and macular degeneration.
DESIGN: Observational case report. METHODS: A 9-year-old boy with visual loss
attributable to optic atrophy and macular degeneration had a diagnostic
examination. RESULTS: The visual acuity levels of both eyes were light perception
at presentation. Fundus examination revealed bilateral optic atrophy and macular 
degenerative changes including retinal pigment epithelial atrophy, macular
scarring, and epiretinal membrane formation. The antimeasles IgG titers were high
both in serum and cerebrospinal fluid samples. Neurologic symptoms of myoclonus, 
ataxia, motor, and mental disabilities occurred 4 months after the onset of first
visual disturbances and 2 weeks after the patient applied to our clinic.
CONCLUSION: Children with optic atrophy and macular degenerative lesions should
be examined for sclerosing panencephalitis, even if the classical neurologic
symptoms of this disease are not present.

Publication Types: 
    Case Reports

PMID: 15531336 [PubMed - indexed for MEDLINE]

2139: Am J Ophthalmol. 2004 Nov;138(5):818-28.

The age-related macular degeneration radiotherapy trial (AMDRT): one year results
from a pilot study.

Marcus DM, Peskin E, Maguire M, Weissgold D, Alexander J, Fine S, Followill D;
AMDRT Research Group.

University of Pennsylvania, Department of Ophthalmology, Philadelphia,
Pennsylvania, USA.

PURPOSE: To assess the short-term safety and efficacy of treating subfoveal
choroidal neovascularization (CNV) with external beam radiation delivered in 5 x 
4 Gy fractions among patients having age-related macular degeneration (AMD).
DESIGN: A multicenter prospective randomized controlled pilot study. METHODS:
Eighty-eight patients were enrolled through 10 sites and were randomized to
radiotherapy (20 Gy delivered in 5 daily fractions of 4 Gy each; 6 MV [N = 41])
or no radiotherapy (sham radiotherapy [N = 22] or observation [N = 25]).
Eligibility criteria included visual acuity of at least 20/320 and subfoveal CNV 
not amenable to treatment. Randomization was stratified by lesion type (new or
recurrent CNV) and blood (<50% or >/=50% of the lesion [N = 13]). The primary
outcome measure was loss of >/=3 lines of visual acuity. Secondary outcome
measures were angiographic response and side effects. RESULTS: At baseline,
patient and ocular characteristics were similar between treatment groups. At six 
months, 9 radiated eyes (26%) and 17 eyes not radiated (49%) lost >/=3 lines of
visual acuity (P = .04; stratified chi(2) test). At 12 months, 13 radiated eyes
(42%) and 9 observed eyes (49%) lost >/=3 visual acuity lines (P = .60). The
radiated group demonstrated smaller lesions and less fibrosis than the
nonradiated group (P = .05 and .004, respectively) at 12 months.
Radiation-induced complications were not observed except for one radiated eye
with numerous cotton wool spots and possible radiation retinopathy. CONCLUSIONS: 
External beam radiation at 5 x 4 Gy may have a modest and short-lived (six month)
benefit in preserving visual acuity.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, U.S. Gov't, P.H.S.

PMID: 15531318 [PubMed - indexed for MEDLINE]

2140: Ophthalmology. 2004 Nov;111(11):2050-6.

Delayed absorption of macular edema accompanying serous retinal detachment after 
grid laser treatment in patients with branch retinal vein occlusion.

Ohashi H, Oh H, Nishiwaki H, Nonaka A, Takagi H.

Department of Ophthalmology and Visual Sciences, Graduate School of Medicine,
Kyoto University, Kyoto, Japan.

PURPOSE: To study the detailed process of macular edema (ME) absorption after
grid laser photocoagulation in patients with branch retinal vein occlusion
(BRVO). The influence of pretreatment serous retinal detachment (SRD) at the
fovea on patient outcome was also evaluated. DESIGN: Retrospective,
interventional, comparative case series. PARTICIPANTS: Thirty-seven BRVO patients
presenting with severe ME. METHODS: Patients were treated with grid laser
photocoagulation with 6 months of follow-up examinations. Baseline and
post-treatment examinations included measurements of visual acuity (VA),
fluorescein angiography, and detailed imaging of ME by optical coherence
tomography (OCT). Macular thickness was defined as the distance from the inner
retinal surface to the outer border of the sensory retina (foveal retinal
thickness) and also to the inner border of the retinal pigment epithelium
including the SRD (total foveal elevation). MAIN OUTCOME MEASURES: Post-treatment
macular thickness with OCT, VA converted to the logarithm of the minimum angle of
resolution, and absorption of SRD, and correlations of macular thickness and VA
both before and after treatment. RESULTS: Total foveal elevation and VA were
significantly improved at 1, 3, and 6 months after treatment. There was also a
significant correlation between reduction of total foveal elevation and increase 
in VA. Fourteen eyes (37.8%) displayed SRD, as evidenced by OCT at the baseline. 
In eyes without SRD, foveal retinal thickness and VA had significantly improved
in a time-dependent manner. However, although SRD itself was almost absorbed 6
months after treatment, the improvement of both VA and total foveal elevation in 
eyes with pretreatment SRD was not significant compared with baseline conditions.
Both post-treatment total foveal elevation and VA of eyes with SRD tended to be
worse than eyes without SRD. CONCLUSION: The presence of subfoveal SRD retards
the absorption of ME and recovery of VA after grid laser photocoagulation in
patients with BRVO.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15522371 [PubMed - indexed for MEDLINE]

2141: Ophthalmology. 2004 Nov;111(11):2044-9.

Intravitreal triamcinolone for diabetic macular edema that persists after laser
treatment: three-month efficacy and safety results of a prospective, randomized, 
double-masked, placebo-controlled clinical trial.

Sutter FK, Simpson JM, Gillies MC.

Save Sight Institute, Department of Clinical Ophthalmology and Eye Health, The
University of Sydney, Sydney, NSW, Australia.

OBJECTIVE: To determine whether an intravitreal injection of triamcinolone
acetonide for persistent diabetic macular edema after adequate laser treatment
improves visual acuity. DESIGN: Prospective, double-masked, placebo-controlled,
randomized clinical trial. PARTICIPANTS AND CONTROLS: Sixty-nine eyes of 43
patients were entered into the study, with 34 eyes randomized to receive active
treatment and 35 randomized to receive a placebo injection. Sixty-five of 69 eyes
(94%) completed the 3-month study visit. INTERVENTION: Using a 27-gauge needle,
0.1 ml of triamcinolone acetonide was injected through the pars plana. The
procedure was performed in a minor procedures area in the outpatient clinic under
sterile conditions and using topical and subconjunctival anesthesia. Eyes
randomized to placebo received a subconjunctival saline injection using the
identical procedure for preparation. MAIN OUTCOME MEASURES: The main outcome
measures were improvement of best-corrected logarithm of the minimum angle of
resolution visual acuity by 5 or more letters and incidence of moderate or severe
adverse events. RESULTS: Eighteen of 33 eyes (55%) treated with triamcinolone
gained 5 or more letters of best-corrected visual acuity compared with 5 of 32
eyes (16%) treated with placebo (P = 0.002). Macular edema was reduced by 1 or
more grades as determined by masked semiquantitative contact lens examination in 
25 of 33 treated eyes (75%) versus 5 of 32 untreated eyes (16%; P<0.0001).
Optical coherence tomography showed a mean reduction of central retinal thickness
of 152 mum in the 21 treated eyes that were examined compared with a reduction of
36 mum in 20 placebo-treated eyes. Infectious endophthalmitis developed in 1
triamcinolone-treated eye that was treated adequately without loss of visual
acuity. CONCLUSIONS: In the short term, intravitreal triamcinolone is an
effective and relatively safe treatment for eyes with diabetic macular edema that
have failed laser treatment. Although it will be essential to study longer-term
outcomes, the use of intravitreal triamcinolone may be considered in 1 eye of
patients who continue to lose vision from diabetic macular edema despite
conventional management.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15522370 [PubMed - indexed for MEDLINE]

2142: Ophthalmology. 2004 Nov;111(11):2007-14.

Comment in:
    Ophthalmology. 2005 Nov;112(11):2055.

Surgery for hemorrhagic choroidal neovascular lesions of age-related macular
degeneration: quality-of-life findings: SST report no. 14.

Childs AL, Bressler NM, Bass EB, Hawkins BS, Mangione CM, Marsh MJ, Miskala PH;
Submacular Surgery Trials (SST) Research Group.

SST Coordinating Center, 550 North Broadway, 9th Floor, Baltimore, MD 21205, USA.
achilds1@jhmi.edu

PURPOSE: To present and compare findings from health-related quality-of-life
(HRQOL) interviews conducted with patients enrolled in the SST Group B Trial
evaluating surgical removal of subfoveal choroidal neovascular lesions associated
with age-related macular degeneration versus observation. DESIGN: Randomized
clinical trial. PARTICIPANTS: Eligible patients had predominantly hemorrhagic
subfoveal choroidal neovascular lesions (total lesion size of >3.5 disc areas,
area of blood at least 50% of the lesion area, and at least 75% of blood
posterior to the equator) and best-corrected visual acuity (VA) of 20/100 to
<20/1600 but at least light perception in the study eye. Three hundred thirty-six
patients enrolled after baseline quality-of-life interviews, 168 assigned to each
of surgery or observation. METHODS: Clinical and HRQOL data were collected before
randomization and at 6, 12, 24, 36, and 48 months after enrollment. Baseline
clinical evidence was used to stratify patients as having unilateral or bilateral
neovascularization at the time of randomization. The HRQOL interviews included
the National Eye Institute Visual Function Questionnaire (NEI-VFQ), the 36-item
Short Form Health Survey, and the Hospital Anxiety and Depression Scale. MAIN
OUTCOMES MEASURE: Two-year change in NEI-VFQ. RESULTS: At 24 months after
enrollment, overall NEI-VFQ scores had a median decrease of 1 point from baseline
in the observation arm (95% confidence interval [CI]: -4 to 3 points) and no
change in the surgery arm (95% CI: -3 to 3 points) (P = 0.70). Changes from
baseline on NEI-VFQ subscales also were similar between treatment arms.
Differences in scores by unilateral or bilateral involvement seen at baseline in 
each treatment arm persisted throughout follow-up for most outcomes. Planned
analyses stratified by VA showed trends (P = 0.17) in favor of surgery at 24
months in the patients with baseline VA greater than 20/200 for the NEI-VFQ scale
(3.5-point median increase from baseline in the surgery arm [95% CI: -4 to 7] vs.
a 1-point median loss from baseline in the observation arm [95% CI: -6 to 4]).
CONCLUSIONS: No difference was detected with respect to vision-targeted
quality-of-life outcomes for patients randomized to surgery or observation in the
SST Group B Trial. This article contains additional online-only material
available at www.ophsource.com/periodicals/ophtha.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15522365 [PubMed - indexed for MEDLINE]

2143: Ophthalmology. 2004 Nov;111(11):1993-2006.

Comment in:
    Ophthalmology. 2005 Nov;112(11):2055.

Surgery for hemorrhagic choroidal neovascular lesions of age-related macular
degeneration: ophthalmic findings: SST report no. 13.

Bressler NM, Bressler SB, Childs AL, Haller JA, Hawkins BS, Lewis H, MacCumber
MW, Marsh MJ, Redford M, Sternberg P Jr, Thomas MA, Williams GA; Submacular
Surgery Trials (SST) Research Group.

SST Coordinating Center, Wilmer Clinical Trials and Biometry, 550 North Broadway,
9th Floor, Baltimore, MD 21205-2010, USA. nmboffice@jhmi.edu

PURPOSE: To present best-corrected visual acuity (BCVA) findings and other
clinical outcomes from eyes of patients enrolled in one of the Submacular Surgery
Trials (SST) evaluating surgical removal versus observation of predominantly
hemorrhagic subfoveal choroidal neovascularization (CNV) associated with
age-related macular degeneration. DESIGN: Randomized clinical trial (SST Group B 
Trial). PARTICIPANTS: Eligible patients had subfoveal choroidal neovascular
lesions greater than 3.5 disk areas (8.9 mm2) composed of at least 50% blood
(either blood or CNV underlying the center of the foveal avascular zone) and BCVA
of 20/100 to light perception in the study eye. INTERVENTION: Patients were
assigned randomly at time of enrollment to observation or surgical removal of
blood and any associated CNV. MAIN OUTCOME MEASURE: A successful outcome was
defined a priori as either improvement in visual acuity (VA), no change in VA, or
a decline in VA of no more than 1 line (7 letters) from baseline to the 24-month 
examination based on an intent-to-treat analysis. RESULTS: Of 336 patients
enrolled, 168 were assigned to each treatment arm; treatment arms were balanced
by baseline characteristics. Of 1501 expected examinations 3 months through 36
months after baseline, 1370 (91%) were performed. Loss of > or =2 lines (> or =8 
letters) of VA occurred in 56% of surgery eyes, versus 59% of observation eyes
examined at 24 months. Although severe loss of VA was not the primary outcome of 
interest, surgery more often prevented such loss: 36% in the observation arm
versus 21% in the surgery arm at the 24-month examination (chi2 P = 0.004). Of
initially phakic eyes, the cumulative percentage that had undergone cataract
surgery by 24 months was 44% in the surgery arm, compared with 6% in the
observation arm. Twenty-seven eyes (16%) in the surgical arm, compared with 3
eyes (2%) in the observation arm, had a rhegmatogenous retinal detachment (RD).
CONCLUSIONS: Submacular surgery as performed in the SST Group B Trial did not
increase the chance of stable or improved VA (the primary outcome of interest)
and was associated with a high risk of rhegmatogenous RD, but did reduce the risk
of severe VA loss in comparison with observation. This article contains
additional online-only material available at
http://www.ophsource.com/periodicals/ophtha.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, U.S. Gov't, P.H.S.

PMID: 15522364 [PubMed - indexed for MEDLINE]

2144: Ophthalmology. 2004 Nov;111(11):1981-92.

Comment in:
    Ophthalmology. 2005 Nov;112(11):2055.

Surgery for subfoveal choroidal neovascularization in age-related macular
degeneration: quality-of-life findings: SST report no. 12.

Miskala PH, Bass EB, Bressler NM, Childs AL, Hawkins BS, Mangione CM, Marsh MJ;
Submacular Surgery Trials (SST) Research Group.

SST Coordinating Center, 550 North Broadway, 9th Floor, Baltimore, MD 21205-2010,
USA.

PURPOSE: To describe health-related quality of life (HRQOL), overall and in
patients with unilateral or bilateral choroidal neovascularization (CNV), in a
clinical trial (Group N Trial) comparing observation and surgical removal of
subfoveal CNV secondary to age-related macular degeneration (AMD). DESIGN:
Randomized clinical trial. PARTICIPANTS: Eligible patients had untreated
subfoveal CNV and AMD, best-corrected visual acuity (VA) of 20/100 to 20/800,
classic CNV on fluorescein angiography, and a total subfoveal lesion size of < or
=9.0 disc areas in the study eye. METHODS: Health-related quality of life data
(the National Eye Institute Visual Function Questionnaire [NEI-VFQ], 36-item
Short Form Health Survey [SF-36], and Hospital Anxiety and Depression Scale
[HADS]) and clinical data were collected at baseline and at 6, 12, 24, 36, and 48
months. Patients were divided into unilateral and bilateral CNV subgroups based
on fluorescein angiographic and clinical evidence. MAIN OUTCOME MEASURE: Two-year
change in the NEI-VFQ. RESULTS: Of 454 patients enrolled, 228 were assigned to
observation and 226 to surgery. At baseline, median overall NEI-VFQ scores were
67 in the observation group and 69 in the surgery group; by 2 years, the
observation group had lost a median of 3 points (95% confidence interval [CI]: -6
to -2), and the surgery group gained a median of 1 point (CI: -1 to 3). The
largest difference was observed for the mental health subscale, where the
observation group lost a median of 5 points (CI: -5 to 0), and the surgery group 
gained a median of 5 points (CI: 0-10) by 2 years. Treatment differences in
median 2-year changes in NEI-VFQ scores favored surgery by up to 10 points for
unilateral cases and up to 8 points for bilateral cases. No treatment difference 
in 2-year change was observed for the SF-36 physical component summary; 2-year
change in the mental component summary favored surgery by 2 points. Few patients 
(2%-4%) had HADS definite anxiety or depression at baseline or at 24 months.
CONCLUSIONS: Although HRQOL outcomes were better in the submacular surgery arm
than in the observation arm, surgery (per protocol) is not recommended because VA
outcomes (reported elsewhere) were similar in the treatment arms. This article
contains additional online-only material available at
http://www.ophsource.com/periodicals/ophtha.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15522363 [PubMed - indexed for MEDLINE]

2145: Ophthalmology. 2004 Nov;111(11):1967-80.

Comment in:
    Ophthalmology. 2005 Nov;112(11):2055.

Surgery for subfoveal choroidal neovascularization in age-related macular
degeneration: ophthalmic findings: SST report no. 11.

Hawkins BS, Bressler NM, Miskala PH, Bressler SB, Holekamp NM, Marsh MJ, Redford 
M, Schwartz SD, Sternberg P Jr, Thomas MA, Wilson DJ; Submacular Surgery Trials
(SST) Research Group.

SST Coordinating Center, Wilmer Clinical Trials and Biometry, 550 North Broadway,
9th Floor, Baltimore, MD 21205-2010, USA. bhawkins@jhmi.edu

PURPOSE: To present visual acuity (VA) and related findings from patients
enrolled in one of the Submacular Surgery Trials (SST) evaluating surgical
removal versus observation of subfoveal choroidal neovascularization secondary to
age-related macular degeneration (SST Group N Trial). DESIGN: Randomized clinical
trial. PARTICIPANTS: Eligible patients had age-related macular degeneration with 
subfoveal choroidal neovascularization, some with a classic pattern on
fluorescein angiography, and best-corrected VA (BCVA) of 20/100 to 20/800 in one 
eye (study eye) that had received no treatment in the macula. Any contiguous
blood had to account for <50% of the total area occupied by the subfoveal lesion 
(maximum size, 9.0 disc areas [22.9 mm2]). METHODS: Randomization was stratified 
by VA and by clinical center. All patients were scheduled for study examinations 
at 3, 6, 12, and 24 months after enrollment for assessment of study outcomes.
MAIN OUTCOME MEASURE: A successful outcome was defined a priori to be either
improvement of BCVA or VA no more than 1 line (7 letters) worse than baseline at 
the 24-month examination. RESULTS: Of 454 patients enrolled, 228 study eyes were 
assigned to observation and 226 to surgery. The percentages of eyes that had
successful outcomes were similar in the 2 arms: 44% assigned to observation and
41% assigned to surgery. Median VA losses from baseline to the 24-month
examination were 2.1 lines (10.5 letters) in the observation arm and 2.0 lines
(10 letters) in the surgery arm. Median VA declined from 20/100 at baseline to
20/400 at 24 months in both arms. No subgroup of patients was identified in which
submacular surgery led to better VA outcomes. In the surgery arm, 55 (39%) of 142
initially phakic eyes had cataract surgery by the 24-month examination, compared 
with 6 (5%) of 133 eyes in the observation arm. Rhegmatogenous retinal detachment
occurred in 12 surgery eyes (5%) and 1 observation eye. CONCLUSIONS: Submacular
surgery, as performed in this clinical trial, did not improve or preserve VA for 
24 months in more eyes than observation and is not recommended for patients with 
similar lesions. This article contains additional online-only material available 
at http://www.ophsource.com/periodicals/ophtha.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15522362 [PubMed - indexed for MEDLINE]

2146: Med J Aust. 2004 Nov 1;181(9):471-2.

Comment in:
    Med J Aust. 2005 Mar 21;182(6):310-1; author reply 311.

Age-related macular degeneration and its possible prevention.

Constable IJ.

Despite well publicised claims of the therapeutic value of dietary supplements
and other new treatments, the evidence for their effectiveness is modest.

Publication Types: 
    Editorial
    Review

PMID: 15516188 [PubMed - indexed for MEDLINE]

2147: Semin Ophthalmol. 2003 Sep;18(3):116-20.

Pars plana vitrectomy for refractory diabetic macular edema.

Grigorian R, Bhagat N, Lanzetta P, Tutela A, Zarbin M.

Institute of Ophthalmology and Visual Science, New Jersey Medical School, Newark 
01701-1709, USA.

OBJECTIVE: The aim of this study is to describe the results of pars plana
vitrectomy (PPV) for refractory diabetic macular edema (DME). METHODS: Review of 
the relevant peer-reviewed scientific literature identified using Medline. MAIN
OUTCOME MEASURES: The anatomical and functional outcome of surgery. RESULTS:
Vitrectomy with or without internal limiting membrane (ILM) peeling can be
beneficial for the treatment of DME that is resistant to laser photocoagulation
or sub-Tenon's steroid injection. Visual improvement has been reported in
approximately 40-90% of patients, with approximately 85-100% experiencing either 
improvement or stabilization of vision. Retinal edema decreases or resolves in
approximately 70-100% of patients. Complications range in severity with
approximately 5-20% of patients developing peripheral retinal breaks,
approximately 1-2% developing retinal detachment, approximately 2% developing
macular hole, and approximately 10-60% developing cataract. Severe complications 
such as rubeosis iridis and the fibrinoid syndrome have also been reported.
CONCLUSION: Pars plana vitrectomy can be an effective treatment for diabetic
macular edema refractory to laser therapy and/or sub-Tenon's capsule steroid
injection.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 15513471 [PubMed - indexed for MEDLINE]

2148: Semin Ophthalmol. 2001 Dec;16(4):218-22.

Cost of care for patients with age-related macular degeneration in Switzerland
and cost-effectiveness of treatment with verteporfin therapy.

Greiner RA.

Project Manager Health Economics, HealthEcon Ltd. Basel, Switzerland.
rgreiner@healthecon.com

The cost-effectiveness of photodynamic therapy with verteporfin in the treatment 
of patients with predominantly classic subfoveal choroidal neovascularization
secondary to age-related macular degeneration was investigated by a Markov Model 
over a time horizon of three years in Switzerland. This model describes patients 
moving between three levels of visual acuity (e.g., good vision, impaired vision,
highly impaired vision) and death in terms of transition probabilities.
Transition probabilities as well as effectiveness values were derived from a
randomized, controlled, double-masked clinical trial. Effectiveness for
verteporfin therapy and for placebo was calculated in terms of vision years:
1.068 and 0.494, respectively. Cost per level of visual acuity was assessed in
ascending order by expert panels from a societal perspective. Cost strongly
increased parallel with vision loss on a patient-per-year basis from 4683 CHF at 
good vision to 8443 CHF at impaired vision, and was highest with 15231 CHF at
highly impaired vision. The model-calculated cost per visionyear were 14907 CHF
for patients in the verteporfin therapy group, versus 21047 CHF for patients in
the placebo group. The incremental cost per vision-year additionally saved
through verteporfin therapy was 9624 CHF. The study demonstrated that greater
effectiveness of verteporfin therapy versus placebo compensated for the cost of
the therapy so that verteporfin therapy was clearly costeffective. Therefore, for
the indicated patients with AMD that causes severe vision loss, verteporfin
therapy can be recommended as the therapy of choice, on both clinical and
economic grounds.

PMID: 15513444 [PubMed - indexed for MEDLINE]

2149: Semin Ophthalmol. 2001 Dec;16(4):207-12.

Verteporfin therapy for subfoveal choroidal neovascularization in age-related
macular degeneration: from clinical trials to clinical practice.

Sickenberg M.

Hopital Opthalmique Jules Gonin, Lauzanne, Switzerland.
michel.sickenberg@bluewin.ch

People with choroidal neovascularization (CNV) due to age-related macular
degeneration (AMD) are at high risk of central vision loss. Until verteporfin
therapy became available, there was no safe and effective treatment for a large
majority of these people. The phase III clinical trials of verteporfin therapy
showed that treatment could safely reduce the risk of vision loss in the majority
of patients presenting with either predominantly classic CNV or with occult with 
no classic CNV, and in selected patients with minimally classic CNV. The decision
to treat patients with subfoveal CNV due to AMD using verteporfin therapy,
requires an understanding of the outcomes of these clinical trials and of
published guidelines. This review presents the key findings of the trials and
outlines the factors that should be considered in clinical practice when deciding
whether verteporfin therapy is indicated.

Publication Types: 
    Review

PMID: 15513442 [PubMed - indexed for MEDLINE]

2150: Semin Ophthalmol. 2001 Dec;16(4):201-6.

Photodynamic therapy with verteporfin: a new treatment in ophthalmology.

Michels S, Schmidt-Erfurth U.

University Eye Hospital, Lübeck, Germany.

Photodynamic therapy (PDT) with verteporfin is a new treatment modality in
ophthalmology that has previously shown its effectiveness in treatment of a
variety of neoplastic pathologies. In this therapeutic approach, the
photosensitizer verteporfin is activated by non-thermal laser light to obtain
closure of neovascular structures. Preclinical and clinical studies have
indicated that PDT is a safe, selective, and effective treatment for choroidal
neovascularization in age-related macular degeneration. No significant damage to 
the neurosensory retina was found, which explains why PDT does not cause loss of 
visual acuity and may be used in a larger population than laser photocoagulation.
This review summarizes the mechanisms of action of PDT, and the results of
preclinical and clinical studies in ophthalmology.

Publication Types: 
    Review

PMID: 15513441 [PubMed - indexed for MEDLINE]

2151: Semin Ophthalmol. 2001 Dec;16(4):181-200.

Photodynamic therapy of age-related macular degeneration: History and principles.

van den Bergh H.

Swiss Federal Institute of Technology, Lausanne, Switzerland.
hubert.vandenbergh@epfl.ch

We briefly review the history and principles of photodynamic therapy (PDT),
especially as it is applied to choroidal neovascularization (CNV) in age-related 
macular degeneration (AMD). After a brief general history of PDT, we discuss the 
relationship between the physicochemical structure and photodynamic activity of
the second-generation photosensitizers, such as those in current clinical use. We
then discuss the basic photophysics of photosensitizer molecules, and describe
the initial chemical reactions induced by activated sensitizers. We outline a
novel method for screening photosensitizers to be used in treating CNV, as well
as the complex biomolecular pathways modulated by PDT-induced oxidative stress
and the vascular effects of PDT in solid tumors. The paper closes with a
discussion of how all this information might be used to improve the selectivity
and efficacy of clinically useful photosensitizers.

Publication Types: 
    Historical Article
    Review

PMID: 15513440 [PubMed - indexed for MEDLINE]

2152: Semin Ophthalmol. 2003 Dec;18(4):251-8.

Diabetic macular edema: classification, medical and laser therapy.

Bandello F, Pognuz R, Polito A, Pirracchio A, Menchini F, Ambesi M.

Department of Ophthalmology, University of Udine, 33100 Udine, Italy.
Francesco.bandelo@dsc.uniud.it

PURPOSE: to propose and describe a new classification of diabetic macular edema
(DME) based on its etiopathogenetic features and to present efficacy and safety
data on medical and laser treatments currently used and under investigation.
METHODS: available literature on DME has been reviewed and information provided
by contact lens biomicroscopy, fluorescein angiography and optical coherence
tomomography has been combined; published data from trials and reports
investigating effectiveness of medical and laser treatments were also analyzed.
RESULTS: DME was classified according to its main etiopathogenetic components:
prevalently retinovascular, tractional and with taut attached posterior hyaloid, 
each of them having peculiar aspects on fundus, angiographic and tomographic
examination. Focal laser treatment remains the only effective intervention, as
shown by a large randomized controlled trial, but new less-invasive
photocoagulation strategies (i.e., light laser photocoagulation and subthreshold 
micropulse diode laser) as well as pharmacological approaches (i.e.,
antioxidants, PKC inhibitors, aldose-reductase and AGE inhibitors, VEGF
inhibitors, intravitreal triamcinolone) are emerging. CONCLUSIONS: based on our
review a classification of DME was developed that may prove useful in making the 
appropriate treatment decision; the new laser and pharmacological treatments
currently investigated are promising and need to be confirmed by large,
controlled clinical trials.

Publication Types: 
    Review

PMID: 15513012 [PubMed - indexed for MEDLINE]

2153: Ophthalmic Genet. 2004 Sep;25(3):219-26.

Association of EFEMP1 with malattia leventinese and age-related macular
degeneration: a mini-review.

Marmorstein L.

Department of Ophthalmology, University of Arizona, Tuscon, USA.
lmarmorstein@eyes.arizona.edu

Malattia leventinese (ML) or Doyne honeycomb retinal dystrophy (DHRD) was the
first clinically and histopathologically described Mendelian maculopathy. The
gene responsible for ML/DHRD, EFEMPI (fibulin-3/SI-5/FBNL) encodes a member of
the fibulin family, a newly recognized family of extracellular matrix proteins.
EFEMPImutations have not been found in age-related macular degeneration (AMD)
patients despite the close phenotypic similarities between ML/DHRD and AMD. This 
non-correlating genotype/phenotype relationship between inherited and age-related
conditions is typical for common age-related diseases. Biochemical pathways
delineated in other diseases indicate that the gene associated with the inherited
condition is nonetheless critical in age-related forms. This review summarizes
current knowledge relating to ML/DHRD and EFEMPI,with discussion of why EFEMPI
mutations are absent in AMD and how EFEMPI may be involved in the pathogenesis of
ML/DHRD and AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.
    Review

PMID: 15512998 [PubMed - indexed for MEDLINE]

2154: Curr Eye Res. 2004 Jun;28(6):421-6.

Mouse model of post-surgical breakdown of the blood-retinal barrier.

Liu H, Demetriades AM, Xiao WH, Campochiaro PA, Vinores SA.

Department of Ophthalmology, The Johns Hopkins University School of Medicine,
Baltimore, Maryland 21287-9289, USA.

PURPOSE: Post-surgical macular edema is an important clinical problem resulting
from breakdown of the blood-retinal barrier (BRB) after surgery. This study was
designed to develop a mouse model of post-surgical BRB breakdown. METHODS: Two
25-gauge needles, one for infusion and one for aspiration, were inserted through 
the limbus and into the lens of one eye of adult male C57BL/6 mice. The anterior 
portion of the lens was aspirated and the fellow eye was untreated. At several
time points after surgery, the integrity of the BRB was assessed quantitatively, 
using [3H]mannitol as a tracer, or qualitatively, using immunohistochemical
staining for albumin. RESULTS: Eyes with partial lens extraction had a
significant increase in retinal vascular leakage one day after surgery, which
persisted two and three days after surgery, but by five days, was not
significantly different from controls. Immunohistochemical staining for albumin
demonstrated that the breech in the barrier was sufficient to allow passage of a 
60kDa protein into the retina, and was localized predominantly to retinal
vessels. CONCLUSIONS: Partial lens extraction in mice results in BRB breakdown
(primarily the inner BRB) that is highly reproducible in the severity of leakage 
and its time course. This provides a valuable tool for investigation of the
molecular pathogenesis and new treatment approaches for post-surgical breakdown
of the BRB.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15512950 [PubMed - indexed for MEDLINE]

2155: Yan Ke Xue Bao. 2002 Mar;18(1):14-9.

Optic coherence tomography of idiopathic macular epiretinal membranes.

Liu X, Ling Y, Huang J, Zheng X.

Zhongshan Ophthalmic center, Sun Yat-sen University, Guangzhou 510060, China.

OBJECTIVES: To study the characteristics of optical coherence tomography (OCT) in
idiopathic macular epiretinal membranes (IMEM) and the relationship between the
thickness of fovea and the vision of affected eyes. METHODS: A total of 67 cases 
(73 eyes) with clinical diagnosis of IMEM using direct, indirect ophthalmoscope, 
three mirror contact lens, fundus color photography or fundus fluorescein
angiography (FFA) were examined with OCT. RESULTS: Epiretinal membranes (ERMs)
with macular edema were found in 32 eyes, proliferative ERMs in 20 eyes, ERMs
with macular pseudoholes in 14 eyes and ERMs with laminar macular holes in 7
eyes. Based on OCT, the ERMs were clearly and partially seperated from the
retinal (27 eyes, 38. 36%), the retinal thickness of the fovea was the thickest
in the proliferative ERMs and the thinnest in the ERMs with laminar macular
holes. The statistical analysis showed there was a negative correlation between
the thickness of fovea and visual acuity (r = - 0. 454, P = 0. 000). CONCLUSION: 
There were four types of images of OCT in IMEM: ERMs with macular edema,
proliferative ERMs, ERMs with macular pseudohole and ERMs with laminar macular
hole; and the thicker the fovea under the OCT, the poorer the vision acuity in
the affected eyes with ERMs.

PMID: 15510668 [PubMed - indexed for MEDLINE]

2156: Eur J Ophthalmol. 2004 Sep-Oct;14(5):430-3.

Spontaneous resolution of vitreomacular traction associated with diabetic macular
edema.

Lecleire-Collet A, Muraine M, Siahmed K, Brasseur G.

Department of Ophthalmology, Rouen University Hospital Charles Nicolle,
Rouen--France. colletamelie@hotmail.com

PURPOSE: Little information is available about the natural history of
vitreomacular traction (VMT) associated with diabetic macular edema. A few cases 
of spontaneous resolution of VMT associated with diabetic macular edema have been
described, but have not been documented by optical coherence tomography (OCT).
The authors report the spontaneous resolution of VMT associated with diabetic
macular edema 1 month after the end of panretinal photocoagulation therapy (PRP).
METHODS: Case report: A 66-year-old woman presented with complicated
proliferative diabetic retinopathy and diabetic macular edema associated with
VMT, documented by OCT, in the right eye. Left eye examination showed complete
PRP and ischemic maculopathy. PRP was immediately realized in the right eye in
regard to the presence of complicated proliferative diabetic retinopathy.
RESULTS: One month after the end of PRP, right eye visual acuity improved. OCT
examination showed complete release of foveal posterior hyaloid traction, and
significant reduction in foveal thickness. The follow-up was 1 year. At the end
of follow-up, visual acuity slightly improved again; only a small residual foveal
retinal thickening remained. CONCLUSIONS: The authors report spontaneous
resolution of VMT associated with diabetic macular edema, probably facilitated by
PRP, with concurrent reduction of macular thickness and visual improvement. As
spontaneous resolution may occur in some eyes with diabetic macular edema
associated with VMT, a period of observation after the end of the PRP may be
considered prior to vitrectomy.

Publication Types: 
    Case Reports

PMID: 15506606 [PubMed - indexed for MEDLINE]

2157: Invest Ophthalmol Vis Sci. 2004 Nov;45(11):4151-60.

Outcome of transplantation of autologous retinal pigment epithelium in
age-related macular degeneration: a prospective trial.

Binder S, Krebs I, Hilgers RD, Abri A, Stolba U, Assadoulina A, Kellner L,
Stanzel BV, Jahn C, Feichtinger H.

Department of Ophthalmology, Rudolf Foundation Clinic, Vienna, Austria.
susanne.binder@wienkav.at

PURPOSE: To present the outcome of a consecutive series of patients who had
foveal choroidal neovascularization (fCNV) in age-related macular degeneration
(AMD) and were treated with subretinal surgery combined with simultaneous
transplantation of autologous retinal pigment epithelial (RPE) cells. METHODS:
Patients with fCNV who were not eligible for laser or photodynamic therapy were
included in the study. They underwent subretinal membrane excision with
simultaneous transplantation of autologous RPE cells. Eyes with membrane excision
alone served as the control. Tests included best corrected visual acuity for far 
and near with Early Treatment Diabetic Retinopathy Study (ETDRS) and Jaeger
charts, multifocal (mf)ERG, central visual field analysis, optical coherence
tomography (OCT), and angiography, before surgery, and 1 month and 3 months after
treatment, and at 3-month intervals thereafter. RESULTS: The results of final
examinations of 53 eyes are presented. In 39 eyes, RPE transplantation was
performed (group 1); 14 eyes had membrane excision alone (group 2). In group 1,
visual acuity improved significantly, two or more lines in 21 (53.8%) patients;
remained stable in 12 patients (30.8%); and decreased two or more lines in 6
patients (15.4%; P=0.0062). In group 2, the corresponding values were 21.1%,
57.8%, and 21.1% (P=0.5377 NS). Statistical analysis of results in the two groups
showed a trend in favor of group 1 (P=0.9714). The difference in reading acuity
was significant between the two groups (mean change in group 1: 1.85 +/- 0.42 vs.
0.43 +/- 0.47 in group 2; P=0.0001). mfERG response density changes were
significantly different between groups 1 and 2 (P=0.0094). No significant
decreases in central visual field defects were detected. OCT showed the
postoperative median retinal thickness in the lesion area in group 1 to be higher
(242.31 +/- 12.30 microm) than in group 2 (202.07 +/- 10.68 microm), showing a
trend (P=0.0682). CONCLUSIONS: Patients undergoing fCNV removal with autologous
transplantation of RPE reached significantly better reading acuity and higher
mfERG-response density than control subjects. The results provide evidence that
autologous transplantation of RPE is a beneficial supplement to membrane excision
alone in patients with fCNV in AMD and may be regarded as a reasonable treatment 
option.

Publication Types: 
    Clinical Trial
    Comparative Study
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 15505069 [PubMed - indexed for MEDLINE]

2158: Diabetes. 2004 Nov;53(11):2883-92.

A prospective study of serum lipids and risk of diabetic macular edema in type 1 
diabetes.

Miljanovic B, Glynn RJ, Nathan DM, Manson JE, Schaumberg DA.

Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical
School, 900 Commonwealth Ave. East, Boston, MA 02215, USA.

We evaluated the relationships between serum lipid levels and clinically
significant macular edema (CSME), hard exudates, and other diabetic retinopathy
(DR) end points in a population with type 1 diabetes. We studied data from serum 
lipids that were measured annually among the 1,441 Diabetes Control and
Complications Trial (DCCT) participants. We used proportional hazards regression 
models to examine the relationship of the cumulative average of lipid levels
(total, LDL, and HDL cholesterol, total-to-HDL cholesterol ratio, and
triglycerides) with development of CSME, hard exudate, DR progression, and
development of proliferative DR (PDR). In models controlling for primary
prevention versus secondary intervention subgroup, randomized treatment
assignment, HbA(1c), and other risk factors, both total-to-HDL cholesterol ratio 
and LDL predicted development of CSME (rate ratio [RR] for extreme quintiles
3.84, P for trend = 0.03 for total-to-HDL cholesterol ratio, and RR 1.95, P for
trend = 0.03 for LDL) and hard exudate (RR 2.44, P for trend = 0.0004 for
total-to-HDL cholesterol ratio, and RR 2.77, P for trend = 0.002 for LDL).
Relationships of lipids with progression of DR and development of PDR were weaker
and not significant after adjustment for HbA(1c). Higher serum lipids are
associated with increased risk of CSME and retinal hard exudate. Lipid-lowering
treatment among type 1 diabetic subjects, recommended to prevent cardiovascular
disease, may also decrease risk of CSME, an important cause of vision loss.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15504969 [PubMed - indexed for MEDLINE]

2159: Yan Ke Xue Bao. 2004 Sep;20(3):158-62.

Photodynamic therapy for age-related macular degeneration.

Jin C, Ge J, Zhou S, Chen H, Zhong X, Jiang R, Chen L, Chen L.

Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.

PURPOSE: To evaluate short-term effects of single photodynamic therapy (PDT) for 
age-related macular degeneration (AMD) accompanied with choroidal
neovascularization (CNV). METHODS: We analyzed retrospectively the effects of
single PDT for 20 patients (20 eyes) with CNV caused by AMD. Corrected visual
acuity, fluorescein angiography (FA) and optic coherence tomography (OCT) were
examined before and after PDT. All patients were followed up at least 3 months.
RESULTS: At the end of 3-month follow-up, 5 eyes had vision progress, 15 eyes had
vision stable and no eye had vision deterioration. Fluorescein angiography one
week post PDT showed cessation of fluorescein leakage in 8 eyes with predominant 
classic CNV, and reduction of fluorescein leakage in 12 eyes with minimal classic
CNV or occult CNV without classic component. At the 3-month following PDT
fluorescein angiography showed fluorescein leakage reappeared in 4 of 8 eyes with
predominant classic CNV. Among 12 eyes with minimal classic CNV or occult CNV
without classic component, 9 eyes showed decreased or unchanged fluorescein
leakage, 3 eyes had a progression of fluorescein leakage. Optic coherence
tomography showed obvious recovery of serous sensory retinal detachment after
PDT. CONCLUSION: PDT may occlude or inhibit CNV caused by AMD in short-term. No
obvious side effects were noticed.

PMID: 15499723 [PubMed - indexed for MEDLINE]

2160: Ophthalmic Surg Lasers Imaging. 2004 Sep-Oct;35(5):395-405.

A novel high-resolution kinetic method for visual field mapping of scotoma in
age-related macular degeneration.

Zur D, Ben Simon GJ, Loewenstein A, Alster Y, Moisseiev J, Ullman S.

Department of Computer Science and Applied Mathematics, Weizmann Institute of
Science, Rehovot, Israel.

BACKGROUND AND OBJECTIVE: To examine a new high-resolution kinetic mapping method
for scotoma in age-related macular degeneration. PATIENTS AND METHODS: A
computer-based program for kinetic visual field mapping was tested in 10 healthy 
subjects and 14 patients with age-related macular degeneration and fixed
preferred retinal locus. The stimulus was presented using a back projector on a
screen located 40 cm from the subject. The findings were then compared with
static results. RESULTS: Control group mapping revealed good congruency with the 
anatomic blind spot. Mapping of the 14 patients with age-related macular
degeneration was rapid and revealed good accuracy. The average deviation of the
mapping border from the anatomic scotoma border was no more than 3.1% of the
scotoma radius. Static mapping of 7 of the patients with age-related macular
degeneration was longer and revealed lower accuracy. CONCLUSIONS: The proposed
method is more rapid, accurate, and consistent than static mapping. It allows
accurate mapping of central scotoma with suprathreshold stimulus, and may be used
in the future for detecting the early stages of age-related macular degeneration 
using subthreshold stimulus.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 15497550 [PubMed - indexed for MEDLINE]

2161: J Am Pharm Assoc (2003). 2004 Sep-Oct;44(5):587-93.

Comparison of ease of swallowing of dietary supplement products for age-related
eye disease.

Brotherman DP, Bayraktaroglu TO, Garofalo RJ.

Consumer Products Clinical, Alcon Research Ltd., Fort Worth, TX 76134-2099, USA.

OBJECTIVE: To examine patients' perceptions on the relative importance of the
physical characteristics and appearance of dietary supplements, and to evaluate
two supplements with the same combination of vitamins and minerals used in the
Age-Related Eye Disease Study (AREDS) with respect to ease of swallowing and
other features in elderly patients. DESIGN: A single-site, single-visit,
crossover design, subject-masked comparison of two dietary supplements (ICaps
AREDS Formula--Alcon; Ocuvite PreserVision-Bausch & Lomb). SETTING: Ophthalmology
practice. PATIENTS: 50 patients aged 50 years or older. INTERVENTIONS: Patients
ranked the importance of eight physical characteristics of a vitamin tablet or
capsule (ease of swallowing, size, shape, color, smell, coating, texture, and
taste) irrespective of the test products used in the study and then took both
test products randomly and were asked to indicate which product they preferred
based on the same eight characteristics. MAIN OUTCOME MEASURES: Overall patient
preference and preference for swallowing two tablets at once. RESULTS: The
highest rated (most important) characteristic in a vitamin supplement was ease of
swallowing, with a median score of 9.0 on a 0-10 visual analogue scale. The
characteristic of least importance was tablet color, with the lowest median score
of 1.0. Statistically significant differences were detected between the products 
with regard to preferences for ease of swallowing, swallowing two tablets at
once, size, and coating (P < or = .0001). Significantly more patients preferred
the ICaps AREDS formula to Ocuvite PreserVision with respect to these
characteristics and overall preference (P < .001). Age, gender, and previous
vitamin use were contributing factors in the rating of physical characteristics
and tablet preferences. CONCLUSION: Based on the results of this study, ease of
swallowing is the most important characteristic of dietary supplement tablets for
elderly patients, followed by taste, size, and smell. Significant differences in 
preference exist between the study products, which contain similar formulations
but have different physical characteristics.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15496045 [PubMed - indexed for MEDLINE]

2162: Cochrane Database Syst Rev. 2004 Oct 18;(4):CD004004.

Radiotherapy for neovascular age-related macular degeneration.

Sivagnanavel V, Evans JR, Ockrim Z, Chong V.

BACKGROUND: Radiotherapy has been proposed as a treatment to prevent new vessel
growth in people with neovascular age-related macular degeneration (AMD).
OBJECTIVES: The aim of this review was to examine the effects of radiotherapy on 
neovascular AMD. SEARCH STRATEGY: We searched the Cochrane Central Register of
Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group
trials register) on The Cochrane Library Issue 2, 2004, MEDLINE (1966 to May
2004), EMBASE (1980 to June 2004) and LILACS (Latin American and Caribbean Health
Sciences Literature Database) (May 2004). We also wrote to investigators of
trials included in the review to ask if they were aware of any other studies.
SELECTION CRITERIA: We included all randomised controlled trials in which
radiotherapy was compared to another treatment, sham treatment, low dosage
irradiation or no treatment in people with subfoveal choroidal neovascularisation
secondary to AMD. DATA COLLECTION AND ANALYSIS: Two reviewers independently
extracted the data. Relative risks were combined using a random effects model.
The percentage of the variability in effect estimates that was due to
heterogeneity, rather than sampling error, was estimated using I2. MAIN RESULTS: 
Eleven trials randomising a total of 1078 people were included in this review.
All trials used a similar method of delivering the radiotherapy treatment
(external beam). Dosage ranged from 7.5 to 24 Gy. Most trials found effects (not 
always significant) that favoured treatment. However, there was considerable
inconsistency in the results between trials (I2 > 50%). As only 11 trials were
included in the review and only some of these trials provided data for each
outcome our ability to determine the causes of the heterogeneity between trials
was limited. Subgroup analyses did not reveal any statistically significant
interactions although with small numbers of trials in each subgroup (range two to
four) this was not surprising. There was some indication that trials with no sham
irradiation reported a greater effect of treatment as did trials with a greater
percentage of participants with classic choroidal neovascularisation. REVIEWERS' 
CONCLUSIONS: This review currently does not provide evidence that external beam
radiotherapy is an effective treatment for neovascular AMD. If further trials are
to be considered to evaluate radiotherapy in AMD then adequate masking of the
control group must be considered. Given the recent evidence that most lesions are
amenable to treatment with photodynamic therapy if identified at a small lesion
size, trials evaluating radiotherapy against photodynamic therapy are warranted.

Publication Types: 
    Meta-Analysis
    Review

PMID: 15495075 [PubMed - indexed for MEDLINE]

2163: Ophthalmic Physiol Opt. 2004 Nov;24(6):594-9.

Reliability, normative data, and the effect of age-related macular disease on the
Eger Macular Stressometer photostress recovery time.

Bartlett H, Davies LN, Eperjesi F.

Neurosciences Research Institute, Aston University, Birmingham B4 7ET, UK.
bartlehe@aston.ac.uk

PURPOSE: To assess repeatability and reproducibility, to determine normative
data, and to investigate the effect of age-related macular disease, compared with
normals, on photostress recovery time measured using the Eger Macular
Stressometer (EMS). METHOD: The study population comprised 49 healthy eyes of 49 
participants. Four EMS measurements were taken in two sessions separated by 1 h
by two practitioners, with reversal of order in the second session. EMS readings 
were also taken from 17 age-related maculopathy (ARM), and 12 age-related macular
degeneration (AMD), affected eyes. RESULTS: EMS readings are repeatable to within
+/-7 s. There is a statistically significant difference between controls and ARM 
affected eyes (t = 2.169, p = 0.045), and AMD affected eyes (t = 2.817, p =
0.016). The EMS is highly specific, and demonstrates sensitivity of 29% for ARM, 
and 50% for AMD. CONCLUSIONS: The EMS may be a useful screening test for ARM,
however, direct illumination of the macula of greater intensity and longer
duration may yield less variable results.

Publication Types: 
    Evaluation Studies
    Research Support, Non-U.S. Gov't

PMID: 15491488 [PubMed - indexed for MEDLINE]

2164: Can J Ophthalmol. 2004 Aug;39(5):517-20.

Identification of fixation location with retinal photography in macular
degeneration.

Somani S, Markowitz SN.

Low Vision Service, Department of Ophthalmology and Vision Sciences, University
of Toronto, Toronto, Ont.

BACKGROUND: Identification of fixation location is an integral part of low vision
assessment and subsequent rehabilitation. We performed a study to determine
whether retinal photography is able to identify fixation location in eyes with
age-related macular degeneration (AMD). METHODS: In a prospective, observational 
case series, consecutive patients with AMD attending a low-vision clinic
underwent monocular fixation attempts at a fixation target of a standard
ophthalmic fundus camera. Inclusion criteria included AMD with documented macular
disease, low vision in both eyes and best-corrected visual acuity of 20/50 to
20/200 in the tested eye. Retinal photography was used to document retinal
location of attempted fixation. Macular perimetry was used to confirm acceptable 
fixation maintenance behaviour. Outcome measures included acceptable fixation
maintenance during retinal photography and retinal location of fixation pattern. 
RESULTS: Twenty-one patients (14 women and 7 men with an average age of 78 [range
53 to 86] years) met the inclusion criteria. In nine cases both eyes met the
study criteria, for a total of 30 eyes. Of the 30 eyes, 24 (80%) had acceptable
fixation maintenance with retinal photography (p = 0.939). In 17 (71%) of the 24 
eyes the retinal fixation location was superior to the macular scar.
INTERPRETATION: The results suggest that retinal photography may provide a
reliable method to identify retinal location of fixation in eyes with AMD.

PMID: 15491036 [PubMed - indexed for MEDLINE]

2165: Semin Ophthalmol. 2001 Jun;16(2):90-6.

Transpupillary thermotherapy of occult CNV with no or minimally classic CNV in
age-related macular degeneration.

Algvere PV, Libert C, Seregard S.

Department of Ophthalmology, Karolinska Institutet, St. Eriks Eye Hospital,
Stockholm, Sweden. peep.algvere@sankterik.se

Transpupillary thermotherapy (TTT) has been suggested as a putative treatment for
choroidal neovascularization (CNV) in age-related macular degeneration (AMD).
This prospective study comprised 66 consecutive patients referred for exudative
AMD with predominantly occult subfoveal CNV. Based on fluorescein angiography,
there were 38 cases with occult CNV only, and 28 eyes with minimally classic CNV 
as well. Visual acuity was determined using the logarithmic ETDRS chart. For TTT 
a diode laser (810nm) with a power of 800 mW or 500-600 mW for a 3.0 mm spot was 
used (duration 60 sec.). Follow-up included clinical examination with
biomicroscopy and fluorescein angiography at 2-3 months and 6 months in all
cases. In the entire case material (n = 66), the mean visual acuity was
preoperatively 20/125 (47.4 letters) and postoperatively 20/160 (41.8 letters)
yielding a decay of 5.6 letters ("one line"). Visual acuity improved in 8 cases
(12.1%), deteriorated in 17 (25.8%), and remained stable in 74.2%. In purely
occult CNV visual acuity remained stable in 81.6% as compared to 64.3% in occult 
& minimally classic CNV; the former subgroup lost on the average 3.6 letters, the
latter 8.3 letters (close to "two lines") over 6 months. The proportion of eyes
losing at least 15 letters was 13.2% in purely occult CNV versus 35.7% in the
occult & minimally classic subgroup. In 39 of 66 cases (59.1%) fluorescein
leakage regressed to staining only concomitant with absorption of subretinal
fluid. Complications associated with deterioration of visual acuity (17 cases)
included postoperative hemorrhage, increase of exudation on angiography, and
progressive fibrosis. The results indicate that TTT stabilizes visual acuity
concomitant with regression of exudation and resorption of subretinal fluid in
the majority of cases with predominantly occult CNV Cases with occult CNV only
seem to do better than those with minimally classic CNV as well. The safety and
complication rate appear to be acceptable. A randomized controlled trial is in
progress.

PMID: 15491010 [PubMed - indexed for MEDLINE]

2166: Semin Ophthalmol. 2001 Jun;16(2):86-9.

Transpupillary thermotherapy of occult choroidal neovascularization in
age-related macular degeneration.

Kim JE, Perkins SL, Schwiesow T, Connor TB Jr, Han DP.

Medical College of Wisconsin, Milwaukee, WI, USA. judykim@mcw.edu

PURPOSE: To evaluate the efficacy of transpupillary thermotherapy (TTT) in
management of occult subfoveal choroidal neovascularization (CNV) in exudative
age-related macular degeneration (AMD). METHODS: Retrospective chart review of
eyes that were treated with TTT and had at least 12 weeks of follow-up. Base-line
and final ETDRS visual acuity and fluorescein angiography (FA) were compared.
RESULTS: For the 48 eyes which met inclusion criteria, mean pre-operative visual 
acuity was 20/128 (range: 20/50-20/500). Average follow-up was 27 weeks (range:
12 weeks-55 weeks). At 3 months after treatment, 12 eyes (25%) improved 2 lines
or more, 18 eyes (37.5%) had no change or 1 line of visual improvement, and 18
eyes (37.5%) worsened 1 or more lines. No significant adverse event was noted
during treatment. Three eyes developed large submacular hemorrhage within 2
months of treatment. Based on clinical examination and FA, 61% of the eyes
appeared to have reduction of subretinal fluid compared to pre-operative
evaluations. CONCLUSION: Visual acuity was stable or improved in 62.5% of eyes in
our series and the treatment was well tolerated. Longer follow up and larger
number of patients would be required to evaluate the ultimate benefit of TTT in
management of occult CNV due to AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15491009 [PubMed - indexed for MEDLINE]

2167: Semin Ophthalmol. 2001 Jun;16(2):81-5.

Efficacy of transpupillary thermotherapy (TTT) in the treatment of occult
subfoveal choroidal neovascularization in age-related macular degeneration.

Ahuja RM, Benner JD, Schwartz JC, Butler JW, Steidl SM.

Department of Ophthalmology, University of Maryland, Baltimore, MD, USA.

PURPOSE: To determine the efficacy of transpupillary thermotherapy (TTT) in the
treatment of occult subfoveal choroidal neovascularization in patients with
age-related macular degeneration (ARMD). METHODS: We conducted a retrospective
review of patients with ARMD treated with TTT from June, 1999 through July, 2000 
at a retina referral practice. TTT was delivered through a slit-lamp using a
modified diode laser at 810 nm wavelength and a spot size of 3 mm delivered at
one location for a minimum of 60 seconds duration. Re-treatment was performed at 
2-month intervals if indicated. RESULTS: 81 eyes of 77 patients were included in 
the study. Vision improved greater than one line Snellen in 18 eyes (22%), vision
was stable within one line Snellen in 38 (47%), and worsened greater than one
line Snellen in 25 (31%). Patients had a mean follow-up of 9 months. The average 
number of treatments was 1.37 (range 1 to 4). Pretreatment vision was less than
or equal to 20/200 in 54% of eyes. CONCLUSIONS: Transpupillary thermotherapy may 
stabilize visual acuity in a majority of patients with occult subfoveal choroidal
neovascularization secondary to ARMD. Proof of therapeutic benefit is best
determined by a randomized clinical trial that is currently underway (TTT4CNV).

PMID: 15491008 [PubMed - indexed for MEDLINE]

2168: Semin Ophthalmol. 2001 Jun;16(2):70-80.

Transpupillary thermotherapy (TTT) for age-related macular degeneration.

Friberg TR, Pandya A, Nazari K.

Department of Ophthalmology, The Eye & Ear Institute, University of Pittsburgh
School of Medicine, 203 Lothrop Street, Room 824, Pittsburgh, PA 15213, USA.

PURPOSE: To review the results of transpupillary thermotherapy (TTT) on choroidal
neovascular membranes associated with age-related macular degeneration (AMD).
MATERIALS AND METHODS: 35 eyes of 35 patients with AMD and choroidal
neovascularization and exudation were treated with TTT and had fundus photographs
and fluorescein angiography (FA) before and at least six months after TTT. 28
eyes had predominantly occult lesions as seen on FA, while 7 demonstrated
primarily classic lesions. All were treated with 650mw power or less using the
810 nm diode laser (3000 micron spot, duration of 60 seconds). Visual acuity,
lesion size, and amount of subretinal fluid were determined by results of
examination and review of photographs and fluorescein angiograms. RESULTS: A 50% 
reduction in subretinal fluid was achieved in 67% of treated eyes overall, with
stabilization of vision (less than three lines of visual acuity lost) in 86%.
Complications from treatment were infrequent (9%) and involved hemorrhage noted
in the region of treatment upon follow-up. CONCLUSION: TTT promotes resolution of
subretinal fluid and appears to stabilize visual acuity in patients with
exudative AMD.

PMID: 15491007 [PubMed - indexed for MEDLINE]

2169: Semin Ophthalmol. 2001 Jun;16(2):55-9.

Transpupillary thermotherapy for age-related macular degeneration: principles and
techniques.

Mainster MA, Reichel E.

Department of Ophthalmology, University of Kansas Medical Center, 3907 Rainbow
Boulevard, Kansas City, KS 66160-7379, USA.

Transpupillary thermotherapy (TTT) is a subthreshold, low irradiance, long
exposure duration, large spot size, infrared diode laser protocol. Retinal
temperature increases in TTT for choroidal neovascularization (CNV) are
substantially lower than those in conventional short-pulse photocoagulation, but 
they are maintained for 60 seconds to achieve therapeutic results. Treatment
power is adjusted for retinal lesion size, chorioretinal pigmentation, macular
elevation and media clarity. TTT uses 810-nm diode laser infrared radiation,
which has no significant retinal phototoxicity. A parfocal laser delivery system 
is required to assure uniformity of irradiance across large diameter treatment
spots. Relative contraindications for TTT include dense subretinal hemorrhage,
prior focal photocoagulation and serous RPE detachment. Adverse events are rare, 
and include decreased vision and retinal arteriole occlusion. Randomized,
prospective multi-center trials are underway to compare the results of TTT for
occult CNV in age-related macular degeneration to the natural history of the
disorder. Imaging, electrophysiologic or thermometric techniques may ultimately
provide intra-operative or post-operative monitoring to assure the adequacy of
TTT for CNV, despite the absence of ophthalmoscopically visible lesions.

Publication Types: 
    Review

PMID: 15491004 [PubMed - indexed for MEDLINE]

2170: Br J Ophthalmol. 2004 Nov;88(11):1443-9.

Enhanced low vision rehabilitation for people with age related macular
degeneration: a randomised controlled trial.

Reeves BC, Harper RA, Russell WB.

Health Services Research Unit, London School of Hygiene, UK.

AIM: To compare the effectiveness of three models of low vision rehabilitation
for people with age related macular degeneration (AMD) referred for low vision
rehabilitation (LVR): (a) an enhanced low vision rehabilitation model (ELVR)
including supplementary home based low vision rehabilitation; (b) conventional
low vision rehabilitation (CLVR) based in a hospital clinic; (c) CLVR with home
visits that did not include rehabilitation (CELVR), intended to act as a control 
for the additional contact time with ELVR. METHOD: A single centre parallel group
randomised controlled trial in participants' homes and the low vision clinic,
Manchester Royal Eye Hospital. People referred for LVR with a primary diagnosis
of AMD and visual acuity worse than 6/18 in both eyes and equal to or better than
1/60 in the better eye. The main outcome measures were vision specific quality of
life (QoL) (primary outcome, VCM1) and generic health related QoL (SF-36);
psychological adjustment to vision loss; measured task performance; restriction
in everyday activities; use of low vision aids (LVAs). RESULTS: 226 participants 
were recruited (median age 82 years); 194 completed the trial (86%). Except for
SF-36 physical and mental component summary scores, arms did not differ
significantly for any of the outcomes. Differences for the VCM1 were ELVR v CLVR,
0.06 (95% CI to 0.17 to 0.30, p = 0.60); ELVR v CELVR, 0.12 (95% CI to 0.11 to
0.34, p = 0.31); CELVR v CLVR, -0.05 (95% CI -0.29 to 0.18, p = 0.64).
Differences for the SF-36 favoured CLVR compared to ELVR (ELVR v CLVR: physical =
-6.05, 95% CI -10.2 to -1.91, p = 0.004; mental = -4.04, 95% CI -7.44 to -0.65, p
= 0.02). At 12 months, 94% of participants reported using at least one LVA.
CONCLUSION: ELVR was no more effective than CLVR. Researchers should be wary of
proposing new LVR interventions without preliminary evidence of effectiveness,
given the manifest lack of effectiveness of the model of enhanced LVR evaluated
in the trial.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15489491 [PubMed - indexed for MEDLINE]

2171: Am J Ophthalmol. 2004 Oct;138(4):665-6.

Association of the M55L and Q192R paraoxonase gene polymorphisms with age-related
macular degeneration.

Baird PN, Chu D, Guida E, Vu HT, Guymer R.

Centre for Eye Research Australia, University of Melbourne, East Melbourne,
Australia. pnb@unimelb.edu.au <pnb@unimelb.edu.au>

PURPOSE: To investigate the reported association of the two single-nucleotide
polymorphisms (SNPs) of the paraoxonase gene (PON1), Met-Leu 55 (M55L) and
Gln-Arg 192 (Q192R), in individuals of Anglo-Celtic descent who have age-related 
macular degeneration (AMD). DESIGN: Case-control association study. METHODS:
Sixty-two individuals with late (end-stage) AMD and 115 control subjects (without
AMD) were included in this study. The M55L and Q192R SNPs were amplified by
polymerase chain reaction and genotyped, and statistical analysis was undertaken.
RESULTS: No association of either SNP was detected in persons of Anglo-Celtic
descent who had AMD, although there was a significant difference in SNP allele
frequency between Anglo-Celtic and Japanese individuals. CONCLUSION: The M55L and
Q192R SNPs of the PON1 gene do not appear to be associated with late AMD in
individuals of Anglo-Celtic descent.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15488805 [PubMed - indexed for MEDLINE]

2172: Am J Ophthalmol. 2004 Oct;138(4):648-50.

Infliximab for chronic cystoid macular edema associated with uveitis.

Markomichelakis NN, Theodossiadis PG, Pantelia E, Papaefthimiou S, Theodossiadis 
GP, Sfikakis PP.

Ocular Inflammation and Immunology Service, Department of Ophthalmology, Laikon
Hospital, Athens University Medical School, Athens, Greece.

PURPOSE: To assess the efficacy of the anti-TNF monoclonal antibody infliximab in
uveitis patients without clinically evident ocular inflammation and impaired
visual acuity because of chronic cystoid macular edema (CME). DESIGN:
Prospective, noncomparative, interventional case series. METHODS: Patients with
refractory CME (14 eyes, mean duration of 14 months), associated with
intermediate uveitis (n = 6), Adamantiades-Behcet disease (n = 2), adult-type
vascular pseudotumor (n = 1), and HLAB27+-related uveitis (n = 1) received an
intravenous infliximab infusion (5 mg/kg); five patients were retreated after 1
month. RESULTS: Macular thickness, measured by ocular coherence tomography, was
reduced from 428 +/- 138 microm to 219 +/- 51 microm at 2 months postbaseline (P 
= .0001), while visual acuity increased from 0.41 +/- 0.18 to 0.83 +/- 0.17 (P < 
.00001). Anatomic and functional improvement was sustained at 6 months in all. No
ocular or extra-ocular side effects were noted. CONCLUSION: These promising
results suggest that TNF may play an important pathogenetic role in chronic CME, 
thus, a controlled trial is warranted.

PMID: 15488796 [PubMed - indexed for MEDLINE]

2173: Am J Ophthalmol. 2004 Oct;138(4):582-7.

Macular pigment density and aging, assessed in the normal elderly and those with 
cataracts and age-related macular degeneration.

Ciulla TA, Hammond BR Jr.

Retina Service, Midwest Eye Institute, Methodist Medical Plaza North,
Indianapolis, Indiana 46280, USA. thomasciulla@yahoo.com <thomasciulla@yahoo.com>

PURPOSE: Increasing evidence has linked retinal lutein and zeaxanthin (termed
macular pigment, MP) to the risk of age-related macular degeneration (AMD).
Currently, however, studies differ regarding the question of whether MP declines 
with age or age has an effect in patient populations being assessed. This study
assessed MP across the lifespan with an emphasis on assessing MP in a
cross-section of elderly including those with lenticular or age-related macular
degeneration, or both. DESIGN: Prospective, observational, cross-sectional study.
METHODS: SETTING: Institution. STUDY POPULATION: Cross-sectional study of normal,
cataractous, and AMD subjects tested in Indianapolis, Indiana, including 390
subjects, 22 with cataracts and 59 with age-related macular degeneration.
OBSERVATIONAL PROCEDURE: MP density was measured with a one-degree diameter test 
field at 460 nm using a psychophysical method based on heterochromatic flicker
photometry. MAIN OUTCOME MEASURES: MP optical density. RESULTS: MP does not
appear to change as a function of age (r = +.04) when examining subjects across
the lifespan (from 18-88 years). There was a slight tendency (slope = -.0027, r =
-.11) for MP to decline when only the elderly subjects were considered, but this 
trend was not significant (P < .12) for any of the groups considered (normal,
cataractous, or AMD). CONCLUSIONS: MP does not change significantly with age,
even when elderly subjects with cataracts and AMD are considered. Using
heterochromic flicker photometry, elderly subjects display a full range of MP
density that is similar to young subjects.

PMID: 15488784 [PubMed - indexed for MEDLINE]

2174: Am J Ophthalmol. 2004 Oct;138(4):567-73.

Apolipoprotein E polymorphisms in Japanese patients with polypoidal choroidal
vasculopathy and exudative age-related macular degeneration.

Gotoh N, Kuroiwa S, Kikuchi T, Arai J, Arai S, Yoshida N, Yoshimura N.

Department of Ophthalmology, Shinshu University School of Medicine, Matsumoto,
Japan.

PURPOSE: To study the genotypes, allelic frequencies, and polymorphisms of
apolipoprotein E (Apo E) in unrelated Japanese patients with polypoidal choroidal
vasculopathy (PCV) or exudative age-related macular degeneration (AMD) and
control subjects without macular degeneration. DESIGN: Cross-sectional study.
METHODS: Blood samples from 225 subjects older than 50 years were used. The 225
subjects included 58 patients with PCV, 85 with AMD, and 82 without macular
degeneration. Coding exons of the Apo E gene were amplified by polymerase chain
reaction, and the DNA sequences were determined by direct sequencing with an
automated sequencer. RESULTS: Apo E epsilon3/epsilon3 was the most frequent
genotype with a prevalence of 79.3% in PCV patients, 76.5% in AMD patients, and
67.1% in the control subjects. However, the differences in the percentages were
not statistically significant among the three groups. The most frequently found
allele in the three groups was epsilon3. Patients with PCV and AMD were less
likely to have epsilon2 and epsilon4 than the control subjects, but the
differences were not statistically significant. Five minor Apo E single
nucleotide polymorphisms, including epsilon5 and epsilon7, were found.
CONCLUSION: Japanese patients with PCV and AMD were less likely to have epsilon2 
and epsilon4 polymorphisms, but the differences from the normals were not
statistically significant for the Apo E genotypes and allelic frequencies.

PMID: 15488782 [PubMed - indexed for MEDLINE]

2175: Am J Ophthalmol. 2004 Oct;138(4):560-6.

Comment in:
    Am J Ophthalmol. 2005 May;139(5):949; author reply 949-50.

Intrasurgical plasmin enzyme in diabetic macular edema.

Azzolini C, D'Angelo A, Maestranzi G, Codenotti M, Della Valle P, Prati M,
Brancato R.

Department of Ophthalmology and Visual Sciences, Vita-Salute San Raffaele
University, Milan, Italy. azzolini.claudio@hsr.it <azzolini.claudio@hsr.it>

PURPOSE: To evaluate in a prospective study the efficacy of intrasurgical
autologous plasmin enzyme (APE) in producing posterior vitreous detachment.
DESIGN: Consecutive, interventional case series. METHODS: A group of 12 eyes of
11 patients with diabetic macular edema secondary to posterior vitreous cortex
contraction was considered. A quantity of 0.1- to 0.2-ml containing 0.8 to 1.2 IU
of APE prepared by our Coagulation Service was injected into the vitreous body 25
minutes before surgery. The efficacy of the APE was subjectively evaluated. A
control group of 10 eyes with the same clinical characteristics underwent the
same surgery without APE injection. Complete eye examinations, including optical 
coherence tomography, were performed on all patients before surgery and during
the 1-year follow-up period. RESULTS: During surgery in the APE-treated group,
the posterior vitreous cortex was judged adherent in three cases, partially
detached in six cases, and totally detached in three cases. In two cases a
complete collapse of the vitreous body was observed. During surgery in the
non-APE-treated group, the posterior vitreous cortex was judged still adherent in
nine of 10 eyes and partially detached in 1 eye. Comparing the postoperative
results between the APE-treated group and the non-APE-treated group, we found no 
significant differences in final postoperative retinal thickness (P = .2552),
whereas we found a significant difference in final visual acuity (P = .0121).
CONCLUSIONS: Autologous plasmin enzyme was useful in inducing a pharmacologic
posterior vitreous detachment and in facilitating surgery. It did not seem to
interfere with the final retinal thickness, and it ameliorates the final visual
acuity.

Publication Types: 
    Comparative Study

PMID: 15488781 [PubMed - indexed for MEDLINE]

2176: Semin Ophthalmol. 2001 Mar;16(1):25-30.

Minimal intensity diode laser (810 nanometer) photocoagulation (MIP) for diffuse 
diabetic macular edema (DDME).

Olk RJ, Akduman L.

The Retina Center of St. Louis County, 11710 Old Ballas Rd., Suite 102, St.
Louis, MO 63141, USA.

BACKGROUND AND OBJECTIVE: To determine the effectiveness of minimal intensity
diode laser (810nm) photocoagulation (MIP) for diffuse diabetic macular edema
(DDME). METHODS: Patients demonstrating diffuse diabetic macular edema (DDME)
were treated with minimal intensity diode 810 laser photocoagulation or modified 
grid photocoagulation consecutively. Patients were seen and reevaluated at
regular follow up visits every 3 to 4 months and retreated if residual diffuse
diabetic macular edema was still present. Selected patients were tested with
Goldmann visual field, pre and post-treatment. Visual improvement, visual loss,
visual field, reduction/elimination of macular edema, and a number of treatments 
were studied. RESULTS: Reduction/elimination of DDME was observed in
approximately 74% of eyes with 24 months follow up. The number of treatments per 
eye ranged from 1 to 5. The presence of cystoid macular edema, initial poor
visual acuity, the presence of coexisting macular ischemia, or a history of
systemic hypertension did not effect the outcome. Patients without a history of
systemic vascular disease had a better chance of visual stabilization or
improvement compared to those patients with a history of systemic vascular
disease. Eighty-eight percent of patients had at least stable visual acuity at
the last follow up visit. No post-treatment subjective complaints of increased
pericentral scotomas were encountered in this group of patients and
post-treatment atrophic scarring was substantially reduced, by using minimal
intensity diode laser 810 photocoagulation, compared to eyes previously treated
with shorter wavelengths and more visible burns. CONCLUSION: Minimal intensity
diode laser 810nm modified grid laser photocoagulation for diffuse diabetic
macular edema (DDME) is effective in reducing/eliminating DDME, although
resolution of edema may be slightly prolonged and may require 1 or 2 additional
treatments compared to eyes previously treated with shorter wavelengths and more 
visible burns. However, this method appears to be advantageous in that it appears
to reduce the objective and subjective effect on the pericentral visual field, as
well as substantially reducing the post-treatment atrophic scarring seen in
patients treated with shorter wavelength lasers and move visible burns.

Publication Types: 
    Case Reports

PMID: 15487695 [PubMed - indexed for MEDLINE]

2177: Semin Ophthalmol. 2001 Mar;16(1):19-24.

Infrared micropulsed laser treatment for diabetic macular edema--subthreshold
versus threshold lesions.

Friberg TR.

University of Pittsburgh, Eye & Ear Institute, 203 Lothrop Street, Room 824,
Pittsburgh, PA 15213, USA. fribergtr@msx.upmc.edu

PURPOSE: To assess the effectiveness of subthreshold (invisible after placement) 
and threshold (barely visible after placement) 810nm laser photocoagulation in
the treatment of clinically significant diabetic macular edema. METHODS: A grid
of subthreshold laser spots was used to treat patients with diabetic edema.
Retrospectively, the results of treatment of 20 eyes of 20 patients were compared
to the results of treatment of 120 eyes of 120 patients using a grid of threshold
laser lesions. RESULTS: At six months, 60% of subthreshold treated eyes and 75%
of threshold treated eyes showed anatomic resolution of macular edema.
Improvement or stabilization of visual acuity was achieved in 85% of threshold or
subthreshold treated eyes. CONCLUSION: Gentle grid treatment of regions of
diabetic macular edema was effective in ameliorating the edema and limiting
visual loss. Subthreshold laser was less effective in promoting resolution of
edema compared to threshold lesions, though the difference was not significant in
this instance.

Publication Types: 
    Comparative Study
    Evaluation Studies

PMID: 15487694 [PubMed - indexed for MEDLINE]

2178: Traffic. 2004 Nov;5(11):884-95.

Unexpected intracellular localization of the AMD-associated cystatin C variant.

Paraoan L, Ratnayaka A, Spiller DG, Hiscott P, White MR, Grierson I.

Unit of Ophthalmology, Department of Medicine, Centre for Cell Imaging, School of
Biological Sciences, University of Liverpool, UK. lparaoan@liv.ac.uk

Cystatin C is abundantly expressed by the retinal pigment epithelium (RPE) of the
eye. Targeting of cystatin C to the Golgi apparatus and processing through the
secretory pathway of RPE cells are dependent upon a 26-amino acid signal sequence
of precursor cystatin C. A variant with an alanine (A) to threonine (T) mutation 
in the penultimate amino acid of the signal sequence (A25T) was recently
correlated with increased risk of developing exudative age-related macular
degeneration. The biochemical consequence of the A25T mutation upon targeting of 
the protein is reported here. Targeting and trafficking of full-length mutant
(A25T) precursor cystatin C-enhanced green fluorescent protein fusion protein
were studied in living, cultured retinal pigment epithelial and HeLa cells.
Confocal microscopy studies were substantiated by immunodetection. In striking
contrast to wild-type precursor cystatin C fusion protein conspicuously targeted 
to the Golgi apparatus, the threonine variant was associated principally with
mitochondria. Some diffuse fluorescence was also observed throughout the
cytoplasm and nucleus (but not nucleoli). Secretion of fusion protein derived
from the threonine variant was reduced by approximately 50% compared with that of
the wild-type cystatin C fusion protein. Expression of the variant fusion protein
did not appear to impair expression or secretion of endogenous cystatin C.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15479453 [PubMed - indexed for MEDLINE]

2179: Arch Ophthalmol. 2004 Oct;122(10):1455-60.

Optical coherence tomography findings in myopic traction maculopathy.

Panozzo G, Mercanti A.

TECLO srl, Vitreoretinal Service, Verona, Italy. g.panozzo@iol.it
<g.panozzo@iol.it>

OBJECTIVE: To describe the features and incidence of epiretinal traction and
related retinal damage in degenerative myopia. DESIGN: Consecutive observational 
case series. METHODS: We retrospectively reviewed medical records and optical
coherence tomography findings of 218 eyes with high myopia of 121 consecutive
patients to detect the incidence and features of epiretinal traction-related
macular damage. The degree of myopia ranged from -8 to -26 spherical equivalent
(mean +/- SD, -16.93 +/- 5.74). Mean +/- SD axial length was 29.75 +/- 2.12 mm.
Excluding eyes with possibly confounding features, 125 eyes were analyzed. MAIN
OUTCOME MEASURE: Detection of epiretinal traction and related macular damage.
RESULTS: Epiretinal traction was found in 58 (46.4%) of 125 eyes and retinal
damage, in 43 eyes (34.4%). Macular retinoschisis was the most frequent form of
macular damage (25 eyes [58%]), followed by retinal thickening, lamellar hole,
and shallow retinal detachment. CONCLUSIONS: Epiretinal traction is a frequent
finding in degenerative myopia and, particularly if associated with the presence 
of staphyloma, can generate a form of macular damage unique to eyes with high
myopia. This damage can affect up to one third of these eyes and should be
considered as a separate cause of visual loss easily detected by optical
coherence tomography at its early stages.

PMID: 15477456 [PubMed - indexed for MEDLINE]

2180: Eye. 2005 Nov;19(11):1142-50.

Contrast sensitivity as an outcome measure in patients with subfoveal choroidal
neovascularisation due to age-related macular degeneration.

Monés J, Rubin GS.

Instituto de Microcirugia Ocular de Barcelona, Barcelona, Spain.
jordi_mones@comb.es

PURPOSE: Although visual acuity is the most frequently used primary outcome
measure in clinical trials of treatments for choroidal neovascularisation (CNV)
due to age-related macular degeneration (AMD), contrast sensitivity may provide
valuable additional information. This paper reviews the evidence for using
contrast sensitivity as a measure of visual function and as an outcome measure in
clinical trials in patients with subfoveal CNV due to AMD. METHODS: Medline
database searches were performed to retrieve relevant articles on contrast
sensitivity. In addition, articles were included from the authors' knowledge of
the literature and from the reference lists of retrieved articles. RESULTS: The
published literature demonstrates that contrast sensitivity is an important
measure of visual function in patients with subfoveal CNV due to AMD. Most
clinical trials of treatments for CNV due to AMD have reported visual acuity as
the primary outcome. However, there is evidence that treatment (such as
verteporfin therapy) may also provide additional benefits in terms of contrast
sensitivity. These benefits may not be completely characterised by measurement of
visual acuity alone. CONCLUSIONS: The inclusion of contrast sensitivity as an
outcome measure in studies of patients with CNV due to AMD may provide a more
complete understanding of the effects of treatment on visual function and the
likely benefits for patients.

Publication Types: 
    Review

PMID: 15467700 [PubMed - indexed for MEDLINE]

2181: Mol Vis. 2004 Sep 24;10:682-7.

A novel diagnostic test detects a low frequency of the hemicentin Gln5345Arg
variant among Northern Irish age related macular degeneration patients.

McKay GJ, Clarke S, Hughes A, McConnell V, Schultz DW, Klein ML, Silvestri G,
Simpson DA.

Department of Ophthalmology and Vision Science, Queen's University of Belfast,
Belfast, Northern Ireland.

PURPOSE: Age related macular degeneration (AMD) is a common cause of severe
vision loss. Identification of genes involved in AMD will facilitate early
detection and ultimately help to identify pathways for treatment for this
disorder. The A16,263G mutation in the HEMICENTIN-1 gene produces a
non-conservative substitution of arginine for glutamine at codon 5345 which has
been implicated in familial AMD. The aim of this study is to develop a rapid
diagnostic assay for the detection of this mutation and to evaluate its frequency
in a sample of AMD patients. METHODS: A primer probe set was designed from exon
104 of the HEMICENTIN-1 gene to differentiate between mutant and wild type
alleles. A region spanning the mutation was amplified by PCR using a LightCycler 
(Roche Diagnostic). The mutation was then detected by melt curve analysis of the 
hybrid formed between the PCR product and a specific fluorescent probe. The
frequency of the mutation within the Northern Ireland population was evaluated by
assaying 508 affected AMD patients, 25 possibly affected and 163 controls.
RESULTS: This assay clearly discriminates between the A16,263G mutant and wild
type HEMICENTIN-1 alleles. The wild type sequence has a single base mismatch with
the probe which decreases the stability of the hybrid, resulting in a lower TM
(TM=51.27 degrees C) than that observed for the perfectly matched mutant allele
(TM=59.9 degrees C). The mutant allele was detected in only one of the 696
subjects, an affected AMD patient. CONCLUSIONS: We describe a rapid assay for the
genotyping of the Gln5345Arg mutation using real-time fluorescence PCR to
facilitate rapid processing of samples through combined amplification and
detection steps. These characteristics are suitable for a clinical setting where 
high throughput diagnostic procedures are required. The frequency of this
mutation within the Northern Ireland population has been estimated at 0.2%,
concurring with previous findings that this mutation is a rare variant associated
with AMD. A rapid diagnostic assay will facilitate a reliable and convenient
evaluation of the frequency of the Gln5345Arg mutation and its association with
AMD within other populations.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15467524 [PubMed - indexed for MEDLINE]

2182: Ophthalmology. 2004 Oct;111(10):1899-904.

Monitoring cystoid macular edema by optical coherence tomography in patients with
retinitis pigmentosa.

Apushkin MA, Fishman GA, Janowicz MJ.

Department of Ophthalmology and Visual Sciences, University of Illinois at
Chicago, Chicago, Illinois 60612, USA.

PURPOSE: To determine the value of optical coherence tomography (OCT) imaging in 
the diagnosis and monitoring of cystoid macular edema (CME) in patients with
retinitis pigmentosa (RP). DESIGN: Prospective, noncomparative, small case
series. PARTICIPANTS: Three patients with RP and cystic-appearing spaces in the
macula on OCT images. INTERVENTION: All 3 patients were treated with a carbonic
anhydrase inhibitor, and 1 also received topical and systemic steroids. MAIN
OUTCOME MEASURES: Changes in OCT images, fluorescein angiography, and
best-corrected visual acuity (VA). RESULTS: Although foveal cysticlike spaces
were evident on OCT images in all 3 patients, only 1 patient showed CME on
fluorescein angiography at baseline. Two of the 3 patients showed funduscopic
evidence of macular cystic lesions, whereas a third showed no clinically evident 
fundus changes in the macula. Optical coherence tomography images documented
improvement in the cystic-appearing spaces after treatment with the carbonic
anhydrase inhibitor. Changes on fluorescein angiography were either not apparent 
or considerably less apparent. An improvement of > or =1 line on a Snellen acuity
chart was recorded in 2 patients, whereas a third showed no change of VA in
either eye. CONCLUSIONS: Optical coherence tomography is a potential method for
the diagnosis and monitoring of CME in patients with RP. It was more sensitive in
this regard than either fluorescein angiography or funduscopic examination.

Publication Types: 
    Case Reports
    Comparative Study
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15465554 [PubMed - indexed for MEDLINE]

2183: Stud Health Technol Inform. 2002;85:133-6.

Imaging and visualization of pathology beneath the retinal surface.

Elsner AE, Si YJ, Mellem-Kairala MB, Miura M.

Schepens Eye Research Institute, Harvard Medical School, Boston, MA 02114, USA.

Pathology beneath the highly reflective surface, such as the human retina, is key
in the detection and management of disease. Advanced imaging techniques can help 
reveal these. Visualization and guiding the imaging to the appropriate area still
remain as problems, in part due to the small scale of the pathology with respect 
to the potential area to be covered.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.

PMID: 15458073 [PubMed - indexed for MEDLINE]

2184: Acta Ophthalmol Scand. 2004 Oct;82(5):591-5.

Unilateral diabetic macular oedema secondary to central retinal vein congestion.

Christoffersen N, Larsen M.

Department of Ophthalmology, Herlev Hospital, University of Copenhagen, Herlev,
Denmark. loja@herlevhosp.kbhamt.dk

PURPOSE: To describe two cases of strictly unilateral diabetic retinopathy with
macular edema where the precipitating factor appears to have been retinal venous 
congestion. METHODS: Retrospective interventional case study. RESULTS:
Examination of fundus photographic records demonstrated generalized venous
dilation in the affected eyes years in advance of the development of unilateral
diabetic macular edema. Relentless progression of edema and visual loss followed 
despite retinal photocoagulation treatment and ultimately the affected eyes in
both patients developed central retinal vein occlusion. The fellow eyes in both
patients remained without retinopathy throughout the period of observation.
CONCLUSION: The sequential and strictly unilateral appearance of retinal venous
dilation, diabetic macular edema, and central retinal vein occlusion in diabetic 
patients without fellow-eye retinopathy suggests that venous congestion induced
the progression from hyperglycemic insult to vascular injury in the affected
eyes. Presumably, diabetes may cause retinal vascular dysfunction that results in
little or no vascular damage unless venous congestion is present. This supports
that venous congestion and increased sensitivity to congestion are important
components of the pathogenesis of diabetic macular edema.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 15453859 [PubMed - indexed for MEDLINE]

2185: Acta Ophthalmol Scand. 2004 Oct;82(5):585-90.

Transpupillary thermotherapy for the treatment of subfoveal choroidal
neovascularization associated with age-related macular degeneration.

Tranos P, Singh M, Peter NM, Dhir L, Kon C, Rassam S.

Department of Ophthalmology, Worthing General Hospital, Worthing, UK.
ptranos@doctors.org.uk

OBJECTIVE: To evaluate the efficacy of transpupillary thermotherapy (TTT) for the
treatment of choroidal neovascularization (CNV) secondary to age-related macular 
degeneration (AMD). DESIGN: Prospective, non-randomized, non-masked,
case-selected series. METHODS: All patients with subfoveal CNV due to AMD and
initial visual acuity (VA) between 6/9 and 6/60 were offered the opportunity to
undergo TTT. Recruited subjects were treated using a diode laser (810 nm) with a 
beam size of 1.2-3.0 mm and power settings of 460-1200 mW. Treatment was applied 
for 60 seconds in a subthreshold manner. MAIN OUTCOME MEASURES: Differences in VA
and changes in the angiographic appearance of CNV. RESULTS: Thirty-one
occult/predominantly occult and five classic/predominantly classic membranes were
treated with TTT and were followed-up for a mean of 6.0 +/- 1.2 months. Following
an average of 1.5 +/- 0.7 (range 1-4) laser sessions, VA remained stable ( -1 to 
+1 Snellen line) in 24 (66.7%) eyes, improved by > 1 line in two (5.6%) eyes and 
decreased significantly (> or = 2 Snellen lines) in 10 (27.8%) eyes.
Angiographically confirmed closure of CNV was detected in 22 (61.1%) patients.
Membranes persisted in 11 (30.6%) eyes and recurred in three (8.3%) eyes. There
was no association between reduction, elimination or persistence of angiographic 
leakage of CNV and change in VA after treatment (p = 0.347). CONCLUSIONS:
Transpupillary thermotherapy may be effective at preserving vision and reducing
CNV leakage in a number of patients with exudative AMD. Further studies are
required to compare TTT with the natural course of subfoveal CNV and alternative 
treatment options.

PMID: 15453858 [PubMed - indexed for MEDLINE]

2186: Eur J Health Econ. 2004 Feb;5(1):22-7.

Direct medical costs of age-related macular degeneration in Italian hospital
ophthalmology departments. A multicenter, prospective 1-year study.

Garattini L, Castelnuovo E, Lanzetta P, Viscarra C, Ricci E, Parazzini F; CARMA
Study Group.

Center for Health Economics, A.A. Valenti-Mario Negri Institute, c/o Villa
Camozzi, Via Camozzi 3, 24020 Ranica, Italy. liviogarattini@tiscalinet.it

This study calculated the resource utilization and direct medical costs related
to age-related macular degeneration (AMD). We conducted a multicenter
observational study in 1999 in seven hospital ophthalmology departments in
northern and central Italy. A total of 476 patients aged over 50 years with the
diagnoses were classified into three prognostic groups: (a) drusen (23.7%), (b)
geographic atrophy (16.4%), and (c) retinal changes associated with choroidal
neovascularization (CNV) (59.9%). In addition to the costs reimbursed by the
Italian National Health Service, we estimated also patients' out of pocket
expenses. The mean cost per patient per year was 383.2 euro; patients with CNV
were by far the most costly (540.1 euro, vs. 158.1 euro for drusen and 147.9 euro
for geographic atrophy). Hospital costs and diagnostics were the main cost
determinants. Services directly paid for by patients (private consultations and
OTCs) amounted to 46.5 euro for patients with CNV, 50.3 euro for drusen, and 68.8
euro for geographic atrophy. The major finding of the study was that the presence
of CNV involved higher expenditure than drusen or geographic atrophy. This
suggests that the costs of AMD rise significantly with the severity of the
illness.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 15452761 [PubMed - indexed for MEDLINE]

2187: Invest Ophthalmol Vis Sci. 2004 Oct;45(10):3733-9.

A model of best vitelliform macular dystrophy in rats.

Marmorstein AD, Stanton JB, Yocom J, Bakall B, Schiavone MT, Wadelius C,
Marmorstein LY, Peachey NS.

Department of Ophthalmology, University of Arizona College of Medicine, Tucson,
Arizona 85711, USA. amarmorstein@eyes.arizona.edu

PURPOSE: The VMD2 gene, mutated in Best macular dystrophy (BMD) encodes
bestrophin, a 68-kDa basolateral plasma membrane protein expressed in retinal
pigment epithelial (RPE) cells. BMD is characterized by a depressed light peak
(LP) in the electro-oculogram. Bestrophin is thought to be the Cl channel that
generates the LP. The goal was to generate an animal model of BMD and to
determine the effects of bestrophin overexpression on the RPE-generated
components of the ERG. METHODS: Bestrophin or bestrophin mutants (W93C or R218C) 
were overexpressed in the RPE of rats by injection of replication-defective
adenovirus. Immunofluorescence microscopy and ERG recordings were used to study
subsequent effects. RESULTS: Bestrophin was confined to the basolateral plasma
membrane of the RPE. Neither wild-type (wt) nor mutant bestrophin affected the a-
or b-waves of the ERG. Wt bestrophin, however, increased the c-wave and fast
oscillation (FO), but not the LP. In contrast, both mutants had little or no
effect on the c-wave and FO, but did reduce LP amplitude. LP amplitudes across a 
range of stimuli were not altered by wt bestrophin, though the luminance response
function was desensitized. LP response functions were unaffected by bestrophin
R218C but were significantly altered by bestrophin W93C. CONCLUSIONS: A model of 
BMD was developed in the present study. Because overexpression of wt bestrophin
shifted luminance response but did not alter the range of LP response amplitudes,
the authors conclude that the rate-limiting step for generating LP amplitude
occurs before activation of bestrophin or that bestrophin does not directly
generate the LP conductance.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, Non-P.H.S.
    Research Support, U.S. Gov't, P.H.S.

PMID: 15452084 [PubMed - indexed for MEDLINE]

2188: Invest Ophthalmol Vis Sci. 2004 Oct;45(10):3713-20.

Receptor for advanced glycation end products and age-related macular
degeneration.

Howes KA, Liu Y, Dunaief JL, Milam A, Frederick JM, Marks A, Baehr W.

Moran Eye Center, University of Utah Health Science Center, Salt Lake City, UT
84112, USA. kim.howes@hsc.utah.edu

PURPOSE: Advanced glycation end products (AGE) exacerbate disease progression
through two general mechanisms: modifying molecules and forming nondegradable
aggregates, thus impairing normal cellular/tissue functions, and altering
cellular function directly through receptor-mediated activation. In the present
study receptor for AGE (RAGE)-mediated cellular activation was evaluated in the
etiology of human retinal aging and disease. METHODS: The maculas of human donor 
retinas from normal eyes and eyes with early age-related macular degeneration
(AMD) and advanced AMD with geographic atrophy (GA) were assayed for AGE and RAGE
by immunocytochemistry. Cultured ARPE-19 cells were challenged with known ligands
for RAGE, AGE, and S100B, to test for activation capacity. Immunocytochemistry,
real-time RT-PCR, immunoblot analysis, and the TUNEL assay were used to determine
the consequences of RPE cellular activation. RESULTS: Little to no immunolabeling
for AGE or RAGE was found in photoreceptor and RPE cell layers in normal retinas.
However, when small drusen were present, AGE and RAGE were identified in the RPE 
or both the RPE and photoreceptors. In early AMD and GA, the RPE and remnant
photoreceptor cells showed intense AGE and RAGE immunolabeling. Both AGE and
S100B activated cultured RPE cells, as revealed by upregulated expression of
RAGE, NFkappaB nuclear translocation, and apoptotic cell death. CONCLUSIONS:
Immunolocalization of RAGE in RPE and photoreceptors coincided with AGE deposits 
and macular disease in aged, early AMD, and GA retinas. Further, AGE stimulated
RAGE-mediated activation of cultured ARPE-19 cells in a dose-dependent fashion.
AGE accumulation, as occurs with normal aging and in disease, may induce
receptor-mediated activation of RPE/photoreceptor cells, contributing to disease 
progression in the aging human retinas.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15452081 [PubMed - indexed for MEDLINE]

2189: Invest Ophthalmol Vis Sci. 2004 Oct;45(10):3435-41.

Pharmacokinetic-pharmacodynamic modeling of the effect of triamcinolone acetonide
on central macular thickness in patients with diabetic macular edema.

Audren F, Tod M, Massin P, Benosman R, Haouchine B, Erginay A, Caulin C, Gaudric 
A, Bergmann JF.

Ophthalmology Department, Hôpital Lariboisière, Université Paris 7, Paris,
France. francoisaudren@hotmail.com <francoisaudren@hotmail.com>

PURPOSE: To develop a population model capable of describing the profile of the
effect of intravitreal triamcinolone acetonide in the treatment of diabetic
diffuse macular edema. METHODS: The results of 51 injections in 37 eyes (33
patients) with diffuse diabetic macular edema were studied, by using population
pharmacokinetic-pharmacodynamic modeling, without triamcinolone concentration
measurements. This approach was supported by the pharmacokinetic hypothesis that 
the intravitreal triamcinolone concentration decreases in accordance with an
exponential biphasic equation. Central macular thickness (CMT), measured by
optical coherence tomography was chosen as the pharmacodynamic parameter.
RESULTS: The pharmacodynamic profile of the effect of triamcinolone on CMT was
characterized by a curve in three phases: a fast decrease, a steady state, and a 
relapse. The confidence interval of most of the estimated parameters of the model
was narrow. The mean estimated half-life of triamcinolone +/- SD was 15.4 +/- 1.9
days, and the mean maximum duration of its effect (+/-SD), 140 +/- 17 days.
CONCLUSIONS: Pharmacokinetic-pharmacodynamic modeling using CMT constitutes a
valid alternative to pharmacokinetic studies. This approach worked excellently in
the present study, and the results are consistent with those published for the
intraocular pharmacokinetics of triamcinolone acetonide in the human eye. The
authors conclude that this type of investigation is of interest, as it avoids
intraocular measurements as far as possible.

PMID: 15452046 [PubMed - indexed for MEDLINE]

2190: Biochem Biophys Res Commun. 2004 Oct 29;323(4):1203-8.

Insulin-like growth factor-1 contributes to neovascularization in age-related
macular degeneration.

Rosenthal R, Wohlleben H, Malek G, Schlichting L, Thieme H, Bowes Rickman C,
Strauss O.

Augenklinik und Augenpoliklinik, Charité-Universitätsmedizin Berlin, Campus
Benjamin Franklin, Berlin, Germany. rita.rosenthal@charite.de
<rita.rosenthal@charite.de>

Choroidal neovascularization (CNV) is a debilitating complication of age-related 
macular degeneration and a leading cause of vision loss. Along with other
angiogenic factors like vascular endothelial growth factor (VEGF), insulin-like
growth factor (IGF)-1 and its receptor, IGF-1R, have been implicated in CNV.
IGF-1 is produced in neurons and retinal pigment epithelium (RPE) but its targets
and impact in CNV are not understood. IGF-1 immunoreactivity was abundant
throughout surgically isolated human CNV tissues and RPE cells were
immunopositive for IGF-1R. Cultured RPE cells obtained from CNV tissues expressed
IGF-1R. IGF-1 stimulation of cultured cells from CNV tissues induced monophasic
sustained rises in intracellular free Ca(2+). VEGF concentration in the medium of
unstimulated RPE cell cultures from CNV tissues increased with time to a
steady-state (8h) which was increased twofold by IGF-1 stimulation. Thus, in RPE 
cells IGF-1 stimulates the second messenger Ca(2+) and increases VEGF secretion
which, in turn, induces neovascularization.

Publication Types: 
    In Vitro
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15451424 [PubMed - indexed for MEDLINE]

2191: Eye. 2005 Aug;19(8):885-90.

Phacoemulsification with intravitreal triamcinolone in patients with cataract and
coexisting diabetic macular oedema: a 6-month prospective pilot study.

Lam DS, Chan CK, Mohamed S, Lai TY, Lee VY, Lai WW, Fan DS, Chan WM.

Department of Ophthalmology & Visual Sciences, The Chinese University of Hong
Kong, Hong Kong Eye Hospital, Hong Kong. dennislam@cuhk.edu.hk

AIMS: To assess the safety and efficacy of phacoemulsification with intravitreal 
triamcinolone (ivTA) injection in diabetics with cataract and clinically
significant macular oedema (CSMO). METHODS: A total of 19 eyes of 15 consecutive 
diabetic patients with cataract and CSMO were prospectively recruited. Patients
underwent phacoemulsification and intraocular lens implantation with 4 mg ivTA
injection at completion of surgery. Patients were followed up on day 1, then
weekly for 1 month, and thereafter monthly until 6 months postoperatively. Best
corrected visual acuity (BCVA), central macular thickness (CMT) measured by
optical coherence tomography, and adverse events were recorded. RESULTS: In
total, 17 eyes completed 6 months of follow-up. In all, 58.8% showed improvement 
in BCVA of >or=2 lines, with statistically significant improvement in mean
Snellen BCVA of 2.4 lines at 6 months. The peak BCVA was achieved at 4 months.
The mean CMT decreased from a baseline of 449 microm to a minimum of 321+/-148
microm (28.5% reduction) achieved at 2 months, with statistically significant
reduction at all postoperative time intervals until 6 months. Of 17 eyes, 4
(23.5%) developed transiently elevated intraocular pressure that normalised by 6 
months in all but one patient. No injection- or surgery-related complications
were encountered. CONCLUSIONS: Phacoemulsification with concurrent 4 mg ivTA
injection appears to be a safe option for managing diabetics with cataract and
CSMO. However, large-scaled randomised controlled trials are necessary for
delineating the relative contributions of cataract removal and CMT reduction to
visual improvement. Moreover, the transient effect on CMT may warrant further
studies to determine optimal timing and dosage of further ivTA injections.

Publication Types: 
    Evaluation Studies
    Research Support, Non-U.S. Gov't

PMID: 15389275 [PubMed - indexed for MEDLINE]

2192: Eye. 2005 Nov;19(11):1169-77.

Monitoring retinal function in early age-related maculopathy: visual performance 
after 1 year.

Feigl B, Brown B, Lovie-Kitchin J, Swann P.

Department of Ophthalmology, University of Graz, Austria. b.feigi@qut.edu.au

PURPOSE: To monitor visual performance in early age-related maculopathy (ARM).
METHODS: We measured monocular visual function-high-contrast visual acuity
(HC-VA), central visual fields (mean sensitivity, MS), colour vision (desaturated
Panel D-15), Pelli-Robson (P-R), and cone- and rod-mediated multifocal
electroretinograms (mfERG) in 13 ARM subjects and 13 age-matched control subjects
with normal fundi at baseline and after 1 year. All had visual acuity of 6/12 or 
better. The mfERG data were compared to templates derived from the control group 
at baseline. We analysed the mfERG results by averaging the central and
peripheral fields and the superior and inferior fields (CP and SI methods) and by
calculating the local responses. RESULTS: The mean rod-mediated responses were
significantly delayed in the ARM group for the CP (P=0.04) and the SI methods
(P=0.03) at baseline compared to the control group. This did not change
significantly after 1 year, whereas the mean cone-mediated responses were within 
the normal range at both times. Although the local analysis revealed lower
amplitudes for the cone- and rod-mediated responses at baseline this was not
found after 1 year and only the local rod-mediated latencies were delayed at both
times (P<0.01). HC-VA, desaturated Panel D-15 and P-R were significantly worse in
the ARM group (P< or =0.01) at baseline but did not show further significant
deterioration. Progressive fundus changes were found in only two subjects (18%). 
CONCLUSION: Although there was significant impairment of retinal function in
early ARM at baseline no further deterioration was evident after 1 year.

PMID: 15389263 [PubMed - indexed for MEDLINE]

2193: Br J Ophthalmol. 2004 Oct;88(10):1270-3.

A prospective study of visual function and quality of life following PDT in
patients with wet age related macular degeneration.

Armbrecht AM, Aspinall PA, Dhillon B.

Princess Alexandra Eye Pavilion, Chalmers Street, Edinburgh EH3 9HA, UK.
amarmbrecht@yahoo.com

AIMS: (1) A prospective study to assess visual function measures and quality of
life (QoL) in patients with wet age related macular degeneration (AMD) treated
with photodynamic therapy (PDT). (2) To assess if PDT prevents severe visual loss
(loss of six or more lines of distance visual acuity) in the treated eye.
METHODS: 48 of 51 recruited patients with predominantly classic subfoveal
choroidal neovascularisation (CNV) secondary AMD who were treated with PDT were
followed up for 1 year. Assessment included distance and near visual acuity,
contrast sensitivity, vision related quality of life and fluorescein angiography.
Photodynamic therapy using Visudyne was carried out according to standard
protocol. Patients were followed up every 3 months and treatment repeated if
there was significant leakage from CNV. RESULTS: At the 12 month follow up, 71%
(n = 34) of the patients lost less than three lines of best corrected distance
visual acuity. Although there were significant decreases in some of the QoL items
tested, patients were significantly less anxious and more independent outdoors at
the 12 month follow up. CONCLUSION: This study is in keeping with published
literature with PDT preventing severe visual loss in two thirds of treated
patients with predominantly classic CNV.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15377549 [PubMed - indexed for MEDLINE]

2194: Int J Mol Med. 2004 Oct;14(4):753-7.

Evaluation of the ABCR and glutathione peroxidase-3 genes in familial and
sporadic cases of exudative age-related macular degeneration.

Shastry BS.

Department of Biological Sciences, Oakland University, Rochester, MI 48309, USA. 
shastry@oakland.edu

Age-related macular degeneration (ARMD) is the most common cause of blindness in 
older patients and is a major health care epidemic in developed countries. The
exact cause of ARMD is not known. It has been recently reported that heterozygous
missense ABCR mutations are associated with age-related macular degeneration. In 
addition, one of the susceptible loci for maculopathy is on chromosome 5 that is 
very close to the plasma glutathione peroxidase (GPX) gene. Since the retina is
highly sensitive to peroxidation and the GPX gene product protects cells from
oxidative damage, and the fact that the ABCR gene is considered as a major
disease gene in macular degeneration we reasoned that they might serve as
candidate genes in a subset of ARMD cases. To test our hypothesis, we have
carried out a pilot study by analyzing 8 exudative ARMD patients for allelic
variations in the GPX gene and three statistically significant mutations in the
ABCR gene (R943Q, G1961E and D2177N). Our analysis failed to identify the above
three major alterations in the ABCR gene as well as mutations in the coding
sequence of the GPX gene. However, we have been able to identify two polymorphic 
heterozygous mutations in the promoter region of the GPX gene in one sporadic
patient. These mutations have not been seen in any other patients. On the other
hand, when 28 individuals from 6 different ethnic backgrounds with no evidence of
ARMD were analyzed, four of them showed the same alterations in the GPX promoter 
region. Although we cannot completely exclude the possibility of alterations in
the coding regions of the GPX gene, the promoter mutation identified in the
present study statistically may not be associated with this disease. However, it 
may be associated with other additive factors as might be expected for a complex 
disorder.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 15375613 [PubMed - indexed for MEDLINE]

2195: Ophthalmic Epidemiol. 2004 Jul;11(3):161-79.

Methodology of the Cardiovascular Health and Age-Related Maculopathy (CHARM)
Study.

Robman L, McNeil J, Dimitrov P, Dowrick A, Tikellis G, Nicolas C, Cameron J,
Guymer R, McGrath B, McCarty C.

Centre for Eye Research Australia, University of Melbourne. liubov@unimelb.edu.au

Age-related macular degeneration (AMD) is responsible for the majority of visual 
impairment in the Western world. Epidemiological studies examining risk factors
for AMD are needed to develop strategies for the prevention of blindness from
this condition. A number of potentially modifiable risk factors for AMD have been
identified; however, only smoking has been a consistent risk factor across the
numerous studies. A growing body of evidence suggests that AMD and cardiovascular
disease may have common risk factors. The Cardiovascular Health and Age Related
Maculopathy (CHARM) Study was established to examine the risk factors for AMD and
its progression, in particular risk factors associated with cardiovascular
disease. Examining risk factors for prevalent AMD, cases with AMD were compared
with age and gender matched controls with no AMD features. For the assessment of 
AMD progression, the study examined in 2001 and 2002 those participants with
early AMD, or age-related maculopathy (ARM), who had undergone baseline
examination between 1992 and 1995 and compared the characteristics of those who
had progression of AMD with those who did not. The CHARM study involved both
ophthalmic and cardiovascular examinations. Standardised clinical eye examination
and grading of the macular stereo photographs were used to determine the AMD
status and progression. To examine cardiovascular status, carotid artery
ultrasound imaging analysis of systemic arterial compliance, augmentation index
and pulse wave velocity were performed. The traditional and novel risk factors
for CVD such as levels of glucose, cholesterol, high density lipoprotein
cholesterol, low density lipoprotein cholesterol, fibrinogen, C-reactive protein,
immunoglobulins A and M, homocysteine, oxidized LDL and the exposure to the
Chlamydia Pneumonia infection were determined. DNA was collected for
apolipoprotein E genotyping. The present paper outlines the primary aims of the
CHARM study, the methodology involved and the recruitment results.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15370549 [PubMed - indexed for MEDLINE]

2196: Ophthalmic Genet. 2004 Jun;25(2):133-45.

A novel RDS/peripherin gene mutation associated with diverse macular phenotypes.

Yang Z, Li Y, Jiang L, Karan G, Moshfeghi D, O'Connor S, Li X, Yu Z, Lewis H,
Zack D, Jacobson S, Zhang K.

Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.

Pattern dystrophy is a heterogeneous group of retinal dystrophies of which
butterfly-shaped pattern dystrophy (BPD) and adult-onset foveomacular dystrophy
(AOFMD) are the two most common forms. BPD is characterized by a
butterfly-shaped, irregular, depigmented lesion at the level of the retinal
pigment epithelium. In contrast, AOFMD is characterized by the presence of
slightly elevated, symmetric, solitary, round to oval, yellow lesions at the
level of the retinal pigment epithelium. We identified three independent kindreds
with pattern dystrophy, one with four patients affected with BPD and the other
two with 14 affected patients with AOFMD. We performed complete ophthalmic
examination, fluorescein angiography, linkage mapping, and mutational screening
in the RDS/peripherin gene in the affected patients. Patients affected with BPD
had a best-corrected vision of 20/20 to 20/25, whereas vision in the eyes of
patients with AOFMD ranged from 20/20 to 20/400. In all three kindreds, sequence 
analysis identified an A-to-G change at nucleotide position 422 of the
RDS/peripherin gene, predicting a novel Tyr-141-Cys substitution. A haplotype
analysis revealed that these three kindreds shared an identical disease haplotype
at the RDS/peripherin locus, indicating that the mutation reflects a founder
effect. The sequence change that segregated with the disease phenotype was not
observed in 200 control chromosomes. Our results identified a novel mutation in
the RDS/ peripherin gene that can cause diverse macular phenotypes. Genetic and
clinical investigation of pattern dystrophy may provide useful diagnostic tools
and new treatment strategies for this disorder.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15370544 [PubMed - indexed for MEDLINE]

2197: Ophthalmic Genet. 2004 Jun;25(2):111-9.

Evaluation of the ARMD1 locus on 1q25-31 in patients with age-related
maculopathy: genetic variation in laminin genes and in exon 104 of HEMICENTIN-1.

Hayashi M, Merriam JE, Klaver CC, Zernant J, Bergen AA, Smith RT, Chang S,
Merriam JC, Allikmets R.

Department of Ophthalmology Columbia University Eye Institute Research, Rm. 715
630 West 168th Street New York, NY 10032 USA.

The age-related maculopathy (ARM) genetics program at Columbia University
utilizes comprehensive genetic analysis of candidate genes in large case-control 
studies to determine genotypes associated with the ARM complex trait. Genes
encoding laminins, a class of extracellular matrix proteins, represent attractive
candidates for two reasons. First, the presence of laminins in the basal lamina
of the retinal pigment epithelium (RPE), Bruch's membrane, and choriocapillaris
suggests a possible role in the pathophysiology of ARM. Second, three laminin
genes, LAMC1, LAMC2, and LAMB3, are located in the 1q25-31 region, within the
previously mapped ARMD1 locus. The entire open reading frame of the three laminin
genes was screened for variants by denaturing high-performance liquid
chromatography (DHPLC) and direct sequencing in at least 92, and up to 368 ARM
patients and matched unaffected controls. Sixty-nine sequence variants were
detected in the 69 exons of the LAMC1, LAMC2, and LAMB3 genes. Screening of exon 
104 of the recently proposed ARMD1 gene, HEMICENTIN-1, residing in the 1q25-31
locus, did not detect the suggested causal variant, Q5345R, in 632 study
subjects. Overall, we did not find statistically significant differences in the
frequency of variants between ARM-affected individuals and age-matched controls. 
Four rare, non-synonymous, variants were detected in single cases of ARM
patients. Our data on relatively limited numbers of study subjects do not suggest
a significant role for genetic variation in the three laminin genes and in exon
104 of HEMICENTIN-1 in predisposing individuals to ARM. However, as in many
instances in similar studies, involvement of rare amino acid-changing variants in
a fraction of ARM cannot be ruled out.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15370542 [PubMed - indexed for MEDLINE]

2198: Curr Eye Res. 2004 Jul;29(1):41-9.

Effect of laser photocoagulation treatment for diabetic macular oedema on
patient's vision-related quality of life.

Tranos PG, Topouzis F, Stangos NT, Dimitrakos S, Economidis P, Harris M, Coleman 
AL.

Department of Ophthalmology, Royal Free Hampstead NHS Trust, Moorfields Eye
Hospital, City Road, London EC1V 2PD, UK. ptranos@doctors.org.uk

PURPOSE: To evaluate the effect of laser photocoagulation for diabetic macular
oedema (DME) on patients' Vision Related Quality Of Life (VR-QOL) and to
investigate associations between changes in self reported VR-QOL and changes in
visual acuity following application of laser treatment. METHODS: Prospective
cohort study of 55 subjects who underwent laser treatment for DME. Eligible
patients with no history of previous laser photocoagulation self-administered the
51-item field-test version of the National Eye Institute Visual Function
Questionnaire (NEI-VFQ) prior to treatment and 3 months following the last
session of laser application. Visual acuity was measured by means of the Early
Treatment of Diabetic Retinopathy (ETDRS) chart. Multi-item scales rating
different aspects of VR-QOL were compared prior and after photocoagulation and
the change in questionnaire's composite score following treatment was correlated 
to change in visual acuity and other determinants previously reported as risk
factors in the diabetic population. RESULTS: Scale scores associated with general
vision, near vision, distance vision, peripheral vision, vision-specific social
functioning, vision-specific mental health, expectations for visual function and 
dependency due to vision were significantly improved following laser treatment.
Multivariate models revealed that improvement of the NEI-VFQ composite score was 
significant in subjects younger than 65 years of age (p = 0.04) who received more
laser burns (p = 0.02) and had worse vision-related QOL prior to laser treatment 
as expressed by the baseline NEI- VFQ composite score (p = 0.03). There was no
statistically significant association between change in the composite score
following laser treatment and stage of diabetic retinopathy, duration of diabetes
or laser settings used during photocoagulation. CONCLUSIONS: Photocoagulation for
DME has a beneficial effect on patients' subjective perception of visual
function. The use of vision-targeted health status questionnaires in conjunction 
with the clinical examination appears to provide a more comprehensive overview of
individuals' daily well- being following laser treatment.

Publication Types: 
    Multicenter Study

PMID: 15370366 [PubMed - indexed for MEDLINE]

2199: Proc Natl Acad Sci U S A. 2004 Sep 21;101(38):13850-5. Epub 2004 Sep 13.

Disruption of ceruloplasmin and hephaestin in mice causes retinal iron overload
and retinal degeneration with features of age-related macular degeneration.

Hahn P, Qian Y, Dentchev T, Chen L, Beard J, Harris ZL, Dunaief JL.

The F. M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute,
University of Pennsylvania, Philadelphia, PA 19104, USA.

Mechanisms of brain and retinal iron homeostasis have become subjects of
increased interest after the discovery of elevated iron levels in brains of
patients with Alzheimer's disease and retinas of patients with age-related
macular degeneration. To determine whether the ferroxidase ceruloplasmin (Cp) and
its homolog hephaestin (Heph) are important for retinal iron homeostasis, we
studied retinas from mice deficient in Cp and/or Heph. In normal mice, Cp and
Heph localize to Müller glia and retinal pigment epithelium, a blood-brain
barrier. Mice deficient in both Cp and Heph, but not each individually, had a
striking, age-dependent increase in retinal pigment epithelium and retinal iron. 
The iron storage protein ferritin was also increased in Cp-/-Heph-/Y retinas.
After retinal iron levels had increased, Cp-/-Heph-/Y mice had age-dependent
retinal pigment epithelium hypertrophy, hyperplasia and death, photoreceptor
degeneration, and subretinal neovascularization, providing a model of some
features of the human retinal diseases aceruloplasminemia and age-related macular
degeneration. This pathology indicates that Cp and Heph are critical for CNS iron
homeostasis and that loss of Cp and Heph in the mouse leads to age-dependent
retinal neurodegeneration, providing a model that can be used to test the
therapeutic efficacy of iron chelators and antiangiogenic agents.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15365174 [PubMed - indexed for MEDLINE]

2200: Am J Ophthalmol. 2004 Sep;138(3):489-92.

Pseudohypopyon after intravitreal triamcinolone acetonide injection for cystoid
macular edema.

Moshfeghi AA, Scott IU, Flynn HW Jr, Puliafito CA.

Department of Ophthalmology, University of Miami School of Medicine, Bascom
Palmer Eye Institute, 900s NW 17th Street, Miami, FL 33136, USA.

PURPOSE: To report pseudohypopyon after intravitreal triamcinolone acetonide
injection for cystoid macular edema. DESIGN: Retrospective, noncomparative,
consecutive case series. METHODS: Records were reviewed of all patients who
developed pseudohypopyon after intravitreal triamcinolone acetonide injection at 
Bascom Palmer Eye Institute between January 1, 2002 and February 1, 2004.
RESULTS: A total of 828 intravitreal triamcinolone acetonide injections were
administered to 686 patients during the study period. A pseudohypopyon (fine
white crystalline opacities in the inferior anterior chamber angle) and suspended
white crystalline opacities in the aqueous humor developed after 7 of the 828
injections (0.8%); all pseudohypopyons occurred within 3 days of injection and
resolved completely within 2 weeks. None of the 686 patients developed clinically
suspected infectious endophthalmitis. CONCLUSIONS: A transient pseudohypopyon may
occur in the early postinjection period after intravitreal triamcinolone
acetonide injection. Unless progressive intraocular inflammation occurs, close
observational management is indicated.

Publication Types: 
    Case Reports

PMID: 15364241 [PubMed - indexed for MEDLINE]

2201: Am J Ophthalmol. 2004 Sep;138(3):354-61.

Optical coherence tomography and confocal scanning laser tomography for
assessment of macular edema.

Degenring RF, Aschmoneit I, Kamppeter B, Budde WM, Jonas JB.

Department of Ophthalmology, Faculty for Clinical Medicine Mannheim,
Ruprecht-Karls-University, Heidelberg, Germany.
robert.degenring@augen.ma.uni-heidelberg.de

PURPOSE: To compare optical coherence tomography (OCT) and confocal scanning
laser tomography (cSLT) for quantitative retinal thickness mapping of the macula 
and their ability to detect macular edema. DESIGN: Prospective, comparative,
clinical observational study. METHODS: The study population of 138 eyes (97
patients) was divided into a study group consisting of 45 (32.6%) eyes with
macular edema and a control group consisting of 93 (67.4%) eyes without macular
edema. All patients underwent OCT and cSLT of the macula. Retinal thickness
measurements obtained by OCT were compared with signal width and edema index,
determined by cSLT. RESULTS: The OCT measurements and cSLT edema index were
significantly (P <.001) correlated with each other. Correlation coefficients
decreased (P <.001) with increasing diameter of the measurement circle. In the
macular edema group, correlation coefficients were significantly (P <.001) higher
than in the control group. To separate the study and control groups, receiver
operator characteristic curves covered a larger area for OCT measurements than
for cSLT measurements. Retinal thickness measurements and edema index correlate
with visual acuity (correlation coefficient r = -.653 for OCT, r = -.608 for
cSLT; P <.001). CONCLUSIONS: Macular edema can be quantitatively mapped by OCT
and cSLT. The retinal thickness and edema index measurements correlate with
visual acuity. The fast and standard examination modes of OCT give similar
measurements. Both OCT and cSLT can differentiate between eyes with and without
macular edema, with OCT showing a higher predictive value.

Publication Types: 
    Comparative Study

PMID: 15364216 [PubMed - indexed for MEDLINE]

2202: Am J Ophthalmol. 2004 Sep;138(3):323-8.

Comment in:
    Am J Ophthalmol. 2004 Sep;138(3):468-70.

The association of prior cytomegalovirus infection with neovascular age-related
macular degeneration.

Miller DM, Espinosa-Heidmann DG, Legra J, Dubovy SR, Sũner IJ, Sedmak DD, Dix RD,
Cousins SW.

Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami
School of Medicine, 900 NW 17th Street, Miami, FL 33136, USA.
dmiller3@med.miami.edu

PURPOSE: To determine if prior exposure to pathogens associated with vascular
disease, cytomegalovirus, Chlamydia pneumoniae, and Helicobacter pylori
correlates with neovascular age-related macular degeneration (AMD). DESIGN: An
experimental study. METHODS: SETTING: Institutional. Bascom Palmer Eye Institute,
October 2001 to December 2002. PATIENT POPULATION: 150 patients (47 neovascular
amd, 36 dry amd, and 67 non-amd controls) were included in the study. exclusion
criteria included hiv infection, malignancy, recent acute illness requiring
hospitalization within 6 months, or immunosuppressive illness. PROCEDURE: Serum
samples were obtained for analysis of cytomegalovirus, chlamydia pneumoniae, and 
helicobacter pylori igg antibody titers by elisa. MAIN OUTCOME MEASURE:
Comparison of the distribution of igg titers between patients with wet amd, dry
amd, and controls. RESULTS: The average cytomegalovirus IgG titer was higher in
patients with wet AMD versus controls (p = 0.02, Student t-test, two-tailed) and 
patients with dry AMD (p = 0.06). Twenty-six (55%) of 47 subjects with wet AMD
had high cytomegalovirus IgG titers compared with 14 (39%) of 36 patients with
dry AMD (odds ratio [OR] = 2.23, 95% confidence interval [CI] = 0.77 to 6.44) and
23 (34%) of 67 control patients (OR = 2.49, 95% CI = 0.98 to 6.33). There was no 
major difference in the distribution of titers for Chlamydia pneumoniae IgG and
Helicobacter pylori IgG in wet and dry AMD patients. Five of 47 patients with wet
AMD (11%) had high antibody titers to all three pathogens, compared with only 1
of 36 patients with dry AMD (3%) (OR = 4.17, 95% CI = 0.46 to 37.36).
CONCLUSIONS: There was a significant association of high cytomegalovirus IgG
titer with neovascular AMD compared with dry AMD and control patients. Chronic
infection with cytomegalovirus may be a novel risk factor for the progression
from dry to neovascular AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15364212 [PubMed - indexed for MEDLINE]

2203: Rev Hosp Clin Fac Med Sao Paulo. 2004 Aug;59(4):157-60. Epub 2004 Sep 9.

Causes of low vision and use of optical aids in the elderly.

Carvalho KM, Monteiro GB, Isaac CR, Shiroma LO, Amaral MS.

Department of Ophthalmology, Faculty of Medical Sciences, State University of
Campinas, Campinas, SP, Brazil. keilammc@fcm.unicamp.br

PURPOSE: To determine the causes of low vision in an elderly population attended 
by a university visual rehabilitation service and to check for the use of
prescribed optical aids. METHOD: A cross-sectional study was carried out on
patients aged 60 years or over attending for the first time a university low
vision service in 2001. Ophthalmic reevaluation and interview were performed by
means of a structured questionnaire in 2002. RESULTS: The sample comprised 50
subjects aged between 60 and 90 years. Severe low vision (< or =20/200) was
present in 68.0% of patients. The main cause of low vision was age-related
macular degeneration (44.0%). Regarding literacy, 16.0% were illiterate and 72.0%
had completed fundamental schooling. Thirty-one patients (62.0%) had been
prescribed optical aids; 54.8% of these patients stated that they use them. A
majority (70.6%) held a favorable opinion of these aids. CONCLUSIONS: The main
cause of low vision was age-related macular degeneration. Approximately half of
those receiving prescriptions reported actually using the aids in their daily
activities. Making best use of residual vision in the elderly population with
visual impairment is a priority, given the social context, if the independence
necessary for enhanced quality of life is to be achieved.

PMID: 15361978 [PubMed - indexed for MEDLINE]

2204: J Formos Med Assoc. 2004 Sep;103(9):692-700.

Erratum in:
    J Formos Med Assoc. 2004 Oct;103(10):806.

Intravitreal triamcinolone injection for macular edema secondary to increased
retinal vascular permeability.

Lee WF, Yang CM.

Department of Ophthalmology, National Taiwan University Hospital, Taipei.

BACKGROUND AND PURPOSE: Macular edema is an important cause of visual loss in
various retinal diseases, and may be refractory to conventional treatment. We
investigated the efficacy of intravitreal injection of triamcinolone acetonide
for the treatment of intractable macular edema. METHODS: A prospective study was 
conducted in 17 patients (18 eyes) with a diagnosis of macular edema unresponsive
to conventional treatment, resulting from inflammatory or retinal vascular
diseases. The underlying diseases associated with the development of macular
edema were: diabetic retinopathy (6 eyes), branch retinal vein occlusion (5
eyes), Irvine-Gass syndrome (3 eyes), and central retinal vein occlusion (4
eyes). Triamcinolone acetonide 4 mg was injected intravitreally. Ophthalmological
examinations, fundus photography, fluorescein angiography, and optical coherence 
tomography were performed before treatment, 3 months and 6 months after
treatment. During the follow-up period, recurrent macular edema was retreated
with the same dosage and followed for another 6 months. RESULTS: Sixteen eyes
received a single injection and 2 others (11%) underwent reinjection after the
3-month follow-up examination. Among the eyes that received a single injection,
10 (63%) showed visual acuity gain of 2 or more Snellen lines at the 6-month
follow-up. The pretreatment central macular thickness averaged 581 microm
[corrected] and reduced to 215 microm [corrected] at the 6-month follow-up. In
the 2 eyes that received reinjection, macular edema also showed significant
reduction 6 months after retreatment. Sterile endophthalmitis was noted in 3 eyes
(17%). Two eyes (11%) developed significant cataract. Three eyes (17%) developed 
high intraocular pressure; 1 of them (5.5%) ultimately required filtering
surgery. CONCLUSIONS: Intravitreal injection of triamcinolone temporarily reduced
refractory macular edema. Potential complications should be monitored after
treatment.

Publication Types: 
    Clinical Trial

PMID: 15361942 [PubMed - indexed for MEDLINE]

2205: Eye. 2005 Jul;19(7):795-9.

Photodynamic therapy for maculopathy due to radiation retinopathy.

Bakri SJ, Beer PM.

Retina Division, Lions Eye Institute, Albany Medical College, Albany, NY 12208,
USA.

BACKGROUND/AIMS: To describe the clinical outcomes of four eyes with macular
oedema due to radiation retinopathy treated with verteporfin photodynamic therapy
(PDT). METHODS: Interventional Case Series. Four charts of four patients who
underwent PDT for macular oedema due to radiation retinopathy were reviewed.
Snellen visual acuities, clinical examination and fundus photographs were
performed before and after PDT. Main outcome measures were visual acuity,
clinical examination before and after PDT. RESULTS: All four eyes had a marked
reduction in hard exudates. Three of four eyes had an improvement in vision
following the PDT. CONCLUSION: PDT may have a role in the treatment of macular
oedema due to radiation retinopathy.

Publication Types: 
    Case Reports

PMID: 15359269 [PubMed - indexed for MEDLINE]

2206: Eye. 2005 Jul;19(7):747-51.

Intravitreal triamcinolone improves vision in eyes with chronic diabetic macular 
oedema refractory to laser photocoagulation.

Negi AK, Vernon SA, Lim CS, Owen-Armstrong K.

Department of Ophthalmology, Eye and ENT Centre, University Hospital, Nottingham,
UK.

PURPOSE: To evaluate the clinical and visual outcome of an intravitreal injection
of triamcinolone in patients with diabetic macular oedema refractory to laser
treatment. MATERIAL AND METHODS: Prospective, interventional nonrandomised case
series of 24 eyes of 24 patients that underwent intravitreal injection of 4 mg
triamcinolone for chronic diabetic macular oedema refractory to previous laser
treatment. All patients had best corrected visual acuity (bcva) on the LogMAR
scale, near vision, slit-lamp biomicroscopy for the presence of clinically
significant macular oedema, and intraocular pressure check at 1, 3, and 6 months.
RESULTS: The average duration of macular oedema before the injection was 38.2
months (range=6-120 months) with the mean number of laser treatments before the
injection being 2.2 (range=1-5). The visual acuity improved in 19 of the 23 (83%)
eyes at 1 month, 16 of the 21 eyes (76%) at 3 months and six of 11 eyes (55%) at 
6 months follow-up. The mean bcva improved by an average of 10, nine, and six
letters, respectively, compared to the baseline at 1, 3, and 6 months (P=0.0002
at 1 month and 0.001 at 3 months with the Wilcoxon signed-ranked test). The
intraocular pressure rose by an average of 2.4, 2.8, and 2.7 mmHg at the same
follow-up visits. CONCLUSION: Intravitreal triamcinolone appears to be promising 
in the short term, for improving the vision in eyes with chronic diabetic macular
oedema unresponsive to conventional laser treatment. Randomised controlled trials
utilising varying doses of steroid are now required to define optimum treatment
regimens.

Publication Types: 
    Clinical Trial

PMID: 15359268 [PubMed - indexed for MEDLINE]

2207: Eye. 2005 Jun;19(6):676-82.

Diabetic vitreopapillary traction and macular oedema.

Karatas M, Ramirez JA, Ophir A.

Department of Ophthalmology, Hillel-Yaffe Medical Centre, Hadera, Israel.

PURPOSE: To describe an association between optic disc traction and diabetic
macular oedema (DME) unresponsive to laser treatment. METHODS: A retrospective
review of all patients with DME who attended our clinic between September 2001
and November 2003 was undertaken. The patients had undergone ophthalmic history
and examination, fluorescein angiography, and optical coherence tomography (OCT) 
of the macular area and optic nerve head (ONH). A total of 10 nonvitrectomized
eyes that were found to have an elevation of the ONH secondary to vitreopapillary
traction were included in the analysis. Eyes with additional traction at the
posterior pole were excluded. RESULTS: Out of the 10 eyes (seven patients, aged
47-79 years) with vitreo-papillary traction, nine had previously undergone argon 
laser photocoagulation(s) for DME. In seven eyes (seven patients), OCT verified
the vitreopapillary traction as the sole traction, whereas in the fellow eyes of 
three patients vitreomacular traction was evident as well. In the seven eyes with
only vitreopapillary traction, OCT demonstrated parapapillary serous retinal
detachment in two eyes and a diffuse DME in all eyes (mean foveal thickness,
396+/-144 microm). Maximal thickness of the papillo-macular bundle site was
adjoining the elevated ONH in three eyes, and was maximal at the central macula
in the other four eyes. Ultrasonography (n=5) revealed an incomplete detachment
of the posterior hyaloid in each, adherent only at the ONH. CONCLUSIONS: Diffuse 
DME unresponsive to laser treatment may be associated with vitreopapillary
traction. Further studies should indicate whether these two phenomena could
suggest a cause and effect in such eyes.

PMID: 15359258 [PubMed - indexed for MEDLINE]

2208: Ophthalmology. 2004 Sep;111(9):1715-24.

Change in visual function after macular translocation with 360 degrees
retinectomy for neovascular age-related macular degeneration.

Mruthyunjaya P, Stinnett SS, Toth CA.

Department of Ophthalmology, Duke University Medical Center, Durham, North
Carolina, USA.

OBJECTIVE: To measure the change in vision and visual outcomes at 12 months after
macular translocation with 360 degrees retinectomy (MT360) and silicone oil
tamponade in patients with bilateral vision loss resulting from subfoveal
choroidal neovascular membranes in age-related macular degeneration (AMD).
DESIGN: A prospective, interventional, consecutive, noncomparative case series.
PARTICIPANTS: Sixty-four patients with bilateral vision loss resulting from
neovascular AMD. METHODS: Eligible patients had AMD with subfoveal choroidal
neovascularization in the operative eye and a maximum of 6 months of central
vision loss. Preoperative and 12-month postoperative evaluations included
standardized testing of near and distance acuity and reading speed. Patients
underwent MT360 with silicone oil tamponade, followed 2 months later by
extraocular muscle surgery and silicone oil removal. MAIN OUTCOME MEASURES:
Change in distance acuity, near acuity, and reading speed at 12 months after
MT360 compared with those values before surgery. RESULTS: Sixty-one patients were
followed up for 12 months. All eyes were translocated successfully. Median
distance acuity letter score improved from 62 letters (Snellen equivalent of
approximately 20/125) before surgery to 69 letters (approximately 20/80) by 12
months after surgery (P = 0.03). Median near acuity improved from 0.70 logarithm 
of the minimum angle of resolution (logMAR) units (approximately 20/100) before
surgery to 0.44 logMAR units (approximately 20/55) at 12 months (P<0.001). Median
reading speed improved from 71 words per minute (wpm) before surgery to 105 wpm
at 12 months after surgery (P<0.001). At 12 months, distance acuity improved by 1
or more lines in 32 patients (52%). In patients with either preoperative distance
or near acuity of 20/80 or better, 74% and 95% of patients, respectively,
remained in this range of acuity. In patients with either preoperative distance
or near acuity of worse than 20/80, 40% and 48% of patients, respectively,
improved to 20/80 or better. Postoperative retinal detachment developed in 5
patients (8%), with the macula involved in 2 patients, and all retinas were
reattached successfully. CONCLUSIONS: Macular translocation with 360 degrees
retinectomy with silicone oil tamponade is effective in significantly improving
visual function in patients with neovascular AMD, as demonstrated by the
improvement in distance and near acuity and reading speed at 12 months after
surgery in these patients. Although this is a complex surgical intervention,
patients with preoperative visual acuity of 20/80 or better at near or distance
are highly likely to retain the 20/80 or better acuity at 12 months after
surgery. Macular translocation with 360 degrees retinectomy is an effective
treatment option for patients with vision loss in their second eye resulting from
neovascular AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15350328 [PubMed - indexed for MEDLINE]

2209: J Nutr Elder. 2004;24(1):1-18.

Consumption of caroltenoid-rich foods and central vision loss:a matched
case-controlled study in Kansas.

Holcomb CA.

Department of Human Nutrition, Kansas State University, Manhatten, KS,
66506-1407, USA. carolann@ksu.edu

The purpose of this study was to explore the association between consumption of
carotenoid-rich foods and risk of central vision loss in 168 rural elders. Food
consumption was estimated using a food frequency questionnaire. Median servings
per week were used as the cut points for consumption levels. Odds ratios (OR) and
95% confidence intervals (CI) were calculated by using discordant pairs. High
consumption of corn bread indicated significant association with central vision
loss (OR 0.4; 95% CI 0.2, 0.9). Insignificant inverse associations were observed 
for seven other foods and the summary index of all selected foods. Prospective
studies are needed to further evaluate the potential protective influence of
carotenoid-rich foods on central vision loss among older adults.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15339717 [PubMed - indexed for MEDLINE]

2210: Expert Opin Biol Ther. 2004 Sep;4(9):1395-402.

Ocular neovascularisation and excessive vascular permeability.

Campochiaro PA.

Department of Ophthalmology, The Johns Hopkins University School of Medicine,
Maumenee 719, 600 N. Wolfe Street, Baltimore, MD 21287-9277, USA. pcampo@jhmi.edu

Diseases complicated by vascular leakage and/or neovascularisation in the eye are
responsible for the vast majority of visual morbidity and blindness in developed 
countries. The molecular signals that control vascular permeability and
neovascularisation in the eye are being defined. Members of the vascular
endothelial growth factor (VEGF) family are key stimulators that interact with
two tyrosine kinase receptors, VEGF receptor (VEGFR)1 and 2; binding to two other
receptors that lack tyrosine kinase activity, the neuropilins, is also important.
Signalling through the VEGF pathway is modulated by the Tie2 receptor and its
binding partners, the angiopoietins. Each of the participants in these two
signalling pathways provides a potential target for intervention. Several
proteins with antiangiogenic activity balance the stimulators and the outcome is 
determined by the net balance. Endostatin suppresses vascular permeability as
well as ocular neovascularisation, suggesting that vascular leakage may also be
regulated by counteracting proteins. Gene transfer provides a useful way to
influence these balances. Clinical trials are underway to test whether these
mechanisms can be translated into new therapies.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.
    Review

PMID: 15335307 [PubMed - indexed for MEDLINE]

2211: Diabetes Care. 2004 Sep;27(9):2184-90.

Endothelial nitric oxide synthase gene is associated with diabetic macular edema 
in type 2 diabetes.

Awata T, Neda T, Iizuka H, Kurihara S, Ohkubo T, Takata N, Osaki M, Watanabe M,
Nakashima Y, Sawa T, Inukai K, Inoue I, Shibuya M, Mori K, Yoneya S, Katayama S.

The Fourth Department of Medicine, Saitama Medical School, 38 Morohongo,
Moroyama, Iruma-gun, Saitama, 350-0495, Japan. awata@saitama-med.ac.jp

OBJECTIVE: We examined the endothelial nitric oxide (eNOS) gene polymorphisms to 
assess its possible association with diabetic retinopathy and macular edema.
RESEARCH DESIGN AND METHODS: A total of 226 patients with type 2 diabetes and 186
healthy subjects were studied. Type 2 diabetic patients consisted of 110 patients
without retinopathy, 46 patients with nonproliferative diabetic retinopathy, and 
71 patients with proliferative diabetic retinopathy. Diabetic macular edema was
present in 48 patients. Three polymorphisms of the eNOS gene were determined:
T-786C in the promoter region, 27-bp repeat in intron 4, and Glu298Asp in exon 7.
RESULTS: Close linkage disequilibrium was observed between the T-786C
polymorphism and the 27-bp repeat, as has been previously reported, but Glu298Asp
was not in linkage disequilibrium with the other two polymorphisms. The eNOS gene
polymorphisms were not significantly associated with the presence of retinopathy 
or with retinopathy severity or type 2 diabetes itself. However, by both
association study and multiple logistic regression analysis, the T-786C and 27-bp
repeat polymorphisms were significantly associated with a risk of developing
macular edema with the -786C allele and the "a" allele increasing the risk.
CONCLUSIONS: The present study suggests that the eNOS gene is a novel genetic
risk factor for diabetic macular edema. The eNOS gene polymorphisms may
contribute to the development of macular edema by impairing basal eNOS expression
and resulting in the breakdown of the blood-retina barrier.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15333482 [PubMed - indexed for MEDLINE]

2212: Health Serv Res. 2004 Oct;39(5):1429-48.

Monitoring visual status: why patients do or do not comply with practice
guidelines.

Sloan FA, Brown DS, Carlisle ES, Picone GA, Lee PP.

Department of Economics, Box 90097, Duke University, Durham, North Carolina,
27708, USA.

OBJECTIVE: To determine factors affecting compliance with guidelines for annual
eye examinations for persons diagnosed with diabetes mellitus (DM) or age-related
macular degeneration (ARMD). DATA SOURCES/STUDY SETTING: Nationally
representative, longitudinal sample of individuals 65+ drawn from the National
Long-Term Care Survey (NLTCS) with linked Medicare claims records from 1991 to
1999. STUDY DESIGN: Medicare beneficiaries were followed from 1991 to 1999,
unless mortality intervened. All claims data were analyzed for presence of ICD-9 
codes indicating diagnosis of DM or ARMD and the performance of eye exams. The
dependent variable was a binary indicator for whether a person had an eye exam or
not during a 15-month period. Independent variables for demographics, living
conditions, supplemental insurance, income, and other factors affecting the
marginal cost and benefit of an eye exam were assessed to determine reasons for
noncompliance. DATA COLLECTION/EXTRACTION METHODS: Panel data were created from
claims files, 1991-1999, merged with data from the NLTCS. PRINCIPAL FINDINGS: The
probability of having an exam reflected perceived benefits, which vary by patient
characteristics (e.g., education, no dementia), and factors associated with the
ease of visit. African Americans were much less likely to be examined than were
whites. CONCLUSIONS: Having an exam reflects multiple factors. However, much of
the variation in the probability of an exam remained unexplained as were reasons 
for the racial differences in use.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.

PMID: 15333116 [PubMed - indexed for MEDLINE]

2213: Eye. 2005 Jun;19(6):686-8.

Intravitreal preservative-free triamcinolone acetonide for the treatment of
macular oedema.

Bakri SJ, Shah A, Falk NS, Beer PM.

Lions Eye Institute, Albany Medical College, Albany, New York, USA.
sbakri@hotmail.com

PURPOSE: To report the use of commercially available preservative-free
intravitreal triamcinolone acetonide for the treatment of macular oedema due to
retinal vascular diseases. DESIGN: Retrospective interventional case series.
METHODS: Charts of eyes that received 4 mg preservative-free intravitreal
triamcinolone acetonide for the treatment of persistent macular oedema due to
retinal vascular diseases were reviewed. Patients were included if they had a
follow-up of at least 3 months. Visual acuity, intraocular pressure, presence of 
an anterior chamber reaction, and mean macular thickness on optical coherence
tomography (OCT) were recorded. RESULTS: A total of 10 eyes of 10 patients were
identified. Visual acuity improved by a mean of 1.1 Snellen lines at 1 month and 
1.3 lines at 3 months. Macular thickness on OCT decreased by a mean of 183.5
microm at 1 month (P<0.0001). Intraocular pressure increased from a mean of 13.5 
mmHg at baseline to 15.3 at 1 month, and 14.5 at 3 months. Only the 1-month
change in intraocular pressure was statistically significant (P=0.0274). There
were no cases of endophthalmitis, anterior chamber reaction, or retinal
detachment. CONCLUSION: In this small retrospective, noncomparative series,
commercially available preservative-free intravitreal triamcinolone acetonide had
no adverse outcomes. Macular oedema was noted to decrease following treatment.

PMID: 15332099 [PubMed - indexed for MEDLINE]

2214: Invest Ophthalmol Vis Sci. 2004 Sep;45(9):3355-60.

Flicker perimetry losses in age-related macular degeneration.

Phipps JA, Dang TM, Vingrys AJ, Guymer RH.

Department of Optometry and Vision Sciences, University of Melbourne, Victoria,
Australia.

PURPOSE: To compare static and flicker perimetry outcomes in patients with early 
age-related macular degeneration (AMD). METHODS: Perimetry was performed in the
central visual field of one eye of each of 25 patients with good visual acuity (>
6/12) and early AMD using static and flickering targets. These results were
compared with data obtained from a single eye of 34 age-matched control subjects,
33 of whom were retested at 1 to 3 months after their initial visits. RESULTS: In
all cases, patients with early AMD had greater mean defects for flickering than
static targets, returning a significantly larger group average in response to
flicker (4.3 +/- 0.6 dB) than to static (1.8 +/- 0.6 dB; P < 0.005). Greater
pattern defect losses were also present in AMD-affected eyes with flicker
compared with static perimetry (P < 0.02). These give a higher diagnostic
sensitivity for flicker (68% vs. 42%, P < 0.05) at 90% specificity. Sensitivity
can be increased to 84% +/- 6% (specificity 92% +/- 4%) if the criterion for
failure is a more than 10-dB loss in the foveal region (1 degrees -3 degrees ).
CONCLUSIONS: Flickering targets expose foveal deficits in early AMD better than
do static targets. Flicker perimetry is an easy, short procedure that may be
useful for monitoring the progression of AMD. Copyright Association for Research 
in Vision and Ophthalmology

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15326161 [PubMed - indexed for MEDLINE]

2215: Invest Ophthalmol Vis Sci. 2004 Sep;45(9):3271-8.

Impact of aging and age-related maculopathy on activation of the a-wave of the
rod-mediated electroretinogram.

Jackson GR, McGwin G Jr, Phillips JM, Klein R, Owsley C.

Department of Ophthalmology, School of Medicine, University of Alabama at
Birmingham, 35294-0009, USA. grjackson@uab.edu

PURPOSE: To examine the impact of aging and age-related maculopathy (ARM) on the 
activation of phototransduction in rod photoreceptors by measuring the a-wave of 
the flash, full-field electroretinogram (ERG). METHODS: Enrollees consisted of
older adults (> or = 60 years of age) in normal retinal health (n = 41) and those
with early (n = 39) or late ARM (n = 7), in whom disease presence and severity
were defined based on grading of stereoscopic color fundus photographs according 
to the Wisconsin Age-Related Maculopathy grading system. Young adults (ages 16-30
years; n = 27) were enrolled for comparison purposes. Previously established
procedures were used to estimate the ERG response to two families of flash
intensities. By computer subtraction of responses, the isolated rod response was 
identified. Each participant's ensemble rod responses were fit with the following
equation to describe the response (R) as function of flash intensity (I), and
time (t): R(I,t) = [1 - exp[-I x S x (t - td)2]] x RmP3, where S is sensitivity, 
td is the delay before onset of the a-wave, and Rm(P3) is the maximum amplitude. 
RESULTS: In analyses of older adults, there was no impact of early ARM presence
or severity on log S, Rm(P3), or td after adjustment for age and intraocular lens
presence. Differences between young and old normal subjects in log S, RmP3, and
td disappeared when analyses were limited to older adults with intraocular
lenses. CONCLUSIONS: When the light absorption of the aged lens is taken into
account and reliable definitions of normal retinal aging and ARM are used, the
activation of the a-wave as measured by the rod-mediated full-field ERG is not
affected by early ARM, nor is it impacted by normal retinal aging. Copyright
Association for Research in Vision and Ophthalmology

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15326151 [PubMed - indexed for MEDLINE]

2216: Exp Eye Res. 2004 Aug;79(2):209-21.

Differential gene expression of early and late passage retinal pigment epithelial
cells.

Wang XF, Cui JZ, Nie W, Prasad SS, Matsubara JA.

Department of Ophthalmology and Visual Sciences, The University of British
Columbia, 2550 Willow Street, Vancouver, BC V5Z 3N9, Canada.

We examined the gene expression profiles of retinal pigment epithelial (RPE)
cells which were aged in vitro by repeated passage. RPE cells from human eyes
were cultured to passage 3-5 (early passage) or 19-21 (late passage) and used to 
study gene expression profiles by cDNA microarray. Results from microarray
analysis were further confirmed by real-time PCR. Microarray analysis showed gene
expression changes among 588 known genes. The expression levels of 15 genes
(2.6%) increased in late passage RPE cells, while 43 genes (7.3%) decreased using
a two-fold criterion. These differentially expressed genes encompassed many
functional classes. A small number of stress genes, such as clusterin,
replication protein A and Ku80, were up-regulated. The down-regulated genes
included many enzymes of energy and biomolecule metabolism as well as cell cycle 
proteins and cell adhesion proteins. Results from real-time PCR were generally
consistent with microarray findings. The expression levels of the examined
angiogenic factors were either unchanged or down-regulated. Comparing early
(p=3-5) and late (p=9-12) passage RPE cells, several categories of differentially
expressed genes were identified. However, there was no enhanced expression of
known angiogenic factors.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15325568 [PubMed - indexed for MEDLINE]

2217: Surv Ophthalmol. 2004 Sep-Oct;49(5):470-90.

Macular edema.

Tranos PG, Wickremasinghe SS, Stangos NT, Topouzis F, Tsinopoulos I, Pavesio CE.

Moorfields Eye Hospital, London, United Kingdom.

Macular edema is the final common pathway of many intraocular and systemic
insults. It may develop in a diffuse pattern where the macula appears generally
thickened or it may acquire the characteristic petaloid appearance referred to as
cystoid macular edema. Although macular edema may be associated with protean
underlying conditions, it is most commonly seen following intraocular surgery,
venous occlusive disease, diabetic retinopathy, and posterior segment
inflammatory disease. As well as clinical suspicion, a wide range of
investigations may lead to the diagnosis of macular edema. Fluorescein
angiography and optical coherence tomography provide enhanced visualization of
the geometry and distribution of macular edema. A variety of approaches to the
treatment of macular edema have been attempted, with a variable degree of
success. These options have included topical and systemic steroids, topical and
oral non-steroidal anti-inflammatory agents and laser photocoagulation treatment.
More recently other therapeutic modalities, including immunomodulators,
intravitreal injection of triamcinolone, and pars plana vitrectomy have also been
employed. Clinical trials are currently looking into the use of a steroid
slow-release intravitreal device for the management of macular edema secondary to
uveitis and diabetes. This article reviews the clinical entity of macular edema
focusing on the current therapeutic strategies for its management.

Publication Types: 
    Review

PMID: 15325193 [PubMed - indexed for MEDLINE]

2218: J Ocul Pharmacol Ther. 2004 Aug;20(4):277-84.

A prospective controlled trial to evaluate the adjunctive role of posterior
subtenon triamcinolone in the treatment of diffuse diabetic macular edema.

Verma LK, Vivek MB, Kumar A, Tewari HK, Venkatesh P.

Rajendra Prasad Center for Ophthalmic Sciences, All India Institute of Medical
Sciences, New Delhi, India.

The aim of the present prospective controlled trial was to evaluate the adjuvant 
role of posterior subtenon triamcinolone in the treatment of diffuse diabetic
macular edema (DDME). Thirty one (31) eyes with DDME were divided into an
interventional group subjected to grid laser photocoagulation and 0.5 mL of 40
mg/mL posterior subtenon triamcinolone, and a noninterventional group subjected
to grid laser photocoagulation only. Best-corrected visual acuity, contrast
sensitivity, and intraocular pressures were assessed at presentation, and at 6,
12, and 24 weeks after intervention. The interventional group showed a
statistically significant (p < 0.05) change in both mean best corrected visual
acuity, from 20/160 to 20/100 (two-line increase on Early Treatment Diabetic
Retinopathy Study (ETDRS)) (p = 0.024), and mean contrast sensitivity, from 0.9
to 1.09 (p = 0.01), at the end of 24 weeks. A significant rise in intraocular
pressure was not described in any of the patients in either group. Posterior
subtenon triamcinolone injection is a useful and safe adjunct to the conventional
management of diabetic macular edema.

Publication Types: 
    Clinical Trial
    Comparative Study
    Controlled Clinical Trial

PMID: 15321022 [PubMed - indexed for MEDLINE]

2219: Br J Ophthalmol. 2004 Sep;88(9):1180-5.

Colour vision testing as an aid to diagnosis and management of age related
maculopathy.

Arden GB, Wolf JE.

Applied Vision Research Centre, Department of Optometry and Visual Science, City 
University, London EC1V 0HB, UK. g.arden@city.ac.uk

AIM: To provide a simple test that detects the onset of age related maculopathy
(ARM), and can be used to monitor its severity. METHODS: Colour contrast
sensitivity was measured using computer graphics techniques. Colour thresholds
were measured along tritan and protan colour confusion axes in the presence of
dynamic luminance noise. Thresholds were determined separately for two sizes of
optotypes (6.5 degrees and 1.5 degrees). Natural pupils were used. Normal values 
for the test have been established. RESULTS: In all patients with unilateral age 
related macular degeneration, the smaller optotype was invisible in that eye and 
in almost all, the larger optotype could not be seen. In the symptomless fellow
eyes (with ARM) the larger optotype thresholds were raised. The degree of loss
was larger for tritan. For the smaller optotype, protan thresholds were elevated 
in the majority of patients. Tritan losses were greater and disproportionate to
the loss seen with the larger optotype. Every person including those with minimal
fundal changes had tritan test results for 1.5 degree optotypes >2 SD above the
normal mean. Tritan thresholds varied with the severity of the ARM. CONCLUSIONS: 
The test is sensitive, simple and quick to administer, and easy for patients.
Therefore, it should be useful in detecting and monitoring elderly people with
age related changes in their fundi before irreversible loss of vision has
occurred.

PMID: 15317712 [PubMed - indexed for MEDLINE]

2220: Br J Ophthalmol. 2004 Sep;88(9):1173-9.

Subthreshold micropulse diode laser treatment in diabetic macular oedema.

Laursen ML, Moeller F, Sander B, Sjoelie AK.

Department of Ophthalmology, Odense University Hospital, DK-5000 Odense C,
Denmark. majbrit.lind.laursen@ouh.fyns-amt.dk

BACKGROUND/AIM: Enlargement of laser scars after retinal argon laser
photocoagulation can give rise to deterioration in visual acuity. Subthreshold
micropulse diode laser may decrease this risk. The aim of this study was to
compare the effectiveness of subthreshold micropulse diode laser (810 nm) and
conventional argon laser (514 nm) photocoagulation for the treatment of
clinically significant macular oedema in diabetic patients. METHODS: 23 eyes of
16 patients were randomised to either treatment. Follow up was conducted for a
minimum of 5 months. Changes in visual acuity and macular oedema measured by
optical coherence tomography were examined. RESULTS: Visual acuity remained
stable in all treatment groups throughout the observation period. Changes in
retinal thickness were small both foveally and perifoveally. In patients with
focal macular oedema a significant reduction in retinal thickness (9%
approximately -26 microm, p = 0.02) was seen foveally 3 months after diode laser 
photocoagulation. CONCLUSION: Subthreshold micropulse diode laser and
conventional argon laser treatment showed an equally good effect on visual
acuity. Subthreshold micropulse diode laser showed a stabilising or even
improving effect on macular oedema. The combination of primary diode laser and
supplementary argon laser might be particularly favourable in reducing diabetic
macular oedema.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 15317711 [PubMed - indexed for MEDLINE]

2221: Br J Ophthalmol. 2004 Sep;88(9):1131-6.

Intravitreal triamcinolone for the treatment of refractory diabetic macular
oedema with hard exudates: an optical coherence tomography study.

Ciardella AP, Klancnik J, Schiff W, Barile G, Langton K, Chang S.

Director of Ophthalmology, Denver Health Medical Center, 777 Bannock Street, Mail
Code 0156, Denver, CO 80204, USA. Antonio.ciardella@dhha.org

AIM: To investigate the use of intravitreal triamcinolone acetonide (IVTA) for
the treatment of diabetic macular oedema (DMO) unresponsive to previous laser
photocoagulation. METHOD: A retrospective, interventional, non-comparative case
series. There were 30 eyes of 22 consecutive patients with refractory DMO. An
intravitreal injection of triamcinolone acetonide at the dose of 4 mg in 0.1 ml
was administered. Best corrected visual acuity was measured at each examination. 
In addition the central macular thickness was quantitatively measured by optical 
coherence tomography (OCT) examination at each visit. The amount of hard exudates
deposition in the macula was subjectively evaluated using colour fundus
photographs. RESULTS: 30 eyes of 22 patients completed 6 months or more of follow
up and were included in the study. Mean (SD) visual acuity improved from 0.17
(0.12) at baseline to 0.34 (0.18), 0.36 (0.16), and 0.31 (0.17) at the 1, 3, and 
6 month follow up respectively. Mean (SD) OCT macular thickness decreased from
476 (98.32) microm at baseline to 277.46 (96.77) microm, 255.33 (95.73) microm,
and 331.25 (146.76) microm at the 1, 3, and 6 month follow up period
respectively. 18 and seven eyes completed 12 months and 18 months of follow up,
respectively. Mean (SD) visual acuity was 0.36 (0.15) and 0.35 (0.16) at the 12
and 18 month follow up period respectively. 12 eyes received two, seven eyes
received three, and two eyes received four IVTA injections. The mean (SD)
interval between the first and second IVTA injection was 5.7 (2.67) months and
between the second and third was 5.7 (3.25) months. Hard exudates were present in
the macula at baseline in all eyes. Progressive reduction in the number and size 
of the hard exudates was noted after IVTA in all cases. Intraocular pressure was 
raised above 21 mm Hg in 12 (40%) of 30 eyes. Two eyes developed posterior
subcapsular cataract and two developed vitreous haemorrhage. CONCLUSIONS: IVTA is
a promising treatment for patients with DMO refractory to laser treatment. IVTA
is effective in improving vision, reducing macular thickness, and inducing
reabsorption of hard exudates. Further investigation is warranted to assess the
safety of IVTA for the treatment of DMO.

PMID: 15317702 [PubMed - indexed for MEDLINE]

2222: Br J Ophthalmol. 2004 Sep;88(9):1125-30.

Reduced vision in older adults with age related macular degeneration interferes
with ability to care for self and impairs role as carer.

Stevenson MR, Hart PM, Montgomery AM, McCulloch DW, Chakravarthy U.

Centre for Ophthalmology and Vision Science, The Queen's University of Belfast
and Royal Group of Hospitals, Grosvenor Road, Belfast BT12 6BA, Northern Ireland,
UK.

AIM: To study the relation between visual impairment and ability to care for
oneself or a dependant in older people with age related macular degeneration
(AMD). METHOD: Cross sectional study of older people with visual impairment due
to AMD in a specialised retinal service clinic. 199 subjects who underwent visual
function assessment (fully corrected distance and near acuity and contrast
sensitivity in both eyes), followed by completion of a package of questionnaires 
dealing with general health status (SF36), visual functioning (Daily Living Tasks
Dependent on Vision, DLTV) and ability to care for self or provide care to
others. The outcome measure was self reported ability to care for self and
others. Three levels of self reported ability to care were identified--inability 
to care for self (level 1), ability to care for self but not others (level 2),
and ability to care for self and others (level 3). RESULTS: People who reported
good general health status and visual functioning (that is, had high scores on
SF36 and DLTV) were more likely to state that they were able to care for self and
others. Similarly people with good vision in the better seeing eye were more
likely to report ability to care for self and others. People with a distance
visual acuity (DVA) worse than 0.4 logMAR (Snellen 6/15) had less than 50%
probability of assigning themselves to care level 3 and those with DVA worse than
1.0 logMAR (Snellen 6/60) had a probability of greater than 50% or for assigning 
themselves to care level 1. Regression analyses with level of care as the
dependent variable and demographic factors, DLTV subscales, and SF36 dimensions
as the explanatory variables confirmed that the DLTV subscale 1 was the most
important variable in the transition from care level 3 to care level 2. The
regression analyses also confirmed that the DLTV subscale 2 was the most
important in the transition from care level 3 to care level 1. CONCLUSIONS:
Ability to care for self and dependants has a strong relation with self reported 
visual functioning and quality of life and is adversely influenced by visual
impairment. The acuity at which the balance of probability shifts in the
direction of diminished ability to care for self or others is lower than the
level set by social care agencies for provision of support. These findings have
implications for those involved with visual rehabilitation and for studies of the
cost effectiveness of interventions in AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15317701 [PubMed - indexed for MEDLINE]

2223: Br J Ophthalmol. 2004 Sep;88(9):1107-12.

Cost effectiveness of photodynamic therapy with verteporfin for age related
macular degeneration: the UK case.

Smith DH, Fenn P, Drummond M.

Center for Health Research, Kaiser Permanente Northwest, 3800 N Interstate Ave,
Portland, OR 97211, USA. David.Smith@kpchr.org

AIM: To estimate the potential cost effectiveness of photodynamic therapy (PDT)
with verteporfin in the UK setting. METHODS: Using data from a variety of sources
a Markov model was built to produce estimates of the cost effectiveness
(incremental cost per quality adjusted life year (QALY) and incremental cost per 
vision year gained) of PDT for two cohorts of patients (one with starting visual 
acuity (VA) of 20/40 and one at 20/100) with predominantly classic choroidal
neovascular disease over a 2 year and 5 year time horizon. A government
perspective and a treatment cost only perspective were considered. Probabilistic 
and one way sensitivity analyses were undertaken. RESULTS: From the government
perspective, over the 2 year period, the expected incremental cost effectiveness 
ratios range from 286 000 (starting VA 20/100) to 76 000 UK pounds (starting VA
20/40) per QALY gained and from 14 000 (20/100) to 34 000 UK pounds (20/40) per
vision year gained. A 5 year perspective yields incremental ratios less than 5000
UK pounds for vision years gained and from 9000 (20/40) to 30 000 UK pounds
(20/100) for QALYs gained. Without societal or NHS cost offsets included, the 2
year incremental cost per vision year gained ranges from 20 000 (20/100) to 40
000 UK pounds (20/40), and the 2 year incremental cost per QALY gained ranges
from 412 000 (20/100) to 90 000 UK pounds (20/40). The 5 year time frame shows
expected costs of 7000 (20/40) to 10 000 UK pounds (20/100) per vision year
gained and from 38 000 (20/40) to 69 000 UK pounds (20/100) per QALY gained.
CONCLUSION: This evaluation suggests that early treatment (that is, treating eyes
at less severe stages of disease) with PDT leads to increased efficiency. When
considering only the cost of therapy, treating people at lower levels of visual
acuity would probably not be considered cost effective. However, a broad
perspective that incorporates other NHS treatment costs and social care costs
suggests that over a long period of time, PDT may yield reasonable value for
money.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15317697 [PubMed - indexed for MEDLINE]

2224: Eur J Ophthalmol. 2004 Jul-Aug;14(4):321-4.

Intravitreal triamcinolone acetonide: valuation of retinal thickness changes
measured by optical coherence tomography in diffuse diabetic macular edema.

Micelli Ferrari T, Sborgia L, Furino C, Cardascia N, Ferreri P, Besozzi G,
Sborgia C.

Departments of Ophthalmology and ORL, Division of Ophthalmology, University of
Bari, Bari, Italy. tommasomicelliferrari@tin.it

PURPOSE: The authors studied the efficacy of intravitreal triamcinolone acetonide
in a case series of patients with diffuse diabetic macular edema without evidence
of vitreous-macular traction refractory to laser photocoagulation. METHODS: Six
eyes with clinically diffuse diabetic macular edema that failed to respond to at 
least two previous sessions of laser photocoagulation were included. The mean age
of selected patients was 72.5+/-13.8 years, with a preoperative best-corrected
visual acuity reduced to 1.48+/-0.18 logMar and a mean baseline intraocular
pressure (IOP) of 15.17+/-2.64 mmHg. The authors also studied macular thickness
measured by optical coherence tomography (OCT 2000 scanner, Humphrey Instruments,
San Leandro, CA) - in the preoperative period it was 640.8+/-171.1 microm - and
the fluorangiographic (Heidelberg Retina Angiograph, Heidelberg Engineering GmbH,
Heidelberg, Germany) patterns, which showed pooling in tardy phases and leakage. 
Mean follow-up was 4 months. RESULTS: In each patient the authors observed a
significant improvement, both functionally and anatomically. Mean best-corrected 
visual acuity increased in the postoperative period to 0.94+/-0.53 logMar. No
patient showed decline of visual acuity at the end of follow-up. Base line
macular thickness was reduced in the postoperative period to 312.2+/-157.65
microm measured by OCT and fluorangiographic patterns showed a reduction of
pooling and of leakage. The most common complications described in the literature
were not observed and the increase of mean IOP in the postoperative period to
18.76+/-5.72 mmHg was not significant. CONCLUSIONS: Intravitreal triamcinolone
acetonide may decrease macular edema and improve visual acuity in eyes with
diffuse diabetic macular edema.

PMID: 15309977 [PubMed - indexed for MEDLINE]

2225: Graefes Arch Clin Exp Ophthalmol. 2004 Aug;242(8):710-6. Epub 2004 Aug 10.

Keypathophysiologic pathways in age-related macular disease.

Roth F, Bindewald A, Holz FG.

Department of Ophthalmology, University of Bonn, Ernst-Abbestrasse 2, 53127 Bonn,
Germany.

PURPOSE: To review current knowledge of key pathogenetic pathways in age-related 
macular disease (AMD). METHODS: Experimental evidence and clinical observations
are reviewed. RESULTS: A number of common downstream pathophysiologic pathways
appear to be relevant in AMD manifestations irrespective of primary heterogeneous
etiologies. These include sequelae of oxidative damage, retinal pigment
epithelium (RPE) cell dysfunction with accumulation of lipofuscin and impairment 
of lysosomal functions, deposition of subsequently incompletely degraded material
at the basal RPE cell side and alterations in Bruch's membrane extracellular
matrix, immunologic responses to extracellular material (drusen) with subsequent 
growth of drusen, induction of choroidal neovascularization as a result of
imbalance between anti-angiogenetic and proangiogenetic factors as well as cell
death (geographic atrophy) without prior neovascular events. CONCLUSIONS:
Understanding is expanding regarding the sequence of events that lead to early
and late lesions in AMD. Therapeutic approaches that focus on the molecular
mechanisms are more likely to succeed than currently available treatment options 
as exemplified by the management of choroidal neovascularisations.

Publication Types: 
    Review

PMID: 15309554 [PubMed - indexed for MEDLINE]

2226: Eye. 2005 Apr;19(4):382-6.

Comment in:
    Eye. 2006 Jul;20(7):861-2; author reply 862-3.

Intravitreal triamcinolone as a primary therapy in diabetic macular oedema.

Karacorlu M, Ozdemir H, Karacorlu S, Alacali N, Mudun B, Burumcek E.

Istanbul Retina Institute, Hakki Yeten Cad., No: 8, Kat: 7, 34349 Fulya Istanbul,
Turkey. retina@pobox.com

PURPOSE: To evaluate the effect of intravitreal triamcinolone in eyes with
diabetic macular oedema that had no previous laser treatment. METHODS: In all, 12
eyes of 12 patients with diabetic retinopathy, aged 47-70 years (mean 59.2), made
up the study. All the eyes had persistent diabetic macular oedema despite having 
received medical treatment for at least 3 months. In this consecutive case
series, none of the eyes received previous laser photocoagulation. Intravitreal
injection of 0.1 ml (4 mg) triamcinolone acetonide was offered to treat macular
oedema. The visual and anatomic responses were observed as well as complications 
related to the injection procedure and corticosteroid medication. RESULTS: The
follow-up period was between 6 and 10 months (mean 7.9 months) and all eyes
completed 6 months of follow-up. Macular oedema was documented for an average of 
3.5 months (ranged 3-5 months) before intravitreal corticosteroid injection.
Baseline mean central macular thickness was 448.6 microm. At 1 month follow-up, a
reduction in mean central macular thickness of 40.8% from 448.6 microm to 265.4
microm was obtained. At 3 and 6 months follow-up, mean central macular
thicknesses, were 310 mum and 294.5 mum, respectively. No eyes lost vision at 1
month and 10 eyes (83.2%) showed improvement. At 3 months, no eyes lost vision
from baseline and 8 eyes (66.6%) showed improvement. At 6 months, again no eyes
lost vision from baseline and 10 eyes (83.2%) maintained improved visual acuity. 
CONCLUSIONS: Intravitreal triamcinolone is a promising therapeutic method in eyes
with diabetic macular oedema without previous application of laser treatment.
Further study with longer follow-up and large series is warranted to assess the
long-term efficacy and safety and the need for retreatment.

Publication Types: 
    Clinical Trial

PMID: 15309024 [PubMed - indexed for MEDLINE]

2227: Ophthalmic Surg Lasers Imaging. 2004 Jul-Aug;35(4):292-7.

A new surgical approach for indocyanine green-assisted internal limiting membrane
peeling.

Avci R, Avci B, Kaderli B, Cavusoglu I.

Department of Ophthalmology, Uludag University Hospital, Bursa, Turkey.

BACKGROUND AND OBJECTIVE: The efficiency of indocyanine green (ICG) dye in the
removal of the internal limiting membrane (ILM) with a fluid needle using passive
aspiration was evaluated. PATIENTS AND METHODS: Eighteen consecutive patients
with diffuse diabetic macular edema were studied. After vitrectomy and total
fluid-air exchange, 0.1 mL of ICG solution 0.25% was left in the macular area for
1 minute. Then the macular ILM was peeled with a specially designed tapered fluid
needle using passive aspiration. RESULTS: In 16 of the 18 eyes, the peeling
procedure could be easily performed with a tapered fluid needle using passive
aspiration. In 11 eyes, partial development of spontaneous ILM detachment prior
to the peeling process was also observed. CONCLUSIONS: ICG solution 0.25% appears
to reduce the adhesive force of the ILM to the sensory retina, which makes the
removal of the ILM much easier by passive aspiration with a fluid needle.

PMID: 15305552 [PubMed - indexed for MEDLINE]

2228: Ophthalmic Surg Lasers Imaging. 2004 Jul-Aug;35(4):270-80.

Effective treatment of diffuse diabetic macular edema by temporal grid pattern
photocoagulation.

Shimura M, Yasuda K, Nakazawa T, Ota S, Tamai M.

Department of Ophthalmology, Tohoku University Graduate School of Medicine,
Sendai, Miyagi, Japan.

BACKGROUND AND OBJECTIVE: To determine the effectiveness of laser grid pattern
photocoagulation to the macula but not the papillomacular bundle for the
treatment of diffuse diabetic macular edema. PATIENTS AND METHODS: Thirty-five
eyes of 23 patients with diffuse diabetic macular edema underwent laser grid
photocoagulation excluding the papillomacular bundle area. Best-corrected visual 
acuity by Snellen chart, foveal thickness using a retinal mapping program by
optical coherence tomography (OCT), and mean deviation sensitivity by Humphrey
automated central perimetry were investigated before and 1, 3, and 6 months after
the treatment. RESULTS: Six months after treatment, the visual acuity was
improved by 2 or more lines in 16 eyes (43%) and the foveal thickness decreased
in 32 eyes (91%). The mean deviation worsened in 34 eyes (97%). There was a
significant correlation between the improvement of visual acuity and the initial 
mean deviation, suggesting that a better visual acuity would be expected with a
preoperative mean deviation of approximately -20 dB. CONCLUSION: Grid pattern
photocoagulation without treatment to the papillomacular bundle area was
effective in treating diffuse diabetic macular edema, especially in eyes with an 
initial mean deviation showing moderate dysfunction.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 15305550 [PubMed - indexed for MEDLINE]

2229: Arch Ophthalmol. 2004 Aug;122(8):1137-40.

Intravitreal triamcinolone for the management of macular edema due to nonischemic
central retinal vein occlusion.

Bashshur ZF, Ma'luf RN, Allam S, Jurdi FA, Haddad RS, Noureddin BN.

Department of Ophthalmology, American University of Beirut - Medical Center,
Lebanon. zb00@aub.edu.lb

OBJECTIVE: To evaluate the efficacy of intravitreal triamcinolone acetonide in
the management of persistent macular edema secondary to nonischemic central
retinal vein occlusion (CRVO). METHODS: Twenty consecutive patients were selected
with a 3- to 4-month history of nonischemic CRVO and persistent macular edema.
These patients received a single intravitreal injection of 4 mg of triamcinolone 
acetonide (40 mg/mL). The follow-up period ranged from 10 to 12 months. The
amount of macular edema was assessed by the amount of retinal thickening on
clinical examination using the Goldmann contact lens and by the area and
intensity of staining on fluorescein angiography. Treated patients were compared 
with a retrospectively matched group of patients who were managed with
observation only. MAIN OUTCOME MEASURES: Changes in visual acuity and amount of
macular edema were assessed in the treated patients and compared with the
observation group. RESULTS: The mean baseline visual acuity in the treatment
group was 20/132 vs 20/123 for the observation group (P =.57). After 1 week, the 
treated group had a mean visual acuity of 20/51. At final follow-up, the treated 
group had a mean visual acuity of 20/37 while the observation group had a mean
visual acuity of 20/110 (P =.001). Sixty percent of treated patients had a final 
visual acuity of 20/40 or better vs only 20% in the observation group (P =.01).
Forty percent of the untreated patients had a final visual acuity worse than
20/200 while none of the treated patients did (P<.001). At final follow-up, 75%
of treated patients had complete resolution of macular edema on clinical
examination vs only 20% of the untreated patients (P<.001). Two of the treated
patients had recurrence of macular edema at 6 months, and 3 had elevated
intraocular pressure. CONCLUSION: This study shows a treatment benefit from
intravitreal triamcinolone in terms of visual acuity and macular edema for
nonischemic CRVO.

Publication Types: 
    Comparative Study

PMID: 15302653 [PubMed - indexed for MEDLINE]

2230: Arch Ophthalmol. 2004 Aug;122(8):1131-6.

Intravitreal triamcinolone for the treatment of macular edema associated with
central retinal vein occlusion.

Ip MS, Gottlieb JL, Kahana A, Scott IU, Altaweel MM, Blodi BA, Gangnon RE,
Puliafito CA.

Department of Ophthalmology and Visual Science, University of Wisconsin, Madison 
53711-1068, USA. msip@wisc.edu

OBJECTIVE: To investigate the safety and efficacy of intravitreal triamcinolone
acetonide as treatment for macular edema associated with central retinal vein
occlusion (CRVO). METHODS: We reviewed the medical records of 13 consecutive
patients (13 eyes) with macular edema associated with CRVO who were treated with 
an injection of intravitreal triamcinolone acetonide (4 mg) at the University of 
Wisconsin and the Bascom Palmer Eye Institute. Each intravitreal injection was
delivered through the pars plana using a 27- or 30-gauge needle. MAIN OUTCOME
MEASURES: Change in Snellen visual acuity, clinical appearance of macular edema, 
measurement of foveal thickening with optical coherence tomography (OCT), and
frequency of complications. RESULTS: The median age of the 13 patients was 67
years (interquartile range, 57-77 years), and the median duration of symptoms
before injection was 8 months (interquartile range, 4-9 months). Mean baseline
visual acuity was 20/500 in the affected eye. Mean visual acuity at the 6-month
follow-up examination was 20/180 in the affected eye. All 13 patients completed
the 6-month examination. Eyes with nonischemic CRVO (n = 5) demonstrated a
significant improvement in visual acuity, whereas eyes with ischemic CRVO (n = 8)
demonstrated a nonsignificant visual acuity improvement. No patient had a
decrease in visual acuity. Mean baseline foveal thickness as measured by OCT was 
590 micro m (retinal thickening = 416 micro m). Mean foveal thickness as measured
by OCT at the 1-month follow-up examination in 12 patients was 212 micro m
(retinal thickening = 38 micro m). At the 3-month follow-up examination, mean
foveal thickness as measured by OCT for 13 patients was 193 micro m (retinal
thickening = 19 micro m). Between the 3- and 6-month follow-up examinations, 4
patients developed a recurrence of macular edema. Three of the 4 patients were
retreated with a second injection of triamcinolone. Two of these 3 patients
experienced an improvement in visual acuity following retreatment. At the 6-month
follow-up examination, mean foveal thickness as measured by OCT for 13 patients
was 281 micro m (retinal thickening = 107 micro m). No adverse effects such as
retinal detachment or endophthalmitis occurred. One patient experienced an
increase in intraocular pressure that was controlled with 2 aqueous suppressants.
CONCLUSIONS: Intravitreal injection of triamcinolone appears to be a possibly
effective treatment in some patients with macular edema associated with CRVO.
Patients with nonischemic CRVO may respond more favorably than patients with
ischemic CRVO, and retreatment may be necessary in some patients. In this case
series, severe complications were not noted.

PMID: 15302652 [PubMed - indexed for MEDLINE]

2231: Prog Retin Eye Res. 2004 Sep;23(5):523-31.

Do blue light filters confer protection against age-related macular degeneration?

Margrain TH, Boulton M, Marshall J, Sliney DH.

School of Optometry and Vision Sciences, Cardiff University, Redwood Building,
King Edward VII Avenue, Cardiff CF10 3NB, UK. margrainth@cardiff.ac.uk

Age-related macular degeneration (AMD) is a major health problem in the developed
world accounting for approximately half of all blind registrations. Current
treatment options are unsuitable for the majority of patients and therefore the
identification of modifiable risk factors that may inform disease prevention
programmes is a priority. This review evaluates the long-held belief that blue
light exposure has a role in the pathogenesis of AMD. Laboratory evidence has
demonstrated that photochemical reactions in the oxygen-rich environment of the
outer retina lead to the liberation of cytotoxic reactive oxygen species (ROS).
These ROS cause oxidative stress which is known to contribute to the development 
of AMD. The precise chromopore that may be involved in the pathogenesis of AMD is
unclear but the age pigment lipofuscin is a likely candidate. Its aerobic
photoreactivity and adverse effects on antioxidant activity combined with its
gradual accumulation over time suggests that its in vivo phototoxicity increases 
with age despite changes in the absorption characteristics of the crystalline
lens. Evidence from animal studies confirms blue light's damaging potential but
the results are not directly applicable to macular degeneration in humans.
Studies of human macular pigment density and the risk of AMD progression
following cataract surgery lend further weight to the hypothesis that blue light 
exposure has a role in the pathogenesis of AMD but the epidemiological evidence
is equivocal. On balance the evidences suggests but does not yet confirm that
blue light is a risk factor for AMD. Given the socio-economic impact of this
disease and urgent need to identify modifiable risk factors, future work should
include a large-scale clinical trial to evaluate the effect of blue blocking
filters on AMD progression rates. Copyright 2004 Elsevier Ltd.

Publication Types: 
    Review

PMID: 15302349 [PubMed - indexed for MEDLINE]

2232: Prog Retin Eye Res. 2004 Sep;23(5):495-522.

Defective cone photoreceptor cytoskeleton, alignment, feedback, and energetics
can lead to energy depletion in macular degeneration.

Eckmiller MS.

C and O Vogt Institute for Brain Research, University Clinic, Heinrich Heine
University of Düsseldorf Medical School, Postfach 101007, Düsseldorf 40001,
Germany. eckmill@hirn.uni-duesseldorf.de

Macular degeneration (MD) is a puzzling disease characterized by disturbance, and
then complete loss, of fine detailed vision in the central macular region of the 
human retina, as a result of disturbed function and then death of photoreceptor
cells. This review describes a possible pathomechanism for MD that involves a
causal relationship between mutated genes, altered photoreceptor cytoskeletal
proteins, defective cone photoreceptor alignment, and disturbed visual feedback
mechanisms that leads to energy depletion and apoptosis of macular cone
photoreceptors. MD may be associated with mutations in genes encoding certain
photoreceptor proteins (ATP-binding cassette transporter retina, retinitis
pigmentosa GTPase regulator, retinal degeneration slow/peripherin) that are
components of, or interact with, microtubule-containing cytoskeletal systems at
the connecting cilium of rods and cones and at the multiple incisures of rod
outer segments (OSs). Vertebrate photoreceptors are directionally sensitive: the 
longitudinal axis of each cell is actively aligned towards the entrance pupil of 
the eye, and the cells are most sensitive to light travelling along this axis (as
in the Stiles-Crawford effect). The mechanisms responsible for photoreceptor
alignment involve movements made by photoreceptors in response to the direction
of incident light, using their cytoskeletons. A model is proposed for
photoreceptor alignment whereby light absorption in the OS causes fast membrane
and slower cytoplasmic changes that spread from the OS to the inner segment
myoid, where they activate feedback-controlled motor functions by cytoskeletal
elements (microtubules and microfilaments) to produce a differential local
bending that adjusts photoreceptor orientation. The fovea at the center of the
human macula has specialized features that enable it to provide uniquely high
visual acuity, if its cones are accurately aligned. Accordingly, it is proposed
that some gene defects in MD cause disturbances at photoreceptor connecting cilia
that lead to gradual defects in photoreceptor alignment; misalignment of central 
macular cones will be initially perceived as blurring, distortions, and decreased
acuity of central vision. Although photoreceptors throughout the retina use their
cytoskeletons for alignment, the accurate alignment of foveal cones is
particularly important because their signals contain fine resolution information 
that is used in visual feedback systems, e.g., for adjusting accommodation and
eye movements. Vision involves multiple feedback loops that are interdependent,
e.g., the accuracy of alignment of foveal cones influences how effectively
changes in accommodation bring images into focus, and the state of accommodation 
in turn influences how light entering the eye is projected onto foveal cones. It 
is proposed that in MD gene defects that disturb the cytoskeleton and alignment
of photoreceptors lead to a disturbance in the normal signalling within these
feedback systems, causing the mechanisms controlling the alignment of cones in
the center of the macula to become progressively more disturbed and the cells to 
unnecessarily expend energy. These disturbances can lead to local energy
depletion within the metabolically fragile central macular cones that trigger
them to die, producing central areas of blindness. If this line of reasoning is
correct, it may be possible to treat the local energy depletion within macular
cones in MD by energy supplementation. Copyright 2004 Elsevier Ltd.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 15302348 [PubMed - indexed for MEDLINE]

2233: Graefes Arch Clin Exp Ophthalmol. 2004 Aug;242(8):638-47. Epub 2004 Aug 6.

Translocation of iris pigment epithelium in patients with exudative age-related
macular degeneration: long-term results.

Lappas A, Foerster AM, Weinberger AW, Coburger S, Schrage NF, Kirchhof B.

Department of Ophthalmology, University of Aachen, Pauwelsstrasse 30, 52057
Aachen, Germany. alappas2000@yahoo.com

PURPOSE: To report the practicability and efficacy of autologous iris pigment
epithelium (IPE) translocation in exudative age-related macular degeneration
(ARMD) over 1 year. METHODS: The consecutive interventional case series included 
56 patients with exudative ARMD. During vitrectomy the submacular neovascular
membrane (CNV) was removed and IPE cells, harvested from a peripheral iridectomy,
were injected into the submacular space. Included were patients with subfoveal
occult CNV (11 eyes), classic CNV (10 eyes), mixed CNV (17 eyes), CNV with a
pigment epithelial detachment (13 eyes) or CNV with a hemorrhage (5 eyes).
Outcome measures were visual acuity, foveal fixation, size of CNV and rate of
recurrence based on fluorescence angiographic imaging. RESULTS: All patients
underwent successful surgical removal of the CNV with consecutive subretinal IPE 
injection. Visual acuity was better than 20/100 in 19 patients preoperatively and
in 18 patients postoperatively. A visual acuity of 20/100 or less was found in 37
patients preoperatively and in 38 patients postoperatively. Mean preoperative
visual acuity (1.0+/-0.3 logMAR units) did not change significantly after 1 year 
(1.0+/-0.3 logMAR units). Ten eyes (18%) developed a recurrence. Fixation within 
the surgically denuded area could be demonstrated in 25 eyes (45%). CONCLUSIONS: 
Autologous IPE translocation for ARMD over one year can preserve foveal function 
on a low level, but cannot improve visual acuity. IPE translocation is
technically feasible with a low rate of complications. Continued research seems
justified to improve functional outcome.

Publication Types: 
    Clinical Trial

PMID: 15300442 [PubMed - indexed for MEDLINE]

2234: Optom Vis Sci. 2004 Aug;81(8):578-85.

Choroiditis, pigment epithelial detachment, and cystoid macular edema as
complications of poststreptococcal syndrome.

Besada E, Frauens BJ, Schatz S.

NOVA Southeastern University, College of Optometry, 1750 NE 167th Street, North
Miami Beach, FL 33162, USA. ebesada@hpd.nova.edu

PURPOSE: Two cases of poststreptococcal uveitis are presented. One patient
developed nongranulomatous anterior uveitis (case 1). A second patient developed 
nongranulomatous anterior uveitis followed by granulomatous uveitis with
concurrent choroiditis, retinal pigment epithelial detachment, and cystoid
macular edema (case 2). Current concepts regarding the pathogenesis of
poststreptococcal syndrome and its ocular sequelae are also discussed. CASE
REPORTS: Case 1: A 31-year-old female patient presented with bilateral
nongranulomatous uveitis after a recent onset of sore throat. A past diagnosis of
rheumatic fever was revealed during acquisition of the patient's history. Blood
chemistry analysis indicated elevated anti-streptolysin O antibody titers as the 
only significant elevated result. Case 2: A 33-year-old female presented
initially with bilateral nongranulomatous uveitis. A history of recurrent sore
throat was reported. Blood chemistry analysis revealed elevated anti-streptolysin
O antibody titers only. "Mutton fat" keratic precipitates eventually developed;
however, the bilateral uveitis resolved after topical cycloplegic and
corticosteroid treatment. An anterior granulomatous uveitis with concurrent
choroiditis, retinal pigment epithelial detachment, and cystoid macular edema
ensued during a recurrent episode. Blood chemistry analysis was unremarkable at
that time. CONCLUSIONS.: Anterior nongranulomatous/granulomatous and posterior
uveitis should be considered clinical manifestations of poststreptococcal
syndrome in patients with a clinical history and/or serological evidence
indicating possible past streptococcal infection. A variation of
host-genetic-predisposed immune response, the patient's human leukocyte antigen
haplotype, pathogen virulence, and/or deposition location of immune circulating
complexes may give rise to the diverse spectrum of clinical ocular sequelae in
poststreptococcal syndrome. Poststreptococcal uveitis may comprise a similar
immunologic pathogenesis to that of acute rheumatic fever, acute
glomerulonephritis, and other autoimmune diseases.

Publication Types: 
    Case Reports

PMID: 15300115 [PubMed - indexed for MEDLINE]

2235: Retina. 2004 Aug;24(4):548-55.

Foveal sensitivity and fixation stability before and after macular translocation 
with 360-degree retinotomy.

Oyagi T, Fujikado T, Hosohata J, Ohji M, Kamei M, Bessho K, Tano Y.

Department of Ophthalmology, Osaka Rosai Hospital, Osaka University Medical
School, Japan. toyagi@orh.go.jp

PURPOSE: To evaluate the functional changes of the fovea by scanning laser
ophthalmoscopy (SLO) fundus perimetry after macular translocation with 360-degree
retinotomy, and to determine whether the preoperative macular function estimated 
by the sensitivity of the fovea and the stability of fixation can predict visual 
acuity after the surgery. METHODS: Macular translocation with 360-degree
retinotomy and simultaneous torsional muscle surgery were performed on 25 eyes of
25 patients with choroidal neovascularization. The index of foveal sensitivity
(Isens) and the index of fixation stability (Ifix) before and after surgery were 
calculated from the microperimetric data. The preoperative Isens and Ifix were
compared with postoperative Isens and Ifix, respectively. The correlations of
preoperative Isens and Ifix with the visual acuity after the translocation
surgery (VApost) were calculated. RESULTS: Isens increased in 14 (56%) of 25
eyes. Ifix improved in 10 (40%) of 25 eyes. The preoperative Isens and VApost
were moderately correlated (r = 0.434, P = 0.0295), while the preoperative Ifix
and VApost were highly correlated (r = - 0.530, P = 0.0057). CONCLUSION: An
increase in foveal sensitivity and an improvement in the fixation stability were 
demonstrated quantitatively by microperimetry. The preoperative foveal
sensitivity and fixation stability were correlated with the postoperative visual 
acuity. Microperimetry using SLO can be used to investigate foveal function
before and after the translocation and to predict the postoperative visual
acuity.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 15300075 [PubMed - indexed for MEDLINE]

2236: Retina. 2004 Aug;24(4):530-40.

Management of macular edema in branch retinal vein occlusion with sheathotomy and
recombinant tissue plasminogen activator.

García-Arumí J, Martinez-Castillo V, Boixadera A, Blasco H, Corcostegui B.

Hospital Vall d'Hebrón, Universidad Autónoma de Barcelona, Spain.
17215jga@comb.es

PURPOSE: The common adventitial sheath that surrounds the retinal venule and
arteriole at the crossing site plays a crucial role in branch retinal vein
occlusion (BRVO). The purpose of this study was to report the surgical
recanalization of the occluded vein using a bimanual technique and recombinant
tissue plasminogen activator (tPA) and its effect on final visual acuity.
METHODS: Arteriovenous sheathotomy was performed, using a bimanual technique,
followed by fluid-air exchange and injection of 25 mg of recombinant tPA over the
area of the occluded vein. RESULTS: Intraoperative sectioning of the common
arteriovenous sheath was achieved in all 40 patients. Thrombus release was
observed in 11 cases (27.5%) and was correlated with early surgery (P < 0.001)
and better final visual recovery (P < 0.06). Optical coherence tomography showed 
macular thickness that decreased by greater than 40% in 31 patients (77.5%)
compared with preoperatively, and correlated to postoperative visual acuity (P < 
0.001). The mean visual acuity increased from 20/100 to 20/40, with 70% of
patients gaining three or more lines of visual acuity (Pearson 0.378, P = 0.016).
CONCLUSION: Surgical venous decompression and injection of recombinant tPA may
effectively manage macular edema secondary to BRVO, thus improving anatomic and
visual outcome. Early surgical intervention may obtain maximum final visual
recovery.

PMID: 15300073 [PubMed - indexed for MEDLINE]

2237: Retina. 2004 Aug;24(4):512-20.

Erratum in:
    Retina. 2004 Dec;24(6):990.

Verteporfin therapy in age-related macular degeneration (VAM): an open-label
multicenter photodynamic therapy study of 4,435 patients.

Bessler NM; Vam Study Writing Committee.

Baltimore, MD 21205, USA. nmboffice@jhmi.edu

PURPOSE: To provide broad clinical experience and to gather safety data on
photodynamic therapy with verteporfin (Visudyne, Novartis AG, Basel,
Switzerland), also termed verteporfin therapy, in patients with predominantly
classic subfoveal choroidal neovascularization (CNV) secondary to age-related
macular degeneration (AMD). The Verteporfin in Age-related Macular Degeneration
(VAM) Study was designed to provide expanded access to verteporfin therapy after 
beneficial results for these cases were reported but before regulatory approval
in North America. METHODS: This open-label multicenter study from September 1999 
through June 2000 enrolled among 222 centers patients 50 years or older in the
United States, or 40 years or older in Canada, with age-related macular
degeneration and subfoveal CNV with a lesion composition that was predominantly
classic CNV on fluorescein angiography. Corrected visual acuity with habitual
eyewear in the office setting was 20/40 to 20/200, inclusive. All patients
received verteporfin therapy and returned for follow-up every 3 months. At those 
follow-up examinations, additional courses of treatment were recommended if any
fluorescein leakage from CNV was identified. Safety information was collected
from patient self-reporting, questioning (in person and by telephone), and
physician evaluation. Safety was assessed by evaluating the effect of treatment
on corrected distance visual acuity and by evaluating adverse events. RESULTS: A 
total of 4,435 patients were enrolled of whom 4,051 (91%) completed the study
after receiving 6,701 treatments. Most patients received only one treatment in
VAM before regulatory approval of verteporfin in the United States and Canada.
Three hundred patients (6.8%) experienced an adverse event considered by the
treating ophthalmologist to be associated with treatment, including 115 (2.6%)
with abnormal or decreased vision, of whom 25 (0.6%) experienced acute severe
visual acuity decrease, and 14 (0.3%) with transient infusion-related back pain. 
Patients were advised to avoid exposure to direct sunlight for 24 hours; however,
after verteporfin administration only 2 (0.05%) reported a photosensitivity
reaction. An additional course of verteporfin therapy was administered to 1,739
of 2,314 patients (75.2%) who had a month 3 examination that was not their
close-out visit and 177 of 266 (66.5%) who had a month 6 examination that was not
their close-out visit. CONCLUSIONS: Verteporfin therapy exhibited no additional
or new safety concerns. The therapy associated with a low incidence of adverse
events when expanded access was provided in a large, open-label, multicenter
study, including a low incidence (0.05%) of reported photosensitivity reactions
despite a short photosensitivity protection period (24 hours) following
verteporfin administration.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 15300071 [PubMed - indexed for MEDLINE]

2238: Graefes Arch Clin Exp Ophthalmol. 2005 Jan;243(1):9-12. Epub 2004 Jul 28.

Safety of posterior juxtascleral depot administration of the angiostatic
cortisene anecortave acetate for treatment of subfoveal choroidal
neovascularization in patients with age-related macular degeneration.

Augustin AJ, D'Amico DJ, Mieler WF, Schneebaum C, Beasley C.

Eye Clinic, Städtisches Klinikum Karlsruhe, Moltkestrasse 90, 76133 Karlsruhe,
Germany. 106020.560@compuserve.com

BACKGROUND: Anecortave acetate is a synthetic derivative of cortisol, but very
specific and irreversible chemical modifications to the cortisol structure have
resulted in the creation of a potent inhibitor of blood vessel growth with no
evidence non-clinically or clinically of glucocorticoid receptor-mediated
bioactivity. The clinical safety of Anecortave Acetate administered as a
posterior juxtascleral depot every 6 months for up to 4 years is reviewed in this
manuscript. METHODS: Clinical safety and efficacy of the novel angiostatic agent 
Anecortave Acetate for Depot Suspension was evaluated in patients with subfoveal 
exudative age-related macular degeneration (AMD) in a masked, randomized,
dose-duration clinical trial completed in June 2003. This safety and efficacy
study enrolled and treated 128 patients at 18 clinical sites in the US and EU.
This was the first clinical trial of Anecortave Acetate for Depot Suspension
administered as a posterior juxtascleral depot. Assessments of clinical safety
were made with general physical examinations including electrocardiograms and
hematology/serum chemistry/urinalysis, detailed ophthalmic evaluations with
fluorescein/indocyanine green angiography and assessments of best-corrected
logMAR visual acuity. All safety reports have been reviewed periodically by an
Independent Safety Committee responsible for overseeing these activities.
RESULTS: No clinically relevant safety issues related to either Anecortave
Acetate for Depot Suspension or the administration procedure have been identified
by an Independent Safety Committee. The most frequent safety issues reported were
cataractous changes, decreased visual acuity, ptosis, ocular pain, abnormal
vision and subconjunctival hemorrhage, but the majority of these were assessed as
unrelated to treatment. CONCLUSIONS: Anecortave Acetate for Depot Suspension (3, 
15 and 30 mg) is clinically safe following administration and re-administration
at 6-month intervals as a posterior juxtascleral depot using a specially designed
curved cannula.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial

PMID: 15290154 [PubMed - indexed for MEDLINE]

2239: Graefes Arch Clin Exp Ophthalmol. 2005 Jan;243(1):20-5. Epub 2004 Jul 31.

Pars plana vitrectomy with internal limiting membranectomy for refractory
diabetic macular edema without a taut posterior hyaloid.

Rosenblatt BJ, Shah GK, Sharma S, Bakal J.

Department of Ophthalmology and Visual Sciences, Washington School of Medicine,
St Louis, MO 63114, USA.

BACKGROUND: This is a retrospective study designed to investigate the effect of
pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling on
diabetic macular edema in eyes that do not have a taut hyaloid and have been
refractory to standard laser treatment. METHODS: Review of 26 eyes of 20 patients
consecutively were treated with PPV with ILM peel for refractory diabetic macular
edema. Eyes were included if they had been unresponsive to conventional treatment
defined as at least two focal laser applications by a retina specialist. Paired
t-testing was performed to determine if a change in both optical coherence
tomography (OCT)-measured retinal thickness and logarithm of the minimum angle of
resolution (logMAR) visual acuity occurred prior to and following PPV with
epiretinal membrane vitrectomy. In addition, we performed multivariate regression
analysis to determine if any clinical variables predicted a change in visual
acuity. RESULTS: The mean age in the sample was 65 years (range 29-81 years). The
mean follow-up time was 242 days (range 35-939). Sixteen of the 26 eyes were
phakic and the remaining ten were pseudophakic. There was a statistically
significant improvement of mean visual acuity from a preoperative logMAR vision
of 1.0 to a best postoperative vision of 0.75 (p=0.016, paired t-test). Thirteen 
(50%) of the 26 eyes gained at least two lines of best-corrected Snellen acuity, 
three (11.5%) had a decline of at least two lines, and ten (38.5%) showed stable 
visual acuity. Regression analysis demonstrated that baseline worse visual acuity
was the only clinical variable that was associated with improvement in visual
acuity (beta=0.602, p=0.016; R (2)=28.7). Fourteen eyes had preoperative and
postoperative OCT. Thirteen eyes (93%) had a significant decrease in foveal
thickness; with an average preoperative thickness of 575 mum compared to a
postoperative average of 311 mum (t=3.65, p=0.002). No surgical complications
were observed during the follow-up period. CONCLUSIONS: Surgery for refractory
diabetic edema without a taut hyaloid is associated with a significant
improvement in visual acuity and diminution of retinal thickness as measured by
OCT. Further investigations are warranted to define the role of surgery in the
management of persistent diabetic macular edema.

Publication Types: 
    Case Reports

PMID: 15290152 [PubMed - indexed for MEDLINE]

2240: Am J Ophthalmol. 2004 Aug;138(2):289-91.

Intravitreal triamcinolone acetonide for the treatment of cystoid macular edema
secondary to Behçet disease.

Karacorlu M, Mudun B, Ozdemir H, Karacorlu SA, Burumcek E.

Istanbul Retina Institute, Istanbul, Turkey. retina@pobox.com

PURPOSE: To evaluate the safety and effectiveness of intravitreal triamcinolone
acetonide in patients with cystoid macular edema (CME) associated with Behçet
disease. DESIGN: Interventional case series. METHODS: Ten eyes of 10 patients
with CME from Behçet disease made up the study population. All eyes had
persistent CME despite medical treatment for at least 2 months. Intravitreal
injection of 4 mg (0.1 ml) of triamcinolone acetonide was offered to treat
macular edema. The visual and anatomic responses were observed. RESULTS: At
1-month follow-up, a reduction in mean foveal thickness of 37.4%, from 416 microm
to 260.5 microm, was attained. At 3-month follow-up, mean foveal thickness was
286.2 microm and at 6 months, 263.7 microm. No eyes had lost vision at 1 month,
and eight eyes (80%) showed improvement in visual acuity. At 3-month and 6-month 
follow-up, three eyes (30%) remained stable and the other eyes had maintained the
improved acuity. CONCLUSION: Intravitreal triamcinolone acetonide is a promising 
therapeutic method for CME from Behçet disease.

PMID: 15289142 [PubMed - indexed for MEDLINE]

2241: Am J Ophthalmol. 2004 Aug;138(2):245-53.

Predictors of structural findings in old disciform lesions.

Riusala AM, Immonen IJ.

Department of Ophthalmology, Helsinki University Hospital Helsinki, Finland.
aila.riusala@hus.fi

PURPOSE: To analyze the baseline findings predictive of the size and type of the 
late exudative age-related macular degeneration (AMD) lesions. DESIGN:
Observational case series. METHODS: Retrospective study. SETTING: University
clinic referral practice. STUDY POPULATION: The records of 167 consecutive
patients initially diagnosed with recent choroidal neovascularization (CNV)
related to AMD were analyzed 4.8 to 9.2 (mean 6.8) years after baseline. Of 121
patients still living, 74 attended the reexamination. After exclusions, data from
61 patients were analyzed. OBSERVATION PROCEDURES: From the fundus photographs
and fluorescein angiographic images taken at baseline and at follow-up the size
and components of AMD lesion were measured. The presence of hemorrhage, pigment
epithelial detachment (PED), classic CNV, laser treatment, and involvement of the
fellow eye were recorded at baseline. MAIN OUTCOME MEASURES: Lesion size,
increase in lesion size, persistent exudative process, subretinal fibrosis, and
chorioretinal anastomosis at the follow-up examination. RESULTS: Large lesion (P 
<.001) and CNV (P =.003) sizes, and the presence of occult, no classic CNV (P
=.013) at baseline predict a large lesion at follow-up. Other factors predicting 
a large lesion were subfoveal (P =.019) and bilateral lesions (P =.017) and the
presence of hemorrhage (P =.012) at baseline. A large (P =.040) and bilateral
lesion (P =.040) and hemorrhage (P =.011) at baseline were correlated with
subretinal fibrosis at follow-up. Occult lesions (P =.002) at baseline were
correlated with chorioretinal anastomosis at follow-up. CONCLUSION: The type and 
size of the late AMD lesion can partly be predicted from baseline
characteristics.

PMID: 15289134 [PubMed - indexed for MEDLINE]

2242: Ophthalmology. 2004 Aug;111(8):1595-8.

Retinotopic mapping of the visual cortex using functional magnetic resonance
imaging in a patient with central scotomas from atrophic macular degeneration.

Sunness JS, Liu T, Yantis S.

Lions Vision Center of the Wilmer Ophthalmologic Institute, Johns Hopkins
University School of Medicine, Baltimore, Maryland 21205, USA. jsunness@jhmi.edu

PURPOSE: To describe retinotopic mapping of the visual cortex when a central
scotoma is present. DESIGN: Single observational case report. METHODS: Scanning
laser ophthalmoscope perimetry was used to define the site and stability of
fixation and the area of dense scotoma. Functional magnetic resonance imaging of 
the visual cortex was performed while the patient viewed an expanding annular
stimulus. RESULTS: Retinotopic mapping of the visual cortex for a patient with a 
horseshoe scotoma from geographic atrophy involving the macular region showed a
loss of stimulation to the cortical areas representing the site of the atrophic
lesion. CONCLUSIONS: Cortical retinotopic mapping can be performed successfully
in patients with central scotomas from macular disease. This study can serve as a
basis for the future investigation of cortical plasticity in visual cortex.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15288993 [PubMed - indexed for MEDLINE]

2243: Qual Life Res. 2004 Aug;13(6):1163-75.

Design of an individualised measure of the impact of macular disease on quality
of life (the MacDQoL).

Mitchell J, Bradley C.

Department of Psychology, Royal Holloway, University of London, Surrey, UK.
j.mitchell@rhul.ac.uk

The aim of this study was to design an individualised questionnaire to measure
the impact of macular disease (MD) on quality of life (QoL). Principles
underlying the Schedule for the Evaluation of Individual Quality of Life (SEIQoL)
interview method and the Audit of Diabetes-Dependent Quality of Life (ADDQoL)
diabetes-specific questionnaire influenced the Macular Disease-Dependent Quality 
of Life (MacDQoL) design. The MacDQoL specifies domains of QoL that were selected
using focus group methodology and refined following a postal pilot study of
members of the UK Macular Disease Society (MDS). Respondents rated the impact of 
MD on each domain and the importance of each domain to their QoL. Mean domain
scores from 69 respondents indicated that MD had a negative impact on all the
domains of QoL investigated in the measure. There was preliminary evidence of
good internal consistency reliability (Cronbach's alpha = 0.93, n = 37).
Respondents who were registered partially sighted (P/S) or blind reported poorer 
QoL than those who were not registered (Kruskal-Wallis: chi2 = 14.03, n = 62, p <
0.001). This evidence suggests that the measure will be sensitive to subgroup
differences. The instrument has been further refined following the pilot study.
The MacDQoL is being used in clinical trials and psychometric evaluation of the
measure will be carried out using trial data. The measure is available for
clinical use and has been linguistically validated in 15 other languages.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15287282 [PubMed - indexed for MEDLINE]

2244: Eye. 2005 Apr;19(4):431-41.

Cone- and rod-mediated multifocal electroretinogram in early age-related
maculopathy.

Feigl B, Brown B, Lovie-Kitchin J, Swann P.

Department of Ophthalmology, University of Graz, Austria. b.feigi@qut.edu.au

PURPOSE: To investigate the cone- and rod-mediated multifocal electroretinograms 
(mfERG) in early age-related maculopathy (early ARM). METHODS AND SUBJECTS: We
investigated the cone- and rod-mediated mfERG in 17 eyes of 17 subjects with
early ARM and 16 eyes of 16 age-matched control subjects with normal fundi. All
subjects had a visual acuity of 6/12 or better. We divided the ARM subjects into 
two groups based on drusen size and retinal pigment epithelium abnormalities-a
less advanced (ARM1) and a more advanced (ARM2) group. The mfERG data were
compared to templates derived from the control group. We analysed the mfERG
results for the central and peripheral fields (CP method) and the superior and
inferior fields (SI method). RESULTS: While the mean cone results showed no
statistically significant difference between the groups, the rods showed
significantly delayed responses in the ARM1 group for the CP and the SI methods, 
but not in the ARM2 group, although there was a trend of longer latencies
compared to the control group. CONCLUSION: Our results show a functional
impairment of the rods in early ARM subjects. As there is histopathological
evidence showing earlier rod than cone impairment in early ARM, following the rod
function with the mfERG might be helpful in diagnosis or for monitoring the
progression of early ARM.

PMID: 15286663 [PubMed - indexed for MEDLINE]

2245: Invest Ophthalmol Vis Sci. 2004 Aug;45(8):2463-74.

Structural and elemental evidence for edema in the retina, retinal pigment
epithelium, and choroid during recovery from experimentally induced myopia.

Liang H, Crewther SG, Crewther DP, Junghans BM.

School of Optometry, University of New South Wales, Sydney, New South Wales,
Australia.

PURPOSE: The purpose of this study was to monitor temporal changes in the retina,
retinal pigment epithelium (RPE), and choroid of chick eyes using biometric,
ultrastructural, and elemental microanalysis techniques as a means of visualizing
more detailed signs of the physiological processes underlying choroidal expansion
and refractive normalization during recovery from form deprivation. METHODS:
Axial dimensions and refractions were measured on form-deprived and fellow eyes
of 117 experimental chickens reared with monocular translucent occlusion from
days 1 to 15 and given different lengths of visual experience (T = 0-144 hours)
before death. Tissue was analyzed ultrastructurally by electron microscopy and
relative sodium (Na) and chloride (Cl) ion abundances, by using x-ray
microanalysis to determine changes in the presence of these indicators of tissue 
hydration. RESULTS: Refractive error decreased from more than 20 D of myopia
almost linearly over the first 144 hours after occlusion. Concurrent changes in
thickness in the retina, RPE, and choroid were seen as a series of thickness
increases and edema, which returned to normal thickness, first in the retina, and
did not reach maximum until 3 days after occluder removal in the choroid. In
freeze-dried tissue, Na and Cl ion concentrations were greatest in the RPE
photoreceptor outer segments and extravascular choroid at T = 0, decreasing
toward fellow eye levels by T = 48 in the RPE and choroid. Na and Cl ion
abundances in the frozen lymph of choroidal lymphatics were nearly at control
levels (T = 0) and increased later as the vessels became more distended after the
extravascular edema became significant. CONCLUSIONS: The results suggest that
occluder removal induces edema across the retina and choroid and that this fluid 
may be the vector eliciting choroidal expansion during recovery from form
deprivation possibly driven by the hyperosmolarity in the choroid, RPE, and
photoreceptor outer segments that accompanies deprivation.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15277465 [PubMed - indexed for MEDLINE]

2246: N Engl J Med. 2004 Jul 22;351(4):346-53.

Comment in:
    N Engl J Med. 2004 Jul 22;351(4):320-2.

Missense variations in the fibulin 5 gene and age-related macular degeneration.

Stone EM, Braun TA, Russell SR, Kuehn MH, Lotery AJ, Moore PA, Eastman CG,
Casavant TL, Sheffield VC.

Center for Macular Degeneration, University of Iowa, Carver College of Medicine, 
Iowa City 52242, USA. edwin-stone@uiowa.edu

BACKGROUND: Age-related macular degeneration (AMD) is the most common cause of
irreversible vision loss in the developed world. The study of a rare mendelian
form of macular degeneration implicated fibulin genes in the pathogenesis of more
common forms of this disease. We evaluated five fibulin genes in a large series
of patients with AMD. METHODS: We studied 402 patients with AMD and 429 control
subjects from the same clinic population. Patients were examined by means of
indirect ophthalmoscopy, slit-lamp microscopy, and fundus photography to
establish the presence and phenotypic pattern of AMD. DNA samples were screened
for sequence variations in five members of the fibulin gene family. RESULTS:
Amino acid-altering sequence variations were found in all five fibulin genes,
many of which were observed only in patients with AMD. Several of the altered
residues have been conserved during evolution. Seven of the 402 patients with AMD
had amino acid-altering sequence variations in the fibulin 5 gene, whereas none
were observed among 429 control subjects (P<0.01). In addition, these seven
patients all had small, circular drusen, which are commonly referred to as basal 
laminar or cuticular drusen. CONCLUSIONS: Missense mutations in the fibulin 5
gene were found in 1.7 percent of patients with AMD. Many variations in other
fibulin genes were also found in these patients, and the evolutionary
conservation of the affected residues suggests that several of these variations
may also be involved in AMD. Copyright 2004 Massachusetts Medical Society

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15269314 [PubMed - indexed for MEDLINE]

2247: Expert Opin Drug Saf. 2004 Jul;3(4):345-61.

Safety of verteporfin for treatment of subfoveal choroidal neovascular membranes 
associated with age-related macular degeneration.

Gaynes BI, Fiscella RG.

Rush University Medical Center, 1725 W. Harrison Street, Suite 909, Chicago, IL
60612, USA. Bgaynes@rush.edu

Photodynamic therapy (PDT) is a novel treatment entity that exploits the
photophysical properties of various photosensitive chemical entities which, upon 
light activation, results in targeted photooxidation and subsequent tissue
destruction. The antiangiogenic properties of PDT have been adapted for treatment
of subfoveal choroidal neovascular membranes due to disease states such as
age-related macular degeneration (AMD). Historically, PDT has been limited by a
lack of suitable photosensitive dyes. However, agents such as verteporfin, a
second-generation benzoporphyrin derivative, appear to be free from the extensive
phototoxicity that limited the success of previous agents. Verteporfin has a high
affinity for choroidal neovascular membranes, typically found with exudative AMD,
and upon photoactivation results in targeted microvascular damage and thrombus
formation with resultant vessel occlusion. Scrutiny of diagnostic indicators for 
verteporfin administration, including critical angiographic evaluation of lesion 
size and visual acuity, is essential to treatment success. Large lesions with
relatively good visual acuity (20/50 or better) may be at particular risk for
marked vision loss following verteporfin administration. Lesion composition also 
appears to influence visual outcome with verteporfin use. The safety of
verteporfin is directly dependent upon the appropriate integration of dosage,
infusion and light activation required for a suitable pharmacotherapeutic
outcome. When used appropriately, and with adequate patient education regarding
photosensitivity, the risk-benefit of verteporfin for the medical treatment of
neovascular AMD is favourable.

Publication Types: 
    Review

PMID: 15268651 [PubMed - indexed for MEDLINE]

2248: Diabetologia. 2004 Aug;47(8):1376-9. Epub 2004 Jul 17.

Elevated serum levels of N(epsilon)-carboxymethyl-lysine, an advanced glycation
end product, are associated with proliferative diabetic retinopathy and macular
oedema.

Boehm BO, Schilling S, Rosinger S, Lang GE, Lang GK, Kientsch-Engel R, Stahl P.

Division of Endocrinology and Diabetes, Department of Internal Medicine,
University of Ulm, Ulm, Germany. bernhard.boehm@medizin.uni-ulm.de

AIMS/HYPOTHESIS: Diabetic retinopathy is a frequent microvascular complication.
In search of novel risk markers, we analysed the association between serum levels
of the major advanced glycation end product N(epsilon)-carboxymethyl-lysine (CML)
and prevalence of advanced stages of retinopathy in Type 2 diabetic patients
without nephropathy. METHODS: We carried out a case-control study of Type 2
diabetic patients with and without advanced stages of diabetic retinopathy.
Retinopathy and macular oedema were defined according to standard criteria. Serum
levels of CML were estimated by means of a novel competition-based ELISA assay.
RESULTS: Serum levels of CML were significantly different between age-matched
controls (n=792; mean value +/- SD: 521+/-134 ng/ml), Type 2 diabetic patients
without severe retinopathy (821+/-141 ng/ml; p<0.0001) and Type 2 diabetic
patients with proliferative retinopathy (1182+/-346 ng/ml; p<0.0001). Levels of
CML greater than 1000 ng/ml represented a 25-fold increase in risk of
proliferative retinopathy. Receiver operating characteristics analysis revealed a
CML threshold of 1087 ng/ml (100% sensitivity, 93% specificity) for clinically
significant macular oedema. CONCLUSIONS/INTERPRETATION: High serum levels of CML 
were associated with advanced stages of retinopathy. Serum levels were shown to
be a progressive risk marker, whereby a level of more than 1000 ng/ml induced a
25-fold increase in risk of proliferative retinopathy and clinically significant 
macular oedema. Our data suggest that serum levels of CML provide a novel risk
marker for advanced stages of diabetic retinopathy in Type 2 diabetic patients.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15258735 [PubMed - indexed for MEDLINE]

2249: Br J Ophthalmol. 2004 Aug;88(8):1060-3.

Alteration of choroidal circulation in the foveal region in patients with type 2 
diabetes.

Nagaoka T, Kitaya N, Sugawara R, Yokota H, Mori F, Hikichi T, Fujio N, Yoshida A.

Department of Ophthalmology, Asahikawa Medical College, Midorigaoka Higashi
2-1-1-1, Asahikawa, 078-8510, Japan. nagaoka@asahikawa-med.ac.jp

AIM: To investigate changes in choroidal blood flow (CBF) in the foveal region in
patients with type 2 diabetes. METHODS: Laser Doppler flowmetry was used to
determine the CBF in the foveal region in 70 patients with type 2 diabetes and 36
age and sex matched healthy subjects (control group). The patients were
classified into three groups: 33 patients (33 eyes) with no diabetic retinopathy 
(NDR), 20 patients (20 eyes) with non-proliferative diabetic retinopathy and no
macular oedema (NPDR/MO-), and 17 patients (17 eyes) with NPDR and MO (NPDR/MO+).
Optical coherence tomography was also used to measure the foveal thickness.
RESULTS: The group averaged CBF values were 13.5 (4.9), 9.4 (2.5), 10.8 (4.8),
and 5.6 (2.0) (arbitrary units) in the control, NDR, NPDR/MO-, and NPDR/MO+
groups, respectively. The group averaged CBF values in the NDR group decreased
(30.2%; p<0.01) compared with the control group. The average CBF value in the
NPDR/MO+ group was also significantly lower (48.2%; p<0.01) compared with that in
the NPDR/MO- group. CONCLUSION: The CBF in the foveal region significantly
decreases in patients with diabetes, especially those with macular oedema.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15258025 [PubMed - indexed for MEDLINE]

2250: Br J Ophthalmol. 2004 Aug;88(8):1055-9.

Indocyanine green mediated photothrombosis for the management of predominantly
classic choroidal neovascularisation caused by age related macular degeneration.

Farah ME, Cardillo JA, Luzardo AC, Calucci D, Williams GA, Costa RA.

Department of Ophthalmology, Instituto da Visão-IPEPO, Federal University of São 
Paulo, School of Medicine, Brazil. mefarah@uol.com.br

AIMS: To study the effectiveness of indocyanine green mediated photothrombosis in
the management of predominantly classic subfoveal choroidal neovascularisation
associated with age related macular degeneration. METHODS: Prospective,
non-comparative, interventional case series of nine patients with predominantly
classic subfoveal choroidal neovascularisation secondary to age related macular
degeneration who declined photocoagulation or verteporfin photodynamic therapy.
Patients were submitted to one or more treatments with an intravenous injection
of a small volume of high concentration indocyanine green solution followed by
low irradiance, large spot 810 nm continuous laser application via a
transpupillary approach. Main outcome measures were change in best corrected
visual acuity and macular exudative manifestations. RESULTS: After 12 months of
follow up, the final best corrected visual acuity was the same (plus or minus two
ETDRS lines) in five eyes (55%), improved more than two ETDRS lines in three eyes
(33%), and worsened by more than two lines in the remaining eye. The improved
vision was probably related to partial or complete restoration of the macular
architecture as a result of fluid resolution, whereas the worsened vision was
primarily the result of treatment failure in achieving substantial choroidal
neovascular occlusion. There were no complications related to the procedure.
CONCLUSION: Indocyanine green mediated photothrombosis may be an effective
alternative treatment for predominantly classic subfoveal choroidal
neovascularisation caused by age related macular degeneration.

PMID: 15258024 [PubMed - indexed for MEDLINE]

2251: Br J Ophthalmol. 2004 Aug;88(8):982-7.

Comment in:
    Br J Ophthalmol. 2004 Aug;88(8):979.

Cost utility of photodynamic therapy for predominantly classic neovascular age
related macular degeneration.

Hopley C, Salkeld G, Mitchell P.

Centre for Vision Research, University of Sydney, Department of Ophthalmology,
Westmead Millennium Institute, Australia.

BACKGROUND/AIM: Age related macular degeneration (AMD) is the leading cause of
severe vision impairment and blindness in older people throughout the developed
world and currently affects around 420 000 UK citizens. Choroidal
neovascularisation (CNV) is treatable with photodynamic therapy (PDT) but is
expensive at over pound 1200 per treatment. The aim of this study was to assess
the cost utility of PDT for better eye, predominantly classic, subfoveal
choroidal neovascular lesions secondary to AMD. METHODS: Cost utility analysis
(CUA) was conducted to estimate the cost effectiveness of PDT for scenarios
involving reasonable (6/12) and poor (6/60) visual acuity. The models
incorporated data from the Treatment of Age-related Macular Degeneration with PDT
(TAP) Study and patient based utilities. The incremental CUA was based on
decision analytical models, comparing treatment to a placebo comparator.
Extensive one way sensitivity analysis of parameters was conducted to determine
the robustness of the model. A discount rate of 6% was used for costs and quality
adjusted life years (QALY). RESULTS: Model 1: in people with reasonable initial
visual acuity, the cost utility of treating applicable neovascular AMD lesions
was pound 31 607 per QALY saved, with a sensitivity analysis range from pound 25 
285 to pound 37 928. Model 2: in people with poor initial visual acuity, the cost
utility was pound 63 214 per QALY saved, with a sensitivity analysis range from
pound 54 183 to pound 75 856. CONCLUSIONS: PDT treatment is the only available
treatment for some forms of neovascular ("wet") AMD. Under these assumptions, PDT
can be considered moderately cost effective for those with reasonable visual
acuity but less cost effective for those with initial poor visual acuity. These
findings have implications for ophthalmic practice and healthcare planning.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15258009 [PubMed - indexed for MEDLINE]

2252: Ophthalmic Epidemiol. 2004 Apr;11(2):131-46.

Vision-specific health-related quality of life in age-related maculopathy
patients presenting for low vision services.

Scilley K, DeCarlo DK, Wells J, Owsley C.

Department of Ophthalmology, School of Medicine, University of Alabama at
Birmingham, Callahan Eye Found. Hosp., Birmingham, AL 35294-0009, USA.
kscilley@uab.edu

Few studies have examined the effectiveness of low vision rehabilitation for
age-related maculopathy (ARM) patients and its impact on vision-specific
health-related quality of life (HRQoL). However, before a multi-site clinical
trial can be conducted, appropriate outcome measures need to be identified for
ARM patients who seek out low vision rehabilitation, including a vision-specific 
HR QoL instrument. The 25-item National Eye Institute Visual Function
Questionnaire (NEI VFQ-25) was developed to assess vision-specific HRQoL for low 
vision patients, including those with ARM. This study examines the performance of
the NEI VFQ-25 among ARM patients who seek out low vision services and examines
its relationship with visual acuity and self-reported use of low vision aids. One
hundred and twenty-seven patients were recruited from a University-affiliated low
vision clinic. During two telephone interviews, subjects completed the NEI VFQ-25
and a short cognitive test and provided information on general health and use of 
low vision aids. Additional information on visual acuity and eye health were
collected from the medical record. Our results indicate that ARM patients who
seek out low vision services report significant impairment in their
vision-specific HRQoL. Their NEI VFQ-25 scores were lower compared to other ARM
and low vision rehabilitation samples previously studied. The VFQ subscales with 
the largest deficits were near and distance visual acuities and psychosocial
issues (near vision, distance vision, role difficulties, dependency, social
functioning, mental health). These subscale scores were lower for those with
greater visual acuity impairment. The VFQ subscale scores most impacted by the
disease had wide variability and were higher for those who used low vision aids, 
suggesting that the NEI VFQ-25 is suitable for measuring further decline and
treatment-related improvements. Thus, it should be strongly considered for a
multi-site clinical trial on the effectiveness of low vision rehabilitation.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15255028 [PubMed - indexed for MEDLINE]

2253: Ophthalmic Epidemiol. 2004 Apr;11(2):117-29.

Methods for a population-based study of the prevalence of and risk factors for
age-related maculopathy and macular degeneration in elderly European populations:
the EUREYE study.

Augood C, Fletcher A, Bentham G, Chakravarthy U, de Jong PT, Rahu M, Seland J,
Soubrane G, Tomazzoli L, Topouzis F, Vioque J, Young I.

Non-Communicable Disease Epidemiology Unit, London School of Hygiene and Tropical
Medicine, Keppel Street, London, UK.

PURPOSE: The aims of the EUREYE study are to evaluate the prevalence of
age-related maculopathy (ARM), including macular degeneration (AMD), in elderly
European populations, to investigate risk factors for ARM and AMD, especially
solar radiation and diet, and to measure the impact of these conditions on
vision-related quality of life. METHODS: A population-based cross-sectional study
with retrospective and current exposure measurements. Risk factor assessment is
via questionnaires (for lifestyle factors such as smoking and alcohol, dietary
risk factors, outdoor exposure) and blood analysis. Participants are people aged 
65 and over. The study is carried out in 7 centres with locations spanning north 
to south Europe. The main outcome measure is grading of fundus photographs (for
stage and type of ARM, using the International ARM Epidemiological Study Group
grading system).

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 15255027 [PubMed - indexed for MEDLINE]

2254: Bull Soc Belge Ophtalmol. 2004;(292):45-51.

Refractory ocular hypertension secondary to intravitreal injection of
triamcinolone acetonide.

Detry-Morel M, Escarmelle A, Hermans I.

St Luc University Hospital UCL, Bruxelles. detry@ofta.ucl.ac.be

PURPOSE: to report a case of severe ocular hypertension occurring as a
complication after a single intravitreal injection of triamcinolone acetonide for
the treatment of a diabetic cystoid macular edema. METHODS: interventional case
report. RESULTS: a 63-year-old pseudophakic diabetic woman developed a severe and
relatively sudden IOP increase to 50 mm Hg one month after receiving a single
4-mg intravitreal injection of triamcinolone acetonide for a chronic progressive 
macular cystoid edema. Previously the patient who did not develop
corticosteroid-induced glaucoma secondary to her cataract surgery was treated
with topical beta-blockers for a mild chronic bilateral ocular hypertension. A
deep sclerectomy had to be performed in emergency to avoid optic nerve damage and
allowed to successfully control the IOP with a 5 month follow-up. Concomitantly
visual acuity could be increased from 0.05 before the intravitreal injection to
0.4. CONCLUSIONS: Although unfrequent in the literature, this observation
confirms the risk of occurrence of a severe ocular hypertension after
intravitreal injection of triamcinolone. A close monitoring of IOP is mandatory
after intravitreal injection, especially in patients with altered trabecular
function. This potentially devastating complication has to be weighed up with the
benefices of intravitreal injection of triamcinolone for improving visual acuity 
in patients with clinically significant diabetic macular edema.

Publication Types: 
    Case Reports

PMID: 15253490 [PubMed - indexed for MEDLINE]

2255: Arch Ophthalmol. 2004 Jul;122(7):1013-8.

Monocyte activation in patients with age-related macular degeneration: a
biomarker of risk for choroidal neovascularization?

Cousins SW, Espinosa-Heidmann DG, Csaky KG.

Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami
School of Medicine, Miami, Fla. 33136, USA. scousins@med.miami.edu

OBJECTIVE: To evaluate the activation state of macrophage function in patients
with age-related macular degeneration (AMD) by quantifying the production of the 
proinflammatory and angiogenic factor tumor necrosis factor alpha (TNF-alpha) and
by correlating its expression with dry and wet AMD. METHODS: Circulating
monocytes were obtained from the blood of patients with AMD or age-matched
control subjects by gradient centrifugation. The monocytes were then analyzed for
either TNF-alpha release from cultured macrophages in response to retinal pigment
epithelium-derived blebs and cytokines or TNF-alpha messenger RNA content by
reverse transcriptase-polymerase chain reaction. RESULTS: In human monocytes
obtained from controls and AMD patients, TNF-alpha was expressed by freshly
isolated monocytes and produced by macrophages in culture after stimulation with 
retinal pigment epithelium-derived blebs. However, wide variability in TNF-alpha 
expression was observed among different patients. Patients with monocytes that
expressed the greatest amount of TNF-alpha demonstrated higher prevalence of
choroidal neovascularization. CONCLUSIONS: Both controls and AMD patients vary in
the activation state (defined as TNF-alpha expression) of circulating monocytes. 
Partially active monocytes, defined as high TNF-alpha expression, may be a
biomarker to identify patients at risk for formation of choroidal
neovascularization. CLINICAL RELEVANCE: Early diagnostic testing may prove useful
to detect those patients who will progress to the more severe complications of
the disease.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.

PMID: 15249366 [PubMed - indexed for MEDLINE]

2256: BMC Genet. 2004 Jul 6;5:18.

Ordered subset linkage analysis supports a susceptibility locus for age-related
macular degeneration on chromosome 16p12.

Schmidt S, Scott WK, Postel EA, Agarwal A, Hauser ER, De La Paz MA, Gilbert JR,
Weeks DE, Gorin MB, Haines JL, Pericak-Vance MA.

Center for Human Genetics, Duke University Medical Center, Durham, NC, USA.
silke.schmidt@duke.edu

BACKGROUND: Age-related macular degeneration (AMD) is a complex disorder that is 
responsible for the majority of central vision loss in older adults living in
developed countries. Phenotypic and genetic heterogeneity complicate the analysis
of genome-wide scans for AMD susceptibility loci. The ordered subset analysis
(OSA) method is an approach for reducing heterogeneity, increasing statistical
power for detecting linkage, and helping to define the most informative data set 
for follow-up analysis. OSA assesses the linkage evidence in subsets of
potentially more homogeneous families by rank-ordering family-specific lod scores
with respect to trait-associated covariates or phenotypic features. Here, we
present results of incorporating five continuous covariates into our genome-wide 
linkage analysis of 389 microsatellite markers in 62 multiplex families: Body
mass index (BMI), systolic (SBP) and diastolic (DBP) blood pressure, intraocular 
pressure (IOP), and pack-years of cigarette smoking. Chromosome-wide significance
of increases in nonparametric multipoint lod scores in covariate-defined subsets 
relative to the overall sample was assessed by permutation. RESULTS: Using a
correction for testing multiple covariates, statistically significant lod score
increases were observed for two chromosomal regions: 14q13 with a lod score of
3.2 in 28 families with average IOP </= 15.5 (p = 0.002), and 6q14 with a lod
score of 1.6 in eight families with average BMI >/= 30.1 (p = 0.0004). On
chromosome 16p12, nominally significant lod score increases (p </= 0.05), up to a
lod score of 2.9 in 32 families, were observed with several covariate orderings. 
While less significant, this was the only region where linkage evidence was
associated with multiple clinically meaningful covariates and the only nominally 
significant finding when analysis was restricted to advanced forms of AMD.
Families with linkage to 16p12 had higher averages of SBP, IOP and BMI and were
primarily affected with neovascular AMD. For all three regions, linkage signals
at or very near the peak marker have previously been reported. CONCLUSION: Our
results suggest that a susceptibility gene on chromosome 16p12 may predispose to 
AMD, particularly to the neovascular form, and that further research into the
previously suggested association of neovascular AMD and systemic hypertension is 
warranted.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15238159 [PubMed - indexed for MEDLINE]

2257: Am J Ophthalmol. 2004 Jul;138(1):158-60.

Duration of the effect of intravitreal triamcinolone acetonide as treatment for
diffuse diabetic macular edema.

Jonas JB, Degenring RF, Kamppeter BA, Kreissig I, Akkoyun I.

Department of Ophthalmology, Faculty of Clinical Medicine Mannheim, University of
Heidelberg, Heidelberg, Germany. Jost.Jonas@ma.augen.uni-heidelberg.de

PURPOSE: To evaluate the duration of the effect of intravitreal triamcinolone
acetonide on visual acuity in patients with diffuse diabetic macular edema.
DESIGN: Clinical interventional case series. METHODS: Subjects were 31 patients
(38 eyes) with diffuse diabetic macular edema who received an intravitreal
injection of 20- to 25-mg triamcinolone acetonide. Mean follow-up time was 13.2
+/- 6.0 months (6.03-25.2 months). RESULTS: Visual acuity and intraocular
pressure began to increase significantly (P =.003) within the first week,
reaching a plateaulike maximum at 1 to 7 months postinjection, returning to
baseline values 8 to 9 months postinjection. CONCLUSIONS: The effect of an
intravitreal injection of approximately 20- to 25-mg triamcinolone acetonide in
patients with diffuse diabetic macular edema lasts approximately 7 to 8 months.
This information may be helpful in determining the optimal dosage of intravitreal
triamcinolone acetonide for the treatment of diffuse diabetic macular edema.

PMID: 15234306 [PubMed - indexed for MEDLINE]

2258: Am J Ophthalmol. 2004 Jul;138(1):91-108.

Health- and vision-related quality of life among patients with choroidal
neovascularization secondary to age-related macular degeneration at enrollment in
randomized trials of submacular surgery: SST report no. 4.

Dong LM, Childs AL, Mangione CM, Bass EB, Bressler NM, Hawkins BS, Marsh MJ,
Miskala P, Jaffee HA, McCaffrey LA; Submacular Surgery Trials Research Group.

Wilmer Clinical Trials and Biometry, The Wilmer Ophthalmologic Institute, 550 N. 
Broadway, 9th Floor, Baltimore, MD 21205-2010, USA.

PURPOSE: To describe the effect of subfoveal choroidal neovascularization (CNV)
from age-related macular degeneration (AMD) on health-related quality of life
(HRQOL) of patients at enrollment in two randomized clinical trials; to examine
the relation of visual acuity to HRQOL; to compare HRQOL scores between
participants with unilateral and bilateral CNV independent of other
characteristics. DESIGN: Randomized clinical trials. METHODS: Two Submacular
Surgery Trials (SST) recruited patients with AMD and either new subfoveal CNV
(Group N Trial) or predominantly hemorrhagic CNV (Group B Trial). Health-related 
quality of life interviews included the National Eye Institute Visual Function
Questionnaire [NEI-VFQ], the SF-36 Health Survey, and the Hospital Anxiety and
Depression Scale [HADS]. Linear correlation and regression analyses were used to 
relate baseline HRQOL scores to visual acuity and bilateral disease. RESULTS:
Interview data were analyzed for 789 AMD patients: 454 patients in the Group N
Trial and 335 patients in the Group B Trial. Participants reported poor
vision-related functioning in many domains measured by the NEI-VFQ (mean overall 
scores of 65 for Group N and 63 for Group B). Visual acuity of the better eye was
strongly associated with NEI-VFQ scores but not with SF-36 or HADS scores. After 
adjusting for visual acuity of the better eye and other factors, bilateral cases 
had NEI-VFQ overall scores six points lower than unilateral cases in Group N
Trial and 10 points lower than unilateral cases in the Group B Trial.
CONCLUSIONS: Subfoveal CNV profoundly affects vision-related quality of life. The
effect is more pronounced with bilateral disease, even after controlling for
visual acuity.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15234287 [PubMed - indexed for MEDLINE]

2259: Am J Ophthalmol. 2004 Jul;138(1):55-63.

Fundus autofluorescence in Stargardt macular dystrophy-fundus flavimaculatus.

Lois N, Halfyard AS, Bird AC, Holder GE, Fitzke FW.

Retina Service, Ophthalmology Department, Aberdeen Royal Infirmary, University of
Aberdeen, Foresterhill, Aberdeen AB25 2ZN, Scotland, UK. noemilois@aol.com

PURPOSE: To quantify autofluorescence (AF) levels in patients with Stargardt
macular dystrophy-fundus flavimaculatus (STGD-FFM), and to identify patterns of
AF. DESIGN: Observational, comparative study. METHODS: Prospective study.
SETTINGS: Patients were recruited at Moorfields Eye Hospital. STUDY POPULATION:
Forty-three STGD-FFM patients aged 20 to 40 years and 35 age-matched normal
volunteers. The right eye was chosen arbitrarily for measures of AF.
INTERVENTION: The AF images were obtained using a confocal scanning laser
ophthalmoscope. Levels of AF across the macula were measured. The distribution of
AF was also evaluated. In 36 patients (84%) pattern electroretinogram (PERG) and 
full-field ERG were obtained and results were evaluated with respect to levels of
AF. MAIN OUTCOME MEASURES: Values of AF, AF distribution, PERG, and ERG. RESULTS:
Normal or high AF at the center of the macula with high AF temporally or nasally 
or both was detected in 17 patients (39%). In nine (21%), low AF at the center of
the macula with normal or low AF temporally or nasally or both was found. Levels 
of AF were normal throughout the macula in six patients (14%). In 11 (26%), high,
normal, and low levels of AF were found. All patients tested with low AF at the
center of the macula and normal or low AF temporally or nasally or both had
peripheral cone/rod dysfunction. None of the patients tested that had normal or
high AF at the fovea and high AF temporally or nasally, or normal AF throughout
the macula, had peripheral cone/rod dysfunction. CONCLUSION: AF is not
universally high in STGD-FFM. Some patients have normal or low AF.
Autofluorescence patterns appear to relate to functional abnormalities.

Publication Types: 
    Comparative Study

PMID: 15234282 [PubMed - indexed for MEDLINE]

2260: Am J Ophthalmol. 2004 Jul;138(1):38-45.

Comment in:
    Am J Ophthalmol. 2004 Jul;138(1):135-6.

Optic disk appearance in advanced age-related macular degeneration.

Law SK, Sohn YH, Hoffman D, Small K, Coleman AL, Caprioli J.

Jules Stein Eye Institute, 100 Stein Plaza 2-235, Los Angeles, CA 90095, USA.
law@jsei.ucla.edu

PURPOSE: To describe and quantify the appearance of the optic disk in patients
with advanced age-related macular degeneration (ARMD). DESIGN: Retrospective
comparative study. METHODS: A total of 316 charts were reviewed. From these, 45
subjects with advanced ARMD (defined as geographic atrophy or disciform scar) in 
at least one eye were enrolled. Patients with glaucoma or glaucoma visual field
defects were excluded. The probability of glaucomatous optic nerve damage was
scored by evaluation of stereoscopic optic disk photographs in a masked fashion, 
according to a predefined evaluation scale and measured with confocal
ophthalmoscopy (Heidelberg Retinal Tomograph; HRT). The area of macular
involvement was measured in units of disk area. The optic disk evaluation scores 
and HRT measurements of a group of eyes with a large area of ARMD were compared
with their fellow eyes with smaller areas of ARMD. The correlations between the
area of macular involvement with the optic disk evaluation scores and HRT
measurements were analyzed. MAIN OUTCOME MEASURES: The optic disk evaluation
scores and the HRT measurements between study groups. RESULTS: Eyes with larger
areas of ARMD had optic disks that were more likely to be classified as
glaucomatous by clinical evaluation (3.45 +/- 0.23 vs 3.05 +/- 0.18, P =.015) and
by HRT imaging analysis (-0.995 +/- 0.423 vs -0.376 +/- 0.249, P =.030) than the 
fellow eyes with smaller areas of ARMD. For eyes with six or more disk areas of
ARMD, larger areas of ARMD correlated with a higher cup/disk ratio (P =.022),
smaller neuroretinal rim area (P =.022), and glaucomatous classification (P
=.040) with HRT discriminant function analysis. CONCLUSIONS: Eyes with large
areas of geographic or diskiform ARMD have optic disk structural alterations that
resemble glaucomatous optic neuropathy. This should be taken into consideration
when evaluating patients with ARMD for glaucomatous damage.

Publication Types: 
    Comparative Study

PMID: 15234280 [PubMed - indexed for MEDLINE]

2261: Ophthalmology. 2004 Jul;111(7):1307-16.

Baseline characteristics, the 25-Item National Eye Institute Visual Functioning
Questionnaire, and their associations in the Complications of Age-Related Macular
Degeneration Prevention Trial (CAPT).

Maguire M; Complications of Age-Related Macular Degeneration Prevention Trial
Research Group.

CAPT Coordinating Center, Philadelphia, PA 19104, USA.

OBJECTIVE: To describe characteristics of participants in the Complications of
Age-Related Macular Degeneration Prevention Trial (CAPT) at baseline and to
investigate associations among visual function, fundus features, and
vision-related quality of life. DESIGN: Cross-sectional study. PARTICIPANTS: The 
1052 participants in CAPT, a multicenter, randomized clinical trial. Eligibility 
criteria for CAPT included > or =10 large drusen and visual acuity > or =20/40 in
each eye. METHODS: At baseline, the visual acuity, contrast sensitivity, and
critical print size for each eye were measured, color stereo photographs of the
disc and macula of each eye were taken, and the 25-item National Eye Institute
Visual Functioning Questionnaire (NEI-VFQ-25) was self-administered. Graders from
a central photograph reading center evaluated the photographs for drusen
characteristics and focal hyperpigmentation. All procedures were performed using 
standardized protocols. Associations among characteristics were assessed by
Spearman correlation coefficients and multiple linear regression. RESULTS: Among 
CAPT participants at baseline, the mean age was 71.0 years, 60.6% were women, and
99.3% were white. The median visual acuity of the better eye was 20/20 and of the
worse eye 20/25. In approximately one third of eyes, drusen covered > or =10% of 
the retina within 3000 microm of the foveal center, and 67.7% of eyes had focal
hyperpigmentation. Drusen area and focal hyperpigmentation were weakly correlated
(r = -0.08 to -0.18) with the measures of visual function. The measures of visual
function were weakly associated with the NEI-VFQ-25 scores. An association of
fundus features with NEI-VFQ-25 scores was not found. CONCLUSION: At baseline,
CAPT participants had good visual function and several risk factors for
progression to neovascular age-related macular degeneration. Scores on the
NEI-VFQ-25 indicated that participants perceived some problems with their vision.
Within this relatively homogeneous group of participants, measures of visual
function were only weakly associated with the measures of vision-related quality 
of life.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, U.S. Gov't, P.H.S.

PMID: 15234130 [PubMed - indexed for MEDLINE]

2262: Ophthalmology. 2004 Jul;111(7):1288-97.

Prevalence of age-related macular degeneration in Latinos: the Los Angeles Latino
eye study.

Varma R, Fraser-Bell S, Tan S, Klein R, Azen SP; Los Angeles Latino Eye Study
Group.

Doheny Eye Institute and Department of Ophthalmology, Keck School of Medicine,
University of Southern California, Los Angeles, California 90033, USA.
rvarma@usc.edu

OBJECTIVE: To estimate the age- and gender-specific prevalence of early
age-related macular degeneration (AMD; drusen and retinal pigmentary
abnormalities) and advanced AMD (exudative AMD and geographic atrophy) in
Latinos. DESIGN: Population-based, cross-sectional study. PARTICIPANTS: Six
thousand three hundred fifty-seven Latinos 40 years and older from 6 census
tracts in Los Angeles, California. METHODS: The study cohort consisted of
self-identified Latinos 40 years and over. Participants underwent a complete
ophthalmologic examination, including stereoscopic macular photographs.
Photographs were graded using a modified Wisconsin Age-Related Maculopathy
Grading System. MAIN OUTCOME MEASURES: Prevalence of early AMD, drusen,
geographic atrophy, and exudative AMD. RESULTS: Of the 7789 eligible subjects,
6357 participants (82%) completed an interview and clinical examination, and 5875
(75%) had gradable photographs. Prevalence of advanced AMD increased from 0% in
those 40-49 years of age to 8.5% in those 80 or older; that of early AMD from
6.2% to 29.7%, that of retinal pigment abnormalities from 4.1% to 19.3%, that of 
large drusen (> or =125 microm in diameter) from 8.5% to 45.3%, that of soft
drusen from 15.4% to 58.1%, and that of soft indistinct drusen from 3.6% to
30.8%. The prevalence of early AMD and advanced AMD lesions increased with age
(P<0.0001). Early AMD was significantly more common in males than in females. Of 
all participants with early or late AMD, only 57% reported ever visiting an eye
care practitioner, and only 21% in the last year. CONCLUSION: Detailed
population-based estimates of AMD in Latinos are provided. Despite relatively
high rates of early AMD, corresponding rates of advanced AMD are not high. Data
on progression of the high rates of early AMD in Latinos require further study.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15234128 [PubMed - indexed for MEDLINE]

2263: Ophthalmology. 2004 Jul;111(7):1280-7.

Risk factors for incident age-related macular degeneration: pooled findings from 
3 continents.

Tomany SC, Wang JJ, Van Leeuwen R, Klein R, Mitchell P, Vingerling JR, Klein BE, 
Smith W, De Jong PT.

Department of Ophthalmology, University of Wisconsin, Madison, Wisconsin 53726,
USA.

OBJECTIVE: To examine risk factors for incident age-related macular degeneration 
(AMD) after combining data from 3 population-based cohort studies. DESIGN:
Population-based cohort study. POPULATION: A population of 9523 adults (age
range, 43-95 years at baseline) living in Australia, The Netherlands, and the
United States who participated in a baseline examination and a follow-up
examination on average 5 or 6 years later. METHODS: Similar procedures were used 
at all study sites. Examinations included a standardized questionnaire, pupillary
dilation, and stereoscopic color fundus photography. Fundus photographs were
graded for lesions associated with AMD using the Wisconsin and International
Age-Related Maculopathy Grading Systems. Senior investigators from each site
adjudicated all photos graded as late AMD. MAIN OUTCOMES MEASURE: Incidence of
late AMD. RESULTS: Among studies, distributions for most risk factors differed,
and overall incidence rates were similar. In the Beaver Dam Eye Study, total
serum cholesterol was inversely associated with incident neovascular AMD. In the 
Blue Mountains Eye Study, current smoking (defined as smoking at the time of the 
baseline examination) was associated with an increased risk of incident
geographic atrophy and late AMD; increased total serum cholesterol, having
diabetes, and older age at menopause were positively associated with incident
geographic atrophy; and an increase in high-density lipoprotein serum cholesterol
was inversely related to incident geographic atrophy. In the Rotterdam Study,
current smoking was associated with an increased risk of incident geographic
atrophy, neovascular AMD, and late AMD; past smoking was associated with an
increased risk of incident neovascular AMD and late AMD; and an increased number 
of years between menarche and menopause was directly related to incident
geographic atrophy. After pooling data, the only statistically significant
relationships found were between smoking and total serum cholesterol and incident
AMD. Current smoking was associated with an increased incidence of geographic
atrophy and late AMD (odds ratios [ORs] relative to nonsmokers: 2.83 and 2.35,
respectively; ORs relative to past smokers: 2.80 and 1.82, respectively), and
total serum cholesterol was associated directly with incident geographic atrophy 
(OR: 1.08 per 10 mg/dl) and inversely with incident neovascular AMD (OR: 0.94 per
10 mg/dl). CONCLUSIONS: Pooled data support a growing body of evidence indicating
that smoking is related to an increased risk of incident AMD. Current smokers
were at higher risk of incident AMD than both past smokers and those who never
smoked. The relationships found in this study between total serum cholesterol and
incident geographic atrophy and neovascular AMD are not readily explained.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15234127 [PubMed - indexed for MEDLINE]

2264: Eye. 2004 Oct;18(10):963-83.

Epidemiology of diabetic retinopathy and macular oedema: a systematic review.

Williams R, Airey M, Baxter H, Forrester J, Kennedy-Martin T, Girach A.

The Clinical School, University of Wales Swansea, Swansea, UK.
D.R.R.Williams@Swansea.ac.uk

AIMS: To systematically review the literature on the prevalence and incidence of 
diabetic retinopathy (DR) and macular oedema (MO). METHODS: A search of the
bibliographic databases (Medline, Embase, CINAHL) was conducted up to October
2001. Selected relevant studies were scrutinized and included in the review.
RESULTS: A total of 359 studies were included. The studies were reported in
nearly 100 different journals and in over 50 countries. The majority of the
studies were US-based, with large studies such as the Wisconsin Epidemiologic
Study of Diabetic Retinopathy dominating the literature. The studies were quite
dated and highly heterogeneous in nature in terms of patient selection with
variable inclusion criteria (age range, gender, diabetes duration and type,
ethnicity, comorbidity, and DR status, assessment, and classification).
CONCLUSIONS: There are inconsistencies between epidemiological studies, and
differences in study methods may contribute to conflicting reports of prevalence 
and incidence of DR and MO in diabetic populations. As new therapies for DR and
its associated complications emerge, the need to capture and monitor new
epidemiological data becomes increasingly important to be able to assess the
impact and effectiveness of these therapies. Robust, longitudinal capture of
patient data is, therefore, essential to evaluate the impact of current practice 
on the epidemiology of diabetic eye complications.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 15232600 [PubMed - indexed for MEDLINE]

2265: Proc Natl Acad Sci U S A. 2004 Jul 13;101(28):10446-51. Epub 2004 Jun 30.

Induction of phase 2 genes by sulforaphane protects retinal pigment epithelial
cells against photooxidative damage.

Gao X, Talalay P.

Lewis B. and Dorothy Cullman Cancer Chemoprotection Center, Department of
Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine,
Baltimore, MD 21205, USA.

The retinal pigment epithelial cell (RPE cell) layer protects the photoreceptors 
of the retina against oxidative stress. The decline of this capacity is believed 
to be a major factor in the impairment of vision in age-related macular
degeneration. Exposure of human adult RPE cells to UV light at predominantly
320-400 nm (UVA light) in the presence of all-trans-retinaldehyde results in
photooxidative cytotoxicity. Significant protection of RPE cells was obtained by 
prior treatment with phase 2 gene inducers, such as the isothiocyanate
sulforaphane or a bis-2-hydroxybenzylideneacetone Michael reaction acceptor. The 
degree of protection was correlated with the potencies of these inducers in
elevating cytoprotective glutathione levels and activities of NAD(P)H:quinone
oxidoreductase. In embryonic fibroblasts derived from mice in which the genes for
the transcription factor Nrf2, the repressor Keap1, or both Nrf2 and Keap1 were
disrupted, the magnitude of resistance to photooxidative damage paralleled the
basal levels of glutathione and NAD(P)H:quinone oxidoreductase in each cell type.
Demonstration of protection of RPE cells against photooxidative damage by
induction of phase 2 proteins may shed light on the role of oxidative injury in
ocular disease. Moreover, the finding that dietary inducers provide indirect
antioxidant protection suggests novel strategies for preventing chronic
degenerative diseases, such as age-related macular degeneration.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15229324 [PubMed - indexed for MEDLINE]

2266: Ophthalmic Physiol Opt. 2004 Jul;24(4):339-49.

An ideal ocular nutritional supplement?

Bartlett H, Eperjesi F.

Neurosciences Research Institute, School of Life and Health Sciences, Aston
University, Birmingham B4 7ET, UK. bartlehe@aston.ac.uk

The role of nutritional supplementation in prevention of onset or progression of 
ocular disease is of interest to health care professionals and patients. The aim 
of this review is to identify those antioxidants most appropriate for inclusion
in an ideal ocular nutritional supplement, suitable for those with a family
history of glaucoma, cataract, or age-related macular disease, or lifestyle
factors predisposing onset of these conditions, such as smoking, poor nutritional
status, or high levels of sunlight exposure. It would also be suitable for those 
with early stages of age-related ocular disease. Literature searches were carried
out on Web of Science and PubMed for articles relating to the use of nutrients in
ocular disease. Those highlighted for possible inclusion were vitamins A, B, C
and E, carotenoids beta-carotene, lutein, and zeaxanthin, minerals selenium and
zinc, and the herb, Ginkgo biloba. Conflicting evidence is presented for vitamins
A and E in prevention of ocular disease; these vitamins have roles in the
production of rhodopsin and prevention of lipid peroxidation respectively. B
vitamins have been linked with a reduced risk of cataract and studies have
provided evidence supporting a protective role of vitamin C in cataract
prevention. Beta-carotene is active in the prevention of free radical formation, 
but has been linked with an increased risk of lung cancer in smokers.
Improvements in visual function in patients with age-related macular disease have
been noted with lutein and zeaxanthin supplementation. Selenium has been linked
with a reduced risk of cataract and activates the antioxidant enzyme glutathione 
peroxidase, protecting cell membranes from oxidative damage while zinc, although 
an essential component of antioxidant enzymes, has been highlighted for risk of
adverse effects. As well as reducing platelet aggregation and increasing
vasodilation, Gingko biloba has been linked with improvements in pre-existing
field damage in some patients with normal tension glaucoma. We advocate that
vitamins C and E, and lutein/zeaxanthin should be included in our theoretically
ideal ocular nutritional supplement.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 15228513 [PubMed - indexed for MEDLINE]

2267: Ophthalmic Physiol Opt. 2004 Jul;24(4):327-33.

Fixation stability and reading speed in patients with newly developed macular
disease.

Crossland MD, Culham LE, Rubin GS.

Division of Vision Rehabilitation Research, Institute of Ophthalmology,
University College London, 11-43 Bath Street, London ECIV 9EL, UK.
m.crossland@ucl.ac.uk

BACKGROUND: Patients with macular disease and central scotomas must use a
peripheral, preferred retinal locus (PRL) in place of their damaged fovea. This
paper investigates the development of the PRL, with particular reference to the
stability of fixation. METHODS: Twenty-five patients with age-related and
juvenile macular disease were recruited. All patients had developed a scotoma in 
their better eye within the previous 2 weeks. Patients were assessed using a
scanning laser ophthalmoscope and an infra-red gazetracker on four further
occasions over the next 12 months. RESULTS: A linear relationship exists between 
reading speed and fixation stability for patients and control subjects. Fixation 
stability was not related to scotoma size, visual acuity or contrast sensitivity.
Changes in fixation stability account for 54% of the variance in change in
reading speed over the course of this study. CONCLUSIONS: The deficit in reading 
speed in patients with macular disease can be partially attributed to impairments
in fixation stability.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15228511 [PubMed - indexed for MEDLINE]

2268: Invest Ophthalmol Vis Sci. 2004 Jul;45(7):2135-42.

Location of lesions associated with age-related maculopathy over a 10-year
period: the Beaver Dam Eye Study.

Knudtson MD, Klein R, Klein BE, Lee KE, Meuer SM, Tomany SC.

Department of Ophthalmology and Visual Sciences, University of Wisconsin Medical 
School, Madison, 53726-2336, USA. knudtson@epi.ophth.wisc.edu

PURPOSE: To describe cumulative incidence and changes in retinal lesions
associated with age-related maculopathy (ARM) by location over a 10-year period
and to examine the relation of location of those lesions to progression of ARM.
METHODS: Persons ranging in age from 43 to 84 years and living in Beaver Dam,
Wisconsin, at the time of a census (1987-1988) were examined two to three times
over a 10-year period (n = 3684). Drusen area, size, and type; retinal pigment
epithelium depigmentation; increased pigment; geographic atrophy; and neovascular
macular degeneration were determined in each of nine macular subfields: central, 
inner and outer superior, inner and outer nasal, inner and outer inferior, and
inner and outer temporal by grading of stereoscopic color fundus photographs.
Late ARM was defined as presence of either geographic atrophy or neovascular ARM.
RESULTS: Lesions were more likely to change or develop in specific locations.
Drusen area increased most in the central circle. Compared with other quadrants, 
drusen greater than 125 micro m in diameter and soft indistinct or reticular
drusen were most likely to develop in the superior or temporal quadrants, whereas
pigmentary abnormalities were most likely to occur in the nasal or superior
quadrants. In general, large drusen, soft indistinct drusen, and pigmentary
abnormalities were more likely to develop in the inner circle versus the central 
and outer circles. The quadrant location of early ARM lesions in 72 persons in
whom late ARM developed was generally similar to that in persons who did not have
late ARM. However, persons who had geographic atrophy were more likely to have
large drusen in the inner circle than in the outer circle, while those who did
not have late ARM were more likely to have large drusen in the outer circle.
CONCLUSIONS: Lesions associated with early ARM were more likely to develop in
specific locations in the macular area, and persons with lesions closer to the
fovea may be related to a higher risk of development of late ARM. The quadrant
location of early ARM lesions does not appear to add additional information to
the risk of development of late ARM.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.

PMID: 15223787 [PubMed - indexed for MEDLINE]

2269: Graefes Arch Clin Exp Ophthalmol. 2004 Oct;242(10):845-52. Epub 2004 Jun
22.

Pars plana vitrectomy and removal of the internal limiting membrane in the
treatment of chronic macular oedema.

Avci R, Kaderli B, Avci B, Simsek S, Baykara M, Kahveci Z, Gelisken O, Yucel AA.

Department of Ophthalmology, Uludag University Faculty of Medicine, 16059 Gorukle
Bursa, Turkey. ravci@uludag.edu.tr

BACKGROUND: To evaluate the results of pars plana vitrectomy with peeling of the 
internal limiting membrane (ILM) in eyes with chronic macular oedema. METHODS:
PPV with indocyanine green (ICG) assisted peeling of the ILM was performed in 33 
eyes with diabetic (21 eyes) or non-diabetic (12 eyes) macular oedema.
Postoperatively, resolution of macular oedema, improvement of visual acuity (VA) 
and complications were documented. The peeled membranes were submitted for light 
and transmission electron microscopic evaluation. RESULTS: The mean follow-up
time was 12.2 months. The macular oedema decreased or was resolved in 17 (81%)
eyes in the diabetic group and in 11 (92%) eyes in the non-diabetic group. VA
improved by at least 2 lines in 11 (52%) eyes in the diabetic group and in 7
(58%) eyes in the non-diabetic group. The difference between visual acuity
improvements of the two groups was not statistically significant (P>0.05).
However, in the diabetic group the difference of visual improvement between
cystoid and diffuse type of macular oedema eyes was statistically significant
(14% versus 71%, P=0.02). Light and transmission electron microscopy showed the
presence of ILM in all specimens. During the follow-up period no recurrence of
macular oedema or epiretinal membrane formation was observed. CONCLUSION: Pars
plana vitrectomy with peeling of the ILM and epiretinal membrane leads to the
resolution of macular oedema in the majority of eyes. This however, is not always
associated with VA improvement. In diabetic eyes, cystoid type of macular oedema 
appears to be a poor prognostic factor for improved VA.

PMID: 15221309 [PubMed - indexed for MEDLINE]

2270: Graefes Arch Clin Exp Ophthalmol. 2004 Aug;242(8):630-7. Epub 2004 Jun 22.

Vitrectomy with removal of the internal limiting membrane in chronic diabetic
macular oedema.

Dillinger P, Mester U.

Department of Ophthalmology, Bundesknappschaft Hospital, An der Klinik 10, 66280 
Sulzbach, Germany. augen@kksulzbach.de

PURPOSE: To assess the effect of pars-plana vitrectomy including peeling of the
internal limiting membrane (ILM) on the resolution of chronic diabetic macular
oedema. METHODS: We performed a prospective evaluation of 60 eyes of 55 patients 
with chronic diabetic macular oedema who underwent pars-plana vitrectomy with ILM
removal. All patients had a history of macular oedema of at least 6 months. In
most of the eyes, grid laser photocoagulation had been performed previously. Eyes
with further vitreoretinal pathologies such as vitreous haemorrhage, evident
macular traction or significant loss of the foveal capillary net were excluded.
Fluorescein angiography, funduscopic examination and the assessment of
best-corrected visual acuity (BCVA) were performed pre- and postoperatively. The 
mean duration of follow-up was 3.0 months. Additionally BCVA was inquired of the 
referring ophthalmologists after a postoperative period of at least 9 months.
RESULTS: Fluorescein angiography and clinical examination revealed a decrease of 
leakage within the macula or a decrease of macular thickening in 55 (93%) eyes.
Mean visual acuity (LogMAR) significantly improved from 1.05 preoperatively to
0.87 postoperatively (P=0.0000034). Twenty-six eyes (43%) gained 2 or more lines 
of vision; four eyes (7%) lost 2 lines. Data concerning BCVA after a follow-up of
at least 9 months were available in 37 patients (41 eyes) and confirmed the
results 3 months postoperatively. CONCLUSION: Pars-plana vitrectomy with ILM
peeling reduced macular oedema in most cases. In contrast, visual acuity improved
significantly in 43% of the treated eyes only. The discrepancy between anatomical
and functional results of ILM removal in chronic diabetic macular oedema is
likely to be caused by structural changes of the macula due to long-standing
oedema.

Publication Types: 
    Clinical Trial

PMID: 15221304 [PubMed - indexed for MEDLINE]

2271: Eye. 2005 Feb;19(2):163-70.

Exudative age-related macular degeneration treated by intravitreal triamcinolone 
acetonide. A prospective comparative nonrandomized study.

Jonas JB, Degenring RF, Kreissig I, Friedemann T, Akkoyun I.

Department of Ophthalmology, Faculty of Clinical Medicine, Mannheim of the
University, Heidelberg, Germany. Jost.Jonas@ma.augen.uni-heidelberg.de

PURPOSE: To report on visual outcome of patients receiving an intravitreal
injection of triamcinolone acetonide as treatment of progressive exudative
age-related macular degeneration. METHODS: The prospective comparative
nonrandomized clinical interventional study included 187 consecutive patients
with progressive exudative age-related macular degeneration, divided into a study
group of 115 patients receiving an intravitreal injection of 25 mg triamcinolone 
acetonide, and a control group of 72 patients without treatment. The mean
follow-up was 6.0+/-4.2 months. RESULTS: Visual acuity increased significantly
(P=0.03) in the study group, and decreased significantly (P=0.01) in the control 
group, at 1 month and 3 months after start of the study. Between the study group 
and control group, the differences in change of visual acuity were significant
(P=0.001). In the study group, the number of patients with an increase in visual 
acuity of 2 or more Snellen lines was significantly (P=0.001) larger than in the 
control group. Correspondingly, the number of patients with a decrease of 2 or
more Snellen lines was significantly (P=0.007) smaller in the study group. In
all, 43 (37.4%) patients of the study group experienced an increase in best
visual acuity by 2 or more Snellen lines. CONCLUSIONS: Visual acuity increased in
patients with exudative age-related macular degeneration at 1 month and 3 months 
after an intravitreal injection of 25 mg triamcinolone acetonide.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial

PMID: 15218517 [PubMed - indexed for MEDLINE]

2272: Proc Natl Acad Sci U S A. 2004 Jul 6;101(27):10030-5. Epub 2004 Jun 24.

The specific binding of retinoic acid to RPE65 and approaches to the treatment of
macular degeneration.

Gollapalli DR, Rando RR.

Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical
School, 45 Shattuck Street, Boston, MA 02115, USA.

RPE65 is essential in the operation of the visual cycle and functions as a
chaperone for all-trans-retinyl esters, the substrates for isomerization in the
visual cycle. RPE65 stereospecifically binds all-trans-retinyl esters with a K(D)
of 47 nM. It is shown here by using a quantitative fluorescence technique, that
Accutane (13-cis-retinoic acid), a drug used in the treatment of acne but that
causes night blindness, binds to RPE65 with a K(D) of 195 nM. All-trans-retinoic 
acid binds with a K(D) of 109 nM. The binding of the retinoic acids to RPE65 is
competitive with all-trans-retinyl ester binding, and this competition inhibits
visual cycle function. A retinoic acid analog that binds weakly to RPE65 is not
inhibitory. These data suggest that RPE65 function is rate-limiting in visual
cycle function. They also reveal the target through which the retinoic acids
induce night blindness. Finally, certain forms of retinal and macular
degeneration are caused by the accumulation of vitamin A-based retinotoxic
products, called the retinyl pigment epithelium-lipofuscin. These retinotoxic
products accumulate during the normal course of rhodopsin bleaching and
regeneration after the operation of the visual cycle. Drugs such as Accutane may 
represent an important approach to reducing the accumulation of the retinotoxic
lipofuscin by inhibiting visual cycle function. The identification of RPE65 as
the visual cycle target for the retinoic acids makes it feasible to develop
useful drugs to treat retinal and macular degeneration while avoiding the
substantial side effects of the retinoic acids.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.

PMID: 15218101 [PubMed - indexed for MEDLINE]

2273: J Cataract Refract Surg. 2004 Jul;30(7):1501-6.

Erratum in:
    J Cataract Refract Surg. 2005 Jan;31(1):14.

Comment in:
    J Cataract Refract Surg. 2005 Jul;31(7):1269-70; author reply 1270.

Retinal thickness measurement after phacoemulsification.

Cohen KL, Patel SB, Ray N.

Department of Ophthalmology, University of North Carolina at Chapel Hill, School 
of Medicine, 5110 Bioinformatics Building, 130 Mason Farm Road, Chapel Hill, NC
27599-7040, USA. klc@med.unc.edu

PURPOSE: To measure macular thickness using the Retinal Thickness Analyzer (RTA) 
(Talia Technologies, Ltd.) before and after routine phacoemulsification. SETTING:
Ophthalmology Clinic, Ambulatory Care Center, University of North Carolina at
Chapel Hill, School of Medicine, and the University of North Carolina Hospitals, 
Chapel Hill, North Carolina, USA. METHODS: Thirty-five nonconsecutive patients
scheduled for phacoemulsification and posterior chamber intraocular lens
implantation were recruited. The best corrected visual acuity (BCVA) and macular 
thickness in the surgical and nonsurgical eyes were measured with the RTA prior
to surgery and 1 and 6 weeks after surgery. Wilcoxon signed rank tests were used 
to evaluate each index of macular thickness--the mean posterior pole, perifoveal,
and foveal thicknesses--over the 3 time periods and to compare the indices before
surgery in surgical and nonsurgical eyes. Spearman correlations were computed for
each index and the BCVA. Significance was assessed at the 5% level. RESULTS:
Preoperatively, all indices were higher in surgical [corrected] eyes than in
nonsurgical [corrected] eyes. In surgical eyes, all indices decreased from
preoperatively to 6 weeks after surgery. In nonsurgical eyes, there was no
change. The BCVA in surgical eyes improved from before surgery to 1 week and 6
weeks after surgery. In surgical eyes, there were nonsignificant negative
correlations between each index and the BCVA before surgery and 1 and 6 weeks
after surgery. In nonsurgical eyes, there were nonsignificant negative
correlations between each index and the BCVA preoperatively and 6 weeks after
surgery, except for a significant negative correlation for the foveal index at 6 
weeks. CONCLUSIONS: Measurements by the RTA indicate that the decrease in macular
thickness indices in surgical eyes from before surgery to 6 weeks after routine
phacoemulsification is an artifact of imaging the retina through hazy media.
Therefore, the results must be interpreted in the context of the clinical
situation.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15210229 [PubMed - indexed for MEDLINE]

2274: FASEB J. 2004 Aug;18(11):1297-9. Epub 2004 Jun 18.

The involvement of sequence variation and expression of CX3CR1 in the
pathogenesis of age-related macular degeneration.

Tuo J, Smith BC, Bojanowski CM, Meleth AD, Gery I, Csaky KG, Chew EY, Chan CC.

Laboratory of Immunology, National Eye Institute, National Institutes of Health, 
Bethesda, Maryland 20892-1857, USA.

This study examined the association between the sequence variation/expression of 
CX3CR1, a chemokine receptor, and age-related macular degeneration (AMD).
Peripheral blood from 85 AMD patients and 105 subjects without AMD (controls), as
well as ocular tissue from 40 pathological sections with AMD and two normal eye
sections, were screened for V249I and T280M, two single nucleotide polymorphisms 
(SNPs) in CX3CR1. An increased prevalence, with the highest odds ratio of 3.57,
of the I249 and M280 carriers was found among the AMD cases as compared with the 
controls. When comparing CX3CR1 expression in the archived eye sections, CX3CR1
transcripts were not detectable in the maculae of AMD eyes bearing T/M280;
however, transcripts were detected in the maculae of normal eyes bearing T/T280
or T/M280 as well as in the AMD maculae bearing T/T280. Furthermore, lower CX3CR1
protein expression was observed in the maculae of AMD eyes bearing T/M280
compared with the controls bearing T/T280. The I249 and M280 alleles result in a 
lowered number of receptor binding sites and a decreased ligand affinity. Our
data suggest that a decrease, caused by sequence variation and/or lower CX3CR1
expression, in CX3CR1-induced cellular activities could contribute to AMD
development.

PMID: 15208270 [PubMed - indexed for MEDLINE]

2275: J Diabetes Complications. 2004 Jul-Aug;18(4):211-5.

Risk factors for diffuse and focal macular edema.

Aroca PR, Salvat M, Fernández J, Méndez I.

Ophthalmologic Service, Departamento de Medicina y Cirugía, Hospital
Universitario Sant Joan de Reus, Universidad Rovira y Virgili, ReusSpain.
promero@grupsagessa.com

OBJECTIVE: The epidemiological risk factors for the different forms of diabetic
macular edema (focal or diffuse) are not differentiated in the literature. In the
present study, the objective was to determine which risk factors influence the
appearance of focal or diffuse macular edema. RESEARCH, DESIGN, AND METHODS: A
4-year prospective study in a population of Type II diabetic patients (NIDDM) in 
three groups, the first with 29 patients with diffuse diabetic macular edema
(Group A), the second with 32 patients with focal macular edema (Group B), and
the third with 32 patients with diabetic retinopathy but without diabetic macular
edema (Group C); the three groups were selected on the basis of sex, age, and
duration of diabetes with similar patterns. We studied the following risk
factors: treatment of diabetes mellitus by insulin, presence of diastolic blood
hypertension, presence of microalbuminuria or diabetic nephropathy, levels of
HbA1c, type of diabetic retinopathy, presence of previous panretinal
photocoagulation, and levels of triglycerides and fractions of cholesterol.
RESULTS: In discriminant analysis and in order of importance, the epidemiological
risk factors for Group A were the following: presence of panretinal laser,
diastolic blood hypertension, diabetic nephropathy, and insulin treatment; for
group B, the risk factors were the following: insulin treatment, presence of
diastolic blood hypertension, and high levels of glycated haemoglobin (HbA1c);
and for group, C the risk factors were the following: diastolic blood
hypertension, insulin treatment of diabetes, and high levels of HbA1c.
CONCLUSIONS: In the present study, the group of patients with focal macular edema
were epidemiologically similar to the group of patients with diabetic retinopathy
without macular edema, the group of patients with diffuse macular edema were
epidemiologically different.

PMID: 15207838 [PubMed - indexed for MEDLINE]

2276: Arch Ophthalmol. 2004 Jun;122(6):883-92.

Prospective study of intake of fruits, vegetables, vitamins, and carotenoids and 
risk of age-related maculopathy.

Cho E, Seddon JM, Rosner B, Willett WC, Hankinson SE.

Channing Laboratory, Department of Medicine, Harvard Medical School and Brigham
and Women's Hospital, Boston, MA 02115, USA. eunyoung.cho@channing.harvard.edu

OBJECTIVE: To examine the intake of antioxidant vitamins and carotenoids as well 
as fruits and vegetables in relation to the development of age-related
maculopathy (ARM). METHODS: We conducted a prospective follow-up study of women
in the Nurses' Health Study and men in the Health Professionals Follow-up Study. 
We followed 77 562 women and 40 866 men who were at least 50 years of age and had
no diagnosis of ARM or cancer at baseline for up to 18 years for women and up to 
12 years for men. Fruit and vegetable intakes were assessed with a validated
semiquantitative food-frequency questionnaire up to 5 times for women and up to 3
times for men during follow-up. RESULTS: A total of 464 (329 women and 135 men)
incident cases of early ARM and 316 (217 women and 99men) cases of neovascular
ARM, all with visual loss of 20/30 or worse due primarily to ARM, were diagnosed 
during follow-up. Fruit intake was inversely associated with the risk of
neovascular ARM. Participants who consumed 3 or more servings per day of fruits
had a pooled multivariate relative risk of 0.64 (95% confidence interval,
0.44-0.93; P value for trend =.004) compared with those who consumed less than
1.5 servings per day. The results were similar in women and men. However, intakes
of vegetables, antioxidant vitamins, or carotenoids were not strongly related to 
either early or neovascular ARM. CONCLUSION: These data suggest a protective role
for fruit intake on the risk of neovascular ARM.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.

PMID: 15197064 [PubMed - indexed for MEDLINE]

2277: Arch Ophthalmol. 2004 Jun;122(6):853-6.

Photodynamic therapy with verteporfin for subfoveal choroidal neovascularization 
in age-related macular degeneration: results of an effectiveness study.

Sharma S, Bakal J, Oliver-Fernandez A, Blair J.

Department of Epidemiology and Ophthalmology, Queen's University, and the
Cost-Effective Ocular Health Policy Unit, Hotel Dieu Hospital, Kingston, Ontario.
sanjay_sharma60@hotmail.com

OBJECTIVE: To determine the postapproval effectiveness of photodynamic therapy
(PDT) with verteporfin for the treatment of predominantly classic subfoveal
choroidal neovascularization (CNV) secondary to age-related macular degeneration.
METHODS: Forty-five consecutive patients treated with PDT for subfoveal CNV were 
compared with an untreated historical control group. Control patients had
subfoveal CNV and were first seen by us within 1 year before Health Canada's
approval of verteporfin. Both groups were followed up for the development of
significant visual loss, stability, or improvement. Multivariate models were
constructed to evaluate the effectiveness of PDT, controlling for multiple
covariates (age, sex, baseline visual acuity, follow-up time, lesion size, and
number of treatments). RESULTS: Significant differences were noted in the change 
in visual acuity between those who did and did not receive PDT (chi(2) = 5.9, P
=.048). Patients who received PDT were 2.9 times (95% confidence interval,
0.9-9.1) less likely to develop a moderate (>2 lines) visual loss (chi(2) = 3.2, 
P =.07). Controlling for covariates, patients who received PDT were 13.7 times
(95% confidence interval, 1.4-132.6) more likely to develop a visual improvement 
of at least 1 line. CONCLUSION: Compared with historical controls, PDT was
demonstrated to be effective for the treatment of predominantly classic subfoveal
CNV.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15197060 [PubMed - indexed for MEDLINE]

2278: Retina. 2004 Jun;24(3):399-406.

Photodynamic therapy and vitelliform lesions.

Ergun E, Costa D, Slakter J, Yannuzzi LA, Stur M.

Department of Ophthalmology, University of Vienna Medical School, Vienna,
Austria. erdem.ergun@akh-wien.ac.at

PURPOSE: To investigate the effect of photodynamic therapy (PDT) with verteporfin
on patients with vitelliform lesions caused by cuticular drusen or adult-onset
foveomacular vitelliform dystrophy (AOFVD). DESIGN: Observational case series.
PATIENTS AND METHODS: Eight eyes of seven patients from two centers were examined
prospectively. Each patient received PDT with verteporfin applied to the
vitelliform lesions. RESULTS: Photodynamic therapy did not significantly affect
the median visual acuity outcome (20/50 before PDT and 20/66 after PDT) in all
seven treated patients. Of note, however, were four eyes of four patients who
experienced a severe decrease in visual acuity after PDT with verteporfin. The
temporary relationship of the vision loss to the treatment suggests that this may
represent an adverse effect from therapy. The fluorescein angiographic appearance
was virtually unchanged in all treated patients, whereas indocyanine green
angiography showed typical PDT-associated reduction of choroidal perfusion in the
treatment area. CONCLUSION: Photodynamic therapy does not have a positive
influence on the visual outcome in patients with vitelliform lesions and may have
a negative impact on vision in some treated patients. It is important for
physicians using PDT to exercise caution in distinguishing between choroidal
neovascular membranes and vitelliform lesions because the outcome in this latter 
group may be worse with application of PDT than with the natural course.

Publication Types: 
    Case Reports
    Multicenter Study

PMID: 15187662 [PubMed - indexed for MEDLINE]

2279: Retina. 2004 Jun;24(3):376-82.

Long-term results of treatment of macular complications in eyes with immune
recovery uveitis using a graded treatment approach.

El-Bradey MH, Cheng L, Song MK, Torriani FJ, Freeman WR.

Shiley Eye Center, San Diego, CA 92093-0946, USA.

PURPOSE: To evaluate the results of a graded treatment approach in a cohort of
eyes with macular complications of immune recovery uveitis. METHODS: A cohort of 
18 eyes of 13 patients representing all eyes with these complications at the
University of California, San Diego AIDS Ocular Treatment Unit was studied. Eyes 
were classified into three groups and treated according to a graded protocol.
RESULTS: Eyes with mild disease (macular edema and vision of 20/30 or better)
were observed. These six eyes maintained good vision with only one dropping to
20/40. In eyes with worse macular edema and vision of 20/30 or worse (10 eyes of 
9 patients), repository sub-Tenon steroid injections were used repeatedly. There 
were no complications of steroid use but visual improvement occurred in only 40% 
of eyes. Macular edema persisted. In eyes with structural macular changes, such
as epiretinal membrane, vitrectomy resulted in vision improvement in three of
four eyes. The cystoid macular edema persisted despite surgery. CONCLUSION: Mild 
cases of immune recovery uveitis and macular edema may be observed. In eyes with 
reduction of vision due to cystoid macular edema, there was only a modest
treatment effect using repository corticosteroids. Eyes with immune recovery
uveitis that develop epiretinal membrane undergo some visual improvement after
removal of the membrane. The macular edema of immune recovery uveitis is
resistant to corticosteroid treatment.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15187659 [PubMed - indexed for MEDLINE]

2280: Retina. 2004 Jun;24(3):356-9.

Retinal choroidal collateral circulation after radial optic neurotomy correlated 
with the lessening of macular edema.

Spaide RF, Klancnik JM Jr, Gross NE.

Vitreous-Retina-Macula Consultants of New York and the Manhattan Eye Ear and
Throat Hospital, New York, New York 10021, USA. vrmny@aol.com

PURPOSE: To evaluate patients who had undergone radial optic neurotomy for
central retinal vein occlusion for the presence of retinal choroidal collateral
circulation and to correlate these collaterals with changes in macular thickness 
during follow-up. Radial optic neurotomy is designed to release proposed pressure
within the scleral canal. METHODS: Retrospective review of patients undergoing
radial optic neurotomy. The patients had a baseline examination including
ophthalmoscopy, fluorescein angiography, and optical coherence tomography. At an 
interval follow-up at approximately 3 months the patients were reevaluated with
ophthalmoscopy, optical coherence tomography, and indocyanine green angiography. 
RESULTS: There were 6 patients, and the mean age was 68.3 years. The mean time
from onset of the central retinal vein occlusion to the radial optic neurotomy
was 2.3 months. One patient had no collateral vessels, three patients had
significant collaterals, and two patients had moderate-caliber collaterals. The
mean central macular thickness preoperatively was 1,021 microm and the mean
central macular thickness postoperatively was 733 microm. The change in macular
thickness was highly correlated with the degree of development of collaterals
from the retinal to the choroidal circulation (P = 0.008, Spearman's rho = 0.93).
CONCLUSION: Although all patients had a radial optic neurotomy a significant
determinant in reduction of macular edema was the presence of retinal-choroidal
collateral circulation. This suggests that there may be additional mechanisms,
other than simple release of alleged pressure in the scleral canal, for any
observed effects from radial optic neurotomy.

PMID: 15187655 [PubMed - indexed for MEDLINE]

2281: Retina. 2004 Jun;24(3):348-55.

Internal limiting membrane peeling for decompression of macular edema in retinal 
vein occlusion: a report of 14 cases.

Mandelcorn MS, Nrusimhadevara RK.

Department of Ophthalmology and Vision Science, University of Toronto, Toronto,
Ontario, Canada. mark.mandelcorn@utoronto.ca

BACKGROUND: Currently, there is no proven treatment for macular edema due to
central retinal vein occlusion (CRVO). Moreover, not all cases with macular edema
due to branch retinal vein occlusion (BRVO) respond to laser photocoagulation. We
postulated that internal limiting membrane (ILM) peeling for decompression of
macular edema in cases of retinal vein occlusion would facilitate egress of blood
and extracellular fluid out of the inner retinal layers, leading to reduction of 
macular edema and improvement in visual acuity. METHODS: Fourteen consecutive
patients with macular edema due to CRVO or selected cases of BRVO, not eligible
for laser photocoagulation, underwent pars plana vitrectomy with removal of
preretinal hyaloid and peeling of the ILM stained with indocyanine green dye.
RESULTS: In all cases, intraretinal blood and retinal thickening diminished
within 6 weeks of surgery. Visual acuity improved in 78.6% of cases. No surgical 
complications occurred, although one patient developed nuclear cataract 10 months
postoperatively. CONCLUSION: Pars plana vitrectomy with ILM peeling in selected
cases of CRVO and BRVO showed improvement in visual acuity in this nonrandomized,
noncontrolled study. This pilot study adds support to the concept that ILM
peeling may of visual benefit when compared with the natural history in these
vaso-occlusive diseases.

Publication Types: 
    Case Reports
    Clinical Trial

PMID: 15187654 [PubMed - indexed for MEDLINE]

2282: Graefes Arch Clin Exp Ophthalmol. 2004 Jul;242(7):541-8. Epub 2004 Jun 5.

Improvement in near visual function after macular translocation surgery with
360-degree peripheral retinectomy.

Toth CA, Lapolice DJ, Banks AD, Stinnett SS.

Department of Ophthalmology, Duke University Medical Center, Box 3802, Durham, NC
27701, USA. toth004@mc.duke.edu

BACKGROUND. Information is limited on how specific near-vision skills are
impacted by therapies such as macular translocation surgery with 360-degree
retinectomy (MT360) for age-related macular degeneration (AMD). METHODS.
Standardized tests of near vision were given to 25 consecutive patients with AMD 
who met entry criteria for this study, preoperatively and 6 and 12 months after
MT360. Tests included: near acuity with the Lighthouse chart, timed reading speed
using Sloan cards, contrast sensitivity, and color vision. Distance acuity was
measured using Bailey-Lovey charts. Measures of preoperative visual function were
analyzed to identify those predictive of visual outcomes. RESULTS. Distance
acuity was 20/80 or better in 52% of patients at 12 months after surgery, and
mean acuity improved from approximately 20/125 preoperatively to approximately
20/100 at 12 months. Mean near acuity improved from 3.2+/-2.5 M before surgery to
1.5+/-1.0 M at 12 months (significant change of -1.5+/-2 M, P<0.001). Gain of
greater than five numbers in contrast sensitivity at 12 months was also
significant ( P<0.001). Mean reading speed improved from 41+/-31 words per minute
(wpm) before surgery to 67+/-44 wpm at 12 months (significant gain of 25+/-33
wpm, P=0.001). Preoperative distance acuity, near acuity, and reading speed were 
each predictors of postoperative near visual function. CONCLUSION. Standardized
testing of near visual function provides important predictive and functional
outcome data for MT360. MT360 significantly improved near visual function
(including near acuity, reading speed and contrast sensitivity) in patients with 
subfoveal lesions from AMD in the second eye.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15185091 [PubMed - indexed for MEDLINE]

2283: Eye. 2005 Jun;19(6):611-6.

Comment in:
    Eye. 2006 Dec;20(12):1374-5; author reply 1375.

An evaluation of photographic screening for neovascular age-related macular
degeneration.

Maberley DA, Isbister C, Mackenzie P, Aralar A.

Department of Ophthalmology, University of British Columbia, Vancouver BC,
Canada. dmaberle@vanhosp.bc.ca

BACKGROUND: Photographic screening for neovascular age-related macular
degeneration (AMD) is not commonly employed because the prevalence of treatable
disease is low and fluorescein angiography is considered necessary for the
diagnosis of this form of AMD. However, there may be a role for colour retinal
imaging in assisting with the diagnosis and triage of subjects with neovascular
AMD. The purpose of this study was to evaluate the utility of colour fundus
photographs for identifying subjects with potentially treatable neovascular AMD. 
METHODS: A total of 74 stereo pairs of Kodachrome colour slides of subjects with 
AMD were evaluated (i) nonstereoscopically, (ii) stereoscopically, and (iii)
stereoscopically with visual acuity and visual symptom data. Two retina
specialists read the images to identify active exudative lesions. RESULTS: The
kappa statistic comparing the retinal specialists diagnosis of treatable
neovascular AMD from color slides was excellent. The sensitivity and specificity 
of nonstereo images for the appropriate categorization of lesions was 0.95 and
0.90 respectively. The evaluation of stereo pairs was more sensitive, but less
specific, 0.98, 0.83, as was the evaluation of stereo-pairs with clinical
histories and visual acuities, 1.00, 0.77. CONCLUSIONS: The evaluation of colour 
images for subjects with suspected exudative macular degeneration can be
diagnostic for neovascular AMD and may expedite the appropriate referral of
patients for more timely angiography and treatment. Incorporating more clinical
information for the image evaluators ((i) stereo image pairs and/or (ii)
presenting symptomatology and visual acuity data) led to a decrease in the
false-negative rate, but also decreased the screening specificity.

Publication Types: 
    Evaluation Studies

PMID: 15184945 [PubMed - indexed for MEDLINE]

2284: Eye. 2004 Jun;18(6):595-9.

Pulsatile ocular blood flow of choroidal neovascularization in asymmetric
age-related macular degeneration after transpupillary thermotherapy.

Chen SJ, Cheng CY, Lee AF, Lee FL, Hsu WM, Liu JH.

Department of Ophthalmology, Taipei Veterans General Hospital, National Yang-Ming
University, School of Medicine, Taipei, Taiwan. sjchen@vghtpe.gov.tw

PURPOSE: A previous study has shown that the pulsatile ocular blood flow (POBF)
in eyes with asymmetric age-related macular degeneration (AMD) differs. Whereas
eyes with drusen have higher POBF than contralateral eyes with disciform
scarring, the POBF of eyes with drusen is lower relative to contralateral eyes
with choroidal neovascularization (CNV). This study was designed to assess
whether the POBF of eyes with CNV changes after transpupillary thermotherapy
(TTT), using the contralateral eyes with drusen or scarring without TTT as
controls. METHODS: In total, 26 patients with CNV in one eye and drusen or
scarring in the other were enrolled in this prospective case series. Eyes with
CNV were treated with TTT. POBF was measured monthly in both eyes of each
subject. RESULTS: Before TTT, the POBF of eyes with CNV was 1179+/-317
microl/min. After TTT, the POBF of CNV eyes had decreased at 1 month (1015+/-273 
microl/min, P=0.002) and 2 months (945+/-398 microl/min, P=0.011) of follow-up,
but had rebounded at 3 months (P=0.441) and 6 months (P=0.084). CONCLUSIONS:
These findings suggest that TTT decreases the pulsatile choroidal blood flow in
eyes with CNV in patients with asymmetric AMD and the effects persist for 2
months. POBF may be used as a modality to monitor the therapeutic effects of CNV 
in asymmetric exudative AMD.

PMID: 15184925 [PubMed - indexed for MEDLINE]

2285: Eye. 2004 Jun;18(6):588-94.

Comment in:
    Eye. 2005 Sep;19(9):1027-8.

The incidence and outcome of photodynamic therapy for macular degeneration in the
Northern region of the UK.

Talks SJ, Setty R, Clarke L.

Department of Ophthalmology, Royal Victoria Infirmary, Newcastle Upon, Tyne, UK. 
James.Talks@ncl.ac.uk

PURPOSE: To assess the patients who have had photodynamic therapy (PDT) in the
Northern region of the UK, in relation to the eligibility criteria found to
benefit in the TAP study (treatment of age-related macular degeneration with
photodynamic therapy study), so as to make an estimate of the number of patients 
who might benefit from this treatment and to present the outcome of the treatment
so far. METHOD: The records and fluorescein angiograms (FFAs) of all patients who
had had PDT in the Northern region between 2001 and 2002 were reviewed for
compliance with the TAP criteria of >50% classic choroidal neovascularization and
>34 letters on the 2 m logMAR Early Treatment Diabetic Retinopathy Study chart.
NHS funding has been available in the Northern Region since January 2001 for
'second eye' involvement. A review of all the angiograms performed for exudative 
macular degeneration in 1 year was also performed. The visual outcome of those
patients 1 year from baseline was measured. RESULTS: A total of 82 'second eye'
patients were treated between January 2001 and December 2002. This gives an
incidence of 65 per 3 million and so about 1300 in the whole of the UK
(population 60 million). In all, 238 FFAs were performed on exudative macular
degeneration, with 21% being found eligible for PDT. As of February 2003, 54 TAP 
criteria, macular degeneration patients were 1 year from initial treatment. Of
these, 12 had incomplete follow-up and 13 patients had lost more than 15 letters.
The responder rate defined as losing <15 letters was 42-13/42=69%. Seven of those
who did not make 1-year follow-up had lost more than 15 letters when last seen,
giving a responder rate of 54-20/54=63%. CONCLUSION: There may not be as many
patients eligible for PDT, using the TAP criteria, as previously hoped. The
outcome of treatment appears similar to that found in the TAP study.

PMID: 15184924 [PubMed - indexed for MEDLINE]

2286: Am J Ophthalmol. 2004 Jun;137(6):1142-3.

Serum levels of triamcinolone acetonide after intravitreal injection.

Degenring RF, Jonas JB.

Department of Ophthalmology, Faculty for Clinical Medicine Mannheim,
Ruprecht-Karls-University, Heidelberg, Mannheim, Germany.
robert.degenring@augen.ma.uni-heidelberg.de

PURPOSE: To evaluate serum levels of triamcinolone acetonide after intravitreal
high-dose injection. DESIGN: Prospective, interventional case series study.
METHODS: For 20 consecutive patients, venous blood samples were taken before and 
13 +/- 19 days (range 4 to 92) after an intravitreal injection of 20 to 25 mg
triamcinolone acetonide as treatment of edematous macular diseases. RESULTS:
Serum levels of triamcinolone acetonide did not differ significantly (P =.174; t 
test for paired matches) preoperatively (0 microg/l) and postoperatively (0.065
microg/l +/- 0.21 microg/l). In 18 eyes (90%), triamcinolone acetonide could not 
be detected in serum samples. For two patients (10%), serum samples taken 5 days 
and 7 days after the injection, respectively, contained 0.5 microg/l
triamcinolone acetonide and 0.8 microg/l triamcinolone acetonide, respectively.
CONCLUSION: After an intravitreal high-dose injection of 20 to 25 mg
triamcinolone acetonide, triamcinolone acetonide is not, or only marginally,
detectable in serum samples obtained within 4 to 92 days after the injection.

PMID: 15183810 [PubMed - indexed for MEDLINE]

2287: Am J Ophthalmol. 2004 Jun;137(6):1116-7.

Interobserver variability in optical coherence tomography for macular edema.

Browning DJ.

Charlotte Eye, Ear, Nose, and Throat Associates, Charlotte, North Carolina 28210,
USA. djbrowning@carolina.rr.com

PURPOSE: To assess the interobserver variability of optical coherence tomography 
(OCT) measurements in patients with macular edema. DESIGN: Noninterventional case
series using a diagnostic instrument. METHODS: Ordinary least products analysis
of OCT data obtained by two masked observers from a set of 20 eyes from 10
patients. SETTING: Private retina practice. RESULTS: Foveal zone thickness
measurements were operator dependent. Fixed and proportional bias was found
between the two observers. Total macular volume measurements were independent of 
observers. CONCLUSION: Foveal zone thickness measurements are not directly
comparable across different observers, but total macular volume measurements are 
directly comparable. Multicenter studies involving OCT measurements and clinical 
users of OCT data will need to factor interobserver variability into conclusions 
drawn from pooled OCT foveal zone thickness measurements.

PMID: 15183798 [PubMed - indexed for MEDLINE]

2288: Am J Ophthalmol. 2004 Jun;137(6):993-1001.

Comment in:
    Am J Ophthalmol. 2005 Feb;139(2):395; author reply 395-6.

A prospective multicenter clinical trial to evaluate the safety and effectiveness
of the implantable miniature telescope.

Lane SS, Kuppermann BD, Fine IH, Hamill MB, Gordon JF, Chuck RS, Hoffman RS,
Packer M, Koch DD.

Associated Eye Care, Stillwater, Minnesota, USA.

PURPOSE: To evaluate the safety and preliminary efficacy of a novel visual
prosthetic device, the Implantable Miniature Telescope, IMT (by Dr Isaac
Lipshitz) (IMT), in a phase I trial in patients with significant bilateral
central vision impairment from late-stage age-related macular degeneration (AMD).
The IMT is designed to reduce the relative size of the scotoma by rendering
enlarged (threefold) central visual field images over the central and peripheral 
retina. DESIGN: Prospective, multicenter, open-label clinical trial. METHODS: In 
this prospective, multicenter phase I trial, 14 patients aged 60 or older with
bilateral geographic atrophy or disciform scar AMD, cataract, and best-corrected 
visual acuity (BCVA) between 20/80 and 20/400 had an IMT implanted in one eye.
Distance and near BCVA, endothelial cell density, and quality of life, measured
as activities of daily life (ADL), were evaluated preoperatively and
postoperatively. RESULTS: At 12 months, 10 (77%) of 13 patients gained 2 more
lines of either distance or near BCVA, and eight (62%) of 13 patients gained 3 or
more lines in either distance or near BCVA. Mean endothelial cell density
decreased by 13%. All adverse events resolved without sequelae. ADL scores
improved in the majority of patients. CONCLUSION: The results of this phase I
trial support further evaluation of the IMT in a larger study population with
late-stage AMD. A phase II/III trial is in progress.

Publication Types: 
    Clinical Trial
    Clinical Trial, Phase I
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 15183782 [PubMed - indexed for MEDLINE]

2289: Exp Eye Res. 2004 Jul;79(1):21-7.

Plasma and macular responses to lutein supplement in subjects with and without
age-related maculopathy: a pilot study.

Koh HH, Murray IJ, Nolan D, Carden D, Feather J, Beatty S.

Optometry Section, School of Chemical and Life Sciences, Singapore Polytechnic,
Singapore. hhkoh@sp.edu.sg

There is a growing body of evidence which suggests that macular pigment (MP),
which is entirely of dietary origin, protects against age-related maculopathy. We
evaluated the effect of a daily 20 mg lutein ester (equivalent of 10 mg/day free 
lutein) supplement in patients with early age-related maculopathy (ARM), in terms
of macular pigment optical density (MPOD) and plasma concentrations of lutein.
MPOD was measured using a flicker photometric technique in seven ARM sufferers
and six age-matched controls over a period of supplementation which lasted 18-20 
weeks. Plasma lutein increased from a mean (SD) baseline concentration of 182
(127)ng ml(-1) to a peak of 1077 (165)ng ml(-1) in ARM patients, and from 152
(57) to 1110 (605)ng ml(-1) in control subjects. Mean MPOD had increased
significantly from baseline of 0.24 to a peak of 0.31 in ARM sufferers. This mean
increment of 0.07 was the same for the age-matched controls (baseline: 0.20;
peak: 0.27). The augmentation of MP, and plasma concentrations of lutein,
following supplementation in subjects with ARM provides the first evidence the
disease is not associated with intestinal malabsorption of the relevant macular
carotenoids, and that a diseased macula can accumulate and stabilise lutein
and/or zeaxanthin. Furthermore, these results suggest that the beneficial effects
of lutein supplementation, if any, may be extended to subjects with established
ARM.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15183097 [PubMed - indexed for MEDLINE]

2290: Clin Experiment Ophthalmol. 2004 Jun;32(3):255-8.

Refractive status and the 5-year incidence of age-related maculopathy: the Blue
Mountains Eye Study.

Wang JJ, Jakobsen KB, Smith W, Mitchell P.

Centre for Vision Research, Department of Ophthalmology and the Westmead
Millennium Institute, University of Sydney, Sydney, Australia.
jiejin_wang@wmi.usyd.edu.au

This study aimed to assess the longitudinal association between refraction and
5-year incident age-related maculopathy (ARM) in the Blue Mountains Eye Study
population. The dataset included 3654 participants aged 49+ (82.4% of eligible)
examined at baseline (1992-1994), and 2335 (75.1% of survivors) examined after 5 
years. Retinal photograph grading followed the International ARM Classification. 
Incident ARM was assessed using a side-by-side comparison. Refraction was
performed using autorefraction with subjective refinement. Spherical equivalent
was calculated from spherical plus half the cylindrical power. After adjusting
for age, sex and smoking, no association was found between baseline spherical
equivalent and 5-year incident late or early ARM. Hyperopic right eyes had
slightly higher incident rates for late (0.8%) and early (6.3%) ARM, compared
with myopic (0.4% and 4.1%, respectively) or emmetropic (0.5% and 5.0%,
respectively) right eyes. After multivariable adjustment, this study found no
significant association between hyperopia and the 5-year incidence of late or
early ARM. Left eyes or the combined data from both eyes had similar findings.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15180836 [PubMed - indexed for MEDLINE]

2291: Adv Exp Med Biol. 2003;533:83-9.

Proteomic approaches to understanding age-related macular degeneration.

Hollyfield JG, Salomon RG, Crabb JW.

Ophthalmic Research, Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, 
OH 44195, USA. hollyfj@ccf.org

Microdissection methods have been developed for isolating drusen and Bruch's
membrane from human eyes. Comparative proteomic studies of these isolates from
normal and AMD donors were pursued for clues to the biochemical pathways involved
in the pathogenesis of AMD. A total of 129 potential drusen proteins were
identified by LC MS/MS and immunocytochemical analyses have confirmed drusen
localization for approximately 16% of the proteins. The most common drusen
proteins appear to be TIMP-3, clusterin, vitronectin and serum albumin. Western
blot analysis suggests that carboxyethyl pyrrole-protein adducts derived from
docosahexaenoate-containing lipids are more abundant in AMD than in normal
tissues. Abnormal protein cross-links and advanced glycation end products were
also observed in drusen and Bruch's membrane. Lipid oxidation products and
oxidative protein modifications may be causally involved in drusen formation and 
Bruch's membrane thickening.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.
    Review

PMID: 15180251 [PubMed - indexed for MEDLINE]

2292: Can J Ophthalmol. 2004 Apr;39(3):245-50.

Pseudophakic cystoid macular edema: ketorolac alone vs. ketorolac plus
prednisolone.

Singal N, Hopkins J.

Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, 
Ont.

BACKGROUND: Pseudophakic cystoid macular edema (CME) following
phacoemulsification is the most common complication after cataract surgery.
Treatment focuses on the reduction of inflammation with topical use of both
steroids and NSAIDS. The latter have been shown to be of benefit in chronic CME, 
but topical NSAID and steroid treatment has only recently been shown to be of
benefit in acute CME. We evaluated the use of topically administered NSAIDS and
steroids in the management of both acute and chronic pseudophakic CME. METHODS:
This was a prospective double-masked randomized controlled trial. Patients with
clinical CME occurring at least 6 weeks following cataract extraction were
referred for consideration of enrolment. Patients were excluded if they had
Snellen vision better than 20/40, no CME on clinical examination, no CME on
angiography, recent use of steroids, preexisting macular disease or diabetic
maculopathy on angiography. Ten patients were randomly assigned to receive either
0.5% ketorolac tromethamine plus placebo (four patients) or 0.5% ketorolac
tromethamine plus 1% prednisolone acetate (six patients); all 10 completed the
study. Patients were assessed at baseline and at 30, 60 and 90 days. Fluorescein 
angiography was performed at baseline and at 90 days. The primary outcome
measures were improvement in Early Treatment Diabetic Retinopathy Study Snellen
equivalent vision and resolution of cysts on clinical examination. RESULTS: No
statistically significant differences were found between the two groups in either
of the outcome measures at any visit. Subgroup analysis of the patients with
chronic CME also showed no significant difference between the two groups.
INTERPRETATION: We found no statistically significant difference in outcome
between patients who received ketorolac and those who received ketorolac plus
prednisolone for acute or chronic CME. The value of topical steroid therapy for
chronic CME remains unproven.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15180141 [PubMed - indexed for MEDLINE]

2293: Ophthalmology. 2004 Jun;111(6):1201-8.

Erratum in:
    Ophthalmology. 2004 Sep;111(9):1640.

Subretinal recombinant tissue plasminogen activator injection and pneumatic
displacement of thick submacular hemorrhage in Age-Related macular degeneration.

Olivier S, Chow DR, Packo KH, MacCumber MW, Awh CC.

Retina-Vitreous Associates, Nashville, Tennessee, USA.

OBJECTIVE: To evaluate the anatomic and visual outcomes after a surgical
procedure for displacement of thick submacular hemorrhage in patients with
age-related macular degeneration. DESIGN: Retrospective, noncomparative,
interventional case series. PARTICIPANTS: Twenty-nine consecutive eyes of 28
patients with thick submacular hemorrhage secondary to age-related macular
degeneration. INTERVENTION: The procedure consisted of a pars plana vitrectomy
with subretinal recombinant tissue plasminogen activator injection (125
micrograms/ml) through a translocation microcannula, followed by fluid-air
exchange and postoperative prone positioning [correction]. MAIN OUTCOME MEASURES:
Intraoperative and postoperative surgical complications, preoperative and
postoperative best-corrected visual acuities, postoperative fluorescein
angiography results, and additional postoperative treatments. RESULTS: Total
subfoveal blood displacement was achieved in 25 eyes, with subtotal displacement 
in the others. Based on fluorescein angiography results, 8 eyes were eligible for
additional postoperative treatments. At 3 months, 17 eyes had gained more than 2 
lines of visual acuity, whereas 3 had lost more than 2 lines. The difference
between preoperative and 3-month postoperative visual acuity was statistically
significant (P = 0.0167). Complications consisted of 2 cases of vitreous
hemorrhage that cleared within 4 weeks. CONCLUSIONS: This surgical technique
seems useful in displacing thick submacular hemorrhage secondary to age-related
macular degeneration, allowing postoperative fluorescein angiography testing and,
potentially, subsequent treatments. No significant complication from the
procedure was identified. However, further controlled studies will be required to
assess its efficacy in the management of this difficult clinical problem.

PMID: 15177972 [PubMed - indexed for MEDLINE]

2294: Ophthalmology. 2004 Jun;111(6):1176-82.

Five-year incidence of age-related maculopathy: the Visual Impairment Project.

Mukesh BN, Dimitrov PN, Leikin S, Wang JJ, Mitchell P, McCarty CA, Taylor HR.

Centre for Eye Research Australia, The University of Melbourne, Melbourne,
Australia. mukesh.bickol@mcrf.mfldclin.edu

PURPOSE: To describe the 5-year incidence of age-related maculopathy (ARM) and
the progression of the early stages of ARM lesions in Melbourne, Australia.
DESIGN: Population-based cohort study. PARTICIPANTS: A total of 3271 participants
aged 40 years and older from Melbourne, Victoria, Australia. MAIN OUTCOME
MEASURES: The 5-year incidence and progression of ARM lesions. METHODS:
Participants were recruited through a cluster random sampling from 9 urban
clusters. Baseline examinations were conducted from 1992 through 1994, and the
follow-up data were collected from 1997 through 1999. Presence of ARM lesions was
graded from color stereo fundus photographs according to the International
Classification and Grading System. RESULTS: The overall cumulative 5-year
incidence of age-related macular degeneration (AMD) was 0.49% (95% confidence
interval [CI], 0.2-0.8) and that of early ARM was 17.3% (95% CI, 8.7-26.0). The
incidence of all ARM lesions increased with age (all P<0.001). The 5-year
incidence of AMD was 0%, 0.69%, 1.7%, and 6.3% and that of early ARM was 13%,
22.7%, 29.8%, and 20% for participants aged 60 years and younger, aged 60 to 69
years, aged 70 to 79 years, and aged 80 years and older at baseline,
respectively. People with soft indistinct drusen with pigmentary abnormalities
had a 9.5 times (95% CI, 1.9-45.6) higher risk of developing AMD compared with
people with soft drusen or pigmentary abnormalities. After adjusting for age,
people with unilateral early ARM at baseline were 3 times (95% CI, 0.98-8.0) as
likely to have early ARM in their second eye when compared with people with no
ARM in both eyes. CONCLUSIONS: These data suggest that 1 in 3 persons aged 70
years or older will have ARM lesions over a 5-year period and that the disease
will progress to a more severe form after the age of 80 years. The presence of
soft indistinct drusen with pigmentary abnormalities significantly increased the 
risk for development of AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15177968 [PubMed - indexed for MEDLINE]

2295: Ophthalmology. 2004 Jun;111(6):1169-75.

Is medication use associated with the incidence of early age-related maculopathy?
Pooled findings from 3 continents.

van Leeuwen R, Tomany SC, Wang JJ, Klein R, Mitchell P, Hofman A, Klein BE,
Vingerling JR, Cumming RG, de Jong PT.

Department of Epidemiology & Biostatistics, Erasmus Medical Center, Rotterdam,
The Netherlands.

OBJECTIVE: To investigate whether there is an association between the use of
medication and the incidence of early age-related maculopathy (ARM). DESIGN:
Pooled data from 3 prospective, population-based cohort studies. PARTICIPANTS:
Subjects without early and late ARM at baseline who participated in the follow-up
of the Beaver Dam Eye Study (n = 3012), the Rotterdam Study (n = 3434), and the
Blue Mountains Eye Study (n = 2203). METHODS: Stereoscopic color fundus
photographs of all participants were graded according to a standardized protocol.
At baseline, current use of prescription and over-the-counter medication was
assessed by interview, and the drug name was confirmed at the research centers.
Procedures and definitions were similar at both baseline and follow-up across the
3 study sites. MAIN OUTCOME MEASURES: Incidence of early ARM, defined as the
presence at follow-up of either soft distinct drusen with pigmentary changes or
soft indistinct or reticular drusen. RESULTS: In the pooled cohort, 53.3% of
participants used at least one of the medications selected for this study. Within
a mean period of 5.6 years, a total of 683 subjects developed early ARM. Users of
antihypertensive medication in general, and beta-blockers in particular, had a
borderline statistically significant increased risk of early ARM (odds ratio [OR]
for beta-blockers, 1.3; 95% confidence interval [CI], 1.0-1.6) when adjusted for 
systolic (or diastolic) blood pressure and other confounders. A protective effect
of borderline significance was found among women using hormone replacement
therapy (OR, 0.6; 95% CI, 0.4-1.0) and in persons using tricyclic antidepressants
(OR, 0.4; 95% CI, 0.2-1.0). In contrast with beta-blockers, the direction and
magnitude of the association with hormone replacement therapy and tricyclic
antidepressants were inconsistent among the 3 study populations. CONCLUSIONS:
Pooled data from 3 population-based studies showed no strong associations between
medication use and the incidence of early ARM. Of borderline significance were a 
slightly increased risk among users of beta-blockers and a reduced risk among
users of hormone replacement therapy and users of tricyclic antidepressants.
Although beta-blocker use could be a proxy for systemic hypertension, these
findings warrant further investigations, preferably including information on the 
dosage and duration of drug exposure.

Publication Types: 
    Meta-Analysis
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15177967 [PubMed - indexed for MEDLINE]

2296: J Cataract Refract Surg. 2004 Jun;30(6):1177-89.

Intraocular telescopic lens evaluation in patients with age-related macular
degeneration.

Alió JL, Mulet EM, José M, Ruiz-Moreno, Sanchez MJ, Galal A.

Instituto Oftalmológico de Alicante, Alicante, Spain. jlalio@oftalio.com

PURPOSE: To evaluate the improvement of distance and near visual acuity after
removal of cataract and implantation of an 3.0x intraocular miniaturized
telescope (IMT) in patients with stable atrophic type age-related macular
degeneration (ARMD). SETTINGS: Instituto Oftalmológico de Alicante and a
multicenter group. METHODS: In this prospective noncomparative multinational
consecutive study, 40 eyes of 40 patients with dry-type ARMD were implanted with 
IMTs at multiple centers. Standard phacoemulsification procedure followed by
enlargement of the incision to 10 mm and implantation in the capsular bag of an
3.0x IMT was carried out in all the cases. Patients were followed for 12 months. 
Evaluation included the differences between preoperative and postoperative
uncorrected and best corrected visual acuity for far and near, position of the
IMT, intraocular pressure, and occurrence of any postoperative complications.
RESULTS: Mean preoperative uncorrected distance visual acuity (UCDVA) in the
operated eye was 0.9 logMAR (0.125 +/- 0.01, range 0.1 to 0.3 in decimal values);
at 1 year postoperatively, mean UCDVA in the operated eye was 0.6 logMAR (0.25
+/- 0.14, range 0.1 to 0.5 in decimal values). Mean preoperative uncorrected near
visual acuity (UCNVA) in the operated eye was 0.8 logMAR (0.16 +/- 0.13, range
0.1 to 0.5 in decimal values); at 1 year postoperatively, mean UCNVA in the
operated eye was 0.4 logMAR (0.4 +/- 0.26, range 0.1 to 1.0 in decimal values).
The differences between pre- and postoperative distance and near visual acuities 
were statistically significant. Six cases were explanted, and 14 developed
adverse effects, 7 of which were persistent. The corneal endothelium tolerated
the procedure well. CONCLUSION: Implantation of IMT is feasible and plays an
effective role in improving far and near visual acuity in patients with stable
dry-type ARMD.

Publication Types: 
    Clinical Trial
    Multicenter Study

PMID: 15177591 [PubMed - indexed for MEDLINE]

2297: Am J Hum Genet. 2004 Aug;75(2):174-89. Epub 2004 May 27.

Age-related maculopathy: a genomewide scan with continued evidence of
susceptibility loci within the 1q31, 10q26, and 17q25 regions.

Weeks DE, Conley YP, Tsai HJ, Mah TS, Schmidt S, Postel EA, Agarwal A, Haines JL,
Pericak-Vance MA, Rosenfeld PJ, Paul TO, Eller AW, Morse LS, Dailey JP, Ferrell
RE, Gorin MB.

Department of Human Genetics, University of Pittsburgh Graduate School of Public 
Health, Pittsburgh, PA, USA.

Age-related maculopathy (ARM), or age-related macular degeneration, is one of the
most common causes of visual impairment in the elderly population of developed
nations. In a combined analysis of two previous genomewide scans that included
391 families, containing up to 452 affected sib pairs, we found linkage evidence 
in four regions: 1q31, 9p13, 10q26, and 17q25. We now have added a third set of
families and have performed an integrated analysis incorporating 530 families and
up to 736 affected sib pairs. Under three diagnostic models, we have conducted
linkage analyses using parametric (heterogeneity LOD [HLOD] scores under an
autosomal dominant model) and nonparametric (Sall statistic) methods. There is
ongoing evidence of susceptibility loci within the 1q31, 10q26, and 17q25
regions. If we treat the third set of families as a replication set, then two
regions (10q26 and 17q25) are replicated, with LOD scores >1.0. If we pool all
our data together, then four regions (1q31, 2q14.3, 10q26, and 17q25) show HLOD
or Sall scores > or =2.0. Within the 1q31 region, we observed an HLOD of 2.72
(genomewide P=.061) under our least stringent diagnostic model, whereas the 17q25
region contained a maximal HLOD of 3.53 (genomewide P=.007) under our
intermediate diagnostic model. We have evaluated our results with respect to the 
findings from several new independent genomewide linkage studies and also have
completed ordered subset analyses (OSAs) with apolipoprotein E alleles, smoking
history, and age at onset as stratifying covariates. The OSAs generate the
interesting hypothesis that the effect of smoking on the risk of ARM is
accentuated by a gene in the 10q26 region--a region implicated by four other
studies.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15168325 [PubMed - indexed for MEDLINE]

2298: J Clin Laser Med Surg. 2004 Apr;22(2):91-7.

Evaluation of trans-scleral diode laser using diopexy probe for subfoveal
choroidal neovascular membrane in age-related macular degeneration.

Venkatesh P, Gupta RK, Verma L, Tewari HK.

Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical
Sciences, New Delhi, India.

OBJECTIVE: To evaluate safety and short-term visual and fluorescein angiographic 
effects of trans-scleral diode laser photocoagulation in patients with subfoveal 
choroidal neovascularization from age-related macular degeneration (ARMD).
BACKGROUND DATA: The visual outcome following treatment of subfoveal choroidal
neovascularization in ARMD is still unsatisfactory. Various forms of therapy such
as laser treatment, photodynamic therapy, radiation therapy, transpupillary
thermotherapy, and surgical excision have been tried with variable results.
MATERIALS AND METHODS: Patients with subfoveal choroidal neo-vascularization were
treated with trans-scleral diode laser using the diopexy probe under indirect
ophthalmoscopic visualization and followed up at 2, 6, and 12 weeks. Standardized
protocol refraction, visual acuity testing, reading speed, contrast requirement
measurement, ophthalmic examinations, color fundus photographs, and fluorescein
angiogram were used to evaluate the results of treatment. RESULTS: Eighteen eyes 
of 18 patients were included in the study between April 2000 and May 2002. At 12 
weeks, 81.5% patients showed stabilization (+/-5 letters) in letter visual acuity
score, and one patient showed improvement (gain of more than five letters) in
letter visual acuity score. Reading speed levels and contrast requirement were
found to be similar to pre-laser level at 3 months followup. At 12 weeks,
moderate fluorescein leakage was seen in one eye, minimal leakage was seen in
five eyes, absence of leakage was seen in 10 eyes, and progression was seen in
two eyes. CONCLUSION: Transcleral diode laser treatment of subfoveal choroidal
neovascular membranes in ARMD may be an effective as well as safe alternative in 
the management of these patients.

Publication Types: 
    Clinical Trial

PMID: 15165382 [PubMed - indexed for MEDLINE]

2299: Klin Monatsbl Augenheilkd. 2004 May;221(5):424-6.

Retinal vasculitis and cystoid macular edema after body tattooing: a case report.

Moschos MM, Guex-Crosier Y.

Jules Gonin Eye Hospital, Lausanne University Hospital, Lausanne, Switzerland.

BACKGROUND: To report a case of retinal vasculitis occurring after the placement 
of permanent tattoos. HISTORY AND SIGNS: A 21-year-old male was referred to our
department with impairment of visual acuity. Permanent tattoos covered the head, 
body, arms and legs. The patient was examined with ophthalmoscopy, fluorescein
angiography, indocyanine green angiography and optical coherence tomography.
Systemic medical and laboratory work-up were performed in order to exclude an
infectious agent or an inflammatory disease. He had no history of intravenous
drug abuse. THERAPY AND OUTCOME: Our patient presented severe posterior uveitis
associated with retinal vasculitis and cystoid macular edema. Laboratory tests
ruled out all diseases causing vasculitis. HIV and B, C hepatitis tests were
negative. Cystoid macular edema and vasculitis were resolved after
immunosuppressive therapy. CONCLUSIONS: This is the first description of a
retinal vasculitis associated with cystoid macular edema in a completely healthy 
individual after the placement of permanent tattoos. A phagocytosis of tattoo
pigments leading to their lysis is described in the literature as a mechanism
causing vasculitis.

Publication Types: 
    Case Reports

PMID: 15162298 [PubMed - indexed for MEDLINE]

2300: Invest Ophthalmol Vis Sci. 2004 Jun;45(6):1705-11.

Mutation spectrum and founder chromosomes for the ABCA4 gene in South African
patients with Stargardt disease.

September AV, Vorster AA, Ramesar RS, Greenberg LJ.

Division of Human Genetics, University of Cape Town, Observatory, Cape Town,
South Africa.

PURPOSE: To assess the mutation spectrum of ABCA4 underlying Stargardt disease
(STGD) in South Africa (SA) and to determine whether there is a single or a few
founder chromosomes in SA STGD families. METHODS: Sixty-four probands exhibiting 
the STGD phenotype were screened for mutations in the 50 exons of ABCA4 by
single-strand conformational polymorphism-heteroduplex analysis sequencing and
restriction fragment length polymorphism analysis. Microsatellite marker
haplotyping was used to determine the ancestry in 10 families. RESULTS:
Fifty-seven ABCA4 disease-associated alleles were identified that comprised 16
different sequence variants, of which two were novel, in 40 individuals of the
cohort of 64 subjects. The most common variants identified included the C1490Y,
L2027F, R602W, V256splice, R152X, and 2588G-->C mutations. The C1490Y variant was
the most common disease-associated variant identified (19/64 subjects) and was
absent in 392 control chromosomes. At least 10 ABCA4 disease-associated
haplotypes were identified. Two of these haplotypes, which carried the C1490Y
mutation, were identified in three unrelated families. CONCLUSIONS: Results
suggest that ABCA4 is the major gene underlying STGD in the cohort investigated. 
Five of the six common sequence variants identified were at a higher frequency in
the SA cohort than reported in published data on individuals of similar ancestry.
The mutation and haplotype data suggests that there are several ancestral
haplotypes underlying STGD in SA. There seems to be at least two different
origins for the common C1490Y mutation, as well as two for the R602W mutation,
thereby suggesting several founder effects for STGD in SA.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15161829 [PubMed - indexed for MEDLINE]

2301: Rehabil Nurs. 2004 May-Jun;29(3):90-4.

Optimizing the functionality of clients with age-related macular degeneration.

McGrory A, Remington R.

University of Massachusetts Lowell, School of Health and Environment, 3 Solomont 
Way, Suite 2, Lowell, MA 01854-5126, USA. Arlene_McGrory@uml.edu

Age-related macular degeneration (ARMD) is a major cause of severe vision loss
and blindness among older people. This condition is progressive, incurable, and
significantly compromises central vision. Rehabilitation nurses have a pivotal
role in the assessment and management of clients with ARMD. An understanding of
incidence and pathophysiology of ARMD, as well as health promotion and a new
treatment for ARMD can help rehabilitation nurses design interventions to help
clients maintain an acceptable quality of life despite declining vision.

Publication Types: 
    Review

PMID: 15152418 [PubMed - indexed for MEDLINE]

2302: Br J Ophthalmol. 2004 Jun;88(6):792-5.

Effect of laser treatment for dry age related macular degeneration on foveolar
choroidal haemodynamics.

Figueroa M, Schocket LS, DuPont J, Metelitsina TI, Grunwald JE.

Department of Ophthalmology, Scheie Eye Institute, School of Medicine, University
of Pennsylvania, Philadelphia, PA 19104, USA.

AIM: Previous studies have suggested that laser photocoagulation therapy is
associated with the resolution of drusen in some age related macular degeneration
(AMD) patients. The main aim of the study was to determine whether low intensity 
laser treatment applied according to the Complications of AMD Prevention Trial
(CAPT) protocol produces changes in the choroidal circulation that may help
explain the mechanism leading to the resolution of drusen material. METHODS: This
ancillary study included 30 CAPT patients with bilateral drusen that were treated
and followed at the University of Pennsylvania. Laser Doppler flowmetry was used 
to measure relative choroidal blood velocity (Ch(vel)), volume (Ch(vol)), and
flow (Ch(flow)) in the centre of the fovea. Measurements were obtained through a 
dilated pupil in both eyes of each patient at the initial CAPT visit before laser
treatment was applied in one eye. Measurements were repeated in both eyes of each
subject three months later. Analysis of laser Doppler measurements was performed 
in a masked fashion. RESULTS: In comparison to baseline, no significant
differences in Ch(vel), Ch(vol), or Ch(flow) were observed three months following
the application of low intensity laser according to the CAPT protocol in the
untreated and treated eyes. In comparison to the untreated eyes, no significant
differences were detected in the treated eyes. Based on the variability of flow
measurements in the untreated eyes, the authors estimated an 85% power to detect 
a 15% change in relative blood flow. CONCLUSIONS: The results suggest that large 
alterations in choroidal blood flow do not occur at three months after low
intensity laser therapy following the CAPT protocol.

PMID: 15148214 [PubMed - indexed for MEDLINE]

2303: Graefes Arch Clin Exp Ophthalmol. 2004 Jun;242(6):456-67. Epub 2004 May 11.

Macular translocation in a patient with adult-onset foveomacular vitelliform
dystrophy with light- and electron-microscopic observations on the surgically
removed subfoveal tissue.

Eckardt C, Eckardt U, Groos S, Luciano L, Reale E.

Augenklinik der Städtischen Kliniken, Frankfurt a. M.-Höchst, Gotenstrasse 6-8,
65929, Frankfurt am Main, Germany. C.Eckardt@em.uni-frankfurt.de

PURPOSE: To correlate the functional results of macular translocation (MT) in a
patient suffering from an adult-onset foveomacular vitelliform dystrophy (AFVD)
with the microscopic findings of the surgically removed subfoveal retinal pigment
epithelium (RPE). METHODS: A 78-year-old woman with AFVD underwent MT with 360
degrees retinotomy 3-4 months after loss of reading ability. Most of the
vitelliform material was lost during surgery; the subfoveal tissue was excised,
fixed in aldehydes, postfixed in reduced OsO4 and embedded in epoxy resin.
Semithin sections were stained with toluidine blue for light microscopy (LM) and 
thin sections with uranyl acetate and lead citrate for transmission electron
microscopy (TEM). RESULTS: Postoperatively, the patient developed a retinal
detachment complicated by proliferative vitreoretinopathy (PVR) requiring two
additional vitreoretinal procedures before finally the silicone oil could be
removed. Twenty-two months after MT the distance visual acuity was unchanged at
0.2; the near visual acuity had improved from less than 0.1 before MT to 0.4. The
retina was completely attached. LM and TEM revealed serious alterations
indicative of a breakdown of the outer layer of the retina. CONCLUSION: Through
the present single case it is not possible to determine whether MT could be a
therapeutic approach in patients with AFVD. The most important cause for the
limited postoperative visual improvement seems to be a primary injury of the
foveal function due to the AFVD. This is supported by the extensive subfoveal
degeneration and necrosis affecting not only the RPE cells but also their
basement membrane and the interposed basal laminar deposits.

Publication Types: 
    Case Reports

PMID: 15138766 [PubMed - indexed for MEDLINE]

2304: Arch Ophthalmol. 2004 May;122(5):758-66.

Relative contributions of reduced vision and general health to NEI-VFQ scores in 
patients with neovascular age-related macular degeneration.

Miskala PH, Bressler NM, Meinert CL.

Department of Ophthalmology, Wilmer Clinical Trials and Biometry, The Johns
Hopkins University School of Medicine, 550 N. Broadway, Ninth Floor, Baltimore,
MD 21205, USA. pmiskala@jhmi.edu

OBJECTIVE: To estimate the relative contributions of central vision loss and
general health to vision-targeted quality of life as measured by the National Eye
Institute Visual Function Questionnaire (NEI-VFQ). METHODS: Data on quality of
life (NEI-VFQ and the 36-Item Short-Form Health Survey [SF-36]) and visual acuity
were collected as part of the Submacular Surgery Trials Pilot Study. Information 
on medical conditions was collected by patient chart review. Twenty-four-month
data for 120 patients were analyzed using linear regression methods. RESULTS:
Median patient age at the 24-month examination was 77 years; 60% were women, and 
98% were non-Hispanic whites. A 3-line decrement in visual acuity in the
better-seeing eye was associated with a 5.1- to 17.1-point decrement in NEI-VFQ
scores after adjustment for general health (SF-36 physical component summary
[PCS] and mental component summary [MCS] scores). A 10-point decrement in the PCS
score was associated with a 4- to 9-point decrement in NEI-VFQ scores after
adjustment for visual acuity in the better-seeing eye and MCS score. A 10-point
decrement in the MCS score was associated with a 4- to 8-point decrement in
NEI-VFQ scores after adjustment for visual acuity in the better-seeing eye and
PCS score. Diabetes, arthritis/rheumatism, and hypertension also had large
effects on NEI-VFQ scores in the adjusted analysis. CONCLUSIONS: The NEI-VFQ is
sensitive to differences in visual acuity in the better-seeing eye, as expected, 
and to differences in general health. Adjustment for general health should be
considered when comparing NEI-VFQ scores between patient groups.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15136325 [PubMed - indexed for MEDLINE]

2305: Arch Ophthalmol. 2004 May;122(5):750-7.

Erratum in:
    Arch Ophthalmol. 2005 Mar;123(3):362.

Sunlight and the 10-year incidence of age-related maculopathy: the Beaver Dam Eye
Study.

Tomany SC, Cruickshanks KJ, Klein R, Klein BE, Knudtson MD.

Department of Ophthalmology and Visual Sciences, Medical School, University of
Wisconsin-Madison, 610 N. Walnut Street, Madison, WI 53726, USA.

OBJECTIVE: To examine the association of sunlight exposure and indicators of sun 
sensitivity with the 10-year incidence of age-related maculopathy (ARM). DESIGN: 
Population-based cohort study. PARTICIPANTS: We included persons aged 43 to 86
years at the baseline examination from 1988 to 1990, living in Beaver Dam, Wis,
of whom 3684 persons underwent 5-year follow-up and 2764 underwent 10-year
follow-up. METHODS: Data on sun exposure and indicators of sun sensitivity were
obtained from a standardized questionnaire administered at baseline and/or
follow-up. We determined ARM status by grading stereoscopic color fundus
photographs using the Wisconsin Age-Related Maculopathy Grading System. MAIN
OUTCOME MEASURES: Incidence and progression of ARM. RESULTS: While controlling
for age and sex, we found that participants exposed to the summer sun for more
than 5 hours a day during their teens, in their 30s, and at the baseline
examination were at a higher risk of developing increased retinal pigment (risk
ratio [RR], 2.99; 95% confidence interval [CI], 1.18-7.60; P =.02) and early ARM 
(RR, 2.20; 95% CI, 1.02-4.73; P =.04) [corrected] by 10 years than those exposed 
less than 2 hours per day during the same periods. In participants reporting the 
highest summer sun exposure levels in their teens and 30s, the use of hats and
sunglasses at least half the time during the same periods was associated with a
decreased risk of developing soft indistinct drusen (RR, 0.55; 95% CI, 0.33-0.90;
P =.02) and retinal pigment epithelial depigmentation (RR, 0.51; 95% CI,
0.29-0.91; P =.02). Participants who experienced more than 10 severe sunburns
during their youth were more likely than those who experienced 1 or no burn to
develop drusen with a 250-microm diameter or larger (RR, 2.52; 95% CI, 1.29-4.94 
[corrected] P =.01) by the 10-year examination. No relationships were found
between UV-B exposure, winter leisure time spent outdoors, skin sun sensitivity, 
or number of bad sunburns experienced by the time of the baseline examination and
the 10-year incidence and progression of ARM or its associated lesions.
CONCLUSIONS: Few significant relationships between environmental exposure to
light and the 10-year incidence and progression of ARM were found in the Beaver
Dam Eye Study. Consistent with results from the baseline and 5-year follow-up
examinations, significant associations were found between extended exposure to
the summer sun and the 10-year incidence of early ARM and increased retinal
pigment. A protective effect of hat and sunglasses use by participants while in
their teens and 30s against the 10-year incidence of soft indistinct drusen and
retinal pigment epithelial depigmentation was also found, but only in those who
reported the highest amount of sun exposure during the same periods.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15136324 [PubMed - indexed for MEDLINE]

2306: Arch Ophthalmol. 2004 May;122(5):716-26.

Associations of mortality with ocular disorders and an intervention of high-dose 
antioxidants and zinc in the Age-Related Eye Disease Study: AREDS Report No. 13.

Clemons TE, Kurinij N, Sperduto RD; AREDS Research Group.

AREDS Coordinating Center, The EMMES Corp., 401 N. Washington Street, Suite 700, 
Rockville, MD 20850-1707, USA. aredspub@emmes.com

OBJECTIVE: To assess the association of ocular disorders and high doses of
antioxidants or zinc with mortality in the Age-Related Eye Disease Study (AREDS).
METHODS: Baseline fundus and lens photographs were used to grade the macular and 
lens status of AREDS participants. Participants were randomly assigned to receive
oral supplements of high-dose antioxidants, zinc, antioxidants plus zinc, or
placebo. Risk of all-cause and cause-specific mortality was assessed using
adjusted Cox proportional hazards models. RESULTS: During median follow-up of 6.5
years, 534 (11%) of 4753 AREDS participants died. In fully adjusted models,
participants with advanced age-related macular degeneration (AMD) compared with
participants with few, if any, drusen had increased mortality (relative risk
[RR], 1.41; 95% confidence interval [CI], 1.08-1.86). Advanced AMD was associated
with cardiovascular deaths. Compared with participants having good acuity in both
eyes, those with visual acuity worse than 20/40 in 1 eye had increased mortality 
(RR, 1.36; 95% CI, 1.12-1.65). Nuclear opacity (RR, 1.40; 95% CI, 1.12-1.75) and 
cataract surgery (RR, 1.55; 95% CI, 1.18-2.05) were associated with increased
all-cause mortality and with cancer deaths. Participants randomly assigned to
receive zinc had lower mortality than those not taking zinc (RR, 0.73; 95% CI,
0.61-0.89). CONCLUSIONS: The decreased survival of AREDS participants with AMD
and cataract suggests that these conditions may reflect systemic rather than only
local processes. The improved survival in individuals randomly assigned to
receive zinc requires further study.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15136320 [PubMed - indexed for MEDLINE]

2307: Arch Ophthalmol. 2004 May;122(5):710-5.

Morphometric analysis of angiograms of exudative lesions in age-related macular
degeneration.

Ali F, Chan WC, Stevenson MR, Muldrew KA, Chakravarthy U.

Eye & Ear Clinic, Royal Victoria Hospital, The Queen's University of Belfast,
Belfast BT12 6BA, Northern Ireland, United Kingdom.

OBJECTIVES: To analyze the morphometric composition of lesion components in
exudative age-related macular degeneration and to study the relationships between
individual lesion components and choroidal neovascularization (CNV) subtype, at 2
time points. METHODS: Morphometric analysis of 98 sets of angiograms separated by
an interval of at least 3 weeks, with no treatment delivered in the intervening
period between angiograms. Area measurements of individual lesion components were
made from digitally captured angiograms. Choroidal neovascularizations were
classified into subtypes based on the proportions of classic CNV. Fully corrected
distance visual acuity measured on logMAR Early Treatment of Diabetic Retinopathy
Study charts was available at baseline and at a subsequent visit in 78 subjects. 
Data were analyzed using parametric and nonparametric tests, linear regression,
and McNemar test of equal proportions. RESULTS: Wholly and predominantly classic 
CNVs were significantly smaller at initial presentation than minimally classic or
occult with no classic CNVs. Lesions containing blood and lipid were also
significantly larger than lesions not exhibiting these features. Lesions
containing any classic CNV expanded at a significantly greater rate than lesions 
without classic CNV. Approximately 40% of lesions categorized as wholly classic
CNV converted to predominantly classic CNV between baseline and the next
follow-up visit. CONCLUSION: The presence of classic leakage in exudative
age-related macular degeneration is the most important risk factor for rapid
expansion of CNV.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15136319 [PubMed - indexed for MEDLINE]

2308: Eur J Ophthalmol. 2004 Mar-Apr;14(2):137-43.

Vitrectomy results for diffuse diabetic macular edema with and without inner
limiting membrane removal.

Stefaniotou M, Aspiotis M, Kalogeropoulos C, Christodoulou A, Psylla M, Ioachim
E, Alamanos I, Psilas K.

University Eye Clinic of Ioannina, Medical School University of Ioannina,
Ioannina, Greece. ophthalm@cc.uoi.gr

PURPOSE: To determine whether vitrectomy for diffuse diabetic macular edema with 
and without internal limiting membrane (ILM) peeling is equally effective in
reducing edema. METHODS: The authors retrospectively analyzed the surgical
outcomes in 73 eyes of 52 patients with diffuse diabetic macular edema. Eighteen 
eyes (Group A) underwent three-port pars plana vitrectomy with posterior hyaloid 
membrane (PHM) removal, while 55 eyes (Group B) had pars plana vitrectomy with
additional ILM peeling after PHM removal. RESULTS: Intraoperatively, the
posterior hyaloid was found to be attached to the macula in all eyes. In Group A,
macular edema resolved completely in 8 eyes (44.4%) with improvement of visual
acuity (VA). In Group B, VA improved in 38 eyes (69.1%) with complete resolution 
of edema. The results of this study indicated that vitrectomy effectively reduced
macular edema but eyes with ILM peeling (Group B) presented better results than
those without ILM peeling. Another important factor related to the outcome seems 
to be the level of glycosylated hemoglobin (HbA1c). CONCLUSIONS: In eyes with
diffuse diabetic macular edema vitrectomy seems to be effective, but additional
ILM peeling presented better results.

Publication Types: 
    Comparative Study

PMID: 15134111 [PubMed - indexed for MEDLINE]

2309: Indian J Ophthalmol. 2004 Mar;52(1):45-9.

Comment in:
    Indian J Ophthalmol. 2004 Sep;52(3):262; author reply 262.

Transpupillary thermotherapy for choroidal neovascular membrane in age related
macular degeneration.

Agarwal M, Shanmugam MP, Gopal L, Shetty N, Bhende M, Gopal L, Sharma T, Thakur
S, Raman R, Nizamuddin SH, Moorthy KR.

Sankara Nethralaya, Chennai, India.

PURPOSE: To evaluate the efficacy of transpupillary thermotherapy (TTT) in
choroidal neovasularisation (CNVM) secondary to age related macular degeneration 
(AMD). MATERIAL AND METHODS: Retrospective, non-randomized study of 28 eyes of 28
patients with subfoveal CNVM (classic, occult or mixed) secondary to AMD.
RESULTS: Fifteen patients (53.57%) maintained their pre-treatment vision, 2
(7.14%) patients showed improvement of more than 2 lines and 11 (39.28%) patients
showed deterioration of vision by >2 lines. Angiographic and clinical regression 
of CNVM was noted in 19 patients (67.8%) on an average follow up of 15.32 +/-
3.31 months. CONCLUSION: TTT leads to stabilisation of vision in 60% of treated
eyes with CNVM due to AMD.

PMID: 15132379 [PubMed - indexed for MEDLINE]

2310: Indian J Ophthalmol. 2004 Mar;52(1):35-40.

Transpupillary thermotherapy in subfoveal choroidal neovascular membrane
secondary to age-related macular degeneration.

Verma L, Tewari HK, Nainiwal S, Ravindranathan J.

Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New
Delhi, India. lalitverma@yahoo.com

PURPOSE: To report our initial experience in the treatment of subfoveal choroidal
neovascular membrane, secondary to age-related macular degeneration (AMD) by
transpupillary thermotherapy (TTT). METHODS: Fifty consecutive patients with
subfoveal choroidal neovascularisation (CNV) secondary to AMD, were included in
the study. The parameters assessed before the TTT were visual acuity by ETDRS
chart, scotoma score by Amsler grid chart, reading speed, fundus examination by
direct and indirect ophthalmoscope as well as +90 Diopter lens followed by
digital fundus photography and fluorescein angiography (FA). RESULTS: The letter 
visual acuity improved or stabilized in 72% cases up to 12 weeks after TTT. Mean 
scotoma score decreased from a mean of 47.56, to 43.56 at 6 weeks and to 37 at 12
weeks. Mean reading speed increased from 27.04 words/minute at pretreatment to
34.52 words/minute at 6 weeks and 37.33 words/minute 12 weeks after TTT.
CONCLUSION: TTT is not only a cheaper alternative to photodynamic therapy (PDT), 
but also is an efficacious tool in stabilisation or improvement of visual acuity 
in the management of subfoveal choroidal neovascular membrane due to AMD.

Publication Types: 
    Comparative Study

PMID: 15132377 [PubMed - indexed for MEDLINE]

2311: Eye. 2004 May;18(5):503-8.

Comment in:
    Eye. 2006 Apr;20(4):506-8; author reply 508-9.    Eye. 2006 Apr;20(4):508; author reply 508-9.

The Amsler chart is of doubtful value in retinal screening for early laser
therapy of subretinal membranes. The West London Survey.

Zaidi FH, Cheong-Leen R, Gair EJ, Weir R, Sharkawi E, Lee N, Gregory-Evans K.

The Western Eye Hospital, Marylebone Road, London, UK. fhz12@hotmail.com

PURPOSE: Validating the current protocol of Amsler chart grid surveillance for
the early detection of subretinal neovascular membrane(SRN) in age-related
macular degeneration(AMD), and investigating its value in facilitating early
laser therapy. METHODS: A retrospective pilot study. Setting: Central London eye 
hospital with dedicated 24-h ophthalmic casualty serving West and West-central
London. Participants: 100 consecutive AMD patients who attended casualty with
vision loss fulfilling the following criteria: patients had received and been
instructed in the use of Amsler charts according to the unit's dispensation
protocol,fluorescein angiography which confirmed new SRN. Patients presented over
20 months. Outcome measures were detection of SRN by the Amsler chart, and laser 
treatment of SRN. RESULTS: The Amsler chart surveillance protocol had detected
SRN in 29 of the 100 patients. The surveillance protocol detected less than 30%
of the specific patients who subsequently underwent laser treatment. A
statistically significant difference was seen on comparing the ages of patients
in whom the screening protocol was successful versus those in whom it was
unsuccessful (student's t-test,P<3.2 x 103). Younger patients were more likely to
be detected using the Amsler chart. A one-tailed Z2 test approached, but did not 
achieve, statistical significance (Z2 = 1.057,P <0.3) suggesting that patients
who have already lost vision to SRN in one eye might not be more likely to be
detected using the surveillance protocol than patients in whom SRN was affecting 
their first eye. In all, 38% of surveillance responders went on to receive laser 
therapy, compared with 37% of surveillance nonresponders. CONCLUSIONS: The
current Amsler chart surveillance protocol is suboptimal for detecting SRN in
AMD, and a proportion of cases suitable for early laser therapy may be missing
rapid detection. The results are especially important since recent advances in
laser therapy for SRN require early detection for optimal effectiveness.

Publication Types: 
    Validation Studies

PMID: 15131682 [PubMed - indexed for MEDLINE]

2312: Eye. 2004 May;18(5):470-3.

Eye nutrient products for age-related macular degeneration: what do they contain?

Arora S, Musadiq M, Mukherji S, Yang YC.

Wolverhampton and Midlands Counties Eye Infirmary, Wolverhampton, Midlands, UK.
seema20@msn.com

BACKGROUND AND PURPOSE: Patients are increasingly well informed about the
availability of antioxidant products and the claims made for their benefits in
age-related macular degeneration (AMD). Consequently, their use is becoming
widespread. The purpose of this study is to conduct a survey of the commonly
encountered products, and to compare their ingredients with the current
Age-Related Eye Disease Study (AREDS) recommendations. METHODS: A search was
undertaken for products sold as 'eye nutrients' at local pharmacies and health
food shops, and for products advertised via the Internet. Information about these
products was collated and analysed. RESULTS: We identified 22 eye nutrient
products. Analysis of their constituents showed that, although over 75% contained
all the constituents used in AREDS, only two matched the dosage profiles
recommended in the study. CONCLUSION: The authors draw no conclusion on the
efficacy of nutritional supplements in the prevention of AMD. In order to advise 
their patients, ophthalmologists should be familiar with these products. The
compiled list in this paper should provide a useful reference for them.

PMID: 15131676 [PubMed - indexed for MEDLINE]

2313: Eye. 2004 May;18(5):455-9.

Polypoidal choroidal vasculopathy and exudative age-related macular degeneration 
in Greek population.

Ladas ID, Rouvas AA, Moschos MM, Synodinos EE, Karagiannis DA, Koutsandrea CN.

Department of Ophthalmology, Medical School of Athens, University Athens, Greece.
ladas@ath.forthnet.gr

PURPOSE: To study the prevalence, the clinical features, and the visual prognosis
without treatment of polypoidal choroidal vasculopathy (PCV) in a large series of
Greek patients presenting with exudative maculopathy. METHODS: The medical
records, photographs,as well as fluorescein and indocyanine green(ICG) angiograms
of a series of 268 consecutive elderly white Greek patients, who were originally 
diagnosed as having exudative age-related macular degeneration (AMD) were
reviewed retrospectively. RESULTS: In all, 22 of the 268 (8.2%) patients
initially suspected of having AMD were ultimately diagnosed with PCV. In 15 of
the 22(68.2%) patients with PCV, the polypoidal lesions were located in the
peripapillary area. Large soft drusen were present in only two fellow eyes of the
10 (20%) patients with unilateral PCV compared with 120 fellow eyes of the 148
(81.1%) patients with unilateral AMD. At the last examination, 11 of the 22(50%) 
patients with PCV and 120 of the 246(48.8%) patients with AMD presented a visual 
acuity of less than 6/60 in at least one eye due to scar formation in the macula.
CONCLUSIONS: PCV is not an infrequent disease in Greece. A measurable number of
Greek patients with findings suggestive of exudative AMD will instead have PCV.
ICG angiography is important in differentiating between these two clinical
entities. In Greeks, polypoidal lesions are predominantly peripapillary and are
not usually associated with macular drusen in the fellow eye. PCV and exudative
AMD do not differ significantly in terms of their natural course and visual
prognosis in Greek patients.

PMID: 15131673 [PubMed - indexed for MEDLINE]

2314: Am J Ophthalmol. 2004 May;137(5):966-8.

Cystoid macular edema in a low-risk patient after switching from latanoprost to
bimatoprost.

Carrillo MM, Nicolela MT.

Department of Ophthalmology, Dalhousie University, 1278 Tower Road, Halifax, Nova
Scotia B3H 2Y9, Canada.

PURPOSE: To report a case of angiographically documented cystoid macula edema
occurring after switching a pseudophakic patient from latanoprost to bimatoprost.
DESIGN: Observational case report. METHODS: A 68-year-old man developed intense
conjunctival hyperemia and cystoid macula edema after switching from latanoprost 
to bimatoprost 9 months after cataract surgery in an eye at low-risk for this
cystoid macular edema. RESULTS: Bimatoprost was discontinued and diclofenac
initiated. After 2 months, visual acuity and ocular hyperemia returned to
baseline levels. Fundus examination revealed resolution of cystoid macula edema. 
CONCLUSION: It is possible that pseudophakic eyes that develop intense
conjunctival hyperemia associated with ocular hypotensive lipids might be at
higher risk for developing cystoid macula edema.

Publication Types: 
    Case Reports

PMID: 15126179 [PubMed - indexed for MEDLINE]

2315: Am J Ophthalmol. 2004 May;137(5):961-3.

Is adjustment of National Eye Institute Visual Function Questionnaire scores for 
general health necessary in randomized trials?

Miskala PH, Bressler NM, Meinert CL.

Department of Ophthalmology, The Johns Hopkins University School of Medicine,
Baltimore, MD, USA. pmiskala@jhmi.edu

PURPOSE: To assess whether treatment comparison of National Eye Institute Visual 
Function Questionnaire (NEI-VFQ) scores in a clinical trial is influenced by
general health to warrant adjusting for it. DESIGN: Two randomized pilot trials. 
METHODS: Patients enrolled in two randomized pilot trials of submacular surgery
versus observation for choroidal neovascularization had quality of life
interviews (NEI-VFQ and the Short Form-36 Health Survey) 24 months after
enrollment. Information on comorbidities was collected through chart reviews.
Data from 120 patients were analyzed using linear regression methods. RESULTS:
Adjustment for comorbidities did not change the magnitude of the treatment effect
on NEI-VFQ scores. However, adjustment for Short Form-36 physical and mental
component summaries produced changes in the estimated treatment effect when
NEI-VFQ scores were compared. CONCLUSIONS: Adjustment of NEI-VFQ scores for
general health may be advisable. The Short Form-36 summary scores may be
appropriate for this purpose.

Publication Types: 
    Comparative Study

PMID: 15126176 [PubMed - indexed for MEDLINE]

2316: Am J Ophthalmol. 2004 May;137(5):959-61.

Optical coherence tomography to detect macular edema in the presence of asteroid 
hyalosis.

Browning DJ, Fraser CM.

Charlotte Eye, Ear, Nose, and Throat Associates, 6035 Fairview Road, Charlotte,
NC 28210, USA. djbrowning@carolina.rr.com

PURPOSE: To propose the use of optical coherence tomography as an effective
diagnostic tool for identifying macular edema in patients with asteroid hyalosis 
obscuring the fundus view. DESIGN: Case report. METHODS: Review of clinical chart
and images. SETTING: Private retina practice. PATIENT: One patient diagnosed with
diabetic retinopathy and asteroid hyalosis, who was experiencing decreased visual
acuity and whose fundus view was inadequate for diagnosis using customary
techniques. RESULTS: Usual methods of diagnosis were ineffective until OCT
obtained a clear image of the fundus and subsequent macular thickening with
vitreomacular adhesion. CONCLUSIONS: Optical coherence tomography is an effective
diagnostic tool for discovering macular edema in cases of dense asteroid hyalosis
where traditional methods fail to obtain a clear image of the fundus.

Publication Types: 
    Case Reports

PMID: 15126175 [PubMed - indexed for MEDLINE]

2317: Am J Ophthalmol. 2004 May;137(5):880-7.

Limited macular translocation compared with photodynamic therapy in the
management of subfoveal choroidal neovascularization in age-related macular
degeneration.

Pawlak D, Glacet-Bernard A, Papp M, Roquet W, Coscas G, Soubrane G.

University Eye Clinic of Créteil, Intercommunal and Henri Mondor (Assistance
Publique des Hôpitaux de Paris) Hospitals, University of Paris XII, 40 avenue de 
Verdun, 94010 Créteil, France. dompawlak@aol.com

PURPOSE: To compare the visual outcome of macular translocation (MT) versus
photodynamic therapy (PDT) for subfoveal predominantly classic neovascularization
in age-related macular degeneration (AMD). DESIGN: Nonrandomized clinical trial. 
METHODS: Retrospective review of 65 consecutive patients with subfoveal
neovascularization due to AMD. The follow-up was at least 6 months. Main outcome 
criteria were final best corrected visual acuity and the gain in visual acuity.
RESULTS: A total of 29 eyes were treated with PDT with verteporfin, and 36
underwent MT with chorioscleral infolding. Both groups were similar for age,
refraction, and lesion size. The initial visual acuity was lower in the MT group 
than in the PDT group (20/200 versus 20/100). Mean follow-up was 11 months for
the PDT group and 14 months for the MT group. The mean displacement of the fovea 
after translocation was 1,274 microm (range, 250 to 1,900 microm). Mean number of
retreatment by PDT was 2.5. At 1 year, both groups had the same final visual
acuity (20/200), but the improvement was more favorable in the MT group (gain of 
0.7 line in the MT group versus loss of 3.4 lines in the PDT group, P =.007). One
eye in the PDT group (4.3%) had a gain of 3 lines or more versus eight eyes (38%)
in the MT group; the lesion size was larger in the PDT group than in MT group (P 
=.036). CONCLUSION: In this retrospective study, MT seemed to allow a better
preservation of visual acuity than PDT in subfoveal neovascularization due to
AMD. Further larger and controlled studies are required.

Publication Types: 
    Clinical Trial
    Comparative Study

PMID: 15126153 [PubMed - indexed for MEDLINE]

2318: Vision Res. 2004;44(13):1537-46.

Evaluation of a new quantitative technique to assess the number and extent of
preferred retinal loci in macular disease.

Crossland MD, Sims M, Galbraith RF, Rubin GS.

Division of Vision Rehabilitation Research, Institute of Ophthalmology,
University College London, 11-43 Bath Street, London EC1V 9EL, UK.
m.crossland@ucl.ac.uk

Patients with scotomas due to macular disease may use more than one preferred
retinal locus (PRL) for fixation. We have developed and evaluated an objective,
quantitative technique to determine the number of PRLs used during an episode of 
fixation and the extent of each locus. In five of eight adults with macular
disease our techniques consistently indicated the presence of multiple PRLs.
Patients with multiple PRLs were more likely to have suffered recent vision loss 
in the tested eye. Our technique describes fixation more fully than the
traditional method of calculating a single bivariate contour ellipse area.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15126063 [PubMed - indexed for MEDLINE]

2319: Ophthalmology. 2004 May;111(5):946-53.

Comment in:
    Ophthalmology. 2005 Feb;112(2):360; author reply 360-1.

Patterns of macular edema in patients with uveitis: qualitative and quantitative 
assessment using optical coherence tomography.

Markomichelakis NN, Halkiadakis I, Pantelia E, Peponis V, Patelis A,
Theodossiadis P, Theodossiadis G.

Ocular Immunology and Inflammation Service, Department of Ophthalmology General
Hospital of Athens, Athens, Greece. marnik@otenet.gr

PURPOSE: To describe the morphologic characteristics of uveitic macular edema by 
the use of optical coherence tomography (OCT) and to investigate the correlation 
between tomographic features and visual acuity (VA). DESIGN: Cross-sectional
study. PARTICIPANTS: Seventy consecutive patients with uveitis in a
university-based practice with a clinical diagnosis of macular edema in at least 
one eye. Inclusion criteria were: (1) verification of macular edema by OCT, (2)
adequate media clarity for fundus visualization, and (3) absence of coexisting
ocular disease limiting visual potential. METHODS: Complete ophthalmic
examination: best-corrected Snellen VA, slit-lamp examination, fundus
biomicroscopy, indirect ophthalmoscopy, and OCT. Fluorescein angiography was
performed in selected cases. MAIN OUTCOME MEASURES: Best-corrected Snellen VA and
tomographic features of the macula, including macular thickness measurement and
correlation of macular thickness with VA. RESULTS: Eighty-four eyes of 60
patients met the inclusion criteria. The mean VA (Snellen test) was 20/36. There 
were 3 patterns of macular edema: diffuse macular edema (DME), cystoid macular
edema (CME), and serous retinal detachment (RD). Serous retinal detachment was
detected in 17 eyes (20.2%). Patients were classified into the following groups: 
DME (46 eyes, 54.8%), CME (21 eyes, 25%), DME and RD (5 eyes, 5.9%), CME and RD
(12 eyes, 14.3%). Epiretinal membrane was detected by OCT in 34 eyes (40.5%).
Eight eyes (9.5%) demonstrated vitreomacular traction. The mean retinal thickness
at the central fovea was 333+/-171 microm (mean +/- standard deviation). Macular 
edema was located mainly in the outer retinal layers. Eyes with CME had
significantly greater retinal thickness measurements than eyes with DME
(P<0.001). Multivariate analysis revealed that VA was negatively correlated with 
increased macular thickness, presence of CME, and RD (P<0.05). CONCLUSIONS:
Optical coherence tomography demonstrated 3 patterns of macular edema in patients
with uveitis: DME, CME, and RD. Epiretinal membrane coexisted in a significant
percentage of patients. In patients with uveitis with clear media, the
morphologic features of macular edema and macular thickness correlated with VA.

PMID: 15121373 [PubMed - indexed for MEDLINE]

2320: Curr Opin Ophthalmol. 2004 Jun;15(3):227-31.

Age-related macular degeneration and quality of life: how to interpret a research
paper in health-related quality of life.

Sharma S, Oliver-Fernandez A.

Cost Effective Ocular Health Policy Unit, Department of Ophthalmology, Queen's
University, Hotel Dieu Hospital, Brock II-224B, 116 Brock Street, Kingston,
Ontario, Canada K7L 5G2. sanjay_sharma60@hotmail.com

PURPOSE OF REVIEW: To review how to critically appraise a research article
pertaining to changes in health-related quality of life (HRQoL) related to
interventions for age-related macular degeneration (AMD). RECENT FINDINGS: We
searched PubMed using a strategy that combined the text-words, "macular
degeneration" and "quality of life" (n = 73; January 17, 2004), while limiting
the search to "clinical trials" (n = 6; of which 3 were published within the past
year). A randomized clinical trial evaluating the efficacy of self-management as 
an intervention for AMD has been selected to introduce the reader to the concept 
of how to critically review a research paper pertaining to HRQoL in AMD. Other
pertinent articles used in this review include recent results published from the 
Age-Related Eye Disease Study and the Submacular Surgery Trial. SUMMARY: The
NEI-VFQ is a reliable, valid, and responsive tool when applied to patients with
AMD. Self-management of patients with AMD has been demonstrated to improve their 
HRQoL by way of an internally valid randomized clinical trial. In this issue of
Current Opinion in Ophthalmology, we confront the issue of how to assess the
validity and importance of a research paper pertaining to the issue of quality of
life. To introduce this topic, we will present a real world clinical example to
better understand how quality of life may aid in medical decision making.

Publication Types: 
    Review

PMID: 15118510 [PubMed - indexed for MEDLINE]

2321: Curr Opin Ophthalmol. 2004 Jun;15(3):221-6.

A review of treatments for macular degeneration: a synopsis of currently approved
treatments and ongoing clinical trials.

Liu M, Regillo CD.

Retina Service, Wills Eye Hospital, Jefferson Medical College, Philadelphia,
Pennsylvania, USA.

PURPOSE OF REVIEW: The purpose of this report is to review recent literature and 
ongoing clinical trials of the treatment of neovascular age-related macular
degeneration. RECENT FINDINGS: Advances in the understanding of the pathogenesis 
of age-related macular degeneration and choroidal neovascularization have
resulted in the emergence of pharmacotherapies targeting various aspects of
angiogenesis. Preliminary results with the new agents have been encouraging.
Moreover, longer follow-up and subgroup analyses of the Treatment of Age-Related 
Macular Degeneration with Photodynamic Therapy and Verteporfin in Photodynamic
Therapy studies have suggested new potential indications for photodynamic
therapy. SUMMARY: Currently a patient with wet macular degeneration may have
multiple investigational options that were unavailable several years ago. Ongoing
clinical trials are aimed at determining the long-term safety and efficacy of
these new pharmacologic and combination therapy modalities.

Publication Types: 
    Review

PMID: 15118509 [PubMed - indexed for MEDLINE]

2322: Curr Opin Ophthalmol. 2004 Jun;15(3):181-3.

Age-related macular degeneration and depression: a review of recent research.

Casten RJ, Rovner BW, Tasman W.

Jefferson Medical College and Wills Eye Hospital, and Jefferson Hospital for
Neuroscience, 900 Walnut Street, 8th floor, Philadelphia, PA 19107, USA.
Robin.Casten@Jefferson.edu

PURPOSE OF REVIEW: The purpose of this review is to summarize current research
findings regarding relationships between depression and age-related macular
degeneration (AMD). RECENT FINDINGS: The current literature indicates that the
prevalence of depression among patients with AMD is fairly high (approximately
30%) and that depression is a major cause of disability among patients with AMD, 
even when severity of vision loss is considered. Interventions to alleviate the
emotional distress associated with vision loss are also discussed. SUMMARY:
Several studies indicate that AMD is a risk factor for depression, and this has
serious consequences for the quality of life among patients with AMD.

Publication Types: 
    Review

PMID: 15118503 [PubMed - indexed for MEDLINE]

2323: J Glaucoma. 2004 Jun;13(3):256-60.

Bleb revision for hypotony maculopathy after trabeculectomy.

Bashford KP, Shafranov G, Shields MB.

Department of Ophthalmology & Visual Science, Yale University School of Medicine,
New Haven, CT 06520, USA.

PURPOSE: To assess the efficacy of a bleb revision technique with regard to
improvement in intraocular pressure (IOP) and visual acuity after hypotony
maculopathy and to evaluate the influence of duration of hypotony on visual
outcome. PATIENTS AND METHOD:: Retrospective review of a series of patients who
underwent bleb revision for hypotony maculopathy (IOP less than 6 mm Hg and loss 
of two or more lines of central vision) following trabeculectomy. Bleb revision
included excision of avascular bleb tissue, dissection posteriorly between
conjunctiva and Tenon's capsule, and advancement and suturing of the conjunctiva 
at the limbus. RESULTS: Fourteen patients were included in the study. The average
age was 49.8 years (range 18-85) and eight were female. Before trabeculectomy,
the mean IOP was 23.2 +/- 11.8 mm Hg, and the visual acuity was 20/30-2 or better
in 13 patients and 20/80 in one patient. The mean IOP before bleb revision was
1.07 +/- 0.73 mm Hg, and 12 patients had lost an average of 4.33 +/- 2.96 lines
of visual acuity from baseline, while one had count fingers and another had hand 
motion vision. The final mean IOP after bleb revision was 11.07 +/- 3.08 mm Hg.
Compared with visual acuity just prior to bleb revision, 12 patients regained an 
average best corrected vision of 3.08 +/- 2.67 lines, with seven returning to the
pre-trabeculectomy vision level. The duration of hypotony prior to bleb revision 
was 1 to 24 months (average 8.36 months) with no correlation (correlation
coefficient -0.13) between duration and visual outcome. CONCLUSION: Bleb revision
for hypotony maculopathy following trabeculectomy is an effective technique for
raising IOP and limiting visual loss, which is not influenced by duration of
hypotony within the time frame of the study.

PMID: 15118473 [PubMed - indexed for MEDLINE]

2324: Optometry. 2004 Apr;75(4):216-30.

Double-masked, placebo-controlled, randomized trial of lutein and antioxidant
supplementation in the intervention of atrophic age-related macular degeneration:
the Veterans LAST study (Lutein Antioxidant Supplementation Trial).

Richer S, Stiles W, Statkute L, Pulido J, Frankowski J, Rudy D, Pei K, Tsipursky 
M, Nyland J.

Department of Veterans'Affairs, Medical Center Eye Clinic, North Chicago,
Illinois 60064-3095, USA. stuart.richer1@med.va.gov

BACKGROUND: Age-related macular degeneration (ARMD) is the leading cause of
vision loss in aging Westem societies. The objective of the lutein antioxidant
supplementation trial (LAST) is to determine whether nutritional supplementation 
with lutein or lutein together with antioxidants, vitamins, and minerals,
improves visual function and symptoms in atrophic ARMD. METHODS: The study was a 
prospective, 12-month, randomized, double-masked, placebo-controlled trial
conducted at an urban midwestern Veterans Administration Hospital from August
1999 to May 2001. Ninety patients with atrophic ARMD were referred by
ophthalmologists at two Chicago-area veterans medical facilities. Patients in
Group 1 received lutein 10 mg (L); in Group 2, a lutein 10
mg/antioxidants/vitamins and minerals broad spectrum supplementation formula
(L/A); and in Group 3, a maltodextrin placebo (P) over 12 months. RESULTS: In
Groups 1 L and 2 L/A, mean eye macular pigment optical density increased
approximately 0.09 log units from baseline, Snellen equivalent visual acuity
improved 5.4 letters for Group 1 L and 3.5 letters for Group 2 L/A, and contrast 
sensitivity improved. There was a net subjective improvement in Amsler grid in
Group 1 L. VFO-14 questionnaires conceming subjective glare recovery were nearly 
significant at 4 months for Group 2 L/A. Patients who received the placebo (Group
3) had no significant changes in any of the measured findings. CONCLUSION: In
this study, visual function is improved with lutein alone or lutein together with
other nutrients. Further studies are needed with more patients, of both genders, 
and for longer periods of time to assess long-term effects of lutein or lutein
together with a broad spectrum of antioxidants, vitamins, and minerals in the
treatment of atrophic age-related macular degeneration.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, Non-P.H.S.

PMID: 15117055 [PubMed - indexed for MEDLINE]

2325: Acta Ophthalmol Scand. 2004 Jun;82(3 Pt 1):298-303.

Angiotensin-converting enzyme inhibitors (ACEIs) and age-related maculopathy
(ARM): cross-sectional findings from the Blue Mountains Eye Study.

Wu KH, Wang JJ, Rochtchina E, Foran S, Ng MK, Mitchell P.

Department of Ophthalmology, Westmead Millennium and Save Sight Institutes,
University of Sydney, New South Wales, Australia.

PURPOSE: To assess the relationship between the use of angiotensin-converting
enzyme inhibitors (ACEIs) and prevalence of age-related maculopathy (ARM).
METHODS: Eligible residents aged >/= 49 years were first examined in 1992-94
(Cross-section 1, n = 3654). Of these, 2335 were re-examined in 1997-99, together
with an additional 1174 who became eligible after 1994 (Cross-section 2, n =
3509). Information regarding ACEI use was obtained and retinal photographs were
graded using the Wisconsin ARM Grading System. RESULTS: In Cross-section 1,
prevalence rates of late and early stage ARM were 1.3% and 4.3% among current
ACEI users, and 2.0% and 4.8% among non-current users, respectively. In
Cross-section 2, prevalence rates of late and early stage ARM were 2.3% and 11.3%
among current ACEI users, and 1.3% and 9.3% among non-current users,
respectively. After adjusting for age, sex and smoking, neither survey found any 
significant association between ACEI use and prevalence of either late or early
ARM. CONCLUSIONS: No significant cross-sectional associations were found between 
ACEI use and ARM prevalence in this population.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15115451 [PubMed - indexed for MEDLINE]

2326: Invest Ophthalmol Vis Sci. 2004 May;45(5):1544-52.

Localization of collagen XVIII and the endostatin portion of collagen XVIII in
aged human control eyes and eyes with age-related macular degeneration.

Bhutto IA, Kim SY, McLeod DS, Merges C, Fukai N, Olsen BR, Lutty GA.

Wilmer Ophthalmological Institute, Department of Ophthalmology, The Johns Hopkins
Hospital, Baltimore, Maryland 21287-9115, USA.

PURPOSE: Endostatin, a C-terminal fragment of collagen XVIII (coll XVIII) formed 
by proteolysis, specifically inhibits endothelial cell migration and
proliferation in vitro and potently inhibits angiogenesis and tumor growth in
vivo. The purpose of this study was to examine the immunolocalization of
endostatin and coll XVIII in the retina and choroid of human donor tissue
sections from aged control donor eyes and to determine whether the localization
or relative levels are changed in age-related macular degeneration (AMD).
METHODS: Ocular tissues were obtained from six aged control donors (age range,
75-86 years; mean age, 80.5 years) without evidence or history of chorioretinal
disease and from nine donors with AMD (age range, 74-105 years; mean age, 88.6
years). Tissues were cryopreserved, and streptavidin alkaline phosphatase
immunohistochemistry was performed with goat anti-human and mouse anti-human
endostatin antibodies and rabbit anti-mouse coll XVIII. Blood vessels were
identified with mouse anti-human CD-34 antibody in adjacent sections. Pigment in 
RPE and choroidal melanocytes was bleached. Three independent observers scored
the immunohistochemical reaction product. RESULTS: In aged control eyes, coll
XVIII and endostatin (the endostatin portion of coll XVIII) immunoreactivity was 
observed in large retinal blood vessels and in capillaries in some individuals,
but the internal limiting membrane (ILM) had the most intense retinal
immunostaining. There was no significant difference in immunoreactivity to both
antibodies in retinal blood vessels in aged control eyes. In the choroid,
endostatin and coll XVIII were localized to blood vessels, Bruch's membrane, and 
RPE basal lamina. AMD retina and choroid had a similar pattern and intensity of
coll XVIII immunostaining, as observed in control eyes but reaction product was
more diffuse in the choroid. Endostatin immunoreactivity was significantly higher
in ILM (P = 0.037) in AMD retina and significantly lower in the choriocapillaris,
Bruch's membrane, and RPE basal lamina of AMD choroids (P < 0.05) and completely 
negative in some areas of AMD choroids. CONCLUSIONS: These data suggest that
reduced levels of the endostatin portion of coll XVIII in Bruch's membrane, RPE
basal lamina, intercapillary septa, and choriocapillaris in eyes with AMD may be 
permissive for choroidal neovascularization.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15111613 [PubMed - indexed for MEDLINE]

2327: Invest Ophthalmol Vis Sci. 2004 May;45(5):1450-5.

Comparison of objective retinal thickness analysis and subjective stereo fundus
photography in diabetic macular edema.

Strøm C, Sander B.

Department of Ophthalmology, Herlev Hospital, University of Copenhagen,
Copenhagen, Denmark.

PURPOSE: To compare assessment of retinal thickening by stereo fundus photographs
and by Retinal Thickness Analysis (RTA). METHODS: Forty-degree stereo fundus
photographs of the macular field, and RTA scans in 99 eyes of 53 diabetic
patients were compared in both location and area of retinal thickening. The
deviation in retinal thickness on RTA from the mean retinal thickness +/-2 SD in 
healthy controls was mapped in a spreadsheet and printed, assuming the same size 
as the grid with the subjectively assessed retinal thickening. Location was
evaluated as retinal thickening being present or absent in nine subfields. Area
was one of four categories: No retinal thickening, <1 disc area (DA), <2 DA, or
<3 DA. Statistics: kappa-statistic. RESULTS: Exact agreement on location was
found in 632 of 891 observations (70.9%). kappa = 0.17 (95% CI: 0.08-0.25).
Pooling observations for subfields 2 to 5 (inner circle), and 6 to 9 (outer
circle) showed exact agreement = 75.8% and kappa = 0.10 (95% CI: -0.06-0.25) and 
exact agreement = 65.2% and kappa = 0.24 (95% CI: 0.13-0.34), respectively.
Twelve eyes, in which both methods assessed the same amount of retinal
thickening, showed no agreement on location, and were compared only on location
of retinal thickening. Exact agreement on area was found in 44 of 87 (50.6%)
eyes. Weighted Kappa = 0.34 (95% CI: 0.23-0.45). CONCLUSIONS: The degree of
agreement between subjectively (with stereo fundus photographs) and objectively
(with RTA) assessed location and area of retinal thickening was poor, and fair,
respectively.

Publication Types: 
    Comparative Study

PMID: 15111601 [PubMed - indexed for MEDLINE]

2328: Invest Ophthalmol Vis Sci. 2004 May;45(5):1311-5.

The epsilon2 and epsilon4 alleles of the apolipoprotein gene are associated with 
age-related macular degeneration.

Baird PN, Guida E, Chu DT, Vu HT, Guymer RH.

Centre for Eye Research Australia, University of Melbourne, East Melbourne,
Victoria, Australia. pnb@unimelb.edu.au

PURPOSE: To date, of all the genes studied in relation to age-related macular
degeneration (AMD), the alleles of the apolipoprotein (apoE) gene have been the
most consistently associated with disease. However, not all apoE studies have
found an association, and among these the associations differ. The current study 
was conducted to investigate further the association of this gene in AMD.
METHODS: Three hundred twenty-two unrelated individuals with diagnosed AMD and
123 unrelated but ethnically matched control subjects were analyzed. All subjects
completed a standard questionnaire and were given a fundus examination. A blood
sample was collected for DNA extraction. The common allelic variants of apoE were
screened through the use of polymerase chain reaction (PCR) and restriction
enzyme digestion followed by statistical analysis. RESULTS: Individuals with the 
epsilon3 epsilon4 genotype of apoE had an approximate halving of disease risk for
late (end-stage) AMD (odds ratio [OR] 0.58, 95% confidence interval [CI]
0.34-0.98) relative to the epsilon3 epsilon3 genotype at age of ascertainment.
Stratification of late AMD into atrophic and neovascular disease revealed that
the greatest protective effect for the epsilon3 epsilon4 genotype was in
individuals with atrophic disease (OR 0.35, 95% CI 0.13-0.92). Men with the
epsilon3 epsilon4 genotype also showed almost a threefold reduction in risk of
disease in late AMD (OR 0.36, 95% CI 0.16-0.82). However, individuals with late
AMD and the epsilon2 epsilon3 genotype had a significantly earlier mean age of
diagnosis of disease (3.4 years, P = 0.015) compared with those with the epsilon3
epsilon3 genotype, and this was most evident in women (3.9 years, P = 0.011) and 
in individuals with neovascular disease (4.7 years, P = 0.003). CONCLUSIONS: The 
alleles of apoE appear to have a role in the etiology of AMD, with the epsilon4
allele being protective, or at the very least, delaying the age of diagnosis of
disease, whereas the epsilon2 allele appears to have a modifier effect by
bringing forward the mean age of disease diagnosis.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15111582 [PubMed - indexed for MEDLINE]

2329: Invest Ophthalmol Vis Sci. 2004 May;45(5):1306-10.

Association of apolipoprotein E alleles with susceptibility to age-related
macular degeneration in a large cohort from a single center.

Zareparsi S, Reddick AC, Branham KE, Moore KB, Jessup L, Thoms S, Smith-Wheelock 
M, Yashar BM, Swaroop A.

Department of Ophthalmology and Visual Sciences, University of Michigan, Ann
Arbor, Michigan 48105, USA.

PURPOSE: To examine the effect of apolipoprotein E (APOE) alleles on age-related 
macular degeneration (AMD) risk and on age at diagnosis of AMD in a large patient
cohort recruited from a single center. METHODS: The frequency of APOE alleles was
analyzed in 632 unrelated AMD patients and 206 unrelated controls, all of whom
were of white ancestry. The presence or absence of disease symptoms in all
patients and controls was based on clinical examination and/or ophthalmic
records. The association with APOE was explored in the context of AMD subtypes,
family history status, possible interaction with smoking, and distribution of age
at diagnosis of AMD. RESULTS: The frequency of the epsilon4 allele was
significantly reduced in patients compared with controls (0.10 vs. 0.14, P < or =
0.02). Gender- and age-adjusted odds ratios indicated that epsilon4-carriers have
significantly lower risk of developing AMD compared to epsilon3epsilon3 subjects 
(OR = 0.55, 95% CI: 0.37-0.82, P = 0.004). In the cohort, AMD patients with a
positive family history exhibited a significant 3.5 years earlier age at
diagnosis (P = 0.001); however, APOE alleles did not appear to modulate the age
at diagnosis of AMD. CONCLUSIONS: The association between the APOE-epsilon4
allele and a reduced risk of AMD was established in a large cohort with
sufficient statistical power. How distinct APOE alleles affect AMD susceptibility
warrants further investigation.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15111581 [PubMed - indexed for MEDLINE]

2330: Invest Ophthalmol Vis Sci. 2004 May;45(5):1281-8.

Modulation of Sub-RPE deposits in vitro: a potential model for age-related
macular degeneration.

Amin S, Chong NH, Bailey TA, Zhang J, Knupp C, Cheetham ME, Greenwood J, Luthert 
PJ.

Division of Pathology, Institute of Ophthalmology, University College, London,
United Kingdom. s.amin@ucl.ac.uk

PURPOSE: Sub-RPE deposits form in a variety of conditions most notably in
age-related macular degeneration. The purpose of this study was to generate
sub-RPE deposits in vitro and to test the hypotheses that high protein
concentrations or retinal homogenate increase deposit formation and that a
challenge with tumor necrosis factor (TNF)-alpha or metalloproteinase (MMP)-2
decreases such deposits. METHODS: ARPE-19 cells were grown on plastic and on
collagen type I-coated membrane inserts in media containing various
concentrations of fetal calf serum (FCS), bovine serum albumin, or porcine
retinal homogenate. In addition, cells grown on membrane inserts were treated
with TNF-alpha or MMP-2. Sub-RPE deposits were assessed by electron microscopy
and classified into fibrillar, condensed, banded, and membranous subtypes. The
area of the micrograph occupied by each type was estimated with a point-counting 
technique. MMP-2 activity was assessed in tissue culture supernatants by
zymography. RESULTS: With increasing time in culture, total deposit formation did
not change, but the amount of condensed material deposited by ARPE-19 cells
increased while the fibrillar component decreased. Albumin challenge resulted in 
an increased amount of deposit, predominantly of the membranous type. Challenge
with retinal homogenate led to a greater net deposit formation with significant
increases in the condensed and banded forms. Cells treated with TNF-alpha or
MMP-2 showed a dramatic reduction in all types of sub-RPE deposit. Zymography
demonstrated that unchallenged cells produced predominantly MMP-2. Retinal
homogenate challenge reduced the total amount of active MMP-2 produced, and
TNF-alpha stimulated MMP-9 production. CONCLUSIONS: Sub-RPE deposits formed in
vitro share ultrastructural features with those seen in vivo. Deposit formation
can be modulated by challenge with retinal homogenate, TNF-alpha, or MMP-2.
Significantly, the results provide proof of the principle that sub-RPE deposits
can be formed and modified in vitro.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15111578 [PubMed - indexed for MEDLINE]

2331: Hum Mutat. 2004 May;23(5):523.

Molecular analysis of the ABCA4 gene in Turkish patients with Stargardt disease
and retinitis pigmentosa.

Ozgül RK, Durukan H, Turan A, Oner C, Ogüs A, Farber DB.

Hacettepe University, Department of Molecular Biology, Beytepe-Ankara, Turkey.
rkozgul@hacettepe.edu.tr

The clinical importance of sequence variations in the ABCA4 gene has been
extensively discussed during the last decade. Mutations in the ABCA4 gene are
involved in several forms of inherited retinal degenerations. We screened all 50 
exons of the ABCA4 gene in a cohort of 5 Stargardt Disease (STGD) and 35
autosomal recessive retinitis pigmentosa (arRP) patients of Turkish descent to
assess the nature of ABCA4 mutant alleles in this population. Our results
revealed the presence of three novel mutations: c.160T>G (p.C54G), c.2486C>T
(p.T829M), and c.973-6C>A; two mutations previously reported, c.634C>T (p.R212C) 
and c.4253+4C>T, and several polymorphic changes in the ABCA4 gene among Turkish 
patients affected with Stargardt and arRP. To our knowledge this report
represents the first published study of ABCA4 mutations in the Turkish population
resulting in STGD. Copyright 2004 Wiley-Liss, Inc.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15108289 [PubMed - indexed for MEDLINE]

2332: Ophthalmologica. 2004 May-Jun;218(3):202-6.

Changes in antioxidant enzyme activity and malondialdehyde level in patients with
age-related macular degeneration.

Yildirim O, Ateş NA, Tamer L, Muşlu N, Ercan B, Atik U, Kanik A.

Department of Ophthalmology, Faculty of Medicine, Mersin University, Mersin,
Turkey. dryildrimoz@hotmail.com

Age-related macular degeneration is the leading cause of legal blindness in the
developed world, and yet its pathogenesis remains poorly understood. Oxidative
stress may play a major role in the etiology and pathogenesis of age-related
disorders such as age-related macular degeneration. Catalase is an antioxidant
enzyme which plays an important role in the detoxification of free oxygen
radicals. Malondialdehyde is a marker that shows free radical damage. We have
measured the erythrocyte activity of catalase and the serum level of
malondialdehyde in 30 patients with age-related macular degeneration and 60
healthy subjects. Patients with age-related macular degeneration showed
significantly lower catalase activity compared to healthy subjects (p = 0.002).
Plasma malondialdehyde level of the patient group was significantly higher than
that of the controls (p = 0.038). Copyright 2004 S. Karger AG, Basel

PMID: 15103217 [PubMed - indexed for MEDLINE]

2333: Ophthalmologica. 2004 May-Jun;218(3):185-92.

Reading ability and central visual field after photodynamic therapy.

Krebs I, Binder S, Stolba U, Brunner S.

Department of Ophthalmology, Rudolf Foundation Clinic, The Ludwig Boltzmann
Institute of Retinology and Biomicroscopic Surgery, Vienna, Austria.
Ilse.Krebs@wienkav.at

PURPOSE: We examined whether photodynamic therapy (PDT) can prevent severe loss
of reading acuity and further depression of the visual field in cases of
predominantly classic subfoveal neovascularization due to age-related macular
degeneration. PATIENTS AND METHODS: Sixty eyes of 52 patients underwent
biomicroscopy, assessment of reading and distance acuity, 10 degrees static
threshold perimetry, distance acuity, and fluorescein angiography at baseline,
after 6 weeks, 3 months and then every 3 months after therapy. RESULTS: After 18 
months only 16.7% had lost more than 3 levels of reading acuity, 23.3% had lost
less than 3 levels, 6.7% had remained unchanged and 53.3% had gained reading
acuity, 18.7% of these more than 3 levels. 81.7% of the eyes lost less than 3
lines of distance acuity. 78.3% did not show any increase of the mean defect in
the central visual field. CONCLUSION: PDT can prevent severe loss of distance and
reading acuity and further deterioration of the central visual field in about 80%
of the eyes. The baseline reading acuity was poor and the patients should be
aware of the fact that loss of reading acuity cannot be regained even after
successful PDT. Copyright 2004 S. Karger AG, Basel

Publication Types: 
    Clinical Trial

PMID: 15103215 [PubMed - indexed for MEDLINE]

2334: Retina. 2004 Apr;24(2):254-62.

Clinical phenotype as a prognostic factor in Stargardt disease.

Oh KT, Weleber RG, Oh DM, Billingslea AM, Rosenow J, Stone EM.

Department of Ophthalmology, University of North Carolina, Chapel Hill, NC, USA.

PURPOSE: To determine the prognostic significance of widespread flecks, described
as fundus flavimaculatus, in patients with Stargardt disease. DESIGN: Historical 
cohort study. SUBJECTS AND METHODS: Patients with Stargardt disease were
identified by searching preexisting databases at the University of Iowa and
Oregon Health Sciences University. The medical records of these patients were
evaluated for the validity of the diagnosis, initial and final visual acuity,
length of follow-up, and initial and final phenotype. Phenotype was graded as I, 
II, or III on the basis of the distribution of flecks and the extent of atrophy. 
The relationship between final visual acuity and final clinical appearance
(phenotype I versus II versus III) was evaluated controlling for length of
follow-up and age using a Cochran-Mantel-Haenszel test. The clinical progression 
of visual acuity loss for each phenotype was analyzed using life tables and
Kaplan-Meier survival analysis for age and length of follow-up effects. RESULTS: 
A total of 214 patients were confirmed to have Stargardt disease; 131 patients
were seen at multiple visits. Eighty-two patients were identified with phenotype 
I, 62 with phenotype II, and 70 with phenotype III. The final visual outcome was 
significantly better for patients whose ophthalmoscopic abnormalities were
limited to the macula (phenotype I): 80 of 82 patients with phenotype I (97.6%)
maintained 20/200 or better visual acuity in at least one eye as compared to
40/62 (64.5%) patients with phenotype II and 13/70 (18.6%) patients with
phenotype III (P < 0.0001). Survival analysis showed a similarly significant
difference in the survival probabilities (likelihood of maintaining 20/200 or
better vision) for the three phenotypes considered over age and over follow-up
length (P < 0.0001), with phenotypes II and III demonstrating significantly more 
deterioration in vision over time. CONCLUSIONS: The presence of midperipheral
flecks, especially early in life, carries a poorer visual prognosis for patients 
with Stargardt disease than when disease is limited to the macula. The
development of midperipheral flecks is an indicator of more extensive fundus
involvement and thus poorer long-term visual prognosis.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15097887 [PubMed - indexed for MEDLINE]

2335: Prog Retin Eye Res. 2004 Mar;23(2):229-49.

Genetic factors of age-related macular degeneration.

Tuo J, Bojanowski CM, Chan CC.

Laboratory of Immunology, Immunopathology Section, National Eye Institute,
National Institutes of Health, Bldg. 10, Rm. 10N103, 10 Center Drive, Bethesda,
MD 20892-1857, USA.

Age-related macular degeneration (AMD) is a leading cause of blindness in the
United States and developed countries. Although the etiology and pathogenesis of 
AMD remain unknown, a complex interaction of genetic and environmental factors is
thought to exist. The incidence and progression of all of the features of AMD are
known to increase significantly with age. The tendency for familial aggregation
and the findings of gene variation association studies implicate a significant
genetic component in the development of AMD. This review summarizes in detail the
AMD-related genes identified by studies on genetically engineered and
spontaneously gene-mutated (naturally mutated) animals, AMD chromosomal loci
identified by linkage studies, AMD-related genes identified through studies of
monogenic degenerative retinal diseases, and AMD-related gene variation
identified by association studies.

Publication Types: 
    Review

PMID: 15094132 [PubMed - indexed for MEDLINE]

2336: J Cataract Refract Surg. 2004 Apr;30(4):752-60.

Macular alterations after small-incision cataract surgery.

Lobo CL, Faria PM, Soares MA, Bernardes RC, Cunha-Vaz JG.

Centre of Ophthalmology, University Hospital and Institute of Biomedical Research
on Light and Image, Faculty of Medicine, University of Coimbra, 3000 Coimbra,
Portugal. clobo@aibili.pt

PURPOSE: To characterize macular edema that occurs after uneventful cataract
surgery. SETTING: Centre of Ophthalmology, University Hospital, Institute of
Biomedical Research on Light and Image, Faculty of Medicine, University of
Coimbra, Coimbra, Portugal. METHODS: Thirty-two eyes of 32 patients had
uneventful phacoemulsification with implantation of a foldable intraocular lens. 
Postoperatively, patients were examined at 3, 6, 12, and 30 weeks. The
examinations included retinal leakage analysis (Zeiss CSLO), optical coherence
tomography (Humphrey Instruments), and retinal thickness analysis (Talia
Technology, Ltd.). Results were compared with those in a control group comprising
healthy subjects. RESULTS: Increases in retinal thickness (ie, over the mean +/- 
2 SD in the control group) reached a maximum at 6 weeks in 13 of 32 eyes (41%),
after which recovery was progressive. At 30 weeks, all eyes had good visual
acuity, but 7 eyes (22%) still had macular edema. The edema was located primarily
in the central macular region. Leaking sites involving the vascular areas of the 
macula, which indicated areas of abnormal blood-retinal barrier permeability,
were a frequent finding. The number of sites remained relatively stable during
the first 12 weeks (88%) and decreased to 68% at 30 weeks, indicating a trend
toward recovery. CONCLUSION: Macular edema after cataract surgery occurred
primarily in the central region of the macula and was associated with the
presence of leaking sites, which were located predominantly in the vascular
regions of the central macula.

PMID: 15093635 [PubMed - indexed for MEDLINE]

2337: Br J Ophthalmol. 2004 May;88(5):638-42.

Clinical features of drusenoid pigment epithelial detachment in age related
macular degeneration.

Roquet W, Roudot-Thoraval F, Coscas G, Soubrane G.

Clinique Ophtalmologique Universitaire de Créteil, France. Service Santé Publique
Hopital Henri-Mondor Créteil, France.

AIM: To analyse clinical features of drusenoid pigment epithelium detachment
(PED) in age related macular degeneration. METHODS: 61 eyes of 32 patients with
untreated drusenoid PED were followed for an average of 4.6 years (range 1-17
years). Drusenoid PED was defined as (1/2) disc diameter (DD) of confluent soft
drusen under the centre of the macula. All patients underwent visual acuity
measurement, biomicroscopic fundus examination, stereoscopic colour photograph,
and fluorescein and indocyanine green angiography. Optical coherence tomography
was performed in selected cases at the last examination. Kaplan Meier survival
analysis was performed to estimate the probability of complications. RESULTS:
Three different natural outcomes were identified: persistence of drusenoid PED
(38%), development of geographic atrophy (49%), and choroidal neovascularisation 
(CNV) (13%). Based on Kaplan Meier survival analysis, drusenoid PED had a 50% of 
chance of developing geographic atrophy after 7 years. If the drusenoid PED was
greater than 2 DD or was associated with metamorphopsia at initial presentation, 
progression to atrophy or ingrowth of CNV occurred after 2 years (p<0.01).
Indocyanine green angiography confirmed fluorescein angiographic features or
ascertained the presence of CNV when fluorescein angiography was equivocal.
Optical coherence tomography was helpful in distinguishing coalescent soft drusen
from drusenoid PED and disclosed the accumulation of sub or intraretinal fluid in
eyes with CNV. CONCLUSION: Drusenoid PED size greater than 2 DD and
metamorphopsia were risk factors identified at presentation which affected
prognosis. The evaluation of the eyes at risk requires the use of all imaging
means in order to ascertain the diagnosis of CNV. At long term (over 10 years),
geographic atrophy and CNV had occurred in 75% and 25% respectively, with a poor 
visual outcome.

PMID: 15090415 [PubMed - indexed for MEDLINE]

2338: Ophthalmic Surg Lasers Imaging. 2004 Mar-Apr;35(2):162-4.

Rapid response of cystoid macular edema related to Nd:YAG laser capsulotomy to
0.5% ketorolac.

Lee MS, Lass JH.

Department of Ophthalmology, Vitreoretinal Diseases and Surgery, Case Western
Reserve University, Cleveland, Ohio, USA.

A 68-year-old woman who had had cataract surgery several years previously
presented with decreasing visual acuity and posterior capsular opacification. She
underwent an Nd:YAG laser capsulotomy, but developed decreased visual acuity
secondary to cystoid macular edema 2 months after the procedure. She was
immediately administered 0.5% ketorolac drops. Several days after initiating
treatment, she noted an improvement in her vision. Eight days later, her vision
had improved from 20/400 to 20/60. Three weeks later, her vision returned to her 
baseline of 20/30 and a fluorescein angiogram showed resolution of the edema.
This may indicate that cystoid macular edema related to Nd:YAG laser capsulotomy 
is caused by prostaglandin release, and that it may be responsive to topical
nonsteroidal drops.

Publication Types: 
    Case Reports

PMID: 15088830 [PubMed - indexed for MEDLINE]

2339: Arch Ophthalmol. 2004 Apr;122(4):598-614.

Current concepts in the pathogenesis of age-related macular degeneration.

Zarbin MA.

Institute of Ophthalmology and Visual Science at the New Jersey Medical School,
University of Medicine and Dentistry of New Jersey, 90 Bergen Street, Suite 6100,
Newark, NJ 07103-2499, USA. zarbin@njmsa.umdnj.edu

OBJECTIVE: To review and synthesize information concerning the pathogenesis of
age-related macular degeneration (AMD). METHODS: Review of the English-language
literature. RESULTS: Five concepts relevant to the cell biology of AMD are as
follows: (1) AMD involves aging changes plus additional pathological changes (ie,
AMD is not just an aging change); (2) in aging and AMD, oxidative stress causes
retinal pigment epithelial (RPE) and, possibly, choriocapillaris injury; (3) in
AMD (and perhaps in aging), RPE and, possibly, choriocapillaris injury results in
a chronic inflammatory response within the Bruch membrane and the choroid; (4) in
AMD, RPE and, possibly, choriocapillaris injury and inflammation lead to
formation of an abnormal extracellular matrix (ECM), which causes altered
diffusion of nutrients to the retina and RPE, possibly precipitating further RPE 
and retinal damage; and (5) the abnormal ECM results in altered
RPE-choriocapillaris behavior leading ultimately to atrophy of the retina, RPE,
and choriocapillaris and/or choroidal new vessel growth. In this sequence of
events, both the environment and multiple genes can alter a patient's
susceptibility to AMD. Implicit in this characterization of AMD pathogenesis is
the concept that there is linear progression from one stage of the disease to the
next. This assumption may be incorrect, and different biochemical pathways
leading to geographic atrophy and/or choroidal new vessels may operate
simultaneously. CONCLUSIONS: Better knowledge of AMD cell biology will lead to
better treatments for AMD at all stages of the disease. Many unanswered questions
regarding AMD pathogenesis remain. Multiple animal models and in vitro models of 
specific aspects of AMD are needed to make rapid progress in developing effective
therapies for different stages of the disease.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 15078679 [PubMed - indexed for MEDLINE]

2340: Arch Ophthalmol. 2004 Apr;122(4):575-80.

Extremely discordant sib-pair study design to determine risk factors for
neovascular age-related macular degeneration.

DeAngelis MM, Lane AM, Shah CP, Ott J, Dryja TP, Miller JW.

Ocular Molecular Genetics Institute, Harvard Medical School, Boston, MA 02114,
USA.

OBJECTIVE: To search for factors that contribute to the development of
neovascular age-related macular degeneration (AMD). METHODS: In a matched-pair
case-control study, we studied sib pairs in which the index sibling had
neovascular AMD in at least 1 eye and the unaffected sibling had normal maculae
(or at most only a few small drusen) and was past the age at which the index case
was diagnosed. Factors studied included sex, iris color, education, alcohol
consumption, body mass index, vitamin use, smoking history, hypercholesterolemia,
aspirin use, hypertension, other cardiovascular disease, any autoimmune disease, 
and non-insulin-dependent diabetes mellitus. Conditional logistic regression was 
performed to identify predictors of neovascular AMD. RESULTS: On the basis of 73 
sib pairs, multivariate regression analysis revealed a statistically significant 
2% increase in risk of neovascular AMD with each pack-year of smoking (odds
ratio, 1.02; 95% confidence interval, 1.01-1.04; P =.007). Suggestive but
nonsignificant associations were also observed for mean lifetime alcohol
consumption, adult lifetime body mass index, and hypertension in multivariate
regression analyses. CONCLUSION: Using extremely discordant sib pairs to study
risk factors for AMD, a novel approach in epidemiological design, we found
evidence that smoking is a risk factor for neovascular AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15078676 [PubMed - indexed for MEDLINE]

2341: Arch Ophthalmol. 2004 Apr;122(4):564-72.

Comment in:
    JAMA. 2004 Apr 21;291(15):1900-1.

Prevalence of age-related macular degeneration in the United States.

Friedman DS, O'Colmain BJ, Muñoz B, Tomany SC, McCarty C, de Jong PT, Nemesure B,
Mitchell P, Kempen J; Eye Diseases Prevalence Research Group.

Wilmer Eye Institute, Wilmer 120, 600 N. Wolfe Street, Baltimore, MD 21287, USA. 
david.friedman@jhu.edu

OBJECTIVE: To estimate the prevalence and distribution of age-related macular
degeneration (AMD) in the United States by age, race/ethnicity, and gender.
METHODS: Summary prevalence estimates of drusen 125 microm or larger, neovascular
AMD, and geographic atrophy were prepared separately for black and white persons 
in 5-year age intervals starting at 40 years. The estimated rates were based on a
meta-analysis of recent population-based studies in the United States, Australia,
and Europe. These rates were applied to 2000 US Census data and to projected US
population figures for 2020 to estimate the number of the US population with
drusen and AMD. RESULTS: The overall prevalence of neovascular AMD and/or
geographic atrophy in the US population 40 years and older is estimated to be
1.47% (95% confidence interval, 1.38%-1.55%), with 1.75 million citizens having
AMD. The prevalence of AMD increased dramatically with age, with more than 15% of
the white women older than 80 years having neovascular AMD and/or geographic
atrophy. More than 7 million individuals had drusen measuring 125 microm or
larger and were, therefore, at substantial risk of developing AMD. Owing to the
rapidly aging population, the number of persons having AMD will increase by 50%
to 2.95 million in 2020. Age-related macular degeneration was far more prevalent 
among white than among black persons. CONCLUSION: Age-related macular
degeneration affects more than 1.75 million individuals in the United States.
Owing to the rapid aging of the US population, this number will increase to
almost 3 million by 2020.

PMID: 15078675 [PubMed - indexed for MEDLINE]

2342: Arch Ophthalmol. 2004 Apr;122(4):453-9.

Photodynamic therapy for occult choroidal neovascularization with pigment
epithelium detachment in age-related macular degeneration.

Axer-Siegel R, Ehrlich R, Rosenblatt I, Kramer M, Priel E, Yassur Y, Weinberger
D.

Department of Ophthalmology, Rabin Medical Center, Beilinson Campus, Petah Tikva 
49100, Israel. seegs@netvision.net.il

OBJECTIVE: To study the visual and angiographic outcome of eyes with neovascular 
age-related macular degeneration associated with pigment epithelium detachment
(PED) treated by photodynamic therapy. METHODS: Review of the medical charts and 
the fluorescein and indocyanine green angiograms of all consecutive patients with
age-related macular degeneration associated with choroidal neovascularization and
serous PED of at least 1 disc diameter, who received photodynamic therapy from
January 1, 2000, to August 31, 2002. RESULTS: Thirty patients (34 eyes) met the
study criteria. Each underwent 1 to 8 treatments (mean, 4); duration of follow-up
was 12 to 36 months (mean, 19 months). Nineteen eyes (56%) lost 3 or more Snellen
lines of visual acuity, 7 eyes (21%) lost 1 or 2 lines, 6 eyes (18%) maintained
their initial acuity, and 2 eyes (6%) gained 1 or 2 lines. Subretinal hemorrhage 
occurred in 5 eyes and retinal pigment epithelium tears in 4 eyes. In 4 eyes,
visual acuity decreased to counting fingers, hand motions, or light perception.
CONCLUSIONS: Although 44% of the 34 eyes with age-related macular degeneration
and PED lost fewer than 3 Snellen lines in acuity, severe visual loss to counting
fingers or less occurred in 4 eyes, 3 of them with choroidal neovascularization
inside the PED. Further studies and treatment modalities are required to improve 
prognosis of neovascular age-related macular degeneration with serous PED.

PMID: 15078661 [PubMed - indexed for MEDLINE]

2343: Insight. 2004 Jan-Mar;29(1):15-6; quiz 17-8.

Nutritional supplements in the prevention of age-related macular degeneration.

Blodi BA.

Department of Ophthalmology and Visual Sciences, 2870 University Ave., Ste. 206, 
Madison, WI 53705, USA.

The benefit of the AREDS study and of nutritional supplements in reducing the
onset or progression of end-stage AMD in those known to be at risk is a step
forward in our understanding of what can be a blinding and debilitating disease. 
Nutritional supplements are not without risks, and their effects must be
diligently and accurately monitored. However, they pose a viable complement in
the venue of treating ocular disease and conditions.

Publication Types: 
    Review

PMID: 15077399 [PubMed - indexed for MEDLINE]

2344: Retina. 2004 Feb;24(1):23-9.

Long-term results of vitrectomy for removal of submacular hard exudates in
patients with diabetic maculopathy.

Takaya K, Suzuki Y, Mizutani H, Sakuraba T, Nakazawa M.

Department of Ophthalmology, Hirosaki University School of Medicine, 5 Zaifu-cho,
Hirosaki 036-8562, Japan.

PURPOSE: To investigate long-term results of vitrectomy for the removal of
submacular hard exudates in patients with diabetic maculopathy. METHODS: Thirteen
eyes of 10 patients with diabetic maculopathy underwent vitrectomy to remove
submacular hard exudates from December 1993 to March 1999. The mean preoperative 
logMAR visual acuity +/- SD was 1.54 +/- 0.43. Preoperatively, the exudates
ranged from 0.5 to 3 disk diameters (average, 1.25 disk diameters). Exudates were
removed using subretinal forceps through a minimal paramacular retinotomy after
vitrectomy. In all cases, 20% SF6 gas tamponade was added. The mean postoperative
observation period was 43.2 months. RESULTS: Visual acuity was improved in 7 eyes
(54%) 1 year after surgery; however, visual acuity over longer periods was
improved in only 5 eyes (38%) as compared with the preoperative findings. The
mean final visual acuity +/- SD was 1.62 +/- 0.59, which did not show
statistically significant improvement over that in the control group. Although
submacular hard exudates and macular edema disappeared during the postoperative
period, atrophic or degenerative changes occurred in many cases. CONCLUSION:
Visual improvement could not be obtained for a long period after removing
submacular hard exudates in most of the patients, suggesting that diabetic
maculopathy should be treated before massive exudate deposits appear in the
macula.

PMID: 15076940 [PubMed - indexed for MEDLINE]

2345: Retina. 2004 Feb;24(1):1-12.

Verteporfin therapy of subfoveal choroidal neovascularization in age-related
macular degeneration: meta-analysis of 2-year safety results in three randomized 
clinical trials: Treatment Of Age-Related Macular Degeneration With Photodynamic 
Therapy and Verteporfin In Photodynamic Therapy Study Report no. 4.

Azab M, Benchaboune M, Blinder KJ, Bressler NM, Bressler SB, Gragoudas ES, Fish
GE, Hao Y, Haynes L, Lim JI, Menchini U, Miller JW, Mones J, Potter MJ, Reaves A,
Rosenfeld PJ, Strong A, Su XY, Slakter JS, Schmidt-Erfurth U, Sorenson JA;
Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP)
Study Group; Verteporfin in Photodynamic Therapy (VIP) Study Group.

PURPOSE: We sought to evaluate the detailed safety profile of photodynamic
therapy with verteporfin in patients with subfoveal choroidal neovascularization 
(CNV) caused by age-related macular degeneration (ARMD) from the combined
analysis of three multicenter, double-masked, placebo-controlled, randomized
24-month clinical trials of similar design (TAP Investigation Studies A and B and
the VIP ARMD Trial), and to clarify the adverse reaction information in the
current verteporfin product prescription information approved in the United
States. METHODS: Nine hundred forty-eight patients were randomly assigned to
verteporfin or placebo. Treatment was administered as described in previous
reports. All general entry criteria were similar, so systemic safety results were
combined for this analysis. Entry criteria for CNV lesion composition and visual 
acuity in the two TAP Investigation trials was different from those used in the
VIP ARMD trial, so ocular safety results for the treated eye were not combined.
RESULTS: The percentage of patients who experienced at least one ocular or
nonocular adverse event, regardless of relationship to therapy, was similar
between the verteporfin and placebo groups (92.3 and 89.1%, respectively, P =
0.114). The overall incidence of study eye adverse events was not significantly
different between verteporfin and placebo. The only clinically relevant ocular
adverse events reported with higher incidence after verteporfin compared with
placebo were visual disturbances (22.1 versus 15.5% in TAP [P = 0.054] and 41.7
and 22.8% in VIP [P < 0.001]). Acute severe visual acuity decrease (defined as a 
visual acuity letter score decrease of at least 20, equivalent to at least
four-line decrease, within 7 days of therapy) occurred in 3 patients treated with
verteporfin in the TAP Investigation (0.7%) and 11 in the VIP ARMD trial (4.9%). 
Systemic adverse events with increased incidence after verteporfin compared with 
placebo, most of which were transient and mild or moderate, were injection site
reactions (13.1 versus 5.6%; P < 0.001), photosensitivity reactions (2.4 versus
0.3%; P = 0.016), and infusion-related back pain (2.4 versus 0%; P = 0.004). No
clinically relevant difference was observed between the verteporfin and placebo
groups in any other adverse event. CONCLUSION: In 948 ARMD patients, verteporfin 
therapy had an overall safety profile similar to that for placebo, with a few
exceptions. Visual disturbances, including acute severe visual acuity decrease,
did not affect the net vision outcome benefits associated with treatment that has
been reported previously. This detailed safety profile of verteporfin therapy
clarifies the adverse reaction information in the current verteporfin product
prescription information.

Publication Types: 
    Meta-Analysis
    Research Support, Non-U.S. Gov't

PMID: 15076937 [PubMed - indexed for MEDLINE]

2346: J Indian Med Assoc. 2003 Aug;101(8):471-4, 476.

Management of age-related macular degeneration.

Mohan KC, Shukla D, Namperumalsamy P, Kim R.

Aravind Eye Hospital and Postgraduate Institute of Ophthalmology, Retina Vitreous
Services, Madurai 625020.

With the increase in life expectancy across the world, the magnitude of blindness
due to age-related macular degeneration (AMD) is expected to rise. Exudative form
is the major cause of visual loss from AMD. Several treatment options are
available for this form of the disease. However, all treatment strategies aim at 
preservation of residual vision rather than regaining the lost vision. Two
well-proven strategies are laser photocoagulation and photodynamic therapy. Other
viable options are submacular surgery, transpupillary thermotherapy and
pharmacological modalities like angiostatic-steroids. Oral anti-oxidants and zinc
appear to be beneficial in preventing disease progression in early cases. Further
research is on to explore more efficient treatments and to prove the safety and
efficacy of large number of emerging newer treatment options.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 15071799 [PubMed - indexed for MEDLINE]

2347: Proc Natl Acad Sci U S A. 2004 Apr 20;101(16):5928-33. Epub 2004 Apr 5.

Light exposure stimulates formation of A2E oxiranes in a mouse model of
Stargardt's macular degeneration.

Radu RA, Mata NL, Bagla A, Travis GH.

Jules Stein Eye Institute and Department of Biological Chemistry, School of
Medicine, University of California, Los Angeles, CA 90095, USA.

Recessive Stargardt's macular degeneration is a blinding disease of children
caused by mutations in the ABCA4 (ABCR) gene. Mice with a knockout mutation in
abcr accumulate toxic lipofuscin pigments in ocular tissues, similar to affected 
humans. The major fluorophore of lipofuscin is the bis-retinoid,
N-retinylidene-N-retinylethanolamine (A2E). In the current study, we sought to
define the effect of increasing light on A2E accumulation. We crossed the
abcr(-/-) mutation onto an albino background. The retinoid profiles in albino
mice indicated higher retinal illuminance than in pigmented mice exposed to
similar ambient light. Unexpectedly, A2E levels were not higher in the albino
mice. Also, A2E levels in abcr(-/-) mice reared under cyclic light at 30, 120, or
1,700 lux were similar. Thus, increased retinal illuminance was not correlated
with higher A2E. A2E has been shown to undergo light-dependent oxidation to yield
a series of A2E epoxides or oxiranes. These oxiranes react with DNA in vitro,
suggesting a potential mechanism for A2E cytotoxicity. We analyzed ocular tissues
from abcr(-/-) mice for A2E oxiranes by mass spectrometry. Unlike A2E, the
oxiranes were more abundant in albino vs. pigmented abcr(-/-) mice, and in
abcr(-/-) mice exposed to increasing ambient light. These observations suggest
that both the biosynthesis of A2E and its conversion to oxiranes are accelerated 
by light. Finally, we showed that the formation of A2E oxiranes is strongly
suppressed by treating the abcr(-/-) mice with Accutane (isotretinoin), an
inhibitor of rhodopsin regeneration.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15067110 [PubMed - indexed for MEDLINE]

2348: Psychol Aging. 2004 Mar;19(1):235-9.

The role of primary and secondary control in adaptation to age-related vision
loss: a study of older adults with macular degeneration.

Wahl HW, Becker S, Burmedi D, Schilling O.

German Center for Research on Aging, University of Heidelberg, Heidelberg,
Germany. wahl@dzfa.uni-heidelberg.de

This study examines the effect of primary and secondary control on 3 major
outcomes experienced by visually impaired older adults, that is, functional
ability, adaptation to vision loss, and positive affect. The authors' theoretical
model is based on the J. Heckhausen and R. Schulz (1995) control framework, as
well as a conceptual integration of these outcomes, and they hypothesized that
control beliefs can substantially contribute to explaining interindividual
differences in these outcomes. A path model applied to data from a sample (N =
90) of visually impaired older adults, suffering from age-related macular
degeneration, the major cause of vision loss in old age, generally supports this 
expectation.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15065949 [PubMed - indexed for MEDLINE]

2349: Am J Ophthalmol. 2004 Apr;137(4):750-2.

Cholesterol and age-related macular degeneration: is there a link?

van Leeuwen R, Klaver CC, Vingerling JR, Hofman A, van Duijn CM, Stricker BH, de 
Jong PT.

Department of Epidemiology and Biostatistics, Erasmus Medical Center, Rotterdam, 
The Netherlands.

PURPOSE: To examine the relation among serum cholesterol, apolipoprotein E
genotype (APOE), and the risk of early and late age-related macular degeneration 
(AMD). DESIGN: The Rotterdam Study, a population based prospective cohort study. 
METHODS: Serum levels of total and high-density lipoprotein (HDL) cholesterol as 
well as APOE genotype were determined at baseline. Of 3,944 subjects, 400 were
diagnosed with incident early and late AMD after a mean follow-up of 5.2 years.
RESULTS: Serum HDL, but not total, cholesterol was associated with an increased
risk of AMD (odds ratio/SD, 1.20; 95% confidence interval; 1.06-1.35). The
association remained unchanged after adjustment for APOE genotype. When
stratifying for APOE genotype, the association was strongest in persons with the 
e 4 allele; an inverse association seemed to be present for e 2 carriers.
CONCLUSION: Elevated HDL but not total cholesterol is associated with an
increased risk of AMD. Apolipoprotein E genotype does not explain this
association but may be an effect modifier.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15059717 [PubMed - indexed for MEDLINE]

2350: Am J Ophthalmol. 2004 Apr;137(4):683-96.

Acute severe visual acuity decrease after photodynamic therapy with verteporfin: 
case reports from randomized clinical trials-TAP and VIP report no. 3.

Arnold JJ, Blinder KJ, Bressler NM, Bressler SB, Burdan A, Haynes L, Lim JI,
Miller JW, Potter MJ, Reaves A, Rosenfeld PJ, Sickenberg M, Slakter JS, Soubrane 
G, Strong HA, Stur M; Treatment of Age-Related Macular Degeneration with
Photodynamic Therapy Study Group; Verteporfin in Photodynamic Therapy Study
Group.

PURPOSE: To describe in detail occurrences of acute severe visual acuity decrease
after photodynamic therapy (PDT) with verteporfin in the Treatment of Age-related
macular degeneration with Photodynamic therapy (TAP) Investigation and the
Verteporfin In Photodynamic therapy (VIP) Trial. DESIGN: Observational case
series. METHODS: Retrospective review of all cases that developed acute severe
visual acuity decrease after treatment. RESULTS: Of 15 acute severe visual acuity
decrease events originally identified in 14 eyes of 14 patients, one event in one
patient was judged unlikely to have been an acute severe visual acuity decrease
event on retrospective review of these events in preparation of this report.
Eleven events occurred after the first treatment. At follow-up, 10 improved by at
least 1 line in visual acuity from the level noted at the time of the event. Of
the nine patients returning for the month 24 examination, visual acuity decreased
at least 3 lines from baseline in six, including at least 6 lines in four, and
remained within 1 line in three. Associated abnormal morphology included three
with a serous macular detachment and abnormal choroidal hypofluorescence, four
with macular hemorrhage, three with a greenish subfoveal hemorrhage, and four
with no abnormality. Events appeared to be more likely when patients had a visual
acuity of 20/50 or better. CONCLUSIONS: Acute severe visual acuity decrease after
PDT with verteporfin was an uncommon event; the risk did not outweigh the
benefits of therapy previously reported. When considering verteporfin therapy,
patients should be warned of the possibility of this serious adverse event.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15059708 [PubMed - indexed for MEDLINE]

2351: Am J Ophthalmol. 2004 Apr;137(4):675-82.

Lipid-lowering drug atorvastatin as an adjunct in the management of diabetic
macular edema.

Gupta A, Gupta V, Thapar S, Bhansali A.

Department of Ophthalmology, Postgraduate Institute of Education and Research,
Chandigarh, India. eyepgi@sify.com

PURPOSE: To determine the efficacy of the lipid-lowering drug atorvastatin in
reducing retinal hard exudates and subfoveal lipid migration after focal/grid
laser photocoagulation in clinically significant macular edema in patients with
diabetes with elevated serum lipids. DESIGN: Randomized case trial. METHODS:
Thirty patients with type 2 diabetes with clinically significant macular edema,
dyslipidemia, and hard exudates of grade 4 and above were assessed in an
institutional setting. All patients were subjected to strict metabolic control
within 4 to 6 weeks of enrollment. In addition, 15 patients in group A received
atorvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A inhibitor; 15 members of
group B did not receive any lipid-lowering therapy. All received laser
photocoagulation after a metabolic control period and were followed up for a
minimum of 18 weeks. The outcome measures were reduction in hard exudates,
subfoveal lipid migration, status of macular edema, and visual acuity. RESULTS:
The study included 21 men and nine women with noninsulin-dependent diabetes
mellitus who could achieve good metabolic control within 4 to 6 weeks of
inclusion in the study. All patients had elevated serum lipids at baseline. Ten
(66.6%) of 15 patients in treatment group A and two (13.3%) of 15 patients in
control group B showed reduction in hard exudates (P =.007). None of the patients
in group A and five (33.3%) of 15 in group B showed subfoveal lipid migration
after laser photocoagulation (P =.04). Regression of macular edema was seen in
nine eyes in group A and five in group B (P =.27). None of the eyes in group A
and three eyes in group B showed worsening of visual acuity (P =.22). CONCLUSION:
Oral atorvastatin therapy in patients with type 2 diabetes with dyslipidemia
reduces the severity of hard exudates and subfoveal lipid migration in clinically
significant macular edema and could be an important adjunct in the management of 
clinically significant macular edema.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 15059707 [PubMed - indexed for MEDLINE]

2352: Am J Ophthalmol. 2004 Apr;137(4):636-8.

Comment in:
    Am J Ophthalmol. 2005 Jan;139(1):216-7; author reply 217.

Valganciclovir therapy for immune recovery uveitis complicated by macular edema.

Kosobucki BR, Goldberg DE, Bessho K, Koh HJ, Rodanant N, Labree L, Cheng L,
Schrier RD, Azen SP, Freeman WR.

UCSD Jacobs Retina Center, Department of Ophthalmology, Shiley Eye Center, La
Jolla, California 92093, USA.

PURPOSE: To determine whether treatment with valganciclovir will improve visual
acuity in eyes with immune recovery uveitis complicated by macular edema. DESIGN:
Prospective open label controlled Phase II drug study. METHODS: Five patients
with chronic macular edema as a result of immune recovery uveitis were studied.
Baseline fluorescein angiograms, best-corrected ETDRS visions, and
cytomegalovirus (CMV) lymphoproliferative T-cell function assays were obtained
and repeated after three months of valganciclovir therapy (900 mg daily) and
again three months after withdrawal of therapy. RESULTS: Vision improved by a
mean of 11 letters in the treatment phase (P =.05). Graded angiograms showed
three patients had treatment reduction of macular edema. One patient had rebound 
increase in macular edema after the withdrawal phase. The CMV lymphoproliferative
response was not affected by the valganciclovir. CONCLUSION: Results suggest
valganciclovir treatment may benefit visual acuity in patients with macular edema
from immune recovery uveitis.

Publication Types: 
    Clinical Trial
    Clinical Trial, Phase II
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15059701 [PubMed - indexed for MEDLINE]

2353: Am J Ophthalmol. 2004 Apr;137(4):615-24.

Comment in:
    Am J Ophthalmol. 2004 Apr;137(4):747-9.    Am J Ophthalmol. 2004 Dec;138(6):1089; author reply 1090.    Am J Ophthalmol. 2004 Oct;138(4):697; author reply 697-8.

Statin and aspirin therapy are associated with decreased rates of choroidal
neovascularization among patients with age-related macular degeneration.

Wilson HL, Schwartz DM, Bhatt HR, McCulloch CE, Duncan JL.

Department of Ophthalmology, UCSF School of Medicine, San Francisco, CA 94143,
USA.

PURPOSE: To investigate the relationship between statin and aspirin use and the
risk of choroidal neovascularization (CNV) in patients with age-related macular
degeneration (AMD). DESIGN: Retrospective consecutive case series. METHODS: All
patients 60 years and older with AMD who were seen between January 1, 1990, and
March 1, 2003, at the San Francisco Veterans Affairs Hospital Eye Clinic with
fundus photographs were included. Patients with other diagnoses predisposing to
CNV or incomplete medical records were excluded. The main outcome measure was
angiographically evident CNV. Diagnosis was based on review of fundus photographs
and fluorescein angiograms in masked fashion; medical records were reviewed for
variables possibly predisposing to CNV or statin use. For patients with CNV, age 
of onset was recorded; those without CNV were treated as censored. Age-related
macular degeneration disease status and time of onset of CNV was compared between
patients treated or not treated with statins for at least 6 months. RESULTS: Of
326 patients with AMD, 104 had CNV, 204 had dry AMD, and 18 had geographic
atrophy (GA). Of CNV subjects, 21 (20%) used statins, compared with 77 (38%) of
dry AMD subjects without GA and 6 (33%) of controls with GA (hazard ratio = 0.51,
95% confidence interval (CI) = 0.31-0.86, P =.01). Aspirin use was also
significantly associated with decreased rates of CNV; 62 CNV subjects (60%) used 
aspirin, compared with 154 (75%) dry AMD subjects without GA or 12 (67%) with GA 
(hazard ratio = 0.63, 95% CI = 0.40-0.98, P =.04). CONCLUSIONS: Therapy with
statins or aspirin is associated with decreased rates of CNV among AMD patients. 
Additional study with a prospective and/or randomized trial of statin and aspirin
use in AMD patients is warranted.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15059698 [PubMed - indexed for MEDLINE]

2354: Prescrire Int. 2004 Feb;13(69):7-9.

Verteporfin: new indication. In certain age-related macular degeneration: too
little evidence.

[No authors listed]

(1) The standard treatment for neovascular forms of age-related macular
degeneration is thermal coagulation by argon or krypton laser, but it is only
suitable for patients with juxtafoveal or extrafoveal neovascularisation. (2)
Verteporfin, a photosensitising agent, is injected intravenously 15 minutes
before non thermal red laser activation. This protocol was initially restricted
to patients with predominantly visible neovascularisation in the subfoveal
choroidal region. In Europe (but not in the United States), this treatment has
now been approved for patients with occult subfoveal neovascularisation, i.e.
poorly defined zones of fluorescein diffusion. (3) Use in this indication is
supported by a single double-blind trial comparing red laser + verteporfin with
red laser + placebo. After one year's treatment there was no difference between
the groups in the number of patients whose loss of visual acuity had stabilised. 
One of the several statistical analyses showed that red laser + verteporfin was
significantly more effective than red laser + placebo at two years, after five
treatment sessions on average. Only a minority of patients benefited, however,
and these cannot yet be identified before treatment. It is unclear whether
efficacy persists in the long term. (4) Some patients experienced a transient
visual deterioration. Verteporfin infusion can provoke local reactions and
thoracic or lumbar pain. Cutaneous photosensitisation can occur for 48 hours
after treatment. (5) Treatment with verteporfin is expensive. (6) In practice,
there is currently no reason to use red laser + verteporfin in patients with
age-related macular degeneration and occult neovascularisation, other than in
clinical trials.

Publication Types: 
    Comparative Study

PMID: 15055207 [PubMed - indexed for MEDLINE]

2355: Ophthalmology. 2004 Apr;111(4):712-5.

Comment in:
    Ophthalmology. 2005 Apr;112(4):734-5; author reply 735.

Comparison of the clinical diagnosis of diabetic macular edema with diagnosis by 
optical coherence tomography.

Browning DJ, McOwen MD, Bowen RM Jr, O'Marah TL.

Charlotte Eye, Ear, Nose, and Throat Associates, 6035 Fairview Road, Charlotte,
NC 28210, USA. djbrowning@carolina.rr.com

PURPOSE: To compare the diagnosis of diabetic macular edema (DME) by stereoscopic
slit-lamp biomicroscopic examination of the fundus with a 78-diopter noncontact
lens with diagnosis by optical coherence tomography (OCT). DESIGN: Prospective,
double-masked, noninterventional diagnostic study. METHODS: Analysis of slit-lamp
biomicroscopic findings compared with OCT measurements. PARTICIPANTS: Patients
with DME from a private retina practice. MAIN OUTCOME MEASURES: Presence or
absence of macular thickening. RESULTS: The reference range for this clinic was
comparable to reference ranges published from other clinics. The clinical
detection of DME was less than detection by OCT. Chance-corrected agreements
(kappa statistic) of the 2 methods were 0.63 for the foveal zone and 0.36 to 0.42
for the 4 parafoveal zones. The errors committed in clinical examination were
primarily of the type in which clinical examination did not detect DME but OCT
did (58%-90%) for the 5 zones analyzed. CONCLUSIONS: Reference ranges for OCT
seem to be similar for different clinical settings, suggesting the usefulness of 
OCT in multicenter studies. The current standard of care for DME detection,
stereoscopic slit-lamp examination of the fundus, is less sensitive than OCT for 
detection of DME. Because the principal therapy for DME, focal laser
photocoagulation, is mainly sight preserving and not sight restoring, the wider
use of OCT may beneficially impact visual disability from DME.

Publication Types: 
    Comparative Study

PMID: 15051203 [PubMed - indexed for MEDLINE]

2356: Ophthalmology. 2004 Apr;111(4):706-11.

Four-year incidence of macular changes in the Barbados Eye Studies.

Leske MC, Wu SY, Hyman L, Hennis A, Nemesure B, Schachat AP; Barbados Eye Studies
Group.

Department of Preventive Medicine, School of Medicine, Stony Brook University, L3
HSC Room 086, Stony Brook, NY 11795-8036, USA. cleske@notes.cc.sunysb.edu

OBJECTIVE: To describe longitudinal macular changes in a black population after 4
years of follow-up. DESIGN: Population-based incidence study. SETTING AND
PARTICIPANTS: The Barbados Incidence Study of Eye Diseases (BISED) reexamined the
Barbados Eye Study cohort, which was based on a random sample of the country's
residents, 40 to 84 years. The BISED included 3427 persons, or 85% of the
eligible cohort. MAIN OUTCOME MEASURES: Four-year incidence of macular changes,
as determined by gradings of color stereoscopic macular photographs. RESULTS:
Among black participants, the overall 4-year incidence of early macular changes
(medium or large drusen or >20 small drusen with retinal pigment epithelium [RPE]
atrophy or pigment) was 5.2% (95% confidence interval, 4.0%-6.6%) and tended to
be higher in women (5.8%) than in men (4.1%). Incidence of related features was
5.2% for medium drusen (64-250 microm), 0.3% for drusen >250 microm, 1.1% for
confluence, 0.5% for pigment, and 0.1% for RPE atrophy. Of the 2362 persons at
risk for late macular changes (geographic atrophy, fluid, lipid, hemorrhage,
disciform scar), exudative features developed in only 1 person in 4 years. Less
than 1% of persons with early macular changes at baseline had disappearance of
related features. CONCLUSIONS: After 4 years, the development of severe macular
disease was rare in this black population, and the incidence of early macular
changes also was lower than in other populations. Results are consistent with the
low risk of macular degeneration in persons of African descent.

PMID: 15051202 [PubMed - indexed for MEDLINE]

2357: J Public Health (Oxf). 2004 Mar;26(1):52-5.

Increasing use of a new health technology during the wait for NICE guidance:
findings from the third national tracker survey of photodynamic therapy.

Foot B, Foy R, Chakravarthy U, Wormald R.

The Royal College of Ophthalmologists, London. barny.foot@moorfields.nhs.uk

BACKGROUND: Photodynamic therapy (PDT) is a relatively new treatment for
neovascular age-related macular degeneration. Trial evidence suggests that
repeated treatments with PDT can decrease the relative risk of a reduction in
visual acuity over 2 years. Concerns raised over the clinical and cost
effectiveness of the treatment prompted a technology appraisal by the National
Institute for Clinical Effectiveness (NICE). Difficulties in assessing the
possible benefit or otherwise of PDT have led to delays in the publication of
guidance. During this time the introduction of PDT into the UK National Health
Service (NHS) has continued. Over three annual tracker surveys, we describe
trends in the provision of PDT in the NHS and potential difficulties in the
implementation of NICE guidance. METHODS: We undertook surveys in each October of
2000, 2001 and 2002 of clinical directors or lead consultants in all NHS eye
units. These sought data on which (if any) patients were referred or treated with
PDT and the thresholds of support for the use of PDT. RESULTS: Response rates
were 82 per cent, 79 per cent and 82 per cent. The proportion of units routinely 
providing PDT for patients with more than 50 per cent classic sub-foveal CNV
increased from 8.5 per cent in 2000 to 31 per cent in 2002 (p <0.001). Units
referring or treating no patients decreased from 35 per cent to 10 per cent
between 2000 and 2002 (p <0.001). There was a significant fall in the proportion 
of units changing policies on provision between 2000-2001 and 2001-2002. The
proportion of respondents requiring further evidence before supporting the use of
PDT decreased from 33 per cent in 2000 to 20 per cent in 2002. CONCLUSION: There 
is evidence of a continuing growth in access to PDT in the absence of NICE
guidance. Although 90 per cent of units offer some pathway to treatment important
variations in reported provision remain. Given that PDT services are becoming
established, there is a risk that clinical policy is determined by local service 
development as much as by national guidance.

PMID: 15044575 [PubMed - indexed for MEDLINE]

2358: Graefes Arch Clin Exp Ophthalmol. 2004 Apr;242(4):273-8. Epub 2004 Mar 23.

Visual outcome of patients with macular edema after pars plana vitrectomy and
indocyanine green-assisted peeling of the internal limiting membrane.

Radetzky S, Walter P, Fauser S, Koizumi K, Kirchhof B, Joussen AM.

Department of Vitreoretinal Surgery, Center for Ophthalmology, Joseph
Stelzmann-Strasse 9, 50931, Cologne, Germany.

PURPOSE: To evaluate the efficacy of inner limiting membrane (ILM) peeling in
persistent macular edema. METHODS: This retrospective review analyzed a series of
23 eyes from 23 patients with persistent macular edema treated by pars plana
vitrectomy (PPV) with indocyanine green (ICG)-assisted peeling of the ILM.
Thirteen female and 10 male patients with a mean age of 57.2+/-15.6 (24-77) years
underwent operation between May 2000 and October 2001. The main diagnoses were
uveitis (anterior, intermediate, posterior and panuveitis) ( n=9), central
retinal vein occlusion (CRVO) (n=4), diabetic retinopathy (DR) ( n=5),
vitreoretinal traction syndrome ( n=2), and Irvine-Gass syndrome ( n=3). Nine
eyes had undergone phacoemulsification (PE) previously and two eyes had been
subjected to combined PE and ILM peeling. The eyes were tamponaded with gas (3), 
silicone oil (5) or air (11). In four cases no endotamponade was used.
Improvement in visual acuity of 2 lines or more was regarded as significant.
RESULTS: Visual acuity improved after 3 months in 9 of the 23 patients. After 6
months and at the follow-up, a significant improvement was found in 6/21 and 7/21
patients. This improvement was predominantly seen in patients with uveitis (5/9),
or diabetic maculopathy (3/5); One patient with Irvine-Gass syndrome showed a
significant reduction, one with vitreoretinal traction an improvement in visual
acuity. The group of patients with CRVO showed no significant change during the
follow-up. The choice of endotamponade did not alter the visual acuity outcome.
CONCLUSIONS: Different patient groups respond differently to ILM peeling.
Although overall significant visual acuity improvement was observed in only one
third of all cases 12 months after ILM peeling for persistent macular edema,
patients with uveitis and nonproliferative diabetic maculopathy demonstrated a
benefit. The lack of long-term improvement in the majority of cases is in
accordance with the hypothesis that ILM peeling may reduce the intraretinal
edema, but does not affect the underlying mechanism causing macular edema. So
far, only diabetics have shown improvement (still unproven) from ILM peeling, and
this study provides no justification for extending the treatment to macular edema
of other causes. Large-scale investigations are needed to evaluate the efficacy
in certain diagnosis groups.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15042375 [PubMed - indexed for MEDLINE]

2359: Exp Eye Res. 2004 Apr;78(4):895-8.

Observation of A2E oxidation products in human retinal lipofuscin.

Avalle LB, Wang Z, Dillon JP, Gaillard ER.

Several retinal dystrophies are associated with the accumulation of lipofuscin in
the retinal pigment epithelium (RPE). The only structurally characterized
component of human retinal lipofuscin is the bis-retinoid pyridinium compound
A2E. We report here on the observation of a monooxygenated product of A2E in the 
organic soluble portion of human retinal lipofuscin and in the organic extract of
bovine RPE cells that have been fed A2E and irradiated. Liquid chromatography
mass spectrometry confirms that the products are identical. This is the first
observation of a photoproduct of A2E in human retinal lipofuscin.

Publication Types: 
    Letter
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15037123 [PubMed - indexed for MEDLINE]

2360: Diabetes Res Clin Pract. 2004 Apr;64(1):71-2.

Sandostatin LAR for cystoid diabetic macular edema: a 1-year experience.

Hernaez-Ortega MC, Soto-Pedre E, Martin JJ.

European Innovative Biomedicine Institute, C/Jardines 2, 1-G, 39700 Cantabria,
Spain. eibi@eurodiab.com

We report the clinical outcome of a 46-year-old diabetic patient with cystoid
macular edema treated with Sandostatin long-acting release (LAR). Because cystoid
changes in both eyes were refractive to conventional treatment (i.e., vitrectomy 
and periocular steroids), the patient was treated with Sandostatin LAR 20 mg
every four weeks. One year later the patient maintained corrected visual acuity
of 20/40 in the right eye and 20/100 in the left eye, the cystoid changes had
disappeared in the right eye and had greatly decreased in the left eye. In
addition, the intraocular pressure had declined and no other complications were
found. Thus, Sandostatin LAR may be considered for the treatment of diabetic
patients with cystoid macular edema.

Publication Types: 
    Case Reports

PMID: 15036829 [PubMed - indexed for MEDLINE]

2361: Brain Res Bull. 2004 Feb 15;62(6):549-53.

Possible therapy for age-related macular degeneration using human telomerase.

Rowe-Rendleman C, Glickman RD.

Department of Pharmacology and Toxicology, InSite Vision, 965 Atlantic Avenue,
Alameda, CA 94501, USA. cherylo@insite.com

Age-related macular degeneration (AMD) is the leading cause of irreversible
blindness in people over 60 years of age in the US and many other developed
countries. Increasingly sophisticated methods for the diagnosis and treatment of 
macular degeneration are not effective for the majority of patients in whom late 
stage disease is present at the time of diagnosis. Research to elucidate the
changes in RPE cell biology during aging has stimulated interest in preventive
and prophylactic therapies for earlier intervention in the degenerative process. 
In the normal retina, the RPE performs the functions of barrier, macrophage, and 
neuroprotective cell layer. During aging and in the presence of disease the
robustness of each of these functions diminishes. The utility of
telomerase-mediated cell and gene therapy to prevent the decline in function of
RPE cells during aging is evaluated.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 15036570 [PubMed - indexed for MEDLINE]

2362: Ann Epidemiol. 2004 Mar;14(3):202-8.

Sex steroids and age-related macular degeneration in older French women: the POLA
study.

Defay R, Pinchinat S, Lumbroso S, Sutan C, Delcourt C; Pola Study Group.

Institut National de la Santé et de la Recherche Médicale , Montpellier, France. 
defay@montp.inserm.fr

PURPOSE: Postmenopausal women are reported to be at higher risk of eye diseases
than men. The purpose of our study is to determine the relationships between
endocrine status, specially plasma sex hormones levels, and the severity of
age-related macular degeneration (AMD) in a large community-based sample of older
French women. METHODS: The POLA (Pathologies Oculaires Liées à l'Age) Study is a 
population-based study on age-related eye diseases and their risk factors. The
study enrolled 2584 residents of Southern France, among whom 1451 women aged 60
years or older were recruited between June 1995 and July 1997. A standardized
international classification and grading system for AMD was used. Circulating sex
hormones levels were measured from fasting blood samples. RESULTS: No association
of hormone replacement therapy (HRT), hysterectomy, or oophorectomy was found
with soft drusen, pigmentary abnormalities, or late AMD. After multivariate
adjustment, higher plasma levels of dehydroepiandrosterone sulfate (DHEAS) were
associated with a higher prevalence of soft drusen (OR = 1.21; 95% CI =
1.01-1.44). CONCLUSION: These results may indicate no beneficial effect of HRT on
AMD. The positive association of DHEAS with AMD requires further investigation.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15036224 [PubMed - indexed for MEDLINE]

2363: Br J Ophthalmol. 2004 Apr;88(4):450-4.

Comment in:
    Br J Ophthalmol. 2005 Feb;89(2):251.

Cost utility of screening and treatment for early age related macular
degeneration with zinc and antioxidants.

Hopley C, Salkeld G, Wang JJ, Mitchell P.

Centre for Vision Research, Department of Ophthalmology and the Westmead
Millennium Institute, University of Sydney, Westmead Hospital, Hawkesbury Road,
Westmead, NSW 2145, Australia.

AIM: To assess the cost effectiveness of high dose zinc and antioxidants for
delaying and reducing the progression of early age related macular degeneration
(AMD). BACKGROUND: AMD is the leading cause of severe vision impairment and
blindness in older people throughout the developed world. It currently affects
around 420 000 people in the United Kingdom. METHODS: A cost utility analysis
(CUA) was conducted to estimate the cost per quality adjusted life year (QALY)
for screening a cohort of men and women, aged 55 years and over, for early AMD
and then treating them with zinc and antioxidants. The incremental CUA was based 
on a decision analytic model, comparing screening with a no screening comparator 
(current practice). Extensive one way sensitivity analysis of parameters was
conducted to determine the robustness of the model. RESULTS: In this model the
cost effectiveness of screening for early AMD was pound 22 722 per quality
adjusted life year (QALY) saved. The cost per QALY decreased to pound 18 948 if
photodynamic therapy with verteporfin savings were included. CONCLUSIONS:
Screening for, and prophylactic treatment of, early AMD is estimated to cost
around pound 22 700 per QALY saved. This cost falls within accepted levels to
warrant further investigation. These findings have implications for ophthalmic
practice and healthcare planning.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15031152 [PubMed - indexed for MEDLINE]

2364: Ir J Med Sci. 2003 Oct-Dec;172(4):185-90.

Current concepts and recent advances in the management of age-related macular
degeneration.

Byrne S, Beatty S.

Department of Ophthalmology, Royal Victoria Infirmary, Newcastle-upon-Tyne, UK.
sineadambyrne@eircom.net

BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of visual
impairment and blindness in the Western World in those aged 65 and older. At
present, several treatment modalities are utilised and several more are
undergoing investigation in an attempt to retard the occurrence and progression
of this devastating condition. AIMS: To provide the non-ophthalmologist with an
understanding of the current treatment options available to patients suffering
from all variants of AMD. METHODS: Medline and Embase search. RESULTS: Several
treatment modalities have been investigated and utilised in the treatment of all 
variants of this condition. While promising results have been reported, no
treatment is ideal. CONCLUSION: While no curative treatment for this condition
currently exists, early recognition and treatment, if indicated, have been shown 
to reduce the risk of severe vision loss in patients with this condition.

Publication Types: 
    Review

PMID: 15029987 [PubMed - indexed for MEDLINE]

2365: Genomics. 2004 Apr;83(4):615-25.

Atrophic macular degeneration mutations in ELOVL4 result in the intracellular
misrouting of the protein.

Ambasudhan R, Wang X, Jablonski MM, Thompson DA, Lagali PS, Wong PW, Sieving PA, 
Ayyagari R.

Kellogg Eye Center, Ophthalmology, University of Michigan, 1000 Wall Street, Ann 
Arbor, MI 48105, USA.

Elongation of very long chain fatty acids 4 (ELOVL4) is a novel member of the ELO
family of genes that are involved in fatty acid metabolism. ELOVL4 encodes a
putative transmembrane protein of 314 amino acids that carries a possible
endoplasmic reticulum (ER) retention/retrieval signal (KXKXX) at the C-terminus. 
Two distinct mutations, a 5-bp deletion and a complex mutation from the same
region in exon 6 of this gene, have been reported so far and are associated with 
autosomal dominant atrophic macular degeneration (adMD/STGD3). Both of these
deletions could result in C-terminal truncation and loss of the ER retention
signal in the mutant protein. We expressed the wild-type and mutant proteins in
COS-7 and CHO cells to study the intracellular distribution of ELOVL4 and to
identify possible implications of the above mutations in its localization.
Immunofluorescence analysis of these proteins along with organelle marker
antibodies revealed predominant ER localization for wild-type ELOVL4. Targeted
deletion of the dilysine motif at the C-terminus of the protein resulted in the
loss of ER localization. Immunoelectron microscopy and immunofluorescence
analysis revealed a similar ER localization pattern for the protein in human
photoreceptors. These data indicate that ELOVL4 is an ER-resident protein, which 
supports its suggested function in fatty acid elongation. We also demonstrate
that the localization of both mutant proteins was dramatically changed from an ER
to a Golgi distribution. Our observations suggest that the consequences of
defective protein trafficking could underlie the molecular mechanism associated
with degeneration of the macula in the patients with adMD/STGD3.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15028284 [PubMed - indexed for MEDLINE]

2366: Ophthalmology. 2004 Feb;111(2):250-5.

Fluorescein angiographic lesion type frequency in neovascular age-related macular
degeneration.

Olsen TW, Feng X, Kasper TJ, Rath PP, Steuer ER.

University of Minnesota, Department of Ophthalmology, Minneapolis, Minnesota
55455-0501, USA. olsen010@tx.umn.edu

OBJECTIVE: To assess the frequency of lesion types using fluorescein angiography 
(FA) in neovascular age-related macular degeneration (nAMD). DESIGN:
Cross-sectional study. PARTICIPANTS: Two hundred cases of nAMD. METHODS:
Fluorescein angiograms from 908 patients (university-based, tertiary retinal
referral practice [UP] = 478; comprehensive, community-based eye clinic [CC] =
430) were reviewed to identify 200 cases of nAMD (100 from each center). Two
graders evaluated the frequency of angiographic subtypes. MAIN OUTCOME MEASURES: 
Identifying (1) the frequency of subfoveal nAMD lesions that meet the definition 
of "predominantly classic," "minimally classic," "occult with no classic"; (2)
lesion location, size, and subtype; and (3) the intergrader agreement (kappa).
RESULTS: There was little difference in the frequency of lesion type between the 
UP and the CC. Most nAMD lesions were subfoveal (78.5%, 157 of 200), and of
these, 20% (32 of 157) were predominantly classic; whereas 73% (114 of 157) were 
occult with no classic, and 7% (11 of 157) were minimally classic. Of the 200
angiograms, 33 (16.5%) were juxtafoveal, and 10 (5%) were extrafoveal. Twenty of 
the 43 juxtafoveal and extrafoveal lesions (47%) were predominantly classic.
Classic with no occult subfoveal lesions were smaller than minimally classic or
occult with no classic (1.7 vs. 3.7 and 2.8 mm; P = 0.001 and 0.01,
respectively). Of 114 subfoveal occult with no classic lesions, 54 (47%) had both
smaller lesion size <==4 disc areas (DA) and lower visual acuity <20/50, whereas 
107 (94%) had a smaller lesion or lower visual acuity. CONCLUSIONS: Most
angiographic lesions of patients who undergo FA for nAMD are subfoveal and
occult. We estimate that 20% of subfoveal lesions are predominantly classic.
Approximately half of the juxtafoveal and extrafoveal lesions are predominantly
classic. Nearly 30% of all nAMD lesions have both small occult lesions (size <==4
DA) and a visual acuity less than 20/50. We found minimal difference in lesion
type between a UP and a CC.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15019371 [PubMed - indexed for MEDLINE]

2367: Ophthalmology. 2004 Feb;111(2):231-7.

Comment in:
    Ophthalmology. 2004 Sep;111(9):1793; author reply 1793-4.

Ultrastructure of internal limiting membrane removed during plasmin-assisted
vitrectomy from eyes with diabetic macular edema.

Asami T, Terasaki H, Kachi S, Nakamura M, Yamamura K, Nabeshima T, Miyake Y.

Department of Ophthalmology, Nagoya University School of Medicine, Nagoya, Japan.

PURPOSE: To study the effect of autologous plasmin enzyme (APE) on the adhesion
of the vitreous cortex to the internal limiting membrane (ILM) in eyes with
diabetic macular edema. DESIGN: Nonrandomized, comparative, interventional case
series. PARTICIPANTS: Ten eyes of 10 patients with diabetic macular edema without
a posterior vitreous detachment (PVD), which were treated with APE as an adjunct 
to conventional pars plana vitrectomy, and 10 eyes of 9 patients without a PVD,
which underwent pars plana vitrectomy without APE, were studied. METHODS: In the 
APE group, 0.4 IU of APE was injected into the midvitreous cavity in 9 eyes, and 
0.8 IU of APE in 1 eye. Thirty minutes after plasmin injection, the eyes
underwent pars plana vitrectomy with ILM peeling. All eyes in the control group
had conventional vitreous surgery with ILM peeling. The removed ILMs were
investigated for the presence of vitreous and for ultrastructural differences by 
transmission and scanning electron microscopy. MAIN OUTCOME MEASURES: The status 
of the vitreous and induction of a PVD during surgery, and the presence of
vitreous and ultrastructural differences of the removed ILM by transmission and
scanning electron microscopy. RESULTS: In APE-treated eyes, the degree of
liquefaction of the vitreous was graded as high in 4 eyes. Spontaneous PVD
occurred in 2 eyes, whereas core vitrectomy with a maximum vacuum of 100 mmHg
induced a PVD in 2 additional eyes. In the control group, 8 eyes required suction
with a maximum of 200 mmHg to induce the PVD. Scanning electron micrography of
the removed ILM in the APE-treated eyes showed a smooth surface on the vitreous
side in 8 eyes and only sparse collagen fibers in 2 eyes. Conversely, in the
control group, dense vitreous fibers were found in 4 eyes, sparse collagen
fibrils in 3 eyes, and a smooth retinal surface in 3 eyes. CONCLUSIONS: These
findings indicate that APE helps separate the vitreous hyaloid from the ILM
surface and may be a useful adjunct to conventional vitreous surgery for diabetic
macular edema.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15019368 [PubMed - indexed for MEDLINE]

2368: Ophthalmology. 2004 Feb;111(2):218-24; discussion 224-5.

Intravitreal triamcinolone acetonide for diabetic diffuse macular edema:
preliminary results of a prospective controlled trial.

Massin P, Audren F, Haouchine B, Erginay A, Bergmann JF, Benosman R, Caulin C,
Gaudric A.

Department of Ophthalmology, Hôpital Lariboisière, Assistance Publique-Hôpitaux
de Paris, Université Paris 7, Paris, France.

OBJECTIVE: To evaluate prospectively the efficacy and safety of 1 intravitreal
injection of 4 mg of triamcinolone acetonide for refractory diffuse diabetic
macular edema. DESIGN: Interventional case series. PARTICIPANTS: Fifteen patients
with bilateral diabetic macular edema unresponsive to laser photocoagulation. In 
all patients, one eye received the injection, and the other served as a control. 
INTERVENTION: Intravitreal injection of 4 mg of triamcinolone acetonide under
subconjunctival anesthesia. MAIN OUTCOME MEASURES: The main outcome measure was
central macular thickness (CMT) at 1, 3, and 6 months, measured by optical
coherence tomography. Secondary outcomes were Early Treatment Diabetic
Retinopathy Study (ETDRS) scores, intraocular pressure, and cataract progression.
RESULTS: In this preliminary report, we give the results for 12 patients who had 
a follow-up of at least 3 months. Seven of them were followed up for 6 months.
Before injection, CMT was 509.6+/-143.5 microm (mean +/- standard deviation [SD])
in injected eyes, versus 474.4+/-82.6 microm in control eyes. Four weeks after
injection, it was 207.3+/-44.2 microm in injected eyes and 506.7+/-122.4 microm
in control eyes (P<0.001, bilateral Wilcoxon test for paired samples), and after 
12 weeks, 207+/-96.7 microm and 469.3+/-117.6 microm, respectively (P = 0.005).
The difference between the CMTs of injected and control eyes was no longer
significant at 24 weeks because of the recurrence of macular edema in 5 of 12
injected eyes. Before triamcinolone injection, the ETDRS score was 47.8+/-13
(mean +/- SD; range, 28-66) in injected eyes, versus 51.9+/-14.6 (range, 31-71)
in control eyes. Twelve weeks thereafter, the corresponding values were
52.7+/-10.8 (range, 34-70) and 50.8+/-14.3 (range, 29-69), respectively, and at
24 weeks, 54.7+/-7.6 (range, 47-68) and 50.6+/-18.4 (range, 28-71). At no time
was the difference between the ETDRS scores for injected and control eyes
significant. In 6 of the 12 injected eyes, intraocular pressure exceeded 25 mmHg,
and was controlled by topical medication. CONCLUSION: Intravitreal injection of
triamcinolone effectively reduces macular thickening due to diffuse diabetic
macular edema, at least in the short term. Further studies are required to
demonstrate that it provides visual benefit.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 15019365 [PubMed - indexed for MEDLINE]

2369: Ophthalmology. 2004 Feb;111(2):211-7.

Comment in:
    Ophthalmology. 2004 Oct;111(10):1945; author reply 1945-6.    Ophthalmology. 2004 Oct;111(10):1946; author reply 1946-7.    Ophthalmology. 2004 Oct;111(10):1947; author reply 1947.

Temporal variation in diabetic macular edema measured by optical coherence
tomography.

Frank RN, Schulz L, Abe K, Iezzi R.

Kresge Eye Institute, Wayne State University School of Medicine, Detroit,
Michigan 48201, USA. rnfrank@med.wayne.edu

PURPOSE: To determine, by optical coherence tomography (OCT), whether there is a 
quantitative decrease in macular edema in diabetic subjects over the course of a 
day. STUDY DESIGN: Observational case series. PARTICIPANTS: Ten subjects with
diabetic macular edema in 1 or both eyes. METHODS: Subjects were admitted to the 
hospital the evening before the study so that they would remain in the recumbent 
position until immediately before study measurements began. They then underwent 4
OCT measurements of macular thickness in both eyes, at 8:00 am, 11:00 am, 2:00
pm, and 5:00 pm. At each of these times, they also had refractions and visual
acuity measurements using the Early Treatment Diabetic Retinopathy Study
protocol. Macular thickness measurements determined by the Zeiss-Humphrey
(Dublin, CA) optical coherence tomograph for each eye of each subject were
plotted as a function of time. MAIN OUTCOME MEASURES: Temporal changes in retinal
thickness in each of the 9 macular sectors defined by the OCT protocol and in the
entire macula of each eye, averaged from all 9 sectors; temporal changes in
refractive error and visual acuity. RESULTS: Four of the 10 subjects showed
consistent decreases in macular thickness over the course of the day in 1 or more
of the retinal sectors in 1 or both eyes. When macular thickness values were
averaged over all 9 sectors for all subjects, both eyes showed consistent
declines in mean thickness throughout the day. By t test, the 8 am value in each 
eye was significantly higher (P<0.0005) than any of the 3 later values, which did
not differ significantly from each other. However, comparison of all 4 values by 
analysis of variance showed no significant differences. With the exception of 1
subject, there were no consistent changes in refractive error or in
best-corrected visual acuity over the course of the study. CONCLUSIONS: This
study, using quantitative OCT determinations, seems to confirm the much earlier
report by Sternberg et al, which used more subjective methods, that macular edema
might vary over the day. That the 8 am value, obtained just after waking, was
higher than the 3 later values (highly significant by 1 test) suggests that the
decrease in macular thickness is most likely due to the shift from recumbent to
upright body position, although our study protocol did not exclude other possible
mechanisms. Although changes in macular thickness over the course of the day did 
not occur in all subjects, therapeutic studies for macular edema that use OCT as 
an outcome measure should control for time of day when these measurements are
carried out.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15019364 [PubMed - indexed for MEDLINE]

2370: Ophthalmology. 2004 Mar;111(3):546-53.

Three families displaying the combination of Stargardt's disease with cone-rod
dystrophy or retinitis pigmentosa.

Klevering BJ, Maugeri A, Wagner A, Go SL, Vink C, Cremers FP, Hoyng CB.

Department of Ophthalmology, University Medical Centre Nijmegen, PO Box 9101,
6500 HB Nijmegen, The Netherlands. B.Klevering@ohk.umcn.nl

OBJECTIVE: To investigate the clinical spectrum and molecular causes of retinal
dystrophies in 3 families. DESIGN: Family molecular genetics study. PARTICIPANTS:
Sixteen patients and 15 relatives in 3 families. METHODS: Members of 3 families
with multiple ABCA4-associated retinal disorders were clinically evaluated.
Deoxyribonucleic acid samples of all affected individuals and their family
members were analyzed for variants in all 50 exons of the ABCA4 gene. MAIN
OUTCOME MEASURES: ABCA4-associated retinal phenotypes and mutations in the ABCA4 
gene. RESULTS: In family A, 2 sisters were diagnosed with Stargardt's disease
(STGD); the eldest sister was compound heterozygous for the mild 2588G-->C and
the severe 768G-->T mutation. Another patient in this family with a severe type
of retinitis pigmentosa (RP) carried the 768G-->T mutation homozygously. In
family B, 2 siblings presented with an RP of severity similar to that encountered
in family A. Both were homozygous for the severe IVS33+1G-->A mutation. Two other
family members with STGD were compound heterozygous for the 2588G-->C and
IVS33+1G-->A mutations. In family C, all 5 siblings of generation II demonstrated
age-related macular degeneration (AMD). In generations III and IV, 2 STGD
patients and 1 cone-rod dystrophy (CRD) patient were present. In 1 STGD patient
we identified a heterozygous 768G-->T mutation. Sequence analysis of the entire
ABCA4 gene did not reveal the remaining 2 mutations. Nevertheless, the 2 patients
with STGD, the patient with CRD, and 2 of the AMD patients shared a common
haplotype spanning the ABCA4 gene. CONCLUSIONS: Different mutations in the ABCA4 
gene are the cause of STGD and RP or CRD in at least 2 and, possibly, 3 families.
Patients with RP caused by ABCA4 mutations are characterized by an early onset
and rapid progression of their retinal dystrophy, with extensive chorioretinal
atrophy resulting in a very low visual acuity. Various combinations of relatively
rare retinal disorders such as STGD, CRD, and RP in one family may not be as
uncommon as once believed, in view of the relatively high carrier frequency of
ABCA4 mutations (about 5%) in the general population.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15019334 [PubMed - indexed for MEDLINE]

2371: Ophthalmology. 2004 Mar;111(3):513-7.

Age-related macular degeneration causing visual impairment in people 75 years or 
older in Britain: an add-on study to the Medical Research Council Trial of
Assessment and Management of Older People in the Community.

Evans JR, Fletcher AE, Wormald RP.

Department of Epidemiology and International Eye Health, Institute of
Ophthalmology, London School of Hygiene and Tropical Medicine, Keppel Street,
London WC1E 7HT, United Kingdom.

PURPOSE: Age-related macular degeneration (AMD) is the most commonly occurring
cause of visual loss in people registered as blind or partially sighted. There
are no nationally representative data on the prevalence of AMD in the British
population. We aimed to estimate the prevalence of AMD causing visual impairment 
in people 75 years or older in Britain. DESIGN: Population-based cross-sectional 
study. PARTICIPANTS: Thirteen thousand nine hundred people 75 years or older in
49 practices taking part in the Medical Research Council Trial of the Assessment 
and Management of Older People in the Community. METHODS: Trial nurses tested
visual acuity in everyone 75 years or older in participating practices. We
collected data on the cause of visual loss for everyone who was visually
impaired. We obtained these data from review of the general practice medical
notes and by sending a questionnaire to the hospital ophthalmologist. Visual
impairment was defined as a binocular acuity of less than 6/18. MAIN OUTCOME
MEASURE: Prevalence of AMD causing visual impairment. RESULTS: There were 976
visually impaired people for whom a cause of visual loss was established. Of
these, 516 (53%) had AMD as a cause of visual loss. We estimate that 3.7% (95%
confidence interval, 3.2%-4.2%) of the population 75 years or older and 14.4%
(11.6%-17.2%) of the population 90 years or older are visually impaired due to
AMD. There are an estimated 192 000 people 75 years or older visually impaired
due to AMD in the United Kingdom (95% confidence interval, 144 000-239 000).
CONCLUSION: Our results, from the largest and most representative study of the
causes of vision loss in older people in the British population, confirm the
substantial burden of AMD in people 75 years and older. As the population ages,
this problem will get worse. The needs of this group for vision aids and other
support in the community should be addressed; research on the causes of AMD and
possible preventive measures should be given priority.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15019328 [PubMed - indexed for MEDLINE]

2372: Am J Ophthalmol. 2004 Mar;137(3):504-10.

Pathogenesis of lesions in late age-related macular disease.

Holz FG, Pauleikhoff D, Klein R, Bird AC.

Department of Ophthalmology (F.G.H.), University of Heidelberg, Heidelberg,
Germany.

PURPOSE: To review the evidence that exists concerning the pathogenesis of
lesions in late age-related macular disease (AMD). DESIGN: Review of the
literature. METHODS: A review of both experimental evidence and clinical
observations that address these problems. RESULTS: There is good evidence that
choroidal neovascularization (CNV) is due to a change in the balance of growth
factors derived from the retinal pigment epithelial basolateral plasma membrane
domain (retinal pigment epithelium). Retinal angiomatous proliferation may also
have a similar pathogenesis involving the apical domain. Detachment of the
retinal pigment epithelium is likely to be a consequence of increased resistance 
of the Bruch membrane to water flow due to deposition of lipids. Geographic
atrophy is preceded by accumulation of autofluorescent material in the retinal
pigment epithelium and possible causal relationships between the two have been
demonstrated. CONCLUSION: There is increasing understanding concerning the
sequence of events that lead to those lesions causing loss of central vision in
AMD. Therapeutic approaches that address the underlying mechanisms are more
likely to succeed than current treatment options. Such an approach has already
been initiated in the management of choroidal neovascularization.

Publication Types: 
    Review

PMID: 15013875 [PubMed - indexed for MEDLINE]

2373: Am J Ophthalmol. 2004 Mar;137(3):486-95.

The epidemiology of age-related macular degeneration.

Klein R, Peto T, Bird A, Vannewkirk MR.

Department of Ophthalmology and Visual Sciences, University of Wisconsin Medical 
School, Madison, Wisconsin 53726, USA. kleinr@epi.ophth.wisc.edu

PURPOSE: To review the epidemiology of age-related macular degeneration (AMD).
DESIGN: Evidence from epidemiologic data regarding the natural history of AMD and
its risk factors are presented. RESULTS: Large, soft drusen associated with
pigmentary abnormalities increase the risk of progression to advanced AMD. Large 
soft drusen may fade over time. Advanced AMD is more likely to be present in
whites than blacks, despite the similar prevalence of soft drusen in both groups.
Neovascular AMD is more frequent than geographic atrophy in most population-based
studies in whites in America, Australia, and the Netherlands than in similar
population-based studies in Iceland and Norway. After age and family history,
there are few consistent relationships of risk factors to AMD. Of these, the
relationship of smoking, hypertension, and cataract surgery to advanced AMD have 
been most consistent. CONCLUSIONS: Long-term epidemiologic studies have provided 
information on the distribution and the natural history of AMD and its associated
risk factors. It is not known what effect reduction of blood pressure and the
cessation of smoking might have on the incidence and progression of AMD.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.
    Review

PMID: 15013873 [PubMed - indexed for MEDLINE]

2374: Am J Ophthalmol. 2004 Mar;137(3):435-44.

The relation of retinal microvascular characteristics to age-related eye disease:
the Beaver Dam eye study.

Klein R, Klein BE, Tomany SC, Wong TY.

Department of Ophthalmology and Visual Sciences, University of Wisconsin Medical 
School, Madison, Wisconsin 53726-2336, USA. kleinr@epi.ophth.wisc.edu

PURPOSE: To examine the relationship between microvascular characteristics
(central retinal artery equivalent [CRAE], central retinal vein equivalent
[CRVE], arteriole-to-venule ratio [AVR], focal retinal arteriolar narrowing,
arteriovenous [A/V] nicking, and retinopathy) associated with systemic
hypertension and ocular disease (age-related maculopathy [ARM], three types of
cataract, and open-angle glaucoma). DESIGN: Population-based cohort study.
METHODS: Standardized grading of microvascular characteristics was performed at
baseline on fundus photographs taken on 4,926 persons aged 43 to 86 years who
participated in the Beaver Dam Eye study at the baseline examination. Age-related
maculopathy, cataract, and glaucoma status were determined at baseline; ARM and
cataract were again determined at 5-year and 10-year follow-up examinations using
standard protocols. RESULTS: While controlling for age and sex, generalized
retinal arteriolar narrowing (lowest quintile of CRAE) was associated with the
10-year cumulative incidence of retinal pigment epithelial (RPE) depigmentation
(risk ratio [RR] 1st vs 5th quintile, 1.93; 95% confidence interval [CI], 1.11,
3.34) and, inversely, with incident nuclear cataract (RR, 0.71; 95% CI, 0.50,
0.99). Arteriovenous nicking was associated with the incidence of early ARM (RR, 
2.39; 95% CI, 1.02, 5.57). Otherwise, there were no statistically significant
associations of focal arteriolar narrowing or retinopathy with incident ARM or
any type of age-related cataract and no relation of CRAE, focal arteriolar
narrowing, A/V nicking, or retinopathy with the prevalence of glaucoma.
CONCLUSION: These data show that retinal vascular characteristics associated with
hypertension are related to the incidence of ARM and nuclear cataract but not to 
prevalent glaucoma. Relationships, however, were weak and inconsistent.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.

PMID: 15013865 [PubMed - indexed for MEDLINE]

2375: Arch Ophthalmol. 2004 Mar;122(3):380-2.

Ophthalmology on the internet: what do our patients find?

Kahana A, Gottlieb JL.

Department of Ophthalmology and Visual Science, University of Wisconsin Hospital,
Madison 53705, USA.

The Internet has become a favorite source of medical information for a growing
number of patients. At the same time, content on the Internet represents an
amalgamation of viewpoints, commercial interests, and various biases. A common
way to access Internet information is through commercial portals with proprietary
search engines. Often these search engines prioritize their rank list based on
commercial interests. We evaluated whether Internet searches of ophthalmic issues
are slanted toward commercial sites and whether any differences exist among the
various search engines. We used age-related macular degeneration as an example.
In this study, we found that some search engines are heavily tilted toward
commercial partnerships, whereas others emphasize sites run by nonprofit and
educational organizations. Our findings may guide physicians in recommending to
their patients some internet portals rather than others. This type of evaluation 
can be conducted intermittently by physicians and other health care professionals
to assess the type of information that reaches their patients and what biases may
be influencing patient knowledge and decision making.

PMID: 15006856 [PubMed - indexed for MEDLINE]

2376: Arch Ophthalmol. 2004 Mar;122(3):336-40.

Safety of an intravitreal injection of triamcinolone: results from a randomized
clinical trial.

Gillies MC, Simpson JM, Billson FA, Luo W, Penfold P, Chua W, Mitchell P, Zhu M, 
Hunyor AB.

Department of Clinical Ophthalmology, School of Public Health, and Sydney Eye
Hospital, University of Sydney, Sydney, New South Wales, Australia.
mark@eye.usyd.edu.au

OBJECTIVE: To determine the safety of a single intravitreal injection of
triamcinolone acetonide (4 mg) in patients with subfoveal choroidal
neovascularization caused by age-related macular degeneration. METHODS: A
double-masked, placebo-controlled, randomized clinical trial was conducted at a
public tertiary referral eye hospital. Patients participating had age-related
macular degeneration with evidence of choroidal neovascularization, any part of
which was classic; age older than 59 years; and best-corrected visual acuity of
20/200 or better. Eyes were assigned to active study treatment or to placebo.
Intraocular pressure and cataract grading were performed every 6 months for 3
years. Adverse events, from mild to vision-threatening or life-threatening, were 
recorded as procedure-related or corticosteroid-related. RESULTS: Seventy-five
eyes were assigned to study treatment and 76 eyes to placebo. There were no
moderate or severe adverse events related to the surgical procedure in either
group. Triamcinolone-treated eyes had a significantly increased risk of
developing mild or moderate elevation of the intraocular pressure. Topical
glaucoma medication reduced intraocular pressure to acceptable levels in all
patients. There was significant progression of cataract in the
triamcinolone-treated eyes. CONCLUSION: Despite a significant adverse event
profile, intravitreal triamcinolone is generally well tolerated by the human eye 
as long as patients are carefully followed up by their surgeon and treated
appropriately, when necessary.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15006845 [PubMed - indexed for MEDLINE]

2377: Arch Ophthalmol. 2004 Mar;122(3):330-5.

Detection of diabetic foveal edema: contact lens biomicroscopy compared with
optical coherence tomography.

Brown JC, Solomon SD, Bressler SB, Schachat AP, DiBernardo C, Bressler NM.

Retinal Vascular Center, Wilmer Eye Institute, The Johns Hopkins University
School of Medicine, Baltimore, MD 21205-2002, USA.

OBJECTIVE: To compare contact lens biomicroscopy with optical coherence
tomography (OCT) for the detection of diabetic foveal edema. METHODS: Study
participants consisted of a convenient cohort of consecutive patients with
diabetes mellitus seen at the Wilmer Eye Institute's Retinal Vascular Center,
Baltimore, MD. Case characteristics were recorded and eyes were examined by 1 of 
4 retina specialists by means of contact lens biomicroscopy. Edema involving the 
center of the macula was assessed as definitely present, questionably present, or
definitely not present. The OCT testing was performed and interpreted by trained 
technicians, masked to the physicians' assessment of foveal edema. Agreement
between OCT and contact lens examination for the absence or presence of foveal
edema was evaluated. RESULTS: One hundred seventy-two eyes of 95 patients with
diabetes were enrolled in August and September 2002. Foveal thickness was
objectively measured by OCT in 170 (99%) of 172 cases. We found excellent
agreement between OCT and contact lens examination for the absence or presence of
foveal edema when OCT thickness was normal (<or=200 microm) or moderately to
severely increased (>300 microm). However, agreement was poor when foveal
thickness was mildly increased on OCT (201-300 microm). CONCLUSIONS: Agreement
between contact lens examination and OCT for the detection of diabetic foveal
edema is poor when OCT thickening is mild. This suggests that contact lens
biomicroscopy is relatively insensitive for the detection of mild foveal
thickening apparent on OCT. Additional studies are needed to investigate the
natural course of cases with mildly increased foveal thickness on OCT that do not
appear thickened clinically.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15006844 [PubMed - indexed for MEDLINE]

2378: Arch Ophthalmol. 2004 Mar;122(3):325-9.

Natural history of minimally classic subfoveal choroidal neovascular lesions in
the treatment of age-related macular degeneration with photodynamic therapy (TAP)
investigation: outcomes potentially relevant to management--TAP report No. 6.

Bressler SB, Pieramici DJ, Koester JM, Bressler NM.

Department of Ophthalmology, The Johns Hopkins University School of Medicine and 
The Johns Hopkins Hospital, Baltimore, MD 20205-2002, USA. nmboffice@jhmi.edu

OBJECTIVE: To determine if there is a rationale for monitoring patients with
age-related macular degeneration who have a minimally classic subfoveal choroidal
neovascular lesion and do not receive treatment at initial examination. METHODS: 
Participants assigned to placebo who had a minimally classic lesion composition
at baseline were identified from the TAP Investigation. Fluorescein angiograms at
baseline and follow-up examinations from these participants were reviewed by
photograph reading center graders to determine if any follow-up angiograms had
converted from a minimally classic lesion composition to a predominantly classic 
lesion composition. MAIN OUTCOME MEASURES: Proportion of minimally classic
lesions at baseline that converted to a predominantly classic lesion composition,
time of this conversion, and visual acuity and lesion size at the time of
conversion. RESULTS: Of the 207 patients assigned to placebo in the TAP
Investigation, 98 were judged to have a minimally classic lesion at baseline in
the study eye when the fluorescein angiograms were reviewed in 2001. Of these 98 
patients, 39 (40%) had lesions that converted to a predominantly classic lesion
composition, including 21 by the month 3 examination. At the time of conversion, 
32 (82%) lesions were no greater than 9 disc areas, including 20 (51%) with
visual acuity of 20/200 or better. CONCLUSIONS: These data would suggest that
patients with minimally classic lesions, in whom no therapy is recommended
initially, should be monitored so that potential conversion to a predominantly
classic lesion can be identified promptly and verteporfin therapy considered.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15006843 [PubMed - indexed for MEDLINE]

2379: Graefes Arch Clin Exp Ophthalmol. 2004 May;242(5):402-8. Epub 2004 Feb 18.

Vitrectomy with internal limiting membrane removal for clinically significant
macular oedema.

Kuhn F, Kiss G, Mester V, Szijártó Z, Kovács B.

Helen Keller Foundation for Research and Education, Birmingham, Alabama, USA.
fkuhn@mindspring.com

BACKGROUND: Little has been published on internal limiting membrane (ILM) removal
for clinically significant macular oedema (CSME) in eyes not improving following 
maximal laser treatment. METHODS: Retrospective review of the charts and
intraoperative video films of 30 consecutive eyes of 27 patients undergoing
vitrectomy, ILM peeling, and gas tamponade by a single surgeon. RESULTS: The
average patient was 52 years old; 56% were males. The oedema was caused by
diabetes in 87% of the eyes, 42% of which had proliferative disease. The oedema
was diffuse in 16 eyes (53%) and cystoid (CME) in 14 (47%). In 21% of eyes,
spontaneous vitreous detachment was present or the eye had already undergone
vitrectomy. All but one eye had at least 6 months of follow-up (mean 12 months). 
The oedema resolved completely in 26 eyes (90%) and partially in 3 eyes (10%).
The visual acuity improved at least two Snellen lines in 19 eyes (66%) and one
line in 4 eyes (14%); the average improvement was 4 lines. The acuity was
unchanged in three eyes (10%) and worsened in three eyes (10%), all due to
cataract. Among the 14 eyes with CME, 11 (79%) became completely dry and the
visual acuity improved in 11 eyes (79%). No ILM-related complication was
encountered in any eye. CONCLUSIONS: Vitrectomy with ILM peeling is a promising
approach to eyes with CSME. It appears to offer visual improvement at a much
higher rate than laser therapy and with a longer-lasting effect than that of
intravitreal triamcinolone. A larger study is necessary to confirm these
preliminary findings.

PMID: 14986010 [PubMed - indexed for MEDLINE]

2380: Invest Ophthalmol Vis Sci. 2004 Mar;45(3):922-31.

Reduction of diabetic macular edema by oral administration of the kinase
inhibitor PKC412.

Campochiaro PA; C99-PKC412-003 Study Group.

Departments of Ophthalmology and Neuroscience, The Johns Hopkins University
School of Medicine, Baltimore, Maryland 21287, USA. pcampo@jhmi.edu

PURPOSE: To evaluate the efficacy and safety of PKC412, an orally administered
kinase inhibitor, in subjects with diabetic macular edema. METHODS: This was a
randomized (1:1:1:1), multicenter, double-masked, parallel-group study in which
subjects (n = 141) received placebo or PKC412 (50, 100, or 150 mg/d) for up to 3 
months. Subjects were 18 to 85 years of age and had retinal thickening that met
predefined criteria and best corrected visual acuity of 55 letters or more.
Efficacy was based on changes in retinal thickening measured by grading of fundus
photographs and optical coherence tomography (OCT) and changes in visual acuity. 
RESULTS: Grading of fundus photographs showed a statistically significant
decrease in the area of greatest retinal thickening in patients receiving 150
mg/d of PKC412 (P = 0.032). OCT demonstrated that the two higher doses of PKC412 
caused a significant decrease in thickening in the region of greatest thickening 
and in the fovea (P < or = 039), with response in the high-dose group
significantly different from that in the placebo group (difference = -66.69 micro
m [95.2% CI: -128.57 to -4.81]; P = 0.030). Retinal volume for all locations also
showed a significant decrease from baseline in the 100- and 150-mg/d PKC412
groups (P < or = 004), and the 150-mg/kg group showed significantly less retinal 
volume than the placebo group at 3 months (difference = -0.46 mm(3) [95.2% CI:
-0.86-0.06]; P = 0.019). There was a small (4.36 letters), but significant (P =
0.007), improvement in visual acuity at 3 months compared with baseline in the
100-mg/d PKC412 group. Gastrointestinal side effects (diarrhea, nausea, and
vomiting) were the most common adverse events attributed to the drug.
Dose-related effects were observed for tolerability, glycemic control, and liver 
toxicity. CONCLUSIONS: Orally administered PKC412 at doses of 100 mg/d or higher 
may significantly reduce macular edema and improve visual acuity in diabetic
subjects. However, concern regarding liver toxicity with systemic therapy makes
local delivery an appealing approach.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 14985312 [PubMed - indexed for MEDLINE]

2381: Am J Clin Nutr. 2004 Mar;79(3):410-7.

Plasma kinetics of zeaxanthin and 3'-dehydro-lutein after multiple oral doses of 
synthetic zeaxanthin.

Hartmann D, Thürmann PA, Spitzer V, Schalch W, Manner B, Cohn W.

Department of Human Nutrition and Health, Roche Vitamins Ltd, Basel, Switzerland.

BACKGROUND: Zeaxanthin is hypothesized to reduce the risk of age-related macular 
degeneration; however, kinetic information is limited. OBJECTIVES: The objective 
was to investigate the plasma kinetics of synthetic zeaxanthin after repeated
oral doses and to assess the possible influence of other carotenoids on plasma
zeaxanthin concentrations. DESIGN: After a run-in of 3 d, 20 healthy volunteers
assigned to 2 parallel dose groups received once daily oral doses of either 1 mg 
(1.76 micro mol) or 10 mg (17.6 micro mol) zeaxanthin for 42 d. Plasma
concentration-time profiles on days 1 and 42, concentrations immediately before
zeaxanthin intake during the dosing period, and concentrations after the last
dose until day 76 were monitored. RESULTS: all-E-Zeaxanthin concentrations
increased from 0.048 +/- 0.026 micro mol/L at baseline to 0.20 +/- 0.07 and 0.92 
+/- 0.28 micro mol/L with 1 and 10 mg zeaxanthin, respectively. The
dose-normalized bioavailability of all-E-zeaxanthin after the10-mg dose was 40%
lower (P < 0.001) than after the 1-mg dose. Other kinetic parameters did not
differ significantly between groups. After 17 d of dosing, >90% of steady state
concentrations were reached, which was compatible with an effective half-life for
accumulation of 5 d. The terminal elimination half-life was 12 +/- 7 d (n = 20). 
The time course of plasma all-E-3-'dehydro-lutein concentrations resembled that
of all-E-zeaxanthin. The data provided evidence that all-E-3-'dehydro-lutein was 
derived from all-E-zeaxanthin. Concentrations of other carotenoids were not
affected. Zeaxanthin was well tolerated. CONCLUSION: Long-term oral intake of 1
and 10 mg zeaxanthin as beadlets increases plasma zeaxanthin concentrations
approximately 4- and 20-fold, respectively. Evidence that all-E-3-dehydro-lutein 
is formed from zeaxanthin was strong.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 14985215 [PubMed - indexed for MEDLINE]

2382: Br J Ophthalmol. 2004 Mar;88(3):344-7.

Intravitreal triamcinolone with photodynamic therapy for subfoveal choroidal
neovascularisation in age related macular degeneration.

Rechtman E, Danis RP, Pratt LM, Harris A.

Department of Ophthalmology, Indiana University School of Medicine, Indianapolis,
IN, USA. ehudrechtman@yahoo.com

AIMS: To report the effects of intravitreal triamcinolone acetonide (iTAAC)
injections as an adjunctive treatment to photodynamic therapy (PDT) with
verteporfin for new subfoveal choroidal neovascularisation (CNV) in age related
macular degeneration (AMD). METHODS: We retrospectively reviewed the records of
all AMD patients who had iTAAC within 6 weeks of their first PDT and had a follow
up of one year or longer. The proportion of eyes after one year follow up that
lost or gained >or=15 and >or=30 ETDRS letters, baseline and one year lesion
greatest linear dimension (GLD), number of PDTs, and side effects were assessed. 
RESULTS: Fourteen patients were evaluated. Eleven received one initial combined
treatment and three received an additional combined treatment after 6 months.
Median follow up was 18 months (range 12 to 25 months). Overall, 7% gained >or=30
letters, 50% maintained stable vision, 14% lost 15-29 letters, and 29% lost
>or=30 letters. Overall, mean GLD increased from 2580 (SD 1088) microm to 3946
(SD 1503) micro m (p = 0.01). The mean number of PDTs during the first year was
2.57. Side effects were mild intraocular pressure elevation in 28.5% and cataract
progression in 50% of phakic eyes. CONCLUSIONS: iTAAC with PDT in AMD was found
to be relatively safe and had reasonable results for lesions with some classic
component.

PMID: 14977766 [PubMed - indexed for MEDLINE]

2383: Ophthalmic Epidemiol. 2004 Feb;11(1):43-51.

TTO utility scores measure quality of life in patients with visual morbidity due 
to diabetic retinopathy or ARMD.

Shah VA, Gupta SK, Shah KV, Vinjamaram S, Chalam KV.

Department of Ophthalmology, University of Florida/College of Medicine,
Jacksonville, Florida 32209, USA.

PURPOSE: To evaluate the utility scores in patients with varying degrees of
visual morbidity due to diabetic retinopathy or ARMD. METHODS: Patients with
vision < or =20/40 in one eye due to diabetic retinopathy or ARMD were enrolled. 
Utility scores were measured by the time trade-off (TTO) method after stratifying
the patient population with visual impairment in the better eye (group 1, 20/20
to 20/40; group 2, 20/50 to 20/100; group 3, 20/200 to no light perception).
RESULTS: Sub-group analysis revealed that subjects in group 1 were willing to
give up a median of 1 year as compared to 3 years by the subjects in group 3 for 
perfect bilateral visual acuity (P<0.05). The median utility score was 0.94 for
group 1, 0.96 for group 2 and 0.80 for group 3. While the utility scores for
groups 1 and 2 were comparable (P>0.05), there was a significant difference in
the utility scores between groups 1 and 3 and between groups 2 and 3 (P<0.05).
There was no significant effect on the utility scores of age, educational level
or prior ocular surgery. CONCLUSION: Substantial visual loss secondary to
diabetic retinopathy or ARMD is associated with a significant decrease in utility
scores. However, TTO scores were not sensitive enough to demonstrate a difference
between subjects with mild (group 1) and moderate (group 2) visual loss in the
better eye secondary to diabetic retinopathy or ARMD.

PMID: 14977496 [PubMed - indexed for MEDLINE]

2384: Am J Hum Genet. 2004 Mar;74(3):482-94. Epub 2004 Feb 16.

Age-related macular degeneration: a high-resolution genome scan for
susceptibility loci in a population enriched for late-stage disease.

Abecasis GR, Yashar BM, Zhao Y, Ghiasvand NM, Zareparsi S, Branham KE, Reddick
AC, Trager EH, Yoshida S, Bahling J, Filippova E, Elner S, Johnson MW, Vine AK,
Sieving PA, Jacobson SG, Richards JE, Swaroop A.

Department of Biostatistics, University of Michigan, Ann Arbor, MI 48105, USA.

Age-related macular degeneration (AMD) is a complex multifactorial disease that
affects the central region of the retina. AMD is clinically heterogeneous,
leading to geographic atrophy (GA) and/or choroidal neovascularization (CNV) at
advanced stages. Considerable data exists in support of a genetic predisposition 
for AMD. Recent linkage studies have provided evidence in favor of several AMD
susceptibility loci. We have performed a high-resolution (5-cM) genome scan of
412 affected relative pairs that were enriched for late-stage disease (GA and/or 
CNV). Nonparametric linkage analysis was performed using two different diagnostic
criteria and also by dividing the affected individuals according to GA or CNV
phenotype. Our results demonstrate evidence of linkage in regions that were
suggested in at least one previous study at chromosomes 1q (236-240 cM in the
Marshfield genetic map), 5p (40-50 cM), and 9q (111 cM). Multipoint analysis of
affected relatives with CNV provided evidence of additional susceptibility loci
on chromosomes 2p (10 cM) and 22q (25 cM). A recently identified Gln5345Arg
change in HEMICENTIN-1 on chromosome 1q25 was not detected in 274 affected
members in the restricted group with AMD, 346 additional patients with AMD, and
237 unaffected controls. Our results consolidate the chromosomal locations of
several AMD susceptibility loci and, together with previous reports, should
facilitate the search for disease-associated sequence variants.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 14968411 [PubMed - indexed for MEDLINE]

2385: J Fr Ophtalmol. 2004 Jan;27(1):75-8.

On the selectivity of photodynamic therapy of choroidal neovascularization
associated with age-related macular degeneration.

van den Bergh H, Ballini JP, Sickenberg M.

Swiss Federal Institute of Technology Lausanne, EPFL/LPAS.
Hubert.vandenBergh@epfl.ch

PURPOSE: This paper discusses the lack of complete selectivity in the
photodynamic closure of choroidal neovasculature (CNV) associated with
age-related macular degeneration. The arguments presented are supported by
examples of clinical observations and may be useful for the design of the next
generation of photosensitizers. RESULTS AND CONCLUSION: Based on worldwide
patient follow-up, it can be concluded that a substantial number of the more than
200000 treatments that have been dispensed so far could have resulted in
stabilization of the disease for at least a number of years. Clinical
observations also indicate that, in addition to the effective closure of the CNV 
observed 1 week after PDT, a significant closure (or at least reduced leakage) of
normal choriocapillaries is observed in the treated area. Some of the concepts
associated with the selectivity of Visudyne photodynamic therapy of choroidal
neovascularization in age-related macular degeneration are also discussed.
DISCUSSION: Novel approaches to improving selectivity could include attaching a
photosensitizer to a targeting moiety such as a monoclonal antibody or a peptide.
The undesirable closure of normal choriocapillaries in the treated area is one
area of possible improvement to be sought for the next generation of drugs.

Publication Types: 
    Comparative Study

PMID: 14968083 [PubMed - indexed for MEDLINE]

2386: Hosp Med. 2004 Jan;65(1):39-43.

Preserving vision with verteporfin photodynamic therapy.

Yang YC.

Wolverhampton Eye Infirmary, Wolverhampton, WV3 9QR.

Wet age-related macular degeneration (AMD) is the leading cause of blindness in
the elderly population. Verteporfin photodynamic therapy (PDT) is significantly
effective in preventing visual loss in patients with subfoveal choroidal
neovascularization caused by exudative AMD. This article reviews verteporfin PDT 
and discusses treatment and evolving appraisal guidance.

Publication Types: 
    Review

PMID: 14964795 [PubMed - indexed for MEDLINE]

2387: Am J Ophthalmol. 2004 Feb;137(2):313-22.

The correlation between fluorescein angiographic and optical coherence
tomographic features in clinically significant diabetic macular edema.

Kang SW, Park CY, Ham DI.

Department of Ophthalmology, Samsung Medical Center, Sungkyunkwan University
School of Medicine, Seoul, South Korea. swkang@smc.samsung.co.uk

PURPOSE: To assess the correlation between the features of optical coherence
tomography (OCT) and fluorescein angiography in clinically significant diabetic
macular edema. DESIGN: Retrospective observational case series. METHODS: This
study involved 145 eyes (91 patients) with clinically significant diabetic
macular edema. The fluorescein angiography features were categorized into focal
leakage type, diffuse leakage type, and diffuse cystoid leakage type. The OCT
features were categorized into four types: type 1, thickening with homogeneous
optical reflectivity; type 2, thickening with markedly decreased optical
reflectivity in the outer retinal layer; type 3A, foveolar detachment without
traction; and type 3B, foveolar detachment with apparent vitreofoveal traction.
The correlation between fluorescein angiography types and OCT types were
analyzed, and their associations with visual acuity, central foveal thickness.
and stages of diabetic retinopathy were evaluated. RESULTS: The prevalence of OCT
type 1 was higher in the focal leakage type (73.0%) and in the diffuse leakage
type (58.9%) than in the diffuse cystoid leakage type (3.8%) of fluorescein
angiography (P <.0001). The prevalence of OCT type 2 and 3A was higher in the
diffuse cystoid leakage type (57.7% and 34.6%, respectively) than in the focal
leakage type (20.6% and 3.2%) or diffuse leakage type(28.6% and 10.7%; P <.0001).
The stages of retinopathy correlated with fluorescein angiography types (P
=.016). Optical coherence tomography type 1 and the focal leakage type of
fluorescein angiography showed the least foveal thickness and the best visual
acuity (P <.05). CONCLUSIONS: There was a significant correlation between the
features of OCT and fluorescein angiography in clinically significant diabetic
macular edema. The combined data from both OCT and fluorescein angiography may
provide a clearer understanding of the anatomic and physiologic characteristics
of clinically significant diabetic macular edema.

Publication Types: 
    Comparative Study

PMID: 14962423 [PubMed - indexed for MEDLINE]

2388: Am J Ophthalmol. 2004 Feb;137(2):258-64.

Photodynamic therapy for age-related macular degeneration in a clinical setting: 
visual results and angiographic patterns.

Axer-Siegel R, Ehrlich R, Yassur Y, Rosenblatt I, Kramer M, Priel E, Benjamini Y,
Weinberger D.

Department of Ophthalmology, Rabin Medical Center, Beilinson, Petah Tiqva,
Israel. seegs@netvision.net.il

PURPOSE: To evaluate the visual outcome of patients with subfoveal choroidal
neovascularization due to age-related macular degeneration, who received
photodynamic therapy (PTD) in a clinical setting and to identify potential
predictive visual and angiographic factors. DESIGN: Interventional case series.
METHODS: The study included 74 patients with subfoveal choroidal
neovascularization who underwent PDT from January 2000 to March 2001 and
completed at least 1 year follow-up. All patients received verteporfin PDT and
were followed clinically, with fluorescein angiography (74 eyes), and with
indocyanine green angiography (65 eyes). A review of the medical records and
angiograms was performed. RESULTS: Mean follow-up was 15.6 months. Patients
received a mean of 3.4 treatments per year. Sixty-six percent lost less than 3
Snellen lines of visual acuity. Three patients (4%) experienced profound visual
acuity loss to finger counting. Final visual acuity was positively correlated
with lesion size and visual acuity at presentation. Visual outcome was worse in
the presence of cystoid macular edema. On indocyanine green angiography, a round 
hypofluorescent spot was seen at the site of the PDT, with maintenance of medium 
and large choroidal vessels. CONCLUSION: Smaller lesion size and better visual
acuity at presentation were good predictive signs, whereas cystoid macular edema 
was found to be a poor prognostic sign for visual outcome following PDT.

PMID: 14962414 [PubMed - indexed for MEDLINE]

2389: JAMA. 2004 Feb 11;291(6):704-10.

Comment in:
    JAMA. 2004 Jul 7;292(1):43; author reply 43.

Association between C-reactive protein and age-related macular degeneration.

Seddon JM, Gensler G, Milton RC, Klein ML, Rifai N.

Epidemiology Unit, Massachusetts Eye and Ear Infirmary, Department of
Ophthalmology, Harvard Medical School, Boston, Mass 02114, USA.
Johanna_Seddon@meei.harvard.edu

CONTEXT: C-reactive protein (CRP) is a systemic inflammatory marker associated
with risk for cardiovascular disease (CVD). Some risk factors for CVD are
associated with age-related macular degeneration (AMD), but the association
between CRP and AMD is unknown. OBJECTIVE: To test the hypothesis that elevated
CRP levels are associated with an increased risk for AMD. DESIGN, SETTING, AND
PARTICIPANTS: A total of 930 (91%) of 1026 participants at 2 centers in the
Age-Related Eye Disease Study (AREDS), a multicenter randomized trial of
antioxidant vitamins and minerals, were enrolled in this case-control study.
There were 183 individuals without any maculopathy, 200 with mild maculopathy,
325 with intermediate disease, and 222 with advanced AMD (geographic atrophy or
neovascular AMD). The AMD status was assessed by standardized grading of fundus
photographs, and stored fasting blood specimens drawn between January 1996 and
April 1997 were analyzed for high-sensitivity CRP levels. MAIN OUTCOME MEASURE:
Association between CRP and AMD. RESULTS: The CRP levels were significantly
higher among participants with advanced AMD (case patients) than among those with
no AMD (controls; median values, 3.4 vs 2.7 mg/L; P =.02). After adjustment for
age, sex, and other variables, including smoking and body mass index, CRP levels 
were significantly associated with the presence of intermediate and advanced
stages of AMD. The odds ratio (OR) for the highest vs the lowest quartile of CRP 
was 1.65 (95% confidence interval [CI], 1.07-2.55; P for trend =.02). The OR for 
CRP values at or above the 90th percentile (10.6 mg/L) was 1.92 (95% CI,
1.20-3.06), and the OR for CRP values at or above the mean plus 2 SDs (16.8 mg/L)
was 2.03 (95% CI, 1.03-4.00). A trend for an increased risk for intermediate and 
advanced AMD with higher levels of CRP was seen for smokers (OR, 2.16; 95% CI,
1.33-3.49) and those who never smoked (OR, 2.03; 95% CI, 1.19-3.46) with the
highest level of CRP. CONCLUSION: Our results suggest that elevated CRP level is 
an independent risk factor for AMD and may implicate the role of inflammation in 
the pathogenesis of AMD.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, U.S. Gov't, P.H.S.

PMID: 14871913 [PubMed - indexed for MEDLINE]

2390: Arch Ophthalmol. 2004 Feb;122(2):218-22.

Intravitreal reinjection of triamcinolone for exudative age-related macular
degeneration.

Jonas JB, Akkoyun I, Budde WM, Kreissig I, Degenring RF.

Department of Ophthalmology, Faculty of Clinical Medicine of Mannheim, University
of Heidelberg, Heidelberg, Germany. Jost.Jonas@ma.augen.uni-heidelberg.de

OBJECTIVE: To evaluate the outcome of repeated intravitreal injections of
triamcinolone acetonide for the treatment of exudative age-related macular
degeneration. METHODS: This prospective, comparative nonrandomized clinical
interventional study included 13 patients with progressive exudative age-related 
macular degeneration with occult, or predominantly occult, subfoveal
neovascularization. All patients had shown an increase or stabilization of visual
acuity after a first intravitreal injection of 25 mg of triamcinolone acetonide. 
They received a second intravitreal injection of 25 mg of triamcinolone acetonide
3.1 to 18 months after the first injection. Mean +/- SD follow-up time after the 
second injection was 5.2 +/- 3.6 months (median, 5.3 months). A control group
included 24 patients with exudative age-related macular degeneration who did not 
receive treatment for their maculopathy. The main outcome measures were visual
acuity and intraocular pressure. RESULTS: In the study group, mean +/- SD visual 
acuity increased significantly (P =.005 and P =.003, respectively) from 0.17 +/- 
0.11 to 0.32 +/- 0.26 and from 0.15 +/- 0.14 to 0.23 +/- 0.19, respectively,
after the first and second injections. An increase in visual acuity was found for
10 patients (77%) after the first and second injections. In the control group,
visual acuity did not vary significantly during follow-up (P =.81). The
difference in change in visual acuity between the study group and control group
was significant (P =.01 [Snellen lines] and P =.05 [logMAR units]). The peak in
visual acuity and, in a chronologically parallel manner, the peak in intraocular 
pressure elevation occurred 2 to 5 months after each injection. CONCLUSIONS:
Repeated intravitreal injection of 25 mg of triamcinolone acetonide may lead to
an increase in visual acuity in patients with exudative age-related macular
degeneration, with the peak in visual acuity and intraocular pressure elevation
occurring about 2 to 5 months after each injection.

Publication Types: 
    Clinical Trial
    Comparative Study

PMID: 14769599 [PubMed - indexed for MEDLINE]

2391: Strahlenther Onkol. 2004 Feb;180(2):91-5.

Long-term results after external radiotherapy in age-related macular
degeneration. A prospective study.

Prettenhofer U, Haas A, Mayer R, Stranzl H, Oechs A, Hackl A.

Department of Radiotherapy, University Medical School, Graz, Austria.
ulrike.prettenhofer@uni-graz.at

PURPOSE: To prospectively evaluate the short- and long-term efficacy of external 
radiotherapy (RT) in patients with age-related macular degeneration (AMD) by
comparing two different dose schedules. PATIENTS AND METHODS: In this
prospective, nonrandomized, comparative study including 80 patients, the efficacy
of external RT with a total dose of 14.4 Gy (group A, n = 40) and 25.2 Gy (group 
B, n = 40) was compared. Patients of group A were irradiated between September
1995 and July 1996, patients of group B between August 1996 and November 1997. 67
patients presented with occult choroidal neovascularization (CNV), 13 with
classic subfoveal lesions. Complete ophthalmologic investigation was performed
before RT, at intervals of 3 months during the 1st year after RT, and of 6 months
thereafter. RESULTS: 12 months after RT, vision deteriorated in 85% (14.4 Gy) and
65% (25.2 Gy) of patients. Central visual field decreased with both dose
schedules. There was no morphological benefit in neovascular changes. After 48
months, complete follow-up was possible in 46 patients who showed a significant
loss of vision similar to the natural course of AMD. CONCLUSION: External RT of
AMD with 14.4 Gy as well as with the escalated dose of 25.2 Gy showed a poor
beneficial outcome after 6 and 12 months, respectively. After a follow-up of 4
years, visual outcome in irradiated patients was similar to the natural course of
the disease. A conspicuous efficacy of RT in prevention of blindness could not be
demonstrated.

Publication Types: 
    Comparative Study

PMID: 14762661 [PubMed - indexed for MEDLINE]

2392: Mol Vis. 2004 Jan 26;10:57-61.

Linkage analysis for age-related macular degeneration supports a gene on
chromosome 10q26.

Kenealy SJ, Schmidt S, Agarwal A, Postel EA, De La Paz MA, Pericak-Vance MA,
Haines JL.

Center for Human Genetics Research, Vanderbilt University Medical Center,
Nashville, TN 37232-0700, USA.

PURPOSE: Age-related macular degeneration (AMD) is a retinal degenerative disease
that is the leading cause of blindness worldwide in individuals over the age of
60. Although the etiology of AMD remains largely unknown, numerous studies have
suggested both genetic and environmental influences. A previous study of affected
multiplex families identified four chromosomal regions that potentially harbor
AMD susceptibility genes. The purpose of our study was to further investigate
these regions with additional microsatellite marker coverage in our independent
data set. METHODS: We examined regions on chromosomes 1q, 9p, 10q, and 17q for
genetic linkage in our 70 multiplex families (consisting of 133 affected
sibpairs). Two point heterogeneity LOD score (HLOD) and nonparametric LOD score
(MLS) analyses were performed for disease models defined by the most severe
status in either eye. Conditional analyses were performed using apolipoprotein E 
(APOE) alleles as covariates in semiparametric LOD (LOD*) score calculations.
RESULTS: Regions on chromosomes 1q, 9p, and 17q did not provide evidence of
linkage in our data set. However, markers D10S1230 and D10S1656 on chromosome
10q26 generated maximum HLOD scores of 1.52 and 1.13, respectively. Marker
D10S1230 also generated an MLS score of 1.56 in stage 4 and 5 individuals.
Controlling for the potential effect of the APOE-epsilon4 allele did not
substantially alter these scores. CONCLUSIONS: With the inclusion of this study, 
at least five AMD data sets provide support of genetic linkage to 10q26. Such
consistency and confirmation of evidence strongly suggests that this region
should be the subject of further detailed genomic efforts for the disease.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.

PMID: 14758336 [PubMed - indexed for MEDLINE]

2393: Curr Opin Mol Ther. 2003 Dec;5(6):673-9.

Technology evaluation: pegaptanib, Eyetech/Pfizer.

Vinores SA.

Johns Hopkins Hospital, Wilmer Ophthalmological Institute, 825 Maumenee, 600 N
Wolfe Street, Baltimore, MD 21287-9289, USA. svinores@jhmi.edu

Eyetech Pharmaceuticals and Pfizer are co-developing the anti-vascular
endothelial growth factor aptamer, pegaptanib, as an angiogenesis inhibitor for
the potential treatment of age-related macular degeneration and diabetic macular 
edema, in addition to other ocular diseases. Gilead was previously investigating 
the aptamer for the potential treatment of cancer, however, no data have been
published for this indication since 1999.

Publication Types: 
    Evaluation Studies

PMID: 14755895 [PubMed - indexed for MEDLINE]

2394: Novartis Found Symp. 2004;255:51-63; discussion 63-7, 177-8.

Isotretinoin treatment inhibits lipofuscin accumulation in a mouse model of
recessive Stargardt's macular degeneration.

Radu RA, Mata NL, Nusinowitz S, Liu X, Travis GH.

Jules Stein Eye Institute, UCLA School of Medicine, Los Angeles, CA 90095, USA.

Recessive Stargardt's macular degeneration is an inherited blinding disease of
children caused by mutations in the ABCR gene. The primary pathologic defect in
Stargardt's discase is accumulation of toxic lipofuscin pigments such as
N-retinylidene-N-retinylethanolamine (A2E) in cells of the retinal pigment
epithelium (RPE). This accumulation appears to be responsible for the
photoreceptor death and severe visual loss in Stargardt's patients. Here, we
tested a novel therapeutic strategy to inhibit lipofuscin accumulation in a mouse
model of recessive Stargardt's disease. Isotretinoin (Accutane) has been shown to
slow the synthesis of 11-cis-retinaldehyde (11cRAL) and regeneration of rhodopsin
by inhibiting 11-cis-retinol dehydrogenase (11cRDH) in the visual cycle. Light
activation of rhodopsin results in its release of all-trans-retinaldehyde
(atRAL), which constitutes the first reactant in A2E biosynthesis. Accordingly,
we tested the effects of isotretinoin on lipofuscin accumulation in abcr-/-
knockout mice. Isotretinoin blocked the formation of A2E biochemically and the
accumulation of lipofuscin pigments by electron microscopy. We observed no
significant visual loss in treated abcr-/- mice by electroretinography.
Isotretinoin also blocked the slower, age-dependent accumulation of lipofuscin in
wild-type mice. These results corroborate the proposed mechanism of A2E
biogenesis. Further, they suggest that treatment with isotretinoin may inhibit
lipofuscin accumulation and thus delay the onset of visual loss in Stargardt's
patients. Finally, the results suggest that isotretinoin may be an effective
treatment for other forms of retinal or macular degeneration associated with
lipofuscin accumulation.

PMID: 14750596 [PubMed - indexed for MEDLINE]

2395: Clin Experiment Ophthalmol. 2004 Feb;32(1):114-8.

Optical coherence tomography of adult-onset fovemacular vitelliform dystrophy.

Sanfilippo P, Troutbeck R, Vandeleur K, Lenton L.

Adult-onset foveomacular vitelliform dystrophy is characterized by a focal, round
or oval shaped, subretinal foveal yellow lesion that presents bilaterally and
usually symmetrically in the fourth or fifth decade of life. In addition to
clinical observation, diagnosis of the disease process has until now been
assisted by electrophysiological and fundus fluorescein studies. Two cases are
presented that correlate the clinical fundus appearance with optical coherence
tomography findings and describe the location of the yellow vitelliform material.

Publication Types: 
    Case Reports
    Letter

PMID: 14746609 [PubMed - indexed for MEDLINE]

2396: Invest Ophthalmol Vis Sci. 2004 Feb;45(2):617-24.

Supplemental oxygen improves diabetic macular edema: a pilot study.

Nguyen QD, Shah SM, Van Anden E, Sung JU, Vitale S, Campochiaro PA.

Department of Ophthalmology, Johns Hopkins University School of Medicine,
Baltimore, Maryland 21287-9277, USA.

PURPOSE: Diabetic macular edema (DME) is the most common cause of moderate visual
disability in persons of working age in the United States. The pathogenesis of
DME is poorly understood. In this study, the effect of retinal hypoxia in the
development and maintenance of DME was investigated. METHODS: Five patients with 
chronic DME despite at least one focal laser photocoagulation treatment (nine
eyes) received 4 L/min of inspired oxygen by nasal cannula for 3 months. Best
corrected visual acuity (VA) and retinal thickness, assessed by optical coherence
tomography (OCT), were measured at baseline, during 3 months of oxygen treatment,
and for 3 months after stopping oxygen. RESULTS: After 3 months of oxygen
therapy, nine of nine eyes with DME at baseline showed a reduction in thickness
of the center of the macula. Foveal thickness (FTH) above the normal range was
reduced by an average of 43.5% (range, 14%-100%), excess foveolar thickness (CEN)
was reduced by an average of 42.1% (range, 13%-100%), and excess macular volume
was reduced by an average of 54% (range, 35%-100%). Statistical analyses
suggested that these changes were unlikely to be due to chance (P = 0.0077 by
Wilcoxon signed-rank test). Three eyes showed improvement in VA by at least 2
lines, one by slightly less than 2 lines, and five eyes showed no change. Three
months after discontinuation of oxygen, five of the nine eyes showed increased
thickening of the macula compared with when oxygen was discontinued. CONCLUSIONS:
Supplemental inspired oxygen may decrease macular thickness due to DME,
suggesting that retinal hypoxia is involved in the development and maintenance of
DME.

Publication Types: 
    Clinical Trial
    Research Support, U.S. Gov't, P.H.S.

PMID: 14744906 [PubMed - indexed for MEDLINE]

2397: Invest Ophthalmol Vis Sci. 2004 Feb;45(2):610-6.

Comparison of Heidelberg Retina Tomograph II and Retinal Thickness Analyzer in
the assessment of diabetic macular edema.

Guan K, Hudson C, Flanagan JG.

Multi-Disciplinary Laboratory for the Research of Sight Threatening Diabetic
Retinopathy, Department of Ophthalmology, University of Toronto, Toronto,
Ontario, Canada.

PURPOSE: To compare the within-session variability of the Macular Edema Module of
the Heidelberg Retinal Tomograph II (HRT II; Heidelberg Engineering, Heidelberg, 
Germany) and the Retinal Thickness Analyzer (RTA, Talia Technology Ltd.,
Neve-Ilan, Israel) in patients with diabetes and nondiabetic subjects and to
determine the agreement of both instruments to clinical observation. METHODS:
Seventeen patients with diabetic macular edema (DME) and 17 nondiabetic subjects 
were examined. Three scans of the posterior pole were acquired for each volunteer
with both the HRT II and the RTA. The edema index and foveal average thickness
were derived for a 600- micro m radius circle centered on the fovea for the HRT
II and RTA scans. The coefficient of variation (COV) was calculated. Clinical
examination of detectable edema was performed using stereo fundus biomicroscopy
and the level of agreement between each instrument and clinical observation was
determined using a zonal analysis. RESULTS: Individual COVs for the HRT II and
RTA ranged from 2.3% to 24.6% (median 8.3%) and 2.1% to 46.7% (median 6.4%),
respectively, in diabetic subjects and 2.0% to 37.5% (median 6.0%) and 2.3% to
14.7% (median 8.5%), respectively, in nondiabetic subjects. Clinical assessment
identified edema in a total of 47 sectors in patients with DME. In comparison to 
clinical assessment, the HRT II gave a sensitivity of 92% and a specificity of
68% and the RTA gave a sensitivity of 57% and a specificity of 71%. CONCLUSIONS: 
Both instruments have good within-session repeatability. The HRT II showed better
agreement with clinical assessment than the RTA. The agreement between
instruments was poor.

Publication Types: 
    Comparative Study
    Evaluation Studies
    Research Support, Non-U.S. Gov't

PMID: 14744905 [PubMed - indexed for MEDLINE]

2398: Invest Ophthalmol Vis Sci. 2004 Feb;45(2):574-83.

Photopic and scotopic fine matrix mapping of retinal areas of increased fundus
autofluorescence in patients with age-related maculopathy.

Scholl HP, Bellmann C, Dandekar SS, Bird AC, Fitzke FW.

Institute of Ophthalmology and Moorfields Eye Hospital, London, United Kingdom.
hendrikscholl@hotmail.com

PURPOSE: To investigate photopic and scotopic sensitivity of retinal areas that
show increased fundus autofluorescence (FAF) in patients with age-related
maculopathy (ARM). METHODS: FAF was imaged with a modified confocal scanning
laser ophthalmoscope (cSLO). Fine matrix mapping (FMM) was performed with a
modified field analyzer. Photopic and scotopic thresholds were obtained at 100
locations on a 9 degrees x 9 degrees matrix with 1 degrees spacing, centered on a
macular area of increased FAF. Inclusion criteria included ARM fundus changes,
areas of increased FAF, central and stable fixation, and visual acuity of 20/40
or better. RESULTS: FAF images were reviewed in 436 patients with age-related
maculopathy (ARM), of whom 38 met the inclusion criteria. FMM was performed in
seven eyes of seven patients. Areas of increased FAF in patients with late ARM
(choroidal neovascularization or geographic atrophy) showed normal or only mildly
abnormal photopic, but severely reduced scotopic, sensitivity. The central area
of increased FAF corresponding to a large foveal druse in a patient with ARM
showed moderately reduced photopic and severely reduced scotopic sensitivity. In 
the other patients with ARM with drusen, areas of increased FAF showed normal or 
near-normal photopic sensitivity, but moderately reduced scotopic sensitivity.
CONCLUSIONS: In retinal areas of increased FAF in patients with ARM, scotopic
sensitivity loss considerably exceeded photopic sensitivity loss. This finding is
in line with histologic data that have demonstrated a preferential loss of rods
in ARM, but does not explain the magnitude of sensitivity loss. The study shows
that increased FAF in ARM has a functional correlate.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 14744901 [PubMed - indexed for MEDLINE]

2399: Invest Ophthalmol Vis Sci. 2004 Feb;45(2):567-73.

Changes in focal macular ERGs after macular translocation surgery with 360
degrees retinotomy.

Terasaki H, Ishikawa K, Niwa Y, Piao CH, Niwa T, Kondo M, Ito Y, Miyake Y.

Department of Ophthalmology, Nagoya University School of Medicine, Nagoya, Japan.
terasaki@med.nagoya-u.ac.jp

PURPOSE: To evaluate the short- and long-term changes of focal macular
electroretinograms (fmERGs) after macular translocation with 360 degrees
retinotomy. METHODS: This was a retrospective study. fmERGs were recorded in 19
eyes of 19 consecutive patients who underwent macular translocation with 360
degrees retinotomy for choroidal neovascularization (CNV) secondary to
age-related macular degeneration (AMD; 17 eyes) or polypoidal choroidal
vasculopathy (2 eyes). The changes in the fmERGs, recorded before, shortly after 
(6-12 months; mean 8.3 months), and more than 18 months (18-30 months; mean 22.4 
months) after surgery from 12 eyes, were analyzed. A 15 degrees stimulus centered
on the fovea was used to elicit the fmERGs. RESULTS: The mean logarithm of
minimum angle of resolution (logMAR) was 1.06 +/- 0.07 (20/230) before surgery,
0.78 +/- 0.08 (20/121) early after surgery (n = 19), and 0.64 +/- 0.07 (20/87)
late after surgery (n = 12). These improvements in visual acuity were significant
(P = 0.0074, P = 0.0050, respectively). Before surgery, the amplitudes of all
components of the fmERGs were markedly reduced in all eyes. The mean b-wave
amplitude in 17 AMD eyes recorded early after surgery was significantly larger (P
= 0.0262), and the mean a-wave amplitude was also increased but not significantly
(P = 0.1180). The mean amplitudes of the a- and b-waves in 10 AMD eyes recorded
after 18 months were significantly larger than those before the surgery (P =
0.0218, and P = 0.0284). The mean implicit time of the b-wave in 17 AMD eyes
decreased early after surgery, and a further decrease was detected at the later
testing time. CONCLUSIONS: These results indicate that macular function is
partially recoverable after macular translocation in some patients.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 14744900 [PubMed - indexed for MEDLINE]

2400: Invest Ophthalmol Vis Sci. 2004 Feb;45(2):531-8.

Macular pigment measurement by heterochromatic flicker photometry in older
subjects: the carotenoids and age-related eye disease study.

Snodderly DM, Mares JA, Wooten BR, Oxton L, Gruber M, Ficek T; CAREDS Macular
Pigment Study Group.

Schepens Eye Research Institute, Boston, Massachusetts, USA. msnodderly@mcg.edu

PURPOSE: To develop a standardized protocol for measuring macular pigment optical
density (MPOD) of experimentally naïve subjects by heterochromatic flicker
photometry (HFP). METHODS: MPOD in eyes of 54 women, age 50 and 79 years (mean,
66), was studied. The spatial profile of MPOD was measured in the right eye, and 
two spatial points were also measured in the left eye. Forty-eight of these
inexperienced subjects completed the protocol on two separate visits. For a
subset of the group, the MPOD at two different wavelengths was measured. RESULTS:
The test-retest correlation at 0.5 degrees eccentricity in the right eye was 0.9.
On the second visit, more than 90% of the subjects were able to perform the HFP
test with results that were consistent with the absorption spectrum of macular
pigment. On the first visit, data from the inexperienced subjects deviated more
from the expected relationships between the two wavelengths, presumably because
they had less skill in performing the task. However, subjects with high or low
macular pigment density were distinguished clearly. CONCLUSIONS: Reliable and
meaningful measurements of macular pigment density in older subjects can be made 
using HFP, with a standardized protocol in the limited time available in large
epidemiologic studies. This protocol will be made freely available to other
researchers on request.

Publication Types: 
    Comparative Study
    Research Support, U.S. Gov't, P.H.S.

PMID: 14744895 [PubMed - indexed for MEDLINE]

2401: Ophthalmol Clin North Am. 2003 Dec;16(4):567-74.

Genetics of age-related macular degeneration.

Klein ML, Francis PJ.

Macular Degeneration Center, Casey Eye Institute, Department of Ophthalmology,
Oregon Health and Sciences University, 3375 Southwest Terwilliger Boulevard,
Portland, OR 97201, USA. kleinm@ohsu.edu

Gene discoveries will lead to more effective them pies for AMD by identifying
specific underlying disease mechanisms that might be corrected by drugs or gene
therapy. For example, investigations are currently being carried out using
pigment epithelium-derived factor (FEDF). The gene for this potent inhibitor of
angiogenesis has been incorporated into an adenoviral vector and delivered into
the eye by intravitreal injection to inhibit growth of new blood vessels in eyes 
with neovascular AMD. In the future, as the genetics of this complex disease are 
unraveled, more effective treatments and preventative measures that target
specific molecular defects underlying the development of AMD can be expected.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.
    Review

PMID: 14740997 [PubMed - indexed for MEDLINE]

2402: Eye. 2004 Jun;18(6):615-8.

Transpupillary thermotherapy for treatment of exudative age-related macular
degeneration in Japanese patients.

Atarashi T, Tamaki Y, Inoue Y, Obata R, Muranaka K, Yanagi Y.

Department of Ophthalmology, University of Tokyo, School of Medicine, Bunkyo-ku, 
Tokyo, Japan.

PURPOSE: To report the therapeutic outcome of transpupillary thermotherapy (TTT) 
for subfoveal choroidal neovascularizarion (CNV) in brown retina using a
diode-laser with the setting of lower energy level compared to the previous
studies on light-pigmented Caucasian patients. METHODS: A total of 19 subfoveal
CNVs in 18 patients were treated with TTT. The power of diode-laser was set 160
mW for 1.2 mm beam, 270 mW for 2.0 mm beam, and 400 mW for 3.0 mm beam, and the
laser was delivered for 1 min through a slit-lamp mounted-delivery system.
Patients were followed up for a mean of 8.8 months (4-12 months). Visual acuity
and the fundus change as judged by funduscopic examination and simultaneous
fluorescein and indocyanine green angiography were evaluated. Visual acuity was
measured by a Japanese standard Landolt visual acuity chart and converted to
logarithm of the minimal angle resolution (log MAR) visual acuity for statistical
analysis. Improvement or decline in vision was defined as change of more than 0.2
in log MAR visual acuity. RESULTS: In eyes with minimally classic or occult only 
CNV, visual acuity improved in two eyes (18%) stabilized in seven eyes (64%) and 
worsened in two eyes (18%). In eyes with predominantly classic CNV, visual acuity
improved in two eyes (25%), stabilized in four eyes (50%) and worsened in two
eyes (25%). In all, 15 (84%) eyes of all studied subjects had improvement in
exudation. Two (11%) and one (5%) eye(s) were noted to have a significant
post-treatment haemorrhage and retinal pigment epithelial tear, respectively.
CONCLUSION: In patients with brown retinal colour, the treatment outcome of TTT
was comparable to that of light-pigmented Caucasian patients with approximately
half the laser power energy. Further randomized control studies are warranted.

Publication Types: 
    Evaluation Studies

PMID: 14739926 [PubMed - indexed for MEDLINE]

2403: Eye. 2004 Jul;18(7):685-90.

Angiographic pattern of recurrent choroidal neovascularization in age-related
macular degeneration.

Battaglia Parodi M, Da Pozzo S, Ravalico G.

Eye Clinic, University of Trieste, Trieste, Italy. maubp@yahoo.it

PURPOSE: To evaluate the angiographic characteristics of recurrent choroidal
neovascularization (R-CNV) in age-related macular degeneration (AMD). METHODS: A 
prospective investigation on 107 consecutive patients with exudative AMD and CNV 
not involving the fovea was conducted. Fluorescein angiography (FA) and
indocyanine green angiography (ICGA) were planned before krypton laser treatment,
and after 3 weeks, 2, 3, 4, 6, 9, 12, 18, and 24 months from photocoagulation.
Laser treatment was FA-guided in eyes with classic CNV, and ICGA-guided in eyes
with occult CNV on FA. RESULTS: At baseline on FA, 23.3% had classic CNV,
whereas, 76.6% showed occult CNV. On ICGA, CNV assumed a focal and a plaque
pattern in 81.3 and 18.6% of cases, respectively. Overall, post-laser CNVs
occurred in 56 eyes. FA identified well-defined and ill-defined R-CNV in 25 and
75% of cases, respectively. ICGA identified three different R-CNV patterns:
focal, annular, and plaque. Focal R-CNV was defined as a single dot-like
hyperfluorescence, which was detected in 69.6% of cases, with subfoveal location 
in half of them. Annular R-CNV was identified by a hyperfluorescent lesion,
partially or completely encircling treated area, which was visible in 19.6% of
cases, all with subfoveal involvement. Plaque R-CNV was defined as a
hyperfluorescent lesion larger than 1 disc diameter in size, and was seen in
10.7% of cases, all with subfoveal location. CONCLUSIONS: ICGA is able to improve
R-CNV visualization identifying three different R-CNV patterns. Focal R-CNV is
the most frequent pattern and can be re-treated in half of the cases.

PMID: 14739913 [PubMed - indexed for MEDLINE]

2404: Br J Ophthalmol. 2004 Feb;88(2):212-7.

Photodynamic therapy with verteporfin is effective, but how big is its effect?
Results of a systematic review.

Meads C, Hyde C.

West Midlands Health Technology Assessment Group, Department of Public Health and
Epidemiology, University of Birmingham, Edgbaston, Birmingham, UK.
c.a.meads@bham.ac.uk

BACKGROUND: In 2001 the National Institute for Clinical Excellence (NICE) was
asked to issue guidance for England and Wales on the use of photodynamic therapy 
(PDT). This process has been protracted, partly because of a dispute over the
magnitude of beneficial effect. This article examines the origins of the debate
about the true treatment effect size for PDT with verteporfin. METHODS: A
systematic review of the clinical effectiveness of PDT compared with current
practice was undertaken. Searches in Medline, Embase, the Cochrane Library, and
the Internet, updated to January 2003, revealed two fully published and four
ongoing randomised controlled trials. RESULTS: The results of the two published
trials (TAP and VIP) consistently showed that overall, PDT with verteporfin is
more effective than placebo in slowing the rate of vision loss. In the TAP trial,
12 or more subgroup analyses were undertaken on the primary outcome measure and
in VIP, 10 subgroup analyses but only on a subset of the trial participants.
Subgroup analysis results were found to be inconsistent between the two trials,
with VIP suggesting that verteporfin was equally effective in occult as in mixed 
lesions and TAP suggesting that verteporfin was more effective in the
predominantly classic subgroup. DISCUSSION: For several reasons it was considered
that the most likely estimate of the predominantly classic subgroup effect size
was the whole trial result. This has implications for the relationship between
cost and benefit, the subject of intense debate. Results of the ongoing trials
should help to clarify this subgroup effect size issue.

Publication Types: 
    Review

PMID: 14736777 [PubMed - indexed for MEDLINE]

2405: Br J Ophthalmol. 2004 Feb;88(2):207-11.

Clinicopathological findings of choroidal neovascularisation following
verteporfin photodynamic therapy.

Gelisken F, Lafaut BA, Inhoffen W, Voelker M, Grisanti S, Bartz-Schmidt KU.

Department of Ophthalmology I, University of Tuebingen, Schleichstrasse 12, 72076
Tuebingen, Germany. Faik.Geilsken@med.uni-tuebingen.de

AIMS: To report the clinicopathologic findings of surgically excised choroidal
neovascularisation (CNV) three days after verteporfin photodynamic therapy (PDT).
METHODS: In three patients (three eyes) with age related macular degeneration,
the CNV was surgically removed three days after PDT. The CNV specimens were
examined by light microscopy. RESULTS: The patients had subfoveal classic CNV.
Fluorescein angiography revealed non-perfusion of the CNV after PDT and before
surgery in all eyes. The light microscopy of the CNV membranes showed swollen and
damaged endothelium. Thrombus formation or vascular occlusion in the CNV vessels 
was not detected. CONCLUSION: PDT did not cause a thrombosis of the vessels
within the CNV three days after PDT. Severe endothelial damage of the CNV was
observed and is likely a primary effect of PDT. Non-perfusion of the CNV at this 
stage is possibly secondary to occlusion at a deeper level, namely the underlying
feeding choroid.

Publication Types: 
    Case Reports

PMID: 14736776 [PubMed - indexed for MEDLINE]

2406: Br J Ophthalmol. 2004 Feb;88(2):186-90.

Case selection in macular relocation surgery for age related macular
degeneration.

Wong D, Stanga P, Briggs M, Lenfestey P, Lancaster E, Li KK, Lim KS, Groenewald
C.

St Paul's Eye Unit, Royal Liverpool University Hospital, Prescot Street,
Liverpool L7 8XP, UK. shdwong@liverpool.ac.uk

BACKGROUND: To date there has been no randomised controlled trial demonstrating
the safety and efficacy of macular relocation surgery (MRS) for age related
macular degeneration (AMD). Vision can be improved in some patients and made
worse in others despite successful surgery or because of complications. PURPOSE: 
To determine which patients would benefit from MRS. METHODS: Twenty nine patients
with exudative AMD took part in a prospective, non-comparative, interventional
study. Macular relocation surgery involved phacoemulsification, vitrectomy, 360
degrees retinotomy, excision of choroidal neovascular membrane, and macular
relocation using an infusion of 5-fluorouracil and low molecular weight heparin
as adjuvant to prevent proliferative vitreoretinopathy. Patients underwent
protocol refraction preoperatively and six-monthly postoperatively by designated 
optometrists. Preoperative fundus fluorescein angiograms were read by masked
observers and the lesions were classified according to a set protocol. The main
outcome measures were visual improvement, final vision of better than 20/400,
reading speed, critical print size. Logistic and multiple stepwise linear
regressions were used to identify independent factors which predicted the main
outcomes. RESULTS: Preoperative visual acuity (20/120 or worse) and lesion type
(predominantly classic or submacular haemorrhage) were significantly associated
with visual improvement (coefficient of regression B = 26.8, p<0.001 and B = 14.9
with p = 0.045 respectively). There were no significant independent factors which
predicted a final distance logMAR visual acuity of 1.3 (20/400) or any arbitrary 
definition of blindness. CONCLUSIONS: The study showed that it was possible to
select cases that were more likely to experience an improvement in vision
following MRS.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 14736769 [PubMed - indexed for MEDLINE]

2407: Exp Eye Res. 2004 Feb;78(2):243-56.

Characterization of beta amyloid assemblies in drusen: the deposits associated
with aging and age-related macular degeneration.

Anderson DH, Talaga KC, Rivest AJ, Barron E, Hageman GS, Johnson LV.

Center for the Study of Macular Degeneration, Neuroscience Research Institute,
University of California, Santa Barbara, CA 93106, USA. d_anders@lifesci.ucsb.edu

PURPOSE: Recent studies strongly suggest that drusen, the extracellular deposits 
associated with age-related macular degeneration (AMD), are a manifestation of
local inflammatory events. New evidence indicates that substructural elements
within drusen contain activated complement components as well as amyloid beta
(Abeta), a major pro-inflammatory component of Alzheimer's disease plaques. We
characterized the ultrastructural organization and histochemical staining
properties of these Abeta-containing elements in order to further assess their
significance in drusen formation and AMD pathogenesis. METHODS: We used
differential interference contrast optics, laser scanning confocal
immunofluorescence, and immunogold electron microscopy to characterize the
structural properties and molecular composition of Abeta-containing elements in
drusen. We obtained estimates of their frequency from montages of electron
micrographs gathered from 152 human donor eyes ranging from 9 to 91 years of age.
RESULTS: Spherical Abeta-containing elements, which are typically organized as
concentric ring-like structures, are common substructural components of drusen.
They stain with thioflavin T, but are not stained by Congo red; nor do they bind 
cationic, lipophilic, or nucleic acid-binding fluorescent dyes.
Ultrastructurally, they are composed of a central core, one or more concentric
inner rings with intervening electron lucent layers, and an electron dense outer 
shell. Immunogold labeling indicates that most Abeta immunoreactivity is
associated with the outer layers that consist of densely-packed spherical
subunits. No longitudinally-oriented fibril arrays, characteristic of aggregated 
amyloid fibrils in the brain, are evident. Other prominent drusen-associated
proteins including the terminal complement complex C5b-9, vitronectin,
apolipoprotein E, serum amyloid P component, and ubiquitin are excluded from the 
spheres.Conclusions. These structures embedded in drusen appear to represent a
new type of macromolecular assembly that contains Abeta as well as activated
complement components. The presence of Abeta in these extracellular deposits is
an additional indication that some of the pathogenic pathways that give rise to
drusen and AMD may be shared with other neurodegenerative diseases characterized 
by misfolded protein deposition and aggregation.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.

PMID: 14729357 [PubMed - indexed for MEDLINE]

2408: Kaohsiung J Med Sci. 2003 Dec;19(12):608-16.

Intravitreous recombinant tissue plasminogen activator and gas to treat
submacular hemorrhage in age-related macular degeneration.

Tsai SC, Lin JM, Chen HY.

Department of Ophthalmology, China Medical University Hospital, Taichung, Taiwan.
d6170@hpd.cmch.org.tw

We evaluated the safety and efficacy of intravitreous recombinant tissue
plasminogen activator (rTPA) and gas for the treatment of submacular hemorrhage
in age-related macular degeneration (ARMD). From January 2000 to April 2002, we
enrolled 15 patients with submacular hemorrhage secondary to ARMD. All patients
received 100 microg rTPA and 0.3 mL perfluoropropane intravitreously.
Postoperatively, all patients were kept in a supine position for 4 hours followed
by a face-down position for 4 days. Anatomic and functional results were
evaluated during a follow-up period of 6 to 19 months. Submacular blood was
completely displaced in 12 patients (80%) and partially in three (20%). Best
postoperative visual acuity improved in all 15 eyes; in seven eyes (47%), the
improvement was two or more lines. Final visual acuity improved in 12 eyes,
remained stable in two eyes, and worsened in one eye. Onset of hemorrhage within 
21 days was associated with better gains of lines in best postoperative (p =
0.0256) and final visual acuity (p = 0.044). Although two patients developed mild
breakthrough vitreous hemorrhage within 1 day after treatment, no rTPA-related
retinal toxicity was observed. Intravitreous injections of rTPA and gas are safe 
and effective in improving visual acuity in patients with submacular hemorrhage
secondary to ARMD. Although the final visual outcome is often limited by the
progression of the disease, significant and stable visual recovery over an
extended follow-up period is possible using this easy and convenient technique.

PMID: 14719558 [PubMed - indexed for MEDLINE]

2409: Menopause. 2004 Jan-Feb;11(1):62-8.

The effect of hormone therapy on the risk for age-related maculopathy in
postmenopausal women.

Abramov Y, Borik S, Yahalom C, Fatum M, Avgil G, Brzezinski A, Banin E.

Department of Obstetrics and Gynecology and the Department of Ophthalmology,
Hadassah Medical Center, Ein-Kerem, Jerusalem, Israel.

OBJECTIVE: To evaluate the effect of postmenopausal hormone therapy (HT) as well 
as the use of oral contraceptives and lifetime endogenous hormone exposure on the
risk for age-related maculopathy (ARM) in postmenopausal women. DESIGN: This was 
a cross-sectional, controlled study. A total of 102 women from 60 to 80 years of 
age who were receiving HT and 100 controls underwent a detailed clinical
funduscopic evaluation and stereoscopic fundus photography for the presence and
grading of ARM. All participants completed a standardized questionnaire regarding
vascular risk factors, HT, and lifetime exogenous and endogenous estrogen and
progesterone exposure. Statistical analysis was performed using Student's t test,
chi2 test, and a multivariate logistic regression model. RESULTS: The HT and the 
non-HT groups did not differ in terms of early (11% v 15%), late (6% v 6%), or
wet (2% v 2%) ARM prevalence rates. Women with ARM were significantly older than 
controls (69 v 66 years; P = 0.001, 95% CI = 0.008 - 0.027) and were more likely 
to have ischemic heart disease (21% v 9%; OR = 2.86, P = 0.03, 95% CI = 0.020 -
0.360). Lifetime exogenous and endogenous hormone exposures and other
cardiovascular risk factors were not significantly different among women with ARM
as compared with controls. CONCLUSION: Postmenopausal HT may not affect the risk 
for either early or late ARM in women aged 60 to 80 years. The risk for both
entities is not necessarily affected by either exogenous or endogenous lifetime
hormone exposure. A history of ischemic heart disease may be associated with an
increased risk for ARM.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 14716184 [PubMed - indexed for MEDLINE]

2410: FASEB J. 2004 Mar;18(3):562-4. Epub 2004 Jan 8.

Inhibition of the ATP-driven proton pump in RPE lysosomes by the major lipofuscin
fluorophore A2-E may contribute to the pathogenesis of age-related macular
degeneration.

Bergmann M, Schütt F, Holz FG, Kopitz J.

Department of Molecular Pathology, University of Heidelberg, Heidelberg, Germany.

Lipofuscin accumulation in the retinal pigment epithelium (RPE) is associated
with various blinding retinal diseases, including age-related macular
degeneration (AMD). The major lipofuscin fluorophor A2-E is thought to play an
important pathogenetic role. In previous studies A2-E was shown to severely
impair lysosomal function of RPE cells. However, the underlying molecular
mechanism remained obscure. Using purified lysosomes from RPE cells we now
demonstrate that A2-E is a potent inhibitor of the ATP-driven proton pump located
in the lysosomal membrane. Such inhibition of proton transport to the lysosomal
lumen results in an increase of the lysosomal pH with subsequent inhibition of
lysosomal hydrolases. An essential task of the lysosomal apparatus of postmitotic
RPE for normal photoreceptor function is phagocytosis and degradation of
membranous discs shed from photoreceptor outer segments (POS) and of biomolecules
from autophagy. When the lysosomes of cultured RPE cells were experimentally
loaded with A2-E, we observed intracellular accumulation of exogenously added POS
with subsequent congestion of the phagocytic process. Moreover, the autophagic
sequestration of cytoplasmic material was also markedly reduced after A2-E
loading. These data support the hypothesis that A2-E-induced lysosomal
dysfunction contributes to the pathogenesis of AMD and other retinal diseases
associated with excessive lipofuscin accumulation.

PMID: 14715704 [PubMed - indexed for MEDLINE]

2411: J Biomed Opt. 2004 Jan-Feb;9(1):149-53.

Three-dimensional computer-automated threshold Amsler grid test.

Fink W, Sadun AA.

California Institute of Technology, Pasadena, California, USA.

We describe a novel method for testing a visual field that employs a computer
monitor with displays of varying contrast that permits unprecedented resolution
and characterization of the structure of scotomas in three dimensions. Patients
are placed in front of a touch-sensitive computer screen at a fixed distance.
With one eye covered, they focus on a central fixation marker and trace with
their finger the areas on an Amsler grid that are missing from their field of
vision. Increasing degrees of contrast of the Amsler grid are simulated by
repeating the test at different gray-scale levels. The results are recorded and
then displayed as topographical contour rings by the computer test program. The
results can also be rendered as an immediate 3-D depiction of the central
hill-of-vision. Several clinical pilot studies have been conducted at the Doheny 
Eye Institute and more than 200 patients have been examined with this system so
far. Conditions such as optic neuritis, anterior ischemic optic neuropathy
(AION), age-related macular degeneration (AMD), glaucoma, and ocular hypertension
have been successfully assessed by this test. Each condition provides unique
patterns that are most evident in 3-D. The 3-D computer-automated threshold
Amsler grid test is an innovative and noninvasive visual field test. It provides 
several advantages over state-of-the-art standard automated perimetry, including:
(1) additional information through 3-D depiction of scotomas, such as location,
extent, slope, depth, and shape; (2) high angular resolution (1 deg compared with
typically 6 deg); (3) a simple test setup (merely a touch-sensitive computer
monitor and the test software); (4) excellent patient compliance (spending 4 to 5
min per eye). In light of its promising initial tests, the 3-D visual field test 
appears to have the potential for the early detection and monitoring of various
diseases over time. (c) 2004 Society of Photo-Optical Instrumentation Engineers.

Publication Types: 
    Evaluation Studies
    Validation Studies

PMID: 14715067 [PubMed - indexed for MEDLINE]

2412: J Biomed Opt. 2004 Jan-Feb;9(1):139-48.

Macular pigment Raman detector for clinical applications.

Ermakov I, Ermakova M, Gellermann W, Bernstein PS.

Department of Physics and Dixon Laser Institute, University of Utah, Salt Lake
City, UT 84112, USA.

Clinical studies of carotenoid macular pigments (MP) have been limited by the
lack of noninvasive, objective instruments. We introduce a novel noninvasive
optical instrument, an MP Raman detector, for assessment of the carotenoid status
of the human retina in vivo. The instrument uses resonant excitation of
carotenoid molecules in the visible wavelength range, and quantitatively measures
the highly specific Raman signals that originate from the single- and double-bond
stretch vibrations of the pi-conjugated carotenoid molecule's carbon backbone.
The instrument is a robust, compact device and suitable for routine measurements 
of MP concentrations in a clinical setting. We characterized and tested the
instrument in clinical studies of human subjects to validate its function and to 
begin to establish its role as a possible screening test for macular pathologies.
We also show that the MP Raman spectroscopy technology has potential as a novel, 
highly specific method for rapid screening of carotenoid antioxidant levels in
large populations at risk for vision loss from age-related macular degeneration, 
the leading cause of blindness of the elderly in the developed world. (c) 2004
Society of Photo-Optical Instrumentation Engineers.

PMID: 14715066 [PubMed - indexed for MEDLINE]

2413: J Biomed Opt. 2004 Jan-Feb;9(1):75-85.

Noninvasive detection of macular pigments in the human eye.

Gellermann W, Bernstein PS.

Department of Physics and Dixon Laser Institute, University of Utah, Salt Lake
City, Utah, USA. werner@physics.utah.edu

There is currently strong interest in developing noninvasive technologies for the
detection of macular carotenoid pigments in the human eye. These pigments,
consisting of lutein and zeaxanthin, are taken up from the diet and are thought
to play an important role in the prevention of age-related macular degeneration, 
the leading cause of blindness in the elderly in the Western world. It may be
possible to prevent or delay the onset of this debilitating disease with suitable
dietary intervention strategies. We review the most commonly used detection
techniques based on heterochromatic flicker photometry, fundus reflectometry, and
autofluorescense techniques and put them in perspective with recently developed
more molecule-specific Raman detection methods. (c) 2004 Society of Photo-Optical
Instrumentation Engineers.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.
    Review

PMID: 14715058 [PubMed - indexed for MEDLINE]

2414: Graefes Arch Clin Exp Ophthalmol. 2004 Apr;242(4):350-4. Epub 2004 Jan 9.

Long-term results after surgical extraction of subfoveal choroidal neovascular
membranes with and without haemorrhage in age-related macular degeneration.

Gabel-Pfisterer A, Laue J, Heimann H, Jandeck C, Kellner U, Bornfeld N, Foerster 
MH.

Augenklinik, Charité Universitätsmedizin Campus Benjamin Franklin, Hindenburgdamm
30, 12200 Berlin, Germany. Agabel@zedat.fu-berlin.de

BACKGROUND: Surgical extraction has been suggested as a treatment of choroidal
neovascular membranes. We demonstrate the long-term results of our patients
regarding complications, risk of recurrence and development of visual acuity.
METHODS: We have retrospectively evaluated the charts and re-examined the
patients who underwent surgical extraction of choroidal neovascular membranes
(CNV) because of age-related macular degeneration (AMD) between March 1994 and
December 2000 in the Department of Ophthalmology of the Benjamin Franklin Clinic,
Berlin. Fifty-two eyes of 49 patients with a minimum follow-up of 12 months after
pars plana vitrectomy with CNV extraction and SF6-endotamponade were included.
Initially, in 15% of all eyes the lesions were obscured by intravitreal
haemorrhage. All visible lesions were located subfoveally. In 40% of all eyes the
lesion was predominantly classic; 21% of the lesions were predominantly occult
and 23% of the lesions were comprised of more than 50% haemorrhage. The maximum
follow-up was 80 months, the mean 46 months. RESULTS: The median initial visual
acuity was 0.08 (range: hand movements to 0.4) and the median final visual acuity
was not significantly different at 0.067 (range: non lux to 0.4). A loss of less 
than three lines of visual acuity occurred in 65.4% of our patients. During
follow-up, 25% of eyes developed a rhegmatogenous retinal detachment and 19.2% of
all eyes suffered from recurrence of CNV. At the end of the follow-up, three eyes
(5.8%) suffered from non-treated retinal detachment and three eyes (5.8%) had
recurrent CNV lesions. All eyes showed a retinal pigment epithelium defect at the
site of former CNV. CONCLUSION: A stabilisation of visual acuity in individual
patients with CNV because of AMD can be achieved by surgical extraction, yet the 
defect of the RPE and the risk of complications limit the benefit. We consider
the surgical extraction of CNV from AMD in patients with low initial visual
acuity who are not amenable to PDT.

PMID: 14714187 [PubMed - indexed for MEDLINE]

2415: Ophthalmology. 2004 Jan;111(1):125-32.

What is lost by digitizing stereoscopic fundus color slides for macular grading
in age-related maculopathy and degeneration?

Scholl HP, Dandekar SS, Peto T, Bunce C, Xing W, Jenkins S, Bird AC.

Institute of Ophthalmology and Moorfields Eye Hospital, London, United Kingdom.
hendrikscholl@hotmail.com

OBJECTIVE: To compare 35-mm stereoscopic slide transparencies with digitized
nonstereoscopic images (resolution 1024x768 pixels) for grading abnormalities in 
age-related maculopathy (ARM) and age-related macular degeneration (AMD). DESIGN:
Comparative observational case series. PARTICIPANTS: Twenty-five patients (50
eyes) with ARM and/or AMD. METHODS: Twenty-five patients with ARM/AMD in at least
1 eye were randomly selected from a large ongoing collection of clinical data and
DNA in a tertiary referral United Kingdom population. Retinal photography was
performed with mydriasis using the Zeiss FF-series 30 degrees fundus camera on
Ektachrome slide transparency film. The images were centered on the macula. The
color transparencies were then digitized. The grading process has been set up
based on the International ARM Epidemiology Study Group. All images were
independently graded by 3 retinal specialists. Both kappa statistics and exact
agreement were calculated to assess agreement between and within observers and
between the 2 master copies derived from the gradings of the color slides and
digitized images. MAIN OUTCOME MEASURE: Agreement between the 2 master copies
derived from the gradings obtained from stereoscopic slide transparencies and
digitized nonstereoscopic images. RESULTS: For small hard and intermediate soft
drusen, agreement ranged between 77% and 91% (kappa, 0.56-0.72) and 83% and 93%
(kappa, 0.31-0.64), respectively, for the 3 macular subfields. Agreement for the 
presence of hyperpigmentation was 12% to 56% (kappa, 0.00-0.27). Agreement was
94% to 96% (kappa, 0.80-0.82) for the presence of geographic atrophy and 93%
(kappa, 0.78) for the area covered. For the presence of choroidal
neovascularization (CNV), agreement was 94% to 98% (kappa, 0.81-0.88), and it was
95% (kappa, 0.83) for the area covered. For individual features of CNV, exact
agreement was 88% to 96% (kappa, 0.22-0.49). In 3 cases of geographic atrophy and
2 cases of CNV, the lesion was missed on digitized images. CONCLUSIONS: Because
of the close agreement for most categories between the grading of stereoscopic
color slides and digitized images, digitized nonstereoscopic color images prove
to be useful for grading ARM and AMD.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 14711724 [PubMed - indexed for MEDLINE]

2416: J Cataract Refract Surg. 2003 Dec;29(12):2378-84.

Treatment of acute pseudophakic cystoid macular edema: Diclofenac versus
ketorolac.

Rho DS.

Department of Ophthalmology, Manhattan Eye, Ear & Throat Hospital, New York, NY, 
USA. dsrho@juno.com

PURPOSE: To investigate whether topical diclofenac sodium 0.1% solution (Voltaren
Ophthalmic) is as efficacious as topical ketorolac tromethamine 0.5% solution
(Acular) in the treatment of established, chronic cystoid macular edema (CME)
after uneventful phacoemulsification cataract extraction with posterior chamber
intraocular lens (IOL) implantation. SETTING: Referral-based vitreoretinal
private practice. METHODS: This randomized prospective study comprised 34
consecutive patients with clinical CME after uneventful phacoemulsification
cataract extraction with posterior chamber IOL implantation who were referred to 
a private vitreoretinal practice for evaluation and management. Exclusion
criteria included a history of previous intraocular surgery, vitreous loss during
cataract surgery, CME, uveitis, and vitreoretinal pathology. The eye with CME was
treated with 1 drop 4 times daily of diclofenac sodium 0.1% solution or ketorolac
tromethamine 0.5% solution. Outcomes were measured by observing for improvement
in CME and visual acuity. RESULTS: Both treatment methods resulted in a
significant reduction in CME and a significant improvement in visual acuity.
Within 26 weeks, diclofenac reduced CME in 16 patients (89%) and ketorolac, in 14
patients (88%) (P =.92, confidence interval [CI] 95%). Within 26 weeks,
diclofenac eliminated CME in 14 patients (78%) and ketorolac, in 12 patients
(75%) (P =.86, CI 95%). The mean time to initial CME reduction was 7.5 weeks with
diclofenac and 8.0 weeks with ketorolac (P =.41, CI 95%). The mean time to CME
resolution was 13.6 weeks with diclofenac and 12.8 weeks with ketorolac (P =.49, 
CI 95%). CONCLUSIONS: Diclofenac sodium 0.1% solution and ketorolac tromethamine 
0.5% topical ophthalmic solution eyedrops were equally effective in reducing the 
severity and duration of CME after uneventful phacoemulsification with posterior 
chamber IOL implantation. Either solution may be considered for CME after
cataract surgery, especially in patients who may not tolerate corticosteroid
treatment.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 14709300 [PubMed - indexed for MEDLINE]

2417: Retina. 2003 Dec;23(6):800-7.

The role of lanreotide in the treatment of choroidal neovascularization secondary
to age-related macular degeneration: a pilot clinical trial.

Papadaki T, Tsilimbaris M, Thermos K, Karavellas M, Samonakis D, Papapdakis A,
Linardakis M, Kouromalis E, Pallikaris I.

Department of Ophthalmology, University of Crete Medical School, Heraklion,
Crete, Greece.

PURPOSE: To evaluate the role of somatostatin in the treatment of subfoveal
choroidal neovascularization (CNV). METHODS: Twenty eyes of 20 patients with CNV 
were included in the study. Patients were randomly allocated to treatment with
lanreotide (10 eyes) or placebo (10 eyes). Patients received one intramuscular
injection of lanreotide or placebo every 15 days for a total of 6 months.
Follow-up lasted for 6 months for the control group and 12 months for the study
group. The changes in visual acuity and fluorescein angiography at 6 months were 
compared between the two groups. In addition, the changes in the same parameters 
within the study group, from 6 to 12 months, were studied. RESULTS: From baseline
to 6 months, the mean visual acuity and surface area of hyperfluorescence
remained stable in the study group, while the intensity of hyperfluorescence
decreased. After discontinuation of treatment, deterioration of all three
parameters was noted in the study group. Statistical analysis, however, failed to
reveal any significant difference from baseline. CONCLUSIONS: During treatment
with lanreotide, a trend for stabilization of visual acuity and intensity of
hyperfluorescence was documented in the study group, but it did not reach
statistically significant levels. Further randomized, controlled clinical trials 
with larger samples and longer duration of treatment and follow-up are warranted 
to evaluate the role of lanreotide in the treatment of age-related CNV.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 14707831 [PubMed - indexed for MEDLINE]

2418: Medicina (Kaunas). 2003;39(12):1231-6.

Age-related maculopathy and consumption of fresh vegetables and fruits in urban
elderly.

Vaicaitiene R, Luksiene DK, Paunksnis A, Cerniauskiene LR, Domarkiene S, Cimbalas
A.

Institute of Cardiology, Kaunas University of Medicine, Sukileliu 17, 3007
Kaunas, Lithuania. klbioch@kmu.lt

The purpose of this study was to investigate the rate of age-related maculopathy 
among elderly males and females in relation to frequency of consumption of fresh 
vegetables and fruit. During ophthalmological investigation of Kaunas city
inhabitants aged 65-74 years (240 males and 206 females) age-related maculopathy 
(early and late) was determined for 22.1% of males and 20.4% of females.
Frequency of usage of fresh (uncooked) vegetables and fruits in winter-spring and
in summer-autumn seasons by investigated persons was determined, using food
frequency questionnaire. In this work an association between age-related
maculopathy and usage of vegetables and fruits has been investigated in 170 males
and 181 females aged 65-74 years without diabetes who never smoked; age-related
maculopathy was found for 18.8% of males and 17.7% of females. Obtained data have
demonstrated an inverse association between consumption of vegetables during
winter-spring season and age-related maculopathy: usage of vegetables two times a
week or more versus usage less than two times a week decreases prevalence of
age-related maculopathy 2.0 times among males (OR=0.42; 95% CI 0.18-1.0; p=0.05) 
and 2.2 times among females (OR=0.37; 95% CI 0.15-0.9; p=0.02). Data have
demonstrated a tendency that increasing consumption of fresh vegetables and
fruits during both seasons can reduce risk of age-related maculopathy among
females. In conclusion, characteristic for Lithuanian urban elderly rare usage of
fresh vegetables during winter-spring season can increase risk of age-related
maculopathy independently from other risk factors.

Publication Types: 
    Comparative Study

PMID: 14704513 [PubMed - indexed for MEDLINE]

2419: Am J Ophthalmol. 2004 Jan;137(1):178-9.

Positioning the obese or large-breasted patient for macular laser
photocoagulation.

Browning DJ.

Charlotte Eye, Ear, Nose, and Throat Associates, Charlotte, North Carolina 28210,
USA. djbrowning@carolina.rr.com

PURPOSE: To report a positioning method for macular laser photocoagulation in
obese or large-breasted patients. DESIGN: Report of a laser technique. METHODS:
Review of clinical experience. SETTING: Private retina practice. RESULTS:
Standing the patient up, leaning forward, and using the examination chair as
buttocks support allows easier positioning of the obese or large-breasted patient
in the slit lamp. The laser surgeon's hand manipulating the slit-lamp joystick
does not fatigue, which allows more careful examination and treatment in these
delicate cases. CONCLUSIONS: The technique described may allow more thorough
diagnostic evaluation and focal laser treatment of obese and large-breasted
patients with macular diseases.

PMID: 14700665 [PubMed - indexed for MEDLINE]

2420: Am J Ophthalmol. 2004 Jan;137(1):84-9.

Association of neovascular age-related macular degeneration and
hyperhomocysteinemia.

Axer-Siegel R, Bourla D, Ehrlich R, Dotan G, Benjamini Y, Gavendo S, Weinberger
D, Sela BA.

Department of Ophthalmology, Rabin Medical Center, Petah Tiqva, Israel.
seegs@netvision.net.il

PURPOSE: To assess the relationship between plasma homocysteine levels and
exudative neovascular age-related macular degeneration (AMD). DESIGN:
Cross-sectional study. METHODS: A prospective comparative cross-sectional study
was conducted in outpatient ophthalmology clinics in a university-affiliated
medical institution. The cohort consisted of 59 patients (25 male, 34 female)
with a mean age of 78 years (standard deviation [SD] = 8.4) with neovascular AMD 
who were candidates for photodynamic treatment. Patients were compared for plasma
homocysteine levels with 58 patients who had dry AMD (24 male, 34 female) with a 
mean age of 76.3 years (SD = 8.4) and with a control group of 56 age-matched
subjects (27 male, 29 female), with a mean age of 77.3 years (SD = 8.2). A 3-ml
venous blood sample was obtained from each participant after an 8-hour fast.
Levels of plasma homocysteine were measured by high performance liquid
chromatography. The main outcome measure was hyperhomocysteinemia, defined as a
plasma homocysteine level above 15 micromol/l. RESULTS: Homocysteine levels were 
higher by 27.9% in the neovascular AMD than in the dry AMD group, and by 21.9%
than in the control group (P <.02). Hyperhomocysteinemia was found in 44.1% of
the study group, in 22.4% of the dry AMD group, and in 21.4% of the control group
(P =.011). CONCLUSIONS: This study suggests an association between an elevated
plasma level of homocysteine and exudative neovascular AMD but not dry AMD.

Publication Types: 
    Comparative Study

PMID: 14700648 [PubMed - indexed for MEDLINE]

2421: Br J Ophthalmol. 2004 Jan;88(1):114-9.

Radiotherapy for recurrent choroidal neovascularisation complicating age related 
macular degeneration.

Marcus DM, Sheils WC, Young JO, McIntosh SB, Johnson MH, Alexander J, Samy CN.

Department of Ophthalmology, Medical College of Georgia, 1120 15th Street,
Augusta, GA 30912, USA. dmarcus@mail.mcg.edu

AIMS: To report the safety and visual outcome data of external beam irradiation
for recurrent choroidal neovascularisation complicating age related macular
degeneration. METHODS: Eighteen consecutive eyes received external beam
irradiation with seven fractions of 2 Gy (total dose 14 Gy). The next 16
consecutive eyes received external beam irradiation with five fractions of 3 Gy
(total dose 15 Gy). Main outcome measure was change in visual acuity. Secondary
outcome variables were contrast sensitivity and fundus photographic/fluorescein
angiographic progression. RESULTS: The 3 Gy fraction group lost fewer lines of
distance visual acuity at the three and six month follow up. At one year follow
up, this difference was not maintained with 2 Gy fraction and 3 Gy fraction eyes.
At one year follow up a decrease in visual acuity of three or more lines
(moderate visual loss) occurred in 58% of 2 Gy and 42% of 3 Gy fraction eyes
(p<0.36). At one year follow up a decrease in visual acuity of six or more lines 
(severe visual loss) occurred in 41% of 2 Gy eyes and 17% of 3 Gy eyes (p<0.23). 
At three months follow up, 3 Gy eyes were less likely (0%) than 2 Gy eyes (47%)
to show moderate visual loss (p<0.003). However, Kaplan Meier curves estimate a
significantly lower rate of severe visual loss in the 3 Gy group (p = 0.02).
There were no significant differences in contrast sensitivity loss or fluorescein
angiographic stabilisation rates. No evidence of radiation toxicity was observed.
CONCLUSION: Our results are consistent with trends for a palliative benefit with 
higher fraction sizes and doses. The radiobiologic differences between low and
high fraction size groups in this study are modest and correlate with the modest 
and short term difference in visual outcomes. These trends support further
investigation of radiotherapy using fraction sizes of 4 Gy or higher.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 14693787 [PubMed - indexed for MEDLINE]

2422: Br J Ophthalmol. 2004 Jan;88(1):104-9.

Retinal vessel wall signs and the 5 year incidence of age related maculopathy:
the Blue Mountains Eye Study.

Wang JJ, Mitchell P, Rochtchina E, Tan AG, Wong TY, Klein R.

Centre for Vision Research, Department of Ophthalmology, University of Sydney,
Westmead Hospital, Hawkesbury Road, Westmead, NSW 2145, Australia.
jiejin_wang@wmi.usyd.edu.au

AIMS: To assess whether retinal arteriolar wall changes (focal narrowing and
arteriovenous nicking) are associated with an increased 5 year risk of age
related maculopathy (ARM). METHODS: The Blue Mountains Eye Study examined 3654
residents aged 49+ years living in a defined area, during 1992-4 (82.4%
participation). After 5 years, 2335 surviving participants (75.1%) were
re-examined during 1997-9. Retinal photographs were graded using the Wisconsin
ARM grading system. Incident late (neovascular or atrophic) or early stage ARM
was defined using a side by side grading method. Focal arteriolar narrowing
(localised constricted arteriolar segments causing a sausage-like appearance),
and arteriovenous (AV) nicking (constriction on both sides of the venule where
crossed by an arteriole), were graded by comparison with standard photographs.
All retinal vessels passing through a circumferential zone 0.5-1.0 disc diameters
from the optic disc margin were measured from digitised images. Summarised
estimates for central retinal arteriolar equivalent (CRAE) represent an average
diameter of arterioles for that eye. Associations were assessed after adjusting
for age, sex, smoking, mean arterial blood pressure, and other vascular risk
factors. RESULTS: Of 2314 baseline participants at risk of late stage ARM, either
late stage lesion developed in 34 participants (1.5%). Of 2203 at risk of early
stage ARM, this sign developed in 197 participants (8.9%). Focal arteriolar
narrowing was present at baseline in at least one eye of 162 survivors (6.9%) and
severe AV nicking was present in 187 people (8.1%). Over 5 years, 4.9% of
subjects with and 1.2% of those without focal narrowing developed either late
stage ARM lesion, age adjusted relative risk (RR) 2.3, 95% confidence interval
(CI) 1.0 to 5.1, multivariate adjusted odds ratios (OR) 2.1 (95% CI 0.9 to 4.9). 
Similarly, 3.7% of subjects with and 1.3% of those without severe AV nicking
developed late ARM lesions, age adjusted RR 2.1 (95% CI 0.9 to 5.1), multivariate
adjusted OR 2.2 (95% CI 0.9 to 5.6). Corresponding age adjusted RR and
multivariate adjusted OR for development of early stage ARM were 1.4 (95% CI 0.9 
to 2.0) and 1.3 (95% CI 0.8 to 2.1) for focal arteriolar narrowing, and 1.6 (95% 
CI 1.0 to 2.3) and 1.8 (95% CI 1.1 to 2.9) for severe AV nicking, respectively.
No associations between baseline CRAE and 5 year incident late or early stage ARM
were found. CONCLUSIONS: Although of borderline statistical significance, the
consistent associations found in this study suggest that structural retinal
arteriolar changes may either contribute to ARM progression or may share common
pathological pathways with ARM.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 14693785 [PubMed - indexed for MEDLINE]

2423: Am J Hum Genet. 2004 Jan;74(1):20-39. Epub 2003 Dec 19.

Dissection of genomewide-scan data in extended families reveals a major locus and
oligogenic susceptibility for age-related macular degeneration.

Iyengar SK, Song D, Klein BE, Klein R, Schick JH, Humphrey J, Millard C, Liptak
R, Russo K, Jun G, Lee KE, Fijal B, Elston RC.

Department of Epidemiology and Biostatistics, Case Western Reserve University,
Cleveland, OH 44109-1998, USA. ski@po.cwru.edu

To examine the genetic basis of age-related macular degeneration (ARMD), a
degenerative disease of the retinal pigment epithelium and neurosensory retina,
we conducted a genomewide scan in 34 extended families (297 individuals, 349 sib 
pairs) ascertained through index cases with neovascular disease or geographic
atrophy. Family and medical history was obtained from index cases and family
members. Fundus photographs were taken of all participating family members, and
these were graded for severity by use of a quantitative scale. Model-free linkage
analysis was performed, and tests of heterogeneity and epistasis were conducted. 
We have evidence of a major locus on chromosome 15q (GATA50C03 multipoint
P=1.98x10-7; empirical P< or =1.0x10-5; single-point P=3.6x10-7). This locus was 
present as a weak linkage signal in our previous genome scan for ARMD, in the
Beaver Dam Eye Study sample (D15S659, multipoint P=.047), but is otherwise novel.
In this genome scan, we observed a total of 13 regions on 11 chromosomes (1q31,
2p21, 4p16, 5q34, 9p24, 9q31, 10q26, 12q13, 12q23, 15q21, 16p12, 18p11, and
20q13), with a nominal multipoint significance level of P< or =.01 or LOD > or
=1.18. Family-by-family analysis of the data, performed using model-free linkage 
methods, suggests that there is evidence of heterogeneity in these families. For 
example, a single family (family 460) individually shows linkage evidence at 8
loci, at the level of P<.0001. We conducted tests for heterogeneity, which
suggest that ARMD susceptibility loci on chromosomes 9p24, 10q26, and 15q21 are
not present in all families. We tested for mutations in linked families and
examined SNPs in two candidate genes, hemicentin-1 and EFEMP1, in subsamples (145
and 189 sib pairs, respectively) of the data. Mutations were not observed in any 
of the 11 exons of EFEMP1 nor in exon 104 of hemicentin-1. The SNP analysis for
hemicentin-1 on 1q31 suggests that variants within or in very close proximity to 
this gene cause ARMD pathogenesis. In summary, we have evidence for a major ARMD 
locus on 15q21, which, coupled with numerous other loci segregating in these
families, suggests complex oligogenic patterns of inheritance for ARMD.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 14691731 [PubMed - indexed for MEDLINE]

2424: Invest Ophthalmol Vis Sci. 2004 Jan;45(1):260-6.

Basal laminar deposit formation in APO B100 transgenic mice: complex interactions
between dietary fat, blue light, and vitamin E.

Espinosa-Heidmann DG, Sall J, Hernandez EP, Cousins SW.

Department of Ophthalmology, Bascom Palmer Eye Institute, Miami, Florida, USA.

PURPOSE: Dietary fat intake has been proposed as a mechanism of sub-RPE deposit
formation. It has been demonstrated recently that sub-RPE deposits develop in 16-
to 18-month-old C57BL/6 mice fed a high-fat diet and exposed to blue-green light.
Hyperlipidemia also develops in these mice after they consume a high-fat diet.
Because hyperlipidemia also develops in young C57BL/6 mice that overexpress APO
B100, the major apolipoprotein in LDL cholesterol, this research was conducted to
determine whether high-fat diet and plasma hyperlipidemia correlate with
formation of basal laminar deposits (BLD) in young transgenic mice. METHODS: APO 
B100 and wild-type C57BL/6 2-month-old mice were fed a high-fat diet for 4.5
months. After the first month, the right eyes were exposed to seven 5-second
doses of nonphototoxic levels of blue-green light (20 mJ of argon 488 nm) over 2 
weeks. Three months later, transmission electron microscopy (TEM) of the retina
was performed to evaluate whether sub-RPE deposits correlate with plasma
cholesterol and triglyceride levels. Several eyes were stained with filipin to
detect cholesterol and osmium-thiocarbohydrazide-osmium (OTO) to detect neutral
lipids in Bruch's membrane (BrM). A third group of APO B100 2-month-old mice were
pretreated with vitamin E subcutaneously twice a week throughout the experiment
and underwent the same light-exposure protocol. RESULTS: Mice fed a high-fat diet
had a more elevated plasma triglyceride and cholesterol level than those that
consumed a regular diet. Young APO B100 mice fed a high-fat diet had blood lipid 
levels higher than those in young wild-type mice that consumed high-fat diets,
and these two groups had higher lipid levels than animals with regular diets, as 
shown previously in wild-type C57BL/6 (old and young). Eyes of APO B100 mice
treated with blue-green light showed a high frequency of "moderate BLD", whereas 
the nonexposed eyes did not. In contrast, no BLD formed in either eye of the
wild-type young mice fed a high-fat diet. In individual affected mice, only a
weak correlation was observed between deposit severity and plasma lipid
concentration. None of the eyes in mice with sustained hyperlipidemia with or
without BLD demonstrated obvious widespread neutral lipid or cholesterol
deposition in BLD or BrM. However, vitamin E-treated mice showed minimal
formation of BLD. CONCLUSIONS: Although a high-fat diet is a necessary
precondition for this model of BLD, the findings demonstrated a convincing direct
correlation between plasma lipidemia and deposit severity. The results suggest
that age, as shown in previous studies, and high-fat predispose to formation of
BLD by altering hepatic and/or RPE lipid metabolism in ways more complicated than
plasma hyperlipidemia alone.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.

PMID: 14691182 [PubMed - indexed for MEDLINE]

2425: Invest Ophthalmol Vis Sci. 2004 Jan;45(1):30-5.

The benign concentric annular macular dystrophy locus maps to 6p12.3-q16.

van Lith-Verhoeven JJ, Hoyng CB, van den Helm B, Deutman AF, Brink HM, Kemperman 
MH, de Jong WH, Kremer H, Cremers FP.

Department of Ophthalmology, University Medical Center Nijmegen, Nijmegen, The
Netherlands.

PURPOSE: To describe the clinical findings and to identify the genetic locus in a
Dutch family with autosomal dominant benign concentric annular macular dystrophy 
(BCAMD). METHODS: All family members underwent ophthalmic examination. Linkage
analysis of candidate retinal dystrophy loci and a whole genome scan were
performed. Five candidate genes from the linked locus were analyzed for mutations
by direct sequencing. RESULTS: The BCAMD phenotype is initially characterized by 
parafoveal hypopigmentation and good visual acuity, but progresses to a retinitis
pigmentosa-like phenotype. Linkage analysis established complete segregation of
the BCAMD phenotype (maximum multipoint LOD score, 3.8) with DNA markers at
chromosome 6, region p12.3-q16. Recombination events defined a critical interval 
spanning 30.7 cM at the long arm of chromosome 6 between markers D6S269 and
D6S300. This interval encompasses several retinal dystrophy loci, including the
ELOVL4 gene, mutated in autosomal dominant Stargardt disease, and the RIM1 gene, 
mutated in autosomal dominant cone-rod dystrophy, as well as the retinally
expressed GABRR1 and -2 genes. Mutation screening of these four genes revealed no
mutations. Sequence analysis of the interphotoreceptor matrix proteoglycan 1 gene
IMPG1, also residing in the BCAMD locus, revealed a single base-pair change
(T-->C) of nucleotide 1866 in exon 13, resulting in a Leu579Pro amino acid
substitution. This mutation was absent in 190 control individuals. CONCLUSIONS:
Significant linkage was found for the BCAMD defect with chromosomal 6, region
p12.3-q16. A Leu579Pro mutation in the IMPG1 gene may play a causal role.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 14691150 [PubMed - indexed for MEDLINE]

2426: Ophthalmic Physiol Opt. 2004 Jan;24(1):17-25.

Effect of light filters on reading speed in normal and low vision due to
age-related macular degeneration.

Eperjesi F, Fowler CW, Evans BJ.

Neurosciences Research Institute, School of Life and Health Sciences, Aston
University, Aston Triangle, Birmingham B4 7ET, UK. f.eperjesi@aston.ac.uk

PURPOSE: To investigate the effects of light filters on reading speed in normal
and low vision due to age-related macular degeneration (AMD). METHODS: Reading
speed was determined for 12 subjects with normal vision and 12 subjects with
non-exudative AMD using stationary lowercase nonsensical print in Times Roman
font and four light filters; a yellow Corning Photochromic Filter (CPF) 450, a
grey neural density (ND) filter, an individual filter obtained using the
Intuitive Colorimeter and a clear filter. RESULTS: There was no statistically
significant light filter effect on reading speed for the normal subjects. The AMD
group demonstrated a statistically significant 5% average improvement in reading 
speed with the CPF450 compared with the other filters although some AMD subjects 
had improvements of 10-15%. CONCLUSIONS: Light filters obtained using the
Intuitive Colorimeter(R) performed poorly when compared with the CPF450, ND and
clear filters for both the study groups. For the AMD group, average reading speed
was statistically greater with the CPF450 than the other filters, however it is
questionable whether the improvement (5%) would be clinically significant. As
some of the subjects with AMD had greater improvements with the CPF450 we
advocate clinical assessment of light filters using existing protocols on an
individual basis.

PMID: 14687197 [PubMed - indexed for MEDLINE]

2427: Cleve Clin J Med. 2003 Dec;70(12):1017-8, 1020, 1023-5 passim.

Age-related macular degeneration: evaluation and treatment.

Moshfeghi DM, Lewis H.

Cole Eye Institute, The Cleveland Clinic Foundation, OH 44195, USA.

Any patient age 50 or older with distorted vision or vision loss may have
age-related macular degeneration and should be immediately referred to an
ophthalmologist. Early diagnosis and treatment are essential to preserve the
current level of vision. We outline risk factors, clinical signs, what happens to
the retina, and what treatments are currently available, as well as
recommendations about vitamin and mineral supplementation.

Publication Types: 
    Review

PMID: 14686682 [PubMed - indexed for MEDLINE]

2428: Graefes Arch Clin Exp Ophthalmol. 2004 Jan;242(1):91-101. Epub 2003 Dec 18.

Role of growth factors and the wound healing response in age-related macular
degeneration.

Schlingemann RO.

Ocular Angiogenesis Group, Department of Ophthalmology, Academic Medical Center, 
Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands. r.schlingemann@amc.uva.nl

Growth factors (GF) are important in several stages of the pathogenesis of
age-related macular disease (AMD). In choroidal neovascularization (CNV) in
exudative AMD, the GF involved are similar to those involved in wound healing of 
the skin. Like granulation tissue of skin, CNV is characterized by clotting,
inflammation, angiogenesis and fibrosis, and like in skin wounds, members of the 
VEGF, angiopoietin, PDGF and TGF-beta families of GF are expressed. However,
several of these GF may also serve physiological functions in the normal eye,
where the retinal pigment epithelium (RPE) employs them to provide trophic
support to the neuroretina and choriocapillaris, in addition to maintaining an
anti-angiogenic state. Derangement of these physiological functions may underlie 
the initiation of CNV in AMD. Basolateral secretion of VEGF-A by the RPE
maintains the choriocapillaris, and is enhanced by hypoxia. Age-related changes
in Bruch's membrane lead to impairment of this trophic function and
choriocapillaris atrophy, as well as to decreased diffusion of oxygen towards the
neuroretina. The resulting outer retina hypoxia may be an important driving force
of CNV formation, by stimulating VEGF overexpression by the RPE, in addition to
the effects of increased oxidative stress and low-grade inflammation. RPE
senescence and hypoxia may also decrease expression of angiogenesis inhibitors
such as PEDF, further shifting the balance to a pro-angiogenic state in the aging
eye.

Publication Types: 
    Review

PMID: 14685874 [PubMed - indexed for MEDLINE]

2429: Arch Ophthalmol. 2003 Dec;121(12):1728-37.

Erratum in:
    Arch Ophthalmol. 2004 Mar;122(3):426.

Progression of age-related macular degeneration: association with dietary fat,
transunsaturated fat, nuts, and fish intake.

Seddon JM, Cote J, Rosner B.

Massachusetts Eye and Ear Infirmary, Epidemiology Unit, Harvard School of Public 
Health, Boston, Massachesetts 02114, USA. johanna_seddon@meei.harvard.edi

BACKGROUND: Individuals with early or intermediate stages of age-related macular 
degeneration (AMD) make up a large, growing segment of the elderly population.
Evidence is sparse regarding modifiable factors that may decrease the risk of
progression to the advanced forms of AMD. OBJECTIVE: To advise patients with a
high risk for advanced forms of AMD about preventive measures through our
evaluation of the relationship between dietary fat intake and the progression of 
early or intermediate AMD to the advanced stages of the disease associated with
visual loss. DESIGN: A prospective cohort study with an average follow-up time of
4.6 years. SETTING: A hospital-based clinical retinal practice specializing in
macular degeneration.Patients The 261 participants were aged 60 years and older
and had some sign of nonexudative AMD and visual acuity of 20/200 or better in at
least 1 eye.Main Outcome Measure Progression to advanced AMD, which was defined
as having geographic atrophy or neovascular disease. RESULTS: Higher total fat
intake increased the risk of progression to the advanced forms of AMD, with a
relative risk (RR) of 2.90 (95% confidence interval, 1.15-7.32) for the highest
fat-intake quartile relative to the lowest fat-intake quartile, after controlling
for other factors (P trend =.01). Animal fat intake was associated with a 2-fold 
increased risk of progression (RR, 2.29 for the highest quartile compared with
the lowest quartile; 95% confidence interval, 0.91-5.72), although the trend for 
increasing risk with higher animal fat intake was not significant (P=.09). Higher
vegetable fat intake had a stronger relationship with increased risk of AMD
progression with an RR of 3.82 (95% confidence interval, 1.58-9.28) for the
highest quartile compared with the lowest quartile (P trend =.003). Saturated,
monounsaturated, polyunsaturated, and transunsaturated fats increased the
likelihood of progression (RR, 2.09 and P trend =.08; RR, 2.21 and P trend =.04; 
RR, 2.28 and P trend =.04; RR, 2.39 and P trend =.008, respectively). Higher fish
intake was associated with a lower risk of AMD progression among subjects with
lower linoleic acid intake. Processed baked goods, which are higher in some of
these fats, increased the rate of AMD progression approximately 2-fold, and nuts 
were protective. CONCLUSIONS: Among individuals with the early or intermediate
stages of AMD, total and specific types of fat intake, as well as some
fat-containing food groups, modified the risk of progression to advanced AMD.
Fish intake and nuts reduced risk. Since advanced AMD is associated with visual
loss and reduced quality of life, these preventive measures deserve additional
research and greater emphasis.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 14662593 [PubMed - indexed for MEDLINE]

2430: Br J Ophthalmol. 2003 Dec;87(12):1497-503.

Palladium-103 plaque radiation therapy for macular degeneration: results of a 7
year study.

Finger PT, Gelman YP, Berson AM, Szechter A.

New York Eye and Ear Infirmary, New York City, New York 10003, USA.
pfinger@maculardegeneration.org

AIM: To report 7 year results of ophthalmic plaque radiotherapy for exudative
macular degeneration. METHODS: In a phase I clinical trial, 30 patients (31 eyes)
were treated with ophthalmic plaque irradiation for subfoveal exudative macular
degeneration. Radiation was delivered to a mean 2 mm from the inner sclera (range
1.2-2.4) prescription point calculated along the central axis of the plaque. The 
mean prescription dose was 17.62 Gy (range 12.5-24) delivered over 34 hours
(range 18-65). Early Treatment Diabetic Retinopathy Study (ETDRS) type
standardised visual acuity determinations, ophthalmic examinations, and
angiography were performed before and after treatment. Clinical evaluations were 
performed in a non-randomised and unmasked fashion. RESULTS: At 33.3 months
(range 3-4), 17 of 31 (55%) eyes had lost 3 or more lines of vision on the ETDRS 
chart, five (16%) had improved 3 or more lines, and the remaining nine (29%) were
within 2 lines of their pretreatment visual acuity measurement. Overall, 45% of
patients were within or improved more than 2 lines of their initial visual
acuity. Five eyes developed macular scars, eight developed subsequent
neovascularisation or haemorrhage, and three progressed through therapy. Two
patients were lost to follow up. The most common finding of patients followed for
6 or more months (n=18 of 29 (62%)) was regression or stabilisation of the
exudative process. No radiation retinopathy, optic neuropathy, or cataracts could
be attributed to irradiation. CONCLUSION: Ophthalmic plaque radiation can be used
to treat exudative macular degeneration. At the dose and dose rates employed,
most patients experienced decreased exudation or stabilisation of their maculas. 
No sight limiting radiation complications were noted during 7 year follow up.
Owing to the variable natural course of this disease, a prospective randomised
clinical trial should be performed to evaluate the efficacy of plaque radiation
therapy for exudative macular degeneration.

Publication Types: 
    Clinical Trial
    Clinical Trial, Phase I
    Research Support, Non-U.S. Gov't

PMID: 14660461 [PubMed - indexed for MEDLINE]

2431: Vision Res. 2004 Feb;44(4):349-56.

Intravitreal triamcinolone does not alter basal vascular endothelial growth
factor mRNA expression in rat retina.

Gao H, Qiao X, Gao R, Mieler WF, McPherson AR, Holz ER.

Department of Ophthalmology, Baylor College of Medicine, Cullen Eye Institute,
6560 Fannin, Suite 2200, Houston, TX 77030, USA. huagao55@hotmail.com

Intravitreal triamcinolone inhibits choroidal neovascularization. To investigate 
if vascular endothelial growth factor (VEGF) is affected, we examined VEGF
expression after intravitreal triamcinolone administration in rat retina. Using
in situ hybridization, we have found dense clustered VEGF mRNA signals in the
retinal pigment epithelium, moderate patchy signals in the inner nuclear layer,
and positive labeling in a sub-population of ganglion cells. Densitometry and
northern blot analysis revealed no significant alteration of VEGF mRNA expression
pattern and level 3-21 days after triamcinolone injection. Our data indicate that
intravitreal triamcinolone does not affect basal VEGF mRNA expression in normal
adult rat retina.

PMID: 14659961 [PubMed - indexed for MEDLINE]

2432: Graefes Arch Clin Exp Ophthalmol. 2004 Mar;242(3):265-7. Epub 2003 Dec 3.

Coats-like lesions in Usher syndrome type II.

Kiratli H, Oztürkmen C.

Department of Ophthalmology, Hacettepe University School of Medicine, Ankara,
Turkey. hkiratli@hacettepe.edu.tr

BACKGROUND: An unusual case of Usher syndrome type II associated with bilateral
Coats-like exudative retinopathy is described. METHODS: A 14-year-old boy with
congenital sensorineural deafness and normal vestibular functions presented with 
a recent history of night blindness. He was followed for 3 years with fundus
photography, intravenous fluorescein angiography, electroretinography and
audiometric testings. His parents refused any form of treatment. RESULTS:
Fundoscopy showed bilateral retinitis pigmentosa and a single focus of subretinal
exudation and overlying telangiectatic retinal vessels inferotemporal to the
vascular arcade in the right eye. He had bilateral mild macular edema. A year
later, a similar lesion developed inferotemporally in the left fundus.
Electroretinography responses, particularly the rod-mediated signals, were
significantly reduced. Audiometric studies documented hearing loss in high
frequencies. His visual acuity declined from 20/40 to 20/80 RE and from 20/80 to 
20/100 LE during follow-up. No new lesions developed. CONCLUSIONS: Coats-type
exudative lesions may develop in patients with Usher syndrome type II. Although
left untreated, only a minimal increase in exudation occurred over 3 years.

Publication Types: 
    Case Reports

PMID: 14652768 [PubMed - indexed for MEDLINE]

2433: Ophthalmology. 2003 Dec;110(12):2403-8.

Morphologic and angiographic assessment of the macula after macular translocation
surgery with 360 degrees retinotomy.

Terasaki H, Ishikawa K, Suzuki T, Nakamura M, Miyake K, Miyake Y.

Department of Ophthalmology, Nagoya University School of Medicine, Nagoya, Japan.
terasaki@med.nagoya-u.ac.jp

PURPOSE: To compare the optical coherence tomographic assessment of retinal
thickness and the fluorescein angiographic appearance after macular translocation
surgery for subfoveal choroidal neovascularization. DESIGN: Retrospective,
noncomparative, interventional case series. PARTICIPANTS: Twenty-three
consecutive eyes. INTERVENTION AND TESTING: Optical coherence tomography and
fluorescein angiography were performed before and 6 to 15 months (mean +/-
standard error [SE], 10.4+/-0.7) after macular translocation surgery with a 360
degrees retinotomy in 23 patients, ages 48 to 79 years, with age-related macular 
degeneration (12 eyes), polypoidal choroidal vasculopathy (2 eyes), and high
myopia (9 eyes). The diameter of the choroidal neovascularizations ranged from
0.3 to 2.6 disc diameters (mean +/- SE, 1.2+/-0.2), and the angle of rotation of 
the retina ranged from 11 degrees to 45 degrees (mean +/- SE, 29.1+/-2.1 degrees 
). RESULTS: The preoperative best-corrected visual acuity ranged from hand
motions to 20/100, and the postoperative best-corrected visual acuity ranged from
20/667 to 20/25. Optical coherence tomography demonstrated a concave foveal
configuration after surgery in all 23 eyes, with a mean foveal thickness of
150+/-11 micro m (mean +/- SE). Fluorescein angiography showed various degrees of
fluorescein leakage with a pattern similar to cystoid macular edema in 16 of 23
eyes (70%). CONCLUSIONS: The newly located macula after macular translocation
surgery with a 360 degrees retinotomy had cystoid macular edema on fluorescein
angiography and normal macular configuration with normal thickness in optical
coherence tomography.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 14644725 [PubMed - indexed for MEDLINE]

2434: Ophthalmology. 2003 Dec;110(12):2386-94.

Quantifying alterations of macular thickness before and after panretinal
photocoagulation in patients with severe diabetic retinopathy and good vision.

Shimura M, Yasuda K, Nakazawa T, Kano T, Ohta S, Tamai M.

Department of Ophthalmology, Tohoku Graduate School of Medicine, Sendai, Japan.
masahiko@oph.med.tohoku.ac.jp

PURPOSE: To investigate the alterations of macular thickness during and after
panretinal photocoagulation (PRP) in patients with severe diabetic retinopathy
and good vision, and to compare the outcomes of weekly and biweekly treatments.
DESIGN: Prospective, comparative interventional case series. PARTICIPANTS:
Thirty-six patients with severe nonproliferative diabetic retinopathy or
non-high-risk proliferative diabetic retinopathy whose visual acuity was 20/20 or
better before PRP. METHODS: Seventy-two eyes of 36 patients underwent scatter PRP
in 4 sessions. The macular thickness was measured by optical coherence
tomography. The photocoagulation sessions were performed weekly to one eye and
biweekly to the other eye. Each eye was selected at random. MAIN OUTCOME
MEASURES: Best-corrected visual acuity and macular thickness. RESULTS: Visual
acuities were maintained in 89% of eyes with weekly treatments and 92% of eyes
with biweekly treatments. Macular thickness was increased transiently in the
central macula in both eyes, more in the weekly treated eyes, and then decreased 
to control levels in eyes treated biweekly but remained thickened in eyes treated
weekly. CONCLUSION: For eyes with severe diabetic retinopathy and good vision,
PRP with either weekly or biweekly treatment did not affect postoperative visual 
acuity. However, biweekly treatments allowed faster recovery of macular
thickening after PRP than weekly treatments.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 14644723 [PubMed - indexed for MEDLINE]

2435: Am J Ophthalmol. 2003 Dec;136(6):1179-81.

Photodynamic therapy with verteporfin for subfoveal choroidal neovascularization 
in best disease.

Andrade RE, Farah ME, Costa RA.

Instituto da Visão-IPEPO, Department of Ophthalmology, Federal University of São 
Paulo, São Paulo, Brazil.

PURPOSE: To describe the effects of photodynamic therapy using verteporfin for
the treatment of subfoveal choroidal neovascularization (CNV) in Best vitelliform
macular dystrophy. DESIGN: Interventional case report. METHODS: A 43-year-old
patient with confirmed Best vitelliform macular dystrophy complicated with
subfoveal CNV received a single photodynamic therapy session with verteporfin.
The patient was prospectively followed with fluorescein angiography and optical
coherence tomography. RESULTS: A regression of the neovascular lesion and
resolution of the exudative manifestations was observed 3 weeks after treatment; 
at that time, visual acuity had improved from 20/60 to 20/25. Optical coherence
tomography disclosed restoration of normal macular architecture due to fluid
resolution and lesion contraction. Up to 2 years from this single treatment, no
further change was observed. CONCLUSIONS: Regression of CNV and resolution of
subretinal hemorrhage as well as exudative manifestations occurred after
photodynamic therapy with verteporfin. Verteporfin therapy may be a viable
treatment for subfoveal neovascular lesions in Best vitelliform macular
dystrophy.

Publication Types: 
    Case Reports

PMID: 14644242 [PubMed - indexed for MEDLINE]

2436: Am J Ophthalmol. 2003 Dec;136(6):1067-78.

Characteristics of visual loss by scanning laser ophthalmoscope microperimetry in
eyes with subfoveal choroidal neovascularization secondary to age-related macular
degeneration.

Fujii GY, De Juan E Jr, Humayun MS, Sunness JS, Chang TS, Rossi JV.

Doheny Retina Institute, Doheny Eye Institute, University of Southern California,
Keck School of Medicine, Los Angeles, California 90033, USA.

PURPOSE: To evaluate the effects of subfoveal choroidal neovascularization
secondary to age-related macular degeneration on functional parameters obtained
by scanning laser ophthalmoscope microperimetry. DESIGN: Retrospective
observational case series and cross-sectional study. METHODS: At the Doheny
Retina Institute and Wilmer Eye Institute a consecutive series of 179 eyes of 175
patients with subfoveal choroidal neovascularization secondary to age-related
macular degeneration was studied. The onset of visual symptoms, best-corrected
visual acuity, fluorescein angiography, evaluation of fundus microperimetry and
fixation pattern using the Rodenstock scanning laser ophthalmoscope were obtained
for each patient. The main outcome measures were central retinal sensitivity and 
fixation pattern (fixation location and fixation stability) in eyes with
subfoveal choroidal neovascularization and their relationship to the length of
disease, type and characteristics of choroidal neovascularization, and visual
acuity. RESULTS: Of 179 eyes, 135 (75%) had central fixation, 27 (15%) had poor
central fixation, and 17 (9%) had predominantly eccentric fixation. Seventy-six
eyes (42%) had stable fixation, 70 eyes (39%) had relatively unstable fixation,
and 33 eyes (18%) had unstable fixation. In 50 eyes (28%) a dense central scotoma
was noted. Eighty-nine of 100 eyes (89%) with length of symptoms of less than 3
months had predominantly central fixation and 58 (58%) had stable fixation; 14 of
34 eyes (41%) with length of symptoms of more than 6 months had predominantly
central fixation, and 5 eyes (15%) had stable fixation. In 15 eyes of patients
who elected not to receive treatment, successive scanning laser ophthalmoscope
microperimetry were obtained over time (follow-up of 18 months after onset of
symptoms). Three months or less after the onset of symptoms, 13 eyes (87.7%) had 
predominantly central fixation and 9 eyes (60%) had stable fixation. More than 3 
months and 6 months or less after the onset of symptoms, 10 eyes (66.7%) had
predominantly central fixation and 7 eyes (46.7%) had stable fixation. This trend
was further demonstrated in eyes more than 6 months after the onset of symptoms. 
CONCLUSIONS: We conclude that the sequence of events leading to visual function
deterioration appears to involve an initial mild decrease in central retinal
sensitivity and visual acuity followed by progressive fixation instability and,
ultimately, development of an absolute central scotoma with totally eccentric
fixation. Increased length of disease is associated with worse fixation pattern
and retinal sensitivity deterioration as assessed by scanning laser
ophthalmoscope microperimetry. A better understanding of the characteristics of
visual loss assessed by fixation pattern evaluation and microperimetry in
age-related macular degeneration may help optimize timing, patient selection, and
treatment options in eyes with this condition.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 14644217 [PubMed - indexed for MEDLINE]

2437: Acta Ophthalmol Scand. 2003 Dec;81(6):648-52.

Intravitreal triamcinolone acetonide for the treatment of chronic pseudophakic
cystoid macular oedema.

Karacorlu M, Ozdemir H, Karacorlu S.

Istanbul Retina Institute, Istanbul, Turkey. retina@pobox.com

PURPOSE: To evaluate the effect of intravitreal triamcinolone acetonide for
chronic pseudophakic cystoid macular oedema (CME) resistant to medical treatment.
METHODS: Six eyes of six patients with chronic pseudophakic CME, aged 58-74 years
(average 66 years), made up the study population. All eyes had persistent CME
despite having received medical treatment for at least 3 months. Intravitreal
injection of 4 mg (0.1 ml) triamcinolone acetonide was offered to treat macular
oedema. The visual and anatomic responses were observed as well as potential
complications related to the injection procedure and corticosteroid medication.
RESULTS: The follow-up period was between 6 and 10 months (mean 8.5 months).
Baseline central macular thickness averaged 504 microm. At 1 month, a reduction
in the mean central macular thickness of 52% from 504 microm to 264 microm was
obtained. At 3 and 6 months, the mean central macular thicknesses were 240 microm
and 232 microm, respectively. Five of the six eyes maintained a visual gain of 15
or more letters from baseline at 6 months. During follow-up no patient had
intraocular pressure (IOP) exceeding 21 mmHg. No injection-related complications 
were encountered. CONCLUSIONS: Intravitreal triamcinolone acetonide is a
promising therapeutic method for chronic pseudophakic CME resistant to medical
treatment. Further study with a longer follow-up period and larger series is
warranted to assess the treatment's longterm efficacy and safety and the need for
retreatment.

PMID: 14641270 [PubMed - indexed for MEDLINE]

2438: Clin Experiment Ophthalmol. 2003 Dec;31(6):522-9.

Comment in:
    Clin Experiment Ophthalmol. 2003 Dec;31(6):461-3.

Measurement of the economic impact of visual impairment from age-related macular 
degeneration in Australia.

Hopley C, Carter R, Mitchell P.

Department of Ophthalmology, University of Sydney, Westmead Hospital, Hawkenbury 
Road, Westmead, Sydney, NSW 2145, Australia. paul_mitchell@wmi.usyd.edu.au

The purpose of this report was to: (i) outline the potential value of health
economic studies into age-related macular degeneration (AMD); (ii) provide an
overview of health economic studies pertinent to AMD; and (iii) outline the basic
frame work of cost-of-illness studies (a useful first step in applying economic
methods). The detection and management of sensory loss in the elderly plays a key
role in the Australian Government's Healthy Ageing Strategy. Age-related macular 
degeneration is currently the leading cause of blindness in elderly Australians. 
Although a large proportion of AMD cases remain untreatable, the introduction of 
photo-dynamic therapy provides a relatively expensive and possibly cost-effective
innovation for others. Antioxidant therapy has also been proven effective in
reducing progression of early to late disease. The discipline of economics can
contribute to an understanding of AMD prevention and treatment through: (i)
describing the current burden of disease; (ii) predicting the changes in the
burden of disease over time, and (iii) evaluating the efficiency of different
interventions. Cost-of-illness studies have been performed in many fields of
medicine. Little work, however, has been done on describing the economic impact
from AMD. A number of different economic evaluation methods can be used in
judging the efficiency of possible interventions to reduce the disease burden of 
AMD. Although complementary in nature, each has specific uses and limitations.
Studies of the economic impact of eye diseases are both feasible and necessary
for informed health care decision-making.

PMID: 14641161 [PubMed - indexed for MEDLINE]

2439: Clin Experiment Ophthalmol. 2003 Dec;31(6):476-81.

Comment in:
    Clin Experiment Ophthalmol. 2003 Dec;31(6):461-3.    Clin Experiment Ophthalmol. 2004 Feb;32(1):119-20.

Photodynamic therapy in practice: a review of the results of the first 12 months 
experience with verteporfin at the Royal Victorian Eye and Ear Hospital.

Essex RW, Qureshi SH, Cain MS, Harper CA, Guymer RH.

Centre for Eye Research Australia, University of Melbourne, East Melbourne,
Victoria 8002, Australia.

PURPOSE: To review the 12-month results of the first 136 eyes treated with
photodynamic therapy (PDT) with verteporfin at a single institution, and to
determine if this treatment when used in the broader community could reproduce
the results achieved in the Treatment of Age-related Macular Degeneration (AMD)
with PDT (TAP) study. METHODS: A record of all patients who first received PDT
with verteporfin at The Royal Victorian Eye and Ear Hospital between the time of 
its introduction in February 2000 and February 2001 was prospectively maintained.
The medical charts of these cases were reviewed and fluorescein angiograms were
graded. Eyes with AMD were classified into three groups: TAP comparable if they
had predominantly classic subfoveal choroidal neovascularization (CNV) and visual
acuity between 6/12 and 6/60; VIP comparable if they had occult but no classic
subfoveal CNV and visual acuity better than 6/36; and PDT ineligible if they fell
outside recommended eligibility guidelines of the TAP/VIP studies. The main
outcome measure was visual acuity change, with total number of treatments a
secondary outcome variable. RESULTS: A total of 136 eyes of 130 patients began
PDT during this period. The baseline angiogram and clinical data were available
for 123 eyes (90%), and these were reviewed. Fourteen eyes had non-AMD related
CNV, while 109 eyes of 105 patients had AMD. Of the 109 AMD related lesions, 72
(66%) were TAP comparable, six (5.5%) were VIP comparable and 31 (28%) were PDT
ineligible. At the 12-month visit the proportion of TAP comparable eyes with same
or better vision was 36/72 (50%), compared to 13/31 (42%) of the PDT ineligible
eyes (P = 0.45). Only 30/72 (42%) of the TAP comparable eyes were still
undergoing regular angiographic and clinical assessment (similar to the TAP
protocol) at the time of the 12 month visit. The number of these who had same or 
better vision at 12 months was 17/30 (57%) compared to 19/42 (44%) TAP comparable
eyes without regular angiographic follow up to 12 months (P = 0.37).
CONCLUSDIONS; When used according to the guidelines established by the TAP study,
the visual acuity results with PDT approached those achieved in the TAP study.
When eyes were either enrolled outside the TAP study eligibility guidelines, or
were not actively followed up over the 12-month period as per TAP study
guidelines, the visual outcome was similar to natural history of CNV secondary to
AMD.

Publication Types: 
    Clinical Trial

PMID: 14641153 [PubMed - indexed for MEDLINE]

2440: Clin Experiment Ophthalmol. 2003 Dec;31(6):465-9.

Comment in:
    Clin Experiment Ophthalmol. 2003 Dec;31(6):461-3.

Iris colour, ethnic origin and progression of age-related macular degeneration.

Nicolas CM, Robman LD, Tikellis G, Dimitrov PN, Dowrick A, Guymer RH, McCarty CA.

Centre for Eye Research Australia, Department of Ophthalmology, University of
Melbourne, Melbourne, Victoria, Australia. cnicolas@unimelb.edu.au

AIM: To investigate the relationship between iris colour, ethnic origin and the
progression of age-related macular degeneration (AMD). METHODS: Participants were
recruited from the population-based Melbourne Visual Impairment Project or the
prospective, randomized, double-masked Vitamin E, Cataract and Age-Related
Macular Degeneration study. From these two cohorts, 171 participants aged between
52 and 93 years who were identified as having early AMD features at their
baseline examination (1992-1995) were followed for an average of 6.8 years (until
2001) to determine the progression rate of early AMD. The participants' iris
colour was categorized as light, intermediate or dark. Ethnic origin was
categorized as Anglo-Saxon or non-Anglo-Saxon, according to the participants'
grandparents' country of birth. RESULTS: In total, 53 (31%) of the 171
participants showed signs of AMD progression. Participants with light iris colour
had twofold the risk of AMD progression of those with dark or intermediate iris
colours, although the age-adjusted and multivariate-adjusted associations were
not significant (both P = 0.13). Age-adjusted and multivariate comparisons of
Anglo-Saxon ethnic origin to non-Anglo-Saxon ethnic origin showed a noticeable
but non-significant association with progression of AMD (P= 0.22 and P= 0.14,
respectively). CONCLUSION: Individuals with light iris colour or of Anglo-Saxon
ethnic origin had a strong tendency to greater progression of AMD. A larger
sample is required to confirm these clinically important, but statistically
non-significant, associations.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 14641151 [PubMed - indexed for MEDLINE]

2441: J Chin Med Assoc. 2003 Sep;66(9):528-32.

The long-term results of one time treatment by continuously fractionated
transpupillary thermotherapy for occult choroid neovascularization membrane of
age-related macular degeneration.

Lin SF, Lin PK, Liu JH.

Department of Ophthalmology, Taipei Veterans General Hospital, Taiwan, ROC.

BACKGROUND: This study was to assess the long-term results of a novel
continuously fractionated transpupillary thermotherapy (cfTTT) in treating occult
choroid neovascularization membrane (CNV) of age-related macular degeneration
(ARMD). METHODS: After informed consent was obtained, 19 patients were treated
with cfTTT in 21 eyes. The diode laser (810 nm) was applied with 6 continuous
9-second sessions to the neovascular membrane. Each session lasted 9 seconds.
Every spot (1 mm on retina) was in close contact with each other to entirely
cover the CNV. RESULTS: The average age was 75.9 years (from 61 to 86 years). The
mean follow-up time was 19.6 months (from 15 to 24 months). Five eyes (23.8%) had
improved visual acuity by 2 or more lines, 6 eyes (28.5%) by 1 line, and 10 eyes 
(47.6%) had no change in visual acuity. None had decreased vision. In final
fluorescein angiography, all eyes treated revealed decreased fluorescein leakage.
CONCLUSIONS: cfTTT shows no deleterious side effects in treating subfoveal or
juxtafoveal CNV of ARMD at long-term follow-up and is at least as effective as
long-pulse TTT.

PMID: 14649676 [PubMed - indexed for MEDLINE]

2442: Ophthalmology. 2003 Dec;110(12):2372-83; discussin 2384-5.

Anecortave acetate as monotherapy for treatment of subfoveal neovascularization
in age-related macular degeneration: twelve-month clinical outcomes.

D'Amico DJ, Goldberg MF, Hudson H, Jerdan JA, Krueger DS, Luna SP, Robertson SM, 
Russell S, Singerman L, Slakter JS, Yannuzzi L, Zilliox P; Anecortave Acetate
Clinical Study Group.

PURPOSE: To evaluate safety and efficacy of the angiostatic agent anecortave
acetate, compared with a placebo, for treatment of subfoveal choroidal
neovascularization (CNV). DESIGN: Ongoing masked, randomized, placebo-controlled,
parallel evaluation of anecortave acetate (30 mg, 15 mg, and 3 mg) versus a
placebo. PARTICIPANTS: There were 128 eyes of 128 patients with subfoveal CNV
secondary to age-related macular degeneration who were enrolled and treated, with
80% (102/128) of eyes presenting with predominantly classic lesions at baseline. 
METHODS: All eyes received a posterior juxtascleral depot application of masked
study medication or a placebo, with retreatment at 6-month intervals if the
masked investigator believed the patient could benefit. Patients received
periodic detailed ophthalmic examinations with both fluorescein and indocyanine
green angiography, general physical examinations with electrocardiograms, and
hematology/serum chemistry/urinalysis. All ophthalmic and systemic safety data
were periodically reviewed by the Independent Safety Committee overseeing the
study. MAIN OUTCOME MEASURES: Best-corrected logarithm of the minimum angle of
resolution (logMAR) vision and fluorescein angiographic lesion characteristics
were compared over time and among treatment groups. RESULTS: At month 12,
anecortave acetate (15 mg) administered at 6-month intervals was statistically
superior to the placebo for 3 measures of clinical efficacy: mean change from
baseline vision (P = 0.0131), stabilization of vision (<3 logMAR line change; P =
0.0323), and prevention of severe vision loss (decrease of > or = 6 logMAR lines 
from baseline; P = 0.0224). Subgroup analysis of predominantly classic lesions
revealed that anecortave acetate (15 mg) was also superior to the placebo at 1
year for each of these 3 measures of visual outcome (Ps = 0.0022, 0.0100, and
0.0299, respectively). Anecortave acetate (15 mg) trended toward significance
over the placebo at month 12 for inhibition of total lesion growth and for
inhibition of both the total CNV component and the classic CNV component in both 
the overall and subgroup analyses. The Independent Safety Committee identified no
clinically relevant treatment-related safety issues. CONCLUSIONS: Anecortave
acetate (15 mg) is safe and clinically efficacious at 1 year for maintaining
vision, preventing severe vision loss, and inhibiting subfoveal CNV lesion
growth.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 14644721 [PubMed - indexed for MEDLINE]

2443: Am J Ophthalmol. 2003 Dec;136(6):1049-61.

Japanese age-related macular degeneration trial: 1-year results of photodynamic
therapy with verteporfin in Japanese patients with subfoveal choroidal
neovascularization secondary to age-related macular degeneration.

Japanese Age-Related Macular Degeneration Tial (JAT) Study Group.

Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

PURPOSE: To determine the effect and safety of verteporfin therapy (Visudyne) in 
Japanese age-related macular degeneration (AMD) patients. DESIGN: Open-label,
multicenter, prospective, noncontrolled study. METHODS: The setting was five
university hospitals in Japan. The study population was patients at least 50
years old, with best-corrected visual acuity of 20/40 to 20/200 inclusive and
fluorescein angiography documenting subfoveal, classic-containing choroidal
neovascularization (CNV) secondary to AMD and a lesion of greatest linear
dimension <or= 5400 microm. For the intervention, patients received verteporfin
intravenously followed by light administration 15 minutes after the infusion
start. Additional treatment was given every 3 months through month 9 if leakage
from CNV was observed on angiogram. The main outcome measure was percentage of
lesions with progression of classic CNV beyond the area of the baseline lesion.
RESULTS: Sixty-four patients were enrolled at five centers, and 61 patients
completed the study. The median number of treatments given during the trial was
three. At the 12-month examination, 12 patients (19%; 95% confidence interval:
11%-31%) had progression of classic CNV whereas 32 (50%) and 49 (77%) patients
had no leakage from classic or occult CNV, respectively. The median visual acuity
score (approximate Snellen equivalent) from baseline to month 12 increased from
50.0 (20/100)-56.5 (20/80(+2)) letters. Fourteen patients (22%) had visual
disturbances, including two patients (3%) with acute vision decrease considered
as serious adverse events and one patient (2%) with infusion-related back pain.
No photosensitivity reactions were reported. CONCLUSIONS: Verteporfin therapy for
subfoveal CNV in these Japanese patients appeared to have a similar or better
angiographic and vision effect as that observed in Caucasian patients, with the
same safety profile, supporting its use in Japanese patients.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 14644215 [PubMed - indexed for MEDLINE]

2444: Jpn J Ophthalmol. 2003 Nov-Dec;47(6):595-8.

Photodynamic therapy with delayed light application for the treatment of
bilateral subfoveal choroidal neovascularization in age-related macular
degeneration.

Karacorlu M, Karacorlu S, Ozdemir H.

The Istanbul Retina Institute, Nisantasi, Istanbul, Turkey.

PURPOSE: To determine if photodynamic therapy (PDT) with delayed light
application at 17 minutes after the start of infusion was effective in the second
eyes of patients with bilateral subfoveal classic choroidal neovascularization
(CNV) secondary to age-related macular degeneration (AMD). METHODS: The records
of 20 patients with bilateral subfoveal classic CNV secondary to AMD who were
treated with bilateral PDT in the same session were reviewed. Treatment for the
second eye of patients was begun 120 seconds after termination of treatment for
the first eye. This time interval was necessary for applying the contact lens and
entering the new laser parameters, and it was kept constant in all cases.
Best-corrected visual acuity (BCVA), ophthalmologic examinations, fluorescein and
indocyanine angiograms were used to evaluate the results of PDT. Follow-up time
ranged from 6 to 12 months with a mean of 8.7 (+/-2.1) months. RESULTS: Mean
(+/-SD) treatment sessions were 1.7 (+/-0.6) in first eyes and 1.7 (+/-0.5) in
second eyes. Among first eyes, BCVA improved in 7 of the 20 eyes (35%);
stabilized in 7 eyes (35%); and worsened in 6 eyes (30%). Among second eyes, BCVA
improved in 5 of the 20 eyes (25%); stabilized in 8 eyes (40%); and worsened in 7
eyes (35%). CONCLUSIONS: In most cases, bilateral PDT in the same session
achieved cessation of fluorescein leakage from CNV without loss of vision or
growth of CNV in the second eyes of patients with bilateral subfoveal classic CNV
secondary to AMD. Further studies with a larger number of patients and longer
follow-up are necessary to confirm whether bilateral PDT in the same session is
beneficial for bilateral subfoveal classic CNV related to AMD.

Publication Types: 
    Clinical Trial

PMID: 14636851 [PubMed - indexed for MEDLINE]

2445: Ophthalmic Surg Lasers Imaging. 2003 Nov-Dec;34(6):478-9.

Macular hole after peeling of the internal limiting membrane in diabetic macular 
edema.

Yoon KC, Seo MS.

Department of Ophthalmology, Chonnam National University Medical School and
Hospital, Chonnam National University Research Institute for Medical Sciences,
Kwangju, Korea.

A 61-year-old man had peeling of the internal limiting membrane using indocyanine
green in combination with pars plana vitrectomy for the treatment of diffuse
diabetic macular edema in the right eye. As the macular edema began to improve, a
small macular hole was noticed, which progressed rapidly. After fluid-gas
exchange with 10% perfluoropropane, the macular hole was closed. Caution may be
needed to reduce the mechanical stress on the fovea when the internal limiting
membrane is peeled in diffuse diabetic macular edema.

Publication Types: 
    Case Reports

PMID: 14620754 [PubMed - indexed for MEDLINE]

2446: Ophthalmic Surg Lasers Imaging. 2003 Nov-Dec;34(6):446-50.

Enlarged diode laser spot using indirect ophthalmoscope delivery in conjunction
with indocyanine green to treat large choroidal neovascularizations.

Reategui-Escalante G, Murillo-Lopez SA, Romero-Castro RM, Suarez-Tata LM,
Guerrero-Naranjo JL, Quiroz-Mercado H.

Hospital Dr. Luis Sánchez Bulnes de la Asociación Para Evitar la Ceguera en
México, San Lucas Coyoacan, Mexico.

BACKGROUND AND OBJECTIVE: To evaluate the effectiveness of a new method of
delivering diode laser (810 nm) spots through an indirect ophthalmoscope in
conjunction with intravenous indocyanine green to treat choroidal
neovascularizations (CNVs) larger than 5,400 microm. PATIENTS AND METHODS: A
prospective, non-comparative, interventional case series study was conducted with
8 patients with CNV secondary to age-related macular degeneration. Laser pulses
were applied to the CNV within 5 minutes of an intravenous injection of 25 mg of 
indocyanine green. The laser spot was enlarged up to one disc diameter by
shortening the distance between the indirect ophthalmoscope and the 20-diopter
viewing lens. The follow-up period was 3 months. RESULTS: Three eyes had an
improvement in visual acuity of more than 2 lines, and fluorescein angiography
showed stabilization of the membrane and reduction of the hemorrhages and
subretinal fluid at the last follow-up. Three other eyes maintained the same
visual acuity and two had a decrease in visual acuity of more than 2 lines at the
3-month follow-up examination. CONCLUSION: Laser treatment delivered through an
indirect ophthalmoscope system may be used as a palliative treatment for CNVs
larger than 5,400 microm.

Publication Types: 
    Clinical Trial

PMID: 14620746 [PubMed - indexed for MEDLINE]

2447: Eur J Ophthalmol. 2003 Oct;13(8):687-92.

Short-term reaction of choroidal neovascularization and choriocapillaris to
photodynamic therapy in age-related macular degeneration.

Eter N, Vogel A, Inhetvin-Hutter C, Spitznas M.

Department of Ophthalmology, University of Bonn Medical Center, Bonn, Germany.
eter@uni-bonn.de

PURPOSE: To identify the number of primary angiographic nonresponders to
photodynamic therapy (PDT) with verteporfin, to determine the rate and speed of
reperfusion of choroidal neovascularization (CNV) within a short observation
period of only 5 weeks, and to examine the reaction of the underlying choroidal
vessels. METHODS: PDT according to the TAP regimen was carried out in 36 eyes
with subfoveal classic CNV secondary to age-related macular degeneration. The
response to PDT was examined 1 (T1) and 5 (T2) weeks following treatment. At all 
visits distant visual acuity was measured and both fluorescein and indocyanine
green angiography was carried out. RESULTS: One week after treatment (T1),
complete closure of classic CNV had not been achieved in 17% of eyes (primary
angiographic nonresponders). At T2, 91% of eyes showed reperfusion of the CNV. In
83% of the primary angiographic nonresponders the CNV size was larger than before
treatment. Choroidal shadowing was present in 82% at T1 and in 48% at T2.
CONCLUSIONS: Primary angiographic PDT nonresponders are relatively rare; however,
in contrast to former reports, they exist and can be identified by follow-up
examination 1 week after PDT. Recurrence of leakage occurred earlier than
expected and may require closer follow-up and earlier retreatment than
recommended by the TAP trial.

PMID: 14620172 [PubMed - indexed for MEDLINE]

2448: Can J Ophthalmol. 2003 Oct;38(6):489-95.

Argon laser vs. subthreshold infrared (810-nm) diode laser macular grid
photocoagulation in nonexudative age-related macular degeneration.

Scorolli L, Corazza D, Morara M, Vismara S, Lugaresi ML, Meduri RA.

Department of Pathophysiological Optics, University of Bologna,
Sant'Orsola-Malpighi Hospital, Bologna, Italy. luciascorolli@yahoo.it

BACKGROUND: A diode laser can be used to create a subthreshold (invisible end
point) lesion in patients with age-related macular degeneration (AMD). This has
the potential benefit of localizing the treatment effect to the retinal pigment
epithelium and sparing more of the overlying sensory retina. We performed a study
to compare the safety and efficacy of argon laser and subthreshold infrared
(810-nm) diode laser macular grid photocoagulation in reducing the number of
drusen in patients with AMD. METHODS: We reviewed the charts of 144 patients with
bilateral early-stage nonexudative AMD, characterized by soft drusen. One eye of 
each patient was treated, and the other eye served as a control. Seventy-eight
eyes of 78 patients with a mean age of 67.5 (standard deviation [SD] 8.3) years
underwent argon laser macular grid photocoagulation at a university-affiliated
hospital in Bologna, Italy, and 66 eyes of 66 patients with a mean age of 66.4
(SD 6.3) years underwent subthreshold infrared (810-nm) diode laser macular grid 
photocoagulation at a private clinic in Bologna. Each group was classified into
three subgroups based on the number of drusen (more than 20, 10 to 20, or less
than 10). The patients underwent fluorescein angiography, fundus examination,
measurement of far (Snellen chart) and near (Jaeger chart) best corrected visual 
acuity, and visual field and contrast sensitivity testing. The mean length of
follow-up was 18 (SD 0.5) months. RESULTS: At 18 months, far and near best
corrected visual acuity were statistically significantly improved in the
treatment groups compared with the untreated group (p < 0.001, Mann-Whitney U
test). There was no significant difference in visual acuity between the treatment
groups. Compared with baseline, the number of drusen was significantly reduced in
both treatment groups (p < 0.001). Evolution of the disease was observed in the
untreated group. The visual field was slightly but significantly reduced after
argon laser treatment (p < 0.001) but not diode laser treatment; the difference
in visual field between the two groups was not significant. There was a slight
reduction in contrast sensitivity, particularly with night vision, after argon
laser treatment but not diode laser treatment. The difference between the two
treatment groups was significant (p < 0.01). INTERPRETATION: Subthreshold
infrared diode macular grid photocoagulation may be a safe and viable method for 
preventing progression of nonexudative AMD.

Publication Types: 
    Comparative Study

PMID: 14620037 [PubMed - indexed for MEDLINE]

2449: Bull Soc Belge Ophtalmol. 2003;(289):53-61.

Optical coherence tomography of adult-onset vitelliform dystrophy.

Hayami M, Decock C, Brabant P, Van Kerckhoven W, Lafaut BA, De Laey JJ.

Department of Ophthalmology, Ghent University Hospital.

PURPOSE: To report the cross-sectional structure of the retina and choroid in
eyes with adult-onset vitelliform macular dystrophy as obtained by optical
coherence tomography (OCT). METHODS: Seven patients with adult-onset vitelliform 
macular dystrophy and one patient with Best disease were examined by fundoscopy, 
fluorescein and indocyanine green angiography and OCT. Three patients underwent
also electro-oculography. RESULTS: 1. Seven cases with adult-onset vitelliform
macular dystrophy showed a well-circumscribed elevation of a highly reflective
band, corresponding to the retinal pigment epithelium 2. In these 7 patients, the
space below this band was inhomogeneous and moderately reflective. 3. Four cases 
out of 7 had a well defined posterior boundary. 4. The patient with Best disease 
disclosed a different aspect on OCT, although the contour of the lesion was
similar to the others. CONCLUSION: Optical coherence tomography disclosed the
structure of the vitelliform lesion in vivo and could be helpful for its
pathological interpretation.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 14619630 [PubMed - indexed for MEDLINE]

2450: Graefes Arch Clin Exp Ophthalmol. 2003 Dec;241(12):1006-12. Epub 2003 Nov
14.

Macular pigment: quantitative analysis on autofluorescence images.

Trieschmann M, Spital G, Lommatzsch A, van Kuijk E, Fitzke F, Bird AC,
Pauleikhoff D.

Department of Ophthalmology, St. Franziskus Hospital, Hohenzollernring 74, 48145 
Münster, Germany.

BACKGROUND: Macular pigment (MP) reduces oxidative damage in the central retina
and can be quantified by flicker-photometric analysis (HFP) of MP optical
density. These analyses demonstrate a very good correlation with central
absorption by MP on autofluorescence (AF) images. With these techniques different
types of MP-distribution have been described. In the present study a
quantification analysis of MP in AF images was developed to verify these MP types
and to compare MP distribution patterns between healthy individuals and those
with age-related macular degeneration (AMD). METHODS: AF images (HRA) were
analysed with respect to the area of central and paracentral absorption in 400
eyes with a computerised analysis program of MP optical density. The patients
were between 41 and 90 years old (mean 67.2 years); 168 were male and 232 female,
and 253 had early AMD and 147 showed no AMD characteristics. The central MP
concentrations (peak) were measured, the amount of MP values within the first
8-pixel radius ("C"), the total amount of MP within a 120-pixel radius ("T") were
calculated as the volume of the MP values over the regarded radius and the C/T
ratio was registered. RESULTS: Four types of MP distribution (type 1, intense
central and paracentral MP; type 2, less intense central and paracentral MP; type
3, only central MP; type 4, only paracentral MP) were identified. The differences
in MP distribution were confirmed and clearly characterised by quantitative
analyses of peak, total MP ("T"), central MP ("C") and C/T ratio: mean peak in
type 1, 0.65; type 2, 0.42; type 3, 0.42; type 4, 0.29; mean total amount of MP
in 120-pixel radius ("T") in type 1, 5829.0; type 2, 4412.5; type 3, 2709; type
4, 4302.8. MP types with lower levels of MP were significantly more often
observed in the AMD group (AMD: type 1, 120=47.4%; types 2-4, 133=52.6%; healthy 
eyes: type 1, 112=76.2%; types 2-4, 35=23.8%) ( P<0.0001) CONCLUSIONS: Analysis
of MP on AF images is a quantitative method for investigation of MP. With this
method a wide variation in concentration and distribution of MP could be seen in 
the population. Four different types of MP distribution could be characterised
and quantitatively distinguished. Reduced levels of MP seem to be associated with
a higher risk of development of AMD as they were significantly more often
observed in the AMD group. This strategy of quantitative MP analysis on AF images
is easily practicable and may be used in further studies to investigate the role 
of MP as a potential risk factor for AMD.

PMID: 14618343 [PubMed - indexed for MEDLINE]

2451: Vision Res. 2003 Dec;43(28):3095-108.

Inherited multifocal RPE-diseases: mechanisms for local dysfunction in global
retinoid cycle gene defects.

Besch D, Jägle H, Scholl HP, Seeliger MW, Zrenner E.

University Eye Hospital, Schleichstr. 12-16, D-72076 Tübingen, Germany.
dorothea.besch@med.uni-tuebingen.de

Alterations of retinoid cycle genes are known to cause retinal diseases
characterized by focal white dot fundus lesions. Fundus appearances reveal
circumscribed RPE-changes, although generalized metabolic defects and global
functional abnormalities are present. As a possible explanation, topographic
inhomogeneities of the human photoreceptor mosaic and the role of a cone specific
visual cycle will be discussed. Due to particular characteristics of
photoreceptor subtypes as well as different pathways for photopigment
regeneration the metabolic demand of individual RPE cells might differ. In
"flecked retina diseases" heterogeneity of metabolic demand in individual RPE
cells could therefore be responsible for their multifocal appearance.

Publication Types: 
    Review

PMID: 14611947 [PubMed - indexed for MEDLINE]

2452: Vision Res. 2003 Dec;43(28):2983-90.

A2E, a byproduct of the visual cycle.

Sparrow JR, Fishkin N, Zhou J, Cai B, Jang YP, Krane S, Itagaki Y, Nakanishi K.

Department of Ophthalmology, Columbia University, 630 W. 168th Street, New York, 
NY 10032, USA. jrs88@columbia.edu

A substantial portion of the lipofuscin that accumulates with age and in some
retinal disorders in retinal pigment epithelial (RPE) cells, forms as a
consequence of light-related vitamin A recycling. Major constituents of RPE
lipofuscin are the di-retinal conjugate A2E and its photoisomers. That the
accretion of A2E has consequences for the cell, with the adverse effects of A2E
being attributable to its amphiphilic structure and its photoreactivity, is
consistent with evidence of an association between atrophic age-related macular
degeneration (AMD) and excessive lipofuscin accumulation.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.
    Review

PMID: 14611934 [PubMed - indexed for MEDLINE]

2453: Arch Ophthalmol. 2003 Nov;121(11):1621-4.

Comment in:
    Arch Ophthalmol. 2003 Nov;121(11):1634-6.

Potential public health impact of Age-Related Eye Disease Study results: AREDS
report no. 11.

Bressler NM, Bressler SB, Congdon NG, Ferris FL 3rd, Friedman DS, Klein R,
Lindblad AS, Milton RC, Seddon JM; Age-Related Eye Disease Study Research Group.

OBJECTIVE: To estimate the potential public health impact of the findings of the 
Age-Related Eye Disease Study (AREDS) on reducing the number of persons
developing advanced age-related macular degeneration (AMD) during the next 5
years in the United States. METHODS: The AREDS clinical trial provides estimates 
of AMD progression rates and of reduction in risk of developing advanced AMD when
a high-dose nutritional supplement of antioxidants and zinc is used. These
results are applied to estimates of the US population at risk, to estimate the
number of people who would potentially avoid advanced AMD during 5 years if those
at risk were to take a supplement such as that used in AREDS. RESULTS: An
estimated 8 million persons at least 55 years old in the United States have
monocular or binocular intermediate AMD or monocular advanced AMD. They are
considered to be at high risk for advanced AMD and are those for whom the AREDS
formulation should be considered. Of these people, 1.3 million would develop
advanced AMD if no treatment were given to reduce their risk. If all of these
people at risk received supplements such as those used in AREDS, more than
300,000 (95% confidence interval, 158,000-487,000) of them would avoid advanced
AMD and any associated vision loss during the next 5 years. CONCLUSION: If people
at high risk for advanced AMD received supplements such as those suggested by
AREDS results, the potential impact on public health in the United States would
be considerable during the next 5 years.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 14609922 [PubMed - indexed for MEDLINE]

2454: Arch Ophthalmol. 2003 Nov;121(11):1613-20.

Autosomal dominant macular degeneration associated with 208delG mutation in the
FSCN2 gene.

Wada Y, Abe T, Itabashi T, Sato H, Kawamura M, Tamai M.

Department of Ophthalmology, Tohoku University School of Medicine, Sendai, Japan.
YUKOW@oph.med.tohoku.ac.jp

OBJECTIVE: To assess the clinical and genetic characteristics of 2 Japanese
families with autosomal dominant macular degeneration (ADMD) associated with a
208delG mutation in the retinal fascin (FSCN2) gene. DESIGN: Case reports with
clinical findings and results of fluorescein angiography, electroretinography,
kinetic visual field testing, and DNA analysis. SETTING: University medical
center. RESULTS: The 208delG mutation in the FSCN2 gene was identified in 14
members of 4 Japanese families with autosomal dominant retinitis pigmentosa and
in 5 members of 2 Japanese families with ADMD. The characteristic features
associated with this mutation led to 2 different phenotypes, autosomal dominant
retinitis pigmentosa and ADMD. CONCLUSIONS: The 208delG mutation in the FSCN2
gene produces not only autosomal dominant retinitis pigmentosa but also ADMD in
the Japanese population. This mutation is relatively common in Japanese patients 
with autosomal dominant retinal degeneration and showed clinical variability.
CLINICAL RELEVANCE: Autosomal dominant retinitis pigmentosa and ADMD can be
caused by the same 208delG mutation. We suggest that mutations in the FSCN2 gene 
can lead to a spectrum of phenotypes.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 14609921 [PubMed - indexed for MEDLINE]

2455: Arch Ophthalmol. 2003 Nov;121(11):1557-61.

Cone dysfunction in patients with late-onset cone dystrophy and age-related
macular degeneration.

Ladewig M, Kraus H, Foerster MH, Kellner U.

Department of Ophthalmology, Universitäts-Klinikum Benjamin Franklin, Freie
Universität Berlin, Berlin, Germany.

OBJECTIVES: To determine the clinical and functional findings in patients with
late-onset cone dystrophy (LOCD) (after the age of 50 years), which is rare; and 
to compare them with those of patients with age-related macular degeneration
(AMD). METHODS: Eleven LOCD patients underwent ophthalmologic and
electroretinographic examinations. Full-field electroretinograms were recorded
according to the International Society for Clinical Electrophysiology of Vision
standard. The results were compared with those of a group of 20 AMD patients and 
a group of 23 age-related control subjects. RESULTS: There was no difference
between LOCD and AMD patients regarding the severity of visual acuity loss, color
vision deficiencies, and central visual field defects. Alterations of the
posterior pole were present in all LOCD and AMD patients. In contrast to the AMD 
group, all LOCD patients did not show drusen and 6 of the 11 LOCD patients
displayed temporal optic disc pallor. The electroretinogram revealed the major
functional difference, with severe reduction of cone-mediated responses and
moderate reduction of rod-mediated responses in LOCD patients. Unexpectedly, the 
30-Hz flicker amplitude was reduced in AMD patients compared with healthy
controls. CONCLUSIONS: Late-onset cone dystrophy and AMD have several features in
common. In elderly patients with progressive visual loss and without drusen, LOCD
should be considered. The electroretinographic results in a small group of AMD
patients indicate a generalized cone dysfunction.

Publication Types: 
    Comparative Study

PMID: 14609911 [PubMed - indexed for MEDLINE]

2456: Br J Ophthalmol. 2003 Nov;87(11):1329-32.

The effect of arteriovenous sheathotomy on cystoid macular oedema secondary to
branch retinal vein occlusion.

Cahill MT, Kaiser PK, Sears JE, Fekrat S.

Duke University Eye Center, Erwin Road, PO Box 3802, Durham, NC 27710, USA.

BACKGROUND: Arteriovenous (AV) sheathotomy, a potential treatment for branch
retinal vein occlusion (BVO), surgically separates retinal vessels at an AV
crossing. Relief of the aetiological obstruction, with resolution of cystoid
macular oedema (CMO), may result in improved visual acuity. METHODS: A
retrospective review of consecutive cases of AV sheathotomy for BVO was
undertaken. Eyes were categorised as having resolution (group 1), reduction
(group 2), or persistence (group 3) of CMO. Intergroup comparisons were made with
regard to preoperative, intraoperative, and postoperative parameters.
Preoperative and postoperative visual acuities were compared within each group.
RESULTS: Of the 27 eyes identified, eight (29.6%) had resolution, 14 (51.8%) had 
reduction, and five (18.6%) had persistence of CMO. Median preoperative visual
acuity was similar in all groups (1.0, 1.0, 1.3, respectively; p = 0.29). Overall
median follow up was 12.0 months (Q1 = 12.0, Q2 = 22.5). Eyes in group 1 had
significantly better median postoperative visual acuity than eyes in groups 2 and
3 (0.6, 1.0, 2.0 respectively; p = 0.01). A significantly higher proportion of
eyes in group 1 had visual acuity improvement compared with eyes in the other
groups (87.5% v 35.7% and 20.0%; p = 0.03). Median postoperative visual acuity
was significantly better than median preoperative visual acuity in group 1 eyes
only (p = 0.02). A higher percentage of group 1 eyes had evidence of
postoperative retinal perfusion (83.0% v 21.43% and 40.0%; p = 0.16).
Postoperative retinal detachment occurred in three eyes (11.1%). CONCLUSION:
Complete resolution of CMO after AV sheathotomy occurred in one third of
patients, and postoperative vision improved significantly in this group. However,
in the majority of cases, despite an improvement in CMO, there was no improvement
in vision after AV sheathotomy.

Publication Types: 
    Comparative Study

PMID: 14609825 [PubMed - indexed for MEDLINE]

2457: Graefes Arch Clin Exp Ophthalmol. 2003 Oct;241(10):797-802. Epub 2003 Aug
29.

Follow-up of age-related macular degeneration patients treated by photodynamic
therapy with optical coherence tomography 3.

Montero JA, Ruiz-Moreno JM, Tavolato M.

Vitreo-Retinal Unit, Instituto Oftalmológico de Alicante, Avenida de Denia 111,
03015 Alicante, Spain.

BACKGROUND: Photodynamic therapy (PDT) has been described to effectively reduce
or delay severe vision loss in eyes with predominantly classic form of choroidal 
neovascularization (CNV) due to age-related macular degeneration (AMD). Optical
coherence tomography 3 (OCT3) is a non-invasive diagnostic procedure which
provides information about retinal thickness and volume at the posterior pole, as
well as about the presence of certain structures under the retina. METHODS:
Prospective interventional study. Eleven eyes (9 patients) with AMD and CNV were 
treated with Verteporfin PDT. A complete ophthalmologic examination was
performed. Fluorescein angiography (FA) and OCT3 scans were performed before
treatment and 1, 2, 4, and 12 weeks after it. RESULTS: Two different patterns of 
changes were observed. One group (7 eyes) showed changes in the amount of
subretinal fluid (decrease, increase, and finally stable decrease), with a
reduction in the CNV and the appearance of a subretinal band of hyperreflective
tissue. The second group (4 eyes) showed little or no changes in retinal
thickness, fluid, or reflectivity. CONCLUSION: Changes observed in OCT3 scans
represent variations in retinal thickness, fluid, and CNV after PDT. OCT3
provides a useful tool in the follow-up and measurement of changes appeared in
eyes with CNV associated to AMD after treatment with PDT.

Publication Types: 
    Case Reports

PMID: 14605900 [PubMed - indexed for MEDLINE]

2458: Nutr Rev. 2003 Oct;61(10):342-6.

Lipofuscin and macular degeneration.

Wolf G.

Department of Nutritional Sciences and Toxicology, University of California,
Berkeley, CA 94720-3104, USA.

The accumulation of the autofluorescent pigment lipofuscin in the retina that
occurs with aging has been explained as a side effect of the visual cycle. It
occurs when two molecules of all-trans-retinal condense with one molecule of
phosphatidylethanolamine in the discs of the rod outer segments, and is followed 
by uptake into retinal pigment epithelium (RPE) and conversion to the stable A2E,
a pyridinium bisretinoid that is toxic to RPE cells. The accumulation of A2E, the
major component of lipofuscin causes RPE cell apoptosis, thereby explaining
age-related macular degeneration and macular degeneration characteristic of
Stargardt disease. The drug isotretinoin (13-cis-retinoic acid) prevents
accumulation of A2E in mice by slowing down the visual cycle and might therefore 
be used to prevent macular degeneration.

Publication Types: 
    Review

PMID: 14604266 [PubMed - indexed for MEDLINE]

2459: Indian J Ophthalmol. 2003 Sep;51(3):243-50.

Comment in:
    Indian J Ophthalmol. 2004 Mar;52(1):84-5; author reply 85.

Transpupillary thermotherapy for treatment of choroidal neovascularization
secondary to age-related macular degeneration in Indian eyes.

Nagpal M, Nagpal K, Sharma S, Puri J, Nagpal PN.

Retina Foundation, Ahmedabad, Gujarat, India. manishad1@sancharnet.in

AIM: To evaluate the efficacy of transpupillary thermotherapy (TTT) for treatment
of subfoveal choroidal neovascularisation (CNV) secondary to age-related macular 
degeneration (AMD), and to define accurate power settings for this procedure in
Indian eyes. METHODS: A prospective, nonrandomised study of 160 eyes of 144
patients with subfoveal CNV. The laser settings included 2 mm spot and 300 mw
power or 3 mm spot and 400-600 mw power. Two separate 3 mm spots were used in
larger lesions. The treatment was given for 60 seconds at each point. RESULTS:
Ninety-nine eyes had classic membranes and 61 eyes had occult membranes.
Following treatment, 79 of 99 (79.8%) classic and 52 of 61 (85%) occult membranes
regressed. Visual improvement (> or = 2 lines) was seen in 29 (29.3%) eyes and 12
(19.6%) eyes; visual stabilisation (1 line) in 39 (39.4%) eyes, and 35 (57.4%)
eyes; and reduction of vision (< or = 2 lines) in 31 (31.3%) eyes and 14 (22.9%) 
eyes with classic and occult membranes respectively. Mean follow-up was 12
months. One patient suffered inadvertant foveal burn. CONCLUSION: TTT is
effective in the management of subfoveal membranes in Indian eyes. They respond
to lower energy levels compared to the Caucasian eyes.

Publication Types: 
    Clinical Trial
    Comparative Study

PMID: 14601850 [PubMed - indexed for MEDLINE]

2460: Am J Ophthalmol. 2003 Nov;136(5):911-4.

Haptoglobin phenotype in age-related macular degeneration patients.

Seider N, Beiran I, Miller-Lotan R, Dori D, Karp J, Miller B, Levy AP.

Alberto Moscona Department of Ophthalmology, Rambam Medical Center, Haifa,
Israel, Israel.

PURPOSE: To investigate a possible role of the haptoglobin phenotype in the
development of exudative age-related macular degeneration (AMD) in human
subjects. DESIGN: Prospective, observational, comparative population study.
METHODS: The study was carried out in an institutional setting. All patients
referred because of exudative AMD in one eye during an 18-month period were
included in the study group. A group of patients treated for other ocular
diseases and not having AMD in either eye served as control. Haptoglobin
phenotype was determined from a blood sample drawn from each patient in both the 
study and control groups. The main outcome measure was the distribution of the
haptoglobin phenotype in the study and control group. RESULTS: One hundred
eighty-five participants were included in the study. Ninety-eight had exudative
AMD, and 87 were AMD-free. The difference between the study and control groups in
distribution of the haptoglobin phenotype was found to be statistically
insignificant. CONCLUSIONS: Our results suggest that the haptoglobin phenotype
has no effect on the prevalence of exudative AMD.

Publication Types: 
    Comparative Study

PMID: 14597045 [PubMed - indexed for MEDLINE]

2461: J Lipid Res. 2004 Feb;45(2):263-71. Epub 2003 Nov 1.

Regulated expression of apolipoprotein E by human retinal pigment epithelial
cells.

Ishida BY, Bailey KR, Duncan KG, Chalkley RJ, Burlingame AL, Kane JP, Schwartz
DM.

Cardiovascular Research Institute, University of California, San Francisco, CA,
USA.

In early age-related macular degeneration (AMD), lipid-containing deposits
(drusen) accumulate in Bruch's membrane underlying the retinal pigment epithelium
(RPE). Recent studies indicate that apolipoprotein E (apoE) may play a role in
lipid trafficking in AMD. Compared with the apoE3 allele, the apoE4 and apoE2
alleles are associated with decreased and increased risk for AMD, respectively;
drusen contain high levels of apoE, and apoE null mice develop lipid deposits in 
Bruch's membrane similar to those observed in AMD. Primary cultures of human RPE 
cells expressing the apoE3 allele were grown on Transwell culture plates. Western
blotting, ELISA assay, and mass spectrometry confirmed that apoE3 was secreted
into the apical and basal chambers and that secretion was upregulated by thyroid 
hormone, 9-cis-retinoic acid, and 22(R)-hydroxycholesterol. In addition, basally 
secreted apoE associated with exogenously added HDL. These results indicate that 
apoE secretion can be regulated by specific hormones and that apoE associates
with HDL. The findings are consistent with a role for apoE in lipid trafficking
through Bruch's membrane and may be relevant to AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, Non-P.H.S.
    Research Support, U.S. Gov't, P.H.S.

PMID: 14594998 [PubMed - indexed for MEDLINE]

2462: Mol Neurobiol. 2003 Oct;28(2):177-94.

Age-related macular degeneration and retinal pigment epithelium wound healing.

Sugino IK, Wang H, Zarbin MA.

Institute of Ophthalmology and Visual Science, University of Medicine and
Dentistry of New Jersey, New Jersey Medical School, 90 Bergen Street, Box 1709,
Newark, NJ 07101-1709, USA.

Choroidal new vessel (CNV) excision may improve vision in patients with
age-related macular degeneration (AMD) by eliminating the source of subretinal
bleeding and scarring. Visual recovery after CNV excision is usually poor in AMD 
patients, probably because of removal of the associated retinal pigment
epithelium (RPE), coupled with the inability of native RPE at the edge of the
dissection bed to resurface the iatrogenic RPE defect. Experiments using in vitro
and in vivo RPE wound-healing models have provided insight into the factors that 
regulate RPE wound healing in situ.Wound-healing studies using aged submacular
human Bruch's membrane in organ culture show that resurfacing of localized RPE
defects is influenced by the depth of damage to Bruch's membrane as well as
factors that are intrinsic to the aged RPE at the wound edge. The Bruch's
membrane organ-culture paradigm provides a surface for RPE wound healing that
closely resembles the surface on which RPE must grow after CNV excision in AMD
patients. An understanding of the factors that influence RPE wound healing might 
lead to treatments that stimulate RPE resurfacing and improve visual outcome
after CNV excision.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.
    Review

PMID: 14576455 [PubMed - indexed for MEDLINE]

2463: Ophthalmologica. 2003 Nov-Dec;217(6):408-12.

Incidence of cystoid macular edema after uncomplicated phacoemulsification.

Mentes J, Erakgun T, Afrashi F, Kerci G.

Department of Ophthalmology, Ege University School of Medicine, Izmir, Turkey.

We determined the incidence and causes of clinical and angiographic cystoid
macular edema (CME) after uncomplicated phacoemulsification and intraocular lens 
implantation in otherwise normal eyes. This study comprised 252 eyes of 252
patients who had uncomplicated phacoemulsification with continuous curvilinear
capsulorhexis and in-the-bag acrylic intraocular lens implantation. The presence 
of clinical and angiographic CME was evaluated 45 days after surgery, using
fundus fluorescein angiography. Age, sex, cataract type, iris color, and real
phacoemulsification time of the patients were also recorded. The mean age of the 
patients was 69.86 (range 60-82) years). Clinical CME was not detected in any eye
at any postoperative visit. There were 23 cases with angiographic CME (9.1%).
There were no significant differences between the groups who were later found to 
be angiographically CME-positive or CME-negative in any variable recorded (p
>0.05). The incidences of clinical and angiographic CME after uncomplicated
phacoemulsification were 0 and 9.1%, respectively. These results indicate that
the occurrence of clinical CME has greatly reduced after uncomplicated
phacoemulsification operations, but the incidence of angiographic CME is still
nearly equal to the incidence of the extracapsular technique. Copyright 2003 S.
Karger AG, Basel

Publication Types: 
    Comparative Study

PMID: 14573973 [PubMed - indexed for MEDLINE]

2464: Ophthalmologica. 2003 Nov-Dec;217(6):401-7.

Is membrane extraction in cases of exudative age-related macular degeneration
still up-to-date? A 4-year résumé.

Schmidt JC, Rodrigues EB, Meyer CH, Kroll P.

Zentrum für Augenheilkunde, Philipps-Universität Marburg, Marburg, Deutschland.

BACKGROUND: Age-related macular degeneration (AMD) is a frequent cause of an
irreversible loss of the ability to read. The non-exudative form of AMD has not
been therapeutically approached in the past in contrast to the exudative form
with choroidal neovascularizations (CNVs). Parafoveal laser coagulation can be
applied, and in cases of subfoveal location a pars plana vitrectomy with
subretinal resection of the CNV is possible. MATERIAL AND METHODS: Since 1995, we
have operated 46 eyes of 45 patients with CNV developing from AMD. Patient ages
ranged from 63 to 85 years (mean 71.8 years). Pre- and postoperatively we
performed vision tests, fluorescence angiographies with sodium fluorescein and
indocyanine green. Follow-up times ranged from 3 to 28 months (mean 12.3 months).
RESULTS: Pre-operative vision was 0.10 (range: hand movements to 0.4).
Postoperative vision at the end of the follow-up period was 0.12 (range: hand
movements to 0.4). Vision at the end of the follow-up was lower in 41%, unchanged
in 20% and improved in 39%. In 43 eyes, a non-exudative form of AMD developed.
Two eyes had a recurrent CNV, which was removed successfully with a second pars
plana vitrectomy. Three patients developed a retinal detachment, which was
successfully treated by pars plana vitrectomy, encircling buckle and gas
tamponade. CONCLUSIONS: We still have to wait for the results of the photodynamic
study trials and a randomized study of macular dislocation. Subretinal removal of
the CNV by pars plana vitrectomy allows a stabilization of the visual function in
most of our cases of AMD. This method inhibits the development of large
pseudotumour-like scars. Postoperatively remaining pigment epithelial defects
with choroidal atrophies however limit a visual rehabilitation so that reading
vision can only be achieved in cases with good pre-operative vision. Long-term
results of photodynamic therapy are still lacking and have to show its
effectiveness over greater time spans. Copyright 2003 S. Karger AG, Basel

PMID: 14573972 [PubMed - indexed for MEDLINE]

2465: Hum Mol Genet. 2003 Dec 15;12(24):3315-23. Epub 2003 Oct 21.

Analysis of the ARMD1 locus: evidence that a mutation in HEMICENTIN-1 is
associated with age-related macular degeneration in a large family.

Schultz DW, Klein ML, Humpert AJ, Luzier CW, Persun V, Schain M, Mahan A, Runckel
C, Cassera M, Vittal V, Doyle TM, Martin TM, Weleber RG, Francis PJ, Acott TS.

Macular Degeneration Center, Casey Eye Institute, Portland, OR 97239-4197, USA.
schultzd@ohsu.edu

Age-related macular degeneration (AMD) is a common cause of severe vision loss.
Identification of the genes involved in AMD will lead to a better understanding
of this disease at the molecular level, which will eventually lead to early
detection, prevention and treatment. Previously, we mapped the ARMD1 gene to
1q25-31 in a large family with AMD. Here, we narrow the ARMD1 locus to 14.9 Mb
between LAMB2 and D1S3469, a region containing 50 known genes. Twenty candidate
genes within this region were screened for mutations. Only one DNA variation, an 
A16,263G transition in exon 104 of HEMICENTIN-1, was found to segregate
exclusively with the disease haplotype in members of this large family with AMD. 
This variation produces a non-conservative substitution of arginine for glutamine
at amino acid position 5345 (Gln5345Arg). It was also identified in 11 other
individuals, all of whom share a haplotype, which envelops HEMICENTIN-1, with the
large AMD family. The affected status of all but one of those individuals
conforms to the age-dependent penetrance observed in AMD. The amino acid at
position 5345 of HEMICENTIN-1 was conserved as glutamine in eight species
analyzed. RT-PCR analysis demonstrated that exon 104 of HEMICENTIN-1 is
alternatively spliced in various cell types. Exclusive segregation of Gln5345Arg 
with the disease haplotype in this large family, amino acid conservation of
glutamine at this position among mammals, the non-conservative nature of the
substitution and similarities to EFEMP1 support the conclusion that HEMICENTIN-1 
is the ARMD1 gene.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 14570714 [PubMed - indexed for MEDLINE]

2466: Ophthalmic Epidemiol. 2003 Dec;10(5):315-22.

Twin study of age-related macular degeneration.

Grizzard SW, Arnett D, Haag SL.

Retina Associates of Florida, Tampa, Florida 33609-4614, USA.

PURPOSE: To evaluate the genetic contribution in age-related macular degeneration
(ARMD) by a disease-ascertained twin study. METHODS: Concordance rates for ARMD
in 25 twins were obtained by using four masked graders to confirm the diagnosis
of ARMD and place subjects in one of three categories; concordant, intermediate, 
or discordant. Demographic features and known risk factors for ARMD were compared
between monozygotic and dizygotic twin pairs. RESULTS: Of the 25 twin pairs, 15
were monzygotic and 10 were dizygotic. All 15 monozygotic twins were concordant
or intermediate for ARMD. Of the dizygotic twin pairs, only one was concordant
and five were discordant. In the demographic and risk factor analysis no unusual 
contributing or confounding variables were detected. CONCLUSIONS: The association
between zygosity and concordance for ARMD suggests a major importance for
genetics in the etiology of ARMD. Our data further support a multi-factorial,
primarily polygenic etiology for the condition.

Publication Types: 
    Comparative Study
    Twin Study

PMID: 14566632 [PubMed - indexed for MEDLINE]

2467: Semin Ophthalmol. 2003 Jun;18(2):74-81.

Role of OCT in the diagnosis and follow up of diabetic macular edema.

Panozzo G, Gusson E, Parolini B, Mercanti A.

TECLO SRL, Vitreoretinal Service, Verona, Italy. g.panozzo@iol.it

The aim is to present, along with a brief literature review, the results of OCT
scan in eyes with diabetic macular edema (DME), as well as examples of the
utility of OCT for different therapeutic approaches. One-hundred and thirty-six
eyes with diabetic retinopathy were analyzed with OCT to explore the different
patterns of DME. Some eyes with DME were studied with OCT pre and postoperatively
to determine the efficacy of photocoagulation and vitrectomy to restore a normal 
macular profile. Sixty-eight eyes with a central foveal thickness of 200 mu or
more were considered "edematous". Three different patterns of DME were recognized
and analyzed: macular thickening, cystoid macular edema and shallow retinal
detachment. The change in macular profile and internal retinal structure after
laser or surgical treatment are well visible with OCT. OCT contributes in
understanding the anatomy of DME and the intraretinal damage and seems to be the 
technique of choice for the follow-up of macular edema. We think that this tool
should always be used in monitoring the effect of therapies in future studies.

Publication Types: 
    Case Reports
    Review

PMID: 14566626 [PubMed - indexed for MEDLINE]

2468: Nat Med. 2003 Nov;9(11):1390-7. Epub 2003 Oct 19.

Comment in:
    Nat Med. 2003 Nov;9(11):1350-1.    Nat Med. 2004 Jul;10(7):663; author reply 663.

An animal model of age-related macular degeneration in senescent Ccl-2- or
Ccr-2-deficient mice.

Ambati J, Anand A, Fernandez S, Sakurai E, Lynn BC, Kuziel WA, Rollins BJ, Ambati
BK.

Department of Ophthalmology, University of Kentucky, 740 South Limestone Street, 
Lexington, Kentucky 40536-0284, USA. jamba2@uky.edu

The study and treatment of age-related macular degeneration (AMD), a leading
cause of blindness, has been hampered by a lack of animal models. Here we report 
that mice deficient either in monocyte chemoattractant protein-1 (Ccl-2; also
known as MCP-1) or its cognate C-C chemokine receptor-2 (Ccr-2) develop cardinal 
features of AMD, including accumulation of lipofuscin in and drusen beneath the
retinal pigmented epithelium (RPE), photoreceptor atrophy and choroidal
neovascularization (CNV). Complement and IgG deposition in RPE and choroid
accompanies senescence in this model, as in human AMD. RPE or choroidal
endothelial production of Ccl-2 induced by complement C5a and IgG may mediate
choroidal macrophage infiltration into aged wild-type choroids. Wild-type
choroidal macrophages degrade C5 and IgG in eye sections of Ccl2(-/-) or
Ccr2(-/-) mice. Impaired macrophage recruitment may allow accumulation of C5a and
IgG, which induces vascular endothelial growth factor (VEGF) production by RPE,
possibly mediating development of CNV. These models implicate macrophage
dysfunction in AMD pathogenesis and may be useful as a platform for validating
therapies.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 14566334 [PubMed - indexed for MEDLINE]

2469: Eur J Epidemiol. 2003;18(9):845-54.

Epidemiology of age-related maculopathy: a review.

van Leeuwen R, Klaver CC, Vingerling JR, Hofman A, de Jong PT.

Department of Epidemiology and Biostatistics, Erasmus Medical Centre, Rotterdam, 
The Netherlands.

Age-related maculopathy (ARM) is a degenerative disease of the retina and the
leading cause of incurable blindness and visual impairment in industrialized
countries. By definition, ARM is confined to the age-category above 50 years. The
aetiology of ARM is still unknown, despite intensive research on many fronts. In 
this paper, we provide a review of the epidemiology of ARM. The most prominent
findings were an exponential increase in frequency with age, a significant
familial and genetic component, and a strong association with smoking. Other risk
factors that were found less consistently were atherosclerosis, low intake of
antioxidant nutrients, and cataract extraction. Future studies, both
observational and experimental, will hopefully identify more risk factors that
are amenable to prevention.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 14561043 [PubMed - indexed for MEDLINE]

2470: Arch Ophthalmol. 2003 Oct;121(10):1462-8.

Estimates of incidence rates with longitudinal claims data.

Sloan FA, Brown DS, Carlisle ES, Ostermann J, Lee PP.

Department of Economics and Center for Health Policy, Law and Management, Duke
University, Durham, NC 27708, USA. fsloan@hpolicy.duke.edu

OBJECTIVE: To estimate incidence rates of the 3 major chronic eye
diseases--diabetic retinopathy (DR), glaucoma, and age-related macular
degeneration (ARMD)--by using longitudinal claims data from Medicare. METHODS:
Longitudinal cases were ascertained by using a national probability sample of
Medicare beneficiaries aged 65 years and older in 1991 who initially had none of 
the eye diseases documented. After adjusting for death and enrollment in a health
maintenance organization, claims filed by optometrists or ophthalmologists with
an International Classification of Diseases, Ninth Revision, Clinical
Modification code for all forms of DR, glaucoma, and ARMD were used to indicate
diagnosis. RESULTS: Annual incidence rates for the 3 conditions after the first
year of observation ranged from 14.3% to 17.7% (higher earlier) across an 8-year 
longitudinal follow-up. Incidence rates among those with diabetes mellitus for
any form of DR varied between 3.8% and 6.5%, while those for glaucoma varied
between 4.6% and 7.8% and those for ARMD varied between 7.5% and 9.3%.
CONCLUSIONS: Longitudinal claims data after the first year provide relatively
stable estimates of incidence rates on an annual basis. These estimates are
comparable with those of the few population-based studies available.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 14557184 [PubMed - indexed for MEDLINE]

2471: Arch Ophthalmol. 2003 Oct;121(10):1452-7.

A peculiar autosomal dominant macular dystrophy caused by an asparagine deletion 
at codon 169 in the peripherin/RDS gene.

van Lith-Verhoeven JJ, van den Helm B, Deutman AF, Bergen AA, Cremers FP, Hoyng
CB, de Jong PT.

Department of Ophthalmology, University Medical Center Nijmegen, The Netherlands.

OBJECTIVE: To describe the clinical and genetic findings in a family with a
peculiar autosomal dominant macular dystrophy with peripheral deposits. METHODS: 
All family members underwent an ophthalmic examination, and their genomic DNA was
screened for mutations in the human retinal degeneration slow (peripherin/RDS)
and rhodopsin genes. In selected cases, fluorescein angiography and
electrophysiologic testing were performed. RESULTS: The age at onset of the
disease was between the third and fourth decades of life, starting with mild
visual acuity loss and periods of metamorphopsia. Clinical signs included
subretinal yellowish macular deposits evolving into geographic atrophy and
retinal hypopigmentation and hyperpigmentation. Electroretinography demonstrated 
rod dysfunction, and electro-oculograms were mildly to severely disturbed. All
affected members were found to carry a 3-base pair deletion affecting codon 169
of the peripherin/RDS gene. This mutation resulted in an asparagine (Asn)
deletion in the peripherin/RDS protein and was not found in 155 control
individuals. CONCLUSION: A deletion of Asn169 in the peripherin/RDS protein
causes a peculiar form of autosomal dominant macular dystrophy in a large family 
from the Netherlands. CLINICAL RELEVANCE: Characterizing the phenotype and
genotype in this family may, in the long term, result in a better understanding
of the precise mechanism underlying this retinal degeneration.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 14557182 [PubMed - indexed for MEDLINE]

2472: Ophthalmology. 2003 Oct;110(10):1960-7.

Cataract surgery and the 5-year incidence of late-stage age-related maculopathy: 
pooled findings from the Beaver Dam and Blue Mountains eye studies.

Wang JJ, Klein R, Smith W, Klein BE, Tomany S, Mitchell P.

Department of Ophthalmology, Westmead Millennium and Save Sight Institutes,
University of Sydney, Hawkesbury Road, Westmead, NSW 2145, Sydney, Australia.

PURPOSE: To assess whether cataract surgery in older persons increases risk for
the development of late-stage age-related maculopathy (ARM). DESIGN: Combined
analysis of longitudinal data from two population-based cohorts, the Beaver Dam
Eye Study and Blue Mountains Eye Study. PARTICIPANTS: The Beaver Dam Eye Study
examined 4926 persons aged 43 years or older at baseline and re-examined 3684
after 5 years. The Blue Mountains Eye Study examined 3654 persons aged 49 years
or older at baseline and re-examined 2335 after 5 years. METHODS: The two studies
used similar protocols for retinal photography and photographic grading. We
defined incident late-stage ARM as the development of neovascular ARM or
geographic atrophy in eyes without either lesion type at baseline that was
confirmed by consensus between the study investigators. Nonphakic eyes included
eyes that were aphakic or pseudophakic at baseline. Eye-specific data were
analyzed. Age- and study site-adjusted relative risks were calculated using the
Cochran-Mantel-Haenszel method. Multivariate-adjusted odds ratios (ORs) were also
estimated using generalized estimating equation models. RESULTS: Of the 6019
participants examined after 5 years, 11,391 eyes were considered at risk for
developing late-stage ARM, including 315 nonphakic and 11,076 phakic eyes.
Late-state ARM (either neovascular ARM or geographic atrophy) developed in 6.0%
to 7.5% of nonphakic eyes (10 of 168 right and 11 of 147 left eyes), compared
with 0.7% of phakic eyes (40 of 5504 right and 37 of 5572 left eyes) during the
5-year period. Age- and study site-adjusted 5-year relative risks were 2.8 (95%
confidence interval [CI], 1.6-5.1) for right and 3.7 (95% CI, 2.1-6.4) for left
eyes. After further adjustment for gender, smoking, and the presence of
indistinct or reticular drusen or pigmentary abnormalities at baseline, nonphakic
eyes had a substantially higher risk for developing either late-stage ARM lesion 
compared with phakic eyes, OR = 5.7 (95% CI, 2.4-13.6). CONCLUSIONS: Pooled
findings from these two large population-based cohorts support the hypothesis
that cataract surgery in older persons may be associated with an increased
subsequent risk for developing late-stage ARM, particularly neovascular ARM.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 14522772 [PubMed - indexed for MEDLINE]

2473: Ophthalmology. 2003 Oct;110(10):1952-9.

Longitudinal rates of annual eye examinations of persons with diabetes and
chronic eye diseases.

Lee PP, Feldman ZW, Ostermann J, Brown DS, Sloan FA.

Department of Ophthalmology, Duke University School of Medicine, Durham, NC
27708, USA.

OBJECTIVE: To assess the rate of annual eye examinations over time among older
Americans with diabetes and chronic eye diseases. DESIGN: Longitudinal analysis
of Medicare claims data. PARTICIPANTS: Random sample of Medicare beneficiaries
aged 65 years or older. METHODS: Beneficiaries were followed between 1991 and
1999, unless mortality or enrollment in a health maintenance organization for > 6
months in a given 12-month period intervened. All claims data (both physician and
facility) during this time were analyzed for the presence of International
Classification of Diseases 9 codes consistent with 1 of the 3 study conditions
and the performance of eye examinations. MAIN OUTCOME MEASURES: Claims submitted 
by optometrists, ophthalmologists, or other providers of eye care for subjects
with diabetes, glaucoma, or age-related macular degeneration (ARMD). Rates were
calculated on the basis of a 15-month time window for annual examinations rather 
than for 12 months to allow for less than full compliance with the guidelines for
various reasons (e.g., bad weather). RESULTS: Among those with diabetes in this
population, 50% to 60% had annual eye examinations in a 15-month period. Of those
followed for at least 75 months after diagnosis, about three quarters had one or 
more 15-month gaps between visits. For subjects diagnosed with glaucoma, most
visit rates were in the 70% to 90% range per 15-month period. The percentage of
subjects with at least one 15-month period with no visits was considerably lower 
than for diabetes. The patterns for those with ARMD were in between those for
diabetes and glaucoma. Over a nine-year period, only slightly over half of
persons with at least one of the study conditions complied with practice
guidelines. CONCLUSIONS: Annual eye examinations for persons diagnosed with
diabetes, glaucoma, and ARMD are important for detecting potentially treatable
vision loss among those already diagnosed with these conditions. Currently,
actual rates of eye examinations for persons diagnosed with the study conditions 
fall far short of recommended rates. As such, approaches to enhancing
longitudinal follow-up of those already in the eye care system are needed.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.

PMID: 14522771 [PubMed - indexed for MEDLINE]

2474: J Cataract Refract Surg. 2003 Sep;29(9):1800-10.

Comment in:
    J Cataract Refract Surg. 2004 Nov;30(11):2252; author reply 2252.

ESCRS Binkhorst lecture 2002: Pseudophakic preservative maculopathy.

Miyake K, Ibaraki N, Goto Y, Oogiya S, Ishigaki J, Ota I, Miyake S.

Shohzankai Medical Foundation, Miyake Eye Hospital, Nagoya, Japan.
miyake@spice.or.jp

Many antiglaucoma eyedrops are reported to cause cystoid macular edema (CME) in
aphakia and pseudophakia. We review 4 clinical and laboratory studies that
compare the incidence of CME in early postoperative pseudophakia in eyes that
received preserved latanoprost and timolol, nonpreserved timolol, and the
preserved and nonpreserved vehicle for these drugs and looked at the
morphological damage to cells and the changes in the indicators of cytokine and
prostaglandin (PG) synthesis caused by latanoprost and timolol and the
preservative benzalkonium chloride. Based on the findings of these studies, which
indicate that the preservative causes increased synthesis of PGs and other
substances and intensified postoperative inflammation, the term pseudophakic
preservative maculopathy is proposed for CME caused by antiglaucoma eyedrops.

Publication Types: 
    Comparative Study
    Lectures

PMID: 14522305 [PubMed - indexed for MEDLINE]

2475: Hum Mutat. 2003 Nov;22(5):418.

Ten novel mutations in VMD2 associated with Best macular dystrophy (BMD).

Krämer F, Mohr N, Kellner U, Rudolph G, Weber BH.

Institut für Humangenetik, Universität Würzburg, D-97072 Würzburg, Germany.

Mutations in the vitelliform macular dystrophy 2 (VMD2) gene encoding besrtophin 
are responsible for Best macular dystrophy (BMD), a juvenile-onset autosomal
dominant disorder of the central retina. Here, we report ten novel VMD2 mutations
identified in clinically diagnosed BMD patients. The heterozygous alterations
include nine missense mutations (c.32A>T, c.76G>C, c.85T>C, c.122T>C, c.122T>C,
c.310G>C, c.722C>A, c.880C>G, c.893T>C) resulting in amino acid changes
(respectively: Asn11Ile, Gly26Arg, Tyr29His, Leu41Pro, Trp102Arg, Asp104His,
Thr241Asn, Leu294Val and Phe298Ser) located within four previously defined
hotspot regions of the gene. In addition, a silent exonic mutation (c.624G>A) was
identified in a two generation BMD pedigree. To determine a possible pathogenic
effect of this variant, the consequences on splicing behaviour and potential
exonic splice enhancer (ESE) motifs were analyzed. Finally, a 1-bp deletion
(c.779delC) resulting in a frameshift mutation (Pro260fsX288) was found in exon
7, representing the first case of a potential frameshift mutation that affects
the N-terminal half of the VMD2 protein. Besides a dominant negative effect which
is likely attributable to the identified missense mutations, the deletion
mutation suggests haploinsufficiency as an infrequent disease-causing mechanism
in BMD. Copyright 2003 Wiley-Liss, Inc.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 14517959 [PubMed - indexed for MEDLINE]

2476: Am J Ophthalmol. 2003 Oct;136(4):737-9.

Intravitreal triamcinolone acetonide for idiopathic cystoid macular edema.

Scott IU, Flynn HW Jr, Rosenfeld PJ.

Bascom Palmer Eye Institute, University of Miami School of Medicine, Miami,
Florida 33101, USA. iscott@bpei.med.miami.edu

PURPOSE: To report intravitreal triamcinolone acetonide for idiopathic cystoid
macular edema (ICME). DESIGN: Interventional case series. METHODS:Two patients
with ICME were treated with intravitreal triamcinolone. RESULTS: In one patient, 
best-corrected acuity was 20/70 before treatment and 20/30 6 months posttreatment
in both eyes. Foveal thickness was 606 microm before and 197 microm posttreatment
in the right eye and 542 microm before and 190 microm posttreatment in the left
eye. In another patient, best-corrected acuity was 20/200 before treatment and
20/50 5 months posttreatment; foveal thickness was 580 microm before and 208
microm posttreatment. Recurrence of macular edema responded to repeat
intravitreal triamcinolone acetonide in both patients. CONCLUSIONS: Intravitreal 
triamcinolone may be associated with reduced edema and improved vision in
patients with ICME; however, these changes may be transient.

Publication Types: 
    Case Reports

PMID: 14516818 [PubMed - indexed for MEDLINE]

2477: Am J Ophthalmol. 2003 Oct;136(4):688-95.

Autologous retinal pigment epithelium and choroid translocation in patients with 
exudative age-related macular degeneration: short-term follow-up.

van Meurs JC, Van Den Biesen PR.

Rotterdam Eye Hospital, Rotterdam, The Netherlands. janvanmeurs@cs.com

PURPOSE: To evaluate the feasibilty of translocating autologous retinal pigment
epithelium cells and choroid after the removal of a subfoveal choroidal
neovascular membrane in patients with exudative age-related macular degeneration.
DESIGN: Interventional case series. METHODS: This was a prospective evaluation of
six patients with a follow-up of 7 to 13 months. All patients had large (> 1 disk
diameter) subfoveal choroidal membranes, five with subretinal hemorrhage.
Preoperative visual acuity ranged from 20/400 to 20/200. After the extraction of 
the neovascular complex, an autologous peripheral full-thickness patch of retinal
pigment epithelium, Bruch membrane, choriocapillary, and choroid was cut out from
the midperiphery and repositioned under the macula. Functional tests included
Early Treatment Diabetic Retinopathy Study vision testing, fixation testing on a 
optical coherence tomography monitor, fluorescein and indocyanine green
angiography, and scanning laser ophthalmoscopy autofluorescence. RESULTS: The
retinal pigment epithelium patch appeared flat and had a brown furry aspect in
four patients. Fixation was on the patch in these four patients. Postoperative
vision ranged from 20/200 to 20/64, with a 2-line increase in three patients.
Revascularization was visible on fluorescein and indocyanide angiography in three
patients examined in this manner. Normal retinal pigment epithelium
autofluorescence was present over the patch in four patients. CONCLUSIONS: The
translocation of a full-thickness patch with autologous peripheral retinal
pigment epithelium to the macula after choroidal neovascular membrane extraction 
was feasible and may result in a surviving and functioning graft for more than 1 
year. Longer follow-up to evaluate its long-term benefit is necessary, as well as
refinement of the surgery.

PMID: 14516809 [PubMed - indexed for MEDLINE]

2478: Am J Ophthalmol. 2003 Oct;136(4):640-8.

Management of ocular torsion and diplopia after macular translocation for
age-related macular degeneration: prospective clinical study.

Freedman SF, Holgado S, Enyedi LB, Toth CA.

Duke University Eye Center, Durham, North Carolina 27710, USA.
freed003@mc.duke.edu

PURPOSE: To report the results of a prospective clinical series to evaluate the
management of both torsion and diplopia in a large group of patients after full
macular translocation (FMT) and extraocular muscle surgery. DESIGN: Prospective
interventional case series. METHODS: Information gathered included demographic,
visual acuity, ocular motility, torsion by Maddox rod, ocular history, and
symptoms of visual disturbance. Surgery on two, three, or four extraocular
muscles was performed based on the magnitude of torsion measured after FMT
surgery. RESULTS: Fifty-three patients were included for both objective and
subjective outcomes and were evaluated after FMT, both before (preoperative) and 
after (postoperative) extraocular muscle surgery. Preoperative torsion for two-
(n = 6), three- (n = 8), and four-muscle (n = 39) surgery groups was 21.2 +/-
4.6, 30.0 +/- 6.3, and 40.5 +/- 8.7 degrees, respectively. At 6 months,
postoperative residual torsion was significantly reduced in each group (to 3.4
+/- 3.2, 5.6 +/- 5.5, and 4.5 +/- 6.8 degrees, respectively, for two-, three-,
and four-muscle groups). Muscle surgery reduced mean hypertropia from 17 +/- 6
prism diopters preoperative to 4 +/- 10 prism diopters postoperative (P <.0001); 
mean exotropia was mildly reduced from 20 +/- 9 prism diopters preoperative to 13
+/- 11 prism diopters postoperative (P <.01). Subjective data regarding diplopia 
and tilted vision after FMT and muscle surgery were available on an additional 10
patients (n = 53 + 10 = 63). Overall, 41% (26/63) of these were free of both
diplopia and tilt, whereas only 5% (3/63) had both symptoms constantly.
CONCLUSIONS: Extraocular muscle surgery is effective at relieving the variable
amounts of torsion produced by FMT when graded to match preoperative torsion. The
majority of patients were free of disabling tilt and diplopia after extraocular
muscle surgery.

Publication Types: 
    Clinical Trial

PMID: 14516803 [PubMed - indexed for MEDLINE]

2479: Clin Experiment Ophthalmol. 2003 Oct;31(5):376-91.

New treatments in age-related macular degeneration.

Hooper CY, Guymer RH.

Centre for Eye Research Australia, University of Melbourne, Department of
Ophthalmology, Melbourne, Victoria, Australia.

Age-related macular degeneration (AMD) is the leading cause of legal blindness in
individuals 50 years and older in the developed world. Choroidal
neovascularization (CNV) in exudative AMD is responsible for the majority of
severe vision loss. Until recently, laser photocoagulation was the only
well-established and widely accepted treatment for CNV. However, it is beneficial
only for a small subset of patients, has a high rate of CNV persistence and
recurrence and results in iatrogenic, collateral damage to the overlying retina. 
These issues make it difficult to recommend in the case of subfoveal lesions.
Consequently, numerous experimental therapeutic interventions are under
investigation with the common objective of destroying the CNV but leaving the
foveal neurosensory retina intact. Treatment modalities can be grouped into five 
major categories: photodynamic therapy; radiotherapy; transpupillary
thermotherapy; anti-angiogenic and angiostatic agents; and surgical intervention.
The present review aims to explain the rationale behind these new treatments,
analyse the evidence for their safety and efficacy, determine their stage of
development and indicate in which patients they are potentially useful.

Publication Types: 
    Review

PMID: 14516424 [PubMed - indexed for MEDLINE]

2480: Medsurg Nurs. 2003 Aug;12(4):238-41, 259.

The genetics of age-related macular degeneration.

Conley YP, Gorin MB.

University of Pittsburgh, School of Nursing, Pittsburgh, PA, USA.

Age-related macular degeneration (ARM) is a progressive, chronic condition that
results when the macula degenerates and central vision is lost. ARM is the
leading cause of vision loss in Americans over age 50 and is a major public
health concern. Very little is known about the etiology of ARM. Deciphering the
genetic susceptibility associated with ARM holds great promise for gaining a
better understanding of the disease, identifying at-risk individuals, and
developing interventions and treatments.

Publication Types: 
    Review

PMID: 14515603 [PubMed - indexed for MEDLINE]

2481: Acta Ophthalmol Scand. 2003 Oct;81(5):455-8.

Age-related macular degeneration: filter lenses help in certain situations.

Langagergaard U, Ganer HJ, Baggesen K.

Department of Ophthalmology, Aalborg Hospital, Aalborg, Denmark. u.j.@webspeed.dk

PURPOSE: To investigate the ability of different filter lenses to enhance the
contrast sensitivity of patients with age-related macular degeneration (AMD).
METHODS: A total of 32 patients with non-exudative AMD and no other significant
eye diseases underwent the study tests using their optimal correction. We used
Hyvärinen's contrast sensitivity tests with 100%, 10%, 5%, 2.5% and 1.25% charts.
All the tests were made without filter lenses and with the Corning 527 and LVI
527 lenses. RESULTS: With the 100% charts, there was a slight tendency towards
contrast sensitivity improvement with LVI filter lenses, but the degree of
improvement was not statistically significant. With the 10% charts, contrast
sensitivity improved significantly with LVI 527 filter lenses, but not with
Corning 527 lenses. It was not possible to perform statistical analyses of the
results with the 5%, 2.5% and 1.25% charts. CONCLUSION: Use of LVI filter lenses 
may improve contrast sensitivity in certain situations in patients with AMD.

PMID: 14510791 [PubMed - indexed for MEDLINE]

2482: Acta Ophthalmol Scand. 2003 Oct;81(5):449-54.

Comment in:
    Acta Ophthalmol Scand. 2003 Oct;81(5):427-9.

Prophylactic laser treatment in early age-related maculopathy: an 8-year
follow-up in a randomized pilot study shows a reduced incidence of exudative
complications.

Frennesson CI.

Department of Ophthalmology, Linköping University, Linköping, Sweden.

PURPOSE: To study the effect of mild laser treatment on the incidence of
exudative complications in patients with soft drusen maculopathy in a longterm
perspective. METHODS: In a prospective study, 38 patients with early age-related 
maculopathy and good visual acuity (VA) were randomized either to laser treatment
using an argon green laser or to observation. At 8 years, 29 patients remained in
the study, 16 in the control group and 13 in the treatment group. RESULTS: During
follow-up, mean VA decreased significantly in both groups, to 0.53 in the
treatment group (p < 0.05) and to 0.25 in the control group (p < 0.001). At 8
years, 9/16 in the control group showed exudative complications, whereas only
2/13 in the treatment group developed such changes (p < 0.03). CONCLUSION: In
this randomized pilot study, mild laser treatment of soft drusen maculopathy
significantly reduced the rate of exudative complications in a longterm
perspective. As the study is small, the results should be viewed with caution.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 14510790 [PubMed - indexed for MEDLINE]

2483: Ophthalmic Surg Lasers Imaging. 2003 Sep-Oct;34(5):398-400.

Treatment of cystoid macular edema related to retinitis pigmentosa with
intravitreal triamcinolone acetonide.

Saraiva VS, Sallum JM, Farah ME.

Department of Ophthalmology, Federal University of São Paulo, São Paulo, Brazil.

A case of cystoid macular edema related to retinitis pigmentosa treated with
intravitreal injection of triamcinolone acetonide is described. A 30-year-old
white man with retinitis pigmentosa and progressive visual loss presented with a 
best-corrected visual acuity of 20/40 in the right eye and 20/80 in the left eye.
Examination revealed cystoid macular edema in both eyes. After failure of
treatment with oral acetazolamide, intravitreal injection of 0.1 mL of
triamcinolone acetonide 0.4% solution was performed in both eyes. In the left
eye, macular edema resorbed and visual acuity improved to 20/50. However, 6
months after injection, visual acuity worsened because of recurrence of cystoid
macular edema. In the right eye, cystoid macular edema also resorbed, but visual 
acuity was unchanged. Intravitreal triamcinolone acetonide may be useful for
selected cases of cystoid macular edema related to retinitis pigmentosa.

Publication Types: 
    Case Reports

PMID: 14509465 [PubMed - indexed for MEDLINE]

2484: Invest Ophthalmol Vis Sci. 2003 Oct;44(10):4465-72.

Changes in focal macular electroretinograms and foveal thickness after vitrectomy
for diabetic macular edema.

Terasaki H, Kojima T, Niwa H, Piao CH, Ueno S, Kondo M, Ito Y, Miyake Y.

Department of Ophthalmology, Nagoya University School of Medicine, Nagoya, Japan.
terasaki@med.nagoya-u.ac.jp

PURPOSE. To evaluate the changes in the focal macular electroretinogram (FMERG)
and foveal retinal thickness after vitrectomy for diabetic macular edema (DME).
METHODS. FMERGs were elicited from 25 eyes of 21 patients (ages 29-75 years) who 
underwent vitrectomy for DME by a 15 degrees stimulus. A posterior vitreous
detachment (PVD) was created during surgery in 19 eyes (group 1), and 4 eyes had 
a PVD before surgery (group 2). In the remaining 2 eyes, a PVD could not be
created (group 3). FMERGs were recorded before and 3, 6, and 12 months after
vitrectomy. The foveal thickness, determined by optical coherence tomography
(OCT), and visual acuity were measured on the same day as the FMERG recordings.
RESULTS. The postoperative visual acuity (logarithm of the minimum angle of
resolution [logMAR]) improved gradually after the surgery and was significantly
better at 12 months in eyes in group 1 (P = 0.0393). The postoperative mean
foveal thickness was significantly less at 3 months after surgery in group 1 eyes
(P = 0.0006), and there was a further decrease thereafter. In the 2 eyes in group
3, the decreased foveal thickness 3 and 6 months after surgery became thicker at 
12 months. The mean b-wave amplitude of the FMERGs increased significantly at 12 
months in group 1 eyes (P = 0.0297). The mean implicit time of a- and b-waves was
more delayed at 3 months, and the change in a-wave was statistically significant 
in group 1 eyes (P = 0.0474). There was a wide range of changes in the b-wave
amplitude at 12 months, however, the increase in the b-wave was correlated with
the decrease in foveal thickness (r =.49, P = 0.012). CONCLUSIONS. A disparity in
the time course and degree of recovery of the foveal thickness and macular
retinal function was found in eyes with DME after vitrectomy. Part of the
functional recovery could be attributed to decreased retinal thickness and the
absorption of the subretinal fluid.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 14507894 [PubMed - indexed for MEDLINE]

2485: Graefes Arch Clin Exp Ophthalmol. 2003 Dec;241(12):968-74. Epub 2003 Sep 6.

Visual acuity and contrast sensitivity in patients with neovascular age-related
macular degeneration. Results from the Radiation Therapy for Age-Related Macular 
Degeneration (RAD-) Study.

Bellmann C, Unnebrink K, Rubin GS, Miller D, Holz FG.

Department of Ophthalmology, University of Heidelberg, INF 400, 69120 Heidelberg,
Germany.

BACKGROUND: Patients with advanced age-related macular degeneration (AMD) suffer 
not only from impairment in central visual acuity (VA), but also from reduction
in contrast sensitivity (CS). We examined VA and CS changes over time in patients
with subfoveal choroidal neovascularizations (CNV) as well as the correlation
between the two parameters. METHODS: VA was determined according to a
standardized protocol with the Early Treatment Diabetic Retinopathy (ETDRS)
chart. CS was measured with Pelli-Robson charts. The angiographic characteristics
of CNV and the presence of CNV in the fellow eye as well as gender and age were
evaluated as possible prognostic factors of VA and CS progression. Two hundred
and five patients with neovascular AMD were recruited within the Radiation
Therapy for Age-Related Macular Degeneration (RAD) Study and were reviewed over 2
years. The treatment and control groups showed no significant difference for VA
or for CS ( P>0.05), and both groups were considered together. RESULTS: At
baseline, mean VA was 55.6+/-14.5 SD letters (EDTRS chart), and mean CS was
22.8+/-6.9 letters (Pelli-Robson chart). Spearman Correlation Coefficient ( r(s))
between VA and CS was r(s)=0.60, P=0.0001. Over 2 years the mean VA loss was
23.6+/-21.4 letters and mean CS reduction was 9.0+/-9.7 letters. Agreement
between change of VA and change of CS was moderate ( r(s)=0.65, P=0.0001; kappa
coefficient (grouped into VA loss < or =15, >15, >30 letters; CS loss < or =6,
>6, >15 letters) kappa=0.43, 95% CI [0.32;0.54]). Proportional hazard models did 
not show any apparent influence of type of CNV, or CNV in the fellow eye, on
change in VA and CS. CONCLUSION: The results indicate that VA and CS do not
always show the same progression in visual function loss although they show a
moderate correlation in eyes with neovascular AMD. Both parameters provide
important information about visual disability and should be evaluated as outcome 
in interventional studies.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 13680248 [PubMed - indexed for MEDLINE]

2486: Ophthalmology. 2003 Sep;110(9):1724-31.

Phenotype and genotype correlations in two best families.

Seddon JM, Sharma S, Chong S, Hutchinson A, Allikmets R, Adelman RA.

Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical
School, Boston, Massachusetts 02114, USA.

OBJECTIVE: To evaluate mutations in the Best mascular dystrophy (VMD2) gene in
two families with Best disease and to describe the phenotype-genotype
correlations of genetically determined affected and unaffected individuals.
DESIGN: Family genetic study. PARTICIPANTS: Two families with Best disease were
identified, and family members were evaluated by ophthalmologic examination or
fundus photography to assess their phenotype. All affected patients and some of
the unaffected family members had a blood sample drawn, and the DNA was analyzed 
for mutations in the VMD2 gene. MAIN OUTCOME MEASURES: Twenty-one subjects in the
two pedigrees with Best disease were studied. One amino acid-changing mutation in
the VMD2 gene was found to segregate independently in each family (P297S or
E300D, respectively). RESULTS: Eleven individuals had some evidence of
maculopathy, including retinal pigment epithelial changes, drusen, pigment
epithelial irregularities, or cicatricial changes. Ten of these 11 patients (91%)
with maculopathy had a mutation in the VMD2 gene, of whom 8 were clinically
diagnosed as having Best disease and 2 were diagnosed as having possible Best
maculopathy. The one patient without a mutation in the VMD2 gene had age-related 
macular degeneration (AMD). Ten family members did not have evidence of
maculopathy, of whom 6 had no mutation in the VMD2 gene. Four family members (2
in each pedigree) had mutations in the VMD2 gene, abnormal electro-oculogram
(EOG) results, but normal maculae at age 40 or older. Of the 7 individuals with
no mutation in the VMD2 gene, 6 were phenotypically normal and the other had
late-onset visual loss resulting from AMD. CONCLUSIONS: All family members with
maculopathy consistent with Best disease (n = 10) had an amino acid-changing
mutation in the VMD2 gene. Four individuals who did not have maculopathy, but did
have an abnormal EOG, also had mutations in the VMD2 gene. The presence of a VMD2
mutation is associated with abnormal retinal function, which can occur in the
absence of phenotypic manifestation of macular disease.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 13129869 [PubMed - indexed for MEDLINE]

2487: Ophthalmology. 2003 Sep;110(9):1690-6.

Vitreous levels of interleukin-6 and vascular endothelial growth factor are
related to diabetic macular edema.

Funatsu H, Yamashita H, Ikeda T, Mimura T, Eguchi S, Hori S.

Department of Ophthalmology, Diabetes Center, Tokyo Women's Medical University,
Tokyo, Japan. tfunatsu@nifty.com

PURPOSE: To investigate whether interleukin-6 (IL-6) or vascular endothelial
growth factor (VEGF) is related to diabetic macular edema (DME) in subjects
without posterior vitreous detachment (PVD). DESIGN: Retrospective case-control
study. PARTICIPANTS: Twenty-six subjects who had DME without PVD and 12 subjects 
who had nondiabetic ocular disease (the control group). METHODS: Vitreous fluid
samples were obtained at vitreoretinal surgery, and the IL-6 and VEGF levels in
vitreous fluid and plasma were measured by enzyme-linked immunosorbent assay.
MAIN OUTCOME MEASURES: Vitreous levels of IL-6 and VEGF in DME subjects without
PVD. RESULTS: The vitreous levels of both IL-6 and VEGF were significantly higher
in the subjects with DME than in control subjects (P<0.0001 and P<0.0001,
respectively). The vitreous level of IL-6 was significantly correlated with that 
of VEGF (P<0.0001). Vitreous levels of both IL-6 and VEGF were significantly
higher in subjects with hyperfluorescent DME than in those with minimally
fluorescent DME (P = 0.0008 and P = 0.0038, respectively). CONCLUSIONS: We found 
that the levels of both IL-6 and VEGF were elevated in the vitreous fluid of
subjects with hyperfluorescent DME. Our results suggest that IL-6 and VEGF may
promote an increase of vascular permeability in DME subjects without PVD.
Interleukin-6 may possibly induce an increase of vascular permeability through a 
paracrine effect on VEGF in these subjects.

PMID: 13129863 [PubMed - indexed for MEDLINE]

2488: Ophthalmology. 2003 Sep;110(9):1677-82.

Comment in:
    Ophthalmology. 2003 Sep;110(9):1675-6.

Proposed international clinical diabetic retinopathy and diabetic macular edema
disease severity scales.

Wilkinson CP, Ferris FL 3rd, Klein RE, Lee PP, Agardh CD, Davis M, Dills D,
Kampik A, Pararajasegaram R, Verdaguer JT; Global Diabetic Retinopathy Project
Group.

Greater Baltimore Medical Center, Baltimore, Maryland, USA.

PURPOSE: To develop consensus regarding clinical disease severity classification 
systems for diabetic retinopathy and diabetic macular edema that can be used
around the world, and to improve communication and coordination of care among
physicians who care for patients with diabetes. DESIGN: Report regarding the
development of clinical diabetic retinopathy disease severity scales.
PARTICIPANTS: A group of 31 individuals from 16 countries, representing
comprehensive ophthalmology, retina subspecialties, endocrinology, and
epidemiology. METHODS: An initial clinical classification system, based on the
Early Treatment Diabetic Retinopathy Study and the Wisconsin Epidemiologic Study 
of Diabetic Retinopathy publications, was circulated to the group in advance of a
workshop. Each member reviewed this using e-mail, and a modified Delphi system
was used to stratify responses. At a later workshop, separate systems for
diabetic retinopathy and macular edema were developed. These were then
reevaluated by group members, and the modified Delphi system was again used to
measure degrees of agreement. MAIN OUTCOME MEASURES: Consensus regarding specific
classification systems was achieved. RESULTS: A five-stage disease severity
classification for diabetic retinopathy includes three stages of low risk, a
fourth stage of severe nonproliferative retinopathy, and a fifth stage of
proliferative retinopathy. Diabetic macular edema is classified as apparently
present or apparently absent. If training and equipment allow the screener to
make a valid decision, macular edema is further categorized as a function of its 
distance from the central macula. CONCLUSIONS: There seems to be a genuine need
for consistent international clinical classification systems for diabetic
retinopathy and diabetic macular edema that are supported with solid evidence.
The proposed clinical classification systems provide a means of appropriately
categorizing diabetic retinopathy and macular edema. It is hoped that these
systems will be valuable in improving both screening of individuals with diabetes
and communication and discussion among individuals caring for these patients.

Publication Types: 
    Consensus Development Conference
    Review

PMID: 13129861 [PubMed - indexed for MEDLINE]

2489: Am J Ophthalmol. 2003 Sep;136(3):555-7.

Potential pitfalls from variable optical coherence tomograph displays in managing
diabetic macular edema.

Browning DJ.

Charlotte Eye, Ear, Nose, and Throat Associates, Charlotte, North Carolina 28210,
USA. djbrowning@carolina.rr.com

PURPOSE: To describe potential pitfalls in the use of optical coherence
tomography for management of diabetic macular edema. DESIGN: Prospective,
noninterventional case series. METHODS: Review of optical coherence tomographs in
13 eyes with clinically significant diabetic macular edema from 11 consecutive
patients in a private retina practice. RESULTS: Optical coherence tomography
displays are based on 3.5-mm or 6-mm diameter circular grids that look very
similar and have identical sector names but schematize different areas of the
macula. The numeric outputs for the identically named sectors in the two displays
do not differ significantly for retinal thickness but differ significantly in all
sectors except the fovea for retinal volume because of the different areas
represented by the sectors. CONCLUSIONS: Failure to explicitly note the scale of 
the optical coherence tomography display can potentially misdirect planned focal 
and grid laser treatment for diabetic macular edema. Failure to explicitly verify
identical optical coherence tomography display scales in longitudinal studies of 
laser treatment for diabetic macular edema can potentially lead to errors in
interpreting treatment efficacy.

PMID: 12967819 [PubMed - indexed for MEDLINE]

2490: Am J Ophthalmol. 2003 Sep;136(3):542-5.

Autosomal dominant Stargardt-like macular dystrophy: identification of a new
family with a mutation in the ELOVL4 gene.

Vrabec TR, Tantri A, Edwards A, Frost A, Donoso LA.

Henry and Corinne Bower Laboratory, the Eye Research Institute and Wills Eye
Hospital, Philadelphia, Pennsylvania 19107, USA.

PURPOSE: To describe the clinical features and identify the mutation responsible 
for an autosomal dominant macular degeneration occurring in a four-generation
family. METHODS: Family members underwent clinical examination and genealogical
characterization. Mutation screening of the ELOVL4 gene was performed. RESULTS:
Patients reported visual loss occurring at a mean age of 20 years. Fundus
examination revealed varying degrees of central macular atrophy with or without
flecks in all affected individuals. DNA sequence analysis showed a 5-bp deletion 
in exon 6 of the ELOVL4 gene, confirming the diagnosis of autosomal dominant
Stargardt-like macular dystrophy. Genealogical analysis showed that this family
represents a new affected branch of a previously described 12-generation family
(31 branches) with this disorder. CONCLUSIONS: We characterized a new branch of a
family with autosomal dominant Stargardt-like macular dystrophy. Identification
of the disease-causing gene allows for improved genetic counseling of affected
individuals.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12967813 [PubMed - indexed for MEDLINE]

2491: Am J Ophthalmol. 2003 Sep;136(3):419-25.

Comment in:
    Am J Ophthalmol. 2004 Mar;137(3):596; author reply 596-7.

Intravitreal triamcinolone acetonide in eyes with cystoid macular edema
associated with central retinal vein occlusion.

Park CH, Jaffe GJ, Fekrat S.

Duke University Eye Center, Durham, North Carolina 27710, USA.

PURPOSE: To evaluate treatment of cystoid macular edema associated with central
retinal vein occlusion with intravitreal triamcinolone acetonide. METHODS: This
study included 10 eyes of nine patients with perfused central retinal vein
occlusion with visual acuity of 20/50 or worse. Following baseline evaluation,
including best-corrected visual acuity, intraocular pressure (IOP), fluorescein
angiography, and volumetric optical coherence tomography (VOCT), triamcinolone
acetonide (4 mg in 0.1 ml) was injected into the vitreous cavity. RESULTS: Mean
duration from the time of diagnosis to the intravitreal injection was 15.4
months. All 10 eyes demonstrated biomicroscopic improvement in cystoid macular
edema with corresponding improvement in VOCT measurements from a mean of 4.2
mm(3) preinjection to a mean of 2.6 mm(3) at last follow-up (P <.001). Mean
best-corrected visual acuity improved from 58 letters (range, 37-72) at baseline 
to 78 letters (range, 50-100 letters) at last follow-up (average, 4.8 months).
The visual acuity improvement was statistically significant (P =.01). Six eyes
(60%) were > or =20/50. There were no significant complications. Three eyes (30%)
without previous history of glaucoma required initiation of topical aqueous
suppressant therapy for IOP elevation at last follow-up. One eye with a previous 
history of open-angle glaucoma required a trabeculectomy. CONCLUSIONS:
Intravitreal injection of triamcinolone acetonide appears to be effective in
reducing cystoid macular edema associated with central retinal vein occlusion.
This reduction often corresponded to an improvement in visual acuity. Further
evaluation is warranted to assess its safety and efficacy in these eyes.

Publication Types: 
    Case Reports
    Research Support, U.S. Gov't, P.H.S.

PMID: 12967793 [PubMed - indexed for MEDLINE]

2492: Am J Ophthalmol. 2003 Sep;136(3):407-18.

Effect of lesion size, visual acuity, and lesion composition on visual acuity
change with and without verteporfin therapy for choroidal neovascularization
secondary to age-related macular degeneration: TAP and VIP report no. 1.

Blinder KJ, Bradley S, Bressler NM, Bressler SB, Donati G, Hao Y, Ma C, Menchini 
U, Miller J, Potter MJ, Pournaras C, Reaves A, Rosenfeld PJ, Strong HA, Stur M,
Su XY, Virgili G; Treatment of Age-related Macular Degeneration with Photodynamic
Therapy study group; Verteporfin in Photodynamic Therapy study group.

nmboffice@jhmi.edu

PURPOSE: To determine whether differences in baseline lesion size and visual
acuity might explain differing results found in three different lesion
compositions (predominantly classic, minimally classic, and occult with no
classic) among three placebo-controlled, randomized clinical trials evaluating
photodynamic therapy with verteporfin (Visudyne, Novartis AG), also termed
verteporfin therapy, in patients with subfoveal choroidal neovascularization
(CNV) due to age-related macular degeneration (AMD). METHODS: Exploratory
analyses were conducted in patients with predominantly classic or minimally
classic lesions at enrollment in the Treatment of AMD with Photodynamic Therapy
(TAP) Investigation and in AMD patients with occult with no classic CNV in the
Verteporfin In Photodynamic Therapy (VIP) Trial. Baseline characteristics of
patients among these three lesion compositions were compared. In addition,
multiple linear regression modeling was used to explore the effect of baseline
lesion size, visual acuity, and lesion composition on mean change in visual
acuity from baseline to 24 months. RESULTS: At baseline, the mean size of
predominantly classic lesions (3.4 disk areas) was smaller than that of minimally
classic (4.7 disk areas) and occult with no classic lesions (4.3 disk areas). In 
the multiple linear regression model of individual lesion compositions, there was
a significant treatment-by-lesion-size interaction for minimally classic and
occult with no classic lesions, but not for predominantly classic lesions.
Interaction between treatment and baseline visual acuity was not significant for 
any lesion composition. Small verteporfin-treated lesions lost less vision than
large verteporfin-treated lesions in each lesion composition. In the multiple
linear regression model that included all lesion compositions, lesion size was a 
more significant predictive factor for the magnitude of treatment benefit than
either lesion composition or visual acuity. Smaller (4.0 disk areas or less)
minimally classic and occult with no classic lesions had similar visual acuity
outcomes to those observed in predominantly classic lesions. CONCLUSIONS: Based
on exploratory analyses, lesion size in the TAP Investigation and VIP Trial was
an important predictor of the magnitude of treatment benefit with verteporfin
therapy in occult with no classic and minimally classic lesion compositions. In
patients with AMD, treating smaller rather than larger neovascular lesions,
regardless of lesion composition, likely will result in a better level of visual 
acuity.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12967792 [PubMed - indexed for MEDLINE]

2493: Arch Ophthalmol. 2003 Sep;121(9):1303-10.

Longitudinal prevalence of major eye diseases.

Lee PP, Feldman ZW, Ostermann J, Brown DS, Sloan FA.

Department of Ophthalmology, School of Medicine, Department of Economics, and
Center for Health Policy, Law, and Management, Duke University, Durham, NC 27708,
USA.

OBJECTIVE: To describe the prevalence across time of 3 chronic eye diseases among
a representative cohort of elderly subjects. STUDY DESIGN: Longitudinal
observation of Medicare claims.Population A random sample of Medicare
beneficiaries 65 years and older, nationally representative at baseline. MAIN
OUTCOME MEASURES: Diagnosis of diabetic retinopathy, glaucoma, and age-related
macular degeneration. METHODS: Beneficiaries were followed from 1991 to 1999
unless mortality or enrollment in a health maintenance organization for 6 or more
months in a year intervened. Claims data were analyzed for the presence of codes 
from the International Classification of Diseases, Ninth Revision, Clinical
Modification, indicating 1 of the 3 conditions. Transitions between severity
stages were also evaluated. RESULTS: Of 20 325 beneficiaries in 1991, 10 476 were
available for analysis in 1999. The prevalence of diabetes mellitus increased
from 14.5% in 1991 to 25.6% by 1999, with diabetic retinopathy among persons with
diabetes mellitus increasing from 6.9% to 17.4%. Primary open-angle glaucoma
increased from 4.6% to 13.8%. The percentage of glaucoma suspects increased from 
1.5% to 6.5%, as did the percentage of narrow-angle glaucoma (0.7%-2.7%). The
prevalence of age-related macular degeneration increased from 5.0% to 27.1%.
Overall, the proportion of subjects with at least 1 of these 3 diseases increased
from 13.4% to 45.4%. CONCLUSIONS: The clinical diagnosis of major chronic eye
diseases associated with aging increased dramatically in a longitudinal sample.
At the end of 9 years, nearly half of the surviving Medicare beneficiaries had at
least 1 of these diseases.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12963614 [PubMed - indexed for MEDLINE]

2494: Arch Ophthalmol. 2003 Sep;121(9):1246-51.

Volumetric analysis of macular edema by scanning laser tomography in immune
recovery uveitis.

Bartsch DU, Aurora A, Rodanant N, Cheng L, Freeman WR.

University of California, San Diego, Shiley Eye Center, University of California,
San Diego, La Jolla, CA 92093, USA. dbartsch@ucsd.edu

OBJECTIVES: To evaluate the macular volume in eyes with immune recovery uveitis
(IRU) and to describe a new method to quantify macular edema with the use of
confocal scanning laser tomography (cSLT). METHODS: A prospective study was
performed to assess the macular volume with cSLT in patients with and without
IRU. None of the patients enrolled had cytomegalovirus retinitis within 3000
micro m of the fovea. Eight eyes had healed cytomegalovirus retinitis with IRU
and cystoid macular edema (group A); 4 eyes had healed cytomegalovirus retinitis 
with IRU and clinically normal maculas (group B); 18 eyes had no IRU (group C);
and 3 eyes underwent pars plana vitrectomy and epiretinal membrane peeling for
epiretinal membranes associated with cystoid macular edema and IRU (group D).
Patients with IRU underwent standard clinical examinations and cSLT. On cSLT,
volume above the reference plane was calculated within a fovea-centered circle of
3 mm in diameter. We devised a novel system for defining the reference plane.
Measurements were performed 3 times in masked fashion and the mean was used for
analyses. RESULTS: The mean macular volume was highest in group A (1.97 mm3).
This was significantly higher (P<.001) than that in groups B (1.15 mm3), C (1.02 
mm3), and D (0.86 mm3). CONCLUSIONS: Macular edema in patients with IRU can be
consistently and objectively quantitated by cSLT. The method of defining the
reference plane used in our study is novel and can be used in other disorders
causing macular edema.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12963607 [PubMed - indexed for MEDLINE]

2495: J Med Genet. 2003 Sep;40(9):641-50.

The genetics of inherited macular dystrophies.

Michaelides M, Hunt DM, Moore AT.

Institute of Ophthalmology, University College London, London, UK.

The inherited macular dystrophies comprise a heterogeneous group of disorders
characterised by central visual loss and atrophy of the macula and underlying
retinal pigment epithelium (RPE). The different forms of macular degeneration
encompass a wide range of clinical, psychophysical and histological findings. The
complexity of the molecular basis of monogenic macular disease is now beginning
to be elucidated with the identification of many of the disease-causing genes.
Age related macular degeneration (ARMD), the leading cause of blind registration 
in the developed world, may also have a significant genetic component to its
aetiology. Genes implicated in monogenic macular dystrophies are good candidate
susceptibility genes for ARMD, although to date, with the possible exception of
ABCA4, none of these genes have been shown to confer increased risk of ARMD. The 
aim of this paper is to review current knowledge relating to the monogenic
macular dystrophies, with discussion of currently mapped genes, chromosomal loci 
and genotype-phenotype relationships. Inherited systemic disorders with a macular
dystrophy component will not be discussed.

Publication Types: 
    Review

PMID: 12960208 [PubMed - indexed for MEDLINE]

2496: Ophthalmic Physiol Opt. 2003 Sep;23(5):383-99.

Comment in:
    Ophthalmic Physiol Opt. 2004 Jan;24(1):61; author reply 61.

Age-related macular degeneration and nutritional supplementation: a review of
randomised controlled trials.

Bartlett H, Eperjesi F.

Neurosciences Research Institute, School of Life and Health Sciences, Aston
University, Aston Triangle, Birmingham B4 7ET, UK. bartlehe@aston.ac.uk

Age-related macular degeneration (AMD) is the leading cause of severe vision loss
in the developed world. The lack of effective treatment modalities, coupled with 
evidence supporting an oxidative pathogenesis, has increased interest in the
potential preventative role of nutritional supplementation. This article reviews 
seven randomised controlled trials (RCTs) that have investigated the role of
nutritional supplementation in AMD. Three of these trials reported a positive
effect of nutritional supplementation on AMD; the Age-related eye study (AREDS), 
the Lutein Antioxidant Supplementation Trial (LAST), and the oral zinc trial by
Newsome et al. (1988). However, the oral zinc trial by Newsome et al. (1988) was 
unlikely to detect any difference between treatments smaller than 72%, and the
AREDS results were based on a subgroup of their study population. Lutein was
considered for the AREDS formulation, but was not commercially available at that 
time. The findings of the LAST support a possible therapeutic role of lutein in
AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 12950886 [PubMed - indexed for MEDLINE]

2497: Am J Hum Genet. 2003 Oct;73(4):780-90. Epub 2003 Aug 22.

A genomewide scan for age-related macular degeneration provides evidence for
linkage to several chromosomal regions.

Seddon JM, Santangelo SL, Book K, Chong S, Cote J.

Ophthalmology/Epidemiology Unit, Massachusetts Eye and Ear Infirmary, Harvard
Medical School, Boston, MA 02114, USA. Johanna_Seddon@meei.harvard.edu

We report the results of a genomewide scan for age-related macular degeneration
(AMD) in 158 multiplex families. AMD classification was based on fundus
photography and was assigned a grade ranging from 1 (no disease) to 5 (exudative 
disease). Genotyping was performed by the National Heart, Lung, and Blood
Institute Mammalian Genotyping Service at Marshfield (404 short tandem repeat
markers). The sample included 158 families with two or more siblings with AMD,
490 affected individuals, 101 unaffected individuals, and 38 whose affection
status was unknown. Relative pairs included 511 affected sibling, 28 avuncular,
53 cousin, 7 grandparent-grandchild, and 9 grand-avuncular pairs. Two-point
parametric and multipoint parametric and nonparametric analyses were performed.
Maximum two-point LOD scores of 1.0-2.0 were found for markers on chromosomes 1, 
2, 8, 10, 14, 15, and 22. Multipoint analyses were consistent with the two-point 
results for chromosomes 1, 2, 8, 10, and 22 and provided evidence for additional 
linkage regions on chromosomes 3, 6, 8, 12, 16, and X. Our signals on chromosomes
1q, 6p, and 10q are consistent with some other previously published results.
Significant linkage to AMD was found for one marker on chromosome 2, two adjacent
markers on chromosome 3, two adjacent markers on chromosome 6, and seven
contiguous markers on chromosome 8, with empirical P values of .00001. The
consistency of many of the other signals across both two-point and multipoint, as
well as parametric and nonparametric, analyses indicate several other regions
worthy of follow-up.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12945014 [PubMed - indexed for MEDLINE]

2498: Hum Mol Genet. 2003 Oct 15;12(20):2657-67. Epub 2003 Aug 27.

Mutation in a short-chain collagen gene, CTRP5, results in extracellular deposit 
formation in late-onset retinal degeneration: a genetic model for age-related
macular degeneration.

Hayward C, Shu X, Cideciyan AV, Lennon A, Barran P, Zareparsi S, Sawyer L, Hendry
G, Dhillon B, Milam AH, Luthert PJ, Swaroop A, Hastie ND, Jacobson SG, Wright AF.

MRC Human Genetics Unit, Western General Hospital, Edinburgh, UK.

A primary feature of age-related macular degeneration (AMD) is the presence of
extracellular deposits between the retinal pigment epithelium (RPE) and
underlying Bruch's membrane, leading to RPE dysfunction, photoreceptor death and 
severe visual loss. AMD accounts for about 50% of blind registrations in Western 
countries and is a common, genetically complex disorder. Very little is known
regarding its molecular basis. Late-onset retinal degeneration (L-ORD) is an
autosomal dominant disorder with striking clinical and pathological similarity to
AMD. Here we show that L-ORD is genetically heterogeneous and that a proposed
founder mutation in the CTRP5 (C1QTNF5) gene, which encodes a novel short-chain
collagen, changes a highly conserved serine to arginine (Ser163Arg) in 7/14 L-ORD
families and 0/1000 control individuals. The mutation occurs in the gC1q domain
of CTRP5 and results in abnormal high molecular weight aggregate formation which 
may alter its higher-order structure and interactions. These results indicate a
novel disease mechanism involving abnormal adhesion between RPE and Bruch's
membrane.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12944416 [PubMed - indexed for MEDLINE]

2499: Diabetes Care. 2003 Sep;26(9):2653-64.

Diabetic retinopathy and diabetic macular edema: pathophysiology, screening, and 
novel therapies.

Ciulla TA, Amador AG, Zinman B.

Midwest Eye Institute, Indianapolis, Indiana, USA.

Diabetic retinopathy (DR) and diabetic macular edema (DME) are leading causes of 
blindness in the working-age population of most developed countries. The
increasing number of individuals with diabetes worldwide suggests that DR and DME
will continue to be major contributors to vision loss and associated functional
impairment for years to come. Early detection of retinopathy in individuals with 
diabetes is critical in preventing visual loss, but current methods of screening 
fail to identify a sizable number of high-risk patients. The control of
diabetes-associated metabolic abnormalities (i.e., hyperglycemia, hyperlipidemia,
and hypertension) is also important in preserving visual function because these
conditions have been identified as risk factors for both the development and
progression of DR/DME. The currently available interventions for DR/DME, laser
photocoagulation and vitrectomy, only target advanced stages of disease. Several 
biochemical mechanisms, including protein kinase C-beta activation, increased
vascular endothelial growth factor production, oxidative stress, and accumulation
of intracellular sorbitol and advanced glycosylation end products, may contribute
to the vascular disruptions that characterize DR/DME. The inhibition of these
pathways holds the promise of intervention for DR at earlier
non-sight-threatening stages. To implement new therapies effectively, more
individuals will need to be screened for DR/DME at earlier stages-a process
requiring both improved technology and interdisciplinary cooperation among
physicians caring for patients with diabetes.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 12941734 [PubMed - indexed for MEDLINE]

2500: Invest Ophthalmol Vis Sci. 2003 Sep;44(9):4061-8.

Improved contrast of subretinal structures using polarization analysis.

Burns SA, Elsner AE, Mellem-Kairala MB, Simmons RB.

The Schepens Eye Research Institute, Boston, Massachusetts 02114, USA.
sburns@vision.eri.harvard.edu

PURPOSE: To improve the ability to detect and quantify the early retinal changes 
associated with aging, age-related maculopathy, and age-related macular
degeneration. METHODS: A computational approach was implemented for analyzing
images using a readily available polarimeter that is used for glaucoma diagnosis.
This device, the GDx Nerve Fiber Analyzer (Laser Diagnostic Technologies, Inc.,
San Diego, CA), takes a series of images as a function of the polarization angle 
of the illuminating light. For each of 20 input polarizations, pairs of retinal
images are digitized. One image is made of the light returning from the eye that 
is polarized parallel to the input light, and the other image is made of the
light that is rotated by 90 degrees from the input polarization. Using the raw
data from these 40 images, and a simplified model of the polarization properties 
of the eye, we calculated the amount of light that returns in a parallel
polarized state, and the amount of light that is depolarized by multiple
scattering. Measurements were made in seven subjects with small drusen. RESULTS: 
The depolarized light image produced a 3.4 times higher contrast of drusen and
subretinal changes than the parallel polarized light images. CONCLUSIONS:
Polarization-sensitive imaging combined with a simple computational approach
allows the measurement of the retinal distribution of multiply scattered light.
With this technique, retinal imaging of age-related changes in retinal and
subretinal tissue can be improved.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12939329 [PubMed - indexed for MEDLINE]

2501: Invest Ophthalmol Vis Sci. 2003 Sep;44(9):3778-82.

Relationship between refraction and prevalent as well as incident age-related
maculopathy: the Rotterdam Study.

Ikram MK, van Leeuwen R, Vingerling JR, Hofman A, de Jong PT.

Department of Epidemiology and Biostatistics, Erasmus Medical Center, Rotterdam, 
The Netherlands.

PURPOSE: To study the relationship between baseline spherical equivalents (SphE) 
of refraction and prevalent as well as incident age-related maculopathy (pARM and
iARM, respectively). METHODS: The study was performed as part of the Rotterdam
Study, a population-based, prospective cohort study. The SphE (in diopters),
measured with autorefraction and subjective optimization, was recorded in 6209
subjects aged 55 years or more. Aphakic or pseudophakic eyes at baseline were
excluded. Stereoscopic transparencies of the macular region were graded according
to the International Classification and Grading System. ARM was defined as large 
soft drusen with pigmentary changes, or indistinct drusen, or atrophic or
neovascular age-related macular degeneration (AMD). For the prevalence analyses, 
ARM was classified into no, p(early)ARM, or pAMD, and in each subject the eye
with the most advanced ARM and the corresponding refraction was selected. After a
mean 5.2 years of follow-up, 4935 subjects had complete data for these incidence 
analyses. In each subject, the eye with iARM was selected. RESULTS: The age- and 
gender-adjusted odds ratio (OR) of pARM (n = 536) for every diopter of progress
toward hyperopia was 1.09 (95% confidence interval [CI]1.04-1.13). For
p(early)ARM (n = 440) the OR was 1.09 (1.04-1.14) and for pAMD (n = 96) the OR
was 1.09 (1.00-1.19). Baseline refraction was significantly associated with
increased risk of iARM (n = 497). For each diopter of progress toward hyperopia
the OR was 1.05 (95% CI 1.01-1.10). Additional adjustments for smoking,
atherosclerosis, and blood pressure did not alter the relationship. CONCLUSIONS: 
These population-based incidence data confirm results from prevalence and
case-control studies that there is an association between hyperopia and ARM.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12939291 [PubMed - indexed for MEDLINE]

2502: Invest Ophthalmol Vis Sci. 2003 Sep;44(9):3771-7.

Blood pressure, atherosclerosis, and the incidence of age-related maculopathy:
the Rotterdam Study.

van Leeuwen R, Ikram MK, Vingerling JR, Witteman JC, Hofman A, de Jong PT.

Department of Epidemiology and Biostatistics, Erasmus Medical Center, Rotterdam, 
The Netherlands.

PURPOSE: To determine whether blood pressure and subclinical atherosclerosis are 
associated with incident age-related maculopathy (ARM). METHODS: The study was
performed within the Rotterdam Study, a population-based, prospective cohort
study in Rotterdam, The Netherlands. A total of 4822 subjects who at baseline
were aged 55 years more, were free of ARM, and participated in at least one of
two follow-up examinations after a mean of 2 and 6.5 years, were included in the 
study. At baseline, blood pressure and the presence of atherosclerosis were
determined. ARM was assessed according to the International Classification and
Grading System and defined as large, soft drusen with pigmentary changes;
indistinct drusen; or atrophic or neovascular age-related macular degeneration.
RESULTS: After a mean follow-up of 5.2 years, incident ARM was diagnosed in 417
subjects. Increased systolic blood pressure or pulse pressure was associated with
a higher risk of ARM. Adjusted for age, gender, smoking, total and high-density
lipoprotein cholesterol, body mass index, and diabetes mellitus, odds ratios (OR)
per 10-mm Hg increase were 1.08 (95% confidence interval [CI]: 1.03-1.14) and
1.11 (95% CI: 1.04-1.18), respectively. Moreover, different measures of
atherosclerosis were associated with the risk of ARM. An increase in carotid wall
thickness (OR per 1 SD, 1.15; 95% CI: 1.03-1.28) increased the risk of ARM. The
lowest compared with the highest tertile of ankle-arm index had an OR of 1.32
(95% CI: 1.00-1.75). A weak association was found between aortic calcifications
and the risk of ARM. CONCLUSIONS: Elevated systolic blood or pulse pressure or
the presence of atherosclerosis may increase the risk of development of ARM.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12939290 [PubMed - indexed for MEDLINE]

2503: Graefes Arch Clin Exp Ophthalmol. 2003 Sep;241(9):710-5. Epub 2003 Aug 23.

Electro-oculographic findings after 360 degrees retinotomy and macular
translocation for subfoveal choroidal neovascularisation in age-related macular
degeneration.

Lüke C, Alteheld N, Aisenbrey S, Lüke M, Bartz-Schmidt KU, Walter P, Kirchhof B.

Center of Ophthalmology, Department of Vitreoretinal Surgery, University of
Cologne, Joseph-Stelzmann-Strasse 9, 50924 Cologne, Germany. aia18@uni-koeln.de

PURPOSE: To evaluate potential electro-oculographic changes after 360 degrees
retinotomy and macular translocation for subfoveal choroidal neovascularisation
in patients with age-related macular degeneration (AMD) in a randomised
comparative (self-controlled) trial. METHODS: A consecutive series of 30 patients
suffering from subfoveal choroidal neovascularisation secondary to age-related
macular degeneration underwent 360 degrees retinotomy and macular translocation. 
The EOG served as the main parameter of the study and was recorded 1 day prior to
the translocation surgery and no earlier than 21 days after the silicone oil
removal. RESULTS: Postoperatively, a statistically significant decrease in mean
dark trough by 64% was found for treated eyes (P<0.001). The mean dark trough of 
the fellow eye remained stable after surgery (P=0.33). The postoperative
difference between the treated und untreated eyes proved to be statistically
significant (P<0.001). The Arden ratio remained stable in the treated and
untreated eyes with mean values of 204% (P=0.81) and 213% (P=0.18), respectively.
A significant correlation between the reduction of the dark trough and the visual
acuity at the 1-year follow-up was found. CONCLUSIONS: A persistent decrease in
the corneofundal potential is associated with 360 degrees retinotomy and macular 
translocation for exudative AMD. This indicates a substantial postoperative
malfunction of retinal pigment epithelial cells and an impaired photoreceptor
regeneration. The impeded recovery of the RPE-photoreceptor complex can be
interpreted as the result of the surgical trauma on the basis of prediseased RPE.
A severe postoperative decrease in dark trough forecasts an incomplete recovery
of visual acuity.

PMID: 12937992 [PubMed - indexed for MEDLINE]

2504: Graefes Arch Clin Exp Ophthalmol. 2003 Oct;241(10):785-91. Epub 2003 Aug
20.

Filling-in phenomenon in patients with age-related macular degeneration:
differences regarding uni- or bilaterality of central scotoma.

Cohen SY, Lamarque F, Saucet JC, Provent P, Langram C, LeGargasson JF.

INSERM U 483, Laboratoire de Biophysique de la Vision, 10 Avenue de Verdun, 75010
Paris, France.

PURPOSE: The purpose of this study was to explore the presence of the filling-in 
phenomenon in patients with uni- or bilateral central scotoma (CS) resulting from
natural history or laser photocoagulation of choroidal neovascularization in
age-related macular degeneration (AMD). METHODS: Sixteen consecutive patients
with unilateral CS and 14 patients with bilateral CS were assessed (44 eyes) with
a scanning laser ophthalmoscope (SLO). Scotoma was delineated by scotometry with 
a point (1 degree x1 degree) moving radially from the periphery to the center of 
the lesion. In addition, patients underwent a line test, consisting of a
horizontal line moving vertically and a vertical line moving horizontally, from
the periphery to the center. The lines were longer than the macular lesion and
were projected onto the retina. Patients were asked to indicate when the lines
seemed interrupted. The perceptual filling-in phenomenon was considered to be
present when limits of the perceived scotoma, determined by the line test, were
smaller than those assessed by scotometry. In patients with bilateral CS, the
results were analyzed to distinguish the less or more severely affected eye.
RESULTS: In all eyes, the limits of the scotoma obtained with the scotometry test
corresponded to the anatomic edges of the macular lesion. In patients with
bilateral CS, the filling-in phenomenon was observed in 12 out of 14 (85%) less
severely affected eyes, but only in one (7%) of their more severely affected
eyes. In patients with unilateral CS, the phenomenon was observed in only one out
of 16 (6%) eyes. CONCLUSION: These results suggest that the filling-in phenomenon
mostly occurs in patients with bilateral central scotoma, and almost always in
their less affected eye. Thus, it did usually not occur in an eye if the fellow
eye was better.

PMID: 12928905 [PubMed - indexed for MEDLINE]

2505: Eye. 2003 Aug;17(6):762-6.

Evaluation of the effect of acetazolamide on cystoid macular oedema in patients
with Behcet's disease.

Lashay AR, Rahimi A, Chams H, Davatchi F, Shahram F, Hatmi ZN, Khalkhali H, Beigi
B.

Department of Ophthalmology Tehran Medical Sciences University Tehran, Iran.

AIM: To study the effect of acetazolamide on cystoid macular oedema (CMO) in
patients with Behcet's disease. PATIENTS AND METHODS: A total of 67 eyes of 35
Behcet's patients with chronic, but well-controlled uveitis, and CMO were
randomised into a double-masked, crossover trial comparing the effect of
acetazolamide vs placebo. The patients received an initial 4-week course of
either 250 mg acetazolamide twice daily (b.i.d.) or placebo, followed by a 4-week
washout period. They then received a 4-week course of the reverse study
medication. An improvement in visual acuity and fundus fluorescein angiographic
findings was assessed. RESULTS: In total, 29 patients (55 eyes) completed the
trial and were available for analysis. Of the 29, 16 men and 13 were women. The
age range was 13-50 years (mean 33.6 years). Patients on acetazolamide showed a
slightly better improvement of angiographic signs (at least by one grade
improvement) over that of placebo (12 vs five eyes). They also had less
deterioration of angiographic signs over that of placebo (three vs seven eyes).
However, these findings were not statistically significant (P=0.99).
Acetazolamide had no statistically significant effect (P=0.53) on the improvement
of visual acuity of patients over that of placebo (13 vs eight eyes), nor on the 
deterioration of visual acuity (three vs 11 eyes). CONCLUSION: Despite seemingly 
favourable results, the 4-week course of acetazolamide (250 mg b.i.d.) has no
statistically significant effect on the improvement of the visual acuity and the 
fluorescein angiographic findings in Behcet's patients with CMO.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 12928692 [PubMed - indexed for MEDLINE]

2506: Eye. 2003 Aug;17(6):717-26.

Adult vitelliform macular degeneration: a clinicopathological study.

Arnold JJ, Sarks JP, Killingsworth MC, Kettle EK, Sarks SH.

Marsden Eye Centre Sydney, Australia.

AIMS/BACKGROUND: The yellow lesions of adult vitelliform macular degeneration
(AVMD) slowly fade, progressing to hyperpigmentation or atrophy. This study aims 
to provide further observations on the location and nature of the vitelliform
material. METHODS: This report describes the clinicopathological correlation of
four eyes with AVMD. A retrospective histopathological study of a further 526
aged eyes previously graded for the stage of age-related macular degeneration
(AMD) found another 10 eyes with similar pathology. RESULTS: The predominant
finding was a collection of extracellular material beneath the sensory retina at 
the fovea. This material was derived internally from photoreceptor outer segments
and externally from the retinal pigment epithelium (RPE), the latter first
undergoing hypertrophy and then disruption and attenuation. Fallout of foveal
cones occurred over these lesions and the inner retina was thinned, which may
explain macular hole formation in this condition. All affected eyes showed
histopathological evidence of AMD. CONCLUSIONS: This study confirms that the
vitelliform lesions of AVMD lie beneath the sensory retina. In contrast to
previous reports, however, it is proposed that the lesions comprise mainly
extracellular material consisting of photoreceptor debris, possibly the result of
faulty phagocytosis by the RPE, mixed with pigment liberated as the RPE undergoes
disruption. The vitelliform lesions therefore are a marker for the area of
maximal RPE disturbance.

Publication Types: 
    Case Reports

PMID: 12928683 [PubMed - indexed for MEDLINE]

2507: Br J Ophthalmol. 2003 Sep;87(9):1159-66.

Differential expression of GFAP in early v late AMD: a quantitative analysis.

Wu KH, Madigan MC, Billson FA, Penfold PL.

Department of Clinical Ophthalmology, Save Sight Institute, University of Sydney,
Sydney NSW 2006, Australia. ppenfold@eye.usyd.edu.au

BACKGROUND/AIMS: Glial fibrillary acidic protein (GFAP) is an established
indicator of retinal stress; its expression in retinal astrocytes and Müller
cells has been demonstrated to be modulated by cytokines and retinal pathology,
including age related macular degeneration (AMD). This study aims to quantify the
modulation of GFAP expression in retinas with drusen and atrophic AMD versus
normal age matched controls. METHODS: Following a histopathological survey, 17
donor retinas were classified into four groups: drusen (n=5), geographic atrophy 
(GA) (n=6), aged normal (n=3), and young normal (n=3). Paramacular cryosections
were immunolabelled with GFAP antibody, examined by confocal microscopy, and
quantified by NIH digital image analysis. Groups were matched for potential
confounding factors including age, sex, and postmortem delay. RESULTS: A
significant increase in GFAP immunolabelling of macroglia was noted in aged
normal compared with young normal retinas (p<0.04). Upregulation of GFAP
immunoreactivity involving astrocytes was observed in drusen retinas compared
with control retinas (p<0.03). GFAP was also upregulated in retinas with GA
compared with controls (p<0.05) and in retinas with GA compared with drusen
(p<0.04), both involving Müller cells. Discrete regions of GFAP upregulation in
Müller cells were associated with drusen formation. In GA specimens atrophied
retinal pigment epithelium (RPE) was substituted by GFAP immunoreactive Müller
cell processes (gliosis). CONCLUSION: This study provides a quantitative
assessment of GFAP modulation in ageing and AMD affected retinas. Morphological
observations were consistent with quantitative analyses indicating differential
modulation of GFAP immunoreactivity in inner and outer retina. Upmodulation of
GFAP in inner retina and astroglial processes was predominantly associated with
drusen, while in outer retina Müller glia upmodulation of GFAP was associated
with disruption of the RPE and blood-retinal barrier.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12928288 [PubMed - indexed for MEDLINE]

2508: Br J Ophthalmol. 2003 Sep;87(9):1121-5.

The association between statin use and age related maculopathy.

McGwin G Jr, Owsley C, Curcio CA, Crain RJ.

Department of Ophthalmology, School of Medicine, University of Alabama at
Birmingham, Birmingham, AL , USA. mcgwin@eyes.uab.edu

AIMS: To evaluate the association between age related maculopathy (ARM) and
statin use. METHODS: A nested case-control study among patients at the Veterans
Affairs Medical Center in Birmingham, Alabama, with newly diagnosed ARM (cases)
between 1997 to 2001 were selected and age matched to non-ARM controls. RESULTS: 
550 incident cases of ARM were identified and matched to 5500 controls. Overall, 
cases were 70% (OR 0.30, 95% CI 0.21 to 0.45) less likely to have received and
filled a statin prescription relative to the controls. This association was
present among both current and past (OR 0.34, 95% CI 0.21 to 0.53 and OR 0.26,
95% CI 0.14 to 0.47, respectively) statin users. When considering use of statin
and/or non-statin lipid lowering medications, a significant risk reduction was
observed for statin only users (OR 0.30, 95% CI 0.20 to 0.45) and combined statin
and non-statin users (OR 0.20, 95% CI 0.06 to 0.64); there was no significant
association for non-statin only users (OR 0.47, 95% CI 0.20 to 1.13).
CONCLUSIONS: The results of this study suggest that subjects with ARM were
significantly less likely to have filled a statin prescription. Future clinical
research initiatives should include a clinical trial to provide direct evidence
of the effectiveness of statins in lowering the incidence and progression of ARM.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12928279 [PubMed - indexed for MEDLINE]

2509: J Biol Chem. 2003 Oct 24;278(43):42027-35. Epub 2003 Aug 15.

Carboxyethylpyrrole protein adducts and autoantibodies, biomarkers for
age-related macular degeneration.

Gu X, Meer SG, Miyagi M, Rayborn ME, Hollyfield JG, Crabb JW, Salomon RG.

Department of Chemistry, Case Western Reserve University, 10900 Euclid Avenue,
Cleveland, Ohio 44106, USA.

Age-related macular degeneration (AMD) is a slow, progressive disease with both
genetic and environmental risk factors. Free radical-induced oxidation of
docosahexaenoate (DHA)-containing lipids generates omega-(2-carboxyethyl)pyrrole 
(CEP) protein adducts that are more abundant in ocular tissues from AMD than
normal human donors. To understand better the role of oxidative damage in AMD, we
have synthesized CEP-modified proteins, produced anti-CEP antibodies, and
initiated analysis of CEP immunoreactivity and autoantibodies in human plasma. A 
highly selective rabbit polyclonal anti-CEP antibody was raised that binds CEP
1000 times more strongly than carboxypropylpyrrole, a close structural analogue. 
The CEP adduct uniquely indicates oxidative modification from DHA derivatives
because CEP protein modifications cannot arise from any other common
polyunsaturated fatty acid. Immunocytochemistry localized CEP to photoreceptor
rod outer segments and retinal pigment epithelium in mouse retina and
demonstrated more intense CEP immunoreactivity in photoreceptors from a human AMD
donor compared with healthy human retina. The mean level of anti-CEP
immunoreactivity in AMD human plasma (n = 19 donors) was 1.5-fold higher (p =
0.004) than in age-matched controls (n = 19 donors). Sera from AMD patients
demonstrated mean titers of anti-CEP autoantibody 2.3-fold higher than controls
(p = 0.02). Of individuals (n = 13) exhibiting both antigen and autoantibody
levels above the mean for non-AMD controls, 92% had AMD. These results suggest
that together CEP immunoreactivity and autoantibody titer may have diagnostic
utility in predicting AMD susceptibility.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.

PMID: 12923198 [PubMed - indexed for MEDLINE]

2510: Ther Apher Dial. 2003 Apr;7(2):263-8.

The effect of membrane differential filtration on the colloid osmotic pressure in
patients with age-related macular degeneration: significance to visual function?

Lüke C, Widder RA, Walter P, Brunner R, Kirchhof B, Borberg H.

Center of Ophthalmology, Department of Vitreoretinal Surgery, University of Köln,
Köln, Germany. aia18@unikoeln.de

To investigate the effect of membrane differential filtration (MDF) on plasma
colloid osmotic pressure (COP) and visual functions in age-related geographic
macular degeneration (AMD). Ten consecutive patients with non-exudative AMD
underwent one MDF cycle. Primary endpoint was COP. Secondary endpoints were
visual acuity and the mean defect of visual field. The COP was markedly reduced
after one MDF cycle by 23.9% (P = 0.001). Compared with the baseline examination,
visual acuity and the mean defect of visual field improved significantly after
MDF. A significant positive correlation was found between the improvement in
visual field and the decrease in COP (Pearson's coefficient = 0.65; P = 0.04).
Membrane differential filtration lowers plasma colloid osmotic pressure in
patients with non-exudative AMD. Based on the observation that visual field and
COP are correlated, one may hope for a means to improve decreased central retinal
function in eyes with geographic AMD by modulation of COP plasma level.

PMID: 12918954 [PubMed - indexed for MEDLINE]

2511: Ophthalmology. 2003 Aug;110(8):1540-4.

Grading of age-related maculopathy for epidemiological studies: is digital
imaging as good as 35-mm film?

van Leeuwen R, Chakravarthy U, Vingerling JR, Brussee C, Hooghart AJ, Mulder PG, 
de Jong PT.

Department of Epidemiology and Biostatistics, and EUREYE Grading Center, Erasmus 
Medical Center, Rotterdam, The Netherlands.

PURPOSE: To compare stereo digital images with stereo 35-mm color transparencies 
as to the quality and reliability of grading age-related maculopathy (ARM) in the
context of a multicenter European epidemiologic study (the EUREYE Study). DESIGN:
Instrument validation study. PARTICIPANTS: Ninety-one subjects (137 eyes) with
varying degrees of ARM, including no ARM. METHODS: From both eyes of the
participants, 35-mm film and digital stereoscopic fundus images were obtained
with two identical Topcon fundus cameras. Two experienced graders classified all 
signs of ARM according to the International Classification System. Agreement
between imaging techniques and between graders was calculated using the weighted 
kappa statistic. MAIN OUTCOME MEASURES: Signs of ARM (number, size, and
morphologic characteristics of drusen; pigmentary changes; geographic atrophy;
and neovascular macular degeneration) as well as an overall staging system of
increasing ARM severity. RESULTS: The weighted kappa value for between-technique 
agreement ranged from 0.41 for number of drusen <63 microm to 0.79 for drusen
type and total area occupied by drusen. The kappa values for atrophic and
neovascular end-stage ARM were 0.87 and 0.94, respectively. The between-technique
agreement on stages of ARM was approximately 0.76. The agreement between graders 
was largely the same for both techniques of imaging. CONCLUSIONS: In the
described setting, digital images were as good as 35-mm film for the grading of
ARM. Considering the practical advantages of digital imaging, this technique may 
serve well in epidemiologic studies of ARM.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't
    Validation Studies

PMID: 12917169 [PubMed - indexed for MEDLINE]

2512: Ophthalmology. 2003 Aug;110(8):1534-9.

Incidence of exudative age-related macular degeneration among elderly Americans.

Javitt JC, Zhou Z, Maguire MG, Fine SL, Willke RJ.

Wilmer Ophthalmological Institute, Johns Hopkins University, Baltimore, Maryland,
USA. jjavitt@healthdirections.net

PURPOSE: To estimate the 3-year incidence of exudative age-related macular
degeneration (AMD) and its treatment by laser photocoagulation in elderly
Americans. DESIGN: Population-based cohort study using insurance claims data.
PARTICIPANTS: A random 5% sample of Medicare beneficiaries, age 65 and older.
METHODS: Incidence of exudative AMD and of laser photocoagulation for this
condition was assessed based on four categories of ascertainment criteria that
included procedure and diagnosis codes associated with exudative AMD, choroidal
neovascularization, and its treatment. MAIN OUTCOME MEASURES: Incidence of AMD
and of associated laser photocoagulation. RESULTS: Overall, the 3-year incidence 
of exudative AMD is estimated to be between 9.4 per 1000 and 11.4 per 1000
Americans age 65 and older (depending on ascertainment criteria), based on those 
diagnosed and treated by ophthalmologists for the condition. These estimates
bracket the measured incidence of exudative AMD in the Beaver Dam Eye Study and
lie within its 95% confidence interval. The 3-year incidence of exudative AMD
with attendant laser photocoagulation was 2.3 per 1000. Women were found to have 
a slightly higher incidence of AMD than men using all ascertainment criteria (P <
0.001), and white Americans were found to have a fivefold-to-sixfold higher
ascertainment criteria than black Americans (P < 0.001). CONCLUSIONS: The
reported incidence of exudative AMD identified in the population of Medicare
beneficiaries suggests that measurements on incidence for this condition derived 
from the Beaver Dam Eye Study can be generalized to the U.S. population.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12917168 [PubMed - indexed for MEDLINE]

2513: Ophthalmology. 2003 Aug;110(8):1526-33.

The relationship between iris color, hair color, and skin sun sensitivity and the
10-year incidence of age-related maculopathy: the Beaver Dam Eye Study.

Tomany SC, Klein R, Klein BE; Beaver Dam Eye Study.

Department of Ophthalmology and Visual Sciences, University of Wisconsin Medical 
School, Madison, Wisconsin 53726-2397, USA.

PURPOSE: To examine the association between iris color, hair color, and skin sun 
sensitivity and the 10-year incidence of age-related maculopathy (ARM). DESIGN:
Population-based cohort study. PARTICIPANTS: A population of 4926 adults (range, 
43-86 years of age at baseline) living in Beaver Dam, Wisconsin, was studied at
baseline (1988-1990); of these, 3684 and 2764 subjects, respectively,
participated in 5-year and 10-year follow-up examinations. METHODS: Data on hair 
color at age 15 years and skin responsiveness to sun exposure were obtained from 
a standardized questionnaire administered at the baseline examination. Iris color
was determined with penlight illumination during the baseline examination by
using photographic standards. Age-related maculopathy status was determined by
grading stereoscopic color fundus photos with the Wisconsin Age-Related
Maculopathy Grading System. MAIN OUTCOME MEASURES: Incidence and progression of
ARM. RESULTS: When controlling for age and gender, people with brown eyes were
significantly more likely to develop soft indistinct drusen (risk ratio [RR],
1.53; 95% confidence interval [CI], 1.19-1.97; P < 0.01) than were people with
blue eyes. However, people with brown eyes were significantly less likely to
develop retinal pigment epithelial depigmentation (RR, 0.58; 95% CI, 0.41-0.82; P
< 0.01) than were people with blue eyes. When compared with persons with blond
hair, persons with brown hair were at decreased risk of developing pigmentary
abnormalities (RR, 0.73; 95% CI, 0.53-1.00; P = 0.05). Iris color, hair color,
and skin sun sensitivity were not associated with the development of late ARM.
CONCLUSION: Iris color and hair color were found to be associated with the
10-year incidence of pigmentary abnormalities. Iris color seems to be
inconsistently related to the 10-year incidence of early ARM lesions and the
progression of ARM.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12917167 [PubMed - indexed for MEDLINE]

2514: Ophthalmologica. 2003 Sep-Oct;217(5):351-7.

Mitotropic compounds for the treatment of age-related macular degeneration. The
metabolic approach and a pilot study.

Feher J, Papale A, Mannino G, Gualdi L, Balacco Gabrieli C.

Ophthalmic Neuroscience Program, Institute of Ophthalmology, University of Rome
La Sapienza, Rome, Italy. j.feher@agora.it

Recent histopathologic studies have shown that mitochondria and peroxisomes of
the retinal pigment epithelium may play a central role in the pathophysiology of 
age-related macular degeneration (AMD). We supposed that compounds which improve 
mitochondrial functions (mitotropic compounds) may show beneficial effects in
preventing AMD. Fourteen patients affected by early AMD were treated with a
mixture containing acetyl-L-carnitine (ALC), polyunsaturated fatty acids (PUFAs),
coenzyme Q10 (CoQ10) and vitamin E, while an equal number of age- and sex-matched
patients affected by early AMD were treated with vitamin E only. Recovery time
after macular photostress, foveal sensitivity and mean defect in the visual field
as well as blood lipid levels were recorded at the beginning and after 3, 6, 9,
12 and 24 months of follow-up. In the treated group, all the visual functions
showed slight improvement which was evident after 3 months of treatment and
remained nearly stationary by the end of 24 months. The same tests in the control
group showed slow worsening. The divergence between treated and control groups
became more marked with time, but the difference was not significant at any time 
of the follow-up. These findings suggest that the blend of ALC, PUFA, CoQ10 and
vitamin E may improve retinal functions in early AMD. Copyright 2003 S. Karger
AG, Basel

Publication Types: 
    Clinical Trial
    Comparative Study
    Controlled Clinical Trial

PMID: 12913326 [PubMed - indexed for MEDLINE]

2515: Arch Ophthalmol. 2003 Aug;121(8):1151-5.

Relation of statin use to the 5-year incidence and progression of age-related
maculopathy.

Klein R, Klein BE, Tomany SC, Danforth LG, Cruickshanks KJ.

Departments of Ophthalmology and Visual Sciences and Population Health Sciences, 
University of Wisconsin Medical School, Madison, WI 53726, USA.

OBJECTIVE: To examine the association of hydroxymethyl glutaryl coenzyme A
reductase inhibitors (statins) with the 5-year incidence of age-related
maculopathy (ARM). DESIGN: Population-based cohort study. Participants included
persons 48 to 91 years old examined March 1, 1993, through June 14, 1995, living 
in Beaver Dam, Wis (N = 3684), of whom 2780 participated in a follow-up 5 years
later. METHODS: Standardized procedures were used for physical examinations,
blood sample collection, and questionnaire administration. Age-related
maculopathy was determined by grading images of the posterior pole using a
standard protocol. Standard univariate and multivariate analyses were performed. 
MAIN OUTCOME MEASURES: Incidence and progression of ARM was measured over the
5-year interval. RESULTS: While controlling for age and sex, statin use was not
found to be associated with the 5-year incidence of early ARM (odds ratio [OR],
1.12; 95% confidence interval [CI], 0.47-2.67), progression of ARM (OR, 1.22; 95%
CI, 0.54-2.76), or incidence of late ARM (OR, 0.41; 95% CI, 0.12-1.45).
CONCLUSIONS: These findings do not suggest an association between statin use and 
incident ARM over a 5-year period. Further investigation of these relationships
in larger studies over a longer period is needed.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12912693 [PubMed - indexed for MEDLINE]

2516: Arch Ophthalmol. 2003 Aug;121(8):1099-105.

Maculas affected by age-related macular degeneration contain increased chelatable
iron in the retinal pigment epithelium and Bruch's membrane.

Hahn P, Milam AH, Dunaief JL.

F. M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University 
of Pennsylvania, Philadelphia, PA 19104, USA.

OBJECTIVE: To investigate whether iron is involved in the pathogenesis of
age-related macular degeneration (AMD). METHODS: Postmortem AMD-affected
(nonexudative or exudative) and healthy maculas were studied using the
3,3'-diaminobenzidine-enhanced Perls Prussian blue stain. The Perls Prussian blue
stain was quantified by computer-assisted analysis of digital images. To
determine whether the iron was chelatable, sections treated with the iron
chelator deferoxamine were compared with adjacent, nonchelated sections. RESULTS:
Compared with healthy maculas, AMD-affected maculas had statistically significant
increases in the total iron level. Some of this iron was chelatable. The iron was
present in retinal pigment epithelium and Bruch's membrane in maculas from
patients who had drusen only, geographic atrophy, and exudative AMD in pathologic
areas and, occasionally, in relatively healthy areas. CONCLUSIONS: Oxidative
stress has been implicated in the pathogenesis of AMD by the Age-Related Eye
Disease Study. Increased concentrations of iron, which generate highly reactive
hydroxyl radicals via the Fenton reaction, may induce oxidative stress in the
macula and lead to AMD. As the increased iron concentrations in AMD-affected eyes
consist in part of a chelatable iron pool, treatment of patients who have AMD
with iron chelators might be considered a potential therapy. While there are, as 
yet, no clinical data indicating that the treatment of patients who have AMD with
iron chelators is beneficial, data presented herein indicate that further
investigation of iron concentrations in postmortem tissues and the mechanisms of 
iron transport in the retina is warranted.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12912686 [PubMed - indexed for MEDLINE]

2517: Doc Ophthalmol. 2003 Jul;107(1):3-11.

RDH5 gene mutations and electroretinogram in fundus albipunctatus with or without
macular dystrophy: RDH5 mutations and ERG in fundus albipunctatus.

Nakamura M, Skalet J, Miyake Y.

Department of Ophthalmology, Nagoya University School of Medicine, 65
Tsuruna-cho, Showa-ku, Nagoya 466-8550, Japan. makonaka@med.nagoya-u.ac.jp

The aim of this study was to analyze the RDH5 gene in patients with fundus
albipunctatus with and without macular dystrophy, and correlate the identified
mutations with the electrophysiological results. Twenty-one patients from 19
unrelated Japanese families with fundus albipunctatus were examined. Ten
unrelated patients had macular dystrophy. In 18 patients, either a homozygous or 
a compound heterozygous mutation in the RDH5 gene was identified. The
bright-flash, mixed rod-cone ERG had a negative configuration with reduced a-wave
amplitudes after a short period of dark-adaptation (20 or 30 min). After a
prolonged dark-adaptation period (2 or 3 h), the waveform attained normal
amplitudes in patients without macular dystrophy but the a-waves were still
subnormal in patients with macular dystrophy. The photopic ERG responses were
significantly reduced in patients with macular dystrophy, indicating that they
also had cone dystrophy. The photopic ERGs were reduced in only some of the
patients without macular dystrophy. In patients without macular dystrophy, the
scotopic b-wave amplitudes were nonrecordable or significantly reduced after a
short dark-adaptation period but then improved to normal levels. However, they
did not fully recover in some patients with macular dystrophy. Three patients
with macular dystrophy in whom a RDH5 gene mutation could not be detected by our 
routine method had atypical ERG responses. We conclude that RDH5 gene mutations
cause a progressive cone dystrophy or macular dystrophy as well as night
blindness. The clinical phenotype including electrophysiological responses varied
among patients with the RDH5 gene mutations.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12906118 [PubMed - indexed for MEDLINE]

2518: Am J Hum Genet. 2003 Sep;73(3):540-50. Epub 2003 Jul 25.

Age-related macular degeneration--a genome scan in extended families.

Majewski J, Schultz DW, Weleber RG, Schain MB, Edwards AO, Matise TC, Acott TS,
Ott J, Klein ML.

Laboratory of Statistical Genetics, Rockefeller University, New York, NY, USA.

We performed a genomewide scan and genetic linkage analysis, to identify loci
associated with age-related macular degeneration (AMD). We collected 70 families,
ranging from small nuclear families to extended multigenerational pedigrees and
consisting of a total of 344 affected and 217 unaffected members available for
genotyping. We performed linkage analyses using parametric and allele-sharing
models. We performed the analyses on the complete pedigrees but also subdivided
the families into nuclear pedigrees. Finally, to dissect potential genetic
factors responsible for differences in disease manifestation, we stratified the
sample by two major AMD phenotypes (neovascular AMD and geographic atrophy) and
by age of affected family members at the time of our evaluation. We have
previously demonstrated linkage between AMD and 1q25-31 in a single large family.
In the combined sample, we have detected the following loci with scores exceeding
a LOD=2 cutoff under at least one of the models considered: 1q31 (HLOD=2.07 at
D1S518), 3p13 (HLOD=2.19 at D3S1304/D3S4545), 4q32 (HLOD=2.66 at D4S2368, for the
subset of families with predominantly dry AMD), 9q33 (LODZlr=2.01 at
D9S930/D9S934), and 10q26 (HLOD=3.06 at D10S1230). Using correlation analysis, we
have found a statistically significant correlation between LOD scores at 3p13 and
10q26, providing evidence for epistatic interactions between the loci and, hence,
a complex basis of AMD. Our study has identified new loci that should be
considered in future mapping and mutational analyses of AMD and has strengthened 
the evidence in support of loci suggested by other studies.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12900797 [PubMed - indexed for MEDLINE]

2519: Am J Ophthalmol. 2003 Aug;136(2):384-6.

Comment in:
    Am J Ophthalmol. 2003 Dec;136(6):1192; author reply 1192-3.

Intravitreal triamcinolone acetonide for pseudophakic cystoid macular edema.

Jonas JB, Kreissig I, Degenring RF.

Department of Ophthalmology, Faculty for Clinical Medicine Mannheim,
Ruprecht-Karls-University, Heidelberg, Germany.
Jost.Janos@ma.augen.uni-heidelberg.de

PURPOSE: To report the clinical outcome of patients undergoing intravitreal
injection of triamcinolone acetonide as treatment of long-standing cystoid
macular edema after phacoemulsification. DESIGN: Prospective clinical
interventional cases series studies. METHODS: The study included five patients
suffering from cystoid macular edema after cataract surgery. They received an
intravitreal injection of 25-mg crystalline triamcinolone acetonide
transconjunctivally with topical anesthesia. RESULTS: In the follow-up period of 
6.6 +/- 4.1 months, visual acuity increased from 0.26 +/- 0.13 to a mean maximal 
visual acuity of 0.60 +/- 0.19. For all patients, visual acuity improved during
the follow-up by at least 0.20. Two (40%) patients developed intraocular pressure
values higher than 21 mm Hg, which could be controlled by topical
antiglaucomatous treatment. CONCLUSIONS: Intravitreal triamcinolone acetonide may
be a therapeutic option for long-standing cystoid macular edema after cataract
surgery.

PMID: 12888077 [PubMed - indexed for MEDLINE]

2520: Am J Ophthalmol. 2003 Aug;136(2):314-7.

The Eger Macular Stressometer: pilot study.

Schmitt NJ, Grover DA, Feldon SE.

University of Rochester Department of Ophthalmology, Rochester, New York 14642,
USA.

PURPOSE: To evaluate the sensitivity of the Eger Macular Stressometer (EMS) for
early screening of age-related macular degeneration (AMD) in a clinical practice.
We examined the null hypothesis that AMD eyes have EMS recovery times (RTs) that 
do not differ from eyes with cataract, diabetic retinopathy, or glaucoma. DESIGN:
The design of this study was a nonrandomized clinical trial. METHODS: Ninety-two 
eyes from 92 patients with vision 20/80 or better, age 50 and older, of either
gender, and any ethnic origin, were recruited into one of four groups: AMD (30
eyes), normal or mild cataract (30 eyes), diabetic retinopathy (16 eyes), and
glaucoma (16 eyes). Recovery times were obtained with the EMS, according to
manufacturer's instructions. RESULTS: The mean (SD) [median] RT for the AMD group
was 11.8 (7.6) [9] seconds, the normal/cataract group 10.0 (4.3) [9] seconds, the
diabetic retinopathy group 8.4 (3.0) [8] seconds, and glaucoma group 8.6 (2.4)
[8] seconds. Recovery time did not appear to be related to group (P =.58), age (P
=.50), visual acuity (P =.52), or sex (P =.23). CONCLUSIONS: We found EMS RT
distributions did not differ between AMD, cataract, diabetic retinopathy, and
glaucoma groups. The EMS in its current form is not a sensitive screening tool
for AMD. Further testing is needed to examine EMS sensitivity with other macular 
diseases such as central serous choroidopathy and diabetic macular edema.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 12888055 [PubMed - indexed for MEDLINE]

2521: Am J Ophthalmol. 2003 Aug;136(2):244-51.

Randomized clinical trial of topical betaxolol for persistent macular edema after
vitrectomy and epiretinal membrane removal.

Kobayashi H, Kobayashi K, Okinami S.

Department of Ophthalmology, Saga Medical School, Nabeshima, Saga, Japan.
kobayas3@post.saga-med.ac.jp

PURPOSE: To report the efficacy and safety of topical betaxolol for treatment of 
persistent macular edema. DESIGN: Randomized clinical trial. METHODS:
Thirty-seven eyes (37 patients) with best-corrected visual acuity between 20/200 
and 20/50 and macular edema that remained for 3 months after vitrectomy and
removal of epiretinal membrane were prospectively, randomly assigned to receive
betaxolol or placebo. Nineteen eyes of 19 patients received betaxolol twice
daily, and 18 eyes of 18 patients received placebo as a randomized comparison
group. The patients were followed up for 6 months. This study evaluated the
effect of betaxolol on best-corrected visual acuity and area of macular edema,
which was digitally measured on serial fluorescein angiogram. Calculations of
mean best-corrected visual acuity were based on logarithm of the minimal angle of
resolution (logMAR). To assess changes in area of edema, the initial
(pretreatment) size of the edema was set to 100%, and all posttreatment
measurements were normalized relative to the initial size. RESULTS: Mean
best-corrected visual acuity at baseline was 0.216 (20 of 92.6) and 0.244 (20 of 
82.0) in the treatment and control group, respectively. Mean area of macular
edema was 2.271 +/- 1.629 mm(2) and 2.273 +/- 1.209 mm(2) in the treatment and
control group; there was no significant difference. The visual acuity at 6 months
after the start of the follow-up was 0.471 (20 of 42.5) in the treatment group
and 0.236 (20 of 84.7) in the control group. Mean changes in logMAR of visual
acuity for 3- and 6-month follow-up were -0.282 +/- 0.191 and -0.337 +/- 0.197 in
the treatment group, and -0.016 +/- 0.186 and +0.015 +/- 0.267 in the control
group; a significant difference was found (P <.0001; P <.0001). Areas of macular 
edema at 6 months after the start of the follow-up were 1.492 +/- 1.357 mm(2) in 
the treatment group and 2.125 +/- 1.434 mm(2)in the control group. Mean change in
area of the edema for 6 months were 76.5% +/- 24.1% and 63.4% +/- 28.3% in the
treatment group and 92.9% +/- 15.4% and 87.4% +/- 25.6% in the control group;
treated patients showed a significantly larger reduction than untreated patients 
at each examination (P =.0193; P =.0102). No complication associated with
treatment or placebo was found. CONCLUSIONS: Topical betaxolol appeared to have a
favorable treatment effect in eyes with macular edema that remained after
vitrectomy and removal of epiretinal membrane. Further investigation of more
cases and longer follow-up are needed.

Publication Types: 
    Case Reports
    Clinical Trial
    Randomized Controlled Trial

PMID: 12888045 [PubMed - indexed for MEDLINE]

2522: Primates. 2003 Jul;44(3):291-4. Epub 2003 Mar 14.

Familial early onset macular degeneration in cynomolgus monkeys (Macaca
fascicularis).

Suzuki MT, Terao K, Yoshikawa Y.

The Corporation for Production and Research of Laboratory Primates, Hachimandai, 
Tsukuba, Ibaragi 305-0843, Japan.

The mode of inheritance of macular degeneration was determined with 45 cynomolgus
monkeys (18 females and 27 males) who were the offspring of one breeding male
with typical macular degeneration. In the first generation, 27 offspring (10
females and 17 males) were born from mating between the macular
degeneration-affected founder male and 5 normal female breeders. Among them, 18
monkeys (9 females and 9 males) were judged as having macular degeneration
(affected). Next, the distribution of affected offspring was examined with 18
offspring who were born from 3 different mating pairs, normal vs normal, affected
vs normal and affected vs affected, when they became 2 years old. All of the 9
monkeys (4 females and 5 males) obtained from the 2 pairs of normal vs normal
were normal. On the other hand, 6 affected monkeys (3 females and 3 males) were
detected in 8 offspring from the mating pair of affected vs normal, and the
single offspring produced by the mating pair of affected vs affected was
affected. These results showed that this degeneration must be early onset
familial macular degeneration controlled by autosomal dominant gene(s).

PMID: 12884119 [PubMed - indexed for MEDLINE]

2523: Invest Ophthalmol Vis Sci. 2003 Aug;44(8):3570-7.

Late-onset autosomal dominant macular dystrophy with choroidal neovascularization
and nonexudative maculopathy associated with mutation in the RDS gene.

Khani SC, Karoukis AJ, Young JE, Ambasudhan R, Burch T, Stockton R, Lewis RA,
Sullivan LS, Daiger SP, Reichel E, Ayyagari R.

Department of Ophthalmology, State University of New York at Buffalo, Buffalo,
New York, USA.

PURPOSE: To examine the molecular genetic basis and phenotypic characteristics of
an unusual late-onset autosomal dominant macular dystrophy with features of
age-related macular degeneration (AMD) in a large family (SUNY901), by using
linkage and mutation analyses. METHODS: Blood samples were collected from 17
affected members, 17 clinically unaffected members, and 5 unrelated spouses.
Clinical analyses included a review of medical history and standard ophthalmic
examination with fundus photography, fluorescein angiography, and
electroretinography. Linkage and haplotype analyses were performed with
microsatellite markers. Mutation analysis was performed by amplification of exons
followed by sequencing. RESULTS: A wide spectrum of clinical phenotypes including
exudative and nonexudative maculopathy was observed, with onset in the late fifth
decade. Linkage analysis excluded most of the previously known maculopathy loci. 
Markers D6S1604 (Z(max) of 3.18 at theta = 0), and D6S282 (Z(max) of 3.18 at
theta = 0) gave significant positive LOD scores and haplotype analysis localized 
the disease gene to a 9-centimorgan (cM) interval between markers D6S1616 and
D6S459. Mutation analysis excluded the GUCA1A and GUCA1B genes and revealed a
missense mutation in the RDS/peripherin gene leading to a Tyr141Cys substitution.
A phenotype and haplotype comparison between this and a separate family with the 
Tyr141Cys mutation suggested the presence of a common ancestral haplotype.
CONCLUSIONS: The RDS mutation in codon 141 is associated with an unusual AMD-like
late-onset maculopathy. An apparent selective bias was noted favoring the
transmission of the mutant allele. These observations broaden the spectrum of
phenotypes associated with RDS gene mutations.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12882809 [PubMed - indexed for MEDLINE]

2524: Br J Ophthalmol. 2003 Aug;87(8):977-9.

Visual hallucinations and Charles Bonnet syndrome after photodynamic therapy for 
age related macular degeneration.

Cohen SY, Bulik A, Tadayoni R, Quentel G.

Centre Ophtalmologique d'Imagerie et de Laser, Paris, France.
sycohen@club-internet.fr

AIMS: To report on visual hallucinations and Charles Bonnet syndrome (CBS) that
may occur in patients with age related macular degeneration (AMD) treated by
photodynamic therapy (PDT) with verteporfin for choroidal neovascularisation
(CNV). METHODS: 100 consecutive patients were asked to respond to an orally
administered questionnaire on visual hallucinations following PDT. Three groups
of patients, respectively without visual hallucinations, with unstructured visual
hallucinations, and with structured hallucinations-that is, CBS, were compared by
ANOVA, Scheffe's test, or the chi(2) test, to establish whether age, sex, or
visual acuity, as scored on ETDRS charts, are risk factors for the occurrence of 
visual hallucinations. RESULTS: Five patients (5%) described transient structured
visual hallucinations, including known or unknown faces and geometric patterns.
Fifteen patients (15%) reported photopsias and flashing lights of various
colours. These symptoms usually occurred a few days after PDT. There was no
significant difference between the group of patients with structured visual
hallucinations and the two other groups, with regard to age (p =0.435), sex (p
=0.406), or visual acuity (p =0.835). CONCLUSIONS: Visual hallucinations and CBS 
appear to be a possible, although unrecognised, side effect of PDT for CNV, which
occur just after treatment. These results suggest the need to include the
possibility of visual hallucinations in the information given to patients before 
PDT.

PMID: 12881339 [PubMed - indexed for MEDLINE]

2525: Clin Experiment Ophthalmol. 2003 Aug;31(4):317-21.

Five-year incidence of age-related maculopathy in relation to iris, skin or hair 
colour, and skin sun sensitivity: the Blue Mountains Eye Study.

Wang JJ, Jakobsen K, Smith W, Mitchell P.

Centre for Vision Research, Department of Ophthalmology, University of Sydney,
Sydney, Australia.

This study aimed to assess longitudinal associations between iris,hair and skin
colour, plus skin sensitivity to sun and the 5-year incidence of age-related
maculopathy (ARM). Of 3654 baseline Blue Mountains Eye Study participants (aged
49+ years), 2335 survivors (75.1%) were re-examined after 5 years.Retinal
photographs were graded using the Wisconsin ARM Grading System and incident ARM
lesions confirmed using side-by-side grading.Iris/skin/hair colour was assessed
and skin sensitivity questions were asked at baseline. After adjusting for age,
sex and smoking, no significant associations were found between iris or hair
colour and incident late or early ARM. Compared to persons with fair skin, those 
with very fair skin had an increased risk of developing geographical atrophy
(odds ratio [OR] 3.5,95% confidence interval [CI] 1.2-10.4).However, persons with
sun-related skin damage were less likely than those without to develop indistinct
soft drusen (OR 0.6, 95% CI 0.4-0.9). Longitudinal data provide no support for
the previously reported cross-sectional association between iris colour and ARM.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12880456 [PubMed - indexed for MEDLINE]

2526: J Biomed Opt. 2003 Jul;8(3):410-7.

Application of an ex ovo chicken chorioallantoic membrane model for two-photon
excitation photodynamic therapy of age-related macular degeneration.

Samkoe KS, Cramb DT.

University of Calgary, Department of Chemistry, 2500 University Drive NW,
Calgary, AB, Canada T2N 1N4.

Two-photon excitation photodynamic therapy (TPE-PDT) is being investigated as a
clinical treatment for age-related macular degeneration (AMD). TPE-PDT has the
potential to provide a more specific and therefore advantageous therapy regime
than traditional one-photon excitation PDT. The highly vascularized 8 to
9-day-old chicken chorioallantoic membrane (CAM) is used to model the rapid
growth of blood vessels in the wet form of AMD. Using an ex ovo model system for 
the CAM, ablation studies were successful in mimicking the leaky vessels found in
AMD. In addition, the distribution and localization of liposomal Verteporfin were
investigated in order to characterize the photosensitizing drug in vivo.
Localization of the photosensitizer appears to be greatest on the upper vessel
wall, which indicates a potentially strong treatment locale for TPE-PDT. (c) 2003
Society of Photo-Optical Instrumentation Engineers.

Publication Types: 
    Evaluation Studies
    Research Support, Non-U.S. Gov't

PMID: 12880346 [PubMed - indexed for MEDLINE]

2527: Transfus Apher Sci. 2003 Aug;29(1):71-84.

Clinical studies to implement Rheopheresis for age-related macular degeneration
guided by evidence-based-medicine.

Klingel R, Fassbender C, Fassbender T, Göhlen B.

Apheresis Research Institute, Stadwaldguertel 77, 50935 Cologne, Germany.
afi@apheresis-research.de

In the majority of age-related macular degeneration (AMD) patients the
therapeutic situation is very unsatisfactory, especially for patients with dry
AMD. Rheopheresis is a safe and effective modality of therapeutic apheresis to
treat microcirculatory disorders, and represents a novel therapeutic approach for
patients with dry AMD and soft drusen. Elimination of a defined spectrum of high 
molecular weight proteins from human plasma including pathophysiologically
relevant risk factors for AMD such as fibrinogen, LDL-cholesterol, alpha
2-macroglobulin, fibronectin, and von-Willebrand factor results in the reduction 
of blood and plasma viscosity as well as erythrocyte and thrombocyte aggregation.
Pulses of lowering blood and plasma viscosity performed as series of Rheopheresis
treatments lead to rapid changes of blood flow, subsequently inducing sustained
improvement of microcirculation, and recovery of retinal function. Two controlled
randomized clinical trials demonstrated safety and efficacy of Rheopheresis for
the treatment of AMD patients, especially with the dry form. Recently the
interim-analysis of the sham-controlled, double blinded, randomized multicenter
MIRA-I trial confirmed these results. The RheoNet-registry and the development
and continuous update of therapy guidelines provide an appropriate framework for 
the quality management of the interdisciplinary cooperation between
ophthalmologists with apheresis specialists. A hypothesis based upon current
knowledge of pathogenic mechanisms of the development and progression of AMD can 
be conclusively linked with the putative mechanism of action of Rheopheresis for 
AMD. A recommendation for high-risk AMD-patients was defined. Based on the
positive results of the MIRA-1 interim analysis eight Rheopheresis treatments are
currently recommended as the initial treatment series.

Publication Types: 
    Review

PMID: 12877897 [PubMed - indexed for MEDLINE]

2528: Dev Ophthalmol. 2003;37:155-69.

Genetics of macular dystrophies and implications for age-related macular
degeneration.

Klaver CC, Allikmets R.

Department of Ophthalmology, Columbia University, New York, N.Y., USA.

Determining the genetic component of the age-related macular degeneration (AMD)
complex trait has been the primary goal of ophthalmic genetics research for
almost a decade. During this time, genes of several Mendelian traits affecting
the macula have been identified. In this review, we will discuss the consequences
of molecular defects in the VMD2, EFEMP1, TIMP3, ELOVL4 and ABCA4 genes, and
their association with macular disease. We will also analyze our current
knowledge on the implications of genetic variations in these genes for AMD by
summarizing data from all studies which have investigated the possible role of
these candidate genes in the etiology of AMD. Finally, we will elaborate on
methods for genetic dissection of complex traits and discuss the appropriate
applications of these methods for identifying genetic determinants of AMD.

Publication Types: 
    Review

PMID: 12876836 [PubMed - indexed for MEDLINE]

2529: Ophthalmology. 2003 Jul;110(7):1292-6.

Is there a direct association between age-related eye diseases and mortality? The
Rotterdam Study.

Borger PH, van Leeuwen R, Hulsman CA, Wolfs RC, van der Kuip DA, Hofman A, de
Jong PT.

Department of Epidemiology & Biostatistics, Erasmus Medical Center, Rotterdam,
The Netherlands.

PURPOSE: To study mortality in subjects with age-related maculopathy (ARM),
cataract, or open-angle glaucoma (OAG) in comparison with those without these
disorders. DESIGN: Population-based prospective cohort study. PARTICIPANTS:
Subjects (n = 6339) aged 55 years and older from the population-based Rotterdam
Study for whom complete information on eye disease status was present. MAIN
OUTCOME MEASURES: Vital status continuously monitored from 1990 until January 1, 
2000. METHODS: The diagnosis of ARM was made according to the International
Classification System. Cataract, determined on biomicroscopy, was defined as any 
sign of nuclear or (sub)cortical cataract, or both, in at least one eye with a
visual acuity of 20/40 or less. Aphakia and pseudophakia in at least one eye were
classified as operated cataract. Definite OAG was defined as a glaucomatous optic
neuropathy combined with a glaucomatous visual field defect. Diagnoses were
assessed at baseline. Mortality hazard ratios were computed using Cox
proportional hazard regression analysis, adjusted for appropriate confounders
(age, gender, smoking status, body mass index, cholesterol level,
atherosclerosis, hypertension, history of cardiovascular disease, and diabetes
mellitus). RESULTS: The adjusted mortality hazard ratio for subjects with AMD (n 
= 104) was 0.94 (95% confidence interval [CI], 0.52-1.68), with biomicroscopic
cataract (n = 951) was 0.94 (95% CI, 0.74-1.21), with surgical cataract (n = 298)
was 1.20 (95% CI, 0.86-1.68), and with definite OAG (n = 44) was 0.39 (95% CI,
0.10-1.55). CONCLUSIONS: Both ARM and cataract are predictors of shorter survival
because they have risk factors that also affect mortality. When adjusted for
these factors, ARM, cataract, and OAG were themselves not significantly
associated with mortality.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12867381 [PubMed - indexed for MEDLINE]

2530: Arch Ophthalmol. 2003 Jul;121(7):967-72.

Resonance Raman measurement of macular carotenoids in retinal, choroidal, and
macular dystrophies.

Zhao DY, Wintch SW, Ermakov IV, Gellermann W, Bernstein PS.

Department of Ophthalmology and Visual Sciences, Moran Eye Center, University of 
Utah School of Medicine, Salt Lake City 84132, USA.

BACKGROUND: It has been hypothesized that the macular carotenoid pigments lutein 
and zeaxanthin may protect against macular and retinal degenerations and
dystrophies. OBJECTIVE: To test this hypothesis by objectively measuring lutein
and zeaxanthin levels in a noninvasive manner in patients who have retinitis
pigmentosa (RP), choroideremia (CHM), and Stargardt macular dystrophy and
comparing them with an age-matched healthy control population. METHODS: Using
resonance Raman spectroscopy, a novel objective noninvasive laser-optical
technique, we measured macular carotenoid levels in 30 patients (54 eyes) who
have RP, CHM, and Stargardt macular dystrophy and compared them with 76
age-matched subjects (129 eyes) who did not have macular pathologic conditions in
a case-control study. RESULTS: As a group, patients with RP and CHM had the same 
macular carotenoid levels as age-matched healthy control subjects (P =.76, 2-way 
analysis of variance). Patients with Stargardt macular dystrophy tended to have
levels of macular carotenoid pigments that, on average, were about 50% lower than
healthy controls (P =.02,unpaired 2-tailed t test). CONCLUSIONS: The patients
with RP and CHM had normal levels of macular carotenoids, suggesting that
nutritional supplementation with macular carotenoids such as lutein, zeaxanthin, 
or both will be unlikely to affect the clinical course of RP and CHM. Although
the number of patients with Stargardt macular dystrophy examined was limited,
their macular carotenoid levels were usually lower than those of subjects of a
similar age with no macular pathologic condition.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12860799 [PubMed - indexed for MEDLINE]

2531: Eye. 2003 Jul;17(5):623-7.

Prophylactic laser treatment appears to promote choroidal neovascularisation in
high-risk ARM: results of an interim analysis.

Owens SL, Bunce C, Brannon AJ, Wormald R, Bird AC; Drusen Laser Study Group.

Medical Retinal Service, Moorfields Eye Hospital, London, UK.
Sarah.Owens@moorfields.nhs.uk

PURPOSE: The Drusen Laser Study (DLS) of high-risk age-related maculopathy (ARM) 
is a randomised, controlled clinical trial designed to answer two questions: (1).
Do drusen resolve after macular laser photocoagulation (2). Does macular laser
photocoagulation prevent choroidal neovascularisation (CNV) in high-risk eyes? In
this report, we present the results of the interim, pooled analysis of CNV
prophylaxis for patients in the Unilateral Group of the DLS. METHODS: The DLS is 
a randomised controlled clinical trial of prophylactic macular photocoagulation
for high-risk ARM. Patients in the Unilateral Group had a neovascular
complication in the first eye; their fellow eye (Study Eye) had visual acuity of 
6/12 or better and drusen. Following informed consent, patients were randomised
to the Treatment Group or the No Treatment Group. Patients randomised to
treatment received 12 light spots of argon laser photocoagulation to their Study 
Eye: four burns were placed 750 microm from the centre of the fovea at 12, 3, 6, 
and 9 o'clock, and the eight remaining burns were placed 1500 microm from the
centre of the fovea at 12, 1:30, 3, 4:30, 6, 7:30, 9, and 10:30 o'clock. Drusen
were treated directly only if they were present at the protocol treatment
locations. All patients were followed in an identical fashion at regular
intervals. Best-corrected visual acuity was measured and recorded by a masked
observer. Fluorescein angiography was performed at baseline and yearly review, as
well as nonprotocol visits if symptoms suggested CNV. Five clinical centres
utilised and conformed to a common DLS protocol. Patient care and data collection
methodologies were deemed sufficiently similar to permit a pooled data analysis. 
RESULTS: There were 156 patients included in the interim analysis, and timed
information was available on 153. CNV occurred in 21 of 81 (26%) patients in the 
Treatment Group and in 13 of 75 (17%) patients in the No Treatment Group
(P=0.19). Kaplan-Meier survival analysis showed earlier onset of CNV in the
Treatment Group compared to patients in the No Treatment Group (statistical
significance not calculated). Visual acuity loss at 2 years occurred in nine of
54 (17%) patients in the Treatment Group compared to the two of 48 (4%) patients 
in the No Treatment Group (P=0.056). CONCLUSIONS: We are only the second group to
identify possible laser-induced CNV despite other similar studies in progress.
Equipoise of the DLS investigators was lost, and recruitment was halted. We feel 
ethically bound to notify the ophthalmic community of this finding.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial

PMID: 12855972 [PubMed - indexed for MEDLINE]

2532: Eye. 2003 Jul;17(5):583-6.

Introduction of photodynamic therapy for the treatment of neovascular age-related
macular degeneration: tracking a moving target.

Foot B, Foy R, Chakravarthy U, Wormald R.

The Royal College of Ophthalmologists, London, UK.

OBJECTIVES: To identify changes in referral and treatment patterns of neovascular
age-related macular degeneration with photodynamic therapy (PDT) within
ophthalmology units in NHS hospitals and assess how beliefs about what would
constitute a worthwhile level of clinical benefit had altered over a 12-month
period. METHODS: Two questionnaire surveys (October 2000 and October 2001) to all
clinical directors or lead consultants in UK NHS eye units. These sought data on 
which (if any) patients were referred or treated with PDT and the threshold of
clinical benefit, in terms of numbers needed to treat, at which they would
support the use of PDT. RESULTS: Response rates were 82% in the first survey and 
79% in the second. The availability of PDT had significantly increased
(P=0.0001). The proportion of units routinely providing PDT for patients with
more than 50% classic subfoveal choroidal neovascularization (CNV) increased from
8 to 23%. Between the 2 surveys, there was a significant reduction in the
threshold of effectiveness at which respondents would support the use of PDT
(P=0.012). The proportion of respondents requiring further evidence before
supporting the use of PDT decreased from 33 to 17% (P=0.009). There was a
significant association between the threshold of support and the level of service
provision for both surveys (P=0.01). CONCLUSIONS: Although substantial variations
exist, availability of PDT has increased over the 12-month period. The differing 
thresholds at which introduction of PDT would be considered justifiable varied
widely. PDT is being introduced into the NHS in a fragmented manner. In common
with other new health technologies, factors other than the strength of evidence
appear to be influencing beliefs about the effectiveness of PDT and its
subsequent provision. While it is unlikely that such an action alone will lead to
evidence-based practice, the variations in beliefs identified by this survey
suggest that sufficient clinical uncertainty exists to support the need for
further clinical trials.

PMID: 12855963 [PubMed - indexed for MEDLINE]

2533: Ocul Immunol Inflamm. 2002 Dec;10(4):239-46.

Medical treatment of cystoid macular edema.

Rothova A.

Uveitis Center, FC Donders Institute of Ophthalmology, University Medical Center 
Utrecht, The Netherlands.

Although cystoid macular edema (CME) represents a major cause of visual loss in
uveitis, the consensus on its treatment has not yet been reached. We performed a 
literature review on the efficacy of diverse medical treatment modalities for
uveitic CME and suggest novel treatment recommendations. A literature search
retrieved 173 citations (MEDLINE, conducted in March 2002, terms: macular edema, 
uveitis, treatment) and relevant publications were studied. The literature
contained information based mainly on case series; the specific treatment targets
were not clear. Causal treatment of the underlying ocular condition was
considered essential and various approaches of symptomatic treatment were
attempted (immunosuppressive and immunomodulatory agents, acetazolamide,
octreotide), all with different inclusion criteria and evaluation protocols. The 
decision to initiate the symptomatic treatment of CME was usually made in cases
with already compromised visual acuity. Despite aggressive treatment, the
progression of CME with accompanying visual loss was common. On the basis of
published results, we recommend starting treatment of CME at an early stage, even
in eyes with full visual acuity. Randomized clinical trials are needed to
determine the efficacy of diverse treatment modalities and to evaluate the
effects of early intervention on inflammatory CME.

Publication Types: 
    Review

PMID: 12854032 [PubMed - indexed for MEDLINE]

2534: Ocul Immunol Inflamm. 2003 Mar;11(1):29-38.

Cystoid macular edema in uveitis.

Okhravi N, Lightman S.

Department of Clinical Ophthalmology, Institute of Ophthalmology, Moorfields Eye 
Hospital, London, UK. nokhravi@hgmp.mrc.ac.uk

Cystoid macular edema (CME) can cause profound visual loss and is one of the
major causes of legal blindness in patients with uveitis. It can complicate
virtually any type of acute or chronic, anterior or posterior uveitis. When mild 
and of short duration, CME may respond to treatment used to control the
intraocular inflammation. However, patients may need more aggressive treatment
with local and systemic steroid therapy and other immunosuppressive drugs.
Unfortunately, CME may become refractory to all currently available therapies and
result in severe visual loss.

Publication Types: 
    Review

PMID: 12854025 [PubMed - indexed for MEDLINE]

2535: Yan Ke Xue Bao. 2003 Mar;19(1):20-4.

Transient macular edema after laser in-situ keratomileusis.

Yang B, Wang Z, Huang G, Liu X, Ling Y, Zheng X.

Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.

PURPOSE: To investigate the macular changes induced by laser in situ
keratomileusisc (LASIK) procedure. METHODS: Optical Coherence Tomography (OCT)
was used to examine 27 eyes of 15 LASIK patients before surgery, and 1 day, 1
week, 1 month after surgery. RESULTS: The mean thickiness of neuroepithelial
layer of macula was (195 +/- 24) microns, (178 +/- 16) microns 1 day and 1 month 
after surgery, respectively, while the baseline was (174 +/- 12) microns. The
increase in macular neuroepithelial thickness was correlated with the degree of
myopia, but not with the duration of suction or the postoperative BCVA.
CONCLUSION: Mild macular edema is common in the first month following LASIK,
especially in high myopia. However, no association with loss of BCVA has been
established.

PMID: 12852083 [PubMed - indexed for MEDLINE]

2536: Yan Ke Xue Bao. 2003 Mar;19(1):15-9.

Scotopic sensitivity of central retina in early age-related macular degeneration.

Chen C, Wu L, Jiang F, Liang J, Wu DZ.

Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.

PURPOSE: To test scotopic sensitivity and investigate whether there is rod system
dysfunction in the central retina in early age-related macular degeneration
(AMD). METHODS: Scotopic (450 nm stimulus) and photopic (white light stimulus)
sensitivity in 24 patients with early AMD was measured at 81 loci in central 25
degrees of retina, and compared with the age-match normal controls. RESULTS: Mean
scotopic sensitivity of AMD patients was significantly lower than that of the
normal controls. The patients of reduced scotopic sensitivity were more than
those of reduced photopic sensitivity. Scotopic sensitivity deficit decreased
with increasing eccentricity with the greatest deficit was 2.5 degrees to 5.0
degrees. CONCLUSIONS: Scotopic sensitivity was decreased in the early stage of
AMD. The parafoveal rod cells were selectively damaged in AMD. Scotopic
sensitivity testing in macula may be a useful tool to diagnose and measure the
fundus dysfunction of AMD.

PMID: 12852082 [PubMed - indexed for MEDLINE]

2537: Am J Ophthalmol. 2003 Jul;136(1):194-6.

Treatment of von Hippel-Lindau retinal hemangioblastoma by the vascular
endothelial growth factor receptor inhibitor SU5416 is more effective for
associated macular edema than for hemangioblastomas.

Girmens JF, Erginay A, Massin P, Scigalla P, Gaudric A, Richard S.

Service d'Ophtalmologie, Hôpital Lariboisière, Assistance Publique-Hôpitaux de
Paris and Université Paris VII, Paris, France.

PURPOSE: To test the efficacy of the novel vascular endothelial growth factor
(VEGF) receptor inhibitor SU5416, in a case of refractory von Hippel-Lindau (VHL)
retinal hemangioblastoma (RHB). DESIGN: Interventional case report. METHODS:
Patient included in a multicenter phase II trial. A 30-year-old woman presenting 
with VHL disease and multiple RHB on her only eye, refractory to conventional
treatments, had decreased visual acuity due to cystoid macular edema (CME).
SU5416 was administered intravenously for 7 months. Best-corrected visual acuity 
(BCVA) and macular thickness were measured by optical coherence tomography.
RESULTS: Under treatment, the size of the RHB did not change, but CME improved
significantly. Best-corrected visual acuity rose from 20/40 to 20/25. However,
CME recurred after the end of the treatment. CONCLUSION: The VEGF receptor
inhibitor SU5416 failed to reduce the size of RHB but was very effective for the 
associated CME.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 12834696 [PubMed - indexed for MEDLINE]

2538: Retina. 2003 Jun;23(3):343-7.

Optical coherence tomography of branch retinal vein occlusion.

Spaide RF, Lee JK, Klancnik JK Jr, Gross NE.

Vitreous-Retina-Macula Consultants of New York and the LuEsther T. Mertz Retina
Research Laboratory, manhattan Eye, Ear, and Throat Hospital, New York, New York 
10021, USA. rickspaide@yahoo.com

PURPOSE: To evaluate the incidence of serous retinal detachment (SRD) secondary
to a branch retinal vein occlusion (BRVO) by using optical coherence tomography
(OCT). METHODS: Fourteen eyes of 14 patients with a BRVO underwent a detailed
history, ophthalmoscopic examination, and fluorescein angiographic evaluation.
They were also studied with OCT. RESULTS: The 14 patients included eight women
and six men with a mean age of 73.6 +/- 10.5 years (range, 55-90 years). Four
eyes were found to have cystoid macular edema by fluorescein angiography, whereas
10 cases were detected by OCT. SRD involving any portion of the macula was found 
in 10 (71.4%) of the 14 eyes, and SRD extending into the fovea was found in six
(42.9%) eyes. Two (14.3%) of the 14 patients also showed a subfoveal hemorrhage
that appeared to have gravitated inferiorly through the SRD to the dependent
portion of the detachment. CONCLUSIONS: That few patients with SRD secondary to a
BRVO discovered by ophthalmoscopy have been reported in the literature would
suggest that this is an uncommon complication. The authors found with OCT that
SRD commonly occurs in BRVO. In addition, subretinal hemorrhage may occur in the 
context of BRVO, and the authors propose that blood gravitates through the
subretinal fluid to settle behind the retina.

PMID: 12824834 [PubMed - indexed for MEDLINE]

2539: Retina. 2003 Jun;23(3):307-14.

Risk factors for choroidal neovascularization and vision loss in the fellow eye
study of CNVPT.

Prenner JL, Rosenblatt BJ, Tolentino MJ, Ying GS, Javornik NB, Maguire MG, Ho AC;
CNVPT Research Group.

Associated Retinal Consultants, Royal Oak, Michigan, USA.

PURPOSE: To identify risk factors for the development of choroidal
neovascularization (CNV) and vision loss in the Fellow Eye Study of the Choroidal
Neovascularization Prevention Trial. METHODS: Retrospective review of 121
patients enrolled in a multicentered, randomized, controlled trial. Patients had 
neovascular age-related macular degeneration in one eye and more than 10 large
drusen in the other eye. Records of patients randomly assigned to laser treatment
or observation were reviewed through 4 years of follow-up. Three candidate risk
factors for the development of CNV and vision loss were evaluated. RESULTS: Eyes 
with hyperfluorescent drusen on fluorescein angiography at 3 minutes appeared to 
have a decreased risk of CNV. Patchy choroidal filling was seen in 14% of
patients. Eyes with patchy choroidal perfusion showed a higher risk of developing
CNV that was not statistically significant, and the increased risk was present
only in treated eyes. Reticular pseudodrusen were present in only three eyes.
CONCLUSIONS: Reticular pseudodrusen were rare. Late drusen fluorescence may
protect against the development of CNV.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12824829 [PubMed - indexed for MEDLINE]

2540: Invest Ophthalmol Vis Sci. 2003 Jul;44(7):3226-32.

Differential effects of light and alcohol on the electro-oculographic responses
of patients with age-related macular disease.

Arden GB, Wolf JE.

Applied Vision Research Centre, City University, London, United Kingdom.

PURPOSE: Alcohol (EtOH) affects the electro-oculogram (EOG) in ways very similar 
to light, although the two agents act on the RPE through different routes. Are
the EOGs to light and to alcohol affected similarly in age-related macular
degeneration (AMD) and age-related maculopathy (ARM)? METHODS: Standard eye
movements and recording of EOGs were used. After 26 minutes of baseline recording
in darkness, subjects were either exposed to 30 cd/m(2) light or drank 226 mg/kg 
alcohol (7.1% vol/vol) in water. RESULTS: In 17 patients with ARM and AMD (aged
67-86 years; mean, 77), the light-EOG was slowed in comparison to normal, and the
voltage changes were somewhat reduced. The mean reduction in the alcohol-EOG
(EtOH-EOG) was much greater. The reduction was equal in the two eyes, regardless 
of uniocular foveal impairment. Some EtOH-EOG loss occurred in patients with
minor fundus changes and no loss of acuity, but the loss was greater in patients 
with "wet" or "dry" ARM and AMD. Grading of RPE changes correlated with the
decrease in EtOH-EOG responsiveness, but not with light-EOG responsiveness.
CONCLUSIONS: EtOH- and light-EOGs are affected differentially. In ARM, even with 
minor fundus changes, patients appear to have a general abnormality in the RPE.
The alcohol response abnormality is correlated to the fundus appearance, but not 
with age. These results provide further evidence that EtOH acts by a pathway
different from that governing the action of light. These results support
histologic and other evidence that in ARM there is a functional barrier between
the choroid and the RPE-retina.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12824275 [PubMed - indexed for MEDLINE]

2541: Invest Ophthalmol Vis Sci. 2003 Jul;44(7):2868-75.

Detailed analysis of allelic variation in the ABCA4 gene in age-related
maculopathy.

Schmidt S, Postel EA, Agarwal A, Allen IC Jr, Walters SN, De la Paz MA, Scott WK,
Haines JL, Pericak-Vance MA, Gilbert JR.

Center for Human Genetics, Duke University Medical Center, Durham, North Carolina
27710, USA.

PURPOSE. Age-related maculopathy (ARM) is one of the most common causes of
blindness in older adults worldwide. Sequence variants in a gene coding for a
retina-specific ATP-binding cassette (ABCA4) transporter protein, which is
responsible for a phenotypically similar Mendelian form of retinal disease, were 
proposed to increase the risk of ARM. To examine the potential relationship of
ABCA4 sequence variation and ARM risk in an independent data set, a clinically
well-characterized population of 165 multiplex patients with ARM from 70
families, 33 unaffected relatives, and 59 unrelated control subjects with
confirmed absence of ARM was screened for variants in any of the 50 exons and
exon-intron boundaries of this gene. METHODS. A combination of denaturing
high-performance liquid chromatography (DHPLC) and bidirectional sequencing was
used to detect ABCA4 sequence variants. The data set was analyzed with both
case-control and family-based association analysis methods. RESULTS. No evidence 
was found of significantly different allele frequencies of ABCA4 sequence
variants in patients compared with control subjects, and no evidence for
association or cosegregation with disease in family-based analyses. CONCLUSIONS. 
This study confirmed the very high degree of ABCA4 sequence polymorphism in the
general population, which makes the detection of potential disease-associated
alleles particularly challenging. While this study does not definitively exclude 
ABCA4 from contributing to a small or moderate fraction of ARM, it adds to the
body of evidence suggesting that ABCA4 is not a major susceptibility gene for
this disorder.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.

PMID: 12824224 [PubMed - indexed for MEDLINE]

2542: Vision Res. 2003 Jul;43(16):1777-87.

Patients with AMD and a large absolute central scotoma can be trained
successfully to use eccentric viewing, as demonstrated in a scanning laser
ophthalmoscope.

Nilsson UL, Frennesson C, Nilsson SE.

Department of Ophthalmology, Linköping University, SE-581 85 Linköping, Sweden.

Twenty patients with age-related macular degeneration, an absolute central
scotoma and a mean visual acuity of 0.04 (20/475) were studied. A scanning laser 
ophthalmoscope (SLO) was used for microperimetry and determination of preferred
retinal locus, often located to the left of the retinal lesion (corresponding to 
a location to the left of the visual field scotoma), which is considered
unfavorable for reading. All 20 patients were trained to use a new and more
favorable retinal locus for reading, above (or occasionally below) the retinal
lesion (corresponding to a location below or above the visual field scotoma),
first by reading scrolled text under simultaneous fixation monitoring and
instruction in the SLO and then by reading printed text, using high magnification
(mean 14.3x). For the 18 patients who learned to use eccentric viewing, reading
speed with adequate magnification prior to training was 9.0+/-5.8 words/min. With
training (mean 5.2 hours), it increased significantly (p<0.001) to 68.3+/-19.4
words per min. Training of eccentric reading has thus proved to be very
successful.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12818347 [PubMed - indexed for MEDLINE]

2543: Vision Res. 2003 Jul;43(16):1765-75.

Macular pigment density and distribution: comparison of fundus autofluorescence
with minimum motion photometry.

Robson AG, Moreland JD, Pauleikhoff D, Morrissey T, Holder GE, Fitzke FW, Bird
AC, van Kuijk FJ.

Moorfields Eye Hospital, City Road, London EC1V 2PD, UK.

Macular pigment (MP) distribution profiles were measured for 18 subjects using a 
Moreland anomaloscope modified for motion photometry. The total amount of MP
within the central 7 degrees was estimated from the distribution profile by
numerical integration. Fundus autofluorescence images were obtained for eight of 
these subjects using a scanning laser ophthalmoscope. Peak optical density of MP 
increased with the total amount present, but the correlation was weakened by
inter-subject differences in MP distribution. The mean MP distribution derived
from mean grey-scale profiles of fundus autofluorescence images correlated
closely with that obtained psychophysically (r=0.96). Autofluorescence imaging
provides a fast non-invasive method for assessing MP in vivo.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12818346 [PubMed - indexed for MEDLINE]

2544: Ophthalmic Res. 2003 Jul-Aug;35(4):192-8.

Vitrectomy for diabetic macular edema: effect of glycemic control (HbA(1c)),
renal function (creatinine) and other local factors.

Kojima T, Terasaki H, Nomura H, Suzuki T, Mori M, Ito Y, Miyake Y.

Department of Ophthalmology, Nagoya University School of Medicine, Nagoya, Japan.

AIMS: To determine the effect of preoperative factors on the foveal thickness
following vitrectomy for diabetic macular edema. METHODS: Fifty-eight eyes of 47 
patients underwent vitrectomy for diabetic macular edema. In all eyes, no clear, 
visible vitreomacular traction was present. Twelve eyes were pseudophakic before 
vitrectomy, and 31 eyes underwent concurrent phacoemulsification and intraocular 
lens (IOL) implantation. Multiple logistic regression analysis was used to assess
the independent effect of age, history of photocoagulation, diabetic retinopathy 
status, preoperative posterior vitreous detachment, HbA(1c) and serum creatinine 
levels within 2 weeks before surgery, lens status after surgery and follow-up
period on the foveal thickness determined by optical coherence tomography.
RESULTS: The median preoperative visual acuity was 20/100 (range from 20/500 to
20/20), and the median postoperative visual acuity was 20/70 (range from 20/500
to 20/13). The preoperative visual acuity (logarithm of minimal angle of
resolution; logMAR) was 0.73 +/- 0.36 (mean +/- SD; 20/107 Snellen acuity), and
the mean postoperative logMAR visual acuity was 0.60 +/- 0.39 (20/80), which was 
significantly better than the mean preoperative value (Wilcoxon signed rank test,
p = 0.011). The mean +/- SD of preoperative foveal thickness was 475.9 +/- 172.5 
micrometer, and the mean postoperative foveal thickness was 277.3 +/- 171.9
micrometer. The mean postoperative foveal thickness was significantly thinner
than the preoperative thickness (Student's paired t test, p < 0.0001). Multiple
logistic regression analysis showed that a preoperative low HbA(1c) and
postoperative pseudophakia were independently associated with the decrease in
foveal thickness (p = 0.01, p = 0.04, respectively). CONCLUSIONS: The greater
reduction in foveal thickness in eyes with an IOL probably resulted from a
relatively larger amount of vitreous being removed during the vitrectomy. Because
the decrease in foveal thickness may be related to the preoperative glycemic
control and the amount of vitreous, these factors should be considered in the
planning for vitrectomy. Copyright 2003 S. Karger AG, Basel

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12815194 [PubMed - indexed for MEDLINE]

2545: Br J Ophthalmol. 2003 Jul;87(7):893-8.

Genetic linkage analysis of a novel syndrome comprising North Carolina-like
macular dystrophy and progressive sensorineural hearing loss.

Francis PJ, Johnson S, Edmunds B, Kelsell RE, Sheridan E, Garrett C, Holder GE,
Hunt DM, Moore AT.

Institute of Ophthalmology, University College London, 11-43 Bath Street, London,
UK.

AIM: To characterise the phenotype and identify the underlying genetic defect in 
a family with deafness segregating with a North Carolina-like macular dystrophy
(NCMD). METHODS: Details of the family were obtained from the Moorfields Eye
Hospital genetic clinic database and comprised eight affected, four unaffected
members, and two spouses. Pedigree data were collated and leucocyte DNA extracted
from venous blood. Positional candidate gene and genetic linkage strategies
utilising polymerase chain reaction (PCR) based microsatellite marker genotyping 
were performed to identify the disease locus. RESULTS: The non-progressive ocular
phenotype shared similarities with North Carolina macular dystrophy.
Electro-oculography and full field electroretinography were normal. Progressive
sensorineural deafness was also present in all affected individuals over the age 
of 20 years. Hearing was normal in all unaffected relatives. Haplotype analysis
indicated that this family is unrelated to previously reported families with
NCMD. Genotyping excluded linkage to the MCDR1 locus and suggested a potential
novel disease locus on chromosome 14q (Z=2.92 at theta=0 for marker D14S261).
CONCLUSION: The combination of anomalies segregating in this family represents a 
novel phenotype. This molecular analysis indicates the disease is genetically
distinct from NCMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12812894 [PubMed - indexed for MEDLINE]

2546: Isr Med Assoc J. 2003 May;5(5):361-4.

Potential applications of matrix metalloproteinase inhibitors in geriatric
practice.

Marder G, Greenwald RA.

Department of Rheumatology, Long Island Jewish Medical Center, New York, NY, USA.
marder@lij.edu, rgreen@lij.edu

Matrix metalloproteinases are a family of enzymes that degrade different
components of extracellular matrix. They play an important role in normal
physiologic processes of maintaining tissue integrity and remodeling, as in wound
healing, processes of development, and regeneration. However, excessive
expression of MMP has been observed in many disease states, including rheumatoid 
arthritis and osteoarthritis, vascular remodeling in atherosclerosis and aortic
aneurysm formation, neoplastic processes, macular degeneration and many others.

Publication Types: 
    Review

PMID: 12811957 [PubMed - indexed for MEDLINE]

2547: Cochrane Database Syst Rev. 2003;(2):CD002030.

Update in:
    Cochrane Database Syst Rev. 2005;(4):CD002030.

Update of:
    Cochrane Database Syst Rev. 2001;(3):CD002030.

Photodynamic therapy for neovascular age-related macular degeneration.

Wormald R, Evans J, Smeeth L, Henshaw K.

Research and Development Department, Moorfields Eye Hospital and Institute of
Ophthalmology (UCL), City Road, London, UK, EC1V 2PD. r.wormald@ucl.ac.uk

BACKGROUND: In neovascular age-related macular degeneration, new vessels grow
under the retina, distorting vision and leading to scarring. This is further
exacerbated if the blood vessels leak. Photodynamic therapy, originally used in
cancer treatment, has been investigated as a way to treat the neovascular
membranes without affecting the retina. OBJECTIVES: The aim of this review is to 
examine the effects of photodynamic therapy in the treatment of neovascular
age-related macular degeneration. SEARCH STRATEGY: We searched for trials in the 
Cochrane Central Register of Controlled Trials - CENTRAL (which includes the
Cochrane Eyes and Vision Group trials register) on the Cochrane Library (Issue 4 
2002), MEDLINE (1966 to November 2002) and EMBASE (1980 to November 2002). We
used the Science Citation Index to search for reports that cited relevant study
reports. We contacted experts in the field and we searched the reference lists of
relevant studies for further trial reports. SELECTION CRITERIA: We included
randomised trials of photodynamic therapy in people with choroidal
neovascularisation due to age-related macular degeneration. DATA COLLECTION AND
ANALYSIS: Two reviewers extracted the data independently. Relative risks were
combined using a fixed effect model after testing for heterogeneity using a
chi-square test. MAIN RESULTS: Two published trials were identified that
randomised 948 participants to verteporfin therapy compared to 5% dextrose in
water. Both trials were performed by the same investigators using largely the
same clinical centres and funded by manufacturers of verteporfin. Outcome data
were available at 12 and 24 months after the first treatment. Participants
received on average five treatments over two years. The relative risk of losing
three or more lines of visual acuity at 24 months comparing the intervention with
the control group was 0.77 (95% confidence interval 0.69 to 0.87). The relative
risk of losing six or more lines of visual acuity at 24 months comparing the
intervention with the control group was 0.62 (95% confidence interval 0.50 to
0.76). The results at 12 months were similar to those at 24 months. REVIEWER'S
CONCLUSIONS: Photodynamic therapy in people with choroidal neovascularisation due
to age-related macular degeneration is effective in preventing visual loss.
Outcomes and potential adverse effects of this treatment should be monitored
closely. Further independent trials of Verteporfin are required to establish that
the effects seen in this study are consistent and to determine important
questions not yet addressed, particularly relating to quality of life and cost.

Publication Types: 
    Review

PMID: 12804420 [PubMed - indexed for MEDLINE]

2548: J Adv Nurs. 2003 Jul;43(1):10-8.

Older men's experiences of living with severe visual impairment.

Moore LW, Miller M.

Department of Nursing, Xavier University, Cincinnati, Ohio 45207-7351, USA.
moore@xavier.edu

BACKGROUND: Little is known about how men react to their health and illness
experiences. Lack of information about the lives of older men is unfortunate
considering the anticipated growth of the older male sector of society and the
fact that older men age differently than older women. One health-related
experience common to many older men is severe visual impairment caused by macular
degeneration, a chronic eye disease that affects central vision. Understanding
the health experiences of older men is imperative if nurses are to provide
quality care to this growing segment of society. AIM: The purpose of this study
was to gain an understanding of the experience of severe visual impairment from
the perspective of older men with macular degeneration. METHOD: A
phenomenological approach was used to investigate the experience of severe visual
impairment in eight older men with macular degeneration. Data were gathered
through audiotaped interviews and analysed using a modified Giorgi method.
FINDINGS: The resultant general structural description revealed six central
themes: (1) older men's lives were circumscribed by what they could and could not
see and could and could not do, (2) cherishing of independence, (3) creation of
strategies, (4) acknowledgment of the progression of visual impairment, (5)
confrontation of uncertainties, skepticism, and fears about their diagnosis and
treatment, and (6) persistence with hope and optimism. CONCLUSIONS: A thorough
nursing history and assessment must be completed, including information about the
progression of the visual impairment, strategies used for living with visual
loss, and presence of other health problems that may complicate life with visual 
impairment. Nurses must be aware that older men with macular degeneration are
often sceptical about their diagnosis and treatment. Therefore, careful education
and clear communication are essential.

PMID: 12801392 [PubMed - indexed for MEDLINE]

2549: Ophthalmology. 2003 Jun;110(6):1273-80.

Comment in:
    Am J Ophthalmol. 2007 Sep;144(3):482-3; author reply 483.

Corrected and republished from:
    Ophthalmology. 2003 Apr;110(4):636-43.

The association of cardiovascular disease with the long-term incidence of
age-related maculopathy: the Beaver Dam Eye Study.

Klein R, Klein BE, Tomany SC, Cruickshanks KJ.

Department of Ophthalmology and Visual Sciences, University of Wisconsin Medical 
School, Madison 53726, USA.

PURPOSE: To examine the association between cardiovascular disease and its risk
factors and the 10-year incidence of age-related maculopathy. DESIGN:
Population-based cohort study. PARTICIPANTS: Persons 43 to 86 years of age at
baseline examination from 1988 to 1990, living in Beaver Dam, Wisconsin, of whom 
3684 persons participated in a 5-year follow-up examination and 2764 participated
in a 10-year follow-up examination. METHODS: Standardized protocols for physical 
examination, blood collection, administration of a questionnaire, and
stereoscopic color fundus photography to determine age-related maculopathy. The
Kaplan-Meier (product-limit) survival approach and discrete linear logistic
regression were used in the data analysis. MAIN OUTCOME MEASURES: Incidence and
progression of age-related maculopathy. RESULTS: When age, gender, and history of
heavy drinking, smoking, and vitamin use were controlled for, higher systolic
blood pressure at baseline was associated with the 10-year incidence of retinal
pigment epithelial depigmentation (risk ratio [RR] per 10 mmHg systolic blood
pressure, 1.10; 95% confidence interval [CI], 1.01-1.18; P = 0.02) and exudative 
macular degeneration (RR, 1.22; 95% CI, 1.06-1.41; P = 0.006). Higher pulse
pressure at baseline was associated with the incidence of retinal pigment
epithelial depigmentation (RR per 10 mmHg, 1.17; 95% CI, 1.07-1.28; P < 0.001),
increased retinal pigment (RR, 1.10; 95% CI, 1.01-1.19; P = 0.03), exudative
macular degeneration (RR, 1.34; 95% CI, 1.14-1.60; P < 0.001), and progression of
age-related maculopathy (RR, 1.08; 95% CI, 1.01-1.17; P = 0.03). Higher serum
high-density lipoprotein cholesterol at baseline was associated with pure
geographic atrophy (RR per 10 mg/dl high-density lipoprotein cholesterol, 1.29;
95% CI, 1.05-1.58; P = 0.01). Physical activity at baseline was associated with
the incidence of geographic atrophy (RR in those who worked up a sweat 5 times a 
week compared with those who did not, 0.12; 95% CI, 0.02-0.91; P = 0.04)
exudative macular degeneration (RR, 0.27; 95% CI, 0.08-0.87; P = 0.05), and
progression of age-related maculopathy (RR, 0.69; 95% CI, 0.47-1.00; P = 0.05).
Neither a history of stroke nor heart attack was associated with the incidence or
progression of age-related maculopathy. CONCLUSIONS: These findings indicate
relationships between higher pulse pressure (a presumed indicator of age-related 
elastin and collagen changes in Bruch's membrane) and systolic blood pressure
with an increased 10-year incidence of some lesions defining early age-related
maculopathy and exudative macular degeneration.

Publication Types: 
    Corrected and Republished Article
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12799274 [PubMed - indexed for MEDLINE]

2550: Ophthalmology. 2003 Jun;110(6):1164-9.

Vitreoretinal surgery for cystoid macular edema associated with retinitis
pigmentosa.

García-Arumí J, Martinez V, Sararols L, Corcostegui B.

Hospital Vall d'Hebrón, Universidad Autónoma de Barcelona, Spain.
17215jga@comb.es

PURPOSE: To evaluate the anatomic and functional outcome of vitreoretinal surgery
in eyes with retinitis pigmentosa (RP) and macular edema. DESIGN: Prospective
noncomparative case series. PARTICIPANTS: Twelve consecutive eyes of eight
patients with RP and a documented decrease in visual acuity (VA) to 20/60 or
worse caused by macular edema refractory to medical therapy. METHODS: Pars plana 
vitrectomy was performed in the 12 eyes, followed by posterior hyaloid
dissection, removal of the posterior inner limiting membrane after staining with 
indocyanine green, and gas tamponade. Preoperative best-corrected VAs ranged from
20/60 to 20/400 (mean, 20/115). MAIN OUTCOME MEASURES: Changes in VA and foveal
thickness as determined by optical coherence tomography (OCT). RESULTS: The mean 
preoperative retinal thickness at the fovea was 477 micro m. Optical coherence
tomography showed a decrease in macular thickness of >40% in 10 eyes (83.3%),
with a mean postoperative foveal thickness of 260 micro m. The mean VA increased 
from 20/115 to 20/45, with an average of three lines of improvement. CONCLUSIONS:
Our results suggest that vitreoretinal surgery may effectively manage macular
edema in RP.

PMID: 12799242 [PubMed - indexed for MEDLINE]

2551: Ophthalmology. 2003 Jun;110(6):1151-8.

Visual acuity loss and clinical observations in a large series of patients with
Stargardt disease.

Rotenstreich Y, Fishman GA, Anderson RJ.

Department of Ophthalmology and Visual Science, University of Illinois at
Chicago, 60612, USA.

PURPOSE: To assess visual acuity impairment in Stargardt disease. DESIGN:
Retrospective clinic-based cross-sectional study. PARTICIPANTS: Three-hundred
sixty-one patients with Stargardt disease. METHODS: Clinical findings in 361
patients were analyzed as part of a cross-sectional evaluation. Visual acuity at 
their most recent visit, fundus photographs, and electroretinographic findings
were reviewed, and patients were categorized into four clinical phenotypes.
Seventy-three patients with 20/40 or better vision and 38 patients with 20/50 to 
20/100 vision in the better seeing eye at their initial visit who were followed
for at least 1 year were included in a survival analysis. For analysis purposes, 
these latter patients were categorized into four 20-year age groups according to 
their age at initial visit. MAIN OUTCOME MEASURES: Best-corrected visual acuity
from the eye with better vision on the most recent visit was used in the
cross-sectional analysis. For the survival analysis, best-corrected visual acuity
was used from the eye with better vision on the initial visit. RESULTS:
Eighty-two of the 361 patients (23%) had 20/40 or better acuity in at least one
eye, 64 (18%) 20/50 to 20/100, and 199 (55%) 20/200 to 20/400, whereas 16 (4%)
had worse than 20/400 in each eye at their most recent visit. In the patients
with visual acuity of 20/40 or better, 59 (72%) had foveal sparing visible on
ophthalmoscopic examination. The median time to develop visual acuity of 20/200
or worse was 22 years for the patients with 20/40 or better visual acuity at
their initial visit. Those seen initially in the first two decades of life with
this level of acuity showed a median time of 7 years to reach a visual acuity of 
20/200 or worse compared with 22 years and 29 years for those who were initially 
seen at ages 21 to 40 or 41 to 60, respectively. Analyzing by the four 20-year
age groups, the log rank statistic indicated significant differences in the
survival experience among the four groups (P = 0.004). The median time to develop
20/200 vision or worse was 6 years for the patients with 20/50 to 20/100 visual
acuity at their initial visit, and this result, based on the log rank statistic, 
was independent of age group at initial visit (P = 0.852). CONCLUSIONS: In a
large cohort of Stargardt patients, a cross-sectional analysis showed that almost
a quarter had vision of 20/40 or better, whereas 4% had acuity of worse than
20/400. The presence of foveal sparing ophthalmoscopically was associated with a 
higher prevalence of 20/40 or better visual acuity. Survival analysis showed that
the prognosis of patients who initially were seen with visual acuity of 20/40 or 
better is related to age at initial visit.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12799240 [PubMed - indexed for MEDLINE]

2552: Minn Med. 2003 Apr;86(4):40-6.

New treatments for age-related macular degeneration.

Mittra RA.

VitreoRetinal Surgery, P.A., Edina, USA.

The estimated increase in life expectancy of the U.S. population will result in a
greater incidence of age-related macular degeneration (AMD) in the next few
decades. Exudative AMD, which is characterized by choroidal neovascularization,
carries a high risk of severe central vision loss and can compromise an
individual's independence and quality of life. The increasing burden of AMD has
created an acute need for more effective treatments. Results from a recent
large-scale study have shown that supplementation with antioxidants and zinc
reduces the risk of progression of dry to exudative AMD. Standard thermal laser
photocoagulation can reduce the risk of central vision loss in exudative AMD in a
limited number of patients. The recent advent of photodynamic laser therapy has
increased the number of patients with exudative AMD who can benefit from
treatment. This paper summarizes the clinical presentation of AMD and reviews
treatments that are currently available, as well as treatments in development.

PMID: 12797657 [PubMed - indexed for MEDLINE]

2553: Arch Ophthalmol. 2003 Jun;121(6):817-20.

Large-spot size transpupillary thermotherapy for the treatment of occult
choroidal neovascularization associated with age-related macular degeneration.

Thach AB, Sipperley JO, Dugel PU, Sneed SR, Park DW, Cornelius J.

Retinal Consultants of Arizona, Phoenix 85064, USA.

OBJECTIVE: To describe the outcome of patients with occult choroidal
neovascularization in age-related macular degeneration treated with
transpupillary thermotherapy. DESIGN: Prospective, nonrandomized, nonmasked case 
series. METHODS: All patients with age-related macular degeneration with a
predominantly occult choroidal neovascular membrane and an initial visual acuity 
of 20/400 or better were offered treatment using transpupillary thermotherapy.
The treatment consisted of using a diode laser, a spot size of about 3000 to 6000
micro m delivered over 60 seconds, and a power of 600 to 1000 mW.Main Outcome
Measures: A stable, improved, or worsened visual acuity and the need for
additional treatment. RESULTS: Sixty-nine patients were treated. All patients
have been followed up for at least 6 months. At the 6-, 9-, and 12-month
follow-up visits, 71% of patients have stable or improved visual acuity and 29%
have lost 2 or more lines of visual acuity on the Snellen letter chart.
CONCLUSION: Large-spot size transpupillary thermotherapy is effective in
stabilizing the visual acuity in those patients who have occult choroidal
neovascularization due to age-related macular degeneration.

Publication Types: 
    Clinical Trial

PMID: 12796252 [PubMed - indexed for MEDLINE]

2554: Arch Ophthalmol. 2003 Jun;121(6):785-92.

Progression of age-related macular degeneration: association with body mass
index, waist circumference, and waist-hip ratio.

Seddon JM, Cote J, Davis N, Rosner B.

Epidemiology Unit, Massachusetts Eye and Ear Infirmary, Boston 02114, USA.
johanna_seddon@meei.harvard.edu

BACKGROUND: Individuals with early or intermediate stages of age-related macular 
degeneration (AMD) make up a large and growing segment of our elderly population.
To advise these high-risk patients regarding preventive measures, we evaluated
anthropomorphic, behavioral, and medical factors associated with progression to
the advanced stages of AMD associated with visual loss. METHODS: The design was a
prospective cohort study in a hospital-based retinal practice. The 261
participants were 60 years or older, with some sign of nonadvanced AMD and visual
acuity of 20/200 or better in at least 1 eye. The average follow-up time was 4.6 
years, and the total person-years of follow-up was 1198. Factors associated with 
rates of progression to advanced AMD were assessed by the Cox proportional
hazards model. OUTCOME MEASURES: Progression to geographic atrophy and
neovascular disease. RESULTS: Higher body mass index (calculated as weight in
kilograms divided by the square of height in meters) increased the risk for
progression to the advanced forms of AMD. Relative risk (RR) was 2.35 (95%
confidence interval [CI], 1.27-4.34) for a body mass index of at least 30, and
2.32 (95% CI, 1.32-4.07) for a body mass index of 25 to 29, relative to the
lowest category (<25) after controlling for other factors (P =.007 for trend).
Higher waist circumference was associated with a 2-fold increased risk for
progression (RR for the highest tertile compared with the lowest, 2.04; 95% CI,
1.12-3.72), with a significant trend for increasing risk with a greater waist
circumference (P =.02). Higher waist-hip ratio also increased the risk for
progression (RR, 1.84; 95% CI, 1.07-3.15) for the highest tertile compared with
lowest (P =.02 for trend). More physical activity tended to be associated with a 
reduced rate of progression (25% reduction for 3 times per week vigorous activity
vs none, P =.05 to P =.07). Relative risks for smoking ranged from 1.48 to 1.99, 
but were not statistically significant. CONCLUSIONS: Results provide new
information regarding modifiable factors for individuals with the early or
intermediate stages of this disease. Overall and abdominal obesity increased the 
risk for progression to advanced AMD, and more physical activity tended to
decrease risk. These preventive measures deserve additional research and greater 
emphasis.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12796248 [PubMed - indexed for MEDLINE]

2555: IDrugs. 2003 May;6(5):464-9.

Status of therapies in development for the treatment of age-related macular
degeneration.

Hunt DW, Margaron P.

QLT Inc, Preclinical Development, 887 Great Northern Way, Vancouver BC, V5T 4T5, 
Canada. dhunt@qltinc.com

Age-related macular degeneration (AMD) is among the leading causes of visual
impairment in the elderly. The FDA has approved only two treatments, laser
photocoagulation and Visudyne photodynamic therapy (PDT), approved for the wet
form of AMD, a progressive condition characterized by the presence of choroidal
neovascularization (CNV). Current pharmaceutical activities aimed at the
treatment of wet-type AMD are largely focused on the development of
anti-angiogenic drugs that would inhibit further CNV formation or even reduce
existing CNV. However, other lines of attack for the treatment of wet AMD include
anti-inflammatory agents as well as new PDT agents. This review will summarize
ongoing activities for these different approaches.

Publication Types: 
    Review

PMID: 12789601 [PubMed - indexed for MEDLINE]

2556: Ophthalmic Genet. 2003 Jun;24(2):75-80.

Erratum in:
    Ophthalmic Genet. 2003 Dec;24(4):253.

The gene for Stargardt disease, ABCA4, is a major retinal gene: a mini-review.

Koenekoop RK.

Department of Ophthalmology, McGill University, Montreal Children's Hospital,
2300 Tupper, Montreal, Quebec H3H 1P3, Canada.

The gene ABCA4 encodes the rod and cone photoreceptor Rim protein, which is a
transmembrane transporter of vitamin A intermediates. ABCA 4 mutations are
responsible for a large variety of retinal degenerations including all cases of
Stargardt macular dystrophy and fundus flavimaculatus, some forms of cone-rod
degeneration, and retinitis pigmentosa, and likely increase the risk of
developing age-related macular degeneration (AMD). The purpose of this
mini-review is to highlight the advances in our understanding of Stargardt
disease and the ABCA4 gene from the first description of the disease by Karl
Stargardt in 1909 to gene discovery by Allikmets and colleagues in 1997. The
knockout mouse model by Mata and co-workers has provided crucial
pathophysiological information that has led to new ideas regarding treatment
possibilities. These hypotheses were tested by Radu and colleagues in the mouse
and shown to be efficacious.

Publication Types: 
    Review

PMID: 12789571 [PubMed - indexed for MEDLINE]

2557: Am J Ophthalmol. 2003 Jun;135(6):917-9.

Macular dystrophy in a Japanese family with fundus albipunctatus.

Hotta K, Nakamura M, Kondo M, Ito S, Terasaki H, Miyake Y, Hida T.

Department of Ophthalmology, Kameda Medical Center, Kamogowa, Japan.
kahotta@kameda.jp

PURPOSE: To report a Japanese family with fundus albipunctatus and macular
dystrophy associated with a mutation in the 11-cis retinol dehydrogenase (RDH5)
gene. DESIGN: Observational case report. METHOD: Ophthalmic examinations and DNA 
analysis were performed. RESULTS: The fundi of a 56-year-old man and his
51-year-old sister showed numerous yellow-white punctata. He also had bull's-eye 
maculopathy and prepappillary arterial loops, whereas she did not, and his
best-corrected visual acuity was impaired, whereas hers was normal. Their kinetic
visual fields did, however, show central or paracentral scotoma, and both had
tritanomalous color vision. Their scotopic electroretinograms were typical of
fundus albipunctatus, and photopic electroretinograms were significantly reduced.
A homozygous Gly107Arg mutation in the RDH5 gene was detected in both siblings.
CONCLUSIONS: We suggest that the macular dystrophy is caused by the RDH5 gene
mutation as a phenotype variation in fundus albipunctatus.

Publication Types: 
    Case Reports

PMID: 12788147 [PubMed - indexed for MEDLINE]

2558: Am J Ophthalmol. 2003 Jun;135(6):849-56.

Comment in:
    Am J Ophthalmol. 2003 Nov;136(5):961.

Is there an association between cataract surgery and age-related macular
degeneration? Data from three population-based studies.

Freeman EE, Munoz B, West SK, Tielsch JM, Schein OD.

Dana Center for Preventive Ophthalmology, Wilmer Eye Institute, Johns Hopkins
University School of Medicine, Baltimore, Maryland 21287-9019, USA.

PURPOSE: To determine whether cataract surgery is associated with an increased
prevalence of age-related macular degeneration (AMD) in three independent
population-based data sets. DESIGN: Cross-sectional study. METHOD: Data were used
from the Salisbury Eye Evaluation (2,520 subjects from Salisbury, Maryland, aged 
65 to 84 years), the Proyecto VER (4,774 Hispanic subjects from Arizona aged 40
years and older), and the Baltimore Eye Survey (4,396 subjects from Baltimore,
Maryland, aged 40 and older). The main outcome measure was AMD as determined by
retinal photographs or clinical examination. RESULTS: A history of cataract
surgery was associated with an increased prevalence of late AMD in all three data
sets after adjusting for age, race, sex, and smoking, but odds ratios (OR) were
not individually statistically significant. The OR for the combined analysis was 
1.7 (95% confidence interval: 1.1-2.6). Having a severe cataract in the eye was
also associated with a slightly higher prevalence of late AMD, although the
combined OR was not statistically significant (OR = 1.4; 95% confidence interval,
0.8%-2.4). Overall, increasing time since cataract surgery was not associated
with late AMD. CONCLUSIONS: A history of cataract surgery may be associated with 
an increased prevalence of late AMD. However, having a severe cataract in the eye
may also be associated with a higher prevalence of late AMD. Additional research 
is needed to investigate whether a causal relationship exists between cataract
surgery and AMD or whether this relationship is due to residual confounding or
bias.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12788126 [PubMed - indexed for MEDLINE]

2559: Curr Opin Ophthalmol. 2003 Jun;14(3):159-62.

Who should receive oral supplement treatment for age-related macular
degeneration?

McBee WL, Lindblad AS, Ferris FL 3rd.

The EMMES Corporation, Rockville, Maryland 20850, USA.

Oxidative damage to the retina has been proposed as a risk factor for age-related
macular degeneration (AMD). Dietary or supplemental antioxidants may play a
protective role. The Age-Related Eye Disease Study (AREDS), a randomized,
multicenter, placebo-controlled clinical trial designed to test the effect of
pharmacologic doses of antioxidants and zinc on the incidence and progression of 
AMD, reported a beneficial effect of high-dose supplements, taken for
approximately 6 years, in delaying the progression of intermediate AMD to
advanced AMD. AREDS and subsequent research on dietary intake or supplement use
have not indicated a protective role of antioxidant or zinc intake or supplement 
use in the incidence or prevalence of early AMD. Numbers of cases were
insufficient to investigate effects on late AMD. Persons with intermediate AMD
and without contraindications should consider using antioxidant and zinc
supplements. There is no evidence to date that earlier use conveys benefit.

Publication Types: 
    Review

PMID: 12777936 [PubMed - indexed for MEDLINE]

2560: Br J Ophthalmol. 2003 Jun;87(6):753-7.

The effects of dorzolamide on choroidal and retinal perfusion in non-exudative
age related macular degeneration.

Harris A, Ciulla TA, Pratt LM, Rechtman E, Kagemann L, Piper HC, Garzozi HJ.

Department of Ophthalmology, Indiana University School of Medicine, IN 46260,
USA. alharris@indiana.edu

AIM: To comprehensively evaluate the effects of dorzolamide on the choroidal and 
retinal circulation in patients with age related macular degeneration (AMD).
METHODS: In this randomised, double masked, parallel study, 36 non-exudative AMD 
patients were randomised in a 2 to 1 fashion to placebo versus topical
dorzolamide and underwent assessment of their choroidal and retinal circulation. 
Scanning laser ophthalmoscope indocyanine green angiograms (ICGA) were analysed
by a new area dilution analysis technique. Four areas in the perifoveal region
and two areas in the temporal peripapillary region were evaluated by plotting
intensity of fluorescence of each area over time. The means of the choroidal
filling times and the heterogeneity of the filling times were assessed. Scanning 
laser ophthalmoscope fluorescein angiography (FA) was evaluated for retinal
arteriovenous passage (AVP) times by plotting intensity of fluorescence of
retinal vessels over time. Assessment was performed at baseline and at 4 months. 
RESULTS: Compared to placebo, AMD patients treated with dorzolamide showed a
significantly increased rapidity of choroidal filling in the superior and
inferior peripapillary regions (p=0.007, p=0.02, respectively). No significant
difference in choroidal filling times was found in any of the perifoveal areas
(p=0.9). Also, on FA assessment, treatment with dorzolamide showed no statistical
differences in AVP times (p=0.19). CONCLUSIONS: Dorzolamide may increase
peripapillary choroidal perfusion in non-exudative AMD patients. Further studies 
are merited.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12770975 [PubMed - indexed for MEDLINE]

2561: Invest Ophthalmol Vis Sci. 2003 Jun;44(6):2461-5.

Lutein and zeaxanthin status and risk of age-related macular degeneration.

Gale CR, Hall NF, Phillips DI, Martyn CN.

Medical Research Council Environmental Epidemiology Unit, University of
Southampton, Southampton General Hospital, Southampton, United Kingdom.
crg@mrc.soton.ac.uk

PURPOSE: To investigate the relation between plasma concentrations of lutein and 
zeaxanthin and age-related macular degeneration in a group of elderly men and
women. METHODS: The Wisconsin Age-Related Maculopathy Grading System was used to 
grade features of early and late macular degeneration in 380 men and women, aged 
66 to 75 years, from Sheffield, United Kingdom. Fasting blood samples were taken 
to assess plasma concentrations of lutein and zeaxanthin. RESULTS: Risk of
age-related macular degeneration (early or late) was significantly higher in
people with lower plasma concentrations of zeaxanthin. Compared with those whose 
plasma concentrations of zeaxanthin were in the highest third of the
distribution, people whose plasma concentration was in the lowest third had an
odds ratio for risk of age-related macular degeneration of 2.0 (95% confidence
interval [CI] 1.0-4.1), after adjustment for age and other risk factors. Risk of 
age-related macular degeneration was increased in people with the lowest plasma
concentrations of lutein plus zeaxanthin (odds ratio [OR] 1.9, 95% CI 0.9-3.5)
and in those with the lowest concentrations of lutein (OR 1.7, 95% CI 0.9-3.3),
but neither of these relations was statistically significant. CONCLUSIONS: These 
findings provide support for the view that zeaxanthin may protect against
age-related macular degeneration.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12766044 [PubMed - indexed for MEDLINE]

2562: Mol Vis. 2003 May 14;9:184-90.

Amyloid-beta is found in drusen from some age-related macular degeneration
retinas, but not in drusen from normal retinas.

Dentchev T, Milam AH, Lee VM, Trojanowski JQ, Dunaief JL.

F. M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute,
Philadelphia, PA, USA.

PURPOSE: Age-related macular degeneration (AMD) is the most common cause of
irreversible vision loss in the elderly. Increased understanding of the
pathogenesis is necessary. Amyloid-beta (Abeta), a major extracellular deposit in
Alzheimer's disease plaques, has recently been found in drusen, the hallmark
extracellular deposit in AMD. The goal of this study was to characterize the
distribution and frequency of Abeta deposits in drusen from AMD and normal post
mortem human retinas to gain additional insight about the potential role of Abeta
in AMD patho genesis. METHODS: Immunocytochemistry was performed with three Abeta
antibodies on sections from 9 normal and 9 AMD (3 early, 3 geographic atrophy, 3 
exudative AMD) retinas. Five sections from each eye were evaluated. Abeta
positive deposits in drusen were identified using epifluorescence and confocal
microscopy. Antibodies were pre-adsorbed with Abeta peptide to verify
specificity. Some sections were stained with PAS-hematoxylin to aid in evaluation
of morphology. RESULTS: To test and optimize immunocytochemistry, Abeta was
detected in amyloid plaques from Alzheimer's brains. Abeta label was blocked by
pre-adsorption of antibody with Abeta peptide, verifying specificity. Four of the
9 AMD retinas and none of the 9 normal retinas had Abeta positive drusen. Two of 
the early AMD eyes had a few A[beta] positive drusen, each with a few
Abeta-containing vesicles, and 2 of the geographic atrophy (GA) eyes had many
Abeta positive drusen with many Abeta containing vesicles. CONCLUSIONS: Abeta was
present in 4 of 9 AMD eyes. Within these eyes, Abeta localized to a subset of
drusen. None of the 9 normal eyes surveyed, some of which had small drusen, were 
A beta positive. Abetapositive vesicles were most numerous in GA eyes at the
edges of atrophy, the region at risk for further degeneration. These results
suggest that Abeta in drusen correlates with the location of degenerating
photoreceptors and retinal pigment epithelium (RPE) cells. Further work will be
necessary to determine whether Abeta deposition in drusen may contribute to or
result from retinal degeneration.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12764254 [PubMed - indexed for MEDLINE]

2563: Semin Ophthalmol. 2002 Sep-Dec;17(3-4):187-95.

Cataract extraction and age-related macular degeneration: associations, diagnosis
and management.

Velez G, Weiter JJ.

Retina Specialists of Boston, Boston, MA, USA. brusie-velez@erols.com

Both cataract and age-related macular degeneration (ARMD) are common findings in 
our aging population. At issue is the progression of ARMD following cataract
extraction. The purpose of this paper is to review the data relevant to this
subject and to offer suggestions as to the management of cataract associated with
macular degeneration. Published data are reviewed and an attempt is made to
interpret the results. Topics discussed include the epidemiology and association 
between the incidence of cataract and ARMD, the role of photo-oxidative damage
and inflammation in the pathogenesis of ARMD, and the possible contribution of
cataract extraction to the exacerbation and acceleration of ARMD through
increased photo-oxidative damage and intraocular inflammation. Recommendations
for the cataract surgeon and specialist are formulated on the basis of existing
literature.

Publication Types: 
    Review

PMID: 12759849 [PubMed - indexed for MEDLINE]

2564: Semin Ophthalmol. 2002 Sep-Dec;17(3-4):181-6.

Cystoid macular edema in aphakia and pseudophakia after use of prostaglandin
analogs.

Halpern DL, Pasquale LR.

Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, MA,
USA. dlhalpern@yahoo.com

Prostaglandin analogs are powerful ocular hypotensive agents that may also be
associated with a breakdown of the blood-retinal barrier and cystoid macular
edema. The association is evident in pseudophakic or aphakic patients. This paper
presents a case of unilateral latanoprost-associated clinical cystoid macular
edema in a bilaterally pseudophakic patient; the only difference between the two 
eyes was the presence of a capsulotomy in the affected eye. We review the
literature concerning prostaglandin analog-associated cystoid macular edema, as
well as the evidence for prostaglandin analog-associated breakdown of the
blood-retinal barrier. Although some evidence is suggestive of a connection
between prostaglandin analogs and cystoid macular edema, many questions
concerning the complex physiology of prostanoids remain. Until our understanding 
of these issues is more advanced, judicious use of prostaglandin analogs in
patients at risk for cystoid macular edema would be prudent.

Publication Types: 
    Case Reports
    Review

PMID: 12759848 [PubMed - indexed for MEDLINE]

2565: Semin Ophthalmol. 2002 Sep-Dec;17(3-4):167-80.

Pseudophakic cystoid macular edema.

Ray S, D'Amico DJ.

Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical
School, Boston, MA 02114, USA. dsray@massmed.org

Cystoid macular edema (CME) following cataract surgery has been recognized for
over 50 years as an important cause of suboptimal post-operative vision. The
incidence of CME varies widely, but is likely in the range of 1-2% using modern
cataract extraction techniques. The diagnosis of CME can generally be made on
clinical examination with evidence of perifoveal cystic spaces and can be
confirmed with use of fluorescein angiography to document the classic petaloid
pattern of leakage mainly into the outer retina. Leak from perifoveal vessels is 
induced by inflammatory mediators and results in intraretinal fluid accumulation 
and corresponding decrease in retinal function. The risk factors most associated 
with CME; rupture of posterior capsule, vitreous loss, iris incarceration, use of
iris fixated lenses, active uveitis and diabetes, may all increase the potency of
these mediators and exacerbate post-operative CME. The treatment of CME remains
controversial but generally starts with conservative observation in isolated
angiographic cases and progresses through topical non-steroidal anti-inflammatory
agents (NSAIDs), topical steroids, peri-ocular steroids, systemic steroids and
surgical intervention in refractory cases. Even more controversial is the role of
NSAID prophylaxis peri-operatively in preventing clinical CME. Though the data is
tantalizing in the short term, there is little to support the long-term benefit
of such prophylaxis with respect to visual outcomes.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 12759847 [PubMed - indexed for MEDLINE]

2566: Biochim Biophys Acta. 2003 May 20;1638(1):20-8.

Expression of mutant and wild-type TIMP3 in primary gingival fibroblasts from
Sorsby's fundus dystrophy patients.

Arris CE, Bevitt DJ, Mohamed J, Li Z, Langton KP, Barker MD, Clarke MP, McKie N.

Department of Rheumatology and Gerentology, University of Newcastle Medical
School, Framlington Place, NE2 4HH, Newcastle, UK.

Gingival fibroblast cell lines were derived from Sorsby's fundus dystrophy (SFD) 
patients carrying the S181C TIMP3 and the E139X TIMP3 mutations. These cell lines
were grown in culture to study expression of the wild-type and mutant tissue
inhibitor of metalloproteinase 3 (TIMP3) alleles from a normal diploid cell type.
Firstly, patient cells were found to co-express the wild-type and mutant TIMP3
alleles, S181C TIMP3 or E139X TIMP3, at the mRNA level using restriction fragment
length polymorphism (RFLP) analysis. A SpeI RFLP for E139X TIMP3 is described.
Low levels of endogenous TIMP3 protein expression were elevated using the natural
polysaccharide calcium pentosan polysulfate (CaPPs) in combination with the
cytokine IL-1alpha. Immunoblotting detected protein expression from both
wild-type and mutant alleles, S181C TIMP3 or E139X TIMP3. S181C TIMP3 from these 
cells was found to dimerise and retain MMP2 inhibitory activity. To facilitate
studies of the E139X TIMP3 protein, the allele was expressed using HighFive
insect cells. In this cell type, the E139X TIMP3 was synthesised as a mixture of 
monomer and dimer. Both monomeric and dimeric E139X TIMP3 protein retained MMP2
inhibitory activity in gelatin zymography. Expression of mutant E139X or S181C
TIMP3 protein from a normal diploid patient-derived fibroblast cell had no effect
on either MMP2 or MMP9 expression or activation whilst transcribed from their
normal promoter context.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12757930 [PubMed - indexed for MEDLINE]

2567: Ophthalmic Surg Lasers Imaging. 2003 May-Jun;34(3):188-92.

Intravitreal dexamethasone effectively reduces postoperative inflammation after
vitreoretinal surgery.

Chalam KV, Malkani S, Shah VA.

Department of Ophthalmology, University of Florida College of Medicine,
Jacksonville 32209, USA.

BACKGROUND AND OBJECTIVE: Corticosteroids remain the mainstay for control of
ocular inflammation after vitreous surgery. A controlled, randomized, prospective
study was performed to evaluate the effectiveness of a single intravitreal
injection of dexamethasone phosphate on postoperative inflammation after simple
vitreous surgery in patients with proliferative diabetic retinopathy and macular 
pucker. PATIENTS AND METHODS: Aqueous cell flare intensity was measured
preoperatively and on days 1, 10, and 90 in 56 consecutive patients who underwent
vitreous surgery for proliferative diabetic retinopathy and macular pucker.
Subjects were consecutively randomized to two groups: 400 microg of intravitreal 
dexamethasone (treatment group) or no dexamethasone (control group) RESULTS:
Before surgery, cell and flare intensity was similar in both groups. Flare
intensity was significandy lower at 10, 30, and 90 days in the proliferative
diabetic retinopathy treatment group (P < .05). CONCLUSION: Intravitreal
dexamethasone significantly alleviates postoperative inflammation after vitreous 
surgery and is a useful adjunct.

Publication Types: 
    Clinical Trial
    Evaluation Studies
    Randomized Controlled Trial

PMID: 12757090 [PubMed - indexed for MEDLINE]

2568: Acta Ophthalmol Scand. 2003 Apr;81(2):110-7.

Transpupillary thermotherapy of predominantly occult choroidal neovascularization
in age-related macular degeneration with 12 months follow-up.

Algvere PV, Libert C, Lindgärde G, Seregard S.

Department of Ophthalmology, Karolinska Institutet, St Erik's Eye Hospital,
Stockholm, Sweden. peep.algvere@sankterik.se

PURPOSE: To perform a phase I/II safety and efficacy study in order to assess the
outcome following transpupillary thermotherapy (TTT) for occult choroidal
neovascularization (CNV) with no or minimally classic CNV in age-related macular 
degeneration. METHODS: The study comprised 113 referred patients (79 females, 34 
males) aged 59-89 years (mean 77.7 years) with predominantly occult CNV. There
were 49 cases of occult with no classic CNV and 64 of occult with minimally
classic CNV. According to their greatest linear dimension, lesions were
classified as being < 3.0 mm or > 3.0 mm. Transpupillary thermotherapy was
delivered with a diode laser, emission at 810 nm, duration 60 seconds, laser
power 500-800 mW. Clinical examination, ETDRS logMAR visual acuity and
fluorescein angiography were carried out at baseline, and at 3, 6 and 12 months
in all cases. RESULTS: The average baseline visual acuity was 0.20 (50.6
letters). Following TTT, it was 0.12 (42.0 letters) at 6 months and 0.12 (38.0
letters) at 12 months. Visual acuity improved in 9/113 eyes (8.0%), remained
unchanged in 46 (40.7%) eyes, and deteriorated in 58 (51.3%) eyes. There was no
significant difference in the proportion of eyes that had lost at least 15
letters at 12 months in the subgroup of occult with no classic CNV (18/49; 36.7%)
versus those with minimally classic lesions < 3.0 mm (15/39; 38.5%). However,
13/25 (52.0%) of cases with minimally classic lesions > 3.0 mm had lost at least 
15 letters at 12 months (p = 0.31). The most common complications in the 46 eyes 
that suffered visual loss comprised subretinal progressive fibrosis (18 eyes) and
atrophy of the retinal pigment epithelium (13 eyes). CONCLUSIONS: This study
shows that TTT generally prevents moderate and severe visual loss at 12 months
follow-up in occult CNV with no classic CNV. Eyes with minimally classic lesions 
with a greatest linear dimension of < 3.0 mm also show the same positive outcome.
These results compare favourably with published data on the natural course of the
disease. However, minimally classic lesions of > 3.0 mm responded poorly in this 
treatment setting.

Publication Types: 
    Clinical Trial
    Clinical Trial, Phase I
    Clinical Trial, Phase II
    Research Support, Non-U.S. Gov't

PMID: 12752047 [PubMed - indexed for MEDLINE]

2569: Ophthalmology. 2003 May;110(5):979-86.

Comment on:
    Ophthalmology. 2003 May;110(5):879-81.

Anti-vascular endothelial growth factor therapy for subfoveal choroidal
neovascularization secondary to age-related macular degeneration: phase II study 
results.

Eyetech Study Group.

PURPOSE: There is evidence to suggest that anti-vascular endothelial growth
factor (anti-VEGF) therapy may be useful in treating ocular neovascularization. A
phase IA single intravitreal injection study of anti-VEGF therapy for patients
with subfoveal choroidal neovascularization (CNV) secondary to age-related
macular degeneration (AMD) revealed a good safety profile. We performed a phase
II multiple injection study of anti-VEGF therapy with and without photodynamic
therapy for patients with subfoveal CNV secondary to AMD to determine the safety 
profile of multiple injection therapy. DESIGN: A phase II multiple-dose safety
study. PARTICIPANTS/METHODS: Twenty-one patients were treated with intravitreal
injection with and without photodynamic therapy. MAIN OUTCOME MEASURES: Clinical 
evidence of toxicity and complications. RESULTS: No drug-related serious adverse 
events were revealed. Ophthalmic evaluation revealed that 87.5% of patients who
received the anti-VEGF aptamer alone showed stabilized or improved vision 3
months after treatment and that 25% of eyes demonstrated a 3 line or greater
improvement in vision on the Early Treatment of Diabetic Retinopathy Study chart 
during this period. A 60% 3 line gain at 3 months was noted in patients who
received both the anti-VEGF aptamer and photodynamic therapy. CONCLUSIONS:
Anti-VEGF therapy is a promising treatment for various forms of ocular
neovascularization, including AMD. Multiple intravitreal injections of the
anti-VEGF aptamer were well tolerated in this phase II study. Further clinical
trials are necessary to demonstrate the efficacy and long-term safety of
anti-VEGF therapy for AMD.

Publication Types: 
    Clinical Trial
    Clinical Trial, Phase II
    Comment
    Multicenter Study

PMID: 12750101 [PubMed - indexed for MEDLINE]

2570: Ophthalmology. 2003 May;110(5):966-70.

Comment in:
    Ophthalmology. 2005 Feb;112(2):357; author reply 357.

Replacing the Amsler grid: a new method for monitoring patients with age-related 
macular degeneration.

Loewenstein A, Malach R, Goldstein M, Leibovitch I, Barak A, Baruch E, Alster Y, 
Rafaeli O, Avni I, Yassur Y.

Department of Ophthalmology, Tel-Aviv Medical Center, Tel-Aviv, Israel.

PURPOSE: To investigate a method that uses hyperacuity, the Macular Computerized 
Psychophysical Test (MCPT), to evaluate the central macular visual field in
patients with age-related macular degeneration (AMD). DESIGN: Prospective
case-control study of a diagnostic test. PARTICIPANTS AND CONTROLS: One hundred
eight eyes of 108 Patients with AMD and 51 eyes of 51 age-matched patients with
no retinal disease. Patients with AMD included 32 (30%) patients with choroidal
neovascularization (CNV), 23 (21%) with geographic atrophy (GA), 35 (32%) with
AMD with high-risk characteristics (HRC), and 18 (17%) with early AMD with
non-HRC. TESTING: Each subject underwent the MCPT, in which a virtual line
composed of dots (white dots on a black background, maximal contrast) is flashed 
across different macular loci to a perifoveal radius of 7 degrees. Patients'
responses were recorded and automatically analyzed using a specific algorithm
developed before the onset of the study. All patients also underwent a supervised
Amsler grid examination on the encounter before or after the MCPT in random
order. MAIN OUTCOME MEASURES: Distortion, scotoma, or blurring perceived by the
patient after a swift change of fixation was considered positive on the MCPT. Any
perception of distortion, scotoma, or blurring was considered positive on the
Amsler grid. RESULTS: Of the 32 patients with CNV, 30 (94%) were found positive
on the MCPT and 11 (34%) were found positive on the Amsler grid. Of the 23 GA
patients, 21 (91%) were found positive on the MCPT and 7 (30%) were found
positive on the Amsler grid. Of the 35 HRC patients, 28 (80%) were found positive
on the MCPT and 3 (9%) were found positive on the Amsler grid, and of the 18
early AMD with non-HRC patients, 8 (44%) were found positive on the MCPT and 3
(17%) were found positive on the Amsler grid. Of the 51 controls, 3 (6%) were
positive on the MCPT and 1 (2%) was positive on the Amsler grid. CONCLUSIONS: The
MCPT was superior to the Amsler grid in detecting AMD-related lesions in this
cohort. Studies are underway to determine whether the MCPT is feasible for home
monitoring to provide early detection of progression to CNV.

Publication Types: 
    Clinical Trial

PMID: 12750099 [PubMed - indexed for MEDLINE]

2571: Biomed Tech (Berl). 2003 Apr;48(4):82-5.

Intraocular microablation of choroidal tissue by a 308 nm AIDA excimer laser for 
RPE-transplantation in patients with age-related macular degeneration.

Holz FG, Bindewald A, Schutt F, Specht H.

Universitäts-Augenklinik Heidelberg Im Neuenheimer Feld 400 D-69120 Heidelberg.
frank_holz@med.uni-heidelberg.de

Age-related macular degeneration (AMD) is the leading cause of legal blindness in
the western nations beyond 50 years of age. The most frequent cause for severe
visual loss is the growth of neovascular membrances from the choroid into the
subretinal space. This usually results in irreversible degeneration of the
overlying retina. Surgical removal of the membrane is feasible, however, usually 
results in functional loss of apposing retinal photoreceptors since retinal
pigment epithelial (RPE) cells are removed concurrently due to their tight
adherence to the neovascular complex. Therefore, various attempts have been
undertaken to fill the resulting RPE cell defect with either heterologous or
autologous RPE cell transplants. So far cell survival, function and subsequent
visual function has been disappointing. To minimize trauma and resulting
dedifferentiation harvesting in the eye and transplantation in whole sheets and
without temporary removal from the eyes would be desirable. This may be achieved 
by isolating grafts consisting of choroid, Bruch's membrance and RPE cells from
the peripheral retina and transplantation of this graft under the neurosensory
retina after removal of the choroidal neovascularization. However, the choroidal 
component of such a graft would be expected to interfere with diffusion of
metabolites to and from the retina. Therefore, outcome would be expected to be
better if the choroidal tissue would be removed before translocation. In
preclinical experiments we used a 308 nm UV AIDA excimer laser to microablate
choroidal tissue from such a graft in human donor eyes.

PMID: 12749285 [PubMed - indexed for MEDLINE]

2572: Eur J Ophthalmol. 2003 Apr;13(3):281-6.

Changes in blood antioxidants and several lipid peroxidation products in women
with age-related macular degeneration.

Nowak M, Swietochowska E, Wielkoszyński T, Marek B, Karpe J, Górski J,
Głogowska-Szelag J, Kos-Kudła B, Ostrowska Z.

Pathophysiology Division, Department of Pathophysiology and Endocrinology,
Silesian University of Medicine, Zabrze, Traugutta 2, Poland. nowak-mar@wp.pl

PURPOSE: The aim of this study was to evaluate the ferric reducing ability of
plasma (FRAP), selected enzymatic and non-enzymatic components of the
antioxidative system, and the intensity of peroxidative processes in the blood of
patients with age-related macular degeneration (AMD). METHODS: In the peripheral 
blood, we evaluated FRAP; concentrations of vitamins C, A, and E; and of thiols. 
We assayed the activity of enzymatic components of the antioxidative
system-superoxide dismutase, catalase, ceruloplasmin and the concentration of
reduced glutathione as an indicator of glutathione peroxidase activity. In order 
to determine the intensity of lipid peroxidation, we measured the concentrations 
of malondialdehyde and hydroxyalkenales (MDA-HNA) and conjugated diens (CD).
RESULTS: We found a significant increase in FRAP in patients with AMD compared
with the control group. The average concentrations of vitamins A and C were low
and vitamins E and GSH were significantly higher in AMD than in the control
group. The activity of almost all the antioxidative enzymes was high. We found a 
significant increase in MDA-HNA but no difference in CD. CONCLUSIONS: The
significantly higher concentration of lipid peroxidation products in patients
with AMD indicates an important pathogenic role of oxido-reduction disturbance.
The high FRAP concentration may be one of the protective mechanisms in oxidation 
stress. The adaptive increase of the antioxidant barrier mostly involves the
enzymatic components.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12747649 [PubMed - indexed for MEDLINE]

2573: Surv Ophthalmol. 2003 May-Jun;48(3):257-93.

Age-related macular degeneration: etiology, pathogenesis, and therapeutic
strategies.

Ambati J, Ambati BK, Yoo SH, Ianchulev S, Adamis AP.

Ocular Angiogenesis Laboratory, Department of Ophthalmology, University of
Kentucky, Lexington, USA.

Age-related macular degeneration is the principal cause of registered legal
blindness among those aged over 65 in the United States, western Europe,
Australia, and Japan. Despite intensive research, the precise etiology of
molecular events that underlie age-related macular degeneration is poorly
understood. However, investigations on parallel fronts are addressing this
prevalent public health problem. Sophisticated biochemical and biophysical
techniques have refined our understanding of the pathobiology of drusen,
geographic atrophy, and retinal pigment epithelial detachments. Epidemiological
identification of risk factors has facilitated an intelligent search for
underlying mechanisms and fueled clinical investigation of behavior modification.
Gene searches have not only brought us to the cusp of identifying the culpable
gene loci in age-related macular degeneration, but also localized genes
responsible for other macular dystrophies. Recent and ongoing investigations,
often cued by tumor biology, have revealed an important role for various growth
factors, particularly in the neovascular form of the condition. Transgenic and
knockout studies have provided important mechanistic insights into the
development of choroidal neovascularization, the principal cause of vision loss
in age-related macular degeneration. This in turn has culminated in preclinical
and clinical trials of directed molecular interventions.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.
    Review

PMID: 12745003 [PubMed - indexed for MEDLINE]

2574: Arch Ophthalmol. 2003 May;121(5):679-83.

Lack of an association of apolipoprotein E gene polymorphisms with familial
age-related macular degeneration.

Schultz DW, Klein ML, Humpert A, Majewski J, Schain M, Weleber RG, Ott J, Acott
TS.

Casey Eye Institute, Oregon Health & Science University, Portland, 97239, USA.
schultzd@ohsu.edu

BACKGROUND: Previously, the epsilon 4 allele of apolipoprotein E (APOE) was
reported to have a significant association with a decreased risk of age-related
macular degeneration (AMD). In addition, the epsilon 2 allele of APOE was
reported to be possibly associated with an increased risk of AMD. OBJECTIVE: To
determine if APOE polymorphisms, previously reported to be associated with AMD,
affect its expression in medium to large families, as well as in unrelated
patients with AMD. METHODS: The APOE genotype was determined by HhaI restriction 
digests of polymerase chain reaction-amplified products in a collection of 259
affected and 207 unaffected individuals from 56 AMD families. Genotypes were
determined similarly in a set of 104 unrelated AMD patients and in 113 unaffected
control subjects. Diagnosis of AMD was based on clinical examination and
evaluation of fundus photographs. Evidence of an association between alleles of
APOE and AMD in families was tested by the following 4 statistical methods: chi2 
analysis of simple allele counting, logistic regression analysis adjusting for
age, construction of likelihood ratios of haplotype frequencies, and the pedigree
disequilibrium test. RESULTS: None of the statistical methods used showed a
significant association between the common alleles of APOE and AMD in our
collection of families or in the set of unrelated AMD patients. CONCLUSIONS: No
evidence was found to support an association between AMD in medium to large
families and the epsilon 4 or epsilon 2 alleles of APOE. Neither was any evidence
found for an association of APOE polymorphisms with the set of unrelated patients
with AMD. However, a trend for a decreased risk of AMD associated with APOE
epsilon 4 was observed in the set of unrelated patients with a family history of 
AMD.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12742846 [PubMed - indexed for MEDLINE]

2575: Arch Ophthalmol. 2003 May;121(5):674-8.

Association of emphysema, gout, and inflammatory markers with long-term incidence
of age-related maculopathy.

Klein R, Klein BE, Tomany SC, Cruickshanks KJ.

Department of Ophthalmology and Visual Sciences, University of Wisconsin Medical 
School, Madison, 53726-2397, USA. kleinr@epi.ophth.wisc.edu

OBJECTIVE: To examine the relationship of 2 diseases associated with systemic
inflammatory response, emphysema and gout, and selected markers of systemic
inflammation with the 10-year incidence of age-related maculopathy. DESIGN:
Population-based cohort study. PARTICIPANTS: We included persons aged 43 to 86
years at baseline examination from 1988 to 1990 living in Beaver Dam, Wis, of
whom 3684 subjects participated in a 5-year follow-up examination and 2764
participated in a 10-year follow-up. METHODS: Standardized protocols for physical
examination, blood collection, administration of a questionnaire, and
stereoscopic color fundus photography to determine the presence of age-related
maculopathy. Standard univariate and multivariate analyses were performed. MAIN
OUTCOME MEASURES: Incidence and progression of age-related maculopathy. RESULTS: 
While controlling for age, sex, and other factors (history of heavy drinking or
smoking, systolic blood pressure, and vitamin use), a higher white blood cell
count at baseline was associated with the 10-year incidence of drusen 125 microm 
or greater in diameter (risk ratio [RR] per 10(6)/ microL = 1.10; 95% confidence 
interval [CI], 1.03-1.17), retinal pigment epithelial depigmentation (RR = 2.08; 
95% CI, 1.01-1.16), and progression of age-related maculopathy (RR = 1.09; 95%
CI, 1.03-1.15). A lower serum albumin level was associated with the incidence of 
exudative macular degeneration (RR per grams per deciliter = 0.31; 95% CI,
0.13-0.76). A history of emphysema at baseline was associated with the incidence 
of retinal pigment epithelial depigmentation (RR = 2.84; 95% CI, 1.40-5.78),
increased retinal pigment (RR = 2.20; 95% CI, 1.11-4.35), and exudative macular
degeneration (RR = 5.12; 95% CI, 1.63-16.06); a history of gout was associated
with the incidence of pure geographic atrophy (RR = 3.48; 95% CI, 1.27-9.53).
CONCLUSIONS: These findings indicate modest relationships between both increased 
white blood cell count and emphysema and the increased 10-year incidence of
lesions defining early and late age-related maculopathy. Further investigation of
these relationships in other studies is needed.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12742845 [PubMed - indexed for MEDLINE]

2576: Arch Ophthalmol. 2003 May;121(5):667-73.

Comment in:
    Arch Ophthalmol. 2004 Oct;122(10):1571-2; author reply 1572.

A randomized clinical trial of a single dose of intravitreal triamcinolone
acetonide for neovascular age-related macular degeneration: one-year results.

Gillies MC, Simpson JM, Luo W, Penfold P, Hunyor AB, Chua W, Mitchell P, Billson 
F.

Save Sight and Eye Health Institute, and the Department of Clinical
Ophthalmology, University of Sydney, New South Wales, Australia.
mark@eye.usyd.edu.au

OBJECTIVE: To determine if a single intravitreal injection of 4 mg of
triamcinolone acetonide in patients with classic choroidal neovascularization
associated with age-related macular degeneration can safely reduce the risk of
severe visual loss. METHODS: A double-masked, placebo-controlled, randomized
clinical trial was performed in patients 60 years or older who had choroidal
neovascularization with any classic component, a duration of symptoms of less
than 1 year, and a visual acuity of 20/200 or better. Best-corrected visual
acuity, intraocular pressure, and cataract grading were performed before the
injection and then at 3, 6, and 12 months. MAIN OUTCOME MEASURE: The development 
of severe loss of vision (30 letters) by survival analysis on an
intention-to-treat basis. RESULTS: One hundred fifty-one eyes were randomized
into the study, and follow-up data were obtained for 73 (97%) of the 75 eyes in
the treated group and for 70 (92%) of the 76 eyes in the control group. There was
no difference between the 2 groups for the development of severe visual loss
during the first year of the study (log-rank chi 2(1) = 0.03, P =.90). In both
groups, the 12-month risk of severe visual loss was 35%, with a hazard ratio of
1.05 (95% confidence interval, 0.59-1.86). The change in size of the neovascular 
membranes, however, was significantly less in eyes receiving triamcinolone than
in those receiving placebo 3 months after treatment (P =.01), although no
difference was noted after 12 months. After 12 months, treated eyes had a
significantly higher risk of an elevated intraocular pressure (31/75 [41%] vs
3/76 [4%]; P<.001), but not of cataract progression (P =.29). CONCLUSIONS: A
single dose of intravitreal triamcinolone had no effect on the risk of loss of
visual acuity during the first year of the study in eyes with age-related macular
degeneration and classic choroidal neovascularization, despite a significant
antiangiogenic effect found 3 months after treatment. This biological effect
warrants further study.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12742844 [PubMed - indexed for MEDLINE]

2577: Arch Ophthalmol. 2003 May;121(5):658-63.

Risk of age-related macular degeneration in eyes with macular drusen or
hyperpigmentation: the Blue Mountains Eye Study cohort.

Wang JJ, Foran S, Smith W, Mitchell P.

Department of Ophthalmology, the Centre for Vision Research, and the Save Sight
and Westmead Millennium Institutes, University of Sydney, Australia.

OBJECTIVE: To quantify the 5-year risk of age-related macular degeneration (AMD) 
in eyes with different macular drusen characteristics (ie, size, type, location, 
and total area) or hyperpigmentation in a population-based cohort. METHODS: The
Blue Mountains Eye Study examined 3654 residents during 1992-1994; 2335 (75.1% of
survivors) were reexamined during 1997-1999. Retinal photographs were graded
using the Wisconsin Age-Related Maculopathy Grading System. Incident AMD lesions 
were defined by development of neovascular AMD or geographic atrophy in eyes
without these lesions at baseline (eyes at risk). Age-adjusted relative risks
(RRs) were determined. Generalized estimating equation models were used to
estimate odds ratios, adjusting for the correlation between eyes and other AMD
risk factors.Main Outcome Measure Incidence of AMD. RESULTS: Of the 4634 eyes at 
risk, 52 (1.1%) developed neovascular or atrophic AMD lesions over 5 years. In
right eyes, presence vs absence of the following macular signs predicted AMD:
drusen that were 125 micro m or larger (13.9 vs 0.6%; age-adjusted RR, 5.7; 95%
confidence interval [CI], 3.6-9.0), indistinct soft or reticular drusen (23.2% vs
0.4%; RR, 9.9; 95% CI, 6.4-15.4), total drusen area of half the disc area or more
(31.4% vs 0.6%; RR, 13.5; 95% CI, 8.0-22.8), and hyperpigmentation (14.4% vs
0.5%; RR, 8.0; 95% CI, 5.4-11.9). After adjusting for age, sex, and smoking
status, eyes with these signs at baseline had a high likelihood of developing
AMD. Eyes with Age-Related Eye Disease Study categories 3 and 4 were 5 times more
likely to develop AMD compared with eyes in categories 1 and 2. CONCLUSION: This 
study quantifies the 5-year risk of AMD in eyes with macular drusen and
hyperpigmentation.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12742843 [PubMed - indexed for MEDLINE]

2578: Exp Eye Res. 2003 Jun;76(6):753-6.

Fate of cystatin C lacking the leader sequence in RPE cells.

Paraoan L, Grierson I, Maden BE.

The study made use of transiently transfected RPE cells expressing mature
cystatin C (lacking the 26 amino acids leader sequence of the precursor cystatin 
C) fused to enhanced green fluorescent protein (EGFP) and, in control
transfections, EGFP on its own. The findings demonstrate that 'leaderless'
cystatin C is not processed through the secretory pathway of RPE cells. Since a
polymorphism in the leader sequence has recently been associated with increased
risk for development of exudative age-related macular degeneration (AMD), the
present findings lend support to the hypothesis that impairment of function of
the leader sequence may contribute to the aetiology of exudative AMD.

Publication Types: 
    Letter
    Research Support, Non-U.S. Gov't

PMID: 12742358 [PubMed - indexed for MEDLINE]

2579: J Org Chem. 2003 May 16;68(10):3749-61.

Oxidatively truncated docosahexaenoate phospholipids: total synthesis,
generation, and Peptide adduction chemistry.

Gu X, Sun M, Gugiu B, Hazen S, Crabb JW, Salomon RG.

Department of Chemistry, Case Western Reserve University, Cleveland, Ohio
44106-7078, USA.

The recent immunological detection of extraordinarily high levels of
carboxyethylpyrrole (CEP) modifications of proteins from the retinas of
individuals with age-related macular degeneration provided presumptive evidence
for the involvement of docosahexaenoate-derived oxidatively truncated
phospholipids in retinal pathology. To facilitate the in vivo detection and
characterization of the chemistry and biological activities of these postulated
naturally occurring molecules, a family of oxidatively truncated phospholipids
was prepared by total syntheses. Their formation in oxidation reactions of a
docosahexaenoate ester of 2-lysophosphatidylcholine (DHA-PC) was also
demonstrated. Free radical-induced oxidative cleavage of DHA-PC promoted by
myeloperoxidase or copper ions generates similar mixtures of these phospholipids.
The most abundant products were
1-palmitoyl-2-succinoyl-sn-glycero-3-phosphatidylcholine (4.7%) and
2-(6-carboxy-4-oxohex-5-enoyl)-1-palmitoyl-sn-glycero-3-phosphatidylcholine
(1.7%). Both of these oxidatively truncated phospholipids are homologues of
biologically active arachidonate-derived phospholipids. A minor product from
DHA-PC,
2-(4-hydroxy-7-oxohept-5-enoyl)-1-palmitoyl-sn-glycero-3-phosphatidylcholine
(0.4% yield), reacted with the epsilon-amino group of a peptide lysyl residue to 
produce a CEP derivative in 0.7% yield. These observations support the previous
conclusion, based on immunological evidence, that CEPs are generated by the
reaction of an oxidatively truncated phospholipid with proteins in the retina and
further indicate that CEP protein modifications probably represent only a tiny
fraction of the products generated upon oxidative damage of DHA-PC in
photoreceptor disk membranes.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.

PMID: 12737551 [PubMed - indexed for MEDLINE]

2580: Eur Rev Med Pharmacol Sci. 2002 Jul-Aug;6(4):75-9.

Potential implications for pathophysiology in a type 1 diabetic patient affected 
by Stargardt disease.

Giusti C.

Department of Ophthalmology, Campus Bio-Medico University, Rome, Italy.

PURPOSE/METHOD: To present a 35-year-old woman affected by type 1 diabetes
mellitus, Stargardt maculopathy and fundus flavimaculatus. To our knowledge, this
association is unusual and not yet described in the ophthalmic literature.
RESULTS/CONCLUSIONS: Visual acuity was reduced to < 20/200 in both eyes, color
vision was absent and computerized perimetry showed an absolute central scotoma. 
Pattern visual evoked potentials and electroretinogram (ERG) (scotopic, photopic 
and flicker) were considerably reduced in amplitudes. Full-field ERG was within
normal limits whereas oscillatory potentials were reduced in number and
amplitude. Fluorescein angiography confirmed the diagnosis of Stargardt
maculopathy and fundus flavimaculatus but no diabetic retinopathy was clinically 
evident. Potential interactions between the diabetic microangiopathy and the
retinal degenerative disorder are hypothesized and discussed.

Publication Types: 
    Case Reports

PMID: 12729035 [PubMed - indexed for MEDLINE]

2581: Eye. 2003 Apr;17(3):350-5.

Serum leptin concentrations are decreased and correlated with disease severity in
age-related macular degeneration: a preliminary study.

Evereklioglu C, Doganay S, Er H, Cekmen M, Ozerol E, Otlu B.

Department of Ophthalmology, Erciyes University Medical Faculty, TR-38020
Kayseri, Turkey. evereklioglu@hotmail.com

BACKGROUND: Age-related maculopathy (ARM) or degeneration (ARMD) is the leading
cause of irreversible blindness in developed countries. Despite several studies
on the morphology of ARMD, the aetiology is unknown and factor(s) contributing to
the pathogenesis remain to be characterised. More recent studies have
demonstrated that cholesterol esters and lipids are present within Bruch's
membrane deposits and drusen, and dietary fat intake is associated with ARMD. The
product of Ob gene, leptin, is a recently discovered peptide participating in
human metabolism. There is a direct relationship between serum leptin and diet,
and lipoprotein metabolism, but the role of leptin in the course of ARMD has not 
previously been investigated. PURPOSE: This cross-sectional case-control study
investigated whether serum leptin level was associated with ARMD as a new
possible risk factor and to assess its relationship with disease severity.Methods
A total of 32 patients with ARM or ARMD (17 men, 15 women) and 20 age- and
sex-matched healthy control subjects without ARMD (11 men, nine women) from a
similar ethnic background were enrolled in this multicentre study. Body mass
index (BMI) (weight (kg)/height (m(2))) was calculated for each group. The
presence of maculopathy was assessed on the basis of colour fundus photographs
using an international classification system. Patients were classified as
early-ARM (n=16) or late-ARMD (n=16) using clinical examination and grading of
photographs. Serum leptin levels were measured by an enzyme-linked immunosorbent 
assay kit. The Mann-Whitney U test or chi(2) test was used for statistics as
indicated, and P&<0.05 was considered to be significant. RESULTS: The age, sex
ratio, and BMI between groups were comparable. Patients with maculopathy had
significantly (P&<0.001) lower leptin levels (mean+/-SD, 6.01+/-2.55 ng/ml) than 
control subjects (13.21+/-2.27 ng/ml). In addition, late-ARMD patients had
significantly lower leptin levels (3.81+/-0.58 ng/ml) than early-ARM patients
(8.21+/-1.68 ng/ml, P&<0.001) or control subjects (P&<0.001). CONCLUSION: Leptin 
seems to be a possible newly associated factor in the course of ARM and may be
involved in the lipid composition of the macular lesions, especially in
late-ARMD.

Publication Types: 
    Multicenter Study

PMID: 12724698 [PubMed - indexed for MEDLINE]

2582: Mol Vis. 2003 Apr 24;9:138-43.

Genetic heterogeneity of butterfly-shaped pigment dystrophy of the fovea.

van Lith-Verhoeven JJ, Cremers FP, van den Helm B, Hoyng CB, Deutman AF.

Department of Ophthalmology, University Medical Center Nijmegen, Nijmegen, The
Netherlands.

PURPOSE: Butterfly-shaped macular dystrophy (BSMD) has so far only been
associated with mutations in the peripherin/RDS gene. The initial aim of our
study was to investigate the peripherin/RDS gene as the causative gene in a
family with BSMD. Subsequently the putative involvement of the ROM-1 gene, 4
genes expressed in cone photoreceptors, all known non-syndromic macular, retinal 
pigment epithelium and choroidal dystrophy loci, all known Leber congenital
amaurosis loci and all known non-syndromic congenital and stationary retinal
disease loci was examined. METHODS: Thirteen members from the original family
with autosomal dominant BSMD were examined. The protein coding exons of the
peripherin/RDS gene were screened for mutations by sequence analysis. Linkage
analysis was performed using markers flanking the peripherin/RDS gene to rule out
the presence of a heterozygous deletion. Likewise, involvement of the ROM-1 gene,
four cone genes, 41 non-syndromic retinal disease loci and one syndromic retinal 
disease locus was investigated. RESULTS: Sequence analysis of the peripherin/RDS 
gene revealed no mutations. In addition, the BSMD phenotype could not be
genetically linked to the peripherin/RDS gene, the ROM-1 gene and the four cone
genes nor to any of the 42 retinal disease loci. CONCLUSIONS: This study reveals 
genetic heterogeneity for BSMD by the identification of a BSMD family, which is
not associated with a mutation in the peripherin/RDS gene nor with any other
known non-syndromic retinal disease gene.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12724643 [PubMed - indexed for MEDLINE]

2583: Graefes Arch Clin Exp Ophthalmol. 2003 Apr;241(4):269-76. Epub 2003 Mar 22.

Clinicopathological correlation of choroidal neovascularization after external
beam radiotherapy in age-related macular degeneration.

Aisenbrey S, Lafaut BA, Reynders S, Szurman P, Grisanti S, Vanden Broecke C,
Walter P, Bartz-Schmidt KU.

Department of Vitreo-Retinal Surgery, Center of Ophthalmology, University of
Cologne, Cologne, Germany.

PURPOSE: To analyze the histopathology of choroidal neovascularization after
external beam radiotherapy in age-related macular degeneration. METHODS: A
retrospective non-case-matched comparative histopathologic study. The
histoarchitecture of nine surgically removed subretinal specimens from nine
patients that had undergone external beam radiotherapy for exudative age-related 
macular degeneration was studied. Seven patients had received 20 Gy in 10
fractions and two 15 Gy in 5 fractions with an average time interval between
radiotherapy and surgical extraction of 14 months (range 3-28). A consecutive
series of classic, mixed and occult choroidal neovascular membranes served as
controls. RESULTS: Clinical findings. Radiation-associated choroidal
neovasculopathy was angiographically suspected in four patients: a coarse net of 
vessels on fluorescein angiography developing at the border of previously
irradiated choroidal neovascularization was observed in three patients; blebs at 
the margin of a plaque on indocyanine green angiography were observed in two
patients. Pathological findings. Diffuse drusen as well as intra-Bruch's
fibrovascular tissue was found in all irradiated specimens. In four specimens an 
edematous vascularized layer was seen between diffuse drusen and normal-appearing
intra-Bruch's fibrovascular tissue. This lesion was not found in the control
specimens. A particular correlation for the bleb lesion was not recognized.
CONCLUSION: The appearance of an edematous subretinal pigment epithelial
vascularized layer between diffuse drusen and normal-appearing fibrovascular
tissue in four of nine irradiated membranes may be secondary to previous
irradiation. It may correlate with the unusual exudative manifestations observed 
after external beam radiotherapy.

PMID: 12719987 [PubMed - indexed for MEDLINE]

2584: Am J Ophthalmol. 2003 May;135(5):725-8.

Foveal thickness in occult macular dystrophy.

Kondo M, Ito Y, Ueno S, Piao CH, Terasaki H, Miyake Y.

Department of Ophthalmology, Nagoya University School of Medicine, Japan.
kondomi@med.nagoya-u.ac.jp

PURPOSE: Occult macular dystrophy (OMD) is an inherited macular dystrophy
characterized by a progressive macular dysfunction without any visible fundus
abnormality. We studied the foveal thickness in patients with OMD using optical
coherence tomography (OCT). DESIGN: Observational case series. Foveal thickness
by OCT images. METHODS: Foveal thickness obtained from 22 eyes of 11 patients
with OMD was compared with that from 27 eyes of 20 age-matched normal controls.
RESULTS: Mean foveal thickness in the patients group (96.5 +/- 19.5 microm) was
significantly thinner than that in the normal controls (133.3 +/- 9.0 microm, P
<.0001, Mann-Whitney U test). Eighteen of 22 eyes with OMD had foveal thickness
that were thinner than the lower limit of the normal range. There was no
statistically significant correlation between the foveal thickness and visual
acuity, age, or duration from onset. CONCLUSION: These results demonstrated that 
there are significant anatomic changes in the macula of patients with OMD.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12719092 [PubMed - indexed for MEDLINE]

2585: Am J Ophthalmol. 2003 May;135(5):715-7.

Comment in:
    Jpn J Ophthalmol. 2006 Jan-Feb;50(1):75-8.

A case of occult macular dystrophy accompanying normal-tension glaucoma.

Nakamura M, Kanamori A, Seya R, Maeda H, Negi A.

Department of Organ Therapeutics, Division of Ophthalmology, Kobe University
Graduate School of Medicine, Japan. manakamu@med.kobe-u.ac.jp

PURPOSE: To present a case of occult macular dystrophy accompanying
normal-tension glaucoma. DESIGN: Observational case report. METHODS: Visual
function and ophthalmoscopic and electroretinographic findings in a 56-year-old
man suffering from gradually progressive photophobia and visual dysfunction were 
followed up over 4 years. RESULTS: Best-corrected visual acuity was below 20/200,
and intraocular pressures remained in the low teens in both eyes. A wedge-shaped 
visual field defect in the right eye, corresponding to the enlarged disk cupping,
and a relative central scotoma in the left were detected. Ophthalmoscopy and
fluorescein angiography detected no apparent abnormality at the macular region in
either eye. Severely attenuated multifocal electroretinographic responses were
recorded from only the central areas, with normal full-field responses.
CONCLUSION: Clinicians must look for additional pathologic conditions in patients
with normal-tension glaucoma who have unexplained central visual dysfunction.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 12719086 [PubMed - indexed for MEDLINE]

2586: Am J Hum Genet. 2003 Jun;72(6):1412-24. Epub 2003 Apr 24.

A whole-genome screen of a quantitative trait of age-related maculopathy in
sibships from the Beaver Dam Eye Study.

Schick JH, Iyengar SK, Klein BE, Klein R, Reading K, Liptak R, Millard C, Lee KE,
Tomany SC, Moore EL, Fijal BA, Elston RC.

Department of Epidemiology and Biostatistics, Case Western Reserve University,
Cleveland, OH 44109-1998, USA. texilene@darwin.EPBI.cwru.edu

Age-related maculopathy (ARM) is a leading cause of visual impairment among the
elderly in Western populations. To identify ARM-susceptibility loci, we genotyped
a subset of subjects from the Beaver Dam (WI) Eye Study and performed a
model-free genomewide linkage analysis for markers linked to a quantitative
measure of ARM. We initially genotyped 345 autosomal markers in 325 individuals
(N=263 sib pairs) from 102 pedigrees. Ten regions suggestive of linkage with ARM 
were observed on chromosomes 3, 5, 6, 12, 15, and 16. Prior to fine mapping, the 
most significant regions were an 18-cM region on chromosome 12, near D12S1300
(P=.0159); a region on chromosome 3, near D3S1763, with a P value of.0062; and a 
6-cM region on chromosome 16, near D16S769, with a P value of.0086. After
expanding our analysis to include 25 additional fine-mapping markers, we found
that a 14-cM region on chromosome 12, near D12S346 (located at 106.89 cM), showed
the strongest indication of linkage, with a P value of.004. Three other regions, 
on chromosomes 5, 6, and 15, that were nominally significant at P< or =.01 are
also appropriate for fine mapping.

Publication Types: 
    Comparative Study
    Research Support, U.S. Gov't, P.H.S.

PMID: 12717633 [PubMed - indexed for MEDLINE]

2587: Invest Ophthalmol Vis Sci. 2003 May;44(5):2277-83.

Loss of cone function in age-related maculopathy.

Phipps JA, Guymer RH, Vingrys AJ.

Department of Optometry and Vision Sciences, University of Melbourne, Victoria,
Australia.

PURPOSE: To evaluate cone visual function of subjects with age-related
maculopathy (ARM). METHODS: Cone thresholds in 16 patients with ARM and 14
age-matched control subjects were compared. All subjects had visual acuity of
6/12 or better in the studied eye. A range of contrast thresholds were measured
to evaluate diverse aspects of cone visual function under steady state conditions
(spatiotemporal, color and luminance, and photopic sensitivity) or after
bleaching (adaptation dynamics). RESULTS: ARM produced a diffuse loss across all 
cone steady state visual functions in 31% to 44% of subjects. The adaptation time
constant of cone recovery was significantly prolonged in most (69%) ARM eyes. A
cross-correlational analysis found adaptational kinetics to be independent of
other steady state losses, with cone photopigment regeneration being the most
affected visual function in ARM (chi(2) = 4.03, P < 0.05). CONCLUSIONS: The
results show that cone-adaptational kinetics are affected in ARM more so than are
steady state thresholds. Given that cone recovery is easy to examine in a
clinical setting, this test may provide a useful index of photopic function in
patients with ARM.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12714671 [PubMed - indexed for MEDLINE]

2588: Invest Ophthalmol Vis Sci. 2003 May;44(5):2192-8.

Insulin-like growth factor-I and its receptor in neovascular age-related macular 
degeneration.

Lambooij AC, van Wely KH, Lindenbergh-Kortleve DJ, Kuijpers RW, Kliffen M, Mooy
CM.

Department of Ophthalmology, Erasmus Medical Center Rotterdam, The Netherlands.
a.lambooij@erasmusmc.nl

PURPOSE: The insulin-like growth factor (IGF)-I protein is a growth-promoting
polypeptide that can act as an angiogenic agent in the eye. The purpose of the
current study was to localize the expression of IGF-I and its receptor (IGF-IR)
mRNA and IGF-IR protein in situ in the normal human eye and to examine the
presence of expression in eyes with neovascular age-related macular degeneration 
(AMD). METHODS: Formalin-fixed, paraffin-embedded slides of 4 normal control eyes
and 14 eyes with choroidal neovascularization (CNV) secondary to AMD were
examined. Three eyes with proliferative diabetic retinopathy were studied as the 
positive control. IGF-I and IGF-IR mRNA was detected by in situ hybridization
with digoxigenin-labeled RNA probes. IGF-IR protein was studied by
immunohistochemistry. RESULTS: In the normal retina, IGF-I and IGF-IR mRNA
expression was found throughout the neuroretinal layers, in the retinal pigment
epithelium (RPE), and in some choriocapillary and retinal capillary endothelial
cells. In eyes with CNV we found IGF and IGF-IR mRNA in capillary endothelial
cells, some transdifferentiated RPE, and fibroblast-like cells. IGF-IR protein
was found in normal eyes in all neuroretinal layers, in the RPE, and in the
choroidal vessels. In eyes with CNV, IGF-IR protein was present in the RPE
monolayer, in transdifferentiated RPE, and in newly formed vessels. CONCLUSIONS: 
The colocalization of protein and receptor indicates an autocrine function of
IGF-I in the normal human retina. Because IGF-I participates in ocular
neovascularization, synthesis of IGF-IR and IGF-I in endothelial cells, RPE
cells, and fibroblast-like cells in CNV may point toward a role for this growth
factor in the pathogenesis of neovascular AMD.

PMID: 12714661 [PubMed - indexed for MEDLINE]

2589: Invest Ophthalmol Vis Sci. 2003 May;44(5):2178-83.

An early-onset autosomal dominant macular dystrophy (MCDR3) resembling North
Carolina macular dystrophy maps to chromosome 5.

Michaelides M, Johnson S, Tekriwal AK, Holder GE, Bellmann C, Kinning E, Woodruff
G, Trembath RC, Hunt DM, Moore AT.

Institute of Ophthalmology, University College London, London, United Kingdom.

PURPOSE: To characterize the phenotype of an autosomal dominant macular dystrophy
and identify the chromosomal locus. METHODS: Thirteen members of a
four-generation, nonconsanguineous British family were examined clinically and
also underwent automated perimetry, fundus fluorescein angiography, and fundus
autofluorescence imaging. After informed consent was obtained, blood samples were
taken for DNA extraction, and genetic linkage analysis was performed. RESULTS:
The retinal changes have an early age of onset and are confined to the macular
region. The macular abnormalities vary from mild retinal pigment epithelium (RPE)
pigmentary change to atrophy. Drusen-like deposits are present to various degrees
and are characteristic of the phenotype. Subretinal neovascular membrane (SRNVM) 
is an established complication. Genetic linkage analysis established linkage to
chromosome 5, region p13.1-p15.33 with a maximum LOD score of 3.61 at a
recombination fraction of 0.00 for marker D5S630. The locus for this autosomal
dominant macular dystrophy lies between flanking markers D5S1981 and D5S2031.
CONCLUSIONS: A novel locus has been identified for early-onset autosomal dominant
macular dystrophy on chromosome 5.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12714659 [PubMed - indexed for MEDLINE]

2590: Invest Ophthalmol Vis Sci. 2003 May;44(5):2147-54.

Sequence of early vascular events after photodynamic therapy.

Michels S, Schmidt-Erfurth U.

University Eye Hospital Lübeck, Lübeck, Germany. stmichels@web.de

PURPOSE: To identify early vascular changes in choroidal neovascularization (CNV)
and in adjacent normal choroid, after photodynamic therapy (PDT). METHODS: In a
prospective study, 40 patients with predominantly classic CNV due to age-related 
macular degeneration (AMD) were treated with PDT performed with verteporfin.
Verteporfin was administered intravenously at a dose of 6 mg/m(2) body surface
area. A near infrared laser light dose of 50 J/cm(2), an irradiance of 600
mW/cm(2) and a wavelength of 692 nm was applied. A scanning laser system was used
to perform confocal fluorescein angiography (FA) and indocyanine green
angiography (ICGA) before treatment and regularly at 5 hours, 1 day, 1 week, and 
3 months after PDT. Images were analyzed for CNV size and leakage area as seen by
FA and ICGA. Collateral damage within the surrounding choroid was documented
based on the hypofluorescence in early- and late-phase ICGA. RESULTS: No
immediate occlusion of the CNV complex was found angiographically, but a dynamic 
change over time was observed in the early perfusion patterns and late-phase
hyper- and hypofluorescence. At 5 hours after treatment, large portions of the
CNV lesion were still perfused. One day after PDT, CNV size in early FA and early
ICGA reached its minimum, at 0.49 mm(2) (15.7%) and 0.78 mm(2) (31.1%) of the
initial area, respectively. In late-phase FA and ICGA, however, an immediate
massive exudation with a continuous increase in hyperfluorescence originated from
the CNV and surrounding choroid, with a maximum in leakage area at 1 day. At 1
week PDT-induced exudation slowly resolved. Eyes in 36 patients showed some
choroidal hypofluorescence by ICGA before treatment. A progressive increase of
the hypofluorescent area surrounding the CNV was observed, which correlated with 
the size of the laser spot. Maximum hypofluorescence was noted at 1 week with an 
average size of 11.1 mm(2) in early- and late-phase ICGA. CONCLUSIONS: In
contrast to findings in experimental animals, PDT in humans with classic CNV did 
not induce immediate thrombosis, but primarily caused a breakdown of vascular
barriers. A characteristic sequence of vascular changes was observed with early, 
enhanced leakage from the CNV and normal choroid followed by nonperfusion later. 
Occlusion of the CNV lesions occurred 1 day after treatment, but closure of the
adjacent choroidal vessels proceeded slowly over as long as 1 week.

PMID: 12714655 [PubMed - indexed for MEDLINE]

2591: Invest Ophthalmol Vis Sci. 2003 May;44(5):2133-40.

Monitoring retinal function during transpupillary thermotherapy for occult
choroidal neovascularization in age-related macular degeneration.

Falsini B, Focosi F, Molle F, Manganelli C, Iarossi G, Fadda A, Dorin G, Mainster
MA.

Institute of Ophthalmology, Catholic University of S Cuore, Rome, Italy.
md0571@cmlink.it

PURPOSE: To use focal electroretinography to evaluate changes in retinal function
during transpupillary thermotherapy (TTT) for neovascular age-related macular
degeneration (ARMD). METHODS: Sixteen eyes of 16 patients with ARMD with occult
choroidal neovascularization (CNV) were studied. A 630-nm photocoagulator aiming 
beam was modified for use as a 41-Hz square-wave focal electroretinogram (fERG)
stimulus. The stimulus was presented on a light-adapting background by a
Goldmann-type lens (visual angle, 18 degrees; mean luminance, 50 cd/m(2)). fERGs 
were continuously monitored before, during, and after TTT for occult CNV. The
amplitude and phase of the fERG's fundamental harmonic were measured. RESULTS: No
suprathreshold or adverse clinical events occurred during the course of the
study. fERG amplitude decreased transiently during TTT (23% +/- 9% [SE]; P <
0.05). The decrease in amplitude was greatest 16 to 20 seconds and 32 to 40
seconds after the onset of TTT. It was followed by a recovery to baseline
amplitude during TTT (48 to 60 seconds after TTT was begun). Within 60 seconds
after TTT was completed, fERG amplitude was within the range of baseline. TTT did
not alter the fERG phase. Mean fERG amplitudes and phases recorded 1 week and 1
month after TTT were comparable to mean pretreatment levels. CONCLUSIONS: fERG
amplitude decreases transiently during TTT, despite the absence of
ophthalmoscopically apparent lesions. Intraoperative amplitude depression may
result from an adaptation effect to laser light energy and/or hyperthermia,
resulting in desensitization of cone photoreceptors and bipolar cells. Treatment 
sites are electrophysiologically functional 1 month after TTT. Detailed
parametric study of a larger patient group is needed to determine whether fERG
testing is potentially useful for monitoring and perhaps for controlling and
optimizing TTT for choroidal neovascularization.

PMID: 12714653 [PubMed - indexed for MEDLINE]

2592: Invest Ophthalmol Vis Sci. 2003 May;44(5):1939-44.

Strabological findings after macular translocation surgery with 360 degrees
retinotomy.

Sato M, Terasaki H, Ogino N, Okamoto Y, Amano E, Ukai K, Hirai T.

Department of Ophthalmology, Hamamatsu University School of Medicine, Handayama, 
Hamamatsu, Japan. mihosato@hama-med.ac.jp

PURPOSE: To examine the strabological findings after macular translocation
surgery with a 360 degrees retinotomy. METHODS: Thirty-two patients who underwent
macular translocation surgery were divided into three groups based on their
responses to the Bagolini striated lenses test: fusion, ignoring the image, and
diplopia. The relevant factors affecting binocularity were compared among the
three groups. RESULTS: Five patients had peripheral fusion and three of these had
gross stereopsis. Fifteen patients ignored the second image, and 12 patients had 
diplopia. The objective angle of macular rotation was smaller in the patients
with peripheral fusion (15.0 +/- 6.1 degrees) than in those with diplopia (32.7
+/- 11.7 degrees). The subjective angle of cyclotorsion in those with peripheral 
fusion (6.0 +/- 4.2 degrees) was smaller than in those who ignored the image
("ignoring" group; 20.5 +/- 9.19 degrees) and the diplopia group (30.7 +/- 12.8
degrees). The amount of torsional sensory compensation in patients with diplopia 
(2.08 +/- 3.83 degrees) was significantly smaller than in those with peripheral
fusion (9.00 +/- 7.42 degrees) and in the ignoring group (6.73 +/- 3.86 degrees).
Patients with peripheral fusion were significantly younger (54.2 +/- 14.3 years) 
than those in the ignoring group (67.7 +/- 10.0 years) and those with diplopia
(68.0 +/- 5.4 years). CONCLUSIONS: Adaptive mechanisms are activated to reduce
the surgically induced objective angle of cyclotorsion, and a cyclodeviation of
15 degrees was the critical angle separating those who had peripheral fusion from
those who did not. This value corresponds to the cyclofusional amplitude in
normal adults.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12714627 [PubMed - indexed for MEDLINE]

2593: Br J Ophthalmol. 2003 May;87(5):615-21.

One year follow up of macular translocation with 360 degree retinotomy in
patients with age related macular degeneration.

Abdel-Meguid A, Lappas A, Hartmann K, Auer F, Schrage N, Thumann G, Kirchhof B.

Department of Ophthalmology, University of Aachen, Aachen, Germany.

AIM: To evaluate the benefits of macular translocation with 360 degree retinotomy
in patients with exudative age related macular degeneration (ARMD). METHODS: A
consecutive interventional case series was performed on patients who underwent
macular translocation between June 1997 and January 2000 at the department of
ophthalmology, University of Aachen, Germany. A retrospective pilot study was set
up with a minimum follow up of 12 months in 39 consecutive patients with
subfoveal choroidal neovascularisation secondary to ARMD. The surgical technique 
included pars plana vitrectomy, induction of retinal detachment, 360 degree
retinotomy, removal of the choroidal neovascular membranes (CNVM), macular
translocation, peripheral laser retinopexy, and silicone oil endotamponade.
RESULTS: 18 patients showed predominantly occult CNVM, six patients had
predominantly classic CNVM, and 15 showed subretinal haemorrhage. At the 12 month
follow up 13 patients (33%) showed an improvement in visual acuity of more than
three lines (logMAR scale), 18 patients (46%) retained stable visual acuity with 
a change of equal or less than three lines (logMAR scale), and eight patients
(21%) showed a decrease in visual acuity of more than three lines (logMAR scale).
Recurrence of CNVM was observed in three (8%) eyes at 5-11 months
postoperatively. Other complications included proliferative vitreoretinopathy
with retinal detachment (n=10), peripheral epiretinal membranes (n=9), macular
pucker (n=2), corneal decompensation (n=2), and hypotony (n=11). 18 patients
(46%) complained about persistent diplopia. CONCLUSION: Macular translocation
surgery is able to maintain or improve distant vision in the majority of patients
with exudative ARMD. Proliferative vitreoretinopathy and diplopia are the two
major complications. A prospective randomised controlled trial comparing macular 
translocation with observation for patients with the occult form of exudative
ARMD may be justified.

PMID: 12714406 [PubMed - indexed for MEDLINE]

2594: Br J Ophthalmol. 2003 May;87(5):609-14.

Identification of lesion components that influence visual function in age related
macular degeneration.

Hogg R, Curry E, Muldrew A, Winder J, Stevenson M, McClure M, Chakravarthy U.

Queen's University Belfast, UK.

AIMS: To explore the relation between lesion composition as assessed by fundus
photography and fluorescein angiography with clinical measures of vision in eyes 
of patients with age related macular degeneration (AMD). METHODS: A standardised 
visual function assessment along with colour stereo pair fundus photography was
carried out in both eyes of 58 subjects with a confirmed clinical diagnosis of
AMD. The size, location, and composition of the macular lesion (blood, exudate,
subretinal fluid, pigment, membrane, atrophy, and fibrosis) were measured on the 
colour photographs using computer assisted image analysis. Of the 58 subjects, 44
also had concurrent fluorescein angiography. Classic and occult choroidal
neovascularisation (CNV), blood, blocked fluorescence, fibrosis, geographic
atrophy, and the total area of abnormal fluorescence were measured. Multiple
linear regression was used to examine the relation between clinical measures of
vision and the location and extent of lesion components identified by both colour
and fluorescein image capture. RESULTS: The composition of the macular lesion
strongly influenced visual function, with atrophy (p=0.001) and fibrosis
(p=0.002) accounting for most of the variation. When the location of the lesion
with respect to the fovea was examined, fibrosis within the fovea significantly
influenced all clinical measures of vision (p=0.008). The regression model
selected the total area of abnormal fluorescence and a composite parameter (a
semiquantitative measure of the following characteristics: atrophy, exudates,
blood, and fibrosis ) from colour photography (r(2) =0.52) as the variables that 
explained most of the variation in clinical measures of vision. CONCLUSIONS: The 
composition and extent of the macular lesion strongly influences visual function 
in eyes with AMD. Both colour photography and angiography yielded information,
which together explained considerably more of the variation in the clinical
measures of vision than either on its own.

PMID: 12714405 [PubMed - indexed for MEDLINE]

2595: Retina. 2003 Apr;23(2):152-8.

Angiographic characteristics in patients undergoing macular translocation for
subfoveal choroidal neovascularization secondary to age-related macular
degeneration.

Kent DL, Fujii GY, Pieramici DJ, Reynolds SM, Melia M, Rossi JV, Humayun MS,
Caffey S, De Juan E.

Vitreoretinal Service, Wilmer Institute, Johns Hopkins University, Baltimore,
Maryland, USA.

PURPOSE: To review in a standardized fashion pre- and postoperative fluorescein
angiographic characteristics in patients undergoing limited macular translocation
(LMT) with scleral imbrication to treat subfoveal choroidal neovascularization
(SFCNV) secondary to age-related macular degeneration (AMD). The current study
was undertaken to assess any potential effects of the translocation procedure on 
altering the angiographic characteristics of SFCNV before laser photocoagulation.
METHODS: A consecutive series of patients undergoing LMT for AMD was identified
retrospectively. The pre- and postoperative fluorescein angiograms were reviewed 
in a masked fashion. Angiographic characteristics evaluated included pre- and
postoperative lesion components, stability of lesion, and the amount of retinal
translocation obtained. RESULTS: Eighty-eight patients (90 eyes) had angiograms
of adequate quality to permit evaluation. Time between the preoperative and the
prelaser angiogram ranged from 2 to 84 days (median 7.5 days). Neovascular
complexes remained unchanged or decreased in size in 79% of patients. There was
no statistically significant difference in lesion size between the pre- and
postoperative periods (P = 0.34). Retinal movement ranged from 160 microm to
3,320 microm (median 960 microm), with 61% of cases undergoing effective
translocation (i.e., the fovea was moved away from the neovascular complex). None
of the lesion components or demographic factors evaluated affected the amount of 
translocation obtained. Larger lesions were more likely to remain subfoveal
following translocation (P = 0.004). CONCLUSION: The size and lesion
characteristics appear relatively stable following translocation. Amount of
retinal movement is not associated with angiographic lesion characteristics. Only
size was associated with achievement of desired translocation in the final model,
with large lesions being less likely to achieve desired translocation. In our
study group, the amount of retinal translocation was variable with 61% of cases
undergoing effective translocation.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12707592 [PubMed - indexed for MEDLINE]

2596: Front Biosci. 2003 May 1;8:e305-14.

Age-related macular degeneration: a new viewpoint.

Hamdi HK, Kenney C.

Ophthalmology Research Laboratories, University of California, Irvine, Medical
Center, 101 The City Drive, Ophthalmology Research, Building 55, Room 206,
Orange, CA 92868, USA. hhamdi@uci.edu

Age-related macular degeneration (AMD) is a major cause of blindness in the
United States. AMD can be categorized into an atrophic (dry) form and a
neovascular (wet, exudative) form. The atrophic form involves alterations of
pigment distribution, loss of RPE cells and photoreceptors and diminished retinal
function due to an overall atrophy of the cells. The neovascular AMD involves
proliferation of abnormal choroidal vessels, which penetrate the Bruch's membrane
and RPE layer into the subretinal space, thereby forming extensive clots and/or
scars. Both environmental and genetic factors are suspected to play a role in
AMD. Despite extensive genetic screening of candidate genes only two associations
have been identified with AMD (Adenosine triphosphate (ATP)-binding cassette rim 
(ABCR) protein and apolipoprotein E gene-ApoE). The ABCR protein is retinal
specific and accounts for only 3% of AMD cases. ApoE is not specific to the
retina, and has been more intriguingly associated with Alzheimer's, another
disease of age. The most consistent major risk factor in AMD is age. Our studies 
on the ACE gene show an association of protection with an Alu element insert,
which might be affecting the level of the ACE gene. The ApoE 4 allele and the ACE
Alu+/+ genotype have both been shown to be a risk for Alzheimer's and protective 
for AMD. Given these recent genetic associations, we should examine possible
common pathways in diseases of age and their interaction with human genetic
polymorphisms.

Publication Types: 
    Review

PMID: 12700041 [PubMed - indexed for MEDLINE]

2597: Am J Epidemiol. 2003 Apr 15;157(8):721-9.

Birth cohort effect on prevalence of age-related maculopathy in the Beaver Dam
Eye Study.

Huang GH, Klein R, Klein BE, Tomany SC.

Department of Population Health Sciences, University of Wisconsin Medical School,
Madison, WI 53726, USA. guanhuahuang@facstaff.wisc.edu

The number of people in the United States with age-related maculopathy is
increasing in recent years because of increasing longevity. However, it is
possible that a birth cohort effect, due to different levels of exposure to risk 
factors, may explain changes in the prevalence of age-related maculopathy by age.
In this report, the authors utilize data from the population-based Beaver Dam Eye
Study (1988-2000) to examine this possibility. They propose a strategy to handle 
issues of longitudinal measurements and risk factor adjustment for analyzing the 
birth cohort effect. Results from the analysis (after adjusting for known risk
factors) showed an apparent independent birth cohort effect on age-related
maculopathy. The authors also found a strong positive association between
age-related maculopathy and age, when comparing participants from the same birth 
cohort. The birth cohort effect was the same across different age groups, except 
for early age-related maculopathy, where older age increased the association. Our
findings demonstrate that the birth cohort effect is likely attributable to
unmeasured risk factors for age-related maculopathy and limitations of risk
factor measurements. Further study of possible unmeasured risk factors that cause
the cohort effect may help us understand the etiology of the disease.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12697576 [PubMed - indexed for MEDLINE]

2598: Eur J Ophthalmol. 2003 Mar;13(2):221-2.

Cystoid macular edema associated with latanoprost therapy in a pseudophakic
vitrectomized patient after removal of silicone oil endotamponade.

Jäger M, Jonas JB.

Department of Ophthalmology, Eye Hospital, Faculty of Clinical Medicine Mannheim,
University of Heidelberg, Mannheim, Germany.

PURPOSE: To describe the occurrence of cystoid macular edema in a pseudophakic
vitrectomized patient following use of latanoprost (0.005%). METHODS: A
58-year-old patient underwent routine cataract surgery with posterior chamber
lens implantation complicated by rhegmatogenous retinal detachment three months
later. A pars plana vitrectomy was performed with silicone oil endotamponade
which was removed six months later. Five months after oil removal, the patient
presented with secondary open-angle glaucoma treated with latanoprost 0.005% eye 
drops once daily. RESULTS: Two weeks after initiation of latanoprost treatment,
visual acuity dropped from 0.8 to 0.3 due to cystoid macular edema confirmed by
fluorescein angiography. After discontinuing latanoprost therapy and with topical
corticosteroid treatment, cystoid macular edema slowly resolved, and within 6
months, visual acuity improved to 0.8. CONCLUSIONS: Despite its marked ocular
hypotensive effect, latanoprost should be carefully used in patients after
uncomplicated cataract surgery if the vitreous body was removed by pars piana
vitrectomy.

Publication Types: 
    Case Reports

PMID: 12696646 [PubMed - indexed for MEDLINE]

2599: Arch Ophthalmol. 2003 Apr;121(4):519-26.

Erratum in:
    Arch Ophthalmol. 2003 Jul;121(7):955.

The risk and natural course of age-related maculopathy: follow-up at 6 1/2 years 
in the Rotterdam study.

van Leeuwen R, Klaver CC, Vingerling JR, Hofman A, de Jong PT.

Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.

OBJECTIVES: To evaluate the natural course of age-related maculopathy (ARM) and
to assess the incidence and absolute risk of its final stage, age-related macular
degeneration (AMD). METHODS: In a population-based prospective cohort study of
6418 persons 55 years and older, we studied the incidence and natural course of
ARM. Subjects underwent identical examinations, including stereoscopic fundus
photography, at baseline and at 2.0 and 6(1/2) years' follow-up. Age-related
maculopathy was graded according to the International Classification and Grading 
System for ARM and AMD, and stratified into 5 exclusive stages. Incidence was
expressed in rates and 5-year absolute risks. RESULTS: At follow-up, 47 new cases
of AMD were identified, with a ratio of neovascular-atrophic AMD of 1.4:1. The
5-year risk of AMD increased with more severe stages to 28.0% for subjects 55
years and older with indistinct drusen and pigmentary irregularities (stage 3).
Age, but not sex, independently increased this risk to a maximum of 42.0% for
subjects with stage 3 ARM who were 80 years and older. Individual ARM fundus
signs that predicted best the development of AMD were 10 or more large drusen (> 
or =125 microm) and 10% or more of the grid area covered by drusen. Subjects who 
developed atrophic AMD showed no significant (P =.25) differences in baseline
fundus signs and natural course compared with subjects who developed neovascular 
AMD. CONCLUSIONS: We provided the absolute risk of AMD as a function of age and
early ARM fundus signs, and showed that both are prominent independent risk
factors. The progression of ARM stages follows, after the appearance of the first
soft drusen, a distinct course at a gradual pace that accelerates with increasing
age.

PMID: 12695249 [PubMed - indexed for MEDLINE]

2600: Arch Ophthalmol. 2003 Apr;121(4):478-82.

Serological association between Chlamydia pneumoniae infection and age-related
macular degeneration.

Kalayoglu MV, Galvan C, Mahdi OS, Byrne GI, Mansour S.

Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Ophthalmic
Education Center, Boston 02114, USA. Murat_Kalayoglu@meei.harvard.edu

BACKGROUND: Age-related macular degeneration (ARMD) is a leading cause of
blindness in the United States, but the mechanisms that initiate and promote the 
disease remain ill defined. There are several risk factors that ARMD shares with 
atherosclerosis, and these diseases may have similar pathogenic mechanisms that
involve inflammation. Chlamydia pneumoniae, a prokaryotic pathogen that causes
chronic inflammation is now emerging as a risk factor in the development of
cardiovascular diseases. It is therefore plausible that this microorganism also
contributes to the pathogenesis of ARMD. METHODS: To examine if C pneumoniae
infection is associated with ARMD, serum samples from 25 consecutive patients
with ARMD and from 18 without the disease were collected and assayed for the
presence of the antibodies to C pneumoniae elementary bodies, Chlamydia
trachomatis heat shock protein 60 (cHsp60), C trachomatis heat shock protein 10
(cHsp10), Escherichia coli GroEL, and E coli GroES. RESULTS: A serological
association was found between ARMD and anti-C pneumoniae antibodies (P =.047) but
not between ARMD and the anti-C trachomatis or anti-E coli heat shock protein
antibodies. The association remained statistically significant after adjusting
for age and smoking, both established risk factors for ARMD. CONCLUSIONS: These
data indicate that C pneumoniae infection may be associated with ARMD. Further
studies on larger cohorts of individuals are necessary to determine if this
pathogen plays a role in the pathogenesis of ARMD.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12695244 [PubMed - indexed for MEDLINE]

2601: Optom Vis Sci. 2003 Apr;80(4):277-9.

Cystic maculopathy with normal capillary permeability secondary to docetaxel.

Teitelbaum BA, Tresley DJ.

Illinois College of Optometry, Chicago 60616, USA. bteitelb@eyecare.ico.edu

BACKGROUND: Cystic maculopathy without leakage on fluorescein angiography has
been described in cases of toxicity to niacin. We present a similar case of
cystic maculopathy due to docetaxel (Taxotere) in the treatment of breast cancer.
CASE REPORT: A 53-year-old Asian female presented with complaints of decreased
vision soon after the initiation of treatment for breast cancer with docetaxel. A
cystic maculopathy with a normal fluorescein angiogram was found on examination. 
Significant improvement in visual acuity along with resolution of the cystic
maculopathy was found after changing to an alternate antineoplastic agent.
CONCLUSION: Docetaxel may be associated with cystic maculopathy that does not
display angiographic evidence of abnormal capillary permeability.

Publication Types: 
    Case Reports

PMID: 12692483 [PubMed - indexed for MEDLINE]

2602: Ophthalmology. 2003 Apr;110(4):636-43.

Corrected and republished in:
    Ophthalmology. 2003 Jun;110(6):1273-80.

The association of cardiovascular disease with the long-term incidence of
age-related maculopathy: the Beaver Dam eye study.

Klein R, Klein BE, Tomany SC, Cruickshanks KJ.

Department of Ophthalmology and Visual Sciences, University of Wisconsin Medical 
School, Madison, Wisconsin 53726-2397, USA.

PURPOSE: To examine the association between cardiovascular disease and its risk
factors and the 10-year incidence of age-related maculopathy. DESIGN:
Population-based cohort study. PARTICIPANTS: Persons 43 to 86 years of age at
baseline examination from 1988 to 1990, living in Beaver Dam, Wisconsin, of whom 
3684 persons participated in a 5-year follow-up examination and 2764 participated
in a 10-year follow-up examination. METHODS: Standardized protocols for physical 
examination, blood collection, administration of a questionnaire, and
stereoscopic color fundus photography to determine age-related maculopathy. The
Kaplan-Meier (product-limit) survival approach and discrete linear logistic
regression were used in the data analysis. MAIN OUTCOME MEASURES: Incidence and
progression of age-related maculopathy. RESULTS: When age, gender, and history of
heavy drinking, smoking, and vitamin use were controlled for, higher systolic
blood pressure at baseline was associated with the 10-year incidence of retinal
pigment epithelial depigmentation (risk ratio [RR] per 10 mmHg systolic blood
pressure, 1.10; 95% confidence interval [CI], 1.01-1.18; P = 0.02) and exudative 
macular degeneration (RR, 1.22; 95% CI, 1.06-1.41; P = 0.006). Higher pulse
pressure at baseline was associated with the incidence of retinal pigment
epithelial depigmentation (RR per 10 mmHg, 1.17; 95% CI, 1.07-1.28; P < 0.001),
increased retinal pigment (RR, 1.10; 95% CI, 1.01-1.19; P = 0.03), exudative
macular degeneration (RR, 1.34; 95% CI, 1.14-1.60; P < 0.001), and progression of
age-related maculopathy (RR, 1.08; 95% CI, 1.01-1.17; P = 0.03). Higher serum
high-density lipoprotein cholesterol at baseline was associated with pure
geographic atrophy (RR per 10 mg/dl high-density lipoprotein cholesterol, 1.29;
95% CI, 1.05-1.58; P = 0.01). Physical activity at baseline was associated with
the incidence of geographic atrophy (RR in those who worked up a sweat 5 times a 
week compared with those who did not, 0.12; 95% CI, 0.02-0.91; P = 0.04)
exudative macular degeneration (RR, 0.27; 95% CI, 0.08-0.87; P = 0.05), and
progression of age-related maculopathy (RR, 0.69; 95% CI, 0.47-1.00; P = 0.05).
Neither a history of stroke nor heart attack was associated with the incidence or
progression of age-related maculopathy. CONCLUSIONS: These findings indicate
relationships between higher pulse pressure (a presumed indicator of age-related 
elastin and collagen changes in Bruch's membrane) and systolic blood pressure
with an increased 10-year incidence of some lesions defining early age-related
maculopathy and exudative macular degeneration.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12689879 [PubMed - indexed for MEDLINE]

2603: J Cataract Refract Surg. 2003 Apr;29(4):686-93.

Cataract surgery in patients with age-related macular degeneration: one-year
outcomes.

Armbrecht AM, Findlay C, Aspinall PA, Hill AR, Dhillon B.

Princess Alexandra Eye Pavilion, Edinburgh, The Royal Infirmary of Edinburgh,
Scotland, United Kingdom.

PURPOSE: To determine whether patients with age-related macular degeneration
(ARMD) benefit from cataract surgery and to assess the risk of progression of
preexisting maculopathy 4 and 12 months postoperatively. SETTING: Princess
Alexandra Eye Pavilion, Royal Infirmary of Edinburgh, Edinburgh, Scotland.
METHODS: Two groups of patients were evaluated prospectively. The study group
comprised patients with ARMD scheduled to have cataract surgery (n = 40). The
control group comprised patients with ARMD not having cataract surgery (n = 43). 
Patients were assessed at baseline (preoperatively) and 4 and 12 months
postoperatively. Assessment included visual function tests and quality of life
(QoL) measures. The mean values for each item tested were obtained for each group
at each visit, and comparisons between visits were done using the Wilcoxon signed
rank test. RESULTS: There were significant benefits of cataract surgery in terms 
of visual function and QoL measures at 4 and 12 months. There was no increased
risk of progression of maculopathy in the study group. There were no significant 
differences in the items tested in the control group. CONCLUSIONS: One year
postoperatively, QoL benefits were maintained in the study group and there was no
increased risk of progression of maculopathy in patients with mild and moderate
degrees of ARMD. Larger numbers of patients must be assessed prospectively for
longer periods to determine the relative risk of progression of different stages 
of ARMD after cataract surgery.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12686235 [PubMed - indexed for MEDLINE]

2604: Int Ophthalmol. 2001;24(4):187-94.

A pilot study of ICG-guided laser photocoagulation for occult choroidal
neovascularization presenting as a focal spot in age-related macular
degeneration.

Da Pozzo S, Parodi MB, Ravalico G.

Eye Clinic of the University, Piazza dell'Ospedale 1, 34129 Trieste, Italy.

PURPOSE: To evaluate the effect of indocyanine green angiography (ICG)-guided
laser photocoagulation in eyes with age-related macular degeneration (AMD) and
occult choroidal neovascularization (O-CNV), appearing as a well-defined focal
spot on ICG. METHODS: Eyes with extrafoveal or juxtafoveal focal spot on ICG,
either without PED (Group A) or with PED (Group B) at baseline, were selected.
The hyperfluorescent area was photocoagulated by krypton red laser within 24
hours from diagnosis on ICG guide. At 1, 3, 6, 9 and 12 months from treatment,
all eyes underwent clinical examination, FA and ICG. Parameters as best corrected
visual acuity (BCVA), CNV closure and recurrence onset were analyzed. RESULTS: 53
eyes were enrolled in Group A and 33 in Group B. After 1 year from treatment, a
stabilized (+/-1 Snellen line) or improved (2 or more Snellen lines) visual
acuity was measured in 37 eyes (43%), 32 in Group A and 5 in Group B. After 1
year, a complete resolution of exudative signs was achieved with one or more
laser sessions in 41 eyes (48%), 34 in Group A and 7 in Group B. After 1 year, 50
eyes (58%) had one or more episodes of recurrent CNV, appearing in 51% of eyes of
Group A and in 70% of eyes of Group B. Most of the recurrences (86%) occurred
during the first trimester after photocoagulation. CONCLUSIONS: ICG-guided laser 
photocoagulation for O-CNV appearing as a focal spot produced encouraging
anatomical and functional outcome in eyes without PED at presentation. When focal
CNV is associated with a PED, our treatment technique produced disappointing
results.

Publication Types: 
    Comparative Study

PMID: 12678394 [PubMed - indexed for MEDLINE]

2605: Doc Ophthalmol. 2003 Mar;106(2):145-52.

Detection of retinal dysfunction in vitelliform macular dystrophy using the
multifocal ERG (MF-ERG).

Palmowski AM, Allgayer R, Heinemann-Vernaleken B, Scherer V, Ruprecht KW.

Augenklinik und Poliklinik, University of the Saarland, Kirrberger Strasse 1, D
66421 Homburg/Saar, Germany. auapal@med-rz.uni-sb.de

Vitelliform macular dystrophy (VMD) is widely known for an abnormal EOG in the
presence of a normal ERG. In this study the multifocal electroretinogram (MF-ERG)
is described as an additional tool to detect retinal dysfunction in VMD. Three
patients aged 30, 37 and 59 years with VMD and a visual acuity of OD: 0.4; OS
0.05 (patient 1), 1.25 OU (patient 2) and OU: 0.6 (patient 3) underwent
additional electrophysiological testing with the MF-ERG. A multifocal-ERG of the 
central 50 degrees of the retina was obtained using the VERIS-system. During
recording 103 hexagons flickered according to a binary m-sequence of 2(15). Mean 
luminance was 100 cd/m2, contrast was set at 99%. The MF-ERG recordings were
compared to age matched control groups. In all three patients the MF-ERG of the
central 6 degrees showed reduced amplitudes for N1P1 (first negative peak to
first positive peak) and for P1N2 (P1 to the second negative peak). Implicit
times were not affected. Therefore the MF-ERG can detect focal retinal
dysfunction in VMD which would not be apparent in the summed retinal response
recorded with the ganzfeld ERG. In contrast to other diseases, amplitudes rather 
than implicit times seem to be affected in the MF-ERG of vitelliform macular
dystrophy.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12678279 [PubMed - indexed for MEDLINE]

2606: Doc Ophthalmol. 2003 Mar;106(2):129-36.

Nitric oxide and lipid peroxidation are increased and associated with decreased
antioxidant enzyme activities in patients with age-related macular degeneration.

Evereklioglu C, Er H, Doganay S, Cekmen M, Turkoz Y, Otlu B, Ozerol E.

Department of Ophthalmology, Erciyes University Medical Faculty, Kayseri, Turkey.
evereklioglu@hotmail.com

BACKGROUND: Nitric oxide (NO), hydroxyl radical (OH*), superoxide anion (O2-) and
hydrogen peroxide (H2O2) are free-radicals released in oxidative stress.
Superoxide dismutase (SOD), glutathione peroxidase (GSHPx) and catalase (CAT) are
antioxidant enzymes, mediating defense against oxidative stress. Excess NO and/or
defective antioxidants cause lipid peroxidation, cellular dysfunction and death. 
Age-related maculopathy (ARM) or degeneration (ARMD) is the leading cause of
irreversible blindness in developed countries. The etiology is unclear and the
molecular factors contributing this disease remain to be specified. AIMS: This
multicenter, double-blind, cross-sectional study aimed to investigate plasma NO
and lipid peroxidation levels with relation to antioxidant enzyme activities in
erythrocyte and plasma of patients with ARMD compared with healthy control
subjects. METHODS: NO, lipid peroxidation (measured as plasma malondialdehyde
[MDA] levels) and the catalytic activity of SOD, GSHPx and CAT were measured in a
group of 41 patients with maculopathy (19 men, 22 women; 67.12 +/- 3.70 years)
and compared with 25 age- and sex-matched healthy control subjects without
maculopathy (12 men, 13 women; 68.04 +/- 3.02 years). NO and MDA levels were
measured in plasma, CAT in red blood cells (RBCs), and SOD and GSHPx in both
plasma and RBCs. Color fundus photographs were used to assess the presence of
maculopathy, and the patients were divided into two groups using clinical
examination and grading of photographs; early-ARM (n = 22) and late-ARMD (n =
19). RESULTS: All patients with maculopathy had significantly (p < 0.001) higher 
plasma NO levels over control subjects (mean +/- SD, 48.58 +/- 8.81 vs. 28.22 +/-
3.39 micromol/l). Plasma MDA levels in patients and control subjects were 4.99
+/- 1.00 and 2.16 +/- 0.24 micromol/l, respectively, and the difference was
significant (p < 0.001). On the other hand, SOD and GSHPx activities were
significantly lower in both RBCs and plasma of patients with maculopathy than in 
control subjects (RBCs-SOD, 3509.30 +/- 478.22 vs. 5033.30 +/- 363.98 U/g Hb, p <
0.001; plasma-SOD, 560.95 +/- 52.52 vs. 704.76 +/- 24.59 U/g protein, p < 0.001; 
RBCs-GSHPx, 663.43 +/- 41.74 vs. 748.80 +/- 25.50 U/g Hb, p < 0.001;
plasma-GSHPx, 98.26 +/- 15.67 vs. 131.80 +/- 8.73 U/g protein, p < 0.001).
RBCs-CAT levels were not different between groups (131.68 +/- 12.89 vs. 133.00
+/- 13.29 k/g Hb, p = 0.811). Late-ARMD patients had significantly lower
antioxidant enzyme levels and higher MDA levels when compared with early-ARM
patients (for each, p < 0.001). In addition, plasma NO and MDA levels were
negatively correlated with SOD and GSHPx activities. CONCLUSIONS: This study
demonstrated for the first time that NO, the most abundant free-radical in the
body, might be implicated in the pathophysiology of ARMD in association with
decreased antioxidant enzymes and increased lipid peroxidation status.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial

PMID: 12678277 [PubMed - indexed for MEDLINE]

2607: Proc Natl Acad Sci U S A. 2003 Apr 15;100(8):4742-7. Epub 2003 Apr 1.

Comment in:
    Proc Natl Acad Sci U S A. 2003 Apr 15;100(8):4353-4.

Treatment with isotretinoin inhibits lipofuscin accumulation in a mouse model of 
recessive Stargardt's macular degeneration.

Radu RA, Mata NL, Nusinowitz S, Liu X, Sieving PA, Travis GH.

Jules Stein Eye Institute and Department of Biological Chemistry, University of
California School of Medicine, Los Angeles, CA 90095, USA.

Recessive Stargardt's macular degeneration is an inherited blinding disease of
children caused by mutations in the ABCR gene. The primary pathologic defect in
Stargardt's disease is accumulation of toxic lipofuscin pigments such as
N-retinylidene-N-retinylethanolamine (A2E) in cells of the retinal pigment
epithelium. This accumulation appears to be responsible for the photoreceptor
death and severe visual loss in Stargardt's patients. Here, we tested a
therapeutic strategy to inhibit lipofuscin accumulation in a mouse model of
recessive Stargardt's disease. Isotretinoin (Accutane) has been shown to slow the
synthesis of 11-cis-retinaldehyde and regeneration of rhodopsin by inhibiting
11-cis-retinol dehydrogenase in the visual cycle. Light activation of rhodopsin
results in its release of all-trans-retinaldehyde, which constitutes the first
reactant in A2E biosynthesis. Accordingly, we tested the effects of isotretinoin 
on lipofuscin accumulation in abcr(-/-) knockout mice. Isotretinoin blocked the
formation of A2E biochemically and the accumulation of lipofuscin pigments by
electron microscopy. We observed no significant visual loss in treated abcr(-/-) 
mice by electroretinography. Isotretinoin also blocked the slower, age-dependent 
accumulation of lipofuscin in wild-type mice. These results corroborate the
proposed mechanism of A2E biogenesis. Further, they suggest that treatment with
isotretinoin may inhibit lipofuscin accumulation and thus delay the onset of
visual loss in Stargardt's patients. Finally, the results suggest that
isotretinoin may be an effective treatment for other forms of retinal or macular 
degeneration associated with lipofuscin accumulation.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12671074 [PubMed - indexed for MEDLINE]

2608: J Cataract Refract Surg. 2003 Mar;29(3):603-8.

Chronic cystoid macular edema in an eye with a capsule defect and posteriorly
dislocated capsular tension ring.

Bopp S, Lucke K.

Tagesklinik Universitaetsallee, Department of Ophthalmology, Bremen, Germany.
S.Bopp@Retina.to.de

A 72-year-old man presented with visual deterioration and cystoid macular edema
(CME) 9 months after cataract surgery elsewhere. A slitlamp examination showed a 
large posterior capsule defect and a slightly decentered intraocular lens (IOL). 
In addition, a curved poly(methyl methacrylate) (PMMA) haptic-like structure was 
seen behind the IOL in the superoanterior vitreous cavity. The foreign body was
entangled by vitreous fibers and moved in accordance with ocular motility. A
broken PMMA haptic was suspected. During vitrectomy for removal of the suspected 
IOL haptic, an intact, posteriorly dislocated capsular tension ring (CTR) was
found. It was cut in 2 and excised carefully via the sclerectomies.
Postoperatively, the CME resolved and vision improved.

Publication Types: 
    Case Reports

PMID: 12663032 [PubMed - indexed for MEDLINE]

2609: Ophthalmologica. 2003 May-Jun;217(3):194-8.

Use of digitized fluorescein angiogram system to guide laser treatment of
diabetic macular edema: a new technique.

Ladas ID.

Athens University School of Medicine, Department of Ophthalmology, Athens,
Greece. ladas@ath.forthnet.gr

We describe our technique to guide laser treatment in diabetic patients with
clinically significant macular edema using a digitized fluorescein angiogram
system. A pretreatment red-free photograph overlaid on a fluorescein angiogram is
processed with the aid of the digitized fluorescein angiogram system in order to 
include all the important traces on it. The processed red-free image is used by
the surgeon as a guide to the laser photocoagulation, improving treatment
accuracy and safety for patients with diabetic macular edema. Copyright 2003 S.
Karger AG, Basel

Publication Types: 
    Case Reports

PMID: 12660482 [PubMed - indexed for MEDLINE]

2610: Invest Ophthalmol Vis Sci. 2003 Apr;44(4):1680-5.

Kinetics of retinal lipoprotein precipitation and elimination after closure of
subretinal new vessels.

Taarnhøj NC, Kjeka O, Larsen M.

Department of Ophthalmology, Herlev Hospital, University of Copenhagen, Denmark. 
loja@herlevhosp.kbhamt.dk

PURPOSE: To study the kinetics of retinal precipitation and elimination of
lipoprotein in relation to photodynamic therapy of subretinal new vessels.
METHODS: This was a retrospective observational study of subretinal precipitate
before and after photodynamic therapy for subfoveal new vessels secondary to
age-related macular degeneration in 14 eyes demonstrating precipitate at one or
more visits, using digital red-free gray-scale fundus photography, intravenous
fluorescein angiography, optical coherence tomography, and morphometric mapping. 
RESULTS: In 14 eyes of 14 patients, the area covered by lipoprotein precipitate
increased from a mean of 0.54 optic disc areas (range, 0-2.61) before treatment
to a mean of 0.65 optic disc areas (range, 0.01-3.04) at 45 d after treatment (P 
= 0.18). Eyes with a serous detachment at baseline, before the initial treatment 
(n = 10) demonstrated more treatment-related precipitation than eyes without a
serous detachment at baseline (n = 4; P = 0.034). Two eyes with a large amount of
precipitate and a long follow-up demonstrated net elimination of precipitate from
approximately 100 days after the initial treatment, with uniexponential
precipitate half-lives of 43 and 32 days. CONCLUSIONS: Photodynamic therapy for
subfoveal new vessels may be associated with retinal precipitation of
lipoprotein, presumably because early extraction of water and salts from the
subretinal fluid increases the concentration of leaked plasma proteins. Despite
reperfusion of the subretinal vessels, macromolecular leakage appears to cease
within 100 days, indicating that functional maturation of the new vessels has
occurred, with an associated decrease in pore size.

PMID: 12657609 [PubMed - indexed for MEDLINE]

2611: Invest Ophthalmol Vis Sci. 2003 Apr;44(4):1673-9.

Multifocal electroretinograms in cases of central areolar choroidal dystrophy.

Nagasaka K, Horiguchi M, Shimada Y, Yuzawa M.

Department of Ophthalmology, Nippon University School of Medicine, Tokyo, Japan.

PURPOSE: To study multifocal electroretinograms (mfERG) in patients with
early-stage central alveolar choroidal dystrophy (CACD) with well-demarcated
atrophic areas. METHODS: Eight eyes of eight patients with CACD (ages, 47-67
years) and 20 normal control subjects were examined. The first- and second-order 
kernels (K1 and K2) were extracted from the responses elicited by 61 standard
hexagonal elements of a visual response imaging system. The amplitudes and peak
times of the focal responses at various retinal eccentricities were studied.
RESULTS: The amplitudes of K1 were reduced in the visibly atrophic areas, and
they were also decreased in areas with no visible atrophy. The peak time was
slightly delayed in many loci, but the delay was not as long as that in
congenital stationary night blindness or diabetic retinopathy. The amplitude of
K2 was very small in the central and peripheral areas, but the K2/K1 ratio in
both areas was not significantly reduced, compared with that in normal subjects. 
CONCLUSIONS: Although the atrophic area was ophthalmoscopically well demarcated
in patients with CACD, the abnormality of retinal function extended beyond the
borders of the ophthalmoscopic and angiographic lesions. The retinal dysfunction 
outside the atrophic areas suggests a centrifugal progression of the disease, and
abnormal K2 and K1 with preserved K2/K1 ratio are consistent with a presynaptic
mechanism for the retinal dysfunction in this disease.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12657608 [PubMed - indexed for MEDLINE]

2612: Invest Ophthalmol Vis Sci. 2003 Apr;44(4):1657-62.

An autosomal dominant bull's-eye macular dystrophy (MCDR2) that maps to the short
arm of chromosome 4.

Michaelides M, Johnson S, Poulson A, Bradshaw K, Bellmann C, Hunt DM, Moore AT.

Institute of Ophthalmology, University College London, London, United Kingdom.

PURPOSE: To describe the phenotype of an autosomal dominant macular dystrophy and
identify the chromosomal locus. METHODS: Eleven members of a five-generation,
nonconsanguineous British family were examined clinically and also underwent
automated perimetry, electrodiagnostic testing, fundus fluorescein angiography,
and fundus autofluorescence imaging. Blood samples were taken for DNA extraction 
and linkage analysis was performed. RESULTS: The phenotype is characterized by
bull's-eye macular dystrophy first evident in the first or second decade of life.
There is mild visual impairment, central scotomata, and electrophysiological
testing indicates that most affected individuals have disease confined to the
central retina but older subjects have more widespread rod and cone
abnormalities, demonstrated by flash ERG. Genetic linkage analysis established
linkage to chromosome 4 at p15.2-16.3 with a maximum lod score of 3.03 at a
recombination fraction of 0.00 for marker D4S391. The locus for this autosomal
dominant macular dystrophy lies between flanking markers D4S3023 and D4S3022, and
overlaps the Stargardt 4 locus. CONCLUSIONS: A new locus was identified for a
bull's-eye macular dystrophy on the short arm of chromosome 4.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12657606 [PubMed - indexed for MEDLINE]

2613: Am J Ophthalmol. 2003 Apr;135(4):477-82.

Reduced oscillatory potentials of the full-field electroretinogram of eyes with
aphakic or pseudophakic cystoid macular edema.

Terasaki H, Miyake K, Miyake Y.

Department of Ophthalmology, Nagoya University School of Medicine, Nagoya, Japan.

PURPOSE: To report reduced oscillatory potentials (OPs) in the full-field
electroretinogram (ERG) of eyes with aphakic or pseudophakic cystoid macular
edema (CME). DESIGN: Observational case series. METHODS: Bright white flash
full-field ERGs were recorded from 19 eyes of 19 patients (ages, 53-84 years)
with aphakic or pseudophakic CME. Seven of the cases had uncomplicated
phacoemulsification (PE) with implantation of a posterior chamber intraocular
lens (PC-IOL) and 6 had posterior capsular rupture during phacoemulsification and
aspiration with implantation of a PC-IOL. Four additional patients had
uncomplicated intracapsular cataract extraction (ICCE), and 2 had secondary
anterior chamber intraocular lens after ICCE. Their fellow eyes without CME
served as controls. Cystoid macular edema was diagnosed as clinically significant
by slit-lamp examination and by fluorescein angiography. The grading for severity
of CME was based on the fluorescein angiography. The visual acuity ranged from
20/200 to 20/16. RESULTS: There were no significant differences in the mean
amplitudes and implicit times of the a-waves and b-waves between the affected
eyes and the fellow eyes. The mean summed amplitude of the OPs was significantly 
reduced in the affected eyes (P =.0003, Wilcoxon signed rank test). This decrease
was strongly correlated with visual acuity (r =.779, P <.0001). The mean implicit
time of the first OP was significantly delayed in the affected eyes (P =.0089,
Wilcoxon signed rank test). CONCLUSIONS: Because the peripheral retina
contributes more significantly to full-field ERGs than the macula, the reduced OP
amplitudes of the full-field ERGs in eyes with aphakic or pseudophakic CME
suggest a functional impairment not only in the macula but also throughout the
retina.

PMID: 12654363 [PubMed - indexed for MEDLINE]

2614: Retina. 2003 Feb;23(1):14-23.

Anecortave acetate as monotherapy for the treatment of subfoveal lesions in
patients with exudative age-related macular degeneration (AMD): interim (month 6)
analysis of clinical safety and efficacy.

D'Amico DJ, Goldberg MF, Hudson H, Jerdan JA, Krueger S, Luna S, Robertson SM,
Russell S, Singerman L, Slakter JS, Sullivan EK, Yannuzzi L, Zilliox P;
Anecortave Acetate Clinical Study Group.

PURPOSE: To evaluate clinical safety and efficacy of the angiostatic agent
anecortave acetate for treatment of subfoveal choroidal neovascularization
secondary to AMD. METHODS: 128 patients were randomized to placebo treatment or
one of three anecortave acetate doses. Study medication was administered as a
posterior juxtascleral injection onto the posterior scleral surface.
Best-corrected logMAR vision was obtained at baseline and follow-up visits.
Fluorescein angiograms were evaluated for eligibility before enrollment and
posttreatment. RESULTS: Six months after a single treatment, visual acuity (mean 
change from baseline logMAR values) was significantly better (P = 0.003) after
anecortave acetate 15 mg than placebo. More patients treated with anecortave
acetate 15 mg than placebo maintained vision (88% versus 70%, P = 0.080),
especially those with predominantly classic lesions (92% versus 65%, P = 0.021). 
Anecortave acetate 15 mg inhibited lesion growth significantly better than
placebo (P = 0.001). Trends favoring the other doses over placebo were observed
for vision preservation and lesion inhibition, but statistical significance was
not achieved. The Independent Safety Committee overseeing this study identified
no clinically relevant treatment-related changes. CONCLUSION: Anecortave acetate 
15 mg is safe and effective for preserving or improving vision and for inhibiting
lesion growth in patients with subfoveal AMD.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial

PMID: 12652226 [PubMed - indexed for MEDLINE]

2615: Retina. 2003 Feb;23(1):1-7; quiz 137-8.

Cystoid macular degeneration in chronic central serous chorioretinopathy.

Iida T, Yannuzzi LA, Spaide RF, Borodoker N, Carvalho CA, Negrao S.

Department of Ophthalmology, Fukushima Medical University School of Medicine,
Japan.

PURPOSE: To describe the optical coherence tomography (OCT) and fluorescein
angiography findings in the macula of eyes with chronic central serous
chorioretinopathy (CSC) and reduced central vision. METHODS: Using OCT, clinical 
examination, and fluorescein and indocyanine green (ICG) angiography, the authors
examined eight eyes of seven patients with CSC, an attached macula, and reduced
central vision of 20/200 or worse. All had a history of chronic CSC with
resolution of the subretinal fluid in the macular area and poor vision. RESULTS: 
Patient ages ranged from 55 to 82 years (mean, 66 years). All eight eyes had some
parafoveal, patchy RPE atrophy with corresponding transmission hyperfluorescence 
(window defect) on fluorescein angiography. Five eyes also had a window defect in
the foveal area. With OCT, the foveal area revealed variable areas of cystoid
change and atrophy in seven of the eight eyes. In four of these eyes, the cystoid
changes were not seen on clinical examination or fluorescein angiography. The
seven eyes with cystoid changes imaged with OCT had no intraretinal leakage of
fluorescein in the foveal region. The authors categorized these eyes as having
cystoid macular degeneration (CMD). One other eye had foveal thinning or atrophy 
without cystoid changes. CONCLUSIONS: Intraretinal cystoid spaces without
intraretinal leakage, or CMD, was a common finding in eyes with chronic CSC and
reduced central vision after resolution of subretinal fluid. OCT was useful to
establish the presence of CMD and foveal atrophy, even when these changes were
not clearly evident on clinical examination or fluorescein angiography. Chronic
foveal detachment and antecedent intraretinal leakage were proposed to be the
mechanisms for the development of the changes. CMD in conjunction with foveal
atrophy was an important clinical finding to account for the poor visual outcome 
in patients with CSC.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12652224 [PubMed - indexed for MEDLINE]

2616: Clin Experiment Ophthalmol. 2003 Apr;31(2):103-9.

Limited macular translocation for subfoveal choroidal neovascularization in
age-related macular degeneration.

Chang AA, Tan W, Beaumont PE, Zeldovich A.

Sydney Retina, Sydney, New South Wales, Australia. achang@sydneyretina.com.au

PURPOSE: To examine the safety and efficacy of limited macular translocation
followed by laser photocoagulation in the management of subfoveal choroidal
neovascularization (CNV) in age-related macular degeneration (AMD). METHODS: A
prospective study was conducted on eight consecutive patients undergoing limited 
macular translocation followed by laser photocoagulation for the treatment of
subfoveal classic CNV form of AMD. Patients were followed up for a minimum of 12 
months. The magnitude of foveal translocation, visual outcomes and complications 
were assessed. RESULTS: In all cases the fovea was successfully translocated
inferiorly, with a median displacement of 1.1 mm. Thermal laser photocoagulation 
was subsequently performed in all cases. Visual acuity improved in five eyes,
remained unchanged in two eyes and worsened in one eye. The mean improvement in
visual acuity was by 0.19 logMAR. At 12 months, six of the eight patients (75%)
achieved Snellen visual acuity of at least 6/15, with four patients (50%)
achieving Snellen visual acuity of 6/9. CONCLUSION: In this small case series,
limited macular translocation was found to be an effective and reproducible means
of treating small well-defined subfoveal CNV.

PMID: 12648041 [PubMed - indexed for MEDLINE]

2617: Graefes Arch Clin Exp Ophthalmol. 2003 Mar;241(3):170-5. Epub 2003 Feb 20.

Changes in macular thickness and depth of anterior chamber in patients after
filtration surgery.

Karasheva G, Goebel W, Klink T, Haigis W, Grehn F.

University Eye Hospital, Josef-Schneider Strasse 11, 97080 Würzburg, Germany.

BACKGROUND: The prospective study was undertaken to analyze retinal thickness of 
the macula and anterior chamber depth in patients undergoing filtration surgery
at different times of follow-up. METHODS: Forty-four patients (45 eyes) were
included. The thickness of the fovea and the extrafoveal retina were measured
using optical coherence tomography (OCT). Anterior chamber depth was determined
using the IOLMaster. All standard clinical examination and measurements were
performed prior to surgery, at the 2nd day (1-3 days), 1 week, 1 month and 3
months after surgery. RESULTS: Preoperative IOP under topical medication was
25.5+/-7.5 mmHg. IOP was significantly decreased at all postoperative visits (
P<0.0001): 10.8+/-5.9 mmHg at the 2nd day, 10.4+/-5.2 mmHg after 1 week,
11.7+/-4.4 mmHg after 1 month and 11.4+/-3.6 mmHg after 3 months. No patient in
our study suffered from prolonged postoperative hypotony (IOP<5 mmHg). Foveal
thickness at the 2nd day, 1 week and 1 month were elevated compared with baseline
( P<0.004). Macular thickness changed from 164+/-20 microm before surgery to
168+/-20 microm after 2 days, 170+/-21 microm after 1 week, 173+/-19 microm after
1 month and 165+/-16 microm after 3 months. Mean thickness of the extrafoveal
retina did not change significantly. Also, there were no significant changes in
anterior chamber depth. There was no significant correlation between reduction of
IOP and retinal thickness or anterior chamber depth. CONCLUSION: The reduction of
IOP after filtration surgery leads to a moderate increase in foveal retinal
thickness over approximately 1 month and is not associated with shallowing of the
anterior chamber, provided that prolonged postoperative hypotony is avoided with 
the surgical technique used.

PMID: 12644938 [PubMed - indexed for MEDLINE]

2618: Br J Ophthalmol. 2003 Apr;87(4):469-72.

Risk factors for age related maculopathy in a Japanese population: the Hisayama
study.

Miyazaki M, Nakamura H, Kubo M, Kiyohara Y, Oshima Y, Ishibashi T, Nose Y.

Department of Medical Information Science, Graduate School of Medical Sciences,
Kyushu University, Fukuoka, Japan. miho-m@info.med.kyushu-u.ac.jp

AIMS: To examine the risk factors for age related maculopathy (ARM) in a sample
Japanese population. METHODS: In 1998, a cross sectional community survey was
conducted among residents of Hisayama. A total of 596 men and 886 women living in
Hisayama, Japan, aged 50 years or older consented to participate in the study.
Each participant underwent a comprehensive examination that included an
ophthalmic examination. The presence of ARM was determined by grading from fundus
examination by indirect ophthalmoscopy, slit lamp examination, and colour fundus 
photographs. Using these cross sectional data, logistic regression analyses were 
performed to determine the risk factors for ARM. The following 10 possible risk
factors were used: age, cataract, hypertension (history), hypertension (history
or examination), diabetes, hyperlipidaemia, current smoker, alcohol intake, BMI, 
and WBC. RESULTS: ARM was detected in 19.5% of men and 14.9% of women. Men were
found to have a significantly higher prevalence of ARM than women. Multiple
logistic regression analysis showed that age and hypertension (history or
examination) were significantly associated with ARM in men, whereas only age was 
a significant risk factor for ARM in women. CONCLUSIONS: This study suggests that
higher age and male sex are relevant risk factors for ARM in Japan. In addition, 
hypertension is a relevant risk factor in men.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12642312 [PubMed - indexed for MEDLINE]

2619: Br J Ophthalmol. 2003 Apr;87(4):462-8.

Intravitreal triamcinolone acetonide for exudative age related macular
degeneration.

Jonas JB, Kreissig I, Hugger P, Sauder G, Panda-Jonas S, Degenring R.

Department of Ophthalmology and Eye Hospital, Faculty for Clinical Medicine
Mannheim, Ruprecht-Karls-University Heidelberg, Germany.
JostJonas@augen.ma.uni-heidelberg.de

AIM: To evaluate the effect of intravitreal triamcinolone acetonide on the visual
acuity of patients with exudative age related macular degeneration, to assess the
duration of a possible effect, and to evaluate clinical side effects of the
treatment. METHODS: The study included 67 patients (71 eyes) who presented with
exudative age related macular degeneration of predominantly or total occult type 
(n = 68) or classic type (n = 3), and who received once, or repeatedly, an
intravitreal injection of 25 mg of crystalline triamcinolone acetonide. Mean
follow up time was 7.46 (SD 3.54) months (range 3.1-19.57 months). RESULTS:
Visual acuity increased significantly (p <0.001) from 0.16 (0.11) to a mean
maximum of 0.23 (0.17). Postoperative visual acuity was highest 1-3 months after 
the injection. 47 (66.2%) eyes gained in maximal visual acuity and 11 (15.5%)
eyes lost in visual acuity. Intraocular pressure increased significantly (p
<0.001) from 15.1 (3.1) mm Hg at baseline to a maximal value of 23.0 (8.25) mm
Hg. At the end of follow up, intraocular pressure again decreased significantly
(p<0.001) to 16.8 (4.9) mm Hg. No cases of postoperative infectious
endophthalmitis, rhegmatogenous retinal detachment, or proliferative
vitreoretinopathy occurred. Owing to a decrease in visual acuity after an initial
increase, six patients received a second intravitreal triamcinolone acetonide
injection after which visual acuity increased again in three eyes. CONCLUSIONS:
Intravitreal injection of 25 mg of crystalline triamcinolone acetonide merits
further study for the treatment of exudative age related macular degeneration.

PMID: 12642311 [PubMed - indexed for MEDLINE]

2620: Br J Ophthalmol. 2003 Apr;87(4):455-61.

Correlation of a scanning laser derived oedema index and visual function
following grid laser treatment for diabetic macular oedema.

Hudson C, Flanagan JG, Turner GS, Chen HC, Young LB, McLeod D.

University Department of Ophthalmology, Royal Eye Hospital, Manchester M13 9WH,
UK. chudson@sciborg.uwarerloo.ca

AIM: To correlate change of an oedema index derived by scanning laser tomography 
with change of visual function in patients undergoing grid laser photocoagulation
for clinically significant diabetic macular oedema (DMO). METHODS: The sample
comprised 24 diabetic patients with retinal thickening within 500 micro m of the 
fovea. Inclusion criteria included a logMAR visual acuity of 0.25, or better.
Patients were assessed twice before a single session of grid laser treatment and 
within 1 week of, and at 1, 2, 4, and 12 weeks after, treatment. At each visit,
patients underwent logMAR visual acuity, conventional and short wavelength
automated perimetry (SWAP), and scanning laser tomography. Each visual function
parameter was correlated with the mean oedema index. The mean oedema index
represented the z-profile signal width divided by the maximum reflectance
intensity (arbitrary units). A Pearson correlation coefficient (Bonferroni
corrected) was undertaken on the data set of each patient. RESULTS: 13 patients
exhibited significant correlation of the mean oedema index and at least one
measure of visual function for the 10 degrees x 10 degrees scan field while 10
patients correlated for the 20 degrees x 20 degrees scan field. Seven patients
demonstrated correlation for both scan fields. Laser photocoagulation typically
resulted in an immediate loss of perimetric sensitivity whereas the oedema index 
changed over a period of weeks. Localised oedema did not impact upon visual
acuity or letter contrast sensitivity when situated extrafoveally. CONCLUSIONS:
Correlation of change of the oedema index and of visual function following grid
laser photocoagulation was not found in all patients. An absence of correlation
can be explained by the localised distribution of DMO in this sample of patients,
as well as by differences in the time course of change of the oedema index and
visual function. The study has objectively documented change in the magnitude and
distribution of DMO following grid laser treatment and has established the
relation of this change to the change in visual function.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12642310 [PubMed - indexed for MEDLINE]

2621: Eye. 2003 Mar;17(2):207-15.

Beta irradiation: new uses for an old treatment: a review.

Kirwan JF, Constable PH, Murdoch IE, Khaw PT.

Department of Epidemiology and International Eye Health Institute of
Ophthamology, London, UK. jfkirwan@ucl.ac.uk

Beta radiation has a long history as a treatment modality in ophthalmology. It is
a convenient and practical method of applying radiation and has the advantage of 
minimal tissue penetration. There has been a recent resurgence in the use of beta
radiation in other areas in medicine, such as the prevention of restenosis after 
coronary artery stenting. Beta radiation has been shown in vitro and in vivo to
inhibit proliferation of human Tenon's fibroblasts, which enter a period of
growth arrest but do not die. Effects on the cell cycle controller p53 have been 
shown to be important in this process. In ophthalmology, beta radiation has been 
used widely for the treatment of pterygium and is under evaluation for treatment 
of age-related macular degeneration and for controlling wound healing after
glaucoma drainage surgery. In this latter role, beta radiation may be
particularly appropriate for use in developing countries to improve the results
of trabeculectomy while potentially avoiding some of the side effects of other
antimetabolites.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 12640408 [PubMed - indexed for MEDLINE]

2622: Optom Vis Sci. 2003 Mar;80(3):207-13.

Driving habits and health-related quality of life in patients with age-related
maculopathy.

DeCarlo DK, Scilley K, Wells J, Owsley C.

Low Vision and Geriatrics, Nova Southeastern University, College of Optometry,
Fort Lauderdale, FL 33328, USA. ddecarlo@nova.edu

PURPOSE: To characterize the driving habits of persons with age-related
maculopathy who present to a low-vision rehabilitation clinic and to examine how 
driving status relates to vision-specific health-related quality of life.
METHODS: The Driving Habits Questionnaire, the National Eye Institute Vision
Function Questionnaire-25, and the Life Space Questionnaire were administered via
telephone interview to 126 patients with age-related maculopathy who presented to
a low-vision clinic during the previous year and were either past or current
drivers. RESULTS: Twenty-four percent of the sample reported being a current
driver. Compared with those who stopped driving, current drivers were more likely
to be male, younger, have better visual acuity and higher National Eye Institute 
Vision Function Questionnaire-25 scores. Drivers reported driving an average of 4
days and 10 miles per week. Over 50% of drivers reported that because of their
vision, they had difficulty with or did not drive at all in rain, at night, on
freeways or interstate highways, in heavy traffic areas, or during rush hour.
Drivers and nondrivers did not differ in their life space, the spatial extent of 
their excursions into their environment. CONCLUSION: Some individuals who present
to a low-vision clinic with age-related maculopathy do drive, although their
driving exposure is low and they report avoiding challenging on-road situations. 
Driving status in age-related maculopathy appears to be related to better eye
visual acuity and vision-specific health-related quality of life.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12637832 [PubMed - indexed for MEDLINE]

2623: Eur J Ophthalmol. 2003 Jan-Feb;13(1):96-8.

Intraocular hemorrhage after systemic thrombolytic therapy in a patient with
exudative macular degeneration.

Djalilian AR, Cantrill HC, Samuelson TW.

Department of Ophthalmology, Regions Hospital, St. Paul, Minnesota, USA.
djaliliana@nei.nih.gov

PURPOSE: To report a hemorrhagic complication from thrombolytic therapy in a
patient with exudative macular degeneration. CASE REPORT: A 75 year old patient
with exudative macular degeneration developed pain and loss of vision in the left
eye shortly after receiving tissue plasminogen activator (t-PA) for a myocardial 
infarction. Examination revealed the patient to be in angle closure. A CT scan
revealed the etiology of the angle closure to be a dense vitreous hemorrhage
pushing the iris-lens diaphragm forward. Intraocular pressure was treated
successfully, but the final visual acuity was only light perception. CONCLUSIONS:
Thrombolytic therapy can lead to devastating intraocular hemorrhages. The
presence of exudative macular degeneration may potentially increase the risk of
developing such complications.

Publication Types: 
    Case Reports

PMID: 12635684 [PubMed - indexed for MEDLINE]

2624: Exp Eye Res. 2003 Apr;76(4):397-403.

Oxidative stress-induced mitochondrial DNA damage in human retinal pigment
epithelial cells: a possible mechanism for RPE aging and age-related macular
degeneration.

Liang FQ, Godley BF.

Retina Foundation of the Southwest, Anderson Vision Research Center, 9900 N.
Central Expressway, Suite 400, Dallas, TX 75231, USA.

Oxidative stress is believed to contribute to the pathogenesis of many diseases, 
including age-related macular degeneration (AMD). Although the vision loss of AMD
results from photoreceptor damage in the central retina, the initial pathogenesis
involves degeneration of RPE cells. Evidence from a variety of studies suggests
that RPE cells are susceptible to oxidative damage. Mitochondrial DNA (mtDNA) is 
particularly prone to oxidative damage compared to nuclear DNA (nDNA). Using the 
quantitative PCR assay, a powerful tool to measure oxidative DNA damage and
repair, we have shown that human RPE cells treated with H(2)O(2) or rod outer
segments resulted in preferential damage to mtDNA, but not nDNA; and damaged
mtDNA is not efficiently repaired, leading to compromised mitochondrial redox
function as indicated by the MTT assay. Thus, the susceptibility of mtDNA to
oxidative damage in human RPE cells, together with the age-related decrease of
cellular anti-oxidant system, provides the rationale for a mitochondria-based
model of AMD.

Publication Types: 
    Review

PMID: 12634104 [PubMed - indexed for MEDLINE]

2625: Annu Rev Nutr. 2003;23:171-201. Epub 2003 Feb 27.

Biologic mechanisms of the protective role of lutein and zeaxanthin in the eye.

Krinsky NI, Landrum JT, Bone RA.

Department of Biochemistry, School of Medicine and the USDA Jean Mayer Human
Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts
02111-1837, USA. norman.krinsky@tufts.edu

The macular region of the primate retina is yellow in color due to the presence
of the macular pigment, composed of two dietary xanthophylls, lutein and
zeaxanthin, and another xanthophyll, meso-zeaxanthin. The latter is presumably
formed from either lutein or zeaxanthin in the retina. By absorbing blue-light,
the macular pigment protects the underlying photoreceptor cell layer from light
damage, possibly initiated by the formation of reactive oxygen species during a
photosensitized reaction. There is ample epidemiological evidence that the amount
of macular pigment is inversely associated with the incidence of age-related
macular degeneration, an irreversible process that is the major cause of
blindness in the elderly. The macular pigment can be increased in primates by
either increasing the intake of foods that are rich in lutein and zeaxanthin,
such as dark-green leafy vegetables, or by supplementation with lutein or
zeaxanthin. Although increasing the intake of lutein or zeaxanthin might prove to
be protective against the development of age-related macular degeneration, a
causative relationship has yet to be experimentally demonstrated.

Publication Types: 
    Review

PMID: 12626691 [PubMed - indexed for MEDLINE]

2626: Arch Ophthalmol. 2003 Mar;121(3):379-85.

The prevalence of age-related maculopathy in iceland: Reykjavik eye study.

Jonasson F, Arnarsson A, Sasaki H, Peto T, Sasaki K, Bird AC.

Department of Ophthalmology, University Iceland, Reykjavik, Iceland.
fridbert@landspitali.is

OBJECTIVE: To examine the age- and sex-specific prevalence of age-related
maculopathy (ARM) and age-related macular degeneration (AMD) in citizens of
Reykjavik, Iceland, who were 50 years and older. DESIGN: Random sample, cross
sectional. MATERIALS AND METHODS: Response rate was 75.8%. The presence and
severity of various characteristics of drusen and pigmentary changes that are
typical of ARM and AMD were determined by grading stereoscopic color fundus
photographs, using the international classification and grading system for ARM
and AMD. RESULTS: We were able to evaluate 1021 right-eye and 1020 left-eye
macular photographs. There was no statistically significant difference between
right and left eyes. In people aged 50 to 59 years, 4.8% of participants (95%
confidence interval [CI], 2.6-7.0) were found to have intermediate soft drusen
measuring 63 to 125 micro m in either eye; 1.2% (95% CI, 0.0-2.3) had large soft 
distinct drusen larger than 125 micro m; and 0.6% (95% CI, 0.0-1.4) had large
soft, crystalline, or semisolid drusen. The same figures for those 80 years and
older were 18.2% (95% CI, 9.8-26.6), 10.9% (95% CI, 4.0-17.8), and 25.5% (95% CI,
18.4-32.6), respectively. Geographic atrophy was found in either eye in 9.2% of
those participants 70 years and older (95% CI, 5.6-12.7), and exudative macular
degeneration was found in 2.3% of participants 70 years and older (95% CI,
0.5-4.1). CONCLUSION: Geographic atrophy was found to be more common in our study
than in other population-based studies.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12617709 [PubMed - indexed for MEDLINE]

2627: Am J Ophthalmol. 2003 Mar;135(3):321-7.

Relation of diabetic macular edema to cytokines and posterior vitreous
detachment.

Funatsu H, Yamashita H, Ikeda T, Mimura T, Shimizu E, Hori S.

Department of Ophthalmology, Diabetes Center, Tokyo Women's Medical University,
Tokyo, Japan. tfunatsu@nifty.com

PURPOSE: To investigate whether angiotensin II (AII) or vascular endothelial
growth factor (VEGF) is related to diabetic macular edema (DME) in patients with 
and without posterior vitreous detachment (PVD). DESIGN: A case-control study.
METHODS: Vitreous fluid samples were obtained at vitreoretinal surgery from 28
eyes of 28 DME patients without PVD, 8 eyes of 8 DME patients with PVD, 14 eyes
of 14 nondiabetic patients, and 8 eyes of diabetic patients without retinopathy. 
The VEGF levels in vitreous fluid and plasma were determined by enzyme-linked
immunosorbent assay, while AII levels were measured by radioimmunoassay.RESULTS: 
The vitreous levels of AII and VEGF were significantly higher in DME patients
with or without PVD than in nondiabetic patients or diabetic patients without
retinopathy (without PVD: P < .0061, P < .0001, P = .0261, and P < .0001; with
PVD: P < .0012, P < .0001, P = .0473, and P < .0001, respectively). There was no 
significant difference in the vitreous levels of AII or VEGF between patients
with or without PVD (P = .4948 and P = .6642, respectively). The vitreous level
of AII significantly correlated with that of VEGF in DME patients without PVD (P 
= .576) or with PVD (P = .488). AII and VEGF levels in vitreous fluid were
significantly higher than the respective plasma levels. CONCLUSIONS: We found
that the vitreous levels of AII and VEGF were elevated in DME patients
irrespective of the status of PVD. Angiotensin II and VEGF may be induced in the 
eyes and be related to the pathogenesis of DME. Copyright 2003 by Elsevier
Science Inc.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12614749 [PubMed - indexed for MEDLINE]

2628: Eur Rev Med Pharmacol Sci. 2002 Jan-Feb;6(1):1-8.

Deflazacort treatment of cystoid macular edema in patients affected by Retinitis 
Pigmentosa: a pilot study.

Giusti C, Forte R, Vingolo EM.

Institute of Ophthalmology, University La Sapienza, Rome, Italy.

BACKGROUND: To investigate the efficacy of a long-term treatment with Deflazacort
(DFZ), a third generation synthetic glucocorticoid, in patients affected by
Retinitis Pigmentosa (RP) complicated by Cystoid Macular Edema (CME). METHODS: A 
randomized group of 10 RP subjects were selected for this pilot study and treated
with DFZ for one year according to a standard protocol. Far and near Best
Corrected Visual Acuity (BCVA), fluorescein angiography (Heidelberg Retina
Angiograph) and computerized perimetry (Humphrey Visual Field Analyzer) were
statistically assessed. RESULTS: Near visual acuities, fluorescein angiographic
findings and perimetric data improved significantly (p < 0.01) while far BCVA
varied only slightly (p < 0.05). No ocular or systemic side effects were
recorded. CONCLUSIONS: Further case-control studies, also involving a larger
number of patients, are required to confirm these preliminary results. However,
the present investigation seem to suggest that DFZ could be effective in reducing
fluorescein angiographic findings and improving perimetric data and near visual
acuities in RP patients, even though the pathogenesis of CME remains poorly
understood.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 12608650 [PubMed - indexed for MEDLINE]

2629: Can J Ophthalmol. 2003 Feb;38(1):33-40.

Autosomal dominant macular dystrophy in a large Canadian family.

Donoso LA, Hageman G, Frost A, Sheffield V, Beck J, Hébert M, MacDonald IM.

Henry and Corinne Bower Laboratory, Eye Research Institute, Wills Eye Hospital,
Philadelphia, PA 19107, USA. ldonoso@vision-research.org

BACKGROUND: We studied a large Canadian family (178 total family members)
spanning seven generations with autosomal dominant macular dystrophy. We
performed a study to identify the gene mutation responsible for the disease in
the family. METHODS: Participating family members were evaluated clinically.
Genetic linkage, genotyping, mutation screening and an extensive genealogic
investigation were performed. RESULTS: The common clinical findings in affected
family members included progressive early- to mid-onset visual loss and extensive
areas of central chorioretinal atrophy. Two-point linkage analysis indicated
linkage to chromosome 6p. Direct DNA sequencing showed a C/T transition in codon 
172 of the retinal degeneration slow (RDS) gene creating an amino acid change to 
Arg172Trp. Haplotype analysis of affected family members using microsatellite
markers distributed around the RDS gene locus revealed that the markers were not 
conserved when compared to members of British families with the Arg172Trp
mutation. Genealogic studies indicated the family immigrated to Canada from
Ireland in 1843. INTERPRETATION: A newly identified large family with autosomal
dominant macular dystrophy is described. The phenotypic appearance of the fundus 
is similar to that of previously described patients with an Arg172Trp mutation in
the RDS gene. Haplotype analysis of markers spanning the disease locus identified
a new founder for this mutation. The identification of the disease-causing gene
in this family allows for better genetic counselling for patients with this
condition and provides a basis to distinguish clinically similar types of macular
dystrophy based on the clinical phenotype.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12608515 [PubMed - indexed for MEDLINE]

2630: Can J Ophthalmol. 2003 Feb;38(1):27-32.

Current use of dietary supplementation in patients with age-related macular
degeneration.

Chang CW, Chu G, Hinz BJ, Greve MD.

Department of Ophthalmology, University of Alberta, Edmonton, Alta.

BACKGROUND: The Age-Related Eye Disease Study (AREDS) Research Group recently
reported significant reduction in the progression of certain categories of
age-related macular degeneration (AMD) with the use of high-dose antioxidant and 
zinc supplementation. We studied the current use of dietary supplementation in
our patients with AMD to determine whether dosages recommended in the AREDS were 
being achieved. We also evaluated the easiest and most cost-effective method to
reach recommended dosages using supplements currently available in Canada.
METHODS: Cross-sectional descriptive study conducted by patient survey from Feb. 
1 to Mar. 31, 2002. All patients with the diagnosis of AMD were surveyed during
an office visit at a retinal specialty clinic in Edmonton. The following
information was collected: demographic information, duration of AMD, smoking
status and current use of dietary supplements. For patients using supplements, we
also noted duration of use, reason for use, who recommended use, and type and
dosage of supplements (including vitamin, mineral and herbal supplements). The
exact dosages were confirmed by follow-up telephone interview. Cost estimates
were determined by averaging retail prices from several local pharmacies. We
compared methods of reaching the recommended dosages using various combinations
of commercially available multivitamin formulations and individual beta-carotene,
vitamin C and E, and zinc supplements. The goal was to match the dosage
recommended in the AREDS (without exceeding it if possible) at maximum
convenience and minimum cost and without increasing the risk of toxic effects.
RESULTS: Of 108 patients with AMD surveyed, 85 (79%) were taking dietary
supplements, and 73 (68%) were taking at least one AREDS ingredient. The mean
dosages of beta-carotene, vitamins C and E, and zinc were all below those
recommended in the AREDS. None of our patients met the recommended dosages for
all four ingredients. We identified four methods of reaching recommended dosages 
using various combinations of ICAPS TR, Ocuvite and Vitalux as well as Centrum
multivitamin and individual supplements. INTERPRETATION: Patients with AMD may
not be receiving the dosages of beta-carotene, vitamins C and E, and zinc
recommended in the AREDS. Until new formulations of high-dose antioxidant and
zinc supplements are available in Canada, patients should be counselled to
attempt to meet recommended dosages by using combinations of currently available 
supplements.

Publication Types: 
    Comparative Study

PMID: 12608514 [PubMed - indexed for MEDLINE]

2631: Ophthalmic Epidemiol. 2003 Feb;10(1):37-48.

Systemic use of anti-inflammatory medications and age-related maculopathy: the
Blue Mountains Eye Study.

Wang JJ, Mitchell P, Smith W, Gillies M, Billson F; Blue Mountains Eye Study.

Department of Ophthalmology and the Save Sight and Westmead Millennium
Institutes, the University of Sydney, Westmead, NSW, Australia.

PURPOSE: To assess whether an association exists between systemic use of
anti-inflammatory medications at baseline and the prevalence or incidence of
either late or early age-related maculopathy (ARM) in a population-based cohort. 
METHODS: 3654 participants of the Blue Mountains Eye Study baseline examination
(1992-94) were followed during 1997-99. Use of anti-inflammatory medication was
recorded during the baseline interview. After excluding 543 persons who died
since baseline, 2334 (75% of the surviving participants) attended 5-year
follow-up examinations. Retinal photographs taken during both examinations were
graded using the Wisconsin Age-Related Maculopathy Grading System. Prevalence
refers to the proportion of participants having ARM at baseline. Incidence refers
to the proportion of participants without ARM at baseline who developed it over
the 5-year period. Known ARM risk factors were adjusted for when assessing the
relationship between use of anti-inflammatory medications and ARM. RESULTS: At
baseline, 1010 (27.6%) of 3654 participants were current users of non-steroidal
anti-inflammatory drugs (NSAIDs), 514 (14.1%) were past users and 1282 (35.1%)
were ever users. The corresponding numbers of subjects reporting current, past or
ever use of corticosteroids (including inhaled steroids) were 225 (6.2%), 519
(14.2) and 564 (15.4), respectively. Late ARM was present in 72 participants
(2.0%) and early ARM was present in 171 participants (4.9%) at the baseline
examination. During the follow-up period, 25 participants (1.1%) developed
incident late ARM and 192 (8.7%) developed incident early ARM. After adjusting
for age, sex, family history of ARM and smoking, no significant associations were
evident for the use of NSAIDs or corticosteroids and the prevalence of either
late or early ARM. There were also no associations found between use of these
medications at baseline and the 5-year incidence of either late or early ARM.
CONCLUSIONS: No association was found between use of systemic anti-inflammatory
medications and either the cross-sectional prevalence or longitudinal incidence
of ARM in this population.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12607158 [PubMed - indexed for MEDLINE]

2632: Invest Ophthalmol Vis Sci. 2003 Mar;44(3):1031-4.

Incidence of blindness in southern Germany due to glaucoma and degenerative
conditions.

Trautner C, Haastert B, Richter B, Berger M, Giani G.

Department of Public Health, University of Applied Sciences,
Braunschweig/Wolfenbüttel, Wolfsburg, Germany. trautner@healthresearch-online.org

PURPOSE: To estimate population-based incidence rates of registered blindness
separately, to determine its main causes. METHODS: The files of all newly
registered blindness-allowance recipients in Württemberg-Hohenzollern, Germany
(population: approximately 5 million), between 1994 and 1998 were reviewed. From 
ophthalmological reports on file the fulfillment of the German criteria for
blindness (visual acuity of 1/50 or less or equivalent reduction of visual
function) was ascertained, and the causes of blindness were obtained. Incidence
rates of blindness due to macular degeneration, glaucoma, cataract, optic
atrophy, and diabetic retinopathy were estimated. RESULTS: There were 3531 newly 
registered blindness-allowance recipients (67.1% female; mean age, 72.8 +/- 21.0 
years). Standardized incidence rates in the general population (per 100,000
person-years; 95% confidence interval): All causes 12.27 (11.87-12.68), macular
degeneration 5.29 (5.02-5.55), cataract 3.32 (3.11-3.52), optic atrophy 2.86
(2.66-3.05), glaucoma 2.43 (2.25-2.61), diabetic retinopathy 2.13 (1.96-2.30),
other or unknown causes 5.17 (4.91-5.43). In many cases, blindness was
attributable to more than one cause. Assuming that incidence rates are the same
in other parts of the country, 9,939 (9,608-10,270) new cases of blindness were
estimated to occur in Germany per year. CONCLUSIONS: The most common single cause
of blindness was macular degeneration. Incidence rates of blindness due to such
treatable conditions as glaucoma were also high. This finding suggests that the
taking of measures for secondary prevention (e.g., early detection and optimal
treatment of patients with glaucoma and diabetic retinopathy) should be
intensified.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12601025 [PubMed - indexed for MEDLINE]

2633: Br J Ophthalmol. 2003 Mar;87(3):312-7.

How big is the burden of visual loss caused by age related macular degeneration
in the United Kingdom?

Owen CG, Fletcher AE, Donoghue M, Rudnicka AR.

Department of Public Health Sciences, St George's Hospital Medical School,
Cranmer Terrace, London SW17 0RE, UK. c.owen@sghms.ac.uk

AIMS: To predict the burden of blindness, partial sight, and visual impairment
(binocular visual acuity 6/18 or less) due to late stage age related macular
degeneration (AMD) in the ageing population of the United Kingdom. METHODS: A
systematic review, followed by a request for data, was used to establish a pooled
prevalence of AMD and corresponding visual loss. Prevalence figures were applied 
to the UK population. Using UK population trends, the future burden of AMD over
the coming decade was established. RESULTS: Pooled data from six studies showed
that the prevalence of visual loss caused by AMD increased exponentially from the
age of 70-85 years of age, with 3.5% (95% CI 3.0 to 4.1) having visual impairment
beyond the age of 75 years. The authors estimate that there are currently 214 000
(95% CI 151 000 to 310 000) with visual impairment caused by AMD (suitable for
registration). This number is expected to increase to 239 000 (95% CI 168 000 to 
346 000) by the year 2011. Currently there are 172 000 (95% CI 106 000 to 279
000) and 245 000 (95% CI 163 000 to 364 000) with geographical and neovascular
AMD, respectively. CONCLUSIONS: Estimates of visual impairment agree with
official statistics for the number registered partially sighted or blind, caused 
by AMD, and are well below other figures often cited. Although these estimates
are associated with wide confidence intervals (CI) and a number of caveats, they 
represent the best available data, which can be used to guide health and social
care provision for older people in the UK setting. Implications for low vision
services are outlined.

Publication Types: 
    Meta-Analysis
    Research Support, Non-U.S. Gov't
    Review

PMID: 12598445 [PubMed - indexed for MEDLINE]

2634: Br J Ophthalmol. 2003 Mar;87(3):307-11.

Comment in:
    Br J Ophthalmol. 2004 Jan;88(1):155.

CNV subtype in first eyes predicts severity of ARM in fellow eyes.

Abugreen S, Muldrew KA, Stevenson MR, VanLeeuwen R, DeJong PT, Chakravarthy U.

Royal Hospitals, Belfast, UK.

AIM: To examine the relation between the type of choroidal neovascularisation
(CNV) in the first eye and age related maculopathy (ARM) severity in the fellow
eye. METHODS: Colour fundus photographs and fluorescein angiograms from 67
subjects with a clinical diagnosis of CNV in one eye were scrutinised. CNV was
classified as wholly classic, predominantly classic, minimally classic, or occult
based on the proportion of classic leakage within the lesion. ARM changes in the 
fellow eye were assigned a severity stage using the system described by the
Rotterdam Eye Study. Logistic regression analysis was employed to examine the
association between CNV subtype and ARM stage. RESULTS: Of subjects with classic 
or predominantly classic CNV in the first eye 78% exhibited least no or early ARM
features in the fellow eye. By contrast, 85% of subjects with minimally classic
or occult CNV in the first eye exhibited more advanced ARM features in the fellow
eye. Kruskall-Wallis one way ANOVA by ranks showed that this was highly
significant (p = 0.002). Logistic regression analysis showed that as the
proportion of occult CNV increased in the first eye, fellow eyes of subjects in
this category were more likely to have been assigned to a higher ARM stage (p =
0.019). The area occupied by the CNV in the first eye also influenced severity of
ARM changes in the fellow eye. CONCLUSION: The type and extent of CNV in the
first affected eye has a distinct relation to ARM severity in the fellow eye.
Fellow eyes of subjects with minimally classic or occult CNV in the first
affected eye show widespread ARM changes suggestive of retinal pigment epithelial
dysfunction. These findings suggest that classic CNV may be focal disease while
occult CNV is essentially a more widespread retinal pigment epithelial disorder.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12598444 [PubMed - indexed for MEDLINE]

2635: Ophthalmologica. 2003 Mar-Apr;217(2):137-42.

Color Doppler imaging of choroidal circulation in patients with asymmetric
age-related macular degeneration.

Uretmen O, Akkin C, Erakgün T, Killi R.

Department of Ophthalmology, Ege University School of Medicine, Izmir, Turkey.
uretmen@med.ege.edu.tr

We aimed at evaluating the possible role of choroidal perfusion abnormalities in 
the development of choroidal neovascularisation (CNV) in patients with
age-related macular degeneration (AMD). Twenty-six patients who had non-exudative
AMD in the first eye and CNV secondary to AMD in the fellow eye were enrolled.
Blood flow velocities, vessel pulsatilities and resistivities were measured from 
ophthalmic artery, nasal and temporal posterior ciliary arteries using colour
Doppler imaging. Systolic and diastolic velocities were lower in eyes with CNV
for all vessels, except for the systolic velocity of the nasal posterior ciliary 
artery (p >0.05). Pulsatility and resistivity indices were higher in eyes with
CNV for all vessels. This difference was statistically significant for the
resistivity index of the nasal and temporal posterior ciliary arteries (p = 0.032
and p = 0.021, respectively) and the pulsatility index of the nasal posterior
ciliary artery (p = 0.035). We have shown that in patients with AMD choroidal
blood flow is more impaired in the eyes with CNV than in the fellow eyes.
Copyright 2003 S. Karger AG, Basel

Publication Types: 
    Comparative Study

PMID: 12592053 [PubMed - indexed for MEDLINE]

2636: Ophthalmologica. 2003 Mar-Apr;217(2):111-4.

ABCA4 sequence variants in Chinese patients with age-related macular degeneration
or Stargardt's disease.

Baum L, Chan WM, Li WY, Lam DS, Wang PB, Pang CP.

Department of Ophthalmology and Visual Sciences, Chinese University of Hong Kong,
Hong Kong, China.

ABCA4 gene sequence alterations cause Stargardt's disease (STGD) and may cause
some age-related macular degeneration (AMD). We sought to shed light on these
associations among Hong Kong Chinese by genotyping 140 AMD, 18 STGD and 95 normal
control subjects for 15 ABCA4 exons which were reported to often contain AMD- or 
STGD-associated mutations. Sequence alterations R212H, T1428M, V1433I, T1572M,
I2166M, IVS6-5T>G and IVS33+1G>T were found in AMD patients. T1428M and R2040X
occurred in STGD patients. Control subjects displayed all the above missense
alterations but no splicing or nonsense changes. Therefore, ABCA4 splicing
mutations may be associated with a small proportion of AMD cases. Copyright 2003 
S. Karger AG, Basel

Publication Types: 
    Comparative Study

PMID: 12592048 [PubMed - indexed for MEDLINE]

2637: Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2679-84. Epub 2003 Feb 14.

Immunotherapy for choroidal neovascularization in a laser-induced mouse model
simulating exudative (wet) macular degeneration.

Bora PS, Hu Z, Tezel TH, Sohn JH, Kang SG, Cruz JM, Bora NS, Garen A, Kaplan HJ.

Department of Ophthalmology and Visual Sciences, University of Louisville,
Louisville, KY 40202, USA.

Age-related macular degeneration (AMD) is the leading cause of blindness after
age 55 in the industrialized world. Severe loss of central vision frequently
occurs with the exudative (wet) form of AMD, as a result of the formation of a
pathological choroidal neovasculature (CNV) that damages the macular region of
the retina. We tested the effect of an immunotherapy procedure, which had been
shown to destroy the pathological neovasculature in solid tumors, on the
formation of laser-induced CNV in a mouse model simulating exudative AMD in
humans. The procedure involves administering an Icon molecule that binds with
high affinity and specificity to tissue factor (TF), resulting in the activation 
of a potent cytolytic immune response against cells expressing TF. The Icon binds
selectively to TF on the vascular endothelium of a CNV in the mouse and pig
models and also on the CNV of patients with exudative AMD. Here we show that the 
Icon dramatically reduces the frequency of CNV formation in the mouse model.
After laser treatment to induce CNV formation, the mice were injected either with
an adenoviral vector encoding the Icon, resulting in synthesis of the Icon by
vector-infected mouse cells, or with the Icon protein. The route of injection was
i.v. or intraocular. The efficacy of the Icon in preventing formation of
laser-induced CNV depends on binding selectively to the CNV. Because the Icon
binds selectively to the CNV in exudative AMD as well as to laser-induced CNV,
the Icon might also be efficacious for treating patients with exudative AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12589025 [PubMed - indexed for MEDLINE]

2638: Jpn J Ophthalmol. 2003 Jan-Feb;47(1):110-2.

Cystoid macular edema associated with latanoprost use in a pseudophakic eye with 
a history of surgical complications.

Watanabe K, Hayasaka S, Hayasaka Y, Nagaki Y, Watanabe K.

Department of Ophthalmology, Toyama Medical and Pharmaceutical University,
Toyama, Japan.

PURPOSE: To report the development of cystoid macular edema following the use of 
topical latanoprost in an eye with glaucoma and pseudophakia. CASE: A 73-year-old
woman with bilateral pseudophakia and glaucoma had been treated with topical
carteolol hydrochloride and isopropyl unoprostone bilaterally. One month later
the unoprostone was replaced by latanoprost bilaterally. After 1 month, the
patient complained of decreased vision in the right eye, which had a history of
surgical complications. RESULTS: Fluorescein angiography showed cystoid macular
edema in the right fundus. The edema disappeared 2 weeks after the
discontinuation of latanoprost. Cystoid macular edema did not develop in the left
eye, which had no history of surgical complications. CONCLUSION: These
observations suggest that latanoprost may cause cystoid macular edema in an eye
with a history of surgical complications.

Publication Types: 
    Case Reports

PMID: 12586189 [PubMed - indexed for MEDLINE]

2639: Optometry. 2003 Feb;74(2):99-110.

Cigarette smoking as a risk factor for cataract and age-related macular
degeneration: a review of the literature.

DeBlack SS.

deblack@conwaycorp.net

BACKGROUND: Cigarette smoking has long been acknowledged as a major risk factor
for many of the leading causes of death. Its role in ocular disease has received 
far less attention. METHODS: This article reviews a large number of recent
studies that have investigated a possible link between cigarette smoking and two 
major causes of blindness--cataract and age-related macular degeneration.
RESULTS: The preponderance of evidence shows a causal relationship between
cigarette smoking and both cataract and age-related macular degeneration.
CONCLUSIONS: As primary eye care providers, optometrists should educate patients 
regarding the dangers of smoking as it relates to ocular health and consider a
role in discouraging patients from starting or continuing this harmful habit.

Publication Types: 
    Review

PMID: 12585737 [PubMed - indexed for MEDLINE]

2640: Arch Ophthalmol. 2003 Feb;121(2):211-7.

National Eye Institute Visual Function Questionnaire in the Age-Related Eye
Disease Study (AREDS): AREDS Report No. 10.

Clemons TE, Chew EY, Bressler SB, McBee W; Age-Related Eye Disease Study Research
Group.

AREDS Coordinating Center, The EMMES Corporation, 401 N Washington Street, Suite 
700, Rockville, MD 20850-1707, USA. aredspub@emmes.com

OBJECTIVES: To describe the vision-targeted, health-related quality of life,
measured with the National Eye Institute Visual Function Questionnaire (NEI-VFQ),
in patients with age-related macular degeneration, cataract, or reduced visual
acuity; to determine the relationship between the NEI-VFQ subscale scores and
clinical measures of visual function; and to assess the internal consistency and 
reliability of the NEI-VFQ subscales. DESIGN: The 39-item NEI-VFQ was
administered at the 5-year clinic visit to 4077 Age-Related Eye Disease Study
participants. RESULTS: The subscales of the NEI-VFQ had moderate to high internal
consistency (Cronbach's alpha = 0.58-0.91). The NEI-VFQ scores for participants
with advanced age-related macular degeneration in 1 or both eyes, severe nuclear 
opacity, reduced visual acuity, or cataract surgery generally were lower than
scores for disease-free participants (P<.001). CONCLUSION: These findings support
the use of the NEI-VFQ as a measure of vision-targeted, health-related quality of
life among patients with age-related macular degeneration, cataract, or reduced
visual acuity.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12583787 [PubMed - indexed for MEDLINE]

2641: Ophthalmology. 2003 Feb;110(2):400-5.

Agreement among ophthalmologists in evaluating fluorescein angiograms in patients
with neovascular age-related macular degeneration for photodynamic therapy
eligibility (FLAP-study).

Holz FG, Jorzik J, Schutt F, Flach U, Unnebrink K.

Department of Ophthalmology, University of Heidelberg, Im Neuenheimer Feld 400,
D-69120 Heidelberg, Germany.

OBJECTIVE: To determine intraobserver and interobserver variation for classifying
types of choroidal neovascularizations (CNV) in exudative age-related macular
degeneration (ARMD). DESIGN: Intraexaminer and interexaminer reliability study.
PARTICIPANTS: Digital high-quality fluorescein angiograms of 40 patients with
neovascular ARMD were evaluated independently by 16 retinal specialists. MAIN
OUTCOME MEASURES: Fluorescein angiographies were presented in two randomized
sequences (series A and B) to each masked reader for classification of type of
CNV into classic, occult, or mixed with classic component of less or greater 50%.
Agreement was evaluated by calculating kappa statistics (kappa) and intraclass
correlation coefficients. RESULTS: The mean kappa coefficient was 0.64 +/- 0.11
for intraobserver variation, with a range from 0.44 to 0.89. For interobserver
variation the intraclass correlation coefficients was calculated as 0.66 (95%
confidence interval [CI] 0.56, 0.77) for series A and as 0.55 (95% CI 0.43, 0.67)
for series B. CONCLUSIONS: Angiographic classification of CNV secondary to ARMD
can vary considerably not only between observers but also for repeated evaluation
by the same observer. Because various current and emerging treatments including
photodynamic therapy are based on specific angiographic characteristics, accurate
interpretation will become more important.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12578787 [PubMed - indexed for MEDLINE]

2642: Ophthalmology. 2003 Feb;110(2):392-9.

Fundus autofluorescence and age-related macular degeneration.

Spaide RF.

Vitreous-Retina-Macula Consultants of New York, 519 East 72nd Street, Suite 203, 
New York, NY 10021, USA.

PURPOSE: To evaluate the autofluorescence images of patients with nonexudative
and the fellow eyes with exudative age-related macular degeneration (AMD).
DESIGN: Observational case series. PARTICIPANTS: Fifty-four patients seen in the 
author's practice. METHODS: A fundus camera-based system for autofluorescence
photographs was used, and the wavelengths for the excitation (580 nm) and barrier
(695 nm) filters were based on known transmission and autofluorescent
characteristics of the ocular media. Patients were also photographed with
red-free and infrared monochromatic imaging. The mean levels of autofluorescence 
were compared between patients without (group 1) and those with exudative AMD.
Comparisons were made among patients with exudative AMD, examining the
autofluorescence pattern in those without retinal vascular contribution to the
exudative process (group 2) to those with retinal vascular contribution (group
3). MAIN OUTCOME MEASURES: Mean amounts and patterns of autofluorescence.
RESULTS: A total of 54 patients was evaluated; 18 were in each group. The mean
age was 75.4 years, and there was no difference in the mean ages among the groups
(P = 0.16). There was no correlation of the autofluorescence measurements and the
degree of nuclear sclerosis (P = 0.14). Patients with exudative AMD had more
autofluorescence in the fellow eye than did eyes of patients without exudative
AMD (P = 0.002). Patients in group 3 were more likely to have focal
hyperpigmentation, particularly as imaged by infrared light (P = 0.015), and
focal areas of intense autofluorescence (P = 0.001) than were patients in group
2. CONCLUSIONS: By use of this method of autofluorescence imaging, it was
determined that the fellow eyes of patients with exudative AMD had larger amounts
of autofluorescence than did the eyes of patients without a history of exudative 
AMD. Patients with retinal vascular anastomosis to the vascular proliferation of 
exudative AMD were much more likely to have focal areas of intense
autofluorescence in their fellow eye that corresponded, for the most part, with
focal areas of hyperpigmentation best seen by infrared monochromatic fundus
photography. Because the amount of fluorescence is directly related to the amount
of lipofuscin, which in turn is related to the cumulative amount of oxidative
damage, these findings suggest possible explanations for certain patterns of
vessel growth seen in exudative AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12578786 [PubMed - indexed for MEDLINE]

2643: Clin Sci (Lond). 2003 Jun;104(6):561-75.

Gene therapy for ocular angiogenesis.

Bainbridge JW, Mistry AR, Thrasher AJ, Ali RR.

Department of Molecular Genetics, Institute of Ophthalmology, University College 
London, 11-43 Bath Street, London EC1V 9EL, U.K. j.bainbridge@ucl.ac.uk

Ocular neovascularization is a central feature of diabetic retinopathy and
age-related macular degeneration. These conditions are the major causes of
blindness in the developed world. Current treatments are of limited efficacy and 
associated with significant adverse effects. Characterization of the molecular
and cellular events involved in angiogenesis has led to the identification of a
number of angiostatic molecules with potential therapeutic value. The systemic
administration of small molecule angiostatic proteins risks significant systemic 
adverse effects and the effect of their intraocular injection is short-lived.
Local gene transfer, however, offers the possibility of targeted, sustained and
regulatable delivery of angiostatic proteins to the retina after a single
procedure to introduce a vector to an intraocular site. The effect of
intra-ocular delivery of recombinant viruses carrying genes encoding angiostatic 
proteins has been demonstrated in rodent models of ocular neovascularization.
Recombinant adeno-associated virus-mediated local gene transfer of a vascular
endothelial growth factor inhibitor controls both retinal and choroidal
neovascularization. The clinical application of this approach may require the
means to regulate gene expression in order to minimize the potential for adverse 
effects. Regulation of transgene expression by means of a hypoxia-responsive
promoter offers an attractive strategy for the targeted and regulated delivery of
angiostatic proteins to the retina in the management of ischaemia-induced ocular 
neovascularization. Preclinical studies of gene transfer in a large animal model 
following subretinal delivery of a recombinant adeno-associated virus vector have
demonstrated efficient sustained reporter gene expression in cells of the outer
retina. Recent progress has enabled the planning of clinical trials of gene
therapy for ocular neovascular disorders.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 12570869 [PubMed - indexed for MEDLINE]

2644: Ophthalmic Surg Lasers Imaging. 2003 Jan-Feb;34(1):17-24.

Oral fluorescein angiography in patients with choroidal neovascularization and
macular degeneration.

Bartsch DU, Elmusharaf A, El-Bradey M, Freeman WR.

Shiley Eye Center, Department of Ophthalmology, University of California San
Diego, 9415 Campus Point Dr, Rm SEC 215, La Jolla 92093-0946, California, USA.

OBJECTIVE: To evaluate image quality of oral fluorescein angiography in patients 
with age-related macular degeneration and choroidal neovascularization. MATERIALS
AND METHODS: Twenty four patients with proven choroidal neovascularization were
examined in a prospective observational case series. Confocal oral and
intravenous fluorescein angiography were performed using the Heidelberg Retina
Angiograph. Oral and intravenous image quality were compared in a masked fashion.
RESULTS: Choroidal neovascularization could be diagnosed in all patients using
intravenous angiograms. Oral fluorescein angiography accurately detected the
presence or absence of choroidal neovascularization in all patients and could
determine the classification of choroidal neovascularization, location, and
extent and borders in 20 (83.3%) of 24 patients. Early, mid, and late phases of
oral angiograms occurred at 8, 15, and 26 minutes, respectively. CONCLUSION: Oral
fluorescein angiography using the confocal Heidelberg Retina Angiograph allowed
detection of choroidal neovascularization in all patients in this study.
Visualization of extent and type of choroidal neovascularization was possible in 
most eyes with choroidal neovascularization. These findings suggest oral
angiography is an excellent screening tool for choroidal neovascularization and
allows guidance of treatment in the majority of cases.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12570000 [PubMed - indexed for MEDLINE]

2645: Ophthalmic Surg Lasers Imaging. 2003 Jan-Feb;34(1):7-16.

A comparison of quantitative mapping and stereoscopic fundus photography grading 
of retinal thickness in diabetic eyes with macular edema.

Yang Y, Vitale S, Ding Y, O'Connell SR, Alexander J, Bressler NM, Schachat AP,
Zeimer R.

Department of Ophthalmology, Wonkwang Medical Science Center, Wonkwang University
School of Medicine, Korea.

OBJECTIVE: To evaluate the ability of a retina specialist's grading of 30 degrees
color stereoscopic fundus photographs to identify areas of significant retinal
thickening as assessed by the Retinal Thickness Analyzer (RTA) and to determine
whether this ability was affected by the presence of retinal pathology. MATERIALS
AND METHODS: Thirty-two eyes in 29 patients clinically diagnosed as having
diabetic macular edema underwent RTA scanning and nonsimultaneous 30 degrees
color stereoscopic fundus photography. Retinal thickness maps of the macular area
were generated, and regions with significant retinal thickening (> or = 2 SD
above normal values) were identified. A retina specialist reader, masked to the
RTA measurements, identified areas with macular edema on the stereoscopic fundus 
photographs, which subsequently were overlaid on the retinal thickness maps. The 
sensitivity (percent of significant retinal thickening areas identified by the
retina specialist grading the stereoscopic fundus photographs) was calculated
separately for areas with and without retinal pathology. Specificity of the
stereoscopic fundus photograph grading was assessed similarly. RESULTS: The
retina specialist's stereoscopic fundus photography grading identified 78.8% of
areas with significant retinal thickening (range over eyes: 20.4%-100%) and was
slightly more likely to identify significant retinal thickening when pathology
was present (89.6%) than when pathology was not present (78.4%; pooled risk
ratio, 1.14 [95% CI = 0.54, 2.42]). Specificity of stereoscopic fundus
photography grading was 58%, ie, 42% of areas without significant retinal
thickening were (incorrectly) identified as edematous by the stereoscopic fundus 
photograph grading. This misidentification was more likely if pathology was
present (76.9%) than if pathology was not present (41.1%; pooled risk ratio, 1.87
[95% CI = 1.28, 2.73]). CONCLUSION: This study shows the determination of macular
edema by a retina specialist reading color stereoscopic fundus photographs is
sensitive but not specific with reference to edema identified by the RTA.
Furthermore, the presence of retinopathy tends to cause false-positive readings
with reference to edema identified by the RTA. These findings indicate the need
to use objective, quantitative methods in clinical studies to detect and monitor 
macular edema.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12569999 [PubMed - indexed for MEDLINE]

2646: Clin Exp Optom. 2003 Jan;86(1):51-6.

Sub-retinal neovascular membrane in exudative macular degeneration.

Harris S.

Victorian College of Optometry, The University of Melbourne, Carlton VIC 3053,
Australia.

Age-related macular degeneration is a major cause of serious vision loss. The
earliest stages of age-related maculopathy may be defined by the size of the
drusen present in the macula and the effects on vision. Further manifestations
may include soft drusen, choroidal neovascularisation, macular haemorrhage and
cicatricial or disciform degeneration of the macula. This report describes a
patient with a macular haemorrhage, a choroidal neovascular membrane and serious 
loss of vision. In addition, the pathogenesis, diagnosis and treatment options of
macular degeneration are reviewed.

Publication Types: 
    Case Reports

PMID: 12568652 [PubMed - indexed for MEDLINE]

2647: Ophthalmic Genet. 2002 Dec;23(4):209-23.

A pooled case-control study of the apolipoprotein E (APOE) gene in age-related
maculopathy.

Schmidt S, Klaver C, Saunders A, Postel E, De La Paz M, Agarwal A, Small K, Udar 
N, Ong J, Chalukya M, Nesburn A, Kenney C, Domurath R, Hogan M, Mah T, Conley Y, 
Ferrell R, Weeks D, de Jong PT, van Duijn C, Haines J, Pericak-Vance M, Gorin M.

Center for Human Genetics, Department of Medicine, Duke University Medical
Center, Durham, NC, USA.

Age-related maculopathy (ARM) is a multifactorial disorder known to have a
substantial genetic component. The epsilon4 allele of the apolipoprotein E gene
(APOE-4) has previously been reported to have a protective effect on ARM risk,
while the APOE-2 allele may increase disease risk. This study combined four
independent data sets (three US and one European) of Caucasian ARM patients and
controls in order to obtain better statistical power to examine the role of APOE 
in ARM. APOE genotype and allele frequencies were compared for 617 ARM cases and 
1260 controls, adjusting for age and sex differences between the two groups via
multiple logistic regression. The protective effect of the APOE-4 allele on ARM
risk was confirmed (age- and sex-adjusted odds ratio (OR) for APOE-4 carriers
0.54, 95% confidence interval (CI) 0.41-0.70, p < 0.0001). The effect of APOE-4
did not differ significantly between males and females and was observed
consistently for both atrophic and neovascular ARM. Evidence for an increased
risk of ARM due to the APOE-2 allele was found for men, but not for women (OR for
men 1.54, 95% CI 0.97-2.45; OR for women 0.74, 95% CI 0.52-1.06, p = 0.01 for
interaction of sex and APOE-2 carrier status). These data confirm that the APOE-4
allele, or an allele in linkage disequilibrium with it, reduces the risk of ARM. 
They also suggest that the effect of the APOE-2 allele may vary by gender, and
that APOE-2 may confer an increased risk only to males.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12567264 [PubMed - indexed for MEDLINE]

2648: Ophthalmologica. 2003 Jan-Feb;217(1):49-52.

Aqueous flare and macular edema in eyes with diabetic retinopathy.

Jandrasits K, Krepler K, Wedrich A.

Department of Ophthalmology, University of Vienna, Austria.
kerstin.jandrasits@univie.ac.at

BACKGROUND: The breakdown of the blood-retina barrier in diabetic patients is
correlated with a dysfunction of the blood-aqueous barrier. In our study, we
wanted to investigate the effect of grid photocoagulation in diabetic macular
edema on the aqueous flare. METHODS: Modified grid pattern photocoagulation was
performed on 20 patients with diabetic macular edema. The aqueous flare intensity
was measured by the laser flare cell meter before and 4 months after laser
treatment. RESULTS: The mean flare value was 9.8 +/- 4.7 photons/ms before laser 
treatment. After grid photocoagulation, the flare value was 7.1 +/- 3.6
photons/ms. Flare values were significantly decreased after laser treatment.
CONCLUSION: Our results suggest a correlation between the effect of grid
photocoagulation on the blood-retina barrier and the permeability of the
blood-aqueous barrier. The laser flare intensity seems to be a quantitative
indicator for the diabetic dysfunction of the blood-retina barrier. Copyright
2003 S. Karger AG, Basel

PMID: 12566873 [PubMed - indexed for MEDLINE]

2649: Am J Ophthalmol. 2003 Feb;135(2):246-9.

Intravitreal triamcinolone for refractory pseudophakic macular edema.

Benhamou N, Massin P, Haouchine B, Audren F, Tadayoni R, Gaudric A.

Department of Ophthalmology, Hôpital Lariboisière, Assistance Publique-Hôpitaux
de Paris, Université Paris 7, Paris, France. nathanael_benhamou@yahoo.fr

PURPOSE: To evaluate the efficacy of intravitreal triamcinolone in refractory
pseudophakic cystoid macular edema. DESIGN: A prospective, interventional case
series. METHODS: Three eyes of three patients with longstanding pseudophakic
cystoid macular edema following uncomplicated cataract surgery, refractory to any
medication, were treated with 8 mg of intravitreal triamcinolone. All three eyes 
were evaluated before injection and throughout follow-up with the Early Treatment
Diabetic Retinopathy Study's visual acuity chart, fluorescein angiography, and
macular mapping using optical coherence tomography. RESULTS: A month after
intravitreal triamcinolone injection, a dramatic decrease in macular thickness
was noted by optical coherence tomography in all three eyes (from a mean of
502-233 microm). Mean improvement in visual acuity was 3.7 Snellen lines. Two to 
4 months after triamcinolone injection, however, the edema recurred in all cases,
to the same degree as before the injection, combined with a decrease in vision.
Two eyes underwent a second injection of triamcinolone, and macular thickness
decreased, but the edema again recurred 3 months after injection. CONCLUSION:
Intravitreal injection of triamcinolone induces striking regression, within 1
month, of chronic refractory macular edema. This regression appears to be
transient, however, even after a second injection.

PMID: 12566041 [PubMed - indexed for MEDLINE]

2650: Am J Ophthalmol. 2003 Feb;135(2):206-12.

Visual function index (VF-14) in exudative age-related macular degeneration of
long duration.

Riusala A, Sarna S, Immonen I.

Department of Ophthalmology, Helsinki University Hospital, Helsinki, Finland.

PURPOSE: To evaluate the Visual Function Index (VF-14) questionnaire for its
effectiveness in assessing visual function in patients with longstanding
exudative age-related macular degeneration (AMD). DESIGN: Observational case
series. METHODS: The records of 167 consecutive patients with recent
neovascularization related to AMD between June 1990 and December 1994 at the
Helsinki University Eye Clinic were analyzed in 1999. Of 121 patients still
living, 74 (61%) attended the reexamination. After exclusions, data from 62
patients were analyzed. The VF-14 score, plus global assessment scores of
satisfaction with vision and quality of vision, in which patients graded the
subjective level of difficulty with their vision, best-corrected visual acuity
(BCVA), contrast sensitivity, the area of the AMD lesion, and the shortest
distance and direction from the center of the fovea to the edge of the subfoveal 
lesion, were analyzed. RESULTS: The VF-14 score correlated significantly with
BCVA (P <.01), contrast sensitivity (P <.01), and global assessment scores (P
<.01), showing stronger correlations with global assessment scores than did BCVA.
In multivariate regression analysis, the global assessment scale of overall
quality of vision and BCVA in the better eye were significant predictors (P
<.001) of the variability in the VF-14 score. CONCLUSIONS: The VF-14 reflects
visual function of patients with late AMD more effectively than BCVA measurement 
alone. The VF-14 can thus be used to compare the visual handicap of late AMD
patients with that of patients with other eye diseases.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12566025 [PubMed - indexed for MEDLINE]

2651: Am J Ophthalmol. 2003 Feb;135(2):169-77.

Optical coherence tomography for evaluating diabetic macular edema before and
after vitrectomy.

Massin P, Duguid G, Erginay A, Haouchine B, Gaudric A.

Department of Ophthalmology, Hôpital Lariboisière, Assistance Publique-Hôpitaux
de Paris, Université Paris 7, Paris, France. p.massin@krb.ap-hop-paris.fr

PURPOSE: To report the use of optical coherence tomography (OCT) for evaluation
of diffuse diabetic macular edema (DME) before and after vitrectomy. DESIGN:
Interventional case series. METHODS: A retrospective study was made of 15
consecutive eyes of 13 patients that had vitrectomy for diffuse DME and OCT
preoperatively and postoperatively. In seven eyes of six patients (group 1),
vitrectomy was performed because of vitreomacular traction observed on
biomicroscopy or OCT. In the other eight eyes of seven patients (group 2),
vitrectomy was performed for DME not responsive to laser photocoagulation, with
no vitreomacular traction on biomicroscopy or OCT. RESULTS: Mean +/- standard
deviation (SD) follow-up after vitrectomy was 18 +/- 10 months (range, 6 to 33
months). In group 1, mean +/- SD retinal thickness decreased significantly from
661 +/- 181 microm preoperatively to 210 +/- 32 microm at the end of follow-up (P
=.018). Median best-corrected visual acuity (BCVA) improved from 20/100 before
surgery (range, 20/250 to 20/50) to 20/80 at the end of follow-up (range, 20/250 
to 20/25; P =.046). In one eye in group 1, vitreomacular traction was only
observed on OCT and not on biomicroscopy. In group 2, mean +/- SD retinal
thickness decreased from 522 +/- 103 microm preoperatively to 428 +/- 121 microm 
at the end of follow-up (P =.2). Median BCVA was 20/100 before vitrectomy (range,
20/320 to 20/63) and 20/200 at the end of follow-up (range, 20/250 to 20/63; P
=.78). CONCLUSIONS: Vitrectomy was beneficial in eyes with diffuse DME combined
with vitreomacular traction but not in eyes without traction. Optical coherence
tomography allowed diagnosis of subtle vitreomacular traction and provided
precise preoperative and postoperative assessments of macular thickness.

PMID: 12566020 [PubMed - indexed for MEDLINE]

2652: Exp Eye Res. 2003 Feb;76(2):203-11.

In vivo micropathology of Best macular dystrophy with optical coherence
tomography.

Pianta MJ, Aleman TS, Cideciyan AV, Sunness JS, Li Y, Campochiaro BA, Campochiaro
PA, Zack DJ, Stone EM, Jacobson SG.

Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, 51
N, 39th Street, Philadelphia, PA 19104, USA. mpianta@optometry.unimelb.edu.au

Best macular dystrophy (BMD) is an autosomal dominant retinopathy caused by
mutations in the VMD2 gene that encodes a chloride channel in the basolateral
membrane of the retinal pigment epithelium (RPE). BMD patients were studied using
optical coherence tomography (OCT) to understand the disease process in the
macula leading to vision loss. BMD patients (ages 5-61), representing four
families with known VMD2 mutations, were included. OCT scans were recorded in the
central retina and longitudinal reflectivity profiles were analysed. The central 
retina in BMD showed different OCT abnormalities at or near the level of the
highly reflective deep retinal band termed the outer retina-choroid complex
(ORCC). Two types of ORCC change were noted to occur either separately or
together: (1) splitting with or without intervening hyporeflective areas; and (2)
elevation. Longitudinal study of a BMD patient indicated that such abnormalities 
were dynamic and changed in type and degree with time. The pathogenetic sequence 
in BMD may begin with defective fluid transport across the RPE secondary to the
channelopathy in the basolateral membrane. In the macula, this leads to an
abnormal interface with adjacent structures at both apical and basal surfaces of 
the RPE. The disease process results in detachments of the neurosensory retina,
such as in central serous chorioretinopathy, and sub-RPE pathology resembling
some stages of age-related macular degeneration, with eventual loss of
photoreceptors, inner retina and central vision. Copyright 2003 Elsevier Science 
Ltd.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12565808 [PubMed - indexed for MEDLINE]

2653: Pharmacoeconomics. 2003;21(3):181-90.

The burden of age-related macular degeneration: results of a cohort study in two 
French referral centres.

Bonastre J, Le Pen C, Soubrane G, Quentel G.

CLP-Santé, Paris, France.

OBJECTIVE: To describe the economic impact of age-related macular degeneration
(AMD) and to assess its medical and non-medical costs. DESIGN AND SETTINGS: An
observational study was carried out in 105 patients in two French centres in a
sample of 105 French patients. All consecutive patients, consulting during a
3-week period, were included provided they were 60 years of age or older and they
presented an exudative form of AMD with a distant visual acuity in the best eye <
or = 20/40. Data collected included clinical items, treatment modalities, medical
follow-up, transport costs, impact of AMD on living conditions and welfare
payments related to visual impairment. Costs were presented in 2000 values.
PERSPECTIVE: General payer perspective (Social Security, private health insurance
and patient). RESULTS: Mean age was 79.3 years and ranged from 62.8-95 years.
Average length of disease evolution was 3.5 years. During a 3-month period,
patients had a mean of 2.6 visits to the ophthalmologist. Thirty percent of the
patients used vascular medications and 72.4% had been previously treated by laser
photocoagulation. Only 10% had benefited from visual rehabilitation. Annual AMD
cost per patient was 3660.29 euros (EUR) [95% CI: 2881.92-4438.62]. Half of these
annual costs were medical costs. Other major cost components were home help costs
EUR904.91 [95% CI: 478.88-1330.94] and transport costs for care EUR542.73 [95%
CI: 146.31-939.14]. Non-medical costs were significantly higher for patients with
more severe disease. CONCLUSIONS: The economic argument that costs are higher in 
patients with the lowest visual acuity emphasises the necessity of early
detection and treatment of patients with AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12558468 [PubMed - indexed for MEDLINE]

2654: Invest Ophthalmol Vis Sci. 2003 Feb;44(2):856-65.

Neuronal migration and glial remodeling in degenerating retinas of aged rats and 
in nonneovascular AMD.

Sullivan R, Penfold P, Pow DV.

Department of Physiology and Pharmacology, School of Biomedical Sciences,
University of Queensland, Brisbane, Australia. r.sullivan@mailbox.uq.edu.au

PURPOSE: To demonstrate structural and immunocytochemical changes associated with
light-induced degeneration in albino rat retinas and human AMD retinas. METHODS: 
Retinas from Wistar rats aged 3, 6, or 10 months were examined by
immunocytochemistry, with antibodies to neuronal and glial markers. Results were 
compared with human nonneovascular AMD retinas. RESULTS: In aging rat retinas,
many photoreceptors were lost in response to normal ambient light exposure.
Photoreceptor loss was preceded by loss of RPE cells. Müller cells extended
processes through gaps in Bruch's membrane, into the choroid. immunolabeling for 
gamma-aminobutyric acid (GABA), the glycine transporter Glyt-1, and the rod
bipolar cell marker PKC revealed the presence of numerous neuronal somata and
processes that appeared to have migrated into the choroidal region. Processes of 
presumptive ganglion cells remodeled and stratified in the choroid, where strong 
labeling for synaptic vesicle antigens was present. Myelination of retinal
ganglion cell axons was also observed, especially in the peripheral retina. In
AMD retinas, glial rearrangement and displacement of neurons suggestive of their 
migration were also observed. CONCLUSIONS: In response to loss of RPE and
photoreceptor cells, adult retinal neurons migrate out of the retina along
remodeled processes of Müller cells. The presence of synaptic vesicle antigens
suggests the formation of new synapses between migrating neurons. The myelination
is probably due to the ingress of Schwann cells from the sclera. The presence of 
some similar changes in human AMD retinas suggests that these findings are of
broad significance for determining the likely events in transplantation of
neurons in the human retina and elsewhere.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12556422 [PubMed - indexed for MEDLINE]

2655: J Cataract Refract Surg. 2003 Jan;29(1):27-33.

Intravitreal triamcinolone acetonide for refractory chronic pseudophakic cystoid 
macular edema.

Conway MD, Canakis C, Livir-Rallatos C, Peyman GA.

Department of Ophthalmology, Tulane University Health Sciences Center, New
Orleans, Louisiana 70112, USA.

PURPOSE: To determine the safety and efficacy of intravitreal triamcinolone
acetonide (TAAC) injections in patients with refractory cystoid macular edema
(CME) after cataract extraction. SETTING: LSU Eye Center, Louisiana State
University Health Sciences Center, New Orleans, Louisiana, USA. METHODS: In this 
nonrandomized retrospective case review, 8 eyes of 8 patients with a history of
pseudophakic CME recalcitrant to current standard treatment modalities were
enrolled. The mean duration of the CME was 20 months. The patients received
intravitreal injections of 1 mg of TAAC and were followed for a mean of 8 months.
The main outcome measures included visual acuity, the presence of CME on
biomicroscopic examination, angiographic evidence of perifoveal leakage,
intraocular pressure (IOP), and complications related to treatment. RESULTS: The 
visual acuity increased in all patients. The magnitude of improvement was mainly 
restricted by underlying macular pathology and correlated well with the level of 
visual acuity at entry into the study. Angiographic improvement occurred in all
patients. Temporary increases in IOP were easily controlled with topical
medications. No other adverse effects could be attributed to this technique.
Repeated injections were required. CONCLUSIONS: Intravitreal administration of
TAAC was safe and effective in recalcitrant cases of pseudophakic CME with a
beneficial effect on the macular edema and visual acuity. A prospective
randomized study is needed to determine with accuracy the efficacy, safety, and
exact timing of this technique and possibly to recognize subtypes with a more
favorable response. Repeated injections were required in all eyes. The
development of a sustained-release intravitreal drug-delivery system would be
beneficial.

PMID: 12551663 [PubMed - indexed for MEDLINE]

2656: Am J Pathol. 2003 Feb;162(2):413-25.

Apolipoprotein B in cholesterol-containing drusen and basal deposits of human
eyes with age-related maculopathy.

Malek G, Li CM, Guidry C, Medeiros NE, Curcio CA.

Department of Ophthalmology, Vision Science Training Program, University of
Alabama at Birmingham, Birmingham, AL 35294-0009, USA.

Lipids accumulate in Bruch's membrane (BrM), a specialized vascular intima of the
eye, and in extracellular lesions associated with aging and age-related
maculopathy (ARM). We tested the hypothesis that ARM and atherosclerotic
cardiovascular disease share molecules and mechanisms pertaining to extracellular
lipid accumulation by localizing cholesterol and apolipoprotein B (apo B) in BrM,
basal deposits, and drusen. Human donor eyes were preserved <4 hours postmortem
and cryosectioned. Sections were stained with traditional lipid stains and
filipin for esterified and unesterified cholesterol or probed with antibodies to 
apo B, apo E, and apo C-III. Normal adult retinal pigment epithelium (RPE) was
subjected to RT-PCR and Western blot analysis for apolipoprotein mRNA and
protein. Esterified and unesterified cholesterol was present in all drusen and
basal deposits of ARM and normal eyes. Both apo B and apo E but not apo C-III
were found in BrM, drusen, and basal deposits. Fewer macular drusen were stained 
by traditional lipid stains and apolipoprotein antibodies than peripheral drusen.
RPE contained apo B and apo E mRNA and protein. Finding cholesterol and apo B in 
sub-RPE deposits links ARM with important molecules and mechanisms in
atherosclerosis initiation and progression. The combination of apo B mRNA and
protein in RPE raises the possibility that intraocular assembly of apo
B-containing lipoproteins is a pathway involved in forming cholesterol-enriched
lesions in ARM.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12547700 [PubMed - indexed for MEDLINE]

2657: Trans Am Ophthalmol Soc. 2002;100:85-106; discussion 106-7.

Multicenter prospective, randomized, double-masked, placebo-controlled study of
Rheopheresis to treat nonexudative age-related macular degeneration: interim
analysis.

Pulido JS; Multicenter Investigation of Rheopheresis for AMD (MIRA-1) Study
Group.

Department of Ophthalmology and Visual Sciences, UIC Eye Center, University of
Illinois at Chicago, USA.

OBJECTIVE: To evaluate the safety and efficacy of Rheopheresis blood filtration
to treat intermediate- to late-stage preangiogenic age-related macular
degeneration (AMD) with soft drusen. DESIGN: Multicenter, prospective,
randomized, double-masked, placebo-controlled clinical trial. PARTICIPANTS: First
43 randomized patients (28 Rheopheresis and 15 placebo-control patients) with
available baseline and 3-month postbaseline best corrected visual acuity (BCVA)
measurements and intermediate- to late-stage preangiogenic AMD with multiple
large soft drusen and elevated serum levels of targeted macromolecules.
INTERVENTION: Patients were randomly assigned to receive eight Rheopheresis or
eight placebo procedures over 10 weeks. MAIN OUTCOME MEASURES: ETDRS BCVA
measurements at baseline, 3, 6, 9, and 12 months postbaseline. RESULTS: In
primary eyes, the mean LogMAR line difference between Rheopheresis and
placebo-control eyes was 1.6 lines at 12 months postbaseline; the difference was 
significant throughout the first posttreatment year (P = .0011, repeated measures
analysis). Thirteen percent of Rheopheresis compared with 0% of placebo-control
eyes had a > or = 3-line improvement in BCVA at 12 months postbaseline. Four
percent of Rheopheresis compared with 18% of placebo-control eyes had a > or =
3-line loss in BCVA. The subgroup of patients whose primary eyes had baseline
BCVA worse than 20/40 demonstrated a mean LogMAR difference between Rheopheresis 
and placebo-control eyes equaling 3.0 lines at 12 months postbaseline; the
difference was significant throughout the first posttreatment year (P = .0014,
repeated measures analysis). Sixteen percent of Rheopheresis compared with 0% of 
the placebo-control eyes had a > or = 3-line improvement in BCVA at 12 months
postbaseline. Five percent of Rheopheresis compared with 29% of placebo-control
eyes had a > or = 3-line loss in BCVA. Fifty-eight percent of Rheopheresis eyes
improved to 20/40 or better, compared with 14% of placebo-control eyes. No
serious treatment-related adverse events were observed. CONCLUSIONS: Rheopheresis
demonstrated statistically significant and clinically relevant effects on BCVA
when compared with placebo controls for the 12-month study interval. Untreated
patients with BCVA worse than 20/40 with intermediate- to late-stage
preangiogenic AMD, soft drusen, and elevated blood factors were at risk for
substantial visual loss. A sample size larger than 43 patients is important to
provide a basis for widespread adoption of novel therapeutic options for AMD such
as Rheopheresis. Therefore, enrollment to 150 patients is continuing.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial

PMID: 12545682 [PubMed - indexed for MEDLINE]

2658: Trans Am Ophthalmol Soc. 2002;100:73-6; discussion 76-7.

Tetrathiomolybdate as an antiangiogenesis therapy for subfoveal choroidal
neovascularization secondary to age-related macular degeneration.

Vine AK, Brewer GJ.

Department of Ophthalmology and Visual Sciences, University of Michigan Medical
Center, Ann Arbor, USA.

PURPOSE: Since previous studies have shown that angiogenesis requires copper,
this study assessed the efficacy and safety of oral tetrathiomolybdate, an
antiangiogenesis drug that binds copper, in subfoveal choroidal
neovascularization (CNV) secondary to age-related macular degeneration. METHODS: 
This phase I trial involved 10 patients with age-related active subfoveal CNV.
After patient consent was obtained and initial laboratory tests were performed,
patients were given a loading dose of tetrathiomolybdate, followed by a
maintenance dose to maintain serum ceruloplasmin (Cp) levels at 5 to 15 mg/dL.
Serum Cp levels are a surrogate marker of copper status. Patient follow-up
consisted of a detailed protocol that included best corrected visual acuity,
measurement of extent of CNV (both classic and occult) on fluorescein angiograms,
and laboratory tests to ensure that anemia did not develop. The study was
approved by the institutional review board of the University of Michigan Medical 
Center and by the Food and Drug Administration. RESULTS: Follow-up of the 10
patients ranged from 4 to 12 months. The targeted serum Cp level was achieved in 
8 of the 10 patients. Initially, patients showed stabilization of CNV, but with
continued follow-up, all patients showed progression of CNV and loss of visual
acuity. Initial mean visual acuity was 20/60; final mean visual acuity was
20/131. At completion of the study, 2 patients showed about a 25% increase in
CNV, 1 patient a 60% increase, 1 patient a 100% increase, and 6 patients a 700%
to 1,600% increase in CNV. CONCLUSION: At the dosages used in this study,
tetrathiomolybdate was ineffective in preventing the progression of CNV secondary
to age-related macular degeneration.

Publication Types: 
    Clinical Trial
    Clinical Trial, Phase I
    Research Support, Non-U.S. Gov't

PMID: 12545680 [PubMed - indexed for MEDLINE]

2659: Graefes Arch Clin Exp Ophthalmol. 2003 Jan;241(1):39-47. Epub 2002 Dec 18.

Inter- and intra-observer variability in grading lesions of age-related
maculopathy and macular degeneration.

Scholl HP, Peto T, Dandekar S, Bunce C, Xing W, Jenkins S, Bird AC.

Institute of Ophthalmology, Moorfields Eye Hospital, 162 City Road, EC1 V2PD,
London, UK. hendrikscholl@hotmail.com

PURPOSE. To introduce a revised version of the grading system established by the 
International ARM Epidemiological Study Group for identifying and quantifying
abnormalities of age-related maculopathy (ARM) and age-related degeneration (AMD)
and to investigate its reliability, specifically the inter- and intra-observer
variability. METHODS. Fifty eyes of 25 patients with ARM or AMD in at least one
eye were randomly selected from a large ongoing collection of clinical data and
DNA in a tertiary referral UK population. Stereoscopic color fundus photographs
were taken with a 30 degrees fundus camera and were centered on the macula.
Presence and severity of fundus abnormalities in ARM and AMD were graded using a 
grid to define macular subfields and standard circles to define the size of
lesions. Inter-observer variability was assessed by having three retinal
specialists evaluate the color slides and intra-observer variability by
re-grading the same set. RESULTS. The inter-observer agreement for all subfields 
was fair to substantial for small hard drusen (70-89%; kappa=0.26-0.63) and
intermediate soft drusen (76-94%; kappa=0.27-0.69). Agreement ranged between 87% 
and 100%, between 50% and 92%, and between 78% and 100% for larger drusen, the
presence of hyperpigmentation, and the presence of hypopigmentation,
respectively. Agreement was moderate to almost perfect for the presence of
geographic atrophy (88-98%; kappa=0.60-0.95) and substantial to almost perfect
for the presence of choroidal neovascularization (84-100%; kappa=0.62-1.00). The 
intra-observer variability for the grading of drusen characteristics and
pigmentary changes was similar in magnitude, but slightly greater for features of
advanced AMD. CONCLUSION. Reproducibility was achieved using a revised version of
the grading system established by the International ARM Epidemiological Study
Group. This grading system may therefore be used for phenotyping of ARM and AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12545291 [PubMed - indexed for MEDLINE]

2660: Graefes Arch Clin Exp Ophthalmol. 2003 Jan;241(1):13-8. Epub 2002 Dec 5.

Retinal hemorrhage after photodynamic therapy in patients with subfoveal
choroidal neovascularization caused by age-related macular degeneration.

Theodossiadis GP, Panagiotidis D, Georgalas IG, Moschos M, Theodossiadis PG.

george@hellasnet.gr

PURPOSE. To report the frequency and the evolution of the extensive retinal
hemorrhages that can appear within 48 h after the application of photodynamic
therapy. METHODS. Two hundred and fifteen individual eyes of 194 consecutive
patients with subfoveal choroidal neovascularization (CNV) due to age-related
macular degeneration who underwent photodynamic treatment were included in the
study. The visual acuity was measured before and after treatment. Color and
red-free photographs were taken. Fluorescein angiography and optical coherence
tomography (OCT) were also performed in order to describe the macular
hemorrhages. RESULTS. Four out of 215 eyes developed macular hemorrhage within 48
h after the photodynamic therapy. Before treatment one of the four patients had
classic CNV, one predominantly classic and two patients occult CNV without any
classic component. In all four cases, the hemorrhage after photodynamic therapy
(PDT) was extensive, it extended beyond the arcades and it was not absorbed
during the follow-up period, which ranged from 11 to 21 months. The greatest
linear dimension of the hemorrhage was extremely high (>12,000 microm).
CONCLUSION. Extensive macular hemorrhage was observed in 1.86% of the studied
cases. The hemorrhage was not related to the type of the CNV lesion before
treatment. The size and the appearance of hemorrhage within 48 h after treatment 
support the view that the hemorrhage is a direct consequence of the photodynamic 
therapy and not related to the natural course of the disease.

Publication Types: 
    Case Reports

PMID: 12545287 [PubMed - indexed for MEDLINE]

2661: Curr Opin Ophthalmol. 2003 Feb;14(1):39-43.

Managing cystoid macular edema after cataract surgery.

Nelson ML, Martidis A.

Retina Service, Wills Eye Hospital, Philadephia, Pennsylvania 19107, USA.

Cystoid macular edema (CME) is a common problem after cataract extraction. It can
occur after uncomplicated surgery in patients with otherwise healthy eyes, after 
complicated surgery, or after surgery in patients with ocular diseases such as
uveitis or diabetic retinopathy. Usually vision loss from cystoid macular edema
is temporary and responds to treatment with topical anti-inflammatory
medications. However, some cases respond poorly to conservative treatment and may
develop permanent visual loss. A review of the medical literature was performed
for all articles published in English between August 1, 2001 and July 31, 2002 on
the topic of cystoid macular edema after cataract surgery. The authors selected
nine articles that were most relevant to the practicing ophthalmologist for
inclusion in this review. Topics of interest included vitreous loss, retained
lens fragments, diabetes, uveitis, retinitis pigmentosa, ocular hypotensive
lipids, internal limiting membrane peeling, and intravitreal triamcinolone
injection.

Publication Types: 
    Review

PMID: 12544809 [PubMed - indexed for MEDLINE]

2662: Br J Ophthalmol. 2003 Feb;87(2):177-83.

Angiographic features after photodynamic therapy for choroidal neovascularisation
in age related macular degeneration and pathological myopia.

Parodi MB, Da Pozzo S, Ravalico G.

Eye Clinic, University of Trieste, Italy. maubp@yahoo.it

AIM: To describe the angiographic features after photodynamic therapy (PDT) with 
verteporfin in choroidal neovascularisation (CNV) associated both with age
related macular degeneration (AMD) and pathological myopia (PM). METHODS: 36
patients affected by subfoveal CNV in AMD and 25 patients with subfoveal CNV in
PM underwent an ophthalmological examination including fluorescein angiography
(FA) and indocyanine green angiography (ICGA) using the IMAGEnet System. Post-PDT
examinations were performed 7, 30, and 90 days later. RESULTS: The typical
angiographic aspect after PDT for AMD related CNV was a round hypofluorescence
visible both on FA and on ICGA, which included both CNV and the surrounding
tissues and corresponded to the area exposed to laser light. In PM the CNV
appeared hypofluorescent during the early phases and gradually became
hyperfluorescent during the late phases on FA, whereas on ICGA it was detectable 
in its whole extension as a hyperfluorescent lesion since the early phases.
Differently from AMD, there was no round hypofluorescence surrounding the CNV on 
FA or on ICGA. Moreover, five patients in the AMD group showed hot spots on ICGA,
which spontaneously disappeared during the follow up. Classic and occult
components of the AMD related CNV revealed a different angiographic response to
PDT, showing with the latter only a partial closure 1 week after PDT followed by 
a complete reopening at the first month in 100% of cases. CONCLUSION: The
post-PDT hypofluorescence typical of AMD related CNV, especially visible on FA,
might be secondary to a combination of choriocapillary occlusion and masking
effect due to swelling of retinal pigment epithelium cells. Hot spots in the AMD 
affected patients could be interpreted as the expression of a non-thermal
choroidal vasculitis secondary to PDT.

PMID: 12543747 [PubMed - indexed for MEDLINE]

2663: Jpn J Ophthalmol. 2002 Nov-Dec;46(6):656-9.

A case of cystoid macular edema associated with latanoprost ophthalmic solution.

Tokunaga T, Kashiwagi K, Saito J, Kobayashi K, Kobori Y, Abe K, Tsukahara S.

Iida Hospital, Iida, Nagano, Japan.

BACKGROUND: Although there have been reports of adverse effects after use, it is 
unclear whether latanoprost ophthalmic solution contributes to the development of
cystoid macular edema (CME). CASE: A 71-year-old man underwent lens extraction,
the insertion of an intraocular lens, and vitrectomy for elevated intraocular
pressure (IOP) associated with lens subluxation in the left eye. After the
surgery, antiglaucoma ophthalmic solutions controlled IOP well for over a year,
maintaining good visual acuity with no abnormalities in the fundus. OBSERVATIONS:
Two months after the previously prescribed antiglaucoma ophthalmic solutions were
replaced by latanoprost, the patient's visual acuity decreased and CME developed.
When latanoprost was replaced by other antiglaucoma ophthalmic solutions for
controlling IOP, CME disappeared and visual acuity returned to the base level.
CONCLUSIONS: Latanoprost may be involved in the development of CME. Patients who 
have undergone vitreous surgery or those with aphakia should be carefully
observed for the possible development of CME associated with the use of
latanoprost, even a long time after surgery.

Publication Types: 
    Case Reports

PMID: 12543193 [PubMed - indexed for MEDLINE]

2664: Jpn J Ophthalmol. 2002 Nov-Dec;46(6):650-5.

Use of scanning laser ophthalmoscope microperimetry in clinically significant
macular edema in type 2 diabetes mellitus.

Mori F, Ishiko S, Kitaya N, Hikichi T, Sato E, Takamiya A, Yoshida A.

Department of Ophthalmology, Asahikawa Medical College, Asahikawa, Hokkaido,
Japan.

PURPOSE: We used scanning laser ophthalmoscope (SLO) microperimetry to evaluate
scotomas in patients with clinically significant diabetic macular edema (CSME) in
type 2 diabetes mellitus. METHODS: We studied 19 patients (mean age = 63 years;
range, 45-78 years) (19 eyes). SLO microperimetry was performed in all eyes. We
divided patients into three groups as follows: dense scotoma, relative scotoma,
and no scotoma. The following variables were documented: age; duration of
diabetes, hemoglobin A(1c) levels; logarithm of the minimum angle of resolution
(Log(MAR)) visual acuity; refractive power; a history of panretinal
photocoagulation; presence or absence of proliferative diabetic retinopathy,
vitreomacular separation, and cystoid changes; the type of macular edema; and
stability of fixation. All variables were compared in the three groups. RESULTS: 
We identified 4 eyes (21.1%) with dense scotoma, 10 (52.6%) with relative
scotoma, and 5 (26.3%) with no scotoma. There were significant differences in
log(MAR) visual acuity among those with dense scotoma (1.4 +/- 0.5), relative
scotoma (0.6 +/- 0.2), and no scotoma (0.2 +/- 0.3) (P <.05), and in the
prevalence of cystoid changes, diffuse edema, and unstable fixation among those
with dense scotoma (75%, 75%, and 100%, respectively), relative scotoma (20%, 30%
and 50%, respectively) and no scotoma (0%, 0% and 0%, respectively) (P <.05).
CONCLUSIONS: Macular scotoma was observed by SLO microperimetry in 74% of the
patients in this study. A scotoma in CSME is related to the formation of cystoid 
changes and the type of macular edema. In eyes with CSME in type 2 diabetes
mellitus, a scotoma in the macula causes visual acuity impairment and unstable
fixation.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12543192 [PubMed - indexed for MEDLINE]

2665: Optometry. 2003 Jan;74(1):16-24.

Awareness of age-related macular degeneration in adults: the results of a
large-scale international survey.

Rosenthal B, Thompson B.

The AMD Alliance International, New York, New York, USA.
brosenthal@lighthouse.org

BACKGROUND: Early detection and prompt implementation of appropriate
rehabilitation services and therapy can help minimize the long-term disability
that results from age-related macular degeneration (ARMD). The level of awareness
of ARMD among the general public may influence early detection of this disease.
METHODS: Random samples of European and North American populations were
interviewed in an international survey designed to assess the attitudes of people
to eye examinations, awareness of the causes of vision loss, awareness of ARMD,
and knowledge of its treatment options. RESULTS: A total of 7,830 adults of at
least 18 years of age were questioned. The main finding was that knowledge of
ARMD is poor-the majority of respondents (70%) were not at all familiar with
ARMD. Only 2% of participants knew that ARMD is the leading cause of severe
vision loss in adults 50 years of age or older, while a majority of those
surveyed (75%) was unaware of treatments available for ARMD. CONCLUSIONS: These
data show that there is low public awareness of ARMD, which may result in people 
with ARMD not receiving prompt medical advice and treatment. There is a need for 
a wide-ranging educational initiative to increase awareness of ARMD and highlight
the importance of undergoing regular eye examinations.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12539889 [PubMed - indexed for MEDLINE]

2666: Curr Eye Res. 2002 Aug;25(2):123-31.

Experimental macular edema induced by macular venule occlusion in monkey.

Ieki Y, Nishiwaki H, Miura S, Yamashiro K, Nishijima K, Nonaka A, Kiryu J, Honda 
Y.

Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School
of Medicine, Kyoto, Japan.

PURPOSE: Visual prognosis after retinal vein occlusion varies, because it may be 
affected by macular edema or an avascular area. The mechanism describing how
macular edema and avascular areas occur, however, has not been clearly
understood. We induced macular edema in cynomolgus monkeys by occluding macular
venules to evaluate the retinal microcirculation. METHODS: We produced venous
occlusion by applying dye laser in three cynomolgus monkeys. Macular edema was
examined by slit lamp biomicroscopy and optical coherence tomography. Acridine
orange leukocyte fluorography (AOLF) and fluorescein angiography were performed
to study blood flow and vascular leakage before and after laser application.
RESULTS: We observed three types of retinal changes in the macular area: (1)
macular edema did not develop; (2) macular edema developed, but improved with
avascular area formation; (3) macular edema developed, but disappeared without
avascular area formation. Under physiological conditions, observation revealed
that leukocytes flowed from arterioles into either superior or inferior venules. 
When macular edema did not develop, most leukocytes from arterioles escaped into 
the adjacent non-occluded venules. In contrast, when macular edema occurred,
leukocyte flow became stagnated. Macular edema developed when capillary leakage
was observed from venules and subsequently arterioles, but disappeared when an
avascular area was formed by arteriole occlusion. CONCLUSIONS: We demonstrated
that experimental macular edema could be induced by macular venule occlusion in
monkeys. According to our observation by AOLF, whether macular edema is induced
or not depends on the function of collateral routes of the remaining non-occluded
venules. We could consider that a gradual increase in intravascular pressure was 
associated with the avascular area formation.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12525967 [PubMed - indexed for MEDLINE]

2667: Arch Ophthalmol. 2003 Jan;121(1):57-61.

Comment in:
    Arch Ophthalmol. 2004 Jul;122(7):1082-3; author reply 1086-8.    Arch Ophthalmol. 2004 Jul;122(7):1082; author reply 1086-8.    Arch Ophthalmol. 2004 Jul;122(7):1083-5; author reply 1086-8.    Arch Ophthalmol. 2004 Jul;122(7):1083; author reply 1086-8.    Arch Ophthalmol. 2004 Jul;122(7):1085-6; author reply 1086-8.

Intravitreal injection of triamcinolone for diffuse diabetic macular edema.

Jonas JB, Kreissig I, Söfker A, Degenring RF.

Department of Ophthalmology and the Eye Hospital, Faculty for Clinical
Medicine-Mannheim, Ruprecht Karls University, Heidelberg, Germany.
jost.jonas@augen.ma.uni-heidelberg.de

OBJECTIVE: To evaluate the clinical outcome of an intravitreal injection of
triamcinolone acetonide as treatment of diffuse diabetic macular edema.
PARTICIPANTS: This prospective, interventional, clinical case series study
included 20 patients (26 eyes) who received an intravitreal injection of 25 mg of
triamcinolone acetonide for treatment of diffuse diabetic macular edema. Mean +/-
SD follow-up time was 6.64 +/- 6.10 months. The study group was compared with a
control group of 16 patients who underwent macular grid laser coagulation. MAIN
OUTCOME MEASURES: Visual acuity and intraocular pressure. RESULTS: In the study
group, visual acuity improved significantly (P<.001), from 0.12 +/- 0.08 at
baseline to a maximum of 0.19 +/- 0.14 during follow-up. Seventeen (81%) of 21
eyes with a follow-up period of more than 1 month had improved visual acuity. In 
the control group, visual acuity did not change significantly. In the study
group, intraocular pressure increased significantly (P<.001), from 16.9 +/- 2.5
mm Hg to a mean maximal value of 21.3 +/- 4.7 mm Hg, and decreased significantly 
(P =.03) to 17.7 +/- 4.7 mm Hg at the study's end. CONCLUSION: Intravitreal
injection of 25 mg of triamcinolone acetonide may be beneficial for improving
visual acuity in patients with clinically significant diffuse diabetic macular
edema.

Publication Types: 
    Clinical Trial
    Comparative Study

PMID: 12523885 [PubMed - indexed for MEDLINE]

2668: Ophthalmol Clin North Am. 2002 Dec;15(4):555-63.

Diabetic macular edema: review and update.

Pelzek C, Lim JI.

University of Southern California-Doheny Eye Institute 1450 San Pablo Street, Los
Angeles, CA 90033, USA. cpelzek@yahoo.com

Impairment in the visual acuity and quality of life of diabetic patients with
macular edema can undeniably be decreased with systemic and ocular therapeutic
intervention, as shown by numerous controlled studies. Such interventions, with
early screening and periodic examination, are even more crucial given the
increasing survival of patients with diabetic retinopathy. In the 1950s, adjusted
5-year survival rates for patients with PDR were less than 30%, whereas by the
end of the century age- and sex-adjusted 5-year survival rates approached 90% for
patients with early-onset diabetes and 60% for patients with late-onset diabetes 
[83]. Furthermore, advances in our understanding of diabetic retinopathy have led
to biochemical adjuncts that offer the potential for further reduction of visual 
loss caused by diabetic macular edema. Despite such advances, the implementation 
of effective treatments has been hampered by concerns over hypoglycemia after
intensive insulin regimens, poor physician compliance regarding guidelines for
dilated ophthalmic examinations, and economic barriers to access [84]. Therefore,
it is imperative for the ophthalmologist not only to discuss the progression and 
treatment of diabetic macular edema and the importance of routine examination
with patients but also to work with other health care professionals to ensure the
evaluation and treatment of associated cardiovascular and neurologic disease.
Educational programs, such as those created by the National Eye Health and
Education Program [85], may also assist the ophthalmologist in providing patients
with the optimal care available in the 21st century.

Publication Types: 
    Review

PMID: 12515087 [PubMed - indexed for MEDLINE]

2669: Ophthalmol Clin North Am. 2002 Dec;15(4):467-72.

Update on pseudophakic cystoid macular edema treatment options.

Levin DS, Lim JI.

Department of Ophthalmology, University of Southern California Keck School of
Medicine, Doheny Eye Institute, 1450 San Pablo Street, Los Angeles, CA 90033,
USA. docretina@yahoo.com

As far as the treatment of chronic pseudophakic CME is concerned, it is important
to understand that postoperative CME usually resolves with time. One must gauge
the various treatment modalities outlined above with improvements in visual
acuity and decreasing clinical macular thickening. Mild cases usually require no 
treatment, whereas those that entail clinically significant reductions in vision 
or macular thickening do require appropriate intervention.

Publication Types: 
    Review

PMID: 12515079 [PubMed - indexed for MEDLINE]

2670: Ophthalmol Clin North Am. 2002 Dec;15(4):453-8.

Antiangiogenesis agents.

Ciardella AP, Donsoff IM, Guyer DR, Adamis A, Yannuzzi LA.

LuEsther T. Mertz Retinal Research Laboratory, Manhattan Eye, Ear and Throat
Hospital, 210 E. 64th Street, New York, NY 10021, USA. aciardella@yahoo.com

Although these preliminary results on the use of antiangiogenesis drugs for the
treatment of neovascular AMD appear promising, double-masked, placebo-controlled,
multicenter clinical trials are needed to demonstrate the therapeutic efficacy of
such treatments. For example, the first antiangiogenesis drug tested in AMD,
interferon alpha-2a, raised great enthusiasm. Indeed, interferon alpha-2a had
been shown to be antiangiogenic in animal and in vitro models. It proved to be
ineffective, however, in halting the progression of neovascular AMD in a
double-masked, placebo-controlled clinical trial [28]. Another antivasogenesis
drug tested in a phase 3 clinical trial is thalidomide [67]. Although the
enrollment of patients is finished, the results are not yet known.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 12515077 [PubMed - indexed for MEDLINE]

2671: Ophthalmol Clin North Am. 2002 Dec;15(4):437-44, v.

Use of radiation in the treatment of age-related macular degeneration.

Flaxel CJ.

Doheny Retina Institute of the Doheny Eye Institute, Keck School of Medicine,
University of Southern California, Los Angeles, CA 90033, USA. flaxel@hsc.usc.edu

In this century, macular degeneration is likely to reach epidemic proportions.
New treatment modalities are being evaluated for wet or neovascular age-related
macular degeneration (AMD) and include radiation treatment. Radiation is known to
potentially destroy vascular tissue, and low-dose radiation has been shown to
inhibit new blood vessel growth. Potential advantages to radiation therapy in
treating AMD include the absence of iatrogenic mechanical or laser damage, the
absence of systemic side effects, and the absence of local side effects caused by
periocular and intraocular injection. An additional advantage is that eyes with
primarily large, occult choroidal neovascularization are potentially eligible for
treatment, and only one treatment would be necessary. The major potential side
effect is radiation retinopathy, which is dose dependent.

Publication Types: 
    Review

PMID: 12515075 [PubMed - indexed for MEDLINE]

2672: Ophthalmol Clin North Am. 2002 Dec;15(4):425-36.

Limited macular translocation: current concepts.

Fujii GY, Au Eong KG, Humayun MS, de Juan E Jr.

Retina Institute, Doheny Eye Institute, Keck School of Medicine, University of
Southern California, DEI-3600, 1450 San Pablo Street, Los Angeles, CA 90033, USA.

Macular translocation is a promising treatment modality that offers patients a
chance to improve their vision, potentially to a level that may allow reading and
driving. Proper patient selection avoids surgery in eyes with permanently damaged
central retina and identifies eyes with the greatest potential for good visual
outcomes. Functionally, those patients with recent-onset subfoveal CNV without
permanent foveal neurosensory retina damage have the greatest likelihood of good 
visual outcome. Use of fixation evaluation by means of the SLO appears to greatly
optimize patient selection. Anatomically, the best candidates have small minimum 
desired translocations and healthy RPE-Bruch membrane-choriocapillaris complex
beyond the borders of the lesion. The exact role of limited macular translocation
for the management of subfoveal CNV in this era of photodynamic therapy remains
to be evaluated, and a pilot multicenter, randomized, clinical trial is under way
to compare the efficacy of limited macular translocation with photodynamic
therapy in eyes with subfoveal CNV secondary to AMD.

Publication Types: 
    Review

PMID: 12515074 [PubMed - indexed for MEDLINE]

2673: Ophthalmology. 2003 Jan;110(1):65-9.

Scotoma size and reading speed in patients with subfoveal occult choroidal
neovascularization in age-related macular degeneration.

Ergun E, Maár N, Radner W, Barbazetto I, Schmidt-Erfurth U, Stur M.

Department of Ophthalmology, University of Vienna Medical School, Vienna,
Austria.

PURPOSE: To investigate the correlation between reading speed and scotoma size in
patients with subfoveal occult with no classic choroidal neovascularization (CNV)
in age-related macular degeneration (AMD) participating at 2 of 28 centers in the
Verteporfin in Photodynamic Therapy trial. DESIGN: Prospective, observational
case series. PARTICIPANTS: Twenty-two eyes of 22 patients with occult with no
classic CNV in AMD. METHODS: Patients' reading speed was examined using a
German-language reading test (Radner Lesetest). Scotoma size was measured using
the microperimetry program 2.01 of the Rodenstock Scanning Laser Ophthalmoscope. 
MAIN OUTCOME MEASURES: Reading acuity, reading speed, size of absolute (AS) and
relative scotoma (RS). RESULTS: There was a significant correlation between the
size of AS and reading speed (r = -0.48, P = 0.023), as well as AS and reading
acuity (r = 0.52, P = 0.013). No correlation was seen between RS and reading
speed or reading capacity. CONCLUSION: The size of absolute scotoma correlated
significantly with reading capacity and reading speed and may influence these
measures.

Publication Types: 
    Clinical Trial
    Multicenter Study

PMID: 12511348 [PubMed - indexed for MEDLINE]

2674: Ophthalmology. 2003 Jan;110(1):51-60; discussion 61.

Influence of short-term antioxidant supplementation on macular function in
age-related maculopathy: a pilot study including electrophysiologic assessment.

Falsini B, Piccardi M, Iarossi G, Fadda A, Merendino E, Valentini P.

Istituto di Oftalmologia, Universitá Cattolica del S. Cuore, Rome, Italy.

PURPOSE: To evaluate the influence of short-term antioxidant supplementation on
retinal function in age-related maculopathy (ARM) patients by recording focal
electroretinograms (FERGs). DESIGN: Nonrandomized, comparative clinical trial.
PARTICIPANTS: Thirty patients with early ARM and visual acuity >/=20/30, divided 
into two groups, similar for age and disease severity: antioxidant group (ARM-A, 
n = 17) and no treatment group (ARM-NT, n = 13). Eight age-matched normal
subjects divided into antioxidant (N-A, n = 4) or no treatment (N-NT, n = 4)
groups. METHODS: ARM-A patients and N-A patients had oral supplementation of
lutein, 15 mg; vitamin E, 20 mg; and nicotinamide, 18 mg, daily for 180 days,
whereas ARM-NT patients and N-NT patients had no dietary supplementation during
the same period. Eight of the 17 ARM-A patients took supplementation for an
additional 180-day period. In all patients and normal subjects, FERG assessment
was performed at the study entry (baseline) and after 180 days. Further testing
was performed at 360 days for the eight ARM-A patients taking supplements and for
one ARM-A patient who had discontinued supplementation after 180 days. FERGs were
recorded in response to a 41-Hz sinusoidally modulated uniform field (93.5%
modulation depth) presented to the macular region (18 degrees ) on a
light-adapting background. In a subgroup of patients (11 ARM-A and 5 ARM-NT),
whose responses had suitable signal-to-noise ratios, FERGs were also recorded at 
different stimulus modulation depths between 8.25% and 93.5%. MAIN OUTCOME AND
MEASURES: Amplitude (in micro V) and phase (in degrees) of the FERG fundamental
harmonic component. FERG modulation thresholds, estimated from the value of log
modulation depth yielding a criterion response. RESULTS: At 180 days, FERGs of
ARM-A patients and N-A patients were increased in amplitude (mean change, 0.11
and 0.15 log micro V, respectively, P </= 0.01) compared with baseline values,
whereas no significant changes in FERG amplitudes of ARM-NT patients and N-NT
patients were found (mean change, -0.004 and -0.023 log micro V, respectively).
In all groups no changes in the FERG phase were found. FERG modulation thresholds
decreased with respect to baseline values (mean change, -0.36 log units, P <
0.01) in ARM-A patients, whereas no significant change (mean change, 0.07 log
units) in ARM-NT patients was seen. At 360 days, FERGs of ARM-A patients taking
supplementation were still increased in amplitude with respect to baseline (P <
0.05) but did not differ from those recorded at 180 days. In the patient who had 
discontinued supplementation, FERG amplitude decreased from the 180 days value,
approaching that recorded at baseline. CONCLUSIONS: Although this study provides 
no evidence for the long-term benefit of antioxidants in ARM, the results suggest
that increasing the level of retinal antioxidants might influence macular
function early in the disease process, as well as in normal aging.

Publication Types: 
    Clinical Trial
    Comparative Study

PMID: 12511345 [PubMed - indexed for MEDLINE]

2675: Ophthalmology. 2003 Jan;110(1):25-33.

Early age-related maculopathy in the cardiovascular health study.

Klein R, Klein BE, Marino EK, Kuller LH, Furberg C, Burke GL, Hubbard LD.

Department of Ophthalmology and Visual Sciences, University of Wisconsin,
Madison, Wisconsin 53726, USA.

OBJECTIVE: To describe the prevalence of early age-related maculopathy (ARM) and 
its relation to atherosclerosis, lipids, hypertension, and inflammatory factors
in a population studied for cardiovascular disease risk factors and outcomes.
DESIGN: Population-based cohort study. PARTICIPANTS: A biracial population of
2361 adults (ranging from 69-97 years of age; 1998 whites and 363 blacks) living 
in four US counties (Allegheny County, Pennsylvania; Forsyth County, North
Carolina; Sacramento County, California; and Washington County, Maryland) were
examined during the interval from 1997 to 1998. METHODS: Drusen and other lesions
typical of ARM were identified by examining a 45 degrees color fundus photograph 
of one eye of each participant and classified by means of a modification of the
Wisconsin Age-Related Maculopathy Grading System. MAIN OUTCOME MEASURES: Early
ARM. RESULTS: Early ARM was present in 15.5% and late ARM in 1.3% of the cohort. 
The overall prevalence of any ARM was lower in blacks (9.1%) compared with whites
(18.2%). While controlling for age, race, gender, and total calories consumed in 
the diet, factors associated with ARM were cerebral white matter disease as
detected by magnetic resonance imaging (odds ratio [OR], 1.50; 95% confidence
interval [CI], 1.05, 2.16, P = 0.027), and lower serum total cholesterol (OR, per
10 mg/dl increase 0.95; 95% CI, 0.91, 0.98, P = 0.02). There were no associations
between hypertension, blood pressure, common carotid artery plaque, or any
systemic inflammatory factors studied and early ARM. CONCLUSIONS: This
population-based study documents the higher prevalence of ARM in whites compared 
with blacks. Although an association was found between signs of white matter
disease and early ARM, there was no evidence of an association of ARM with either
hypertension or inflammatory factors.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12511342 [PubMed - indexed for MEDLINE]

2676: Eur J Ophthalmol. 2002 Nov-Dec;12(6):482-7.

Macular thickness measured by optical coherence tomography (OCT) in diabetic
patients.

Lattanzio R, Brancato R, Pierro L, Bandello F, Iaccher B, Fiore T, Maestranzi G.

Department of Ophthalmology and Visual Sciences, University Hospital S. Raffaele,
Milano, Italy.

PURPOSE: 1) To compare macular thickness (MT) by optical coherence tomography
(OCT) in diabetics and controls; 2) to assess the relationship between MT and
stage of diabetic retinopathy (DR) and macular edema (ME); 3) to quantify MT
changes after laser treatment for ME. METHODS: One-hundred and thirty-seven
patients with diabetes mellitus (216 eyes) were admitted to the study and
examined by stereo-color fundus photos, retinal fluorangiography and OCT. DR was 
classified as: 1) no DR (46 eyes: 21.3%); 2) background DR (66 eyes: 30.6%); 3)
pre-proliferative DR (50 eyes: 23.1%); 4) proliferative DR (54 eyes: 25%). The
study group was then divided into three ME groups: 1) no edema (65 eyes: 30.1%); 
2) not clinically significant ME (no CSME) (45 eyes: 20.8%); 3) clinically
significant macular edema (CSME) (106 eyes: 49.1%). Three-month follow-up
tomograms were taken to evaluate eyes laser-treated only for ME. The control
group consisted of 50 eyes of 50 non-diabetic, age- and sex-matched subjects.
RESULTS: MT was 369.3 +/- 163.2 microm in diabetics and 161.9 +/- 12.9 microm in 
controls (p < 0.001). In the four DR groups it was: 1) 211.0 +/- 37.6 microm; 2) 
370.8 +/- 159.6 microm; 3) 419.1 +/- 138.2 microm; 4) 456.1 +/- 162.0 microm
(p<0.001). In the three ME groups, MT was: 1)227.8 +/- 53.4 microm; 2) 321.8 +/- 
124.2 microm; 3) 476.2 +/-146.6 microm (p < 0.001). In the 52 eyes treated with
laser photocoagulation of the posterior pole only and with a follow-up > 3
months, MT before and after treatment was 468.2 +/- 83. 17 microm and 372.1 +/-
120.63 microm. CONCLUSIONS: MT was greater in diabetics than controls and tended 
to increase with DR and ME severity. OCT is a sensitive technique for detecting
early diabetic macular abnormalities and quantifying their reduction after laser 
treatment.

Publication Types: 
    Comparative Study

PMID: 12510717 [PubMed - indexed for MEDLINE]

2677: Eur J Ophthalmol. 2002 Nov-Dec;12(6):467-72.

Optical coherence tomography (OCT) angiomatous prolifieration (RAP) in retinal.

Brancato R, Introini U, Pierro L, Setaccioli M, Forti M, Bolognesi G, Tremolada
G.

Department of Ophthalmology and Visual Sciences, San Raffaele University
Hospital, Milano, Italy. brancato.rosario@hsr.it

PURPOSE: To verify the utility of optical coherence tomography (OCT) for
diagnosing retinal angiomatous proliferations (RAP) in patients with exudative
age-related macular degeneration (AMD). METHODS: Multiple cross-sections were
taken with OCT from 41 eyes of 39 consecutive patients with AMD and RAP. The
presence and the location of the angiomatous complexes had already been
documented by fluorescein angiography (FA) and high-speed confocal indocyanine
green videoangiography (ICGA). RESULTS: RAP was detectable by OCT scans in all 41
eyes, appearing as a focal hyper-reflecting area in the neuroretinal layers; it
was frequently located close to the inner surface of the retinal pigment
epithelium (29 eyes [70. 7%]). All eyes had either no or only a low-reflecting
OCTsignal surrounding the RAP, caused by serous intraretinal edema. Only 13 eyes 
(31.7%), however, had large serous retinal detachment (SRD). OCT detected pigment
epithelium detachment in 31 eyes (75.6%), but none had underlying choroidal
neovascularization. CONCLUSIONS: OCT findings confirm the intraretinal
localization of the RAP which are always associated with impressive exudative
phenomena. OCT is therefore a useful diagnostic tool, adding information to FA
and high-speed ICGA.

PMID: 12510715 [PubMed - indexed for MEDLINE]

2678: Eur J Ophthalmol. 2002 Nov-Dec;12(6):443-9.

The protective effects of melatonin, vitamin E and octreotide on retinal edema
during ischemia-reperfusion in the guinea pig retina.

Yilmaz T, Celebi S, Kükner AS.

Department of Ophthalmology, School of Medicine, Firat University, Elazig,
Turkey. tvilmaz23@yahoo.com

PURPOSE: The purpose of this study is to provide evidence that free radical
damage is a component of retinal ischemia-reperfusion (I/R) injury, and to
determine whether melatonin, vitamin E and octreotide can protect retina from
this injury. METHODS: The right eyes of 50 male guinea pigs weighing 500-600 g
were used. The animals were randomly assigned to group 1 (control), group 2
(I/R), group 3 (melatonin + I/R), group 4 (vitamin E + I/R) and group 5
(octreotide + I/R). Groups 3, 4 and 5 received four subcutaneous injections at
six-hour intervals for total dosage of 10 mg/kg melatonin, 150 mg/kg vitamin E
and 22 microg/kg octreotide respectively. The first dose of each substance was
administered 5 minutes before retinal ischemia. Retinal ischemia was induced for 
1.5 hours, then followed by reperfusion for 24 hours. Infections of all three
substances were repeated at 6, 12 and 18 hours during reperfusion. The animals
were killed at 24 hours of reperfusion. Sagittal sections of 4 microm were cut
and stained with hematoxylin and eosin for light microscopic evaluation. The
average thickness (edema) of the inner plexiform layer for each eye was measured 
in sagittal sections near the optic nerve and expressed in microns. RESULTS: The 
efficacy of each compound had the following relationships: melatonin>vitamin
E>octreotide in preventing retinal damage by ischemia-reperfusion. The mean
thickness of the inner plexiform layer was 13.3 +/- 0.8 microm, 25.9 +/- 2. 0
microm, 20.0 +/- 0. 7 microm, 21.6 +/- 0.7 microm, 23.9 +/- 0.8 microm
respectively in the control, I/R, I/R plus melatonin, I/R plus vitamin E and I/R 
plus octreotide groups. The thickness of the inner plexiform layer in group 1
(control) was significantly less than the other groups (p<0.001). The inner
plexiform layer was thicker in the I/R group than with I/R plus melatonin, I/R
plus vitamin E and I/R plus octreotide (all p < 0.01). The inner plexiform layer 
was thicker in the I/R plus octreotide group than the I/R plus vitamin E and I.R 
plus melatonin groups both (p < 0.05). Compared to the I/R plus melatonin group, 
the inner plexiform layer was significantly thicker in the I/R plus vitamin E
group (p < 0. 05). CONCLUSIONS: This study demonstrates a protective effect of
melatonin, vitamin E and octreotide on the retina during retinal
ischemia-reperfusion injury.

Publication Types: 
    Comparative Study

PMID: 12510712 [PubMed - indexed for MEDLINE]

2679: Surv Ophthalmol. 2002 Dec;47 Suppl 2:S263-9.

The potential role of PKC beta in diabetic retinopathy and macular edema.

Aiello LP.

Harvard Medical School and Joslin Diabetes Center, Boston, Massachussetts, USA.

Diabetic retinopathy is one of the most debilitating complications of diabetes
mellitus. Despite major advances in understanding the pathogenesis of this
disease and the efficacy of current therapies, diabetic retinopathy remains the
leading cause of new-onset blindness among working-age people. The mainstay of
current therapy, laser photocoagulation, is useful in preventing blindness and
severe vision loss but is not often effective in restoring lost visual acuity. In
addition, troublesome side effects and potentially serious complications may
occur. Diabetic retinopathy is characterized by a progression of abnormalities.
Nonproliferative retinopathy results from a series of biochemical and cellular
changes that ultimately cause progressive retinal ischemia. The subsequent
elaboration of growth factors in response to ischemia leads to the development of
proliferative retinopathy, which is characterized by aberrant neovacularization
of the retina-potentially leading to severe, irreversible visual loss. Increased 
retinal vascular leakage may also occur at any stage in this process, resulting
in macular edema and possible progressive visual impairment. Although numerous
biochemical factors are thought to play a role in the development of retinopathy,
activation of protein kinase C (PKC), specifically the beta isoform of PKC (PKC
beta), is implicated for both the early and late-stage manifestations of
retinopathy. Studies suggest that orally administered LY333531, a beta-isoform
specific PKC inhibitor, may be effective in ameliorating retinopathy progression,
proliferation, and retinal vascular leakage. The status of ongoing clinical
trials aimed at addressing the efficacy of PKC beta with regard to
diabetes-induced retinal complications and perspectives on the role of PKC beta
are presented.

Publication Types: 
    Review

PMID: 12507628 [PubMed - indexed for MEDLINE]

2680: Am J Ophthalmol. 2003 Jan;135(1):120-1.

Foveal congenital hypertrophy of the retinal pigment epithelium in the setting of
geographic atrophy from age-related macular degeneration.

Apte RS, Bressler NM.

Retinal Vascular Center, The Wilmer Ophthalmological Institute, The Johns Hopkins
University School of Medicine, Baltimore, Maryland, USA.

PURPOSE: To report a case of presumed congenital hypertrophy of the retinal
pigment epithelium in the fovea of an 88-year-old woman in the setting of
geographic atrophy from age-related macular degeneration. DESIGN: Observational
case report. METHODS: An 88-year-old woman was examined. RESULTS: Best-corrected 
visual acuity was 20/63 in the right eye and 20/50 in the left eye. Multifocal
areas of geographic atrophy and large-sized drusen were seen in the maculae of
both eyes. Biomicroscopic examination of the right eye showed hyperpigmentation
consistent with congenital hypertrophy of the retinal pigment epithelium through 
the center of the macula. No prior photographic documentation of the retina was
available. CONCLUSION: This case suggests that foveal congenital hypertrophy of
the retinal pigment epithelium may be seen in the setting of macular geographic
atrophy. Although it is theoretically possible that the hyperpigmentation is
reactive rather than congenital, the pigmentation is typical for congenital
hypertrophy and is unlike any reactive pigmentation in our experience or
described in a MEDLINE search of features of age-related macular degeneration.
The case suggests that a hypertrophic process of the retinal pigment epithelium
may coexist within or immediately adjacent to the anatomic boundaries of an
atrophic process such as geographic atrophy from age-related macular
degeneration.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 12504720 [PubMed - indexed for MEDLINE]

2681: Am J Ophthalmol. 2003 Jan;135(1):116-8.

Resolution of diabetic cystoid macular edema associated with spontaneous
vitreofoveal separation.

Yamaguchi Y, Otani T, Kishi S.

Department of Ophthalmology, Gunma University School of Medicine, Maebashi,
Gunma, Japan. yamame@showa.gunma-u.ac.jp

PURPOSE: To report spontaneous resolution of diabetic cystoid macular edema (CME)
associated with spontaneous vitreofoveal separation. DESIGN: Interventional case 
series. METHODS: Optical coherence tomography (OCT) was performed on three eyes
of three diabetic patients with CME before and after vitreofoveal separation.
RESULTS: In all three eyes, OCT showed cystic changes at the fovea with a
slightly detached posterior hyaloid, which remained attached to the optic disk
and the fovea. After spontaneous separation of the hyaloid at the fovea, there
was resolution of the cystic cavities and restoration of the foveal depression.
CONCLUSIONS: In some eyes of diabetic patients, CME is caused by a vitreous
traction. Resolution of CME may occur after spontaneous vitreofoveal separation.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 12504718 [PubMed - indexed for MEDLINE]

2682: Am J Ophthalmol. 2003 Jan;135(1):114-6.

Photodynamic therapy for choroidal neovascularization after thermal laser
photocoagulation for diabetic macular edema.

Shah GK.

Barnes Retina Institute, Washington University School of Medicine, St. Louis,
Missouri 63144, USA. shah@vision.wustl

PURPOSE: To report the use of photodynamic therapy for treating a choroidal
neovascular membrane secondary to thermal laser photocoagulation. DESIGN:
Interventional case report. METHODS: A 61-year-old man with a choroidal
neovascular membrane secondary to thermal laser photocoagulation for diabetic
macular edema was treated with photodynamic therapy. RESULTS: Subjective and
objective improvement in visual acuity and improvement of fluorescein angiogram
have been demonstrated for more than a year after treatment. CONCLUSIONS:
Photodynamic therapy may be useful for treating patients with choroidal
neovascularization secondary to thermal laser photocoagulation.

Publication Types: 
    Case Reports

PMID: 12504717 [PubMed - indexed for MEDLINE]

2683: Am J Ophthalmol. 2003 Jan;135(1):14-9.

Early postoperative retinal thickness changes and complications after vitrectomy 
for diabetic macular edema.

Yamamoto T, Hitani K, Tsukahara I, Yamamoto S, Kawasaki R, Yamashita H, Takeuchi 
S.

Department of Ophthalmology, Toho University Sakura Hospital, Chiba, Japan.
tei-yamamoto@sakura.med.toho-u.ac.jp

PURPOSE: To determine the early postoperative changes in retinal thickness and
complications after pars plana vitrectomy for diabetic macular edema. DESIGN:
Consecutive interventional case series. METHODS: Studied retrospectively, pars
plana vitrectomy was performed on 65 consecutive eyes of 63 patients with
diabetic macular edema. The follow-up interval ranged from 6 to 36 months (12.6
+/- 7.4 months [mean +/- standard deviation (SD)]). The indications of pars plana
vitrectomy in this study were (1) diffuse diabetic macular edema, (2)
preoperative visual acuity less than 20/40, and (3) noneffective macular
photocoagulation therapy. Preoperative and postoperative examinations by
stereoscopic biomicroscopy, color fundus photography of the macula and optical
coherence tomography (OCT) were performed on all eyes. Preoperatively, direct
photocoagulation to microaneurysms in the macula had been performed in 48 eyes,
and focal/grid photocoagulation had been performed in five eyes. Preoperative
examination showed that epiretinal membranes were observed in 20 eyes, cystoid
macular edema in 40 eyes, and 23 eyes had a complete posterior vitreous
detachment (PVD). Epimacular membranes, removed during surgery, were examined
histopathologically. RESULTS: The postoperative mean best-corrected visual acuity
(logarithm of the minimum angle of resolution [logMAR] = 0.696 +/- 0.491 [mean
+/- SD]) was significantly better than the preoperative mean best-corrected
visual acuity (0.827 +/- 0.361; P <.0001; Wilcoxon signed-rank test). The final
visual acuity improved by 2 or more lines in 32 of 65 eyes (45%), remained
unchanged in 32 of 65 eyes (49%), and exacerbated after the surgery in 4 of 65
eyes (6%) due to neovascular glaucoma (2 eyes) and residual cystoid macular edema
(2 eyes). The postoperative foveal retinal thickness (224.9 +/- 116.9 microm) at 
the last visit was significantly thinner than the preoperative foveal retinal
thickness (463.7 +/- 177.3 microm; P <.0001; Wilcoxon signed-rank test). The
foveal retinal thickness did not decrease linearly but fluctuated: The mean
postoperative retinal thickness had decreased significantly 7 days after surgery,
then remained unchanged for approximately 1 month, and thereafter gradually
decreased until 4 months. The intraoperative and postoperative complications
included peripheral retinal tear in 3 of 65 (4.6%) eyes, postoperative
rhegmatogenous retinal detachment in 1 of 65 (1.5%) eyes, neovascular glaucoma in
3 of 65 (5%) eyes, recurrent vitreous hemorrhage in 1 of 65 (1.5%) eyes, hard
exudates in the center of the macula in 3 of 56 (4.6%) eyes, postoperative
epiretinal membrane formation in 9 of 65 (13.8%) eyes, and a lamellar macular
hole in 1 of 65 (1.5%) eyes. CONCLUSIONS: Vitrectomy for diabetic macular edema
is an effective procedure for reducing the edema and improving visual acuity.
Because the postoperative reduction in retinal thickness is not complete until 4 
months, the assessment of vitrectomy on foveal thickness should not be made until
this time. In addition, there are severe complications from vitrectomy for
diabetic macular edema, and careful preoperative and postoperative examinations
and surgical methods are required.

PMID: 12504691 [PubMed - indexed for MEDLINE]

2684: Br J Ophthalmol. 2003 Jan;87(1):24-7.

Comment in:
    Br J Ophthalmol. 2004 Apr;88(4):598; author reply 598.

Intraocular pressure after intravitreal injection of triamcinolone acetonide.

Jonas JB, Kreissig I, Degenring R.

Department of Ophthalmology, Faculty of Clinical Medicine Mannheim of the
University Heidelberg, Germany. Jost.Jonas@ma.augen.uni-heidelberg.de

AIM: To investigate the intraocular pressure (IOP) response after intravitreal
injections of triamcinolone acetonide as treatment of intraocular neovascular or 
oedematous diseases. METHODS: The prospective consecutive non-comparative
interventional case series study included 71 patients (75 eyes) with progressive 
exudative age related macular degeneration (n = 64 eyes) or diffuse diabetic
macular oedema (n = 11 eyes), who received an intravitreal injection of 25 mg
triamcinolone acetonide. Mean follow up time was 6.86 (SD 2.52) months (range
3.1-14.47 months). RESULTS: IOP increased significantly (p<0.001) from 15.43
(3.26) mm Hg preoperatively to a mean maximum of 23.38 (8.37) mm Hg (range 13-64 
mm Hg) postoperatively. An IOP rise to values higher than 21 mm Hg was observed
in 39 (52%) eyes. Elevation of IOP occurred about 2 months after the injection.
Preoperative predictive factor for the rise in IOP was younger age (p=0.013). It 
was statistically independent of refractive error, presence of diabetes mellitus,
and indication for the injection. In all but one eye, IOP could be lowered to the
normal range with topical medication, without development of glaucomatous optic
nerve head changes. In the eyes with an elevation of IOP, IOP normalised about 6 
months after the injection, without further medication. Eyes undergoing
repeatedly intravitreal injections of triamcinolone acetonide showed only an
elevation of IOP, if after the first injection a rise of IOP had occurred.
CONCLUSIONS: After intravitreal injections of 25 mg of triamcinolone acetonide,
an IOP elevation can develop in about 50% of eyes, starting about 1-2 months
after the injection. In the vast majority, IOP can be normalised by topical
medication, and returns to normal values without further medication about 6
months after the injection.

PMID: 12488256 [PubMed - indexed for MEDLINE]

2685: Br J Ophthalmol. 2003 Jan;87(1):8-12.

Quality of life with macular degeneration: perceptions of patients, clinicians,
and community members.

Stein JD, Brown MM, Brown GC, Hollands H, Sharma S.

Center for Evidence-Based Health Care Economics, Flourtown, PA 19031, USA.
Lissa1011@aol.com

BACKGROUND/AIMS: Age related macular degeneration (ARMD) is a common
ophthalmological disorder that can significantly impair a patient's ability to
function independently and potentially have a dramatic impact on health related
quality of life. The aim of this study is to evaluate the quality of life of
patients with ARMD, through the use of utility evaluation, and assess whether
clinicians and healthy volunteers appreciate the impact of ARMD on health related
quality of life. METHODS: A standardised questionnaire using the time-tradeoff
method of utility analysis was created to assess health related quality of life. 
This questionnaire was distributed to 115 patients with ARMD. A similar
questionnaire was distributed to 142 healthy volunteers and 62 clinicians who
were asked to assume that they had ARMD. Comparisons were made among the
responses from the members of the three groups. RESULTS: There was a significant 
difference in the utility scores among respondents with mild, moderate, and
severe ARMD when compared to members of the general public and clinicians who
were asked to assume they had each severity of ARMD. For mild ARMD the mean
utility scores were 0.932, 0.960, and 0.832, for the general public, clinicians, 
and patients respectively (F = 21.7; p <0.001). No significant difference was
found between the community members and clinicians (p <0.166); however, the
patient group differed significantly from the general public (p<0.001) and
clinician (p <0.001) groups. The utility scores for moderate ARMD for the general
public, clinicians, and patients were 0.918, 0.877, and 0.732, respectively. (F =
34.6, p <0.001). There was no significant difference between the general public
and clinicians (p <0.143); however, the patient group differed significantly
compared with the general public (p <0.001) and clinician (p <0.001) groups. The 
utility scores for people with severe ARMD in the general public, clinician, and 
patient groups were 0.857, 0.821, and 0.566, respectively (F = 45.5; p <0.001).
No significant difference was shown between the community members and clinicians 
(p <0.386); however, a significant difference was seen when comparing the patient
group with the community member and clinician (p<0.001) groups. CONCLUSION:
Clinicians and community members may greatly underestimate the impact of mild,
moderate, and severe ARMD on health related quality of life.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12488253 [PubMed - indexed for MEDLINE]

2686: Retina. 2002 Dec;22(6):759-67.

Retinal thickness in diabetic retinopathy: a study using optical coherence
tomography (OCT).

Goebel W, Kretzchmar-Gross T.

Departmnent of Ophthalmology, University of Würzburg, Josef-Schneider-Strasse 11,
97080 Würzburg, Germany.

BACKGROUND AND OBJECTIVE: The authors conducted a controlled study to quantify
macular retinal thickness in diabetic retinopathy using optical coherence
tomography (OCT) as an objective and noninvasive tool. The relationship between
retinal thickness and standard methods of evaluating macular edema was
investigated. PATIENTS AND METHODS: A total of 136 patients in different stages
of diabetic retinopathy were examined with OCT. In addition, fluorescein
angiograms as well as standard eye examinations were conducted. The control group
consisted of 30 individuals with a normal macula. RESULTS: In the controls,
retinal thickness was 153 +/- 15 microm in the fovea, 249 +/- 19 microm in the
temporal parafoveal region, and 268 +/- 20 microm in the nasal parafoveal region.
In diabetic patients, retinal thickness was increased to 307 +/- 136 microm in
the fovea, 337 +/- 88 microm in the temporal retina, and 353 +/- 95 microm in the
nasal retina, respectively. The differences between diabetics and controls were
highly significant (P < 0.001). Retinal thickening correlated with fluorescein
leakage in the angiograms to some extent. There was an intermediate correlation
between retinal thickness and visual acuity, particularly in patients without
macular ischemia. Sensitivity of detecting clinically significant macular edema
by measuring foveal retinal thickness was 89% and specificity was 96%.
CONCLUSION: Optical coherence tomography allows us to quantify retinal thickness 
in diabetic retinopathy with excellent reproducibility. OCT is able to detect
sight-threatening macular edema with great reliability.

PMID: 12476103 [PubMed - indexed for MEDLINE]

2687: Retina. 2002 Dec;22(6):683-90.

Variability in fluorescein angiography interpretation for photodynamic therapy in
age-related macular degeneration.

Kaiser RS, Berger JW, Williams GA, Tolentino MJ, Maguire AM, Alexander J,
Madjarov B, Margherio RM.

Retina Service, Wills Eye Hospital, 9th and Walnut Streets, Philadelphia, PA
19107, USA. KaiserRick@AOL.com

OBJECTIVES: To investigate the variability in fluorescein angiography
interpretation for photodynamic therapy in age-related macular degeneration.
METHODS: Eight graders, who included two TAP-certified ophthalmologists, three
other retinal specialists, two fellows in vitreoretinal diseases, and a senior
fundus photograph grader, evaluated fluorescein angiograms of six patients
treated according to the Treatment for ARMD With Verteporfin (TAP) protocol at a 
single center. Each patient's baseline angiogram was evaluated to determine
whether the CNV lesion was predominantly (> or =50%) classic. For each follow-up 
angiogram, at 3, 6, 12, and 24 months, the grader was required to determine
whether fluorescein leakage was present. Six months after the initial gradings,
each reader was again presented with the baseline angiogram for each patient and 
once again asked to determine whether the CNV lesion was predominantly classic
without knowledge of the previous grading. All gradings were performed without
knowledge of the clinical course. RESULTS: In grading initial visit and follow-up
visit angiograms, the overall concordance rates were 81% and 82%, respectively.
Concordance rates were not statistically different between the group as a whole
when compared with the gradings of the two TAP-certified ophthalmologists. When
initial visit angiograms were regraded, an intraobserver variability of 17% was
noted. Overall, gradings were discordant with the majority opinion in
approximately 19% of decisions. CONCLUSIONS: Considerable variability can be
expected in fluorescein angiography interpretation as the results of the TAP
investigation are applied to clinical practice.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12476092 [PubMed - indexed for MEDLINE]

2688: Am J Ophthalmol. 2002 Dec;134(6):905-6.

Proton therapy for exudative age-related macular degeneration: a randomized,
sham-controlled clinical trial.

Ciulla TA, Danis RP, Klein SB, Malinovsky VE, Soni PS, Pratt LM, Pugh NO, Morphis
JG, Bloch C, Cameron J.

Retina Service, Department of Ophthalmology, Indiana University School of
Medicine, Indianapolis, Indiana, USA. thomasciulla@yahoo.com

PURPOSE: To examine the effect of proton beam irradiation on subfoveal choroidal 
neovascular membranes (CNVM) associated with age-related macular degeneration
(AMD).Randomized, prospective, sham-controlled, double-masked treatment trial.
METHODS: Thirty-seven subjects with subfoveal CNVM due to AMD were randomly
assigned to 16-Gy proton irradiation delivered in two fractions 24 hours apart or
to sham control treatment. Recruitment was halted at 37 subjects for ethical
reasons regarding randomization to sham treatment when Food and Drug
Administration approval of Visudyne was anticipated. RESULTS: Proton irradiation 
was associated with a trend toward stabilization of visual acuity, but this
association did not reach statistical significance. No correlations were found
within the fluorescein angiography data, including greatest linear dimension of
CNVM total size, area of active leakage, area of associated subretinal
hemorrhage, and intensity. CONCLUSIONS: With the acceptance of photodynamic
therapy, future studies will require more complex design and larger sample size
to determine whether radiation can play either a primary or adjunctive role in
treating these lesions.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12470761 [PubMed - indexed for MEDLINE]

2689: Am J Ophthalmol. 2002 Dec;134(6):857-62.

Impact of graphical user interface screen features on computer task accuracy and 
speed in a cohort of patients with age-related macular degeneration.

Scott IU, Feuer WJ, Jacko JA.

Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami
School of Medicine, Miami, Florida 33101, USA. iscott@bpei.med.miami.edu

PURPOSE: To investigate the impact of graphical user interface screen features on
computer task performance in patients with age-related macular degeneration
(AMD). DESIGN: Interventional case series. METHODS: Eighteen patients with visual
impairment due to AMD were recruited from the Bascom Palmer Eye Institute Low
Vision Clinic. Each patient underwent evaluation of visual acuity using the Early
Treatment Diabetic Retinopathy Study protocol, contrast sensitivity using a
Pelli-Robson chart, binocular simultaneous visual field using the Esterman
program on an automated perimeter, and color vision using Farnsworth D-15. Each
subject then completed computer icon identification tasks while the following
screen features of the graphical user interface were varied: size of icons
displayed, icon set size (number of icons displayed), and background color. Each 
patient performed all 125 computer tasks with each of five icon sizes (9.2 mm,
14.6 mm, 23.2 mm, 36.8 mm, 58.3 mm), each of five icon set sizes (2, 3, 4, 5, 6),
and each of five different background colors (black, white, red, green, blue) in 
a randomly ordered fashion. Relationships between computer task performance
(accuracy and speed) and graphical user interface screen features were studied.
RESULTS: Icon size and icon set size are significantly associated with computer
task accuracy (P <.001), whereas background color is not a significant predictor 
of task accuracy (P =.63). The impact of icon size on accuracy is nonlinear, with
the data indicating that no additional improvement in accuracy is associated with
increasing the icon size beyond 23.2 mm. The impact of icon set size on accuracy 
is linear, with a smaller icon set size significantly associated with greater
computer accuracy. A larger icon size is significantly associated with a shorter 
time to task completion (P =.001); this relationship is largely linearly related 
to icon size. There was no significant impact of background color (P =.11) or set
size (P =.37) on time to task completion. CONCLUSIONS: Modifications of graphical
user interface design may permit improved computer task performance among
patients with visual impairment due to AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, Non-P.H.S.

PMID: 12470754 [PubMed - indexed for MEDLINE]

2690: Am J Ophthalmol. 2002 Dec;134(6):849-56.

Reading ability after macular translocation surgery with 360-degree retinotomy.

Fujikado T, Asonuma S, Ohji M, Kusaka S, Hayashi A, Ikuno Y, Kamei M, Oda K, Tano
Y.

Department of Visual Science, Osaka University Medical School, Osaka, Japan.
fujikado@ophthal.med.osaka-u.ac.jp

PURPOSE: To report reading ability using a standardized reading chart after
macular translocation with 360-degree retinotomy in eyes with age-related macular
degeneration (AMD) or with myopic choroidal neovascularization (mCNV). DESIGN:
Interventional case series. METHODS: In 34 eyes of 34 patients with subfoveal
choroidal neovascular membrane (AMD, 23; mCNV, 11), macular translocation surgery
with 360-degree retinotomy and simultaneous extraocular muscle surgery were
performed. The average age was 67.4 +/- 7.9 years, and the average follow-up
period was 7.6 +/- 3.3 months. The best-corrected far visual acuity (FVA) was
measured with a standardized visual acuity chart using Landolt Cs, and the
critical print size (CPS) was determined with the Japanese version of the
Minnesota reading chart (MNREAD-J Chart) preoperatively and postoperatively.
Preoperative and postoperative change in the CPS was compared with the subjective
visual improvement as assessed by a questionnaire. RESULTS: The postoperative
improvement of FVA was statistically significant in eyes with mCNV (P =.010) but 
not significant in eyes with AMD (P =.495). The postoperative improvement of CPS 
was statistically significant both in eyes with AMD (P =.027) and in eyes with
mCNV (P =.004). The subjective visual improvement was significantly correlated
with the change of CPS in patients after a second better eye surgery.
CONCLUSIONS: After macular translocation with 360-degree retinotomy, the
improvement of reading ability was significant in eyes with both AMD and mCNV. We
conclude that this surgical method is well suited to improve reading ability of
patients with AMD or mCNV.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 12470753 [PubMed - indexed for MEDLINE]

2691: Am J Ophthalmol. 2002 Dec;134(6):842-8.

Association between reproductive and hormonal factors and age-related maculopathy
in postmenopausal women.

Snow KK, Cote J, Yang W, Davis NJ, Seddon JM.

Massachusetts Eye and Ear Infirmary, Epidemiology Unit, Boston, Massachusetts
02114, USA.

PURPOSE: The relationships between reproductive risk factors, including use of
hormone replacement therapy and oral contraceptives and severity of age-related
maculopathy (ARM) among postmenopausal women were evaluated. We hypothesized that
exposure to endogenous or exogenous estrogens would be associated with a reduced 
risk of advanced ARM. DESIGN: Cross-sectional study. METHODS: The 394 subjects
were postmenopausal women with ARM. Logistic regression analysis was used to
compare the effects of several reproductive factors across two groups: 193
subjects with nonadvanced ARM and 201 subjects with advanced ARM. RESULTS: Women 
with ARM who had used postmenopausal estrogen therapy in the past had
significantly lower odds of advanced ARM than nonusers, after controlling for
other known and potential risk factors (odds ratio [OR] = 0.5, 95% confidence
interval [CI] = 0.30 to 0.98). Older age at menarche was associated with
increased odds of advanced ARM (OR = 1.16, 95% CI = 1.00 to 1.35). CONCLUSIONS:
These findings suggest that exposure to exogenous estrogens may have a beneficial
effect of reducing the risk of advanced types of ARM in postmenopausal women with
ARM. Few therapeutic or preventive measures currently exist for ARM; therefore,
these results deserve further evaluation.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12470752 [PubMed - indexed for MEDLINE]

2692: Am J Ophthalmol. 2002 Dec;134(6):828-35.

Is early age-related maculopathy related to cognitive function? The
Atherosclerosis Risk in Communities Study.

Wong TY, Klein R, Nieto FJ, Moraes SA, Mosley TH, Couper DJ, Klein BE, Boland LL,
Hubbard LD, Sharrett AR.

Singapore Eye Research Institute & Department of Ophthalmology, National
University of Singapore, Singapore. ophwty@nus.edu.sg

PURPOSE: Age-related maculopathy (ARM) and cognitive impairment are both
neurodegenerative disorders associated with aging and have been hypothesized to
share common pathogenic pathways. We describe the association between cognitive
function and ARM in middle-aged persons. DESIGN: Population-based,
cross-sectional study involving participants of the Atherosclerosis Risk in
Communities Study, an ongoing cardiovascular investigation of persons 51 to 70
years of age, examined every 3 years between 1987 to 1998. METHODS: At visit
three (1993-1995), retinal photographs were obtained and evaluated for ARM using 
a modification of the Wisconsin ARM Grading System. Cognitive function was
assessed using standardized tests (Delayed Word Recall, Digit Symbol, and Word
Fluency) at visits two (1990-1992) and four (1996-1998) and averaged for
analysis. Severe cognitive impairment was defined as scores falling in the lowest
10th percentile of the population. RESULTS: Data were available in 9286 persons
after exclusion of persons with stroke or using antipsychotic medication. After
adjusting for age, gender, race, education, diabetes, hypertension, cigarette
smoking, and alcohol consumption, persons with severe cognitive impairment based 
on Word Fluency Test scores were more likely to have early ARM (odds ratio [OR]: 
1.6, 95% confidence interval [CI]: 1.1-2.2) and its components, soft drusen (OR: 
1.6; 95% CI: 1.1-2.3) and pigmentary abnormality (OR: 1.5; 95% CI: 0.9-2.5) than 
those without severe impairment. However, severe cognitive impairment in scores
of the other two cognitive function tests was not associated with ARM.
CONCLUSION: These population-based data suggest a weak association between
cognitive function and early ARM in middle-aged persons.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.

PMID: 12470750 [PubMed - indexed for MEDLINE]

2693: Am J Ophthalmol. 2002 Dec;134(6):822-7.

Detachment of subfoveal choroidal neovascularization in age-related macular
degeneration.

Rumelt S, Kaiserman I, Rehany U, Ophir A, Pikkel J, Loewenstein A.

Department of Ophthalmology, Hadassah University Hospital, Jerusalem, Israel.

PURPOSE: To report the entity of partial detachment and folding of subfoveal
choroidal neovascularization (CNV) in age-related macular degeneration (ARMD).
DESIGN: Interventional case reports. METHODS: Review of the features of CNV
detachment in two patients with CNV due to ARMD by contact lens slit-lamp
biomicroscopy, fluorescein angiography, optical coherence tomography, and
three-dimensional confocal scanning laser indocyanine green (ICG) angiography.
RESULTS: One patient out of approximately 300 (0.5%) ARMD patients treated by
photodynamic therapy (PDT) developed partial CNV detachment and folding 6 weeks
after the second PDT treatment. Another patient out of approximately 100 (1.0%)
ARMD patients treated by transpupillary thermotherapy (TTT) developed partial CNV
detachment and folding 6 weeks after the second TTT treatment. The CNVs were
large (2,500 microm to 4,500 microm) and located between the retina and the
retinal pigment epithelium. In each, these findings were clearly visualized by
slit-lamp biomicroscopy. Fluorescein angiography demonstrated an associated
retinal pigment epithelium tear in one patient. Optical coherence tomography
showed distinctive features and confocal scanning laser ICG further delineated
the detached folded CNV. The best-corrected visual acuity improved in one patient
from 20/80 to 20/40 and in the other from counting fingers at 6 feet to 20/200
after the CNV detachment. CONCLUSIONS: Partial CNV detachment and folding
represent a unique, not previously reported, and possibly favorable outcome of
PDT and TTT. The low energy and selectivity of these treatments may explain this 
phenomenon.

Publication Types: 
    Case Reports

PMID: 12470749 [PubMed - indexed for MEDLINE]

2694: Med Image Anal. 2003 Mar;7(1):95-108.

Detection and segmentation of drusen deposits on human retina: potential in the
diagnosis of age-related macular degeneration.

Rapantzikos K, Zervakis M, Balas K.

Department of Electronic Computer Engineering, Digital Image and Signal
Processing Laboratory, Technical University of Crete, GR-73100 Crete, Greece.

Assessment of the risk for the development of age-related macular degeneration
requires reliable detection and quantitative mapping of retinal abnormalities
that are considered as precursors of the disease. Typical signs for the latter
are the so-called drusen that appear as abnormal white-yellow deposits on the
retina. Segmentation of these features using conventional image analysis methods 
is quite complicated mainly due to the non-uniform illumination and the
variability of the pigmentation of the background tissue. This paper presents a
novel segmentation algorithm for the automatic detection and mapping of drusen in
retina images acquired with the aid of a digital Fundus camera. We employ a
modified adaptive histogram equalization, namely the multilevel histogram
equalization (MLE) scheme, for enhancing local intensity structures. For the
detection of drusen in retina images, we develop a novel segmentation technique, 
the histogram-based adaptive local thresholding (HALT), which extracts the useful
information from an image without being affected by the presence of other
structures. We provide experimental results from the application of our technique
to real images, where certain abnormalities (drusen) have slightly different
characteristics from the background. The performance of the algorithm is
established through statistical analysis of the results. This analysis indicates 
that the proposed drusen detector gives reliable detection accuracy in both
position and mass size.

PMID: 12467724 [PubMed - indexed for MEDLINE]

2695: Ophthalmology. 2002 Dec;109(12):2272-8.

Dietary antioxidant intake and incidence of early age-related maculopathy: the
Blue Mountains Eye Study.

Flood V, Smith W, Wang JJ, Manzi F, Webb K, Mitchell P.

Department of Public Health and Community Medicine, Westmead Hospital, University
of Sydney, Sydney, Australia.

OBJECTIVE: To investigate associations between dietary intake, including modest
supplement intake, of antioxidant vitamins and zinc at baseline and the 5-year
incidence of early age-related maculopathy (ARM). DESIGN: Population-based cohort
study. PARTICIPANTS: From 1992 through 1994, 3654 persons aged 49 years or more
(82% of those eligible) living in two postcode areas west of Sydney, Australia,
were examined for the Blue Mountains Eye Study baseline. Five years later, 2335
persons (75% of known survivors) were reexamined. METHODS: A 145-item Food
Frequency Questionnaire (FFQ) was used to assess nutrient intakes. Of the 2335
people who attended a follow-up visit, 1989 (85%) had completed a FFQ at
baseline. The nutrients examined in this study included: alpha-carotene,
beta-carotene, beta-cryptoxanthin, lutein and zeaxanthin, lycopene, retinol,
vitamin A, vitamin C, and zinc. MAIN OUTCOME MEASURES: Early ARM was assessed by 
masked grading of stereo retinal photographs. Definitions for incidence closely
followed those used in the Beaver Dam Eye Study. RESULTS: Early ARM developed in 
192 persons (8.7% 5-year incidence) who did not have either late or early ARM at 
baseline. Of these, 159 persons completed the FFQ at baseline. After adjusting
for age, gender, family history of ARM, and smoking status at baseline, no
associations, or any trends suggesting possible association, were found between
baseline intake of the nutrients examined, apart from vitamin C, and the 5-year
incidence of early ARM. Compared with the lowest quintile, increasing baseline
intakes of vitamin C, from diet and supplements, was associated with an increased
risk of incident early ARM (odds ratio [OR], 1.7; 95% confidence interval [CI],
1.0-3.0; and OR, 2.3; 95% CI, 1.3-4.0 for the fourth and fifth quintiles,
respectively). CONCLUSIONS: Our cohort study of an older population could not
find evidence of protection associated with usual dietary antioxidant or zinc
intakes (including use of supplements) on the 5-year incidence of early ARM.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12466170 [PubMed - indexed for MEDLINE]

2696: Optom Vis Sci. 2002 Nov;79(11):697-707.

Vision and mobility performance of subjects with age-related macular
degeneration.

Hassan SE, Lovie-Kitchin JE, Woods RL.

Centre for Eye Research, School of Optometry, Queensland University of
Technology, Australia. shirin@lions.med.jhu.edu

PURPOSE: To investigate the effects of age-related macular degeneration (ARMD) on
mobility performance and to identify the vision determinants of mobility in
subjects with ARMD. METHODS: Walking speed and the number of obstacle contacts
made on a 79-m indoor mobility course were measured in 21 subjects with ARMD and 
11 age-matched subjects with normal vision. The mobility measures were
transformed to percentage preferred walking speed and contacts score. The vision 
functions assessed included binocular visual acuity, contrast sensitivity, and
visual field. RESULTS: In this study, subjects with ARMD did not walk
significantly slower or make significantly more obstacle contacts on the mobility
course than the normally sighted subjects of similar age. Between 29% and 35% of 
the variance in the ARMD mobility performance was accounted for by visual field
and contrast sensitivity measures. The most significant predictor of mobility
performance scored as percentage preferred walking speed was the size of a
binocular central scotoma. CONCLUSION: As the size of a binocular central scotoma
increases, mobility performance decreases.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12462538 [PubMed - indexed for MEDLINE]

2697: J Struct Biol. 2002 Sep;139(3):181-9.

Collagen VI assemblies in age-related macular degeneration.

Knupp C, Amin SZ, Munro PM, Luthert PJ, Squire JM.

Biological Structure and Function Section, Biomedical Sciences Division, Imperial
College Faculty of Medicine, London, UK. c.knuup@ic.ac.uk

Age-related macular degeneration (AMD) is the most common cause of incurable
blindness in the developed world. Little is known about the pathogenesis of this 
condition, but deposits in Bruch's membrane and immediately beneath the retinal
pigment epithelium are frequent findings associated with this disease. Within
these deposits, molecular assemblies with an approximately 100-nm axial
periodicity are seen. Two types of assembly are present: one exhibiting
transverse double bands of protein density that are 30nm apart and repeat axially
every approximately 100nm; the other with transverse double bands of protein
density, 30nm apart and repeating axially every approximately 50nm. In this
second type of assembly, more prominent pairs of bands alternate with less
prominent ones. By comparison with analogous aggregates found in the vitreous of 
a patient with a full-thickness macular hole, collagen VI was singled out as the 
most probable protein constituent of the AMD aggregates. Possible models for the 
aggregation patterns of these assemblies are discussed in terms of collagen VI
dimers and tetramers. Understanding the structure and chemical composition of the
assemblies within the AMD basal deposits may prove of great help in understanding
the pathophysiology of AMD itself.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12457848 [PubMed - indexed for MEDLINE]

2698: Invest Ophthalmol Vis Sci. 2002 Dec;43(12):3641-5.

Relation between size at birth and risk of age-related macular degeneration.

Hall NF, Gale CR, Syddall H, Martyn CN, Phillips DI.

Medical Research Council Environmental Epidemiology Unit, University of
Southampton, Southampton General Hospital, United Kingdom. nfh@mrc.soton.ac.uk

PURPOSE: To determine whether poor fetal growth, as determined by size at birth, 
is associated with increased risk of age-related macular degeneration. METHODS: A
total of 660 men and women born in Sheffield, United Kingdom, between 1922 and
1930 and whose size at birth was available were traced and invited to take part
in the study. Of these, 392 attended for ophthalmic examination. Age-related
macular degeneration in these volunteers was determined by the Wisconsin
Age-Related Maculopathy Grading System. RESULTS: The mean birth weight of
subjects with macular degeneration (early or late) was heavier than that of those
without (7.6 lb vs. 7.3 lb, respectively; P = 0.03). After adjustment for age,
gender, and risk factors for macular degeneration, a significantly increased risk
of macular degeneration was found in subjects with higher birth weight (odds
ratio [OR] 1.5, 95% confidence interval [CI] 1.1-2.0 for each SD [1 lb, 5 oz]
increase in birth weight). Other parameters describing size at birth showed a
weaker relation or no relation with macular degeneration, but one of the measures
of fetal proportion (head circumference-to-birth weight ratio) was significantly 
associated with risk of macular degeneration. Subjects with macular degeneration 
had a significantly lower head circumference-to-birth weight ratio than did those
without (11.2 vs. 12.0 respectively, P = 0.01). CONCLUSIONS: The finding that
age-related macular degeneration was associated with increased rather than
decreased birth weight was unexpected. Failure of the developing fetus's normal
brain-sparing mechanism is a possible explanation for our finding of a lower head
circumference-to-birth weight ratio among subjects with macular degeneration.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12454030 [PubMed - indexed for MEDLINE]

2699: Diabetes Care. 2002 Dec;25(12):2328-34.

Macular edema reflects generalized vascular hyperpermeability in type 2 diabetic 
patients with retinopathy.

Knudsen ST, Bek T, Poulsen PL, Hove MN, Rehling M, Mogensen CE.

Medical Department M (Diabetes & Endocrinology), Aarhus Kommunehospital, Denmark.
stk@dadlnet.dk

OBJECTIVE: Diabetic maculopathy (DMa) is the most prevalent sight-threatening
type of retinopathy in type 2 diabetes and a leading cause of visual loss in the 
western world. The disease is characterized by hyperpermeability of retinal blood
vessels and subsequent formation of hard exudates and macular edema, the degree
of which can be estimated by measurement of retinal thickness. We examined
associations between retinal thickness as evaluated by optical coherence
tomography scanning (OCT), glomerular leakage as evaluated by urinary albumin
excretion rate (UAE), and general vascular leakage as evaluated by the
transcapillary escape rate of albumin (TER(alb)) in type 2 diabetic patients with
and without DMa. RESEARCH DESIGN AND METHODS: In 20 type 2 diabetic patients with
DMa and 20 type 2 diabetic patients without retinopathy matched for age, sex, and
duration of diabetes, we performed OCT, fundus photography, fluorescein
angiography, and 24-h ambulatory blood pressure measurement. UAE was determined
by radioimmunoassay. TER(alb) was determined as the initial disappearance of
intravenously injected (125)I-labeled human serum albumin. RESULTS: Patients with
diabetic maculopathy had higher HbA(1c) (8.5 +/- 1.5 vs. 7.4 +/- 1.2%, P < 0.05) 
and higher total cholesterol (5.8 +/- 0.7 vs. 5.2 +/- 0.9 mmol/l, P < 0.05) than 
patients without retinopathy. UAE was higher in the DMa group than in the group
with no retinopathy (9.3 x// 3.1 vs. 3.9 x// 1.9 micro g/min, P < 0.01). There
was no difference in TER(alb) between the two groups (6.0 +/- 1.6 vs. 6.6 +/-
1.5%, NS). In the group with DMa, OCT, TER(alb), and UAE correlated significantly
(OCT versus TER(alb): r = 0.55, P < 0.05; OCT versus UAE: r = 0.58, P < 0.01; UAE
versus TER(alb): r = 0.81, P < 0.01). Conversely, there were no correlations
between these three parameters in the group without retinopathy. CONCLUSIONS:
Macular edema seems to reflect a generalized vascular leakage in type 2 diabetic 
patients.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12453981 [PubMed - indexed for MEDLINE]

2700: Br J Ophthalmol. 2002 Dec;86(12):1330-5.

Cataract surgery and quality of life in patients with age related macular
degeneration.

Lundström M, Brege KG, Florén I, Lundh B, Stenevi U, Thorburn W.

Department of Ophthalmology, Blekinge Hospital, SE-371 85 Karlskrona, Sweden.
mats.lundstrom@ltblekinge.se

BACKGROUND: The coexistence of cataract and age related macular degeneration
(AMD) is not unusual, especially in the very elderly. The outcome of cataract
surgery in these cases depends on the effect of AMD on vision. In this study the 
authors have compared the outcome of cataract patients with AMD to that of
cataract patients with no vision threatening ocular comorbidity, and analysed
possible predictors of good or poor outcome. METHODS: An observational
prospective study on consecutive cases operated for cataract during 1 month at
six surgical departments affiliated to the Swedish National Cataract Register
(NCR). Data were collected according to the protocol of NCR and subjects
completed the Catquest questionnaire before and 6 months after surgery. 90
subjects with AMD were compared to 335 subjects with no sight threatening ocular 
comorbidity. RESULTS: Difficulties in performing various daily life activities
improved significantly for AMD subjects after surgery (p<0.001, Wilcoxon signed
rank test). Satisfaction with vision also improved significantly after surgery
(p<0.001, Wilcoxon signed rank test). Activity level and independence were
unchanged. Subjects with no ocular comorbidity had a still better outcome. The
most important variable related to a good self assessed functional outcome was
postoperative visual acuity irrespective of the presence of AMD. AMD subjects
scheduled for second eye surgery and AMD subjects dissatisfied with their vision 
before surgery had a poorer outcome. CONCLUSION: Subjects with various stages of 
dry AMD and cataract improved their self assessed visual function and
satisfaction with vision significantly after cataract extraction.

Publication Types: 
    Multicenter Study

PMID: 12446358 [PubMed - indexed for MEDLINE]

2701: Retina. 2002 Oct;22(5):557-68.

The nature of focal areas of hyperfluorescence or hot spots imaged with
indocyanine green angiography.

Fernandes LH, Freund KB, Yannuzzi LA, Spaide RF, Huang SJ, Slakter JS, Sorenson
JA.

LuEsther T Mertz Retinal Research Center, Manhattan Eye, Ear and Throat Hospital,
New York, NY 10021, USA. VRMNY@aol.com

PURPOSE: To clarify the frequency and nature of ICG angiographic "hot spots" seen
in patients with neovascular age-related macular degeneration (ARMD). METHODS: A 
consecutive series of newly diagnosed patients with neovascular ARMD and
fluorescein angiographic evidence of occult choroidal neovascularization (occult 
CNV) was imaged with ICG angiography. Eyes with ICG angiographic "hot spots" were
identified and further classified. A hot spot was defined as any area of abnormal
hyperfluorescence, in the mid to late stages of ICG angiography, measuring less
than 1 disk area in size. RESULTS: From a total of 190 patients (220 eyes) with
neovascular ARMD, 30 patients and 34 eyes (16%) with hot spots were identified.
Hot spots were noted to be of three distinct patterns: polypoidal choroidal
neovascularization (polypoidal CNV) in 21 of 34 eyes, or 62%; retinal angiomatous
proliferation (RAP) in 11 of 34 eyes, or 30%; and focal occult CNV in 2 of 34
eyes, or 8%. CONCLUSIONS: A focal area of intense hyperfluorescence or so-called 
hot spot seen on ICG angiography in neovascular ARMD is due to one of three
possible forms of neovascularization: most frequently polypoidal CNV, less
commonly RAP, and infrequently nonspecific, focal occult CNV. Since neovascular
ARMD may be caused by different types of neovascularization, each with distinct
clinical manifestations, natural course, visual prognosis, and response to
treatment, it is important to identify the precise nature of hot spots to
establish an accurate diagnosis and, when appropriate, a specific form of
management.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12441720 [PubMed - indexed for MEDLINE]

2702: Retina. 2002 Oct;22(5):536-44.

Effects of verteporfin therapy on contrast on sensitivity: Results From the
Treatment of Age-Related Macular Degeneration With Photodynamic Therapy (TAP)
investigation-TAP report No 4.

Rubin GS, Bressler NM; Treatment of Age-Related Macular Degeneration with
Photodynamic therapy (TAP) study group.

Institute of Ophthalmology, University College London, United Kingdom.
g.rubin@ucl.ac.uk

BACKGROUND: In the Treatment of Age-Related Macular Degeneration With
Photodynamic Therapy (TAP) investigation, verteporfin therapy reduced the risk of
at least moderate vision loss (defined as a loss of at least 15 letters of visual
acuity) in patients with subfoveal choroidal neovascularization (CNV) secondary
to age-related macular degeneration (ARMD). This report presents detailed
analyses of 24-month contrast sensitivity outcomes in these patients. METHODS:
The patients included in the TAP investigation had subfoveal CNV secondary to
ARMD and received verteporfin therapy (n = 402) or placebo (n = 207) at the first
visit, with retreatment at each 3-month follow-up visit if angiography revealed
fluorescein leakage from CNV. Contrast sensitivity was determined at each visit
using a Pelli-Robson chart. RESULTS: At the month 24 examination,
verteporfin-treated patients were less likely to lose at least 6 or 15 letters of
contrast sensitivity than placebo-treated patients (86 [21%] versus 94 [45%], and
27 [7%] versus 24 [12%], respectively; P < 0.05 for both comparisons). The
superiority of verteporfin therapy over placebo was greater in patients with
predominantly classic CNV at baseline, although verteporfin-treated patients with
minimally classic CNV also had better contrast sensitivity outcomes. CONCLUSIONS:
Consistent with visual acuity outcomes, verteporfin therapy reduced the risk of a
clinically relevant loss of contrast sensitivity in the total study population,
with the greatest effect in patients with predominantly classic subfoveal CNV
secondary to ARMD. Verteporfin-treated patients with minimally classic CNV also
had better contrast sensitivity outcomes than patients who received placebo.
Given the association between contrast sensitivity and visual disability, the
beneficial effects of verteporfin therapy on contrast sensitivity outcomes are
expected to have a favorable impact on patients' daily activities.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12441717 [PubMed - indexed for MEDLINE]

2703: Arch Ophthalmol. 2002 Nov;120(11):1443-54.

Verteporfin therapy of subfoveal choroidal neovascularization in patients with
age-related macular degeneration: additional information regarding baseline
lesion composition's impact on vision outcomes-TAP report No. 3.

Bressler NM, Arnold J, Benchaboune M, Blumenkranz MS, Fish GE, Gragoudas ES,
Lewis H, Schmidt-Erfurth U, Slakter JS, Bressler SB, Manos K, Hao Y, Hayes L,
Koester J, Reaves A, Strong HA; Treatment of Age-Related Macular Degeneration
with Photodynamic Therapy (TAP) Study Group.

Wilmer Photograph Reading Center, The Johns Hopkins University School of
Medicine, Baltimore, MD 21205-2002, USA. nmboffice@jhmi.edu

OBJECTIVE: To explore how baseline lesion composition influenced vision outcomes 
in patients with age-related macular degeneration (AMD) undergoing photodynamic
therapy with verteporfin (Visudyne) for subfoveal choroidal neovascularization
(CNV) in the Treatment of Age-Related Macular Degeneration With Photodynamic
Therapy Investigation. METHODS: Patients with subfoveal lesions secondary to AMD 
with evidence of classic CNV were categorized into 2 subgroups based on baseline 
color photographs and fluorescein angiograms assessed by graders at the Wilmer
Photograph Reading Center (The Johns Hopkins University School of Medicine)
before any outcome analyses as follows: (1) predominantly classic CNV (area of
classic CNV >/=50% of the area of the entire lesion) or (2) minimally classic CNV
(area of classic CNV <50% but >0% of the area of the entire lesion). Additional
exploratory analyses were performed in the predominantly classic subgroup to
investigate the effects of visual acuity, lesion size, prior laser
photocoagulation, phakic status, micronutrient use, and presence of occult CNV on
vision outcomes. MAIN OUTCOME MEASURES: Subgroup analyses of vision and
fluorescein angiographic outcomes at 1 and 2 years after study enrollment were
examined in an intent-to-treat analysis from 2 multicenter, double-masked,
placebo-controlled, randomized clinical trials. RESULTS: Compared with patients
who had minimally classic CNV, patients with predominantly classic CNV had a
worse initial mean visual acuity and smaller lesions and were more likely to have
lesions that included blood or blocked fluorescence. When evaluated by treatment 
assignment and lesion composition, 84% to 88% completed the month 24 examination.
In the subgroup with predominantly classic lesions, visual acuity outcomes were
consistently better in verteporfin-treated patients. Outcomes for patients with
predominantly classic lesions without occult CNV tended to be better than
outcomes for patients with predominantly classic lesions with occult CNV,
although the former tended to have smaller lesions and lower levels of visual
acuity at baseline. Contrast sensitivity and fluorescein angiographic outcomes
(total lesion size, progression of classic CNV, and absence of classic CNV) were 
better in verteporfin-treated patients than in placebo-treated patients in the
predominantly classic and the minimally classic CNV subgroups. In patients with
predominantly classic CNV, no interaction of the treatment benefit by phakic
status, micronutrient use, or prior laser photocoagulation therapy was noted.
CONCLUSIONS: Verteporfin therapy can safely reduce the risk of moderate and
severe vision loss in patients with subfoveal lesions that are predominantly
classic CNV secondary to AMD. While this benefit seemed to be even greater in the
absence of occult CNV, the effect may be related to the smaller lesions and worse
visual acuity associated with predominantly classic lesions without occult CNV
and not solely to the lesion composition itself. These analyses support initial
reports that verteporfin therapy should be used to treat patients with AMD who
have predominantly classic CNV, with or without occult CNV, but suggest that
further investigations should be performed to determine if lesions with a
minimally classic composition might benefit when they are smaller and have lower 
levels of visual acuity.

Publication Types: 
    Clinical Trial
    Comparative Study
    Meta-Analysis
    Randomized Controlled Trial

PMID: 12427056 [PubMed - indexed for MEDLINE]

2704: Eye. 2002 Nov;16(6):689-93.

Comment in:
    Eye. 2004 Jan;18(1):107-8.    Eye. 2004 Jan;18(1):108-9.

The role of serum lipids in exudative diabetic maculopathy: is there a place for 
lipid lowering therapy?

Chowdhury TA, Hopkins D, Dodson PM, Vafidis GC.

Department of Medicine, Central Middlesex Hospital, London, UK.
Tahseen.Chowdhury@bartsandthelondon.nhs.uk

Diabetic maculopathy is a common complication of diabetes mellitus, characterised
by macular oedema and frequently accompanied by lipid exudation. It is the major 
cause of loss of vision from diabetic retinopathy. There is some evidence to
implicate serum lipids in exudative maculopathy; cross-sectional studies suggest 
that higher serum lipid levels are found in patients with macular exudates, and
prospective studies have shown an increased risk of exudative maculopathy if
baseline cholesterol is higher.The treatment for diabetic maculopathy is laser
photocoagulation of the pigment epithelium. With the advent of systemic lipid
lowering therapy over the last decade, there may be potential for medical therapy
also. There is some anecdotal evidence of the effect of lipid lowering agents
(particularly statins) in reducing exudate, and a number of studies have shown
that lipid lowering therapy may reduce macular exudates, but numbers in these
trials are small. A randomised controlled trial is now required to investigate
whether the use of systemic lipid lowering therapy is of benefit in patients with
exudative maculopathy, even in the absence of dyslipidaemia.

Publication Types: 
    Review

PMID: 12439660 [PubMed - indexed for MEDLINE]

2705: Ageing Res Rev. 2003 Jan;2(1):11-24.

Adenosine triphosphate-binding cassette transporter genes in ageing and
age-related diseases.

Efferth T.

Virtual Campus Rhineland-Palatinate, Rodeneck Platz 2, 55126, Mainz, Germany.
efferth@vcrp.de

The family of adenosine triphosphate (ATP)-binding cassette (ABC) transporters is
the largest gene family known. While some ABC transporters translocate single
substances across membranes with high specificity, others transport a wide
variety of different lipophilic compounds. They are responsible for many
physiological processes and are also implicated in a number of diseases. The
present review focuses on ABC transporter genes which are involved in ageing and 
age-related diseases. Expression of ABCB1 (MDR1, P-glycoprotein) increases with
age in CD4(+) and CD8(+) T-lymphocytes indicating that P-glycoprotein may be
involved in the secretion of cytokines, growth factors, and cytotoxic molecules. 
As T cells in aged individuals are hyporesponsive leading to a reduced
immunodefence capability, a role of ABCB1 in age-related immunological processes 
is presumed. The ABCA1 (ABC1) gene product translocates intracellular cholesterol
and phospholipids out of macrophages. Genetic aberrations in ABCA1 cause
perturbations in lipoprotein metabolism and contribute to atherosclerosis. ABCA4 
(ABCR) represents a retina-specific ABC transporter expressed in rod
photoreceptor cells. The ABCA4 gene product translocates retinyl-derivatives.
Mutations in the ABCA4 gene contribute to age-related macular degeneration.
Polymorphisms in the sulfonylurea receptor gene (ABCC8, SUR1) are associated with
non-insulin-dependent diabetes mellitus (NIDDM). Sulfonylureas inhibit potassium 
conductance and are used to treat NIDDM by stimulation of insulin secretion
across ATP-sensitive potassium channels in pancreatic beta-cell membranes.
Possible diagnostic and therapeutic implications of ABC transporters for
age-related diseases are discussed.

Publication Types: 
    Review

PMID: 12437993 [PubMed - indexed for MEDLINE]

2706: Zhonghua Yi Xue Za Zhi (Taipei). 2002 Sep;65(9):435-40.

Frequency doubling technology perimetry in age-related macular degeneration.

Sheu SJ, Chen YY, Chou LC, Wu TT, Cheng KK.

Department of Ophthalmology, General Hospital, Kaohsiung, Taiwan, ROC.
sjsheu@isca.vghks.gov.tw

BACKGROUND: The role of frequency doubling technology perimetry (FDT) in glaucoma
has been promising in terms of speed and simplicity as well as in its high
sensitivity and specificity compared to conventional automatic perimetry. In this
study, we investigated the possible role of FDT in exudative type age-related
macular degeneration (ARMD). METHODS: FDT using full-threshold C-20 mode was
performed in patients with ARMD. The macula was classified into 3 zones by the
distance from the fovea center (zone I: central 1 degrees, zone II: central 3
degrees except zone I, zone III: central 5 degrees except zones I & II). The
lesion was scored into 3 ranks by the area ratio of involvement in each zone. The
retinal scores, visual acuity and disease duration were compared with the FDT
scores of the central target, which was graded into 5 ranks according to the
probability level of abnormal points on total deviation plots using Spearsman's
rank correlation method. RESULTS: Measurements from 32 eyes (30 patients) with
exudative ARMD were collected. The FDT scores of the central target correlated
significantly with the lesion scores in zone III (p = 0.033), but not with the
lesion scores in central 3 degrees (zone I: p = 0.383, zone II: p = 0.077).
Visual acuity was weakly correlated with the FDT scores of the central target (p 
= 0.022), and the lesion scores in zone III (p = 0.038), but strongly correlated 
with the lesion scores in zone I and zone II (p < 0.001). The FDT scores of the
central target were within normal limit in 20 eyes. CONCLUSIONS: Our results
suggest that FDT using full-threshold C-20 mode is not sensitive enough for the
detection of small macular lesions in ARMD. Therefore, it might not be a useful
functional evaluation in ARMD. Further modification of the central target of FDT 
is necessary to detect small macular lesions in ARMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12433030 [PubMed - indexed for MEDLINE]

2707: Am J Ophthalmol. 2002 Nov;134(5):765-8.

Macular infarction after transpupillary thermotherapy for subfoveal choroidal
neovascularization in age-related macular degeneration.

Benner JD, Ahuja RM, Butler JW.

Delmarva Vitreoretinal Center, Salisbury, Maryland, USA. bennerjeffrey@msn.com

PURPOSE: To report the complication of macular infarction after transpupillary
thermotherapy (TTT) for the treatment of subfoveal choroidal neovascularization
(CNV) due to age-related macular degeneration (AMD). DESIGN: Interventional case 
reports. METHODS: Among 107 consecutive patients with subfoveal CNV due to AMD, a
73-year-old woman with recurrent subfoveal classic choroidal neovascularization
and a 76-year-old man with subfoveal occult choroidal neovascularization with
adjacent areas of geographic retinal pigment epithelium atrophy noted a severe
decrease in visual acuity and photopsias within hours of undergoing TTT. RESULTS:
Both patients had marked whitening of the macula clinically and closure of the
perifoveal capillaries on fluorescein angiography. Immediately after treatment
their visual acuity decreased from 20/200 to 6/200 and from 20/400 to 2/200,
respectively. Several months later, all exudation had resolved and their visual
acuity had stabilized at 20/100 and 20/200, respectively. CONCLUSIONS: Macular
infarction is a rare complication that occurred in two of 107 patients undergoing
TTT for subfoveal CNV due to AMD. The presence of geographic retinal pigment
epithelium atrophy or a previous laser treatment scar in the macular region may
predispose patients to this complication.

Publication Types: 
    Case Reports

PMID: 12429257 [PubMed - indexed for MEDLINE]

2708: Am J Ophthalmol. 2002 Nov;134(5):675-80.

Optical coherence tomography findings in adult-onset foveomacular vitelliform
dystrophy.

Pierro L, Tremolada G, Introini U, Calori G, Brancato R.

Department of Ophthalmology & Visual Sciences, University Hospital S. Raffaele,
Milan, Italy.

PURPOSE: The purpose of this article is to analyze cross-sectional images of a
subretinal macular lesion, using optical coherence tomography (OCT) in eyes with 
adult-onset foveomacular vitelliform dystrophy (AOFVD), to compare thickness of
the neurosensory retina over the lesion with best-corrected visual acuity (BCVA) 
of each eye, and to compare OCT tomograms of AOFVD patients with OCT of Best
disease. DESIGN: Observational case series. METHODS: This is a retrospective
study which took place in a clinical practice. Forty-three patients (72 eyes)
with AOFVD and 12 patients (24 eyes) with Best's disease were studied. The
observation procedures used were biomicroscopic fundus examination, fluorescein
angiography (FA), indocyanine green angiography (ICGA), and optical coherence
tomography (OCT). The main outcome measures were a description of the typical
picture of AOFVD in OCT tomograms, the relationship between the neurosensory
retinal thickness over the lesion, the BCVA expressed in decimal terms, and a
comparison with description of OCT in Best disease. RESULTS: Of the 43 patients
affected by AOFVD, 29 had bilateral macular lesions. Fluorescein angiography
showed a central hypofluorescent spot surrounded by an irregular hyperfluorescent
ring in 65 of the 72 eyes. Indocyanine green angiography demonstrated a central
nonfluorescent spot and a hyperfluorescent area surrounding the central spot in
22 of 27 eyes examined. In all 72 eyes of 43 patients, OCT showed a well-defined 
central region of thickening in the reflective band representing the retinal
pigment epithelium (RPE). The relationship between the thickness of neurosensory 
retina over the lesion and BCVA was significant (P =.001, r(2) = 0.61). Optical
coherence tomography in all 24 eyes with Best disease showed a well-defined
central serous retinal detachment. CONCLUSION: In the 72 eyes with AOFVD, FA and 
ICGA presented different features. Instead, OCT tomograms showed a well-defined
subretinal thickening of the RPE in all the eyes. The lack of difference in OCT
patterns between cases with or without the hypofluorescent spot on angiography
was useful for confirming the diagnosis of AOFVD. Moreover, a reduced visual
acuity was evident in patients with a thinner neurosensory retinal layer over
AOFVD lesion. Finally, OCT images were also useful for distinguishing AOFVD from 
Best disease.

Publication Types: 
    Comparative Study

PMID: 12429242 [PubMed - indexed for MEDLINE]

2709: Clin Experiment Ophthalmol. 2002 Dec;30(6):419-23.

Analysis of the Arg345Trp disease-associated allele of the EFEMP1 gene in
individuals with early onset drusen or familial age-related macular degeneration.

Guymer RH, McNeil R, Cain M, Tomlin B, Allen PJ, Dip CL, Baird PN.

Centre for Eye Research Australia, Department of Ophthalmology, University of
Melbourne, East Melbourne, Victoria, Australia. rhg@unimelb.edu.au

BACKGROUND: A single base change within the EFEMP1 gene has been associated with 
malattia leventinese and Doyne honeycomb retinal dystrophy, two dominantly
inherited macular diseases with early onset drusen. The aim of this study was to 
determine whether the same disease allele was also associated with other forms of
early onset drusen or familial cases of age-related macular degeneration.
METHODS: Thirteen index cases of early onset drusen together with 15 other family
members were examined. In addition, 54 familial cases of age-related macular
degeneration were examined. Blood was taken for DNA analysis and screened for the
Arg345Trp disease-associated allele of the EFEMP1 gene. Twenty-four cases of
malattia leventinese or Doyne honeycomb retinal dystrophy were also screened as
positive controls. Another 150 ethnicity- and age-matched individuals acted as
controls. RESULTS: The Arg345Trp disease-associated allele in the EFEMP1 gene was
confirmed in individuals with malattia leventinese and Doyne honeycomb retinal
dystrophy. However, involvement of this allele was not evident in either early
onset drusen or familial age-related macular degeneration. CONCLUSIONS: The
Arg345Trp disease-associated allele of the EFEMP1 gene does not appear to be
associated with cases of early onset drusen that fall outside the diagnosis of
malattia leventinese or Doyne honeycomb retinal dystrophy, nor does it appear to 
play a role in familial age-related macular degeneration. These findings do not
exclude the involvement of other alleles of the EFEMP1 gene in either phenotype. 
The genetic mechanisms involved in the heterogeneous group of early onset drusen 
remain to be elucidated but should lead to insights into the genetic causes of
macular diseases.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12427233 [PubMed - indexed for MEDLINE]

2710: Clin Experiment Ophthalmol. 2002 Dec;30(6):404-10.

Low vision rehabilitation in patients with age-related macular degeneration at a 
tertiary eye care centre in southern India.

Khan SA, Das T, Kumar SM, Nutheti R.

Meera & LB Deshpande Centre for Sight Enhancement, LV Prasad Eye Institute,
Banjara Hills, Hyderabad, India. sarfaraz@lvpeye.stph.net

PURPOSE: To evaluate the specific needs and types of low vision devices (LVDs) in
patients with age-related macular degeneration (AMD) so as to use the residual
vision effectively. METHODS: One hundred consecutive patients with diagnosis of
AMD were evaluated to ascertain the degree of visual disability. Different LVDs
were used to suit the specific needs of individual patients. The distribution of 
LVDs for distance and near and other rehabilitation measures were stratified for 
vision >or=6/18 and <6/18. Statistical analysis was performed using chi2
test/Fisher's exact test and paired t-test. RESULTS: The percentage of patients
with visual acuity <6/18 reduced from 72.2% (26/36) to 47.2% (17/36) with the use
of standard spectacles (P = 0.03). Similarly, the percentage of patients with
visual acuity <6/18 reduced from 85.7% (6/7) to 14.3% (1/7) with the use of a
telescope (P = 0.029). The optical devices for near tasks included spectacle
magnifiers (n = 59), stand magnifiers (n = 19), and hand magnifiers (n = 18).
With these LVDs, the near vision improved from 0.13 (decimal notations) to 0.39
(P < 0.001). Eighty-six patients were given at least one of the LVDs and 20% were
prescribed more than one near device (bifocals, spectacle magnifiers, hand
magnifiers, stand magnifiers). Additionally, patients also needed counselling (n 
= 89) and training on eccentric viewing (n = 39), coin identification (n = 45),
and independent mobility (n = 41). CONCLUSION: The overall management of a
patient with AMD must include counselling, prescription of appropriate LVDs and
training to utilize the residual vision to its fullest advantage. This is
expected to improve the patient's quality of life.

PMID: 12427230 [PubMed - indexed for MEDLINE]

2711: Arch Ophthalmol. 2002 Nov;120(11):1551-8.

The association of cataract and cataract surgery with the long-term incidence of 
age-related maculopathy: the Beaver Dam eye study.

Klein R, Klein BE, Wong TY, Tomany SC, Cruickshanks KJ.

Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison,
610 N Walnut St, 460 WARF, Madison, WI 53726-2397, USA. kleinr@epi.ophth.wisc.edu

OBJECTIVE: To examine the association between cataract and cataract surgery and
the 10-year incidence of age-related maculopathy (ARM). METHODS: A
population-based cohort study of persons aged 43 to 86 years at baseline, living 
in Beaver Dam, Wis, of whom 3684 participated in a 5-year and 2764 in a 10-year
follow-up. We used standardized protocols for physical examination, blood
collection, health history, slitlamp and retroillumination photography of the
lenses to determine the presence of cataract, and stereoscopic color fundus
photography to determine the presence of ARM. We used the Kaplan-Meier
(product-limit) survival approach and discrete linear logistic regression in
analyses. MAIN OUTCOME MEASURES: The risk ratios (RRs) of persons with cataract
or cataract surgery at baseline. RESULTS: While controlling for age, sex,
systolic blood pressure, history of heavy drinking and smoking, and vitamin use, 
cataract at baseline was associated with incidence of early ARM (RR, 1.30; 95%
confidence interval [CI], 1.04-1.63), soft indistinct drusen (RR, 1.38; 95% CI,
1.08-1.75), increased retinal pigment (RR, 1.38; 95% CI, 1.07-1.79), and
progression of ARM (RR, 1.37; 95% CI, 1.06-1.77). We found no association with
the incidence of late ARM. In contrast, cataract surgery before baseline was
associated with incidence of late ARM (RR, 3.81; 95% CI, 1.89-7.69), increased
retinal pigment (RR, 1.89; 95% CI, 1.18-3.03), retinal pigment epithelial
depigmentation (RR, 1.95; 95% CI, 1.17-3.25), pure geographic atrophy (RR, 3.18; 
95% CI, 1.33-7.60), exudative macular degeneration (RR, 4.31; 95% CI, 1.71-10.9),
and progression of ARM (RR, 1.97; 95% CI, 1.29-3.02), but not with the incidence 
of early ARM. CONCLUSIONS: These findings indicate an association of cataract
with subsequent risk for early ARM. Cataract surgery increased the risk for late 
ARM.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12427071 [PubMed - indexed for MEDLINE]

2712: Arch Ophthalmol. 2002 Nov;120(11):1477-83.

Self-management of age-related macular degeneration and quality of life: a
randomized controlled trial.

Brody BL, Roch-Levecq AC, Gamst AC, Maclean K, Kaplan RM, Brown SI.

Shiley Eye Center, Department of Ophthalmology, University of California-San
Diego, 9415 Campus Point Dr, La Jolla, CA 92093-0946, USA.
sbrown@eyecenter.ucsd.edu

OBJECTIVE: To assess the effectiveness of an age-related macular degeneration
(AMD) self-management program, consisting of health education and enhancement of 
problem-solving skills, to improve quality of life as shown by measures of mood
and function. METHODS: Two hundred thirty-one community-dwelling cognitively
intact volunteers (mean age, 80.6 years) with advanced macular degeneration were 
randomly assigned to a 12-hour self-management program (n = 86), a series of 12
hours of tape-recorded health lectures (n = 74), or to a waiting list (n = 72).
MAIN OUTCOME MEASURES: The primary outcome measure was emotional distress
(Profile of Mood States). Secondary outcome measures included function (National 
Eye Institute Visual Function Questionnaire), social support (Duke Social Support
Index), outlook on life (Life Optimism Test-Revised), and self-confidence to
handle AMD-specific challenges in daily life (AMD Self-Efficacy Questionnaire).
Clinical depression was determined in accord with the Structured Clinical
Interview for the Diagnostic and Statistical Manual of Mental Disorders, Axis I, 
Fourth Edition, Research Version. RESULTS: The self-management group showed
significant improvement in measures of mood and function compared with controls. 
These changes were significantly greater for the depressed than for the
nondepressed subjects. Decreased emotional distress was associated with increased
self-efficacy, while improvements in function were associated with increases in
self-efficacy and perceived social support. CONCLUSIONS: These findings suggest
that the AMD self-management program was an effective intervention to enhance
well-being in older persons with poor eyesight due to AMD, particularly in those 
who were initially depressed.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, U.S. Gov't, P.H.S.

PMID: 12427060 [PubMed - indexed for MEDLINE]

2713: Arch Ophthalmol. 2002 Nov;120(11):1435-42.

The role of apoptosis in age-related macular degeneration.

Dunaief JL, Dentchev T, Ying GS, Milam AH.

305 Stellar Chance Labs, University of Pennsylvania, Philadelphia, PA 19104, USA.
jdunaief@mail.med.upenn.edu

OBJECTIVE: To investigate apoptosis in human age-related macular degeneration
(AMD). METHODS: Postmortem retinas with AMD and normal retinas were studied by
terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) to identify 
dying cells, and by immunocytochemistry with cell-specific antibodies to identify
rods and cones. Sections were also labeled for Fas, a cell surface receptor that 
triggers apoptosis in other cell types. The maculas with AMD had geographic
atrophy (GA) or exudative AMD. RESULTS: Maculas with AMD had statistically
significant increases in TUNEL-positive cells in the inner choroid, retinal
pigment epithelium (RPE), photoreceptors, and inner nuclear layers compared with 
normal retinas. In eyes with GA, TUNEL-positive rod and RPE cell nuclei were
present near edges of RPE atrophy. Photoreceptors in the maculas of eyes with AMD
were strongly Fas-positive, while normal photoreceptors were only weakly labeled.
CONCLUSIONS: Evidence in this study suggests that in human AMD, RPE,
photoreceptors, and inner nuclear layer cells die by apoptosis. Most
TUNEL-positive RPE and photoreceptor cells were at edges of atrophy, correlating 
with clinically observed expansion of atrophic areas with vision loss in patients
with GA. Increased Fas labeling in AMD photoreceptors indicates that the Fas/Fas 
ligand system may be involved in photoreceptor apoptosis. This information is
essential for developing rational therapy for AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12427055 [PubMed - indexed for MEDLINE]

2714: Ophthalmologica. 2002 Sep-Oct;216(5):363-7.

A novel relation of fatty acid with age-related macular degeneration.

Ouchi M, Ikeda T, Nakamura K, Harino S, Kinoshita S.

Department of Ophthalmology, Kyoto Prefectural University of Medicine, 465
Kawaramachi, Hirokoji agaru, Kajiicho, Kamigyo-ku Kyoto City, Kyoto 602-8566,
Japan. mouchi@ophth.kpu.m.ac.jp

To evaluate the relation between fatty acids and age-related macular degeneration
(ARMD), the fatty acid fractions within the red blood cell (RBC) membrane and
plasma of 11 ARMD patients and 10 healthy individuals (controls) were determined 
and compared. RBC arachidonic acid (AA) and docosahexaenoic acid (DHA) exhibited 
significantly higher values in the ARMD patients than in the controls. RBC levels
of palmitic, palmitoleic, oleic and linoleic acids, however, showed significantly
higher values in the controls than in the ARMD patients. No significant
variations were observed between the two groups in terms of plasma levels of AA, 
DHA, palmitic, palmitoleic, oleic and linoleic acids. Our findings indicate that 
polyunsaturated fatty acids, vulnerable to free radicals and reactive oxygen
species, and easily peroxidized, may be related to ARMD induction. Copyright 2002
S. Karger AG, Basel

PMID: 12424405 [PubMed - indexed for MEDLINE]

2715: Clin Chim Acta. 2002 Dec;326(1-2):97-104.

Is age-related macular degeneration associated with serum lipoprotein and
lipoparticle levels?

Abalain JH, Carre JL, Leglise D, Robinet A, Legall F, Meskar A, Floch HH, Colin
J.

Laboratoire de Biochimie, Faculté de Médecine, 22 Avenue Camille Desmoulins,
29200 Brest, France. jean-herve.abalain@univ-brest.fr

OBJECTIVE: The etiology of age-related macular degeneration (ARMD) is poorly
understood. Risk factors for cardiovascular disease have been thought to be
associated with ARMD. Our purpose was to measure the concentration of atherogenic
apolipoproteins (apo) and lipoparticles in serum from ARMD patients. METHODS: We 
analyzed lipids, lipoparticles and apolipoproteins concentrations in 84 unrelated
patients with ARMD and compared the results with those of age- and sex-matched
control subjects (n=62). Serum lipid concentrations were determined
enzymatically; apolipoproteins levels by kinetic nephelometry and lipoparticles
by electroimmunodiffusion. RESULTS: No difference in total cholesterol,
triglycerides, phospholipids, high- and low-density lipoprotein-cholesterol
(lHDL-C and LDL-C) concentrations were observed between ARMD patients and
controls. Apo E and LpE non-B concentrations were found to be higher in serum
from patients than in serum from controls. In contrast, Apo C-III and LpC-III
non-B concentrations were lower in serum from patients than in serum from
controls. CONCLUSIONS: The main differences observed between ARMD patients and
controls are in Apo E, Apo C-III, LpC-III non-B and LpE non-B concentrations.
These lipoparticles belong to the HDL family, which is considered to consist of
anti-atherogenic lipoproteins. These results raise the possibility that
cardiovascular risk factors are not associated with ARMD. Furthermore, we can
hypothesize that ARMD development is linked to perturbations of HDL metabolism.

Publication Types: 
    Comparative Study

PMID: 12417100 [PubMed - indexed for MEDLINE]

2716: Ophthalmology. 2002 Nov;109(11):2165-9.

Detection of drusen in the fellow eye of Japanese patients with age-related
macular degeneration using scanning laser ophthalmoscopy.

Ishiko S, Akiba J, Horikawa Y, Yoshida A.

Department of Ophthalmology, Asahikawa Medical College, Asahikawa, Japan.
ishiko@asahikawa-med.ac.jp

OBJECTIVE: To study the prevalence of drusen in the fellow eye of Japanese
patients with age-related macular degeneration (AMD). DESIGN: Retrospective,
cross-sectional study. PARTICIPANTS: Seventeen eyes of 17 Japanese patients with 
unilateral AMD. MAIN OUTCOME MEASURES: To compare the frequency of drusen based
on photography and scanning laser ophthalmoscopy with confocal and ring apertures
and a diode laser (780 nm). RESULTS: Using the scanning laser ophthalmoscope
(SLO) with a ring aperture, drusen were detected clearly as in topographic
imaging. In the fellow eyes of the study patients with AMD, photography showed
drusen in 10 cases (58.8%); however, SLO imaging detected drusen in 15 cases
(88.2%). The number of drusen detected using SLO imaging was significantly
greater than when using photography (P < 0.05). CONCLUSIONS: Scanning laser
ophthalmoscope imaging is superior to photography for detecting drusen in the
fellow eyes of Japanese patients with unilateral AMD. The prevalence of drusen in
the fellow eye of Japanese patients with AMD is much higher than previously
speculated.

Publication Types: 
    Comparative Study

PMID: 12414434 [PubMed - indexed for MEDLINE]

2717: Graefes Arch Clin Exp Ophthalmol. 2002 Oct;240(10):802-9. Epub 2002 Sep 14.

Macular pigment and visual acuity in Stargardt macular dystrophy.

Zhang X, Hargitai J, Tammur J, Hutchinson A, Allikmets R, Chang S, Gouras P.

Department of Ophthalmology, Columbia University, New York, NY 10032, USA.

PURPOSE: To test the hypothesis that macular pigment reflects foveal cone
function and possibly the presence of foveal cones in recessive Stargardt macular
dystrophy. METHODS: Sixteen patients (32 eyes) diagnosed to have Stargardt
macular dystrophy by clinical criteria were studied with a scanning laser
ophthalmoscope (SLO) comparing argon laser blue (488 nm), green (514),
helium-neon laser red (633 nm) and infrared diode laser (780 nm) images for the
presence or absence of macular pigment in the fovea. Fifteen of the patients were
screened for mutations in the ABCR gene. Eyes were graded into three categories: 
those without foveal macular pigment, those with partial pigment and those with
normal amounts of macular pigment. These categories were compared with visual
acuity determined by the Snellen chart. RESULTS: All patients with a visual
acuity of 20/200 or worse had no macular pigment in the fovea. All patients with 
visual acuity of 20/40 or better had a normal amount of macular pigment in the
fovea. Patients with partial macular pigment had intermediary acuity values
except for two eyes, one with 20/20 and another with 20/200 acuity. Infrared
light revealed more retinal abnormalities than blue light at early stages of the 
disease. CONCLUSION: Foveal macular pigment is related to foveal cone acuity in
Stargardt macular dystrophy and may be a marker for the presence of foveal cones.
Infrared light is a sensitive monitor of early Stargardt macular dystrophy.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.

PMID: 12397427 [PubMed - indexed for MEDLINE]

2718: Proc Natl Acad Sci U S A. 2002 Nov 12;99(23):14682-7. Epub 2002 Oct 21.

Comment in:
    Proc Natl Acad Sci U S A. 2002 Nov 12;99(23):14619-21.

Drusen proteome analysis: an approach to the etiology of age-related macular
degeneration.

Crabb JW, Miyagi M, Gu X, Shadrach K, West KA, Sakaguchi H, Kamei M, Hasan A, Yan
L, Rayborn ME, Salomon RG, Hollyfield JG.

Cole Eye Institute and Lerner Research Institute, Cleveland Clinic Foundation,
and Department of Chemistry, Case Western Reserve University, OH 44195, USA.
crabbj@ccf.org

Drusen are extracellular deposits that accumulate below the retinal pigment
epithelium on Bruch's membrane and are risk factors for developing age-related
macular degeneration (AMD). The progression of AMD might be slowed or halted if
the formation of drusen could be modulated. To work toward a molecular
understanding of drusen formation, we have developed a method for isolating
microgram quantities of drusen and Bruch's membrane for proteome analysis. Liquid
chromatography tandem MS analyses of drusen preparations from 18 normal donors
and five AMD donors identified 129 proteins. Immunocytochemical studies have thus
far localized approximately 16% of these proteins in drusen. Tissue
metalloproteinase inhibitor 3, clusterin, vitronectin, and serum albumin were the
most common proteins observed in normal donor drusen whereas crystallin was
detected more frequently in AMD donor drusen. Up to 65% of the proteins
identified were found in drusen from both AMD and normal donors. However,
oxidative protein modifications were also observed, including apparent
crosslinked species of tissue metalloproteinase inhibitor 3 and vitronectin, and 
carboxyethyl pyrrole protein adducts. Carboxyethyl pyrrole adducts are uniquely
generated from the oxidation of docosahexaenoate-containing lipids. By Western
analysis they were found to be more abundant in AMD than in normal Bruch's
membrane and were found associated with drusen proteins. Carboxymethyl lysine,
another oxidative modification, was also detected in drusen. These data strongly 
support the hypothesis that oxidative injury contributes to the pathogenesis of
AMD and suggest that oxidative protein modifications may have a critical role in 
drusen formation.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12391305 [PubMed - indexed for MEDLINE]

2719: J Cataract Refract Surg. 2002 Oct;28(10):1814-8.

Comment in:
    J Cataract Refract Surg. 2003 Jun;29(6):1053-4.    J Cataract Refract Surg. 2003 Jun;29(6):1054-5.    J Cataract Refract Surg. 2003 Jun;29(6):1055-6.

Latanoprost and clinically significant cystoid macular edema after uneventful
phacoemulsification with intraocular lens implantation.

Yeh PC, Ramanathan S.

Department of Ophthalmology and Visual Science, The University of Chicago,
Chicago, Illinois 60637, USA.

PURPOSE: To elucidate an association between latanoprost and clinically
significant cystoid macular edema (CME) in patients after uneventful
phacoemulsification with intraocular lens implantation. SETTING: Bergman Eye
Center, Department of Ophthalmology, The University of Chicago Hospitals,
Chicago, Illinois, USA. METHODS: One hundred forty-five consecutive patients (162
eyes) who had phacoemulsification from July 1999 to December 2000 were
retrospectively reviewed to determine which patients developed CME. Patients with
a history of inflammation and pseudoexfoliation, previous intraocular procedures,
or current intraoperative complications were excluded from the study. All cases
of CME were diagnosed on the basis of a fundus examination showing typical CME
accompanied by a decrease in visual acuity. Upon diagnosis, latanoprost was
discontinued and ketorolac was prescribed. The data were analyzed using the
Fisher exact test. Of the records reviewed, 134 patients (151 eyes) were included
in the study; 11 eyes were excluded secondary to intraoperative complications, a 
history of ocular inflammation, or both. Among the patients included, 12 were
receiving latanoprost preoperatively. RESULTS: Four cases of CME were identified;
all 4 patients were taking latanoprost. Latanoprost was discontinued in 8
patients 1 week preoperatively, and none of them developed CME. Therefore, in
this series, only patients receiving latanoprost developed CME after uneventful
cataract surgery. This difference was statistically significant. In addition, all
cases of CME resolved upon discontinuation of latanoprost and administration of
ketorolac. CONCLUSIONS: his retrospective study shows a clinical association
between latanoprost use and postoperative CME after uneventful
phacoemulsification. Given the absence of other coexisting risk factors for CME, 
this series suggests latanoprost is a significant etiologic factor for the
development of postoperative CME.

PMID: 12388034 [PubMed - indexed for MEDLINE]

2720: Am J Ophthalmol. 2002 Oct;134(4):577-85.

Predictors of drusen reduction after subthreshold infrared (810 nm) diode laser
macular grid photocoagulation for nonexudative age-related macular degeneration.

Rodanant N, Friberg TR, Cheng L, Aurora A, Bartsch D, Toyoguchi M, Corbin PS,
El-Bradey MH, Freeman WR.

Shiley Eye Center, University of California San Diego, La Jolla 92093, USA.

PURPOSE: To determine the predictors of drusen reduction in eyes with
nonexudative age-related macular degeneration (ARMD) treated with subthreshold
infrared (810 nm) diode laser macular grid photocoagulation. Additionally, to
determine the relationship of laser-induced drusen reduction and best-corrected
visual acuity (BCVA) 18 months after laser treatment.DESIGN: Randomized
controlled clinical trial.METHODS: Fifty patients (100 eyes) with bilateral
nonexudative ARMD were enrolled at two centers. One eye of each patient was
randomized to the observation; the other eye was treated with 48 subthreshold
(invisible end point) applications of infrared (810 nm) diode laser in a macular 
grid pattern. The eyes that received subthreshold laser treatment were compared
with the eyes that received no treatment. The baseline fundus characteristics
(number, size, and distribution of drusen, as well as focal hyperpigmentation)
from two macula areas (central 1500 micro diameter, pericentral 1500 micro ring
area) on stereo color photographs, the number of laser-induced lesions, and the
area of laser induced retinal pigment epithelial (RPE) lesions on fluorescein
angiography 3 months after treatment were studied as predictors of major drusen
reduction (> or = 50% drusen reduction from baseline) 18 months after laser
treatment. BCVA at baseline and 18 months later was compared in observation eyes 
and in laser-treated eyes.RESULTS: Eighteen months after randomization, 24 (48%) 
of 50 eyes treated with subthreshold laser had major drusen reduction compared
with three (6%) of 50 observation eyes (P =.00001). At 3 months post-treatment in
laser-treated eyes with major drusen reduction, the mean number of laser-induced 
lesions on fluorescein angiography was 30.7 and the mean area of RPE change was
0.81 mm(2) compared with 14.8 laser-induced lesions and 0.35 mm(2) area of RPE
change in eyes without major drusen reduction (P =.0001 and P =.0003,
respectively). At baseline, fundus characteristics were not significantly
different between observation eyes and laser-treated eyes or between the major
drusen reduction group and the nonmajor drusen reduction group. At 18 months
after treatment, BCVA was not significantly different in laser-treated eyes and
in observation eyes.CONCLUSIONS: Subthreshold infrared (810 nm) diode laser
macular grid photocoagulation in eyes with nonexudative ARMD significantly
reduced drusen 18 months after laser treatment. Both the number of subthreshold
laser lesions and the area of RPE changes visible on fluorescein angiography 3
months after treatment appeared to be predictors for major drusen reduction 18
months after treatment. However, it remains to be determined whether
laser-induced drusen reduction is beneficial for visual acuity or reduces the
incidence of choroidal neovascularization (CNV) in eyes with nonexudative ARMD.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12383815 [PubMed - indexed for MEDLINE]

2721: Am J Ophthalmol. 2002 Oct;134(4):560-5.

Comment in:
    Am J Ophthalmol. 2003 May;135(5):748-9; author reply 749.

Macular translocation with 360 degree retinotomy for management of age-related
macular degeneration with subfoveal choroidal neovascularization.

Pertile G, Claes C.

Department of Ophthalmology, Zivojnovic Foundation, Middelheim Hospital, Antwerp,
Belgium. grazia.pertile@belgacom.net

PURPOSE: The aim of this study is to evaluate the functional outcome in a group
of patients treated with full macular translocation (FMT) with 360-degree
retinotomy for treatment of age-related macular degeneration (ARMD) with
subfoveal choroidal neovascularization.DESIGN: Consecutive interventional case
series.METHODS: Fifty consecutive eyes (50 patients) with ARMD and subfoveal
neovascularization who underwent a FMT in our department from January 1999 to
July 2000 are included in this study. Compensatory muscle surgery, as described
by Eckardt and associates, was performed on all the eyes. The median follow-up is
21 months (range, 12 to 36; SD, 5.4).RESULTS: The best-corrected postoperative
visual acuity (BCVA) was improved by 2 or more Snellen lines in 33 eyes (66%) and
remained stable (+/-1 line) in 14 eyes (28%). Only 3 eyes (6%) experienced a
deterioration of the BCVA of 2 or more lines. The final BCVA was 20/50 or better 
in 32% of the cases; only 8 eyes (16%) had a final BCVA < 20/200. Thirty-four
(68%) patients are able to read newspaper print (3.3/10) with normal (+3 diopters
to +4 diopters) or increased (+5 diopters to +8 diopters) reading ads. Other
patients are able to read with magnifying systems. Complications included
proliferative vitreoretinopathy (PVR) in 9 eyes (18%), recurrent choroidal
neovascularization in 5 eyes (10%), diplopia in 3 eyes (6%), choroidal hemorrhage
in 2 eyes (4%), macular hole in 1 eye, and temporary hypotony in 1
eye.CONCLUSIONS: As 68% of the patients in the study group regained reading
vision with reading glasses, FMT can be considered an effective approach in cases
of subfoveal choroidal neovascularization. Further investigations are necessary
to determine which patients will have the most benefit from this complex
therapeutic method.

PMID: 12383813 [PubMed - indexed for MEDLINE]

2722: Arch Ophthalmol. 2002 Oct;120(10):1307-14.

Verteporfin therapy for subfoveal choroidal neovascularization in age-related
macular degeneration: three-year results of an open-label extension of 2
randomized clinical trials--TAP Report no. 5.

Blumenkranz MS, Bressler NM, Bressler SB, Donati G, Fish GE, Haynes LA, Lewis H, 
Miller JW, Monés JM, Potter MJ, Pournaras C, Reaves A, Rosenfeld PJ, Schachat AP,
Schmidt-Erfurth U, Sickenburg M, Singerman LJ, Slakter JS, Strong A, Vannier S;
Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP)
Study Group.

OBJECTIVE: To report vision and safety outcomes from an extension of a 2-year
investigation evaluating verteporfin photodynamic therapy in patients with
age-related macular degeneration with subfoveal choroidal neovascularization
(CNV). DESIGN AND SETTING: Open-label extension of selected patients from 2
multicenter, double-masked, placebo-controlled, randomized clinical trials, the
Treatment of Age-Related Macular Degeneration With Photodynamic Therapy (TAP)
Investigation, at 22 ophthalmology practices in Europe and North America.
PARTICIPANTS: Patients enrolled in the TAP Investigation and followed up for at
least 24 months in whom verteporfin therapy to CNV might reduce the risk of
further vision loss. METHODS: Before receiving verteporfin therapy in the
extension, eligible patients signed a written informed consent form accompanied
by an oral consent process approved by local institutional review boards. Methods
were similar to those described for 1- and 2-year results, with follow-up
examinations beyond 2 years continuing at 3-month intervals with a few
exceptions, including that extension patients with fluorescein leakage from CNV
were to receive open-label verteporfin therapy irrespective of their original
treatment assignment. RESULTS: Of 402 patients in the verteporfin group, 351
(87.3%) completed the month 24 examination; 320 (91.2%) of these enrolled in the 
extension study. The enrolled participants included 124 (78.0%) of the 159
verteporfin-treated patients with lesions composed of predominantly classic CNV
at baseline, of whom 105 (84.7%) completed the month 36 examination.
Verteporfin-treated patients with this lesion composition at baseline who
participated in the extension study, with or without a month 36 examination,
appeared more likely to have a younger age, better level of visual acuity,
absence of fluorescein leakage from classic CNV, or no progression of classic CNV
beyond the baseline boundaries of the lesion at the month 24 examination compared
with those who did not enroll in the extension. For the 105 patients with a
predominantly classic baseline lesion composition who completed the month 36
examination, an average of 1.3 treatments were given from the month 24
examination up to, but not including, the month 36 examination. A letter score
loss in the study eye of at least 15 from baseline for these patients occurred in
39 (37.5%) at the month 24 examination compared with 44 (41.9%) of these patients
at the month 36 examination. Visual acuity changed little from the month 24
examination (mean, -1.9 lines) to the month 36 examination (mean, -2.0 lines) for
these eyes. Verteporfin-treated patients had little change in the mean visual
acuity lost and few or no additional instances of infusion-related back pain or
photosensitivity reactions from month 24 to month 36. Two patients originally
assigned to placebo had acute severe vision decrease within 7 days after
verteporfin treatment during the extension. One patient originally assigned to
verteporfin had acute severe vision decrease after verteporfin treatment of the
fellow eye during the extension. CONCLUSIONS: Vision outcomes for
verteporfin-treated patients with predominantly classic lesions at baseline
remained relatively stable from month 24 to month 36, although only approximately
one third of the verteporfin-treated patients originally enrolled with this
lesion composition had a month 36 examination. From these results, the TAP Study 
Group identified no safety concerns to preclude repeating photodynamic therapy
with verteporfin. Additional treatment was judged likely to reduce the risk of
further vision loss. Caution appears warranted in the absence of comparison with 
an untreated group during the extension and since not all patients in the TAP
Investigation participated in the TAP Extension.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12365909 [PubMed - indexed for MEDLINE]

2723: Am J Pathol. 2002 Oct;161(4):1515-24.

Progressive age-related changes similar to age-related macular degeneration in a 
transgenic mouse model.

Rakoczy PE, Zhang D, Robertson T, Barnett NL, Papadimitriou J, Constable IJ, Lai 
CM.

Center for Ophthalmology and Visual Science, The University of Western Australia,
Crawley, Australia. rakoczy@cyllene.uwa.edu.au

Age-related macular degeneration (AMD) is the major cause of blindness in the
developed world. Its pathomechanism is unknown and its late onset, complex
genetics and strong environmental components have all hampered investigations.
Here we demonstrate the development of an animal model for AMD that reproduces
features associated with geographic atrophy; a transgenic mouse line (mcd/mcd)
expressing a mutated form of cathepsin D that is enzymatically inactive thus
impairing processing of phagocytosed photoreceptor outer segments in the retinal 
pigment epithelial (RPE) cells. Pigmentary changes indicating RPE cell atrophy
and a decreased response to flash electroretinograms were observed in 11- to
12-month-old mcd/mcd mice. Histological studies showed RPE cell proliferation,
photoreceptor degeneration, shortening of photoreceptor outer segments, and
accumulation of immunoreactive photoreceptor breakdown products in the RPE cells.
An accelerated photoreceptor cell death was detected in 12-month-old mcd/mcd
mice. Transmission electron microscopy demonstrated presence of basal laminar and
linear deposits that are considered to be the hallmarks of AMD. Small hard drusen
associated with human age-related maculopathy were absent in the mcd/mcd mouse
model at the ages analyzed. In summary, this model presents several features of
AMD, thus providing a valuable tool for investigating the underlying biological
processes and pathomechanism of AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12368224 [PubMed - indexed for MEDLINE]

2724: Arch Ophthalmol. 2002 Oct;120(10):1357-63.

Smoking and the 5-year incidence of age-related maculopathy: the Blue Mountains
Eye Study.

Mitchell P, Wang JJ, Smith W, Leeder SR.

Centre for Vision Research, Department of Ophthalmology, Westmead Hospital,
University of Sydney, Hawkesbury Road, Westmead, New South Wales, Australia 2145.
paulmi@westgate.wh.usyd.edu.au

OBJECTIVE: To assess the relationship between baseline smoking and the 5-year
incidence of late and early age-related maculopathy (ARM) in an older population 
cohort. METHODS: The Blue Mountains Eye Study examined 3654 participants aged 49 
years or older during 1992 to 1994 and then 2335 survivors (75.1%) after 5 years.
Retinal photographs were graded using the Wisconsin Age-Related Maculopathy
Grading System. Those with any ARM lesions at either examination were regraded in
detail using a side-by-side method similar to that developed for the Beaver Dam
Eye Study. We also used similar definitions for incident ARM lesions. Smoking
status was recorded at interview. RESULTS: Age-standardized incidence rates for
any late ARM lesions were 3.1%, 1.2%, and 1.4%, respectively, among baseline
current, past, or never smokers. Corresponding age-standardized incidence rates
for early ARM were 10.6%, 8.2%, and 9.3%, respectively. The mean age for cases
with incident late ARM was 67 years for baseline current smokers, 73 years for
past smokers, and 77 years for those who had never smoked (P =.02). After
adjusting for age, current smokers, compared with never smokers, had an increased
risk of incident geographic atrophy (age-adjusted relative risk [RR], 3.6; 95%
confidence interval [CI], 1.1-11.3) and any late ARM lesions (RR, 2.5; 95% CI,
1.0-6.2). Current smokers had an increased risk of incident retinal pigmentary
abnormalities (RR, 1.7; 95% CI, 1.1-2.7), with the risk higher in men (RR, 2.8;
95% CI, 1.4-5.6). OUTCOME MEASURES: Five-year incidence of early ARM, late ARM,
and ARM lesions. CONCLUSIONS: In this cohort, persons who were current smokers
had an increased risk of 5-year incident late ARM lesions and retinal pigmentary 
abnormalities. Current smokers developed late ARM at a significantly earlier age 
than never or past smokers.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12365915 [PubMed - indexed for MEDLINE]

2725: Ophthalmology. 2002 Oct;109(10):1780-7.

Resonance Raman measurement of macular carotenoids in normal subjects and in
age-related macular degeneration patients.

Bernstein PS, Zhao DY, Wintch SW, Ermakov IV, McClane RW, Gellermann W.

Department of Ophthalmology and Visual Sciences, Moran Eye Center, University of 
Utah School of Medicine, Salt Lake City, Utah 84132, USA.
paul.bernsteinhsc@hsc.utah.edu

PURPOSE: Dietary carotenoids lutein and zeaxanthin may play a protective role
against visual loss from age-related macular degeneration (AMD) through
antioxidant and light screening mechanisms. We used a novel noninvasive objective
method to quantify lutein and zeaxanthin in the human macula using resonance
Raman spectroscopy and compared macular pigment levels in AMD and normal
subjects. DESIGN: Observational study of an ophthalmology clinic-based
population. PARTICIPANTS AND CONTROLS: Ninety-three AMD eyes from 63 patients and
220 normal eyes from 138 subjects. METHODS: Macular carotenoid levels were
quantified by illuminating the macula with a low-power argon laser spot and
measuring Raman backscattered light using a spectrograph. This technique is
sensitive, specific, and repeatable even in subjects with significant macular
pathologic features. MAIN OUTCOME MEASURE: Raman signal intensity at 1525 cm(-1) 
generated by the carbon-carbon double-bond vibrations of lutein and zeaxanthin.
RESULTS: Carotenoid Raman signal intensity declined with age in normal eyes (P < 
0.001). Average levels of lutein and zeaxanthin were 32% lower in AMD eyes versus
normal elderly control eyes as long as the subjects were not consuming high-dose 
lutein supplements (P = 0.001). Patients who had begun to consume supplements
containing high doses of lutein (> or =4 mg/day) regularly after their initial
diagnosis of AMD had average macular pigment levels that were in the normal range
(P = 0.829) and that were significantly higher than in AMD patients not consuming
these supplements (P = 0.038). CONCLUSIONS: These findings are consistent with
the hypothesis that low levels of lutein and zeaxanthin in the human macula may
represent a pathogenic risk factor for the development of AMD. Resonance Raman
measurement of macular carotenoid pigments could play an important role in
facilitating large-scale prospective clinical studies of lutein and zeaxanthin
protection against AMD, and this technology may someday prove useful in the early
detection of individuals at risk for visual loss from AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12359594 [PubMed - indexed for MEDLINE]

2726: Ophthalmology. 2002 Oct;109(10):1767-79.

Ten-year incidence and progression of age-related maculopathy: The Beaver Dam eye
study.

Klein R, Klein BE, Tomany SC, Meuer SM, Huang GH.

Department of Ophthalmology and Visual Sciences, University of Wisconsin Medical 
School, Madison, Wisconsin 53726-2397, USA.

PURPOSE: The aim of the study was to describe the 10-year incidence and
progression of retinal drusen, retinal pigmentary abnormalities, and signs of
late age-related maculopathy. DESIGN: Population-based cohort study.
PARTICIPANTS: The study included 4926 persons, 43 to 86 years of age at the time 
of a baseline examination from 1988 through 1990, living in Beaver Dam,
Wisconsin, of whom 3684 participated in a 5-year follow-up examination and 2764
participated in a 10-year follow-up. METHODS: Characteristics of drusen and other
lesions typical of age-related maculopathy were determined by grading
stereoscopic color fundus photographs using the Wisconsin Age-Related Maculopathy
Grading System. MAIN OUTCOMES MEASURES: Incidence of drusen type and size,
pigmentary abnormalities, geographic atrophy, and exudative degeneration.
RESULTS: The 10-year incidence of early age-related maculopathy was 12.1% and of 
late age-related maculopathy it was 2.1%. There was a statistically significant
increased incidence of age-related maculopathy lesions with age (P < 0.05).
Individuals 75 years of age or older at baseline had significantly (P < 0.01)
higher 10-year incidences of the following characteristics than people 43 to 54
years of age: larger sized drusen (125 micro m-249 micro m, 26.3% vs. 3.3%; > or 
=250 micro m, 16.2% vs. 1.0%), soft indistinct drusen (22.2% vs. 2.2%), retinal
pigment abnormalities (19.5% vs. 0.8%), exudative macular degeneration (4.1% vs. 
0%), and pure geographic atrophy (3.1% vs. 0%). Compared with those with small
numbers of only small, hard drusen (1-2), those with large numbers of only hard
drusen (8 or more) had an increased 10-year incidence of both soft drusen (12.3% 
vs. 6.7%) and pigmentary abnormalities (4.9% vs. 1.7%). Eyes with soft indistinct
drusen or retinal pigmentary abnormalities at baseline, were more likely to
develop late age-related macular degeneration at follow-up than eyes without
these lesions (15.1% vs. 0.4% and 20.0% vs. 0.8%, respectively). CONCLUSIONS:
These population-based estimates document the high incidence of signs of
age-related maculopathy in people 75 years of age or older. Our findings
demonstrate that large numbers of hard drusen predict the incidence of soft
drusen and pigmentary abnormalities and that the presence of the latter lesions
significantly increases the risk for the development of geographic atrophy and
exudative macular degeneration.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12359593 [PubMed - indexed for MEDLINE]

2727: Ophthalmic Surg Lasers. 2002 Sep-Oct;33(5):362-7.

Retinal microaneurysmal closure following focal laser photocoagulation in
diabetic macular edema.

Gogi D, Gupta A, Gupta V, Pandav SS, Dogra MR.

Department of Ophthalmology, Postgraduate Institute of Medical Education &
Research, Chandigarh, India.

OBJECTIVE: To determine the temporal relationship of microaneurysmal dosure
following focal laser photocoagulation in diabetic macular edema. PATIENTS AND
METHODS: This prospective study included 25 eyes of 23 diabetic patients with
clinically significant macular edema. Ten to 20 well-defined microaneurysms were 
preselected and marked on an enlarged photograph of the prelaser fundus
fluorescein angiogram. These preselected microaneurysms were focally lasered and 
followed up angiographically at 48 hours, 1 week, 3 weeks, 6 weeks, and 12 weeks 
after photocoagulation. Thereafter, the average time span between
photocoagulation and the closure of the microaneurysms was determined. RESULTS:
The mean number of preselected microaneurysms at baseline was 18.24 +/- 3.51,
which remained the same at 48 hours. However, the mean microaneurysmal count
decreased to 11.76 +/- 2.65 (35% reduction) at 1 week, 9.12 +/- 2.53 (50%
reduction), 7.12 +/- 2.26 (61% reduction), and 4.56 +/- 1.32 (75% reduction) at
3, 6, and 12 weeks, respectively. The majority of the microaneurysms (35%) closed
between 48 hours and 1 week. CONCLUSIONS: The microaneurysmal closure following
focal laser photocoagulation is a delayed process. None of the preselected
microaneurysms showed closure within 48 hours, and 75% of the preselected
microaneurysms closed at the end of 12 weeks.

PMID: 12358288 [PubMed - indexed for MEDLINE]

2728: South Med J. 2002 Sep;95(9):1079-80.

Bilateral phakic cystoid macular edema associated with Crohn's disease.

Mason JO 3rd.

Department of Ophthalmology and Vitreoretinal Surgery, University of Alabama at
Birmingham School of Medicine, 35233, USA.

I report an association between Crohn's disease and bilateral phakic cystoid
macular edema. A 51-year-old man with a diagnosis of Crohn's disease was referred
for evaluation of decreased vision bilaterally. He had bilateral phakic cystoid
macular edema, with a vision of 20/40 in the right eye and 20/60 in the left eye.
Over a 2-year period, the patient was treated with nonsteroidal agents, as well
as steroids, systemically, topically, and periocularly. Each recurrence of the
Crohn's disease was associated with a worsening of the bilateral phakic cystoid
macular edema. During the treatment period, the patient did not have clinical
evidence of intraocular inflammation. Bilateral phakic cystoid macular edema may 
be associated with Crohn's disease, despite the lack of clinical evidence of
intraocular inflammation.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 12356117 [PubMed - indexed for MEDLINE]

2729: Indian J Ophthalmol. 2002 Sep;50(3):201-4.

Age-related changes in the macula. A histopathological study of fifty Indian
donor eyes.

Biswas J, Raman R.

Medical and Vision Research Foundation, Sankara Nethralaya, 18 College Road,
Chennai-600 006, India. drjb@sankaranethralaya.org

PURPOSE: Age-related macular degeneration (ARMD) is clinically less common in
India compared to the West. Therefore, clinicians are unfamiliar with
histopathologic evidence of age-related macular changes in the Indian population.
METHODS: Fifty consecutive human donor eyes removed for corneal grafting were
studied for gross, microscopic and histochemical features of age-related changes 
in the macula in the Indian population. A horizontal block was cut from the globe
including the optic disc, and the macula. Six sections, 6 microns thick, were cut
from three levels in the macula at a distance of 140 microns. These were stained 
with haemotoxylin-eosin, periodic acid-Schiff, Mallory, Masson trichrome, alcian 
blue and von Kossa stains. The presence of basal laminar deposits, drusen and
thickening and calcification of Bruch's membrane in the macula were assessed at
400 x magnification using a modified version of Sark's classification. RESULTS:
Twenty-four donor eyes (48%) had some form of age-related macular change. These
included basal laminar deposits, hard drusen, soft drusen, extensive retinal
pigment epithelium atrophy of the macula, and disciform degeneration of macula. A
combination of changes was often seen. Age-related changes were more common in
the seventh and eighth decade. CONCLUSION: Our study shows that histological
changes characteristic of the early stages of age-related macular degeneration
are fairly common in the Indian population. However, advanced macular changes are
significantly rare.

Publication Types: 
    Comparative Study

PMID: 12355694 [PubMed - indexed for MEDLINE]

2730: Ophthalmic Genet. 2002 Sep;23(3):167-74.

Use of denaturing HPLC and automated sequencing to screen the VMD2 gene for
mutations associated with Best's vitelliform macular dystrophy.

Marchant D, Gogat K, Dureau P, Sainton K, Sternberg C, Gadin S, Dollfus H,
Brasseur G, Hache JC, Dumur V, Puech V, Munier F, Schorderet DF, Marsac C,
Menasche M, Dufier JL, Abitbol M.

Centre de recherche thérapeutique en ophtalmologie, équipe d'accueil 2502 MENRT, 
Université René Descartes Paris V, Faculté de Médecine Necker-Enfants Malades,
Paris, France.

We identified three novel VMD2 mutations in patients with Best's macular
dystrophy. DHPLC analysis of the 11 VMD2 exons revealed abnormal profiles in exon
8. Direct sequencing showed that these abnormal profiles were due to monoallelic 
transitions and transversions. We also found three polymorphic sequence changes
that have been reported previously and annotated to an online database
(http://www.uni-wuerzburg.de/humangenetics/vmd2.html).

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12324875 [PubMed - indexed for MEDLINE]

2731: Am J Clin Nutr. 2002 Oct;76(4):897-902.

Relation of blood homocysteine and its nutritional determinants to age-related
maculopathy in the third National Health and Nutrition Examination Survey.

Heuberger RA, Fisher AI, Jacques PF, Klein R, Klein BE, Palta M, Mares-Perlman
JA.

Department of Ophthalmology, University of Wisconsin Medical School, Madison
53705-2397, USA.

BACKGROUND: Blood homocysteine and its nutritional determinants folate and
cyanocobalamin (vitamin B-12) have been shown to affect the risk of vascular
disease. The pathogenesis of age-related maculopathy (ARM) is related to adverse 
vascular changes. OBJECTIVE: The objective was to evaluate the associations
between homocysteine, its nutritional determinants, and ARM in persons aged >or= 
40 y participating in the third National Health and Nutrition Examination Survey.
DESIGN: A nonmydriatic fundus photograph of one eye, taken in a mobile
examination center, was used to ascertain ARM status. Phlebotomy was performed
for measurement of homocysteine, cyanocobalamin, and erythrocyte folate in
participants of phase 2 of the survey (n = 3828). Logistic regressions were used 
to compute odds ratios and 95% CIs by quintile of serum analyte by using sample
weights and jackknife replication methods to adjust for the complex survey
design. The final analyses were adjusted for potential risk factors that
influenced odds ratios. RESULTS: Total serum homocysteine, red blood cell folate,
and serum cyanocobalamin were unrelated to ARM in the overall sample. However,
red blood cell folate was inversely related to one type of early ARM lesion (soft
drusen) in non-Hispanic blacks. CONCLUSIONS: ARM does not appear to be associated
with homocysteine or its dietary determinants in this survey. There is a need for
further investigation to rule out potential associations in subgroups with low
folate status that may not have been detected because of the cross-sectional
survey design.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12324306 [PubMed - indexed for MEDLINE]

2732: Graefes Arch Clin Exp Ophthalmol. 2002 Sep;240(9):782-3. Epub 2002 Aug 13.

Intravitreal triamcinolone acetonide as treatment of macular edema in central
retinal vein occlusion.

Jonas JB, Kreissig I, Degenring RF.

Department of Ophthalmology and Eye Hospital, Faculty for Clinical Medicine,
Mannheim, Ruprecht-Karls-University Heidelberg, Germany.
jost.jonas@augen.ma.uni-heidelberg.de

PURPOSE: To report the clinical outcome of a patient receiving an intravitreal
injection of triamcinolone acetonide as treatment of bilateral, long-standing,
cystoid macular edema due to central retinal vein occlusion. METHODS: A
70-years-old patient suffering from bilateral central retinal vein occlusion for 
2 years and 1.5 years, respectively, received transconjunctivally an intravitreal
injection of 25 mg of crystalline triamcinolone acetonide in each eye, with 10
weeks between injections. RESULTS: During the follow-up period of 4 months (OD)
and 6 weeks (OS), respectively, visual acuity increased from 0.05 to 0.25 in his 
right eye and from 0.125 to 0.25 in his left eye. Fluorescein angiography showed 
a decrease of fluorescein leakage in the macular area. CONCLUSIONS: Intravitreal 
injection of triamcinolone acetonide may be a therapeutic option for
long-standing cystoid macular edema due to central retinal vein occlusion.

PMID: 12271378 [PubMed - indexed for MEDLINE]

2733: Graefes Arch Clin Exp Ophthalmol. 2002 Sep;240(9):735-8. Epub 2002 Aug 21.

Cataract surgery in patients with diabetic retinopathy: visual outcome,
progression of diabetic retinopathy, and incidence of diabetic macular oedema.

Krepler K, Biowski R, Schrey S, Jandrasits K, Wedrich A.

Department of Ophthalmology, University of Vienna, Währinger Gürtel 18-20, 1090
Vienna, Austria. katharina.krepler@akh-wien.ac.at

BACKGROUND: Compared to non-diabetic patients, outcome after cataract surgery was
reported to be worse in diabetic patients--especially in those with diabetic
retinopathy. This prospective study was planned to evaluate visual outcome,
progression of diabetic retinopathy, and incidence of clinically significant
macular oedema (CSME) in a homogenous group of patients with non-proliferative
diabetic retinopathy (NPDR) without CSME at baseline 1 year after cataract
surgery. METHODS: Over a period of 18 months, all consecutive patients with
mild-to-moderate diabetic retinopathy who had cataract surgery with
phacoemulsification and posterior chamber lens implantation were prospectively
followed up. Outcomes were assessed 1 year postoperatively and included visual
acuity (VA), progression of retinopathy, and incidence of CSME. Progression of
retinopathy and incidence of CSME were compared to the non-operated fellow eyes. 
RESULTS: Of 50 patients included, 42 completed the 1-year follow-up. VA improved 
in 85% of patients, and was better than 0,5 in 71%. Progression of retinopathy
occurred in 12% of eyes after cataract surgery and in 10.8% of non-operated
fellow eyes. No patient developed proliferative diabetic retinopathy in the
operated eye. CSME occurred in 13 operated eyes (31%), five of them with retinal 
ischemia, and in five non-operated eyes (13.5%). Patients with ischemic macular
oedema had the worst prognosis regarding VA. CONCLUSION: Modern cataract surgery 
seems to have no influence on the progression of diabetic retinopathy. A visual
improvement is achieved in the majority of patients with NPDR, but poorer visual 
outcome is observed in patients developing macular oedema.

PMID: 12271370 [PubMed - indexed for MEDLINE]

2734: Graefes Arch Clin Exp Ophthalmol. 2002 Sep;240(9):717-20. Epub 2002 Jul 24.

Tissue plasminogen activator plus gas injection in patients with subretinal
hemorrhage caused by age-related macular degeneration: predictive variables for
visual outcome.

Schulze SD, Hesse L.

Department of Ophthalmology, Philipps University Marburg, Robert Koch Strasse 4, 
35033 Marburg, Germany. stephan.schulze5@epost.de

PURPOSE: To assess factors predicting final visual outcome after displacement of 
subretinal hemorrhage (SRH) by intravitreally injected tissue plasminogen
activator (TPA) and gas in patients suffering from age-related macular
degeneration (ARMD). METHODS: We evaluated retrospectively the records of 67
patients (32 men, 35 women, mean age 77.2 years) suffering from SRH caused by
ARMD who underwent TPA and gas injection between April 1996 and October 2000.
Visual acuity (VA; preoperative, 1 week and 3 months postoperative) was analyzed 
with respect to duration and dimension of bleeding (diameter and thickness) and
patient's age. RESULTS: Mean preoperative VA was 0.063, compared with 0.1 at 3
months after injection. Twenty-nine of 47 patients (76%) had an increase in VA 1 
week after treatment but 14 of these eyes worsened slightly during follow-up.
Visual outcome 3 months after therapy was negatively correlated to thickness (
P<0.05) and diameter ( P<0.001) of the SRH. In a statistical model of a multiple 
regression analysis, postoperative VA and the shift of VA could be predicted by
preoperative VA and diameter of SRH. Patient's age, duration and thickness of SRH
had no prognostic value for postoperative visual outcome. CONCLUSION: After SRH
caused by ARMD, the best visual outcome after TPA + gas injection can be expected
in patients with preoperative VA of less than 0.1 caused by a small SRH. In the
presence of large SRH (diameter >5 mm) an increase in VA after therapy is
unlikely.

Publication Types: 
    Comparative Study

PMID: 12271367 [PubMed - indexed for MEDLINE]

2735: Am J Epidemiol. 2002 Oct 1;156(7):589-98.

Ten-year incidence of age-related maculopathy and smoking and drinking: the
Beaver Dam Eye Study.

Klein R, Klein BE, Tomany SC, Moss SE.

Department of Ophthalmology and Visual Sciences, University of Wisconsin Medical 
School, Madison, WI 53726-2397, USA. kleinr@epi.ophth.wisc.edu

The authors examined associations between smoking and alcohol consumption and the
long-term incidence of age-related maculopathy (ARM) in people in the Beaver Dam 
Eye Study who were aged 43-86 years (n = 3,684) in 1988-1990 and examined over a 
10-year period. ARM status was determined by grading stereoscopic color fundus
photographs. After controlling for age, sex, and other factors, the authors found
that people who had smoked more were more likely to develop large (> or =250
micro m in diameter) soft drusen (risk ratio (RR) per 10 pack-years smoked =
1.08, 95% confidence interval (CI): 1.02, 1.14) and pigmentary abnormalities (RR 
= 1.09, 95% CI: 1.04, 1.14) and to have progression of early ARM (RR = 1.05, 95% 
CI: 1.00, 1.10) than people who had smoked less. Smoking was not associated with 
the incidence of late ARM. People who reported being heavy drinkers at baseline
were more likely to develop late ARM (RR = 6.94, 95% CI: 1.85, 26.1) than people 
who reported never having been heavy drinkers. Smoking appears to have a modest, 
positive association with early but not late signs of ARM, and heavy drinking
appears to be related to an increased risk of late ARM, although the exposure and
outcome were infrequent, and the effect is based on few exposed cases.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12244027 [PubMed - indexed for MEDLINE]

2736: Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):13067-72. Epub 2002 Sep 19.

Aberrant accumulation of EFEMP1 underlies drusen formation in Malattia
Leventinese and age-related macular degeneration.

Marmorstein LY, Munier FL, Arsenijevic Y, Schorderet DF, McLaughlin PJ, Chung D, 
Traboulsi E, Marmorstein AD.

Cole Eye Institute, and Department of Cell Biology, Lerner Research Institute,
Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
marmorl@ccf.org

Malattia Leventinese (ML), an inherited macular degenerative disease, is closely 
reminiscent of age-related macular degeneration (AMD), the most common cause of
incurable blindness. Both ML and AMD are characterized by extracellular deposits 
known as drusen between the retinal pigment epithelium (RPE) and Bruch's
membrane. The mechanism underlying drusen formation is unknown. An Arg to Trp
mutation in a gene of unknown function, EFEMP1, is responsible for ML, indicating
EFEMP1 may be important in drusen formation. Here, we show that wild-type EFEMP1 
is a secreted protein whereas mutant EFEMP1 is misfolded, secreted inefficiently,
and retained within cells. In normal eyes, EFEMP1 is not present at the site of
drusen formation. However, in ML eyes, EFEMP1 accumulates within the RPE cells
and between the RPE and drusen, but does not appear to be a major component of
drusen. Furthermore, in AMD eyes, EFEMP1 is found to accumulate beneath the RPE
immediately overlaying drusen, but not in the region where there is no apparent
retinal pathology observed. These data present evidence that misfolding and
aberrant accumulation of EFEMP1 may cause drusen formation and cellular
degeneration and play an important role in the etiology of both ML and AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12242346 [PubMed - indexed for MEDLINE]

2737: Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):13090-5. Epub 2002 Sep 18.

Autologous transplantation of genetically modified iris pigment epithelial cells:
a promising concept for the treatment of age-related macular degeneration and
other disorders of the eye.

Semkova I, Kreppel F, Welsandt G, Luther T, Kozlowski J, Janicki H, Kochanek S,
Schraermeyer U.

Center for Molecular Medicine Cologne (ZMMK), Center of Ophthalmology, Department
of Retinal Surgery, Institute for Anatomy, University of Cologne, Kerpener
Strasse 34, D-50931 Cologne, Germany.

Age-related macular degeneration (ARMD) is the leading cause for visual
impairment and blindness in the elder population. Laser photocoagulation,
photodynamic therapy and excision of neovascular membranes have met with limited 
success. Submacular transplantation of autologous iris pigment epithelial (IPE)
cells has been proposed to replace the damaged retinal pigment epithelium
following surgical removal of the membranes. We tested our hypothesis that the
subretinal transplantation of genetically modified autologous IPE cells
expressing biological therapeutics might be a promising strategy for the
treatment of ARMD and other retinal disorders. Pigment epithelium-derived factor 
(PEDF) has strong antiangiogenic and neuroprotective activities in the eye.
Subretinal transplantation of PEDF expressing IPE cells inhibited pathological
choroidal neovascularization in rat models of laser-induced rupture of Bruch's
membrane and of oxygen induced ischemic retinopathy. PEDF expressing IPE
transplants also increased the survival and preserved rhodopsin expression of
photoreceptor cells in the RCS rat, a model of retinal degeneration. These
findings suggest a promising concept for the treatment of ARMD and other retinal 
disorders.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, Non-P.H.S.

PMID: 12239351 [PubMed - indexed for MEDLINE]

2738: Br J Ophthalmol. 2002 Oct;86(10):1139-42.

Diabetic macular oedema: the effect of photocoagulation on fluorescein transport 
across the blood-retinal barrier.

Sander B, Larsen M, Engler C, Moldow B, Lund-Andersen H.

Department of Ophthalmology, Herlev Hospital, University of Copenhagen, Dk 2730
Herlev, Denmark. bsander@idea.dk

BACKGROUND/AIM: The visual loss secondary to diabetic macular oedema can be
controlled to some extent by photocoagulation, though the mechanism of action is 
largely unknown. The purpose of the present study was to quantitate the effect of
photocoagulation on the blood-retinal barrier using fluorescein as a tracer of
passive and active transport. METHODS: A prospective study of 46 eyes in 34
patients with clinically significant macular oedema (CSMO) examined by vitreous
fluorometry before and 6 months after macular photocoagulation treatment.
RESULTS: In 23 eyes CSMO was not present at follow up (responding eyes), in
another 23 other eyes CSMO was still present (non-responding eyes). With
reference to the presence or absence of CSMO at follow up, the passive transport 
(permeability) for responding eyes decreased after photocoagulation in contrast
with an increase in non-responding eyes; the difference between the groups at
follow up was significant (p=0.03). The active transport for responding eyes
decreased slightly at follow up, while it increased for non-responding eyes; the 
difference between the groups at follow up was not significant (p=0.09).
CONCLUSION: Following photocoagulation a reduction of diabetic macular oedema,
defined as disappearance of CSMO, is paralleled by a decrease of the passive
permeability while the hypothesis of an increase in the active transport from the
retina to the blood could not be supported by this study.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12234895 [PubMed - indexed for MEDLINE]

2739: Br J Ophthalmol. 2002 Oct;86(10):1080-4.

Knowledge about cataract, glaucoma, and age related macular degeneration in the
Hong Kong Chinese population.

Lau JT, Lee V, Fan D, Lau M, Michon J.

Centre for Clinical Trials and Epidemiological Research, Chinese University of
Hong Kong.

AIMS: Patients' knowledge and participation in their care are important in
prevention of blindness from common eye diseases such as cataract, glaucoma, and 
age related macular degeneration (AMD). The aim of this study was to measure
knowledge of these conditions in the Hong Kong Chinese population. METHODS:
Subjects aged 40 and above in the Shatin district of Hong Kong were randomly
selected as part of a larger study of causes of adult visual loss. The subjects
received eye examinations in which the primary cause of visual disability was
recorded. The respondents were asked by trained interviewers in a standardised
fashion about their knowledge of cataract, glaucoma, and AMD. Their answers were 
rated for accuracy by a senior ophthalmologist. RESULTS: Out of the 2538 eyes
examined, 7.0% had visual acuity less than 6/18. Fully 69.6% of the visual
disability for those aged 60 or above was caused by cataract, AMD, or glaucoma.
Awareness of cataract in particular was high, in that over 90% of respondents had
heard of it. However, only 22.9% of them could describe cataract symptoms
correctly, and these percentages were even lower in glaucoma (10.2%) and AMD
(<1%). Over 40% of subjects did not know that surgery was an appropriate
treatment for cataract. CONCLUSION: This sample of the Hong Kong Chinese
population had limited knowledge of common eye diseases. Educational programmes
to enhance public awareness may be needed to improve the effectiveness of health 
promotion and thus prevent unnecessary blindness.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12234882 [PubMed - indexed for MEDLINE]

2740: Jpn J Ophthalmol. 2002 Jul-Aug;46(4):455-9.

Vitrectomy combined with phacoemulsification and intraocular lens implantation
for diabetic macular edema.

Amino K, Tanihara H.

Amino Eye Clinic, Shimonoseki, Yamaguchi Prefecture, Japan.

PURPOSE: The outcome of vitrectomy combined with phacoemulsification and
intraocular lens implantation (PEA+IOL) for diabetic macular edema was evaluated.
METHODS: Included in this study were 31 patients (42 eyes) with clinically
significant diabetic macular edema, in whom posterior vitreous detachment was not
observed. Pars plana vitrectomy combined with PEA+IOL was performed on 15 eyes.
Sixteen phakic eyes and 11 pseudophakic eyes were followed up without vitrectomy 
as controls. Visual acuity and the state of macular edema were evaluated.
RESULTS: After follow-up of 18 +/- 7 (mean +/- SD) months, clinically significant
macular edema remained in 3 eyes (20%) of the vitrectomy group, in 11 eyes (69%) 
of the phakic control group, and in 9 eyes (82%) of the pseudophakic control
group. The logarithm of the minimal angle of resolution (Log(MAR)) of the
best-corrected visual acuity of the vitrectomy group eyes significantly improved 
from 1.09 +/- 0.27 to 0.80 +/- 0.35 (P <.01), while that of pseudophakic control 
eyes significantly decreased from 0.59 +/- 0.17 to 0.86 +/- 0.28 (P <.05). The
Log(MAR) of phakic control eyes also decreased from 0.82 +/- 0.36 to 0.93 +/-
0.30, but there was no significant difference (P =.19). CONCLUSION: Vitrectomy
combined with PEA+IOL is an effective surgical modality to improve visual acuity 
in eyes with clinically significant diabetic macular edema.

PMID: 12225826 [PubMed - indexed for MEDLINE]

2741: Strabismus. 2002 Jun;10(2):111-7.

Strabological results in patients with macular translocation surgery and
counterrotation of the globe as a secondary procedure.

Sterker I, Wolf S, Wiedemann P.

Department of Ophthalmology, University of Leipzig, Germany.
sterkeri@medizin.unileipzig.de

INTRODUCTION: Age-related macular degeneration is the most common cause of
irreversible loss of visual acuity, including the ability to read, in elderly
patients. One of the surgical treatment options is macular translocation with 360
degrees retinotomy. The orthoptic results of torsional muscle surgery as a second
procedure are demonstrated. MATERIALS AND METHODS: Between January 1999 and
December 2000, the macula was rotated upward by 12-45 degrees in 10 eyes
following complete artificial detachment and a 360 degrees retinotomy. In these
patients, torsional surgery was carried out as a second procedure. Depending on
the resulting cyclotorsion, we performed surgery on the oblique muscles only in
four patients with a cyclotropia of 12-20 degrees and a combination of oblique
muscle surgery with surgery of two or four rectus muscles in the remaining six
eyes (cyclotropia over 21 degrees ). The pre- and postoperative diagnostic
techniques included visual acuity, reading vision and the orthoptic status.
RESULTS: Due to the unilateral ectopia of the macula, all patients presented
postoperative strabismus with a vertical deviation of 2-10 degrees and a
subjective cyclotropia between 12 degrees and 40 degrees. After surgery on the
oblique muscles, the patients showed a residual cyclotropia of 0-6 degrees. In
patients in whom surgery on the oblique muscles was accompanied by rectus muscle 
surgery, the remaining cyclotorsion was 5-13 degrees. Four patients excluded the 
non-operated fellow eye, six patients experienced double vision under binocular
conditions and thus required prescription of additional prism glasses.
CONCLUSION: Macular translocation causes diplopia under binocular conditions
because of the unilateral ectopia of the macular region with cyclotropia and
vertical deviation. These problems can be resolved or reduced by oblique muscle
surgery or in combination with additional surgery on the rectus muscles,
depending on the range of the cyclotorsion. Performing the torsional surgery as a
second procedure after macular rotation with an exact preoperative measurement of
the subjective cyclodeviation appears to be useful.

PMID: 12221489 [PubMed - indexed for MEDLINE]

2742: Sci Prog. 2002;85(Pt 2):131-50.

Clinical aspects of photodynamic therapy.

Barr H, Kendall C, Reyes-Goddard J, Stone N.

Department of Surgery, Cranfield Postgraduate Medical School, Gloucestershire
Royal Hospital, Great Western Road, Gloucester GL1 3NN, UK.
prof.barr@themail.co.uk

Photodynamic therapy is a method for local destruction of tissue or organisms by 
generating toxic oxygen and other reactive species using light absorbed by an
administered or an endogenously generated photosensitiser. It is a highly
promising treatment for patients with cancer. More recently it has found
increasing use as a method of therapy for non-cancerous illnesses. It depends on 
the exploitation of natural and vital reactions widespread in nature that have
driven and preserved life on this planet. Following administration of a
photosensitiser or its precursor there is an accumulation or retention in areas
of cancer and disease relative to adjacent normal tissue. The photosensitiser is 
inactive until irradiated by light, following which cellular destruction occurs. 
The clear attraction of this method is the possibility of some targeting of the
disease by drug and by the area irradiated. This explanation although
oversimplified has been the reason for the scientific and clinical interest in
photodynamic therapy. An understanding of evolutionary photobiology is enormously
helpful to understand disease response and clinical outcomes.

PMID: 12216278 [PubMed - indexed for MEDLINE]

2743: Ophthalmology. 2002 Sep;109(9):1737-44.

Patient selection for macular translocation surgery using the scanning laser
ophthalmoscope.

Fujii GY, de Juan E Jr, Sunness J, Humayun MS, Pieramici DJ, Chang TS.

Doheny Retina Institute at the Doheny Eye Center, University of Southern
California, Keck School of Medicine, Los Angeles, California. Wilmer
Ophthalmological Institute, The Johns Hopkins Hospital. Baltimore, Maryland, USA.

OBJECTIVES: To evaluate the use of the scanning laser ophthalmoscope (SLO) as a
predictor for potential visual improvement in eyes with subfoveal choroidal
neovascularization (CNV) secondary to age-related macular degeneration (AMD)
undergoing limited macular translocation. DESIGN: Retrospective noncomparative
case series. PARTICIPANTS: Consecutive series of 71 eyes of 70 patients with
subfoveal CNV secondary to AMD that underwent effective and uncomplicated limited
macular translocation at the Wilmer Ophthalmological Institute. METHODS:
Evaluation of the fundus microperimetry and fixation pattern was conducted on all
patients using the Rodenstock scanning laser ophthalmoscope (G. Rodenstock
Instrument GmbH, Munich, Germany) within 72 hours before surgery. MAIN OUTCOME
MEASURES: Sensitivity and specificity in addition to positive and negative
predictive values of SLO findings for visual outcome after macular translocation.
RESULTS: Stable fixation presented the highest positive predictive value for
visual acuity equal to or better than 20/100 (30 of 33 = 0.91), and predominantly
eccentric fixation had the highest negative predictive value for visual acuity
worse than 20/100 (7 of 9 = 0.78). Sensitivity was higher for the presence of
predominantly central fixation (42 of 48 = 0.87), and specificity was higher for 
relatively unstable/unstable fixation (20 of 23 = 0.87). CONCLUSIONS: Eyes with
stable and central fixation (without dense central scotoma) good preoperative
visual acuity, and short length of symptoms are those with the greatest chance to
achieve good vision after macular translocation. The knowledge of the fixation
and microperimetry pattern enables better understanding of the macular function
in eyes with AMD and may be useful for evaluation of baseline retinal cell
viability. Incorporation of these testing modalities may help to optimize patient
selection for macular translocation or other future techniques aimed at rescuing 
photoreceptors.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12208725 [PubMed - indexed for MEDLINE]

2744: Ophthalmology. 2002 Sep;109(9):1726-36.

Angiographic and flow patterns of retinal choroidal anastomoses in age-related
macular degeneration with occult choroidal neovascularization.

Axer-Siegel R, Bourla D, Priel E, Yassur Y, Weinberger D.

Department of Ophthalmology, Rabin Medical Center, Beilinson Campus, Petah Tiqva,
Israel. seegs@netvision.net.il

OBJECTIVE: To identify the angiographic features of retinal choroidal anastomoses
(RCAs) in patients with newly diagnosed occult choroidal neovascularization (CNV)
in the setting of age-related macular degeneration (AMD) and to determine the
sequence of flow between the RCA and the CNV. DESIGN: Retrospective
cross-sectional study. PARTICIPANTS: The angiograms of 205 eyes of 153
consecutive patients with occult CNV on fluorescein angiography (FA) and focal
hot spots on indocyanine green angiography (ICGA) were evaluated retrospectively.
METHODS OF TESTING: Red-free photographs and sequential digital fluorescein and
indocyanine green angiograms obtained by confocal scanning laser ophthalmoscope
(the Heidelberg Retina Angiograph; Heidelberg Engineering GmbH, Dossenheim,
Germany). MAIN OUTCOME MEASURES: The angiograms were evaluated for the presence
of RCA. The following angiographic characteristics were recorded: number and type
of anastomoses, location, distance from fovea, area of CNV, presence of pigment
epithelium detachment (PED), cystoid macular edema on FA, and intraretinal
leakage on ICGA. The direction of flow between the RCA and the CNV was identified
by analyzing high-speed angiograms. RESULTS: Retinal choroidal anastomoses were
identified in 57 eyes (28%), in 49 of 154 eyes with PED (32%), and in 8 of 51
eyes without PED (16%). Of 109 anastomoses, 70% were venous and 30% were
arterial. Ninety-six percent of the eyes had at least one venous anastomosis, 49%
of the eyes had an arterial anastomosis, and 46% of the eyes had both. Cystoid
macular edema was seen on FA in 37 eyes (65%), and intraretinal indocyanine green
leakage was noted in 52 eyes (91%). Twenty-two eyes that underwent high-speed
ICGA were analyzed for the direction of flow. All 15 eyes having arterial and
venous anastomoses demonstrated a filling pattern from the retinal arteriole to
the CNV, followed by the retinal venule. Seven eyes with venous RCA showed flow
sequence from the CNV to the collecting retinal venule. CONCLUSIONS: Our study
supports the presence of RCA in the early stages of acute exudative AMD with
occult CNV, mainly with serous PED. High-speed angiography helps to identify the 
filling sequence of the RCA and the CNV, and therefore may guide the clinician in
planning treatment strategies.

PMID: 12208724 [PubMed - indexed for MEDLINE]

2745: Surv Ophthalmol. 2002 Aug;47 Suppl 1:S203-18.

Prostaglandins and cystoid macular edema.

Miyake K, Ibaraki N.

Shohzankai Medical Foundation, Miyake Eye Hospital, 1070-Kami 5,
Higashiozone-cho, kita-ku, Nagoya 462-8023, Japan.

This review discusses the roles and interactions of prostaglandins and other
possible chemical mediators in cystoid macular edema. Prostaglandins have been
studied as a potential causative factor of cystoid macular edema following
cataract/intraocular lens surgery. The authors' hypothesis and data with regard
to the mechanisms of postoperative cystoid macular edema and other inflammatory
conditions are presented. The effects of nonsteroidal anti-inflammatory drugs,
which are antagonists of prostaglandin biosynthesis, on postoperative
inflammatory conditions including cystoid macular edema are also reviewed.
Lastly, a mechanism for the induction of cystoid macular edema by anti-glaucoma
eyedrops, including prostaglandin analogs is proposed. The results from two
clinical trials recently conducted by the authors suggest that the preservative
rather than the active ingredient is the causative factor.

Publication Types: 
    Review

PMID: 12204717 [PubMed - indexed for MEDLINE]

2746: Neuroscience. 2002;114(2):389-401.

Preservation of visual responsiveness in the superior colliculus of RCS rats
after retinal pigment epithelium cell transplantation.

Sauvé Y, Girman SV, Wang S, Keegan DJ, Lund RD.

Moran Eye Center, University of Utah Health Sciences Center, 50 North Medical
Drive, Salt Lake City, UT 84132, USA. yves.sauve@hsc.utah.edu

The dystrophic RCS rat undergoes progressive photoreceptor degeneration due to a 
primary defect in retinal pigment epithelial (RPE) cells. This has a major impact
on central visual responsiveness. Here we have examined how functional
deterioration is contained by subretinal transplantation of immortalized human
RPE cells. Transplantation was done at three to four weeks of age prior to
significant photoreceptor loss and recipients were kept on cyclosporin. At six
months of age, sensitivity maps and multi-unit response properties were obtained 
across the visual field by recording at 76 equidistant sites encompassing the
whole superior colliculus.A significant degree of functional protection, both in 
terms of area of responsive retina and response characteristics was observed
following RPE transplantation. At best, the sensitivity, latency of onset, and
response rise time were all maintained within normal ranges and this was achieved
with no more than half of the normal complement of photoreceptors. Although
partial, the degree of anatomical preservation (both in terms of outer nuclear
layer thickness and area of rescue) correlated well with the level of preserved
visual sensitivities. Sham injections also resulted in rescue, though the area of
preservation was strictly confined to the needle injury site and the response
properties were significantly worse than with RPE injections.This study shows
that central physiological responsiveness and correlated retinal morphology can
be preserved in an animal model of retinal disease by implantation of an
immortalized cell line. The use of retinal sensitivity measurements provides a
background for assessing higher visual functions in these animals and a direct
comparison for human perimetry measures.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12204208 [PubMed - indexed for MEDLINE]

2747: Invest Ophthalmol Vis Sci. 2002 Sep;43(9):2869-73.

Refractive errors and 10-year incidence of age-related maculopathy.

Wong TY, Klein R, Klein BE, Tomany SC.

Department of Ophthalmology and Visual Sciences, University of Wisconsin,
Madison, Wisconsin, USA. ophwty@nus.edu.sg

PURPOSE: To describe the relationship of refractive errors to the 10-year
incidence of age-related maculopathy (ARM) in a defined white population.
METHODS: Persons aged 43 to 86 years of age in Beaver Dam, Wisconsin, were
invited for a baseline examination from 1988 through 1990, and follow-up
examinations 5 and 10 years later (n = 3684). Refraction was measured at
baseline, with myopia defined as a spherical equivalent of -1.00 D or less,
emmetropia as -0.75 to +0.75 D and hyperopia as +1.00 D or more. At each
examination, signs of ARM were ascertained from grading stereoscopic color fundus
photographs based on a standard protocol. The association between baseline
refractive status and the 10-year incidence and progression of ARM was analyzed. 
RESULTS: The 10-year cumulative incidence for early ARM was 7.1%, 7.7%, and
11.7%, in eyes with myopia, emmetropia, and hyperopia, respectively. The
corresponding 10-year cumulative incidence for late ARM was 0.3%, 0.8%, and 2.2%.
When age was controlled for, there was no association between myopia and incident
early (relative risk [RR] 1.0, 95% confidence interval [CI], 0.7-1.3) and late
(RR 0.5, 95% CI, 0.2-1.5) ARM. Similarly, after controlling for age, hyperopia
was not associated with incident early (RR 0.9, 95% CI, 0.7-1.1) or late (RR 1.2,
95% CI, 0.6-2.3) ARM. CONCLUSIONS: These prospective population-based data
provide no evidence of an association between refractive errors and risk of ARM.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12202504 [PubMed - indexed for MEDLINE]

2748: Invest Ophthalmol Vis Sci. 2002 Sep;43(9):2819-24.

ABCA4 gene mutations in Japanese patients with Stargardt disease and retinitis
pigmentosa.

Fukui T, Yamamoto S, Nakano K, Tsujikawa M, Morimura H, Nishida K, Ohguro N,
Fujikado T, Irifune M, Kuniyoshi K, Okada AA, Hirakata A, Miyake Y, Tano Y.

Department of Ophthalmology, Osaka University Graduate School of Medicine, Osaka,
Japan.

PURPOSE: To evaluate photoreceptor cell-specific adenosine triphosphate
(ATP)-binding cassette transporter (ABCA4) gene mutations in Japanese patients
with Stargardt disease (STGD) and the correlation of these mutations to clinical 
phenotypes. METHODS: Serum was obtained from 10 unrelated Japanese patients with 
STGD and 96 unrelated Japanese patients with autosomal recessive retinitis
pigmentosa (arRP). All 50 ABCA4 gene exons of the patients with STGD were
screened for mutations by a combination of single-strand conformation
polymorphism analysis and polymerase chain reaction (PCR) direct-sequencing
techniques. By restriction enzyme digestion, primer extension analysis, and PCR
direct sequencing techniques, the patients with arRP were screened for three
segregated, presumably null ABCA4 gene mutations observed in Japanese patients
with STGD. RESULTS: Three novel, presumably null mutations of the ABCA4 gene,
IVS7-45_952delinsTCTGACC, IVS12+2T-->G, and 1894delA, were identified. The
Arg2149stop mutation that had been found in a white patient with STGD in a prior 
study was also found in a Japanese patient. Two arRP-affected siblings and two
unrelated patients with STGD were found to be homozygous for the same
IVS12+2T-->G mutation, and three other arRP-affected siblings were carriers of
the IVS12+2T-->G mutation and/or the IVS7-45_952delinsTCTGACC mutation. These
three siblings with arRP showed only atrophic degeneration in the macula early
after the onset of the disease, and STGD had been diagnosed. CONCLUSIONS: Three
novel ABCA4 gene mutations were identified in Japanese patients with STGD and
arRP. Mutations in the ABCA4 gene can cause panretinal degeneration that changes 
its clinical appearance from STGD to arRP over time.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12202497 [PubMed - indexed for MEDLINE]

2749: Int Ophthalmol. 2001;24(2):79-88.

Is acetazolamide effective in the treatment of diabetic macular edema? A pilot
study.

Giusti C, Forte R, Vingolo EM, Gargiulo P.

University La Sapienza , Rome, Italy. crigiust@tin.it

AIM: To investigate whether acetazolamide, already found to be helpful in
decreasing cystoid macular edema in patients with retinitis pigmentosa, was also 
effective in the treatment of diabetic macular edema in nonproliferative
retinopathy. METHODS: Two randomized age- and sex-matched groups (cases and
controls) of 12 diabetics (five Type 1 and seven Type 2) were selected for this
pilot study and graded for retinopathy (Early Treatment of Diabetic Retinopathy
Study-Airlie House Classification). Cases were treated with acetazolamide for
three months according to a standard protocol. The Early Treatment of Diabetic
Retinopathy Study chart was used for assessing far-best corrected visual-acuity, 
and fluorescein angiography was performed using the Heidelberg Retina Angiograph.
The Amsler grid-test and computerized-perimetry (Octopus 2000R) were also
performed. RESULTS: Fluorescein-angiographic findings and perimetric data
improved significantly (p < 0.01) in the acetazolamide-treated cases compared to 
the controls while visual-acuity varied only slightly (p > 0.01). The Amsler
grid-test resulted insignificant in our study (p > 0.05). No adverse effects or
significant variations in laboratory tests were recorded. CONCLUSION: Further
clinical investigations involving larger numbers of patients and a longer
follow-up are required to confirm these preliminary results. However, the present
study seems to suggest that acetazolamide could be effective in reducing
fluorescein-angiographic findings and improving perimetric data in diabetics with
macular edema, even though the mechanism of action remains obscure. Visual-acuity
varied only slightly.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 12201348 [PubMed - indexed for MEDLINE]

2750: Neuro Endocrinol Lett. 2002 Aug;23(4):370-2.

Treatment of macular degeneration (a controlled case).

Soucek P, Cihelková I.

The Eye Department, University Hospital, Srobárova 50, 100-34 Prague, Czech
Republic. soucek@fnkv.cz

Our controlled case describes the drug possibility to stabilize the exudative
form of Age-related Macular Degeneration. The new approach of selective
destruction of choroidal neovascularization (CNV) can be applied in patients with
subfoveal lesions. Photodynamic therapy (PDT) is based on the reaction of
photoactivable drug with the light of low-energy laser beam. So far only
verteporfin [Visudyne, Novartis] as sensitizer is marketed and laser with
wavelength of 689 nm is used. But it is questionable whether to apply this very
costly treatment to extremely old people. An example of treatment of 90-year old 
woman with AMD with classic form of CNV is presented. Her BCVA was 0.05 OD. She
underwent four session of PDT. At the last visit (eighteen months after initial
and ten months after last session of PDT) the BCVA remained 0.05 OD. The patient 
is using a special magnifying lens for reading achieving near vision of 0.32. The
presented example indicates the necessity of detailed study of every case to
promote the therapeutic decisions for the benefit of progress in the field.

Publication Types: 
    Case Reports

PMID: 12195243 [PubMed - indexed for MEDLINE]

2751: Eye. 2002 Sep;16(5):580-6.

Retrobulbar circulation in patients with age-related maculopathy.

Dimitrova G, Tamaki Y, Kato S.

Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo,
Japan. galina-tky@umin.ac.jp

PURPOSE: To investigate retrobulbar circulation in stages of age-related
maculopathy (ARM) and in normal fellow eyes of patients with unilateral exudative
ARM. METHODS: Color Doppler Imaging was used to measure circulatory parameters
(peak-systolic velocity--PSV, end-diastolic velocity--EDV, pulsatility index--PI 
and resistivity index--RI) in the central retinal, posterior ciliary and
ophthalmic arteries of 44 patients with age-related maculopathy (ARM) and 32
control subjects. Patients with ARM consisted of 11 with early ARM and 33 with
late ARM. Twenty-one patients from the exudative ARM group were also included in 
a study of unilateral exudative ARM circulation. RESULTS: In the study of
patients with ARM divided into stages, the PI and RI in the posterior ciliary
artery of patients with late ARM were significantly higher than that of the
control group (P = 0.0064; P = 0.0124). In the early ARM group, circulatory
parameters did not differ significantly from those of the control group.In the
study of unilateral exudative ARM, the affected eye showed significantly higher
RI, as compared to the control group (P = 0.0157), and the fellow eye had
significantly decreased EDV as compared to the control group (P = 0.0164). There 
was no significant difference in circulatory parameters between the affected and 
normal fellow eyes of patients with unilateral exudative ARM. CONCLUSION: PI and 
RI in patients with late ARM and EDV in fellow eyes of patients with unilateral
exudative ARM showed significant changes in the posterior ciliary artery compared
to normal controls. Altered circulation in the posterior ciliary artery may be
involved in the pathogenesis of ARM.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12194073 [PubMed - indexed for MEDLINE]

2752: Graefes Arch Clin Exp Ophthalmol. 2002 Aug;240(8):666-71. Epub 2002 Jul 24.

A new instrument for the quantification of macular pigment density: first results
in patients with AMD and healthy subjects.

Wüstemeyer H, Jahn C, Nestler A, Barth T, Wolf S.

Department of Ophthalmology, University of Leipzig, Liebigstrasse 10-14, 04103
Leipzig, Germany.

BACKGROUND: There is growing evidence that the development of age-related macular
degeneration (AMD) is related to oxidative damage. This makes macular pigment
(MP) an interesting target for research, as antioxidative quality is related to
MP. As studies have shown that MP density (MPD) can be increased by dietary
supplementation, MP may also offer a therapeutic or preventive approach to AMD.
METHODS: Using scanning laser techniques, we quantified MPD in healthy subjects
and patients with dry AMD. We introduce a modified scanning laser ophthalmoscope 
(SLO) which includes several advantages for the use in the clinical routine
compared to the standard SLO. RESULTS: We examined 10 healthy subjects without
ocular pathology and 10 patients with dry AMD (geographic atrophy). Eyes of
patients with AMD had a significantly lower MPD (mean value 0.094+/-0.022 density
units, DU) than healthy eyes (mean value 0.184+/-0.023 DU). CONCLUSIONS: It is
possible to quantify MPD using a scanning laser ophthalmoscope in a clinical
setting. The modified SLO offers several improvements with regard to the special 
requirements of the clinical situation. Using the new instrument, we were able to
detect differences in MPD between patients with dry AMD and young healthy
subjects. Further studies are needed to evaluate the reliability and
reproducibility of the method.

PMID: 12192461 [PubMed - indexed for MEDLINE]

2753: Graefes Arch Clin Exp Ophthalmol. 2002 Aug;240(8):628-38. Epub 2002 Jul 4.

Phenotypes of 16 Stargardt macular dystrophy/fundus flavimaculatus patients with 
known ABCA4 mutations and evaluation of genotype-phenotype correlation.

Gerth C, Andrassi-Darida M, Bock M, Preising MN, Weber BH, Lorenz B.

Department of Paediatric Opthalmology, Strabismology and Opthalmogenetics,
Klinikum, University of Regensburg, Germany.

PURPOSE: To determine the phenotypic variability in patients with compound
heterozygous or homozygous ABCA4 mutations, and to correlate the phenotypes with 
the functional properties of the altered protein. METHODS: Sixteen patients from 
13 families with signs of Stargardt macular dystrophy/fundus flavimaculatus and
known mutations on both alleles of the ABCA4 gene (15 compound heterozygous, one 
homozygous) were characterized by clinical examination, fundus autofluorescence, 
psychophysics (color vision, kinetic and two-color dark- and light-adapted static
threshold perimetry), and electrophysiology (Ganzfeld, multifocal ERG, EOG).
RESULTS: The homozygous 5917delG mutation resulted in the earliest disease
manifestation (at 5 years) and a general cone-rod dysfunction, whereas the
compound heterozygous mother (5917delG, G1961E) exhibited a very mild phenotype. 
Compound heterozygotes for the IVS40+5G-->A and the C1488Y or Y362X mutation
showed also an early age of onset but only a central dysfunction. The effect of
the 2588G-->C mutation, the G1961E mutation, and the complex mutation
L541P-A1038V depended on the mutation in the second allele. Genotype-phenotype
correlation appeared possible in most instances. Psychophysics revealed a
simultaneous yet not necessarily congruent cone and rod dysfunction. CONCLUSIONS:
The type and combination of ABCA4 mutations in compound heterozygous patients
determined were compatible with the severity of the phenotype as to age of onset 
and the functional consequences in the majority of patients. Unexplained
phenotypic differences indicate the influence of other factors. ABCA4 mutations
result in cone and rod dysfunction. Different disease durations limit the power
of presently available genotype-phenotype correlations.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12192456 [PubMed - indexed for MEDLINE]

2754: Acta Ophthalmol Scand. 2002 Aug;80(4):368-71.

Neovascular age-related macular degeneration and its relationship to antioxidant 
intake.

Snellen EL, Verbeek AL, Van Den Hoogen GW, Cruysberg JR, Hoyng CB.

Department of Epidemiology and Biostatistics, University Medical Centre,
Nijmegen, Netherlands.

PURPOSE: Experimental and epidemiological studies suggest that low antioxidant
intake may be associated with the occurrence of neovascular age-related macular
degeneration (AMD). METHODS: We investigated this hypothesis further with a
case-control study involving 72 case and 66 control patients attending the
Ophthalmology Department of the University Hospital in Nijmegen. Data were
collected by interview on antioxidant intake (i.e. in fruit and vegetables),
cigarette smoking, sunlight exposure and familial predisposition. Antioxidant
intake was calculated according to the method described in the Framingham Eye
Study. Logistic regression analysis was used to estimate odds ratios (OR) and 95%
confidence intervals (CI). RESULTS: The prevalence rate of AMD in patients with
low antioxidant intake and low lutein intake (dichotomized at the median value)
was about twice as high as that in patients with high intake: OR = 1.7, 95% CI
(0.8-3.7), and OR = 2.4, 95% CI (1.1-5.1). Further specification of intake data
into quartiles of antioxidant intake and lutein/zeaxanthine intake showed a clear
dose-response relationship. CONCLUSION: The effect of dietary antioxidants upon
macular health warrants preventive studies.

PMID: 12190777 [PubMed - indexed for MEDLINE]

2755: Proc Natl Acad Sci U S A. 2002 Sep 3;99(18):11830-5. Epub 2002 Aug 20.

The Alzheimer's A beta -peptide is deposited at sites of complement activation in
pathologic deposits associated with aging and age-related macular degeneration.

Johnson LV, Leitner WP, Rivest AJ, Staples MK, Radeke MJ, Anderson DH.

Center for the Study of Macular Degeneration, Neuroscience Research Institute,
University of California, Santa Barbara, CA 93016, USA.
l.johnson@lifesci.ucsb.edu

Age-related macular degeneration (AMD) is a leading cause of irreversible vision 
loss in older individuals worldwide. The disease is characterized by abnormal
extracellular deposits, known as drusen, that accumulate along the basal surface 
of the retinal pigmented epithelium. Although drusen deposition is common in
older individuals, large numbers of drusen and/or extensive areas of confluent
drusen represent a significant risk factor for AMD. Widespread drusen deposition 
is associated with retinal pigmented epithelial cell dysfunction and degeneration
of the photoreceptor cells of the neural retina. Recent studies have shown that
drusen contain a variety of immunomodulatory molecules, suggesting that the
process of drusen formation involves local inflammatory events, including
activation of the complement cascade. Similar observations in Alzheimer's disease
(AD) have lead to the hypothesis that chronic localized inflammation is an
important element of AD pathogenesis, with significant neurodegenerative
consequences. Accordingly, the amyloid beta (A beta) peptide, a major constituent
of neuritic plaques in AD, has been implicated as a primary activator of
complement in AD. Here we show that A beta is associated with a substructural
vesicular component within drusen. A beta colocalizes with activated complement
components in these "amyloid vesicles," thereby identifying them as potential
primary sites of complement activation. Thus, A beta deposition could be an
important component of the local inflammatory events that contribute to atrophy
of the retinal pigmented epithelium, drusen biogenesis, and the pathogenesis of
AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12189211 [PubMed - indexed for MEDLINE]

2756: Ophthalmic Genet. 2002 Jun;23(2):129-33.

Identification of a novel VMD2 mutation in Japanese patients with Best disease.

Yanagi Y, Sekine H, Mori M.

Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo,
Japan. yanagi-tky@umin.ac.jp

PURPOSE: To report a novel VMD2 gene mutation in a Japanese family with Best
disease and the clinical phenotype of the patients. PATIENTS AND METHODS:
Mutational analysis for VMD2 was performed by direct sequencing in two members of
a Japanese family with Best disease. Clinical examination included visual acuity,
electro-oculography (EOG), and fundus examination. RESULTS: A T990C mutation of
the VMD2 gene was found in the 20-year-old boy and his 47-year-old mother. The
boy had bilateral vitelliform cyst-like lesions in both eyes and showed a
pathological Arden ratio of 1.0 on EOG. The mother had a normal fundus appearance
with an Arden ratio of 1.0 on EOG. CONCLUSION: A novel disease-causing mutation
in the VMD2 gene (T990C) was found in Japanese patients with Best disease.

Publication Types: 
    Case Reports

PMID: 12187431 [PubMed - indexed for MEDLINE]

2757: Ophthalmic Epidemiol. 2002 Oct;9(4):283-95.

Use of vitamin and zinc supplements and age-related maculopathy: the Blue
Mountains Eye Study.

Kuzniarz M, Mitchell P, Flood VM, Wang JJ.

Department of Ophthalmology and the Save Sight and Westmead Millennium
Institutes, the University of Sydney Centre for Vision Research, Westmead
Hospital, Westmead, NSW, Australia.

PURPOSE: To investigate relationships between vitamin and zinc supplement use and
age-related maculopathy in a population-based sample. METHODS: We studied 2873
(79%) of the 3654 participants aged 49- 97 years who attended the cross-sectional
Blue Mountains Eye Study and completed a detailed food frequency questionnaire,
including type, dose and duration of supplement use. ARM was assessed during a
masked grading of macular photographs. Odds ratios (OR) and 95% confidence
intervals (CI) were calculated using logistic regression. RESULTS: After
adjusting for multiple confounders, we found that no vitamin or zinc supplements 
were significantly associated with reduced prevalence of any ARM lesions in
either eye. The OR for use of any vitamin supplement was 1.3 (CI 0.9-1.7, p =
0.11) for individuals with any retinal pigment changes. It was 1.1 (CI 0.8-1.5, p
= 0.59) for those with any soft (large) drusen and 1.5 (CI 0.7-3.0, p = 0.31) for
those with late ARM lesions. The lack of association between supplement intake
and ARM persisted regardless of their duration of use, dose or the smoking status
of participants. The Breslow-Day test for heterogeneity was 0.24 with an OR for
early ARM lesions among smokers of 0.7 (CI 0.4-1.3, p = 0.27), and 1.2 (CI
0.9-1.5, p = 0.24) among non-smokers. CONCLUSION: This cross-sectional
population-based study investigated associations between vitamin and zinc
supplement use and the prevalence of ARM lesions. Our findings provide no support
for a protective association between vitamin and zinc supplement use and lesions 
indicating early ARM. The small numbers of subjects with late ARM lesions
precluded any detailed investigation of benefits from supplement use on the
prevalence of these lesions.

PMID: 12187426 [PubMed - indexed for MEDLINE]

2758: Br J Ophthalmol. 2002 Sep;86(9):1019-26.

Face recognition in age related macular degeneration: perceived disability,
measured disability, and performance with a bioptic device.

Tejeria L, Harper RA, Artes PH, Dickinson CM.

Research Group in Eye and Vision Science, Manchester Royal Eye Hospital,
University of Manchester, Oxford Road, UK.

AIMS: (1) To explore the relation between performance on tasks of familiar face
recognition (FFR) and face expression difference discrimination (FED) with both
perceived disability in face recognition and clinical measures of visual function
in subjects with age related macular degeneration (AMD). (2) To quantify the gain
in performance for face recognition tasks when subjects use a bioptic telescopic 
low vision device. METHODS: 30 subjects with AMD (age range 66-90 years; visual
acuity 0.4-1.4 logMAR) were recruited for the study. Perceived (self rated)
disability in face recognition was assessed by an eight item questionnaire
covering a range of issues relating to face recognition. Visual functions
measured were distance visual acuity (ETDRS logMAR charts), continuous text
reading acuity (MNRead charts), contrast sensitivity (Pelli-Robson chart), and
colour vision (large panel D-15). In the FFR task, images of famous people had to
be identified. FED was assessed by a forced choice test where subjects had to
decide which one of four images showed a different facial expression. These tasks
were repeated with subjects using a bioptic device. RESULTS: Overall perceived
disability in face recognition did not correlate with performance on either task,
although a specific item on difficulty recognising familiar faces did correlate
with FFR (r = 0.49, p<0.05). FFR performance was most closely related to distance
acuity (r = -0.69, p<0.001), while FED performance was most closely related to
continuous text reading acuity (r = -0.79, p<0.001). In multiple regression,
neither contrast sensitivity nor colour vision significantly increased the
explained variance. When using a bioptic telescope, FFR performance improved in
86% of subjects (median gain = 49%; p<0.001), while FED performance increased in 
79% of subjects (median gain = 50%; p<0.01). CONCLUSION: Distance and reading
visual acuity are closely associated with measured task performance in FFR and
FED. A bioptic low vision device can offer a significant improvement in
performance for face recognition tasks, and may be useful in reducing the
handicap associated with this disability. There is, however, little evidence for 
a correlation between self rated difficulty in face recognition and measured
performance for either task. Further work is needed to explore the complex
relation between the perception of disability and measured performance.

PMID: 12185131 [PubMed - indexed for MEDLINE]

2759: Retina. 2002 Aug;22(4):471-7.

Morphometric analysis of the macula in eyes with disciform age-related macular
degeneration.

Kim SY, Sadda S, Pearlman J, Humayun MS, de Juan E Jr, Melia BM, Green WR.

The Wilmer Ophthalmological Institute, The Johns Hopkins University School of
Medicine, Baltimore, Maryland 21287-9277, USA.

PURPOSE: To evaluate the extent of neural cell death in eyes with disciform
age-related macular degeneration. METHODS: Six eyes with disciform degeneration
at various stages and five age-matched control eyes were selected for
morphometric analysis using digitized light microscopic images. Disciform scars
were classified as subneurosensory retinal, subretinal pigment epithelial, or
combined lesions. The nuclei of the ganglion cell, inner nuclear, and outer
nuclear layers were counted in contiguous 100 microm segments spanning a distance
from 1,500 microm nasal to 1,500 microm temporal to the fovea. RESULTS: The outer
nuclear layer was most severely attenuated in eyes with disciform scars,
demonstrating a 69.4% reduction in cell number relative to control eyes. A loss
in retinal ganglion cells (by 7.3%) and an increase in inner nuclear layer cells 
(by 10%) were observed, but these changes were not significant. Photoreceptor
loss was most pronounced when the disciform scar was not covered by the retinal
pigment epithelium. CONCLUSION: The nuclei of the outer nuclear layer are
significantly attenuated in eyes with disciform age-related macular degeneration,
while the ganglion cell and inner nuclear layers are relatively preserved. These 
findings suggest that replacement of outer nuclear function, by either retinal
transplantation or implantation of the intraocular retinal prosthesis, might be a
feasible therapeutic option for patients with this condition.

PMID: 12172115 [PubMed - indexed for MEDLINE]

2760: Retina. 2002 Aug;22(4):464-70.

Morphometric analysis of the macula in eyes with geographic atrophy due to
age-related macular degeneration.

Kim SY, Sadda S, Humayun MS, de Juan E Jr, Melia BM, Green WR.

Wilmer Ophthalmological Institute, The Johns Hopkins University School of
Medicine, Baltimore, Maryland 21287-9277, USA.

PURPOSE: To evaluate the extent of neural cell death in eyes with geographic
atrophy (GA). METHODS: Ten eyes with GA and five age-matched control eyes were
selected for morphometric analysis. The nuclei of the ganglion cell, inner
nuclear, and outer nuclear layers were counted in contiguous 100-microm segments 
from 1,500 microm nasal to 1,500 microm temporal to the fovea. RESULTS: The outer
nuclear layer was most severely attenuated in eyes with GA, demonstrating a 76.9%
reduction relative to control eyes (P < 0.0001). A significant loss of ganglion
cells (by 30.7%) was also observed (P = 0.0008). There was no significant
difference in the inner nuclear layer cells (P = 0.30). Among the GA eyes, the
nuclei in all three layers were significantly reduced in segments in which the
retinal pigment epithelium was completely absent (P </= 0.0003). CONCLUSION:
Although the nuclei of the outer nuclear layer in eyes with GA were markedly
attenuated, the nuclei of the inner nuclear layer were relatively preserved.
There was also a significant reduction in ganglion cells in GA eyes, but
considerable numbers remained even in the areas of complete retinal pigment
epithelium atrophy. This finding suggests that therapies aimed at replacing outer
nuclear function (such as neural retinal and retinal pigment epithelium
transplantation or implantation of the intraocular retinal prosthesis) may be
feasible for restoring vision in these patients.

PMID: 12172114 [PubMed - indexed for MEDLINE]

2761: Retina. 2002 Aug;22(4):406-11.

Retinal microangiopathies overlying pigment epithelial detachment in age-related 
macular degeneration.

Weinberger D, Lichter H, Goldenberg-Cohen N, Priel E, Bahar I, Yassur Y,
Axer-Siegel R.

Department of Ophthalmology, Rabin Medical Center, Beilinson Campus, Petah Tiqva,
Israel.

PURPOSE: To evaluate alterations in the retinal vasculature overlying pigment
epithelial detachments (PED) in exudative age-related macular degeneration (ARMD)
using indocyanine green and fluorescein angiography. METHODS: Forty-one patients 
(41 eyes) with a clinical diagnosis of exudative ARMD with PED underwent
simultaneous fluorescein and indocyanine green angiography, also under high (10
degrees ) magnification. Vascular abnormalities in the retina were compared
between patients with vascularized (n = 34, group 1) and nonvascularized (n = 7, 
group 2) PED on indocyanine green angiography and correlated with the size of the
PED and the presence of serous retinal detachment. RESULTS: In all, 67 vascular
abnormalities were found by indocyanine green angiography and only 22 by
fluorescein angiography; this finding was statistically significant (P < 0.0001).
The finding of retinal vasculopathy (32 patients in group 1 and two patients in
group 2) was directly correlated with the presence of choroidal
neovascularizations (P = 0.002). There was also a direct correlation between the 
presence of choroidal neovascularization and size of the PED (P = 0.03). The
number of retinal vascular findings was not significantly correlated with serous 
elevation of the retina. CONCLUSIONS: Retinal vasculopathies may be observed in
eyes with PED and are detectable by indocyanine green and fluorescein
angiography.

PMID: 12172105 [PubMed - indexed for MEDLINE]

2762: Ther Apher. 2002 Aug;6(4):271-81.

Rheopheresis for age-related macular degeneration: a novel indication for
therapeutic apheresis in ophthalmology.

Klingel R, Fassbender C, Fischer I, Hattenbach L, Gümbel H, Pulido J, Koch F.

Apheresis Research Institute, Cologne, Germany. afi@apheresis-research.de

Age-related macular degeneration (AMD) is the leading cause of visual impairment 
and blindness in the elderly. Successful therapy is not yet available for the
majority of patients, especially not for patients with dry AMD. AMD at cellular
and molecular levels is at least in part a microcirculatory disorder of the
retina. Rheopheresis is a safe and effective modality of therapeutic apheresis to
treat microcirculatory disorders and represents a novel treatment option for
patients with dry AMD. Elimination of a defined spectrum of high molecular weight
proteins from human plasma including pathophysiologically relevant risk factors
for AMD such as fibrinogen, cholesterol, von Willebrand factor, and alpha
2-macroglobulin results in the reduction of blood and plasma viscosity as well as
erythrocyte and thrombocyte aggregation. Pulses of lowering blood and plasma
viscosity performed as a series of Rheopheresis treatments lead to rapid changes 
of blood flow, subsequently inducing sustained improvement of microcirculation
and recovery of retinal function. Two controlled randomized clinical trials
demonstrated the safety and efficacy of Rheopheresis for the treatment of AMD
patients, especially for those with the dry form. Recently the interim analysis
of the sham-controlled, double blind, randomized multicenter Multicenter
Investigation of Rheopheresis for AMD (MIRA-I) trial confirmed these results. The
framework of completed and still ongoing controlled clinical trials in
combination with postcertification studies including the RheoNet registry
represents a comprehensive quality management approach for this novel
interdisciplinary therapy for AMD. The development and continuous update of
guidelines for the precise indication of Rheopheresis for AMD follows the
requirements of evidence-based medicine.

Publication Types: 
    Review

PMID: 12164796 [PubMed - indexed for MEDLINE]

2763: Ophthalmic Physiol Opt. 2002 Jul;22(4):300-11.

Benefit of coloured lenses for age-related macular degeneration.

Wolffsohn JS, Dinardo C, Vingrys AJ.

Neurosciences Research Institute, School of Life and Health Sciences, Aston
University, Birmingham, UK. j.s.w.wolffsohn@aston.ac.uk

PURPOSE: To evaluate and compare the functional and perceived benefits of wearing
coloured lenses by patients with age-related macular degeneration (ARMD). METHOD:
Ten subjects with early ARMD and five elderly controls wore a selection of NoIR
wrap-around coloured lenses (yellow 29.7% light transmission, orange 22.9%, red
16.8% and grey 10.3%), each for a duration of 7 days. Contrast sensitivity,
colour vision, visual acuity, the effect of glare and peripheral sensitivity were
measured for each lens and compared with a control (no lens) condition.
Subjective ratings of visual performance were also scored. RESULTS: Compared with
the no filter condition, red and grey lenses reduced contrast sensitivity whereas
yellow and orange lenses increased contrast sensitivity. These objective changes 
were supported by subjective ratings in subjects with ARMD. Grey lenses reduced
the loss of contrast sensitivity usually suffered in the presence of glare,
whereas visual acuity and peripheral sensitivity decreased with red lenses.
Colour vision became distorted with red lenses in control subjects, but was
relatively unaffected by the use of coloured lenses in subjects with ARMD.
CONCLUSIONS: The subjective benefit of coloured lenses appears to be due to a
minor enhancement of contrast sensitivity.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial

PMID: 12162481 [PubMed - indexed for MEDLINE]

2764: Genomics. 2002 Aug;80(2):166-71.

X-linked recessive atrophic macular degeneration from RPGR mutation.

Ayyagari R, Demirci FY, Liu J, Bingham EL, Stringham H, Kakuk LE, Boehnke M,
Gorin MB, Richards JE, Sieving PA.

Department of Ophthalmology and Visual Sciences, University of Michigan, Ann
Arbor, Michigan, 48105, USA.

We mapped a new X-linked recessive atrophic macular degeneration locus to
Xp21.1-p11.4 and show allelic involvement of the gene RPGR, which normally causes
severe peripheral retinal degeneration leading to global blindness. Ten affected 
males whom we examined had primarily macular atrophy causing progressive loss of 
visual acuity with minimal peripheral visual impairment. One additional male
showed extensive macular degeneration plus peripheral loss of retinal pigment
epithelium and choriocapillaries. Full-field electroretinograms (ERGs) showed
normal cone and rod responses in some affected males despite advanced macular
degeneration, emphasizing the dissociation of atrophic macular degeneration from 
generalized cone degenerations, including X-linked cone dystrophy (COD1). The
RPGR gene nonsense mutation G-->T at open reading frame (ORF)15+1164 cosegregated
with the disease and may create a donor splice site. Identification of an RPGR
mutation in atrophic maculardegeneration expands the phenotypic range associated 
with this gene and provides a new tool for the dissection of the relationship
between clinically different retinal pathologies.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12160730 [PubMed - indexed for MEDLINE]

2765: Ophthalmology. 2002 Aug;109(8):1492-8.

Comment in:
    Ophthalmology. 2003 Nov;110(11):2262.

Retinal pigment epithelium translocation after choroidal neovascular membrane
removal in age-related macular degeneration.

Stanga PE, Kychenthal A, Fitzke FW, Halfyard AS, Chan R, Bird AC, Aylward GW.

The Institute of Ophthalmology, University College London, England UK.

PURPOSE: To test the feasibility of a new surgical technique and to assess visual
function over the translocated retinal pigment epithelium (RPE) cells in patients
operated on for subfoveal choroidal neovascularization (CNV) secondary to
age-related macular degeneration (ARMD). DESIGN: Retrospective, noncomparative,
interventional case series. PARTICIPANTS: Nine patients with previously untreated
exudative ARMD underwent surgical excision of the subfoveal CNV with RPE
translocation and were observed for 12 to 32 months. METHODS: The surgery
consisted of a standard three-port pars plana vitrectomy, excision of the CNV,
and RPE translocation. Pre- and postoperative ocular examination included
best-corrected visual acuity measurement, fundus color stereo photography, and
fundus fluorescein angiography. Optical coherence tomography and confocal laser
scanning ophthalmoscopy (cLSO) were performed after surgery. A crossfixation
target and a single-point flashing light were projected on different areas of the
posterior pole using a cLSO. Photopic 10 to 2 perimetry, photopic fine matrix
mapping, and cLSO microperimetry were also performed after surgery in six
patients. MAIN OUTCOME MEASURES: Optical coherence tomography cross-sectional
scans and cLSO RPE autofluorescence were recorded to detect the presence of
viable translocated RPE. Visual acuity, fixation, photopic 10 to 2 perimetry,
photopic fine matrix mapping, and cLSO microperimetry were used to test central
visual function. RESULTS: Retinal pigment epithelium was translocated
successfully at the time of CNV removal from the edge of the RPE defect to a
subfoveal location in seven of nine patients. One patient experienced
proliferative vitreoretinopathy, but significant hemorrhage was not a feature.
Optical coherence tomography showed the translocated RPE as an area of increased 
optical reflectivity with optical shadowing external to it. Confocal laser
scanning ophthalmoscopy showed autofluorescence of the translocated RPE. The
crossfixation target was seen when projected on the translocated RPE. During
eccentric fixation, the patients could see a flashing point-target projected on
the translocated RPE. Photopic 10 to 2 perimetry, photopic fine-matrix mapping,
and cLSO microperimetry showed the presence of central visual function.
CONCLUSIONS: The authors propose that translocation of RPE at the time of CNV
removal, from the edge of the RPE defect to a subfoveal location, may have a role
in the surgical management of ARMD.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 12153801 [PubMed - indexed for MEDLINE]

2766: Arch Ophthalmol. 2002 Aug;120(8):1041-4.

Effect of depression on vision function in age-related macular degeneration.

Rovner BW, Casten RJ, Tasman WS.

Department of Psychiatry, Philadelphia, PA, USA. Barry.Rovner@mail.tju.edu

OBJECTIVES: To report the prevalence rate of depression in older patients with
recent vision loss due to age-related macular degeneration (AMD) and to describe 
the effect of depression on self-reported vision function during 6 months.
METHODS: Prospective cohort study of 51 older patients with recent-onset
bilateral AMD attending the Retina Clinic of Wills Eye Hospital, Philadelphia,
Pa. Main outcome measures included the Center for Epidemiological Studies
Depression Scale, visual acuity, Functional Vision Screening Questionnaire,
Chronic Disease Score, and Community Disability Scale. RESULTS: Seventeen
patients (33%) were depressed at baseline and had worse visual acuity (P =.04)
and greater levels of vision-specific (P =.03) and general (P =.002) physical
disability than nondepressed patients. The correlations of Center for
Epidemiological Studies Depression Scale score with visual acuity and
visual-specific disability, however, were not significant after controlling for
general physical disability. An increase in depressive symptoms over time
predicted decline in self-reported vision function independent of changes in
visual acuity or medical status (P<.05). CONCLUSIONS: The prevalence and
disabling effects of depression in older patients with AMD are substantial.
Recognizing that depression is a treatable disorder that exacerbates the effects 
of AMD will lead to improved outcomes. Innovative interventions to prevent or
treat depression in specialty eye clinics are possible.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12149057 [PubMed - indexed for MEDLINE]

2767: Arch Ophthalmol. 2002 Aug;120(8):1029-38.

Visual outcomes in the subfoveal radiotherapy study: a randomized controlled
trial of teletherapy for age-related macular degeneration.

Hart PM, Chakravarthy U, Mackenzie G, Chisholm IH, Bird AC, Stevenson MR, Owens
SL, Hall V, Houston RF, McCulloch DW, Plowman N.

Department of Ophthalmology, The Royal Victoria Hospital, Queen's University of
Belfast, Northern Ireland.

OBJECTIVE: To determine whether teletherapy with 6-mV photons can reduce visual
loss in patients with subfoveal choroidal neovascularization in age-related
macular degeneration. DESIGN: A multicenter, single-masked, randomized controlled
trial of 12 Gy of external beam radiation therapy delivered to the macula of an
affected eye vs observation only. SETTING: Three United Kingdom-based hospital
units. PARTICIPANTS: Patients with age-related macular degeneration, aged 60
years and older, who had subfoveal choroidal neovascularization and a visual
acuity of 20/200 (logMAR 1.0) or better. METHODS: Two hundred three patients were
randomly assigned to radiotherapy or observation. Treatment was undertaken at
designated radiotherapy centers, and patients assigned to the treatment group
received a total dosage of 12 Gy of 6-mV photons in 6 fractions. Follow-up was
scheduled at 3, 6, 12, and 24 months. After excluding protocol violators, the
data from 199 patients were analyzed. MAIN OUTCOME MEASURES: The primary outcome 
measure was mean loss of distance visual acuity in the study eye at 12 and 24
months. Other outcome variables analyzed were near visual acuity and contrast
sensitivity. The proportions of patients losing 3 or more or 6 or more lines of
distance and near acuity and 0.3 or more or 0.6 or more log units of contrast
sensitivity at each follow-up were also analyzed. RESULTS: At all time points,
mean distance visual acuity was better in the radiotherapy-treated group than in 
the control group, but the differences did not reach statistical significance. At
24 months, analysis of the proportions of patients with loss of 3 or more
(moderate) (P =.08) or 6 or more (severe) (P =.29) lines of distance vision
showed that fewer treated patients had severe losses, but there was no
statistically significant difference between groups. For near visual acuity,
although there was no evidence of treatment benefit at 12 and 24 months, a
significant difference in favor of treatment was present at 6 months (P =.048).
When analyzed by the proportions of patients losing 3 lines of contrast
sensitivity, there was a significant difference in favor of treatment at 24
months (P =.02). No adverse retinal effects were observed during the study, but
transient disturbance of the precorneal tear film was noted in treated patients. 
CONCLUSION: The results of the present trial do not support the routine clinical 
use of external beam radiation therapy in subjects with subfoveal choroidal
neovascularization in age-related macular degeneration.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12149056 [PubMed - indexed for MEDLINE]

2768: Invest Ophthalmol Vis Sci. 2002 Aug;43(8):2741-8.

Altered recovery of macular function after bleaching in Stargardt's
disease-fundus flavimaculatus: pattern VEP evidence.

Parisi V, Canu D, Iarossi G, Olzi D, Falsini B.

Cattedra di Clinica Oculistica, Università di Roma Tor Vergata, Roma, Italy.

PURPOSE: To evaluate recovery of pattern visual evoked potentials (VEPs) after
macular bleaching in patients with Stargardt's disease-fundus flavimaculatus
(STD/FF). METHODS: Sixteen unrelated patients with STD/FF (age, 26-52 years;
visual acuity, 0.2-1.0; phenotype I, n = 6; phenotype II, n = 8; or phenotype
III, n = 2) and 15 age-matched control subjects were evaluated. VEPs were
recorded in response to counterphased (two reversals per second) checkerboards
(check size, 15 minutes; mean luminance, 80 cd/m(2); contrast, 80%; stimulus
field size, 18 degrees ) in baseline condition and at 20, 40, and 60 seconds
after a 30-second exposure to a bleaching light (3.58 log photopic trolands),
presented to the central (6 degrees field) retina. In all patients, macular focal
electroretinograms (FERGs) to an 18 degrees uniform field, flickering at 41 Hz,
were also recorded in separate sessions. RESULTS: At every postbleaching time,
VEPs were delayed and suppressed in amplitude, compared with prebleaching values,
in both patients and control subjects. However, the amount of delay and
suppression was, on average, more pronounced (P < 0.001) in patients than in
control subjects. This difference was not accounted for by eccentric fixation in 
patients (n = 8) with central scotoma and was still substantial when only
patients (n = 8) with normal visual field and acuity were considered. In
individual patients, baseline FERG amplitudes correlated (r = -0.6, P < 0.01)
with the suppression of VEP amplitude at 40-seconds after bleaching. CONCLUSIONS:
The results indicate an altered recovery of pattern VEPs after macular bleaching 
in STD/FF and suggest adaptation abnormalities in macular cone photoreceptors,
occurring at disease stages with relatively preserved central visual field and
acuity.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12147611 [PubMed - indexed for MEDLINE]

2769: Invest Ophthalmol Vis Sci. 2002 Aug;43(8):2732-40.

A mouse model for Sorsby fundus dystrophy.

Weber BH, Lin B, White K, Kohler K, Soboleva G, Herterich S, Seeliger MW, Jaissle
GB, Grimm C, Reme C, Wenzel A, Asan E, Schrewe H.

Institute of Human Genetics, Biocenter, University of Wuerzburg, Germany.
bweb@biozentrum.uni-wuerzburg.de

PURPOSE: Sorsby fundus dystrophy (SFD) is a rare, late-onset macular dystrophy
caused by mutations in the tissue inhibitor of metalloproteinases-3 (TIMP3) gene.
The known mutations introduce potentially unpaired cysteine residues in the C
terminus of the protein and result in the formation of higher-molecular-weight
protein complexes of as yet unknown composition and functional consequences in
the pathologic course of SFD. To facilitate in vivo investigation of mutant
TIMP3, the authors generated a knock-in mouse carrying a disease-related
Ser156Cys mutation in the orthologous murine Timp3 gene. METHODS: Site-directed
mutagenesis and homologous recombination in embryonic stem (ES) cells was used to
generate mutant ES cells carrying the Timp3(S156C) allele. Chimeric animals were 
obtained, of which two displayed germline transmission of the mutated allele.
Molecular genetic, biochemical, electron microscopic, and electrodiagnostic
techniques were used for characterization. RESULTS: At 8 months of age, knock-in 
mice showed abnormalities in the inner aspect of Bruch's membrane and in the
organization of the adjacent basal microvilli of the retinal pigment epithelium
(RPE). Changes resembling those in the mutant animals were also present to some
extent in normal littermates, but only at an advanced age of 30 months. Long-term
electrodiagnostic recordings indicated normal retinal function throughout life.
The biochemical characteristics of the mutant protein appear similar in humans
and knock-in mice, suggesting common molecular pathways in the two species. The
localization of the mutant protein in the eye is normal, although there is
evidence of increased Timp3 levels in Bruch's membrane of mutant animals.
CONCLUSIONS: The knock-in mice display early features of age-related changes in
Bruch's membrane and the RPE that may represent the primary clinical
manifestations of SFD. In addition, our immunolabeling studies and biochemical
data support a model proposing that site-specific excess rather than absence or
deficiency of functional Timp3 may be the primary consequence of the known Timp3 
mutations.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12147610 [PubMed - indexed for MEDLINE]

2770: Br J Ophthalmol. 2002 Aug;86(8):892-7.

Polypoidal choroidal vasculopathy in Chinese patients.

Kwok AK, Lai TY, Chan CW, Neoh EL, Lam DS.

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong
Kong, Hong Kong, People's Republic of China. kwokak@ha.org.cn

AIMS: To report the clinical features and outcomes of polypoidal choroidal
vasculopathy (PCV) in Chinese patients with or without laser treatment. METHODS: 
A consecutive series of 204 indocyanine green angiographies (ICGA) performed for 
patients with a provisional diagnosis of age related macular degeneration were
reviewed retrospectively. Inclusion criteria were ICGA with angiographic features
of PCV and patients of Chinese ethnic origin. Medical records were then reviewed 
and patients were recalled for further assessments. RESULTS: 22 eyes of 19
patients (9.3%) were included. The mean follow up period was 27.4 months (range
4-60 months). The mean age of patients at presentation was 65.1 years (range
51-77 years). The commonest clinical feature at presentation was subretinal
haemorrhage (63.6%), followed by retinal exudation (59.1%) and haemorrhagic
pigment epithelial detachment (59.1%). There was a predominance of males (68.4%),
unilaterality (84.2%), and macular location of polyps (63.6%). Nine eyes received
laser photocoagulation. The median initial visual acuity for both the laser and
non-laser groups was 6/18. Stable or improved vision was attained in 56% and 31% 
of laser and non-laser groups, respectively (Fisher's exact test, p=0.38). Mean
loss of Snellen lines was 3.1 and 1.1 for the two groups, respectively (two
sample t test, p=0.31). At the last follow up, 15 (68.2%) eyes had poor visual
acuity of 6/60 or worse, mostly attributed to disciform scar or exudative
maculopathy. CONCLUSIONS: There is a predominance of males, unilaterality, and
macular location of polyps in Chinese patients with PCV. The overall visual
prognosis is guarded regardless of treatment. There is a large amount of
variation in the natural course of PCV among different ethnic groups.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 12140211 [PubMed - indexed for MEDLINE]

2771: Am J Ophthalmol. 2002 Aug;134(2):228-39.

Optimizing treatment of choroidal neovascularization feeder vessels associated
with age-related macular degeneration.

Flower RW.

Department of Ophthalmology, University of Maryland School of Medicine,
Baltimore, Maryland 21030, USA. rflow001@umaryland.edu

PURPOSE: To optimize the method of treating choroidal neovascularization (CNV)
associated with age-related macular degeneration (AMD). DESIGN: Experimental
study and interventional case series. METHODS: The parameters associated with
locating and then photocoagulating CNV feeder vessels were identified and
optimized using published data and data derived from modeling the choroidal
vasculature. Based on these optimized parameters, a prototype
diagnostic/treatment system was designed that captures high-speed indocyanine
green (ICG) angiogram images and facilitates analysis of the images by enhancing 
visualization of dye movement through CNV feeder vessels (FVs). The system also
permits precise aiming and delivery of 810- nm wavelength photocoagulation laser 
energy to target FVs on a real-time ICG angiogram image of the choroidal
vasculature. Target FVs are tracked by a joy-stick controlled laser aiming beam
until an intravenously-injected high-concentration ICG dye bolus is observed to
enter the target vessel, at which time the laser is fired. Proof of principle of 
the combined diagnosis/treatment system design for performing dye-enhanced
photocoagulation (DEP) in the clinical setting and determination of the minimum
DEP laser energy needed to close CNV FVs was made in 11 AMD patients requiring
treatment of CNV, but for whom other treatment was not appropriate. RESULTS:
Using ICG-DEP, CNV feeder vessels were closed with single pulse laser energy,
delivering as little as 0.6 to 1.8 J of energy to the fundus, producing no
visible change in the fundus. Successful FV closure was usually indicated
immediately by presence of incarcerated ICG dye in the vessel adjacent to the
burn site. The prototype system proved relatively easy to operate. After
acquiring and interpreting diagnostic angiograms and repositioning a patient in
front of the device, feeder vessel DEP and treatment evaluation required 15 to 20
minutes. CONCLUSIONS: Indocyanine green dye-enhanced photocoagulation of CNV
feeder vessels, facilitated by use of a device that permits real-time
visualization of the choroidal circulation while aiming the treatment laser beam,
appears to minimize the amount of energy applied to the fundus and the volume of 
fundus tissue affected by treatment, compared with other treatment modalities.
The combination diagnosis/treatment device should be useful in optimizing FV
treatment and in refining and evaluating the efficacy of DEP in future clinical
trials.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12140030 [PubMed - indexed for MEDLINE]

2772: Am J Ophthalmol. 2002 Aug;134(2):220-7.

Pigment epithelium-derived factor is deficient in the vitreous of patients with
choroidal neovascularization due to age-related macular degeneration.

Holekamp NM, Bouck N, Volpert O.

Barnes Retina Institute, St. Louis, Missouri 63141, USA. nholekamp@pol.net

PURPOSE: Pigment epithelium-derived growth factor (PEDF) is a potent inhibitor of
angiogenesis that is found in the normal eye. The purpose of this study is to
report decreased levels of PEDF in the vitreous of eyes with choroidal
neovascularization (CNV) due to age-related macular degeneration (AMD). DESIGN:
Prospective case-control study. METHODS: In a prospective case-control study,
undiluted vitreous was collected from nine eyes of nine patients with CNV due to 
AMD and from an age-matched control group of 12 eyes of 12 patients with retinal 
disorders not involving neovascularization. Vitreous PEDF and vascular
endothelial growth factor (VEGF) concentrations were determined by Western blot
analyses and enzyme-linked immunosorbent assay (ELISA), respectively. Angiogenic 
activities of the vitreous samples were assessed in vitro using an endothelial
cell chemotaxis assay. RESULTS: In vitreous samples from nine eyes with CNV due
to AMD the mean +/- SD PEDF level was 2.8 ng/microl +/- 1.3 ng/microl. In
vitreous samples from 12 age-matched control eyes the mean +/- SD PEDF level was 
16.4 ng/microl +/- 7.1 ng/microl. The difference between the two groups was
statistically significant (P =.00003). No significant difference in vitreous VEGF
concentration was seen between CNV/AMD samples and control samples (P =.23). All 
CNV/AMD vitreous samples induced endothelial cell migration in vitro. No sample
from age-matched non-age-related macular degeneration controls could induce
endothelial cell migration, and 11 of 12 were able to block VEGF-induced
migration in vitro. This inhibitory activity required active PEDF. CONCLUSION:
The vitreous of patients with CNV due to AMD contained lower levels of PEDF and
lacked the antiangiogenic activity of vitreous from age-matched controls. This
suggests that loss of PEDF creates a permissive environment for CNV patients with
AMD.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.

PMID: 12140029 [PubMed - indexed for MEDLINE]

2773: Am J Ophthalmol. 2002 Aug;134(2):214-9.

A controlled study of vitrectomy for diabetic macular edema.

Otani T, Kishi S.

Department of Ophthalmology, Gunma University School of Medicine, Maebashi,
Gunma, Japan. otanito@showa.gunma-u.ac.jp

PURPOSE: To compare eyes that underwent surgery with untreated fellow eyes to
assess the efficacy of vitrectomy for diabetic macular edema. METHODS: In a
nonrandomized clinical trial, seven adult patients with mean age of 53 years
(range 42 to 64) and the same degree and duration of diabetic macular edema in
both eyes were followed up for more than 5 months after unilateral vitrectomy.
The treated eye was selected at random, but if visual disparity between the both 
eyes was more than 3 lines, we operated on the worse side. We compared the
preoperative and postoperative foveal thicknesses (the distance between the inner
retinal surface and retinal pigment epithelium) and the best-corrected visual
acuity by a certified examiner with those of the untreated fellow eye. RESULTS:
In the seven eyes that underwent surgery, the foveal thickness decreased by an
average of 622 to 269 microm (P =.027, Wilcoxon signed-rank test). In the fellow 
eyes, the average decrease in foveal thickness was from 617 to 546 microm (P
=.176, Wilcoxon signed-rank test). The best-corrected postoperative visual acuity
in the eyes that underwent surgery improved more than 2 lines in four eyes (57%) 
and remained the same in three eyes (43%). In the fellow eyes, it improved more
than 2 lines in one eye (14%), remained the same in three eyes (43%), and
decreased more than 2 lines in three eyes (43%). CONCLUSION: In eyes with
diabetic macular edema that underwent surgery, the foveal thickness significantly
decreased after vitrectomy. Vitrectomy may be effective for treating diabetic
macular edema.

Publication Types: 
    Case Reports
    Clinical Trial
    Comparative Study
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 12140028 [PubMed - indexed for MEDLINE]

2774: Graefes Arch Clin Exp Ophthalmol. 2002 Jul;240(7):539-42. Epub 2002 Jun 27.

Visual prognosis of second eyes in patients with unilateral late exudative
age-related macular degeneration.

Pauleikhoff D, Radermacher M, Spital G, Müller C, Brumm G, Lommatzsch A, Bird AC.

Department of Ophthalmology, St. Franziskus Hospital, Hohenzollernring 74, 48145 
Münster, Germany. dapauleikhoff@muenster.de.

PURPOSE: A prospective longitudinal study was initiated to analyze the
correlation between the prognosis for the second eyes of patients with unilateral
late exudative AMD and the disease phenotype. METHODS: Of the187 patients with
unilateral late exudative AMD recruited, 130 (69.5%) had predominantly classic
CNV without pigment epithelium detachment (PED) (CNV group), and 57 (30.5%) had
occult CNV with serous PED (PED group). Patients were reexamined by
ophthalmoscopy and angiography every 6 months for up to 80 months. The end point 
was ETDRS visual acuity change of 3 lines or more due to late AMD in the second
eye. RESULTS: During follow-up 53 (28.3%) patients reached the end point: 32
(24.6%) in the CNV group and 21 (36.8%) in the PED group. The major prognostic
factor for the risk of visual loss in the second eye was the type of late AMD in 
the first eye (CNV group 6-7% per year, PED group 15-16% per year ( P<0.001).
There was significant symmetry between the new exudative lesion in the second eye
and that in the first, and significant differences in the density and
fluorescence of drusen in the second eye between the two groups. CONCLUSIONS:
Patients with occult CNV with serous PED in the first eye have a significantly
higher risk of visual loss in the second eye than patients with CNV without PED. 
This distinction may be important for future clinical studies. In addition,
segregation of AMD by phenotype is necessary in the analysis of genes conferring 
risk of AMD.

PMID: 12136283 [PubMed - indexed for MEDLINE]

2775: Ophthalmic Surg Lasers. 2002 Jul-Aug;33(4):343-8.

Aqueous infiltration into an implantable miniaturized telescope.

Werner L, Kaskaloglu M, Apple DJ, Pandey SK, Macky TA, Izak AM, Trivedi RH,
Heredia M, Morse SE.

Center for Research on Ocular Therapeutics and Biodevices, Storm Eye Institute,
Medical University of South Carolina, Charleston 29425-5536, USA.

The implantable miniaturized telescope (IMT) is the first intraocular magnifying 
system proposed for optical correction in patients with age-related macular
degeneration (ARMD). The optical component is embedded in a carrying device
designed as an intraocular lens that is implanted after cataract surgery. In this
study, we report findings on an IMT that was explanted because of aqueous
infiltration into its optic and describe the configuration of this device and the
surgical technique required for its implantation. The patient, a 75-year-old male
with bilateral cataract and nonexudative ARMD, underwent phacoemulsification with
implantation of an IMT in the right eye. The rigid device, weighing 46.1 mg in
aqueous, has an overall diameter of 13.5 mm and requires implantation through a
large limbal incision. It is fixated at the 6 to 12 o'clock meridian. Follow-up
examination revealed the presence of numerous droplets inside the IMT optic. The 
device was explanted and sent to our center for evaluation. A large fissure was
found on the carrying device. However, it was unlikely the site for aqueous
infiltration. Microdefects at the level of the sealing of the optical cylinder
appeared to provide the opening for the inflow of aqueous that formed droplets.
Based on the findings of this report the manufacturer has modified the sealing
technique to avoid this complication. Current clinical trials are now ongoing to 
assess the efficacy of this device in providing visual rehabilitation for ARMD
patients.

Publication Types: 
    Case Reports

PMID: 12135001 [PubMed - indexed for MEDLINE]

2776: Ophthalmic Surg Lasers. 2002 Jul-Aug;33(4):340-2.

Use of an oil-hydraulic microinjection pump for subretinal infusions.

Weichel J, Valtink M, Engelmann K, Richard G.

Department of Ophthalmology, University of Hamburg, Germany.

The injection of cell suspensions or drugs into the subretinal space is a new
promising option of vitreoretinal surgery for the treatment of degenerative
retinal disorders. We used a manual oil-hydraulic microinjection pump to
subretinally inject suspensions of retinal pigment epithelial cells in Royal
College of Surgeons rats and in patients suffering from age-related macular
degeneration with geographic atrophy. The histological examination of the treated
rat eyes showed that cell suspensions could be placed precisely in the subretinal
space. Intra- and postoperative outcome of the patients in the clinical trial
revealed no retinal complications during 6 months of follow up. We suggest the
oil-hydraulic microinjection pump to be a valuable instrument for controlled and 
precisely dosed atraumatic infusion or aspiration of small volumes of cell
suspensions, fluids or drugs in vitreoretinal surgery.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12135000 [PubMed - indexed for MEDLINE]

2777: Exp Eye Res. 2002 Jul;75(1):99-108.

Phosphatidylglycerol potently protects human retinal pigment epithelial cells
against apoptosis induced by A2E, a compound suspected to cause age-related
macula degeneration.

Shaban H, Borrás C, Viña J, Richter C.

Institute of Biochemistry, Swiss Federal Institute of Technology (ETH),
Universitätstr, 16, CH-8092, Zurich, Switzerland.

Age-related macular degeneration (AMD) affects about one fifth of the population 
older than 65 years and is one of the main causes of poor vision in the elderly
in industrialized nations. The endogenous lipophilic and cationic compound
N-retinyl-N-retinylidene ethanolamine (A2E) is suspected to cause the dry form of
the disease, which currently cannot be treated. The authors recently reported
that A2E induces apoptosis in several cell types including porcine retinal
pigment epithelial cells, detaches pro-apoptotic proteins from mitochondria, and 
inhibits cytochrome c oxidase. A2E acts primarily at the level of
cardiolipin/cytochrome c oxidase, which in the light becomes permanently
inactivated by A2E. The authors now report that A2E at low concentrations causes 
apoptosis in cultured human retinal pigment epithelial cells. These cells are
more sensitive to A2E in the light than in the dark. Phosphatidylglycerol, a
negatively charged phospholipid and immediate biosynthetic precursor of
cardiolipin readily inhibits apoptosis. Exposure of cells to A2E results in the
formation of reactive oxygen and nitrogen species, and exposure of mitochondria
to A2E results in oxidative stress. Accordingly, the potent antioxidant coenzyme 
Q also protects cells against A2E-induced apoptosis. These findings are highly
relevant for the treatment and/or prevention of AMD.

PMID: 12123641 [PubMed - indexed for MEDLINE]

2778: Eye. 2002 Jul;16(4):469-71.

A new health technology: where is the consensus on a clinically worthwhile
benefit?

Foot B, Foy R, Chakravarthy U, Wormald R.

The Royal College of Ophthalmologists London, UK. Barny.Foot@moorfielsd.nhs.uk

AIM: New therapies are often introduced into the NHS prior to full evaluation,
leading to inequities in provision. Uncertainty exists regarding the value of
photodynamic therapy in the treatment of neovascular age-related macular
degeneration. We ascertained the availability of this treatment and the
information used to inform clinical policy. METHODS: A postal survey of all
clinical directors/lead consultants in the UK sought data on which (if any)
patients were referred or treated with PDT by their unit, the sources of evidence
informing clinical policy and the threshold of clinical benefit at which
respondents would support the use of PDT. RESULTS: 123/152 questionnaires were
returned. 42% of units make some provision for PDT on the NHS, including routine 
provision by 9%. 14.5% of units offer the option of care in the private sector,
whilst 26.5% treated or referred no patients. The threshold at which respondents 
considered introduction of PDT would be justifiable varied widely. Respondents
cited local literature review, advice from clinicians, guidance from the Royal
College and information from the pharmaceutical industry as most influential in
determining current policy. However, the National Institute for Clinical
Excellence (NICE) and the Cochrane Library were anticipated as playing a greater 
role in shaping future practice. CONCLUSIONS: Substantial variation exists in the
availability of PDT. Advocates of PDT may interpret our data as an indication of 
the NHS failing to provide an effective therapy equitably, whilst others may
deduce that patients are receiving an under-evaluated treatment in routine
clinical practice. The differing thresholds at which clinicians believe treatment
would be justified may further exacerbate variations and the priority given to
PDT.

PMID: 12101457 [PubMed - indexed for MEDLINE]

2779: Biochem Biophys Res Commun. 2002 Jul 19;295(3):668-72.

Alu DNA polymorphism in ACE gene is protective for age-related macular
degeneration.

Hamdi HK, Reznik J, Castellon R, Atilano SR, Ong JM, Udar N, Tavis JH, Aoki AM,
Nesburn AB, Boyer DS, Small KW, Brown DJ, Kenney MC.

Department of Surgery, Ophthalmology Research Laboratories, Burns and Allen
Research Institute, Cedars-Sinai Medical Center, UCLA Medical School Affiliate,
90048, USA. hkhamdi@aol.com

Age-related macular degeneration (AMD) is the leading cause of blindness in the
elderly. We report an association between an Alu polymorphism in the
angiotensin-converting enzyme (ACE) gene with the dry/atrophic form of AMD. Using
the polymerase chain reaction (PCR) on genomic DNA isolated from patients with
AMD (n=173), and an age-matched control population (n=189), we amplified a region
polymorphic for an Alu element insertion in the ACE gene. The Alu(+/+) genotype
occurred 4.5 times more frequently in the control population than the
dry/atrophic AMD patient population, (p=0.004). The predominance of the Alu(+/+) 
genotype within the unaffected control group represents a protective insertion
with respect to the human ocular disease, dry/atrophic AMD. This is the first
demonstration of an Alu element insertion exerting protective effects against a
known human disease. (c) 2002 Elsevier Science (USA).

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12099691 [PubMed - indexed for MEDLINE]

2780: BMJ. 2002 Jul 6;325(7354):11.

Comment in:
    BMJ. 2002 Jul 6;325(7354):1-2.

Vitamin E supplementation and macular degeneration: randomised controlled trial.

Taylor HR, Tikellis G, Robman LD, McCarty CA, McNeil JJ.

Centre for Eye Research Australia, University of Melbourne, Locked Bag 8, East
Melbourne, Victoria, Australia, 8002. h.taylor@unimelb.edu.au

OBJECTIVE: To determine whether vitamin E supplementation influences the
incidence or rate of progression of age related maculopathy (AMD). DESIGN:
Prospective randomised placebo controlled clinical trial. SETTING: An urban study
centre in a residential area supervised by university research staff.
PARTICIPANTS: 1193 healthy volunteers aged between 55 and 80 years; 73% completed
the trial on full protocol. INTERVENTIONS: Vitamin E 500 IU or placebo daily for 
four years. MAIN OUTCOME MEASURES: Primary outcome: development of early age
related macular degeneration in retinal photographs. Other measures included
alternative definitions of age related macular degeneration, progression, changes
in component features, visual acuity, and visual function RESULTS: The incidence 
of early age related macular degeneration (early AMD 3) was 8.6% in those
receiving vitamin E versus 8.1% in those on placebo (relative risk 1.05, 95%
confidence interval 0.69 to 1.61). For late disease the incidence was 0.8% versus
0.6% (1.36, 0.67 to 2.77). Further analysis showed no consistent differences in
secondary outcomes. CONCLUSION: Daily supplement with vitamin E supplement does
not prevent the development or progression of early or later stages of age
related macular degeneration.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12098721 [PubMed - indexed for MEDLINE]

2781: Am J Ophthalmol. 2002 Jul;134(1):69-74.

Inferior limited macular translocation for subfoveal choroidal neovascularization
secondary to age-related macular degeneration: 1-year visual outcome and
recurrence report.

Fujii GY, de Juan E Jr, Pieramici DJ, Humayun MS, Phillips S, Reynolds SM, Melia 
M, Schachat AP.

Doheny Retina Institute at the Doheny Eye Center, University of Southern
California, Keck School of Medicine, Los Angeles 90033, USA.

PURPOSE: To report the 1-year visual outcomes and incidence of persistent and
recurrent choroidal neovascularization (CNV) after limited macular translocation 
(LMT) for subfoveal CNV in patients with age-related macular degeneration (ARMD).
DESIGN: Interventional case series. METHODS: Retrospective review of 102
consecutive eyes of 101 patients that had the inferior limited macular
translocation procedure for subfoveal choroidal neovascularization secondary to
ARMD. The outcome measures were visual acuity at 12 months after surgery, change 
in visual acuity from baseline, the proportion of eyes with moderate (3 or more
lines) or severe (6 or more lines) visual acuity loss, and cumulative incidence
of persistent or recurrent CNV and its impact on visual acuity. Cumulative
incidence was estimated using Kaplan-Meier survival analysis methods. Association
between persistence and recurrence of CNV and the Snellen visual acuity recorded 
at each follow-up visit was evaluated using the Wilcoxon rank-sum test. RESULTS: 
Eighty-six (84.3%) of 102 eyes completed the 1-year follow-up. By 12 months
postoperatively, 35 (40.7%) of the 86 eyes achieved visual acuity of 20/100 or
better while 34 (39.5%) of the 86 eyes experienced 2 or more Snellen lines of
visual improvement. In the 52 eyes with effective translocation and complete
laser photocoagulation of the CNV complex with sparing of the sensory fovea, the 
estimated incidence of recurrence was 34.6% at 12 months (95% confidence interval
of 21%-48%). Sixty-five percent of the recurrences were subfoveal and caused a
decrease in visual acuity. There was a trend toward worse median change in visual
acuity in eyes with persistent or recurrent CNV. CONCLUSIONS: Limited macular
translocation for the treatment of subfoveal CNV secondary to ARMD is associated 
with improvement in visual acuity in approximately 39.5% of eyes and enables
complete laser photocoagulation of the neovascular complex with sparing of the
sensory macula in approximately 60.4% of eyes that complete 1 year follow-up.
Persistence and recurrence of CNV are common after LMT and are important causes
of vision loss. Further studies are warranted to more precisely evaluate the
risks and benefits of LMT in ARMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12095810 [PubMed - indexed for MEDLINE]

2782: Ophthalmology. 2002 Jul;109(7):1235-42.

Early age-related maculopathy and self-reported visual difficulty in daily life.

Scilley K, Jackson GR, Cideciyan AV, Maguire MG, Jacobson SG, Owsley C.

Department of Ophthalmology, School of Medicine, University of Alabama at
Birmingham, 700 S 18th Street, Birmingham, AL 35294-0009, USA.

PURPOSE: To determine whether early age-related maculopathy (ARM) is associated
with visual difficulty in daily activities beyond the difficulty that would be
expected based on normal retinal aging; to determine whether scotopic sensitivity
and visual acuity are associated with visual difficulties in these older adults. 
STUDY DESIGN: Comparative, cross-sectional questionnaire study. SUBJECTS:
Ninety-two older adults with early ARM in at least one eye as defined by one or
more large (>63 microm) drusen and/or focal hyperpigmentation but no choroidal
neovascularization or geographic atrophy, acuity of 20/60 or better, and a
reference group of 55 older adults in the same age range without these fundus
features and acuity of 20/35 or better in each eye. METHOD: Tests of visual
acuity and scotopic sensitivity and a general health questionnaire were carried
out. The Activities of Daily Vision Scale (ADVS) was administered to assess
self-reported visual difficulties in everyday tasks and expressed on a scale of 0
(extreme difficulty) to 100 (no difficulty). Fundus photographs were taken and
graded to characterize the presence and severity of ARM to determine eligibility.
RESULTS: For purposes of analysis, the early ARM group was divided into those
whose fellow eye (FE) was 20/60 or better and those whose FE was worse than
20/60. ADVS subscale scores were substantially lower in the early ARM group with 
FE worse than 20/60 (medians, 58-83) compared with the normal retinal health
group (medians, 97-100). Even for those with early ARM with FE 20/60 or better,
four of five subscale scores were lower (medians, 81-97), albeit slightly in some
cases, than those of the reference group. For both ARM subgroups, the night
driving subscale had the lowest scores of all subscales. Persons with early ARM
with FE 20/60 or better were more likely to report difficulty on the night
driving (odds ratio [OR], 4.3; 95% confidence interval [CI], 1.6-11.4), near
vision (OR, 5.0; 95% CI, 1.9-12.9), and glare disability (OR, 2.7; 95% CI,
1.1-6.3) subscales compared with those in normal retinal health, adjusting for
age, gender, medical comorbidities, and lens density. For early ARM patients with
FE worse than 20/60, there was widespread reporting of difficulty on all
subscales (ORs ranging from 4.7-52.9). Poor scotopic sensitivity was highly
associated with difficulty on the night driving subscale (OR, 6.6; 95% CI,
1.2-35.5) but not with any other subscale. Acuity worse than 20/25 in both eyes
was significantly associated with difficulty on all ADVS subscales; when this
acuity impairment was present in one eye only, associations were still
significantly present on some subscales, although they were weaker. CONCLUSIONS: 
Persons in the early phases of ARM, even when their fellow eye has relatively
good acuity, are more likely to experience difficulty in night driving, near
vision tasks, and glare disability compared with those in good retinal health.
Scotopic dysfunction, a functional marker of early ARM, is linked to reported
night driving problems. Even when acuity impairment occurs in one eye only,
patients report difficulties with day driving and near and far vision tasks.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12093644 [PubMed - indexed for MEDLINE]

2783: Invest Ophthalmol Vis Sci. 2002 Jul;43(7):2435-41.

Spectral profiling of autofluorescence associated with lipofuscin, Bruch's
Membrane, and sub-RPE deposits in normal and AMD eyes.

Marmorstein AD, Marmorstein LY, Sakaguchi H, Hollyfield JG.

Department of Ophthalmic Research, Cole Eye Institute, The Cleveland Clinic
Foundation, Cleveland, Ohio 44195, USA. marmora@ccf.org

PURPOSE: To compare the autofluorescence spectra of retinal pigment epithelium
(RPE)-associated lipofuscin, Bruch's membrane, and sub-RPE deposits (drusen and
basal laminar-linear deposits) in eyes of donors with age-related macular
degeneration (AMD) against eyes of age-matched control donors. METHODS:
Cryosections were cut from the maculae of unfixed human donor eyes with AMD or
from age-matched control eyes. Tissues were excited at wavelengths of 364, 488,
568, and 633 nm. Emission spectra were collected with a confocal microscope
equipped with a spectrophotometric detector at 10-nm wavelength intervals between
400 and 800 nm. RESULTS: RPE lipofuscin had strong autofluorescent emissions that
were excited at all wavelengths. Bruch's membrane exhibited strong
autofluorescence with an emission peak of 485 +/- 5 nm when excited with 364-nm
light. At 488-, 568-, and 633-nm excitations, Bruch's membrane and sub-RPE
deposits in normal eyes exhibited minimal autofluorescence. In AMD eyes, however,
both the 364- and 488-nm excitation wavelengths stimulated substantial blue-green
emissions from sub-RPE deposits and Bruch's membrane, with average pixel
intensities substantially exceeding that elicited in the yellow-orange range by
RPE lipofuscin. CONCLUSIONS: These data suggest that an increase in blue-green
autofluorescence of Bruch's membrane relative to the yellow-orange
autofluorescence of RPE-associated lipofuscin is associated with AMD. Knowledge
of these spectra will be useful in evaluating animal models of macular
degenerative disease and in diagnosis of AMD, and will provide a novel signature 
for further analysis of the molecular entities emitting these fluorescent
signatures.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12091448 [PubMed - indexed for MEDLINE]

2784: Br J Ophthalmol. 2002 Jul;86(7):777-81.

Comment in:
    Br J Ophthalmol. 2003 Mar;87(3):375.    Br J Ophthalmol. 2004 Mar;88(3):439-40.

Perceived quality of health care in macular disease: a survey of members of the
Macular Disease Society.

Mitchell J, Bradley P, Anderson SJ, Ffytche T, Bradley C.

Department of Psychology, Royal Holloway, University of London, Egham, Surrey,
UK. J.Mitchell@rhul.ac.uk

AIM: To investigate the experiences of people with macular disease within the
British healthcare system. METHOD: The Macular Disease Society Questionnaire, a
self completion questionnaire designed to survey the experiences of people with
macular disease, was sent to 2000 randomly selected members of the Macular
Disease Society. The questionnaire incorporated items about people's experiences 
with health professionals and the information and support provided by them at the
time of diagnosis and thereafter. RESULTS: Over 50% thought their consultant eye 
specialist was not interested in them as a person and 40% were dissatisfied with 
their diagnostic consultation. 185 people thought their general practitioner (GP)
was well informed about macular disease but twice as many people thought their GP
was not well informed. About an equal number of people thought their GP was
supportive as those who thought their GP was not supportive. A total of 1247
people were told "nothing can be done to help with your macular disease." A
number of negative emotional reactions were experienced by those people as a
result, with 61% of them reporting feeling anxious or depressed. Of 282 people
experiencing visual hallucinations after diagnosis with macular disease, only
20.9% were offered explanations for them. CONCLUSIONS: Many people with macular
disease have unsatisfactory experiences of the healthcare system. Many of the
reasons for dissatisfaction could be resolved by healthcare professionals if they
were better informed about macular disease and had a better understanding of and 
empathy with patients' experiences.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12084749 [PubMed - indexed for MEDLINE]

2785: Expert Opin Pharmacother. 2002 Jul;3(7):931-8.

An update on photodynamic therapy in age-related macular degeneration.

Rechtman E, Ciulla TA, Criswell MH, Pollack A, Harris A.

Department of Ophthalmology, Indiana University School of Medicine, Indianapolis,
46202, USA.

Age-related macular degeneration (AMD) is the leading cause of irreversible loss 
of central vision in people aged > 50 years in the western world. Until recently,
the only proven treatment to reduce the risk of vision loss from its more severe 
neovascular form was laser photocoagulation, but this treatment was suitable for 
only 15% of cases. Photodynamic therapy (PDT) with verteporfin was recently
proposed to be effective in reducing the risk of visual loss for an estimated 20 
- 30% of neovascular AMD patients. This review covers AMD epidemiology, the
mechanism of PDT, the 2-year results of the two major clinical studies of PDT
with verteporfin, the cost-effectiveness of PDT and the current research status
of other drugs for PDT in AMD.

Publication Types: 
    Review

PMID: 12083992 [PubMed - indexed for MEDLINE]

2786: Cochrane Database Syst Rev. 2002;(2):CD000254.

Update in:
    Cochrane Database Syst Rev. 2006;(2):CD000254.

Update of:
    Cochrane Database Syst Rev. 2002;(1):CD000254.

Antioxidant vitamin and mineral supplements for age-related macular degeneration.

Evans JR.

Research and Development Department, Institute of Ophthalmology (UCL) and
Moorfields Eye Hospital, City Road, London, UK, EC1V 2PD.
jennifer.evans@ucl.ac.uk

BACKGROUND: It has been proposed that antioxidants may prevent cellular damage in
the retina by reacting with free radicals produced in the process of light
absorption. OBJECTIVES: The objective of this review is to assess the effects of 
antioxidant vitamin and/or mineral supplementation on the progression of
age-related macular degeneration. SEARCH STRATEGY: The Cochrane Controlled Trials
Register - CENTRAL/CCTR, which contains the Cochrane Eyes and Vision Group
specialised register (Cochrane Library Issue 3 2001), MEDLINE (1966 to August
2001), EMBASE (1980 to September 2001), the Science Citation Index, and the
reference lists of relevant articles were searched. Investigators of included
studies were contacted for further information. SELECTION CRITERIA: Randomised
trials comparing an antioxidant vitamin and/or mineral supplement (alone or in
combination) to control in people with age-related macular degeneration are
included in this review. DATA COLLECTION AND ANALYSIS: The reviewer extracted
data and assessed trial quality. Due to the variable methods of collecting and
presenting outcome data, no statistical summary measure was calculated. MAIN
RESULTS: Seven trials, which randomised 4119 people with signs of age-related
macular degeneration, are included in this review. One unpublished trial of zinc 
supplementation (170 participants) is awaiting assessment. The majority of people
(88%) were randomised in one trial that found a modest beneficial effect of
antioxidant and zinc supplementation on progression to advanced age-related
macular degeneration (odds ratio 0.72, 99% confidence interval 0.52 to 0.98).
People supplemented with antioxidants and zinc were less likely to lose 15 or
more letters of visual acuity (equivalent to a doubling of the visual angle)
(odds ratio 0.79, 99% confidence interval 0.60 to 1.04). This effect was seen
more strongly in people with moderate to severe disease. There were few events in
people with early signs of the disease. The trial evaluated many safety outcomes,
of which hospitalisation for genitourinary problems was more common in people
taking zinc and yellowing of skin was more common in people taking antioxidant
micronutrients. The other six trials in this review were small and the results
were inconsistent. REVIEWER'S CONCLUSIONS: The evidence as to the effectiveness
of antioxidant vitamin and mineral supplementation in halting the progression of 
age-related macular degeneration is dominated by one large trial that showed
modest benefit in people with moderate to severe signs of the disease. There is
no evidence at present that people with early signs of the disease should take
supplementation, however, current studies are underpowered to answer that
question. Long term harm from supplementation cannot be ruled out, particularly
in smokers. The generalisability of these findings to other populations with
different nutritional statuses is not known. Further large well-conducted
randomised controlled trials in other populations are required.

Publication Types: 
    Review

PMID: 12076389 [PubMed - indexed for MEDLINE]

2787: Exp Eye Res. 2002 May;74(5):571-6.

Cultivation of retinal pigment epithelial cells from human choroidal neovascular 
membranes in age related macular degeneration.

Schlunck G, Martin G, Agostini HT, Camatta G, Hansen LL.

Department of Ophthalmology, Universitätsklinikum Freiburg, Freiburg, Germany.

A method is described for cultivating retinal pigment epithelial cells from
choroidal neovascular membrane (CNV) specimens that were surgically removed in
patients with age-related macular degeneration (AMD). CNV specimens of 43
patients were available for cultivation. They were incubated in supplemented
DMEM/Ham's F12 cell culture medium on microporous semipermeable filter membranes.
Thirty-four specimens gave rise to cell cultures, 28 of which could be
subcultivated for up to 15 passages. The membrane type as classified by
fluorescence angiography was compared with cellular growth in vitro.
Immunocytochemistry revealed a uniform expression of cytokeratin 18 and vimentin,
while factor 8, glial fibrillary acidic protein and alpha smooth muscle actin
were absent in all 21 cultures stained. The expression of RPE markers cellular
retinaldehyde binding protein (CRALBP) and RPE65 was detected by RT-PCR in all
cultures tested. An epithelial character of the cultures was supported by the
presence of apical microvilli as determined by electron microscopical studies.
Therefore, the cell cultures from CNV in AMD bear characteristics of retinal
pigment epithelial cells. For the first time, this cell culture system holds the 
potential to study human RPE cells in the context of neovascular AMD in vitro.
Copyright 2002 Elsevier Science Ltd.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12076078 [PubMed - indexed for MEDLINE]

2788: J AAPOS. 2002 Jun;6(3):154-62.

Erratum in:
    J AAPOS 2002 Aug;6(4):246.

Strabismus surgery for large-angle cyclotorsion after macular translocation
surgery.

Freedman SF, Rojas M, Toth CA.

Duke University, Durham, North Carolina, USA.

PURPOSE: We report the results of a new strabismus surgical procedure to address 
the large-angle cyclotorsion induced by macular translocation surgery for severe 
age-related macular degeneration. METHODS: The strabismus surgery described is a 
modification of earlier-described surgery(1) and was performed for symptomatic
incyclotorsion measuring 20 degrees or more (by Maddox rod testing) after macular
translocation. Surgery included superior oblique tenotomy and inferior oblique
advancement, with transposition of the lateral and medial recti to the insertions
of the superior and inferior recti, respectively, in the affected eyes. Minimum
follow-up time was 6 weeks. RESULTS: Fifteen patients (15 eyes) had macular
translocation surgery with incyclotorsion of 20 degrees or more. Mean
incyclotorsion after macular translocation (36.1 +/- 9.4 degrees; range, 20-55)
was reduced to 1.5 +/- 6.4 degrees after strabismus surgery (P <.0001), with 2
overcorrections and no surgical complications. Mean follow-up time was 24.8 +/-
13.4 weeks. All patients showed a hypertropia of the fellow eye. The mean pre-op 
hypertropia of 22 +/- 8 PD was reduced to 3 +/- 9 PD after strabismus surgery (P 
<.0001). The mean exotropia was minimally altered by strabismus surgery (21 +/-
10 PD pre vs 17 +/- 8 PD postop). All patients were symptomatic prior to
strabismus surgery: 4 of 15 patients with "tilt" (objects appearing subjectively 
rotated with respect to their true orientation); 2 of 15 patients with diplopia; 
and 9 of 15 patients with both. Postoperatively, 7 patients had residual milder
symptoms: tilt, 2 patients; diplopia, 3 patients; and both, 2 patients. Two
patients required additional muscle surgery (on the fellow eye) for persistent
symptoms. No patient showed binocular function (stereopsis or motor fusion) after
macular translocation, either before or following strabismus surgery for
cyclotorsion. CONCLUSION: The strabismus surgery described is effective at
reducing the large degree of cyclotorsion (>or= 20 degrees) often resulting from 
macular translocation surgery, but does not allow reestablishment of binocular
function.

PMID: 12075291 [PubMed - indexed for MEDLINE]

2789: Graefes Arch Clin Exp Ophthalmol. 2002 May;240(5):337-41. Epub 2002 Mar 23.

Side effects after radiotherapy of age-related macular degeneration with the
Nijmegen technique.

Hoyng CB, Tromp AI, Meulendijks CF, Leys A, van der Maazen RW, Deutman AF,
Vingerling JR.

Department of Ophthalmology, University Medical Centre Nijmegen, P.O. Box 9101,
The Netherlands. c.hoyng@ohk.azn.nl

BACKGROUND: In a randomized trial concerning radiotherapy for age-related macular
degeneration, fluorescein angiograms were taken of controls and patients. In this
study the frequency of side effects in eyes receiving radiotherapy with the
Nijmegen technique is compared with the findings in the eyes of controls.
METHODS: Patients receiving treatment were irradiated by two isocentric photon
beams in four fractions of 6 Gy that were directed to the macular area at 30
degrees and -30 degrees with regard to the optical axis. The most recent
fluorescein angiograms of the randomized eyes (32 treated and 31 control eyes)
were scored by two independent researchers, using a scoring form with nine
features of radiation retinopathy: nonperfusion, macular edema, microaneurysms,
retinal hemorrhages, cotton-wool spots, perifoveal telangiectasis, vascular
sheathing, retinal neovascularization, and radiation-associated choroidal
neovasculopathy. The results were graded as: no retinopathy (grade 0), mild
retinopathy (grade 1), moderate retinopathy (grade 2), and severe retinopathy
(grade 3). RESULTS: In the treated group 6 patients (18.8%) were grade 1, 10
patients (31.2%) were grade 2 and 7 patients (21.9%) were grade 3. In the control
group 9 patients (29.0%) were grade 1, 11 patients (35.5%)were grade 2 and 2
patients (6.5%) were grade 3. There were no patients with retinal
neovascularization. CONCLUSION: With the Nijmegen technique a relatively high
dose of radiation can be applied to a small retinal area. In only a minority of
cases does some evidence of radiation retinopathy occur.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 12073055 [PubMed - indexed for MEDLINE]

2790: Ageing Res Rev. 2002 Jun;1(3):381-96.

Photoreceptor degeneration and dysfunction in aging and age-related maculopathy.

Jackson GR, Owsley C, Curcio CA.

Department of Ophthalmology, School of Medicine, University of Alabama,
Birmingham, AL 35294-0009, USA.

The relative rate of rod and cone degeneration is a fundamental characteristic of
any disorder affecting photoreceptors, including aging and age-related
maculopathy (ARM). The human macula consists of a small cone-dominated fovea
surrounded by a rod-dominated parafovea. In aging and early ARM, rods degenerate 
before cones, a decline in scotopic (rod-mediated) sensitivity is more prominent 
than a decline in photopic (cone-mediated) sensitivity, and the time course of
dark adaptation of rods slows dramatically. The topography of rod dysfunction and
loss in early ARM matches the location of pathology in the retinal pigment
epithelium (RPE)/Bruch's membrane complex visible in the ocular fundus. Rod
dysfunction and loss in aging and ARM may be due to retinoid deficiency at the
level of the photoreceptors cause by impaired retinoid translocation across the
RPE/Bruch's membrane complex, a hypothesis deserving of further investigation.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.
    Review

PMID: 12067593 [PubMed - indexed for MEDLINE]

2791: Ophthalmologica. 2002 May-Jun;216(3):209-14.

Detection of inducible nitric oxide synthase and vascular endothelial growth
factor in choroidal neovascular membranes.

Hattenbach LO, Falk B, Nürnberger F, Koch FH, Ohrloff C.

Klinik für Augenheilkunde, Klinikum der Johann-Wolfgang-Goethe-Universität,
Frankfurt am Main, Deutschland. Hattenbach@em.uni-frankfurt.de

Vascular endothelial growth factor (VEGF) is among the cytokines which have been 
implicated in the pathogenesis of choroidal neovascularization secondary to
age-related macular degeneration (ARMD). There is, however, evidence that
intercellular signaling molecules, such as nitric oxide (NO), are involved in
this process. NO is synthesized via the inducible isoform of NO synthase (iNOS), 
which is expressed after induction by cytokines. In the current study, we
investigated whether VEGF and iNOS are coexpressed in choroidal neovascular
membranes (n = 7) from patients with ARMD. Immunohistochemistry was performed on 
cryosections with anti-iNOS and anti-VEGF. Moderate to intense immunostaining for
iNOS and VEGF was observed in retinal pigment epithelial cells, macrophages, and 
in spatial relation to vessel walls. As scored by light microscopy, we found a
significant correlation between immunoreactivity for VEGF and iNOS (p < 0.0341)
in vascular endothelial cells. Our study supports a significant role for iNOS in 
the pathogenesis of neovascularization and membrane growth in ARMD. Moreover, our
findings suggest a possible relationship between NO and VEGF in the regulation of
pathologic angiogenesis in this disease. Copyright 2002 S. Karger AG, Basel

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12065859 [PubMed - indexed for MEDLINE]

2792: J Struct Biol. 2002 Jan-Feb;137(1-2):31-40.

Analysis of the collagen VI assemblies associated with Sorsby's fundus dystrophy.

Knupp C, Chong NH, Munro PM, Luthert PJ, Squire JM.

Biological Structure and Function Section, Biomedical Sciences Division, Imperial
College Faculty of Medicine, London SW7 2AZ, United Kingdom.

Age-related macular degeneration is the leading cause of blindness in the Western
world, and the pathophysiology of the condition is largely unknown. However, it
shares many clinical and pathological features with Sorsby's fundus dystrophy
(SFD), an autosomal dominant disease, known to be associated with mutations in
the TIMP-3 gene. In Bruch's membrane of both conditions, there are molecular
assemblies with distinct transverse bands occurring with a periodicity of about
100 nm. Similar assemblies were also found in the vitreous of a patient with
full-thickness macular holes and were identified as being made of collagen VI.
The assemblies found in the eye with SFD can be classified into two types, both
with a 105-nm axial repeat, but one showing pairs of narrow bands about 30 nm
apart and the other showing a single broad band in every repeat. By comparison
with the assemblies in the vitreous, collagen VI is considered to be the most
likely protein in these assemblies. Furthermore, both of the assemblies
associated with SFD can be explained in terms of collagen VI tetramers, one in
which the tetramers bind to the mutant tissue inhibitor of metalloproteinases-3
(the gene product of TIMP-3) and the other in which little or no binding occurs. 
TIMP-3 bound to collagen VI may be more resistant to degradation and create an
imbalance between the normal amount of TIMP-3 and matrix metalloproteinases (the 
substrate of TIMPs) in Bruch's membrane with consequent disruption of the normal 
metabolic processes. Understanding the structure of these collagen VI/TIMP
assemblies in Bruch's membrane may prove to be important for understanding the
pathophysiology of age-related macular degeneration. (c) 2002 Elsevier Science
(USA).

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12064931 [PubMed - indexed for MEDLINE]

2793: Ophthalmol Clin North Am. 2002 Mar;15(1):93-100, viii.

Understanding the etiology of Stargardt's disease.

Glazer LC, Dryja TP.

Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical
School, 243 Charles Street, Boston, MA 02114, USA. lcglazer@netscape.net

Stargardt's disease is a form of juvenille macular degeneration. Patients with
Stargardt's disease typically present in the first or second decade of life,
complaining of decreased visual acuity. Recent research allows for a three-step
explanation of the pathophysiology of Stargardt's disease: 1) Defective Rim
Protein, a protein encoded by the ABCA4 gene, causes an accumulation of
protonated N-retinylidene-PE in the rod outer segments; 2) A2-E, a byproduct of
N-retinylidene-PE, then accumulates in the RPE cells and is toxic to them; 3)
Photoreceptors eventually die secondary to loss of the RPE support function. With
our new knowledge of the etiology of Stargardt's disease, we can devise future
studies directed at treating affected patients.

Publication Types: 
    Review

PMID: 12064087 [PubMed - indexed for MEDLINE]

2794: Ophthalmol Clin North Am. 2002 Mar;15(1):87-91.

Mechanisms of age-related macular degeneration.

Husain D, Ambati B, Adamis AP, Miller JW.

Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical
School, 243 Charles Street, Boston, MA 02114, USA. Deeba_Husain@meei.harvard.edu

AMD is a poorly understood disease at this time. Since it is the leading cause of
blindness in the elderly in the developed world, there is a pressing need for
better treatment. Therefore, there is extensive ongoing research in both
pathogenesis and therapy of AMD. Epidemiological studies have shown significant
risk associated with increasing age and cigarette smoking, future studies may
identify environmental risk factors though at present studies have been
inconclusive. Genetic studies may identify subgroups of disease and thus help
provide a selective approach to treatment. The vascular model of AMD may provide 
better understanding of the blood flow and post capillary resistance and help in 
early and newer intervention in the disease. Vascular endothelial growth factor
has been extensively studied in choroidal neovascularization. It has been
demonstrated in human and animal models of CNV and VEGF antagonists are currently
in clinical trial. Extensive work is ongoing to prevent and treat CNV with
antiangiogenic agents.

Publication Types: 
    Review

PMID: 12064086 [PubMed - indexed for MEDLINE]

2795: Jpn J Ophthalmol. 2002 May-Jun;46(3):315-22.

Vitrectomy for diabetic cystoid macular edema.

Sato Y, Lee Z, Shimada H.

Department of Ophthalmology, Nihon University School of Medicine, Tokyo, Japan.

PURPOSE: We evaluated visual outcomes following vitrectomy for diabetic cystoid
macular edema. METHODS: Visual outcomes and factors possibly influencing final
visual acuity were assessed and documented retrospectively in 45 eyes of 40
patients, all of whom were followed up for at least 6 months postoperatively.
RESULTS: Compared with the preoperative logarithm of the minimum angle of
resolution (logMAR) visual acuity, final logMAR visual acuity improved 0.2 or
more in 51% of the eyes, was unchanged in 47%, and decreased 0.2 or more in 2%. A
final postoperative visual acuity of 0.5 or better was achieved in 38%.
Preoperative visual acuity and the extent of the cystoid space on fluorescein
angiography were significantly related to final visual acuity. A final
postoperative visual acuity of 0.5 or better was noted in 8% of eyes with a
preoperative visual acuity below 0.1, in 50% of eyes with a preoperative visual
acuity of 0.1 or better, in 71% of eyes with a cystoid space smaller than 5 disc 
areas, and in 20% of eyes with a cystoid space of 5 disc areas or more. The state
of the posterior vitreous membrane did not influence final visual acuity. There
were no complications that decreased visual acuity. CONCLUSIONS: We conclude that
diabetic cystoid macular edema is a good indication for vitrectomy, regardless of
the state of the posterior vitreous membrane. A preoperative visual acuity of 0.1
or better and/or a cystoid space smaller than 5 disc areas may be indications for
surgery aimed at achieving a final postoperative visual acuity of 0.5 or better.

PMID: 12063043 [PubMed - indexed for MEDLINE]

2796: Ann Acad Med Singapore. 2002 May;31(3):399-404.

Age-related macular degeneration: what's new.

Koh AH, Ang CL.

Singapore National Eye Centre, 11 Third Hospital Avenue, Singapore 168751.
adrian_koh@snec.com.sg

INTRODUCTION: Age-related macular degeneration (AMD) is the leading cause of
irreversible blindness in the developed western world, accounting for
approximately 50% of all cases of registered blindness. The rising prevalence of 
this disease in Asia seems to parallel the same trend in the developed world.
Because of the socio-economic impact of this disorder, much attention has been
paid to elucidating the underlying pathogenic mechanisms, as well as seeking
alternative forms of treatment. This review discusses the latest advances in AMD 
diagnosis, treatment and prophylaxis. METHODS: Medline search with emphasis on
randomised controlled clinical trials and large case-control series. Only
articles cited on the Index Medicus were included in this review. RESULTS: Recent
advances in the diagnosis and treatment of AMD include conventional argon laser
photocoagulation, photodynamic therapy (PDT), radiation therapy, surgical options
and gene therapy. CONCLUSIONS: There have been numerous advances in the
management of AMD and exciting new research applications have emerged. The
introduction of exciting new modalities, such as PDT, has revolutionised the
approach to treating CNVM and their effects on central vision. However, there has
been no breakthrough in achieving satisfactory outcomes with the available
techniques for treating occult neovascular lesions. As results of large
prospective randomised clinical trials evaluating new treatment alternatives
become available, a treatment algorithm for neovascular AMD will emerge that best
minimises visual loss and may even result in visual improvement.

Publication Types: 
    Review

PMID: 12061304 [PubMed - indexed for MEDLINE]

2797: Am J Occup Ther. 2002 May-Jun;56(3):322-30.

A health education program for elderly persons with visual impairments and
perceived security in the performance of daily occupations: a randomized study.

Dahlin Ivanoff S, Sonn U, Svensson E.

Department of Ophthalmology, Department of Geriatric Medicine, Institute of
Occupational Therapy and Physiotherapy, Göteborg University, Göteborg, Sweden.
sydi@fhs.gu.se

OBJECTIVE: The purpose of this randomized, longitudinal study was to investigate 
the impact of a health education program on perceived security in the performance
of daily occupations 4 months after the intervention period. METHOD: Two groups
of persons with age-related macular degeneration were compared: Those who had
followed a newly developed health education program that was based on occupation 
and those who took part in a standard individual intervention program. RESULTS:
Significant differences in the level of perceived security between the groups
were found for 13 of 28 occupations. Participants in the health education group
maintained or improved their level of perceived security in 22 daily occupations,
whereas those in the individual intervention group declined to a lower level in
17 daily occupations. CONCLUSION: This study provides support for the
effectiveness of the health education program to enhance security and hinder a
progressive decline in perceived security in daily occupations.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12058521 [PubMed - indexed for MEDLINE]

2798: Retina. 2002 Jun;22(3):309-16.

The ultra-late phase of indocyanine green angiography for healthy subjects and
patients with age-related macular degeneration.

Mori K, Gehlbach PL, Nishiyama Y, Deguchi T, Yoneya S.

Department of Ophthalmology, Saitama Medical School, Saitama, Japan.
keisuke@saitama-med.ac.jp

PURPOSE: To compare the characteristics of residual fundus fluorescence observed 
in the ultra-late phase of indocyanine green (ICG) angiography, in normal
subjects and in patients with age-related macular degeneration (ARMD). METHODS:
ICG angiography was performed on 38 patients, 21 had ARMD, 9 were normal subjects
aged >62, and 8 were normal subjects aged <36. The intensity and pattern of
fluorescence from angiograms obtained in the ultra-late phase, 24 hours after dye
injection, was also recorded and analyzed. RESULTS: In the ultra-late phase, 95% 
of ARMD eyes with CNV showed geographic hypofluorescent lesions. All of the CNV
that could be delineated with fluorescein and/or ICG angiography were located in 
these geographic lesions. In 73% of ARMD eyes without CNV, these hypofluorescent 
lesions occurred, while age-matched normal subjects had no hypofluorescent
lesions. The mean intensity of fluorescence in the normal older subject group was
significantly higher than that seen in the normal young subject group.
CONCLUSIONS: Increased fluorescence, associated with older subjects, in the
ultra-late phase of ICG angiography may reflect aging changes in the
chorioretinal complex. Geographic hypofluorescent areas, demonstrated only in the
ultra-late phase, associate with ARMD and may represent areas predisposed to CNV 
development.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12055464 [PubMed - indexed for MEDLINE]

2799: Retina. 2002 Jun;22(3):300-8.

Grading of infrared confocal scanning laser tomography and video displays of
digitized color slides in exudative age-related macular degeneration.

Miura M, Elsner AE, Beausencourt E, Kunze C, Hartnett ME, Lashkari K, Trempe CL.

The Schepens Eye Research Institute, Boston, Massachusetts 02114, USA.

PURPOSE: To detect and localize exudative lesions in exudative age-related
macular degeneration and to compare images obtained from infrared scanning laser 
tomography and video displays of digitized color slides in detection and
localization of exudation. METHODS: In a prospective study, 11 eyes of 11
patients with exudative age-related macular degeneration were studied. From 32
images with infrared scanning laser tomography, confocal images were chosen in
the following focal planes: anterior to the retina, the retinal surface, and the 
deep retina. Using the fluorescein angiogram as a standard, three retinal
specialists rank-ordered the ability to discern the lesion in these confocal
images, the summary of confocal images, and video displays of digitized color
slides that were adjusted to the same resolution as that of the confocal images
(approximately 23 microm per pixel). RESULTS: For choroidal neovascularization,
both the retinal surface image and the summary image were rated superior to video
displays of digitized color slides (P < 0.004). The confocal images were ranked
in the following fashion: best, retinal surface; next, deep retina; and then,
anterior to the retina (P < 0.01). For pigment epithelial detachment, all three
confocal images and summary images were superior to video displays of digitized
color slides (P < 0.002). There were no significant differences among the
confocal images (P = 0.95). CONCLUSION: Infrared confocal imaging was superior to
video displays of digitized color slides for visualization of both pigment
epithelial detachment and choroidal neovascularization. This technique could have
an impact on epidemiologic studies.

Publication Types: 
    Comparative Study
    Research Support, U.S. Gov't, P.H.S.

PMID: 12055463 [PubMed - indexed for MEDLINE]

2800: J Am Acad Nurse Pract. 2002 May;14(5):207-13.

Gaining insight into age-related macular degeneration.

Frock TL.

TLFRNEDD@aol.com

PURPOSE/OBJECTIVE: To enhance nurse practitioner (NP) recognition of clients with
age-related macular degeneration (AMD) based on history and physical examination 
findings, to encourage prompt initial referral of these clients to an
ophthalmologist for a treatment evaluation, and to acquaint NPs with low vision
rehabilitation services. DATA SOURCES: Government documents, professional
association practice guidelines, original research articles, journal articles,
and Internet resources. CONCLUSIONS: Age-related macular degeneration is a
common, chronic vision-threatening condition necessitating prompt recognition and
professional evaluation. If not recognized early, AMD can lead to low vision and 
a diminished quality of life for the elderly client. IMPLICATIONS FOR PRACTICE:
Even though NPs have a limited role in the treatment of AMD, they are in an
instrumental position as a primary care providers to screen for this disease
chiefly by: (a) adherence to eye examinations intervals, (b) recognition of risk 
factors, (c) use of the Amsler grid, (d) awareness of psychosocial dimensions,
(e) making appropriate referrals, and (f) advocating low vision rehabilitation
services.

Publication Types: 
    Review

PMID: 12051144 [PubMed - indexed for MEDLINE]

2801: Arch Ophthalmol. 2002 Jun;120(6):731-7.

Decreased visual acuity associated with cystoid macular edema in neovascular
age-related macular degeneration.

Ting TD, Oh M, Cox TA, Meyer CH, Toth CA.

Department of Ophthalmology, Duke University Medical Center, Box 3802, Erwin
Road, Durham, NC 27710, USA.

OBJECTIVE: To determine the prevalence and visual significance of cystoid macular
edema (CME) in eyes with subfoveal neovascular age-related macular degeneration
using optical coherence tomography (OCT). MATERIALS AND METHODS: The medical
records of 61 consecutive patients initially seen with nondisciform subfoveal
neovascular age-related macular degeneration were retrospectively reviewed. All
patients underwent fluorescein angiography and OCT imaging. Eyes with
intraretinal hyporeflective spaces in the macula in the OCT images were
considered to have CME. RESULTS: Twenty-eight (46%) of 61 eyes demonstrated CME
on the OCT images. The presence of CME and increased foveal thickness correlated 
with decreased visual acuity, but not with the duration of symptoms. Twenty-six
(93%) of 28 eyes with CME contained classic choroidal neovascularization, whereas
16 (48%) of 33 eyes without CME contained classic choroidal neovascularization.
CONCLUSIONS: Cystoid macular edema is a common finding in patients with choroidal
neovascularization associated with age-related macular degeneration. The presence
of CME and foveal thickening is associated with worse visual acuity in these
patients. Cystoid macular edema is more common with choroidal neovascularization 
containing classic component. The OCT is a useful test to detect the presence of 
CME in these patients since CME may be difficult to identify on fluorescein
angiogram.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12049577 [PubMed - indexed for MEDLINE]

2802: Ophthalmology. 2002 Jun;109(6):1092-7.

Erratum in:
    Ophthalmology 2002 Sep;109(9):1588.

Five-year incidence of age-related maculopathy lesions: the Blue Mountains Eye
Study.

Mitchell P, Wang JJ, Foran S, Smith W.

Department of Ophthalmology and the Save Sight and Westmead Millennium
Institutes, the University of Sydney, Westmead, nsw, Australia.

PURPOSE: To describe the 5-year incidence and progression of early and late
age-related maculopathy (ARM) lesions. DESIGN: Population-based cohort study.
PARTICIPANTS: Three thousand six hundred fifty-four noninstitutionalized
residents, aged 49 years or older, living in the Blue Mountains area west of
Sydney, Australia, participated in the study during 1992 to 1994. The cohort was 
reexamined after 5 years (1997-1999). Excluding 543 participants who died since
the baseline, 2335 (75%) survivors attended 5-year follow-up examinations.
METHODS: Retinal photographs from both examinations were graded using the
Wisconsin ARM Grading System. Photographs of participants with any ARM lesions at
either examination were regraded in detail using a modification of the
side-by-side method developed for the Beaver Dam Eye Study. MAIN OUTCOME
MEASURES: Incidence and progression of ARM lesions were defined in a similar
manner to that used in the Beaver Dam Eye Study. RESULTS: Incidence rates for all
ARM lesions increased significantly with age. For late ARM lesions (geographic
atrophy and neovascular ARM), the overall 5-year incidence was 1.1%. The combined
late ARM incidence was 0.0%, 0.6%, 2.4%, and 5.4% for participants aged 60 years 
and younger, 60 to 69 years, 70 to 79 years, and 80 years and older at baseline, 
respectively. After excluding participants with either early or late ARM in
either eye at baseline, the overall 5-year incidence of early ARM was 8.7%,
including 3.2%, 7.4%, 18.3%, and 14.8% for the corresponding age groups. The
incidence of neovascular ARM in women was double that for men (P = 0.1).
CONCLUSIONS: This study has documented the incidence of ARM lesions in an older
Australian population. The slightly higher incidence of hyperpigmentation found
in our population compared with the Beaver Dam Eye Study may be due to sample
variability, or this could reflect real differences between the two populations. 
Our lower incidence of soft drusen could have resulted from our non-inclusion of 
intermediate soft drusen in the soft distinct and indistinct drusen categories.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12045049 [PubMed - indexed for MEDLINE]

2803: Invest Ophthalmol Vis Sci. 2002 Jun;43(6):2055-62.

Shape discrimination in age-related macular degeneration.

Wang YZ, Wilson E, Locke KG, Edwards AO.

Retina Foundation of the Southwest, Dallas, Texas 75231, USA.
yiwang@retinafoundation.org

PURPOSE: Recent studies suggest that a global shape-discrimination task is
sensitive to neural undersampling and/or irregular sampling, but is not affected 
by normal aging. In this study, the ability of patients with age-related macular 
degeneration (AMD) to perform the shape-discrimination task was examined.
METHODS: Twenty patients with AMD (age range, 66-81 years) were selected on the
basis of Snellen visual acuity of 20/50 or better in at least one eye and prior
clinical documentation. A control group consisted of 10 older subjects (age
range, 61-93 years) with normal findings in a fundus examination. Radial
frequency (RF) patterns were used as stimuli. A spatial paradigm and a temporal
two-alternative, forced-choice (2AFC) staircase paradigm were used. In each
trial, two RF patterns (one deformed and one undeformed) were presented, and
patients were asked to identify the deformed pattern. The peak spatial frequency 
of RF patterns was 5 cyc/deg; the radial modulation frequency was 8 cyc/360
degrees; mean radii were 0.5 degrees, 1 degrees, 2.0 degrees, or 2.5 degrees; and
stimulus contrast was 80%. Thresholds for detecting the deformation were
estimated by a maximum-likelihood fitting procedure. RESULTS: Thirty-five of 40
eyes with AMD had 20/50 or better acuity. Among them, 29 eyes had early AMD
(drusen, hyperpigmentation, hypopigmentation), 5 had extrafoveal geographic
atrophy, and 1 had exudative AMD. With the spatial 2AFC, 91% (32/35) of eyes with
AMD showed significant elevation of the threshold for detecting radial
deformation of RF patterns when compared with normal control eyes. With the
temporal 2AFC, 97% (31/32) of eyes with AMD showed significant threshold
elevations, and the degree of the deficit in the shape discrimination did not
correlate significantly with visual acuity loss (r = 0.3, P = 0.094). Comparison 
of the severity of AMD with shape-discrimination performance revealed that the
average detection threshold of the eyes with extrafoveal geographic atrophy was
significantly higher than that of the eyes with drusen only (P < 0.01), even
though average acuity showed no significant difference. CONCLUSIONS: Patients
with AMD had significant deficits in performing the global shape-discrimination
task. The dissociation of shape discrimination with visual acuity suggests that
the shape-discrimination task may provide distinguishable information about the
integrity of the photoreceptor mosaic in AMD.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 12037018 [PubMed - indexed for MEDLINE]

2804: Invest Ophthalmol Vis Sci. 2002 Jun;43(6):1986-93.

Quantifying changes in RPE and choroidal vasculature in eyes with age-related
macular degeneration.

McLeod DS, Taomoto M, Otsuji T, Green WR, Sunness JS, Lutty GA.

Wilmer Ophthalmological Institute, Johns Hopkins Hospital, Baltimore, Maryland
21287-9115, USA.

PURPOSE: An image-analysis technique was developed to quantify changes in the
retinal pigment epithelium (RPE) and choriocapillaris in eyes of deceased donors 
with age-related macular degeneration (AMD). METHODS: Both eyes of two donors
with AMD and of one normal control donor were used to develop this technique.
After removal of the anterior segments, the eyecups were hemisected through the
macula, with the disc included in one half of the eyecup. The choroid with RPE
cells was dissected from the sclera and incubated for alkaline phosphatase
(APase) activity, and the pigment was partially bleached with H2O2. The
APase-incubated choroid was flat embedded and sectioned after image and
morphometric analyses. Quantitative computer-assisted morphometric analyses of
the two AMD-affected eyes (cases 1 and 2) were compared with analysis of the
normal eye of a 70-year-old control subject (case 3). RESULTS: The right eye in
case 1 had geographic atrophy (GA) and demonstrated a large area in the posterior
pole with very few RPE cells (90% loss of RPE), but the border of the area of RPE
atrophy was not well defined. The density of choroidal blood vessels in this area
was reduced 30% to 50%, compared with the same regions in the control eye. No
area was completely devoid of choriocapillaris. Clinically undetected choroidal
neovascularization (CNV) was observed in the right eye in case 1 in both the
periphery and the macula and was generally associated with surviving RPE cells.
The right eye in case 2 had GA (areolar RPE atrophy) and demonstrated a reduction
in vascular density in the area from disc to macula that was even greater than
that in the eye in case 1 (53% reduction in the submacular region). RPE atrophy
between the disc and macula was almost complete. The border of the RPE defect was
clearly delineated and coincided closely with the area of decreased choroidal
vascular density. Surviving choriocapillaris in the area of RPE atrophy was
significantly narrower than choriocapillaris in the control subject and in normal
areas of the eyes with GA (P < 0.0001). CONCLUSIONS: In these eyes with GA, RPE
atrophy was more severe than loss of choriocapillaris. Surviving choriocapillaris
in areas with complete RPE loss was highly constricted. The association of
surviving RPE cells with CNV suggests that RPE cells may furnish a stimulus for
new vessel formation or stabilization.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12037009 [PubMed - indexed for MEDLINE]

2805: Invest Ophthalmol Vis Sci. 2002 Jun;43(6):1928-32.

Macular pigment and melanin in age-related maculopathy in a general population.

Berendschot TT, Willemse-Assink JJ, Bastiaanse M, de Jong PT, van Norren D.

Department of Ophthalmology, University Medical Center Utrecht, Utrecht, The
Netherlands. tosb@isi.uu.nl

PURPOSE: It has been suggested that macular pigment (MP) and melanin may protect 
against age-related maculopathy (ARM). To check this, MP and melanin optical
density were measured in a random population-based sample of subjects 55 years of
age or older. METHODS: Spectral fundus reflectance of the fovea was measured in
one eye per subject in a 2.3 degrees detection field with a fundus reflectometer.
The sample consisted of 199 men and 236 women. Analysis with a fundus reflectance
model yielded individual estimates for the MP and melanin optical density.
Diagnosis of ARM was based on grading of standardized fundus transparencies. Eyes
were stratified in four exclusive stages of ARM. RESULTS: MP optical density (at 
460 nm) was 0.33 +/- 0.15 in eyes without ARM (n = 289) and 0.33 +/- 0.16 in eyes
at any stage of ARM (n = 146). Melanin optical density (at 500 nm) was 1.18 +/-
0.19 in eyes without ARM and 1.20 +/- 0.21 in eyes at any stage of ARM. We found 
no gender differences for either MP or melanin optical density. CONCLUSIONS: No
differences in MP and melanin optical density were found between eyes with and
without ARM or between the various ARM stages.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12037001 [PubMed - indexed for MEDLINE]

2806: Am J Ophthalmol. 2002 Jun;133(6):801-8.

Comment in:
    Am J Ophthalmol. 2003 Jan;135(1):124-5; author reply 125.

Clinical observations supporting a theoretical model of choriocapillaris blood
flow in treatment of choroidal neovascularization associated with age-related
macular degeneration.

Staurenghi G, Flower RW.

Department of Ophthalmology, University of Brescia, Brescia, Italy.

PURPOSE: To report clinical observations consistent with conclusions from a
previous theoretical investigation indicating that photocoagulation of choroidal 
neovascularization (CNV) efferent vessels can be, in some instances, an effective
treatment. DESIGN: Interventional case series. METHODS: In five eyes with
age-related macular degeneration (five patients with mean age +/- SD of 65 +/- 11
years, range 55-79 years) requiring treatment of CNV. In each case, the
appropriate treatment was location and photocoagulation of the CNV efferent
vessels, since the afferent vessels were not identifiable or were located beneath
the fovea. Targeted vessels were determined to be draining vessels by analysis of
pretreatment high-speed indocyanine green (ICG) angiograms, and successful vessel
closure by photocoagulation was demonstrated by posttreatment ICG angiograms. The
eyes subsequently were followed from 2 to 12 months. RESULTS: After
photocoagulation of efferent vessels, CNV-related retinal edema was significantly
reduced or resolved within 1 to 4 days. Visual acuity became stabilized in three 
eyes and improved in two eyes. In a few days, metamorphopsia disappeared in four 
of the eyes and was stable for a period longer than the duration of the
associated efferent vessel closure. Initial efferent vessel closure by
photocoagulation persisted on average for 7 to 15 days, after which additional
treatment was required. It is significant that in no case did hemorrhage result
from the photocoagulation treatment. CONCLUSIONS: These observations are
consistent with the earlier theoretical study prediction that photocoagulation of
efferent CNV vessels can be effective in reducing CNV-associated edema. That no
hemorrhage was induced by photocoagulation is consistent with the theoretical
concept that there appears to be no direct hydrostatic connection between the CNV
and its afferent vessels. Rather, that connection appears to be a functional one 
made through the choriocapillaris, which may dissipate excess CNV hydrostatic
pressure produced by occlusion of a draining vessel. However, this finding is not
intended to be a recommendation to attempt CNV efferent vessel photocoagulation.

PMID: 12036672 [PubMed - indexed for MEDLINE]

2807: Br J Ophthalmol. 2002 Jun;86(6):663-9.

Eligibility for treatment and angiographic features at the early stage of
exudative age related macular degeneration.

Haddad WM, Coscas G, Soubrane G.

Department of Ophthalmology, University Paris XII, Creteil, France.

AIMS: To determine the eligibility for laser photocoagulation treatment or for
photodynamic therapy (PDT) with verteporfin in eyes at the earliest stage (first 
month of symptoms) of exudative age related macular degeneration (AMD) based on
fluorescein angiographic (FA) features; to evaluate the potential contribution of
indocyanine green angiography (ICG-A) for occult choroidal neovascularisation
(CNV) at this stage. METHODS: Retrospective review of 252 consecutive patients
(269 eyes) examined within the first month of symptoms of exudative AMD. RESULTS:
On FA, 97 eyes (36%) had classic CNV alone. Occult CNV associated with
fibrovascular retinal pigment epithelium detachments (PEDs) was observed in 71
eyes (26%) and without fibrovascular PED in 101 eyes (38%). 91 eyes (34%) met the
Macular Photocoagulation Study criteria for laser photocoagulation. 53 eyes (20%)
met the Verteporfin In PDT (VIP) or Treatment of AMD with PDT (TAP) studies
criteria. By ICG-A, occult CNV was visualised as focal spots in 49% of eyes
examined within 15 days v 32% of eyes examined between 16 and 30 days after the
onset of symptoms (p=0.07). 8.5% of late staining plaques disclosed in eyes
examined within 15 days were combined with focal spots v 36% in eyes examined
between 16 and 30 days (p<0.01). CONCLUSIONS: Early examination of eyes with
exudative AMD would allow the treatment of 47% of eyes. 60% of eyes with
subfoveal CNV would be eligible for PDT with verteporfin. Up to half of eyes with
occult CNV would be converted by ICG-A into well delineated focal spots.

PMID: 12034690 [PubMed - indexed for MEDLINE]

2808: Br J Ophthalmol. 2002 Jun;86(6):623-6.

Retinal topography and thickness mapping in atrophic age related macular
degeneration.

Shahidi M, Blair NP, Mori M, Gieser J, Pulido JS.

AIM: To determine the relation between alterations in the retinal topography and 
thickness, visual acuity, and retinal pigment epithelium hypopigmentation in
atrophic age related macular degeneration (AMD). METHODS: 22 patients, mean age
74 (SD 8) years, with atrophic AMD were recruited. An optical imaging system
based on the retinal thickness analyser (RTA) was applied to generate a series of
20 optical section images that encompass 2 mm x 2 mm retinal areas. The optical
section images were digitised and analysed to provide topographic maps of the
vitreoretinal and chorioretinal surfaces and the retinal thickness. Vitreoretinal
and chorioretinal surface elevations and retinal thickness were determined.
RESULTS: Variation in the vitreoretinal surface height was moderately correlated 
with visual acuity (r = -0.4; p = 0.03; n = 22). Increase in variation of
chorioretinal surface height was correlated with decrease in visual acuity (r =
-0.5; p = 0.01; n = 22). The retinal thickness was not associated with visual
acuity (r = 0.2; p = 0.2; n=22). Relative height of the vitreoretinal surface in 
eyes with retinal pigment epithelium (RPE) hypopigmentation was significantly
less than eyes without RPE hypopigmentation (p = 0.005). Eyes with and without
RPE hypopigmentation had a similar relative height of the chorioretinal surface
(p = 0.4). Retinal thickness in eyes with RPE hypopigmentation was less than in
eyes without RPE hypopigmentation (p = 0.04). CONCLUSION: Mapping of
chorioretinal and vitreoretinal topography and retinal thickness provides
objective and quantitative measurements of retinal structural abnormalities and
shows promise as an adjunct for the evaluation of retinal structural changes due 
to AMD.

Publication Types: 
    Letter
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12034682 [PubMed - indexed for MEDLINE]

2809: J Interferon Cytokine Res. 2002 Apr;22(4):421-6.

IFN-alpha antibodies in patients with age-related macular degeneration treated
with recombinant human IFN-alpha2a.

Ross C, Engler CB, Sander B, Bendtzen K.

Institute for Inflammation Research, Rigshospitalet University Hospital,
Copenhagen, Denmark.

We tested for development of binding and neutralizing antibodies to
interferon-alpha (IFN-alpha) during IFN-alpha2a therapy of patients with
age-related macular degeneration (AMD) of the eyes. Antibodies were investigated 
retrospectively in sera of 34 patients treated with 3 x 10(6) IU IFN-alpha2a
(Roceron-A), Hoffmann La-Roche, Basel, Switzerland) three times weekly for
periods of 8-16 weeks with or without a drug-free 4-12-week intermission.
Additionally, 10 patients were investigated prospectively; 7 received 1.5-6 x
10(6) IU IFN-alpha2a three times weekly for 12 months, and 3 received placebo.
Binding antibodies were tested by molecular size and protein G affinity
chromatography using 125I-IFN-alpha2a. Neutralizing activities were tested by
antiviral neutralization bioassay. IgG antibodies were detected in 24 of 34
IFN-alpha2a-treated patients (71%). Significantly higher anti-IFN-alpha levels
were observed in patients who after discontinuation were readministered
IFN-alpha2a (p < 0.02). Three of the IFN-alpha2a-treated patients in the
prospective study had high and 1 had low antibody titers. Neutralizing antibody
titers were high against IFN-alpha2a and IFN-alpha2c and low against
lymphoblastoid and leukocyte IFN-alpha. Impaired clinical responses were observed
in antibody-positive patients (p < 0.01). The development of neutralizing
anti-IFN-alpha antibodies in patients with AMD during recombinant human IFN-alpha
therapy may explain the often poor clinical effect of IFN-alpha treatment.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 12034024 [PubMed - indexed for MEDLINE]

2810: Biol Chem. 2002 Mar-Apr;383(3-4):537-45.

A2E and blue light in the retina: the paradigm of age-related macular
degeneration.

Shaban H, Richter C.

Institute of Biochemistry, Swiss Federal Institute of Technology (ETH), Zurich.

The photoreceptors in the retina, designed to initiate the cascade of events
which link the incoming light to the sensation of 'vision', are susceptible to
damage by light, particularly blue light. The damage can lead to cell death and
diseases. The turnover of retinal, an essential element of the visual process, is
the basis of the events that lead to damage. Free retinal, absorbing in the blue 
region of the visible spectrum, is phototoxic, and is a precursor of the
(photo)toxic compound A2E, which specifically targets cytochrome oxidase and
thereby induces cell death by apoptosis. Cell death induced by A2E in the dark is
prevented by negatively charged phospholipids. The blue light-filtering molecules
lutein and zeaxanthin are tailor-made substances protecting the retina. In vitro,
they protect cytochrome oxidase against the permanent damage caused by A2E in
combination with light. These novel findings should enable us to prevent or cure 
the dry form of age-related macular degeneration, the leading cause of severe
visual impairment in humans living in developed countries.

Publication Types: 
    Review

PMID: 12033441 [PubMed - indexed for MEDLINE]

2811: Eur J Ophthalmol. 2002 Mar-Apr;12(2):102-8.

Retinal thickness in healthy and diabetic subjects measured using optical
coherence tomography mapping software.

Massin P, Erginay A, Haouchine B, Mehidi AB, Paques M, Gaudric A.

Department of Ophthalmology, Hĵpital Lariboisière, Assistance Publique - Hĵpitaux
de Paris, Université Paris 7, France. p.massin@lrb.ap-hop-paris.fr

PURPOSE: To define the normal retinal thickness in healthy subjects using optical
coherence tomography (OCT) mapping software and to assess the ability of OCT to
detect early macular thickening in diabetic patients. METHODS: Six radial scans
centered on the fixation point were done on 60 healthy eyes and 70 eyes of 35
diabetic patients without macular edema on biomicroscopy. Retinal thickness was
measured automatically with OCT mapping software. Mean retinal thickness was
compared in subgroups of healthy patients based on age, sex, and eye, and in the 
eyes of diabetic patients and healthy subjects. Thickening was diagnosed if mean 
retinal thickness of an area was greater than the mean thickness + 2SD in the
corresponding area in healthy subjects; or if the difference between right and
left eye exceeded the mean difference + 2 SD in a given area in healthy subjects.
RESULTS: In healthy subjects, mean retinal thickness in the central macular area 
1000 microm in diameter was 170+/-18 microm. There was no significant difference 
according to age, or left or right eye, but central macular thickness was
significantly greater in men than women (p=0.0139). No difference was observed
between the eyes of healthy subjects and diabetic patients without macular edema 
on biomicroscopy, but OCT detected early macular thickening in 12 diabetic eyes. 
CONCLUSIONS: In this study average retinal thickness and mean local variations in
a normal population were defined using a commercially available mapping software.
OCT seems a sensitive tool for detecting early retinal thickening.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12022281 [PubMed - indexed for MEDLINE]

2812: Klin Monatsbl Augenheilkd. 2002 Apr;219(4):250-3.

Transpupillary thermotherapy for occult subfoveal neovessels in age-related
macular degeneration: importance of patient pigmentation for the determination of
laser settings.

Auer C, Tao Tran V, Herbort CP.

La Source Eye Center, Lausanne, Switzerland.

BACKGROUND: Presently the indication for transpupillary thermotherapy (TTT) is
the treatment of retrofoveal occult subretinal neovascular membranes (OSRNM) for 
which PDT (photodynamic therapy) has a limited effect. The diode laser power
settings given by the manufacturer (Iridex Co, Mountain View, California) have to
be modulated according to several criteria including patient pigmentation. The
purpose here was to report on a group of patients that presented chorioretinal
atrophy after TTT. METHODS: Thirty-eight eyes of 37 patients with OSRNM due to
age-related macular degeneration underwent TTT. Indications to treat were diffuse
exudative membranes, limited subfoveal OSRNM with a visual acuity of less than
0.4, or a drop of visual acuity of 3 Snellen lines or more since the previous
examination. Dual fluorescein and indocyanine green angiography were used for
angiographic follow-up. Treatment was performed according to the manufacturer's
parameters. The group of patients that presented chorioretinal atrophy after TTT 
was analysed in this study RESULTS: Five patients presented a limited or
spot-size related post-TTT chorioretinal atrophy. Pre-laser visual acuity was
0.34 +/- 0.13 and post-TTT visual acuity was 0.25 +/- 0.15. The OSRNM had
disappeared in all cases. The common denominator in these patients was that they 
were white haired but upon questioning all happened to be dark-haired in their
youth. CONCLUSIONS: Evolution towards atrophy can occur after TTT and probably
depends on several factors. We showed that pigmentation is a parameter to be
evaluated carefully before TTT and that laser power settings should progressively
be diminished with increasing patient pigmentation. In white haired persons the
original pigmentary status should be part of the patient history.

PMID: 12022011 [PubMed - indexed for MEDLINE]

2813: Biogerontology. 2002;3(1-2):61-6.

A model for a blinding eye disease of the aged.

Zhang D, Lai MC, Constable IJ, Rakoczy PE.

Lions Eye Institute, Nedlands, Perth, Australia.

This work aims to investigate the effect of compromised lysosomal enzyme activity
on the accumulation of photoreceptor-derived debris in the retinal pigment
epithelial (RPE) cells and to examine if this accelerated debris accumulation can
induce retinal abnormalities similar to those observed in aged individuals. A
mutated, enzymatically inactive form of cathepsin D (CatD), generated by
site-directed mutagenesis was used to produce stable cell lines and transgenic
mice. There was a strong increase in enzymatically inactive CatD protein
production in the mutated CatD DNA transfected D407 cells (D407MCD). The presence
of the inactive CatD has been linked to an impairment in bovine rod outer segment
(BROS) digestion and was confirmed by a statistically significant increase of
undigested residual BROS in the medium of D407MCD when compared to the control
vector-transfected D407 cells (t-test, P < or = 0.016, P < or = 0.003) or
untransfected D407 cells (t-test, P < or = 0.008, P < or = 0.003). The impairment
was also confirmed in vivo by demonstration of BROS-derived debris accumulation
in the RPE cell layer of transgenic mice. These results demonstrated that the
mutated and inactive CatD form could lead to impairment of photoreceptor outer
segments (POS) proteolysis. It is proposed that this initial impairment of POS
proteolysis may result in the accumulation of CatD-opsin-like complexes in the
pigment epithelium, which further compromises RPE cell functions and thus causes 
the changes observed in aging humans.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12014844 [PubMed - indexed for MEDLINE]

2814: Curr Opin Ophthalmol. 2002 Jun;13(3):171-5.

Risk factors for age-related macular degeneration: an update.

Hyman L, Neborsky R.

Stony Brook University, Department of Preventive Medicine, Stony Brook, New York 
11794-8036, USA. lhyman@notes.cc.sunysb.edu

Age-related macular degeneration (AMD) is the leading cause of irreversible
vision loss in the United States and other western nations. Limited treatment is 
available, and there are no established means of prevention. The detection of
modifiable risk factors is important to suggest preventive behaviors that can
reduce disease occurrence or prevent the progression to the late stages of AMD.
Results of recent studies suggest that the etiology and pathogenesis of AMD are a
complex interaction of genetic and external factors. Although a number of factors
seem promising, only age and cigarette smoking are confirmed as increasing AMD
risk. Other factors that most likely play a significant role in AMD are
nutritional factors, e.g., antioxidants, and hypertension or other underlying
atherosclerotic disease processes. The results of the Age-Related Eye Disease
Study suggest a moderate beneficial effect of antioxidant, vitamin, and zinc
supplementation in reducing progression to severe AMD.

Publication Types: 
    Review

PMID: 12011686 [PubMed - indexed for MEDLINE]

2815: Clin Experiment Ophthalmol. 2002 Jun;30(3):183-6.

Reading speed test for potential central vision measurement.

Pesudovs K, Patel B, Bradbury JA, Elliott DB.

Department of Optometry, University of Bradford, Bradford, West Yorkshire, United
Kingdom. K.Pesudovs@bradford.ac.uk

This study examines the validity and reliability of a reading speed test as a
measure of potential central vision. Reading speed was calculated in words per
minute (wpm) from the time taken to read 30 words of 1.20 logMAR size text.
Scores were obtained from subjects with cataract (n = 48), macular disease(n =
35), peripheral vision loss(n = 14) and normal eyes (n = 10).Subjects with
macular disease (27.0 +/- 13.2 wpm) read much slower than subjects with cataract 
(91.9 +/- 13.6 wpm). Little difference was found between subjects with cataract, 
peripheral vision loss (91.5 +/- 14.7 wpm)and normal eyes (103.8 +/- 15.5
wpm).Repeat testing gave values within +/- 16% of reading speed. These results
suggest that a reading speed test using large text could be useful as a potential
central vision test in cataract patients.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12010211 [PubMed - indexed for MEDLINE]

2816: J Electron Microsc (Tokyo). 2002;51(2):127-31.

Role of matrix metalloproteinase-7 in angiogenesis associated with age-related
macular degeneration.

Yazama F, Kadonosono K, Itoh N, Ohno S.

Department of Anatomy, School of Medicine, Yokohama City University, Kanagawa,
Japan. fyzma@med.yokohama-cu.ac.jp

To investigate the possible role of matrix metalloproteinase-7 in choroidal
neovascularization associated with age-related macular degeneration,
immunoelectron microscopy using ultrathin frozen sections and conventional
transmission electron microscopy were performed in subfoveal fibrovascular
membranes from patients with age-related macular degeneration. immunoelectron
microscopy revealed that matrix metalloproteinase-7 was expressed within basal
laminar deposits and amorphous materials around the retinal pigment epithelial
cells. The results support a role for matrix metalloproteinase-7 in the
development of choroidal neovascularization in age-related macular degeneration.

PMID: 12005165 [PubMed - indexed for MEDLINE]

2817: Arch Ophthalmol. 2002 May;120(5):579-84.

Symmetry of bilateral lesions in geographic atrophy in patients with age-related 
macular degeneration.

Bellmann C, Jorzik J, Spital G, Unnebrink K, Pauleikhoff D, Holz FG.

Department of Ophthalmology, University of Heidelberg, Im Neuenheimer Feld 400,
D-69120 Heidelberg, Germany.

BACKGROUND: As a cause for severe visual loss, geographic atrophy of the retinal 
pigment epithelium is about half as common as choroidal neovascularization in
patients with advanced age-related macular degeneration. To assess symmetry, we
determined intraindividual variations of various features of bilateral geographic
atrophy in patients with atrophic age-related macular degeneration in a
cross-sectional study. METHODS: Patients were examined with the use of a confocal
scanning laser ophthalmoscope (Heidelberg Retina Angiograph; Heidelberg
Engineering, Heidelberg, Germany). Digital infrared reflection images
(excitation, 830 nm) and fundus autofluorescence images (excitation, 488 nm) were
recorded. The eyes of each patient were compared regarding number, size, and
convex hull of the atrophic areas with the use of image analysis software and
with respect to fundus autofluorescence changes in the junctional zone. RESULTS: 
Seventy-two patients (mean +/- SD age, 76.3 +/- 7.9 years) were examined. The
number of atrophic areas ranged from 1 to 23 (mean +/- SD, 4.9 +/- 4.6); the size
of geographic atrophy, from 0.18 to 30.20 (mean +/- SD, 7.0 +/- 6.6) mm(2); and
the size of the convex hull, from 0.18 to 39.20 (mean +/- SD, 11.7 +/- 8.4)
mm(2). No statistically significant difference was found when comparing these
variables between each left and right eye: number, P =.62; size, P =.81; and
convex hull, P =.78. Identical patterns of fundus autofluorescence were observed 
in 43 (80%) of 54 patients. CONCLUSIONS: There is intraindividual symmetry in
eyes with bilateral geographic atrophy in the presence of a wide range of
interindividual variability. The findings are in accordance with the view that
age-related macular degeneration is not merely the result of a nonspecific aging 
process. Symmetric manifestations, rather, reflect specific individual
determinants in the pathogenesis and manifestation of the disease.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12003606 [PubMed - indexed for MEDLINE]

2818: J Am Board Fam Pract. 2002 Mar-Apr;15(2):142-52.

Early detection and treatment of neovascular age-related macular degeneration.

Bressler NM.

The Wilmer Ophthalmological Institute, The Johns Hopkins University School of
Medicine, Baltimore 21205-2005, USA.

BACKGROUND: The neovascular form of age-related macular degeneration (AMD) can
rapidly lead to severe loss of central vision and adversely affect the patient's 
quality of life. During the 1990s the only proven treatment for neovascular AMD
was laser photocoagulation. Only a minority of patients are eligible to receive
this treatment, however, and the treatment itself can cause acute retinal damage 
with immediate vision loss. Verteporfin therapy is a new treatment option
involving photodynamic therapy that was recently shown to be relatively safe and 
effective in reducing the risk of vision loss in selected cases. METHODS: Recent 
literature was reviewed on management of choroidal neovascularization caused by
AMD that proved beneficial in large-scale randomized clinical trials. These
studies were selected through a MEDLINE search of files from 1982 to the present 
using the keywords "randomized clinical trials," "choroidal neovascularization," 
and "age-related macular degeneration," as well as through personal knowledge of 
recently completed trials. RESULTS AND CONCLUSIONS: Primary care physicians can
effect good treatment outcomes by detecting early signs of AMD and educating
patients about the necessity of prompt referral to an ophthalmologist. Immediate 
referral is increasingly important because, compared with laser photocoagulation,
current photodynamic therapy with verteporfin is applicable to more patients.
Greater patient awareness of neovascular AMD and the importance of self-testing
of vision can also be communicated to patients in primary care.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 12002198 [PubMed - indexed for MEDLINE]

2819: Optom Vis Sci. 2002 Apr;79(4):218-24.

Recent advances in the management of age-related macular degeneration.

Mittra RA, Singerman LJ.

VitreoRetinal Surgery, Minneapolis, Minnesota, USA.

Choroidal neovascularization (CNV) secondary to age-related macular degeneration 
(AMD) can cause rapid and severe central vision loss in many older people. Until 
recently, the only treatment proven beneficial was thermal laser
photocoagulation, which was applicable to only a small subset of patients.
Furthermore, the thermal laser damaged the retina overlying the CNV, which is
especially problematic for lesions involving the foveal center. Photodynamic
therapy is a new treatment consisting of intravenous infusion of a drug that is
then activated by a low-energy laser, causing damage to CNV. Photodynamic therapy
with verteporfin (Visudyne, Novartis AG) has been shown to reduce the risk of
moderate and severe vision loss in patients with predominantly classic subfoveal 
CNV secondary to AMD. With the advent of verteporfin therapy, eye care providers 
will play an increasingly important role in managing patients with AMD,
especially in the early detection and rapid referral of appropriate cases.

Publication Types: 
    Review

PMID: 11999147 [PubMed - indexed for MEDLINE]

2820: Int Ophthalmol. 2001;24(1):13-9.

Radiotherapy for age-related macular degeneration: is there a benefit for classic
CNV?

Eter N, Schüller H, Spitznas M.

Department of Ophthalmology, University of Bonn Medical Center, Germany.
eter@uni-bonn.de

AIM: To evaluate the efficacy of radiotherapy in the treatment of subfoveal
classic and occult choroidal neovascularization (CNV) in age-related macular
degeneration (AMD) under strict fixation control. METHODS: Twenty-seven eyes of
27 patients with subfoveal CNV as a result of AMD were treated with a total dose 
of 20 Gy in 10 fractions (10 well-defined, 17 occult). Fixation monitoring was
achieved by installing a TV camera with an attached fixation light 3 cm from the 
cornea of the eye being treated. Visual acuity and fluorescein angiography were
obtained before and 6 months after treatment. Fifteen eyes of 15 patients served 
as controls (4 well-defined, 11 occult). RESULTS: After 6 months the treated
group showed an average decrease in visual acuity of 27%; the control group
experienced a decrease of 31%. Membrane size increased by 56% in the treated
group and by 28% in the control group. There was no statistically significant
difference. Within the subgroup analysis, however, patients with classic CNV
suffered significantly less visual loss than in the control group. CONCLUSION:
Radiation therapy under optimized treatment conditions by fixation monitoring
failed to control further growth in membrane size in both classic and occult CNV.
Regarding visual acuity, however, patients with classic CNV seem to benefit from 
radiation treatment compared to the natural course.

PMID: 11998881 [PubMed - indexed for MEDLINE]

2821: Am J Geriatr Psychiatry. 2002 May-Jun;10(3):305-10.

Activity loss and depression in age-related macular degeneration.

Rovner BW, Casten RJ.

Department of Psychiatry and Human Behavior, Jefferson Medical College at Wills
Eye Hospital, Philadelphia, PA 19107, USA. rovner1@aol.com

Age-related macular degeneration (AMD) is the most frequent cause of severe
vision loss in older persons and is associated with high rates of disability and 
depression. The authors evaluated 51 patients with bilateral AMD to investigate
the interrelationships of disease severity, disability, and depression and
focused on loss of valued activities as an emblematic disabling consequence of
AMD. They characterized depression by the Center for Epidemiologic
Studies-Depression (CES-D) score, a syndromal state based on the CES-D, and as a 
level of distress (Index of Affective Suffering; IAS). Thirty subjects (58.8%)
had loss of a valued, discretionary activity. They had worse visual acuity and
more depressive symptoms and were represented in higher IAS levels than other
subjects. Visual acuity was significantly correlated with IAS levels, but not
with CES-D scores or syndromal depression. A regression model demonstrated that
activity loss mediated the relationship between visual acuity and IAS level.
Affective distress occurs in AMD, largely to the extent that valued activities
are relinquished because of vision loss. IAS levels best illuminated this
relationship, suggesting the value of this dimension of affective functioning in 
studies of the consequences of chronic disease.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11994218 [PubMed - indexed for MEDLINE]

2822: Am J Ophthalmol. 2002 May;133(5):665-72.

A double-blind placebo-controlled evaluation of the acute effects of sildenafil
citrate (Viagra) on visual function in subjects with early-stage age-related
macular degeneration.

Birch DG, Toler SM, Swanson WH, Fish GE, Laties AM.

Retina Foundation of the Southwest, Dallas, Texas 75231, USA.
dbirch@retinafoundation.org

PURPOSE: To assess the effects of a single 100-mg dose of sildenafil citrate on
visual function in men with early-stage age-related macular degeneration. DESIGN:
Randomized double-blind placebo-controlled clinical trial. METHODS: Nine men
(mean age 71 years, range 59-85 years) with early-stage (minimal visual
impairment and large drusen in the macula) age-related macular degeneration and
20/40 or better-corrected visual acuity in at least one eye were prospectively
randomized to receive either placebo or sildenafil citrate (Viagra; Pfizer Inc,
New York, New York) 100 mg as a single oral dose. After 7-14 days, they received 
the alternate treatment. Subjects underwent visual acuity, Amsler grid, color
discrimination (D15), traffic light, Humphrey perimetry, and photo-stress testing
in each eye before and at specific intervals within 8 hours after dosing.
RESULTS: Compared with placebo, no pattern of errors were evident in any visual
function test following sildenafil administration. No statistically or clinically
relevant changes from baseline were observed in visual acuity, Humphrey perimetry
(corrected pattern standard deviation), D15 color discrimination, or photo-stress
tests. No clinically relevant changes were observed in the Amsler grid or traffic
light tests. Sildenafil treatment was associated with transient mild or moderate 
headache, flushing, and rhinitis. There were no visual adverse events
spontaneously reported to the investigator. CONCLUSION: A single 100-mg dose of
sildenafil was well tolerated and produced no acute visual effects or
exacerbation of preexisting visual impairment in nine men with early-stage
age-related macular degeneration.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11992864 [PubMed - indexed for MEDLINE]

2823: Ophthalmology. 2002 May;109(5):920-7.

Intravitreal triamcinolone for refractory diabetic macular edema.

Martidis A, Duker JS, Greenberg PB, Rogers AH, Puliafito CA, Reichel E, Baumal C.

Wills Eye Hospital, Philadelphia, Pennsylvania 19107, USA.

PURPOSE: To determine if intravitreal injection of triamcinolone acetonide is
safe and effective in treating diabetic macular edema unresponsive to prior laser
photocoagulation. DESIGN: Prospective, noncomparative, interventional case
series. PARTICIPANTS: Sixteen eyes with clinically significant diabetic macular
edema (CSME) that failed to respond to at least two previous sessions of laser
photocoagulation. METHODS: Eyes were diagnosed with CSME and treated with at
least two sessions of laser photocoagulation according to Early Treatment
Diabetic Retinopathy Study guidelines. At least 6 months after initial laser
therapy, the response was measured by clinical examination and optical coherence 
tomography (OCT). Eyes with a residual central macular thickness of more than 300
microm (normal, 200 microm) and visual loss from baseline were offered
intravitreal injection of 4 mg triamcinolone acetonide. The visual and anatomic
responses were observed as well as complications related to the injection
procedure and corticosteroid medication. MAIN OUTCOME MEASURES: Visual acuity and
quantitative change in OCT macular thickening were assessed. Potential
complications were monitored, including intraocular pressure response, cataract
progression, retinal detachment, vitreous hemorrhage, and endophthalmitis.
RESULTS: All patients completed 3 months of follow-up, and 8 of 16 patients (50%)
completed 6 or more months of follow-up. Mean improvement in visual acuity
measured 2.4, 2.4, and 1.3 Snellen lines at the 1-, 3-, and 6-month follow-up
intervals, respectively. The central macular thickness as measured by OCT
decreased by 55%, 57.5%, and 38%, respectively, over these same intervals from an
initial pretreatment mean of 540.3 microm (+/-96.3 microm). Intraocular pressure 
exceeded 21 mmHg in 5, 3, and 1 eye(s), respectively, during these intervals. One
eye exhibited cataract progression at 6 months. No other complications were noted
over a mean follow-up of 6.2 months. Reinjection was performed in 3 of 8 eyes
after 6 months because of recurrence of macular edema. CONCLUSIONS: Intravitreal 
triamcinolone is a promising therapeutic method for diabetic macular edema that
fails to respond to conventional laser photocoagulation. Complications do not
appear to be prohibitive. Further study is warranted to assess the long-term
efficacy and safety, and the need for retreatment.

Publication Types: 
    Clinical Trial

PMID: 11986098 [PubMed - indexed for MEDLINE]

2824: Clin Chim Acta. 2002 Jun;320(1-2):111-5.

Serum oxidative and antioxidant parameters in a group of Italian patients with
age-related maculopathy.

Simonelli F, Zarrilli F, Mazzeo S, Verde V, Romano N, Savoia M, Testa F, Vitale
DF, Rinaldi M, Sacchetti L.

Dipartimento di Clinica Oculistica, Facoltà di Medicina e Chirurgia, II
Università di Napoli, Naples, Italy.

OBJECTIVES: The purpose of this study was to measure the oxidative and
antioxidant biochemical parameters in the serum of Italian patients with
age-related maculopathy (ARM) and in a similar age control group from the same
area, in order to determine the weight of oxidative status as risk factor in the 
early stage of macular degeneration onwards. DESIGN AND METHODS: Forty-eight ARM 
patients (19 early and 29 late form) and 46 normal subjects, similar for age, sex
and life-style, were studied. A series of serum and/or plasma antioxidants
(vitamins C, E, A, total and individual carotenoids, zinc, total plasma
antioxidant capacity--TRAP) and oxidative parameters (reactive oxygen
metabolites--ROM, oxidized-low-density lipoprotein antibodies-anti-Ox-LDL) were
evaluated in both groups, also with regard to age and disease stage. RESULTS:
Levels of vitamins C, E, total carotenoids and beta-cryptoxanthine were lower in 
late ARM than in early ARM (p<0.05). Of the serum carotenoids investigated, only 
lycopene was lower in the two ARM forms than in controls (p<0.05). The main
biochemical parameters, TRAP, zinc, anti-Ox-LDL and ROM were similar in the two
groups. CONCLUSIONS: A deficit of antioxidants (vitamins C, E and carotenoids)
seems to be associated with ARM in Italian patients, particularly the advanced
form, it is also suggested that in ARM patients macular susceptibility to
oxidative damage is not related with age.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 11983208 [PubMed - indexed for MEDLINE]

2825: Graefes Arch Clin Exp Ophthalmol. 2002 Apr;240(4):279-85. Epub 2002 Mar 7.

Clinicopathologic correlation in hemorrhagic age-related macular degeneration.

Reynders S, Lafaut BA, Aisenbrey S, Broecke CV, Lucke K, Walter P, Kirchhof B,
Bartz-Schmidt KU.

Ghent University Hospital, Ophthalmology, Ghent, Belgium.

PURPOSE: To analyze and compare the histopathology of surgically extracted
membranes in hemorrhagic age-related macular degeneration (AMD) versus extracted 
classic, mixed and occult choroidal neovascularization (CNV) in AMD. METHODS:
Thirty consecutive membranes, surgically removed in hemorrhagic AMD, were
analyzed and compared with consecutive series of 50 classic, 20 mixed and 20
occult membrane specimens in exudative AMD. The specimens were serially sectioned
and stained in a stepped fashion with hematoxylin-eosin, Masson trichrome and
periodic acid-Schiff stain. RESULTS: Diffuse drusen were observed in all
hemorrhagic AMD specimens, fibrovascular tissue was found in 29 of 30 specimens
which was located subretinally in 11 specimens and/or in Bruch's membrane in 28
specimens. A hemorrhage was located subretinally in 21 specimens, in the stroma
of the fibrovascular tissue in 17 specimens, at the choroidal side of the diffuse
drusen adjacent to fibrovascular tissue in 13 specimens and at the choroidal side
of the fibrovascular tissue in Bruch's membrane in 8 specimens. Grossly dilated
thin-walled vessels were identified in one hemorrhagic AMD case, suggestive of
polypoidal choroidal vasculopathy. Scarred tears of the retinal pigment
epithelium were identified in two specimens. CONCLUSION: A large spectrum of
histo-architectural lesions is recognized in hemorrhagic maculopathy. Hemorrhages
do not only characteristically appear in the subretinal space or in the stroma of
the neovascular tissue but also at the choroidal side of the diffuse drusen
adjacent to the neovascular complex and at the choroidal side of the
intra-Bruch's fibrovascular tissue.

Publication Types: 
    Comparative Study

PMID: 11981641 [PubMed - indexed for MEDLINE]

2826: Graefes Arch Clin Exp Ophthalmol. 2002 Apr;240(4):244-64. Epub 2002 Mar 15.

Comment in:
    Graefes Arch Clin Exp Ophthalmol. 2002 Apr;240(4):241-3.    Graefes Arch Clin Exp Ophthalmol. 2002 Oct;240(10):874-5; author reply 876-7.

Monitoring retinal function in neovascular maculopathy using multifocal
electroretinography - early and long-term correlation with clinical findings.

Jurklies B, Weismann M, Hüsing J, Sutter EE, Bornfeld N.

University Eye Hospital Essen, Hufelandstrasse 55, 45122 Essen, Germany.
bernhard.jurklies@uni-essen.de

PURPOSE: To objectively investigate and longitudinally monitor retinal function
in patients with choroidal neovascularization (CNV) due to exudative age-related 
macular degeneration (AMD) and myopia using multifocal electroretinography
(mfERG). METHODS: Patients with classic and occult subfoveal CNV secondary either
to AMD or to myopia were enrolled in the study. The mfERGs were performed at the 
beginning of the study and every 3 months subsequently during a follow-up period 
of 15 months. In addition, standardized visual acuity testing, ophthalmologic
examinations, color fundus photographs and fluorescein angiography were
performed. The mfERG records were derived with the VERIS-System
(Electro-Diagnostic Imaging, San Mateo, Calif., USA); 103 locations within the
central 50 degrees in diameter were stimulated concurrently by means of the
m-sequence technique. Fixation stability was monitored throughout the recording
session with an infrared eye monitoring system (VERIS Refractor/Camera unit). The
first-order response component was extracted for each stimulated retinal
location. The response densities of the first-order kernel were evaluated as a
function of eccentricity from the center (ring 1) to the periphery of the
stimulated area (ring 6). The results were compared to those derived from
age-matched normal control groups. For each patient mfERG responses measured on
follow-up visits were compared to each other to evaluate and monitor changes in
retinal function. These changes were tested for correlation with those observed
in other clinical and electroretinographic findings. Statistical analysis was
performed using the Pearson coefficient. RESULTS: Subfoveal neovascular
maculopathy was associated with a reduction in response density most prominent
within the central 5 degrees over the area affected by CNV detected either at the
beginning of the study or at the follow-up recordings. During the follow-up
period patients 1 and 4 showed stabilization or a slight increase in response
densities over the neovascular lesion-complex and a corresponding stabilization
or slight increase in visual acuity accompanied by a decrease in the activity of 
the neovascular lesion as determined by fluorescein angiography. Patient 2
revealed an increase in response density correlating with an increase in visual
acuity and decrease in lesion size. In the contralateral eye of this patient the 
response density dropped in the area of new subfoveal CNV. In patient 3
continuous progression of the disease was documented by fluorescein angiography
and visual acuity. It correlated well with a continuous decrease in retinal
response densities during the follow-up. CONCLUSIONS: Objective monitoring of
retinal function and correlation with morphological and psychophysical findings
was at least in part possible in patients suffering from AMD and myopia. In all
of four patients whose subfoveal CNV was documented by fluorescein angiography.
Response densities were reduced particularly in the central 5 degrees and in
visual acuity. The mfERG data showed a moderate to high statistical correlation
with visual function as measured by visual acuity. On the other hand, the
greatest linear dimension of the lesion size showed only a weak to moderate
statistical correlation with both the response densities of the mfERG and the
visual acuity. We conclude that the size of the CNV complex does not represent an
accurate measure of retinal function in neovascular maculopathy. The good
correlation of the mfERG data with visual acuity suggests that it may serve for
objective assessment of retinal function, of the areas overlying the CNV. It
shows potential as a valuable tool for longitudinal monitoring of AMD patients.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11981638 [PubMed - indexed for MEDLINE]

2827: Br J Ophthalmol. 2002 May;86(5):565-71.

A prospective, case controlled study of the natural history of diabetic
retinopathy and maculopathy after uncomplicated phacoemulsification cataract
surgery in patients with type 2 diabetes.

Squirrell D, Bhola R, Bush J, Winder S, Talbot JF.

Department of Ophthalmology, Royal Hallamshire Hospital, Sheffield S10 2RX, UK.

AIM: To determine if uncomplicated phacoemulsification cataract surgery is
associated with an accelerated rate of progression of diabetic retinopathy or
maculopathy postoperatively. METHODS: A prospective trial of 50 type 2 diabetics 
undergoing monocular phacoemulsification cataract surgery by a single consultant 
surgeon. The grade of diabetic retinopathy and diabetic maculopathy in the
operated and non-operated fellow eye was assessed preoperatively and for 12
months postoperatively. RESULTS: Overall, retinopathy progression was observed in
11 patients. In seven the retinopathy progressed in both eyes, in three it
progressed in the operated eye alone, and in one it progressed in the fellow eye 
alone. Macular oedema was observed in 13 eyes postoperatively. Four had transient
pseudophakic cystoid macular oedema and nine true diabetic maculopathy. Where
maculopathy progressed it did so symmetrically in five patients, it progressed in
the operated eye alone in four patients, and the fellow eye alone in two
patients. There was no significant difference in the number of operated and
fellow eyes whose retinopathy or maculopathy progressed postoperatively. In both 
the operated (OE) and non-operated (NoE) eyes retinopathy progression was
associated with a higher mean HbA(1)C (OE p=0.003; NoE p=0.001) and insulin
treatment (OE p=0.008, NoE p=0.04). CONCLUSION: Uncomplicated phacoemulsification
cataract surgery does not cause acceleration of diabetic retinopathy
postoperatively and any progression that is observed probably represents the
natural history of the disease. Although macular oedema is common after cataract 
surgery it may follow a benign course and in many patients the development of
clinically significant macular oedema postoperatively probably represents natural
disease progression rather than being a direct effect of surgery.

PMID: 11973256 [PubMed - indexed for MEDLINE]

2828: Insight. 2002 Jan-Mar;27(1):5-7.

The age-related eye disease study: the results of the clinical trial.

Sackett CS, Schenning S.

Wilmer Institute Woods, 265 600 North Wolfe Street, Johns Hopkins Medical
Institutions, Baltimore, MD 21287, USA.

The Age-Related Eye Disease Study (AREDS) is a multi-center study sponsored by
the National Eye Institute to determine the natural history and risk factors
associated with both cataract and age-related macular degeneration (AMD). AREDS
incorporated a clinical trial to determine what role micro nutrients may play in 
the development and progression of cataracts and AMD. The micro nutrients studied
were the antioxidants vitamins E,C, beta-carotene and zinc with copper.
Participants were randomized to either antioxidants, mineral, a combination of
antioxidants and minerals or placebo. The participants were categorized, by the
presence of drusen and diagnosis of AMD into one of four groups: no AMD, early
AMD, intermediate AMD or advanced AMD. They were followed for an average of 6.3
years. There was no statistically significant difference in the cataract trial
between treatment and placebo. In the AMD trial groups, those at high risk of
developing advanced AMD lowered their risk by about 25% when treated with the
mega dosages of the combination of antioxidants and minerals.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial

PMID: 11962062 [PubMed - indexed for MEDLINE]

2829: Graefes Arch Clin Exp Ophthalmol. 2002 Jan;240(1):31-4.

Presentation delay in patients affected with exudative age-related macular
degeneration.

Haddad WM, Seres A, Coscas G, Soubrane G.

Department of Ophthalmology, University of Paris XII, Créteil, France.

BACKGROUND: Presentation delay (i.e. duration of visual symptoms before initial
presentation) is an established critical parameter for visual prognosis in
patients with exudative age-related macular degeneration (ARMD) considering the
natural history of the disease and the limitations of current treatments. The
purpose of this study was to determine the duration of presentation delay and its
evolution in two periods 4 years apart. METHODS: Presentation delay in 1598
patients affected with exudative ARMD was retrospectively reviewed during two
similar 8-month periods in 1994 and 1998 in a tertiary referral center. RESULTS: 
The proportions of patients examined either within 1 month, between 1 and 3
months, and between 3 and 6 months after onset of symptoms, respectively,
increased between 1994 and 1998 from 23% to 33%, from 27% to 32.5%, and from 14% 
to 18.5%. The proportions of patients examined between 6 and 12 months and after 
12 months decreased from 16% to 12% and from 20% to 4%, respectively.
Furthermore, the proportion of patients presenting with a first eye involvement
during the first month following the onset of symptoms rose from 42% in 1994 to
52% in 1998. All these differences were statistically significant. CONCLUSION:
This first specific review of presentation delay in exudative ARMD showed a
significant decrease in this parameter between 1994 and 1998 that should be taken
into account when assessing the overall evolution of visual outcome. Further
studies are warranted to ascertain that these findings reflect a global
improvement in the management of macular diseases.

PMID: 11954778 [PubMed - indexed for MEDLINE]

2830: Graefes Arch Clin Exp Ophthalmol. 2002 Jan;240(1):21-30.

Effect of simultaneous oblique muscle surgery in foveal translocation by 360
degrees retinotomy.

Fujikado T, Shimojyo H, Hosohata J, Tsujikawa K, Fukui T, Ohji M, Tano Y.

Department of Applied Medical Engineering, Osaka University Medical School,
Suita-shi, Japan. fujikado@ophthal.med.osaka-u.ac.jp

PURPOSE: To assess the effect of simultaneous oblique muscle surgery during
foveal translocation surgery with 360 degrees retinotomy in patients with
neovascular maculopathy. METHODS: Foveal translocation with 360 degrees
retinotomy was performed on 31 eyes of 31 patients with neovascular maculopathy
(21 with age-related macular degeneration 9 with myopic neovascular maculopathy, 
and 1 with idiopathic neovascular maculopathy). All eyes had simultaneous
torsional muscle surgery with recession of the superior oblique muscle and
tucking of the inferior oblique muscle. Visual acuity, binocular vision, and
degree of cyclotorsion were assessed pre- and postoperatively. The angles of
retinal and global rotation, distance of foveal shift, and surgical complications
were also investigated. RESULTS: With a mean postoperative follow-up of 10.0
months, vision improved (>0.2 log MAR units) in 13 eyes, was unchanged in 9 eyes,
and worsened (>0.2 log MAR units) in 9 eyes. Ten of 31 eyes (32%) had a final
visual acuity of 20/50 or better. Eleven patients had binocular fusion, 13
patients showed suppression, and 7 patients developed diplopia that was managed
by spectacles with prisms or by secondary muscle surgery. The mean retinal and
global rotations were 30.3 degrees and 23.7 degrees, respectively. The average
size of the choroidal neovascular membrane was 1.3 disc diameters (DD), while the
average shift of the fovea was 1.5 DD. After the primary surgery, six eyes
developed retinal detachment, two eyes macular hole, and three eyes proliferative
vitreoretinopathy. These complications were successfully managed by additional
surgery. CONCLUSION: Foveal translocation with 360 degrees retinotomy is
effective in restoring vision in 40% of patients with neovascular maculopathy.
Simultaneous oblique muscle surgery was effective in rotating the globe by about 
20 degrees, corresponding to to a foveal shift of 1.5 DD. While the development
of torsional diplopia is generally prevented by simultaneous oblique muscle
surgery, the relatively high incidence of surgical complications with this
procedure should be taken into account.

PMID: 11954777 [PubMed - indexed for MEDLINE]

2831: Graefes Arch Clin Exp Ophthalmol. 2002 Jan;240(1):12-6.

Changes in fluorescein angiogram early after surgical removal of choroidal
neovascularization in age-related macular degeneration.

Sawa M, Kamei M, Ohji M, Motokura M, Saito Y, Tano Y.

Department of Ophthalmology, Osaka University Medical School, Suita, Japan.

BACKGROUND: Retinal pigment epithelial (RPE) defects inevitably occur in surgical
removal of choroidal neovascularization (CNV) in age-related macular degeneration
(AMD). RPE can proliferate and cover the denuded area, but the healing process
has not been investigated in humans. To understand the RPE wound-healing process,
we estimated the changes in fluorescein angiograms early after CNV removal.
METHODS: Ten consecutive patients with exudative AMD underwent CNV removal
without gas tamponade. Fluorescein angiography was performed within 4 days of
surgery and again 1 or 2 weeks postoperatively. Areas of leakage were measured
using a computer-assisted image analyser. The decreasing rate of leakage was
calculated as the change in disc areas of leakage per day (DA/day). RESULTS: The 
rates of decreasing leakage ranged from 0 to 0.42 DA/day (mean, 0.24 +/- 0.15
DA/day; median, 0.26 DA/day). The rate of decreasing leakage correlated with
changes in visual acuity (r = 0.642, P = 0.0456). CONCLUSION: The retinal pigment
epithelial wound after surgical removal of choroidal neovascularization may heal 
at the rate of 0.24 disc areas/day based on the blood retinal barrier function in
patients with age-related macular degeneration. A faster rate of decreasing
leakage may be associated with better visual prognosis.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11954774 [PubMed - indexed for MEDLINE]

2832: Acta Ophthalmol Scand. 2002 Apr;80(2):216-8.

Optical coherence tomography in choroidal neovascular membrane associated with
Best's vitelliform dystrophy.

Andrade RE, Farah ME, Cardillo JA, Höfling-Lima AL, Uno F, Costa RA.

Department of Ophthalmology, Paulista School of Medicine, Federal University of
São Paulo, Brazil.

A 29-year-old black male with Best's dystrophy presented an elevated choroidal
neovascular membrane in the right eye that was diagnosed and followed with
fluorescein-indocyanine green angiography and optical coherence tomography. The
subretinal neovascularization was successfully treated with argon laser
photocoagulation. One month later, the visual acuity improved and an optical
coherence tomography confirmed regression of the serous macular detachment. The
final clinical picture remained stable for 12 months of follow-up.

Publication Types: 
    Case Reports

PMID: 11952492 [PubMed - indexed for MEDLINE]

2833: Acta Ophthalmol Scand. 2002 Apr;80(2):136-43.

Age-related maculopathy: pathogenetic features and new treatment modalities.

Algvere PV, Seregard S.

Department of Ophthalmology, Karolinska Institutet, St. Erik's Eye Hospital,
Stockholm, Sweden. peep.algvere@sankterik.se

A considerable amount of new information on putative pathogenetic mechanisms in
age-related maculopathy and degeneration has emerged in recent years. This
comprises experimental studies on retinal pigment epithelium (RPE) and rod
photoreceptor ageing, lipofuscin accumulation, the roles of oxidative stress and 
free radical formation, as well as antioxidants and other defensive mechanisms
operating against environmental factors and ageing. The current application of
photodynamic therapy (PDT) using verteporfin marks a new era in the treatment of 
subfoveal classical choroidal neovascularization. Several new treatment
modalities, such as transpupillary thermotherapy (TTT) and anti-vascular
endothelial growth factor (VEGF) agents for inhibition of neovascularization,
have emerged and are undergoing multicentre clinical trials. A period of dynamic 
development in this field has commenced.

Publication Types: 
    Review

PMID: 11952478 [PubMed - indexed for MEDLINE]

2834: Mol Vis. 2002 Mar 19;8:67-71.

Genomic structure and assessment of the retinally expressed RFamide-related
peptide gene in dominant cystoid macular dystrophy.

Schulz HL, Stoehr H, White K, van Driel MA, Hoyng CB, Cremers F, Weber BH.

Institut für Humangenetik, Universität Würzburg, D-97074 Würzburg, Germany.

PURPOSE: Computer-assisted sampling of EST data contained within the UniGene
human sequences collection is being used to establish a catalog of novel genes
that are expressed exclusively or predominantly in the human retina. This
provides a valuable source for candidate genes possibly involved in retinal
degeneration. In this report we present the characterization of the C7orf9 gene
locus encoding RFamide-related peptides (RFRPs) and its evaluation in dominant
cystoid macular dystrophy (CYMD). METHODS: Bioinformatics and cDNA library
screening were used to isolate the full-length cDNA sequence and to determine the
genomic organization of C7orf9. Expression profiling was done by RT-PCR and
Northern blot analysis. C7orf9 was evaluated as a candidate gene for CYMD by DNA 
sequencing and Southern blot analysis in two affected individuals from an
extended Dutch CYMD family. RESULTS: The C7orf9 cDNA transcript consists of 1190 
bp and is organized into 3 exons on the short arm of chromosome 7 within the
critical region for CYMD. The transcript is specifically expressed in the retina 
but not in a large range of other human tissues. No disease-causing mutations or 
larger gene rearrangements were found. CONCLUSIONS: We provide the genomic
organization of the RFamide-related peptide gene, C7orf9, which encodes a
precursor protein for at least two small neuropeptides, referred to as NPSF
(alias RFRP-1) and NPVF (alias RFRP-3) and show that it is abundantly expressed
in the human retina. Results of our comprehensive mutation analysis suggests that
C7orf9 is not the CYMD gene.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11951088 [PubMed - indexed for MEDLINE]

2835: Drugs Aging. 2002;19(2):101-33.

Age-related macular degeneration: epidemiology and optimal treatment.

la Cour M, Kiilgaard JF, Nissen MH.

Eye Department, National University Hospital (Rigshospitalet), Copenhagen,
Denmark. m.la.cour@dadlnet.dk

Age-related macular degeneration (AMD) is a common macular disease affecting
elderly people in the Western world. It is characterised by the appearance of
drusen in the macula, accompanied by choroidal neovascularisation (CNV) or
geographic atrophy. The disease is more common in Caucasian individuals than in
pigmented races. In predominantly Caucasian populations, the age-standardised
prevalence of AMD in at least one eye is 7760 cases per million. The
age-standardised cumulated 1-year incidence of AMD in at least one eye is 1051
cases per million individuals. AMD is the most important single cause of
blindness among Caucasian individuals in developed countries. Blindness resulting
from AMD rarely occurs before age 70, and most cases occur after age 80. The
age-standardised 1-year incidence of legal blindness resulting from AMD is 212
cases per million. Two-thirds of AMD cases have CNV (exudative cases); the
remainder has only geographic atrophy. In cross-sectional population-based
studies about 45% of eyes with AMD have visual acuity reduced to 20/200 or worse.
This is true both for exudative AMD and pure geographic atrophy. Age and genetic 
predisposition are known risk factors for AMD. Smoking is probably also a risk
factor. Preventive strategies using macular laser photocoagulation are under
investigation, but their efficacy in preventing visual loss is as yet unproven.
There is no treatment with proven efficacy for geographic atrophy. Optimal
treatment for exudative AMD requires a fluorescein angiographic study and a
physician capable of interpreting it. For CNV not involving the foveal centre,
the only evidence-based treatment is laser photocoagulation. For AMD cases with
subfoveal CNV, good visual acuity, and predominantly classic fluorescence pattern
on fluorescein angiography, photodynamic therapy with verteporfin is the
treatment of choice. Photodynamic therapy is also effective in eyes with pure
occult CNV and evidence of recent disease progression. For new subfoveal CNV with
poor vision and recurrent CNV, laser photocoagulation can be considered.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 11950377 [PubMed - indexed for MEDLINE]

2836: Int Ophthalmol. 2001;23(4-6):347-53.

A new method for the measurement of oxygen saturation at the human ocular fundus.

Schweitzer D, Thamm E, Hammer M, Kraft J.

Department of Experimental Ophthalmology, University of Jena, Germany.

Measurements of the transmission and the reflectance spectra of whole blood
exhibit a different dependence of the thickness of the blood layer. Whereas the
transmission spectra decrease at all wavelengths, in the reflectance two ranges
with different behaviour have to distinguish. In the absorption dominated range
between about 500 and 600 nm, there is only a marginal influence of the thickness
of the blood layer. In contrast, in the scattering dominated range higher than
about 600 nm the reflectance increases if the thickness of the blood layer
increases. Proofed by Monte Carlo simulation, the reflected light, which will be 
measured in ophthalmologic devices, consists both of light which penetrates a
vessel once and will be reflected at the background and of light which is
internally reflected at the blood column. Only in small vessels (diameter < 50
microm) the transmitted part dominates. With increasing diameter of the vessels
the internally reflected light dominates. Especially under the conditions of a
confocal laser scanner, the transmitted part of light is always small. As the
measured light consists of both parts of light, a new model for the approximation
of the measured reflected light is given, containing an expression for the
transmitted and for the internally reflected light. The model was applied for the
approximation of the reflectance of blood in a cuvette with an coloured
background, delivering sufficient exact result. The oxygen saturation was
determined in 256 measurements of 30 healthy persons using an ophthalmo imaging
spectrometer. The mean arterial oxygen saturation was 91 +/- 5%, the mean venous 
oxygen saturation was 59 +/- 9% and the arterio-venous difference in the oxygen
saturation was 35%, which is in good agreement with the arterio-venous difference
known in the brain. First measurements of the oxygen saturation in age-related
macular degeneration point to partly different pathological changes of the
retinal microcirculation in dry and in wet AMD.

PMID: 11944861 [PubMed - indexed for MEDLINE]

2837: Int Ophthalmol. 2001;23(4-6):297-307.

Retinal pigment epithelium translocation and central visual function in age
related macular degeneration: preliminary results.

Stanga PE, Kychenthal A, Fitzke FW, Halfyard AS, Chan R, Bird AC, Aylward GW.

The Institute of Ophthalmology, University College London, UK.

PURPOSE: To test the feasibility of a new surgical technique, and to assess
visual function over the translocated retinal pigment epithelium (RPE) cells in
patients operated upon for subfoveal choroidal neovascularization (CNV) secondary
to age-related macular degeneration (AMD). MATERIALS AND METHODS: Six patients
presenting previously untreated exudative AMD underwent surgical excision of the 
subfoveal CNV with RPE translocation and were followed from 1 to 10.5 months. The
surgery consisted of a standard three port pars plana vitrectomy (TPPPV),
excision of the CNV and RPE translocation. Pre and post-operative ocular
examination included best-corrected visual acuity measurement, fundus color
stereo photography and fundus fluorescein angiography. Optical coherence
tomography (OCT) and confocal laser scanning ophthalmoscopy (cLSO) were performed
post-operatively. A cross fixation target and a single-point flashing light were 
projected on different areas of the posterior pole using a cLSO. Photopic 10-2
perimetry, photopic fine matrix mapping, cLSO microperimetry were also performed 
pre and post-operatively in four patients. OCT cross-sectional scans and cLSO RPE
autofluorescence were recorded to detect the presence of viable translocated RPE.
Visual acuity, fixation, photopic 10-2 perimetry, photopic fine matrix mapping
and cLSO microperimetry were tested for the presence of central visual function. 
RESULTS: RPE could be effectively translocated at the time of CNV removal from
the edge of the RPE defect to a subfoveal location. OCT showed the translocated
RPE as an area of increased optical reflectivity with optical shadowing external 
to it. cLSO showed autofluorescence of the translocated RPE. The cross fixation
target was seen when projected on the translocated RPE. During eccentric
fixation, the patients could see a flashing point-target projected on the
translocated RPE. Photopic 10-2 perimetry, photopic fine matrix mapping and cLSO 
microperimetry showed presence of central visual function. CONCLUSIONS: The
authors propose that translocation of RPE at the time of CNV removal, from the
edge of the RPE defect to a subfoveal location, may have a role in the surgical
management of AMD.

Publication Types: 
    Case Reports
    Clinical Trial

PMID: 11944854 [PubMed - indexed for MEDLINE]

2838: Int Ophthalmol. 2001;23(4-6):245-50.

Detecting AMD with multiply scattered light tomography.

Elsner AE, Zhou Q, Beck F, Tornambe PE, Burns SA, Weiter JJ, Dreher AW.

Schepens Eye Research Institute, San Diego, USA.

PURPOSE: to use a novel technique, Multiply Scattered Light Tomography (MSLT), to
provide a comfortable, rapid, and noninvasive method for detection and management
of Age-related Macualar Degeneration. METHODS: two patient groups were studied in
clinical settings with MSLT and confocal scanning laser tomography. In Poway, CA,
21 retinal patients underwent tomography, and the 17 patients with suspicion of
exudation also had ICG. An Angio-Scan (Laser Diagnostic Technologies, Inc.) was
used to provide simultaneous fundus reflectance and ICG imaging. In Methuen, MA, 
20 retinal patients underwent tomography with fluorescein angiography for
suspicion of exudation. The MSLT was based on the TopSS (Laser Diagnostic
Technologies, Inc.), with a Vertical Cavity Surface Emitting Laser array at 850
mm as the illumination source. The central laser produced confocal images. The
surrounding lasers produced multiply scattered light images. RESULTS: MSLT
emphasized structures beneath the retina such as drusen, choroidal new vessel
membranes, and pigment epithelial detachments. Exudation seen on angiography was 
visualized by MSLT as topographical structures with distinct borders. Superficial
structures, e.g., cysts and epiretinal membranes, were visualized in 850 nm
images. DISCUSSION: confocal tomography and MSLT provided a rapid, noninvasive
method to detect and localize macular degeneration and pathological structures
found in eyes of older patients.

PMID: 11944848 [PubMed - indexed for MEDLINE]

2839: Graefes Arch Clin Exp Ophthalmol. 2002 Mar;240(3):169-75. Epub 2002 Feb 9.

Angiographic findings in patients with exudative age-related macular
degeneration.

Bermig J, Tylla H, Jochmann C, Nestler A, Wolf S.

Klinik und Poliklinik für Augenheilkunde, Universität Leipzig, Liebigstrasse
10-14, 04103 Leipzig, Germany.

PURPOSE: Exudative age-related macular degeneration (ARMD) is the leading cause
for severe visual loss in the elderly. A series of clinical trials has
established the efficacy of laser photocoagulation and photodynamic therapy (PDT)
in special subgroups of patients with exudative ARMD. We analyzed the fluorescein
and indocyanine green angiograms (ICG) of patients with exudative ARMD to
characterize the nature of the CNV in order to estimate the percentage of
patients amenable for one of the therapies. METHODS: Patients with acute symptoms
related to exudative ARMD were recruited for the study. All patients underwent
fluorescein and ICG angiography. We analyzed the type of the CNV (classic,
occult, or mixed) and location relative to the fovea from the fluorescein
angiograms. Additionally, we recorded the presence of a visible capillary network
in the early ICG angiograms, as well as hot spots and plaque hyperfluorescence in
the late ICG angiographic frames. RESULTS: We included 191 patients aged 53-92
years in the study. The angiograms revealed in 17 (9%) patients classic CNV (12
subfoveal), in 114 (60%) occult CNV, and in 60 (31%) mixed CNV. Of these 19 had a
classic component >50%. In the early ICG angiograms a capillary network was
visible in 50 eyes with occult CNV. Hot spots were present in 29 eyes and a
hyperfluorescent plaque in 54 eyes. CONCLUSION: In total, only 18% of eyes
included in our study were eligible for laser photocoagulation or for
photodynamic therapy (PDT). These numbers highlight the deficiencies of current
treatment modalities for exudative ARMD. For this reason, alternative treatment
should be further investigated to offer better treatment to patients with
exudative ARMD.

PMID: 11935273 [PubMed - indexed for MEDLINE]

2840: Vision Res. 2002 Apr;42(8):1053-61.

Mapping of retinal function in Best macular dystrophy using multifocal
electroretinography.

Scholl HP, Schuster AM, Vonthein R, Zrenner E.

Department of Pathophysiology of Vision and Neuro-Ophthalmology, University Eye
Hospital, Schleichstrasse 12-16, 72076 Tübingen, Germany.
hendrik.scholl@uni-tuebingen.de

In order to evaluate the function of the retina in Best macular dystrophy (BMD)
18 patients were examined by means of the multifocal electroretinogram (mfERG).
The mfERG peak amplitudes of the central and pericentral responses were
significantly reduced in the BMD patients (p<0.001). The ERG amplitude decrease
of the central response was significantly correlated with visual acuity loss and 
with the funduscopic staging. The implicit times in more eccentric groups were
slightly but significantly increased. The markedly reduced mfERG amplitudes with 
only slightly increased implicit times may indicate cone photoreceptor cell loss 
or damage to the cone outer segments.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11934455 [PubMed - indexed for MEDLINE]

2841: Arch Ophthalmol. 2002 Apr;120(4):485-90.

Butterfly-shaped pattern dystrophy: a genetic, clinical, and histopathological
report.

Zhang K, Garibaldi DC, Li Y, Green WR, Zack DJ.

Department of Ophthalmology, Johns Hopkins University School of Medicine, 809
Maumenee, 600 N Wolfe St, Baltimore, MD 21287, USA. dzack@bs.jbmi.edu

OBJECTIVES: To identify the disease-causing mutation in a large family
segregating dominantly inherited butterfly-shaped pattern dystrophy (BPD) and to 
describe the microscopic pathological changes observed in a member of this
family. METHODS: Seventeen individuals at risk for dominantly inherited BPD in a 
family were examined and blood samples obtained. Linkage analysis and mutation
screening of the human retinal degeneration slow (RDS)/peripherin locus were
performed. Light and electron microscopic examinations were performed on 1
postmortem eye of 1 affected individual. RESULTS: Four individuals demonstrated
macular degenerative changes with diminished visual acuity, and 3 others
exhibited early signs of atrophy without visual deficits. Microscopic examination
of the left eye of 1 patient revealed an area of total loss of the retinal
pigment epithelium (RPE) and photoreceptor cell layer with intact
choriocapillaris and lipofuscin-containing cells in the subretinal space. Outside
the area of RPE atrophy, the RPE was greatly distended by lipofuscin. The disease
locus in this family was mapped to 6p21.2, the region of the RDS/peripherin gene.
Further analysis identified a G-->A change at nucleotide position 637 of
RDS/peripherin, predicting a novel Cys213Tyr substitution in all affected members
of the family. CONCLUSIONS: This study describes a new RDS/peripherin mutation
for BPD and provides the first combined genetic-pathological study of this
condition, to our knowledge. CLINICAL RELEVANCE: Accumulation of lipofuscin in
RPE is a prominent feature of several retinal disorders, including age-related
macular degeneration. Further elucidation of the cellular and molecular mechanism
of BPD may provide insight into pathogenesis and lead to novel treatment
approaches for this and other macular degenerations.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11934323 [PubMed - indexed for MEDLINE]

2842: Arch Ophthalmol. 2002 Apr;120(4):481-4.

Quality of life with visual acuity loss from diabetic retinopathy and age-related
macular degeneration.

Brown MM, Brown GC, Sharma S, Landy J, Bakal J.

Center for Evidence-Based Health Care Economics, Suite 210, 1107 Bethlehem Pike, 
Flourtown, PA 19031, USA. lissa1011@aol.com

OBJECTIVE: To compare the quality of life in patients with visual acuity loss
occurring secondary to diabetic retinopathy with visual acuity loss occurring
secondary to age-related macular degeneration (ARMD). METHODS: Consecutive
patients with diabetic retinopathy and ARMD were evaluated using the time
trade-off method of utility value analysis. Both groups were stratified according
to the degree of visual acuity loss in the better-seeing eye (group 1:
20/20-20/25, group 2: 20/30-20/40, group 3: 20/50-20/100, group 4: < or =20/200).
Utility values obtained from the patients, once stratified for visual acuity
group, were compared with use of the t test and the Mann-Whitney U test. In
addition, a 2-way analysis of variance was performed to control for potential
confounding variables. RESULTS: No difference was found between the utility value
means of the diabetic retinopathy (n = 333) and ARMD (n = 246) subgroups
stratified according to visual acuity levels: group 1, P =.54; group 2, P =.96;
group 3, P =.09; and group 4, P =.32. A 2-way analysis of variance demonstrated
that, among the variables of ocular disease, sex, age, and visual acuity in the
better-seeing eye, only visual acuity was significantly associated with utility
values (P =.003). CONCLUSIONS: At similar levels of visual acuity loss, that
associated with diabetic retinopathy causes a similar reduction in quality of
life to that associated with ARMD. This information has important implications
for use in cost-utility analyses of ophthalmic interventions.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 11934322 [PubMed - indexed for MEDLINE]

2843: Arch Ophthalmol. 2002 Apr;120(4):451-9.

Macular translocation with 360 degrees retinotomy for exudative age-related
macular degeneration.

Aisenbrey S, Lafaut BA, Szurman P, Grisanti S, Lüke C, Krott R, Thumann G, Fricke
J, Neugebauer A, Hilgers RD, Esser P, Walter P, Bartz-Schmidt KU.

Department I, University Eye Clinic Tuebingen, Schleichstrasse 12-16, 72076
Tuebingen, Germany.

BACKGROUND: Macular rotation surgery comprises surgical extraction of choroidal
neovascular membranes in age-related macular degeneration (AMD) and translocation
of the foveal neural retina over adjacent retinal pigment epithelium. OBJECTIVE: 
To determine whether macular translocation with 360 degrees retinotomy can
stabilize and/or improve visual acuity in patients with subfoveal choroidal
neovascularization (CNV) secondary to AMD. DESIGN: This study consisted of a
standardized surgical procedure on a series of 90 consecutive patients and
follow-up examinations at fixed intervals for 12 months. PARTICIPANTS: All
patients in this study had experienced recent visual loss resulting from
subfoveal CNV caused by AMD. Twenty-six patients had major macular subretinal
hemorrhage, 39 patients had occult subfoveal CNV, and 25 patients had classic
subfoveal CNV. METHODS: Macular translocation surgery was performed between 1997 
and 1999. The patients were examined preoperatively and at 3, 6, and 12 months
postoperatively, including visual acuity, microperimetry, angiography, and
orthoptic assessment. RESULTS: Visual acuity increased by 15 or more letters in
24 patients, remained stable in 37 patients, and deteriorated by 15 or more
letters in 29 patients at 12 months postoperatively. A secondary procedure was
necessary in 17 patients because of severe complications; proliferative
vitreoretinopathy was observed in 17 eyes, macular pucker in 5 eyes, and macular 
hole in 1 patient. CONCLUSION: Macular translocation is a technically demanding
surgical procedure. Although the procedure has a high rate of surgical and
postoperative complications, the functional and anatomical results appear to be
promising for selected patients with subfoveal CNV secondary to AMD.

PMID: 11934318 [PubMed - indexed for MEDLINE]

2844: Graefes Arch Clin Exp Ophthalmol. 2002 Feb;240(2):73-8.

Analysis of digital scanning laser ophthalmoscopy fundus autofluorescence images 
of geographic atrophy in advanced age-related macular degeneration.

Schmitz-Valckenberg S, Jorzik J, Unnebrink K, Holz FG; FAM Study Group.

Department of Ophthalmology, University of Heidelberg, Germany.

BACKGROUND: Fundus autofluorescence (AF) imaging using confocal scanning laser
ophthalmoscopy (cSLO) has been shown to be superior to fundus photography or
angiography for delineating areas of geographic atrophy (GA) in retinal pigment
epithelium (RPE) and for recording variation over time. We have evaluated a
method for automated computerized detection and quantitation of RPE atrophy.
METHODS: AF images in vivo were recorded with a confocal scanning laser
ophthalmoscope (exc. 488 nm, em. >500 nm; Heidelberg Retina Angiograph). The
intensity of AF in atrophic areas was markedly decreased. Two independent readers
analysed these areas in 24 right eyes manually by outlining GA areas using a
mouse-driven arrow (method A) and automatically by image analysis software
(Global Lab Image/2) after subjective adjustment of thresholding (method B).
Agreement between observers and between methods A and B was assessed by the
Bland-Altman design for method-comparison studies. RESULTS: Larger areas were
measured using method A than B by both readers (agreement A/B: reader 1 mean
difference 1.04 mm, 95% CI [0.66,1.42]; reader 2 mean difference 0.62 mm, 95% CI 
[0.43,0.81]). The agreement between the readers was mean difference 0.39 mm (95% 
CI [0.02,0.76]) for A and mean difference -0.03 mm (95% CI [-0.23,0.18]) for B.
Features making the delineation of borders of GA difficult included large
choroidal vessels with autofluorescent properties in the GA area and media
opacities. CONCLUSIONS: Fundus AF cSLO imaging provides a reliable means to
delineate areas of GA. The automated image analysis allows more accurate
detection and quantitative documentation of atrophic areas than manual outlining.
This method will be useful in longitudinal natural history studies and for
monitoring effects of future therapeutic interventions to slow down GA
progression in patients with advanced atrophic ARMD and other retinal diseases
associated with outer retinal atrophy.

Publication Types: 
    Clinical Trial
    Evaluation Studies
    Research Support, Non-U.S. Gov't

PMID: 11933894 [PubMed - indexed for MEDLINE]

2845: J Ophthalmic Nurs Technol. 2000 Sep-Oct;19(5):252-4.

The nursing process in photodynamic therapy.

Sahota B, Potter MJ.

Department of Ophthalmology, University of British Columbia, Vancouver, British
Columbia, Canada.

The results from the TAP Study have been found to be significant, but remember
this is not a cure. There are no quick and easy solutions to this devastating
disease, which can creep up so suddenly and without warning. Ophthalmologists may
be able to stabilize the vision without allowing it to become worse, but the key 
words are "without allowing it to become worse." Unfortunately, to most patients,
it is already worse. Nurses must address the patients' feelings and concerns
first, before offering a physical solution that is only a temporary "band aid."
After 10 years of working in the area of ophthalmology, specifically low vision, 
it has come to the authors' attention that a large percentage of patients
suffering from AMD display depressive symptoms such as feelings of sadness,
worthlessness, and hopelessness, and low self-esteem. Many appear to go through a
grieving process. Keeping this is mind, the overall goal in nursing care should
be to help patients with AMD use available resources so they have the potential
to maintain a satisfying quality of life, physically and emotionally.

PMID: 11933323 [PubMed - indexed for MEDLINE]

2846: J Ophthalmic Nurs Technol. 2000 Sep-Oct;19(5):250-1.

New surgical treatments for macular degeneration.

York J, Glaser B, Murphy R.

Glaser Murphy Retina Treatment Center, 901 Dulaney Valley Road, Suite 200,
Baltimore, MD 21204, USA.

The new surgical techniques described in this article expand the list of new
treatments becoming available for people with macular degeneration.

PMID: 11933322 [PubMed - indexed for MEDLINE]

2847: Am J Ophthalmol. 2002 Apr;133(4):572-5.

Photodynamic therapy increases the eligibility for feeder vessel treatment of
choroidal neovascularization caused by age-related macular degeneration.

Piermarocchi S, Lo Giudice G, Sartore M, Friede F, Segato T, Pilotto E, Midena E.

Department of Ophthalmology, University of Padova, Padova, Italy.
stefano.piermarocchi@unipd.it

PURPOSE: To report angiographic observations about feeder vessel identification
after photodynamic therapy in patients with choroidal neovascularization caused
by age-related macular degeneration. DESIGN: Cohort study. METHODS: We analyzed
fluorescein and indocyanine green dynamic angiography in 156 eyes of 145 patients
before and after photodynamic therapy to identify the feeder vessels of the
choroidal neovascular membrane. RESULTS: Before photodynamic therapy one or more 
feeder vessel could be detected in 35 (22.4%) out of 156 eyes with choroidal
neovascularization. Three months after photodynamic therapy, a feeder vessel
could be identified in 112 (84.2%) out of 133 eyes with persistent choroidal
neovascularization. Among these, 16 eyes received direct laser photocoagulation
of the feeder vessel and did not need any further photodynamic therapy.
CONCLUSION: Previous photodynamic therapy improves the detection of the feeder
vessel of the choroidal neovascularization. A sequential combined therapy
(photodynamic and feeder vessel treatment) could be considered as an alternative 
to multiple photodynamic treatments.

PMID: 11931801 [PubMed - indexed for MEDLINE]

2848: Am J Ophthalmol. 2002 Apr;133(4):571-2.

The effect of internal limiting membrane peeling on chronic recalcitrant
pseudophakic cystoid macular edema: a report of two cases.

Peyman GA, Canakis C, Livir-Rallatos C, Conway MD.

Department of Ophthalmology, Tulane University Health Sciences Center, New
Orleans, Louisiana 70112-2699, USA. mchiass1@tulane.edu

PURPOSE: To describe the effect of internal limiting membrane peeling in chronic 
recalcitrant pseudophakic cystoid macular edema. DESIGN: Two interventional case 
reports. METHODS: Two consecutive patients with chronic pseudophakic cystoid
macular edema of 11-22 months duration, after uncomplicated cataract surgery,
unresponsive to previous treatment, were enrolled. The surgical technique
consisted of pars plana vitrectomy and internal limiting membrane peeling. Main
outcome measures included best-corrected visual acuity, biomicroscopic
appearance, and perifoveal leakage on fluorescein angiography. Optical coherence 
tomography scans were performed postoperatively. RESULTS: Pars plana vitrectomy
with internal limiting membrane peeling resulted in anatomical, angiographic, and
functional improvement in both patients, for total follow-up periods of 8 and 11 
months, respectively. CONCLUSION: To our knowledge, this is the first report of
chronic pseudophakic cystoid macular edema that favorably responded to pars plana
vitrectomy with internal limiting membrane peeling, as concluded after a MEDLINE 
search.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 11931800 [PubMed - indexed for MEDLINE]

2849: Am J Ophthalmol. 2002 Apr;133(4):537-43.

Angiotensin II and vascular endothelial growth factor in the vitreous fluid of
patients with diabetic macular edema and other retinal disorders.

Funatsu H, Yamashita H, Ikeda T, Nakanishi Y, Kitano S, Hori S.

Department of Ophthalmology, Diabetes Center, Tokyo Women's Medical University,
Tokyo, Japan. tfunatsu@nifty.com

PURPOSE: To investigate the correlation between angiotensin II (AII) or vascular 
endothelial growth factor (VEGF) levels in the vitreous fluid and the severity of
diabetic macular edema (DME). DESIGN: A case-control study. METHODS: Vitreous
fluid samples were obtained at the time of vitreoretinal surgery from 20 eyes of 
20 patients with DME, 6 eyes of 6 diabetic patients without retinopathy, and 14
eyes of 14 nondiabetic patients. The VEGF levels in vitreous fluid and plasma
were determined by enzyme-linked immunosorbent assay, while AII levels were
measured by radioimmunoassay. RESULTS: The vitreous concentration of VEGF was
significantly higher in patients with DME than in nondiabetic patients or
diabetic patients without retinopathy (P <.0001 and P <.0001, respectively).
Vitreous levels of AII were also higher in patients with DME than in nondiabetic 
patients (P =.0082). The vitreous concentration of AII was significantly
correlated with that of VEGF (P =.0022). Vitreous concentrations of both AII and 
VEGF were significantly higher in patients with hyperfluorescent DME than in
those with hypofluorescent (P =.0228 and P =.0068, respectively). CONCLUSIONS: We
found that the levels of both AII and VEGF were elevated in the vitreous fluid of
patients with hyperfluorescein DME. Our results suggest that both AII and VEGF
are related to the increase of vascular permeability in DME.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11931788 [PubMed - indexed for MEDLINE]

2850: Am J Ophthalmol. 2002 Apr;133(4):521-9.

Radiotherapy for subfoveal choroidal neovascularization in age-related macular
degeneration: a randomized clinical trial.

Valmaggia C, Ries G, Ballinari P.

Department of Ophthalmology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
valmaggia@freesurf.ch

PURPOSE: To report results of 18-month follow up of external beam radiation
therapy with photons for subfoveal classic or occult choroidal neovascularization
(CNV) in age-related macular degeneration (ARMD). DESIGN: Randomized clinical
trial. METHODS: A total of 161 patients with subfoveal CNV in ARMD were recruited
in a prospective double-masked study. The posterior pole of the afflicted eye was
given 1 Gy (4 x 0.25 Gy) in the control group and 8 Gy (4 x 2 Gy) or 16 Gy (4 x 4
Gy) in the treatment groups. At the time of treatment, and 6, 12, and 18 months
post treatment, best-corrected visual acuity (BCVA), reading ability, and CNV
size were measured. RESULTS: At the completion of the study 150 (93.2%), 139
(86.3%), and 137 (85.1%) patients were followed for 6, 12, and 18 months,
respectively. The mean number of lines lost in the BCVA was -1.69, -2.2, and
-3.23 in the 1 Gy group; -0.94, -1.25, and -1.73 in the 8 Gy group; -0.51, -0.67,
and -1.93 in the 16 Gy group. The difference was significant after 12 months (P
=.016 for 8 Gy vs. 1 Gy; P =.006 for 16 Gy vs. 1 Gy), and 18 months (P =.011 for 
8 Gy vs. 1 Gy; P =.05 for 16 Gy vs. 1 Gy). The patients with classic CNV, or with
an initial distance visual acuity >or=20/100, benefited more from treatment. A
significant difference was not found between control group and treatment groups
in the reading ability and in the CNV size. No radiation-associated side effects 
were reported thus far. CONCLUSION: The number of lines lost in the BCVA was less
in the 8 Gy and 16 Gy treatment groups than in the control group during the
complete follow up examination. Radiation therapy with 8 Gy and 16 Gy, without
showing any difference in efficacy, resulted in a near stabilization of the BCVA 
in patients with subfoveal classic or occult CNV in ARMD. Further studies are
necessary to determine the significance of repeated radiotherapy series with a
dose of 8 Gy to improve the effect on the CNV size and thereby to prolong
stabilization of distance visual acuity.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 11931786 [PubMed - indexed for MEDLINE]

2851: Graefes Arch Clin Exp Ophthalmol. 2002 Feb;240(2):90-5.

Dark adaptation in age-related macular degeneration: relationship to the fellow
eye.

Haimovici R, Owens SL, Fitzke FW, Bird AC.

Institute of Ophthalmology, University College, London, UK.
Robert.Haimovici@bmc.org

BACKGROUND: Abnormalities of dark adaptation have been documented in patients
with age-related macular degeneration (AMD), but the relationship with the
various forms of this disorder has not been studied systematically. METHODS:
Dark-adapted retinal sensitivities and kinetics of dark adaptation were studied
using a Humphrey visual field analyzer adapted for these purposes in patients
over 64 years of age. One eye per patient was studied. Study eyes had a normal
visual acuity and macular drusen only. The fellow eye was categorized as follows:
group I, pigment epithelial detachments and tears of the retinal pigment
epithelium (RPE); group II, choroidal neovascularization; and group III, drusen
only. The results of psychophysical tests of the study eyes (group I and II and
one eye of group III patients) were compared with one another and with older
patients without evidence of AMD (group IV). RESULTS: Retinal sensitivity was
found to be most consistently abnormal nearest the fovea. The time course of dark
adaptation was prolonged beyond 45 min in 10/11 patients (91%) in group I, 6/10
patients (60%) in group II, and 6/10 (60%) in group III and 1/11 (9%) in group
IV. CONCLUSION: In a high proportion of patients with visual loss from AMD in one
eye, the fellow eye shows abnormal dark adaptation. These changes appear to be
most pronounced in patients with detachments of the RPE in the fellow eye.

Publication Types: 
    Comparative Study

PMID: 11931085 [PubMed - indexed for MEDLINE]

2852: Retina. 2002 Apr;22(2):143-52.

Preclinical and phase 1A clinical evaluation of an anti-VEGF pegylated aptamer
(EYE001) for the treatment of exudative age-related macular degeneration.

Eyetech Study Group.

BACKGROUND: Recent studies have suggested that vascular endothelial growth factor
(VEGF) is an important stimulus for the growth of new blood vessels in the eye.
Anti-VEGF therapy is thus a potential treatment for exudative macular
degeneration and diabetic retinopathy. METHODS: Previously described animal
models of vascular leakage and ocular neovascularization, including the Miles
assay, the rat corneal angiogenesis model, and the mouse retinopathy of
prematurity (ROP) model, were used to study this drug. After these studies, a
phase IA single ascending dose study of intravitreal injections of the drug was
performed in 15 patients with subfoveal choroidal neovascularization secondary to
exudative age-related macular degeneration (AMD). RESULTS: The Miles assay model 
showed almost complete attenuation of VEGF-mediated vascular leakage following
addition of EYE001, and the corneal angiogenesis model also showed a significant 
reduction in neovascularization with EYE001. The ROP model showed inhibition of
80% of the retinal neovascularization compared with controls (P = 0.0001). The
phase IA safety study of patients with exudative AMD showed no significant safety
issues related to the drug. Ophthalmic evaluation revealed that 80% of patients
showed stable or improved vision 3 months after treatment and that 27% of eyes
demonstrated a three-line or greater improvement in vision on the Early Treatment
for Diabetic Retinopathy Study chart at this time. CONCLUSION: Anti-VEGF therapy 
is a promising new avenue for the treatment of neovascular diseases of the eye,
including exudative macular degeneration and diabetic retinopathy. Preclinical
data from studies with EYE001 support clinical evaluation of its efficacy in such
diseases. This report is the first to describe administration of anti-VEGF
therapy in humans for exudative macular degeneration and shows the safety of such
therapy for single injections. Further clinical studies are necessary to
determine the safety of multiple intravitreal injections of EYE001 and larger
studies are needed to prove the efficacy of this novel, potentially therapeutic
agent for neovascular AMD.

Publication Types: 
    Clinical Trial
    Clinical Trial, Phase I
    Evaluation Studies
    Multicenter Study

PMID: 11927845 [PubMed - indexed for MEDLINE]

2853: Ophthalmology. 2002 Apr;109(4):730-6.

Genetic influence on early age-related maculopathy: a twin study.

Hammond CJ, Webster AR, Snieder H, Bird AC, Gilbert CE, Spector TD.

Twin Research and Genetic Epidemiology Unit, St. Thomas' Hospital, Lambeth Palace
Road, London SE1 7EH, England, UK.

OBJECTIVE: Age-related macular degeneration (AMD) is the most common cause of
blindness in industrialized countries. There has been considerable interest in
the genetics of early age-related maculopathy (ARM) and AMD, because they have
phenotypes similar to inherited diseases where mutations have been identified,
but the heritability of ARM and AMD is unknown. DESIGN: A classical twin study
was performed to compare the concordance in monozygotic (MZ) and dizygotic (DZ)
twins in an unselected sample of female volunteer twins. PARTICIPANTS: Five
hundred six twin pairs, 226 MZ and 280 DZ, with a mean age of 62 years, were
examined. METHODS: ARM was graded from stereoscopic macular photographs of 501 of
the twin pairs (99%) according to the International ARM Epidemiologic Study Group
grading system. The casewise concordance was calculated for twin pairs from 2 x 2
contingency tables of affected/unaffected twins, and these tables were used in
maximum likelihood genetic modeling to estimate the heritabilities of phenotypes 
graded. MAIN OUTCOME MEASURES: Prevalence of ARM; concordance in MZ and DZ twins 
of the phenotypes of ARM, soft drusen >63 microm and > or =125 microm diameter,
pigmentary changes and hard drusen (<20 and > or =20 in number); heritability of 
ARM and subphenotypes. RESULTS: The overall prevalence of ARM was 14.6% (95%
confidence interval [CI], 12.4%-16.8%). The concordance for ARM in MZ twins was
0.37 compared with 0.19 in DZ twins, suggesting a role for genes. Modeling
confirmed a genetic effect for phenotypes of ARM, soft drusen, pigmentary
changes, and > or =20 hard drusen, although there was little genetic effect for
scattered (<20) hard drusen. The heritability of ARM was estimated as 45% (95%
CI, 35%-53%). The most heritable phenotypes were soft drusen > or =125 microm
(57%) and > or =20 hard drusen (81%), with the latter being dominantly inherited.
CONCLUSIONS: This study confirms a significant genetic influence in ARM and
suggests that future genetic studies should examine phenotypes of large (> or
=125 microm) soft drusen and > or =20 hard drusen, because these seem to be the
most heritable components.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't
    Twin Study

PMID: 11927430 [PubMed - indexed for MEDLINE]

2854: J Nutr. 2002 Apr;132(4):697-702.

The effect of five-year zinc supplementation on serum zinc, serum cholesterol and
hematocrit in persons randomly assigned to treatment group in the age-related eye
disease study: AREDS Report No. 7.

Age-Related Eye Disease Study Research Group.

aredspub@emmes.com

The effects of long-term supplementation with pharmacologic doses of zinc oxide
on serum levels of zinc, lipids and hematocrit have not been studied
systematically to date. Eleven Clinical Centers enrolled 4757 participants from
1992 to 1998 as part of the Age-Related Eye Disease Study (AREDS). Of these, 3640
participants, aged 55-80 y, who had early-to-late age-related macular
degeneration (AMD) were randomly assigned to daily supplementation with or
without 80 mg of zinc as zinc oxide plus 2 mg of copper as cupric oxide to study 
the effects of zinc supplementation on the progression to late AMD. This paper
reports on the effect of a 5-y supplementation with zinc oxide and cupric oxide
on serum zinc, copper, lipids, and hematocrit for 717 participants from three
clinical centers. At the 5-y exam, the median increase in serum zinc levels for
participants assigned to zinc formulations was 17% compared with a 2% increase
for participants not assigned to zinc (P < 0.001). The differential effect on
serum zinc was observed at 1 y and remained fairly constant over the 5-y period. 
After 5 y, no significant differences in changes in serum hematocrit, copper or
lipids were found between participants assigned to formulations containing zinc
and copper, and those assigned to formulations without zinc and copper. Estimates
from a modified Block Food-Frequency Questionnaire suggest the AREDS population
at baseline had a zinc intake from diet similar to that of the general
population.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11925463 [PubMed - indexed for MEDLINE]

2855: Invest Ophthalmol Vis Sci. 2002 Apr;43(4):1248-56.

Alterations of slow and fast rod ERG signals in patients with molecularly
confirmed Stargardt disease type 1.

Scholl HP, Besch D, Vonthein R, Weber BH, Apfelstedt-Sylla E.

Department of Pathophysiology of Vision and Neuroophthalmology, University Eye
Hospital Tübingen, Tübingen, Germany.

PURPOSE: To investigate the slow and fast rod signals of the scotopic 15-Hz
flicker ERG in patients with molecularly confirmed Stargardt disease type I
(STGD1). There is evidence that these slow and the fast rod ERG signals can be
attributed to the rod bipolar-AII cell pathway and the rod-cone coupling pathway,
respectively. METHODS: Twenty-seven patients with STGD1 with mutations in both
alleles of the ABCA4 gene were included. Scotopic ERG response amplitudes and
phases to flicker intensities ranging from -3.37 to -0.57 log scotopic troland x 
sec (log scot td x sec) were measured at a flicker frequency of 15 Hz. In
addition, scotopic standard ERGs were obtained. Twenty-two normal subjects served
as controls. RESULTS: The amplitudes of both the slow and fast rod ERG signals
were significantly reduced in the STGD1 group. The phases of the slow rod signals
lagged significantly, whereas those of the fast rod signals did not. The standard
scotopic ERG did not reveal significant alterations. CONCLUSIONS: The results
provide evidence that a defective ABCA4 transporter can functionally affect both 
the rod bipolar-AII cell pathway and the rod-cone coupling pathway. In STGD1, the
scotopic 15-Hz flicker ERG may reveal subtle abnormalities at different sites
within the rod system that remain undetected by standard ERG techniques.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11923272 [PubMed - indexed for MEDLINE]

2856: J Biol Chem. 2002 Jun 14;277(24):21759-67. Epub 2002 Mar 27.

Biochemical defects in retina-specific human ATP binding cassette transporter
nucleotide binding domain 1 mutants associated with macular degeneration.

Suárez T, Biswas SB, Biswas EE.

Department of Laboratory Sciences, Program in Biotechnology, Thomas Jefferson
University, Philadelphia, Pennsylvania 19107, USA.

The retina-specific human ABC transporter (ABCR) functions in the retinal
transport system and has been implicated in several inherited visual diseases,
including Stargardt disease, fundus flavimaculatus, cone-rod dystrophy, and
age-related macular degeneration. We have previously described a general
ribonucleotidase activity of the first nucleotide binding domain (NBD1) of human 
ABCR (Biswas, E. E. (2001) Biochemistry 40, 8181-8187). In this communication, we
present a quantitative study analyzing the effects of certain disease-associated 
mutations, Gly-863 --> Ala, Pro-940 --> Arg, and Arg-943 --> Gln on the
nucleotide binding, and general ribonucleotidase activities of this domain. NBD1 
proteins, harboring these mutations, were created through in vitro site-specific 
mutagenesis and expressed in Escherichia coli. Results of the enzyme-kinetic
studies indicated that these mutations altered the ATPase and CTPase activities
of NBD1. The G863A and P940R mutations were found to have significant attenuation
of the rates of nucleotide hydrolysis and binding affinities. On the other hand, 
the R943Q mutation had small, but detectable reduction in its nucleotidase
activity and nucleotide binding affinity. We have measured the nucleotide binding
affinities of NBD1 protein and its mutants quantitatively by fluorescence
anisotropy changes during protein binding to ethenoadenosine ATP (epsilonATP), a 
fluorescent ATP analogue. We have correlated the dissociation constant (K(D)) and
the rates of nucleotide hydrolysis (V(max)) of NBD1 and its mutants with the
available genetic data for these mutations.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11919200 [PubMed - indexed for MEDLINE]

2857: Am J Ophthalmol. 2002 Mar;133(3):393-7.

Comment on:
    Am J Ophthalmol. 2002 Mar;133(3):403-5.

Cystoid macular edema in the era of ocular hypotensive lipids.

Wand M, Shields BM.

University of Connecticut School of Medicine, Farmington, USA. nodhilwand@aol.com

PURPOSE: To review cystoid macular edema in relationship with ocular hypotensive 
lipids and to present recommendations for use in eyes at increased risk of
cystoid macular edema. DESIGN: Focused literature review and authors' clinical
experience. METHODS: Cystoid macular edema in association with cataract surgery, 
epinephrine therapy, and ocular hypotensive lipid therapy is reviewed. RESULTS:
Cystoid macular edema may be associated with a variety of therapeutic
interventions, predominantly in eyes at increased risk with open or absent
posterior lens capsule and ocular inflammation. Based primarily on experience
with latanoprost, the association between ocular hypotensive lipids and cystoid
macular edema, even in high-risk eyes, although present, appears to be low.
CONCLUSIONS: Considering the low incidence of cystoid macular edema associated
with latanoprost therapy, the authors feel that after maximal tolerable medical
therapy and with proper precautions, the use of an ocular hypotensive lipid is an
acceptable alternative to filtration surgery in high-risk eyes.

Publication Types: 
    Comment
    Review

PMID: 11915838 [PubMed - indexed for MEDLINE]

2858: Br J Ophthalmol. 2002 Apr;86(4):434-9.

Limited macular translocation with scleral retraction suture.

Sullivan P, Filsecker L, Sears J.

Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.

BACKGROUND/AIMS: Macular translocation with scleral imbrication is a new
technique for treating subfoveal choroidal neovascular membranes (CNV). This
procedure shortens the sclera but may result in a minimal decrease in the
internal circumference of the globe and limits the amount of foveal displacement.
The authors propose a new scleral retraction suture aimed at decreasing the
internal circumference of the globe in an effort to increase foveal displacement.
METHODS: Using a cadaver model, they compared the amount of scleral shortening
using a standard scleral imbrication technique and a modified three suture
scleral retraction technique. Sections of the globes were digitised and
specialised software was used to estimate the amount of scleral shortening. Three
patients with subfoveal choroidal neovascularisation underwent limited macular
translocation using pars plana vitrectomy and macular detachment with the
modified scleral suture technique. The main outcome measures were visual acuity, 
foveal displacement, and complications. RESULTS: In the cadaver model, the
scleral retraction suture resulted in a flatter internal scleral fold compared to
the standard suture technique and created approximately 890 microm of effective
scleral shortening. In the patients who underwent macular translocation and laser
photocoagulation of the CNV, visual acuity improved in two patients and worsened 
in one patient. The range of foveal displacement was 1400-2400 microm.
CONCLUSION: The foveal displacements achieved in this limited study compared to
median displacement previously published using standard suture techniques
demonstrates that the scleral retraction suture technique may be a useful adjunct
to limited macular translocation. The advantage of this type of suture in
conjunction with translocation may depend on the effective scleral shortening
offered by this retraction suture.

Publication Types: 
    Case Reports

PMID: 11914214 [PubMed - indexed for MEDLINE]

2859: Eye. 2002 Jan;16(1):81-4.

Inflammatory pigmented paravenous retinochoroidal atrophy.

Batioglu F, Atmaca LS, Atilla H, Arslanpençe A.

Ankara University School of Medicine, Eye Clinic, Turkey. batioglu@hotmail.com

PURPOSE: To describe an active inflammatory cause of pigmented paravenous
retinochoroidal atrophy. METHODS: A 54-year-old female patient presented with
complaints of worsening visual acuity and poor night vision was examined. Fundus 
examination was performed and color fundus photographs were taken. In addition to
fluorescein angiography, visual field examinations and electroretinographic tests
were performed. Macular evaluation was performed with optical coherence
tomography. RESULTS: Both fundi showed circumscribed patches of retinochoroidal
atrophy and pigmentation along the retinal veins. She had also marked vitreous
cells with snow ball opacities and cystoid macular edema in both eyes.
Fluorescein angiography confirmed the presence of a hyperfluorescence due to
widespread paravenous retinal pigment epithelial defect while ICG angiography
disclosed hypofluorescence in all phases. The electroretinogram showed reduced
responses especially in the left eye. Visual field tests showed scotomas
corresponding with areas of atrophy along the retinal veins. CONCLUSIONS: This is
a report of the findings in pigmented paravenous retinochoroidal atrophy that is 
a nonspecific degenerative disease and may occur in association with systemic
infections or inflammation. Ocular inflammation with cystoid macular edema is an 
unusual manifestation of the disease.

Publication Types: 
    Case Reports

PMID: 11913895 [PubMed - indexed for MEDLINE]

2860: DNA Seq. 2001 Dec;12(5-6):431-5.

The gene causing the Best's macular dystrophy (BMD) encodes a putative ion
exchanger.

Gómez A, Cedano J, Oliva B, Piñol J, Querol E.

Departament de Bioquímica i Biologia Molecular, Institut de Biotecnologia i
Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, Spain.

Best's macular dystrophy (BMD), also known as vitelliform macular degeneration
type 2, is an autosomal dominant disease that causes loss of vision. The
causative gene encodes a 585 amino acids protein called bestrophin with unknown
function. From bioinformatics analysis, a putative ion exchanger function for
bestrophin can be suggested.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11913792 [PubMed - indexed for MEDLINE]

2861: Ophthalmic Genet. 2002 Mar;23(1):13-9.

The epsilon4 allele of apolipoprotein E gene is a potential risk factor for the
severity of macular edema in type 2 diabetic Mexican patients.

Santos A, Salguero ML, Gurrola C, Muñoz F, Roig-Melo E, Panduro A.

Instituto de Oftalmología y Ciencias Visuales, Mexico. asantos@retina.com.mx

PURPOSE: The objective of this study was to determine the relationship between
APOE polymorphism and the severity of retinal hard exudates in Mexican patients
with type 2 diabetes. METHODS: We studied 36 patients with diabetic retinopathy
and 22 unrelated and apparently healthy age-matched individuals. Blood samples
for DNA genotyping and lipid profile were taken. Genotyping of polymorphic APOE
alleles was done after polymerase chain reaction amplification of genomic DNA,
digestion with HhaI, and agarose gel electrophoresis. Stereoscopic 35 degrees
color fundus photographs were taken of seven standard fields. Diabetic
retinopathy, macular edema and hard exudates were graded according to a
standardized procedure. RESULTS: The results showed that the lipid profile was
higher but not statistically significant (p > 0.05) in e4 allele carriers, with
the exception of total lipids (p > 0.05). The frequency of severe retinal hard
exudates was higher in those epsilon4 allele carriers (p < 0.05). The higher
frequency of visual impairment (VA < 0.5 Log MAR) in epsilon4 carriers showed a
tendency towards statistical significance (p = 0.057). CONCLUSION: Our results
suggest that the epsilon4 allele of the ApoE gene is a potential risk factor for 
the severity of retinal hard exudates and visual loss in type 2 diabetic Mexican 
patients with diabetic retinopathy.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11910554 [PubMed - indexed for MEDLINE]

2862: Diabet Med. 2001 Dec;18(12):1003-6.

Use of oral fluorescein angiography in the diagnosis of macular oedema within a
diabetic retinopathy screening programme.

Razvi FM, Kritzinger EE, Tsaloumas MD, Ryder RE.

Birmingham City Hospital NHS Trust and Birmingham Midland Eye Centre, Birmingham,
UK. fgsummerfield@cs.com

AIMS: To assess if oral fluorescein angiography (OFA) is a suitable screening
method to detect macular oedema in diabetic retinopathy. METHODS: Eighty-four
diabetic patients were included in the study. They were from a consecutive series
of patients attending the diabetic eye-screening clinic, with retinopathy at the 
macula requiring ophthalmology assessment. All patients were subsequently
examined in the eye hospital, by ophthalmologist slit lamp biomicroscopy
assessment as the gold standard, followed by oral fluorescein angiography.
RESULTS: This study indicates a sensitivity of 92% and specificity of 81%. Only
4.8% of patients developed a minor reaction to oral fluorescein; 84.5% of images 
were of good quality. CONCLUSIONS: Oral fluorescein angiography is an efficient
and highly sensitive tool for the detection of macular oedema. It can be used as 
an adjunct in the diabetic screening service to identify patients with oedema
within a disc diameter of the macula. Ultimately it will ensure that only
necessary and smaller numbers of patients are referred to ophthalmologists.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11903401 [PubMed - indexed for MEDLINE]

2863: Retina. 2002 Feb;22(1):59-64.

Comparison of nonmydriatic digitized video fundus images with standard 35-mm
slides to screen for and identify specific lesions of age-related macular
degeneration.

Lim JI, Labree L, Nichols T, Cardenas I.

Doheny Eye Institute, University of Southern California, Los Angeles, USA.

PURPOSE: The purpose of this study was to compare nonmydriatic digitized images
obtained using a digital imaging system (resolution of 640 x 480 pixels) with
35-mm slide images for detecting specific findings of age-related macular
degeneration (AMD) and to evaluate its usefulness as a screening tool in
detecting signs of AMD. METHODS: Seventeen consecutive patients (33 eyes)
underwent digital color imaging (with a nonmydriatic, 45-degree, fundus camera
attached to a digital back) and standard 35-mm, 30-degree retinal color
photography of the fundus: posterior pole, nasal retina, and temporal retina. The
images were later reviewed for the presence or absence of specific retinal
findings. The images were not compressed. Primary outcome measures included the
presence or absence of drusen, hard exudate, choroidal neovascularization (CNV), 
subretinal hemorrhage, retinal pigment epithelial (RPE) changes, subretinal
fibrosis, pigment epithelial detachment (PED), and subretinal fluid. Presence of 
drusen, with or without any one of the other findings, and presence of disciform 
scar or geographic atrophy were positive indications in screening for AMD.
RESULTS: Agreement between image type was highest for PED (97%), CNV (91%), and
subretinal fibrosis (91%); and lowest for RPE changes (63%). Sensitivity,
specificity, positive predictive value, and negative predictive values were
determined using the 35 mm-slide images as the reference for comparison.
Sensitivity ranged from 40% (hard exudates) to 75% (subretinal hemorrhage).
Specificity ranged from 88% (drusen) to 100% (hard exudate, CNV, RPE changes,
PED). Positive predictive value ranged from 67% (subretinal hemorrhage) to 100%
(hard exudate, CNV, RPE changes, PED). Negative predictive value ranged from 44% 
(drusen) to 97% (PED). For the purposes of screening for any evidence of AMD, the
system was 70% sensitive. CONCLUSION: This digital fundus imaging system with 640
x 480 pixel resolution has low sensitivity and high specificity, as compared with
35-mm slide images, for detection of early AMD, but higher sensitivity for late
findings (CNV, scar, atrophy) of AMD. Because of sensitivity for detecting any
AMD coupled with the low sensitivity for detecting CNV, the system is not useful 
for evaluating AMD patients who require close follow-up and who are at risk for
more severe visual loss.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11884880 [PubMed - indexed for MEDLINE]

2864: Retina. 2002 Feb;22(1):6-18.

Guidelines for using verteporfin (visudyne) in photodynamic therapy to treat
choroidal neovascularization due to age-related macular degeneration and other
causes.

Verteporfin Roundtable 2000 and 2001 Participants; Treatment of age-related
macular degeneration with photodynamic therapy (TAP) study group principal
investigators; Verteporfin in photodynamic therapy (VIP) study group principal
investigators.

Novartis Ophthalmics Inc., Duluth, GA 30097, USA.

OBJECTIVE: Guidelines were developed based on best available scientific data as
well as consensus of expert opinion in absence of controlled clinical trial data 
to: 1) assist ophthalmologists with selection of patients for whom photodynamic
therapy with verteporfin, termed "verteporfin therapy," should be considered; and
2) offer suggestions regarding treatment, follow-up, and re-treatment. METHODS:
Consensus from roundtable of retina specialists who either participated in
randomized clinical trials evaluating verteporfin therapy or had clinical
experience with verteporfin therapy was based on results of these trials and
expert opinion. Additional input and advice were received from representatives on
behalf of the Macula Society, the Retina Society, and the Vitreous Society, as
well as principal investigators of randomized clinical trials evaluating
verteporfin therapy. RESULTS: Patient selection criteria included the following: 
1) in cases due to age-related macular degeneration (AMD), lesion composition
either predominantly classic choroidal neovascularization (CNV) or occult with no
classic CNV; 2) CNV location subfoveal or so close to the foveal center that
conventional laser photocoagulation treatment almost certainly would extend under
the center; 3) lesion etiology from AMD, pathologic myopia, or other causes in
which the outcome without treatment is likely to be worse than with treatment; 4)
vision at a level where further loss would be recognized as detrimental to the
quality of life of the patient. Criteria did not include lesion size, except in
cases composed of occult with no classic CNV in AMD in which therapy for lesions 
>4 Macular Photocoagulation Study (MPS) disc areas usually should be considered
only when presenting with lower levels of best-corrected visual acuity. Criteria 
also did not include patient age, history of systemic arterial hypertension, or
prior laser photocoagulation. Therapy should occur ideally within 1 week of the
initial fluorescein angiogram on which the clinical decision to treat is based.
Patients should return for follow-up at least as often as every 3 months after
any initial or subsequent treatment to determine if there is fluorescein leakage 
from CNV. Re-treatment should be considered as often as every 3 months if
fluorescein leakage from CNV is noted at that time. Re-treatment could be
deferred if the biomicroscopic and fluorescein angiographic appearance of the
lesion is unchanged and shows minimal leakage, especially when there is no
subretinal fluid or fluorescein leakage from CNV underlying the center of the
foveal avascular zone. Patients should avoid exposure of skin or eyes to direct
sunlight or bright indoor light for 48 hours after treatment or until resolution 
of any swelling or discoloration from extravasation. CONCLUSION: These
recommendations provide guidelines on the role of verteporfin therapy in the
management of CNV due to AMD and other causes. Revisions of these guidelines may 
be required as new data become available.

Publication Types: 
    Consensus Development Conference
    Guideline
    Practice Guideline
    Research Support, Non-U.S. Gov't
    Review

PMID: 11884872 [PubMed - indexed for MEDLINE]

2865: Exp Eye Res. 2002 Jan;74(1):141-54.

Drusen are Cold Spots for Proteolysis: Expression of Matrix Metalloproteinases
and Their Tissue Inhibitor Proteins in Age-related Macular Degeneration.

Leu ST, Batni S, Radeke MJ, Johnson LV, Anderson DH, Clegg DO.

Department of Molecular, Cellular and Development Biology, University of
California, Santa Barbara, CA 93106, USA.

Drusen are abnormal extracellular matrix deposits characteristic of age-related
macular degeneration (AMD), a leading cause of blindness in the aging human
population. The mechanisms underlying drusen formation are not well
characterized. The purpose of this study was to examine the expression of matrix 
metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in 
drusen, and in the surrounding cells and tissue. To assess the extent of MMP and 
TIMP expression by retinal pigment epithelial (RPE) cells, cDNA arrays were
screened with probes generated from cultured human RPE cells. The distribution of
MMP-1, -2 and -3 and TIMP-1, -2, -3 and -4 was determined using
immunohistochemistry in human RPE choroid from donor eyes with and without a
clinical history of AMD. Gelatinase activity was assessed in unfixed frozen
sections using in situ zymography. In cultured RPE cells, expression of 10 MMP
and all four known TIMP mRNAs was detected. MMP immunoreactivity was widespread
in the RPE choroid, but was absent from the interior of drusen. TIMP-3, but not
other TIMPs, was detected in the drusen interior. Likewise, metal ion dependent
gelatinase activity could be detected in RPE choroid, but not in drusen. These
results show that, while metalloproteinase activity is widespread throughout the 
RPE choroid, drusen are cold spots for proteolysis. The data lead to the
speculation that high TIMP-3 concentrations within drusen could inhibit MMPs and 
as a result slow the proteolytic degradation of these deposits. Copyright 2002
Elsevier Science Ltd.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11878827 [PubMed - indexed for MEDLINE]

2866: Int J Radiat Oncol Biol Phys. 2002 Feb 1;52(2):489-95.

Radiotherapy in age-related macula degeneration.

Gripp S, Stammen J, Petersen C, Hartmann A, Willers R, Althaus C.

Department of Radiation Oncology, Heinrich-Heine- University, Duesseldorf,
Germany. stephan.gripp@uni-duesseldorf.de

PURPOSE: To ascertain the benefit from radiotherapy in age-related macula
degeneration in a single-arm longitudinal study. METHODS AND MATERIALS: From 1997
to 1998, 39 patients with occult and 33 patients with classic choroidal
neovascularization (CNV) were irradiated with 16 Gy. Fluorescein angiography and 
measurements of visual acuity were performed before and 3, 6, and 12 months after
irradiation. RESULTS: Complete follow-up data for 1 year were available from 69
patients. The mean patient age was 72 years (range 49-92). Vision decreased in
43, was stable in 18, and improved in 8 cases. The mean vision deteriorated
significantly (p = 0.02, Wilcoxon test), particularly within the first 3 months. 
Patients with occult CNV did significantly better than did those with classic CNV
(p = 0.03). The proportion of patients retaining vision > or = 0.2 fell from 65% 
to 42% (p <0.01), for classic and occult CNV from 50% to 23%, and for occult CNV 
from 77% to 56% (p < 0.02), respectively. CNV size increased in 30 patients and
was stable in 38. Neither age (p = 0.17) nor gender (p = 0.21, chi-square test)
influenced prognosis. Four patients reported transitional complaints. CONCLUSION:
Low-dose fractionated radiotherapy with 16 Gy is well tolerated. However, vision 
and reading ability were not preserved in most patients.

PMID: 11872297 [PubMed - indexed for MEDLINE]

2867: Cochrane Database Syst Rev. 2002;(1):CD000254.

Update in:
    Cochrane Database Syst Rev. 2002;(2):CD000254.

Update of:
    Cochrane Database Syst Rev. 2000;(2):CD000254.

Antioxidant vitamin and mineral supplements for age-related macular degeneration.

Evans JR.

Research and Development Department, Institute of Ophthalmology (UCL) and
Moorfields Eye Hospital, City Road, London, UK, EC1V 2PD.
jennifer.evans@ucl.ac.uk

BACKGROUND: It has been proposed that antioxidants may prevent cellular damage in
the retina by reacting with free radicals produced in the process of light
absorption. OBJECTIVES: The objective of this review is to assess the effects of 
antioxidant vitamin and/or mineral supplementation on the progression of
age-related macular degeneration. SEARCH STRATEGY: The Cochrane Controlled Trials
Register - CENTRAL/CCTR, which contains the Cochrane Eyes and Vision Group
specialised register (Cochrane Library Issue 3 2001), MEDLINE (1966 to August
2001), EMBASE (1980 to September 2001), the Science Citation Index, and the
reference lists of relevant articles were searched. Investigators of included
studies were contacted for further information. SELECTION CRITERIA: Randomised
trials comparing an antioxidant vitamin and/or mineral supplement (alone or in
combination) to control in people with age-related macular degeneration are
included in this review. DATA COLLECTION AND ANALYSIS: The reviewer extracted
data and assessed trial quality. Due to the variable methods of collecting and
presenting outcome data, no statistical summary measure was calculated. MAIN
RESULTS: Seven trials, which randomised 4119 people with signs of age-related
macular degeneration, are included in this review. One unpublished trial of zinc 
supplementation (170 participants) is awaiting assessment. The majority of people
(88%) were randomised in one trial that was conducted in a relatively
well-nourished American population. This trial found a modest beneficial effect
of antioxidant and zinc supplementation on progression to advanced age-related
macular degeneration (odds ratio 0.72, 99% confidence interval 0.52 to 0.98).
People supplemented with antioxidants and zinc were less likely to lose 15 or
more letters of visual acuity (equivalent to a doubling of the visual angle)
(odds ratio 0.79, 99% confidence interval 0.60 to 1.04). The other six trials in 
this review were small and the results were inconsistent. REVIEWER'S CONCLUSIONS:
The evidence as to the effectiveness of antioxidant vitamin and mineral
supplementation in halting the progression of age-related macular degeneration is
dominated by one large trial in a relatively well-nourished American population
that showed modest benefit in people with moderate to severe signs of the
disease. There is no evidence at present that people with early signs of the
disease should take supplementation, however, current studies are underpowered to
answer that question. The generalisability of these findings to other populations
with different nutritional status is not known. Further large well-conducted
randomised controlled trials in other populations are required.

Publication Types: 
    Review

PMID: 11869572 [PubMed - indexed for MEDLINE]

2868: Br J Ophthalmol. 2002 Mar;86(3):316-20.

Diabetic macular oedema: a comparison of vitreous fluorometry, angiography, and
retinopathy.

Sander B, Larsen M, Engler C, Strøm C, Moldow B, Larsen N, Lund-Andersen H.

Department of Ophthalmology, Herlev Hospital, University of Copenhagen, Dk 2730
Herlev, Denmark. bsander@idea.dk

AIM: To evaluate the relation between the quantitative measurement of vitreous
fluorescein with fluorescein angiography and retinopathy in diabetic patients
with and without clinically significant macular oedema (CSMO). METHODS: In a
prospective cross sectional study, passive permeability and active, outward
transport of fluorescein across the blood-retinal barrier were quantitated with
vitreous fluorometry in 61 eyes from 48 patients with CSMO and 22 fellow eyes
without CSMO, after exclusion of eyes with previous macular laser treatment and
vitreous liquification. All patients were recruited from the university
hospital's outpatient clinic. Retinopathy and fluorescein angiograms were
evaluated on 60 degree photographs. RESULTS: The passive permeability in CSMO was
significantly correlated with the severity of leakage on fluorescein angiograms
(r=0.73), the level of retinopathy (r=0.61), and visual acuity (r=0.45).
Significant differences between eyes with CSMO and eyes without CSMO were found
for passive permeability (p<0.001), fluorescein leakage (p<0.001), visual acuity 
(p=0.02), and retinopathy (p=0.002). CONCLUSION: Passive permeability of
fluorescein quantitated with vitreous fluorometry was correlated both with
semiquantitative fluorescein angiography and retinopathy, and a significant
increase in passive permeability was found when comparing eyes with CSMO to eyes 
without CSMO. No such pattern was found for the active transport indicating that 
passive and not the outward, active transport is the factor of most importance in
the development of CSMO.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 11864891 [PubMed - indexed for MEDLINE]

2869: Am J Ophthalmol. 2002 Mar;133(3):410-3.

Autosomal recessive cerebellar ataxia with bull's-eye macular dystrophy.

Cruysberg JR, Eerola KU, Vrijland HR, Aandekerk AL, Kremer HP, Deutman AF.

Institutes of Ophthalmology, University Medical Centre Nijmegen, Nijmegen, The
Netherlands. j.cruysberg@ohk.azn.nl

PURPOSE: In 1980, we published in the American Journal of Ophthalmology two
siblings with hereditary ataxia and atrophic maculopathy. The report is cited in 
the literature as autosomal dominant cerebellar ataxia with retinal degeneration.
The purpose of the present study is to document the progression of the
neurodegenerative disorder and to review the diagnosis. DESIGN: Observational
case report. METHODS: Twenty years after the original publication, the
52-year-old male patient had new ocular and neurologic examinations, fluorescein 
angiography, molecular genetic analysis, and biochemical testing. RESULTS:
Fluorescein angiography showed marked progression of the macular dystrophy to a
bull's-eye configuration. Genetic analysis of the patient did not show CAG
trinucleotide repeat expansion in the various spinocerebellar ataxia genes. This 
excludes the diagnosis of autosomal dominant cerebellar ataxia with macular
degeneration (ADCA type II) with mutation of the spinocerebellar ataxia 7 gene.
Major causes of autosomal recessive cerebellar ataxia with retinal degeneration, 
including Friedreich ataxia and congenital disorders of glycosylation, were also 
excluded. CONCLUSION: The two patients, previously published in the American
Journal of Ophthalmology by Eerola and coworkers, did not suffer from presently
recognized disorders with cerebellar ataxia and retinal degeneration. The Eerola 
syndrome probably represents a separate neurodegenerative entity characterized by
autosomal recessive cerebellar ataxia and progressive macular dystrophy with a
bull's-eye pattern.

Publication Types: 
    Case Reports

PMID: 11860984 [PubMed - indexed for MEDLINE]

2870: Am J Ophthalmol. 2002 Mar;133(3):403-5.

Comment in:
    Am J Ophthalmol. 2002 Mar;133(3):393-7.

Cystoid macular edema associated with ocular hypotensive lipids.

Wand M, Gaudio AR.

University of Connecticut School of Medicine, Farmington, Connecticut, USA.
nodhilwand@aol.com

PURPOSE: To report angiographically documented cystoid macula edema associated
with the use of each of the three newly available ocular hypotensive lipids:
unoprostone, travaprost, and bimatoprost. DESIGN: Observational case series.
METHODS: Retrospective review of three patients in a clinical practice who had
uncontrolled glaucoma on maximal tolerable therapy except for an ocular
hypotensive lipids. All three patients also had previous cataract and filtration 
surgery, and all had an absent or open posterior lens capsule. The patients were 
informed of the potential risks of cystoid macula edema associated with the use
of an ocular hypotensive lipids versus the risks of repeat filtration surgery.
RESULTS: An ocular hypotensive lipids was started in the affected eye in each
patient, and the patient was instructed to check visual acuity everyday and
report back any change in vision occurred. CONCLUSION: Decreased vision of at
least two lines caused by angiographically confirmed cystoid macula edema was
noted in each of three patients started, respectively, on unoprostone,
travaprost, and bimatoprost. The visual acuity returned to baseline, and the
cystoid macula edema was angiographically resolved after discontinuation of the
ocular hypotensive lipids and the initiation of a topical steroid and
non-steroidal anti-inflammatory eyedrops. Until a causal relationship between
cystoid macula edema and ocular hypotensive lipids is proved or disproved,
caution in their use in high-risk eyes would be prudent.

Publication Types: 
    Case Reports

PMID: 11860980 [PubMed - indexed for MEDLINE]

2871: Am J Ophthalmol. 2002 Mar;133(3):350-7.

Impact of visual function on computer task accuracy and reaction time in a cohort
of patients with age-related macular degeneration.

Scott IU, Feuer WJ, Jacko JA.

Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami
School of Medicine, Miami, Florida 33101, USA. iscott@bpei.med.miami.edu

PURPOSE: To investigate the impact of visual function parameters on computer task
performance in patients with age-related macular degeneration (AMD). DESIGN:
Interventional case series. METHODS: Eighteen patients with visual impairment due
to age-related macular degeneration underwent evaluation of visual acuity using
the Early Treatment Diabetic Retinopathy Study protocol, contrast sensitivity
using a Pelli-Robson chart, binocular simultaneous visual field using the
Esterman program on an automated perimeter, and color vision using Farnsworth
D-15. Each subject then completed 125 computer icon identification tasks.
Relationships between computer task performance (accuracy and speed) and visual
function parameters (visual acuity, contrast sensitivity, visual field, and color
vision) were analyzed. RESULTS: Visual acuity and contrast sensitivity in the
better eye, weighted average contrast sensitivity, and color vision defects are
significantly associated with computer task accuracy. Visual acuity in the better
eye, weighted average visual acuity, and color vision defects are significantly
associated with performance speed. Visual function parameters and clinical
features significantly associated with computer task accuracy in a multiple
regression model include weighted average contrast sensitivity (P = 0.001),
protan color vision defect (P = 0.002), cataract severity in the better-seeing
eye (P = 0.036), and geographic atrophy outside the central macula (P = 0.046).
Visual function parameters and clinical features significantly associated with
computer task speed in a multiple regression model include color vision defects
(deutan, P < 0.001; protan, P < 0.001) and gender (P = 0.05). CONCLUSIONS: Among 
this cohort of patients with AMD, visual acuity, contrast sensitivity, and color 
vision defects are significant predictors of computer task performance. Visual
function parameters of the better eye played a more significant role than
parameters of the worse eye, and contrast sensitivity is the most significant
predictor of computer task accuracy.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, Non-P.H.S.

PMID: 11860972 [PubMed - indexed for MEDLINE]

2872: Am J Ophthalmol. 2002 Mar;133(3):341-9.

Comment in:
    Am J Ophthalmol. 2002 Sep;134(3):468; author reply 468-9.

Fundus autofluorescence in patients with age-related macular degeneration and
high risk of visual loss.

Lois N, Owens SL, Coco R, Hopkins J, Fitzke FW, Bird AC.

Medical Retinal Service, Moorfields Eye Hospital, London, England.
noemilois@aol.com

PURPOSE: To describe fundus autofluorescence (AF) patterns and their change over 
time in patients with age-related macular degeneration (AMD) and high risk of
visual loss participating in the drusen laser study (DLS). DESIGN: Randomized
clinical trial. METHODS: The study population consisted of 29 patients (35 eyes) 
participating in the DLS, which is a prospective, randomized, controlled clinical
trial of prophylactic laser therapy in patients with AMD and high risk of
neovascular complications. The intervention consisted of 16 eyes having
prophylactic laser and 19 receiving no treatment. The main outcome measures were 
changes in the distribution of drusen and AF. Patients were reviewed for a median
follow-up or 24 months (range 12-36 months). RESULTS: At baseline, four patterns 
of fundus AF were recognized: focal increased AF (n = 18), reticular AF (n = 3), 
combined focal and reticular AF (n = 2), and homogeneous AF (n = 12). At last
follow-up, fundus AF remained unchanged in 15 untreated (78%) and in seven
treated (43%) eyes. In only one untreated eye, focal areas of increased AF
returned to background levels and were no longer detectable at last follow-up,
compared with six treated eyes. This difference was statistically significant (P 
=.03). Only large foveal soft drusen (drusenoid pigment epithelium detachments)
consistently corresponded with focal changes in AF, whereas no obvious
correspondence was found between small soft drusen located elsewhere and changes 
in AF. CONCLUSION: The lack of obvious correspondence between the distribution of
drusen and of AF found in this study appears to indicate that drusen and AF
represent independent measures of aging in the posterior pole.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11860971 [PubMed - indexed for MEDLINE]

2873: Nurse Pract. 2002 Feb;27(2):15-6, 21-3; quiz 24-5.

Drug and device approval highlights from 2001.

Kupecz D, Berardinelli C.

University of Phoenix, USA.

The U.S. Food and Drug Administration approved more than 100 drugs and devices in
2001. This article discusses several of the new approvals, including ophthalmic
drugs, contraceptive therapies, mental health medications, and medical devices.

PMID: 11858583 [PubMed - indexed for MEDLINE]

2874: Jpn J Ophthalmol. 2002 Jan-Feb;46(1):108-13.

Visual evoked potentials elicited by pseudorandom stimulation from patients with 
macular degeneration.

Nemoto N, Mori H, Kiyosawa M, Wang WF, Mochizuki M, Momose K.

Department of Ophthalmology and Visual Science, Tokyo Medical and Dental
University, Graduate School, Tokyo, Japan.

PURPOSE: To investigate the effect of a central scotoma on the amplitude,
implicit time (IT), and temporal frequency characteristics (TFC) of the visual
evoked potentials (VEPs) elicited by a pseudorandom binary sequence (PRBS)
stimulus in age-related macular degeneration (AMD) patients. METHODS: Twenty-six 
patients with AMD, 17 eyes with visual acuity of less than 20/100, and 9 eyes
with visual acuity between 20/70 and 20/25, were examined. Nine eyes of
age-matched healthy volunteers served as controls. To elicit the PRBS-VEPs, one
eye was stimulated with a PRBS stimulus. The first-order kernel was calculated
from a cross-correlation between the PRBS and the VEPs. The Fourier transformed
first-order kernel was used as the TFC of the visual system. RESULTS: The mean IT
of P2 (second positive peak) of the first-order kernel was significantly delayed 
(t-test, P <.05), and the P2-N2 (peak-to-peak of P2 and second negative peak N2) 
amplitude was significantly reduced (t-test, P <.01) in eyes with AMD. A
depression of the TFC values in the 6-18 Hz band was prominent in patients with
AMD (t-test, P <.01). CONCLUSION: PRBS-VEPs demonstrated a prolonged IT and
reduced amplitude of the first-order kernel, and reduced TFC with a reduction of 
visual acuity in patients with macular degeneration.

PMID: 11853725 [PubMed - indexed for MEDLINE]

2875: Jpn J Ophthalmol. 2002 Jan-Feb;46(1):78-83.

Plasma level of interleukin-6 is an indicator for predicting diabetic macular
edema.

Shimizu E, Funatsu H, Yamashita H, Yamashita T, Hori S.

Department of Ophthalmology, Diabetes Center, Tokyo Women's Medical University,
Tokyo, Japan.

PURPOSE: To find a predictor in the pathogenesis of macular edema, we
investigated ocular and systemic risk factors. METHODS: One hundred and
fifty-nine patients with mild diabetic retinopathy who showed one or more soft
exudates were recruited. We selected the possible predictors on the basis of
relevant factors, including concentration of vascular endothelial growth factor, 
interleukin-6 (IL-6), transforming growth factor (TGF)-beta(1), tumor necrosis
factor (TNF)-alpha, and lipoprotein(a) in plasma, and serum level of von
Willebrand factor and thrombomodulin. RESULTS: Macular edema was not detected in 
94 eyes; focal macular edema was detected in 46 eyes; diffuse macular edema was
detected in 18 eyes; and cystoid macular edema was present in 1 eye. The plasma
level of IL-6 concentration and the state of the posterior vitreous detachment
(PVD) correlated significantly with the severity of macular edema (odds ratios = 
3.68, 1.70, respectively). Other risk factors were not significantly associated
with macular edema. We estimated the probability of macular edema according to
the IL-6 level in plasma and the state of the PVD, and were able to predict the
probability of macular edema. CONCLUSION: The results of the present study
indicate that IL-6 concentration in plasma and the state of the PVD can be
predictors of macular edema.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11853719 [PubMed - indexed for MEDLINE]

2876: Curr Eye Res. 2001 Oct;23(4):271-5.

Photodynamic therapy with indocyanine green for occult subfoveal choroidal
neovascularization caused by age-related macular degeneration.

Costa RA, Farah ME, Cardillo JA, Belfort R Jr.

Department of Ophthalmology, Federal University of São Paulo, Paulista School of 
Medicine, São Paulo, Brazil.

PURPOSE: To report two cases of occult subfoveal choroidal neovascularization
(CNV) due to age-related macular degeneration (AMD) that were successfully
treated utilizing large spot, low irradiance 810-nm light and intravenous
injection of small-volume, high-concentration indocyanine green (ICG) bolus,
termed ICG-mediated photodynamic therapy (i-PDT). METHODS: Case report. Two
patients with occult subfoveal CNV (two eyes) due to AMD were treated with i-PDT 
and were prospectively followed with fluorescein and indocyanine green
angiography as well as optical coherence tomography (OCT). RESULTS: Both patients
presented a 3-line increase in visual acuity by twelve months of follow-up. A
significant regression of the CNV was demonstrated by fluorescein angiography
within one week following treatment. OCT revealed diminishing of the subretinal
fluid. There were no complications related to the procedure. CONCLUSION: i-PDT
induced CNV regression and improved the visual acuity in these particular cases, 
suggesting a new and promising way to treat neovascular AMD. The partial
anatomical restoration associated to the improvement of the visual function
observed in both patients suggests that a selective therapeutic effect was
achieved. Further studies are required not only to assess the clinical value of
this treatment but also to better understand the major mechanism of action
involving this novel treatment modality.

Publication Types: 
    Case Reports

PMID: 11852428 [PubMed - indexed for MEDLINE]

2877: Exp Eye Res. 2001 Dec;73(6):887-96.

Complement activation and inflammatory processes in Drusen formation and age
related macular degeneration.

Johnson LV, Leitner WP, Staples MK, Anderson DH.

Center for the Study of Macular Degeneration, Neuroscience Research Institute,
University of California, Santa Barbara, CA 93106, USA.

Recent studies implicate inflammation and complement mediated attack as early
events in drusen biogenesis. The investigations described here sought to
determine whether primary sites of complement activation could be identified
within drusen substructure, and whether known inhibitors of the terminal pathway 
of complement are present in drusen and/or retinal pigmented epithelial (RPE)
cells that lie in close proximity to drusen. Immunohistochemical examination
shows two fluid phase regulators of the terminal pathway, vitronectin (Vn,
S-protein) and clusterin (apolipoprotein J), to be present in drusen; Vn also
accumulates in the cytoplasm of RPE cells that are closely associated with
drusen. The membrane associated complement inhibitor, complement receptor 1, is
also localized in drusen, but it is not detected in RPE cells
immunohistochemically. In contrast, a second membrane associated complement
inhibitor, membrane cofactor protein, is present in drusen associated RPE cells, 
as well as in small, spherical substructural elements within drusen. These
previously unidentified elements also show strong immunoreactivity for
proteolytic fragments of complement component C3 that are characteristically
deposited at sites of complement activation. It is proposed that these structures
represent residual debris from degenerating RPE cells that are the targets of
complement attack. It is likely that RPE cell debris entrapped between the RPE
monolayer and Bruch's membrane serves as a chronic inflammatory stimulus and a
potential nucleation site for drusen formation. Thus, the process of drusen
biogenesis may be envisaged as a secondary manifestation of primary RPE pathology
that is exacerbated by consequences of local inflammatory processes. Copyright
2001 Academic Press.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.

PMID: 11846519 [PubMed - indexed for MEDLINE]

2878: Matrix Biol. 2002 Jan;21(1):75-88.

Sorsby's fundus dystrophy tissue inhibitor of metalloproteinases-3 (TIMP-3)
mutants have unimpaired matrix metalloproteinase inhibitory activities, but
affect cell adhesion to the extracellular matrix.

Yeow KM, Kishnani NS, Hutton M, Hawkes SP, Murphy G, Edwards DR.

School of Biological Sciences, University of East Anglia, Norwich, Norfolk NR4
7TJ, UK.

The TIMP family of matrix metalloproteinase inhibitors consists of four members, 
of which TIMP-1, -2 and -4 are secreted, freely diffusible proteins, whereas
TIMP-3 is ECM-associated. Mutations in the TIMP3 gene have been linked to
Sorsby's fundus dystrophy (SFD), an autosomal dominant inherited retinal
degenerative disease that leads to blindness. The SFD mutations characterized
result in introduction of an unpaired cysteine residue in the C-terminal domain
of TIMP-3. We have expressed four SFD mutant TIMP-3 proteins in baby hamster
kidney (BHK) cells and evaluated their characteristics alongside wild-type
TIMP-3. Analysis of the mutant proteins (Ser156Cys, Gly167Cys, Tyr168Cys and
Ser181Cys) by SDS-PAGE and reverse zymography revealed that each of the mutants
retained gelatinase A and gelatinase B inhibitory activity, and were localized to
the ECM. Association rate constants for Ser156Cys TIMP-3 with gelatinase-A,
gelatinase-B, stromelysin-1 and collagenase-3 were only moderately reduced
compared to wild-type TIMP-3. However, all of the mutants displayed aberrant
protein-protein interactions, resulting in the presence of additional proteins or
complexes in ECM preparations. Two of the mutants (Ser156Cys and Ser181Cys)
showed a marked propensity to form multiple higher molecular-weight complexes
that retained TIMP activity on reverse zymography. Expression of the SFD mutant
TIMP-3 (and to a lesser extent, wild-type TIMP-3) proteins in BHK cells conferred
increased cell adhesiveness to the ECM. Our findings indicate that the
pathogenesis of Sorsby's fundus dystrophy cannot be attributed to a failure to
localize SFD TIMP-3 proteins to the ECM or defects in MMP inhibition, but may
involve the formation of aberrant TIMP-3-containing protein complexes and altered
cell adhesion.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11827795 [PubMed - indexed for MEDLINE]

2879: Eye. 2001 Dec;15(Pt 6):719-22.

Co-morbidity in patients with sight-threatening diabetic retinopathy.

Bailey CC, Sparrow JM.

Royal College of Ophthalmologists, London, UK. ccbailey@doctors.org.uk

PURPOSE: To describe the level of co-morbidity in patients with sight-threatening
diabetic retinopathy in the United Kingdom. METHODS: Questionnaires were
completed by patients undergoing first photocoagulation treatment for diabetic
maculopathy or proliferative retinopathy during a 2 month period throughout the
UK. RESULTS: Overall 15% of patients described angina, 9% had suffered a
myocardial infarction and 6% a stroke. Self-reported renal disease was present in
8.5%. Foot ulceration was described by 10% of patients, and 4% had undergone an
amputation. 35.5% of patients were on treatment for hypertension. 17.5% of
patients had been hospitalised in the previous 6 months, and 3% of patients had
died within 9 months of the laser treatment. CONCLUSIONS: There was significant
co-morbidity in these patients, which may affect the management of their
retinopathy.

PMID: 11826989 [PubMed - indexed for MEDLINE]

2880: Eye. 2001 Dec;15(Pt 6):712-8.

Frequency-doubled Nd:YAG laser for the treatment of exudative diabetic
maculopathy.

Saeed M, Parmar D, McHugh D.

Ophthalmology Department, King's College Hospital, London, UK.
manzarsaeed@hotmail.com

PURPOSE: To determine the clinical efficacy of frequency-doubled Nd:YAG (FD YAG) 
laser for the treatment of diabetic clinically significant macular oedema (CSMO).
METHODS: A prospective pilot study was carried out on 55 eyes with CSMO. FD YAG
laser exposures were applied in a focal or grid pattern. The results were
evaluated by Snellen visual acuity, slit-lamp biomicroscopy, colour photography
and fundus fluorescein angiography. RESULTS: At mean review of 5.3 months,
macular oedema had resolved either completely or partly in 44 (80%) eyes, was
unchanged in 10 (18%) eyes and progressed in 1 (2%) eye. Visual acuity improved
in 11 (20%), stabilised in 40 (73%) and deteriorated in 4 (7%) eyes. CONCLUSION: 
FD YAG laser therapy is effective in the treatment of CSMO. It combines the
ergonomic advantages of a solid-state laser with the benefits of its wavelength. 
A comparison between the clinical results of FD YAG and other lasers used in the 
treatment of CSMO is, however, required.

PMID: 11826988 [PubMed - indexed for MEDLINE]

2881: Ophthalmology. 2002 Feb;109(2):267-74.

High-resolution stereoscopic digital fundus photography versus contact lens
biomicroscopy for the detection of clinically significant macular edema.

Rudnisky CJ, Hinz BJ, Tennant MT, de Leon AR, Greve MD.

Department of Ophthalmology, University of Alberta, Edmonton, Alberta, Canada.

PURPOSE: The purpose of this study was to compare high-resolution stereoscopic
digital photography to contact lens biomicroscopy (CLBM) for the diagnosis of
clinically significant macular edema. STUDY DESIGN: Comparative, prospective,
observational case series. PARTICIPANTS: One hundred twenty diabetic patients.
METHODS: Patients underwent clinical retinal examination with CLBM by a retinal
specialist. On the same day as clinical grading, patients received
high-resolution stereoscopic digital imaging of the macula. The stereoscopic
digital images were viewed using liquid crystal shutter goggles at least 2 months
after clinical examination by a single masked grader for the presence or absence 
of diabetic retinopathy. MAIN OUTCOME MEASURES: Presence or absence of the Early 
Treatment of Diabetic Retinopathy Study criteria for clinically significant
macular edema (CSME) overall, CSME 1, CSME 2, CSME 3, macular edema,
microaneurysms, intraretinal hemorrhage, and hard exudate. RESULTS: Two hundred
seven eyes of 105 patients had complete data sets from both diagnostic
modalities. Exact agreement was high for all identified pathologic conditions:
CSME overall, 83.6%; CSME 1, 83.6%; CSME 2, 96.1%; CSME 3, 88.5%; macular edema, 
75.0%; microaneurysms, 77.9%; intraretinal hemorrhage, 83.7%; and hard exudate,
73.1%. Sensitivity ranged from 50.0% (CSME 2) to 90.6% (CSME overall).
Specificity ranged from 90.0% (macular edema) to 99.0% (CSME 2). CONCLUSIONS:
High-resolution stereoscopic digital photography is both sensitive and specific
when identifying CSME and correlates well with the accepted standard of CLBM for 
the diagnosis of CSME.

Publication Types: 
    Comparative Study

PMID: 11825807 [PubMed - indexed for MEDLINE]

2882: Doc Ophthalmol. 2001 Nov;103(3):201-9.

A 5-year follow-up study for distance visual acuity after low dose radiation on
subfoveal choroidal neovascularization in age-related macular degeneration.

Valmaggia C, Ries G, Ballinari P.

Department of Ophthalmology, Kantonsspital St. Gallen, Switzerland.
valmaggia@freesurf.ch

In a prospective study with a 5-year follow-up, we assessed the effect of a
single series of low-dose radiation on the distance visual acuity in eyes with
angiographically confirmed subfoveal choroidal neovascularization (CNV) in
age-related macular degeneration (ARMD). The posterior pole of 12 eyes was
treated with 5 Gy (4 x 1.25 Gy), and 34 eyes treated with 8 Gy (4 x 2 Gy). The
best corrected distance visual acuity was measured at the time of treatment, and 
annually thereafter for 5 years. The study obtained complete follow-up for 11
patients in the 5-Gy group (nine classic, two occult CNVs), and 29 patients in
the 8-Gy group (12 classic, 17 occult CNVs). At baseline, the mean distance
visual acuity of the treated eyes was 0.16 (20/125) in the 5-Gy group, and 0.2
(20/100) in the 8-Gy group. Five years later, an average loss of 3.2 lines was
present in the 5-Gy group, and 4 lines in the 8-Gy group. After 5 years, an
average loss of 2 lines was found in a control group consisting of 18 second eyes
with low stage dry ARMD, with a mean distance visual acuity of 0.5 (20/40) at
baseline. Statistical analyses with Wilcoxon and Mann-Whitney U-tests showed that
a single series of low dose radiation with either 5 Gy or 8 Gy was not able to
stabilize the distance visual acuity of eyes with subfoveal CNV in ARMD during a 
5-year follow-up.

PMID: 11824657 [PubMed - indexed for MEDLINE]

2883: Curr Eye Res. 2001 Jul;23(1):33-7.

Is age-related macular degeneration associated with pinguecula or scleral plaque 
formation?

Loeffler KU, Sastry SM, McLean IW.

Department of Ophthalmology, University of Bonn, Bonn, Germany.

PURPOSE: To evaluate whether ocular changes indicating an increased exposure to
UV irradiation are associated with the development of age-related macular
degeneration (ARMD). METHODS: Using histology, we have investigated a possible
association of ocular changes that might be attributed to actinic damage, namely 
pinguecula and scleral plaque, with findings of both atrophic and disciform ARMD.
A total of 74 eyes, could be used for evaluation. RESULTS: Features of ARMD were 
present in 36 eyes (11 with disciform degeneration and 25 with an atrophic form).
A pinguecula was identified in 36 eyes (small in 22 eyes, large in 14 eyes), and 
a scleral plaque was seen in 5 eyes. While scleral plaque showed an association
with ARMD, there was no significant association between pinguecula and ARMD.
CONCLUSIONS: Our results support the concept of solar radiation having an effect 
on the development of ARMD but also indicate that it is a multifactorial disease.

PMID: 11821983 [PubMed - indexed for MEDLINE]

2884: J Biol Chem. 2002 Apr 19;277(16):13394-400. Epub 2002 Jan 30.

Expression of Sorsby's fundus dystrophy mutations in human retinal pigment
epithelial cells reduces matrix metalloproteinase inhibition and may promote
angiogenesis.

Qi JH, Ebrahem Q, Yeow K, Edwards DR, Fox PL, Anand-Apte B.

Department of Ophthalmic Research, Cole Eye Institute, Cleveland Clinic
Foundation, Cleveland, Ohio 44195, USA.

Sorsby's fundus dystrophy (SFD) is an autosomal dominant degenerative disease of 
the macula caused by mutations in the tissue inhibitor of metalloproteinase-3
(TIMP-3) gene. Choroidal neovascularization is a hallmark of this disease, which 
closely resembles the exudative form of age-related macular degeneration.
However, the mechanism by which TIMP-3 mutations induce the disease phenotype in 
SFD remains unknown. To address this question we established human retinal
pigment epithelial cell lines expressing wild type or S156C (Ser(156) changed to 
cysteine) mutant TIMP-3. S156C TIMP-3 had reduced matrix metalloproteinase (MMP) 
inhibitory activity in retinal pigment epithelial cells and resulted in increased
secretion and activation of gelatinase A and B. The conditioned medium from these
cells induced angiogenesis in "in vivo" chick chorioallantoic membrane assays
that could be reversed with recombinant wild type TIMP-3. Our data indicate that 
the choroidal neovascularization in SFD may be a result of increased MMP
activity, which could lead to the stimulation of angiogenesis. These results also
suggest the potential therapeutic use of TIMP-3 or synthetic MMP inhibitors in
this disease.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11821400 [PubMed - indexed for MEDLINE]

2885: Graefes Arch Clin Exp Ophthalmol. 2001 Dec;239(12):927-36.

Visual function after removal of subretinal neovascular membranes in patients
with age-related macular degeneration.

Abe T, Yoshida M, Kano T, Tamai M.

Department of Ophthalmology, School of Medicine, Sendai, Miyagi, Japan.
toshi@oph.med.tohoku.ac.jp

BACKGROUND: Retinal pigment epithelial (RPE) cells have been transplanted to
replace the RPE cells lost after surgical excision of choroidal neovascular
membranes (CNV) associated with age-related macular degeneration. The purpose of 
this study was to analyze the visual function of eyes with altered RPE after
surgical excision of choroidal neovascular membranes (CNV) associated with
age-related macular degeneration, and to determine the effect of proliferated or 
migrated RPE cells on visual function. METHODS: Forty-seven patients with
age-related macular degeneration underwent excision of CNVs following vitrectomy 
and tamponade with sulfur hexafluoride (SF6) or silicone oil. The appearance of
pre- or subretinal fibrosis and pigmentation of the lesion was considered to
indicate proliferation and migration of RPE cells. Microperimetry was also
performed. RESULTS: A significant correlation was found between the size of CNVs 
removed by surgery and the size estimated by indocyanine green angiography
(P=0.0126). The mean number of RPE cells lost was estimated at 1.52 x 10(4). Pre-
or subretinal fibrosis or pigmentation was observed in 37 patients (75.5%). The
number of eyes with fibrosis was significantly higher in eyes with silicone oil
tamponade than with SF6 tamponade (P=0.0016). A statistically significant
correlation was not found between the presence of fibrosis or pigmentation and
the postoperative visual acuity. Not all patients used the area of pigmentation
for fixation, and microperimetry showed that some of the patients had scotomas in
well-pigmented areas. CONCLUSIONS: Fibrosis and pigmentation after excision of
CNVs may not always indicate normal function in these areas. These observations
are especially relevant for transplantation of pigment epithelial cells in the
future.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11820698 [PubMed - indexed for MEDLINE]

2886: Graefes Arch Clin Exp Ophthalmol. 2001 Dec;239(12):923-6.

External beam radiotherapy for age-related macular degeneration causes transient 
objective changes in tear-film function.

Eter N, Schüller H.

Department of Ophthalmology, University of Bonn Medical Center, Germany.
eter@uni-bonn.de

PURPOSE: Dry-eye symptoms have been described as possible radiation side effects 
after external beam radiotherapy for age-related macular degeneration. We
therefore investigated tear-film function before and after treatment. METHODS:
Thirty-nine patients with no apparent history of dry-eye symptoms were treated
with a 6 MV linear accelerator using a 2x2 cm lateral field angled 10 degrees
posteriorly. A total dose of 20 Gy, divided into 10 fractions of 2 Gy and
administered 3 times a week, was delivered. Before and 1, 3, and 6 months after
radiotherapy, tear secretion was measured by means of tear-film fluorophotometry.
The fellow eyes served as controls. RESULTS: At baseline, mean tear secretion as 
measured by tear-film fluorophotometry was 7.15 microl/min in the eyes receiving 
radiation and 5.89 microl/min in the control eyes. No statistically significant
differences were found between the two eyes at baseline (signed rank test). One
month after treatment, again no significant differences could be found between
the two eyes; 3 months after radiation, however, tear secretion was significantly
lower in the irradiated eyes than in the fellow eyes (P=0.0017). Six months after
treatment this effect could no longer be detected. CONCLUSION: External beam
radiotherapy using 20 Gy in 10 fractions and a 2x2 cm lateral field causes a
statistically significant difference in tear secretion 3 months after radiation. 
This effect seems to be transient, as it had disappeared in later follow-up
examinations.

PMID: 11820697 [PubMed - indexed for MEDLINE]

2887: Graefes Arch Clin Exp Ophthalmol. 2001 Dec;239(12):900-8.

Early angiographic changes after laser treatment of choroidal neovascularisation 
in age-related macular degeneration.

Battaglia Parodi M, Da Pozzo S, Ravalico G.

Eye Clinic, University of Trieste, Ospedale Maggiore, Italy. maubp@yahoo.it

PURPOSE: To describe angiographic features detectable on fluorescein angiography 
(FA) and indocyanine green angiography (ICGA) early after laser photocoagulation 
of choroidal neovascularisation (CNV) in age-related macular degeneration (AMD). 
METHODS: Thirty-five eyes of patients with AMD and juxtafoveal or extrafoveal CNV
referred to the angiographic centre of the Eye Clinic of Trieste were considered.
Ophthalmological assessment included FA and ICGA performed 2 days before and 30
min after laser treatment, and then 1, 2, 7, 14, 21 and 28 days after
photocoagulation. Further clinical angiographic examinations were carried out 2, 
3, 4 and 6 months after treatment. Photocoagulation was performed for classic CNV
on FA and occult CNV on FA, appearing as well-defined focal spot on ICGA.
RESULTS: Our results show that interpretation of early post-treatment
angiographic examinations may be awkward because diffuse leakage on FA and hot
spots on ICGA are normally detectable soon after laser treatment and thereafter
during the first 2 weeks. Later, at the 3-week control, leakage on FA and hot
spots on ICGA are visible in 62.8% and in 37% of cases respectively; they
disappear completely by the 4-week control. CONCLUSION: Difficulty in analysing
FA and ICGA in the early post-photocoagulation period underlines the importance
of the decision regarding when to perform the first reliable post-laser control
and how to improve its interpretation. We suggest that the first angiographic
control be performed 3 weeks after treatment, strictly monitoring those eyes
showing leakage or marginal hot spots over the following weeks. Overlapping the
post-laser hypofluorescent area on the pre-laser lesion can ensure the complete
coverage of CNV, and analysis of the retinal and choroidal vascular pattern
inside and near the photocoagulated area during the different angiographic
phases, albeit difficult, is essential for the interpretation of the angiographic
lesions.

PMID: 11820694 [PubMed - indexed for MEDLINE]

2888: Ophthalmic Surg Lasers. 2002 Jan-Feb;33(1):16-8.

Combined cataract surgery and vitrectomy for breakthrough vitreous hemorrhage
from age-related macular degeneration.

Chaudhry NA, Flynn HW, Murray TG, Belfort A.

Department of Opthalmology Bascom Palmer Eye Institute, University of Miami
School of Medicine, Florida, USA.

PURPOSE: To report combined cataract extraction (CE), posterior chamber
intraocular lens (PCIOL) implantation, and pars plana vitrectomy (PPV) for
concurrent cataract and breakthrough vitreous hemorrhage from age-related macular
degeneration (AMD). METHODS: Retrospective case series. RESULTS: Six eyes were
included in the study. The postoperative follow-up interval ranged from 3 to 22
months (mean 8 months). Preoperative visual acuity (VA) ranged from 20/400 to
hand motion. Postoperatively, 5/6 eyes had 2 or more lines of visual improvement.
Three eyes were better than 20/200. CONCLUSIONS: Combined CE, PCIOL insertion,
and PPV in selected patients with cataract and breakthrough vitreous hemorrhage
from AMD was successful in improving VA in the majority of patients.

PMID: 11820658 [PubMed - indexed for MEDLINE]

2889: Invest Ophthalmol Vis Sci. 2002 Feb;43(2):466-73.

Genotype-phenotype analysis of ABCR variants in macular degeneration probands and
siblings.

Bernstein PS, Leppert M, Singh N, Dean M, Lewis RA, Lupski JR, Allikmets R,
Seddon JM.

Department of Ophthalmology and Visual Sciences, Moran Eye Center, University of 
Utah School of Medicine, Salt Lake City, Utah 84132, USA.
paul.berstein@hsc.utah.edu

PURPOSE: Single-copy variants of the autosomal recessive Stargardt disease
(STGD1) gene ABCR (ABCA4) have been shown to confer enhanced susceptibility to
age-related macular degeneration (AMD). To investigate the role of ABCR alleles
in AMD further, genotype-phenotype analysis was performed on siblings of patients
with AMD who had known ABCR variants. This genetically related population
provides a cohort of subjects with similar age and ethnic background for
genotype-phenotype comparison to the original probands. METHODS: All available
siblings of 26 probands carrying probable disease-associated ABCR variants were
examined clinically. Blood samples were collected from these siblings for
genotype analysis to search for the ABCR variant alleles corresponding to the
isofamilial proband. RESULTS: Nineteen of 33 siblings from 15 families carried
the respective proband's variant ABCR allele. Some families exhibited concordance
of ABCR alleles with macular degeneration phenotype, but others did not.
Exudative AMD was uncommon among both probands and siblings. CONCLUSIONS:
Although population studies have indicated that some ABCR variant alleles may
enhance susceptibility to AMD, investigation of the extent of ABCR involvement by
kindred analysis is complicated by a plethora of environmental and other
hereditary factors not investigated in the current study that may also play
important roles.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11818392 [PubMed - indexed for MEDLINE]

2890: Coll Antropol. 2001;25 Suppl:89-96.

Brachytherapy--optional treatment for choroidal neovascularization secondary to
age-related macular degeneration.

Sarić B, Sikić J, Katusić D, Vukojević N.

Department of Ophthalmology, School of Medicine, University of Zagreb, Zagreb,
Croatia.

Age-related macular degeneration (ARMD) presents the main cause of irreversible
loss of central vision in older population, due to a progressive neuroretinal
damage and damage of retinal pigment epithelium of foveal area. This observation 
emphasizes the insufficiency of all presently used therapeutic procedures.
Therefore, investigation has been conducted at the University Eye Clinic Zagreb
for the last three years testing the effects of brachytherapy with direct
episcleral application of ruthenium applicators to the posterior pole of the
globe. Forty-two patients aged 58-79 were followed for a min. of 12 months.
During this period their central visual acuities remained stable. Six patients
showed one-line improvement of visual acuity and 8 patients showed no changes.
Twenty-one patient lost 1-2 lines of visual acuity and 7 patients lost more than 
2 lines. According to this we can conclude that patients treated with
brachytherapy showed significantly better results compared to the control
subjects, which is very encouraging.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial

PMID: 11817022 [PubMed - indexed for MEDLINE]

2891: Ophthalmic Epidemiol. 2002 Feb;9(1):1-10.

Incremental cost-effectiveness of laser therapy for visual loss secondary to
branch retinal vein occlusion.

Brown GC, Brown MM, Sharma S, Busbee B, Brown H.

Center for Evidence-Based Health Care Economics, Flourtown, PA 19031, USA.
Garyo514@aol.com

PURPOSE: To ascertain the incremental cost-effectiveness of therapeutic
interventions for improving visual loss associated with branch retinal vein
occlusion. METHODS: A cost-utility analysis incorporating data from the Branch
Vein Occlusion Study Group was performed using patient-based preferences obtained
from time tradeoff utility analysis, decision analysis with Markov modeling, and 
economic modeling with future value analysis. The cost-effectiveness results are 
expressed in dollars/QALY (dollars expended per quality-adjusted life-year)
gained. This unique model takes into account the visual acuity in the better
seeing eye and the recurrent risk for visual loss in the contralateral eye.
RESULTS: Laser therapy for macular edema secondary to branch retinal vein
occlusion was associated with an incremental dollars/QALY gained of 6118 dollars 
(in year 2000 U.S. dollars). Two-way sensitivity analysis, varying the discount
rate and the proportion of patients developing a vascular occlusion in the
contralateral eye, revealed a range of dollars/QALY gained from 3370 dollars to
19,299 dollars. CONCLUSIONS: Laser therapy appears to be a cost-effective
intervention for improving visual loss associated with macular edema secondary to
branch retinal vein occlusion. Variants of the methodology employed to calculate 
the incremental cost-effectiveness of this intervention can be widely applied
across all specialties in medicine.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 11815891 [PubMed - indexed for MEDLINE]

2892: Ocul Immunol Inflamm. 2001 Sep;9(3):177-83.

HLA-B27-associated uveitis and cystoid macular edema.

Uy HS, Christen WG, Foster CS.

Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, MA
02114, USA.

OBJECTIVE: To determine which ocular and systemic characteristics are associated 
with cystoid macular edema (CME) in patients with HLA-B27-associated uveitis.
METHODS: The authors reviewed the records of 129 patients (157 eyes) with
HLA-B27-associated uveitis seen at the Massachusetts Eye and Ear Infirmary from
June 1980 to June 1995. Data obtained from the records included: age, gender,
duration of uveitis, follow-up duration, ocular and systemic findings, presence
of CME, therapeutic intervention, and visual outcome. RESULTS: Twenty-one of 157 
eyes (13.4%) with HLA-B27-associated uveitis presented with or subsequently
developed CME. In 14 (67%) eyes with CME, vitreous cells were noted either at
presentation or during follow-up. Forty-nine of 136 eyes (36%) without CME had
vitreous cells at presentation or developed vitreous cells during follow-up. The 
estimated odds ratio for developing CME associated with the presence of vitreous 
cells was 2.9 (95% confidence interval: 1.0-8.3). No other demographic, ocular,
or systemic characteristics appeared to be associated with the presence of CME.
CONCLUSION: The presence of vitreous cells in patients with HLA-B27-associated
uveitis may indicate an increased risk of CME development.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11815886 [PubMed - indexed for MEDLINE]

2893: J Antimicrob Chemother. 2002 Feb;49(2):421-2.

Rifabutin-induced cystoid macular oedema.

Vaudaux JD, Guex-Crosier Y.

Jules Gonin Eye Hospital, University Department of Ophthalmology, Avenue de
France 15, 1004 Lausanne, Switzerland.

Rifabutin is a semi-synthetic antimycobacterial agent mainly used in the
treatment of Mycobacterium avium-complex (MAC) in AIDS patients.
Rifabutin-induced anterior uveitis has been reported previously. We report the
case of a rifabutin-induced cystoid macular oedema (CMO) in an immunocompetent
patient with pulmonary MAC infection. As far as we know, CMO secondary to
rifabutin therapy has not been described previously.

Publication Types: 
    Case Reports

PMID: 11815593 [PubMed - indexed for MEDLINE]

2894: Br J Ophthalmol. 2002 Feb;86(2):214-9.

CST3 genotype associated with exudative age related macular degeneration.

Zurdel J, Finckh U, Menzer G, Nitsch RM, Richard G.

Department of Ophthalmology, University Hospital Hamburg-Eppendorf, University of
Hamburg, Germany. zurdel@uke.uni-hamburg.de

AIMS: To determine whether allelic variants of the cystatin C gene CST3 are
genetically associated with exudative age related macular degeneration (ARMD).
Cystatin C is a cysteine protease inhibitor that regulates the activity of
cathepsin S, a protease with central regulatory functions in retinal pigment
epithelial cells. METHODS: CST3 of 167 patients with exudative ARMD was genotyped
by using polymerase chain reaction of genomic DNA and restriction enzyme
digestion with KspI and compared with those of 517 control subjects. Patients and
controls were white. RESULTS: There was a significant difference in genotype
counts between patients and controls (chi(2) = 7.158, df = 2; Fisher's exact
test: p = 0.037). There was no significant difference in allele frequencies
between patients and controls and between controls from Germany, Switzerland,
Italy, and United States. The significant difference in genotype counts between
patients and controls could be explained completely by an excess of the
homozygous CST3 genotype B/B in patients with exudative ARMD (6.6%) over controls
(2.3%), suggesting an odds ratio for ARMD in association with CST3 B/B of 2.97
(95% CI: 1.28-6.86). The results also suggest a stronger association of B/B with 
ARMD in males than in females. However, in both males and females there was a
similar and significant effect of CST3 B/B on disease free survival assessed by
Kaplan-Meier analysis. The mean disease free survival time in pooled males and
females with genotypes A/A or A/B was 85 years (SE 1; 95% CI: 83-86) and 76 years
(SE 2; 95% CI: 72-79) respectively in B/B homozygotes (log rank p = 0.0006).
CONCLUSION: Genotyping data, the absence of a significant difference in allele
frequencies between patients and controls, and survival analyses suggest an
increased susceptibility for ARMD in CST3 B/B homozygotes. Therefore, CST3 B may 
be a recessive risk allele, significantly contributing to disease risk in up to
6.6% of German ARMD patients. Functional correlates of the allelic CST3 variants 
A and B remain to be investigated.

PMID: 11815350 [PubMed - indexed for MEDLINE]

2895: Br J Ophthalmol. 2002 Feb;86(2):209-13.

Choroidal perfusion perturbations in non-neovascular age related macular
degeneration.

Ciulla TA, Harris A, Kagemann L, Danis RP, Pratt LM, Chung HS, Weinberger D,
Garzozi HJ.

Department of Ophthalmology, Indiana University School of Medicine, Indianapolis,
USA.

AIM: Choroidal perfusion, affected in age related macular degeneration (AMD), is 
difficult to objectively assess given the overlying retinal circulation. This
study more objectively compared choroidal perfusion parameters in a group with
non-neovascular AMD to an unaffected age matched control group. METHODS: 21
non-neovascular AMD subjects and 21 age matched control subjects without evidence
of AMD underwent assessment of their choroidal blood flow in a case-control
study. Scanning laser ophthalmoscope indocyanine green (ICG) angiograms were
analysed by a new area dilution analysis technique. Four areas in the perifoveal 
region and two areas in the temporal peripapillary retina were evaluated by
producing a graph of intensity of fluorescence of each area over time. The mean
of the filling times and the heterogeneity of the filling times were assessed.
RESULTS: The means of the filling times within the perifoveal regions and the
hetereogeneity of the filling times between regions within the same eyes were
significantly greater in the AMD patients compared with the control subjects.
CONCLUSIONS: Delayed and heterogeneous filling of the choroid was objectively
demonstrated in eyes with non-neovascular AMD compared with age matched controls 
without evidence of AMD, using an area dilution analysis technique applied to ICG
angiography.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11815349 [PubMed - indexed for MEDLINE]

2896: Am J Ophthalmol. 2002 Feb;133(2):278-80.

Macular dystrophy in a 9-year-old boy with fundus albipunctatus.

Nakamura M, Miyake Y.

Department of Ophthalmology, Nagoya University School of Medicine,
65-Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan. makonaka@med.nagoya-u.ac.jp

PURPOSE: To report a 9-year-old boy with fundus albipunctatus and macular
dystrophy. DESIGN: Observational case report. METHODS: A complete ophthalmic
examination was performed. The 11-cis retinol dehydrogenase gene (RDH5) was
examined by direct genomic sequencing. RESULTS: The fundi of the 9-year-old boy
showed numerous yellow-white punctata as well as foveal atrophic lesions in both 
eyes. His corrected visual acuity was RE: 0.5 and LE: 0.3. Scotopic full-field
electroretinograms were not present after 20 minutes of dark-adaptation but were 
normal after 3 hours of dark-adaptation. Full-field cone and 30-Hz flicker
electroretinograms were normal; however, focal macular cone electroretinograms
were significantly reduced. A compound heterozygous mutation of Tyr281His and
Leu310GluVal in RDH5 was detected. CONCLUSION: We suggest that the macular
dystrophy is caused by the RDH5 mutation as a phenotype variation in fundus
albipunctatus.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 11812441 [PubMed - indexed for MEDLINE]

2897: Am J Ophthalmol. 2002 Feb;133(2):215-25.

Comment in:
    Am J Ophthalmol. 2002 Sep;134(3):468; author reply 468-9.

Transplantation of autologous retinal pigment epithelium in eyes with foveal
neovascularization resulting from age-related macular degeneration: a pilot
study.

Binder S, Stolba U, Krebs I, Kellner L, Jahn C, Feichtinger H, Povelka M, Frohner
U, Kruger A, Hilgers RD, Krugluger W.

Department of Ophthalmology, The Ludwig Boltzmann Institute of Retinology and
Biomicroscopic Lasersurgery, Rudolf Foundation Clinic, Vienna, Austria.
susanne.binder@kar.magwien.gv.at

PURPOSE: To describe the indications, surgical technique, and clinical results of
14 eyes in 13 patients with age-related macular degeneration and foveal choroidal
neovascularization, in which subretinal surgery was combined with simultaneous
transplantation of autologous retinal pigment epithelial cells. METHODS: Between 
March 1999 and February 2000, in a prospective study, 14 eyes (13 patients) with 
age-related macular degeneration underwent subretinal surgery because of foveal
choroidal neovascularization with simultaneous transplantation of retinal pigment
epithelium harvested from the nasal subretinal area of the same eye.
Preoperatively, 1 month postoperatively, 3 months postoperatively and at 3-month 
intervals thereafter, examinations were performed including best-corrected visual
acuity, visual field, biomicroscopy of anterior and posterior segment, tonometry,
fluorescein and indocyanine angiographies, autofluorescence, scotometry, and
fixation tests. RESULTS: Postoperatively, after median observation of 17 months
(range, 12 to 24 months) best-corrected visual acuity was improved 2 or more
lines in eight eyes (57.1%), remained the same (+/- 1 line) in five eyes (35%),
and decreased by more than 2 lines in one eye (7.1%). Pairwise t test showed
significant improvement after 1 month (P = .0031, P = .0062) as well as 1 year (P
= .0066, P = .0105). Satisfactory reading vision between Jaeger 1 and 4 was
achieved in three eyes (21.2%). No significant intraoperative or postoperative
complications occurred in any eye. No recurrence of choroidal neovascularization 
was observed during the observation period. CONCLUSIONS: In eyes with age-related
macular degeneration and foveal choroidal neovascularization, autotransplantation
of retinal pigment epithelium was performed in addition to conventional removal
of the choroidal neovascularization without significant intraoperative or
postoperative complications. Visual acuity improvement of 2 or more lines in 57% 
of the eyes was achieved. No recurrent choroidal neovascularization formation was
observed during the observation period. The results of this pilot study suggest
that autologous transplantation of retinal pigment epithelium combined with
submacular surgery might be a reasonable treatment option for patients with
foveal choroidal neovascularization secondary to age-related macular
degeneration.

Publication Types: 
    Clinical Trial

PMID: 11812425 [PubMed - indexed for MEDLINE]

2898: J Bioenerg Biomembr. 2001 Dec;33(6):523-30.

Mechanistic studies of ABCR, the ABC transporter in photoreceptor outer segments 
responsible for autosomal recessive Stargardt disease.

Sun H, Nathans J.

Department of Molecular Biology and Genetics, Johns Hopkins University School of 
Medicine, Baltimore, Maryland 21205, USA.

ABCR is an ABC transporter that is found exclusively in vertebrate photoreceptor 
outer segments. Mutations in the human ABCR gene are responsible for autosomal
recessive Stargardt disease, the most common cause of early onset macular
degeneration. In this paper we review our recent work with purified and
reconstituted ABCR derived from bovine retina and from cultured cells expressing 
wild type or site-directed mutants of human ABCR. These experiments implicate
all-trans-retinal (or Schiff base adducts between all-trans-retinal and
phosphatidylethanolamine) as the transport substrate, and they reveal asymmetric 
roles for the two nucleotide binding domains in the transport reaction. A model
for the retinal transport reaction is presented which accounts for these
experimental observations.

Publication Types: 
    Review

PMID: 11804194 [PubMed - indexed for MEDLINE]

2899: Ophthalmic Genet. 2001 Dec;22(4):233-9.

Erratum in:
    Ophthalmic Genet 2002 Sep;23(3):198.

Evaluation of the ELOVL4 gene in patients with age-related macular degeneration.

Ayyagari R, Zhang K, Hutchinson A, Yu Z, Swaroop A, Kakuk LE, Seddon JM,
Bernstein PS, Lewis RA, Tammur J, Yang Z, Li Y, Zhang H, Yashar BM, Liu J,
Petrukhin K, Sieving PA, Allikmets R.

Department of Ophthalmology and Visual Sciences, University of Michigan, Ann
Arbor, MI, USA.

Stargardt-like macular degeneration (STGD(3)) and autosomal dominant macular
degeneration (adMD) share phenotypic characters with atrophic age-related macular
degeneration (AMD). Mutations in a photoreceptor cell-specific factor involved in
the elongation of very long chain fatty acids (ELOVL(4)) were shown to be
associated with STGD(3), adMD, and pattern dystrophy. We screened 778 patients
with AMD and 551 age-matched controls to define the role of sequence variants in 
the ELOVL(4) gene in age-related macular degeneration. We detected three sequence
variants in the non-coding region and eight variants in the coding region. No
statistically significant association was observed between sequence variants in
the ELOVL(4) gene and susceptibility to AMD. However, for the detection of modest
effects of multiple alleles in a complex disease, the analysis of larger cohorts 
of patients may be required.

Publication Types: 
    Evaluation Studies
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11803489 [PubMed - indexed for MEDLINE]

2900: Med Phys. 2001 Dec;28(12):2410-9.

Comment in:
    Med Phys. 2002 Dec;29(12):2960; author reply 2961.

Mathematical morphology in computerized analysis of angiograms in age-related
macular degeneration.

Barthes A, Conrath J, Rasigni M, Adel M, Petrakian JP.

Interface Physique-Biologie-Médecine, Case EC1, Université d'Aix-Marseille III,
Faculté des Sciences et Techniques de Saint Jérĵme, France.

This paper deals with image processing of numerical retinal angiograms in order
to facilitate diagnosis and follow-up in age-related macular degeneration (AMD)
which is currently the main cause of blindness in industrialized countries. A
computerized scheme using principally mathematical morphology operators is
proposed for detecting and counting drusen, which are precursor lesions of the
ocular fundus. In order to check the feasibility of this approach, results
relative to 58 retinal images are compared with those given by three retinal
specialists independently. From manual counting measures it is found that
interobserver correlation coefficients lie in the range 0.71-0.78. On the other
hand, a correlation coefficient of 0.89 is obtained when the average of the three
expert countings is compared with the drusen number given by the computerized
method. This coefficient is improved from 0.89 to 0.93 by processing only frames 
captured immediately after the appearance of a dye consecutive to intravenous
sodium fluorescein injection. Compared to the manual analysis which is, among
other things, tedious and time consuming, the computerized analysis is both
quicker and more objective. Validation by the practitioner is however necessary, 
given possible detection errors. The proposed computerized scheme for detecting
and counting drusen may be easily automated and so should prove useful in
clinical studies which involve high volume analysis of retinal angiograms.

PMID: 11797943 [PubMed - indexed for MEDLINE]

2901: Trans Am Ophthalmol Soc. 2001;99:233-7; discussion 237-8.

North Carolina macular dystrophy: clinicopathologic correlation.

Small KW, Voo I, Flannery J, Udar N, Glasgow BJ.

Department of Ophthalmology, UCLA School of Medicine, Jules Stein Eye Institute, 
USA.

PURPOSE: To describe the clinical and histopathologic findings in a 72-year-old
woman with North Carolina macular dystrophy. METHODS: Clinical examination was
performed by slit-lamp biomicroscopy, indirect ophthalmoscopy, color fundus
photography, and focal electroretinography. Histopathologic examination of the
enucleated left eye consisted of light microscopy. RESULTS: Light microscopy
demonstrated a discrete macular lesion characterized by focal absence of
photoreceptor cells and retinal pigment epithelium. Bruch's membrane was
attenuated in the center of the lesion and associated with marked atrophy of the 
choriocapillaris. Adjacent to the central lesion, some lipofuscin was identified 
in the retinal pigment epithelium. CONCLUSIONS: North Carolina macular dystrophy 
has both clinical and microscopic appearances of a well-demarcated retinal and
pigment epithelial lesion confined to the macula. This is consistent with the
clinical impression that it is a focal macular dystrophy.

Publication Types: 
    Case Reports
    Research Support, U.S. Gov't, P.H.S.

PMID: 11797312 [PubMed - indexed for MEDLINE]

2902: Ann Pharmacother. 2001 Dec;35(12):1593-8.

Verteporfin for age-related macular degeneration.

Messmer KJ, Abel SR.

Richard L Roudebush Veterans Affairs Medical Center, Indianapolis, IN, USA.

OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical efficacy,
adverse effects, drug-drug interactions, and the therapeutic issues concerning
the use of verteporfin in patients with age-related macular degeneration (AMD).
DATA SOURCES: Published articles and abstracts in English were identified by
MEDLINE (1990-August 2000) searches using the search terms verteporfin, treatment
of age-related macular degeneration, and photodynamic therapy (PDT). Additional
references were identified from the bibliographies of the retrieved articles.
Data were also obtained from approved product labeling. DATA EXTRACTION: The
literature was assessed for adequate description of patients, methodology, and
outcomes. DATA SYNTHESIS: Verteporfin is a synthetic benzoporphyrin derivative
and a cytotoxic photosensitizing agent, which is one component of PDT. PDT
involves administration of verteporfin for injection and nonthermal red light at 
a wavelength of 689 nm. It is metabolized, to a small extent, to its diacid
metabolite by liver and plasma esterases. Information concerning drug
interactions is limited. In clinical trials, verteporfin was effective in
patients with wet AMD as demonstrated in standard visual acuity scores. Adverse
events were related to injection site reactions and visual disturbances.
CONCLUSIONS: Verteporfin is a welcome alternative to laser photocoagulation,
which can result in damage to the retina and lead to visual loss. Although
long-term trials have not been performed in humans, results from monkeys indicate
possible improvement in vision following PDT with verteporfin.

Publication Types: 
    Review

PMID: 11793628 [PubMed - indexed for MEDLINE]

2903: Ophthalmol Clin North Am. 2001 Dec;14(4):651-9, ix.

Postcataract cystoid macular edema.

Nagpal M, Nagpal K, Nagpal PN.

Eye Research Center and Retina Foundation, Asopalov Eye Hospital, Gujarat, India.
manish@ad1.vsnl.net.in

Ocular tissues, like those of other organs, exhibit well-defined morphologic
reactions to local trauma and insult in the form of hyperemia, vasodilation,
increased permeability of blood vessels, and edema. Cystoid macular edema (CME)
following cataract surgery is one such manifestation, and it can result in either
temporary, or rarely, a permanent reduction of visual acuity. Although its cause 
remains obscure, the relationship of CME to the details of the surgical
procedures and their complications are becoming clearer. Likewise more insight
into the phenomenon is being imparted by the agents being used in the
preventative or curative line of management in CME.

Publication Types: 
    Review

PMID: 11787744 [PubMed - indexed for MEDLINE]

2904: Ophthalmol Clin North Am. 2001 Dec;14(4):581-93.

Prevention of posterior segment complications of phacoemulsification.

Fine IH, Packer M, Hoffman RS.

Casey Eye Institute, Department of Ophthalmology, Oregon Health Sciences
University, Portland, USA.

The prevention of posterior segment complications of cataract surgery depends on 
the maintenance of an intact lens capsule and zonular apparatus. The
phacoemulsification techniques presented here, including cortical cleaving
hydrodissection, hydrodelineation, ultrasound power modulation, and management of
the epinucleus and cortex, together with the special techniques presented for
management of small pupils and compromised zonule, minimize the risk of damage to
the posterior capsule by maximizing control of nuclear disassembly and
evacuation. Choo-choo chop and flip phacoemulsification, in particular, provides 
a management strategy for cataracts of all grades of nuclear hardness whether in 
the presence of a small pupil or compromised zonule.

Publication Types: 
    Review

PMID: 11787738 [PubMed - indexed for MEDLINE]

2905: Am J Ther. 2002 Jan-Feb;9(1):25-8.

Serum iron, transferrin saturation, ferritin, and dietary data in age-related
macular degeneration.

Richer S, Rudy D, Statkute L, Karofty K, Frankowski J.

Department of Family Medicine, Finch University of Health Sciences/Chicago
Medical School, North Chicago, IL 60064, USA.

Iron (Fe) is a tightly metabolically controlled mineral and growth factor for all
living cells. Iron not bound in erythrocyte hemoglobin is transported by the
plasma iron transport protein transferrin (Tf) and bound within cells by
ferritin. Apo-Tf and apo-hemopexin are also known to be made locally in the
retina. Free Fe is cytotoxic, promotes oxidation/lipid peroxidation, has been
implicated as a risk factor in cardiac disease, and is itself associated with
age-related macular degeneration (ARMD), the leading cause of blindness in aging 
western societies. The authors evaluated Fe overload serum markers and dietary
intake in patients with atrophic ARMD. After obtaining informed consent, an Fe
panel consisting of serum Fe, total Fe binding capacity (TIBC), and ferritin was 
performed on 75 veterans (70 men, five women) with an average age of 75 years
with a diagnosis of atrophic ARMD by combined criteria of International Retinal
Classification and psychophysical/symptom abnormalities. Tf saturation was
calculated by dividing serum Fe concentration by TIBC. Dietary iron with and
without supplementation and vitamin C intake were determined for 86 patients
using the Harvard School of Public Health/Department of Nutrition Food Frequency 
Questionnaire. Statistically significant correlations (P <0.1) were found between
serum and dietary Fe (r = -.26), between serum Fe and serum ferritin (r =.34),
and between dietary Fe and dietary vitamin C (r =.30). The data on mostly male
geriatric veterans with atrophic ARMD indicate that single time-point assessment 
of systemic Fe status and dietary Fe is not useful. However, serial multiple-year
data, correlating Fe markers with disease, may still be important. Also, because 
Fe transport proteins do not cross the blood-retina barrier, the local cellular
toxic effects of Fe must also be considered.

PMID: 11782816 [PubMed - indexed for MEDLINE]

2906: Acta Ophthalmol Scand. 2001 Dec;79(6):546-59.

Short wavelength automated perimetry.

Wild JM.

Department of Optometry and Vision Sciences, Cardiff University, Redwood
Building, King Edward VII Avenue, Cathays Park, Cardiff CF10 3NB, Wales, UK.
wildjm@cardiff.ac.uk

Short Wavelength Automated Perimetry (SWAP) utilizes a blue stimulus to
preferentially stimulate the blue cones and a high luminance yellow background to
adapt the green and red cones and to saturate, simultaneously, the activity of
the rods. This review describes the theoretical aspects of SWAP, highlights
current limitations associated with the technique and discusses potential
clinical applications. Compared to white-on-white (W-W) perimetry, SWAP is
limited clinically by: greater variability associated with the estimation of
threshold, ocular media absorption, increased examination duration and an
additional learning effect. Comparative studies of SWAP and W-W perimetry have
generally been undertaken on small cohorts of patients. The conclusions are
frequently unconvincing due to limitations for SWAP in the delineation of
abnormality and of progressive field loss. SWAP is almost certainly able to
identify glaucomatous visual field loss in advance of that by W-W perimetry
although the incidence of progressive field loss is similar between the two
techniques. Increasing evidence suggests that functional abnormality with SWAP is
preceded by structural abnormality of the optic nerve head and/or the retinal
nerve fibre layer. SWAP appears to be beneficial in the detection of diabetic
macular oedema and possibly in some neuro-ophthalmic disorders.

Publication Types: 
    Review

PMID: 11782218 [PubMed - indexed for MEDLINE]

2907: J Opt Soc Am A Opt Image Sci Vis. 2002 Jan;19(1):223-8.

Binocular contrast inhibition in subjects with age-related macular degeneration.

Valberg A, Fosse P.

Norwegian University of Science and Technology, Department of Physics, Trondheim.
arne.valberg@phys.ntnu.no

In subjects with normal vision, binocular contrast sensitivity is generally
higher than monocular sensitivity, indicating summation of contrast in the two
eyes. We have compared monocular and binocular contrast sensitivity and acuity
for a group of 13 subjects with age-related macular degeneration (AMD). Relative 
to a normal control group, many of the AMD subjects showed reduced binocular
contrast summation, and binocular inhibition was found for eight subjects for a
narrow or an extended frequency band. A better monocular than binocular function 
may have practical implications for reading and orientation in AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11778728 [PubMed - indexed for MEDLINE]

2908: J Opt Soc Am A Opt Image Sci Vis. 2002 Jan;19(1):215-22.

Cone photopigment in older subjects: decreased optical density in early
age-related macular degeneration.

Elsner AE, Burns SA, Weiter JJ.

Schepens Eye Research Institute and Harvard University, Boston, Massachusetts
02114, USA.

We measured changes to cone photoreceptors in patients with early age-related
macular degeneration. The data of 53 patients were compared with normative data
for color matching measurements of long- and middle-wavelength-sensitive cones in
the central macula. A four-parameter model quantified cone photopigment optical
density and kinetics. Cone photopigment optical density was on average less for
the patients than for normal subjects and was uncorrelated with visual acuity.
More light was needed to reduce the photopigment density by 50% in the steady
state for patients. These results imply that cone photopigment optical density is
reduced by factors other than slowed kinetics.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11778727 [PubMed - indexed for MEDLINE]

2909: Invest Ophthalmol Vis Sci. 2002 Jan;43(1):267-73.

Phenotypic variation of retinal pigment epithelium in age-related macular
degeneration.

Guidry C, Medeiros NE, Curcio CA.

Department of Ophthalmology, University of Alabama at Birmingham, Birmingham,
Alabama 35294-0009, USA.

PURPOSE: To determine whether retinal pigment epithelium (RPE) in eyes with
age-related macular degeneration (ARMD) express vimentin and alpha smooth muscle 
actin (alphaSMA), two cytoskeletal proteins associated with phenotypic variation 
in culture. METHODS: Six eyes with late ARMD and three age-matched control eyes
were preserved in buffered 4% paraformaldehyde and cryosectioned at 10 microm.
Stages of RPE morphology and pigmentation were assessed by the Alabama
Age-Related Macular Degeneration Grading System. Vimentin, alphaSMA, and glial
fibrillary acidic protein (GFAP) expression was detected by indirect
immunofluorescence. These results were compared with regional variations in
disease severity. RESULTS: RPE changes in ARMD included acquired expression of
vimentin, but alphaSMA-positive cells were rare. GFAP expression increased in
Müller cells in the neural retina in association with RPE changes and
photoreceptor degeneration. CONCLUSIONS: The initial stages of RPE changes in
eyes with ARMD mimic those reported for cultured RPE cells. The absence of
alphaSMA-positive cells in regions of RPE atrophy suggests that RPE are lost
rather than persist in a dedifferentiated state.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11773041 [PubMed - indexed for MEDLINE]

2910: Invest Ophthalmol Vis Sci. 2002 Jan;43(1):241-5.

Diabetic macular edema assessed with optical coherence tomography and stereo
fundus photography.

Strøm C, Sander B, Larsen N, Larsen M, Lund-Andersen H.

Department of Ophthalmology, Herlev Hospital, University of Copenhagen,
Copenhagen, Denmark. charlotte_strom@dadlnet.dk

PURPOSE: To compare retinal thickening in diabetic macular edema assessed
subjectively by evaluation of stereo fundus photographs with that assessed
objectively by optical coherence tomography (OCT). METHODS: Forty-degree stereo
fundus photographs of the macular field and OCT scans in 84 eyes of 47 patients
with diabetes were compared in terms of both location and area of retinal
thickening. Six radiating 6-mm OCT scans at intervals of 30 degrees were
obtained, and the retinal thickness was compared with the mean retinal thickness 
+/- 2 SD of healthy control subjects (33 eyes). Subsequently, retinal thickness
was mapped topographically and the subjectively assessed retinal thickening map
was overlaid. The degree of agreement on location was evaluated as retinal
thickening present or absent in nine subfields of the fundus. Area of retinal
thickening was divided into four categories: no retinal thickening, less than 1
disc area (DA), less than 2 DAs, or less than 3 DAs, expressed as the kappa
statistic. RESULTS: Exact agreement on location was found in 676 of 756 (84 x 9) 
observations (89.4%; kappa = 0.69; 95% confidence interval [CI]: 0.63-0.75). Two 
eyes in which both methods assessed the same amount of retinal thickening showed 
no agreement on location. These eyes were compared only in terms of location.
Exact agreement on area was found in 69 (84.1%) of 82 eyes. Weighted kappa
(kappa(w)) = 0.79; 95% CI: 0.76-0.82). CONCLUSIONS: The degree of agreement
between subjectively and objectively assessed retinal thickening was very good,
implying that changes in diabetic macular edema can be accurately and
prospectively measured with OCT.

Publication Types: 
    Comparative Study

PMID: 11773037 [PubMed - indexed for MEDLINE]

2911: Ophthalmology. 2002 Jan;109(1):132-6.

Fluorescein angiographic features of tubulointerstitial nephritis and uveitis
syndrome.

Matsuo T.

Department of Ophthalmology, Okayama University Medical School, 2-5-1
Shikata-cho, Okayama City 700-8558, Japan. matsuot@cc.okayama-u.ac.jp

OBJECTIVE: To explain fluorescein angiographic features in patients with
tubulointerstitial nephritis and uveitis syndrome. DESIGN: Retrospective
observational case series. PARTICIPANTS: Four consecutive patients with
tubulointerstitial nephritis and uveitis syndrome seen at Uveitis Service of
Okayama University Hospital from 1995 to 2000. METHODS: Patients' characteristics
obtained from medical records were analyzed. In addition, characteristics of 15
patients reported previously as case reports in the Japanese literature were
reviewed. MAIN OUTCOME MEASURES: Clinical and fluorescein angiographic features. 
RESULTS: The present four patients showed varying degrees of retinal capillary
leakage on fluorescein angiography, ranging from capillary leakage limited to the
peripheral fundus to cystoid macular edema. The same angiographic features were
found in 15 patients reported previously in the Japanese literature. CONCLUSIONS:
Retinal capillary leakage of varying degrees was a common fluorescein
angiographic feature in patients with tubulointerstitial nephritis and uveitis
syndrome. Fluorescein angiography is valuable in assessing the extent of retinal 
involvement.

Publication Types: 
    Review

PMID: 11772592 [PubMed - indexed for MEDLINE]

2912: Geriatrics. 2001 Dec;56(12):27-31; quiz 32.

Ophthalmology. Screening and treatment of age-related and pathologic vision
changes.

Rosenthal BP.

Department of Ophthalmology, Mount Sinai School of Medicine, New York, USA.

In the older adult, deterioration of normal vision is caused by age-related
physiologic and pathologic changes. Vision impairment undermines quality of life 
by reducing independence, mobility, and the enjoyment that goes with seeing
clearly. The most common causes of vision impairment are age-related macular
degeneration (AMD), glaucoma, cataract, and diabetic retinopathy. Key to
successful management of vision impairment is early detection of signs and
symptoms, patient education regarding preventive strategies, and swift medical or
surgical intervention for established or emerging conditions. Vision
rehabilitation is an important management option.

Publication Types: 
    Review

PMID: 11766560 [PubMed - indexed for MEDLINE]

2913: Qual Life Res. 2001;10(5):465-73.

Psychometric evaluation of the 12-item Well-being Questionnaire for use with
people with macular disease.

Mitchell J, Bradley C.

Department of Psychology, University of London, Egham, Surrey, UK.
j.mitchell@rhul.ac.uk

This paper reports the evaluation of a generic measure of psychological
well-being, the 12-item Well-being Questionnaire (W-BQ12), for use with people
who have the chronic eye condition, macular disease (MD). The W-BQ12 was
incorporated in a self-administered questionnaire which was completed by 1421
members of the Macular Disease Society (MD Society). Unforced factor analysis
elicited the expected three factors representing constructs of positive
well-being, energy and negative well-being. A forced single-factor solution
supported use of the whole scale to measure total general well-being. High
Cronbach's alpha coefficients demonstrated good internal consistency reliability 
in the entire scale (alpha = 0.87) and in subscales (alpha > 0.78). The factor
structure matched that found in samples of people with diabetes for whom the
W-BQ12 was first developed, indicating construct validity. Expected subgroup
differences in the MD sample indicated significantly poorer well-being in women
than in men and also in participants who were registered blind or partially
sighted compared to those who were not registered. The W-BQ12 will be useful in
measuring outcomes in rehabilitative and medical interventions and in researching
factors affecting adjustment to MD.

Publication Types: 
    Evaluation Studies
    Research Support, Non-U.S. Gov't

PMID: 11763208 [PubMed - indexed for MEDLINE]

2914: Bull Soc Belge Ophtalmol. 2000;(278):49-53.

Clinicopathologic correlation of surgically removed submacular tissue.

Lafaut BA.

Ghent University Hospital, Ophthalmology, De Pintelaan 185, B-9000 Gent, Belgium,
University Eye Clinic, Joseph-Stelzmann-Strasse 9, D-50931 Cologne, Germany.

The histologic appearance of a consecutive series of 200 neovascular membranes
was analyzed. Specific angiographic manifestations of exudative age-related
macular degeneration such as classic or occult choroidal neovascularization,
vascularized pigment epithelial detachment, tear of the retinal pigment
epithelium, polypoidal choroidal vasculopathy and deep retinal vascular anomalous
complex correspond with specific histoarchitectural patterns.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11761561 [PubMed - indexed for MEDLINE]

2915: Graefes Arch Clin Exp Ophthalmol. 2001 Oct;239(10):729-32.

Surgical posterior vitreous detachment combined with gas/air tamponade for
treating macular edema associated with branch retinal vein occlusion: retinal
tomography and visual outcome.

Saika S, Tanaka T, Miyamoto T, Ohnishi Y.

Department of Ophthalmology, Wakayama Medical University, School of Medicine,
Kimiidera, Japan. shizuya@wakayama-med.ac.jp

PURPOSE: To assess the effectiveness of surgical posterior vitreous detachment
(PVD) together with gas/air tamponade in treating visual impairment from macular 
edema associated with branch retinal vein occlusion (BRVO-macular edema).
METHODS: A cohort study was conducted. To treat visual disturbance caused by
BRVO-macular edema in 19 consecutive patients at a University Hospital,
phacoemulsification, intraocular lens implantation, and vitrectomy were
performed, together with gas/air tamponade. Patients were followed up
postoperatively for 3-18 months. Foveal structure was defined using optical
coherence tomography (OCT). Preoperative visual acuity, central retinal
thickness, and interval between BRVO onset and operation were compared between
patients with postoperative visual improvement and those without improvement.
RESULTS: Ten patients recovered normal or near-normal foveal configuration, while
nine patients did not. Mean postoperative visual acuity in the former group of
patients was significantly higher than in the latter. Mean foveal retinal
thickness decreased significantly after the operation. The interval from onset of
BRVO until operation was significantly shorter in patients with improved
postoperative vision than in other patients, and patients operated on within 11
months had significantly increased postoperative visual acuity. CONCLUSIONS:
Surgical PVD and gas/air tamponade appears effective in treating BRVO-macular
edema, although relatively short duration from disease onset until operation is
critical for improvement of vision. When a good postoperative foveal contour is
seen, it seems to be associated with better visual outcome.

PMID: 11760031 [PubMed - indexed for MEDLINE]

2916: Retina. 2001;21(6):596-601.

Comparison of foveal thickness measured with the retinal thickness analyzer and
optical coherence tomography.

Neubauer AS, Priglinger S, Ullrich S, Bechmann M, Thiel MJ, Ulbig MW, Kampik A.

Department of Ophthalmology, Ludwig-Maximilians-Universität, Munich, Germany.
aneubaue@ak-i.med.uni-muenchen.de

PURPOSE: To assess and compare the reliability and reproducibility of retinal
thickness measurements for the retinal thickness analyzer (RTA) and optical
coherence tomography (OCT) in normal and edematous retina. METHODS: The authors
measured the foveal thickness of 21 normal eyes and 9 eyes with macular edema
with both methods in random order. With the RTA, the fovea was measured 10 times;
with the OCT, six scans (one horizontal and five vertical cross-sections) of the 
fovea were obtained. RESULTS: Mean foveal thickness of normal eyes measured 153
microm with OCT and 181 microm with RTA (median for both methods 150 microm).
Coefficients of variation (CV) within the same subjects were 10% (OCT) and 9%
(RTA) reducing to 9% (OCT) and 7% (RTA) when scans were repeated only five times 
for both methods. The RTA, however, yielded an interpatient CV of 33% (OCT 17%), 
which was caused by several falsely high readings in normal individuals. In eyes 
with retinal thickening the OCT measured a mean of 324 microm with 15% intra- and
58% interpatient CV. The RTA yielded a mean of 403 microm with CV of 18% and 73%,
respectively. CONCLUSION: Both methods yield reproducible measurements of foveal 
thickness in normal individuals and individuals with macular edema. However,
falsely high measurements may occur with the RTA, reducing its reliability as
compared to the OCT.

Publication Types: 
    Comparative Study

PMID: 11756882 [PubMed - indexed for MEDLINE]

2917: Retina. 2001;21(6):575-80.

Visual outcome following subretinal hemorrhage in Best disease.

Chung MM, Oh KT, Streb LM, Kimura AE, Stone EM.

The Department of Ophthalmology, The University of Southern California, Los
Angeles, CA, USA.

PURPOSE: To review cases of Best disease associated with subretinal hemorrhage to
better understand their long-term visual prognosis. SUBJECT AND METHODS: Patients
were identified through the photographic file database at the University of Iowa.
Seventy-eight files of patients with clinical evidence of Best disease were
reviewed and 12 patients (14 eyes) were identified with subretinal hemorrhage.
The visual acuity and clinical course were reviewed in all of these patients when
possible. Three patients demonstrated subretinal hemorrhage on their last
follow-up visit. Nine patients (11 eyes) were followed through to resolution of
subretinal hemorrhage. Eight patients were screened on the VMD2 gene and all were
found to have disease-causing sequence variations. RESULTS: All patients noted
visual loss at presentation with subretinal hemorrhage (median 20/100; range
20/30-20/400). The median final visual acuity in the 11 eyes with follow-up was
20/50 (20/16-20/400 range). Ten of 11 eyes demonstrated improvement of vision
with 9/11 having a final visual acuity of 20/50 or better. CONCLUSION: The
natural history of patients with Best disease with subretinal hemorrhage and
moderate visual loss is relatively good. The presence of subretinal hemorrhage in
Best disease may be related to mild, incidental trauma.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11756879 [PubMed - indexed for MEDLINE]

2918: Am J Ophthalmol. 2002 Jan;133(1):147-9.

Foreign body reaction with delayed extrusion of ganciclovir implant in a patient 
with immune recovery vitritis syndrome.

Taguri AH, Dhillon B, Wharton SB, Kamal A.

Princess Alexandra Eye Pavilion, Edinburgh, Scotland, United Kingdom.
taguri@hotmail.com

PURPOSE: To report a case of delayed extrusion of primary ganciclovir implants in
a patient with immune recovery vitritis syndrome. METHOD: Interventional case
report. A 54-year-old HIV positive male patient with immune recovery vitritis
syndrome had spontaneous extrusion of bilateral ganciclovir devices 4 years after
primary implantation. RESULT: The extruded ganciclovir implants were removed from
both eyes, and removal was complicated by vitreous hemorrhage in one eye.
Histopathological examination of the extruded implant, LE, showed marked
inflammation and evidence of foreign body reaction. CONCLUSION: Excess
inflammation in eyes with immune recovery vitritis syndrome may trigger a foreign
body reaction that results in a delayed extrusion of primary ganciclovir
implants. The site of ganciclovir implants in patients with immune recovery
vitritis syndrome should be regularly inspected for eroding struts to prevent
secondary endophthalmitis.

Publication Types: 
    Case Reports

PMID: 11755856 [PubMed - indexed for MEDLINE]

2919: Am J Ophthalmol. 2002 Jan;133(1):70-7.

Increased levels of vascular endothelial growth factor and interleukin-6 in the
aqueous humor of diabetics with macular edema.

Funatsu H, Yamashita H, Noma H, Mimura T, Yamashita T, Hori S.

Department of Ophthalmology, Diabetes Center, Tokyo Women's Medical University,
Tokyo, Japan. tfunatsu@nifty.com

PURPOSE: To investigate the relationship between diabetic macular edema and the
levels of vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) in
aqueous humor and plasma.DESIGN: Comparative cross-sectional study. METHODS:
Fifty-four eyes from 54 diabetic patients were used. The concentrations of VEGF
and IL-6 in undiluted aqueous specimens (obtained from the eyes during cataract
surgery) and in plasma were measured by an enzyme-linked immunosorbent assay. To 
assess blood-aqueous barrier function, the aqueous flare intensity was measured
by a laser flare-cell meter as an estimate of the aqueous protein level. RESULTS:
The aqueous levels of VEGF and IL-6 were significantly correlated with the
severity of macular edema (rho = 0.628, P <.001 and rho = 0.517, P <.01,
respectively), as well as with the aqueous protein concentration (rho = 0.618, P 
<.001 and rho = 0.588, P <.001, respectively). Aqueous levels of VEGF and IL-6
were significantly higher than their respective plasma levels (both P <.001). In 
addition, the aqueous level of VEGF was significantly correlated with that of
IL-6 (rho = 0.537, P <.01). Furthermore, the status of the posterior vitreous
significantly correlated with the severity of macular edema (rho = 0.618, P
<.0001). CONCLUSIONS: These results suggest that both VEGF and IL-6 are produced 
together in the intraocular tissues, and are involved in the pathogenesis of
macular edema.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 11755841 [PubMed - indexed for MEDLINE]

2920: Arch Ophthalmol. 2001 Dec;119(12):1833-8.

Relationship of dietary fat to age-related maculopathy in the Third National
Health and Nutrition Examination Survey.

Heuberger RA, Mares-Perlman JA, Klein R, Klein BE, Millen AE, Palta M.

Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison,
610 N Walnut St, 460 WARF, Madison, WI 53705-2397, USA.

OBJECTIVE: To evaluate the associations between dietary fat and age-related
maculopathy (ARM) in persons 40 years or older who participated in the Third
National Health and Nutrition Examination Survey. METHODS: We used a single,
nonmydriatic, fundus photograph of 1 eye to ascertain ARM status in 7883 of 11
448 survey participants. Intake of fat was estimated from 24-hour recall, and
specific sources of dietary fat were estimated from responses to food frequency
questionnaires. Logistic regression was used to compute odds ratios (ORs) and 95%
confidence intervals (CIs) that accounted for complex survey design, nonresponse,
and potential risk factors for ARM (age, smoking, race, sex, body mass index,
history of cardiovascular disease or hypertension, eye color, and sedentary
lifestyle). Persons aged 40 to 79 years (n = 7405) were included in analyses for 
early ARM (n = 644); those 60 years or older (n = 4294) were included in analyses
for late ARM (n = 53). RESULTS: After adjustment for age, race, eye color, and
sedentary lifestyle, OR for early ARM was 1.4 (95% CI, 0.9-2.2; P for trend,.10) 
among persons in high vs low quintiles of total fat intake (percentage of total
energy). Associations for specific types of fatty acids (as percentages of
caloric intake) were in the same direction and unrelated to ARM. The OR for late 
ARM was 0.7 (95% CI, 0.2-2.6; P for trend,.60) in persons 60 years or older.
Further adjustments for other potential confounders did not significantly affect 
the ORs. CONCLUSION: Age-related maculopathy was not significantly associated
with dietary fat in this large cross-sectional survey.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11735796 [PubMed - indexed for MEDLINE]

2921: J Cell Physiol. 2001 Dec;189(3):323-33.

Novel mechanism for age-related macular degeneration: an equilibrium shift
between the angiogenesis factors VEGF and PEDF.

Ohno-Matsui K, Morita I, Tombran-Tink J, Mrazek D, Onodera M, Uetama T, Hayano M,
Murota SI, Mochizuki M.

Department of Ophthalmology and Visual Science, Graduate School, Tokyo Medical
and Dental University, Yushima, Bunkyo-ku, Tokyo, Japan. k.ohno.oph@med.tmd.ac.jp

We investigated gene expression profiles of vascular endothelial growth factor
(VEGF) and pigment epithelium-derived factor (PEDF) in differentiated and
non-differentiated retinal pigment epithelial (RPE) cells during oxidative
stress. Human RPE cells were grown in culture on laminin-coated flasks to obtain 
differentiated features. Cells cultured on plastic were used as
non-differentiated controls. After confluence, hydrogen peroxide (H2O2) was added
for 48 h, then, total RNA was extracted and used for RT-PCR and Northern blot
analysis. Medium conditioned by RPE was used for ELISA, Western blotting, and in 
vitro angiogenesis assay. As a result, differentiated RPE cells expressed
significantly higher levels of VEGF protein, as compared to their
non-differentiated counterparts. The expression pattern remained consistent even 
after cellular exposure to H2O2. Conversely, while elevated levels of PEDF
transcript and protein were seen in differentiated RPE cells, compared to
non-differentiated cells, a marked decrease at both PEDF mRNA and protein levels 
was seen after treatment with H2O2. Moreover, this decrease in PEDF expression
was dosage dependent. In in vitro angiogenesis assay, conditioned medium from
differentiated human RPE cells after exposure to H2O2 showed a dramatic increase 
in tubular formation and migratory activity of microvascular endothelial cells.
These data suggest that, in physiological conditions, a critical balance between 
PEDF and VEGF exists, and PEDF may counteract the angiogenic potential of VEGF.
Under oxidative stress, PEDF decreases disrupting this balance. This equilibrium 
shift may be significant in promoting a pathological condition of RPE cells and
contributing to choroidal neovascularization in age-related macular degeneration.
Copyright 2001 Wiley-Liss, Inc.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11748590 [PubMed - indexed for MEDLINE]

2922: Exp Eye Res. 2001 Nov;73(5):601-15.

Changes of astrocytes in retinal ageing and age-related macular degeneration.

Ramírez JM, Ramírez AI, Salazar JJ, de Hoz R, Triviño A.

Instituto de Investigaciones Oftalmológicas Ramón Castroviejo, Facultad de
Medicina, Pab VI, 4(a) planta, Ciudad Universitaria s/n. Universidad Complutense,
28040 Madrid, Spain.

Most studies of age-related macular degeneration (AMD) have focused on the outer 
retina but little has been done on the involvement of astrocytes in this disease.
We examined normal (young and old) and pathological (AMD) human retinas for the
presence of changes in morphology and distribution of the astrocytes. Electron
microscopy and inmunohistochemical techniques (anti-GFAP) were used for this
study. Astrocytes in the ageing group showed: (1) higher GFAP immunoreactivity
and more cytoplasmic organelles and glial filaments than astrocytes from younger 
retinas; (2) lipofucsin deposits; (3) a significantly smaller number of cells in 
the honeycomb astroglial plexus in the ganglion cell layer than in the younger
group; and (4) Spaces with no GFAP reactivity in the nerve fiber layer. Changes
observed in the AMD group were: (1) the basal membrane of the retinal capillaries
was considerably thicker than in normal old individuals; (2) There were numerous 
non-functional capillaries; (3) There were hypertrophic astrocytes that
phagocytosed dead ganglion cells; and (4) There were glial membranes constituted 
by astrocytes and Müller cells located between the vitreous humour and internal
limiting membrane. These observations suggested that the extensive retinal
ischaemia that can occur with AMD, together with the loss of astroglial cells
accompanying normal ageing, could cause the death of the ganglion cells which
cannot be protected from oxidative damage. Extensive ischaemia could cause the
astrocytes to migrate to the vitreous humour where there is a metabolic reserve. 
(C) 2001 Academic Press.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11747361 [PubMed - indexed for MEDLINE]

2923: Br J Ophthalmol. 2001 Dec;85(12):1432-6.

Short wavelength automated perimetry in age related maculopathy.

Remky A, Lichtenberg K, Elsner AE, Arend O.

Department of Ophthalmology, Medical School of the Technical University of
Aachen, Pauwelsstrasse 30, 52057 Aachen, Germany.

BACKGROUND/AIMS: Previous studies reported the predictive value of the short
wavelength sensitive (SWS) cone mediated sensitivity for visual outcome in age
related macular degeneration. In this study SWS sensitivity was measured by
commercially available blue on yellow perimetry in patients with non-exudative
age related maculopathy (ARM) and compared with the presence of morphological
risk factors and the status of the fellow eye. METHODS: In a prospective cross
sectional study, 126 patients (57 males, 69 females, mean age 71 (SD 6) years)
with ARM (visual acuity >20/50) were tested. Central visual fields (blue on
yellow) were obtained with a conventional perimeter. Fundus slides were graded by
two independent observers for soft drusen and presence of focal
hyperpigmentation. RESULTS: Mean sensitivity and standard deviation of all
patients exhibited a significant reduction with age. Patients with soft drusen
had significantly lower sensitivity than those without, whereas there were no
differences in visual acuity (log MAR). Sensitivity was also reduced in those
eyes with fellow eyes having a sight threatening complication of age related
macular degeneration (AMD). Eyes with focal hyperpigmentation compared with those
without had no loss of sensitivity, but did have a significant decrease in the
central part of the field compared with the more eccentric. CONCLUSION: SWS
sensitivity loss is associated with common risk factors for progression to AMD.
Short wavelength automated perimetry is moderately rapid and readily available.
It may serve as a tool in future ARM trials.

Publication Types: 
    Evaluation Studies

PMID: 11734515 [PubMed - indexed for MEDLINE]

2924: Br J Ophthalmol. 2001 Dec;85(12):1429-31.

Clinical features of a novel TIMP-3 mutation causing Sorsby's fundus dystrophy:
implications for disease mechanism.

Clarke M, Mitchell KW, Goodship J, McDonnell S, Barker MD, Griffiths ID, McKie N.

Department of Ophthalmology, Royal Victoria Infirmary, Newcastle upon Tyne NE2
4HH, UK. M.P.Clarke@ncl.ac.uk

AIMS: To describe the phenotype in three family members affected by a novel
mutation in the gene coding for the enzyme tissue inhibitor of
metalloproteinase-3 (TIMP-3). METHODS: Three members of the same family were seen
with a history of nyctalopia and visual loss due to maculopathy. Clinical
features were consistent with Sorsby's fundus dystrophy. Exon 5 of the gene
coding for TIMP-3 was amplified by the polymerase chain reaction, single strand
conformation polymorphism analysis undertaken and exon 5 amplicons were directly 
sequenced. RESULTS: Onset of symptoms was in the third to fourth decade. Five of 
six eyes had geographic macular atrophy rather than neovascularisation as a cause
for central visual loss. Peripheral retinal pigmentary disturbances were present.
Scotopic ERGs were abnormal in all three. Mutation analysis showed a G-->T
transversion in all three resulting in a premature termination codon, E139X,
deleting most of the carboxy terminal domain of TIMP-3. CONCLUSIONS: The patients
described had a form of Sorsby's fundus dystrophy which fell at the severe end of
the spectrum of this disease. Postulated disease mechanisms include deposition of
dimerised TIMP-3 protein.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 11734514 [PubMed - indexed for MEDLINE]

2925: Br J Ophthalmol. 2001 Dec;85(12):1426-8.

Plasma malondialdehyde and nitric oxide levels in age related macular
degeneration.

Totan Y, Cekiç O, Borazan M, Uz E, Sögüt S, Akyol O.

Department of Ophthalmology, Turgut Ozal Medical Centre, Inönü University School 
of Medicine, 44300 Malatya, Turkey. ytotan@usa.net

AIMS: To evaluate alteration of plasma malondialdehyde (MDA) and nitric oxide
(NO) levels in patients with exudative age related macular degeneration (ARMD).
METHODS: Plasma nitrite plus nitrate concentrations as an index of plasma NO
levels and plasma MDA level as a marker of lipid peroxidation were measured in
patients with exudative ARMD and age and sex matched healthy subjects. RESULTS:
Significantly higher MDA and lower NO levels were detected in plasma of patients 
with ARMD compared with their controls (p=0.01, p=0.001, respectively).
CONCLUSION: The results may support involvement of oxidative damage and vascular 
theory in the pathogenesis of ARMD as part of the ageing process.

PMID: 11734513 [PubMed - indexed for MEDLINE]

2926: Br J Ophthalmol. 2001 Dec;85(12):1411-5.

Comment in:
    Br J Ophthalmol. 2001 Dec;85(12):1399-400.

Pulsatile ocular blood flow in asymmetric exudative age related macular
degeneration.

Chen SJ, Cheng CY, Lee AF, Lee FL, Chou JC, Hsu WM, Liu JH.

Department of Ophthalmology, Taipei Veterans General Hospital, 201 Section 2,
Shih-Pai Road, Taipei 112, Taiwan, ROC. sjchen@vghtpe.gov.tw

BACKGROUND/AIMS: Decreased perfusion or increased vascular resistance of the
choroidal vessels had been proposed as the vascular pathogenesis for age related 
macular degeneration (AMD). This study planned to answer the question whether
pulsatile ocular blood flow (POBF) was different in patients with asymmetric
exudative AMD between eyes with drusen, choroidal neovascularisation (CNV), or
disciform scar. METHODS: 37 patients with asymmetric exudative AMD were enrolled 
in this observational case series study. POBF were measured in both eyes of each 
subject. Eyes with high myopia, anisometropia, recent laser treatment, and
glaucoma were excluded. RESULTS: After adjusting for ocular perfusion pressure,
intraocular pressure, and pulse rate, multivariate regression analysis with
generalised estimating equation showed POBF was significantly higher in eyes with
CNV (1217 (SD 476) microl/min) than the contralateral eyes with drusen (1028
(385) microl/min) (p = 0.024). Eyes with disciform scar had lower POBF than the
contralateral eyes with drusen (999 (262) microl/min and 1278 (341) microl/min,
respectively, p<0.001). There was no significant correlation between the POBF and
the lesion size of the CNV. CONCLUSION: The POBF in eyes with drusen was lower
than their fellow eyes with CNV, but higher than their fellow eyes with disciform
scar. This finding suggests that haemodynamic differences between fellow eyes in 
individuals are relevant to the development of CNV and the formation of disciform
scar. Further studies on the follow up patients might shed light on the
pathogenesis of exudative AMD.

PMID: 11734510 [PubMed - indexed for MEDLINE]

2927: Am J Ophthalmol. 2001 Dec;132(6):933-5.

North Carolina macular dystrophy: clinicopathologic correlation.

Voo I, Glasgow BJ, Flannery J, Udar N, Small KW.

Department of Ophthalmology, Jules Stein Eye Institute, University of California 
at Los Angeles School of Medicine, 100 Stein Plaza, Los Angeles, CA 90095, USA

PURPOSE: To describe the clinical and histopathologic findings of a 72-year-old
female with North Carolina macular dystrophy. METHODS: Observational case report 
with histopathologic correlation. Clinical examination includes slit-lamp
biomicroscopy, indirect ophthalmoscopy, color fundus photography, and focal
electroretinography. Histopathologic examination of the enucleated left eye
performed with light microscopy. RESULTS: Light microscopy demonstrated a
discrete macular lesion characterized by focal absence of photoreceptor cells and
retinal pigment epithelium with attenuation of the Bruch membrane and focal
atrophy of the choriocapillaris. Adjacent to the macular lesion, some lipofuscin 
was identified in the retinal pigment epithelium. CONCLUSION: North Carolina
macular dystrophy has both clinical and microscopic appearances of a
well-demarcated lesion confined to the macula, which involves the retina, pigment
epithelium, and choriocapillaris.

Publication Types: 
    Case Reports
    Research Support, U.S. Gov't, P.H.S.

PMID: 11730667 [PubMed - indexed for MEDLINE]

2928: Am J Ophthalmol. 2001 Dec;132(6):897-902.

Scotoma and fixation patterns using scanning laser ophthalmoscope microperimetry 
in patients with macular dystrophy.

Mori F, Ishiko S, Kitaya N, Takamiya A, Sato E, Hikichi T, Yoshida A.

Department of Ophthalmology, Asahikawa Medical College, Midorigaoka Higashi
2-1-1-1, Asahikawa 078-8510, Japan. morinao@d5.dion.ne.jp

PURPOSE: We used scanning laser ophthalmoscope microperimetry to evaluate the
retinal scotoma and the fixation points in the patients with macular dystrophy.
METHODS: We studied 10 eyes of five patients with macular dystrophy (three
patients with cone dystrophy and two patients with Stargardt disease). The mean
patient age was 37 years (range, 13 to 64 years). An estimation of scotoma and
fixation points on the retina was performed using scanning laser ophthalmoscope
microperimetry. RESULTS: All 10 eyes (100%) had one of two types of dense
scotoma: type one was a dense ring scotoma (five eyes, 50%), and type two was a
dense central scotoma (five eyes, 50%) that included the center of the fovea. In 
all eyes with a dense ring scotoma, the fixation points were stable and did not
shift. In all eyes with a dense central scotoma, the fixation shifted. The
logarithm of minimal angle of resolution of the visual acuity in the eyes with
the dense central scotoma was significantly worse than that of eyes with the
dense ring scotoma type (P =.005). CONCLUSIONS: Scanning laser ophthalmoscope
microperimetry findings demonstrate two types of dense scotoma (dense ring
scotoma and dense central scotoma) in the patients with macular dystrophy. The
two types of dense scotoma affect the shifting of the fixation points and the
stability of fixation and may result in the difference in visual acuity in the
patients with macular dystrophy.

PMID: 11730655 [PubMed - indexed for MEDLINE]

2929: Am J Ophthalmol. 2001 Dec;132(6):888-96.

Comparison of three techniques of foveal translocation in patients with subfoveal
choroidal neovascularization resulting from age-related macular degeneration.

Ohji M, Fujikado T, Kusaka S, Hayashi A, Hosohata J, Ikuno Y, Sawa M, Kubota A,
Hashida N, Tano Y.

Department of Ophthalmology, Osaka University Medical School, 2-2 Yamadaoka,
Suita, 565-0871, Japan. ohji@ophthal.med.osaka-u.ac.jp

PURPOSE: To report the results of three methods of foveal translocation in the
presence of subfoveal choroidal neovascular membrane resulting from age-related
macular degeneration. METHODS: We treated 51 eyes of 51 consecutive patients with
subfoveal choroidal neovascular membranes resulting from age-related macular
degeneration with one of three techniques of foveal translocation surgery: foveal
translocation with partial retinotomy (n = 6), limited translocation (n = 9), and
translocation with 360-degree retinotomy (n = 36). All patients were followed for
at least 6 months postoperatively. The size of the choroidal neovascular membrane
and the amount of foveal displacement, the best-corrected visual acuity, and
complications were recorded preoperatively and postoperatively. RESULTS: The mean
distance of the foveal translocation was greater in the 360-degree retinotomy
group (3340 microm) than in the partial retinotomy (1060 microm, P <.001) and the
limited translocation groups (1120 microm, P <.001). A final visual acuity of
20/200 or better was achieved in two eyes (33%) in the partial retinotomy group, 
seven eyes (78%) in the limited translocation group, and 23 eyes (64%) in the
360-degree retinotomy group. The final visual acuity improved by 0.2 logarithm of
minimal angle of resolution (logMAR) unit or more in one eye (17%), one eye
(11%), and seven eyes (19%), respectively. The final visual acuity was maintained
within 1 line in zero eyes, five eyes (56%), and 19 eyes (53%), respectively. A
retinal detachment developed postoperatively in five eyes (83%), zero eyes (0%), 
and 15 eyes (42%), respectively. CONCLUSIONS: A significant number of patients
improved or maintained best-corrected visual acuity after translocation with
360-degree retinotomy, and limited translocation, whereas translocation with
360-degree retinotomy is suitable for larger choroidal neovascular membranes
because it resulted in the greatest foveal displacement among the three
translocation procedures.

Publication Types: 
    Case Reports
    Comparative Study

PMID: 11730654 [PubMed - indexed for MEDLINE]

2930: Hum Gene Ther. 2001 Nov 1;12(16):2029-32.

Clinical protocol. An open-label, phase I, single administration, dose-escalation
study of ADGVPEDF.11D (ADPEDF) in neovascular age-related macular degeneration
(AMD).

Rasmussen H, Chu KW, Campochiaro P, Gehlbach PL, Haller JA, Handa JT, Nguyen QD, 
Sung JU.

Clinical Research & Regulatory Affairs, USA.

Age-Related Macular Degeneration (AMD) is, together with Diabetic Retinopathy,
the most common cause of vision loss among adults in the U.S. and other developed
countries. In the U.S., at least 1.7 million people have impaired vision due to
AMD. Every year, more than 165,000 people contract AMD and 16,000 go blind from
it, predominantly from a rapidly progressing form of the disease called "wet"
AMD. Wet AMD is characterized by serious or hemorrhagic detachment of the retinal
pigment epithelium and choroidal neovascularization. The macula has the highest
concentration of photoreceptors facilitating central vision and permitting
high-resolution visual acuity. The damage caused by the leakage and fibrovascular
scarring in wet AMD leads to profound loss of central vision and severe loss of
visual acuity (usually 20/200 or worse). People with wet AMD have several
limitations, including inability to read, inability to recognize faces or drive, 
and the disease often leads to blindness. The onset of severe visual changes in
wet AMD can occur suddenly. More than 400,000 Americans are currently affected by
this form of the disease, and the incidence is rising rapidly with the aging of
the population. Therefore, the serious consequences of this disease along with
the limited treatment options and their effectiveness make this a very good
candidate for a gene transfer treatment approach. The investigational agent,
Ad(GV)PEDF.11D, is an E1-, partial E3-, E4- deleted replication-deficient,
adenovirus serotype 5, gene transfer vector. The transgene in this vector is the 
cDNA for human pigment epithelium-derived factor (PEDF). PEDF is one of the most 
potent known antiangiogenic proteins found in humans. While Ad(GV)PEDF.11D is
able to transduce many somatic cell types, the natural barrier to other tissues
created by the retina limits the ability of Ad(GV)PEDF.11D to affect tissues
other than in the eye. Intravitreal administration of Ad(GV)PEDF.11D provides a
convenient means of delivering PEDF to the relevant cells within the eye likely
to result in a more prolonged duration of effect versus administration of the
PEDF protein alone. In three murine disease models (the laser-induced choroidal
neovascularization model, the VEGF transgenic model, and the retinopathy of
prematurity model) significant inhibition of neovascularization (up to 85%) was
demonstrated with doses of Ad(GV)PEDF vectors ranging from 1 x 10(8) to 1 x 10(9)
pu. In toxicology studies performed in Cynomolgus monkeys, a dose-related
inflammatory response was observed. A dose of 1 x 10(8) pu caused no adverse
effects, while the inflammatory response observed at 1 x 10(9) pu was minimal and
fully reversible. The observed inflammatory response at doses of 1 x 10(10) and 5
x 10(10) pu were increasingly severe. The proposed clinical trial is an
open-label, dose-escalation, phase I study to investigate the safety,
tolerability and potential activity of intravitreal injection of Ad(GV)PEDF.11D
in patients with wet AMD. Ad(GV)PEDF.11D will be injected once via intravitreal
injection into the eye with the most advanced AMD based on visual acuity.
Subjects will be age 50 or over and have severe wet AMD in at least one eye
defined by a best-corrected vision of 20/200 or worse. The primary objectives of 
this investigation are: (1) to assess the safety, tolerability and feasibility of
intravitreal injection of Ad(GV)PEDF.11D in patients with severe, neovascular
AMD, (2) to identify the maximum tolerated dose (MTD) of Ad(GV)PEDF.11D, and (3) 
to get some indication of potential activity of Ad(GV)PEDF.11D.

Publication Types: 
    Clinical Trial
    Clinical Trial, Phase I

PMID: 11727737 [PubMed - indexed for MEDLINE]

2931: Invest Ophthalmol Vis Sci. 2001 Dec;42(13):3337-40.

Transpupillary thermotherapy for subfoveal occult choroidal neovascularization:
effect on ocular perfusion.

Ciulla TA, Harris A, Kagemann L, Danis RP, Maturi R, McNulty L, Pratt LM, Xiao M,
Criswell MH, Weinberger D.

Department of Ophthalmology, Indiana University School of Medicine, 702 Rotary
Circle, Indianapolis, IN 46260, USA. tciulla@iupui.edu

PURPOSE: To perform a descriptive analysis of the effects on ocular blood flow of
transpupillary thermotherapy (TTT) for occult subfoveal choroidal neovascular
membranes (CNVMs) in age-related macular degeneration (AMD). METHODS: Eleven
subjects with occult subfoveal CNVM due to AMD were assessed in a masked fashion 
by color Doppler imaging (CDI) within 24 hours before, 24 hours after, and 1
month after undergoing TTT. RESULTS: In the posterior ciliary arteries (PCAs),
there were no statistically significant changes observed in the peak systolic
velocity (PSV), end diastolic velocity (EDV), or resistive index (RI) at 24
hours. At 1 month, the mean EDV decreased 36% (P = 0.0105) and the mean RI
increased 3.8% (P = 0.0305) in the nasal PCA. Although there was a similar trend 
in the temporal PCA, the differences did not reach statistical significance. In
the central retinal artery (CRA), the mean PSV decreased 16% (P = 0.0137), and
the mean EDV decreased 21% (P = 0.0222) at 24 hours after treatment. There were
no statistically significant differences in the CRA blood flow indices at 1 month
after treatment. In the ophthalmic artery, there were no statistically
significant differences observed in the mean PSV, EDV, or RI at 24 hours or 1
month after treatment. CONCLUSIONS: TTT is associated with transiently decreased 
volumetric blood flow in the retinal circulation 24 hours after treatment. In the
posterior ciliary arteries that supply the choroid, there were no changes
observed at 24 hours, but at 1 month, there was a decrease in the mean EDV and an
increase in the RI in the nasal and temporal PCAs, reaching statistical
significance in the nasal PCA only. This study suggests that TTT could lead to
alterations in choroidal blood flow, as assessed by CDI. Further study is
warranted.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11726642 [PubMed - indexed for MEDLINE]

2932: Invest Ophthalmol Vis Sci. 2001 Dec;42(13):3331-6.

Diverse macular dystrophy phenotype caused by a novel complex mutation in the
ELOVL4 gene.

Bernstein PS, Tammur J, Singh N, Hutchinson A, Dixon M, Pappas CM, Zabriskie NA, 
Zhang K, Petrukhin K, Leppert M, Allikmets R.

Department of Ophthalmology and Visual Sciences, Moran Eye Center, Columbia
University, 630 West 168th Street, New York, NY 10032, USA.

PURPOSE: A 5-bp deletion in ELOVL4, a photoreceptor-specific gene, has been
associated with autosomal dominant (ad) macular dystrophy phenotypes in five
related families, in which phenotypes range from Stargardt-like macular dystrophy
(STGD3; Mendelian Inheritance in Man 600110) to pattern dystrophy. This has been 
the only mutation identified in ELOVL4 to date, which is associated with macular 
dystrophy phenotypes. In the current study, the potential involvement was
investigated of an ELOVL4 gene variation in adSTGD-like and other macular
dystrophy phenotypes segregating in a large unrelated pedigree from Utah (K4175).
METHODS: The entire open reading frame of the ELOVL4 gene was analyzed by direct 
sequencing in a proband from the K4175 family. The combination of denaturing
high-performance liquid chromatography (DHPLC) analysis and direct sequencing of 
all available family members was used to further assess segregation of identified
ELOVL4 variants in the pedigree. RESULTS: A complex mutation, two 1-bp deletions 
separated by four nucleotides, was detected in all affected members of the
family. The mutation results in a frameshift and the truncation of the ELOVL4
protein, similar to the effect of the previously described 5-bp deletion.
CONCLUSIONS: The discovery of a second mutation in the ELOVL4 gene segregating
with macular dystrophy phenotypes confirms the role of this gene in a subset of
dominant macular dystrophies with a wide range of clinical expressions and
suggests a role for modifying genes and/or environmental factors in the disease
process.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11726641 [PubMed - indexed for MEDLINE]

2933: Invest Ophthalmol Vis Sci. 2001 Dec;42(13):3123-9.

Organization of the human IMPG2 gene and its evaluation as a candidate gene in
age-related macular degeneration and other retinal degenerative disorders.

Kuehn MH, Stone EM, Hageman GS.

Department of Ophthalmology and Visual Sciences, The University of Iowa Center
for Macular Degeneration, 11190 PFP, 200 Hawkins Drive, Iowa City, IA 52242, USA.

PURPOSE: To characterize the genomic organization of human IMPG2, the gene
encoding the retinal interphotoreceptor matrix (IPM) proteoglycan IPM 200, to
evaluate its relationship to IPM 150, and to evaluate its involvement in
inherited retinopathies, such as age-related macular degeneration, retinitis
pigmentosa, and Leber congenital amaurosis. METHODS: After isolation of human
genomic clones, the structure of IMPG2 was determined by sequence analysis.
Mutational analyses were conducted on genomic DNA isolated from 316 probands
using single-strand conformation polymorphism analysis. RESULTS: The IMPG2 gene
is organized into 19 exons, and the structure of the gene is highly similar to
that of the IMPG1 gene, which encodes another retinal proteoglycan, IPM 150.
Mutational analyses indicate that the observed sequence changes are present at
approximately equal rates in donors with and without retinal disease. Additional 
data derived from RT-PCR and Northern blot analysis show that IMPG2 is processed 
in the human retina into multiple alternatively sized transcripts that may
represent splicing isoforms. CONCLUSIONS: Analysis of the overall relationship of
human IMPG2 (located on chromosome 3q12.2-12.3) to human IMPG1 (located on
chromosome 6q14) suggests that these genes have evolved from a common ancestral
gene. Although this is an excellent candidate gene for hereditary retinopathies, 
single-strand conformation polymorphism analyses provided no evidence that
variations in IMPG2 coding region are responsible for the inherited retinopathies
examined.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11726612 [PubMed - indexed for MEDLINE]

2934: Hum Mol Genet. 2001 Nov 1;10(23):2671-8.

Cosegregation and functional analysis of mutant ABCR (ABCA4) alleles in families 
that manifest both Stargardt disease and age-related macular degeneration.

Shroyer NF, Lewis RA, Yatsenko AN, Wensel TG, Lupski JR.

Program in Cell and Molecular Biology, Department of Molecular and Human
Genetics, Baylor College of Medicine, Houston, TX 77030, USA.

Mutations in ABCR (ABCA4) have been reported to cause a spectrum of autosomal
recessively inherited retinopathies, including Stargardt disease (STGD), cone-rod
dystrophy and retinitis pigmentosa. Individuals heterozygous for ABCR mutations
may be predisposed to develop the multifactorial disorder age-related macular
degeneration (AMD). We hypothesized that some carriers of STGD alleles have an
increased risk to develop AMD. We tested this hypothesis in a cohort of families 
that manifest both STGD and AMD. With a direct-sequencing mutation detection
strategy, we found that AMD-affected relatives of STGD patients are more likely
to be carriers of pathogenic STGD alleles than predicted based on chance alone.
We further investigated the role of AMD-associated ABCR mutations by testing for 
expression and ATP-binding defects in an in vitro biochemical assay. We found
that mutations associated with AMD have a range of assayable defects ranging from
no detectable defect to apparent null alleles. Of the 21 missense ABCR mutations 
reported in patients with AMD, 16 (76%) show abnormalities in protein expression,
ATP-binding or ATPase activity. We infer that carrier relatives of STGD patients 
are predisposed to develop AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11726554 [PubMed - indexed for MEDLINE]

2935: Am J Clin Nutr. 2001 Dec;74(6):796-802.

Relation between dietary intake, serum concentrations, and retinal concentrations
of lutein and zeaxanthin in adults in a Midwest population.

Curran-Celentano J, Hammond BR Jr, Ciulla TA, Cooper DA, Pratt LM, Danis RB.

Department of Animal and Nutritional Sciences, University of New Hampshire,
Durham, NH 03824, USA. joannec@christa.unh.edu

BACKGROUND: Information on concentrations of retinal carotenoids (macular
pigment, or MP) is of particular interest because MP protects against age-related
macular degeneration, the leading cause of irreversible blindness in the United
States. OBJECTIVE: This study was designed to evaluate the relation between
dietary intake, blood concentrations, and retinal concentrations of carotenoids
in a large group of volunteers. DESIGN: Two hundred eighty volunteers in the
Indianapolis area completed health and diet questionnaires, donated a blood
sample, and participated in MP density assessment to determine retinal carotenoid
status. Dietary intake was assessed by food-frequency questionnaire. Serum
concentrations of lutein, zeaxanthin, and beta-carotene were measured by HPLC. MP
optical density (MPOD) was determined psychophysically with a 460-nm, 1 degrees
test stimulus. RESULTS: Average MPOD was 0.21 +/- 0.13. Average intakes of lutein
+ zeaxanthin and beta-carotene were 1101 +/- 838 and 2935 +/- 2698 microg/d,
respectively. Although several key dietary intake variables (eg, lutein +
zeaxanthin and beta-carotene) differed by sex, no significant sex differences
were found in either serum concentrations of lutein and zeaxanthin or MPOD. Serum
beta-carotene concentrations were significantly higher in women than in men.
Serum lutein + zeaxanthin and dietary intake of lutein + zeaxanthin were
significantly correlated and significantly related to variations in MPOD (r =
0.21, P < 0.001, and r = 0.25, P < 0.001, respectively). CONCLUSIONS: Retinal
carotenoids can be measured in epidemiologic studies. In this study, MPOD was
associated with lutein + zeaxanthin in the diet and the serum. Retinal
concentrations, however, were influenced by other factors as well. To understand 
the effect of dietary lutein + zeaxanthin intake on the retina and risk of
age-related eye disease, future studies should include measures of macular
concentrations of these pigments.

PMID: 11722962 [PubMed - indexed for MEDLINE]

2936: Ophthalmic Res. 2001 Nov-Dec;33(6):325-8.

Apolipoprotein E polymorphisms in age-related macular degeneration in an Italian 
population.

Simonelli F, Margaglione M, Testa F, Cappucci G, Manitto MP, Brancato R, Rinaldi 
E.

Department of Ophthalmology, Seconda Università di Napoli, Italy. franctes@tin.it

OBJECTIVE: Apolipoprotein E (apoE) is an important regulator of cholesterol and
lipid transport during compensatory synaptogenesis. Our purpose was to
investigate the role of apoE gene polymorphisms in Italian patients with
age-related macular degeneration (AMD). METHODS: We used the polymerase chain
reaction technique to analyze apoE genotypes in 87 patients with AMD, in 47
age-matched controls and in 1,287 individuals from a general reference
population. RESULTS: The frequency of allele epsilon4 carriers was significantly 
higher (p = 0.002) in the general population than in AMD patients, while the
frequency of allele epsilon2 was higher in the patients (p = 0.069) with an
increased risk for AMD in the patients versus the population-based controls (odds
ratio = 1.7; 95% confidence interval: 1.0-2.9). Allele epsilon4 was associated
with a decreased risk for AMD in the patients versus the population-based
controls (odds ratio = 0.3; 95% confidence interval: 0.1-0.8). CLINICAL
RELEVANCE: These data suggest that apoE testing may represent a tool for the
evaluation of the relative risk of AMD. Consequently, a preventive strategy can
be initiated at an early stage of the disorder. CONCLUSION: The apoE gene
polymorphism showed a significant association with the risk of AMD. The lower
frequency of the epsilon4 allele in AMD patients suggests that the apoE gene
could play a protective role in the pathogenesis of the disease. In contrast, the
epsilon2 allele was found associated with a slightly increased risk of AMD,
although we did not find a statistically significant effect. Copyright 2001 S.
Karger AG, Basel

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11721184 [PubMed - indexed for MEDLINE]

2937: Prescrire Int. 2001 Jun;10(53):78-81.

Verteporfin: new preparation. In combination with laser therapy: helpful in some 
forms of age-related macular degeneration.

[No authors listed]

(1) The reference treatment for neovascular forms of age-related macular
degeneration is laser coagulation of the neovessels, but it is not applicable to 
subfoveal lesions. (2) Verteporfin, a photosensitising agent, is injected 15
minutes before red laser therapy in patients with neovascularisation
predominantly visible in the subfoveal choroidial region. (3) The clinical file
mainly comprises two double-blind placebo-controlled trials with identical
designs, in which verteporfin was injected before laser therapy. These trials
show that verteporfin-laser combination therapy sometimes improves visual acuity 
(16% of eyes, versus 7% with laser therapy alone). It also moderately reduces the
loss of vision measured at 2 years: 53% of patients have a limited loss, compared
with 38% of patients treated with laser alone. The impact of this difference on
daily life activities is not known. (4) A retrospective subgroup analysis
suggests that only patients with predominantly visible neovascularisation benefit
from treatment with verteporfin. (5) The main adverse effects of verteporfin are 
visual. Prolonged reduction in visual acuity has mainly been reported in patients
with occult neovascularisation. The main systemic risk is of photosensitivity
reactions, and precautions must be taken for 48 hours following treatment. (6) In
practice, only patients with subfoveal neovessels are likely to benefit from red 
laser + verteporfin combination therapy. (7) Verteporfin therapy is very
expensive.

PMID: 11718169 [PubMed - indexed for MEDLINE]

2938: Ophthalmology. 2001 Nov;108(11):2060-7.

Assessment of mutations in the Best macular dystrophy (VMD2) gene in patients
with adult-onset foveomacular vitelliform dystrophy, age-related maculopathy, and
bull's-eye maculopathy.

Seddon JM, Afshari MA, Sharma S, Bernstein PS, Chong S, Hutchinson A, Petrukhin
K, Allikmets R.

Department of Ophthalmology, Massachusetts Eye Ear Infirmary, Harvard Medical
School, Boston, Massachusetts 02114, USA. Johanna_Seddon@meei.harvard.edu

PURPOSE: To study the presence of Best macular dystrophy (VMD2) gene mutations in
patients diagnosed with maculopathies other than classic Best disease and to
describe the clinical characteristics of these subjects. DESIGN: Case-comparison 
study of phenotype-genotype correlations. METHODS: Patients with either
age-related maculopathy (ARM; n = 259) or maculopathies other than classic Best
disease (n = 28) were screened for mutations in the Best gene (VMD2; OMIM
153700). These cases were compared with ethnically similar subjects in the same
age range without maculopathy (n = 196). All patients underwent a complete
dilated ocular examination, and all affected individuals underwent fundus
photography. Phenotype-genotype comparisons were made. MAIN OUTCOME MEASURES:
Presence of mutations in the Best gene (VMD2; OMIM 153700) and the clinical
phenotype. RESULTS: Three of 259 patients (1%) with ARM and 2 of 28 patients (7%)
with other maculopathies including 1 of 3 patients with adult-onset foveomacular 
vitelliform dystrophy and 1 of 5 patients with a bull's eye maculopathy, but none
of the controls, were found to possess amino acid-changing variants in the VMD2
gene. These included a man with confluent drusen and retinal pigment epithelial
detachments (variant in exon 6; T216I), a man with geographic atrophy and
numerous soft drusen (variant in exon 10; L567F), a woman with drusen and retinal
pigment epithelial alterations (variant in exon 10; L567F), a woman with drusen
and retinal pigment epithelial alterations resembling bull's-eye maculopathy
(variant in exon 4; E119Q), and a woman diagnosed with adult-onset foveomacular
vitelliform dystrophy (variant in exon 4; A146K). CONCLUSIONS: Novel mutations in
the VMD2 gene were found in patients diagnosed with maculopathies other than
classic Best disease. Some cases diagnosed as adult-onset vitelliform
foveomacular dystrophy may represent a variant of Best disease with delayed
onset. The VMD2 gene does not play a major role in the development of ARM.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11713080 [PubMed - indexed for MEDLINE]

2939: Ophthalmology. 2001 Nov;108(11):2051-9.

Comment in:
    Ophthalmology. 2003 Apr;110(4):626-7; author reply 627-8.    Ophthalmology. 2003 Jun;110(6):1263-4; author reply 1264-5.

The cost-effectiveness of photodynamic therapy for fellow eyes with subfoveal
choroidal neovascularization secondary to age-related macular degeneration.

Sharma S, Brown GC, Brown MM, Hollands H, Shah GK.

The Cost-Effective Ocular Health Policy Unit, Hotel Dieu Hospital, Queen's
University, Kingston, Ontario, Canada.

PURPOSE: Photodynamic therapy (PDT) has recently been demonstrated to be
beneficial for the treatment of subfoveal choroidal neovascularization secondary 
to age-related macular degeneration (AMD). Herein, we determine the
cost-effectiveness of PDT for the treatment of subfoveal choroidal
neovascularization (CNV) in patients with disciform degeneration in one eye and
whose second and better-seeing eye develops visual loss secondary to
predominantly classic subfoveal CNV. The analysis was performed from the
perspective of a for-profit third-party insurer. DESIGN: Cost-utility Markov
models were created to determine the cost-effectiveness of PDT under two
different scenarios, by using efficacy data derived from the Treatment of
Age-Related Macular Degeneration with Photodynamic Therapy (TAP) Study and
patient-based utilities. METHODS: Decision analyses were performed by
incorporating data from the TAP Study, expected longevity data, and patient-based
utilities. Cost-effective models were then created by incorporating incremental
medical costs. Various sensitivity analyses were carried out to determine the
robustness of our models. A Monte Carlo simulation was also used to determine
whether there was a significant difference in quality-of-life adjusted years
(QALYs) gained between PDT therapy and the placebo. RESULTS: For the hypothetical
patient whose second and better-seeing eye becomes affected and who has 20/40
vision at baseline in this affected eye (base case 1), PDT was associated with a 
10.7% relative increase in their quality-of-life (treatment conferred an
additional undiscounted 0.1342 QALYs over a 2-year period). For the hypothetical 
patient whose second and better-seeing eye becomes affected and who has 20/200
vision at baseline in this affected eye (base case 2), PDT was associated with a 
7.8% relative increase in their quality-of-life (treatment conferred an
additional undiscounted 0.0669 QALYs over a 2-year period). Sensitivity analysis 
showed our models were robust and that PDT was usually the dominant treatment
choice. Our cost-effective model demonstrated that the cost for a QALY was
$86,721 (US dollars discounted at 3%) for base case 1, assuming 5.5 treatments;
and $173,984 (USD discounted at 3%) for base case 2. CONCLUSIONS: PDT will cost a
third-party insurer $86,721 for an AMD patient with 20/40 vision in the
better-seeing eye to obtain one QALY and $173,984 for an AMD patient with 20/200 
vision in the better-seeing eye to obtain one QALY. PDT can be considered to be a
treatment that is of only minimal cost-effectiveness for AMD patients who have
subfoveal CNV in their second and better-seeing eyes and who have good presenting
visual acuity at baseline. It is a cost-ineffective treatment for AMD patients
who have poor visual acuities in their affected better-seeing eyes.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11713079 [PubMed - indexed for MEDLINE]

2940: J Cataract Refract Surg. 2001 Nov;27(11):1751-5.

Medium-term results of implantable miniaturized telescopes in eyes with
age-related macular degeneration.

Kaşkaloğlu M, Uretmen O, Yağci A.

Ege University Faculty of Medicine, Ophthalmology Department, Izmir, Turkey.
mahmut@med.ege.edu.tr

PURPOSE: To evaluate the efficacy of an implantable miniaturized telescope, the
IMT, in patients with age-related macular degeneration (ARMD). SETTING: Ege
University Faculty of Medicine, Ophthalmology Department, Izmir, Turkey. METHODS:
Among 15 patients meeting the inclusion criteria for IMT implantation, 3 were
willing to participate in this prospective clinical trial and had cataract
extraction with IMT implantation. The effect of the IMT on visual outcome and
daily activities was assessed over 18 months. RESULTS: All patients had some
improvement in distance and near vision. However, this did not lead to
significant improvements in the ability to perform daily activities. One patient 
had 2 attacks of mild iritis that were controlled with topical medications. In
another patient, bubbles that were noted inside the IMT soon after implantation
were still present at 1 year. In this patient, the IMT was replaced with a
conventional poly(methyl methacrylate) intraocular lens. CONCLUSIONS:
Implantation of an IMT may positively affect the visual outcome and daily
activities in some ARMD patients. However, proper patient selection and fully
informed patient consent and understanding are mandatory.

Publication Types: 
    Case Reports
    Clinical Trial

PMID: 11709247 [PubMed - indexed for MEDLINE]

2941: Am J Ophthalmol. 2001 Nov;132(5):794-6.

Aqueous humor and plasma vascular endothelial growth factor in uveitis-associated
cystoid macular edema.

Fine HF, Baffi J, Reed GF, Csaky KG, Nussenblatt RB.

Harvard Medical School, Boston, Massachusetts, USA. hfine@alum.mit.edu

PURPOSE: To determine the association between cystoid macular edema and vascular 
endothelial growth factor concentration in the aqueous humor and plasma of
uveitis patients. METHODS: Cross-sectional study. Vascular endothelial growth
factor concentrations were measured by enzyme-linked immunosorbent assay in the
aqueous humor of 20 uveitis patients (9 with and 11 without cystoid macular
edema), and in the plasma of 40 uveitis patients (20 with and 20 without cystoid 
macular edema) and 20 healthy volunteers. RESULTS: Mean aqueous humor vascular
endothelial growth factor concentrations for uveitis patients with and without
cystoid macular edema were 152.3 and 109.5 pg/ml, respectively, P =.044. Mean
plasma vascular endothelial growth factor concentrations in uveitis patients with
and without cystoid macular edema and in healthy volunteers were 32.2, 29.6, and 
55.0 pg/ml, respectively. Uveitis patients had lower plasma vascular endothelial 
growth factor levels than did healthy volunteers, P =.0002. CONCLUSION: In
uveitis patients, vascular endothelial growth factor concentration is increased
in the aqueous humor of eyes with cystoid macular edema. It may be useful to
investigate vascular endothelial growth factor antagonists as a treatment for
uveitis-associated cystoid macular edema.

Publication Types: 
    Comparative Study

PMID: 11704050 [PubMed - indexed for MEDLINE]

2942: Am J Ophthalmol. 2001 Nov;132(5):682-92.

Age-related maculopathy: an expanded genome-wide scan with evidence of
susceptibility loci within the 1q31 and 17q25 regions.

Weeks DE, Conley YP, Tsai HJ, Mah TS, Rosenfeld PJ, Paul TO, Eller AW, Morse LS, 
Dailey JP, Ferrell RE, Gorin MB.

Department of Human Genetics, University of Pittsburgh Graduate School of Public 
Health and School of Medicine, Pittsburgh, Pennsylvania 15261, USA.

PURPOSE: We seek to identify genetic loci that contribute to age-related
maculopathy susceptibility. METHODS: Families consisting of at least two siblings
affected by age-related maculopathy were ascertained using eye care records and
fundus photographs. Additional family members were used to increase the power to 
detect linkage. Microsatellite genotyping was conducted by the National Heart,
Lung and Blood Institute Mammalian Genotyping Service and the National Institutes
of Health Center for Inherited Disease Research. Linkage analyses were conducted 
with parametric (autosomal dominant; heterogeneity lod score) and nonparametric
methods (S(all) statistic) using three diagnostic models. False-positive rates
were determined from simulations using actual pedigrees and genotyping data.
RESULTS: Under our least stringent diagnostic model, model C, 860 affected
individuals from 391 families (452 sib pairs) were genotyped. Sixty-five percent 
of the affected individuals had evidence of exudative disease. Four regions,
1q31, 9p13, 10q26, and 17q25, showed multipoint heterogeneity lod scores or
S(all) scores of 2.0 or greater (under at least one model). Under our most
stringent diagnostic model, model A, the 1q31 heterogeneity lod score was 2.46
between D1S1660 and D1S1647. Under model C, the 17q25 heterogeneity lod score at 
D17S928 was 3.16. Using a threshold of 1.5, additional loci on chromosomes 2 and 
12 were identified. CONCLUSIONS: The locus on chromosome 1q31 independently
confirms a report by Klein and associates mapping an age-related maculopathy
susceptibility gene to this region. Simulations indicate that the 1q31 and 17q25 
loci are unlikely to be false positives. There was no evidence that other known
macular or retinal dystrophy candidate gene regions are major contributors to the
genetics of age-related maculopathy.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11704029 [PubMed - indexed for MEDLINE]

2943: Am J Ophthalmol. 2001 Nov;132(5):668-81.

The Age-Related Eye Disease Study system for classifying age-related macular
degeneration from stereoscopic color fundus photographs: the Age-Related Eye
Disease Study Report Number 6.

Age-Related Eye Disease Study Research Group.

PURPOSE: To describe the system for grading age-related macular degeneration from
fundus photographs in the Age-Related Eye Disease Study. This is a prospective
multicenter cohort study of the course of age-related macular degeneration and a 
placebo-controlled clinical trial of the effect of high-dose vitamin and mineral 
supplements on development of advanced age-related macular degeneration. METHODS:
Standardized stereoscopic 30-degree color fundus photographs are taken at 11
clinical centers and evaluated by graders at a reading center for quality and
age-related macular degeneration abnormalities. Macular subfields are defined by 
a grid, and presence and severity of various age-related macular degeneration
abnormalities are graded using standard/example photographs and measuring
circles. Advanced age-related macular degeneration abnormalities
(presence/absence) include retinal pigment epithelial detachment, serous (or
hemorrhagic) sensory retinal detachment, hard exudates, subretinal/subretinal
pigment epithelial hemorrhage, subretinal fibrous tissue, and photocoagulation
scars. Other abnormalities (multistep scales) include retinal pigment epithelial 
abnormalities (geographic atrophy, depigmentation, and increased pigment), and
drusen (size, type [hard versus soft distinct or indistinct], and total area).
Contemporaneous variability is tested by having different graders evaluate
samples of photographs, and temporal variability by annual regrading of a
dedicated subset. RESULTS: In a cumulative sample of 1230 eyes for
contemporaneous reproducibility, agreement on advanced age-related macular
degeneration was 96% (kappa = 0.88) and for four-step age-related macular
degeneration level was 83% (kappa = 0.77). Agreement was moderate for pigment
epithelial detachment (kappa = 0.54) and substantial for serous sensory retinal
detachment, hard exudates, subretinal/subretinal pigment epithelial hemorrhage,
subretinal fibrous tissue, and central geographic atrophy (kappa = 0.73-0.82).
For pigment abnormalities, agreement was substantial for geographic atrophy
(kappa = 0.63; kappa(weighted) = 0.71, 0.75 weight for one-step disagreements),
and moderate for depigmentation (kappa = 0.41, kappa(weighted) = 0.51) and
increased pigment (kappa = 0.54, kappa(weighted) = 0.71). For drusen, agreement
was moderate to substantial for presence/maximum size (kappa = 0.50,
kappa(weighted) = 0.68), type (kappa = 0.61, kappa(weighted) = 0.69), and area
(kappa = 0.56, kappa(weighted) = 0.77). Six annual regrades of 119 eyes showed
little temporal drift in grading of various age-related macular degeneration
abnormalities, except for drusen type. CONCLUSIONS: The Age-Related Eye Disease
Study has demonstrated satisfactory reliability for detecting onset of advanced
age-related macular degeneration in a cohort, and moderate to substantial
agreement on various abnormalities across the age-related macular degeneration
spectrum. The Age-Related Eye Disease Study system for classification of
age-related macular degeneration is suitable for longitudinal multicenter
studies.

Publication Types: 
    Clinical Trial
    Comparative Study
    Controlled Clinical Trial
    Multicenter Study
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11704028 [PubMed - indexed for MEDLINE]

2944: Bull Soc Belge Ophtalmol. 2001;(281):75-84.

Features of age-related macular degeneration on optical coherence tomography.

Van Kerckhoven W, Lafaut B, Follens I, De Laey JJ.

Department of Ophthalmology, Ghent University.

PURPOSE: To describe Optical Coherence Tomographic (OCT) findings in age-related 
macular lesions. PATIENTS AND METHODS: We selected 6 patients with characteristic
features of age-related macular disease on OCT, 4 of whom presented with
Choroidal New Vessels (CNV). OCT is analogous to ultrasound, except that light is
used instead of sound. The reflected light is analysed with the technique of
low-coherence interferometry. RESULTS: Classic CNV present with well-defined
boundaries on OCT, whereas occult CNV can present with well- or poorly defined
boundaries. Findings in Chronic Central Serous Chorioretinopathy (CSCR) and Adult
Onset Vitelliform Dystrophy (AOVD) need angiographic correlation when compared to
findings in CNV. CONCLUSION: OCT cannot replace conventional diagnostic
techniques in exsudative Age-related Macular Degeneration. Although it accurately
depicts associated changes and especially the associated serous detachment in
macular disease, the imaging of neovascular membranes faces limited penetration
and resolution. The interpretation of the tomograms requires further
clinico-histological correlation.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 11702647 [PubMed - indexed for MEDLINE]

2945: Hum Genet. 2001 Sep;109(3):326-38.

Mutational scanning of the ABCR gene with double-gradient denaturing-gradient gel
electrophoresis (DG-DGGE) in Italian Stargardt disease patients.

Fumagalli A, Ferrari M, Soriani N, Gessi A, Foglieni B, Martina E, Manitto MP,
Brancato R, Dean M, Allikmets R, Cremonesi L.

Unit of Genetics and Molecular Diagnostics, University Hospital San Raffaele, Via
Olgettina 58-60, 20132 Milan, Italy.

Mutations in the retina-specific ABC transporter (ABCR) gene are responsible for 
autosomal recessive Stargardt disease (arSTGD). Mutation detection efficiency in 
ABCR in arSTGD patients ranges between 30% and 66% in previously published
studies, because of high allelic heterogeneity and technical limitations of the
employed methods. Conditions were developed to screen the ABCR gene by
double-gradient denaturing-gradient gel electrophoresis. The efficacy of this
method was evaluated by analysis of DNA samples with previously characterized
ABCR mutations. This approach was applied to mutation detection in 44 Italian
arSTGD patients corresponding to 36 independent genomes, in order to assess the
nature and frequency of the ABCR mutations in this ethnic group. In 34 of 36
(94.4%) STGD patients, 37 sequence changes were identified, including 26
missense, six frameshift, three splicing, and two nonsense variations. Among
these, 20 had not been previously described. Several polymorphisms were detected 
in affected individuals and in matched controls. Our findings extend the spectrum
of mutations identified in STGD patients and suggest the existence of a subset of
molecular defects specific to the Italian population. The identification of at
least two disease-associated mutations in four healthy control individuals
indicates a higher than expected carrier frequency of variant ABCR alleles in the
general population. Genotype-phenotype analysis in our series showed a possible
correlation between the nature and location of some mutations and specific
ophthalmoscopic features of STGD disease.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11702214 [PubMed - indexed for MEDLINE]

2946: Invest Ophthalmol Vis Sci. 2001 Nov;42(12):3016-22.

Mitochondrial abnormalities in ageing macular photoreceptors.

Barron MJ, Johnson MA, Andrews RM, Clarke MP, Griffiths PG, Bristow E, He LP,
Durham S, Turnbull DM.

School of Neurosciences and Psychiatry, University of Newcastle-upon-Tyne, UK.

PURPOSE: To evaluate somatic mitochondrial (mt)DNA mutations in the macula during
ageing. METHODS: Ten 30-microm cryostat sections from the macula (foveal and
perifoveal regions) and peripheral retina of 14 donors (aged 14-94 years) were
cut for cytochrome c oxidase cytochemistry. The photoreceptor layer was
microdissected and DNA extracted for 4977-bp mtDNA (mtDNA(4977)) quantification
using PCR. Dual cytochemistry for cytochrome c oxidase and succinate
dehydrogenase allowed the detection of cytochrome c oxidase-deficient cones.
RESULTS: Findings showed a progressive accumulation of mtDNA(4977) from ages 14
to 94 years. From ages 14 to 60 years there was an increase from 0.006% to 0.25%,
and from ages 60 to 94 years there was a steeper increase from 0.25% to 5.39%.
Counts of cones in the dual-reacted preparations showed more cytochrome c
oxidase-deficient cones in the foveal region than elsewhere. CONCLUSIONS: The
results show that mitochondrial DNA deletions and cytochrome c oxidase-deficient 
cones accumulate in the ageing retina, particularly in the foveal region. These
defects may contribute to the changes in macular function observed in ageing and 
age-related maculopathy.

PMID: 11687550 [PubMed - indexed for MEDLINE]

2947: Invest Ophthalmol Vis Sci. 2001 Nov;42(12):2757-61.

Null missense ABCR (ABCA4) mutations in a family with stargardt disease and
retinitis pigmentosa.

Shroyer NF, Lewis RA, Yatsenko AN, Lupski JR.

Program in Cell and Molecular Biology, Department of Molecular and Human
Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.

PURPOSE: To determine the type of ABCR mutations that segregate in a family that 
manifests both Stargardt disease (STGD) and retinitis pigmentosa (RP), and the
functional consequences of the underlying mutations. METHODS: Direct sequencing
of all 50 exons and flanking intronic regions of ABCR was performed for the STGD-
and RP-affected relatives. RNA hybridization, Western blot analysis, and
azido-adenosine triphosphate (ATP) labeling was used to determine the effect of
disease-associated ABCR mutations in an in vitro assay system. RESULTS: Compound 
heterozygous missense mutations were identified in patients with STGD and RP.
STGD-affected individual AR682-03 was compound heterozygous for the mutation
2588G-->C and a complex allele, [W1408R; R1640W]. RP-affected individuals
AR682-04 and-05 were compound heterozygous for the complex allele [W1408R;
R1640W] and the missense mutation V767D. Functional analysis of the mutation
V767D by Western blot and ATP binding revealed a severe reduction in protein
expression. In vitro analysis of ABCR protein with the mutations W1408R and
R1640W showed a moderate effect of these individual mutations on expression and
ATP-binding; the complex allele [W1408R; R1640W] caused a severe reduction in
protein expression. CONCLUSIONS: These data reveal that missense ABCR mutations
may be associated with RP. Functional analysis reveals that the RP-associated
missense ABCR mutations are likely to be functionally null. These studies of the 
complex allele W1408R; R1640W suggest a synergistic effect of the individual
mutations. These data are congruent with a model in which RP is associated with
homozygous null mutations and with the notion that severity of retinal disease is
inversely related to residual ABCR activity.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11687513 [PubMed - indexed for MEDLINE]

2948: Cochrane Database Syst Rev. 2001;(3):CD002030.

Update in:
    Cochrane Database Syst Rev. 2003;(2):CD002030.

Update of:
    Cochrane Database Syst Rev. 2000;(2):CD002030.

Photodynamic therapy for neovascular age-related macular degeneration.

Wormald R, Evans J, Smeeth L, Henshaw K.

Research and Development Department, Moorfields Eye Hospital and Institute of
Ophthalmology (UCL), City Road, London, UK, EC1V 2PD. r.wormald@ucl.ac.uk

BACKGROUND: In neovascular age-related macular degeneration, new vessels grow
under the retina, distorting vision and leading to scarring. This is further
exacerbated if the blood vessels leak. Photodynamic therapy, originally used in
cancer treatment, has been investigated as a way to treat the neovascular
membranes without affecting the retina. OBJECTIVES: The aim of this review is to 
examine the effects of photodynamic therapy in the treatment of neovascular
age-related macular degeneration. SEARCH STRATEGY: We searched for trials in the 
Cochrane Controlled Trials Register - CENTRAL (which includes the Cochrane Eyes
and Vision Group specialised register), MEDLINE and EMBASE. We used the Science
Citation Index to search for reports that cited relevant study reports. We
contacted experts in the field and we searched the reference lists of relevant
studies for further trial reports. SELECTION CRITERIA: We included randomised
trials of photodynamic therapy in people with choroidal neovascularisation due to
age-related macular degeneration. DATA COLLECTION AND ANALYSIS: Two reviewers
extracted the data independently. As only one trial met the inclusion criteria,
meta-analysis was not performed. MAIN RESULTS: One published trial was identified
which randomised 609 participants. Outcome data were available at 12 and 24
months after the first treatment. Participants in the treatment group received an
average of 3.4 treatments in the first year, and 2.2 in the second year. The
relative risk of losing three or more lines of visual acuity at 24 months
comparing the intervention with the control group was 0.75 (95% confidence
interval 0.65 to 0.88). The relative risk of losing six or more lines of visual
acuity at 24 months comparing the intervention with the control group was 0.61
(95% confidence interval 0.45 to 0.81). The results at 12 months were similar to 
those at 24 months. Subgroup analyses suggest that the benefits may be confined
to people with no occult choroidal neovascularisation. REVIEWER'S CONCLUSIONS:
Photodynamic therapy in people with classic choroidal neovascularisation due to
age-related macular degeneration is effective in preventing visual loss. This
evidence is drawn from a subgroup analysis of 143 participants in one trial.
Outcomes and potential adverse effects of this treatment should be monitored
closely. There is no evidence that photodynamic therapy is beneficial for people 
with evidence of occult choroidal neovascularisation. These people should be
offered treatment only in the context of a randomised trial.

Publication Types: 
    Review

PMID: 11687007 [PubMed - indexed for MEDLINE]

2949: Eur J Ophthalmol. 2001 Jul-Sep;11(3):309-12.

Tamoxifen side effects, age-related macular degeneration (AMD) or cancer
associated retinopathy (CAR)?

Sadowski B, Kriegbaum C, Apfelstedt-Sylla E.

Dept of Neuro-Ophthalmology and Pathophysiology of Vision, University Eye
Hospital, Tuebingen, Germany.

PURPOSE. Differential diagnosis of maculopathies can be difficult but is
important if patients also suffer from other diseases such as breast cancer
treated with antiestrogens. The main possible diagnoses, especially in the
elderly, are age-related macular degeneration, tamoxifen and cancer-associated
retinopathy (CAR). METHODS. We describe an 84-year-old patient with breast and
colon cancer, who complained of a decrease in visual acuity after treatment with 
low-dose antiestrogens. She underwent a general ophthalmological investigation,
perimetry and electroretinographic examination with multifocal (m-ERG) and
flash-electroretinogram (flash-ERG). RESULTS. Visual acuity was reduced to 1/50
and 0.3. The ophthalmological examination was normal, except for extensive
bilateral maculopathy with shining crystalline deposits, central and peripheral
visual field defects, slightly affected scotopic and photopic potentials in the
flash-ERG, and an abnormal m-ERG. CONCLUSIONS. The findings are expected with
age-related macular degeneration with crystalline drusen, but also with CAR. Even
if the single and total dosage of antiestrogens given to the patient is
sufficient to cause tamoxifen retinopathy, this diagnosis can be excluded
because, in tamoxifen retinopathy unlike in the case presented here, the deposits
are not distributed in all retinal layers.

Publication Types: 
    Case Reports

PMID: 11681514 [PubMed - indexed for MEDLINE]

2950: Doc Ophthalmol. 2001 Jul;103(1):47-61.

Pattern ERG and psychophysical functions in Best's disease.

Jarc-Vidmar M, Popović P, Hawlina M, Brecelj J.

University Eye Clinic, Medical Center Ljubljana, Slovenia.
Martina.Jarc-Vidmar@mf.uni-lj.si

The aim of the study was to asses the neurosensory retinal function in 12
patients (24 eyes) with different stages of Best's disease, by determining how
pattern and full field flash ERG responses were related to visual acuity, stage
of disease and extent of visual field loss. All patients had typically abnormal
EOG responses and normal full field-flash ERG responses. Patients were stratified
in two groups according to visual acuity. In the first group 12 eyes with visual 
acuity better than 0.5, all amplitudes and latencies of PERG P50 and N95
responses were in the normal range. Small central scotoma was detected by static 
perimetry in four of these eyes. In the second group of 12 eyes with visual
acuity 0.5 or less, PERG showed reduced both P50 and N95 amplitudes in five eyes,
and N95 solely, in two eyes. All patients had central scotomas detected by static
perimetry. Progression of the disease, seen in deterioration of visual acuity and
progression of central visual field defects, corresponded well with reduction of 
both PERG P50 and N95 amplitudes. There was no correlation found between visual
acuity and EOG responses. Our results show that in Best's distrophy, pattern ERG 
is getting abnormal with progression of the disease, indicating relative
preservation of neurosensory retina in initial stages of the disease. In contrast
to EOG - being abnormal in all the patients regardless of the stage of disease - 
and full field-flash ERG - being normal in most of the patients - PERG gives
opportunity for electrophysiological determination of the progression of the
disease.

PMID: 11678160 [PubMed - indexed for MEDLINE]

2951: Insight. 2001 Jul-Sep;26(3):73-6.

Macular translocation--what our patients need to know.

Gleadall R, Navarro VB, Dejuan E.

The Wilmer Institute, Johns Hopkins Hospital, Baltimore, MD 21209, USA.

Age-related macular degeneration is the most common cause of rapid and
irreversible central vision loss among persons older than 60 years in the United 
States. Vision loss occurs as a result of choroidal neovascularization in which
abnormal blood vessels in the choroid bleed and scar beneath the fovea. If this
is caught early, a new approach called macular translocation surgery can be
considered. In this procedure, the surgeon moves (translocates) the macula to a
healthy area of the retina where it may recover and maintain its function. Moving
the fovea allows the surgeon to use laser to destroy the abnormal blood vessels
and spare the fovea. As with any procedure, it is important for the patient to
have a positive perioperative experience, to be able to report and prevent
postoperative complications, arrange follow-up care and transportation, and have 
realistic expectations of visual outcomes. To this end, a patient education
brochure has been developed to ensure a more informed, involved, and satisfied
patient. Our topics include: (1) a brief description of macular degeneration, (b)
perioperative examinations and procedures, (3) the procedure itself, surgical
risks, and postoperative care, (4) appointments for follow-up and laser
procedures a few days after surgery, and (5) possible improvements in visual
outcomes. Our objectives are to describe macular translocation surgery as it
pertains to the management of choroidal neovascularization in age-related macular
degeneration and to identify the essential perioperative elements that patients
need to know about macular translocation surgery.

PMID: 11677505 [PubMed - indexed for MEDLINE]

2952: Hum Mol Genet. 2001 Oct 1;10(20):2285-92.

Molecular genetics of age-related macular degeneration.

Stone EM, Sheffield VC, Hageman GS.

Department of Ophthalmology, The University of Iowa College of Medicine, 200
Hawkins Drive, Iowa City, IA 52242, USA. edwin-stone@uiowa.edu

The numerous conditions that clinicians group under the term 'age-related macular
degeneration' (AMD) are collectively the most common cause of severe visual loss 
in the developed world. Moreover, the number of people affected by these diseases
is expected to nearly double in the next 25 years. A growing body of data
suggests that a large fraction of AMD is caused by genetic factors. As a result, 
numerous investigators have sought genes that contribute to this disorder. At
least six genes have now been identified that cause heritable macular disease,
but none of these seem to cause even a moderate fraction of AMD. Affected
pedigree member studies suggest that some regions of the genome do harbor AMD
predisposing genes, but none have yet been identified by this approach. Studies
of human donor tissue have yielded important new insights into pathways
associated with AMD. These studies, when combined with the power of genetic
approaches, are likely to ultimately reveal a set of genes responsible for a
sizeable fraction of AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.
    Review

PMID: 11673412 [PubMed - indexed for MEDLINE]

2953: Hum Mol Genet. 2001 Oct 1;10(20):2209-14.

Sequence variation and disease in the wake of the draft human genome.

Goodstadt L, Ponting CP.

MRC Functional Genetics Unit, Department of Human Anatomy and Genetics,
University of Oxford, South Parks Road, Oxford OX1 3QX, UK.

The sequencing phase of the human genome project will soon be over. In its wake, 
repertoires of sequence polymorphisms among the human population are being
sampled and a battery of functional genomics projects, from gene and protein
expression studies to whole proteome interaction experiments, are generating vast
quantities of data. Now that the data, or the means to generate data, are
available it is the application of this information in enhancing our
understanding of biology that represents the next formidable challenge. Two
prominent issues should be considered. First, existing data must be analysed
using the best methods available. The prediction of enzymatic activity for
bestrophin, whose gene is mutated in Best macular dystrophy, is described in this
review. This is an example of the experimentally testable hypotheses that can
result from such detailed and exhaustive analyses. Secondly, the torrents of data
from high-throughput studies will need to be made more accessible to all using
web-based resources that integrate and digest complementary data types. The
internet sites that showcase the human genome sequence are blazing a new trail.
Ultimately, the success of genome sequencing and functional genomics will be
measured not by the quantity and accuracy of raw data generated, but how rapidly 
they can be harnessed to span the divide between genotype and phenotype.

Publication Types: 
    Review

PMID: 11673403 [PubMed - indexed for MEDLINE]

2954: Arch Ophthalmol. 2001 Oct;119(10):1463-8.

Light exposure and the risk of age-related macular degeneration: the Pathologies 
Oculaires Liées à l'Age (POLA) study.

Delcourt C, Carrière I, Ponton-Sanchez A, Fourrey S, Lacroux A, Papoz L; POLA
Study Group.

INSERM Unité 500, 39 Avenue Charles Flahault, 34093 Montpellier, CEDEX 5, France.
delcourt@montp.inserm.fr

BACKGROUND: The role of light exposure in the development of age-related macular 
degeneration (ARMD) has been questioned. We present the relationship between
lifetime light exposure and ARMD as examined in the Pathologies Oculaires Liées à
l'Age (POLA) study. METHODS: The POLA study is a population-based study on
cataract and ARMD and their risk factors. It included 2584 residents of the town 
of Sète, located in the South of France. The presence of early and late ARMD was 
assessed on the basis of 50 degrees color fundus photographs using an
international classification system. A questionnaire about light exposure was
administered. RESULTS: Late ARMD (n = 38) was not significantly associated with
any light exposure variable. Subjects exposed to high ambient solar radiation and
those with frequent leisure exposure to sunlight had a decreased risk of
pigmentary abnormalities (odds ratio [OR] = 0.61; 95% confidence interval [CI],
0.39-0.93, and OR = 0.70; 95% CI, 0.52-0.95, respectively) and of early signs of 
ARMD (OR = 0.73; 95% CI, 0.54-0.98, and OR = 0.80; 95% CI, 0.64-1.00,
respectively). Subjects who had used sunglasses regularly had a decreased risk of
soft drusen (OR = 0.81; 95% CI, 0.66-1.00). These relationships were not modified
by further adjustments for potential confounders. CONCLUSION: Our study does not 
support a deleterious effect of sunlight exposure in ARMD.

PMID: 11594945 [PubMed - indexed for MEDLINE]

2955: Arch Ophthalmol. 2001 Oct;119(10):1455-62.

Risk factors for age-related maculopathy: the Visual Impairment Project.

McCarty CA, Mukesh BN, Fu CL, Mitchell P, Wang JJ, Taylor HR.

Centre for Eye Research Australia, University of Melbourne, East Melbourne, VIC, 
Australia.

OBJECTIVE: To describe the risk factors and associated population attributable
risk for age-related maculopathy (ARM) and age-related macular degeneration (AMD)
in Australians aged 40 years and older. METHODS: Residents were recruited from 9 
randomly selected urban clusters and 4 randomly selected rural clusters in
Victoria, Australia. At locally established test sites, the following information
was collected: visual acuity, medical and health history, lifetime sunlight
exposure, dietary intake, and fundus photographs. Age-related maculopathy and AMD
were graded from the fundus photographs using an international classification and
grading system. Backwards logistic regression was used to identify the
independent risk factors for ARM and AMD. RESULTS: The participation rate was 83%
(n = 3271) among the urban residents and 92% (n = 1473) among the rural
residents. Gradable fundus photographs of either eye were available for 4345
(92%) of the 4744 participants. There were 656 cases of ARM, giving a weighted
prevalence of 15.1% (95% confidence limit [CL], 13.8, 16.4); and there were 30
cases of AMD, giving a weighted prevalence of 0.69% (95% CL, 0.33, 1.03). In
multiple logistic regression, the risk factors for AMD were as follows: age (odds
ratio [OR], 1.23; 95% CL, 1.17, 1.29), smoked cigarettes for longer than 40 years
(OR, 2.39; 95% CL, 1.02, 5.57), and ever taken angiotensin-converting enzyme
inhibitors (OR, 3.26; 95% CL, 1.33, 8.01). The magnitude of all of these risk
factors was slightly less for ARM, and having ever taken blood
cholesterol-lowering medications was also significant (OR, 1.67; 95% CL, 1.12,
2.47; P =.001). CONCLUSION: Smoking is the only modifiable risk factor for ARM
and AMD, among the many environmental and systemic factors that were assessed.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11594944 [PubMed - indexed for MEDLINE]

2956: Arch Ophthalmol. 2001 Oct;119(10):1417-36.

Erratum in:
    Arch Ophthalmol. 2008 Sep;126(9):1251.

Comment in:
    Arch Ophthalmol. 2001 Oct;119(10):1533-4.    Arch Ophthalmol. 2002 Jan;120(1):100-1.    Arch Ophthalmol. 2002 Jul;120(7):997; author reply 997-9.    Arch Ophthalmol. 2002 Nov;120(11):1602.    Arch Ophthalmol. 2003 Mar;121(3):416-7.    Arch Ophthalmol. 2008 Jan;126(1):146-7; author reply 147.    J Fam Pract. 2002 Feb;51(2):105.    JAMA. 2001 Nov 21;286(19):2466-8.

A randomized, placebo-controlled, clinical trial of high-dose supplementation
with vitamins C and E, beta carotene, and zinc for age-related macular
degeneration and vision loss: AREDS report no. 8.

Age-Related Eye Disease Study Research Group.

BACKGROUND: Observational and experimental data suggest that antioxidant and/or
zinc supplements may delay progression of age-related macular degeneration (AMD) 
and vision loss. OBJECTIVE: To evaluate the effect of high-dose vitamins C and E,
beta carotene, and zinc supplements on AMD progression and visual acuity. DESIGN:
The Age-Related Eye Disease Study, an 11-center double-masked clinical trial,
enrolled participants in an AMD trial if they had extensive small drusen,
intermediate drusen, large drusen, noncentral geographic atrophy, or pigment
abnormalities in 1 or both eyes, or advanced AMD or vision loss due to AMD in 1
eye. At least 1 eye had best-corrected visual acuity of 20/32 or better.
Participants were randomly assigned to receive daily oral tablets containing: (1)
antioxidants (vitamin C, 500 mg; vitamin E, 400 IU; and beta carotene, 15 mg);
(2) zinc, 80 mg, as zinc oxide and copper, 2 mg, as cupric oxide; (3)
antioxidants plus zinc; or (4) placebo. MAIN OUTCOME MEASURES: (1) Photographic
assessment of progression to or treatment for advanced AMD and (2) at least
moderate visual acuity loss from baseline (> or =15 letters). Primary analyses
used repeated-measures logistic regression with a significance level of.01,
unadjusted for covariates. Serum level measurements, medical histories, and
mortality rates were used for safety monitoring. RESULTS: Average follow-up of
the 3640 enrolled study participants, aged 55-80 years, was 6.3 years, with 2.4% 
lost to follow-up. Comparison with placebo demonstrated a statistically
significant odds reduction for the development of advanced AMD with antioxidants 
plus zinc (odds ratio [OR], 0.72; 99% confidence interval [CI], 0.52-0.98). The
ORs for zinc alone and antioxidants alone are 0.75 (99% CI, 0.55-1.03) and 0.80
(99% CI, 0.59-1.09), respectively. Participants with extensive small drusen,
nonextensive intermediate size drusen, or pigment abnormalities had only a 1.3%
5-year probability of progression to advanced AMD. Odds reduction estimates
increased when these 1063 participants were excluded (antioxidants plus zinc: OR,
0.66; 99% CI, 0.47-0.91; zinc: OR, 0.71; 99% CI, 0.52-0.99; antioxidants: OR,
0.76; 99% CI, 0.55-1.05). Both zinc and antioxidants plus zinc significantly
reduced the odds of developing advanced AMD in this higher-risk group. The only
statistically significant reduction in rates of at least moderate visual acuity
loss occurred in persons assigned to receive antioxidants plus zinc (OR, 0.73;
99% CI, 0.54-0.99). No statistically significant serious adverse effect was
associated with any of the formulations. CONCLUSIONS: Persons older than 55 years
should have dilated eye examinations to determine their risk of developing
advanced AMD. Those with extensive intermediate size drusen, at least 1 large
druse, noncentral geographic atrophy in 1 or both eyes, or advanced AMD or vision
loss due to AMD in 1 eye, and without contraindications such as smoking, should
consider taking a supplement of antioxidants plus zinc such as that used in this 
study.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11594942 [PubMed - indexed for MEDLINE]

2957: Retina. 2001;21(5):478-86.

Clinicopathologic studies of age-related macular degeneration with classic
subfoveal choroidal neovascularization treated with photodynamic therapy.

Ghazi NG, Jabbour NM, De La Cruz ZC, Green WR.

Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland,
USA.

BACKGROUND: Photodynamic therapy (PDT) is a relatively new modality that is
currently under clinical and experimental evaluation for treatment of subfoveal
choroidal neovascularization (CNV). The authors report the case of an 82-year-old
woman who underwent verteporfin-mediated PDT for classic subfoveal CNV.
Fluorescein angiography performed 2 weeks after treatment disclosed reduction of 
the initial area of neovascularization and leakage by approximately 60%. Three
weeks after PDT, however, the area of leakage was almost the same size as that
before treatment. The patient underwent submacular membranectomy almost 4 weeks
after treatment. The authors describe the ultrastructural vascular changes after 
PDT and a clinicopathologic study of classic CNV. METHODS: The submacular
membrane was studied by light and electron microscopy and immunohistochemical
techniques. RESULTS: Ultrastructural examination of the peripheral vessels showed
evidence of endothelial cell degeneration with platelet aggregation and thrombus 
formation. Occasional occluded vessels were surrounded by macrophages, a
phenomenon previously reported to describe the process of resorption of such
blood vessels. The vessels in the center of the membrane were unremarkable.
CONCLUSION: Photodynamic therapy causes endothelial cell damage, thrombus
formation, and vascular occlusion of classic CNV in age-related macular
degeneration.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 11642377 [PubMed - indexed for MEDLINE]

2958: Retina. 2001;21(5):416-34.

Comment in:
    Retina. 2002 Aug;22(4):509-11; author reply 512.

Retinal angiomatous proliferation in age-related macular degeneration.

Yannuzzi LA, Negrão S, Iida T, Carvalho C, Rodriguez-Coleman H, Slakter J, Freund
KB, Sorenson J, Orlock D, Borodoker N.

LuEsther T. Mertz Retinal Research Center of Manhattan Eye, Ear and Throat
Hospital, New York, New York 10021, USA. VRMNY@aol.com

BACKGROUND: It is known that choroidal neovascularization (CNV) in age-related
macular degeneration (ARMD) may erode through the retinal pigment epithelium,
infiltrate the neurosensory retina, and communicate with the retinal circulation 
in what has been referred to as a retinal-choroidal anastomosis (RCA). This is
extremely common in the end stage of disciform disease. In recent years, the
reverse also seems to be possible, as angiomatous proliferation originates from
the retina and extends posteriorly into the subretinal space, eventually
communicating in some cases with choroidal new vessels. This form of neovascular 
ARMD, termed retinal angiomatous proliferation (RAP) in this article, can be
confused with CNV. PURPOSE: The purpose of this article is 1) to review the
clinical and angiographic characteristics of a series of patients with RAP and 2)
to propose a theoretical sequence of events that accounts for the neovascularized
process. METHODS: In this retrospective clinical and angiographic analysis, 143
eyes with RAP (108 patients) were reviewed and classified based on their
vasogenic nature and course. Clinical biomicroscopic examination, fluorescein
angiography, and indocyanine green angiography were used to evaluate patients.
RESULTS: The results of this series suggest that angiomatous proliferation within
the retina is the first manifestation of the vasogenic process in this form of
neovascular ARMD. Dilated retinal vessels and pre-, intra-, and subretinal
hemorrhages and exudate evolve, surrounding the angiomatous proliferation as the 
process extends into the deep retina and subretinal space. One or more dilated
compensatory retinal vessels perfuse and drain the neovascularization, sometimes 
forming a retinal-retinal anastomosis. Fluorescein angiography in these patients 
usually revealed indistinct staining simulating occult CNV. Indocyanine green
angiography was useful to make an accurate diagnosis in most cases. It revealed a
focal area of intense hyperfluorescence corresponding to the neovascularization
("hot spot") and other characteristic findings. Based on understanding of the
nature and progression of the neovascularized process, patients with RAP were
classified into three vasogenic stages. Stage I involved proliferation of
intraretinal capillaries originating from the deep retinal complex (intraretinal 
neovascularization [IRN]). Stage II was determined by growth of the retinal
vessels into the subretinal space (subretinal neovascularization [SRN]). Stage
III occurred when CNV could clearly be determined clinically or angiographically.
A vascularized pigment epithelial detachment and RCA were inconsistent features
of this stage. CONCLUSIONS: Retinal angiomatous proliferation appears to be a
distinct subgroup of neovascular ARMD. It may present in one of three vasogenic
stages: IRN, SRN, or CNV. Whereas ICG angiography is helpful in diagnosing RAP
and in documenting the stage of the neovascularized process, it is frequently
difficult to determine the precise nature and location of the new vessel
formation. It is important for clinicians to recognize the vasogenic potential
and the associated manifestations of this peculiar form of neovascular ARMD so
that a proper diagnosis can be made, and when possible, an appropriate management
administered.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11642370 [PubMed - indexed for MEDLINE]

2959: Acta Ophthalmol Scand. 2001 Oct;79(5):524-30.

Different clinical expressions in two families with Stargardt's macular dystrophy
(STGD1).

Eksandh L, Ekström U, Abrahamson M, Bauer B, Andréasson S.

Department of Ophthalmology, University Hospital of Lund, Sweden.
louise.eksandh@telia.com

PURPOSE: To describe the clinical expressions, with emphasis on
electrophysiological examinations, in two Swedish families with Stargardt's
macular dystrophy (STGD1). METHODS: Two pairs of siblings with STGD1, for whom
diagnosis had been confirmed by genetic linkage to the ABCA4 gene region, were
examined regarding visual acuity, kinetic perimetry, fundus photography,
full-field ERG and multifocal ERG (MERG). Possible disease-causing mutations were
screened for by DNA sequencing of selected regions of the ABCA4 gene. RESULTS:
All STGD1 patients had visual acuity 0.07-0.1. The two families presented
different fundus appearances, MERGs and implicit times on 30 Hz flicker white
light full-field ERGs. Genetic analysis revealed one unique sequence variation in
exon 19 of the ABCA4 gene, in one allele from the patients of one of the
families. This point mutation causes the amino acid substitution T972N in the
ABCR protein. CONCLUSION: Two pairs of siblings with STGD1 presented two
different expressions of the disease regarding the distribution of the retinal
dysfunction. One possible molecular explanation to the different clinical
expressions may be the T972N substitution present in the ABCR protein in one of
the STGD1 families investigated.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11594993 [PubMed - indexed for MEDLINE]

2960: Prog Retin Eye Res. 2001 Nov;20(6):705-32.

An integrated hypothesis that considers drusen as biomarkers of immune-mediated
processes at the RPE-Bruch's membrane interface in aging and age-related macular 
degeneration.

Hageman GS, Luthert PJ, Victor Chong NH, Johnson LV, Anderson DH, Mullins RF.

Department of Ophthalmology and Visual Sciences, The University of Iowa Center
for Macular Degeneration, PFP 11190E, 200 Hawkins Drive, The University of Iowa, 
Iowa City, IA 52240, USA. gregory-hageman@uiowa.edu

Age-related macular degeneration (AMD) is a blinding disease that afflicts
millions of adults in the Western world. Although it has been proposed that a
threshold event occurs during normal aging which leads to AMD, the sequelae of
biochemical, cellular, and/or molecular events leading to the development of AMD 
are poorly understood. Although available data provide strong evidence that a
significant proportion of AMD has a genetic basis, no gene(s) has yet been
identified that causes a significant proportion of AMD. Moreover, no major
molecular pathways involved in the etiology of this disease have been
elucidated.Drusen, pathological deposits that form between the retinal pigmented 
epithelium (RPE) and Bruch's membrane, are significant risk factors for the
development of AMD. In our view, the development of testable new hypotheses of
drusen origins has been hindered significantly by the absence of a comprehensive 
profile of their molecular composition. In this review, we describe an integrated
ultrastructural, histochemical, molecular biological, and biochemical approach to
identify specific molecular pathways associated with drusen biogenesis. The
implicit assumption underlying these recent investigations has been that a
thorough understanding of the composition of drusen and source(s) of
drusen-associated material is likely to provide fresh insight into the
pathobiology underlying AMD. Significantly, these studies have revealed that
proteins associated with inflammation and immune-mediated processes are prevalent
among drusen-associated constituents. Transcripts that encode a number of these
molecules have been detected in retinal, RPE, and choroidal cells. These data
have also lead to the observations that dendritic cells, potent
antigen-presenting cells, are intimately associated with drusen development and
that complement activation is a key pathway that is active both within drusen and
along the RPE-choroid interface.We propose herein a unifying hypothesis of drusen
biogenesis that attempts to incorporate a large body of new and previously
published structural, histochemical, and molecular data pertaining to drusen
composition and development. This theory is put forth with the acknowledgment
that numerous AMD genotypes may exist. Thus, only some aspects of the proposed
hypothesis may be involved in any given AMD genotype. Importantly, this
hypothesis invokes, for the first time, the potential for a direct role of cell- 
and immune-mediated processes in drusen biogenesis.We acknowledge that the
proposed hypothesis clearly represents a paradigm shift in our conceptualization 
pertaining to pathways that participate in the development of drusen and
age-related macular degeneration. It is our hope that other investigators will
test, validate and/or refute various aspects of this hypothesis, and in so doing,
increase our overall understanding of the biological pathways associated with
early AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.
    Review

PMID: 11587915 [PubMed - indexed for MEDLINE]

2961: Optom Vis Sci. 2001 Sep;78(9):683-8.

Improvements in measures of vision and self-reported visual function after
cataract extraction in patients with late-stage age-related maculopathy.

Mallah MK, Hart PM, McClure M, Stevenson MR, Silvestri G, White ST, Chakravarthy 
U.

Ophthalmology and Vision Science, Royal Victoria Hospital and Queen's University 
of Belfast, United Kingdom.

PURPOSE: A recent study indicated that patients with cataracts and early
age-related maculopathy may benefit from cataract extraction. To ascertain
whether cataract extraction in the presence of concurrent advanced age-related
maculopathy was also associated with a clear benefit, we studied visual function 
and self-reported visual functioning in a cohort of 12 patients pre- and
post-phakoemulsification. METHODS. All 12 patients had a diagnosis of advanced
age-related maculopathy in the eye scheduled for cataract surgery. Preoperative
assessment included refraction and recording of best corrected distance and near 
acuity and contrast sensitivity in both eyes. The Daily Living Tasks Dependent on
Vision questionnaire was administered. After phakoemulsification and intraocular 
lens implantation, all patients were reviewed and assessed. RESULTS: After
surgery, improvement in acuity was recorded in nine operated eyes, whereas acuity
remained unchanged in three eyes. Improvement in contrast sensitivity in the
operated eye occurred in 10 patients, but in two patients contrast was reduced
postoperatively. In terms of self-reported visual functioning, improvement in the
ability to undertake many daily living tasks dependent on vision was recorded
after cataract surgery. CONCLUSIONS: Significant improvements in specific areas
of self-reported visual functioning and measures of vision were recorded after
cataract surgery. During the follow-up period, none of the operated eyes suffered
a fall in visual acuity. There was also no evidence of worsening of the
pre-existing macular lesion as judged by clinical examination and fundus
photography.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11587203 [PubMed - indexed for MEDLINE]

2962: Graefes Arch Clin Exp Ophthalmol. 2001 Aug;239(8):556-61.

Comparison of different high resolution multifocal electroretinogram recordings
in patients with age-related maculopathy.

Heinemann-Vernaleken B, Palmowski AM, Allgayer R, Ruprecht KW.

Universitäts-Augenklinik, Homburg/Saar, Germany. aubhei@med-rz.uni-sb.de

AIM: to compare two different resolutions of multifocal electroretinogram
recordings (MF-ERG) in patients with age-related macular degeneration (AMD).
PATIENTS AND METHODS: in 20 eyes (14 patients) with early or late stages of AMD, 
MF-ERGs of 8 min duration were recorded using a low and a high resolution. The
central 50 degrees of the retina were stimulated by 103 as well as by 241
stimulus elements. Results were compared with one another and with an age-matched
control group. RESULTS: when response averages of equal eccentricity were
analysed, amplitudes of the MF-ERG differed significantly from normal within the 
central 40 degrees. This held true for both low (103) and high (241) resolutions.
Sixteen of 20 eyes also showed focal retinal dysfunction at both resolutions. In 
one case, the high resolution MF-ERGs could detect functional deficits that could
not be seen with the lower resolution. However, due to a reduced signal-to-noise 
ratio three high resolution recordings could not be analysed. CONCLUSION: high
resolution MF-ERG seems more sensitive than low resolution MF-ERG. However, the
low resolution (103) MF-ERG is recommended for routine application in the clinic 
because of its better signal-to-noise ratio.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 11585310 [PubMed - indexed for MEDLINE]

2963: Jpn J Ophthalmol. 2001 Sep-Oct;45(5):533-7.

Adult-onset foveomacular vitelliform dystrophy with retinal folds.

Yamaguchi K, Yoshida M, Kano T, Itabashi T, Yoshioka Y, Tamai M.

Department of Ophthalmology, Tohoku University School of Medicine, Sendai,
Miyagi-ken, Japan.

BACKGROUND: Adult-onset foveomacular vitelliform dystrophy is characterized by a 
solitary, oval, slightly elevated, yellowish subretinal lesion of the fovea. We
examined a patient with adult-onset foveomacular vitelliform dystrophy with
stellate retinal folds by optical coherence tomography and scanning laser
ophthalomoscopy. CASE: A 58-year-old Japanese woman with a complaint of decreased
vision in her right eye was diagnosed as having adult-onset foveomacular
vitelliform dystrophy. OBSERVATIONS: Ophthalmoscopic examination revealed a
yellowish lesion of one-third disc diameter in size at the fovea in the right
eye. Fluorescein angiography demonstrated an irregular block of choroidal
fluorescence corresponding to the yellowish lesion, which was surrounded by
stellate retinal folds. Optical coherence tomography images showed a steep
elevation of the retinal pigment epithelium (RPE) as a focally protruded
reflective band over an optically clear space. Scanning laser ophthalmoscopy
provided morphologic enhancement in the specifically affected layers of the
macula. Using an argon green laser, band-shaped bright reflexes were seen in the 
right fovea. The helium-neon laser revealed a bright patch corresponding to the
yellowish lesion over the fovea, which was surrounded by stellate retinal folds. 
The diode laser revealed a bright patch corresponding to the yellowish lesion.
CONCLUSION: The stellate retinal folds of this patient were considered to be
caused by the steep elevation of the RPE with an extracellular accumulation of
the vitelliform deposits.

Publication Types: 
    Case Reports

PMID: 11583679 [PubMed - indexed for MEDLINE]

2964: Invest Ophthalmol Vis Sci. 2001 Oct;42(11):2652-63.

A novel gene for autosomal dominant Stargardt-like macular dystrophy with
homology to the SUR4 protein family.

Edwards AO, Donoso LA, Ritter R 3rd.

Department of Ophthalmology, University of Texas Southwestern Medical Center,
Dallas, TX 75390-9057, USA. albert.edwards@utsouthwestern.edu

PURPOSE: To describe a novel gene causing a Stargardt-like phenotype in a family 
with dominant macular dystrophy and the exclusion of all known genes within the
disease locus. METHODS: Meiotic breakpoint mapping in a family of 2314
individuals enabled refinement of the location of the disease gene. The genomic
organization and expression profile of known and putative genes within the
critical region were determined using bioinformatics, cDNA cloning, and RT-PCR.
The coding sequence of genes expressed within the retina was scanned for
mutations, by using DNA sequencing. RESULTS: The disease-causing gene (STGD3) was
further localized to 562 kb on chromosome 6 between D6S460 and a new polymorphic 
marker centromeric to D6S1707. Of the four genes identified within this region,
all were expressed in the retina or retinal pigment epithelium. The only coding
DNA sequence variant identified in these four genes was a 5-bp deletion in exon 6
of ELOVL4. The deletion is predicted to lead to a truncated protein with a net
loss of 44 amino acids, including a dilysine endoplasmic reticulum retention
motif. The ELOVL4 gene is the fourth known example of a predicted human protein
with homology to mammalian and yeast enzymes involved in the membrane-bound fatty
acid chain elongation system. The genomic organization of ELOVL4 and primer sets 
for exon amplification are presented. CONCLUSIONS: ELOVL4 causes macular
dystrophy in this large family distributed throughout North America and
implicates fatty acid biosynthesis in the pathogenesis of macular degeneration.
The PCR-based assay for the 5-bp deletion will facilitate more accurate genetic
counseling and identification of other branches of the family.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11581213 [PubMed - indexed for MEDLINE]

2965: Ophthalmology. 2001 Oct;108(10):1893-900; discussion 1900-1.

Depression, visual acuity, comorbidity, and disability associated with
age-related macular degeneration.

Brody BL, Gamst AC, Williams RA, Smith AR, Lau PW, Dolnak D, Rapaport MH, Kaplan 
RM, Brown SI.

Department of Ophthalmology, University of California, San Diego, La Jolla,
California 92093-0946, USA.

OBJECTIVE: To examine (1) the prevalence of depressive disorders in
community-dwelling adults with advanced age-related macular degeneration (AMD)
and (2) the relationship in this population between depression, visual acuity,
the number of comorbid medical conditions, disability caused by vision loss as
measured by the National Eye Institute-Vision Function Questionnaire (NEI-VFQ)
and the vision-specific Sickness Impact Profile (SIPV), and disability caused by 
overall health status as measured by the Sickness Impact Profile-68 (SIP).
DESIGN: Analysis of cross-sectional baseline data from a randomized clinical
trial. PARTICIPANTS: Participants were 151 adults aged 60 and older (mean age, 80
years) with advanced macular degeneration whose vision was 20/60 or worse in
their better eye. METHODS: Subjects were interviewed using measures of
depression, disability, and chronic medical conditions. Visual acuity was
obtained. Nonparametric correlation analyses and linear regression analyses were 
performed. MAIN OUTCOME MEASURES: Structured Clinical Interview for DSM-IV
(SCID-IV), Geriatric Depression Scale (GDS), NEI-VFQ, SIPV, and SIP. RESULTS: Of 
the participants, 32.5% (n = 49) met SCID-IV criteria for depressive disorder,
twice the rate observed in previous studies of community-dwelling elderly. Over
and above depression (GDS), visual acuity aided in prediction of the level of
vision-specific disability (NEI-VFQ and SIPV). CONCLUSIONS: Depressive disorder
is a significant problem for the elderly afflicted with advanced macular
degeneration. Further research on psychopharmacologic and psychotherapeutic
interventions for depressed AMD patients is warranted to improve depression and
enhance functioning. Over and above depression, visual acuity aided in predicting
vision-specific disability. Treatment strategies that teach patients to cope with
vision loss should be developed and evaluated.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, U.S. Gov't, P.H.S.

PMID: 11581068 [PubMed - indexed for MEDLINE]

2966: Surv Ophthalmol. 2001 Sep-Oct;46(2):149-63.

Autosomal dominant Stargardt-like macular dystrophy.

Donoso LA, Edwards AO, Frost A, Vrabec T, Stone EM, Hageman GS, Perski T.

Henry and Corinne Bower Laboratory for Macular Degeneration, Eye Research
Institute, Wills Eye Hospital, Philadelphia, PA 19107, USA.
ldonoso@vision-research.org

Autosomal dominant Stargardt-like macular dystrophy is one of the early onset
macular dystrophies. It is characterized clinically in its early stages by visual
loss and by the presence of atrophic macular changes with or without the presence
of yellowish flecks. It is an important retinal dystrophy to study, not only
because it has implications in the care and treatment of patients with the
condition, but because it also provides important information regarding retinal
function. Review of the literature suggests that many of the reported families
are linked to chromosome 6q. Genetic and genealogical evidence suggests that
these families have descended from a common ancestor or founder. The recent
identification of a disease-causing gene that is involved in fatty acid
metabolism may have implications in the study of the more common age-related
macular degeneration. We review the recent clinical, genetic, and genealogical
aspects of autosomal dominant Stargardt-like macular dystrophy.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.
    Review

PMID: 11578648 [PubMed - indexed for MEDLINE]

2967: Arch Ophthalmol. 2001 Sep;119(9):1354-9.

Medication use and the 5-year incidence of early age-related maculopathy: the
Beaver Dam Eye Study.

Klein R, Klein BE, Jensen SC, Cruickshanks KJ, Lee KE, Danforth LG, Tomany SC.

Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison,
610 N Walnut St, 460 WARF, Madison, WI 53705-2397, USA.

OBJECTIVE: To evaluate incident early age-related maculopathy (ARM) after a
5-year interval with respect to medication use. DESIGN: Population-based
incidence study. SETTING: Participants were adults aged 43 to 86 years living in 
Beaver Dam, Wis, when first examined in 1988-1990 (n = 4926); they were
reexamined in 1993-1995 (n = 3684). METHODS: All participants were examined and
interviewed and stereoscopic color fundus photographs were taken. All procedures 
were done by standard protocol at both examinations. Incidence of ARM was based
on grading using the Wisconsin ARM Grading System. All prescribed and
over-the-counter medications in current use were brought to the examination site 
and the names were recorded at that time. RESULTS: There were 678 drug
preparations (active ingredients) being used at the baseline examination. No
relations were found between most antihypertensive drugs, most central nervous
system medications, aspirin and other nonsteroidal anti-inflammatory agents,
estrogens, lipid-lowering agents, and incident early ARM over the 5-year period. 
Age- and sex-adjusted logistic regression analyses suggested possible
associations (P<.10) between the use of phenothiazine antidopaminergics (odds
ratio [OR], 2.83; 95% confidence interval [CI], 0.97-8.23; P =.06), desiccated
thyroid hormones (OR, 2.32; 95% CI, 0.89-6.07; P =.09), and calcium channel
blockers (OR, 1.70; 95% CI, 0.93-3.12; P =.08) with incident ARM. When additional
information on past use was included in the regression model, the association
remained for calcium channel blockers, but not for phenothiazines and desiccated 
thyroid hormones. A lower incidence of early ARM occurred in those who took
antidepressants (OR, 0.34; 95% CI, 0.12-0.94; P =.04) at the baseline
examination. CONCLUSION: Although many different medications were being used at
the baseline examination in the Beaver Dam Eye Study cohort, there were no
striking associations with the 5-year incidence of early ARM.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11545642 [PubMed - indexed for MEDLINE]

2968: Arch Ophthalmol. 2001 Sep;119(9):1287-90.

Comment in:
    Arch Ophthalmol. 2002 May;120(5):673-4; author reply 674-5.

Optical coherence tomography demonstrates subretinal macular edema from
papilledema.

Hoye VJ 3rd, Berrocal AM, Hedges TR 3rd, Amaro-Quireza ML.

Department of Ophthalmology, Tufts University School of Medicine, Boston, MA,
USA.

OBJECTIVE: To evaluate macular changes in eyes with papilledema from increased
intracranial pressure using optical coherence tomography (OCT). METHODS:
Fifty-five patients with papilledema seen during 1998 and 1999 were studied with 
OCT of the optic nerve and retinal nerve fiber layer. Nineteen of these also had 
OCT of the macula during periods of acute, subacute, or recurrent papilledema and
were evaluated in detail for this report. RESULTS: Seven patients had OCT
evidence of subretinal fluid involving the macula. All had some reduction in
visual acuity. The subretinal fluid appeared to arise from the peripapillary
region, and all showed some improvement in central vision as the fluid resolved. 
CONCLUSIONS: Subretinal fluid accumulations can cause decreased visual acuity in 
patients with papilledema. Optical coherence tomography can demonstrate
subretinal fluid and can be used to follow the course of this important visual
complication of papilledema.

Publication Types: 
    Case Reports

PMID: 11545633 [PubMed - indexed for MEDLINE]

2969: Arch Ophthalmol. 2001 Sep;119(9):1259-65.

Body mass index and the incidence of visually significant age-related maculopathy
in men.

Schaumberg DA, Christen WG, Hankinson SE, Glynn RJ.

Division of Preventive Medicine, Brigham and Women's Hospital, 900 Commonwealth
Ave E, Boston, MA 02215, USA. dschaumberg@rics.bwh.harvard.edu

BACKGROUND: Reports have suggested relationships of body weight with age-related 
maculopathy (ARM), particularly its nonneovascular (dry) forms, but results are
inconsistent and prospective data are scarce. OBJECTIVE: To examine prospectively
relationships of body mass index (BMI; calculated as weight in kilograms divided 
by the square of height in meters) with visually significant dry and neovascular 
ARM during an average of 14.5 years of follow-up. METHODS: Incident ARM was
assessed by medical record confirmation of self-reported ARM among the 21 121 men
participating in the Physicians' Health Study who (1) were followed up for at
least 7 years, (2) were free of visually significant ARM at baseline, and (3) had
information on BMI and cigarette smoking. We used proportional hazards regression
models to estimate rate ratios (RRs) and 95% confidence intervals (CIs) for
visually significant dry ARM (256 cases) and neovascular ARM (84 cases) within 4 
categories of BMI: lean (< 22.0), normal (22.0-24.9), overweight (25.0-29.9), and
obese (> or = 30.0). RESULTS: Adjusting for age, randomized aspirin and beta
carotene assignments, and cigarette smoking, the incidence for visually
significant dry ARM was lowest in men with a normal BMI. Compared with these men,
the RRs (95% CIs) were as follows: 1.43 (1.01-2.04) for lean, 1.24 (0.93-1.66)
for overweight, and 2.15 (1.35-3.45) for obese men. Although there was no
significant relationship of BMI with the diagnosis of neovascular ARM, due to the
small number of cases these analyses could not rule out an important
relationship. CONCLUSIONS: Obesity is a risk factor for visually significant ARM 
in men, in particular for dry ARM. However, the relationship of BMI with dry ARM 
appears to be J-shaped, and the leanest individuals also appear to be at
increased risk.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 11545630 [PubMed - indexed for MEDLINE]

2970: Br J Ophthalmol. 2001 Oct;85(10):1153-7.

Prevalence of age related maculopathy in a representative Japanese population:
the Hisayama study.

Oshima Y, Ishibashi T, Murata T, Tahara Y, Kiyohara Y, Kubota T.

Department of Ophthalmology, Faculty of Medicine, Kyushu University, Fukuoka,
Japan.

AIM: To determine the prevalence of age related maculopathy (ARM) in a
representative older Japanese population. METHODS: 1486 residents of Hisayama
town, Fukuoka, Japan, aged 50 years or older were examined and the presence of
ARM was determined by grading from fundus examination by indirect ophthalmoscope,
slit lamp, and colour fundus photographs. RESULTS: The prevalence rate of drusen,
which occurred with comparable frequency in men and women, was 9.6%. The
frequency of drusen increased with age (p <0.01). Hyperpigmentation and/or
hypopigmentation of the retina was present in 3.2%, geographic atrophy in 0.2%,
and neovascular age related macular degeneration in 0.67%. The frequency of
neovascular age related macular degeneration was significantly higher in the men 
(1.2% v. 0.34%, p <0.01). CONCLUSIONS: Early and late stage ARM is less common
among Japanese people than among white people in Western countries, while late
stage ARM is more common among Japanese than among black people.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11567955 [PubMed - indexed for MEDLINE]

2971: J Cataract Refract Surg. 2001 Sep;27(9):1397-401.

Latanoprost and cystoid macular edema in high-risk aphakic or pseudophakic eyes.

Wand M, Gaudio AR, Shields MB.

Hartford Hospital, Hartford, Connecticut, USA.

PURPOSE: To determine the magnitude of the association between latanoprost use
and cystoid macular edema (CME) in high-risk aphakic or pseudophakic eyes.
SETTING: Single referral glaucoma practice. METHODS: In a referral glaucoma
practice, 40 consecutive patients with glaucoma uncontrolled on maximally
tolerated medications without latanoprost were studied. Seven eyes were aphakic, 
and 33 eyes were pseudophakic. All eyes had an absent or open posterior capsule, 
and 29 eyes had 1 or more additional risk factors for developing CME. Latanoprost
0.005%, 1 drop at bedtime, was added to the patients' current regimen. Patients
were instructed to check their vision in the treated eye daily at home and to
report any perceived decrease promptly. Patients without a change in vision or
other side effects were reexamined 1 month after initiating latanoprost and every
3 months thereafter. If there was a greater than 1 line decrease in visual
acuity, a retinal evaluation and fundus fluorescein angiography (FFA) were
performed by a retina specialist. RESULTS: Two eyes had to discontinue
latanoprost because of side effects before the 1 month visit. They were excluded 
from the analysis. At the 1 month follow-up, the mean intraocular pressure was
18.2 mm Hg +/- 6.5 (SD), a decrease from the pretreatment mean of 21.5 +/- 5.7 mm
Hg. The visual acuity was within 1 line of baseline in 36 eyes and decreased by 2
lines in 2 eyes. In these 2 eyes, symptomatic CME was documented by FFA. The CME 
clinically resolved, with visual acuity returning to baseline after the
latanoprost was discontinued and a nonsteroidal antiinflammatory drug started.
There were no additional cases of CME after a mean follow-up of 5.7 months.
CONCLUSION: Approximately 5% of high-risk eyes treated with latanoprost developed
clinically symptomatic and angiographically documented CME. The temporal
relationship between initiation of treatment and the decreased vision in our 2
cases suggests but does not establish a causal relationship between CME and
latanoprost. With appropriate informed consent and attentive follow-up,
clinicians should not be deterred from using this important glaucoma medication.

PMID: 11566522 [PubMed - indexed for MEDLINE]

2972: Arch Biochem Biophys. 2001 Oct 1;394(1):111-6.

Cytochrome c oxidase inhibition by N-retinyl-N-retinylidene ethanolamine, a
compound suspected to cause age-related macula degeneration.

Shaban H, Gazzotti P, Richter C.

Institute of Biochemistry, Swiss Federal Institute of Technology (ETH),
Universitätstr. 16, Zurich, CH-8092, Switzerland.

The endogenous lipophilic and cationic compound N-retinyl-N-retinylidene
ethanolamine (A2E) is suspected to cause age-related macula degeneration. It
inhibits cytochrome c oxidase, detaches proapoptotic proteins from mitochondria, 
and induces apoptosis in mammalian retinal pigment epithelial cells (M. Suter, C.
E. Remé, C. Grimm, A. Wenzel, M. Jäättela, P. Esser, N. Kociok, M. Leist, and C. 
Richter, 2000, J. Biol. Chem. 275, 39625-39630). The inhibition of cytochrome c
oxidase is highly specific for A2E and is observed with the solubilized and
reconstituted enzyme. In the dark, inhibition is overcome by cardiolipin or other
acidic phospholipids. With illumination, inhibition is stronger, becomes complete
with prolonged exposure, and is then no longer abrogated by cardiolipin.
Cardiolipin effectively displaces A2E from cytochrome c oxidase, suggesting
noncovalent binding of A2E to the enzyme. We conclude that A2E is a potent
cytochrome c oxidase-specific inhibitor which interferes with the binding of
cytochrome c to cytochrome c oxidase and, in the light, causes persistent
modifications of the enzyme. Copyright 2001 Academic Press.

PMID: 11566033 [PubMed - indexed for MEDLINE]

2973: Ophthalmic Surg Lasers. 2001 Sep-Oct;32(5):397-405.

Efficacy of various laser wavelengths in the treatment of clinically significant 
macular edema in diabetics.

Gupta V, Gupta A, Kaur R, Narang S, Dogra MR.

Department of Ophthalmology, Postgraduate Institute of Medical Education and
Research, Chandigarh, India.

BACKGROUND AND OBJECTIVE: To compare various laser wavelengths: argon green (514 
nm), vs krypton red (647 nm), vs frequency doubled Nd:YAG (532 nm), and vs diode 
(810 nm), for laser photocoagulation treatment in clinically significant macular 
edema (CSME) in diabetics. PATIENTS AND METHODS: Four different wavelengths were 
used to sequentially treat 271 eyes of 164 diabetic patients with CSME. Follow up
was conducted for a minimum of 6 months (9.8 +/- 1.3 months). Retreatment was
performed if residual edema involving the foveal avascular zone persisted at 3
months. RESULTS: Reduction/elimination of CSME was observed in 93.3% of
argon-treated eyes, 88.5% in krypton red group, 92.9% with frequency doubled
Nd:YAG, and 84.8% with diode laser with no statistically significant difference
between the groups (P > 0.05 for all groups). The number of eyes requiring
retreatment was highest with the diode laser having 44.3% of eyes requiring
retreatment and least with frequency doubled Nd:YAG having only 15.5% of eyes
requiring retreatment (P = 0.0002). CONCLUSIONS: All lasers are equally effective
in reducing/eliminating CSME. However, Nd:YAG may have an advantage because of
requiring fewer retreatments.

Publication Types: 
    Case Reports
    Comparative Study

PMID: 11563784 [PubMed - indexed for MEDLINE]

2974: Doc Ophthalmol. 2001 May;102(3):237-50.

Diagnosis and classification of macular degenerations: an approach based on
retinal function testing.

Scullica L, Falsini B.

Istituto di Oftalmologia, Universita' Cattolica del S. Cuore, Rome, Italy.

The results from literature concerning some aspects of retinal function in
macular degenerations (MDs) were reviewed in order to evaluate whether (a)
specific patterns of retinal dysfunction may be linked to different clinical
phenotypes, and (b) distinct functional profiles may help in orienting molecular 
diagnosis of diseases. Examined clinical phenotypes included: Stargardt
disease/fundus flavimaculatus (St/FF), age-related maculopathy (ARM) and macular 
degeneration (AMD), pattern dystrophies (PD), Best vitelliform dystrophy (BVD),
Sorsby's fundus dystrophy (SFD), autosomal cone-rod dystrophies (CRD). The
following functional tests were evaluated: (1) electroretinogram (ERG) (scotopic 
and photopic according to ISCEV standards, rod and cone photoresponses, rod and
cone b-wave intensity-response function, focal ERGs); (2) dark adaptometry
(pre-bleach sensitivity and post-bleach recovery kinetics); (3) fundus
reflectometry (pigment density and regeneration kinetics). Specific patterns of
retinal dysfunction were identified for St/FF, ARM/AMD, SFD and BVD, whereas
partially overlapping profiles were found for PD and CRD. Specific functional
patterns were associated with different peripherin/RDS gene mutations, as well as
with CRX mutations. Combined analysis of different retinal function tests may
help to identify different phenotypes of MD, and to orient molecular diagnosis
for selected genotypes.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 11556487 [PubMed - indexed for MEDLINE]

2975: Doc Ophthalmol. 2001 May;102(3):197-236.

Genotype-phenotype correlations and differential diagnosis in autosomal dominant 
macular disease.

Iannaccone A.

Retinal Degeneration Research Center, Department of Ophthalmology, University of 
Tennessee, Memphis, USA. iannacca@mail.eye.utmem.edu

In the past few years, great progress has been made in the understanding of
macular diseases. A number of disease-causing genes have been cloned, and
numerous loci for other conditions have been mapped. The purpose of this article 
is to provide an overview of the current understanding of the genotype-phenotype 
correlations in autosomal dominant macular diseases with an emphasis on
differential diagnostic issues. Whenever possible, the molecular correlates have 
been reviewed and the implications for age-related macular degeneration have been
discussed. The many similarities of these diseases to age-related macular
degeneration of the atrophic or exudative type, which can be misleading in
elderly subjects, have also been addressed. While some conditions yield disease
truly confined to the macula, others show widespread retinal involvement on
functional testing. Clear-cut genotype-phenotype correlations are possible only
for some forms of macular diseases. To further complicate the diagnostic process,
there is a considerable degree of clinical overlap between many of them, making
the differential diagnostic process potentially challenging. Functional testing, 
careful assessment of family history and extensive family work-up are essential
in differentiating at the clinical level most, but not all, of these disease
entities. Awareness of all of these conditions is required to direct correctly
diagnostic investigations, to formulate an accurate prognosis, and for proper
genetic counseling.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 11556486 [PubMed - indexed for MEDLINE]

2976: Doc Ophthalmol. 2001 May;102(3):165-77.

Molecular genetics of macular degeneration.

Musarella MA.

Long Island College Hospital, Department of Ophthalmology, Brooklyn, NY 11231,
USA. mariaeyes2@aol.com

Macular degeneration is a leading cause of blindness that affects the aged
population. The complexity of the molecular basis of macular disease is now
beginning to be elucidated with the identification of disease-causing genes. For 
example, mutations in the ABCR gene, (recently identified in cones as well) which
codes for retinal rod-specific ABCR protein is responsible for Stargardt macular 
dystrophy/fundus flavimaculatus, an autosomal recessive macular dystrophy with
juvenile onset, which accounts for 7% of human retinal degenerative diseases. The
gene mutant in X-linked juvenile retinoschisis, XLRS1, is the first macular
dystrophy gene to be isolated by positional cloning. Mutations in the
peripherin/RDS gene have been shown to be associated with a variety of distinct
forms of macular degenerations. The tissue inhibitor of metalloproteinase 3
(TIMP3) is implicated in autosomal dominant Sorsby fundus dystrophy. Best
vitelliform macular dystrophy was mapped to 11q12-q13. The cloned gene product is
the protein bestrophin, which is a retinal specific gene expressed in the RPE and
possibly involved in the metabolism and transport of polyunsaturated fatty acids.
The cloning of genes for rare heritable forms of macular degeneration will
increase our understanding of the basic pathogenesis of the disease process. In
the future this should also allow us to test the hypothesis that the coincidence 
of subclinical mutations in a number of genes involved in the formation and
function of the macula can be responsible for cases of age-related
macula-degeneration which is by far the most common form of these macular
disorders.

Publication Types: 
    Review

PMID: 11556484 [PubMed - indexed for MEDLINE]

2977: J Am Geriatr Soc. 2001 Aug;49(8):1097-100.

Neuroticism predicts depression and disability in age-related macular
degeneration.

Rovner BW, Casten RJ.

Department of Psychiatry and Human Behavior, Jefferson Medical College,
Philadelphia, Pennsylvania, USA.

OBJECTIVES: Age-related macular degeneration (AMD) is a common, disabling
disorder of older age that is associated with depression. We investigated the
incidence rate of depression and its risk factors and consequences in this
6-month longitudinal study. DESIGN: A prospective cohort study in which subjects 
were interviewed 6 weeks after the onset of bilateral vision loss and 6 months
later. SETTING: The sample was recruited from the retinovascular clinic of a
specialty eye hospital. PARTICIPANTS: Subjects were 51 patients with new onset
bilateral AMD. MEASUREMENTS: We assessed depressive symptoms, personality traits,
visual acuity, and vision and physical functioning. Additionally, we interviewed 
informants to obtain independent assessments of subjects' personality traits.
RESULTS: The baseline prevalence rate of syndromal depression was 23.5% and high 
levels of depressive symptoms persisted over time. The 6-month incidence rate of 
depression was 27.8%. The strongest risk factors for incident depression were
self-rated and informant-rated neuroticism. Patients who developed syndromal
depression were 8.3 times (95% confidence interval = 1.1-63.4) more likely than
nondepressed patients to become disabled in vision function, independent of
change in visual acuity. CONCLUSION: AMD is associated with high rates of
depression and visual disability independent of severity of vision loss. The
personality trait of neuroticism is highly predictive of incident depression and 
identifies patients at high risk for excess disability. Psychotherapeutic
treatments targeted to this group may prevent depression and reduce disability.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11555073 [PubMed - indexed for MEDLINE]

2978: Am J Ophthalmol. 2001 Sep;132(3):458-61.

Corrected and republished from:
    Am J Ophthalmol. 2001 Jul;132(1):81-4.

Optical coherence tomography of tractional macular elevations in eyes with
proliferative diabetic retinopathy.

Imai M, Iijima H, Hanada N.

Department of Ophthalmology, Yamanashi Medical University, Tamaho, Yamanashi
409-3898, Japan. mimai@res.yamanashi-med.ac.jp

PURPOSE: To document the findings of optical coherence tomography in eyes with
tractional macular elevation associated with proliferative diabetic retinopathy, 
paying special attention to differentiating between tractional retinal detachment
and retinoschisis. DESIGN: Observational case series. METHODS: We retrospectively
reviewed images of optical coherence tomography obtained from 17 consecutive eyes
(17 patients) with proliferative diabetic retinopathy without vitreous opacity
and showing tractional macular elevation with or without foveal involvement.
RESULTS: Tractional retinal detachment and retinoschisis could be differentiated 
in the cross-sectional images of optical coherence tomography. Retinoschisis with
or without associated retinal detachment was observed in 16 of 17 eyes (94%),
whereas retinal detachment was observed in only six of 17 eyes (35%). Five eyes
showed both findings of retinal detachment and retinoschisis. CONCLUSIONS:
Optical coherence tomography is useful for distinguishing tractional
retinoschisis from retinal detachment in eyes with proliferative diabetic
retinopathy and macular elevation. Tractional retinoschisis with or without
retinal detachment is the most frequent pattern of tractional macular elevation
in eyes with proliferative diabetic retinopathy.

Publication Types: 
    Corrected and Republished Article

PMID: 11530091 [PubMed - indexed for MEDLINE]

2979: Am J Ophthalmol. 2001 Sep;132(3):437-9.

Role of Fas-ligand in age-related maculopathy not established.

Lambooij AC, Kliffen M, Mooy CM, Kuijpers RW.

Department of Ophthalmology, Erasmus University Rotterdam, PO Box 1738, 3000 DR
Rotterdam, The Netherlands. lambooij@gen.fgg.eur.nl

PURPOSE: Fas-ligand expression on retinal pigment epithelium is hypothesized to
have an inhibitory effect on human ocular neovascularization. METHODS: We studied
Fas-ligand expression in the aging retinal pigment epithelium and in early and
late stages of age-related maculopathy. Immunohistochemistry with antibodies
against Fas-ligand was performed on paraffin-embedded sections of 23 human eye
bank eyes (aged 45 to 96 years) and 12 eyes with exudative age-related
maculopathy. RESULTS: Fas-ligand expression in retinal pigment epithelium was not
related to age or to the presence of early age-related maculopathy. Furthermore, 
Fas-ligand expression in retinal pigment epithelium was similar in subretinal and
subretinal pigment epithelium choroidal neovascular membranes. CONCLUSION: It
appears to be unlikely that Fas-ligand expressed on retinal pigment epithelium
controls the extension of choroidal neovascular membranes from subretinal pigment
epithelium to subretinal.

PMID: 11530074 [PubMed - indexed for MEDLINE]

2980: Am J Ophthalmol. 2001 Sep;132(3):425-7.

Intraocular injection of crystalline cortisone as adjunctive treatment of
diabetic macular edema.

Jonas JB, Söfker A.

Department of Ophthalmology and Eye Hospital, Faculty of Clinical Medicine
Mannheim, University of Heidelberg, Heidelberg, Germany.
Jost.Jonas@augen.ma.uni-heidelberg.de

PURPOSE: To report the clinical outcome of a diabetic patient with macular edema 
treated with an intravitreal injection of crystalline cortisone. METHODS:
Interventional case report. A 73-year-old patient with diabetes mellitus
presented with clinically significant diffuse macular edema caused by
nonproliferative diabetic retinopathy. Despite grid laser coagulation in the
macular region, cystoid macular edema progressed, and within 6 months before the 
cortisone injection, visual acuity declined from 0.25 to 0.16 and, finally, to
0.10. The patient received a single intravitreal injection of triamcinolone
acetonide with topical anesthesia. RESULTS: After the intravitreal injection of
triamcinolone acetonide, visual acuity improved from 0.10 to 0.40 during the
follow-up period spanning 5 months. Intraocular pressure increased to values up
to 30 mm Hg before antiglaucomatous treatment. CONCLUSION: Intravitreal injection
of triamcinolone acetonide may be useful for treatment of diabetic macular edema 
resistant to conventional therapy.

Publication Types: 
    Case Reports

PMID: 11530068 [PubMed - indexed for MEDLINE]

2981: Am J Ophthalmol. 2001 Sep;132(3):369-77.

Vitrectomy for diabetic macular edema: the role of posterior vitreous detachment 
and epimacular membrane.

Yamamoto T, Akabane N, Takeuchi S.

Department of Ophthalmology, Toho University Sakura Hospital, 564-1 Shimoshizu,
Sakura, Chiba 2858741, Japan. sakteiko@med.toho-u.ac.jp

PURPOSE: To evaluate the surgical efficacy of pars plana vitrectomy on eyes with 
diabetic macular edema in the presence or absence of a complete posterior
vitreous detachment and with or without an epimacular membrane. METHODS: Pars
plana vitrectomy was performed on 30 eyes of 29 cases with diabetic macular
edema. Visual acuity was measured, and retinal thickness was determined by
optical coherence tomography before and after vitrectomy. To evaluate the
relationship between the effects of vitrectomy and the presence or absence of
posterior vitreous detachment and/or epimacular membrane, all eyes were placed
into one of four groups: group A, eyes with posterior vitreous detachment and
epimacular membrane; B, eyes with posterior vitreous detachment and without
epimacular membrane; C, eyes without posterior vitreous detachment and with
epimacular membrane; and D, eyes without posterior vitreous detachment and
without epimacular membrane. The expression of vascular endothelial growth factor
and interleukin-6 was investigated immunohistochemically in epimacular membrane
specimens obtained from seven eyes with diffuse diabetic macular edema. RESULTS: 
The postoperative mean visual acuity (0.653 +/- 0.350: mean +/- SD logarithm of
minimal angle of resolution [logMAR]) was significantly better than the mean
preoperative visual acuity (0.891 +/- 0.319 logMAR; Wilcoxon signed-rank test, P 
=.0007). The postoperative foveal thickness (264.5 +/- 118.6 microm) was
significantly thinner than the preoperative foveal thickness (477.8 +/- 147.7
microm; Wilcoxon signed-rank test, P <.0001). There were no significant
differences in the improvement of visual acuity and decrease of foveal thickness 
between the four groups (Kruskal-Wallis test, P =.13, P =.65, respectively). All 
of the epimacular membranes obtained at surgery expressed vascular endothelial
growth factor and interleukin-6. CONCLUSIONS: These results demonstrated that
vitrectomy with removal of epimacular membrane is generally an effective
procedure in reducing diabetic macular edema, and the outcome does not depend on 
the presence absence of posterior vitreous detachment and epimacular membrane.

Publication Types: 
    Case Reports
    Comparative Study

PMID: 11530050 [PubMed - indexed for MEDLINE]

2982: Am J Ophthalmol. 2001 Sep;132(3):363-8.

Comment in:
    Am J Ophthalmol. 2002 Apr;133(4):587-8; author reply 588.

Macular changes after peeling of the internal limiting membrane in macular hole
surgery.

Haritoglou C, Gass CA, Schaumberger M, Ehrt O, Gandorfer A, Kampik A.

Department of Ophthalmology, Ludwig-Maximilians-University, Mathildenstrasse 8,
80336 Munich, Germany.

PURPOSE: To report the incidence of macular changes following pars plana
vitrectomy with peeling of the internal limiting membrane (ILM) for idiopathic
macular hole. DESIGN: Prospective consecutive series. METHODS: In a prospective
study 105 eyes of 105 patients underwent vitrectomy for idiopathic macular holes.
Surgery consisted of a standard three-port vitrectomy, induction of a posterior
hyaloid detachment, removal of epiretinal membranes including the ILM, fluid-air 
exchange and intraocular gas tamponade (15% hexafluoroethane (C2F6) gas mixture) 
followed by head-down positioning for at least five days. No adjuvants were used 
during surgery. In addition to the clinical examination, static microperimetry
using a Rodenstock scanning laser ophthalmoscope (SLO-105) was performed pre- and
6 or 12 weeks postoperatively. The stimulus size was 0.2 degrees (Goldmann II),
intensities employed were 0 and 12 dB. For all tests, 20-degree fields were used.
RESULTS: Anatomic closure of macular holes was achieved in 92 (87.6%) of 105
patients by one operation. Eight patients underwent a successful second
procedure. The closure rate after two operations was 95.2%. Best corrected visual
acuity increased from a median of 0.2 (range 0.05 to 0.5) preoperatively to a
median of 0.5 (range 0.05 to 1.0) postoperatively. Anatomical macular changes
were found in 8 (7.6%) patients: There were two cases of macular edema following 
secondary cataract extraction and six cases of retinal pigment epithelium
changes. Formation of postoperative epiretinal membranes or late reopenings were 
not noted. Small, mostly asymptomatic paracentral scotomata were seen in 59
(56.2%) of 105 patients. CONCLUSION: Anatomical changes of the macula following
vitrectomy with removal of the ILM are infrequent. However, paracentral scotomata
observed in our series might be caused by a trauma to the nerve fibers during ILM
peeling. To achieve reliable results a standardized procedure for microperimetry 
should be developed.

PMID: 11530049 [PubMed - indexed for MEDLINE]

2983: Invest Ophthalmol Vis Sci. 2001 Sep;42(10):2237-41.

Incidence and progression rates of age-related maculopathy: the Rotterdam Study.

Klaver CC, Assink JJ, van Leeuwen R, Wolfs RC, Vingerling JR, Stijnen T, Hofman
A, de Jong PT.

Department of Epidemiology and Biostatistics, Erasmus University Medical School, 
Rotterdam, The Netherlands.

PURPOSE: To describe the incidence rate of age-related macular degeneration (AMD)
and the progression rates of early stages of age-related maculopathy (ARM), and
to study the hierarchy of fundus features that determine progression. METHODS: A 
group of 4953 subjects aged 55 years and older living in Rotterdam, The
Netherlands, was studied at baseline and at 2-year follow-up to determine the
incidence of neovascular and atrophic AMD. A subgroup of 1244 subjects was
studied for progression of early stages of ARM. Fundus transparencies were graded
for features of ARM using the International Classification System. ARM was
stratified in four exclusive stages, according to type of drusen and presence of 
pigmentary irregularities. RESULTS: The overall 2-year cumulative incidence of
AMD was 0.2%, increasing to 1.8% in subjects of 85 years and older. Of those in
the early stages, one fourth showed progression to a more severe stage. The most 
important predictors for progression were more than 10% of macular area covered
by drusen (odds ratio [OR] 5.7, 95% confidence interval [CI] 2.9-11.3), presence 
of depigmentation (OR 4.0, 95% CI 2.5-6.4), and hyperpigmentation (OR 3.4, 95% CI
2.1-5.4). CONCLUSIONS: The incidence of AMD appears to be lower in The
Netherlands than in the United States. Progression of early ARM stages occurs in 
a distinct pattern at a stable rate, with a large area of drusen and presence of 
pigmentary changes as the most important predictors.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 11527936 [PubMed - indexed for MEDLINE]

2984: Invest Ophthalmol Vis Sci. 2001 Sep;42(10):2229-36.

Mutations in ABCR (ABCA4) in patients with Stargardt macular degeneration or
cone-rod degeneration.

Briggs CE, Rucinski D, Rosenfeld PJ, Hirose T, Berson EL, Dryja TP.

Ocular Molecular Genetics Institute, Massachusetts Eye and Ear Infirmary, Boston,
Massachusetts 02114, USA.

PURPOSE: To determine the spectrum of ABCR mutations associated with Stargardt
macular degeneration and cone-rod degeneration (CRD). METHODS: One hundred
eighteen unrelated patients with recessive Stargardt macular degeneration and
eight with recessive CRD were screened for mutations in ABCR (ABCA4) by
single-strand conformation polymorphism analysis. Variants were characterized by 
direct genomic sequencing. Segregation analysis was performed on the families of 
20 patients in whom at least two or more likely pathogenic sequence changes were 
identified. RESULTS: The authors found 77 sequence changes likely to be
pathogenic: 21 null mutations (15 novel), 55 missense changes (26 novel), and one
deletion of a consensus glycosylation site (also novel). Fifty-two patients with 
Stargardt macular degeneration (44% of those screened) and five with CRD each had
two of these sequence changes or were homozygous for one of them. Segregation
analyses in the families of 19 of these patients were informative and revealed
that the index cases and all available affected siblings were compound
heterozygotes or homozygotes. The authors found one instance of an apparently de 
novo mutation, Ile824Thr, in a patient. Thirty-seven (31%) of the 118 patients
with Stargardt disease and one with CRD had only one likely pathogenic sequence
change. Twenty-nine patients with Stargardt disease (25%) and two with CRD had no
identified sequence changes. CONCLUSIONS: This report of 42 novel mutations
brings the growing number of identified likely pathogenic sequence changes in
ABCR to approximately 250.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11527935 [PubMed - indexed for MEDLINE]

2985: Graefes Arch Clin Exp Ophthalmol. 2001 Jul;239(7):539-43.

Radiotherapy of exudative age-related macular degeneration; a clinical and
pathologic study.

Lambooij AC, Kuijpers RW, Mooy CM, Kliffen M.

Department of Ophthalmology, Erasmus University Rotterdam, The Netherlands.
lambooij@gen.fgg.eur.nl

BACKGROUND: Radiotherapy has recently been employed to treat patients with
exudative macular degeneration in order to prevent severe visual loss.
Radiotherapy affects the evolution of exudative macular degeneration directly by 
endothelial toxicity, leading to capillary closure, and/or indirectly through its
attenuating effects on the inflammatory response, mediated by macrophages and
other inflammatory cells. METHODS: In this study we describe the histopathologic 
findings in a patient with exudative age-related macular degeneration (AMD) in
both eyes whose right eye was treated with radiotherapy (5 times 2 Gy) 3 years
before he died. The eyes were enucleated post mortem and investigated by light
microscopy. Additionally, immunohistochemical investigation with antibodies
against CD34 and CD68 was performed to identify patent endothelial cells and
macrophages. RESULTS: Both eyes showed neovascular AMD consisting of mixed
fibrocellular and fibrovascular membranes. Capillaries in both the
choriocapillaris and the neovascular membrane were patent in both eyes.
Macrophages were present in the choroidal neovascularization of both eyes.
Neither preexistent choroidal, intraretinal, nor neovascular vessels showed
increased wall thickness as sign of radiation damage. CONCLUSION: No
radiation-related histopathologic effect could be demonstrated 3 years after
radiation therapy in this patient with AMD.

Publication Types: 
    Case Reports

PMID: 11521699 [PubMed - indexed for MEDLINE]

2986: Graefes Arch Clin Exp Ophthalmol. 2001 Jul;239(7):474-81.

Pars-plana vitrectomy in cystoid macular edema associated with intermediate
uveitis.

Wiechens B, Nölle B, Reichelt JA.

Department of Ophthalmology, Universitäsklinikum Kiel, Germany.
burkhard.wiechens.nordstadt@klinikum-hannover.de

BACKGROUND: Cystoid macular edema (CME) is a common complication in the course of
intermediate uveitis. In spite of systemic therapy with steroids or carbonic
anhydrase inhibitors, persistence of CME is observed. Pars plana vitrectomy (PPV)
is known to influence the course of intermediate uveitis positively. The present 
study was performed to investigate the role of PPV in the therapy of CME in
intermediate uveitis. MATERIALS AND METHODS: Forty-two eyes of 32 patients were
re-examined after PPV for CME. In all eyes fluorescein angiography was performed.
Average age at the time of surgery was 31.9 years (range 6-64 years). All
patients had received systemic corticosteroid and/or immunosuppressive treatment 
during the course of their disease. In some patients systemic therapy with
carbonic anhydrase inhibitors was performed. The mean duration of postoperative
follow-up was 20.2 months (range 6-102 months). RESULTS: Preoperative visual
acuity (VA) in all eyes was between 1/10 and 0.5. Total regression of CME after
surgery was observed in 18 of 42 eyes (42.8%), partial improvement in 7 eyes
(16.7%). In 13 of 42 eyes (30.9%) the CME remained unchanged. Twenty-one of 42
eyes (50.0%) experienced a postoperative improvement of VA of 2 lines or more. In
18 of 42 eyes (42.8%) there was no change; in 3 eyes (7.2%) VA was less. In the
long-term follow-up the corresponding results were slightly worse (17/17/8 eyes) 
due to secondary complications. In the majority of patients systemic medical
therapy could be reduced or discontinued. CONCLUSION: Pars-plana vitrectomy led
to regression of CME in 59% of cases and to subsequent improvement of VA in 50%
of eyes with intermediate uveitis. PPV should be considered soon after medical
therapy has been shown to be ineffective.

PMID: 11521690 [PubMed - indexed for MEDLINE]

2987: Retina. 2001;21(4):352-60.

Findings on retinal topography and thickness mapping in age-related macular
degeneration.

Gieser JP, Mori M, Blair NP, Shahidi M.

Department of Ophthalmology and Visual Sciences, UIC Eye Center, University of
Illinois at Chicago, 60612, USA.

PURPOSE: To report alterations in the retinal topography and thickness in typical
cases of age-related macular degeneration (ARMD). METHODS: An optical imaging
system was applied to patients with ARMD with alterations in the retinal
structures. The system generates a series of 20 optical section images that
encompass a 2 mm x 2 mm retinal area. The optical sections are digitized and
analyzed to provide topographic maps of the vitreo-retinal and chorio-retinal
surfaces and the retinal thickness. RESULTS: Retinal topography and thickness
mapping in a normal eye corresponded to normal anatomy. Topographic mapping in a 
patient with confluent drusen indicated elevation of the vitreo-retinal surface. 
Retinal topography in a patient with retinal pigment epithelium detachment
displayed localized elevation of the chorio-retinal surface. The thickness map in
a patient with geographic atrophy of the retinal pigment epithelium revealed
retinal thinning. In the patients with choroidal neovascularization, the
vitreoretinal and chorio-retinal surfaces were elevated. The chorio-retinal
surface map in a patient with evolving disciform scar displayed topographic
variations corresponding to the fibrovascular tissue underlying the serous
detachment. CONCLUSION: Retinal topography and thickness mapping is useful for
visualization and evaluation of pathologic alterations in retinal structures due 
to ARMD.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11508882 [PubMed - indexed for MEDLINE]

2988: Arthritis Rheum. 2001 Aug;44(8):1959-61.

Early hydroxychloroquine macular toxicity.

Warner AE.

This report describes the case of an appropriately dosed patient who developed
maculopathy <8 years after starting hydroxychloroquine (HCQ) therapy for systemic
lupus erythematosus. Risk factors and screening for HCQ-associated maculopathy
are discussed.

Publication Types: 
    Case Reports

PMID: 11508449 [PubMed - indexed for MEDLINE]

2989: Arch Ophthalmol. 2001 Aug;119(8):1191-9.

Dietary fat and risk for advanced age-related macular degeneration.

Seddon JM, Rosner B, Sperduto RD, Yannuzzi L, Haller JA, Blair NP, Willett W.

Epidemiology Unit, Department of Ophthalmology, Massachusetts Eye and Ear
Infirmary, Harvard Medical School, Boston, MA 02114, USA.
Johanna_Seddon@meei.harvard.edu

OBJECTIVE: To evaluate the relationship between intake of total and specific
types of fat and risk for advanced age-related macular degeneration (AMD), the
leading cause of irreversible blindness in adults. DESIGN: A multicenter eye
disease case-control study. SETTING: Five US clinical ophthalmology centers.
PATIENTS: Case subjects included 349 individuals (age range, 55-80 years) with
the advanced, neovascular stage of AMD diagnosed within 1 year of their
enrollment into the study who resided near a participating clinical center.
Control subjects included 504 individuals without AMD but with other ocular
diseases. Controls were from the same geographic areas as cases and were
frequency-matched to cases by age and sex. MAIN OUTCOME MEASURES: Relative risk
for AMD according to level of fat intake, controlling for cigarette smoking and
other risk factors. RESULTS: Higher vegetable fat consumption was associated with
an elevated risk for AMD. After adjusting for age, sex, education, cigarette
smoking, and other risk factors, the odds ratio (OR) was 2.22 (95% confidence
interval [CI], 1.32-3.74) for persons in the highest vs those in the lowest
quintiles of intake (P for trend,.007). The risk for AMD was also significantly
elevated for the highest vs lowest quintiles of intake of monounsaturated (OR,
1.71) and polyunsaturated (OR, 1.86) fats (Ps for trend,.03 and.03,
respectively). Higher consumption of linoleic acid was also associated with a
higher risk for AMD (P for trend,.02). Higher intake of omega-3 fatty acids was
associated with a lower risk for AMD among individuals consuming diets low in
linoleic acid, an omega-6 fatty acid (P for trend,.05; P for continuous
variable,.03). Similarly, higher frequency of fish intake tended to reduce risk
for AMD when the diet was low in linoleic acid (P for trend,.05). Conversely,
neither omega-3 fatty acids nor fish intake were related to risk for AMD among
people with high levels of linoleic acid intake. CONCLUSION: Higher intake of
specific types of fat--including vegetable, monounsaturated, and polyunsaturated 
fats and linoleic acid--rather than total fat intake may be associated with a
greater risk for advanced AMD. Diets high in omega-3 fatty acids and fish were
inversely associated with risk for AMD when intake of linoleic acid was low.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11483088 [PubMed - indexed for MEDLINE]

2990: Arch Ophthalmol. 2001 Aug;119(8):1143-9.

Age-related maculopathy in a randomized trial of low-dose aspirin among US
physicians.

Christen WG, Glynn RJ, Ajani UA, Schaumberg DA, Chew EY, Buring JE, Manson JE,
Hennekens CH.

Division of Preventive Medicine, Department of Medicine, Harvard Medical School
and Brigham and Women's Hospital, Boston, MA 02215-1204, USA.

OBJECTIVE: To examine the development of age-related maculopathy (ARM) in a
large-scale trial of low-dose aspirin treatment. METHODS: The Physicians' Health 
Study I was a randomized, double-masked, placebo-controlled trial of low-dose
aspirin (325 mg every other day) and beta carotene (50 mg every other day) in the
prevention of cardiovascular disease and cancer conducted among 22 071 US male
physicians aged 40 to 84 years in 1982. A total of 21 216 participants did not
report ARM at baseline, were followed up for at least 7 years, and are included
in this analysis. MAIN OUTCOME MEASURES: Total ARM, defined as a self-report
confirmed by medical record evidence of an initial diagnosis subsequent to
randomization, and ARM with vision loss, defined as total ARM but with vision
loss to 20/30 or worse attributable to ARM. RESULTS: Early termination of the
randomized aspirin component of the Physicians' Health Study I, after an average 
of 60.2 months of treatment and follow-up due to a statistically extreme 44%
reduced risk of first myocardial infarction, resulted in a far lower number of
incident cases of ARM during the aspirin treatment period than would have accrued
without early termination. Thus, during an average of 60.2 months of follow-up, a
total of 117 cases of ARM were confirmed, including 57 cases responsible for
vision loss to 20/30 or worse. There were 51 cases of ARM in the aspirin group
and 66 in the placebo group (relative risk, 0.77; 95% confidence interval,
0.54-1.11). For ARM with vision loss, there were 25 cases in the aspirin group
and 32 in the placebo group (relative risk, 0.78; 95% confidence interval,
0.46-1.32). CONCLUSIONS: These randomized trial data tend to exclude any large
beneficial effect of 5 years of low-dose aspirin treatment on ARM. However, a
smaller, but potentially important, beneficial effect cannot be ruled out and
would require testing in randomized trials of adequate size and duration.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, U.S. Gov't, P.H.S.

PMID: 11483080 [PubMed - indexed for MEDLINE]

2991: Optometry. 2001 Jul;72(7):435-40.

Sorsby's fundus dystrophy.

Weisinger HS, Pesudovs K.

Department of Food Science, Royal Melbourne Institute of Technology University,
Victoria, Australia. harrison.weisinger@rmit.edu.au

BACKGROUND: Sorsby's fundus dystrophy describes the condition in which an
autosomal-dominant inherited macular dystrophy with bilateral central visual loss
is accompanied by progressive atrophy of the peripheral choroid and,
subsequently, the outer retina. The first symptom of this condition is
nyctalopia, whereas (typically) the first sign is the appearance of white-yellow 
deposits in the posterior pole. CASE REPORT: We report a case of Sorsby's fundus 
dystrophy, manifested with central visual loss in the fifth decade of life. A
battery of tests--including ophthalmoscopy, electroretinography, color vision,
Pelli-Robson contrast sensitivity, and fluorescein angiography--were used to
evaluate the condition. CONCLUSIONS: While advances in understanding the etiology
of Sorsby's fundus dystrophy have been made, the condition remains difficult to
treat and the outcome is often devastating. The benefits of various methods of
treatment, such as laser photocoagulation and dietary supplementation are unclear
Patients affected by this condition should be managed in a manner similar to that
for end-stage sufferers of age-related macular degeneration.

Publication Types: 
    Case Reports

PMID: 11486938 [PubMed - indexed for MEDLINE]

2992: Nagoya J Med Sci. 2001 May;64(1-2):1-9.

Rescue of retinal function by macular translocation surgery in age-related
macular degeneration and other diseases with subfoveal choroidal
neovascularization.

Terasaki H.

Department of Protective Care for Sensory Disorders, Nagoya University School of 
Medicine, Japan. terasaki@med.nagoya-u.ac.jp

Age-related macular degeneration (AMD) is the leading cause of legal blindness
among the elderly. In AMD and some other macular diseases, subfoveal choroidal
neovascularization (CNV) damages the underlying retinal pigment epithelium (RPE),
and because retinal function is dependent on a healthy RPE, vision is markedly
reduced by a subfoveal CNV. To treat such CNVs, macular translocation surgery has
been performed to move the sensory retina from the damaged RPE to healthier RPE. 
At present, this surgery is the only possible treatment to improve the visual
acuity of patients with subfoveal CNV. Macular translocation surgery involves the
detachment of the entire retina from the RPE by a subretinal infusion of fluid
and creating a 360 degrees circumferential retinotomy followed by the rotation of
the retina. Severe postoperative complications such as recurrent retinal
detachment have been reported in about 30% of the cases after macular
translocation. To determine the efficacy of this surgery, it is necessary to
demonstrate an improvement in macular and overall retinal function objectively as
well as subjectively. To this end, we have assessed the changes in visual
function by measuring the visual acuity subjectively, and the macular function
objectively by focal macular ERGs (FERGs). We shall show that there is an
improvement in the FERGs in most patients after retinal translocation surgery but
the full-field ERGs were reduced by about 30%. Thus, macular translocation
surgery with 360-degree retinotomy may be feasible for macular function, although
some degree of peripheral retinal function is lost.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 11486596 [PubMed - indexed for MEDLINE]

2993: Am J Epidemiol. 2001 Aug 1;154(3):207-11.

Risk of incident age-related eye diseases in people with an affected sibling :
The Beaver Dam Eye Study.

Klein BE, Klein R, Lee KE, Moore EL, Danforth L.

Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison 
Medical School, Madison, WI 53705-2397, USA. kleinb@epi.ophth.wisc.edu

The purpose of this investigation was to determine whether age-related cataract
and maculopathy in older siblings predicts development of the same in younger
siblings. A population-based study of age-related eye diseases was conducted in
1988--1990 in Beaver Dam, Wisconsin, and a follow-up examination was performed 5 
years later. Diagnoses of age-related eye diseases were assigned on the basis of 
gradings of study photographs. There were 1,088 people from 488 sibships with at 
least two siblings who could contribute information for these analyses. The
authors computed odds ratios and 95% confidence intervals for developing the
specific lesion and identifying it 5 years later if an older sibling had it at
baseline. The odds ratios were 1.65 (95% confidence interval (CI): 0.91, 2.99)
for nuclear cataract, 1.62 (95% CI: 0.92, 2.85) for cortical cataract, 1.95 (95% 
CI: 0.48, 7.95) for posterior subcapsular cataract, 1.82 (95% CI: 0.91, 3.66) for
soft drusen, 8.18 (95% CI: 3.34, 20.08) for retinal pigment epithelium
depigmentation, 3.59 (95% CI: 1.71, 7.57) for increased retinal pigment, and
10.32 (95% CI: 0.83, 128.58) for exudative age-related maculopathy. These
findings suggest that strong family determinants of lesions of age-related
maculopathy are likely, less so for age-related cataract, which confer risk of
the same lesion in a younger sibling.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.

PMID: 11479184 [PubMed - indexed for MEDLINE]

2994: Am J Ophthalmol. 2001 Aug;132(2):271-3.

The relation of coffee and caffeine to the 5-year incidence of early age-related 
maculopathy: the Beaver Dam Eye Study.

Tomany SC, Klein R, Klein BE.

Department of Ophthalmology and Visual Sciences, University of Wisconsin Medical 
School, Madison, Wisconsin 53705-2397, USA.

PURPOSE: To examine the relationship between coffee and caffeine consumption and 
the 5-year incidence of early age-related maculopathy and its component lesions, 
soft indistinct drusen or pigmentary abnormalities. DESIGN: A prospective cohort 
study conducted from 1988 to 1995 with an average follow-up of 4.8 years.
METHODS: Data from baseline and 5-year follow-up examinations were analyzed for
Beaver Dam Eye Study participants (n = 3435). The Wisconsin Age-Related
Maculopathy Grading System was used to assess the presence and severity of early 
age-related maculopathy. RESULTS: Men were more likely to be coffee and caffeine 
drinkers than were women. For both men and women, coffee and caffeine intake
decreased with age. Coffee and caffeine consumption were not associated with the 
5-year incidence of early age-related maculopathy, soft indistinct drusen, or
pigmentary abnormalities. CONCLUSION: Neither a history of coffee nor caffeine
consumption is associated with incident early age-related maculopathy.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11476699 [PubMed - indexed for MEDLINE]

2995: Am J Ophthalmol. 2001 Aug;132(2):191-5.

Paraoxonase gene polymorphisms and plasma oxidized low-density lipoprotein level 
as possible risk factors for exudative age-related macular degeneration.

Ikeda T, Obayashi H, Hasegawa G, Nakamura N, Yoshikawa T, Imamura Y, Koizumi K,
Kinoshita S.

Department of Ophthalmology, Osaka Medical College, Osaka, Japan.
tikeda@ophth.kpu-m.ac.jp

PURPOSE: Paraoxonase (E.C.3.1.1.2) is a polymorphic protein shown to prevent
low-density lipoprotein oxidation. Our purpose is to evaluate the hypothesis that
paraoxonase gene polymorphisms and plasma oxidized low-density lipoprotein level 
play a role in the occurrence of exudative age-related macular degeneration.
METHODS: We analyzed paraoxonase genotypes (A/B, Gln-Arg192 and L/M, Leu-Met54)
and plasma oxidized low-density lipoprotein levels in 72 unrelated Japanese
patients with exudative age-related macular degeneration and compared the results
with those of 140 age-matched and sex-matched control subjects. RESULTS: The
distribution of paraoxonase 192 and paraoxonase 54 polymorphisms was
significantly different between the patients with age-related macular
degeneration and control subjects (chi-square = 6.226, P =.0445, and chi-square =
6.863, P =.0323, respectively). The high frequency of the BB genotype at position
192 was observed in the exudative age-related macular degeneration group compared
with control subjects (52.8% vs 35.0%, respectively; P =.0127). The high
frequency of the LL genotype at position 54 was observed in the patients more
than the controls (91.7% vs 77.1%, respectively; P =.0090). The mean (+/- SE)
oxidized low-density lipoprotein levels in the patients was significantly higher 
than in the controls (19.1 +/- 1.0 vs 16.2 +/- 0.6 U/ml, P <.01). CONCLUSION:
These results indicate that the paraoxonase gene polymorphisms may represent a
possible genetic risk factor for age-related macular degeneration and that
increased plasma oxidized low-density lipoprotein may be involved in the
pathogenesis of age-related macular degeneration.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 11476678 [PubMed - indexed for MEDLINE]

2996: Am J Ophthalmol. 2001 Aug;132(2):156-63.

Macular translocation with chorioscleral outfolding: a pilot clinical study.

Lewis H.

The Cole Eye Institute and the Division of Ophthalmology, The Cleveland Clinic
Foundation, Cleveland, Ohio 44195, USA. lewish@ccf.org

PURPOSE: A new surgical technique to translocate the macula was used to treat
patients with subfoveal choroidal neovascularization secondary to age-related
macular degeneration (AMD). DESIGN: Prospective, interventional case series.
METHODS: Twenty-five eyes of 25 patients underwent macular translocation with
either circumferential or radial chorioscleral outfolding using three clip sizes:
2-mm, 3-mm, and 4-mm. Postoperative photocoagulation was performed on only those 
eyes that had an extrafoveal choroidal neovascular membrane following surgery.
RESULTS: The surgery successfully displaced the fovea in 22 (88%) of the eyes.
The median postoperative foveal displacement was 1142 microm (range 0 to 3200
microm). Patients who had radial outfolding with 4-mm clips had the greatest
displacement of the fovea (range 1644 to 3200 microm median 1977 microm). The
fovea was successfully displaced to a location outside the choroidal neovascular 
membrane in 17 (68%) of the 25 eyes. The best-corrected visual acuity improved in
11 eyes (median, 17 letters), remained unchanged in 4 eyes, and decreased in 10
eyes (median, 12 letters). Visual acuity increased by a median of 2 letters. The 
final best-corrected visual acuity was 20/64 in 3 eyes; 20/80 in 3 eyes; 20/100
in 4 eyes; 20/126 in 4 eyes; 20/200 in 4 eyes; 20/250 in 4 eyes; and 20/400 in 3 
eyes. CONCLUSIONS: Macular translocation with radial chorioscleral outfolding
using 4-mm clips resulted in the best foveal displacement and improvement in
visual function, and was associated with the least amount of vision loss and
complications. Further refinements are needed to make this surgical procedure
more predictable, and more research (randomized clinical trials) is needed to
determine the role of macular translocation in the treatment of subfoveal
choroidal neovascularization in patients with AMD.

Publication Types: 
    Clinical Trial

PMID: 11476673 [PubMed - indexed for MEDLINE]

2997: Doc Ophthalmol. 2001 Jan;102(1):41-62.

Visual evoked cortical potential can be used to differentiate between uncorrected
refractive error and macular disorders.

Perlman I, Segev E, Mazawi N, Merhav-Armon T, Lei B, Leibu R.

The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology,
Haifa.

The visual evoked cortical potential (VECP) is widely used to verify complaints
of reduced visual performance and to identify the site of the disorder. In this
study, we investigated the correlation between reduced visual acuity and VECP in 
volunteers with normal corrected visual acuity and in patients suffering from
inherited macular degeneration or from age related macular degeneration (ARMD).
Flash evoked VECP was not affected by the visual acuity in the cases of
refractive error and in ARMD patients but was reduced in amplitude and delayed in
implicit time in the patients suffering from inherited macular degeneration. The 
VECP elicited by pattern reversal checkerboard (PVECP) was not affected by the
quality of the visual image in volunteers with uncorrected refractive error when 
checks of 60' or larger were used but were considerably reduced in size and
prolonged in implicit time for checks smaller than 15'. In both groups of
patients suffering from macular dysfunction, pattern reversal VECP was very
subnormal and was characterized by prolonged implicit time compared to values
expected from their visual acuity. These findings indicate that the PVECP does
not directly correlate with visual acuity but rather with foveal function.
Therefore, we suggest that recordings of PVECP can be used to differentiate
between refractive error and macular disorders as causing reduction in visual
acuity when other clinical signs are missing or not available.

Publication Types: 
    Comparative Study

PMID: 11475365 [PubMed - indexed for MEDLINE]

2998: Diabet Med. 2001 May;18(5):388-94.

Association of macular involvement with proliferative retinopathy in Type 2
diabetes.

Tong L, Vernon SA, Kiel W, Sung V, Orr GM.

Department of Ophthalmology, University Hospital, Queen's Medical Centre,
Nottingham, UK.

AIMS: To determine whether documented evidence of pre-existing maculopathy is
present in Type 2 diabetic patients who require photocoagulation or vitrectomy
for proliferative disease. This is a retrospective case notes review. METHODS:
The study was performed at Queen's Medical Centre, UK. All patients listed in the
laser register and operating theatre register over 5 years (March 1994 to March
1999) who had undergone pan retinal photocoagulation (PRP) for diabetic
retinopathy, in one consultant firm, were studied. The medical records of
patients who had undergone vitrectomy as their first treatment for proliferative 
diabetic retinopathy in a vitreo-retinal firm over the 5 years were examined. The
proportion of patients with documented maculopathy before development of
proliferative retinopathy was determined. RESULTS: All except 1/134 or 0.7% (95% 
confidence interval 0.1-4.5%) patients had documentation of macular signs in at
least one eye prior to the patient's first session of PRP. Of the remaining 133, 
104 (78%) had had focal or grid photocoagulation of the macula. The median time
between the documentation of maculopathy before the first PRP treatment session
was 16 months (interquartile range 7-36). Fourteen patients had vitrectomy and
endolaser performed as the initial treatment for proliferative disease. All
patients had documented maculopathy before the onset of proliferative disease.
CONCLUSIONS: The results of this study suggest that in Type 2 diabetes,
proliferative disease occurs relatively late compared with maculopathy. In such
patients, maculopathy is almost invariably present when proliferative disease is 
detected.

PMID: 11472450 [PubMed - indexed for MEDLINE]

2999: Ophthalmic Epidemiol. 2001 Sep;8(4):251-62.

Measures of obesity and age-related eye diseases.

Klein BE, Klein R, Lee KE, Jensen SC.

Department of Ophthalmology and Visual Sciences, University of Wisconsin Medical 
School, Madison, WI 53705-2397, USA. klienb@epi.ophth.wisc.edu

OBJECTIVE: To compare body mass index with waist-to-hip ratio as correlates of
age-related eye disease. DESIGN: Population-based cross-sectional study.
PARTICIPANTS: Participants of the Beaver Dam Eye Study at 5-year follow-up
examinations. METHODS: Body mass index was computed from weight and height, and
waist-to-hip ratio was computed from measurements all done at the 5-year
examination. Presence of ocular lesions was based on gradings of standard
photographs of the retina and lens. MAIN OUTCOME MEASURES: Presence of early and 
late age-related maculopathy and nuclear, cortical, and posterior subcapsular
cataracts. RESULTS: In women, early age-related maculopathy was significantly
associated with both body mass index and waist-to-hip ratio. The relationship
between waist-to-hip ratio and late age-related maculopathy was of borderline
significance. When analyzed as continuous measures, waist-to-hip ratio was more
strongly associated with nearly every outcome compared to body mass index. In
men, there was little difference between body mass index and waist-to-hip ratio
as correlates of age-related eye diseases. The reason for differences between men
and women is not clear, but is unlikely to be due to current exposure to
estrogen. CONCLUSIONS: In women in our analyses, waist-to-hip ratio is more
strongly associated with age-related eye disease than is body mass index. When
adiposity is considered as a risk factor itself, or as a confounder of risk
factors for age-related ocular disease, waist-to-hip ratio may be the better
measure to use in women.

Publication Types: 
    Comparative Study
    Research Support, U.S. Gov't, P.H.S.

PMID: 11471093 [PubMed - indexed for MEDLINE]

3000: Ophthalmic Epidemiol. 2001 Sep;8(4):237-49.

Associations of cardiovascular disease and its risk factors with age-related
macular degeneration: the POLA study.

Delcourt C, Michel F, Colvez A, Lacroux A, Delage M, Vernet MH; POLA Study Group.

INSERM Unité 500, Montpellier, 34093, France. delcourt@montp.inserm.fr.

The POLA study (June 1995 through July 1997) is a population-based study on
cataract and age-related macular degeneration (AMD) and their risk factors in
2584 residents of Séte (South of France), aged 60--95 years. Classification of
AMD was performed on 50 degrees fundus photographs, according to an international
classification. The presence of cardiovascular disease and its risk factors was
determined by interviewer-based questionnaire, clinical examination
(anthropometry, blood pressure) and fasting plasma measurements. Using a logistic
model adjusted for age and gender, late AMD was not significantly associated with
a history of cardiovascular disease, diabetes, use of hypocholesterolemic drugs, 
hypertension, blood pressure or plasma lipids. Obese subjects (body mass index
greater than 30 kg/m( 2)) had a 2.29-fold (95% confidence interval (CI):
1.00--5.23) and 1.54-fold (CI: 1.05--2.26) increased risk of late AMD and
pigmentary abnormalities in comparison with lean subjects. Finally, the risk of
soft drusen was decreased in those subjects with a history of cardiovascular
disease (odds-ratio (OR) = 0.72, CI: 0.54--0.97), and increased with increasing
levels of HDL-cholesterol (OR = 1.52, CI: 1.14--2.02). None of these results were
modified by further adjustments for smoking, educational level and plasma
alpha-tocopherol. These results need to be confirmed by other studies, which
ideally should be longitudinal and prospective.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11471092 [PubMed - indexed for MEDLINE]

3001: Br J Ophthalmol. 2001 Aug;85(8):969-75.

Evaluation of the G protein coupled receptor-75 (GPR75) in age related macular
degeneration.

Sauer CG, White K, Stöhr H, Grimm T, Hutchinson A, Bernstein PS, Lewis RA,
Simonelli F, Pauleikhoff D, Allikmets R, Weber BH.

Institute of Human Genetics, University of Würzburg, Germany.

BACKGROUND: A long term project was initiated to identify and to characterise
genes that are expressed exclusively or preferentially in the retina as
candidates for a genetic susceptibility to age related macular degeneration
(AMD). A transcript represented by a cluster of five human expressed sequence
tags (ESTs) derived exclusively from retinal cDNA libraries was identified.
METHODS: Northern blot and RT-PCR analyses confirmed preferential retinal
expression of the gene, which encodes a G protein coupled receptor, GPR75.
Following isolation of the full length cDNA and determination of the genomic
organisation, the coding sequence of GPR75 was screened for mutations in 535 AMD 
patients and 252 controls from Germany, the United States, and Italy. Employed
methods included single stranded conformational polymorphism (SSCP) analysis,
denaturing high performance liquid chromatography (DHPLC), and direct sequencing.
RESULTS: Nine different sequence variations were identified in patients and
control individuals. Three of these (-30A>C, 150G>A, and 346G>A) likely represent
polymorphic variants. Each of six alterations (-4G>A, N78K, P99L, S108T, T135P,
and Q234X) were found once in single AMD patients and were considered variants
that could affect the protein function and potentially cause retinal pathology.
CONCLUSION: The presence of six potential pathogenic variants in a cohort of 535 
AMD patients alone does not provide statistically significant evidence for the
association of sequence variation in GPR75 with genetic predisposition to AMD.
However, a possible connection between the variants and age related retinal
pathology cannot be discarded. Functional studies are needed to clarify the role 
of GPR75 in retinal physiology.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11466257 [PubMed - indexed for MEDLINE]

3002: Br J Ophthalmol. 2001 Aug;85(8):928-32.

Electrophysiological changes after 360 degrees retinotomy and macular
translocation for subfoveal choroidal neovascularisation in age related macular
degeneration.

Lüke C, Aisenbrey S, Lüke M, Marzella G, Bartz-Schmidt KU, Walter P.

Zentrum für Augenheilkunde, Universität Köln, Germany. asia18@uni-koeln.de

AIM: To evaluate electrophysiological changes after 360 degrees retinotomy and
macular translocation for subfoveal choroidal neovascularisation in patients with
age related macular degeneration (AMD). METHODS: A consecutive series of 32
patients suffering from subfoveal choroidal neovascularisation secondary to AMD
underwent 360 degrees retinotomy and macular translocation. The ERG served as the
main parameter of the study and was recorded 1 day before the translocation
surgery and no earlier than 4 weeks after the silicone oil removal. RESULTS: The 
scotopic ERG amplitudes were significantly reduced after translocation surgery.
Depending on the applied flash luminance the mean b-wave amplitude reduction of
the scotopic ERG varied between 67% (0.2 cd.s/m2) and 74% (0.03 cd.s/m2). The
a-waves and b-waves of the saturating light response decreased significantly by
46% and 59%, respectively. The photopic a-wave and b-wave amplitudes were
significantly lower after the translocation surgery resulting in a mean reduction
of 27% and 43%, respectively. CONCLUSIONS: Although macular translocation may
provide the potential of preserving and even restoring vision in patients with
subfoveal choroidal neovascular membranes secondary to AMD the present study
indicates that a significant electrophysiological decrease is caused by surgical 
procedures associated with this technique. Further research is necessary to
clarify if certain modifications of the surgical procedure are able to
substantially reduce the neuroretinal trauma.

PMID: 11466247 [PubMed - indexed for MEDLINE]

3003: Br J Ophthalmol. 2001 Aug;85(8):925-7.

Is the pulse rate useful in assessing risk of diabetic retinopathy and macular
oedema? The Wisconsin Epidemiological Study of Diabetic Retinopathy.

Wong TY, Moss SE, Klein R, Klein BE.

Department of Ophthalmology, University of Wisconsin Medical School, Madison,
Wisconsin 53705-2397, USA. tienyinwong@yahoo.com

AIM: To describe the relation between pulse rate and incident diabetic
retinopathy. METHODS: Population based cohort study of people with diabetes.
Resting pulse rate was measured in 30 second intervals. Diabetic retinopathy was 
evaluated from masked gradings of fundus photographs. RESULTS: People with higher
pulse rates were more likely to have 4 year progression of retinopathy,
progression to proliferative retinopathy, and incident macular oedema than those 
with lower pulse rates. However, these associations were attenuated after
controlling for blood pressure, glycosylated haemoglobin, and other risk factors.
CONCLUSION: Pulse rate may be a clinical indicator of overall risk of diabetic
retinopathy, but is not independently associated with the condition.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11466246 [PubMed - indexed for MEDLINE]

3004: Curr Eye Res. 2001 Mar;22(3):221-8.

Macular dystrophy with protan genotype and phenotype studied with cone type
specific ERGs.

Scholl HP, Kremers J, Wissinger B.

Laboratories of Electrophysiology, Department of Experimental Ophthalmology,
University Eye Hospital Tübingen, Germany. hendrik.scholl@uni-tuebingen.de

PURPOSE: To determine the L- and M-cone driven ERG responses in a male patient
with macular dystrophy and a protan phenotype. METHODS: We measured large field
ERG thresholds to stimuli which modulated exclusively the L- or the M-cones or
the two in various combinations (both in-phase and in counterphase). In none of
the stimuli, the S-cones were modulated. Additionally, standard and multifocal
ERGs were measured. Analysis of the L- and M-cone pigment genes was performed by 
means of PCR, RFLP analysis and DNA sequencing techniques. RESULTS: Macular
dystrophy was revealed by the markedly abnormal multifocal ERGs in presence of
near normal standard ERGs. The large field ERG responses were exclusively driven 
by the M-cones with enlarged thresholds when compared with otherwise normal
protanopes. In addition, the M-cone driven ERG response phases were abnormal.
Pigment gene analysis confirmed a protan genotype with the presence of a single
5'red/3'green hybrid pigment gene. CONCLUSIONS: Our novel stimulus technique
allows a reliable analysis of the separate cone pathways even in cases with
macular dysfunction. The increased thresholds and the abnormal phase behavior of 
the M-cone driven ERGs reflect altered mechanisms of the retinal physiology in
this patient. The data strongly suggest that the macular dystrophy and the
protanopia have independent origins.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 11462159 [PubMed - indexed for MEDLINE]

3005: Eur J Ophthalmol. 2001 Apr-Jun;11(2):145-9.

A quantitative in vivo study of retinal thickness before and after laser
treatment for macular edema due to retinal vein occlusion.

De Geronimo F, Glacet-Bernard A, Coscas G, Soubrane G.

University Eye Clinic of Créteil, France.

PURPOSE: To evaluate quantitatively the effect of grid laser photocoagulation in 
macular edema due to central and branch retinal vein occlusion, using the retinal
thickness analyzer. METHODS: Five patients with cystoid and non-cystoid macular
edema were studied before and after argon grid laser treatment. All were examined
clinically, with fluorescein angiography, and measurement of retinal thickness.
Macular thickness was correlated to visual acuity measured on the ETDRS chart.
RESULTS: Laser-slit images obtained with the retinal thickness analyzer in
patients with macular edema disclosed discrete intraretinal changes after
photocoagulation. Biomicroscopy and fluorescein angiography were insensitive to
these small changes in the retinal thickness. No patient had any change in visual
acuity after three months, but the retinal thickness was greater at this
interval. The retinal thickening may be explained by a postoperative inflammatory
response or by altered retinal blood flow or, in two of the eyes, by the effect
of combined peripheral photocoagulation. CONCLUSIONS: The retinal thickness
analyzer offers a refined tool for the diagnosis of subclinical changes of
macular edema in retinal vein occlusion and is therefore also useful for
assessing the effects of treatment.

PMID: 11456015 [PubMed - indexed for MEDLINE]

3006: Eye. 2001 Jun;15(Pt 3):424-9.

Neovascular age-related macular degeneration: present and future treatment
options.

Votruba M, Gregor Z.

Moorfields Eye Hospital, London, UK.

PURPOSE: To review treatment strategies in neovascular age-related macular
degeneration (ARMD). METHODS: Medline and Embase search. RESULTS: Age-related
macular degeneration (ARMD) is the commonest cause of blindness in the developed 
world in individuals over 50 years of age. ARMD may lead to loss of vision by
atrophy of the retinal pigment epithelium or by the development of choroidal
neovascular membranes (CNVM) under the macula, which leak serous fluid and blood 
and ultimately cause a blinding disciform scar. Treatment options currently being
investigated fall into three main approaches: elimination of the CNVM from the
subfoveal area (by laser or surgery), modification of the CNVM (by laser,
radiotherapy or chemotherapeutic agents) or lastly prevention of the formation of
CNVM (by laser prophylaxis, diet or gene targeting). Whilst almost no therapy
restores normal visual acuity, any significant visual improvement over the
natural history may be regarded as beneficial. CONCLUSIONS: Both the current and 
immediate future potential therapies for choroidal neovascularisation in ARMD
require considerable advances to be made before they will make any impact on
blindness caused by ARMD. Of the current treatments none are curative and the
treatment benefits are small. There is an urgent need for new therapies.

Publication Types: 
    Review

PMID: 11450768 [PubMed - indexed for MEDLINE]

3007: Eye. 2001 Jun;15(Pt 3):401-6.

Strategies for mapping susceptibility genes in age-related maculopathy.

Wright AF.

MRC Human Genetics Unit, Western General Hospital, Edinburgh, UK.

The prospects for mapping genes conferring susceptibility to common disorders
such as age-related maculopathy have increased as a result of advances in
high-throughput genotyping using single nucleotide polymorphisms. This should not
obscure the magnitude of the task of identifying what are potentially a diverse
group of genetic variants with small or intermediate effects on disease
susceptibility. Strategies for increasing the odds of success in such an
endeavour are discussed.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 11450765 [PubMed - indexed for MEDLINE]

3008: Eye. 2001 Jun;15(Pt 3):376-83.

Photoreceptor topography in ageing and age-related maculopathy.

Curcio CA.

Department of Ophthalmology, University of Alabama at Birmingham 35294-0009, USA.
curcio@uab.edu

The relative rate of rod and cone degeneration is a fundamental characteristic of
any disorder affecting photoreceptors, including ageing and age-related
maculopathy (ARM). The macula consists of a small cone-dominated fovea surrounded
by a rod-dominated parafovea. In donor eyes with grossly normal maculas, the
number of foveal cones is stable and the number of parafoveal rods decreases by
30% over adulthood. These trends continue in early ARM. In exudative ARM, the
photoreceptors that survive over disciform scars are largely cones, and rods
decline precipitously in relation to thick subretinal pigment epithelium
deposits. The preferential vulnerability of rods over cones has been confirmed by
recent functional studies showing that the loss of scotopic sensitivity is
greater than the loss of photopic sensitivity throughout adulthood and in
patients with early ARM. A hypothesis that these effecfs are due to to retinoid
deficiency at the level of the photoreceptors is proposed. The topography of rod 
loss in ageing and ARM is consistent with the location of early ARM lesions
described in population-based studies and is not consistent with the location of 
fundus autofluorescence due to lipofuscin.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.
    Review

PMID: 11450761 [PubMed - indexed for MEDLINE]

3009: Graefes Arch Clin Exp Ophthalmol. 2001 Apr;239(4):264-70.

Vitrectomy results in diabetic macular oedema without evident vitreomacular
traction.

La Heij EC, Hendrikse F, Kessels AG, Derhaag PJ.

Department of Ophthalmology, Academic Hospital Maastricht, P.O. Box 5800, P.
Debyelaan 25, 6202 AZ Maastricht, The Netherlands.

PURPOSE: To determine the effectiveness of vitrectomy in eyes with diabetic
macular oedema without evident traction from a thickened vitreous membrane.
METHODS: Twenty-one consecutive eyes from 19 patients with diabetic macular
oedema that had undergone vitrectomy were analysed retrospectively. All eyes had 
an attached posterior hyaloid membrane in the macular region, but without
thickening and without evident traction on the macula. A standard pars plana
vitrectomy with the creation of a posterior vitreous detachment was performed.
RESULTS: Median duration of macular oedema at the time of vitrectomy was
approximately 11.0 months (range 2-36 months). The median preoperative
best-corrected visual acuity of 0.08 (range hand motions/0.003 to 0.4), improved 
by 5 lines to a median final postoperative best-corrected visual acuity of 0.25
(range 0.025-0.5) (P = 0.001). Seven eyes without preoperative macular
photocoagulation had a median visual acuity improvement of 77%, range 32-400%,
while 12 eyes with preoperative macular laser treatment had a median visual
acuity improvement of 14.8%, range 0-66.1% (P = 0.02, CI 95%, after multivariate 
regression analysis). In all 21 eyes, macular oedema was no longer visible on
microscopic examination after a median period of 3.0 months (range 1-9 months)
after vitrectomy. CONCLUSIONS: In eyes with diabetic macular oedema without
evident macular traction from a thickened vitreous membrane, vitrectomy resulted 
in the resolution of macular oedema, with an improvement in visual acuity in the 
majority of cases. Eyes without preoperative macular photocoagulation had a
significantly higher percentage visual improvement than eyes without preoperative
macular laser treatment. A randomised controlled prospective trial of primary
vitrectomy versus macular photocoagulation is needed to determine the role of
vitrectomy as treatment modality for diabetic macular oedema.

PMID: 11450490 [PubMed - indexed for MEDLINE]

3010: Ophthalmic Genet. 2001 Jun;22(2):107-15.

Best's vitelliform macular dystrophy caused by a new mutation (Val89Ala) in the
VMD2 gene.

Eksandh L, Bakall B, Bauer B, Wadelius C, Andréasson S.

Department of Ophthalmology, University Hospital, Lund, Sweden.
louise.eksandh@telia.com

PURPOSE: To describe the clinical phenotype in a family with Best's vitelliform
macular dystrophy (BMD) and a new mutation (Val89Ala) in the VMD2 gene. METHODS: 
The genotype was determined by direct sequence analysis of the individual exons
of VMD2. Nine members of a family with BMD were examined. The examination
included best-corrected visual acuity, electro-oculography (EOG), fundus
examination, and photography. Four of the patients were also examined with
full-field ERG and three with multifocal ERG. RESULTS: A T-to-C substitution was 
identified at position 370 in the cDNA of VMD2, leading to a Val89Ala change in
the protein. Six patients, five with the Val89Ala mutation and a nine-year-old
boy without the mutation, presented with a pathological Arden ratio on EOG
examination. Most of the patients with BMD in this family had an onset of visual 
failure by the age of 40-50 years. The older patients in the family demonstrated 
atrophic macular dystrophy. CONCLUSIONS: Patients with BMD and the Val89Ala
mutation in the VMD2 gene can present with a phenotype of a mostly late-onset
visual failure. These BMD patients, who present with visual failure and macular
degeneration in middle age, can be misdiagnosed as being affected with
adult-onset macular dystrophies instead of BMD, because the latter is often
regarded as a disease of childhood and adolescence.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11449320 [PubMed - indexed for MEDLINE]

3011: Clin Experiment Ophthalmol. 2001 Jun;29(3):188-92.

Effects of triamcinolone acetonide on microglial morphology and quantitative
expression of MHC-II in exudative age-related macular degeneration.

Penfold PL, Wong JG, Gyory J, Billson FA.

Save Sight Institute, Department of Clinical Ophthalmology, University of Sydney,
New South Wales, Australia. ppenfold@eye.usyd.edu.au

Animal models, in vitro assays and pilot clinical studies suggest that
intravitreal triamcinolone acetonide may be useful in the treatment of
age-related macular degeneration. The present case study reports the effect of
intravitreal triamcinolone acetonide injection on a subretinal neovascular
lesion, microglial morphology and quantitative expression of MHC-II antigens.
Triamcinolone acetonide significantly decreased MHC-II expression consistent with
immunocytochemical observations which revealed condensed microglial morphology.
The modulation of subretinal oedema and microglial morphology correlates with in 
vitro observations suggesting that downregulation of inflammatory markers and
endothelial cell permeability are significant features of the mode of action of
triamcinolone acetonide.

Publication Types: 
    Case Reports

PMID: 11446466 [PubMed - indexed for MEDLINE]

3012: J Glaucoma. 2001 Jun;10(3):233-6.

Cystoid macular edema associated with topical latanoprost in glaucomatous eyes
with a normally functioning blood-ocular barrier.

Furuichi M, Chiba T, Abe K, Kogure S, Iijima H, Tsukahara S, Kashiwagi K.

Department of Ophthalmology, Yamanashi Medical University, Tamaho, Japan.

PURPOSE: To study prospectively using optical coherence tomography (OCT) whether 
topical latanoprost induces retinal disorders, such as cystoid macular edema, in 
patients with glaucoma and a normally functioning blood-ocular barrier. METHODS: 
Sixty-eight eyes of 38 patients with glaucoma and no history of intraocular
surgery, uveitis, or laser trabeculoplasty were studied. Before initiation of
latanoprost treatment and after 1, 3, and 6 months of treatment, OCT images were 
taken, and the following tests were performed: visual acuity examination, fundus 
ophthalmoscopy, intraocular pressure measurement, and fundus color photography.
To evaluate retinal thickness in the fovea accurately. OCT scanning was repeated 
six times, and the smallest value was used as the retinal thickness in the fovea.
RESULTS: Latanoprost ophthalmic solution did not influence retinal thickness in
the fovea at any investigated time points compared with the time before
instillation, and no changes were observed in visual acuity, ophthalmoscopic
findings, and fundus photographs. The intraocular pressure was reduced
significantly at all investigated time points compared with the time before
instillation. CONCLUSIONS: It is unlikely that topical latanoprost induces
retinal disorders, such as cystoid macular edema, in glaucomatous eyes with a
normally functioning blood-ocular barrier.

PMID: 11442189 [PubMed - indexed for MEDLINE]

3013: Am J Ophthalmol. 2001 Jul;132(1):128-31.

The relation of socioeconomic factors to the incidence of early age-related
maculopathy: the Beaver Dam eye study.

Klein R, Klein BE, Jensen SC, Moss SE.

Department of Ophthalmology and Visual Sciences, University of Wisconsin Medical 
School, Madison, Wisconsin 53705-2397, USA. kleinr@epi.ophth.wisc.edu

PURPOSE: To investigate the relationship between socioeconomic factors and the
5-year incidence of age-related maculopathy. METHODS: The Beaver Dam Eye Study, a
population-based cohort study, examined 3681 adults (range, 43-86 years of age at
baseline) living in Beaver Dam, Wisconsin, at baseline and 5 years later.
Standardized protocols for physical examination, including administration of a
questionnaire that included questions regarding income, education level, and
status and type of employment, and fundus photography to determine age-related
maculopathy, were performed. RESULTS: While controlling for age and sex, less
education, and being in a service-related occupation compared with a white collar
professional occupation, was associated (P <.05) with the incidence of early
age-related maculopathy. CONCLUSION: These data show an association of education 
and occupation but not income with the incidence of early age-related maculopathy
that appears independent of smoking or vitamin supplement use status.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11438075 [PubMed - indexed for MEDLINE]

3014: Am J Ophthalmol. 2001 Jul;132(1):122-3.

Postsurgical evaluation of idiopathic vitreomacular traction syndrome by optical 
coherence tomography.

Uchino E, Uemura A, Doi N, Ohba N.

Department of Ophthalmology, Kagoshima University Faculty of Medicine,
Kagoshima-shi, Japan.

PURPOSE: To report a case of idiopathic vitreomacular traction syndrome with
preoperative and postoperative evaluation by optical coherence tomography.
DESIGN: Interventional case report. METHODS: A 62-year-old woman presented with
blurred vision in the left eye because of idiopathic vitreomacular traction
syndrome, and she underwent a pars plana vitrectomy. Optical coherence tomography
was performed before and after surgery. RESULTS: Preoperative optical coherence
tomography, right eye, revealed residual adhesion of incomplete posterior
vitreous detachment and edematous, thickened outer retina in the macula. A
successful vitrectomy relieved vitreoretinal traction with nearly complete
resolution of cystoid macular edema within 1 month after surgery, followed in
subsequent months by gradual foveal depression resembling a lamellar macular
hole. Resolution of subretinal serous fluid was delayed with complete
disappearance, some 12 months after surgery, which correlated with a gradual
improvement in visual acuity. CONCLUSION: Optical coherence tomography provides a
sensitive anatomical evaluation of vitreomacular traction syndrome.
Reorganization of retinal tissue after surgical intervention for vitreoretinal
traction may be slower than is apparent from conventional examinations.

Publication Types: 
    Case Reports

PMID: 11438072 [PubMed - indexed for MEDLINE]

3015: Am J Ophthalmol. 2001 Jul;132(1):85-93.

Theoretical investigation of the role of choriocapillaris blood flow in treatment
of subfoveal choroidal neovascularization associated with age-related macular
degeneration.

Flower RW, von Kerczek C, Zhu L, Ernest A, Eggleton C, Topoleski LD.

Department of Ophthalmology, University of Maryland, Baltimore, USA.

PURPOSE: To investigate the relationship between choriocapillaris blood flow and 
blood flow through an overlying choroidal neovascularization, as it relates to
photocoagulation-induced changes in the choriocapillaris circulation. METHODS: A 
theoretical model that simulates the blood flow in the choriocapillaris and
choroidal neovascularization of the human eye was developed, based on
histologically determined vascular geometry and experimentally measured blood
pressure gradients. The choriocapillaris blood pressure and blood flow were
examined before and after simulated photocoagulation of various Sattler layer
vessels entering the choriocapillaris in the vicinity of the choroidal
neovascularization. (The Sattler layer is the inner layer of medium-sized
choroidal vessels that includes both arterioles and venules that supply the
choriocapillaris.) RESULTS: The theoretical model showed that both partial and
complete occlusion of either Sattler arteriole or venous vessels in the vicinity 
of the capillary-like vessels connecting a choroidal neovascularization to the
underlying choriocapillaris results in significant choroidal neovascularization
blood flow reduction. These theoretical results are similar to clinically
observed changes induced by laser photocoagulation of feeder vessels. (In this
discussion, the term "feeder vessels" refers to those vessels in an indocyanine
green angiogram image that appear to supply blood to a choroidal
neovascularization; these vessels appear to be Sattler layer vessels, rather than
the histologically demonstrated short, capillary-like vessels that form
choriocapillaris-choroidal neovascularization communications.) CONCLUSIONS:
Reduction of choriocapillaris blood flow underlying a choroidal
neovascularization may be sufficient to reduce the blood flow rate in the
choroidal neovascularization and thereby reduce the associated retinal edema. The
results also suggest that reduction of choriocapillaris blood flow may be the
common hemodynamic event associated with the successful application of several
currently practiced methods of choroidal neovascularization treatment, including 
feeder vessel photocoagulation, photodynamic therapy, transpupillary
thermotherapy, and prophylactic drusen photocoagulation. Ultimately, this model
may be useful in determining optimal placement of laser photocoagulation burns to
achieve a desirable perturbation in choroidal blood flow distribution and thereby
reduce choroidal neovascularization blood flow to the extent necessary to
obliterate associated retinal edema.

PMID: 11438059 [PubMed - indexed for MEDLINE]

3016: Am J Ophthalmol. 2001 Jul;132(1):81-4.

Corrected and republished in:
    Am J Ophthalmol. 2001 Sep;132(3):458-61.

Optical coherence tomography of tractional macular elevations in eyes with
proliferative diabetic retinopathy.

Imai M, Iijima H, Hanada N.

Department of Ophthalmology, Yamanashi Medical University, Tamaho, Yamanashi,
Japan. mimai@res.yamanashi-med.ac.jp

PURPOSE: To document the findings of optical coherence tomography in eyes with
tractional macular elevation associated with proliferative diabetic retinopathy, 
paying special attention to differentiating between tractional retinal detachment
and retinoschisis. DESIGN: Observational case series. METHODS: We retrospectively
reviewed images of optical coherence tomography obtained from 17 consecutive eyes
(17 patients) with proliferative diabetic retinopathy without vitreous opacity
and showing tractional macular elevation with or without foveal involvement.
RESULTS: Tractional retinal detachment and retinoschisis could be differentiated 
in the cross-sectional images of optical coherence tomography. Retinoschisis with
or without associated retinal detachment was observed in 16 of 17 eyes (94%),
whereas retinal detachment was observed in only six of 17 eyes (35%). Five eyes
showed both findings of retinal detachment and retinoschisis. CONCLUSIONS:
Optical coherence tomography is useful for distinguishing tractional
retinoschisis from retinal detachment in eyes with proliferative diabetic
retinopathy and macular elevation. Tractional retinoschisis with or without
retinal detachment is the most frequent pattern of tractional macular elevation
in eyes with proliferative diabetic retinopathy.

PMID: 11438058 [PubMed - indexed for MEDLINE]

3017: Isr Med Assoc J. 2001 Jun;3(6):443-8.

Ocular blood flow measurements and their importance in glaucoma and age-related
macular degeneration.

Garzozi HJ, Shoham N, Chung HS, Kagemann L, Harris A.

Department of Ophthalmology, HaEmek Medical Center, Afula, Israel.

This survey of methods for assessing ocular hemodynamics in glaucoma and
age-related macular degeneration is not complete, but it does cover those likely 
to be encountered in the literature. A fundamental problem in getting to grips
with the ocular blood flow literature is the difficulty in comparing the results 
of similar studies employing different assessment techniques. As evident from the
discussion above, each technique evaluates a portion of the ocular circulation in
a distinct way. Some of the methods overlap with regard to the tissues that can
be used for examination, while others are directed at entirely different parts of
the ocular vasculature. Despite these difficulties, hemodynamic studies of
glaucoma and AMD are likely to grow in importance. On the basis of accumulating
epidemiological and clinical evidence, it is becoming apparent that intraocular
pressure is not the sole etiological factor in glaucoma, and retinal pigment
epithelium senescence is not the sole etiological factor in AMD. Circumstantial
evidence of vascular involvement in glaucoma and AMD has now been bolstered by
experimental evidence. If the current pace of refinement of newly established
technologies for evaluating ocular blood flow is maintained, they will soon be
ready for deployment in the clinic. The only problem is the availability of
expensive instruments and trained personnel. The ultimate beneficiaries of work
in this area will not be researchers, but patients.

Publication Types: 
    Review

PMID: 11433640 [PubMed - indexed for MEDLINE]

3018: Invest Ophthalmol Vis Sci. 2001 Jul;42(8):1945-9.

Development of a reading speed test for potential-vision measurements.

Elliott DB, Patel B, Whitaker D.

Department of Optometry, University of Bradford, Bradford, West Yorkshire BD7
1DP, United Kingdom. d.elliott1@bradford.ac.uk

PURPOSE. Previous studies suggest that optimal reading speed is unaffected by
cataract, yet is significantly reduced in age-related macular degeneration (ARMD 
). This raises the question of whether a reading speed test could be developed to
assess potential vision after cataract surgery. METHODS. Nineteen subjects with
cataract, 15 with ARMD, and 13 control subjects with normal, healthy eyes read
Bailey-Lovie word charts aloud, and subsequently, critical print size and optimal
reading speed were calculated. Measurements were also taken with the charts in
reversed-contrast polarity and after pupillary dilation. RESULTS. Although the
subjects with cataract had reduced word acuity and increased critical print size,
optimal reading speed was similar to that of the control group at a mean of
approximately 100 wpm. Optimal reading speed in the subjects with ARMD was
substantially worse (mean of 39 wpm). Reversing the contrast polarity of the
charts slightly increased the word acuity and optimal reading speed of the
subjects with cataract. CONCLUSIONS. The results suggest that optimal reading
speed would be useful as a potential-vision test. The proposed test would use
text size of at least 1.32 degrees (1.2 log minimum angle of resolution
[logMAR]), and pupil dilation would be unnecessary. A reading test with black
letters on a white background would be adequate, because charts with
reversed-contrast polarity made minimal difference in reading speed.

Publication Types: 
    Comparative Study
    Evaluation Studies
    Research Support, Non-U.S. Gov't

PMID: 11431465 [PubMed - indexed for MEDLINE]

3019: Invest Ophthalmol Vis Sci. 2001 Jul;42(8):1685-90.

Delayed dark-adaptation and lipofuscin accumulation in abcr+/- mice: implications
for involvement of ABCR in age-related macular degeneration.

Mata NL, Tzekov RT, Liu X, Weng J, Birch DG, Travis GH.

Jules Stein Eye Institute, UCLA School of Medicine, 100 Stein Plaza, Los Angeles,
CA 90095-7008, USA.

PURPOSE. To examine the ocular phenotype in mice heterozygous for a null mutation
in the abcr gene. METHODS. Retinas and retinal pigment epithelia (RPE) were
prepared from wild-type, abcr+/-, and abcr-/- mice. Fresh tissues were
homogenized and analyzed by normal phase high-performance liquid chromatography
(HPLC) for the presence of retinoids and phospholipids. In another study, fixed
tissues were sectioned and analyzed by light and electron microscopy. Finally,
anesthetized mice were studied by electroretinography (ERG) at different times
after exposure to strong light. RESULTS. A2E, the major fluorophore of
lipofuscin, and its precursors, A2PE-H(2) and A2PE, were approximately fourfold
more abundant in 8-month-old abcr+/- than in the wild-type retina and RPE. The
levels of these substances in abcr+/- mice were approximately 40% those in
abcr-/- mice. Lipofuscin pigment-granules were also visible in abcr+/- RPE cells 
by electron microscopy. Accumulation of A2PE-H(2) and A2E in abcr+/- retina and
RPE, respectively, was strongly dependent on light exposure. Heterozygous mutants
also exhibited delayed recovery of rod sensitivity by ERG. This delay was
correlated with elevated levels of all-trans-retinaldehyde (all-trans-RAL) in
retina after a photobleach and was not caused by a reduction in quantum-catch due
to depletion of 11-cis-retinaldehyde (11-cis-RAL). CONCLUSIONS. Partial loss of
the ABCR or rim protein is sufficient to cause a phenotype in mice similar to
recessive Stargardt's disease (STGD) and age-related macular degeneration (AMD)
in humans. These data are consistent with the suggestion that the STGD
carrier-state may predispose to the development of AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11431429 [PubMed - indexed for MEDLINE]

3020: Insight. 2001 Apr;26(2):44-8.

Photodynamic therapy: the nurse's role.

Rich D, Lane AM, Miller JW.

Morse Laser Center, Massachusetts Eye and Ear Infirmary, Boston, 02114, USA.

Patients with neovascular (wet) age-related macular degeneration, the leading
cause of blindness in persons older than 50 years in developed countries,
experience severe visual loss due to choroidal neovascularization, the growth of 
abnormal vessels under the retina. Photodynamic therapy is a new treatment
modality that combines an intravenous injection of a photosensitizing drug, such 
as verteporfin, and nonthermal laser light application, which destroys choroidal 
neovascularization without damaging normal surrounding tissue. It has led to new 
challenges for nurses working in the ambulatory laser setting, including
medication preparation, drug administration, and education regarding precautions 
and potential systemic side effects of photodynamic therapy.

PMID: 11426204 [PubMed - indexed for MEDLINE]

3021: Insight. 2001 Apr;26(2):40-3.

Psychosocial implications of clinical trials on patients with age-related macular
degeneration and pathologic myopia as seen in the photodynamic therapy trials.

Porter T, Nesbitt P.

Submacular Surgery Trial, The Wilmer Eye Institute, The Johns Hopkins Hospital,
Baltimore, MD 21287, USA.

Photodynamic therapy is a combination of the systemically injected
photosensitizing drug, verteporfin, and the subsequent exposure of the affected
retina to a low-beam diode laser. Eligible participants in the photodynamic
therapy clinical trial were those with "wet" cases of age-related macular
degeneration with subfoveal, predominantly classic lesions. The expected outcome 
of the treatment is to preserve vision, not to restore lost vision. Study
participants are frustrated in their performance of daily activities and often
have unrealistic expectations of photodynamic therapy treatment outcomes (eg,
improved vision). Frustration and fear are evident at visits during which their
actual vision loss is measured. One of our goals is to help the patients have
realistic expectations of treatment outcomes.

PMID: 11426203 [PubMed - indexed for MEDLINE]

3022: Ophthalmology. 2001 Jul;108(7):1203-8.

Induced corneal astigmatism after macular translocation surgery with scleral
infolding.

Kim T, Krishnasamy S, Meyer CH, Toth CA.

Cornea Service, Department of Ophthalmology, Duke University Medical Center,
Durham, North Carolina 27710-3802, USA. terry.kim@duke.edu

OBJECTIVE: To document the corneal astigmatism that occurs with macular
translocation after scleral infolding surgery. DESIGN: Retrospective case series 
of a nonrandomized clinical trial. PARTICIPANTS: Eight consecutive age-related
macular degeneration patients (eight eyes) with choroidal neovascularization who 
underwent macular translocation with scleral infolding at the Duke University Eye
Center from December 1998 through October 1999. METHODS: We retrospectively
reviewed the charts of eight consecutive patients who underwent macular
translocation surgery involving scleral infolding in the superotemporal quadrant.
Two patients subsequently underwent release of scleral infolding. MAIN OUTCOME
MEASURES: After surgery, these eyes were evaluated for corneal astigmatism with
manifest refraction, keratometry, and computerized corneal topography. RESULTS:
All eight eyes of eight patients revealed marked degrees of corneal astigmatism. 
Measurement of astigmatism via manifest refraction, keratometry, and corneal
topography confirmed postoperative astigmatism corresponding to the axis of the
scleral infolding. The amount of corneal astigmatism ranged from 1.75 to 7.37
diopters (D; mean, 4.60 D), with steepening along the axis of scleral infolding
in the superotemporal quadrant of each eye (mean, 42.50 degrees from vertical;
range, 24 degrees -66 degrees from vertical). Release of scleral infolding in two
patients resulted in significant reduction of corneal astigmatism. CONCLUSIONS:
Scleral shortening procedures used in macular translocation surgery may induce
large amounts of corneal astigmatism. These patients should be assessed with
keratometry and corneal topography to determine the accurate amount and axis.
Thereafter, contact lens fitting or scleral infolding release may be considered
as therapeutic options for large amounts of astigmatism persisting after surgery.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11425676 [PubMed - indexed for MEDLINE]

3023: Ophthalmology. 2001 Jul;108(7):1196-202.

Delays in rod-mediated dark adaptation in early age-related maculopathy.

Owsley C, Jackson GR, White M, Feist R, Edwards D.

Department of Ophthalmology, School of Medicine, University of Alabama at
Birmingham, 35294-0009, USA. owsley@eyes.uab.edu

OBJECTIVE: To determine whether there are disturbances in the rod-mediated
kinetics of dark adaptation in early age-related maculopathy (ARM). DESIGN:
Comparative, observational case series. PARTICIPANTS: Twenty older adults with
early ARM as defined by one or more large (> 63 microm) drusen, focal
hyperpigmentation, or both, but no choroidal neovascularization or geographic
atrophy, and 16 adults in the same age range with none of these fundus features. 
All participants had 20/25 visual acuity or better in the tested eye. METHODS:
Dark adaptation functions were measured using a modified Humphrey Field Analyzer 
(Zeiss Humphrey Systems, Dublin, CA) to assess the rate of rod-mediated
sensitivity recovery at 12 degrees on the vertical meridian in the inferior
visual field after exposure to the equivalent of a 98% bleach. Baseline
(prebleach) scotopic sensitivity, visual acuity, contrast sensitivity, and
photopic sensitivity were also measured. MAIN OUTCOME MEASURES: Rod-cone break;
second and third components of rod-mediated dark adaptation; time to baseline
sensitivity; and baseline (prebleach) scotopic sensitivity. RESULTS: Although
their visual acuity was at least 20/25, patients with early ARM on average
exhibited deficits in almost all rod-mediated parameters of dark adaptation as
compared with age-similar healthy participants. For example, the rod-cone break
was delayed approximately 10 minutes in early ARM patients as compared with
healthy participants. Age-related maculopathy patients were more likely to fall
outside the normal reference range for variables representing dark adaptation
kinetics than for steady-state visual functions such as scotopic sensitivity. For
example, 85% of ARM patients fell outside the normal reference range in at least 
one dark adaptation kinetic parameter, whereas only 25% of ARM patients fell
outside the normal reference range for steady-state scotopic sensitivity.
CONCLUSIONS: Rod-mediated kinetic parameters of dark adaptation, which reflect
the sensitivity recovery of the visual cycle, are disrupted early in ARM
pathogenesis.

Publication Types: 
    Comparative Study
    Research Support, U.S. Gov't, P.H.S.

PMID: 11425675 [PubMed - indexed for MEDLINE]

3024: Am J Med Genet. 2001 Jul 1;101(3):195-7.

Ectodermal dysplasia, ectrodactyly and macular dystrophy (EEM syndrome) in
siblings.

Senecky Y, Halpern GJ, Inbar D, Attias J, Shohat M.

Department of Developmental Pediatrics, Schneider Children's Medical Center of
Israel, Petah Tikva, Israel. senekimi@mail.iol.co.il

We report a brother and sister with ectodermal dysplasia, ectrodactyly, and
macular dystrophy (the EEM syndrome). Both children had abnormalities of the
hands and the hair, and bilateral macular degeneration. The clinical picture in
both is similar to, but less severe than, that described in the previously
reported cases of this rare syndrome. Even though the parents are not related,
they are both of Jewish Yemenite origin, and the possibility of a common ancestor
cannot be ruled out. This would suggest autosomal recessive inheritance. The
clinical picture in these patients suggests either variable expression or genetic
heterogeneity in the EEM syndrome and further delineates the clinical and genetic
spectrum of this condition. Copyright 2001 Wiley-Liss, Inc.

Publication Types: 
    Case Reports
    Review

PMID: 11424132 [PubMed - indexed for MEDLINE]

3025: Undersea Hyperb Med. 2000 Winter;27(4):195-204.

Adjunctive hyperbaric oxygenation in macular edema of vascular origin.

Krott R, Heller R, Aisenbrey S, Bartz-Schmidt KU.

Department of Vitreoretinal Surgery, University of Cologne,
Joseph-Stelzmann-Str., Weyertal 76, 50931 Cologne, Germany.

Macular edema (ME) is a primary reason for permanent decreases of visual acuity
(VA) in diabetic retinopathy and retinal vein occlusions. The standard treatment 
(photocoagulation, rheological treatment) provide only a limited success. We have
therefore studied the additional use of hyperbaric oxygenation (HBO2) in patients
with persistent ME. Five patients (1 female, 4 male; 7 eyes) were treated by
adjunctive HBO2. The average age of the patients was 60.6 (38.9-76.8) yr. The VA 
was measured with Early Treatment Diabetic Retinopathy Study charts before and
after HBO2 with a monthly follow up. Fluorescein angiography was performed before
and after HBO2 with a follow up every 3 mo. Each patient received 10-30 HBO2
treatments (median 15). The follow-up period was 15 mo. for every patient. The
mean increase in VA was 3.5 (2-4) lines after HBO2. Retinal photocoagulation was 
performed in six eyes. Diabetic macular edemas showed no morphologic change,
while ME originating from retinal vein occlusions (CME) regressed. The VA in our 
patients with ME of vascular origin seemed to improve with HBO2. Photocoagulation
was necessary in most cases. Visual function correlated with the angiographic
presentation only for CME.

Publication Types: 
    Case Reports

PMID: 11419360 [PubMed - indexed for MEDLINE]

3026: Bioorg Med Chem Lett. 2001 Jun 18;11(12):1533-40.

Fluorescent pigments of the retinal pigment epithelium and age-related macular
degeneration.

Ben-Shabat S, Parish CA, Hashimoto M, Liu J, Nakanishi K, Sparrow JR.

Department of Chemistry, Columbia University, New York, NY 10027, USA.

The major hydrophobic fluorophore of the retinal pigment epithelium (RPE) is A2E,
a pyridinium bis-retinoid derived from all-trans-retinal and
phosphatidyl-ethanolamine. The accumulation of fluorophores such as A2E is
implicated in the pathogenesis of age-related macular degeneration (AMD), a
disease associated with the deterioration of central vision and a leading cause
of blindness in the elderly. Recent chemical and biological studies have provided
insight into the synthesis and biosynthesis of A2E, the spectroscopic properties 
of this pigment, and the role of A2E and RPE cell death.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.
    Review

PMID: 11412975 [PubMed - indexed for MEDLINE]

3027: Ophthalmologica. 2001 Jul-Aug;215(4):247-53.

Early detection, diagnosis and management of choroidal neovascularization in
age-related macular degeneration: the role of ophthalmologists.

Sickenberg M.

Hôpital Ophtalmique Universitaire Jules Gonin, Lausanne, Switzerland.
michel.sickenberg@bluewin.ch

Choroidal neovascularization (CNV) secondary to age-related macular degeneration 
(AMD) is a serious condition which, if unrecognized and untreated, can result in 
the rapid deterioration of vision. Early detection and prompt referral to a
retina specialist may potentially reduce the high risk of severe vision loss. The
majority of AMD patients with CNV who present to an ophthalmologist will have
been referred by either a primary care physician or an optometrist. Following
referral, ophthalmologists will confirm diagnosis and identify the location and
composition of the CNV. This information will provide the basis for a decision on
what treatment, if any, is indicated. Until last year, laser photocoagulation was
the only clinically-proven treatment option for neovascular AMD in large-scale
randomized clinical trials, although many patients were not eligible for this
treatment. Verteporfin (Visudyne(TM)) therapy is a new treatment option that uses
photodynamic therapy in patients with predominantly classic subfoveal CNV
secondary to AMD. Retrospective analyses show that the introduction of
verteporfin therapy is likely to increase the number of patients with neovascular
AMD who can be treated. Early detection, prompt referral and treatment, together 
with appropriate use of low vision aids, will help to optimize patient outcomes
and quality of life. Copyright 2001 S. Karger AG, Basel

Publication Types: 
    Review

PMID: 11399930 [PubMed - indexed for MEDLINE]

3028: Acta Ophthalmol Scand. 2001 Jun;79(3):266-70.

Quantitative assessment of retinal thickness in diabetic patients with and
without clinically significant macular edema using optical coherence tomography.

Yang CS, Cheng CY, Lee FL, Hsu WM, Liu JH.

Department of Ophthalmology, Taipei Veterans General Hospital and National
Yang-Ming University School of Medicine, Taipei, Taiwan.

PURPOSE: To assess patients with diabetic macular edema quantitatively using
optical coherence tomography (OCT). METHODS: OCT was performed in 14 eyes with
diabetic retinopathy and ophthalmoscopic evidence of clinically significant
macular edema (CSME) and in 19 diabetic eyes without CSME. Retinal thickness was 
computed from the tomograms at fovea and other 36 locations throughout the
macula. RESULTS: The mean +/- standard deviation foveal thickness was 255.6 +/-
138.9 microm in eyes with CSME, and 174.6 +/- 38.2 microm in eyes without CSME (p
= 0.051). Within 2000 microm of the center of the macula, eyes with CSME had
significantly thicker retina in the inferior quadrant than those without CSME (p 
< 0.01). The foveal thickness was correlated with logMAR visual acuity (gamma =
0.68, p < 0.01). OCT identified sponge-like retinal swelling and/or cystoid
macular edema in 11 (58%) eyes without CSME, and in 12 (86%) eyes with CSME.
CONCLUSIONS: Criteria of CSME seem to be insufficient in really identifying
macular edema. OCT may be more sensitive than a clinical examination in assessing
diabetic macular edema and is a quantitative tool for documenting changes in
macular thickening.

PMID: 11401636 [PubMed - indexed for MEDLINE]

3029: Ann Epidemiol. 2001 Jul;11(5):328-36.

Prospective study of zinc intake and the risk of age-related macular
degeneration.

Cho E, Stampfer MJ, Seddon JM, Hung S, Spiegelman D, Rimm EB, Willett WC,
Hankinson SE.

Departments of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA.
eunyoung.cho@channing.harvard.edu

PURPOSE: Zinc is found in high concentrations in the retina and is hypothesized
to reduce the risk of age-related macular degeneration (AMD). Any long-term
benefit associated with dietary zinc intake has not been evaluated. METHODS: We
followed 66,572 women and 37,636 men who were > or = 50 years old and had no
diagnosis of AMD or cancer. Zinc intake from food, multivitamins, and supplements
was assessed with a semiquantitative food-frequency questionnaire at baseline (in
1984 for women and in 1986 for men) and repeated during follow-up (twice for
women, once for men). RESULTS: During 10 years of follow-up for women and 8 years
of follow-up for men, we confirmed 384 incident cases of AMD (195 cases of the
early form and 189 cases of the late form) associated with a visual acuity loss
of 20/30 or worse. After multivariate adjustment for potential risk factors, the 
pooled relative risk was 1.13 (95% confidence interval [CI], 0.82 to 1.57;
p-value, test for trend, 0.74) among participants in the highest quintile of
total zinc intake (energy-adjusted median; 25.5 mg/day for women and 40.1 mg/day 
for men) compared with those in the lowest quintile (energy-adjusted median; 8.5 
mg/day for women and 9.9 mg/day for men). The relative risk for highest compared 
with lowest quintile was 1.04 (95% CI, 0.59 to 1.83; p-value, test for trend,
0.54) for zinc intake from food. Subjects who took zinc supplements had a pooled 
multivariate relative risk of 1.04 (95% CI, 0.75 to 1.45). CONCLUSIONS: In these 
two large prospective studies, moderate zinc intake, either in food or in
supplements, was not associated with a reduced risk of AMD.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.

PMID: 11399447 [PubMed - indexed for MEDLINE]

3030: Hum Mutat. 2001 Jun;17(6):504-10.

Spectrum of ABCA4 (ABCR) gene mutations in Spanish patients with autosomal
recessive macular dystrophies.

Paloma E, Martínez-Mir A, Vilageliu L, Gonzàlez-Duarte R, Balcells S.

Departament de Genètica, Universitat de Barcelona, Barcelona, Spain.

The ABCA4 gene has been involved in several forms of inherited macular dystrophy.
In order to further characterize the complex genotype-phenotype relationships
involving this gene, we have performed a mutation analysis of ABCA4 in 14 Spanish
patients comprising eight STGD (Stargardt), four FFM (fundus flavimaculatus), and
two CRD (Cone-rod dystrophy) patients. SSCP (single-strand conformation
polymorphism) analysis and DNA sequencing of the coding and 5' upstream regions
of this gene allowed the identification of 16 putatively pathogenic alterations, 
nine of which are novel. Most of these were missense changes, and no patient was 
found to carry two null alleles. Overall, the new data agree with a working model
relating the different pathogenic phenotypes to the severity of the mutations.
When considering the information presented here together with that of previous
reports, a picture of the geographic distribution of three particular mutations
emerges. The R212C change has been found in French, Italian, Dutch, German, and
Spanish but not in British patients. In the Spanish collection, R212C was found
in a CRD patient, indicating that it may be a rather severe change. In contrast, 
c.2588G>C, a very common mild allele in the Dutch population, is rarely found in 
Southern Europe. Interestingly, the c.2588G>C mutation has been found in a double
mutant allele together with the missense R1055W. Finally, the newly described
L1940P was found in two unrelated Spanish patients, and may be a moderate to
severe allele. Copyright 2001 Wiley-Liss, Inc.

PMID: 11385708 [PubMed - indexed for MEDLINE]

3031: Optom Vis Sci. 2001 May;78(5):325-34.

Eye movements and reading with large print and optical magnifiers in macular
disease.

Bowers AR, Lovie-Kitchin JE, Woods RL.

Department of Vision Sciences, Glasgow Caledonian University, Glasgow, Scotland, 
United Kingdom. a.bowers@gcal.ac.uk

PURPOSE: Reading rate has been the main performance measure in studies that have 
compared reading with large print and optical magnifiers; eye movement
characteristics have not been considered. We compared both eye movement
characteristics and reading rates for subjects with macular disease reading
without and with a range of low-vision devices. METHODS: Silent reading rate and 
eye movement characteristics for text passages at critical print size of 21
subjects aged 14 to 88 years with macular disease were measured with and without 
their preferred low-vision device. Saccadic frequency was determined from a
sequencing task comprising five letters each separated by 5 degrees. Eye
movements were recorded using an infrared limbal reflection system. RESULTS:
There were no significant differences in reading rate, fixation durations,
saccade numbers per word, or percent retrace time when using a low-vision device 
compared with reading without a low-vision device. The percentage of regressions 
was, however, lower with the low-vision device. Saccadic frequency in the
sequencing task was predictive of reading performance with and without a
low-vision device. CONCLUSIONS: When reading at critical print size, in terms of 
reading rate or saccades per word, there was no advantage to using large print
over an optical low-vision device.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 11384010 [PubMed - indexed for MEDLINE]

3032: Optom Vis Sci. 2001 May;78(5):290-6.

Low-vision patients with age-related maculopathy read RSVP faster when word
duration varies according to word length.

Aquilante K, Yager D, Morris RA, Khmelnitsky F.

SUNY College of Optometry, New York, New York 10036, USA. aquilante@sunyopt.edu

Normally sighted younger and elder subjects as well as subjects with central
visual field loss (CFL) from age-related maculopathy read rapid serial visual
presentation (RSVP) text with words presented at a constant rate and at three
different rates where word presentation duration varied according to word length.
The elder subjects reading sentences foveally read fastest when word duration was
constant. The younger group reading random words peripherally read faster at a
variable word duration rate. The subjects with CFL read sentences an average of
33% faster when the presentation rate varied with word length. There was a trend 
for slow readers with CFL to benefit more than fast readers with CFL. We conclude
that varying word duration based on word length in rapid serial visual
presentation reading would improve reading rates for low-vision patients with
CFL.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.

PMID: 11384006 [PubMed - indexed for MEDLINE]

3033: Ophthalmology. 2001 Jun;108(6):1140-4.

Pars plana vitrectomy for cystoid macular edema secondary to sarcoid uveitis.

Kiryu J, Kita M, Tanabe T, Yamashiro K, Miyamoto N, Ieki Y.

Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School
of Medicine, Kyoto, Japan.

OBJECTIVE: To examine the results of pars plana vitrectomy for cystoid macular
edema secondary to sarcoid uveitis resistant to medical treatment. DESIGN:
Retrospective, interventional, noncomparative case series. SUBJECTS: Fourteen
consecutive subjects (18 eyes) with cystoid macular edema associated with sarcoid
uveitis resistant to medical treatment. INTERVENTION: All eyes underwent pars
plana vitrectomy. Nine eyes also underwent peeling of the epiretinal membrane or 
removal of the posterior vitreous cortex. MAIN OUTCOME MEASURES: Status of
macular edema, visual acuity, and complications. RESULTS: Ten eyes (56%) improved
2 or more lines of Snellen visual acuity within 12 months. Six eyes (33%)
remained unchanged, within a line of preoperative Snellen visual acuity, and two 
eyes (11%) worsened by 2 or more lines of Snellen visual acuity. Slit-lamp
biomicroscopy showed that cystoid macular edema had resolved in 14 eyes (78%)
within 9 months postoperatively. One eye (6%) had minimal edema, whereas three
eyes (17%) remained unchanged biomicroscopically at the final visit.
Postoperative complications included cataract formation, glaucoma, optic nerve
atrophy, epiretinal membrane formation, and tractional retinal detachment. No
severe postoperative inflammation was noted. CONCLUSIONS: Pars plana vitrectomy
seems to have a beneficial effect on cystoid macular edema caused by sarcoidosis 
resistant to medical treatment.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11382643 [PubMed - indexed for MEDLINE]

3034: Graefes Arch Clin Exp Ophthalmol. 2001 Feb;239(2):96-101.

Morphological and functional analyses of diabetic macular edema by optical
coherence tomography and multifocal electroretinograms.

Yamamoto S, Yamamoto T, Hayashi M, Takeuchi S.

Department of Ophthalmology, Toho University Sakura Hospital, 564-1 Shimoshizu,
Sakura, Chiba 285-8741, Japan. shuyama@med.toho-u.ac.jp

PURPOSE: To determine the correlation between the tomographic features and the
visual functions of eyes with diabetic macular edema. METHODS: Optical coherence 
tomographic (OCT) images and multifocal electroretinograms were obtained from 45 
eyes of 25 patients with diabetic macular edema and from 21 eyes of 21 normal
subjects. RESULTS: The OCT images showed cystoid macular edema in 18 eyes and
diffuse retinal swelling without cystoid edema in the other 27 eyes. The fovea
was significantly thicker in eyes with cystoid macular edema and in those with
diffuse retinal swelling than in normal eyes. The fovea of eyes with cystoid
edema was significantly thicker than the fovea of eyes with diffuse swelling. The
best-corrected visual acuity and the electrical response density from the macular
area were significantly reduced in eyes with diabetic macular edema, particularly
in those with cystoid edema. The best-corrected visual acuity and macular
response density of the multifocal ERGs were inversely correlated, and the
implicit times were directly correlated with foveal thickness. CONCLUSION: The
visual acuity was correlated significantly with morphological changes revealed by
OCT and with multifocal ERGs. The combination of OCT and multifocal ERGs may
provide objective criteria for the evaluation and assessment of diabetic macular 
edema.

PMID: 11372551 [PubMed - indexed for MEDLINE]

3035: Graefes Arch Clin Exp Ophthalmol. 2001 Feb;239(2):71-80.

Clinical electrophysiology of two rod pathways: normative values and clinical
application.

Scholl HP, Langrová H, Weber BH, Zrenner E, Apfelstedt-Sylla E.

University Eye Clinic, Schleichstrasse 12-16, 72076 Tübingen, Germany.
hendrik.scholl@uni-tuebingen.de

BACKGROUND: The scotopic 15-Hz flicker electroretinogram (ERG) has two limbs
(slow and fast ERG rod signals), and these have been attributed to two retinal
rod pathways (the ON rod bipolar and AII amacrine pathway and the rodcone
gap-junction pathway). The aim of this study was to provide normative values of
the scotopic 15-Hz flicker ERG, to estimate the inter-individual variability, and
to apply this method to a clinical setting. METHODS: Twenty-two normal subjects, 
one patient with retinitis pigmentosa (RP), and two patients with Stargardt's
mascular dystrophy (SMD) participated in the study. The SMD patients were
screened for mutations in the 50 exons of the ABCA4 (formerly ABCR) gene. We
measured ERG response amplitudes and phases to flicker intensities ranging from
-3.37 to -0.57 log scotopic trolands s at a flicker frequency of 15 Hz. RESULTS: 
The normal scotopic 15-Hz flicker ERG showed a biphasic amplitude pattern with a 
minimum at about-1.57 log scotopic trolands s, where there was an abrupt phase
shift of about 180 deg. The inter-individual variability in ERG amplitude ranged 
from 47% to 67% for the slow and from 41% to 64% for the fast rod signal. Both
the RP patient and the SMD patients (who were compound heterozygotes for
mutations in the ABCA4 gene) showed reduced amplitudes for the two rod ERG
pathways. CONCLUSION: The inter-individual variability might be explained by
anatomical differences between individual retinae. In the RP patient, the
amplitude reductions corresponded well with the standard rod ERG. In the SMD
patients, however, the scotopic 15-Hz flicker ERG revealed rod dysfunction,
whereas the standard rod ERG was within normal limits. The scotopic 15-Hz flicker
method may be more sensitive than the standard rod ERG.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11372548 [PubMed - indexed for MEDLINE]

3036: Br J Ophthalmol. 2001 Jun;85(6):708-13.

Yellow dye laser thermotherapy of choroidal neovascularisation in age related
macular degeneration.

Beintema MR, Oosterhuis JA, Hendrikse F.

University Eye Department, Maastricht, Netherlands. mbei@soog.azm.nl

AIM: A pilot study of the feasibility of using dye laser thermotherapy (LTT) at a
subcoagulation temperature to occlude newly formed vessels in patients with age
related macular degeneration (AMD). METHODS: Choroidal neovascularisation (CNV)
in 24 eyes with exudative AMD was treated with a continuous wave yellow laser at 
578 nm. Parameters were an exposure time of 2 or 5 seconds, a spot size of 750 or
1000 microm, and a laser power of 100-200 mW. The clinical end point was a
greyish discoloration at the treatment site. The effect of thermotherapy was
documented by ophthalmoscopic and fluorescein angiographic examination. The
follow up after LTT was 4-16 months, mean 5 months. RESULTS: LTT resulted in
total occlusion of newly formed vessels in 15 eyes (62.5%). Neovascular outgrowth
within 6 weeks and recurrences 2-4 months after LTT were observed, each in three 
eyes. In six of the nine eyes with occlusion of CNV without recurrence the
choriocapillaris remained perfused; in two eyes only the large choroidal vessels 
remained perfused. In six eyes pigmentary changes were the only ophthalmoscopic
and fluorescein angiographic signs of treatment. The effect of LTT is rather
unpredictable. CONCLUSION: CNV in AMD can effectively be treated by yellow dye
laser thermotherapy with preservation of choroidal perfusion. The technique
requires dosimetric adaptation.

PMID: 11371493 [PubMed - indexed for MEDLINE]

3037: Jpn J Ophthalmol. 2001 May-Jun;45(3):270-5.

Acute angle-closure glaucoma resulting from spontaneous hemorrhagic retinal
detachment in age-related macular degeneration: case reports and literature
review.

Chen SN, Ho CL, Ho JD, Guo YH, Chen TL, Chen PF.

Department of Ophthalmology, Chang-Gung Memorial Hospital, R.O.C, Taoyuan,
Taiwan.

PURPOSE: Acute angle-closure glaucoma resulting from massive subretinal
hemorrhage is a rare and catastrophic complication in age-related macular
degeneration. Anticoagulant usage had been strongly correlated with this
complication in previously reported cases. METHODS: Four patients (4 eyes), 3 men
and 1 woman, developed angle-closure glaucoma with diffuse subretinal hemorrhage 
and total hemorrhagic retinal detachment. RESULTS: Serial funduscopic
examinations and echographic studies in 2 eyes showed that the blood gradually
accumulated in the subretinal space. It took more than 10 days for the bleeding
to build up to bullous hemorrhagic retinal detachment and secondary glaucoma.
Anti-glaucomatous agents were given and sclerotomy was performed in 3 of the 4
patients. Phthisical changes were observed subsequently in these 3 eyes. The eye 
that received early drainage of blood was an exception, and a small degree of
residual acuity was retained. Three of the 4 patients had diabetes mellitus, and 
hypertension and vascular diseases were also present in the same 3 patients.
CONCLUSIONS: Diabetes mellitus might be a predisposing factor for the impaired
hemostasis. Anti-glaucomatous agents were of no effect in the management of
intraocular pressure. Sclerotomy and drainage of blood help control intraocular
pressure and relieve ocular pain. Poor final visual acuity is inevitable.
However, phthisical changes might be prevented with early sclerotomy and drainage
of blood.

Publication Types: 
    Case Reports
    Review

PMID: 11369377 [PubMed - indexed for MEDLINE]

3038: Arch Ophthalmol. 2001 May;119(5):745-51.

Comment in:
    Arch Ophthalmol. 2001 May;119(5):752-3.

Variation of codons 1961 and 2177 of the Stargardt disease gene is not associated
with age-related macular degeneration.

Guymer RH, Héon E, Lotery AJ, Munier FL, Schorderet DF, Baird PN, McNeil RJ,
Haines H, Sheffield VC, Stone EM.

Department of Ophthalmology, University of Iowa College of Medicine, Iowa City,
IA 52242, USA.

OBJECTIVES: To investigate the role of 2 specific alleles of the Stargardt
disease gene (ABCA4) in the pathogenesis of age-related macular degeneration
(AMD). Secondary objectives were to investigate differences in frequency of the
G1961E allele in selected ethnic groups as well as to examine the segregation of 
both G1961E and D2177N alleles in 5 multiplex families with AMD. METHODS: Five
hundred forty-four patients with AMD and 689 controls were ascertained from 3
continents. Blood samples from 62 normal individuals of Somalian ancestry were
also obtained. Participants were screened for the presence of these ABCA4 alleles
with a combination of restriction digestion and single-strand conformation
polymorphism analysis of polymerase chain reaction amplification products.
Detected alleles were confirmed by DNA sequencing. The number of subjects
exhibiting the G1961E or D2177N variants were compared between AMD and control
groups using a 2-tailed Fisher exact test. RESULTS: There was no significant
difference (P >.1) in the frequency of the G1961E and D2177N alleles in patients 
with AMD (2.2%) vs controls (1.0%). In contrast, there was a significant
difference (P< .001) in the frequency of the G1961E alleles between normal
individuals of Somali ancestry (11.3%) and normal individuals from other
populations (0.4%). There was no evidence of cosegregation of these alleles and
the AMD phenotype in the 5 multiplex families with AMD examined. These two ABCA4 
alleles were slightly more frequent in patients with AMD with choroidal
neovascularization (2.7%) than those without this complication (2.5%).
CONCLUSIONS: Somali ancestry is more than 100 times more strongly associated with
presence of the G1961E allele than the AMD phenotype. This study did not find any
statistically significant evidence for involvement of the G1961E or D2177N
alleles of the ABCA4 gene in AMD. CLINICAL RELEVANCE: The ABCA4 gene is
definitively involved in the pathogenesis of Stargardt disease and some cases of 
photoreceptor degeneration. However, it does not seem to be involved in a
statistically significant fraction of AMD cases.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11346402 [PubMed - indexed for MEDLINE]

3039: Ther Apher. 2001 Apr;5(2):128-33.

The role of rheology in hemapheresis.

Borberg H, Brunner R, Gaczkowski A, Michel M, Schreiner T, Tauchert M.

German Hemapheresis Center, University of Koln.

Rheological therapy attempts to favorably influence the blood flow mechanics for 
the treatment of diseases, mainly of the microcirculation but also of the
macrocirculation. Hemapheresis, originally used only for the elimination of an
excess of cellular or plasmatic components, was shown to also influence the
hemorheology favorably. As extracorporeal therapy affects the rheology much more 
than conventional hemorheotherapy, not only cellular or plasmatic hyperviscosity 
syndromes but also many more diseases associated with organ perfusion problems
due to diseases of the micro- and macrocirculation, especially in the elderly,
were and are increasingly considered to be indicated. Technical progress led away
from plasma exchange as an unspecific and unselective procedure to plasma
differential separation using precipitation. adsorption, and filtration. With our
recent development, we demonstrated that rheohemapheresis is the most advanced
technical procedure. The mechanism of action can well be related to a synergetic 
consideration of rheology. However. one has to keep in mind that the elimination 
of blood components such as lipids, immunoglobulins, and endothelial factors may 
well contribute to the explanation and understanding of the positive clinical
effects observed. These speculative aspects need further investigation.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 11354297 [PubMed - indexed for MEDLINE]

3040: Drugs Aging. 2001;18(4):233-41.

Age-related macular degeneration: cost-of-illness issues.

Oneill C, Jamison J, McCulloch D, Smith D.

School of Public Policy, Economics and Law, University of Ulster at Jordanstown, 
Newtownabbey, Northern Ireland. c.oneill2@ulst.ac.uk

Macular degeneration refers to the breakdown of cells in the centre of the
retina. Some degeneration is an inevitable consequence of the aging process;
however, when this is associated with loss of sight in the central part of the
field of vision an underlying pathology is considered present. Among those aged
55 years, the prevalence of the disease in the US was estimated at 1% rising to
approximately 15% among those aged 80 years. Other studies estimate the
prevalence of the disease to be higher and to be increasing. The main effect of
the disease is to reduce the ability of the individual to engage in everyday
activities that require clear central vision. It may also be associated with
elevated risks of depression and increased levels of dependency. Currently there 
is no effective treatment for the majority of patients. For a minority (< 10%)
laser photocoagulation therapy may be effective in reducing the risk of severe
vision loss. Another treatment, photodynamic therapy, is in development and many 
others are at an experimental stage. This review sought to establish current
knowledge on the cost of illness associated with age-related macular degeneration
(ARMD). A search of the literature, together with direct communication with
researchers in related fields and patient support/advocacy groups, was undertaken
to ascertain current knowledge on the cost of illness of ARMD. While literature
on the disease is extensive and literature on treatments is emerging, no
substantive information on direct or indirect costs was found although evidence
that loss of earnings may occur is beginning to emerge. Some information does
exist on cost of illness in diabetic retinopathy, a disease with similarities to 
ARMD, though even for this disease gaps in knowledge are apparent and wide
variations exhibited. Given current knowledge, it is not possible to report on
the cost of illness for ARMD with confidence. The lack of information on the cost
of illness in ARMD presents difficulties for researchers and policy makers in
assessing the cost effectiveness of the existing treatment, as well as new
treatments as they become available. Given developments in treatments and the
increasing prevalence of the disease, it is important that cost-of-illness
information is gathered for ARMD.

Publication Types: 
    Review

PMID: 11341471 [PubMed - indexed for MEDLINE]

3041: Indian J Ophthalmol. 2000 Dec;48(4):263-78.

Comment in:
    Indian J Ophthalmol. 2001 Jun;49(2):141; author reply 141-2.

New approaches in the management of choroidal neovascular membrane in age-related
macular degeneration.

Verma L, Das T, Binder S, Heriot WJ, Kirchhof B, Venkatesh P, Krebs I, Stolba U, 
Jahn C, Feichtinger H, Kellner L, Krugluger H, Pawelka I, Frohner U, Kruger A, Li
W, Tewari HK.

R.P Centre for Ophthalmic Sciences, AIIMS, New Delhi, India.

Age-related macular degeneration (AMD) is a leading cause of blindness in the
elderly population. The prevalence is reported to be 1.2-1.4% in several
population-based epidemiological studies. Currently 25-30 million people
worldwide are blind due to AMD. With the aging world population it is bound to
increase significantly, and could become a significant public health problem in
next two decades, with serious socio-economic implications. Several strategies
are today available to treat the wet form of AMD, which is responsible for
significant visual loss. These were until recently confined to laser
photocoagulation, and subretinal surgery, but today two other modalities, namely,
radiation and photodynamic therapy, are available. These treatment modalities
however, are aimed at preservation of vision only, and not at reversing the
process of the disease. Further research on antiangiogenic drugs and gene therapy
could significantly help AMD patients.

Publication Types: 
    Review

PMID: 11340884 [PubMed - indexed for MEDLINE]

3042: Am J Ophthalmol. 2001 May;131(5):664-6.

Transient formed visual hallucinations following macular translocation for
subfoveal choroidal neovascularization secondary to age-related macular
degeneration.

Au Eong KG, Fujii GY, Ng EW, Humayun MS, Pieramici DJ, de Juan E Jr.

Wilmer Ophthalmological Institute, Johns Hopkins University School of Medicine,
Johns Hopkins Hospital, Baltimore, Maryland 21287-9277, USA.

PURPOSE: To report the occurrence of transient formed visual hallucinations
following macular translocation. METHODS: Two case reports. RESULTS: Two white
women aged 84 and 83 years with bilateral age-related macular degeneration and
unilateral subfoveal choroidal neovascularization underwent macular translocation
with punctate retinotomy (limited macular translocation) and chorioscleral
infolding in the eye with neovascularization. They complained of formed visual
hallucinations which began within 24 hours following macular translocation and
ceased 7 and 3 days postoperatively, respectively. Their symptoms occurred in the
presence of normal cognition, orientation and insight, were not associated with
other psychiatric symptoms, and were characteristic of Charles Bonnet syndrome
(CBS). CONCLUSION: The temporary deliberate retinal detachment and/or poor vision
following macular translocation may be associated with postoperative CBS, and
this report extends the spectrum of conditions associated with CBS.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 11336950 [PubMed - indexed for MEDLINE]

3043: Am J Ophthalmol. 2001 May;131(5):541-60.

Comment in:
    Am J Ophthalmol. 2002 Feb;133(2):294-6.    Am J Ophthalmol. 2002 Jan;133(1):168-9.    Am J Ophthalmol. 2002 Jun;133(6):857; author reply 857-9.

Verteporfin therapy of subfoveal choroidal neovascularization in age-related
macular degeneration: two-year results of a randomized clinical trial including
lesions with occult with no classic choroidal neovascularization--verteporfin in 
photodynamic therapy report 2.

Verteporfin In Photodynamic Therapy Study Group.

PURPOSE: To determine if photodynamic therapy with verteporfin (Visudyne;
Novartis AG, Bülach, Switzerland), termed verteporfin therapy, can safely reduce 
the risk of vision loss compared with a placebo (with sham treatment) in patients
with subfoveal choroidal neovascularization caused by age-related macular
degeneration who were identified with a lesion composed of occult with no classic
choroidal neovascularization, or with presumed early onset classic choroidal
neovascularization with good visual acuity letter score. METHODS: This was a
double-masked, placebo-controlled (sham treatment), randomized, multicenter
clinical trial involving 28 ophthalmology practices in Europe and North America. 
The study population was patients with age-related macular degeneration, with
subfoveal choroidal neovascularization lesions measuring no greater than 5400
microm in greatest linear dimension with either 1) occult with no classic
choroidal neovascularization, best-corrected visual acuity score of at least 50
(Snellen equivalent approximately 20/100), and evidence of hemorrhage or recent
disease progression; or 2) evidence of classic choroidal neovascularization with 
a best-corrected visual acuity score of at least 70 (better than a Snellen
equivalent of approximately 20/40); assigned randomly (2:1) to verteporfin
therapy or placebo therapy. Verteporfin (6 mg per square meter of body surface
area) or placebo (5% dextrose in water) was administered by means of intravenous 
infusion of 30 ml over 10 minutes. Fifteen minutes after the start of the
infusion, a laser light at 689 nm delivered 50 J/cm(2) by application of an
intensity of 600 mW/cm(2) over 83 seconds using a spot size with a diameter 1000 
microm larger than the greatest linear dimension of the choroidal
neovascularization lesion on the retina. At follow-up examinations every 3
months, retreatment with the same regimen was applied if angiography showed
fluorescein leakage. The main outcome measure was at least moderate vision loss, 
that is, a loss of at least 15 letters (approximately 3 lines), adhering to an
intent-to-treat analysis with the last observation carried forward to impute for 
missing data. RESULTS: Two hundred ten (93%) and 193 (86%) of the 225 patients in
the verteporfin group compared with 104 (91%) and 99 (87%) of the 114 patients in
the placebo group completed the month 12 and 24 examinations, respectively. On
average, verteporfin-treated patients received five treatments over the 24 months
of follow-up. The primary outcome was similar for the verteporfin-treated and the
placebo-treated eyes through the month 12 examination, although a number of
secondary visual and angiographic outcomes significantly favored the
verteporfin-treated group. Between the month 12 and 24 examinations, the
treatment benefit grew so that by the month 24 examination, the
verteporfin-treated eyes were less likely to have moderate or severe vision loss.
Of the 225 verteporfin-treated patients, 121 (54%) compared with 76 (67%) of 114 
placebo-treated patients lost at least 15 letters (P =.023). Likewise, 67 of the 
verteporfin-treated patients (30%) compared with 54 of the placebo-treated
patients (47%) lost at least 30 letters (P =.001). Statistically significant
results favoring verteporfin therapy at the month 24 examination were consistent 
between the total population and the subgroup of patients with a baseline lesion 
composition identified as occult choroidal neovascularization with no classic
choroidal neovascularization. This subgroup included 166 of the 225
verteporfin-treated patients (74%) and 92 of the 114 placebo-treated patients
(81%). In these patients, 91 of the verteporfin-treated group (55%) compared with
63 of the placebo-treated group (68%) lost at least 15 letters (P =.032), whereas
48 of the verteporfin-treated group (29%) and 43 of the placebo-treated group
(47%) lost at least 30 letters (P =.004). Other secondary outcomes, including
visual acuity letter score worse than 34 (approximate Snellen equivalent of
20/200 or worse), mean change in visual acuity letter score, development of
classic choroidal neovascularization, progression of classic choroidal
neovascularization and size of lesion, favored the verteporfin-treated group at
both the month 12 and month 24 examination for both the entire study group and
the subgroup of cases with occult with no classic choroidal neovascularization at
baseline. Subgroup analyses of lesions composed of occult with no classic
choroidal neovascularization at baseline suggested that the treatment benefit was
greater for patients with either smaller lesions (4 disc areas or less) or lower 
levels of visual acuity (letter score less than 65, an approximate Snellen
equivalent of 20/50(-1) or worse) at baseline. Prospectively planned
multivariable analyses confirmed that these two baseline variables affected the
magnitude of treatment benefit. (ABSTRACT TRUNCATED)

Publication Types: 
    Clinical Trial
    Evaluation Studies
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11336929 [PubMed - indexed for MEDLINE]

3044: Expert Opin Pharmacother. 2001 Feb;2(2):351-61.

Verteporfin: a milestone in opthalmology and photodynamic therapy.

Brown SB, Mellish KJ.

Centre for Photobiology and Photodynamic Therapy, School of Biochemistry and
Molecular Biology, University of Leeds, Leeds LS2 9JT, UK. s.b.brown@leeds.ac.uk

During the past year, a photosensitiser named benzoporphyrin derivative (BPD) has
been approved in 26 countries under the generic name verteporfin (Visudynetrade
mark, Novartis), for the treatment of patients with a certain type of the wet
form of age-related macular degeneration (AMD) by photodynamic therapy (PDT). AMD
is the leading cause of blindness in the developed world, with approximately half
a million new cases of the wet form per year. The approval of Visudynetrade mark 
therapy represents a major milestone in ophthalmology since AMD was previously
untreatable by any modality which would preserve existing vision. It was also a
milestone in the development of PDT, not only because it represented the first
breakthrough in the use of PDT to treat an otherwise untreatable condition, but
also because it represented the first mass market for a PDT treatment where
prospects of a substantial financial return on many years of investment appear to
be likely. In this article, we look at the background to the development of BPD, 
primarily for its use in AMD, but also in other applications.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 11336591 [PubMed - indexed for MEDLINE]

3045: Drug Ther Bull. 2001 Apr;39(4):30-2.

Can [symbol: see text] verteporfin help in macular degeneration?

[No authors listed]

Age-related macular degeneration (AMD), a disorder affecting older people, is the
commonest cause of severe visual impairment in the UK. It involves degeneration
of the central retina (the macula) that results in diminished capacity for
detailed visual tasks, such as reading, writing and recognising faces. For most
people with AMD there is no effective treatment. [symbol: see text]Verteporfin
(Visudyne--Novartis Ophthalmics) was licensed last year for use in conjunction
with laser activation (photodynamic therapy) for the treatment of "age-related
macular degeneration in patients with predominantly classic subfoveal
neovascularisation". Here, we review the place of this treatment.

Publication Types: 
    Review

PMID: 11329798 [PubMed - indexed for MEDLINE]

3046: Invest Ophthalmol Vis Sci. 2001 May;42(6):1380-9.

L- and M-cone-driven electroretinograms in Stargardt's macular dystrophy-fundus
flavimaculatus.

Scholl HP, Kremers J, Vonthein R, White K, Weber BH.

Department of Experimental Ophthalmology, University Eye Hospital, Röntgenweg 11,
72076 Tübingen, Germany.

PURPOSE. To study the dynamics of the long (L)- and middle
(M)-wavelength-sensitive cone-driven pathways and their interactions in patients 
with Stargardt's macular dystrophy-fundus flavimaculatus (SMD-FF) and to
correlate them with other clinical parameters and individual genotypes. METHODS. 
Forty-seven patients with SMD-FF participated in the study. In addition to
standard 30-Hz flicker electroretinograms (30-Hz fERG), ERG responses were
measured to stimuli that modulated exclusively the L or the M cones (L/M cones)
or the two simultaneously. Blood samples were screened for mutations in the 50
exons of the ABCA4 gene. RESULTS. Patients with SMD-FF did not show a decrease in
the mean L/M-cone-driven ERG sensitivity, but there was a significant increase in
the interindividual variability. The mean L-/M-cone weighting ratio was normal.
However, the L-cone-driven ERG was significantly phase delayed, whereas the
M-cone-driven ERG was significantly phase advanced. These phase changes were
significantly correlated with disease duration. The amplitude and implicit time
of the standard 30-Hz fERG both correlated significantly with the L/M-cone-driven
ERG sensitivity and with the phase difference between the L/M-cone-driven ERGs,
indicating the complex origin of the standard 30-Hz fERG. Probable
disease-associated mutations in the ABCA4 gene were found in 40 of 45 patients,
suggesting that they form a genetically fairly uniform SMD-FF study group. There 
was no correlation between the genotype and the L/M-cone-driven ERGS:
CONCLUSIONS. The changes in L/M-cone-driven ERG sensitivity and phase possibly
represent two independent disease processes. The phase changes are similar to
those found in patients with retinitis pigmentosa and possibly are a general
feature of retinal dystrophies.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11328755 [PubMed - indexed for MEDLINE]

3047: Invest Ophthalmol Vis Sci. 2001 May;42(6):1179-89.

An analysis of allelic variation in the ABCA4 gene.

Webster AR, Héon E, Lotery AJ, Vandenburgh K, Casavant TL, Oh KT, Beck G, Fishman
GA, Lam BL, Levin A, Heckenlively JR, Jacobson SG, Weleber RG, Sheffield VC,
Stone EM.

Department of Ophthalmology, The University of Iowa College of Medicine, 200
Hawkins Drive, Iowa City, IA 52242, USA.

PURPOSE. To assess the allelic variation of the ATP-binding transporter protein
(ABCA4). METHODS. A combination of single-strand conformation polymorphism (SSCP)
and automated DNA sequencing was used to systematically screen this gene for
sequence variations in 374 unrelated probands with a clinical diagnosis of
Stargardt disease, 182 patients with age-related macular degeneration (AMD), and 
96 normal subjects. RESULTS. There was no significant difference in the
proportion of any single variant or class of variant between the control and AMD 
groups. In contrast, truncating variants, amino acid substitutions, synonymous
codon changes, and intronic variants were significantly enriched in patients with
Stargardt disease when compared with their presence in subjects without Stargardt
disease (Kruskal-Wallis P < 0.0001 for each variant group). Overall, there were
2480 instances of 213 different variants in the ABCA4 gene, including 589
instances of 97 amino acid substitutions, and 45 instances of 33 truncating
variants. CONCLUSIONS. Of the 97 amino acid substitutions, 11 occurred at a
frequency that made them unlikely to be high-penetrance recessive disease-causing
variants (HPRDCV). After accounting for variants in cis, one or more changes that
were compatible with HPRDCV were found on 35% of all Stargardt-associated alleles
overall. The nucleotide diversity of the ABCA4 coding region, a collective
measure of the number and prevalence of polymorphic sites in a region of DNA, was
found to be 1.28, a value that is 9 to 400 times greater than that of two other
macular disease genes that were examined in a similar fashion (VMD2 and EFEMP1).

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11328725 [PubMed - indexed for MEDLINE]

3048: Optom Vis Sci. 2001 Mar;78(3):162-8.

Retinal illuminance and the dissociation of letter and grating acuity in
age-related macular degeneration.

Fosse P, Valberg A, Arnljot HM.

Tambartun National Resource Centre of the Visually Impaired, Melhus, Norway.
per.fosse@eunet.no

PURPOSE: To report on the differential effect of retinal illuminance on letter
and grating acuity. METHODS: For 13 subjects with age-related macular
degeneration (ARMD) and four subjects with normal vision, standard distance and
near letter acuity, as well as grating acuity data were obtained at mesopic to
high-photopic light levels. RESULTS: In general, both acuity forms improved with 
increasing light level, but not in proportion with one another. The ratio of
letter/grating acuity separated the ARMD subjects into two subgroups, one with
relatively low letter acuity scores for which the dissociation of the two acuity 
forms increased with retinal illuminance, and another with higher letter acuity
values for which the ratio converged toward unity. CONCLUSIONS: These findings
demonstrate that both letter and grating acuity increase with retinal illuminance
and that equating grating acuity with optotype acuity is untenable in subjects
with ARMD, irrespective of light levels. The latter conclusion is of importance
whenever acuity is used as a criterion to classify the visually impaired with
regard to their legal and social status.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11327678 [PubMed - indexed for MEDLINE]

3049: Geriatr Nurs. 2001 Mar-Apr;22(2):96-9.

Macular degeneration in older adults.

Moore LW.

Department of Nursing at Xavier University in Cincinnati, Ohio, USA.

Macular degeneration, a chronic, progressive eye disease, is the leading cause of
blindness in older Americans. As the aging segment of society grows, the number
of seniors diagnosed with macular degeneration will increase. Caring for
individuals with this disease is a task that will be increasingly allotted to
nurses. This article presents information on the disease process, risk factors,
medical therapies, and nursing implications involved in caring for individuals
with this condition. When nurses gain a thorough understanding of macular
degeneration and the implications of living with this disease, quality care can
be provided to an expanding segment of society.

Publication Types: 
    Review

PMID: 11326218 [PubMed - indexed for MEDLINE]

3050: J Opt Soc Am A Opt Image Sci Vis. 2001 Apr;18(4):747-54.

Origin of deficits in the flicker electroretinogram of the cone system in
X-linked retinoschisis as derived from response nonlinearities.

Alexander KR, Barnes CS, Fishman GA.

Department of Ophthalmology and Visual Sciences, University of Illinois at
Chicago, 60612, USA. kennalex@uic.edu

The aim of this study was to identify the origin of a high-frequency attenuation 
in the flicker electroretinogram (ERG) of patients with X-linked retinoschisis
(XLRS) through an analysis of nonlinearities in the ERG response. The ERGs of six
patients with XLRS and six age-similar control subjects were recorded in response
to stimuli that consisted of pairs of sinusoids that had varying temporal
frequencies and that differed by either 8 or 16 Hz. Compared with the control
subjects, the patients with XLRS showed a significant reduction in the amplitude 
of the difference frequency to high-frequency stimuli that paralleled the
high-frequency attenuation of their ERG response fundamental. This result
indicates that a response attenuation at an initial linear filter, most likely
photoreceptoral, was a major determinant of the reduced ERG amplitude of the XLRS
patients at high temporal frequencies. Additional analyses of nonlinearities in
the ERG responses provided evidence of a postreceptoral component to the flicker 
ERG deficits of the XLRS patients, as well.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11318324 [PubMed - indexed for MEDLINE]

3051: Eye. 2001 Feb;15(Pt 1):34-8.

Ischaemic heart disease may predispose to pseudophakic cystoid macular oedema.

Jain R, Stevens JD, Bunce CV, Garrett C, Hykin PG.

Moorfields Eye Hospital, London, UK.

PURPOSE: Pseudophakic macular oedema (PMO) is uncommon following uncomplicated
phacoemulsification and lens implantation and the cause of infrequent cases is
rarely understood. This study was undertaken to determine whether a relationship 
exists between ischaemic heart disease (IHD) and PMO. METHODS: Retrospective case
note review was carried out of 177 (252 eyes) consecutive patients without
pre-existing retinal disease who underwent phacoemulsification and intraocular
lens implantation during a 12 month period. Patients with a post-operative best
corrected visual acuity < 6/9 underwent slit-lamp biomicroscopy and fluorescein
angiography to identify PMO. IHD was defined on clinical and electrocardiographic
grounds. The incidence of IHD was compared in patients with and without PMO and
statistical analysis performed using the Fisher's exact test. RESULTS: PMO
occurred in 4 patients (6 eyes), all of whom had IHD, whereas no PMO occurred in 
the remaining 173 patients (246 eyes) (p = 0.04). CONCLUSIONS: Pseudophakic
macular oedema represents an important complication following modern
phacoemulsification and intraocular lens implantation and is associated
significantly with ischaemic heart disease.

PMID: 11318291 [PubMed - indexed for MEDLINE]

3052: Eye. 2001 Feb;15(Pt 1):12-7.

Erratum in:
    Eye 2001 Apr;15(Pt 2):257.

Cystoid macular oedema in uveitis: an unsolved problem.

Freeman G, Matos K, Pavesio CE.

Moorfields Eye Hospital, London, UK.

Most papers on the subject of CMO associated with uveitis are retrospective,
combine patients with different disease aetiologies, at different stages of
evolution, and often describe patients who were previous treatment failures with 
other therapies besides the one under consideration. There are almost no
prospective randomised double-masked controlled studies. This is perhaps in part 
due to the relative sparsity of uveitis patients seen by many uveitis centres. At
the moment, treatment is largely empirical, based in large part on the studies,
and others, quoted above. The need to regularly repeat courses of therapy, loss
of efficacy of certain form of therapy after repeated use, and cumulative
side-effects, all need to be taken into consideration when interpreting results
and deciding upon the best approach to be adopted. The risks to the patient's
well-being increase with the addition of systemic medication, and long-term
steroid use can cause hypertension, induce or exacerbate diabetes, cause
premature osteoporosis, cushingoid features, peptic ulceration and aseptic
necrosis of the femoral head. Immunosuppressive drugs can be nephrotoxic,
hepatotoxic, cause hypertension, gastric disturbances and excessive hair growth. 
The assessment of macular changes, both structurally and functionally, is the key
aspect in understanding visual loss in CMO and also in predicting potential
visualrecovery. The combined use of the various tools mentioned here, such as
SLO, OCT and electrodiagnostic tests, may give us some of the necessary answers
in this process. However, all these tests will need to be validated. A
prospective analysis of CMO in cases of uveitis, especially if coupled with
therapeutic intervention, will give us the opportunity to achieve this objective.

Publication Types: 
    Review

PMID: 11318279 [PubMed - indexed for MEDLINE]

3053: Arch Ophthalmol. 2001 Apr;119(4):564-70.

Comment in:
    Arch Ophthalmol. 2001 Apr;119(4):573-5.

Autosomal dominant Stargardt-like macular dystrophy: founder effect and
reassessment of genetic heterogeneity.

Donoso LA, Frost AT, Stone EM, Weleber RG, MacDonald IM, Hageman GS, Cibis GW,
Ritter R 3rd, Edwards AO.

Department of Ophthalmology, University of Texas Southwestern Medical Center,
5323 Harry Hines Blvd, Dallas, TX 75390-9057. Albert.Edwards@UTSouthwestern.edu

OBJECTIVES: To characterize a disease-associated haplotype in 7 families with
autosomal dominant Stargardt-like macular dystrophy and to determine whether
these families share a common ancestor. METHODS: Twenty-five polymorphic DNA
markers spanning known dominant Stargardt-like gene loci were used to determine
the haplotype associated with disease. In addition, an extensive genealogical
investigation searching for a common ancestor shared by all of the 7 families was
performed. RESULTS: We clinically evaluated 171 patients and genotyped 145
samples. The same DNA haplotype on chromosome 6q16 was shared by all evaluated
affected members within the 7 families. In addition, we were able to
genealogically join all of the families into one larger family consisting of 31
branches and 2314 individuals. Twenty-seven branches have known living
descendants, with 7 branches having affected family members. In addition, we
refined the critical region for the gene to approximately 1000 kilobases (kb) and
eliminated part or all of 9 candidate disease-causing genes. CONCLUSIONS: Our
study indicates that most reported cases of autosomal dominant Stargardt-like
macular dystrophy in North America are part of a single larger family associated 
with a gene locus on chromosome 6q16. Furthermore, the DNA haplotype associated
with disease is useful in excluding individuals with phenotypically similar
retinal conditions. CLINICAL RELEVANCE: The disease-associated haplotype allows
for more accurate genetic counseling to be given to individuals with a
Stargardt-like phenotype inherited in an autosomal dominant pattern.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11296022 [PubMed - indexed for MEDLINE]

3054: Arch Ophthalmol. 2001 Apr;119(4):547-53.

Comment in:
    Arch Ophthalmol. 2001 Apr;119(4):576-8.

How many steps of progression of diabetic retinopathy are meaningful? The
Wisconsin epidemiologic study of diabetic retinopathy.

Klein R, Klein BE, Moss SE.

MPH, Department of Ophthalmology and Visual Sciences, University of
Wisconsin-Madison, 610 N Walnut St, 460 WARF, Madison, WI 53705-2397, USA.

OBJECTIVE: To determine whether a 1-step or more or 2-step or more progression on
the Early Treatment Diabetic Retinopathy Study retinopathy severity scale over a 
4-year period is meaningful in predicting the subsequent incidence of
proliferative diabetic retinopathy (PDR) and clinically significant macular edema
(CSME) over the following 6 years. DESIGN: Population-based study of diabetic
persons with 10 years of follow-up. SETTING AND PATIENTS: Eleven-county area in
southern Wisconsin. There were 1025 persons with diabetes who had fundus
photographs at baseline and at 4- and 10-year follow-up examinations. MAIN
OUTCOME MEASURES: Incidence of PDR or CSME between the 4- and 10-year follow-up
examinations as determined by masked grading of color stereoscopic fundus
photographs of 7 standard fields. RESULTS: In a univariate analysis, those with 1
or more steps of progression (n = 551) over the first 4 years of the study were
significantly (P<.0001) more likely to develop PDR over the next 6 years than
those with no progression (n = 474) (26% vs 4%) (relative risk, 5.85; 95%
confidence interval, 4.05-8.47). Similarly, those with 2 or more (n = 364) (33%) 
or 3 or more (n = 231) (41%) steps of progression over the first 4 years of the
study were significantly (P<.0001) more likely to develop PDR over the next 6
years than those with lesser progression (n = 661 [7%] and n = 794 [9%],
respectively) (relative risk, 5.10; 95% confidence interval, 3.83-6.80; and
relative risk, 4.61; 95% confidence interval, 3.57-5.99, respectively). Similar
associations were apparent at every level of retinopathy, duration of diabetes,
and glycosylated hemoglobin, and by type of diabetes at baseline. There were also
associations between retinopathy progression and incidence of CSME. CONCLUSIONS: 
It seems that 1 or more or 2 or more steps of progression of retinopathy over a
4-year period strongly predict the development of PDR over the next 6 years.
Therefore, using these end points of progression would result in the need for
fewer subjects or shorter follow-up in some clinical trials.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.

PMID: 11296020 [PubMed - indexed for MEDLINE]

3055: Arch Ophthalmol. 2001 Apr;119(4):539-44.

Hydraulic conductivity of fixed retinal tissue after sequential excimer laser
ablation: barriers limiting fluid distribution and implications for cystoid
macular edema.

Antcliff RJ, Hussain AA, Marshall J.

GKT Department of Ophthalmology, The Rayne Institute, Saint Thomas' Hospital,
Lambeth Palace Road, London SE1 7EH, England.

OBJECTIVES: To measure the hydraulic conductivity (HC) of human retina and to
determine the presence and location of high-resistance barriers to fluid movement
through the retina. METHODS: Forty-one pairs of human eyes were investigated
using an HC chamber. Once baseline HC had been determined, the effect of ablating
through varying thickness of retina from the vitreous or photoreceptor surface
using an excimer laser (193 nm) was investigated. Tissue samples were then
processed for histological investigation. RESULTS: The HC of fixed intact human
retina was 2.54 x 10(-10) m/s per pascal at 539 Pa (range, 0.6 x 10(-10) to 3.3 x
10(-10) m/s per pascal; SD, 0.6 x 10(-10) m/s per pascal [1 mm Hg equals 133
Pa]). Ablation from either surface resulted in little change in HC until a
critical depth was reached, at which point there was an order of magnitude
increase. The critical depth was approximately 170 microm from the inner limiting
membrane when ablating from the vitreous surface and 70 microm from the inner
limiting membrane when ablating from the photoreceptor surface. Histological
specimens showed that these barriers were the synaptic portion of the outer
plexiform layer, and the inner plexiform layer, respectively. CONCLUSIONS: The 2 
high-resistance barriers to fluid flow through the retina are the synaptic
portion of the outer plexiform layer, and the inner plexiform layer. CLINICAL
RELEVANCE: These observations help to explain the distribution of cystoid macular
edema seen in histological studies and with optical coherence tomography.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11296019 [PubMed - indexed for MEDLINE]

3056: Br J Ophthalmol. 2001 May;85(5):592-7.

Passive permeability and outward active transport of fluorescein across the
blood-retinal barrier in early ARM.

Moldow B, Larsen M, Sander B, Lund-Andersen H.

Department of Ophthalmology, Herlev Hospital, University of Copenhagen, Denmark. 
b.moldow@ofir.dk

AIM: To study the passive and active transport of fluorescein across the
blood-retina barrier in early age related maculopathy (ARM) (soft drusen > 63
microm, hyperpigmentation and/or hypopigmentation in patients above 50 years of
age). METHODS: 15 patients and 10 healthy subjects were included. Morphological
changes were graded from 30 degrees fundus photographs using a simplified version
of the epidemiological ARM study group classification system. Differential
vitreous spectrofluorophotometry was used to assess the transport properties of
the blood-retina barrier (that is, passive permeability and unidirectional
permeability caused by outward active transport from the vitreous to the blood). 
RESULTS: The passive permeability of the patient group was not significantly
different from that of the control group. Four patients with passive permeability
more than 3 SD above the mean of the control group (mean 1.8 (SD 0.7) nm/s, range
1.0-3.0 nm/s, data normally distributed) all had centrally located drusen > 500
microm and superjacent pigment clumps of 63-500 microm in diameter. There was no 
significant difference between the unidirectional permeabilities for the patient 
group and for the control group (mean 47.4 (29.3) nm/s, range 12.7-91.1 nm/s).
CONCLUSION: There was no significant difference in the passive permeability and
in the unidirectional permeability of fluorescein. However, the study may
indicate that the combination of very large drusen and superjacent pigment clumps
in ARM may be associated with a deterioration of the blood-retina barrier.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11316723 [PubMed - indexed for MEDLINE]

3057: Br J Ophthalmol. 2001 May;85(5):531-3.

Comment in:
    Br J Ophthalmol. 2001 May;85(5):510-2.

Pulsatile ocular blood flow study: decreases in exudative age related macular
degeneration.

Mori F, Konno S, Hikichi T, Yamaguchi Y, Ishiko S, Yoshida A.

Department of Ophthalmology, Asahikawa Medical College, Asahikawa, Japan.
morinaod5.dion.ne.jp

BACKGROUND: Pulsatile ocular blood flow (POBF) is a parameter for evaluating
choroidal blood flow. POBF in the patients with non-exudative and exudative age
related macular degeneration (AMD) was investigated. METHODS: POBF, pulse
amplitude (PA), systolic and diastolic blood pressures, intraocular pressure
(IOP), refractive error, and axial length were compared among 10 patients with
non-exudative AMD, 11 patients with exudative AMD, and 69 age matched controls. A
Langham OBF computerised tonometer was used with the participants in the sitting 
position to measure POBF and PA. RESULTS: No significant differences were found
in age, systolic and diastolic blood pressures, IOP, or refractive error between 
patients with exudative and non-exudative AMD and the control subjects. In the
patients with exudative AMD the POBF (median, 372.7 microl/min) and PA (median,
1.2 mm Hg) were significantly lower than in the patients with non-exudative AMD
(median, 607.0 microl/min (p = 0.02) and 2.2 mm Hg (p = 0.04), respectively) and 
control subjects (median, 547.4 microl/min (p = 0.01) and 2.0 mm Hg (p = 0.01),
respectively). CONCLUSIONS: These data show that the POBF and PA in the patients 
with exudative AMD are lower than in the patients with non-exudative AMD and
normal subjects. Decreased choroidal blood flow may have a role in the
development of choroidal neovascularisation in AMD.

PMID: 11316708 [PubMed - indexed for MEDLINE]

3058: Jpn J Ophthalmol. 2001 Mar-Apr;45(2):192-8.

Surgical excision versus laser photocoagulation for subfoveal choroidal
neovascular membrane with age-related macular degeneration: comparison of visual 
outcomes.

Yuzawa M, Isomae T, Mori R, Shimada H, Utsunomiya I.

Department of Ophthalmology, Nihon University, Surugadai Hospital, Tokyo, Japan

PURPOSE: This study was designed to compare visual acuity after laser
photocoagulation with visual acuity after surgical excision of the subfoveal
choroidal neovascular membrane in patients with age-related macular degeneration 
(AMD). METHODS: We studied 54 patients (56 eyes) who underwent laser
photocoagulation and 52 patients (52 eyes) who underwent surgical excision for
new subfoveal choroidal neovascular membrane occurring with AMD. We compared mean
log of minimal angle of resolution (MAR) visual acuity, and the percentages of
eyes showing visual improvement and a visual acuity of 0.1 or better, between the
two treatment groups at 12 months after treatment. The groups were also compared 
according to choroidal neovascular membrane size, ie, 1 disc diameter (DD) or
smaller vs larger than 1 DD. RESULTS: Mean corrected visual acuity (P <.01),
percentage of eyes with improved vision (P <.01), and percentage with a visual
acuity of at least 0.1 (P <.01) were higher in surgically treated eyes. The
differences in mean log MAR visual acuity and the percentages were significant
only for choroidal neovascular membrane of one DD or less in size. CONCLUSIONS:
Postoperative eyes, especially those with choroidal neovascular membranes 1 DD or
less in size, had better visual outcomes. Patients who meet our eligibility
criteria, especially with small choroidal neovascular membranes 1 DD or less in
size, should undergo surgical excision.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 11313054 [PubMed - indexed for MEDLINE]

3059: J Ophthalmic Nurs Technol. 2000 Jul-Aug;19(4):194-7.

Inhibitors of neovascularization.

York J, Glaser B, Murphy R.

Glaser Murphy Retina Treatment Center, 901 Dulaney Valley Road, Suite 200,
Baltimore, MD 21204, USA.

The use of neovascular inhibitors in the treatment of CNV will no doubt have a
profound impact in the future. However, complex issues surround the use of these 
agents. Careful clinical trials will be necessary to determine the optimal
parameters for their use. Furthermore, it must be determined whether these
inhibitors will be most efficacious as primary agents or as agents used to
augment the efficacy of photoreactive laser treatment or feeder vessel treatment.

Publication Types: 
    Review

PMID: 11309996 [PubMed - indexed for MEDLINE]

3060: Semin Ophthalmol. 2000 Jun;15(2):78-80.

Vitrectomy for refractory diabetic macular edema.

Capone A Jr, Panozzo G.

Associated Retinal Consultants, William Beaumont Hospital, Royal Oak, MI 48703,
USA.

Diabetic macular edema may occur or worsen as a consequence of vitreomacular
traction in some eyes. The precise role of the posterior hyaloid in the
pathogenesis of diabetic maculopathy remains unclear. The determination of which 
eyes might benefit from vitrectomy is the most challenging aspect in the
treatment of this condition. Fluorescein angiography, B-scan untrasonography, and
optical coherence tomography may be helpful in this regard. Most often, vitreous 
surgery is performed when diabetic macular edema persists despite multiple laser 
treatments. All reports published to date regarding vitrectomy for diabetic
macular edema are uncontrolled and nonrandomized patient series. Visual
improvement after vitrectomy is related to the duration of edema, as well as the 
extent of intraretinal lipid and vascular nonperfusion.

Publication Types: 
    Review

PMID: 11309739 [PubMed - indexed for MEDLINE]

3061: Ophthalmology. 2001 Apr;108(4):765-72.

Intravitreal triamcinolone for uveitic cystoid macular edema: an optical
coherence tomography study.

Antcliff RJ, Spalton DJ, Stanford MR, Graham EM, ffytche TJ, Marshall J.

GKT Department of Ophthalmology, Rayne Institute, St Thomas' Hospital, Lambeth
Palace Road, London SE1 7EH, England, UK.

PURPOSE: To investigate the use of intravitreal injection of triamcinolone
acetonide (TA) for the treatment of refractory uveitic cystoid macular edema
(CME). DESIGN: Prospective, nonrandomized, self-controlled comparative trial.
PARTICIPANTS: Six patients with chronic CME resistant to treatment with systemic 
steroids, orbital floor steroids, and cyclosporine A. Three patients were
followed for more than 1 year, and the other three for between 3 and 9 months.
INTERVENTION: Injection of 2 mg of TA into the vitreous cavity. TESTING: Optical 
coherence tomography scanning of the fovea before and after injection and
logarithmic minimal angle of resolution visual acuity. MAIN OUTCOME MEASURES:
Visual acuity, retinal thickness, cystoid space height, and intraocular pressure.
RESULTS: There was complete anatomic resolution of CME in five of the six cases
within 1 week after injection. Cystoid spaces began to return between 6 weeks and
3 months after injection. Two patients with longer term follow-up responded to
further orbital floor steroid injection and had no CME 1 year later. One patient 
had raised intraocular pressure develop, requiring a trabeculectomy. Mean
improvement in visual acuity after 12 months was 0.27 (range, 0.14-0.42).
CONCLUSIONS: Complete anatomic and, to some extent, functional recovery can be
induced by intravitreal TA despite long-term refractory inflammatory CME. Optical
coherence tomography aids in the management of these cases.

Publication Types: 
    Case Reports
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 11297495 [PubMed - indexed for MEDLINE]

3062: Ophthalmology. 2001 Apr;108(4):705-10.

Age-related macular degeneration is associated with increased vascular
endothelial growth factor, hemorheology and endothelial dysfunction.

Lip PL, Blann AD, Hope-Ross M, Gibson JM, Lip GY.

Haemostasis Thrombosis and Vascular Biology Unit, University Department of
Medicine, City Hospital, Birmingham B18 7QH, England, UK.

OBJECTIVE: To investigate laboratory evidence of abnormal angiogenesis,
hemorheologic factors, endothelial damage/dysfunction, and age-related macular
degeneration (ARMD). DESIGN: Comparative cross-sectional study. PARTICIPANTS: We 
studied 78 subjects (26 men and 52 women; mean age 74 years; standard deviation
[SD] 9.0) with ARMD attending a specialist referral clinic. Subjects were
compared with 25 healthy controls (mean age, 71 years; SD, 11). INTERVENTION AND 
OUTCOME MEASURES: Levels of vascular endothelial growth factor (VEGF, an index of
angiogenesis), hemorheologic factors (plasma viscosity, hematocrit, white cell
count, hemoglobin, platelets), fibrinogen (an index of rheology and hemostasis), 
and von Willebrand factor (a marker of endothelial dysfunction) were measured.
RESULTS: Median plasma VEGF (225 vs. 195 pg/ml, P = 0.019) and mean von
Willebrand factor (124 vs. 99 IU/dl, P = 0.0004) were greater in ARMD subjects
than the controls. Mean plasma fibrinogen and plasma viscosity levels were also
higher in the subjects (both P < 0.0001). There were no significant differences
in other indices between cases and controls. When "dry" (drusen, atrophy, n = 28)
and "exudative" (n = 50) ARMD subjects were compared, there was no significant
differences in VEGF, fibrinogen, viscosity, or von Willebrand factor levels.
There were no significant correlations between the measured parameters. Stepwise 
multiple regression analysis did not demonstrate any significant clinical
predictors (age, gender, smoking, body mass index, history of vascular disease,
or hypertension) for plasma VEGF or fibrinogen levels, although smoking status
was a predictor of plasma von Willebrand factor levels (P < 0.05). CONCLUSIONS:
This study suggests an association between markers of angiogenesis (VEGF),
hemorheologic factors, hemostasis, endothelial dysfunction, and ARMD. The
interaction between abnormal angiogenesis and the components of Virchow's triad
for thrombogenesis may in part contribute to the pathogenesis of ARMD.

Publication Types: 
    Comparative Study

PMID: 11297487 [PubMed - indexed for MEDLINE]

3063: Ophthalmology. 2001 Apr;108(4):697-704.

Risk factors for age-related macular degeneration: Pooled findings from three
continents.

Smith W, Assink J, Klein R, Mitchell P, Klaver CC, Klein BE, Hofman A, Jensen S, 
Wang JJ, de Jong PT.

National Centre for Epidemiology & Population Health, Australian National
University, Canberra, Australia.

OBJECTIVE: To assess the prevalence and potential risk factors for late
age-related macular degeneration (AMD) in three racially similar populations from
North America, Europe, and AUSTRALIA: DESIGN: Combined analysis of
population-based eye disease prevalence data. PARTICIPANTS: There were 14,752
participants with gradable photographs from the Beaver Dam Eye Study (n = 4756), 
Rotterdam Study (n = 6411), and Blue Mountains Eye Study (n = 3585). MAIN OUTCOME
MEASURES: AMD diagnosis was made from masked grading of stereo macular
photographs. Final classification of AMD cases was agreed by consensus between
study investigators. RESULTS: AMD prevalence was strongly age related. Overall,
AMD was present in 0.2% of the combined population aged 55 to 64 years, rising to
13% of the population older than 85 years. Prevalence of neovascular AMD (NV)
increased from 0.17% among subjects aged 55 to 64 years to 5.8% for those older
than 85 years. Prevalence of pure geographic atrophy (GA) increased from 0.04% to
4.2% for these age groups. There were no significant gender differences in the
prevalence of NV or GA. Subjects in the Rotterdam population had a significantly 
lower age-adjusted and smoking-adjusted risk of NV than subjects in the Beaver
Dam and Blue Mountains populations. Apart from age, tobacco smoking was the only 
risk factor consistently associated with any form of AMD in all sites separately 
and in pooled analyses over the three sites. CONCLUSIONS: These combined data
from racially similar communities across three continents provide strong and
consistent evidence that tobacco smoking is the principal known preventable
exposure associated with any form of AMD.

Publication Types: 
    Meta-Analysis

PMID: 11297486 [PubMed - indexed for MEDLINE]

3064: Am J Ophthalmol. 2001 Apr;131(4):472-80.

Retinal pigment epithelial cell transplantation after subfoveal membranectomy in 
age-related macular degeneration: clinicopathologic correlation.

Del Priore LV, Kaplan HJ, Tezel TH, Hayashi N, Berger AS, Green WR.

Department of Ophthalmology and Visual Sciences, Washington University School of 
Medicine, St. Louis, Missouri, USA.

PURPOSE: To report the histopathology after retinal pigment epithelial cell
transplantation and subfoveal membranectomy in age-related macular degeneration. 
METHODS: An 85-year-old white woman with bilateral choroidal neovascularization
underwent subfoveal membranectomy combined with transplantation of a sheet of
human adult retinal pigment epithelium (retinal pigment epithelium) under the
foveal center in the right eye. The patient was immunosuppressed postoperatively 
with prednisone, cyclosporine, and azathioprine. The patient died from congestive
heart failure 114 days after surgery. RESULTS: A patch of hyperpigmentation was
visible at the transplant site under the foveola after surgery. Mound-like
clusters of individual round, large densely pigmented cells were present in the
subretinal space and outer retina in this area. There was loss of the
photoreceptor outer segments and native retinal pigment epithelium in the center 
of the transplant bed, with disruption of the outer nuclear layer predominantly
over regions of multilayered pigmented cells. Cystic spaces were present in the
inner and outer retina. A residual intra-Bruchs membrane component of the
original choroidal neovascular complex was present under the transplant site.
CONCLUSIONS: The transplant site contained clusters of round, pigmented cells
that did not form a uniform monolayer in most areas. The morphology at the
transplant site is consistent with the lack of visual improvement seen after
surgery in this patient.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 11292411 [PubMed - indexed for MEDLINE]

3065: Prog Retin Eye Res. 2001 May;20(3):385-414.

Immunological and aetiological aspects of macular degeneration.

Penfold PL, Madigan MC, Gillies MC, Provis JM.

Department Clinical Ophthalmology, Save Sight Institute, University of Sydney,
NSW 2006, Australia. ppenfold@eye.usyd.edu.au

Aetiological and immunological aspects of AMD, a leading cause of blindness in
Western countries, have been reviewed. Developmental studies suggest that
anatomical features unique to the fovea result in a critical relationship between
metabolic demand and blood supply at the macula, which is maintained throughout
life. Recent studies show a sufficient degree of consistency in the link between 
smoking and both dry and wet AMD to regard it as causative. Dry AMD is considered
to be the natural endstage of the disease; epidemiological and morphological
studies point to choroidal vascular atrophy as the causative event and it is
suggested that signals associated with acute vascular compromise lead to the
development of subretinal neovascularisation. The relationship between
sub-pigment epithelial deposits, including basal laminar deposit, and the
pathogenesis of AMD is examined. Much of the literature is consistent with a
choroidal origin for the constituents of drusen. The blood-retinal barrier
preserves the physiological environment of the neural retina and limits
inflammatory responses. The factors, including cytokines, adhesion molecules and 
the presence of resident immunocompetent cells (microglia), which determine the
immune status of the retina are considered. Historical descriptions of the
involvement of inflammatory cells are provided, evidence implicating inflammation
in the pathogenesis of AMD involving macrophages, giant cells and microglia has
been derived from observations of human and animal subretinal neovascular
lesions. The role of humoral factors such as anti-retinal autoantibodies and
acute phase proteins together with clinical observations has been surveyed. Taken
together these data demonstrate the involvement of both cellular and humoral
immunity in the pathogenesis of AMD. It remains to be determined to what degree
the influence of immunity is causative or contributory in both wet and dry AMD,
however, the use of anti-inflammatory agents to ameliorate the condition further 
indicates the existence of an inflammatory component.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 11286898 [PubMed - indexed for MEDLINE]

3066: Acta Ophthalmol Scand. 2001 Apr;79(2):108-15.

Ocular perfusion and age-related macular degeneration.

Ciulla TA, Harris A, Martin BJ.

Indiana University School of Medicine, Indianapolis, Indiana, USA.

PURPOSE: To review the role of ocular perfusion in the pathophysiology of
age-related macular degeneration (AMD), the leading cause of irreversible
blindness in the industrialized world. METHODS: Medline search of the literature 
published in English or with English abstracts from 1966 to 2000 was performed
using various combinations of relevant key words. RESULTS: Vascular defects have 
been identified in both nonexudative and exudative AMD patients using fluorescein
angiographic methods, laser Doppler flowmetry, indocyanine green angiography, and
color Doppler imaging. CONCLUSION: Although these studies lend some support to
the vascular pathogenesis of AMD, it is not possible to determine if the
choroidal perfusion abnormalities play a causative role in nonexudative AMD, if
they are simply an association with another primary alteration, such as a primary
RPE defect or a genetic defect at the photoreceptor level, or if they are more
strongly associated with one particular form of this heterogeneous disease.
Further study is warranted.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.
    Review

PMID: 11284745 [PubMed - indexed for MEDLINE]

3067: Invest Ophthalmol Vis Sci. 2001 Apr;42(5):1051-6.

Fundus autofluorescence and development of geographic atrophy in age-related
macular degeneration.

Holz FG, Bellman C, Staudt S, Schütt F, Völcker HE.

Department of Ophthalmology, University of Heidelberg, Germany.
frank_holz@med.uni-heidelberg.de

PURPOSE: To describe the development of new and enlargement of preexisting
atrophy confined to areas with abnormally high levels of in vivo autofluorescence
in eyes with geographic atrophy (GA) associated with age-related macular
degeneration (ARMD). METHODS: The spatial distribution and intensity of fundus
autofluorescence as well as the spread of GA and occurrence of new GA was
recorded over a period of 3 years in three patients with ARMD using a confocal
scanning laser ophthalmoscope. RESULTS: A diffuse irregular increased
autofluorescence at the posterior pole was recorded at baseline in the presence
of unifocal or multifocal patches of geographic atrophy. Within these areas of
elevated autofluorescence, new atrophic areas developed, and existing patches of 
atrophy enlarged during the review period, whereas this was not observed in areas
with normal background autofluorescence. The total area of abnormal
autofluorescence also showed enlargement over time. CONCLUSIONS: These
preliminary findings suggest that areas of increased autofluorescence precede the
development and enlargement of outer retinal atrophy in eyes with ARMD. Because
the dominant fluorophores of fundus autofluorescence are part of lipofuscin
granules of RPE cells, the observations indicate that excessive RPE lipofuscin
accumulation may be of significance in the pathogenesis of GA associated with
ARMD. With GA being a major cause for severe visual loss in ARMD, in vivo fundus 
autofluorescence recording over time may allow identification of prognostic
determinants and may give important clues to the understanding of mechanisms of
disease.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 11274085 [PubMed - indexed for MEDLINE]

3068: Clin Experiment Ophthalmol. 2001 Feb;29(1):2-6.

Comment in:
    Clin Experiment Ophthalmol. 2001 Feb;29(1):1.

Safety and efficacy of intravitreal triamcinolone for cystoid macular oedema in
uveitis.

Young S, Larkin G, Branley M, Lightman S.

Department of Clinical Ophthalmology, Institute of Ophthalmology, Moorfields Eye 
Hospital, London, UK.

PURPOSE: To report the safety and efficacy of intravitreal triamcinolone in the
treatment of inflammatory cystoid macular oedema (CMO) in six patients who were
resistant to other forms of therapy. METHODS: An open-label unmasked prospective 
nonrandomized pilot study of six patients with idiopathic uveitis and visually
significant macular oedema, resistant to periocular and/or systemic
corticosteroid treatment, was carried out. Baseline examination and
investigations were performed, including fundus fluorescein angiography, and the 
patients were given a single intravitreal injection of triamcinolone (4 mg/0.1
mL). The primary outcome measure was angiographic resolution of CMO. Patients
were reviewed at intervals of 2-4 weeks for 12 months. RESULTS: A single
intravitreal injection of triamcinolone induced clinical and angiographic
resolution of inflammatory macular oedema in all patients for varying periods of 
time up to 6 months. Five patients experienced increased intraocular pressure to 
30 mmHg or greater which required treatment. Two patients developed posterior
subcapsular cataract. CONCLUSION: One injection of intravitreal triamcinolone was
an effective short-term treatment for resistant CMO in uveitis. As with steroids 
given by other routes, raised intraocular pressure and cataract may occur. As it 
was so effective in these eyes with resistant CMO, a larger study is warranted to
evaluate this form of therapy.

Publication Types: 
    Case Reports
    Clinical Trial

PMID: 11272779 [PubMed - indexed for MEDLINE]

3069: Clin Experiment Ophthalmol. 2001 Feb;29(1):17-21.

Contrast sensitivity following focal laser photocoagulation in clinically
significant macular oedema due to diabetic retinopathy.

Talwar D, Sharma N, Pai A, Azad RV, Kohli A, Virdi PS.

Dr Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical
Sciences, New Delhi. dosonlin@bol.net

PURPOSE: To evaluate the influence of focal aser photocoagulation on contrast
sensitivity in diabetic patients with clinically significant macular oedema
(CSMO). METHODS: A prospective non-comparative interventional study was performed
on a group of patients with CSMO at Dr Rajendra Prasad Centre for Ophthalmic
Sciences, New Delhi, a tertiary eye care centre. Thirteen diabetc patients (14
eyes) with CSMO and no history of prior photocoagulation were recruited for this 
study. Direct focal photocoagulation of all leaking microaneurysms was performed 
using an argon green laser (514 nm). A contact lens was used as a slit lamp
delivery system. Evaluation of the best corrected Snellen visual acuity, contrast
senstivity, slit lamp biomicroscopy, macular status on direct ophthalmoscopy and 
fluorescein angiography was carried out 1 month and 3 months after laser
photocoagulation. RESULTS: Following direct focal laser photocoagulation, focal
CSMO resolved completely in all but one eye, 4-8 weeks later, as seen on slit
lamp biomicroscopy and/or fluorescein angiography. Post-treatment, visual acuity 
remained stationary in eight eyes, improved by one line in three eyes, by two
lines in two eyes and by three lines in one eye. The mean +/- SD pretreatment and
post-treatment decimal visual acuities were 0.49+/-0.30 and 0.59+/-0.28,
respectively. The mean +/- SD pre-laser contrast sensitivity score was
121.3+/-83.6, which increased significantly to a mean +/- SD of 151.6+/-80.5 fo
lowing direct focal photocoagulation. CONCLUSION: Focal argon laser
photocoagulation in CSMO in diabetics helps in improving the contrast sensitivity
and stabilizes the visual acuity. The changes in contrast sensitivity and visual 
acuity are independent of each other.

PMID: 11272778 [PubMed - indexed for MEDLINE]

3070: Graefes Arch Clin Exp Ophthalmol. 2001 Jan;239(1):66-8.

Lack of association of mutations of the bestrophin gene with age-related macular 
degeneration in non-familial Japanese patients.

Akimoto A, Akimoto M, Kuroiwa S, Kikuchi T, Yoshimura N.

BACKGROUND: Heterozygous mutations of the bestrophin gene are associated with
Best macular dystrophy (BMD). The bestrophin gene is specifically expressed in
the retinal pigment epithelium. BMD is a hereditary form of macular degeneration 
that may develop subretinal neovascularisation similar to the wet type of
age-related macular degeneration (AMD). PURPOSE: To study whether mutations of
the bestrophin gene occur in non-familial Japanese AMD patients. METHODS: A total
of 85 non-familial AMD patients (average age 67.5 years; 71 male, 14 female)
diagnosed by indocyanine green angiography were screened. Among them, 69 patients
(81 %) were classified as having wet type AMD. Genomic DNA was purified from the 
total blood and used as the template for polymerase chain reaction (PCR). All the
exons of bestrophin gene were amplified by PCR. Mutation analysis was performed
by SSCP using the ABI Prism 310 Genetic Analyzer (Perkin Elmer). Nucleotide
sequence was determined by direct sequencing of the PCR amplicons. As the
control, 105 non-AMD patients (average age 62.0 years; 52 male, 53 female) were
screened by the same method. RESULTS: Only one AMD patient had a specific
polymorphism in exon 2, but no mutations leading to amino acid substitutions were
found. In exon 2 and 3, two further polymorphisms were detected in all AMD
patients as well as normal controls. CONCLUSION: No mutations were found in the
bestrophin gene in nonfamilial Japanese patients with AMD or in normal controls.

Publication Types: 
    Letter

PMID: 11271465 [PubMed - indexed for MEDLINE]

3071: Graefes Arch Clin Exp Ophthalmol. 2001 Jan;239(1):5-11.

Clinicopathological correlation in exudative age-related macular degeneration:
recurrent choroidal neovascularization.

Lafaut BA, Aisenbrey S, Vanden Broecke C, Di Tizio F, Bartz-Schmidt KU.

University Eye Clinic, Cologne, Germany. bart.lafaut@rug.ac.be

PURPOSE: To report the pathology of surgically removed submacular tissue in
recurrent choroidal neovascularization after laser photocoagulation of classic
choroidal neovascularization in age-related macular degeneration. METHODS: A
recurrent subfoveal choroidal neovascular membrane was surgically removed in two 
patients. The recurrence was identified as a classic membrane on fluorescein
angiography at the foveal border of the laser scar. A net was visualized in the
early venous phase of the indocyanine green angiogram, with associated late
hyperfluorescence. Both patients had undergone laser photocoagulation for a
classic interpapillomacular choroidal neovascular membrane about 1 1/2 years
earlier. The specimens were serially sectioned and stained with
hematoxylin-eosin, periodic acid-Schiff, Masson trichrome and phosphotungstic
acid-hematoxylin. RESULTS: The two specimens consisted of subretinal
fibrovascular tissue with fibrin exudation. Fibrovascular tissue bordered
subretinal fibrous tissue adherent to Bruch's membrane and remnants of the
choroid in one patient. The fibrovascular portion most likely corresponded to the
recurrence, whereas the fibrous portion represented the original membrane, being 
obliterated after photocoagulation. Some peripapillary tissue was additionally
removed in the other patient. The latter lesion was invisible on fluorescein
angiography but stained in the late phase of indocyanine green angiography and
corresponded histopathologically to poorly vascularized intra-Bruch's
fibrovascular tissue. Granular deposits, periodic acid-Schiff positive and
metachromatically purple on Masson trichrome stain, representing diffuse drusen
(basal laminar/linear deposits), were identified in the three specimens.
CONCLUSION: A subretinal fibrovascular membrane corresponded with the classic
recurrent choroidal neovascularization.

Publication Types: 
    Case Reports
    Review

PMID: 11271462 [PubMed - indexed for MEDLINE]

3072: Br J Ophthalmol. 2001 Apr;85(4):454-60.

Clinicopathological correlation of retinal pigment epithelial tears in exudative 
age related macular degeneration: pretear, tear, and scarred tear.

Lafaut BA, Aisenbrey S, Vanden Broecke C, Krott R, Jonescu-Cuypers CP, Reynders
S, Bartz-Schmidt KU.

University Eye Clinic, Joseph-Stelzmann- Strasse 9, D-50931 Cologne, Germany.
bart.lafaut@rug.ac.be

AIMS: To analyse the histopathology of vascularised pigment epithelial
detachments and tears of the retinal pigment epithelium (RPE) in age related
macular degeneration (AMD). METHODS: The light microscopic architecture of 10
surgically removed subretinal specimens-three vascularised pigment epithelial
detachments, four recent tears, and three scarred tears as a manifestation of
AMD-were studied and correlated with the angiographic findings. RESULTS: Recent
tears: a large fibrovascular membrane was found to be originally situated in
Bruch's membrane. About half of the surface of the fibrovascular tissue was
denuded of RPE and diffuse drusen. The RPE and diffuse drusen had retracted and
rolled up, covering a neighbouring part of the intra-Bruch's fibrovascular
membrane. The rolled up RPE and diffuse drusen were not interspersed with
fibrovascular tissue but lay superficial to the intra-Bruch's fibrovascular
membrane itself. Scarred tears: a collagen capsule surrounded the rolled up
diffuse drusen and RPE. Fibrovascular tissue was found inside the rolled up
material, predominantly at its choroidal side. CONCLUSION: The area of choroidal 
neovascularisation associated with a vascularised pigment epithelial detachment
and a tear of the RPE may be larger than was hitherto thought or indicated by
fluorescein angiography. This neovascular tissue may be present within the bed of
the RPE tear, as well as at the site of the scrolled up RPE.

PMID: 11264137 [PubMed - indexed for MEDLINE]

3073: Ophthalmic Epidemiol. 2000 Dec;7(4):259-70.

Evaluating the effectiveness of a vision rehabilitation intervention using an
objective and subjective measure of functional performance.

McCabe P, Nason F, Demers Turco P, Friedman D, Seddon JM.

Department of Ophthalmology, Vision Rehabilitation Center, Massachusetts Eye &
Ear Infirmary, Harvard Medical School, Boston, Massachusetts 02114, USA.
cpmccabe@meei.harvard.edu

PURPOSE: To test the hypothesis that vision rehabilitation using optometry,
occupational therapy and social work services increases patients' functional
ability and to assess whether involving families in the intervention results in
more successful outcomes. METHODS: We conducted an outcome study of 97 patients
new to the Vision Rehabilitation Service. Subjects were between the ages of 19
and 91 years, with a median age of 76. Their visual acuities were 20/100 or worse
in the better eye, with 50% of the subjects having acuities worse than 20/200.
Macular degeneration was the most prevalent diagnosis. Subjects were assigned to 
either an individually focused (n=48) or a family focused (n=49) intervention.
The outcome measure was change in function, as assessed by speed and accuracy of 
performance (objective measure) and by the patients' self-reports of difficulty
and dependency in performing daily activities (subjective measures). Data were
collected before and after the intervention. RESULTS: Most patients had
documented improvement after rehabilitation on both objective (p=.0001) and
subjective (decreased dependency, p=.01) measures of function. The sample size
did not provide adequate statistical power to show differences between family
focused and individually focused interventions. CONCLUSIONS: This study documents
significant improvement after vision rehabilitation for a predominantly elderly
population. Patients in both family and individually focused interventions
improved comparably.

Publication Types: 
    Clinical Trial
    Comparative Study
    Evaluation Studies
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11262673 [PubMed - indexed for MEDLINE]

3074: J Cataract Refract Surg. 2001 Mar;27(3):432-6.

Cystoid macular edema after pediatric intraocular lens implantation: fluorescein 
angioscopy results and literature review.

Rao SK, Ravishankar K, Sitalakshmi G, Ng JS, Yu C, Lam DS.

Sankara Nethralaya, Medical & Vision Research Foundations, Tamil Nadu, India.
MDSAAA35@giasmd01.vsnl.net.in

PURPOSE: To evaluate the occurrence of cystoid macular edema (CME) after lens
extraction, anterior vitrectomy, and intraocular lens implantation (IOL) in
children using angioscopy after administration of oral fluorescein. SETTING:
Centers in Tamil Nadu, India, and Hong Kong, China. METHODS: This study comprised
18 children (28 eyes) who had cataract extraction, posterior capsulorhexis,
anterior vitrectomy, and in-the-bag IOL implantation. The presence of CME was
evaluated 1 week and 4 to 6 weeks after surgery using fluorescein angioscopy.
RESULTS: Anterior chamber fibrin occurred in 4 eyes (14.3%). Fluorescein
angioscopy was performed 1 week after surgery in all eyes and after 1 month in 25
eyes (89.3%). No eye demonstrated the presence of CME on fluorescein angioscopy. 
CONCLUSIONS: Cystoid macular edema did not occur in the early period after
pediatric cataract surgery using current surgical techniques. Longer follow-up is
required to ascertain the incidence of CME in the late postoperative period.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't
    Review

PMID: 11255057 [PubMed - indexed for MEDLINE]

3075: Arch Ophthalmol. 2001 Mar;119(3):387-94.

Enhanced disruption of the blood-aqueous barrier and the incidence of
angiographic cystoid macular edema by topical timolol and its preservative in
early postoperative pseudophakia.

Miyake K, Ota I, Ibaraki N, Akura J, Ichihashi S, Shibuya Y, Maekubo K, Miyake S.

Shohzankai Medical Foundation, Miyake Eye Hospital, 1070-Kami 5,
Higashiozone-cho, Kita-ku, Nagoya, 462-0823, Japan. miyake@spice.or.jp

OBJECTIVE: To investigate the effects of timolol maleate with preservative and
its preserved (PV) and nonpreserved vehicles (NPV) (benzalkonium chloride) on the
blood-aqueous barrier and angiographic cystoid macular edema (CME) in early
postoperative pseudophakia. PATIENTS AND METHODS: Patients with ocular
hypertension, normal tension glaucoma, and primary open-angle glaucoma who
underwent surgery for cataracts. The study included a double-masked trial for
timolol, PV, and NPV and a single-masked trial on the effect of diclofenac sodium
and fluorometholone acetate on all three. The patients were divided into 6
groups, each of which were simultaneously administered the following different
combinations of compounds: timolol and diclofenac (group A), timolol and
fluorometholone (group B), PV and diclofenac (group C), PV and fluorometholone
(group D), NPV and diclofenac (group E), and NPV and fluorometholone (group F).
The 6 groups were then compared using a laser flare cell meter to determine the
degree of disruption of the blood-aqueous barrier and fluorescein angiography to 
investigate angiographic CME. The differences in mean daily fluctuations in
intraocular pressure were compared on the preoperative baseline day and for 5
weeks postoperatively. Twice daily administration of 0.5% timolol maleate or the 
vehicles was started 2 days before surgery, and continued until 5 weeks after
surgery. Diclofenac or fluorometholone drops were instilled in the eyes 4 times
preoperatively, on the day of surgery, and 3 times daily for 5 weeks
postoperatively. RESULTS: The flare amount was higher on the third and seventh
days in group B than in group D, but was the same after the seventh day. The
incidence of angiographic CME was the same between both groups. These 2 factors
were significantly lower in group F. These 2 factors were also significantly
lower in the 3 groups that received diclofenac instead of fluorometholone, with
no difference among these groups. The intraocular pressure decline was
significant in groups that received timolol compared with groups that received PV
or NPV. CONCLUSIONS: Timolol and its preservative, benzalkonium chloride, cause
disruption of the blood-aqueous barrier in early postoperative pseudophakia and
increased incidence of angiographic CME. The concurrent administration of
nonsteroidal anti-inflammatory drug such as diclofenac prevents these adverse
effects without interfering with the drop in intraocular pressure caused by
timolol. The addition of benzalkonium chloride to timolol contributes
considerably to these adverse effects. CLINICAL RELEVANCE: The present results
suggest the cause of similar complications produced by other antiglaucoma
eyedrops containing similar preservatives.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 11231772 [PubMed - indexed for MEDLINE]

3076: Arch Ophthalmol. 2001 Mar;119(3):359-69.

Phenotypic subtypes of Stargardt macular dystrophy-fundus flavimaculatus.

Lois N, Holder GE, Bunce C, Fitzke FW, Bird AC.

Medical Retina Service, Moorfields Eye Hospital, City Road, London EC1V 2PD,
England.

OBJECTIVE: To determine if phenotypic subtypes exist in Stargardt macular
dystrophy-fundus flavimaculatus (SMD-FFM). METHODS: A cross-sectional study of 63
patients with autosomal recessive SMD-FFM was undertaken. The age of onset,
duration of symptoms, visual acuity, and clinical features on fundus examination,
color fundus photographs, and fundus autofluorescence images were recorded.
Electrophysiological tests, including pattern, focal, and full-field
electroretinogram (ERG), electro-oculogram, and color-contrast sensitivity
measurement, were also performed. RESULTS: Based on electrophysiological
attributes (ERG), patients with SMD-FFM could be classified into 3 groups. In
group 1, there was severe pattern ERG abnormality with normal scotopic and
full-field ERGs. In group 2, there was additional loss of photopic function, and 
in group 3, there was loss of both photopic and scotopic function. Differences in
scotopic or photopic function among groups were not explained on the basis of
differences in age of onset or duration of disease. CONCLUSIONS: Patients with
SMD-FFM can be classified into 3 groups based on the absence or presence of
generalized loss of either photopic or photopic and scotopic function. It appears
that these 3 groups may represent distinct phenotypic subtypes in SMD-FFM.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11231769 [PubMed - indexed for MEDLINE]

3077: J Ophthalmic Nurs Technol. 2000 May-Jun;19(3):134-41.

Photodynamic therapy of eye diseases.

Rivellese MJ, Baumal CR.

Tufts University School of Medicine, Department of Vitreoretinal Surgery, New
England Eye Center, 750 Washington Street, Box 450, Boston, MA 02111, USA.

Photodynamic therapy is presently being used to treat several cutaneous cancers. 
The production of new second generation photosensitizers with better absorption
spectra and systemic tolerance has lead to active investigation of these
compounds in ophthalmology. The selective tissue damage with PDT is achieved by
sequestration of the photosensitizer in the target tissue and focal activation of
the photosensitizer by low energy directed light. The potential uses for PDT
include the treatment of ocular tumors, neovascularization and ciliary body
ablation. Visudyne already has been approved by the FDA for the treatment of
subfoveal choroidal neovascularization, and many patients already have been
treated with this drug.

Publication Types: 
    Review

PMID: 11249242 [PubMed - indexed for MEDLINE]

3078: Hum Mutat. 2001 Mar;17(3):235.

Identification of novel VMD2 gene mutations in patients with best vitelliform
macular dystrophy.

Marchant D, Gogat K, Boutboul S, Péquignot M, Sternberg C, Dureau P, Roche O,
Uteza Y, Hache JC, Puech B, Puech V, Dumur V, Mouillon M, Munier FL, Schorderet
DF, Marsac C, Dufier JL, Abitbol M.

Centre de recherche thérapeutique en ophtalmologie, Equipe d'accueil 2502 MENRT, 
Université René Descartes Paris V, Faculté de Médecine Necker-Enfants Malades,
156 rue de Vaugirard, 75015 Paris, France.

ABSTRACT We report five novel VMD2 mutations in Best's macular dystrophy patients
(S16F, I73N, R92H, V235L, and N296S). An SSCP analysis of the VMD2 11 exons
revealed electrophoretic mobility shifts exclusively in exons 2, 3, 4, 6 and 8.
Direct sequencing indicated that these shifts are caused by mono-allelic
transition in exons 2, 4, 6, 8 and transversion in exons 3 and 6. Five novel
"silent" polymorphisms are also reported: 213T>C, 323C>A, 1514A>G, 1661C>T, and
1712T>C. Hum Mutat 17:235, 2001. Copyright 2001 Wiley-Liss, Inc.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11241846 [PubMed - indexed for MEDLINE]

3079: Am J Ophthalmol. 2001 Mar;131(3):384-6.

Serous retinal detachment and cystoid macular edema in hypotony maculopathy.

Kokame GT, de Leon MD, Tanji T.

Division of Ophthalmology, Department of Surgery, University of Hawaii School of 
Medicine, Honolulu, Hawaii 96701, USA. retinahi@aol.com

PURPOSE: To report the foveal structural findings of hypotony maculopathy imaged 
with optical coherence tomography. METHODS: Case report of a 39-year-old white
woman with a 20 year history of uveitis, who underwent pars plana vitrectomy and 
pars plana Baerveldt implant for intractable glaucoma. Four months
postoperatively, decreased vision and hypotony maculopathy ensued. Optical
coherence tomographic (OCT) images were taken horizontally through the macula.
RESULTS: OCT demonstrated large intraretinal cysts, serous macular detachment,
and choroidal folds, which resolved upon resolution of hypotony. CONCLUSION:
Cystic macular changes and serous macular detachment can be prominent features of
hypotony maculopathy.

Publication Types: 
    Case Reports

PMID: 11239878 [PubMed - indexed for MEDLINE]

3080: Am J Pathol. 2001 Mar;158(3):1161-72.

Intrachoroidal neovascularization in transgenic mice overexpressing vascular
endothelial growth factor in the retinal pigment epithelium.

Schwesinger C, Yee C, Rohan RM, Joussen AM, Fernandez A, Meyer TN, Poulaki V, Ma 
JJ, Redmond TM, Liu S, Adamis AP, D'Amato RJ.

Albert Ludwigs University, Freiburg, Germany.

Choroidal neovascularization in age-related macular degeneration is a frequent
and poorly treatable cause of vision loss in elderly Caucasians. This choroidal
neovascularization has been associated with the expression of vascular
endothelial growth factor (VEGF). In current animal models choroidal
neovascularization is induced by subretinal injection of growth factors or
vectors encoding growth factors such as VEGF, or by disruption of the Bruch's
membrane/retinal pigment epithelium complex with laser treatment. We wished to
establish a transgenic murine model of age-related macular degeneration, in which
the overexpression of VEGF by the retinal pigment epithelium induces choroidal
neovascularization. A construct consisting of a tissue-specific murine retinal
pigment epithelium promoter (RPE(65) promoter) coupled to murine VEGF(164) cDNA
with a rabbit beta-globin-3' UTR was introduced into the genome of albino mice.
Transgene mRNA was expressed in the retinal pigment epithelium at all ages
peaking at 4 months. The expression of VEGF protein was increased in both the
retinal pigment epithelium and choroid. An increase of intravascular adherent
leukocytes and vessel leakage was observed. Histopathology revealed
intrachoroidal neovascularization that did not penetrate through an intact
Bruch's membrane. These results support the hypothesis that additional insults to
the integrity of Bruch's membrane are required to induce growth of choroidal
vessels into the subretinal space as seen in age-related macular degeneration.
This model may be useful to screen for inhibitors of choroidal vessel growth.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11238064 [PubMed - indexed for MEDLINE]

3081: Am J Ophthalmol. 2001 Feb;131(2):270-2.

Correction of cyclovertical strabismus induced by limited macular translocation
in a case of age-related macular degeneration.

Ohtsuki H, Shiraga F, Hasebe S, Kono R, Yamane T, Fujiwara H.

Department of Ophthalmology, Okayama University Medical School, 2-5-1
Shikata-cho, 700-8558 Okayama, Japan.

PURPOSE: To report a case of strabismus surgery performed to treat cyclovertical 
strabismus induced by limited macular translocation. METHODS: Case report.
RESULTS: A 62-year-old man suffering with age-related macular degeneration and
subfoveal choroidal neovascularization, RE, underwent limited macular
translocation surgery. The fovea was rotated downward, and his visual acuity
improved from 20/100 to 20/25 postoperatively. Cyclovertical diplopia persisted
for 6 months after the operation. A Hess screen test revealed a pattern that
simulated an underaction of the superior oblique muscle and inferior rectus
muscle with an overaction of the ipsilateral inferior oblique muscle. To treat
the diplopia, advancement of the superior oblique muscle tendon and resection of 
the ipsilateral inferior rectus muscle were performed. Binocular single vision
with 140 seconds of arc for stereopsis was obtained. CONCLUSION: Cyclovertical
strabismus after limited macular translocation is corrective with conventional
surgery on the treated eye.

Publication Types: 
    Case Reports

PMID: 11228313 [PubMed - indexed for MEDLINE]

3082: Am J Ophthalmol. 2001 Feb;131(2):208-15.

Pars plana vitrectomy, subretinal injection of tissue plasminogen activator, and 
fluid-gas exchange for displacement of thick submacular hemorrhage in age-related
macular degeneration.

Haupert CL, McCuen BW 2nd, Jaffe GJ, Steuer ER, Cox TA, Toth CA, Fekrat S, Postel
EA.

Duke University Eye Center, Durham, North Carolina 27710, USA.

PURPOSE: To evaluate a new procedure for displacement of large, thick submacular 
hemorrhage in patients with age-related macular degeneration. METHODS:
Retrospective review of 11 eyes of 11 patients with age-related macular
degeneration and thick submacular hemorrhage (defined as causing retinal
elevation detectable on stereo fundus photographs) treated with vitrectomy,
subretinal injection of tissue plasminogen activator (25 or 50 microg), and
fluid-gas exchange with postoperative prone positioning. Outcome measures
included displacement of hemorrhage from the fovea, best postoperative visual
acuity, and final postoperative visual acuity. RESULTS: In the 11 affected eyes
of 11 patients (seven men and four women; mean age, 76 years), preoperative
visual acuity ranged from 20/200 to hand motions. With surgery, subretinal
hemorrhage was displaced from the fovea in all 11 cases. Mean postoperative
follow-up was 6.5 months (range, 1 to 15 months). Best postoperative visual
acuity varied from 20/30 to 5/200, with improvement in nine (82%) cases and no
change in two cases. Eight eyes (73%) measured 20/200 or better, with four of
these eyes (36%) 20/80 or better. Final postoperative visual acuity ranged from
20/70 to light perception, with improvement in eight (73%) cases, no change in
one case, and worsening in two cases. A statistically significant difference was 
found between preoperative and best postoperative visual acuity (P =.004) but not
between preoperative and final visual acuity (P =.16). Hemorrhage recurred in
three (27%) eyes, causing severe visual loss in one eye. CONCLUSIONS: This
technique displaces submacular hemorrhage from the fovea and can improve vision
in patients with age-related macular degeneration. However, recurrence of
hemorrhage occurred in 27% of eyes and caused severe visual loss in one eye. A
randomized, prospective clinical trial is necessary to determine the efficacy of 
this technique in comparison with other proposed treatments.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11228297 [PubMed - indexed for MEDLINE]

3083: Am J Epidemiol. 2001 Mar 1;153(5):424-32.

Lutein and zeaxanthin in the diet and serum and their relation to age-related
maculopathy in the third national health and nutrition examination survey.

Mares-Perlman JA, Fisher AI, Klein R, Palta M, Block G, Millen AE, Wright JD.

Department of Ophthalmology and Visual Sciences, University of Wisconsin Medical 
School, 610 North Walnut Street, 460 WARF, Madison, WI 53705-2397, USA.
maresp@epi.ophth.wisc.edu

Relations of the carotenoids lutein and zeaxanthin in the diet and serum to
photographic evidence of early and late age-related maculopathy (ARM) among
persons over age 40 years (n = 8,222) were examined. Inverse relations of these
carotenoids in the diet or serum to any form of ARM were not observed overall.
There was a direct relation of dietary levels to one type of early ARM (soft
drusen). However, relations differed by age and race. In the youngest age groups 
who were at risk for developing early (ages 40-59 years) or late (ages 60-79
years) ARM, higher levels of lutein and zeaxanthin in the diet were related to
lower odds for pigmentary abnormalities, one sign of early ARM (odds ratio among 
persons in high vs. low quintiles = 0.1, 95 percent confidence interval: 0.1,
0.3) and of late ARM (odds ratio = 0.1, 95 percent confidence interval: 0.0, 0.9)
after adjustment for age, gender, alcohol use, hypertension, smoking, and body
mass index. Relations of these carotenoids to ARM may be influenced by age and
race and require further evaluation in separate populations and in prospective
studies.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11226974 [PubMed - indexed for MEDLINE]

3084: Ophthalmic Physiol Opt. 2001 Jan;21(1):36-44.

Randomised controlled trial of an integrated versus an optometric low vision
rehabilitation service for patients with age-related macular degeneration: study 
design and methodology.

Russell W, Harper R, Reeves B, Waterman H, Henson D, McLeod D.

Academic Department of Ophthalmology, Manchester Royal Eye Hospital, Oxford Road,
Manchester M13 9WH, UK.

A number of studies have measured the outcomes of low vision care but these have 
usually been longitudinal case series, thus constituting very low quality of
evidence for effectiveness. To date, there have been no randomised controlled
trials (RCTs) which have evaluated the effectiveness and cost effectiveness of
different models of care in low vision. The size of the low vision population and
the paucity of systematic evaluation have created a pressing need for evidence
about cost-effectiveness in order to inform service developments for low vision
rehabilitation. This paper describes the study design and methodology of a
three-arm RCT currently under way in Manchester. The baseline population
recruited is also described. A traditional hospital-based optometric service is
being compared with an integrated service (comprising the addition of
community-based rehabilitation officer input) and with more generic community
input (which is non-integrated and is not vision specific). A wide range of
outcome measures are being assessed at recruitment and 12 months
post-intervention, including low vision specific and generic quality of life
measures, patterns of low vision aid use, and task performance. The rationale for
the trial is discussed and the main study outcomes are described.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11220039 [PubMed - indexed for MEDLINE]

3085: Invest Ophthalmol Vis Sci. 2001 Mar;42(3):795-803.

Preservation of ganglion cell layer neurons in age-related macular degeneration.

Medeiros NE, Curcio CA.

Retinal Specialists of North Alabama, Huntsville, AL, USA.

PURPOSE. To determine the number of neurons remaining in the ganglion cell layer 
(GCL) of eyes with nonexudative and exudative age-related macular degeneration
(NEAMD and EXAMD, respectively) in relation to photoreceptor loss in the same
retinas. METHODS. The study design was a clinicopathologic correlation. Macular
photoreceptors and GCL neurons were counted in unstained retinal wholemounts from
eyes of patients with NEAMD (n = 6) and EXAMD (n = 5) and from control patients
without grossly visible drusen or pigmentary change (n = 15; age range, 60-95
years). The authors determined the percentage of counting sites with significant 
cell loss relative to control eyes and for photoreceptors, the percentage of
sites where rod or cone loss predominated. The total numbers of cones, rods, and 
GCL neurons were determined within the 6-mm-diameter macula. Fellow eyes were
prepared for light and electron microscopic evaluation of retinal pigment
epithelium and Bruch's membrane disease. RESULTS. EXAMD eyes had severe
photoreceptor loss. The total number of macular photoreceptors in NEAMD eyes was 
similar to the number in control eyes, despite moderate loss in the parafovea. In
9 of 11 AMD eyes, rod loss was greater than cone loss at the same locations.
EXAMD eyes had 47% fewer GCL neurons than control eyes. GCL neurons in NEAMD eyes
did not differ significantly from control eyes. CONCLUSIONS. Interventions
targeted at the outer retina early in the progression of neovascular disease
should benefit from the full age-appropriate complement of GCL neurons.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11222543 [PubMed - indexed for MEDLINE]

3086: Br J Ophthalmol. 2001 Mar;85(3):287-90.

Reduced amplitude and delayed latency in foveal response of multifocal
electroretinogram in early age related macular degeneration.

Li J, Tso MO, Lam TT.

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong
Kong.

AIM: To explore the use of multifocal electroretinograms (MERG) in detecting
early changes in age related macular degeneration (AMD). METHOD: 15 pre-AMD or
early AMD eyes showing retinal drusen or irregular fundus pigmentation with
window defects by fluorescein angiography (FA) and mildly decreased visual acuity
were examined and compared with their asymptomatic fellow eyes. 20 age matched
normal eyes were included as controls. MERG was recorded by a Veris system
(version 3.0) using a 103 hexagon stimulus and 218 second total recording time
per eye. The first order kernel was used to calculate amplitudes and latencies in
three configurations: the nasal and the temporal areas, the superior and the
inferior areas, and six concentric rings centred on the fovea. RESULTS: There
were no significant differences in the amplitudes and the latencies between the
different regions (nasal versus temporal and superior versus inferior) of the
retina as well as between the different groups of eyes (normal, pre-AMD or early 
AMD, and the asymptomatic fellow eyes) in each region. Using the concentric
configuration, the foveal amplitude of pre-AMD or early AMD eyes was
significantly suppressed when compared with the age matched control group and
their average latency was longer in the fovea than in outer rings and
significantly prolonged when compared with the normal control group. Similar
changes in amplitude and latency were also observed in the asymptomatic fellow
eyes. CONCLUSION: Significant abnormality in the foveal amplitude and the foveal 
latency of MERG could be detected in pre-AMD or early AMD eyes as well as their
asymptomatic contralateral eyes, suggesting MERG as a sensitive tool in detecting
early foveal abnormalities in AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11222332 [PubMed - indexed for MEDLINE]

3087: Disabil Rehabil. 2001 Jan 20;23(2):69-79.

Development of an ADL instrument targeting elderly persons with age-related
macular degeneration.

Dahlin-Ivanoff S, Sonn U, Svensson E.

Department of Ophthalmology, Göteborg University, Sweden.

BACKGROUND: In order to estimate the needs of early intervention in a health
education program, an ADL instrument measuring feelings of (in)security was
needed. The instrument was intended to detect early signs of decline and to
evaluate ADL performance among persons with AMD. An evaluative instrument must
have a high level of responsiveness, which is the ability to detect true changes 
over time but must also show a high level of intra-individual agreement in a
test-retest assessment. PURPOSE: The purpose of this study was to develop an ADL 
instrument for evaluative purposes and to establish the reliability and the
responsiveness of the instrument. METHOD: The target group comprised all persons 
referred by an ophthalmologist for low vision rehabilitation, 65 years and older,
living at home, with aged-related macular degeneration as the primary diagnosis
and with distance visual acuity of the better eye with best correction not lower 
than 0.1. A non-parametric statistical method that is developed for paired
ordered parametrical data was applied in order to measure the systematic and
occasional intra-rater disagreement separately and to measure the responsiveness.
CONCLUSION: The test-retest study showed that the ADL-instrument had a high level
of test-retest stability, which is a condition for responsiveness. The instrument
was found to be responsive. It could therefore detect true longitudinal changes
and be used for evaluative purposes targeting elderly with AMD.

Publication Types: 
    Comparative Study
    Evaluation Studies
    Research Support, Non-U.S. Gov't

PMID: 11214718 [PubMed - indexed for MEDLINE]

3088: South Med J. 2001 Jan;94(1):22-5.

Information about age-related macular degeneration on the Internet.

Stone TW, Jumper JM.

Department of Ophthalmology, Duke University Eye Center, Durham NC, USA.

BACKGROUND: A great deal of health information has become available on the
Internet over the past several years. Some of this information is inaccurate or
misleading to patients. We attempted to determine the accuracy of information on 
the Internet concerning age-related macular degeneration (ARMD). METHODS: The
term "macular degeneration" was entered in each of seven Internet search engines,
and the subsequent links were followed and categorized. The number of sites that 
discussed treatment inconsistent with the peer-reviewed standard of care for ARMD
was tabulated. RESULTS: Of the 80 unique sites regarding ARMD that we identified,
17 (21%) featured nonconventional information. CONCLUSIONS: Many Internet sites
feature unproven and costly nonconventional information about ARMD. Each
physician should be prepared to address these sites and to suggest reliable sites
concerning health information on the Internet.

Publication Types: 
    Evaluation Studies
    Review

PMID: 11213937 [PubMed - indexed for MEDLINE]

3089: Doc Ophthalmol. 2000 Sep;101(2):115-24.

The multifocal electroretinogram in age-related maculopathies.

Huang S, Wu D, Jiang F, Ma J, Wu L, Liang J, Luo G.

Zhongshan Ophthalmic Center Sun Yat-sen University of Medical Sciences,
Guangzhou, China. lypzoc@gzsums.edu.cn

To measure and compare the multifocal electroretinogram in control group and
patients with age-related maculopathies, 17 eyes of control subjects, 9 eyes of
wet-form ARMD, 8 eyes of dry-form ARMD and 14 eyes of idiopathic macular hole
were tested with VERIS Sciences 4.0. The latencies and average response densities
of 6 ring retinal regions in control eyes were compared with those in ARMD and
macular hole. The amplitude depression and latency prolongation were found in
age-related maculopathies. The changes of multifocal ERG were dramatic in
wet-form ARMD and moderate in dry-form ARMD and IMH, which were correspondent
with the pathological changes of the diseases. Our results suggest that the
multifocal electroretinogram can be used to quantity the visual function in
age-related maculopathies.

Publication Types: 
    Comparative Study

PMID: 11200545 [PubMed - indexed for MEDLINE]

3090: Graefes Arch Clin Exp Ophthalmol. 2000 Dec;238(12):960-4.

Changes of retinal capillary blood flow in age-related maculopathy.

Remsch H, Spraul CW, Lang GK, Lang GE.

Universitäts-Augenklinik Ulm, Prittwitzstrasse 43, 89075 Ulm, Germany.

BACKGROUND: To investigate retinal capillary blood flow characteristics in
patients with age-related maculopathy (ARM). METHODS: Retinal capillary blood
volume (VOL), blood flow (FLOW), and velocity (VEL) were measured in four macular
sectors (I, II, III, IV) and in two areas beyond the temporal superior and
inferior major vessel arcades (V and VI) in: 10 eyes with early ARM (drusen > or 
= 63 microns and/or atrophy of the retinal pigment epithelium, RPE, < 175 microns
and/or proliferation of RPE), 13 with late ARM (exudative), 10 with late ARM
(fibrotic), 14 normal eyes of 14 children of patients with ARM, and in 4 age- and
sex-matched control groups using the Heidelberg retinal flowmeter (HRF).
Statistical analysis was performed with the exact Wilcoxon test using an
additional adjustment procedure by Bonferroni-Holm. RESULTS: As compared to the
control group, there was no significant change of VOL, FLOW, and VEL in patients 
with early ARM. In patients with late ARM (exudative), there was a significant
higher FLOW in sectors I, II, and IV and a higher VOL and VEL in sectors III and 
IV. The group with late ARM (fibrotic) showed a reduction of VOL and FLOW in
sectors I-IV and of VEL in sectors II and IV. In children of ARM patients, VOL,
FLOW, and VEL of sectors I-VI did not differ from the control group. CONCLUSION: 
HRF measurements in patients with ARM indicate an increased macular retinal
capillary blood flow in patients with the exudative form of late ARM and a
decreased macular perfusion in those with the fibrotic form.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11196358 [PubMed - indexed for MEDLINE]

3091: Eur J Ophthalmol. 2000 Oct-Dec;10(4):338-40.

Birdshot retinochoroidopathy: measurement of the posterior fundus spots and
macular edema using a retinal thickness analyzer, before and after treatment.

De Geronimo F, Glacet-Bernard A, Coscas G, Soubrane G.

University Eye Clinic of Créteil, France.

PURPOSE: To measure the retinal thickness in the macular area and at the typical 
fundus spots in a patient with birdshot retinochoroidopathy, using the retinal
thickness analyzer (RTA), a new image analyzer involving laser-slit
biomicroscopy, and to quantify the changes after systemic corticosteroid therapy.
CASE REPORT: A 54-year-old man with posterior uveitis underwent visual acuity
measurement, fluorescein and indocyanine green (ICG) angiographies, optical
coherence tomography (OCT) and RTA measurements before and after steroid
treatment. RESULTS: The thickness at the birdshot spots measured with RTA
remained unchanged after treatment, but the thickness at the fovea decreased in
both eyes. Fluorescein and ICG angiographies and OCT showed no change with
treatment. CONCLUSIONS: RTA seems a more sensitive method for assessing changes
in macula thickness in the course of birdshot retinochoroidopathy and can help
document the effect of treatment.

Publication Types: 
    Case Reports

PMID: 11192845 [PubMed - indexed for MEDLINE]

3092: Chang Gung Med J. 2000 Nov;23(11):672-80.

Macular translocation--an innovative treatment for macular degenerative diseases.

Ho CL.

Department of Ophthalmology, Chang Gung Memorial Hospital, 5 Fu-Shin Street,
Kweishan, Taoyuan, Taiwan, R.O.C. clho@tpts5.seed.net.tw

BACKGROUND: Age-related macular degeneration with subfoveal choroidal
neovascularization (CNV) is difficult to handle with any treatment modality so
far. Macular translocation is an innovative surgical approach to this disease.
METHODS: The "full" macular translocation comprises phacoemulsification, complete
vitrectomy, artificial retinal detachment, 360 degrees retinotomy, removal of the
CNV, translocation of the neurosensory retina, and endotamponade with silicone
oil. The "limited" macular translocation is accomplished by partial retinal
detachment and scleral imbrication. The CNV can be removed during the operation
or ablated by a laser postoperatively. RESULTS: Full macular translocation was
performed on 3 eyes, and upward macular displacement was achieved from 10 to 45
degrees. Limited macular translocation was performed on 2 eyes, and downward
macular displacement was achieved from 350 to 900 microns. One eye had visual
improvement, 2 eyes remained stationary, and another 2 eyes had worse visual
acuity postoperatively. No proliferative vitreoretinopathy occurred in any of
these eyes. CONCLUSION: Macular translocation can relocate the macula to a
healthy adjacent retinal pigment epithelium-choroid bed and is a promising
surgical treatment for macular degenerative disorders. Further trials are
mandatory to evaluate its benefits.

Publication Types: 
    Case Reports

PMID: 11190376 [PubMed - indexed for MEDLINE]

3093: Trans Am Ophthalmol Soc. 2000;98:109-15; discussion 115-7.

Race, iris color, and age-related macular degeneration.

Frank RN, Puklin JE, Stock C, Canter LA.

Kresge Eye Institute, Wayne State University School of Medicine, Detroit,
Michigan, USA.

PURPOSE: While most observers agree that age-related macular degeneration (AMD)
is much more common in white persons than in persons of black African ancestry,
the influence of iris color has been more controversial. We reexamined
relationships between race, iris color, and AMD in a series of patients from our 
retina clinic. METHODS: We evaluated, in masked fashion, stereoscopic photographs
of the retinas and irides in 306 sequential patients 60 years of age or older
from our retina clinics. Four readers judged whether AMD was present, absent, or 
questionable in the retinal photographs and labeled iris color as blue, hazel, or
brown. Presence or absence of AMD and presence and severity of the various
macular lesions were determined by "majority vote" of the readers. We evaluated
inter-rater agreement using the kappa statistic. We compared the prevalence of
AMD and of specific AMD lesions as a function of race, sex, and iris color by
contingency table analysis. RESULTS: The kappa statistic showed good
inter-observer agreement, being 0.466 (P < 10(-6)) for definite or questionable
AMD and ranging from 0.185 to 0.522 (P = 0.0047 to P < 10(-6)) for most lesions. 
We found significantly more AMD in white patients than in black patients (X2 =
27.54, P < 10(-4)). There was no significant difference in AMD prevalence by sex.
In white patients, AMD was significantly more prevalent in individuals with blue 
or hazel irides than in those with brown irides (X2 = 15.04, P = .02).
CONCLUSIONS: We confirm previous findings of a higher prevalence of AMD in white 
persons than in black persons. We also agree with those observers who claim that 
white subjects with light-colored irides have a higher prevalence of AMD than
those with dark-colored irides. We suggest that differences in the association
between iris pigmentation and AMD in different studies using different research
methods may reflect genetic difference in the groups being studied.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11190014 [PubMed - indexed for MEDLINE]

3094: Ophthalmology. 2000 Dec;107(12):2314-7.

Photodynamic therapy with verteporfin for age-related macular degeneration.
American Academy of Ophthalmology.

[No authors listed]

OBJECTIVE: This document describes photodynamic therapy (PDT) with verteporfin
for age-related macular degeneration (AMD) and examines the evidence to answer
the key question about whether the treatment is safe and effective in reducing
visual loss from AMD. METHODS: A literature search that was conducted in April
2000 retrieved eight relevant citations, and the reference lists of these
articles were consulted for additional citations. Panel members reviewed this
information, and a methodologist reviewed and rated all articles according to the
strength of evidence. RESULTS: The published literature contains a report of the 
combined results from two identically designed, double-masked randomized
controlled trials. Ninety-four percent of participants completed the one-year
follow-up. Patients treated with verteporfin had a decreased risk of at least
moderate visual loss over this one-year period, but the beneficial effect on
visual acuity was greatest among eyes in which the area of classic choroidal
neovascularization (CNV) occupied 50% or more of the entire lesion area. There
was no statistically significant difference in visual acuity outcomes at one year
for yees in which the classic CNv was more than 0% but less than 50% of the area 
of the entire lesion. Serious systemic complications were rare. Severe vision
decrease (equivalent to four lines or more of vision) within 7 days of treatment 
with verteporfin has been reported in 1% to 4% of patients. Partial recovery of
vision was observed in many of these patients. CONCLUSIONS: To date, evidence
suggests that PDT using verteporfin can reduce the risk of visual loss in
patients with predominantly classic subfoveal CNV from AMD at one year. The rate 
of ocular and systemic complications is low. Additional clinical research is
needed to determine the long-term effectiveness of treatment and the comparitive 
effectiveness with existing and new treatment modalities under investigation.

PMID: 11186878 [PubMed - indexed for MEDLINE]

3095: Arch Ophthalmol. 2001 Feb;119(2):251-9.

Macular edema and retinal hard exudates in African Americans with type 1
diabetes: the New Jersey 725.

Roy MS, Klein R.

University of Medicine and Dentistry, New Jersey Medical School, Department of
Ophthalmology, 90 Bergen St, Room 6164, Newark, NJ 07103, USA.

OBJECTIVE: To determine frequency and associated risk factors for macular edema
and retinal hard exudates in hospitalized African Americans with type 1 diabetes.
SUBJECTS AND METHODS: Included were 725 African Americans with type 1 diabetes
who participated in the New Jersey 725. Clinical evaluations consisted of a
structured clinical interview, ocular examination, stereoscopic fundus
photographs, and blood pressure measurements. Presence of macular edema and hard 
exudates was determined via masked grading of fundus photographs. Biological
evaluations included blood and urine assays. RESULTS: Of the 725 patients, 89
(12.3%) had macular edema and 149 (20.6%) had retinal hard exudates in at least 1
eye. The presence of macular edema and hard exudates was significantly associated
with older age at examination, longer duration of diabetes, and severity of
diabetic retinopathy. Presence of proteinuria, missing insulin injections at
least once a week, and longer duration of diabetes were significantly and
independently associated with macular edema. Presence of proteinuria, male sex,
higher low-density lipoprotein cholesterol levels, and longer duration of
diabetes were significantly and independently associated with severity of retinal
hard exudates. CONCLUSION: Macular edema and hard exudates are common in African 
Americans with type 1 diabetes, particularly in patients with evidence of renal
disease.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.

PMID: 11176988 [PubMed - indexed for MEDLINE]

3096: Arch Ophthalmol. 2001 Feb;119(2):246-50.

Sunlight and the 5-year incidence of early age-related maculopathy: the beaver
dam eye study.

Cruickshanks KJ, Klein R, Klein BE, Nondahl DM.

Department of Ophthalmology and Visual Sciences, University of Wisconsin, 610 N
Walnut St, Room 460, WARF Building, Madison, WI 53705-2397, USA.
cruickshanks@epi.ophth.wisc.edu

OBJECTIVE: To investigate the relation of sunlight exposure and indicators of sun
sensitivity with the 5-year incidence of early age-related maculopathy (ARM).
DESIGN: Longitudinal, population-based study. Participants (aged 43-86 years at
baseline) in the Beaver Dam Eye Study were reexamined from 1993 to 1995, 5 years 
after the baseline examination. Questionnaire data about sunlight exposure and
sun sensitivity were obtained at baseline. Additional information about earlier
life patterns of exposure was ascertained at follow-up. Stereoscopic color fundus
photographs were graded to determine the presence of ARM at the 5-year follow-up 
in eyes free from signs of early ARM at the baseline examination. RESULTS:
Leisure time spent outdoors while persons were teenagers (aged 13-19 years) and
in their 30s (aged 30-39 years) was significantly associated with the risk of
early ARM (odds ratio, 2.09; 95% confidence interval, 1.19-3.65). There was a
slight, but nonsignificant, protective effect associated with use of hats and
sunglasses while persons were teenagers and in their 30s (odds ratio, 0.72; 95%
confidence interval, 0.50-1.03). People with red or blond hair were slightly more
likely to develop early ARM than people with darker hair (odds ratio, 1.33; 95%
confidence interval, 0.97-1.83). There were no associations between estimated
ambient UV-B exposure or markers of sun sensitivity and the incidence of early
ARM. CONCLUSION: Exposure to sunlight may be associated with the development of
early ARM.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11176987 [PubMed - indexed for MEDLINE]

3097: Arch Ophthalmol. 2001 Feb;119(2):198-207.

Comment in:
    Arch Ophthalmol. 2005 Sep;123(9):1283-5.

Photodynamic therapy of subfoveal choroidal neovascularization in age-related
macular degeneration with verteporfin: two-year results of 2 randomized clinical 
trials-tap report 2.

Bressler NM; Treatment of Age-Related Macular Degeneration with Photodynamic
Therapy (TAP) Study Group.

OBJECTIVE: To report 24-month vision and fluorescein angiographic outcomes from
trials evaluating photodynamic therapy with verteporfin (Visudyne; CIBA Vision
Corp, Duluth, Ga) in patients with subfoveal choroidal neovascularization (CNV)
caused by age-related macular degeneration (AMD). DESIGN: Two multicenter,
double-masked, placebo-controlled, randomized clinical trials. SETTING:
Twenty-two ophthalmology practices in Europe and North America. PARTICIPANTS:
Patients with subfoveal CNV lesions caused by AMD with greatest linear dimension 
on the retina measuring 5400 micrometer or less, with evidence of classic CNV and
best-corrected visual acuity (approximate Snellen equivalent) between 20/40 and
20/200. METHODS: The methods were similar to those described in our 1-year
results, with follow-up examinations beyond 1 year continuing every 3 months
(except for Photograph Reading Center evaluations, which occurred only at month
18 and month 24 examinations). During the second year, the same regimen (with
verteporfin or placebo as applied at baseline) was used if angiography showed
fluorescein leakage from CNV. The primary outcome was the proportion of eyes with
fewer than 15 letters (approximately 3 lines) of visual acuity loss at the month 
24 examination, adhering to an intent-to-treat analysis. The last observation was
carried forward to impute for any missing data. RESULTS: Three hundred fifty-one 
(87%) of 402 patients in the verteporfin group compared with 178 (86%) of 207
patients in the placebo group completed the month 24 examination. Beneficial
outcomes with respect to visual acuity and contrast sensitivity noted at the
month 12 examination in verteporfin-treated patients were sustained through the
month 24 examination. At the month 24 examination for the primary outcome, 213
(53%) of 402 verteporfin-treated patients compared with 78 (38%) of 207
placebo-treated patients lost fewer than 15 letters (P<.001). In subgroup
analyses for predominantly classic lesions (in which the area of classic CNV
makes up at least 50% of the area of the entire lesion) at baseline, 94 (59%) of 
159 verteporfin-treated patients compared with 26 (31%) of 83 placebo-treated
patients lost fewer than 15 letters at the month 24 examination (P<.001). For
minimally classic lesions (in which the area of classic CNV makes up <50% but >0%
of the area of the entire lesion) at baseline, no statistically significant
differences in visual acuity were noted. Few additional photosensitivity adverse 
reactions and injection site adverse events were associated with verteporfin
therapy in the second year of follow-up. CONCLUSIONS: The visual acuity benefits 
of verteporfin therapy for AMD patients with predominantly classic CNV subfoveal 
lesions are safely sustained for 2 years, providing more compelling evidence to
use verteporfin therapy for these cases. For AMD patients with subfoveal lesions 
that are minimally classic, there is insufficient evidence to warrant routine use
of verteporfin therapy.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11176980 [PubMed - indexed for MEDLINE]

3098: Arch Ophthalmol. 2001 Feb;119(2):171-80.

Comment in:
    Arch Ophthalmol. 2001 Feb;119(2):275-6.

External beam irradiation of subfoveal choroidal neovascularization complicating 
age-related macular degeneration: one-year results of a prospective,
double-masked, randomized clinical trial.

Marcus DM, Sheils W, Johnson MH, McIntosh SB, Leibach DB, Maguire A, Alexander J,
Samy CN.

Medical College of Georgia, Department of Ophthalmology, 1120 15th St, Augusta,
GA 30912, USA. dmarcus@mail.mcg.edu

OBJECTIVES: To determine the effects of low-dose external beam irradiation
compared with observation on the visual function of eyes with subfoveal choroidal
neovascularization (CNV) complicating age-related macular degeneration (ARMD).
DESIGN: Prospective, double-masked, randomized clinical trial. Patients
randomized to the radiation group received external beam irradiation at a dose of
14 Gy in 7 fractions of 2 Gy. Patients randomized to the observation group
received sham radiation. SETTING: Tertiary care retinal referral practice.
PATIENTS: Individuals with classic, mixed, or occult subfoveal CNV secondary to
ARMD. MAIN OUTCOME MEASURES: Change in visual acuity from baseline to specified
time periods. Secondary outcome variables were contrast sensitivity and fundus
photographic/fluorescein angiographic progression. RESULTS: Forty-two eyes were
randomized to observation; 41 eyes, to radiation. Baseline characteristics and
demographics did not differ between groups. The median distance visual acuity
(DVA) in radiation-treated eyes decreased from 20/80 at baseline to 20/320 (mean 
loss rate, 4.14 lines) at 1-year follow-up. The median DVA in observation group
eyes decreased from 20/125 at baseline to 20/250 (mean loss rate, 3.39 lines) at 
1-year follow-up. There were no statistically significant differences in changes 
in DVA, contrast sensitivity, or fluorescein angiographic progression from
baseline between groups at any follow-up period. CONCLUSIONS: At 1-year
follow-up, low-dose external beam irradiation at 14 Gy in 7 fractions of 2 Gy is 
neither beneficial nor harmful for subfoveal CNV complicating ARMD.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11176977 [PubMed - indexed for MEDLINE]

3099: Prog Retin Eye Res. 2001 Mar;20(2):227-53.

Risk factors for age-related macular degeneration.

Evans JR.

Department of Epidemiology and International Eye Health, Institute of
Ophthalmology, Bath street, EC1V 9EL, London, UK. jennifer.evans@ucl.ac.uk

There is an increasing body of evidence as to the risk factors for age-related
macular degeneration. Age and genetic make-up are the most important risk factors
identified to date. Over the next decade, the different genes that are involved
in the development of age-related macular degeneration will be identified. There 
is reasonably consistent evidence that smoking cigarettes results in increased
risk of the disease. The question as to whether antioxidant vitamin and mineral
supplementation prevents or delays the development of the disease will be
resolved as the results of large ongoing trials become available in the next few 
years. Currently, there is conflicting evidence as to their benefits and some
indication as to possible harm. Other risk factors such as alcohol consumption,
oestrogen replacement and lifetime light exposure require further study. The
study of the epidemiology of age-related macular degeneration would be
facilitated by a greater standardization of methods. Studies with large numbers
of late stage disease are needed in order to provide the power to investigate
moderate risks. This may either be achieved by adding on macular degeneration
studies to large cohort studies already in place, or by pooling data from smaller
studies.

Publication Types: 
    Comparative Study
    Review

PMID: 11173253 [PubMed - indexed for MEDLINE]

3100: Acta Ophthalmol Scand. 2000 Dec;78(6):667-71.

Photocoagulation of diabetic macular oedema--complications and visual outcome.

Lövestam-Adrian M, Agardh E.

Department of Ophthalmology, University Hospital, Lund, Sweden.
monica.lovestam_adrian@oft.lu.se

PURPOSE: To describe complications and visual outcome of photocoagulation for
clinically significant macular oedema. SUBJECTS AND METHODS: Evaluation of
macular oedema and complications of photocoagulation in 194 eyes, defined as
subretinal fibrosis, atrophic creep of the pigment epithelium and subretinal
neovascularization was based on stereo fundus photo grading. The study included
25 patients with type 1 and 93 patients with type 2 diabetes (age 32 +/- 10 and
65 +/- 9 years, respectively). The statistical evaluations were based on one eye 
per patient. RESULTS: Follow-up time was 5.5 +/- 2.4 years (mean +/- SD).
Complications within 1/3 ODD from the centre of the macula were seen in 4% (1/23)
of eyes of patients with type 1 diabetes, compared to 26% (20/76) of eyes among
patients with type 2 diabetes (p=0.02). Hard exsudates before treatment were more
common in type 2 than in type 1 diabetic eyes, 70/82 vs. 11/23 (p<0.001). In all 
eyes, hard exsudates were more often associated with subretinal fibrosis or
atrophic creep (35/133 eyes) than diffuse oedema (5/44 eyes) (p=0.04).
CONCLUSION: Photocoagulation for clinically significant macular oedema with hard 
exudates, particularly when subfoveally located, was more often associated with
subretinal fibrosis or atrophic creep of the pigment epithelium than
photocoagulation of oedema without hard exudates. Hard exudates as well as
complications after photocoagulation were more common in type 2 than in type 1
diabetes, resulting in poorer visual outcome in this group of patients.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11167229 [PubMed - indexed for MEDLINE]

3101: Am J Ophthalmol. 2001 Jan;131(1):78-89.

Translocation of the macula for management of subfoveal choroidal
neovascularization: comparison of results in age-related macular degeneration and
degenerative myopia.

Glacet-Bernard A, Simon P, Hamelin N, Coscas G, Soubrane G.

Department of Ophthalmology, University of Paris XII, Créteil, France.
agnes.glacet@chicreteil.fr

PURPOSE: To report the results of limited macular translocation in subfoveal
choroidal neovascularization resulting from age-related macular degeneration or
degenerative myopia. METHODS: The first consecutive 32 patients (23 age-related
macular degeneration eyes and nine myopic eyes) were operated on with the limited
macular translocation technique described by de Juan. Before and after surgery, a
complete examination included fluorescein and indocyanine-green angiographies and
optical coherence tomography. Mean follow-up was 9 months in the age-related
macular degeneration group (range, 6 to 14 months) and 10 months in the myopic
group (range, 6 to 15 months). RESULTS: The improvement in visual acuity was
better in the myopic group than in the age-related macular degeneration group and
was correlated with younger age in the myopic group (P <.05). At the end of
follow-up, visual acuity improved by 2 lines or more in seven age-related macular
degeneration eyes (30%), including four eyes (13%) with an improvement of 6 lines
or more, and in six myopic eyes (67%), including two eyes (22%) with an
improvement of 6 lines or more. Final visual acuity was unchanged in four
age-related macular degeneration eyes (17%) and three myopic eyes (33%), and
decreased in 12 age-related macular degeneration eyes (52%). Conversely, the mean
foveal displacement was greater in age-related macular degeneration than in
myopia (1,105 microm and 685 microm, respectively; P <.05). Main complications
were retinal detachment (six eyes), neovascularization at the injection site (two
eyes), and recurrence of neovascularization (43% of the age-related macular
degeneration group and 11% of the myopic group). CONCLUSIONS: Limited macular
translocation allowed a significant improvement in visual acuity in some eyes
with subfoveal neovascularization and resulted in a moderate rate of
complications. Longer follow-up and additional studies are required to confirm
these findings.

Publication Types: 
    Comparative Study

PMID: 11162982 [PubMed - indexed for MEDLINE]

3102: Am J Ophthalmol. 2001 Jan;131(1):55-60.

Comment in:
    Am J Ophthalmol. 2002 Mar;133(3):428-9.

Perimetric sensitivity and retinal thickness in eyes with macular edema resulting
from branch retinal vein occlusion.

Imasawa M, Iijima H, Morimoto T.

Department of Ophthalmology, Yamanashi Medical University, Tamaho, Yamanashi,
Japan.

PURPOSE: To document and study the relationship between perimetric sensitivity
and retinal thickness at the foveal and parafoveal points in eyes with macular
edema associated with branch retinal vein occlusion. METHODS: A prospective study
was performed using the central 10-2 Humphrey perimetry program and optical
coherence tomography. Seventeen eyes with branch retinal vein occlusion were
eligible showing macular edema without macular nonperfusion or massive retinal
hemorrhage. RESULTS: The sensitivity and retinal thickness were significantly
correlated at the fovea (r = -0.629, P =.006) as well as 1 (r = -0.656, P <.0001)
and 3 (r = -0.885, P <.0001) degrees apart from the fovea. The visual acuity that
is expressed as a logarithm of the minimum angle of resolution (LogMAR) also
correlated with retinal thickness (r = 0.591, P =.011). CONCLUSION: The increased
retinal thickness resulting from macular edema is closely correlated with retinal
sensitivity as measured by automated static perimetry both at the fovea and
parafovea. Measuring the retinal thickness using optical coherence tomography may
be useful in monitoring macular edema in eyes with branch retinal vein occlusion.

PMID: 11162980 [PubMed - indexed for MEDLINE]

3103: Am J Ophthalmol. 2001 Jan;131(1):50-4.

Tomographic findings of foveal hard exudates in diabetic macular edema.

Otani T, Kishi S.

Department of Ophthalmology, Gunma University School of Medicine, Maebashi,
Gunma, Japan. otanito@showa.gunma-u.ac.jp

PURPOSE: To report the intraretinal location of foveal hard exudates after
vitrectomy to treat diabetic macular edema and to evaluate the visual outcome.
METHODS: In a prospective study, the tomographic features of 11 eyes (8 patients)
with diabetic macular edema were evaluated with optical coherence tomography
after vitrectomy. The intraretinal location of hard exudates at the fovea
(anatomic foveola) and the relationship with visual acuity were investigated.
RESULTS: With optical coherence tomography, hard exudates were observed as highly
reflective spots in the cross-sectional images. In six of 11 eyes (54.5%), the
hard exudates were in the inner portion of the neurosensory retina; the final
best-corrected visual acuity averaged 20/70 in the six eyes. In the remaining
five eyes (45.5%), hard exudates were deposited not only in the neurosensory
retina but also in the subretinal space. In optical coherence tomographic images,
subretinal hard exudates were observed as highly reflective plaques, which were
slightly elevated over the retinal pigment epithelium. The five eyes developed a 
serous retinal detachment at the fovea before or after vitrectomy. Subretinal
hard exudates bridged the detached neurosensory retina and the retinal pigment
epithelium in two eyes. The average final visual acuity level in the five eyes
was 20/300. The visual outcome was significantly worse in five eyes with
subretinal hard exudates than in six eyes with an intraretinal one (P <.05,
Wilcoxon rank sum tests). CONCLUSIONS: If serous retinal detachment develops
before or after vitrectomy for diabetic macular edema, hard exudates tend to
accumulate not only in the neurosensory retina but also in the subretinal space. 
The visual prognosis is worse in cases of subretinal exudation.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11162979 [PubMed - indexed for MEDLINE]

3104: Am J Ophthalmol. 2001 Jan;131(1):44-9.

Comment in:
    Am J Ophthalmol. 2001 Jan;131(1):123-5.    Am J Ophthalmol. 2001 Oct;132(4):599-600.

Macular traction detachment and diabetic macular edema associated with posterior 
hyaloidal traction.

Kaiser PK, Riemann CD, Sears JE, Lewis H.

Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA.
kaiserp@ccf.org

PURPOSE: To review the clinical, photographic, fluorescein angiographic, and
optical coherence tomographic findings in patients with the diabetic macular
traction and edema (DMTE) associated with posterior hyaloidal traction (PHT).
METHODS: We performed a prospective review of nine eyes of nine patients with
diabetic macular edema (DME) and PHT on clinical examination. The patients had a 
comprehensive ophthalmic history and examination, color photographs, fluorescein 
angiography, and optical coherence tomography (OCT). RESULTS: All patients had
diabetic retinopathy and DME. Of the nine eyes, eight patients had previous focal
or grid photocoagulation. All nine eyes had a thickened, taut, glistening
posterior hyaloid on clinical biomicroscopic examination with no posterior
vitreous separation. Fluorescein angiography was performed on seven eyes, and all
had early hyperfluorescence with deep, diffuse, late leakage in the macular area 
consistent with DMTE associated with PHT. Optical coherence tomography scans of
the macular region revealed retinal thickening in all eyes with a mean retinal
thickness of 556.9 +/- 114.7 microns. In addition, eight of the nine eyes had a
shallow macular traction detachment associated with PHT. CONCLUSION: Eyes with
DME associated with PHT may have a shallow, subclinical, macular detachment.
Optical coherence tomography may be useful in evaluating patients with DME to see
if a macular detachment is present.

PMID: 11162978 [PubMed - indexed for MEDLINE]

3105: Br J Ophthalmol. 2001 Feb;85(2):184-8.

Relation between macular morphology and visual function in patients with
choroidal neovascularisation of age related macular degeneration.

Doris N, Hart PM, Chakravarthy U, McCleland J, Stevenson M, Hudson C, Jackson J.

School of Biomedical Science, University of Ulster.

AIM: To examine the relation between three measures of visual function (distance 
acuity, near acuity, and contrast sensitivity) and specific fluorescein
angiographic characteristics of the macular lesion in patients with subfoveal
choroidal neovascularisation (CNV) due to age related macular degeneration (AMD).
METHODS: Visual evaluation and digital fundus fluorescein angiography were
performed in 93 patients with subfoveal CNV. Standard morphometric techniques
were used on two frames from the angiographic series closest to 30 seconds and 60
seconds respectively, to ascertain total lesion size (defined as the entire area 
of abnormal fluorescence), the size of the classic component, and the distance
from the fovea to the closest point of healthy retina. Correlations were sought
using Pearson's correlation coefficients. Stepwise regression was used to
minimise multiple colinearity. RESULTS: When the study eye was the better eye of 
a patient's pair of eyes, the strongest correlation was between the size of the
classic component and contrast sensitivity (r= 0.48, p <0.001) and was highly
significant. When the study eye was the worse eye, significant correlations were 
observed between total lesion size and all three measures of visual function. The
strongest correlation was observed between overall lesion size and contrast
sensitivity (r = 0.52, p <0.001). CONCLUSIONS: This study has shown that the
status of the study eye (that is, better or worse eye of a pair of eyes)
influences the impact of macular pathology in AMD on visual function. The
distance of the fovea from healthy retina was found to be an important factor in 
predicting visual function.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11159483 [PubMed - indexed for MEDLINE]

3106: Br J Ophthalmol. 2001 Feb;85(2):169-72.

Comment in:
    Br J Ophthalmol. 2001 Jun;85(6):762.

Optokinetic nystagmus in patients with central scotomas in age related macular
degeneration.

Valmaggia C, Charlier J, Gottlob I.

Department of Ophthalmology, Kantonsspital, CH-9007 St Gallen, Switzerland.
valmaggia@freesurf.ch

BACKGROUND: Reports on the impact of a loss in the central field of vision on
optokinetic nystagmus (OKN) are varied. A study was therefore undertaken to
reassess the role of the central retina in the generation of OKN in a large group
of patients with age related macular degeneration. METHODS: Four groups of 20
patients were examined: a control group without scotoma and three groups with
absolute central scotomas measuring 1 degrees--10 degrees, 11 degrees--20
degrees, and 21 degrees--30 degrees. OKN was elicited with black and white
stripes moving nasally to temporally or temporally to nasally on a screen
subtending 54 degrees x 41 degrees at four velocities (15, 30, 45, and 60 degrees
/s). OKN gain was measured using infrared oculography. RESULTS: There was no
significant difference in OKN gain between the control group and those with
scotomas of 1 degrees--10 degrees and 11 degrees--20 degrees. A significant
difference in OKN gain was found between the group with scotomas of 21
degrees--30 degrees and all other groups at stimulus velocities of 30, 45, and 60
degrees/s (p<0.05). OKN gain significantly diminished with increasing stimulus
velocity (p<0.05). No statistically significant difference was found in OKN gain 
between stimuli moving temporally to nasally and nasally to temporally.
CONCLUSION: Abnormalities of OKN gain were noted only in patients with large
scotomas. An intact macula is therefore not necessary for the generation of OKN.

PMID: 11159480 [PubMed - indexed for MEDLINE]

3107: Invest Ophthalmol Vis Sci. 2001 Feb;42(2):439-46.

Macular pigment and risk for age-related macular degeneration in subjects from a 
Northern European population.

Beatty S, Murray IJ, Henson DB, Carden D, Koh H, Boulton ME.

University Department of Ophthalmology, Manchester Royal Eye Hospital,
Manchester, UK. stephen@stiofanbetagh.demon.co.uk

PURPOSE: Age and advanced disease in the fellow eye are the two most important
risk factors for age-related macular degeneration (AMD). In this study, the
authors investigated the relationship between these variables and the optical
density of macular pigment (MP) in a group of subjects from a northern European
population. METHODS: The optical density of MP was measured psychophysically in
46 subjects ranging in age from 21 to 81 years with healthy maculae and in 9
healthy eyes known to be at high-risk of AMD because of advanced disease in the
fellow eye. Each eye in the latter group was matched with a control eye on the
basis of variables believed to be associated with the optical density of MP (iris
color, gender, smoking habits, age, and lens density). RESULTS: There was an
age-related decline in the optical density of macular pigment among volunteers
with no ocular disease (right eye: r(2) = 0.29, P = 0.0006; left eye: r(2) =
0.29, P < 0.0001). Healthy eyes predisposed to AMD had significantly less MP than
healthy eyes at no such risk (Wilcoxon's signed rank test: P = 0.015).
CONCLUSIONS: The two most important risk factors for AMD are associated with a
relative absence of MP. These findings are consistent with the hypothesis that
supplemental lutein and zeaxanthin may delay, avert, or modify the course of this
disease.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11157880 [PubMed - indexed for MEDLINE]

3108: Invest Ophthalmol Vis Sci. 2001 Feb;42(2):433-8.

Diabetic macular edema: passive and active transport of fluorescein through the
blood-retina barrier.

Sander B, Larsen M, Moldow B, Lund-Andersen H.

Department of Ophthalmology, Herlev Hospital, University of Copenhagen, Denmark. 
bsander@idea.dk

PURPOSE: To investigate the passive bidirectional and active outward transport of
fluorescein through the blood-retina barrier (BRB) in diabetic patients with
clinically significant macular edema and in healthy controls. METHODS: The
passive and active transport of fluorescein through the BRB was quantitated by
vitreous fluorometry. A previously developed method was used to model passive
transport. A new simulation model was developed and evaluated for estimation of
active transport. The study included 10 eyes of 5 healthy controls and 31 eyes of
20 diabetic patients with clinically significant diabetic macular edema (CSME) in
at least one eye, totalling 25 eyes with CSME. RESULTS: Passive permeability of
fluorescein was increased by a factor of 12 in eyes with edema compared to
healthy controls (edema, 23.7 nm/sec; healthy subjects, 1.9 nm/sec, P < 0.01),
whereas the active transport was doubled (edema, 84.1 nm/sec; healthy subjects,
43.5 nm/sec, P < 0.01). Unlike active transport, passive permeability was related
to the degree of retinopathy, in that eyes with severe non-proliferative diabetic
retinopathy had a passive permeability that was significantly increased compared 
to moderate retinopathy (32.1 nm/sec and 14.6 nm/sec, respectively, P: < 0.05).
The passive movement quantitated with vitreous fluorometry was larger for diffuse
and mixed leakage compared to focal (P = 0.07). CONCLUSIONS: Insofar as the
movement of fluorescein can be taken as a probe for the movement of electrolytes 
and water, the pathogenesis of diabetic macular edema seems to involve a
disruption of the BRB, presumably its inner component. The active resorptive
functions of the blood-retina barrier appear to be compensatorily increased to
counteract edema formation, although the increase is too small to prevent edema
in the face of severe leakage through the blood-retina barrier.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11157879 [PubMed - indexed for MEDLINE]

3109: Am J Clin Nutr. 2001 Feb;73(2):209-18.

Prospective study of dietary fat and the risk of age-related macular
degeneration.

Cho E, Hung S, Willett WC, Spiegelman D, Rimm EB, Seddon JM, Colditz GA,
Hankinson SE.

Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA. 
eunyoung.cho@channing.harvard.edu

BACKGROUND: The relation between intakes of total fat and specific types of fat
and age-related macular degeneration (AMD) remains unclear. OBJECTIVE: Our
objective was to examine prospectively the association between fat intake and
AMD. DESIGN: We conducted a prospective follow-up study of participants in the
Nurses' Health Study and the Health Professionals Follow-up Study. At baseline
(1984 for women and 1986 for men), the study included 42743 women and 29746 men
aged > or = 50 y with no diagnosis of AMD who were followed until 1996. Fat
intake was assessed with a food-frequency questionnaire. RESULTS: We accrued 567 
patients with AMD with a visual loss of 20/30 or worse. The pooled multivariate
relative risk (RR) for the highest compared with the lowest quintile of total fat
intake was 1.54 (95% CI: 1.17, 2.01; P for trend = 0.008). Linolenic acid was
positively associated with risk of AMD (top versus bottom quintile of RR: 1.49;
95% CI: 1.15, 1.94; P for trend = 0.0009). Docosahexaenoic acid had a modest
inverse relation with AMD (top versus bottom quintile of RR: 0.70; 95% CI: 0.52, 
0.93; P for trend = 0.05), and >4 servings of fish/wk was associated with a 35%
lower risk of AMD compared with < or = 3 servings/mo (RR: 0.65; 95% CI: 0.46,
0.91; P for trend = 0.009). CONCLUSIONS: Total fat intake was positively
associated with risk of AMD, which may have been due to intakes of individual
fatty acids, such as linolenic acid, rather than to total fat intakes per se. A
high intake of fish may reduce the risk of AMD.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.

PMID: 11157315 [PubMed - indexed for MEDLINE]

3110: J Neurosurg. 2000 Dec;93 Suppl 3:172-6.

Gamma knife treatment of subfoveal, classic neovascularization in age-related
macular degeneration: a pilot study.

Haas A, Papaefthymiou G, Langmann G, Schröttner O, Feigl B, Leber KA, Hanselmayer
R, Pendl G.

Department of Ophthalmology, Karl-Franzens-University, Graz, Austria.
anton.haas@kfunigraz.ac.at

OBJECT: Age-related macular degeneration (AMD) is the leading cause of severe
vision loss in people older than age 65 years in the western world. The visual
acuity loss usually results from the ingrowth of new vessels from the choroid
capillaries, so called choroidal neovascularization (CNV). The aim of this pilot 
study was to investigate the effect of a single-fraction gamma knife radiosurgery
(GKS) on visual acuity and the growth pattern of CNV in patients with AMD.
METHODS: Ten patients with a mean age of 75 years and with a subfoveal, classic
CNV due to AMD were enrolled in this study. All patients were treated with GKS in
one fraction with a prescription dose of 10 Gy. The treatment target was the CNV 
located in the macula. Computerized tomography scans of the globe were obtained. 
After a follow up of 1 year visual acuity was stable in six patients and
decreased in four. The size of the CNV could be stabilized in four patients, and 
in six an enlargement of these neovascular complexes was shown. No side effects, 
such as cataract formation, development of radiation-induced retinopathy, or
optic neuropathy, have been observed so far. CONCLUSIONS: Gamma knife
radiosurgery seemed to have a beneficial effect on visual acuity in patients with
AMD, but it failed to control growth of CNV in six patients. A longer follow up, 
a larger study population, and a randomized and controlled study are necessary
for a final conclusion.

Publication Types: 
    Comparative Study

PMID: 11143240 [PubMed - indexed for MEDLINE]

3111: Mol Vis. 2000 Dec 31;6:287-93.

Association of the apolipoprotein E gene with age-related macular degeneration:
possible effect modification by family history, age, and gender.

Schmidt S, Saunders AM, De La Paz MA, Postel EA, Heinis RM, Agarwal A, Scott WK, 
Gilbert JR, McDowell JG, Bazyk A, Gass JD, Haines JL, Pericak-Vance MA.

Department of Medicine and Center for Human Genetics, Duke University Medical
Center, Durham, NC 27710, USA. sschmidt@chg.mc.duke.edu

PURPOSE: Age-related macular degeneration (AMD) is a complex disorder affecting
older adults in which genetic factors are likely to play a role. It has been
previously suggested that the e4 allele of the apolipoprotein E (APOE) gene may
have a protective effect on AMD risk and that the e2 allele may increase disease 
risk. The purpose of our study was to examine whether an independent data set
would support the proposed role of APOE in AMD etiology. METHODS: We compared AMD
cases (n=230) to controls (n=372) with respect to APOE genotypes using c2 tests
and logistic regression analysis. We also conducted separate analyses for
familial (n=129) and sporadic (n=101) AMD cases since these groups may have a
different disease etiology. RESULTS: We did not find evidence for the
risk-increasing effect attributed to the e2 allele in either familial or sporadic
AMD. No evidence for a protective effect of the e4 allele was obtained for
sporadic AMD. The age- and sex-adjusted odds ratio (OR) for e4 carriers among
familial AMD cases compared to controls was 0.66 (95% confidence interval:
0.38-1.12, p=0.13). In the subgroup of individuals younger than 70 years of age, 
an OR of 0.24 (95% confidence interval: 0.08-0.72, p=0.004) was obtained.
CONCLUSIONS: Our data modestly support a protective effect of the APOE-e4 allele 
on AMD risk, but emphasize the need to investigate more thoroughly whether the
effect could be restricted to cases with a family history of AMD and whether it
varies across age and sex groups.

Publication Types: 
    Comparative Study
    Research Support, U.S. Gov't, P.H.S.

PMID: 11141572 [PubMed - indexed for MEDLINE]

3112: Nat Genet. 2001 Jan;27(1):89-93.

A 5-bp deletion in ELOVL4 is associated with two related forms of autosomal
dominant macular dystrophy.

Zhang K, Kniazeva M, Han M, Li W, Yu Z, Yang Z, Li Y, Metzker ML, Allikmets R,
Zack DJ, Kakuk LE, Lagali PS, Wong PW, MacDonald IM, Sieving PA, Figueroa DJ,
Austin CP, Gould RJ, Ayyagari R, Petrukhin K.

Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore,
Maryland, USA.

Stargardt-like macular dystrophy (STGD3, MIM 600110) and autosomal dominant
macular dystrophy (adMD) are inherited forms of macular degeneration
characterized by decreased visual acuity, macular atrophy and extensive fundus
flecks. Genetic mapping data suggest that mutations in a single gene may be
responsible for both conditions, already known to bear clinical resemblance. Here
we limit the minimum genetic region for STGD3 and adMD to a 0.6-cM interval by
recombination breakpoint mapping and identify a single 5-bp deletion within the
protein-coding region of a new retinal photoreceptor-specific gene, ELOVL4, in
all affected members of STGD3 and adMD families. Bioinformatic analysis of ELOVL4
revealed that it has homology to a group of yeast proteins that function in the
biosynthesis of very long chain fatty acids. Our results are therefore the first 
to implicate the biosynthesis of fatty acids in the pathogenesis of inherited
macular degeneration.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11138005 [PubMed - indexed for MEDLINE]

3113: Invest Ophthalmol Vis Sci. 2001 Jan;42(1):235-40.

Erratum in:
    Invest Ophthalmol Vis Sci 2001 Mar;42(3):548.

Macular pigment in donor eyes with and without AMD: a case-control study.

Bone RA, Landrum JT, Mayne ST, Gomez CM, Tibor SE, Twaroska EE.

Department of Physics, Florida International University, Miami, Florida 33199,
USA. bone@fiu.edu

PURPOSE: To determine whether there is an association between the density of
macular pigment in the human retina and the risk of age-related macular
degeneration (AMD). METHODS: Retinas from 56 donors with AMD and 56 controls were
cut into three concentric regions centered on the fovea. The inner, medial, and
outer regions covered the visual angles 0 degrees to 5 degrees, 5 degrees to 19
degrees, and 19 degrees to 38 degrees, respectively. The amounts of lutein (L)
and zeaxanthin (Z) extracted from each tissue sample were determined by
high-performance liquid chromatography. RESULTS: L and Z levels in all three
concentric regions were less, on average, for the AMD donors than for the
controls. The differences decreased in magnitude from the inner to medial to
outer regions. The lower levels found in the inner and medial regions for AMD
donors may be attributable, in part, to the disease. Comparisons between AMD
donors and controls using the outer (peripheral) region were considered more
reliable. For this region, logistic regression analysis indicated that those in
the highest quartile of L and Z level had an 82% lower risk for AMD compared with
those in the lowest quartile (age- and sex-adjusted odds ratio = 0.18, 95%
confidence interval = 0.05-0.64). CONCLUSIONS: The results are consistent with a 
theoretical model that proposes an inverse association between risk of AMD and
the amounts of L and Z in the retina. The results are inconsistent with a model
that attributes a loss of L and Z in the retina to the destructive effects of
AMD.

Publication Types: 
    Comparative Study
    Research Support, U.S. Gov't, P.H.S.

PMID: 11133874 [PubMed - indexed for MEDLINE]

3114: Retina. 2000;20(6):650-4.

Polypoidal choroidal vasculopathy pattern in age-related macular degeneration: a 
clinicopathologic correlation.

Lafaut BA, Aisenbrey S, Van den Broecke C, Bartz-Schmidt KU, Heimann K.

Department of Ophthalmology, University of Cologne, Germany.
bart.lafaut@rug.ac.be

PURPOSE: To report the histopathologic features of surgically removed submacular 
tissue from an elderly patient with a pattern of polypoidal choroidal
vasculopathy on indocyanine green angiography. METHODS: Clinical examination
including fluorescein and indocyanine green angiography and light microscopy of
surgical specimen. RESULTS: A thick yellow proteinaceous subretinal fluid was
seen in the right macula of an 81-year-old white man. Fluorescein angiography
indicated progressive leakage from undetermined source apart from a few focal
hyperfluorescent points. Indocyanine green angiography showed several polyps as
well as dilated choroidal vessels in the macula and along the superior temporal
arcade. A large plaque was visualized in the late phase. Microscopically, the
specimen consisted of a thick fibrovascular membrane located on the choroidal
side of the retinal pigment epithelium (RPE). The RPE layer was discontinuous
whereas on its choroidal side an almost intact layer of diffuse drusen was
observed. A group of dilated thin-walled vessels were found that appeared to be
saccular on serial sections. Some of these were located almost immediately under 
the diffuse drusen. CONCLUSION: Histologic examination of submacular tissue
removed from an eye with polypoidal choroidal vasculopathy showed several
aneurysmal dilatations located directly under diffuse drusen within a sub-RPE,
intra-Bruch's fibrovascular membrane.

Publication Types: 
    Case Reports

PMID: 11131419 [PubMed - indexed for MEDLINE]

3115: Retina. 2000;20(6):638-49.

Adult-onset foveomacular pigment epithelial dystrophy: clinicopathologic
correlation of three cases.

Dubovy SR, Hairston RJ, Schatz H, Schachat AP, Bressler NM, Finkelstein D, Green 
WR.

Wilmer Ophthalmological Institute, and Department of Pathology, The Johns Hopkins
Medical Institutions, Baltimore, Maryland, USA.

PURPOSE: The authors describe the clinicopathologic features of three patients
with adult onset foveomacular pigment epithelial dystrophy (AOFPED). METHODS: The
eyes of three patients were studied ophthalmoscopically and by fluorescein
angiography, and obtained postmortem and studied by light and electron
microscopy. RESULTS: Histopathologic study of the three patient's eyes disclosed 
central loss of the retinal pigment epithelium and photoreceptor cell layer with 
a moderate number of pigment-containing macrophages present in the subretinal
space and outer retina. To either side, the retinal pigment epithelium was
distended with much lipofuscin. Basal laminar and basal linear deposits were
present throughout the central area. No discontinuities of Bruch membrane were
present. CONCLUSION: The findings in the eyes of three patients with AOFPED
included marked aging changes that are similar to those seen in age-related
macular degeneration. Pigmented cells with lipofuscin in the subretinal space
account for the vitelliform appearance.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11131418 [PubMed - indexed for MEDLINE]

3116: Ophthalmologica. 2001 Jan-Feb;215(1):51-4.

Does coenzyme Q10 play a role in opposing oxidative stress in patients with
age-related macular degeneration?

Blasi MA, Bovina C, Carella G, Genova ML, Jansen AM, Lenaz G, Brancato R.

Department of Ophthalmology, University of L'Aquila, L'Aquila, Italy.

To seek some specific biochemical markers of age-related macular degeneration
(AMD), coenzyme Q10 (CoQ10) levels were determined in plasma and platelets from
19 exudative AMD patients and 19 age-matched controls. Lipid peroxidation was
followed in plasma in vitro after the addition of a free radical initiator. Most 
patients had lower plasma CoQ10 content than most controls. Plasma from controls 
showed greater capacity to oppose the oxidative damage. These results support the
concept that free radicals play a pathogenic role in AMD and that CoQ10 may have 
a protective effect.

PMID: 11125270 [PubMed - indexed for MEDLINE]

3117: Am J Ophthalmol. 2000 Dec;130(6):782-9.

Juvenile macular dystrophy associated with deficient activity of fatty aldehyde
dehydrogenase in Sjögren-Larsson syndrome.

Willemsen MA, Cruysberg JR, Rotteveel JJ, Aandekerk AL, Van Domburg PH, Deutman
AF.

Department of Pediatric Neurology, University Hospital Nijmegen, Nijmegan, The
Netherlands. m.willemsen@ckskg.azn.nl

PURPOSE: To report the ocular manifestations associated with the Sjögren-Larsson 
syndrome in a series of patients with proven fatty aldehyde dehydrogenase
deficiency. To emphasize the clinical importance of the ophthalmological features
of the Sjögren-Larsson syndrome. To discuss the metabolic disturbances that might
give rise to the ophthalmological picture. METHODS: Fifteen patients with
Sjögren-Larsson syndrome underwent a standardized ophthalmological examination.
In patients of appropriate age, and who were able to cooperate, additional
investigations were performed. RESULTS: All patients exhibited bilateral,
glistening yellow-white crystalline deposits that were located in the innermost
retinal layers and appeared during the first 2 years of life. Repeated fundus
photography in individual patients showed that the dots became more numerous as
the patients got older. Photophobia, subnormal visual acuity, myopia, and
astigmatism were found in most of the patients. Fluorescein angiography was
performed in three patients and showed a mottled hyperfluorescence of the retinal
pigment epithelium, without leakage. Color vision, electroretinography, and
electro-oculography could be performed in only a small number of patients and
showed no abnormalities. Visual evoked potentials were found to be abnormal in
six of eight patients. CONCLUSIONS: In Sjögren-Larsson syndrome, patients exhibit
highly characteristic bilateral, glistening yellow-white retinal dots from the
age of 1 to 2 years onward. The number of dots increases with age. The extent of 
the macular abnormality does not correlate with the severity of the ichthyosis or
with the severity of the neurological abnormalities. A high percentage of
patients shows additional ocular signs and symptoms, notably marked photophobia.

PMID: 11124298 [PubMed - indexed for MEDLINE]

3118: Am J Ophthalmol. 2000 Dec;130(6):769-73.

Comment in:
    Am J Ophthalmol. 2008 Jul;146(1):146; author reply 146-7.

Genetic association of manganese superoxide dismutase with exudative age-related 
macular degeneration.

Kimura K, Isashiki Y, Sonoda S, Kakiuchi-Matsumoto T, Ohba N.

Department of Ophthalmology, Kagoshima University Faculty of Medicine,
Sakuragaoka, Kagoshima-shi, Japan.

PURPOSE: To elucidate whether any polymorphic genes for xenobiotic-metabolizing
and antioxidant enzymes are associated with the development of exudative
age-related macular degeneration. METHODS: A hospital-based case-control study
was performed on a consecutive series of 102 Japanese patients with the exudative
form of age-related macular degeneration who were recruited between 1993 and 1998
in the Kagoshima University Hospital. Controls were 200 systemically healthy
individuals who had no senescent ocular disorders and were over 50 years of age. 
There was no evidence of age-related macular degeneration in the 200 controls.
Genomic DNA from peripheral bloods was examined using polymerase chain reaction
and defined for the genetic polymorphisms of cytochrome P-450 1A1, glutathione
S-transferases, microsomal epoxide hydrolase, and manganese superoxide dismutase.
RESULTS: We found a significant association of manganese superoxide dismutase
gene polymorphism, valine/alanine polymorphism at the targeting sequence of the
enzyme, with age-related macular degeneration. The patients had an increased
frequency of alanine allele and alanine/alanine genotype (odds ratio = 10.14, 95%
confidence interval = 4.84 to 2.13; P =.0005 after Bonferroni correction). We
also observed a weak association of microsomal epoxide hydrolase exon-3
polymorphism with age-related macular degeneration (odds ratio = 2.20, 95%
confidence interval = 4. 02 to 1.20; P =.020 after Bonferroni correction).
Cytochrome P-450 1A1, glutathione S-transferases, and microsomal epoxide
hydrolase exon-4 were polymorphic, but their genotype frequency distributions did
not show a statistically significant difference between the patients and
controls. CONCLUSIONS: The results suggest that manganese superoxide dismutase
gene polymorphism is associated with exudative age-related macular degeneration. 
Microsomal epoxide hydrolase is another enzyme that may be associated with the
disease. The exudative form of age-related macular degeneration may have genetic 
risk factors against oxidative stress and/or effects of xenobiotics. Further
association studies in other polymorphic genes for xenobiotic-metabolizing
enzymes are needed to elucidate the environmental-genetic interaction in the
underlying cause of age-related macular degeneration.

PMID: 11124296 [PubMed - indexed for MEDLINE]

3119: Am J Ophthalmol. 2000 Dec;130(6):740-4.

Perifoveal microcirculation before and after vitrectomy for diabetic cystoid
macular edema.

Kadonosono K, Itoh N, Ohno S.

Department of Ophthalmology, Yokohama City University School of Medicine,
Yokohama, Japan. kado@med.yokohama-cu.ac.jp

PURPOSE: To quantify the perifoveal microcirculation in diabetic eyes before and 
after successful vitreous surgery for cystoid macular edema without posterior
vitreous detachment, and to determine whether improvement in perifoveal
microcirculation is associated with improvement in postoperative visual acuity.
METHODS: In a prospective study, vitreous surgery was performed on 11 eyes of
nine consecutive diabetic patients with cystoid macular edema, and their mean
perifoveal capillary blood flow velocity was measured by fluorescein angiography 
with a scanning laser ophthalmoscope. Visual acuity was measured preoperatively
and postoperatively, and the results were converted to the logarithm of the
minimum angle of resolution (logMAR). The correlation between changes in logMAR
visual acuity and capillary blood flow velocity was evaluated. RESULTS: In all
nine eyes of seven patients with successful vitreous surgery, the cystoid macular
edema resolved within 6 months after surgery, and the mean capillary blood flow
velocity was significantly increased compared with that before surgery (2.19 mm
per second versus 2.68 mm per second, P =.021); the changes in capillary blood
flow velocity were significantly correlated with the changes in the logMAR visual
acuity (P =.024). CONCLUSIONS: Vitreous surgery may improve perifoveal
microcirculation in the eyes of diabetic patients with cystoid macular edema and 
resolve the macular edema. Improvement of perifoveal microcirculation may be an
important factor affecting visual outcome.

PMID: 11124292 [PubMed - indexed for MEDLINE]

3120: Eye. 2000 Oct;14 Pt 5:691-4.

Deep intramuscular methylprednisolone for the treatment of cystoid macular oedema
in uveitis.

Tehrani NN, Saeed T, Murray PI.

Birmingham and Midland Eye Centre, Birmingham, UK.

PURPOSE: To study the use of intramuscular methylprednisolone in the treatment of
cystoid macular oedema in patients with uveitis. METHODS: A total of 32 patients 
with various types of uveitis with unilateral cystoid macular oedema were
recruited. Patients received 160 mg of intramuscular methylprednisolone into the 
thigh and were reassessed 6-8 weeks later. In 17 patients in whom there had been 
no significant improvement, a further injection of methylprednisolone was given; 
a total of 49 injections. RESULTS: After a first injection a significant
improvement in vision (an increase of > or = 2 Snellen lines) was seen in 15 of
32 eyes (47%), and 17 of 32 eyes (53%) showed no significant change. After the
second injection 7 of 17 eyes (41%) showed a significant improvement but there
was no change in 9 of 17 eyes (53%). Only one eye deteriorated more than 2 lines 
of Snellen acuity. There were minimal ocular or systemic side effects associated 
with this form of treatment. CONCLUSIONS: Despite limited success, deep
intramuscular methylprednisolone may have a role as an alternative mode of
treatment in uveitis patients with unilateral cystoid macular oedema, thus
avoiding the potential hazards of periocular injections. In comparison with
orally administered systemic corticosteroids, an injection ensures patient
compliance and is associated with fewer side effects.

PMID: 11116686 [PubMed - indexed for MEDLINE]

3121: Exp Anim. 2000 Oct;49(4):275-80.

Erratum in:
    Exp Anim 2001 Jan;50(1):99.

Ocular fundus abnormalities detected by fluorescein and indocyanine green
angiography in the Royal College of Surgeons dystrophic rat.

Satoh T, Yamaguchi K.

Department of Ophthalmology, Yamagata University School of Medicine, Japan.

The ocular fundi of the Royal College of Surgeons (RCS) dystrophic rats were
examined by conventional fundus photography, fluorescein angiography (FA) and
indocyanine green angiography (IA). In the fundus, a reddish colored background
was observed in the RCS dystrophic rats at 3 weeks of age. At 9 weeks of age, the
background had changed to pale in color. In FA, the RCS dystrophic rats at 3 week
of age demonstrated background fluorescence with homogeneous brightness.
Fluorescent dye leakage was observed in the late phase of the postinjection
period at 9 weeks of age. In IA, the RCS dystrophic rats at 3 weeks of age had
background fluorescence with homogeneous brightness, and at 5 weeks of age, spots
of hyperfluorescence were scattered over the dark background. At 7 weeks of age, 
numerous delimited, irregular round spots of hyperfluorescence appeared over the 
dark background. Such hyperfluorescent lesions had further increased in number
and size in the RCS dystrophic rats at 9 weeks of age. In this way, ocular
findings related to abnormalities in the retinal pigment epithelium and choroid
in the RCS dystrophic rat were demonstrated by fundus photography, fluorescein
angiography and indocyanine green angiography.

PMID: 11109553 [PubMed - indexed for MEDLINE]

3122: Optometry. 2000 Nov;71(11):715-21.

Intravitreal injection of tissue plasminogen activator and gas bubble for
treatment of subretinal hemorrhage in ARMD.

Hay SR, Madonna RJ.

VA Hudson Valley Health Care System, Castle Point, New York 12511, USA.

BACKGROUND: Subretinal hemorrhage (SRH) can arise from any number of underlying
etiologies and can stem from either the choroidal and/or retinal circulation. It 
is most commonly associated with age-related macular degeneration (ARMD), in
which a choroidal neovascular membrane is the usual source of bleeding. Vision
loss resulting from SRH can be secondary to toxic, tractional, and barrier
effects from persistent blood. To minimize long-term visual loss from SRH,
several treatment modalities have evolved over the past few years. The
most-recent therapeutic techniques involve treatment with the thrombolytic agent 
tissue plasminogen activator The value of surgical removal of subretinal
hemorrhage to improve visual outcome remains unsubstantiated, as definitive
studies have not been completed. CASE REPORT: A 73-year-old man manifested a
1-day history of decreased vision in his right eye. A large submacular hemorrhage
had developed as a result of exudative age-related macular degeneration.
Treatment included intravitreal injection of tissue plasminogen activator,
followed by intravitreal injection of SF6 gas, which displaced the subretinal
hemorrhage away from the fovea and resulted in clearance of the submacular blood.
This case describes a new treatment for submacular hemorrhage secondary to ARMD. 
CONCLUSIONS: Subretinal hemorrhage secondary to ARMD can cause significant
permanent visual loss. A thorough understanding of the pathogenesis of vision
loss and the treatment options available are essential in successful management
of these patients. Intravitreal injection of tissue plasminogen activator and gas
bubble may provide an effective treatment for subretinal hemorrhage in
age-related macular degeneration.

Publication Types: 
    Case Reports

PMID: 11101129 [PubMed - indexed for MEDLINE]

3123: Ophthalmology. 2000 Dec;107(12):2224-32.

Risk factors associated with age-related macular degeneration. A case-control
study in the age-related eye disease study: Age-Related Eye Disease Study Report 
Number 3.

Age-Related Eye Disease Study Research Group.

AREDS Coordinating Center, The EMMES Corporation, 11325 Seven Locks Road, Suite
214, Potomac, MD 20854-3205, USA. aredspub@emmes.com

OBJECTIVE: To investigate possible risk factors for age-related macular
degeneration (AMD) in participants in the Age-Related Eye Disease Study (AREDS). 
DESIGN: Case-control study. PARTICIPANTS: Of the 4757 persons enrolled in AREDS, 
4519 persons aged 60 to 80 years were included in this study. The lesions
associated with AMD ranged from absent in both eyes to advanced in one eye. MAIN 
OUTCOME MEASURES: Stereoscopic color fundus photographs of the macula were used
to place participants into one of five groups, based on the frequency and
severity of lesions associated with AMD. Participants with fewer than 15 small
drusen served as the control group. RESULTS: Staged model building techniques
were used to compare each of the four case groups with the control group.
Increased age was a consistent finding of all four of the case groups compared
with the control group, and all the following associations were age adjusted.
Persons with either intermediate drusen, extensive small drusen, or the pigment
abnormalities associated with AMD (group 2) were more likely to be female, more
likely to have a history of arthritis, and less likely to have a history of
angina. Persons with one or more large drusen or extensive intermediate drusen
(group 3) were more likely to use hydrochlorothiazide diuretics and more likely
to have arthritis. Hypertension, hyperopia, presence of lens opacities, and white
race were also found more frequently in this group as well as in persons with
neovascular AMD (group 5). Only persons in group 5 were more likely to have an
increased body mass index, whereas persons with geographic atrophy (group 4) as
well as those in groups 3 and 5 were more likely to have completed fewer years in
school or to be smokers. Those with geographic atrophy were also more likely to
use thyroid hormones and antacids. CONCLUSIONS: Our findings for smoking and
hypertension, which have been noted in previous studies, suggest that two
important public health recommendations, the avoidance of smoking and the
prevention of hypertension, may reduce the risk of developing AMD. Other
associations, such as those for hyperopia, lens opacities, less education, female
gender, increased body mass index, and white race, which have been noted in other
studies, are also seen in the AREDS population. The increased use of thyroid
hormones and antacids in persons with geographic atrophy and the increased
likelihood of arthritis or hydrochlorothiazide use in persons with one or more
large drusen or extensive intermediate drusen have not been previously reported
and need additional investigation.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, U.S. Gov't, P.H.S.

PMID: 11097601 [PubMed - indexed for MEDLINE]

3124: Clin Experiment Ophthalmol. 2000 Oct;28(5):367-72.

Methods for detecting age-related maculopathy: a comparison between photographic 
and clinical assessment.

Tikellis G, Robman LD, Harper A, McNeil JJ, Taylor HR, McCarty CA.

Department of Epidemiology and Preventive Medicine, Monash University, Clayton,
Victoria, Australia. tikelis@austin.unimelb.edu.au

PURPOSE: To examine the sensitivity, specificity and overall agreement between
photographic and clinical assessment in detecting age-related maculopathy (ARM)
features in the context of an epidemiological study, the Vitamin E, Cataract and 
Age-related Maculopathy Study (VECAT). METHODS: A total of 1204 volunteers aged
between 55 and 80 years of age, who were enrolled in the VECAT Study, had both
slit-lamp biomicroscopy examination and fundus photos taken as part of the
baseline ophthalmic examination. The Nidek 3-DX fundus camera (Nidek, Gamagori,
Japan) was used to produce paired, one-framed, coloured, 15 degrees stereoslides 
of the macular area at a fixed angle. An International Classification and Grading
System for Age-related Maculopathy and Age-related Macular Degeneration was used 
to grade the stereoslides. Agreement in the detection of drusen, pigment
abnormalities, and late stage ARM features was assessed using unweignted kappa
statistic. Cases of disagreement were verified using clinical data records,
grading documentation and the review of stereoslides. RESULTS: Macula status was 
available for 2386 eyes. For drusen of size < 63 microm, sensitivity was 47%,
specificity was 68% with a kappa value of 0.20. For drusden > or = 125 microm,
sensitivity and specificity were > or =81%. Kappa values ranged from 0.56 to
0.71. Levels of agreement for pigment abnormalities and late ARM were in the
substantial range (i.e. kappa values from 0.70 to 1.00). CONCLUSIONS: Slit-lamp
biomicroscopy was found to be comparable to photograding (using the Nidek 3-DX
fundus camera) for detecting features pertaining to ARM. However, given the
objectivity and permanency of stereoslides, photograding is still the more
reliable and the preferred system of assessing ARM in the context of an
epidemiological study.

Publication Types: 
    Clinical Trial
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 11097285 [PubMed - indexed for MEDLINE]

3125: Surv Ophthalmol. 2000 Nov-Dec;45(3):195-214.

Mechanisms of action of photodynamic therapy with verteporfin for the treatment
of age-related macular degeneration.

Schmidt-Erfurth U, Hasan T.

University Eye Hospital, Lübeck, Germany.

Age-related macular degeneration, especially the neovascular form of the disease,
is the leading cause of blindness in elderly people in developed countries.
Thermal photocoagulation is still the preferred treatment for choroidal
neovascularization that does not involve the fovea, but it is suitable for only a
small number of patients and it can lead to immediate loss of visual acuity.
Photodynamic therapy with use of photochemical light activation of verteporfin as
a photosensitizer (verteporfin therapy) has been shown to be effective in
treating vascularized tumors, and its potential to treat other conditions
involving neovascularization has also been suggested. Preclinical and clinical
studies have indicated that verteporfin therapy can be used to treat choroidal
neovascularization secondary to age-related macular degeneration effectively and 
safely. Selective occlusion of choroidal neovasculature by this therapy causes
minimal damage to the neurosensory retina and, therefore, does not induce loss of
visual acuity. This benefit allows verteporfin therapy to be used in the large
proportion of patients who are not eligible for treatment by laser
photocoagulation. The mechanistic aspects of the mode of action of
light-activated verteporfin are described in this review.

Publication Types: 
    Research Support, U.S. Gov't, Non-P.H.S.
    Research Support, U.S. Gov't, P.H.S.
    Review

PMID: 11094244 [PubMed - indexed for MEDLINE]

3126: Jpn J Ophthalmol. 2000 Nov-Dec;44(6):668-76.

A retrospective pilot study of indocyanine green enhanced diode laser
photocoagulation for subfoveal choroidal neovascularization associated with
age-related macular degeneration.

Obana A, Gohto Y, Nishiguchi K, Miki T, Nishi S, Asada A.

Department of Ophthalmology, Osaka City University Medical School, Osaka, Japan.

PURPOSE: The effectiveness and limitations of indocyanine green (ICG) enhanced
diode laser photocoagulation in treating subfoveal choroidal neovascularization
(CNV) associated with age-related macular degeneration (AMD) were investigated
retrospectively. METHODS: Thirty-eight eyes of 37 patients with subfoveal CNV
received ICG enhanced diode laser (wavelength, 805 nm) photocoagulation in our
preliminary series. Nineteen eyes had classic CNV and the others had occult CNV, 
which was well-delineated on ICG angiography. The rate of anatomical success and 
functional outcomes were investigated. Factors prognostic of a final visual
acuity of 0.1 or better were analyzed. The follow-up period ranged from 6 to 51
months (mean +/- SD = 26.5 +/- 14.4 months). RESULTS: Occlusion of CNV was
achieved in 35 of 38 eyes (92%), and 7 eyes (18%) showed recurrence, which was
occluded by retreatment in all but 1 eye. Ten eyes (26.3%) showed improvement of 
visual acuity; 16 (42.1%) showed no change; and in 12 eyes (31.6%) visual acuity 
deteriorated. Factors prognostic of a final visual acuity of 0.1 or better were
good preoperative visual acuity (Mann-Whitney U-test, P =.0028), and a relatively
short distance between the edge of laser burns and the center of the foveal
avascular zone (unpaired t-test, P =.0285). CONCLUSION: Indocyanine green
enhanced photocoagulation achieved a higher anatomical success rate but
functional outcomes equal to those with argon or krypton laser photocoagulation. 
A controlled prospective study is necessary to prove the efficacy of this
treatment.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 11094185 [PubMed - indexed for MEDLINE]

3127: Jpn J Ophthalmol. 2000 Nov-Dec;44(6):653-60.

Radiation therapy for small choroidal neovascularization in age-related macular
degeneration.

Matsuhashi H, Noda Y, Takahashi D, Mariya Y.

Department of Ophthalmology, Hirosaki University School of Medicine, Hirosaki,
Japan.

PURPOSE: To evaluate the effects of radiation therapy on age-related macular
degeneration with subfoveal or juxtafoveal choroidal neovascularization < or =1
disc area. METHODS: Fourteen patients (14 eyes) received a total radiation dose
of 10-20 Gy in 5-10 fractions. The mean follow-up time was 22 months. Ten
patients (10 eyes) in a control group were followed up for an average of 16
months without treatment. RESULTS: At a 12-month posttreatment examination,
funduscopic and angiographic findings showed improvement in 7 eyes (50%), no
change in 1 eye (7%), and deterioration in 6 eyes (43%) among the treated
patients. The same findings demonstrated improvement in 1 eye (10%), no change in
2 eyes (20%), and deterioration in 7 eyes (70%) among the control patients. This 
difference was determined to be statistically significant between the two groups 
by the Mann-Whitney U-test. Visual acuity had improved in 4 eyes (29%), was
unchanged in 6 eyes (43%), and had declined in 4 eyes (29%), among the treated
patients. Among the control patients, visual acuity had improved in none of the
eyes (0%), was unchanged in 6 eyes (60%), and had declined in 4 eyes (40%). The
difference in visual acuity between the two groups was not statistically
significant. CONCLUSIONS: Radiation therapy inhibited small choroidal
neovascularization, as seen by funduscopy and angiography, but its effectiveness 
in improving visual prognosis was not always evident.

PMID: 11094183 [PubMed - indexed for MEDLINE]

3128: Int J Fertil Womens Med. 2000 Sep-Oct;45(5):301-13.

Age-related eye diseases: impact of hormone replacement therapy, and reproductive
and other risk factors.

Snow KK, Seddon JM.

Massachusetts Eye and Ear Infirmary, Epidemiology Unit, Boston 02114, USA.

In Western countries, age-related macular degeneration is the leading cause of
legal blindness in the population over 60 years of age, and cataract is the
leading cause of visual impairment worldwide. Because postmenopausal women are
living longer, they have a greater probability of developing a variety of
age-related visual disorders. As the population ages, the physical and emotional 
toll of these ailments, as well as the burden on the health care system, will
escalate. Currently, interventional therapy for age-related macular degeneration 
is limited to a small subpopulation of patients who can benefit from laser
treatment, whereas surgery is the only effective treatment for cataract. The need
for other therapeutic options and preventive measures remains a major challenge
for the future. Studies among women have suggested that exposure to estrogens is 
associated with a reduction in risk of developing ocular diseases associated with
aging. This article addresses the epidemiology of age-related macular
degeneration and cataract, focusing on the specific risks for women, and
discusses factors that may influence development or progression of these visual
disorders.

Publication Types: 
    Review

PMID: 11092701 [PubMed - indexed for MEDLINE]

3129: Diabetes Care. 2000 Nov;23(11):1672-8.

Age-related macular degeneration in newly diagnosed type 2 diabetic patients and 
control subjects: a 10-year follow-up on evolution, risk factors, and prognostic 
significance.

Voutilainen-Kaunisto RM, Teräsvirta ME, Uusitupa MI, Niskanen LK.

Department of Ophthalmology, Kuopio University Hospital, Finland.

OBJECTIVE: To investigate the evolution of visual acuity, age-related macular
degeneration (AMD), and its relation to 10-year cardiovascular mortality and risk
factors in patients with newly diagnosed type 2 diabetes and control subjects.
RESEARCH DESIGN AND METHODS: A 10-year prospective study consisting of a
representative group of 133 (70 men, 63 women) newly diagnosed type 2 diabetic
patients diagnosed at health centers between 1979 and 1981 and 144 (62 men, 82
women) nondiabetic control subjects recruited from the population register was
performed. The frequency of AMD was determined by grading of 45 degrees
stereoscopic fundus photographs. The subjects were studied at baseline and after 
5 and 10 years. RESULTS: By the 10-year follow-up, visual acuity had declined
more markedly in the diabetic patients than in the control subjects. Although the
frequency of AMD was nearly the same in both groups (11-19%), it decreased visual
acuity earlier in the diabetic patients than in the control group. AMD at
baseline predicted 10-year cardiovascular mortality independently of adjustment
for other risk factors in the diabetic patients (odds ratio [95% CI] 4.7
[1.1-19.3], P = 0.033). CONCLUSIONS: Visual acuity deteriorated earlier in newly 
diagnosed type 2 diabetic patients than in the control group although the
cross-sectional frequency of AMD was nearly the same in both groups.
Interestingly, AMD was an independent risk factor for cardiovascular mortality in
type 2 diabetic patients, but the background mechanism(s) behind this association
is unknown.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 11092291 [PubMed - indexed for MEDLINE]

3130: Can J Ophthalmol. 2000 Oct;35(6):315-24.

Autosomal dominant Stargardt-like macular dystrophy segregating in a large
Canadian family.

Lagali PS, MacDonald IM, Griesinger IB, Chambers ML, Ayyagari R, Wong PW.

Department of Biological Sciences, University of Alberta, Edmonton.

BACKGROUND: Inherited macular dystrophies account for a major fraction of the
cases of retinal degenerative disease that lead to permanent blindness. We
describe the clinical and genetic findings in a Canadian family with a form of
macular dystrophy resembling autosomal dominant Stargardt-like macular dystrophy.
METHODS: Standard ophthalmologic examinations were performed in members of a
single five-generation Alberta family. Tests of visual acuity and colour vision, 
fundus photography, fluorescein angiography and electroretinography were
performed in 15 affected people. Blood was collected from 24 family members, and 
DNA was extracted for genotyping. Genetic linkage analysis was performed using
polymorphic short tandem repeat microsatellite markers located on chromosome 6q, 
a region containing loci for several macular disorders. RESULTS: Affected family 
members display clinical characteristics resembling autosomal dominant
Stargardt-like macular dystrophy, previously assigned to chromosome 6q (STGD3).
Linkage analysis generated a peak lod score of 5.50 at an estimated recombination
fraction of 0.00 for marker locus D6S300. INTERPRETATION: The family described
has an autosomal dominant macular dystrophy that resembles Stargardt-like macular
dystrophy. The disease locus for this family maps to an interval on chromosome 6q
that overlaps that for STGD3 and other retinal dystrophy loci. These findings
provide further evidence that human chromosome 6q represents a "hot spot" for
retinal disorders.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 11091913 [PubMed - indexed for MEDLINE]

3131: Br J Ophthalmol. 2000 Dec;84(12):1415-9.

The APO(*)E3-Leiden mouse as an animal model for basal laminar deposit.

Kliffen M, Lutgens E, Daemen MJ, de Muinck ED, Mooy CM, de Jong PT.

Department of Pathology, Erasmus University, Rotterdam, Netherlands.

AIM: To investigate the APO(*)E3-Leiden mouse as an animal model for age related 
maculopathy (ARM) related extracellular deposits. METHODS: Eyes were obtained
from APO(*)E3-Leiden transgenic mice on a high fat/cholesterol (HFC) diet (n=12) 
or on a normal mouse chow (n=6), for 9 months. As controls, eyes were collected
from APO-E knockout mice on the same diets. From each mouse one eye was processed
for microscopic evaluation and immunohistochemistry with a polyclonal antibody
directed against human apo-E. Electron microscopy was also performed. RESULTS:
All 12 eyes of the APO(*)E3-Leiden mice on an HFC diet contained basal laminar
deposit (BLD; class 1 to class 3), whereas two of six APO(*)E3-Leiden mice on
normal chow showed BLD class 1. The ultrastructural aspects of this BLD were
comparable with those seen in early BLD in humans, and BLD showed immunoreaction 
with anti-human-apo-E antibodies. No BLD was found in any of the control mice.
Drusen were not detected in any of the mice. CONCLUSION: These results indicate
that APO(*)E3-Leiden mice can be used as animal model for the pathogenesis of
BLD, and that a HFC diet enhances the accumulation of this deposit. Furthermore, 
this study supports the previously suggested involvement of dysfunctional apo-E
in the accumulation of extracellular deposits in ARM.

PMID: 11090485 [PubMed - indexed for MEDLINE]

3132: Br J Ophthalmol. 2000 Dec;84(12):1343-8.

Comment in:
    Br J Ophthalmol. 2000 Dec;84(12):1337-8.

Is cataract surgery justified in patients with age related macular degeneration? 
A visual function and quality of life assessment.

Armbrecht AM, Findlay C, Kaushal S, Aspinall P, Hill AR, Dhillon B.

Princess Alexandra Eye Pavilion, The Royal Infirmary of Edinburgh, Edinburgh EH3 
9HA, UK.

AIMS: To determine whether patients with age related macular degeneration (ARMD) 
benefit from cataract surgery in terms of visual function and quality of life
measures, and to assess the impact of surgery on the progression of ARMD.
METHODS: A prospective study was carried out of patients with and without ARMD
undergoing cataract surgery. Data were collected from 187 patients at the
Princess Alexandra Eye Pavilion, Edinburgh and the Oxford Eye Hospital, Oxford.
The patients were divided into three groups: (1) a control group with ARMD and no
surgery (n=41), (2) a study group of patients with ARMD who underwent cataract
surgery (n=90), and (3) a second control group of patients without ocular
comorbidities who underwent cataract surgery (n=56). Visual function and quality 
of life assessments were carried out at baseline and 3-5 months after baseline or
surgery. RESULTS: There were significant improvements both in terms of quality of
life and visual function measures in the study group. Benefits were greater in
patients with moderate cataract irrespective of the degree of ARMD. No increased 
incidence in progression to the "wet" form of ARMD was found. Improvements in
quality of life measures and visual function were more pronounced in patients
with no ocular comorbidities. CONCLUSIONS: Patients with mild and moderate
degrees of ARMD do benefit from cataract surgery and the benefits are greater in 
patients with moderate degrees of lens opacity. Longer follow up is required to
assess the risk of increased ARMD progression.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 11090470 [PubMed - indexed for MEDLINE]

3133: Am J Ophthalmol. 2000 Nov;130(5):669-70.

Optical coherence tomography in uveitis patients.

Hassenstein A, Bialasiewicz AA, Richard G.

University Eye Hospital Eppendorf, Hamburg, Germany.

PURPOSE: To evaluate optical coherence tomography in allergy-prone uveitis
patients. METHODS: Thirty-four patients (43 eyes) with posterior uveitis (31
eyes) and intermediate uveitis (12 eyes) were evaluated by fluorescein
angiography, indocyanine green angiography, and optical coherence tomography.
Follow-up examinations used optical coherence tomography in allergy-prone
patients. RESULTS: Optical coherence tomography identified epiretinal membranes, 
which were removed surgically (three eyes); persistent cystoid macular edema,
which resolved with cytotoxic treatment (12 eyes); and juxtafoveolar membranes,
which were treated by diode laser (six eyes) and excision (two eyes). CONCLUSION:
Optical coherence tomography may provide useful information on complications
developing in uveitis patients.

PMID: 11078850 [PubMed - indexed for MEDLINE]

3134: Am J Ophthalmol. 2000 Nov;130(5):617-35.

Age-related macular degeneration: long-term results of radiotherapy for subfoveal
neovascular membranes.

Kobayashi H, Kobayashi K.

Department of Ophthalmology, Amagasaki Hospital, (Dr H. Kobayashi), Hyogo, Japan.
kobaya3@post.saga-med.ac.jp

PURPOSE: To study results of 2-year follow-up of radiotherapy for subfoveal
choroidal neovascular membrane associated with age-related macular degeneration. 
METHODS: In a randomized prospective clinical study, 101 patients received a
low-dose radiotherapy or no treatment. In the treatment group, subfoveal
choroidal neovascular membranes were treated with 20 Gy of 6-MV photons to the
macula of the affected eye. RESULTS: The overall complete follow-up rate was
84.2% (85/101). No measurable treatment-related morbidity was seen during or
after treatment. Mean changes in log of minimal angle of resolution (logMAR) of
visual acuity and area of choroidal neovascular membrane for 2-year follow-up
were +0.226 +/- 0.373 and 143.5 +/- 53.1% in the treatment group, and +0.563 +/- 
0.370 and 190. 3 +/- 81.4% in the control group; a significant difference was
found (P <.0001; P =.0008). In patients with smaller choroidal neovascular
membrane (</=1.5 mm(2)) or better visual acuity (>/=60/200) at baseline, the
treatment group showed a significantly smaller increase in area of choroidal
neovascular membrane and a significantly smaller decrease in LogMAR visual acuity
for 2 years, whereas there was no significant difference in patients with larger 
choroidal neovascular membrane (>1.5 mm(2)) or poorer visual acuity (<60/200).
CONCLUSIONS: Radiotherapy appeared to have a favorable treatment effect in eyes
with subfoveal neovascular membrane associated with AMD. Favorable factors for
radiotherapy were a smaller area of choroidal neovascular membrane and better
visual acuity.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11078841 [PubMed - indexed for MEDLINE]

3135: Eur J Ophthalmol. 2000 Jul-Sep;10(3):266-9.

Vascularized pigment epithelial detachment in adult-onset foveomacular
vitelliform dystrophy.

Battaglia Parodi M, Di Crecchio L, Ravalico G.

Eye Clinic, University of Trieste, Italy.

PURPOSE: To report a case showing adult-onset foveomacular vitelliform dystrophy 
(AOFVD), associated with vascularized pigment epithelial detachment. CASE REPORT:
A 72-year-old female affected by AOFVD complained with blurred vision and
metamorphopsia in her right eye, seven months after a routinary clinical
examination. Visual acuity in right eye dropped from 0.6 to 0.3, and
biomicroscopic fundus examination revealed a serous pigment epithelial detachment
arising from the temporal margin of the pseudovitelliform lesion. Fluorescein
angiography showed an uneven filling of the pigment epithelial detachment,
suggesting the presence of a subfoveal choroidal neovascularisation, which was
confirmed by indocyanine green angiography. DISCUSSION: The association between
AOFVD and vascularized pigment epithelial detachment, supports the hypothesis
that AOFVD may be a different subgroup of age-related macular degeneration with
specific genetic predisposition.

Publication Types: 
    Case Reports

PMID: 11071039 [PubMed - indexed for MEDLINE]

3136: Eur J Ophthalmol. 2000 Jul-Sep;10(3):233-8.

Cystoid macular edema in patients with acquired immune deficiency syndrome and
cytomegalovirus retinitis.

Eid Farah M, Muccioli C, Rinkevicius M, Barata Lima L, Belfort R Jr.

Department of Ophthalmology, Paulista School of Medicine, Federal University of
São Paulo, Brazil. mefarah@uol.com.br

PURPOSE: To describe cystoid macular edema in patients with acquired immune
deficiency syndrome treated with highly active anti-retroviral therapy, who had
or had not already had cytomegalovirus retinitis. MATERIALS AND METHODS: Case
report. RESULTS: Five acquired immune deficiency syndrome (AIDS) patients,
successfully treated with highly active anti-retroviral therapy, were studied.
Two had inactive cytomegalovirus retinitis and cystoid macular edema in both
eyes. Two had inactive cytomegalovirus retinitis in both eyes and cystoid macular
edema in one eye. One patient had inactive cytomegalovirus retinitis in one eye
and cystoid macular edema in both eyes. CONCLUSIONS: Cystoid macular edema may
occur in AIDS patients treated with highly active anti-retroviral therapy even in
cases without previous retinitis.

Publication Types: 
    Case Reports

PMID: 11071031 [PubMed - indexed for MEDLINE]

3137: Ophthalmology. 2000 Nov;107(11):2034-8;discussion 2039.

Ketorolac versus prednisolone versus combination therapy in the treatment of
acute pseudophakic cystoid macular edema.

Heier JS, Topping TM, Baumann W, Dirks MS, Chern S.

Ophthalmic Consultants of Boston, Boston, Massachusetts, USA.
jsheier@eyeboston.com

OBJECTIVE: To evaluate the efficacy of ketorolac tromethamine 0.5% ophthalmic
solution, prednisolone acetate 1.0% ophthalmic solution, and ketorolac and
prednisolone combination therapy in the treatment of acute, visually significant,
cystoid macular edema (CME) occurring after cataract extraction surgery. DESIGN: 
Randomized, double-masked, prospective trial. PARTICIPANTS: Twenty-eight patients
who had undergone cataract extraction and in whom clinical CME developed within
21 to 90 days after cataract surgery. METHODS: Patients were randomized to
topical therapy with ketorolac (group K), prednisolone (group P), or ketorolac
and prednisolone combination therapy (group C) four times daily. Treatment was
continued until CME resolved or for 3 months, whichever occurred first. Treatment
was then tapered over 3 weeks. Examinations were monthly and included Snellen
visual acuity, contrast sensitivity, Amsler grid, slit-lamp examination, dilated 
fundus examination, and fluorescein angiography. RESULTS: Twenty-six of 28
patients completed the study. Patients were enrolled an average of 48 days after 
surgery. The average improvements in Snellen visual acuity were as follows: 1.6
lines in group K, 1.1 lines in group P, and 3.8 lines in group C. This reached
statistical significance for all visits when group C was compared with group P,
and for visits 4 and 5 when group C was compared with group K. Group C reached a 
mean change of two lines or more by visit 2; at no time did either group K or P
reach a mean two-line improvement. At no time was a significant difference
detected between group K and P with regard to visual acuity or change from
baseline. A two-line or more improvement in Snellen acuity was achieved in 16 of 
26 patients (61%). Analysis by group revealed four of eight patients (50%) in
group P, six of nine patients (67%) in group K, and eight of nine patients (89%) 
in group C who had achieved a two-line or more improvement. In patients who did
improve two lines or more, improvement occurred an average of 2.75 months after
initiating therapy in group P, 1.43 months in group K, and 1.33 months in group
C. Improvements in contrast sensitivity and leakage on fluorescein angiography
tended to mirror improvements in Snellen acuity. CONCLUSIONS: Treatment of acute,
visually significant pseudophakic CME with ketorolac and prednisolone combination
therapy appears to offer benefits over monotherapy with either agent alone.
Patients were more likely to experience recovery of two lines or more of visual
acuity. Patients treated with combination therapy or ketorolac monotherapy
responded more quickly than did patients treated with prednisolone alone.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 11054327 [PubMed - indexed for MEDLINE]

3138: Invest Ophthalmol Vis Sci. 2000 Nov;41(12):4048-53.

Photoreceptor function in eyes with macular edema.

Lardenoye CW, Probst K, DeLint PJ, Rothova A.

Department of Ophthalmology, F. C. Donders Institute, University Hospital
Utrecht, The Netherlands. ch.lardenoye@oogh.azu.nl

PURPOSE: The irreversible loss of visual acuity in macular edema is usually
attributed to permanent loss of photoreceptor cells, although there is hardly any
information on changes in photoreceptor function in macular edema. The purpose of
this study was to assess photoreceptor function in various stages of macular
edema and to relate the findings to visual acuity and angiographic changes.
METHODS: Directional sensitivity (optical Stiles-Crawford effect) and visual
pigment density of foveal cones was measured with a custom-built scanning laser
ophthalmoscope (SLO) in 19 eyes of 19 patients. Twelve eyes exhibited macular
edema: five of inflammatory origin, and seven of diabetic origin. Seven eyes with
an intraocular inflammatory disease without clinical or angiographic evidence of 
edema were also included (four of which had previous macular edema and one of
which had shown development of macular edema at the 1-year follow-up). Results of
SLO measurements were related to findings using fluorescein angiography and
Snellen visual acuity, both assessed at the time of SLO measurement and 6 months 
thereafter. RESULTS: Eyes with macular edema exhibited diminished directional
sensitivity of photoreceptor cells in the fovea compared with eyes without (P =
0.02). Visual pigment density of eyes with macular edema was decreased and
associated with both initial and follow-up visual function and with the
angiographic macular edema grade at follow-up. Abnormal directional sensitivity
and pigment density were already present in eyes with slight edematous changes
and normal visual acuity. CONCLUSIONS: Eyes with inflammatory or diabetic macular
edema showed decreased directional sensitivity and visual pigment density in the 
macular area. These findings may support a role for SLO measurements in detecting
retinal damage due to macular edema.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11053311 [PubMed - indexed for MEDLINE]

3139: Invest Ophthalmol Vis Sci. 2000 Nov;41(12):3936-42.

Age-related retinal pigment epithelium and Bruch's membrane degeneration in
senescence-accelerated mouse.

Majji AB, Cao J, Chang KY, Hayashi A, Aggarwal S, Grebe RR, De Juan E Jr.

Wilmer Ophthalmological Institute, The Johns Hopkins University, School of
Medicine, Baltimore, Maryland, USA.

PURPOSE: To investigate age-related changes in the retinal pigment epithelium
(RPE), Bruch's membrane, and choriocapillaris in the senescence-accelerated mouse
(SAM). METHODS: The external and eyecup features and light and electron
microscopic findings were examined in three male and two female mice of a
senescence-prone mouse strain (SAM P(8)) monthly for 12 months. These results
were compared with those in age-matched mice of similar background but senescence
resistant (SAM R(1)). Choroidal vascular casts were prepared at 12 months in
seven mice each of the SAM P(8) and SAM R(1) strains. Quantitative analysis of
area of choriocapillaris was performed by automated image analysis, and the
results were analyzed by paired Student's t-test. RESULTS: We found in the SAM
P(8) strain that hair loss, coarseness of hair texture, and ulceration of skin
appeared and increased as the age advanced (at approximately 5-9 months). Eyecup 
examination showed no differences. Light and electron microscopy revealed
progressively more prominent abnormalities in the RPE and Bruch's membrane mice
older than 10 months. Two of the five SAM P(8) mice older than 11 months showed
what appeared to be intra-Bruch's membrane choroidal neovascularization. The RPE 
and Bruch's membrane appeared normal in the SAM R(1) strain. In the SAM P(8),
vascular casts of the choriocapillaris showed a mild but significant decrease in 
vascular area when compared with the SAM R(1) strain at 12 months (P = 0.011).
CONCLUSIONS: Senescence accelerated mice develop progressive age-related changes 
in the RPE-Bruch's-choriocapillaris complex that have features that may be
relevant in the study of age-related macular changes in humans.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.

PMID: 11053297 [PubMed - indexed for MEDLINE]

3140: Br J Ophthalmol. 2000 Nov;84(11):1269-74.

Clinicopathological correlation of deep retinal vascular anomalous complex in age
related macular degeneration.

Lafaut BA, Aisenbrey S, Vanden Broecke C, Bartz-Schmidt KU.

University Eye Clinic, Joseph-Stelzmann- Strasse 9, D-50931 Cologne, Germany.
bart.lafaut@rug.ac.be

AIMS: To analyse the histopathology of "deep retinal vascular anomalous complex" 
or "chorioretinal anastomosis". METHODS: Six patients with a deep retinal
vascular anomalous complex (age range 66-88 years) had fundus photography and
fluorescein angiography not more than 14 days before foveal translocation
surgery. Four patients were also documented with indocyanine green angiography.
The surgical specimens were serially sectioned and stained in a stepped fashion
with Masson trichrome, periodic acid Schiff, and phosphotungstic acid
haematoxylin, a histochemical stain for fibrin. RESULTS: A subretinal
fibrovascular membrane was surrounded by a rim consisting of diffuse drusen
(basal laminar deposits), retinal pigment epithelium, and amorphous, fibrinous
material interspersed with remains of outer segments in all specimens. In two
specimens vascular structures were identified that left the specimen towards the 
retina. Amorphous material with the remains of outer segments was not found on
the retinal side of the fibrovascular tissue itself but in four specimens a small
neuroretinal portion (outer nuclear layer) was adherent to the complex. In three 
specimens a thin fibrocellular membrane was seen at the choroidal side of the
diffuse drusen. CONCLUSION: Deep retinal vascular anomalous complex represents
histologically neovascularisation growing out of the neuroretina, into the
subretinal space, which mimics choroidal neovascularisation. The term therefore
appears rightly chosen.

PMID: 11049953 [PubMed - indexed for MEDLINE]

3141: Ophthalmic Physiol Opt. 2000 Sep;20(5):360-70.

Oral and silent reading performance with macular degeneration.

Lovie-Kitchin JE, Bowers AR, Woods RL.

Centre for Eye Research, School of Optometry, Queensland University of
Technology, Australia. j.lovie-kitchin@qut.edu.au

Previous studies have shown that reading rate for very large print (6 degrees,
1.86 logMAR character size) is a strong predictor of oral reading rate with low
vision devices (LVDs). We investigated whether this would apply using large print
sizes more readily available in clinical situations (e.g. 2 degrees, 1.4 logMAR),
for subjects with macular degeneration. We assessed rauding rates--reading for
understanding. A combination of near word visual acuity and large print reading
rate (without LVDs) provided the best prediction of oral rauding rates (with
LVDs). However, near word visual acuity alone was almost as good. Similarly,
silent rauding rate was predicted best by near word visual acuity alone. We give 
near visual acuity limits as a clinical guide to expected oral and silent reading
performance with LVDs for patients with macular degeneration.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11045244 [PubMed - indexed for MEDLINE]

3142: Retina. 2000;20(5):492-9.

Clinicopathologic correlation of fluorescein and indocyanine green angiography in
exudative age-related macular degeneration.

Lauer AK, Wilson DJ, Klein ML.

Macular Degeneration Center and Leonard Christenen Eye Pathology Laboratory,
Casey Eye Institute, Oregon Health Sciences University, Portland 97201-4197, USA.

PURPOSE: To correlate the clinical and histopathologic features of an eye with
age-related macular degeneration studied with fluorescein (FA) and indocyanine
green (ICG) angiography 4.5 months before the patient's death. METHODS:
Histopathologic features from serial sections through the macula of a 76-year-old
man with occult choroidal neovascularization (CNV) were reconstructed in a scaled
two-dimensional map and compared with FA and ICG angiogram images obtained 4.5
months before his death. RESULTS: The region of prior laser photocoagulation was 
identified as a well-demarcated hypofluorescent region in the early frames of the
FA and the early and late phases of the ICG angiogram. This corresponded
histopathologically to a well-circumscribed area of absence of the
choriocapillaris, loss of the outer retina and retinal pigment epithelium, and
scarring of the choroid. Occult CNV characterized by elevated late
hyperfluorescence on the FA and intense well-defined hyperfluorescence on the ICG
angiogram corresponded to a thick fibrovascular membrane in the subretinal space 
and within Bruch's membrane. Thin extensions of both the subretinal and
intra-Bruch's membrane fibrovascular membrane components corresponded to
nonelevated stippled late hyperfluorescence on the FA and mild late
hyperfluorescence on the ICG angiogram. CONCLUSION: Histopathologic mapping
revealed a large fibrovascular complex located subretinally and within Bruch's
membrane with thin and thick components that correlate well with findings of
occult CNV on FA and ICG angiography.

Publication Types: 
    Case Reports
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 11039424 [PubMed - indexed for MEDLINE]

3143: Retina. 2000;20(5):483-91.

Influence of membrane differential filtration on the natural course of
age-related macular degeneration: a randomized trial.

Brunner R, Widder RA, Walter P, Lüke C, Godehardt E, Bartz-Schmidt KU, Heimann K,
Borberg H.

Klinik und Poliklinik für Augenheilkunde, Universität zu Köln, Germany.

PURPOSE: Membrane differential filtration is able to optimize rheologic
parameters by eliminating high molecular weight proteins and lipoproteins from
the blood. Following the hypothesis that these changes result in an improvement
of the microcirculation, the authors tested the efficacy of membrane differential
filtration in improving visual function in patients with age-related macular
degeneration (ARMD). METHODS: Forty patients (40 eyes) were randomized into two
groups. The treatment group was treated five times over a period of 21 weeks. In 
both groups, 9/20 of the eyes showed subfoveolar subretinal neovascularization.
The main parameter of the study was visual acuity (VA). Electroretinogram (ERG), 
electrooculogram, and macular visual evoked potentials were also recorded. Plasma
and whole blood viscosity and erythrocyte aggregation were measured. RESULTS: The
20 patients treated repeatedly over a period of 21 weeks showed a mean
improvement of 0.63 lines (SD 1.8) of VA on Early Treatment Diabetic Retinopathy 
Study charts. The control group showed a deterioration of 0.94 lines (SD 1.7)
compared to VA at baseline examination. The amplitude of the ERG photopic a-wave 
and the flicker ERG was significantly increased. The rheologic parameters were
lowered in all treated patients. CONCLUSION: Repetitive treatment with membrane
differential filtration is able to improve visual acuity of patients with ARMD
and the natural course of this disease. Several questions arise from the results 
of this study. Further research will show if it is possible to optimize the
selection of patients for subgroups with predictive responses through morphologic
and functional tests and how to create an optimized and individual treatment
strategy determined by the quality, intensity, and frequency of treatment
sessions.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 11039423 [PubMed - indexed for MEDLINE]

3144: Jpn J Ophthalmol. 2000 Sep-Oct;44(5):530-7.

Long-term outcome after radiation therapy for subfoveal choroidal
neovascularization associated with age-related macular degeneration.

Mandai M, Takahashi M, Miyamoto H, Hiroshiba N, Kimura H, Ogura Y, Honda Y, Sasai
K.

Departments of Ophthalmology and Visual Science, Kyoto University Graduate School
of Medicine, Kyoto, Japan.

PURPOSE: The purpose of this study was to investigate the long-term effect of
low-dose radiation therapy on subfoveal choroidal neovascularization associated
with age-related macular degeneration. METHODS: The clinical course and visual
outcome were compared retrospectively among two treated groups and a control
group; 15 patients (15 eyes) received 10 Gy, another 15 patients (15 eyes)
received 20 Gy. The control group consisted of 15 patients (15 eyes) without
treatment. All patients were followed up for at least 18 months, and most were
followed up for 3 years. The macula was irradiated with either 10 Gy in 5
fractions or with 20 Gy in 10 fractions after computed tomography (CT) simulation
enabled real-time treatment planning from multiple CT slices. RESULTS: During the
3 years of follow-up, the lesions became better in 5 eyes, unchanged in 1, and
worse in 9 with 10 Gy radiation; better in 7 eyes, unchanged in 1, and worse in 7
eyes with 20 Gy; and better in 1 eye and worse in 14 with no treatment. The
difference between the groups treated with radiation and the control was
statistically significant (P <.05). Visual acuity was also significantly better
in the group receiving 20 Gy than in the control group up to 2 years after
radiation (P <.01). CONCLUSION: Radiation may extend the period of good visual
function substantially by reducing subfoveal choroidal neovascularization
activity.

Publication Types: 
    Case Reports
    Comparative Study

PMID: 11033133 [PubMed - indexed for MEDLINE]

3145: Surv Ophthalmol. 2000 Sep-Oct;45(2):115-34.

The role of oxidative stress in the pathogenesis of age-related macular
degeneration.

Beatty S, Koh H, Phil M, Henson D, Boulton M.

Academic Department of Ophthalmology, Manchester Royal Eye Hospital, Manchester, 
United Kingdom.

Age-related macular degeneration (AMD) is the leading cause of blind registration
in the developed world, and yet its pathogenesis remains poorly understood.
Oxidative stress, which refers to cellular damage caused by reactive oxygen
intermediates (ROI), has been implicated in many disease processes, especially
age-related disorders. ROIs include free radicals, hydrogen peroxide, and singlet
oxygen, and they are often the byproducts of oxygen metabolism. The retina is
particularly susceptible to oxidative stress because of its high consumption of
oxygen, its high proportion of polyunsaturated fatty acids, and its exposure to
visible light. In vitro studies have consistently shown that photochemical
retinal injury is attributable to oxidative stress and that the antioxidant
vitamins A, C, and E protect against this type of injury. Furthermore, there is
strong evidence suggesting that lipofuscin is derived, at least in part, from
oxidatively damaged photoreceptor outer segments and that it is itself a
photoreactive substance. However, the relationships between dietary and serum
levels of the antioxidant vitamins and age-related macular disease are less
clear, although a protective effect of high plasma concentrations of
alpha-tocopherol has been convincingly demonstrated. Macular pigment is also
believed to limit retinal oxidative damage by absorbing incoming blue light
and/or quenching ROIs. Many putative risk-factors for AMD have been linked to a
lack of macular pigment, including female gender, lens density, tobacco use,
light iris color, and reduced visual sensitivity. Moreover, the Eye Disease
Case-Control Study found that high plasma levels of lutein and zeaxanthin were
associated with reduced risk of neovascular AMD. The concept that AMD can be
attributed to cumulative oxidative stress is enticing, but remains unproven. With
a view to reducing oxidative damage, the effect of nutritional antioxidant
supplements on the onset and natural course of age-related macular disease is
currently being evaluated.

Publication Types: 
    Review

PMID: 11033038 [PubMed - indexed for MEDLINE]

3146: Arch Ophthalmol. 2000 Oct;118(10):1415-21.

Macular degeneration associated with aberrant expansion of trinucleotide repeat
of the SCA7 gene in 2 Japanese families.

Abe T, Tsuda T, Yoshida M, Wada Y, Kano T, Itoyama Y, Tamai M.

Department of Ophthalmology, Tohoku University School of Medicine, 1-1
Seiryoumachi Aobaku Sendai, Miyagi 980-8574, Japan. toshi@oph. med.tohoku.ac.jp

OBJECTIVE: To evaluate the macular function of Japanese patients with a
trinucleotide repeat expansion in the spinocerebellar ataxia type 7 (SCA7) gene. 
METHODS: Ophthalmic findings in patients whose DNA analysis revealed expanded
alleles of the trinucleotide repeat in the SCA7 gene were evaluated. RESULTS:
Trinucleotide repeat was expanded from 40 to 48 in affected patients (control
subjects, 12 repeats). Affected patients were characterized by different degrees 
of visual acuity decrease (0.09-0.9), a tritan axis color vision, a coarse
granular appearance of the macular region on scanning laser ophthalmoscopy,
depression of multifocal electroretinograms, and macular degeneration. However,
pigmentary changes were not observed in the retina. The trinucleotide repeat was 
longer and the onset of macular dysfunction was earlier in the younger
generation. One patient in a family manifested decreased visual acuity 10 years
preceding other neurologic signs. CONCLUSIONS AND CLINICAL RELEVANCE: Patients
with SCA7 mutations showed macular dysfunction or degeneration with expansion of 
CAG repeat in the SCA7 gene. However, the lesions were less pigmented than those 
previously reported. Patients also showed ophthalmologic anticipation, which has 
not been reported for the ocular changes in other patients who have trinucleotide
repeat expansion of the responsible genes.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 11030825 [PubMed - indexed for MEDLINE]

3147: Am J Ophthalmol. 2000 Oct;130(4):419-28.

Comment in:
    Am J Ophthalmol. 2001 Aug;132(2):289-90.

Limited inferior macular translocation for the treatment of subfoveal choroidal
neovascularization secondary to age-related macular degeneration.

Pieramici DJ, De Juan E Jr, Fujii GY, Reynolds SM, Melia M, Humayun MS, Schachat 
AP, Hartranft CD.

Wilmer Ophthalmological Institute, The Johns Hopkins Hospital, Baltimore,
Maryland 21287, USA. Dpieramici@jhmi.edu

PURPOSE: To review a series of patients with age-related macular degeneration
undergoing limited macular translocation for the treatment of subfoveal choroidal
neovascularization, to determine short-term visual acuity outcomes, to measure
amounts of attainable retinal movement, and to identify prognostic
factors.METHODS: A retrospective review was conducted on a consecutive series of 
patients undergoing inferior limited macular translocation with scleral
imbrication for the treatment of subfoveal choroidal neovascularization secondary
to age-related macular degeneration. The main outcome measures investigated were 
distance of macular translocation, visual acuity at 3 and 6 months after surgery,
change in visual acuity from baseline, and the development of intraoperative and 
postoperative complications. Univariate and multivariate analyses of a number of 
potential prognostic factors were undertaken.RESULTS: Macular translocation was
achieved in all 102 eyes (101 patients) included in this study. The range of
movement varied from 200 to 2,800 microm with a median movement of 1, 200 microm.
Nearly 33% of the study group achieved a visual acuity better than 20/100 at 3
months, and 49% achieved this vision at 6 months. At 3 and 6 months, 37% and 48% 
of the study group, respectively, experienced 2 or more lines of improvement on
visual acuity testing, and by 6 months 16% experienced greater than 6 lines of
visual improvement. Good baseline vision, achieving the desired amount of macular
translocation, a greater amount of macular translocation, and recurrent choroidal
neovascularization at baseline were associated with better visual acuities at 3
and 6 months. Poor preoperative vision and the development of complications were 
associated with worse vision at 3 and 6 months. CONCLUSIONS: Limited macular
translocation is a technically feasible procedure that can lead to significant
visual improvement and good visual acuity in some patients presenting with
subfoveal choroidal neovascularization associated with age-related macular
degeneration. A randomized prospective clinical trial of this surgical technique 
is warranted.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 11024414 [PubMed - indexed for MEDLINE]

3148: Am J Ophthalmol. 2000 Oct;130(4):408-18.

Submacular surgery trials randomized pilot trial of laser photocoagulation versus
surgery for recurrent choroidal neovascularization secondary to age-related
macular degeneration: II. Quality of life outcomes submacular surgery trials
pilot study report number 2.

[No authors listed]

PURPOSE: To summarize findings from health-related quality-of-life interviews
with patients who had recurrent subfoveal choroidal neovascularization secondary 
to age-related macular degeneration and participated in a randomized pilot trial 
(focal confluent laser photocoagulation versus submacular surgery) that may
assist in planning future assessments of health-related quality of life in
patients with age-related macular degeneration. PATIENTS AND METHODS: Of 70
patients enrolled in the pilot trial, 54 were interviewed before random
assignment to treatment and provided the data analyzed for this report. Patients 
were scheduled for follow-up interviews at 6, 12, and 24 months after enrollment.
The 36-Item Short-Form Health Survey was used in all cases and was administered
by an interviewer. The summary scales, Physical Component Summary and Mental
Component Summary, were the focus of this analysis. RESULTS: Median Physical
Component Summary and Mental Component Summary score at baseline were 47 and 53, 
respectively. Distributions of scores at baseline and throughout the 2-year
follow-up period were similar in the two treatment arms and consistent with those
of a sample of the general US population of similar age. Distributions of both
Physical Component Summary scores and Mental Component Summary scores for
individual patient subgroups at baseline suggested sensitivity to some measures
of baseline vision. During 2 years of follow-up interviews, median changes in
Physical Component Summary scores were decreases of six points in the laser arm
and three points in the surgery arm; in both treatment arms, median change in
Mental Component Summary scores was an increase of 2 points. Two-year changes in 
visual acuity had no discernible effect on Physical Component Summary scores or
Mental Component Summary scores; baseline scores were the strongest predictors of
2-year changes in Physical Component Summary and Mental Component Summary scores.
CONCLUSIONS: Overall, summary scores from the 36-Item Short-Form Health Survey
and changes in scores over 2 years in this pilot trial were consistent with the
ophthalmic outcome measures (reported elsewhere) that showed no important
differences between the treatment arms. These health-related quality-of-life
findings provided assurance that the similarity of ophthalmic outcomes in the two
treatment arms did not mask changes potentially important to patients that were
not captured as part of the clinical outcome data.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11024413 [PubMed - indexed for MEDLINE]

3149: Am J Ophthalmol. 2000 Oct;130(4):387-407.

Comment in:
    Am J Ophthalmol. 2001 Nov;132(5):802-3.

Submacular surgery trials randomized pilot trial of laser photocoagulation versus
surgery for recurrent choroidal neovascularization secondary to age-related
macular degeneration: I. Ophthalmic outcomes submacular surgery trials pilot
study report number 1.

Bressler NM, Bressler SB, Hawkins BS, Marsh MJ, Sternberg P Jr, Thomas MA;
Submacular Surgery Trials Pilot Study Investigators.

PURPOSE: To report complications and changes in vision during 2 years of
follow-up of patients with age-related macular degeneration assigned randomly to 
surgical removal or to laser photocoagulation of subfoveal recurrent neovascular 
lesions in a pilot trial designed to test methods, to refine estimates of outcome
rates, and to project patient accrual rates for a larger multicenter randomized
trial to evaluate submacular surgery. PATIENTS AND METHODS: Eligible patients
with previous laser photocoagulation of extrafoveal or juxtafoveal choroidal
neovascularization secondary to age-related macular degeneration were enrolled at
15 collaborating clinical centers. Assignments to treatment arm were made by
personnel at a central coordinating center. Adherence to eligibility criteria and
treatment assignment was assessed centrally at a photograph reading center.
Patients were examined at 3, 6, 12, and 24 months after treatment for data
collection purposes. Outcome measures reported include treatment complications,
adverse events, requirements for additional treatment, and 2-year changes in
visual acuity from baseline. RESULTS: Of 70 patients enrolled, 36 were assigned
to laser photocoagulation and 34 to submacular surgery; all were treated as
assigned. One patient in each group died before the 2-year examination. Visual
acuity was measured at the 2-year examination for 31 of the surviving patients
(89%) in the laser arm and for 28 of the surviving patients (85%) in the surgery 
arm. The 2-year measurements for 36 of the 59 patients (61%) were made by an
examiner masked to treatment assignment and to the identity of the study eye.
Improvements and losses of visual acuity were observed in both treatment arms; 20
of 31 study eyes (65%) in the laser arm and 14 of 28 study eyes (50%) in the
surgery arm had visual acuity 2 years after enrollment that was better than or no
more than 1 line worse than the baseline level. Changes in visual acuity and the 
size of the central macular lesions from baseline to the 2-year examination were 
similar in the treatment arms. Few serious complications were observed in either 
arm at the time of initial treatment; serious adverse events were rare. During
follow-up, 11 laser-treated eyes and 18 surgically treated eyes had additional
intraocular procedures. CONCLUSIONS: The data from this pilot trial suggest no
reason to prefer submacular surgery over laser photocoagulation for treatment of 
patients with age-related macular degeneration who have lesions similar to those 
studied in this pilot trial. Any clinical trial designed to compare submacular
surgery with laser photocoagulation in eyes with age-related macular degeneration
and subfoveal recurrent neovascular lesions must enroll several hundred patients 
in order to reach a statistically valid conclusion regarding differences between 
these two methods of treatment with respect to either changes in visual acuity or
complication rates.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11024412 [PubMed - indexed for MEDLINE]

3150: J Am Coll Nutr. 2000 Oct;19(5 Suppl):522S-527S.

The potential role of dietary xanthophylls in cataract and age-related macular
degeneration.

Moeller SM, Jacques PF, Blumberg JB.

Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University,
Boston, Massachusetts 02111, USA.

The carotenoid xanthophylls, lutein and zeaxanthin, accumulate in the eye lens
and macular region of the retina. Lutein and zeaxanthin concentrations in the
macula are greater than those found in plasma and other tissues. A relationship
between macular pigment optical density, a marker of lutein and zeaxanthin
concentration in the macula, and lens optical density, an antecedent of
cataractous changes, has been suggested. The xanthophylls may act to protect the 
eye from ultraviolet phototoxicity via quenching reactive oxygen species and/or
other mechanisms. Some observational studies have shown that generous intakes of 
lutein and zeaxanthin, particularly from certain xanthophyll-rich foods like
spinach, broccoli and eggs, are associated with a significant reduction in the
risk for cataract (up to 20%) and for age-related macular degeneration (up to
40%). While the pathophysiology of cataract and age-related macular degeneration 
is complex and contains both environmental and genetic components, research
studies suggest dietary factors including antioxidant vitamins and xanthophylls
may contribute to a reduction in the risk of these degenerative eye diseases.
Further research is necessary to confirm these observations.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, Non-P.H.S.
    Research Support, U.S. Gov't, P.H.S.
    Review

PMID: 11023002 [PubMed - indexed for MEDLINE]

3151: Am J Ophthalmol. 2000 Sep;130(3):322-6.

Reproductive exposures, incident age-related cataracts, and age-related
maculopathy in women: the beaver dam eye study.

Klein BE, Klein R, Lee KE.

Department of Ophthalmology and Visual Sciences, University of Wisconsin Medical 
School, Madison, Wisconsin 53705-2397, USA. kleinb@epi.ophth.wisc.edu

PURPOSE: To evaluate the relationship of reproductive exposures and incident
age-related cataract and maculopathy in women. METHODS: This was a
population-based cohort study including all adults 43 to 84 years of age living
in Beaver Dam, Wisconsin (a representative midwestern community) who were
identified during a census in 1987 to 1988. They were evaluated initially in 1988
to 1990 and at follow-up in 1993 to 1995. Evaluations included medical histories 
and both fundus and lens photography. All procedures were done according to
protocols that were the same at both examinations. All photographs were graded by
trained observers using defined grading schemes. The severities of age-related
cataracts and maculopathy were determined by grading of photographs. Information 
on hormone exposures was ascertained from structured interviews. RESULTS: After
adjusting for age, the only significant finding for lens end points was a trend
indicating a possible protective effect of increasing number of live births and
incident posterior subcapsular cataract. There were no significant associations
of any reproductive exposure with lesions of early or late age-related
maculopathy. CONCLUSIONS: In these population-based data, there is little
evidence of association of hormone exposures with incident age-related eye
disease in women 5 years later. Longer follow-up of this population, whose mean
age is approaching that of heightened incidence, may disclose significant
relationships.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.

PMID: 11020411 [PubMed - indexed for MEDLINE]

3152: Ophthalmic Surg Lasers. 2000 Sep-Oct;31(5):359-73.

Transpupillary thermotherapy for age-related macular degeneration: long-pulse
photocoagulation, apoptosis, and heat shock proteins.

Mainster MA, Reichel E.

Department of Ophthalmology, University of Kansas Medical Center, Kansas City
66160-7379, USA.

OBJECTIVE: To provide a biophysical foundation for using transpupillary
thermotherapy (TTT) to manage choroidal neovascularization in age-related macular
degeneration (ARMD). METHODS: Retinal temperature rise in laser therapy is
proportional to retinal irradiance (laser power/area) for a particular spot size,
exposure duration, and wavelength. TTT is a low irradiance, large spot size,
prolonged exposure (long-pulse), infrared laser photocoagulation protocol.
Results from an experimentally confirmed, finite element model of retinal light
absorption and heat conduction are used to analyze laser parameter selection and 
its consequences. Results from apoptosis, heat shock protein and hyperthermia
research are used to examine how chorioretinal damage from clinical procedures
might be reduced. RESULTS: Chorioretinal thermal equilibration occurs during
long-pulse TTT photocoagulation. Retinal temperature increases are similar in the
RPE where laser radiation absorption is significant and in the adjacent neural
retina where there is negligible radiation absorption. For parameters used to
treat occult choroidal neovascularization in lightly-pigmented fundi (800-mW,
810-nm, 3-mm retinal spot diameter, 60-sec exposure duration), the maximum
chorioretinal temperature elevation is calculated to be roughly 10 degrees C,
significantly lower than the 20 degrees C temperature elevations measured in
threshold, conventional short-pulse retinal photocoagulation. CONCLUSIONS: To
achieve a preselected temperature rise, TTT laser power must be increased or
decreased in proportion to the diameter rather than the area of the laser spot.
Clinical power settings should be adjusted for fundus pigmentation and media
clarity because both of these factors affect absorbed retinal irradiance and thus
retinal temperature rise. Noninvasive thermal dosimetry currently is unavailable 
for clinical retinal photocoagulation, but potential thermometric techniques
include MRI, liposomal-encapsulated dyes, multispectral imaging or reflectometry,
and subretinal or episcleral thermometry. TTT may be useful not only as
independent therapy, but also as an adjunct to PDT, antiangiogenic drugs and
ionizing radiation therapy in the management of neovascular ARMD. Low
temperature, long-pulse photocoagulation is a potential strategy for decreasing
neural retinal damage in subsequent TTT or short-pulse photocoagulation and
perhaps even for treating glaucoma or retinal degenerations.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 11011704 [PubMed - indexed for MEDLINE]

3153: Graefes Arch Clin Exp Ophthalmol. 2000 Aug;238(8):664-8.

Counterrotation of the globe in macular translocation.

Fricke J, Neugebauer A, Nobis H, Bartz-Schmidt KU, Rüssmann W.

Zentrum für Augenheilkunde der Universität zu Köln, Cologne, Germany.

BACKGROUND: Macular translocation is a new treatment option in age-related
maculopathy. The aim of this study was to report experience with the handling of 
the sensory problems concerning subjective cyclorotation and binocularity that
arise with this technique. METHODS: The data of 33 patients who had undergone
macular translocation and counterrotation of the globe by muscle surgery in a
first operation, followed by silicone oil removal and sometimes revision of the
eye muscles in a second operation, were evaluated. The counterrotation consisted 
of a partial transposition of the rectus muscles and extensive surgery on the
anterior margins of the oblique eye muscles. Subjective monocular cyclorotation, 
motility and binocularity were tested. RESULTS: In 5 patients after the two
operations binocular single vision was proved; in one of these cases there was
even stereoscopic function. Seventeen patients excluded one eye: 13 excluded the 
operated eye, 4 the fellow eye. Eleven patients experienced double vision or
tilted images under binocular viewing conditions and thus required further
surgery or occlusion of one eye. CONCLUSION: The majority of patients were not
hindered by subjective cyclorotation. Nevertheless, in a large proportion of
patients binocularity could not be reestablished because of still reduced visual 
acuity or cyclotropia. The data show that the aim of restoring binocularity can
be achieved but in practice is often not attained.

Publication Types: 
    Comparative Study
    Evaluation Studies

PMID: 11011686 [PubMed - indexed for MEDLINE]

3154: Graefes Arch Clin Exp Ophthalmol. 2000 Aug;238(8):631-41.

Iris pigment epithelial cell translocation in exudative age-related macular
degeneration. A pilot study in patients.

Lappas A, Weinberger AW, Foerster AM, Kube T, Rezai KA, Kirchhof B.

Augenklinik, Universitätsklinikum der RWTH Aachen, Germany.
alappas@post.klinikum.rwth-aachen.de

BACKGROUND: This prospective, non-controlled pilot study investigates the
practicability of IPE translocation and functional outcome in ARMD patients.
Removal of submacular choroidal neovascularization (CNV) in age-related macular
degeneration (ARMD) is usually associated with RPE damage and poor visual
prognosis. Homologous RPE transplants fail to preserve macular function, possibly
due to immune rejection. Instead of homologous RPE, we suggest translocating
autologous iris pigment epithelium (IPE), building on earlier evidence from
animal and in vitro investigations that IPE can substitute RPE functions in the
experimental animal. Immunological cell rejection is avoided. METHODS: Four eyes 
with well-defined and eight eyes with ill-defined subfoveal CNV were submitted to
operation and followed up for a minimum of 6 months. IPE cells were harvested
from a peripheral iridectomy. A vitrectomy was performed. Submacular membranes
were removed, and isolated IPE cells were injected into the subretinal space.
Examinations included ETDRS visual acuity, fluorescein angiography, and SLO
microperimetry. RESULTS: All patients underwent successful surgical removal of
CNV and subretinal IPE injection. Compared to preoperative visual acuity
(20/400-20/100) no significant change was observed after 6 months (20/320-16/80).
A change of more than two ETDRS chart lines was defined as significant. One eye
with preoperative ill-defined CNV developed a recurrence, leading to reduced
visual acuity. In all patients, postoperative fluorescence angiography revealed
early hyperfluorescence (window defect) in the surgically denuded area. Central
fixation was demonstrated in 50% of eyes. CONCLUSIONS: Preliminary data suggests 
that IPE translocation in submacular surgery for ARMD can preserve but not
improve preoperative visual acuity over 6 months. Functional results are
promising compared to submacular membrane extraction alone and RPE
transplantation. Continued research on improvement of IPE translocation seems
justified.

Publication Types: 
    Clinical Trial
    Comparative Study

PMID: 11011682 [PubMed - indexed for MEDLINE]

3155: J Biol Chem. 2000 Dec 15;275(50):39625-30.

Age-related macular degeneration. The lipofusion component
N-retinyl-N-retinylidene ethanolamine detaches proapoptotic proteins from
mitochondria and induces apoptosis in mammalian retinal pigment epithelial cells.

Suter M, Remé C, Grimm C, Wenzel A, Jäättela M, Esser P, Kociok N, Leist M,
Richter C.

Institute of Biochemistry, Swiss Federal Institute of Technology, Universitätstr.
16, CH-8092 Zurich, Switzerland.

10-20% of individuals over the age of 65 suffer from age-related macular
degeneration (AMD), the leading cause of severe visual impairment in humans
living in developed countries. The pathogenesis of this complex disease is poorly
understood, and no efficient therapy or prevention exists to date. A precondition
for AMD appears to be the accumulation of the age pigment lipofuscin in lysosomes
of retinal pigment epithelial (RPE) cells. In AMD, these cells seem to die by
apoptosis with subsequent death of photoreceptor cells, and light may accelerate 
the disease process. Intracellular factors leading to cell death are not known.
Here we show that the lipophilic cation N-retinyl-N-retinylidene ethanolamine
(A2E), a lipofuscin component, induces apoptosis in RPE and other cells at
concentrations found in human retina. Apoptosis is accompanied by the appearance 
of the proapoptotic proteins cytochrome c and apoptosis-inducing factor in the
cytoplasm and the nucleus. Biochemical examinations show that A2E specifically
targets cytochrome oxidase (COX). With both isolated mitochondria and purified
COX, A2E inhibits oxygen consumption synergistically with light. Inhibition is
reversed by the addition of cytochrome c or cardiolipin, a negatively charged
phospholipid that facilitates the binding of cytochrome c to membranes. Succinate
dehydrogenase activity is not altered by A2E. We suggest that A2E can act as a
proapoptotic molecule via a mitochondria-related mechanism, possibly through
site-specific targeting of this cation to COX. Loss of RPE cell viability through
inhibition of mitochondrial function might constitute a pivotal step toward the
progressive degeneration of the central retina.

PMID: 11006290 [PubMed - indexed for MEDLINE]

3156: Invest Ophthalmol Vis Sci. 2000 Oct;41(11):3655-64.

Retinal function in diabetic macular edema after focal laser photocoagulation.

Greenstein VC, Chen H, Hood DC, Holopigian K, Seiple W, Carr RE.

Department of Ophthalmology, New York University School of Medicine, Columbia
University, New York, New York 10016, USA. vcg1@is3.nyu.edu

PURPOSE: To assess the effects of focal photocoagulation on retinal function in
the macular and perimacular areas in patients with diabetes who have clinically
significant macular edema. METHODS: Eleven patients were assessed after focal
laser treatment. Multifocal electroretinogram (ERG) and full-field ERG techniques
were used to evaluate the effects of treatment on macular, paramacular, and
peripheral retinal function. A modified visual field technique was used to obtain
local threshold fields. The posttreatment results were compared with pretreatment
results. Changes in local ERG response amplitudes and implicit times were
calculated for each patient and presented as difference fields. The changes in
local ERG responses were compared with the changes in local field sensitivity.
RESULTS: After treatment, the results of the psychophysical tests suggested
little or no change in visual function, but changes in retinal function were
observed with the multifocal ERG technique. Local ERG responses showed increases 
in implicit time and decreases in amplitude, compared with pretreatment values.
Timing was affected more than amplitude. CONCLUSIONS: The results suggest that
focal treatment produces changes in retinal function, and these changes are not
restricted to the treated macular area.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11006264 [PubMed - indexed for MEDLINE]

3157: Invest Ophthalmol Vis Sci. 2000 Oct;41(11):3643-54.

The nature and extent of retinal dysfunction associated with diabetic macular
edema.

Greenstein VC, Holopigian K, Hood DC, Seiple W, Carr RE.

Department of Ophthalmology, New York University School of Medicine, Columbia
University, New York, New York 10016, USA. vcg1@is3.nyu.edu

PURPOSE: To evaluate the nature and extent of retinal dysfunction in the macular 
and surrounding areas that occurs in patients with diabetes with clinically
significant macular edema (CSME). METHODS: Eleven patients were evaluated before 
focal laser treatment. Multifocal electroretinogram (ERG) and full-field ERG
techniques were used to assess the effects of diabetic retinopathy and CSME on
macular, paramacular, and peripheral retinal function. A modified visual field
technique was used to obtain local threshold fields. The relationship between
local sensitivity changes and local ERG changes was determined. RESULTS: Local
ERG responses were significantly delayed and decreased in amplitude, and timing
changes were observed in a larger area of the retina than amplitude changes.
Visual field deficits were similarly widespread with marked sensitivity losses
occurring in retinal areas with normal ERG amplitudes and in areas that appeared 
to be free of fundus abnormalities. Despite this similarity and the finding that 
retinal areas with elevated thresholds have timing delays, timing delays were not
good predictors of the degree of threshold elevation. CONCLUSIONS: The results
demonstrate the widespread nature of timing deficits and visual field deficits
that are associated with CSME.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11006263 [PubMed - indexed for MEDLINE]

3158: Am J Ophthalmol. 2000 Aug;130(2):203-8.

Clinical spectrum of chromosome 6-linked autosomal dominant drusen and macular
degeneration.

Stefko ST, Zhang K, Gorin MB, Traboulsi EI.

The Wilmer Ophthalmological Institute, Johns Hopkins Hospital, Baltimore,
Maryland, USA.

PURPOSE: To describe the clinical phenotype and the intrafamilial variation in
retinal findings in a North American family with an autosomal dominant drusen
disorder that maps to chromosome 6q14. METHODS: Ophthalmic examinations were
carried out on participating family members. Fundus photographs were obtained
whenever possible. Electroretinography was performed on the proband and her
father. Blood was drawn for DNA analysis. RESULTS: Twelve family members had
drusen and/or atrophic macular degeneration. The disease in asymptomatic young
adults is characterized by fine drusen that are most conspicuous in the macula.
The proband presented at 3 years of age with atrophic maculopathy and drusen. Her
cousin was found to have atrophic macular lesions and drusen in the first year of
life. Two older affected individuals have reduced vision from cicatricial and
atrophic macular changes. The gene for the disease was mapped to chromosome 6q14 
and appears to be adjacent to but distinct from the locus for North Carolina
macular dystrophy. CONCLUSIONS: There is extreme variability in the clinical
expression of this dominant form of drusen and macular degeneration. Most young
adults have fine macular drusen and good vision. Affected infants and children
may have congenital atrophic maculopathy and drusen. There is historical evidence
of progression of the disease in late adulthood with moderate visual loss.

Publication Types: 
    Case Reports

PMID: 11004295 [PubMed - indexed for MEDLINE]

3159: Am J Ophthalmol. 2000 Aug;130(2):197-202.

A new locus for dominant drusen and macular degeneration maps to chromosome 6q14.

Kniazeva M, Traboulsi EI, Yu Z, Stefko ST, Gorin MB, Shugart YY, O'Connell JR,
Blaschak CJ, Cutting G, Han M, Zhang K.

MCDB Department and Howard Hughes Medical Institute, University of Colorado at
Boulder, Colorado, USA.

PURPOSE: To report the localization of a gene causing drusen and macular
degeneration in a previously undescribed North American family. METHODS: Genetic 
mapping studies were performed using linkage analysis in a single family with
drusen and atrophic macular degeneration. RESULTS: The clinical manifestations in
this family ranged from fine macular drusen in asymptomatic middle-aged
individuals to atrophic macular lesions in two children and two elderly patients.
We mapped the gene to chromosome 6q14 between markers D6S2258 and D6S1644.
CONCLUSIONS: In a family with autosomal dominant drusen and atrophic macular
degeneration, the gene maps to a 3.2-cM region on chromosome 6q14. This locus
appears to be distinct from, but adjacent to, the loci for cone-rod dystrophy 7
(CORD7) and North Carolina macular dystrophy (MCDR1). Future identification of
the gene responsible for the disease in this family will provide a better
understanding of macular degeneration.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11004294 [PubMed - indexed for MEDLINE]

3160: Am J Ophthalmol. 2000 Aug;130(2):178-86.

Vitrectomy for diffuse diabetic macular edema associated with a taut premacular
posterior hyaloid.

Pendergast SD, Hassan TS, Williams GA, Cox MS, Margherio RR, Ferrone PJ,
Garretson BR, Trese MT.

Retina Associates of Cleveland, Inc, Beachwood, Ohio 44122, USA. Spender0@aol.com

PURPOSE: To evaluate the role of vitrectomy in eyes with diffuse diabetic macular
edema associated with a taut posterior hyaloid. METHODS: Records of 55 eyes of 50
patients with diabetic retinopathy and diffuse clinically significant diabetic
macular edema who underwent vitrectomy with stripping of the premacular posterior
hyaloid were reviewed. In all 55 eyes, diffuse diabetic macular edema was present
on contact lens examination and confirmed with fluorescein angiography. On fundus
examination, the premacular posterior hyaloid was attached and appeared taut.
RESULTS: The mean preoperative best-corrected visual acuity was 20/160, and the
mean final best-corrected visual acuity was 20/80 (P <.0001, Wilcoxon signed rank
test), with 27 (49.1%) of the 55 eyes demonstrating improvement in best-corrected
visual acuity of 2 or more lines. Fifty-two (94.5%) of the 55 vitrectomized eyes 
showed improvement in clinically significant macular edema and in 45 eyes (81.8%)
the macular edema resolved completely during a mean period of 4.5 months (range, 
1 to 13 months). Eyes with macular ischemia and preoperative best-corrected
visual acuity of 20/200 or less tended to respond less favorably to vitrectomy
than eyes lacking these characteristics. All eyes had at least 6 months of
follow-up after surgery, with a mean follow-up of 23.2 months. CONCLUSION: In
eyes with persistent diffuse diabetic macular edema with a taut premacular
posterior hyaloid face unresponsive to laser therapy, vitrectomy with removal of 
the posterior hyaloid appears to be beneficial in some cases. Careful selection
of eyes with favorable preoperative clinical characteristics may improve surgical
outcomes.

PMID: 11004291 [PubMed - indexed for MEDLINE]

3161: Am J Ophthalmol. 2000 Jul;130(1):76-81.

Scleral outfolding for macular translocation.

Lin SB, Glaser BM, Gould D, Baudo TA, Lakhanpal RR, Murphy RP.

Glaser Murphy Retina Treatment Center, Chevy Chase, Maryland 20815, USA.

PURPOSE: To report experimental study and clinical observation of scleral
outfolding for macular translocation.METHODS: In six human cadaver eyes,
circumferential mattress sutures to create sclera infoldings were compared with
radial-interrupted mattress sutures to create scleral outfoldings. In a
75-year-old man with macular degeneration and choroidal neovascular membrane,
radial-interrupted mattress sutures were used for macular translocation.RESULTS: 
In the human cadaver eyes, circumferential mattress sutures for scleral infolding
created an average decrease in corresponding internal anteroposterior retinal
contour of 0.36 mm. Radial-interrupted mattress sutures for scleral outfoldings
created an average decrease in the corresponding internal anteroposterior retinal
contour of 4. 61 mm. The statistical significance of the difference between
infoldings of the sclera versus outfoldings of the sclera had a P value of.0001. 
CONCLUSIONS: Initial experimental and clinical study suggests that
radial-interrupted mattress sutures may generate more shortening of the internal 
scleral surface and greater macular translocation than circumferential mattress
sutures. Additional studies are needed to evaluate the long-term effects of
radial-interrupted mattress sutures and macular translocation for treatment of
subfoveal choroidal neovascularization secondary to age-related macular
degeneration.

Publication Types: 
    Case Reports

PMID: 11004262 [PubMed - indexed for MEDLINE]

3162: Vision Res. 2000;40(22):3159-68.

L- and M-cone driven ERGs are differently altered in Best's macular dystrophy.

Scholl HP, Kremers J, Apfelstedt-Sylla E, Zrenner E.

University Eye Hospital, Schleichstr. 12-16, 72076, Tübingen, Germany.

To study the L- and M-cone pathways and their interactions in patients with
Best's macular dystrophy (BMD), ERG response thresholds were measured to stimuli 
which modulated exclusively the L- or the M-cones, or both in various
combinations. The ERG threshold data could be described with a vector addition
model. Compared with normals, BMD patients showed generally larger amplitudes of 
the L-cone driven ERGs. However, the M-cone driven ERGs were similar in amplitude
but significantly phase advanced. The data confirm our previous observations that
L- and M-cone pathways can be affected differently by retinal degeneration,
despite their large physiological and biochemical similarities.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10996618 [PubMed - indexed for MEDLINE]

3163: Acta Ophthalmol Scand. 2000 Aug;78(4):465-7.

The luminance fall in anomaloscope examination: clinical examples.

Pinckers A, Uvijls A.

Department of Ophthalmology, University of Nijmegen, The Netherlands.

PURPOSE: The evaluation of the anomaloscope slope quotient in patients with
acquired colour vision deficiency. METHODS: Two patients with Stargardt's disease
in combination with protanomaly and deuteranomaly, respectively, were selected
and also 3 patients with a presumed dominant optic atrophy of the protan type.
The anomaloscope examination was performed according to the Linksz procedure. The
luminance fall was calculated as the slope quotient SQ:Y units luminance fall per
X units width of the matching range. RESULTS: The SQ of the 2 Stargardt patients 
was steeper than the SQ of congenital colour vision defectives, especially at the
red end of the anomaloscope green-red mixture scale, indicating pathologic
scotopization superimposed on the congenital deficiency. In optic atrophy of the 
protan type the SQ was flatter than in congenital deficiency, indicating that
this deficiency has nothing to do with congenital protan deficiency. CONCLUSION: 
Calculation of the slope quotient SQ is helpful for the diagnosis of acquired
colour vision deficiency, especially when the subject also has a congenital
colour vision deficiency or is supposed to have such a deficiency.

Publication Types: 
    Case Reports

PMID: 10990053 [PubMed - indexed for MEDLINE]

3164: Acta Ophthalmol Scand. 2000 Aug;78(4):460-4.

Pars plana vitrectomy for regression of choroidal neovascularization with
age-related macular degeneration.

Ikeda T, Sawa H, Koizumi K, Yasuhara T, Yamasaki T.

Department of Ophthalmology, Osaka Medical College, Japan.
tikeda@poh.osaka-med.ac.jp

OBJECTIVE: In age-related macular degeneration, the posterior vitreous surface
often remains attached to a higher degree than expected for the patient's age,
suggesting the involvement of the posterior vitreous membrane in the
pathophysiology of choroidal neovascularization. Thus, we performed simple pars
plana vitrectomy and artificial posterior vitreous detachment in order to induce 
regression of choroidal neovascularization. METHODS: Vitrectomy was performed in 
12 eyes of 11 patients with age-related macular degeneration in whom the
posterior vitreous surface remained attached, and in whom there was evidence of
highly active choroidal neovascularization. The posterior vitreous membrane was
artificially detached during surgery, but photocoagulation and/or a subretinal
procedure for choroidal neovascularization was not performed. Patients underwent 
fluorescein and indocyanine green angiography both pre- and postoperatively to
assess the status of choroidal neovascularization. RESULTS: Six months after
surgery, 6 of the 12 eyes showed regression of choroidal neovascularization, and 
in 2 eyes it had disappeared completely. Subretinal exudative changes in 8 eyes
had improved. Visual acuity testing showed improved vision in 4 eyes, unchanged
vision in 4 eyes, and worsening of vision in 4 eyes. The final best corrected
visual acuity was 10/20 or better in one eye, 10/ 20 to 20/200 in 7 eyes, and
20/200 or worse in 4 eyes. CONCLUSION: The results of the present study suggest
the involvement of the posterior vitreous membrane in the pathophysiology of
age-related macular degeneration. Furthermore, the minimally invasive pars plana 
vitrectomy may represent a new treatment for age-related macular degeneration.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10990052 [PubMed - indexed for MEDLINE]

3165: Acta Ophthalmol Scand. 2000 Aug;78(4):456-9.

Arterial crimping in branch retinal vein occlusion with macular edema.

Erdöl H, Akyol N.

Department of Ophthalmology, Medical School, Karadeniz Technical University,
Trabzon, Turkey. h.erdol@veezy.com

PURPOSE: To evaluate the effects of arterial crimping plus grid pattern laser
photocoagulation on the macular edema due to branch retinal vein occlusion.
PATIENTS AND METHODS: Seventy two eyes (70 patients) with macular edema due to
BRVO were divided into two similar groups according to age, gender, location and 
extent of the occluded area. Grid pattern laser photocoagulation alone was
applied in 34 eyes (group A), whereas arterial crimping plus grid pattern laser
was used in 38 eyes (group B). Visual acuity, central 30 degree perimetry, and
fundus fluorescein angiography were carried out in all patients at each
examination. Patients were followed up for an average of 23 mo (ranging from 11
to 34 mo). FINDINGS: A rate of 62% and 79% improvement in macular edema was
recorded in groups A and B, respectively (p=0.057). The perimetric performance
value improved more in group B than in group A (p=0.028). In addition, visual
acuity improved more in group B than group A (p=0.041). CONCLUSION: In patients
with BRVO, grid pattern retinal photocoagulation treatment plus arterial crimping
resulted in better visual performance two years after treatment than did grid
pattern photocoagulation alone.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 10990051 [PubMed - indexed for MEDLINE]

3166: Acta Ophthalmol Scand. 2000 Aug;78(4):443-7.

Hyperfluorescence associated with serous retinal pigment epithelial detachment on
indocyanine green angiography.

Parodi MB, Saviano S, Bondel E, Panetta P, Iustulin D, Fachin S, Ravalico G.

Eye Clinic, University of Trieste, Ospedale Maggiore, Italy.

PURPOSE: Indocyanine green angiography has been reported to improve detection and
delineation of occult choroidal neovascularisation in serous pigment epithelium
detachment in age-related macular degeneration. The study aims to evaluate the
visual acuity results of eyes affected by serous pigment epithelium detachment in
age-related macular degeneration, having had indocyanine green-directed laser
photocoagulation, and to correlate them to the pattern of serous pigment
epithelium detachment on indocyanine green angiography. METHODS: Thirty-four eyes
of 31 patients affected by serous pigment epithelium detachment in age-related
macular degeneration were prospectively considered. Each patient underwent an
ophthalmological examination including fluorescein and indocyanine green
angiography one day before, and 6 weeks, 3 months, 6 months, 9 months, 12 months 
and 24 months after krypton-laser treatment. The serous pigment epithelium
detachment was classified in the late-phases angiograms as either
hypofluorescent, isofluorescent or hyperfluorescent comparing the fluorescence of
the serous pigment epithelium detachment with the choroidal background
fluorescence. RESULTS: The indocyanine green-guided laser treatment was
associated with a temporary stabilization and a long-term progressive reduction
of visual acuity: after 24 months visual acuity improved in 2.9%, stabilized in
26.5% and worsened in 70.5% of cases. Serous pigment epithelium detachment
presenting a pretreatment hyperfluorescence had a final visual acuity of 0.06,
with subfoveal choroidal neovascularisation development in 100% of cases, whereas
serous pigment epithelium detachment presenting a pretreatment hypofluorescence
and isofluorescence showed a final visual acuity of 0.12, with subfoveal
choroidal neovascularisation development in 43.5% of eyes, with statistically
significant difference. CONCLUSION: Overall visual acuity decreases with time
after indocyanine green-guided laser treatment of choroidal neovascularisation in
serous pigment epithelium detachment, and serous pigment epithelium detachment
becoming hyperfluorescent in the late-phases of indocyanine green angiography has
the worst functional outcome.

PMID: 10990048 [PubMed - indexed for MEDLINE]

3167: Curr Opin Ophthalmol. 2000 Jun;11(3):175-9.

The cost-effectiveness of grid laser photocoagulation for the treatment of
diabetic macular edema: results of a patient-based cost-utility analysis.

Sharma S, Brown GC, Brown MM, Hollands H, Shah GK.

Unit for Cost-Effective Ocular Health Policy, Hotel Dieu Hospital, Kingston,
Ontario, Canada.

Grid laser therapy has been demonstrated to be of benefit for the treatment of
diabetic macular edema. The purpose of the present study was to determine the
cost-effectiveness of grid laser therapy for the treatment of diabetic macular
edema. The analysis was performed from the perspective of a third-party insurer. 
Decision analyses and cost-effectiveness analyses were performed by incorporating
the data from the Early Treatment Diabetic Retinopathy Study, expected longevity 
data, and patient-based utilities. Various sensitivity analyses were performed to
determine the robustness of the models. Laser treatment conferred an overall
improvement in quality-of-life adjusted years of approximately 3 months over the 
duration of disease for a hypothetical patient. The unadjusted cost per
quality-of-life adjusted year (QALY) was US$3,101. Net present value analysis
demonstrated that the cost per QALY could increase to $3,655, assuming a 5%
discount rate. Overall, grid laser photocoagulation for diabetic macular edema is
a very cost-effective treatment based on the results of this cost-utility
analysis.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 10977223 [PubMed - indexed for MEDLINE]

3168: Curr Opin Ophthalmol. 2000 Jun;11(3):171-4.

Adventitial sheathotomy for treatment of macular edema associated with branch
retinal vein occlusion.

Shah GK.

Washington University, St. Louis, Missouri, USA.

Laser therapy has been shown to be of benefit in eyes with branch retinal vein
obstruction. More recently, pars plana vitrectomy with adventitial sheathotomy
has also been shown to be of benefit, particularly for those eyes with branch
retinal vein obstruction and poorer vision. The technique and results of this new
therapeutic modality are discussed herein.

Publication Types: 
    Review

PMID: 10977222 [PubMed - indexed for MEDLINE]

3169: Jpn J Ophthalmol. 2000 Jul-Aug;44(4):360-7.

Indocyanine green angiography and histopathology of choroidal neovascular
membrane in age-related macular degeneration.

Nakajima M, Shimada H, Sato M, Asayama N, Yuzawa M.

Department of Ophthalmology, Nihon University School of Medicine, Tokyo, Japan.

PURPOSE: Histopathological investigation of the choroidal neovascular membrane
(CNM) in age-related macular degeneration (AMD) patients who showed various
findings in indocyanine green angiography (IA). METHODS: Before surgery, 20 eyes 
of 20 patients were classified into four types based on IA findings (Type I: both
early and late phase hyperfluorescence; Type II: hyperfluorescence only in the
early phase; Type III: hyperfluorescence only in the late phase; Type IV:
virtually no hyperfluorescence in any phase). Seventeen surgically excised
specimens stained with hematoxylin-eosin and azan, were examined by light
microscopy. Three other specimens were examined by electron microscopy. RESULTS: 
Type I membrane showed many vascular channels not present in the surrounding
retinal pigment epithelium (RPE) cells, and little fibrous tissue. Type II
membrane had many vascular channels but RPE cells surrounded the CNM. Type III
membrane showed few vascular channels and RPE cell proliferation. Type IV
membrane showed dense fibrous tissue. CONCLUSION: The IA findings in AMD agreed
with the CNM membrane structure in regard to the number of vascular channels,
maturity of vessels, the extent of envelopment of RPE cells and the amount of
fibrous tissue.

Publication Types: 
    Comparative Study

PMID: 10974291 [PubMed - indexed for MEDLINE]

3170: Optometry. 2000 Mar;71(3):165-76.

Stargardt's macular dystrophy--a patient's perspective.

Miedziak AI, Perski T, Andrews PP, Donoso LA.

Henry and Corinne Bower Laboratory for Macular Degeneration, Wills Eye Hospital, 
Jefferson Medical College, Thomas Jefferson University, Philadelphia,
Pennsylvania, USA.

PURPOSE: The purpose of this paper was to evaluate life experience, including
disease characteristics, daily-living activities, employment, interactions with
health care professionals, and support services in patients diagnosed with
Stargardt's macular dystrophy. METHODS: More than 200 patients with Stargardt's
disease responded to a 68-question survey. Results were analyzed using SAS
Statistical Analysis Package. RESULTS: Of 203 responders, 142 (70%) were women.
Early disease onset occurred in more than 60% of patients. Blurred vision (134,
66%) and glare (183, 90.1%) were the leading symptoms reported. Reading (116,
57.1%), driving (86, 42.4%), and recognizing faces (66, 32.5%) were daily-living 
activities most difficult to perform. Patients with early disease onset had worse
vision at presentation (p = 0.001), faster progression of visual loss (p =
0.007), and were more often diagnosed with a non-physiological visual loss (p =
0.007). Patients with late disease onset had more difficulty with orientation and
coping skills (p = 0.02). Sixty-five percent of evaluated adults (108 of 165)
were employed. CONCLUSIONS: Although the study illustrates that patients with
Stargardt's disease can contribute and function well in contemporary society,
issues related to depression, and availability and quality of health care, are
still major concerns for this patient population. The study shows differences in 
progression of visual loss between patients, with early versus late disease onset
indicating that age at onset and visual acuity at presentation might be two
important factors influencing patient's visual prognosis. Finally, the study
suggests parallels in psychological profiles between late age at onset
Stargardt's disease and age-related macular degeneration patients.

Publication Types: 
    Comparative Study
    Research Support, U.S. Gov't, P.H.S.

PMID: 10970260 [PubMed - indexed for MEDLINE]

3171: Kaohsiung J Med Sci. 2000 May;16(5):266-8.

Choroidal retinal anastomosis in age-related macular degeneration as demonstrated
by fluorescein angiography--a case report.

Ding PC, Chen MT, Tseng SC.

Department of Ophthalmology, Kaohsiung Medical University, Taiwan.

Pathological choroidal retinal anastomosis is relatively rare. It has been
described in age-related macular degeneration (AMD) with fibrous scarring or
occult pigment epithelial detachment or actively proliferating classic choroidal 
neovascular membrane (CNV). We report a case of disciform macular scar with the
occurrence of a choroidal retinal anastomosis, which directed blood flow from an 
occult choroidal neovascular membrane into a retinal vein through the fovea in a 
52-year-old female with unilateral AMD. Fluorescein angiography (FA) clearly
demonstrated the anastomosis.

Publication Types: 
    Case Reports

PMID: 10969523 [PubMed - indexed for MEDLINE]

3172: Invest Ophthalmol Vis Sci. 2000 Sep;41(10):3142-8.

Histologic correlation of human neural retinal transplantation.

del Cerro M, Humayun MS, Sadda SR, Cao J, Hayashi N, Green WR, del Cerro C, de
Juan E Jr.

Department of Ophthalmology, University of Rochester School of Medicine, New
York, USA.

PURPOSE: To describe the histologic findings of the transplanted eye of a
94-year-old man with neovascular age-related macular degeneration, who 3 years
earlier underwent subretinal transplantation of both a fetal neural retinal sheet
and a retinal microaggregrate suspension. METHODS: Serial sections of the
posterior segment of the eye and the transplanted areas were processed and
studied by routine histologic techniques, including both light and transmission
electron microscopy (TEM). Transplanted areas were also examined for the presence
of glial, neuronal, and photoreceptor cell markers by standard
immunohistochemical methods. RESULTS: After transplantation in this patient,
there was no visual improvement. Light microscopic examination disclosed survival
of the transplanted cells in the subretinal space with no evidence of
inflammation or rejection. The neural retinal sheet transplant developed a
layered configuration. The retinal pigment epithelium (RPE) was absent over much 
of the posterior pole, including the area of transplantation. TEM examination and
immunohistochemical analysis disclosed the presence of neuronal and glial cells
within the transplant. A few transplant neuronal cell processes overlying a focus
of residual RPE cells were positive for S-antigen, but well-developed
photoreceptor outer segments were not present. CONCLUSIONS: Long-term survival of
transplanted neural retinal tissue can be achieved in human patients without
immunosuppression. The lack of photoreceptor development in this patient may be
the result of absent or dysfunctional RPE. Nonetheless, the long-term survival of
grafted tissue in the human subretinal space in the absence of immunosuppressive 
treatment is promising for future efforts in the field of neural retinal
transplantation.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 10967076 [PubMed - indexed for MEDLINE]

3173: Invest Ophthalmol Vis Sci. 2000 Sep;41(10):3100-6.

Human neural retinal transplantation.

Humayun MS, de Juan E Jr, del Cerro M, Dagnelie G, Radner W, Sadda SR, del Cerro 
C.

Department of Ophthalmology, Wilmer Ophthalmological Institute, the Johns Hopkins
Medical Institutions, Baltimore, Maryland 21287, USA.

PURPOSE: A pilot study of human neural retinal transplantation was undertaken to 
investigate three major issues: whether a safe surgical procedure could be
devised for transplantation of neural retinal tissue into the subretinal space,
whether the transplant would be accepted in the subretinal space, and whether an 
improvement in vision could be achieved. METHODS: Eight patients with bare light 
perception (LP) vision due to retinitis pigmentosa (RP) and one patient with bare
LP vision due to advanced neovascular age-related macular degeneration (AMD)
received subretinal transplants of human fetal retinal microaggregate suspensions
without postoperative systemic immunosuppression. The patient with AMD also
received a fetal retinal sheet transplant. The ages of the patients ranged from
31 to 94 years (median, 55 years). The pre- and postoperative evaluations
included visual function testing, detailed fundus examinations, fundus
photography, fluorescein angiography, macular perimetry using a scanning laser
ophthalmoscope (SLO), and full field and focal electroretinograms (ERGs).
RESULTS: Three of the eight RP patients demonstrated possible improved light
sensitivity during the initial months of follow-up. However, visual improvement
disappeared between 3 and 13 months of follow-up. After transplantation, no
subject showed any changes in the ERG recordings or SLO macular perimetry
relative to their preoperative baseline. No patient experienced a retinal
detachment, infection, or extensive bleeding. None of the patients developed
retinal vasculitis or intraocular inflammation. In one RP patient, fluorescein
angiography and fundus photography documented the formation and maturation of new
host retinal vessels in the area of the transplant. CONCLUSIONS: Transplantation 
of fetal retinal photoreceptor suspensions into the subretinal space was achieved
safely in nine subjects. Although a definite positive effect on visual function
could not be demonstrated, the apparent high tolerance for graft tissue is
promising for future efforts in the field of neural retinal transplantation.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 10967070 [PubMed - indexed for MEDLINE]

3174: Invest Ophthalmol Vis Sci. 2000 Sep;41(10):2972-7.

Influence of experimental chronic high-pressure glaucoma on age-related macular
degeneration in rhesus monkeys.

Jonas JB, Hayreh SS.

Department of Ophthalmology and Eye Hospital, Friedrich-Alexander University of
Erlangen-Nürnberg, Germany.

PURPOSE: To assess prospectively whether development of age-related macular
degeneration is influenced by experimentally induced chronic high-pressure
glaucoma, and whether age-related macular degeneration influences the appearance 
of the optic nerve head in experimental chronic high-pressure glaucoma in older
rhesus monkeys. METHODS: The longitudinal study included 102 eyes of 52 rhesus
monkeys. The total study group was divided into a group with experimentally
induced unilateral chronic high-pressure glaucoma (n = 40 eyes) and a normal
control group (n = 62 eyes). Additionally, arterial hypertension and
atherosclerosis were experimentally induced in both study groups in a similar
percentage of monkeys. Mean monkey age at the end of the study was 19.6 +/- 3.1
years (range, 13-24 years). The macular region, optic disc, and retinal nerve
fiber layer were morphometrically evaluated by color wide-angle fundus
photographs taken at baseline and at the end of the study. RESULTS: The degree of
age-related macular degeneration, measured as number and area of drusen in the
foveal and extrafoveal region of the macula, did not differ significantly between
the two study groups. In the glaucomatous group, the degree of macular
degeneration was statistically independent of the development of parapapillary
atrophy, loss of neuroretinal rim, and decrease in the visibility of the retinal 
nerve fiber layer. CONCLUSIONS: Development of age-related macular degeneration
in rhesus monkeys is independent of concomitant chronic high-pressure glaucoma,
including the development of glaucomatous parapapillary chorioretinal atrophy.
Conversely, age-related macular degeneration does not markedly influence the
course of experimental chronic high-pressure glaucoma or the development of
parapapillary atrophy in monkeys.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 10967053 [PubMed - indexed for MEDLINE]

3175: Br J Ophthalmol. 2000 Sep;84(9):1018-23.

The second eye of Japanese patients with unilateral exudative age related macular
degeneration.

Uyama M, Takahashi K, Ida N, Miyashiro M, Ando A, Takahashi A, Yamada E, Shirasu 
J, Nagai Y, Takeuchi M.

Department of Ophthalmology, Kansai Medical University, Moriguchi, Osaka
570-8507, Japan.

AIM: To clarify the incidence of choroidal neovascularisation (CNV) and
predisposing findings for development of CNV in the second eye of Japanese
patients with unilateral exudative age related macular degeneration (AMD).
METHODS: The second eyes of unilaterally affected patients with exudative
(neovascular) AMD treated in our clinic during the past 10 years (1988-97) were
carefully followed up for more than a year. Evidence of CNV was confirmed by
fluorescein and indocyanine green angiography. Macular lesions in patients, in
whom CNV developed in the second eye, were retrospectively evaluated from patient
records. RESULTS: 170 patients met the criteria. The average follow up period was
47 months (range 12-108 months). All patients were Japanese. CNV developed in the
second eye in 12 (7%) of 170 patients, 30.3 months on average after the first
examination. Cumulative incidence of developing CNV in the second eye using
Kaplan-Meier life table analysis was: 0.6% by 1 year, 5.6% by 3 years, and 12.3% 
by 5 years, and was relatively low compared with that in white patients. CNV
developed most frequently from serous pigment epithelial detachment (PED) in the 
macula (58%). Soft drusen were not prevalent and risk of developing CNV was not
very high (18%). CONCLUSION: It was confirmed that there were some differences in
the incidence and predisposing findings for CNV developing in AMD among Japanese 
and other Asian patients compared with those in white people. It is important to 
recognise these differences between the two populations to understand the
pathogenesis and epidemiology of AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10966957 [PubMed - indexed for MEDLINE]

3176: Br J Ophthalmol. 2000 Sep;84(9):952-6.

Comment in:
    Br J Ophthalmol. 2000 Sep;84(9):944-5.

Amblyopia: is visual loss permanent?

El Mallah MK, Chakravarthy U, Hart PM.

Ophthalmology and Vision Science, Queen's University, Royal Victoria Hospital,
Belfast BT 12 6BA.

AIM: To ascertain whether recovery of visual function in amblyopic eyes is likely
to occur when the fellow eye is lost as a result of age related macular
degeneration. METHODS: The records of 465 patients with an established diagnosis 
of age related macular degeneration who had attended a specialist macular clinic 
between 1990 and 1998 were scrutinised. A full clinical examination and
standardised refraction had been carried out in 189 of these cases on a minimum
of two occasions. Cases were looked for where an improvement of one or more lines
of either distance or near acuity was recorded in the eye unaffected by macular
disease. In each one of these cases the improvement in visual acuity could not be
attributed to treatment of other existing pathology. RESULTS: 12 such cases were 
detected. In nine of these the eye showing improvement of acuity had a history of
amblyopia. The mean improvement in distance and near acuity in amblyopic eyes by 
12 months was 3.3 and 1.9 lines logMAR respectively. The improvement in acuity
generally occurred between 1 and 12 months from baseline and remained stable over
the period of follow up. CONCLUSIONS: Older people with a history of amblyopia
who develop visual loss in the previously normal eye can experience recovery of
visual function in the amblyopic eye over a period of time. This recovery in
visual function occurs in the wake of visual loss in the fellow eye and the
improvement appears to be sustained.

PMID: 10966943 [PubMed - indexed for MEDLINE]

3177: Ophthalmologica. 2000 Sep-Oct;214(5):312-9.

Unusual visual evoked potentials in patients with age-related macular
degeneration.

Walter P, Königsfeld P, Soudavar F, Brunner R.

Department of Ophthalmology, University of Cologne, Germany.
peter.walter@uni-koeln.de

Among a series of patients with age-related macular degeneration (ARMD), a few
individuals could be identified showing larger amplitudes of pattern reversal
visual evoked potentials (prVEP) after stimulation of a central 3 degrees field
compared to stimulation of a 13 degrees field although in the majority of ARMD
patients and in normals, VEP amplitudes increased with increasing field size. An 
analysis of prVEPs recorded after stimulation of different macular zones showed
that the 3 degrees central area and the perifoveal zone contributed differently
to the 13 degrees response or macular response. Perifoveal activity in this
subgroup of ARMD patients seemed to mask the foveal contribution to the macular
prVEP. The cortical magnification factor in ARMD may be higher than in normal
controls. Small-field stimulation techniques are therefore also recommended in
patients with central retinal pathology. Copyright 2000 S. Karger AG, Basel

Publication Types: 
    Comparative Study

PMID: 10965243 [PubMed - indexed for MEDLINE]

3178: Am J Hum Genet. 2000 Oct;67(4):800-13. Epub 2000 Aug 24.

A comprehensive survey of sequence variation in the ABCA4 (ABCR) gene in
Stargardt disease and age-related macular degeneration.

Rivera A, White K, Stöhr H, Steiner K, Hemmrich N, Grimm T, Jurklies B, Lorenz B,
Scholl HP, Apfelstedt-Sylla E, Weber BH.

Institut für Humangenetik, Universität Würzburg, D-97074 Würzburg, Germany.

Stargardt disease (STGD) is a common autosomal recessive maculopathy of early and
young-adult onset and is caused by alterations in the gene encoding the
photoreceptor-specific ATP-binding cassette (ABC) transporter (ABCA4). We have
studied 144 patients with STGD and 220 unaffected individuals ascertained from
the German population, to complete a comprehensive, population-specific survey of
the sequence variation in the ABCA4 gene. In addition, we have assessed the
proposed role for ABCA4 in age-related macular degeneration (AMD), a common cause
of late-onset blindness, by studying 200 affected individuals with late-stage
disease. Using a screening strategy based primarily on denaturing gradient gel
electrophoresis, we have identified in the three study groups a total of 127
unique alterations, of which 90 have not been previously reported, and have
classified 72 as probable pathogenic mutations. Of the 288 STGD chromosomes
studied, mutations were identified in 166, resulting in a detection rate of
approximately 58%. Eight different alleles account for 61% of the identified
disease alleles, and at least one of these, the L541P-A1038V complex allele,
appears to be a founder mutation in the German population. When the group with
AMD and the control group were analyzed with the same methodology, 18 patients
with AMD and 12 controls were found to harbor possible disease-associated
alterations. This represents no significant difference between the two groups;
however, for detection of modest effects of rare alleles in complex diseases, the
analysis of larger cohorts of patients may be required.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10958763 [PubMed - indexed for MEDLINE]

3179: J Glaucoma. 2000 Aug;9(4):317-21.

Visually significant cystoid macular edema in pseudophakic and aphakic patients
with glaucoma receiving latanoprost.

Lima MC, Paranhos A Jr, Salim S, Honkanen R, Devgan L, Wand M, Gaudio AR, Shields
MB.

Department of Ophthalmology and Visual Science, Yale University School of
Medicine, New Haven, Connecticut, USA.

PURPOSE: To investigate the incidence of visually significant cystoid macular
edema associated with the use of latanoprost in patients with glaucoma after
cataract surgery. PATIENTS AND METHODS: This is a multicenter, retrospective
study of 185 patients, of whom 173 were pseudophakic (212 eyes) and 12 were
aphakic (13 eyes), who were treated for glaucoma with latanoprost 0.005%. The
posterior lens capsule was intact in 125 eyes, open or absent as a result of
surgery in 25 eyes, and status-post-yttrium-aluminum-garnet capsulotomy in 75
eyes. Visual acuity was documented before and after initiating latanoprost
therapy, and patients with a reduction of two or more lines on the Snellen chart 
were examined by fluorescein angiography for cystoid macular edema. RESULTS:
Visual reduction was documented in four (2.16%) patients. Three of the four
patients had cystoid macular edema, and the fourth was thought to have lost a
central island of vision from glaucoma. The three patients with cystoid macular
edema all had ruptured posterior capsules, requiring anterior vitrectomy, and one
had a previous episode of cystoid macular edema 3 years before starting
latanoprost therapy. CONCLUSION: These findings suggest that visually significant
cystoid macular edema associated with latanoprost therapy in pseudophakic or
aphakic patients is uncommon. If there is a cause-and-effect relationship between
latanoprost therapy and clinically significant cystoid macular edema, the
incidence appears to be low.

Publication Types: 
    Case Reports
    Comparative Study
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 10958605 [PubMed - indexed for MEDLINE]

3180: Retina. 2000;20(4):325-30.

Laser treatments with verteporfin therapy and its potential impact on retinal
practices.

Margherio RR, Margherio AR, DeSantis ME.

Beaumont Eye Institute, Associated Retinal Consultants, PC, Royal Oak, Michigan
48073, USA. margherio@beaumont.edu

BACKGROUND: In the 1990s, the only available treatment for neovascular
age-related macular degeneration (ARMD) was laser photocoagulation, but a
minority of patients could be treated. Photodynamic therapy with verteporfin
potentially allows many more patients to be treated. The authors' aim was to
assess the impact of this increase on retinal practices. METHODS: The number of
patients who received laser photocoagulation in 1998 was determined. Based on
that number and a retrospective review of 1000 consecutive records of new
patients with ARMD referred to the Associated Retinal Consultants practices
during 1998, estimates were made of how many patients would have been eligible
for verteporfin therapy. RESULTS: Of the 1000 patients, 171 had predominantly
classic subfoveal choroidal neovascularization secondary to ARMD and would have
been eligible for verteporfin therapy, compared with 99 treated with laser
photocoagulation according to Macular Photocoagulation Study guidelines. If this 
patient population is representative of the general population, approximately
84,000 patients would be eligible for verteporfin therapy in the United States
per year, compared with 42,000 for laser photocoagulation. This would lead to
286,000 verteporfin treatments per year if retreatments are required.
CONCLUSIONS: This increase in treatments for neovascular ARMD will have a
considerable impact on retinal practices. Although the resources that will need
to be expended are high, the potential benefit of verteporfin therapy in reducing
vision loss will outweigh the costs.

Publication Types: 
    Review

PMID: 10950407 [PubMed - indexed for MEDLINE]

3181: Graefes Arch Clin Exp Ophthalmol. 2000 Jun;238(6):482-5.

Relationship between anticoagulant medication and massive intraocular hemorrhage 
in age-related macular degeneration.

Tilanus MA, Vaandrager W, Cuypers MH, Verbeek AM, Hoyng CB.

Institute of Ophthalmology, University Hospital Nijmegen, The Netherlands.
m.tilanus@ohk.azn.nl

BACKGROUND: A massive intraocular hemorrhage in the course of age-related macular
degeneration (AMD) is a devastating event. We set out to determine the role of
anticoagulant therapy prescribed for vascular or cardiac indications in the
development of a massive hemorrhage. METHODS: A retrospective case-controlled
study was conducted of 50 cases of age-related macular degeneration complicated
by massive subretinal and vitreous hemorrhage. The control group consisted of 50 
cases of AMD with small subretinal hemorrhage. RESULTS: There was a significant
difference in the use of anticoagulant medication (warfarin sodium) between the
groups. The difference in the use of antiplatelet medication (aspirin) between
the groups was not significant. A patient with a massive intraocular hemorrhage
and AMD is 11.6 times more likely to use anticoagulant medication. It appeared
that more than 50% of the patients in the massive hemorrhage group were allowed
to stop the anticoagulant medication. CONCLUSION: Anticoagulant medication poses 
a significant risk in the development of a massive intraocular hemorrhage in
patients with exudative AMD. Antiplatelet medication poses a less significant
risk. Physicians prescribing anticoagulant medication should be informed about
the macular status of the patient. the In case of neovascular AMD, anticoagulant 
medication should be prescribed only for absolute systemic indications.

Publication Types: 
    Comparative Study

PMID: 10943671 [PubMed - indexed for MEDLINE]

3182: West J Nurs Res. 2000 Aug;22(5):571-88; discussion 588-95.

Severe visual impairment in older women.

Moore LW.

Department of Nursing, Xavier University, USA.

The purpose of this qualitative, phenomenological study was to uncover the
meaning of severe visual impairment to older women diagnosed with macular
degeneration, a leading cause of blindness in older adults. The research question
for the study was, What is the lived experience of severe visual impairment in
older women diagnosed with macular degeneration? Participants were eight women,
aged 63 to 85 years, who had been diagnosed with macular degeneration and who had
severe visual deficits. Data were gathered through audiotaped interviews.
Interview recordings were transcribed and later analyzed using a modified Giorgi 
methodology. The meaning of severe visual impairment emerged as "persisting
toward unfolding ways of being in the world sparked by personal discoveries
amidst enveloping losses while embracing a realistic awareness with steadfast
positivism." Findings from this study were congruent with the theory of Human
Becoming. Study findings highlight factors that may place older women with severe
visual deficits at risk for lower levels of well-being.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10943172 [PubMed - indexed for MEDLINE]

3183: Ophthalmic Surg Lasers. 2000 Jul-Aug;31(4):292-300.

Combined modified grid and panretinal photocoagulation for diffuse diabetic
macular edema and proliferative diabetic retinopathy.

Lee CM, Olk RJ, Akduman L.

New York University School of Medicine, New York, USA.

PURPOSE: To determine the effectiveness of combined macular modified grid and
peripheral panretinal photocoagulation in diabetic eyes with both macular edema
and proliferative retinopathy. MATERIAL AND METHODS: We evaluated 52 eyes with
diffuse diabetic macular edema and proliferative diabetic retinopathy. Treatment 
was performed in two sessions consisting of initial modified grid to the macula
and panretinal photocoagulation to the inferior half of the peripheral retina,
followed 2 to 4 weeks later by panretinal photocoagulation to the superior half. 
RESULTS: At one year, visual acuity was improved in 8%, stable in 79%, and worse 
in 13%. At two years, visual acuity was improved in 4%, stable in 72%, and worse 
in 24%. Macular edema resolved in 43 of 46 eyes (93%), and proliferative
retinopathy was reduced in 25 of 29 eyes (86%) at last examination. CONCLUSION:
Combined macular modified grid and peripheral panretinal photocoagulation is an
effective treatment approach in diabetic eyes with both macular edema and
proliferative retinopathy. Laser photocoagulation in those diabetic eyes with
diffuse diabetic macular edema and proliferative diabetic retinopathy can be
completed in less number of treatment sessions with this method, compared to
conventional treatment techniques.

Publication Types: 
    Comparative Study

PMID: 10928666 [PubMed - indexed for MEDLINE]

3184: Bull Soc Belge Ophtalmol. 2000;276:83-92.

No efficacious treatment for age-related macular degeneration.

Roodhooft J.

Department of Ophthalmology, Algemeen Ziekenhuis Sint-Jozef, Turnhout, Belgium.

PURPOSE: The purpose of this paper is to explain that many trials have been done 
unsuccessfully to improve age-related macular degeneration. METHODS: Different
trials that have been done to improve this degeneration and that have been
published in a peer reviewed journal are discussed. RESULTS: There is not yet a
preventive therapy that has a significant impact on blindness due to age-related 
maculopathy. There is no therapy for geographic atrophy. There are limited forms 
of therapy with the objective of destroying new vessels arising in the choroid
and of limiting the visual loss. CONCLUSION: There is a need for more efforts to 
find ways that influence the survival of the complex photoreceptor--retinal
pigment epithelium--Bruch's membrane in the aging population.

Publication Types: 
    Review

PMID: 10925530 [PubMed - indexed for MEDLINE]

3185: Ophthalmology. 2000 Aug;107(8):1601-6.

A comparison of stereoscopic fluorescein angiography with indocyanine green
videoangiography in age-related macular degeneration.

Watzke RC, Klein ML, Hiner CJ, Chan BK, Kraemer DF.

Casey Eye Institute, Oregon Health Sciences University, Portland, Oregon, USA.

PURPOSE: To correlate features of indocyanine green (ICG) videoangiography with
stereo film fluorescein angiography (FA) in the analysis of age-related macular
degeneration (AMD). DESIGN: A retrospective study with concurrent comparison of
two methods of assessment on one set of patients with AMD undergoing sequential
FA-ICG videoangiography. METHODS: One hundred four patients with AMD who had
undergone immediately sequential FA-ICG videoangiography were selected in a
consecutive fashion from the photographic files of the Casey Eye Institute. Three
interpreters independently graded in an unbiased fashion the FA features of AMD. 
These were compared with ICG videoangiography features of hypocyanescence (ICG
videoangiography hypofluorescence), moderate or intense hypercyanescence (ICG
videoangiography hyperfluorescence), or absence of fluorescence over background
(ICG videoangiography isocyanescence). We also assessed ICG videoangiography
features in the opposite eye of those with choroidal neovascularization (CNV) by 
FA in one eye by examining an additional 96 FA-ICG videoangiography scans. MAIN
OUTCOME MEASURES: Outcomes were the ICG videoangiography characteristics of
classic and occult CNV, serous pigment epithelial detachments (SPEDs) both with
and without CNV, macular hemorrhage, and the comparative size of these features. 
RESULTS: There were 25 eyes that had significant macular hemorrhage by FA. Of
these, the FA revealed CNV in its entirety under or near the hemorrhage in 11.
The ICG examination revealed all 11 plus an additional 12 hypercyanescent
features that were not visible by FA. Although 26 of 32 SPEDs had CNV by FA
analysis, 31 of 32 had well-defined hypercyanescence under or at the SPED edge by
ICG videoangiography. Eighty-seven percent of eyes with classic choroidal
neovascular membranes (CCNV; 20 of 23) and 93% of eyes with fibrovascular pigment
epithelial detachments (FVPED; 66 of 71) were hypercyanescent with distinct
edges. Fifty percent of eyes with only late leakage of undetermined source (LLUS)
were hypercyanescent, whereas 50% were isocyanescent on ICG videoangiography.
There were four of 104 eyes in which ICG videoangiography revealed poorly defined
hypercyanescent areas when, by FA, there were only drusen or elevated blocked
fluorescence. Indocyanine green videoangiography revealed only three eyes with
poorly defined hypercyanescence of 200 fellow eyes in patients with unilateral
AMD. CONCLUSIONS: Indocyanine green videoangiography correlated fairly well with 
stereoscopic FA for the presence of CCNV or FVPED, but correlated poorly when
LLUS was present. In certain cases where CNV was associated with SPED or macular 
hemorrhage, ICG videoangiography demonstrated features not apparent on FA.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 10919917 [PubMed - indexed for MEDLINE]

3186: Ophthalmology. 2000 Aug;107(8):1593-600.

The prevalence of age-related maculopathy: the visual impairment project.

VanNewkirk MR, Nanjan MB, Wang JJ, Mitchell P, Taylor HR, McCarty CA.

Centre for Eye Research Australia, The University of Melbourne, East Melbourne,
Australia.

PURPOSE: To determine the prevalence of age-related maculopathy (ARM) lesions in 
residents of the state of Victoria, Australia. DESIGN: Population-based
cross-sectional study. PARTICIPANTS: Total of 5147 residential and
institutionalized persons aged 40 years and older, living in Victoria. METHODS:
Participants were recruited through a cluster, stratified, random sampling from
nine urban clusters and four rural clusters. The presence of ARM lesions was
graded from color stereo fundus photographs as well as slit-lamp stereo
biomicroscopy according to the International Classification and Grading System.
MAIN OUTCOME MEASURES: The presence of ARM lesions. RESULTS: The mean age of
participants was 60.2 years, and 55% were females. Gradable fundus photographs
were available for at least one eye in 4345 (92%) of the participants. The
weighted prevalence of neovascular age-related macular degeneration (AMD) was
0.39% (95% confidence limits [CL] = 0.20, 0.58), atrophic AMD was 0. 27% (95% CL 
= 0.04, 0.50), and total AMD was 0.68% (95% CL = 0.30, 1. 1). Prevalence of AMD
was strongly related to age (P < 0.001). Prevalence of early ARM was 15.1% (95%
CL = 13.7, 16.4). Large drusen, 125 micrometer or more, were present in 6.3% of
the participants. There was a higher prevalence of soft distinct drusen (7.5%)
than soft indistinct drusen (4.3%). Retinal pigmentary abnormalities were present
in 8.2% (95% CL = 7.2, 9.2). The prevalence of large drusen, soft drusen, and
pigmentary abnormalities increased with age (P < 0. 001). Prevalence of retinal
pigmentary abnormalities increased with increasing drusen size (P < 0.001). Soft 
indistinct drusen were more common in women aged 70 years or older (P < 0.001).
Bilaterality of any ARM was strongly age related, and women appeared to have a
higher risk of both bilateral early ARM and AMD. CONCLUSIONS: These data provide 
age- and gender-specific prevalence of ARM and its component lesions in an
ethnically diverse Australian population. Early ARM and AMD prevalence rates
increased sharply from ages 70 and 80 years, respectively, in all ethnic groups. 
These higher rates will continue to increase the importance of AMD as our
population ages.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10919916 [PubMed - indexed for MEDLINE]

3187: Hum Mol Genet. 2000 Jul 22;9(12):1873-9.

Retinoschisin, the X-linked retinoschisis protein, is a secreted photoreceptor
protein, and is expressed and released by Weri-Rb1 cells.

Grayson C, Reid SN, Ellis JA, Rutherford A, Sowden JC, Yates JR, Farber DB, Trump
D.

Department of Medical Genetics, The Wellcome Trust Centre for Molecular
Mechanisms in Disease, Cambridge Institute for Medical Research, University of
Cambridge, Addenbrookes Hospital, Hills Road, Cambridge CB2 2QQ, UK.

X-linked retinoschisis is characterized by microcystic-like changes of the
macular region and schisis within the inner retinal layers, leading to visual
deterioration in males. Many missense and protein-truncating mutations of the
causative gene RS1 have now been identified and are thought to be inactivating.
RS1 encodes a 224 amino acid protein, retinoschisin, which contains a discoidin
domain but is of unknown function. We have generated a polyclonal antibody
against a peptide from a unique region within retinoschisin, which detects a
protein of approximately 28 kDa in retinal samples reduced with dithiothreitol,
but multimers sized >40 kDa under non-reducing conditions. A screen of human
tissues with this antibody reveals retinoschisin to be retina specific and the
antibody detects a protein of similar size in bovine and murine retinae. We
investigated the expression pattern in the retina of both RS1 mRNA (using in situ
hybridization with riboprobes) and retinoschisin (using immunohistochemistry).
The antisense riboprobe detected RS1 mRNA only in the photoreceptor layer but the
protein product of the gene was present both in the photoreceptors and within the
inner portions of the retina. Furthermore, differentiated retinoblastoma cells
(Weri-Rb1 cells) were found to express RS1 mRNA and to release retinoschisin.
These results suggest that retinoschisin is released by photo-receptors and has
functions within the inner retinal layers. Thus, X-linked retinoschisis is caused
by abnormalities in a putative secreted photoreceptor protein and is the first
example of a secreted photo-receptor protein associated with a retinal dystrophy.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 10915776 [PubMed - indexed for MEDLINE]

3188: Jpn J Ophthalmol. 2000 May-Jun;44(3):308-11.

mRNA expression of proto-oncogenes and platelet-derived growth factor in
proliferative vitreoretinal diseases.

Ren G, Fuse N, Abe T, Tamai M.

Department of Ophthalmology, Tohoku University School of Medicine, Sendai, Japan.

PURPOSE: To detect the expression of mRNA of protooncogenes ets-1, c-jun, c-fos, 
and platelet-derived growth factor (PDGF) in proliferative membranes of patients 
with proliferative diabetic retinopathy (PDR) and proliferative vitreoretinopathy
(PVR). METHODS: cDNA was synthesized from mRNA of proliferative membranes from
patients with PDR, PVR, premacular fibrosis (PMF), acute retinal necrosis (ARN), 
and age-related macular degeneration (ARMD). Ets-1, c-jun, c-fos, PDGF-A, and
PDGF-B cDNA were amplified using reverse transcriptase-polymerase chain reaction 
(PCR). RESULTS: Proto-oncogene mRNA was highly expressed in membranes from
patients with severe PDR, grade D PVR. PDGF mRNA was expressed in almost all
samples. CONCLUSIONS: Our results suggest that not only PDGF mRNA was expressed
in the membranes of patients with PDR and PVR, but proto-oncogenes ets-1, c-jun, 
and c-fos mRNA were also expressed.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 10913653 [PubMed - indexed for MEDLINE]

3189: Jpn J Ophthalmol. 2000 May-Jun;44(3):290-5.

Familial cases with age-related macular degeneration.

Yoshida A, Yoshida M, Yoshida S, Shiose S, Hiroishi G, Ishibashi T.

Department of Ophthalmology, Faculty of Medicine, Kyushu University, Fukuoka,
Japan.

BACKGROUND: The pathogenesis of age-related macular degeneration (AMD) remains
unknown. Genetic and environmental factors are thought to be associated with AMD.
Although some studies have reported familial cases of AMD in the United States,
as far as we know, familial cases of AMD have rarely been reported in Japan.
CASES: We describe three families with two members of each family affected with
AMD and one family with three affected members. OBSERVATIONS: In one family, two 
siblings were affected with AMD with choroidal neovascularization and two other
siblings had retinal pigment epithelial abnormalities or drusen of the maculas,
suggesting the heterogeneity of the maculas in the family. However, the other
families did not show such heterogeneity of the fundus. Among the four families, 
six of nine affected individuals had a smoking habit, a risk factor for AMD.
CONCLUSIONS: These findings suggest that the development and progression of AMD
might be associated with genetic factors and environmental factors.

Publication Types: 
    Case Reports

PMID: 10913649 [PubMed - indexed for MEDLINE]

3190: Jpn J Ophthalmol. 2000 May-Jun;44(3):245-9.

Molecular genetic analysis of ABCR gene in Japanese dry form age-related macular 
degeneration.

Fuse N, Suzuki T, Wada Y, Yoshida M, Shimura M, Abe T, Nakazawa M, Tamai M.

Department of Ophthalmology, Tohoku University School of Medicine, Sendai,
Miyagi, Japan.

PURPOSE: To explore whether the mutation in the retina-specific ATP-binding
cassette transporter (ABCR) gene, the Stargardt's disease gene, contributes to
the prevalence of the dry form of age-related macular degeneration (dry AMD) in
Japanese unrelated patients. METHODS: Twenty-five Japanese unrelated patients
with dry AMD who were diagnosed by fluorescein angiography and indocyanine green 
angiography were chosen as the dry AMD group. None of these cases had apparent
choroidal neovascularization. To detect the mutations in the ABCR gene, genomic
DNA was extracted from leukocytes of peripheral blood, and 26 exons of the ABCR
gene were amplified by polymerase chain reaction (PCR). All the PCR products were
then directly sequenced. When a mutation was detected, the occurrence of a
mutation was compared between these AMD patients and the control group. RESULTS: 
After direct sequencing, a point mutation in exon 29 was found in one of the 25
dry AMD patients. In addition, a polymorphism in exon 45 was found in two other
patients, and three sequence variations in exon 23 were detected in all patients.
The incidence in AMD patients in whom a mutation in exon 29 (4%) was detected was
less than that in controls (5%). Screening of the intron-exon boundaries also led
to the identification of intronic mutation in intron 33. CONCLUSION: In this
study we found no relationship between allelic variation in the ABCR gene and the
prevalence of dry AMD in Japanese unrelated patients.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 10913642 [PubMed - indexed for MEDLINE]

3191: Br J Ophthalmol. 2000 Aug;84(8):871-6.

Maculopathy in patients with diabetes mellitus type 1 and type 2: associations
with risk factors.

Zander E, Herfurth S, Bohl B, Heinke P, Herrmann U, Kohnert KD, Kerner W.

Clinic for Diabetes and Metabolic Diseases, Karlsburg, Germany.
ProfKerner@drguth.de

AIM: To examine possible relation between diabetic maculopathy and various risk
factors for diabetic complications in patients with diabetes mellitus type 1 and 
type 2. METHODS: Cross sectional study of two cohorts of diabetic patients,
comprising 1796 patients with type 1 diabetes (mean age 47 years, mean duration
of diabetes 24 years) and 1563 patients with type 2 diabetes (mean age 62 years, 
mean duration of diabetes 16 years). Retinopathy levels (R0-RV) and maculopathy
were assessed by fluorescence angiography and fundus photography and binocular
biomicroscopy. Diabetic neuropathy was assessed by means of computer assisted
electrocardiography and by thermal and vibratory sensory examination. Patients
were classified as normoalbuminuric (<20 microg/min) or microalbuminuric (20-200 
microg/min) according to their albumin excretion rates measured in urine
collected overnight. Using univariate analyses, the effects of selected patient
characteristics on the presence of maculopathy were evaluated. Multiple logistic 
regression analyses were performed to determine independent effects of risk
variables on diabetic maculopathy. RESULTS: Background retinopathy (RII) was
found to be present in 28% of type 1 diabetic patients and in 38% of type 2
diabetic patients. The prevalence of maculopathy in these patients was remarkably
high (42% in type 1 and 53% in type 2 diabetic patients). Patients with
maculopathy had significantly impaired visual acuity. Multiple logistic
correlation analysis revealed that in both types of diabetes maculopathy
exhibited independent associations with duration of diabetes and with neuropathy 
(p <0. 01); in type 1 diabetic patients there were significant associations with 
age at diabetes onset, serum triglyceride and total cholesterol levels (p <0.05);
in type 2 diabetes with serum creatinine levels and with hypertension (p <0.05). 
CONCLUSIONS: Irrespective of the type of diabetes, diabetic patients with long
standing diabetes have a high risk for the development of diabetic maculopathy.
Diabetic maculopathy is closely associated with diabetic nephropathy and
neuropathy and with several atherosclerotic risk factors which suggests that
these factors might have an important role in the pathogenesis of maculopathy.
However, prospective trials are necessary to evaluate the predictive value of
such factors. The findings of the present cross sectional study reinforce the
arguments of previous studies by others for tight control of hypertension and
hyperglycaemia.

PMID: 10906094 [PubMed - indexed for MEDLINE]

3192: Tohoku J Exp Med. 2000 May;191(1):7-20.

Auto iris pigment epithelial cell transplantation in patients with age-related
macular degeneration: short-term results.

Abe T, Yoshida M, Tomita H, Kano T, Sato M, Wada Y, Fuse N, Yamada T, Tamai M.

Department of Ophthalmology, Tohoku University, School of Medicine, Sendai,
Japan. toshi@oph.med.tohoku.ac.jp

Autologous iris pigment epithelial cell transplantation was performed on patients
with exudative age-related macular degeneration (AMD). Autologous IPE cell
culture was performed using autologous serum after iridectomy in 7 patients with 
AMD. The cell suspensions (2 approximately 20 x 10(4) cells) were transplanted
into the submacular lesion of individuals after removal of neovascular membranes.
Subsequent ophthalmological examinations, including best corrected visual acuity 
and fluorescein or indocyanine green angiography, were performed. In addition, 15
patients with AMD, who underwent removal of neovascular membrane without
transplantation, were evaluated as non randomized controls. Varying degrees of
atrophy or defects of choriocapillaris and retinal pigment epithelium were
observed in all of the patients. No cystoid macular edema or fluorescein leakage 
was observed after treatment, but window defects were present. No patient had
decreased visual acuity. One treated patient developed mild subretinal fibrosis
and an other patient developed mild preretinal fibrosis, however no difference
was significant when compared with the control. In conclusion, the treatment
resulted in no significant improvement in macular function, as compared with the 
control; however, no rejection or deterioration in visual acuity occurred up to
the 13 month follow up.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10896035 [PubMed - indexed for MEDLINE]

3193: Invest Ophthalmol Vis Sci. 2000 Jul;41(8):2329-35.

Somatostatin receptor 2A expression in choroidal neovascularization secondary to 
age-related macular degeneration.

Lambooij AC, Kuijpers RW, van Lichtenauer-Kaligis EG, Kliffen M, Baarsma GS, van 
Hagen PM, Mooy CM.

Department of Ophthalmology, Erasmus University Rotterdam, The Netherlands.
lambooji@gen.fgg.eur.nl

PURPOSE: The growth of ocular neovascularization is regulated by a balance
between stimulating and inhibiting growth factors. Somatostatin affects
angiogenesis by inhibiting the growth hormone-insulin-like growth factor axis and
also has a direct antiproliferative effect on human retinal endothelial cells.
The purpose of our study is to investigate the expression of somatostatin
receptor (sst) subtypes and particularly sst subtype 2A (sst2A) in normal human
macula, and to study sst2A in different stages of age-related maculopathy (ARM), 
because of the potential anti-angiogenic effect of somatostatin analogues.
METHODS: Sixteen eyes (10 enucleated eyes, 4 donor eyes, and 2 surgically removed
choroidal neovascular [CNV] membranes) of 15 patients with eyes at different
stages of ARM were used for immunohistochemistry. Formaldehyde-fixed
paraffin-embedded slides were incubated with a polyclonal anti-human sst2A
antibody. mRNA expression of five ssts and somatostatin was determined in the
posterior pole of three normal human eyes by reverse transcriptase-polymerase
chain reaction. RESULTS: The immunohistochemical expression of sstA in newly
formed endothelial cells and fibroblast-like cells was strong in fibrovascular
CNV membranes. mRNA of sst subtypes 1, 2A, and 3, as well as somatostatin, was
present in the normal posterior pole; sst subtypes 4 and 5 were not detectable.
CONCLUSIONS: Most early-formed CNV in ARM express sst2A. The presence of mRNA of 
sst subtype 2A was observed in normal human macula, and subtypes 1 and 3 and
somatostatin are also present. sst2A receptors bind potential anti-angiogenic
somatostatin analogues such as octreotide. Therefore, somatostatin analogues may 
be an effective therapy in early stages of CNV in ARM.

PMID: 10892880 [PubMed - indexed for MEDLINE]

3194: Invest Ophthalmol Vis Sci. 2000 Jul;41(8):2035-42.

Ultrastructural changes in Bruch's membrane of apolipoprotein E-deficient mice.

Dithmar S, Curcio CA, Le NA, Brown S, Grossniklaus HE.

Department of Ophthalmology, Emory University School of Medicine, Atlanta,
Georgia, USA.

PURPOSE: To examine the histologic and ultrastructural changes in Bruch's
membrane (BM) in apolipoprotein E deficient [ApoE(-)] mice in comparison with
age-matched control animals. METHODS: Two-month-old (group 1) and 8-month-old
(group 2) normal control C57BL/6 mice and 2-month-old (group 3) and 8-month-old
(group 4) ApoE(-) mice were studied. All groups of mice were fed a standard
rodent diet. The mice were killed, serum lipid levels were determined, and the
eyes were ultrastructurally examined using standard techniques to measure the
thickness of BM. The area fraction of electron-lucent (EL) particles in BM was
quantified using point-counting stereology. RESULTS: The serum cholesterol levels
of the ApoE(-) mice were significantly higher than those of the control mice (P =
0.0001). There was a significant thickening and EL particle accumulation in BM
associated with age in the control animals. Group 2 had a thicker BM and more EL 
particle accumulation than group 1 (P = 0.0410 for thickness; P = 0.0042 for
particle accumulation). Age-related changes were not seen in ApoE(-) mice;
thickness and accumulation were similar in groups 3 and 4 (P = 0.50, thickness; P
approximately/= 1.0, accumulation). Significant thickening and accumulation were 
seen in young ApoE(-) mice (group 3) versus young control animals (group 1; P =
0.008, thickening; P < 0.0001, EL particle accumulation). Group 4 ApoE(-) mice
did not have a thicker BM or more EL particles than group 2 control animals (P = 
0.2910, thickness; P = 0.35, EL particle accumulation). "Membrane-bounded"
material (material between two membranes) was present significantly more
frequently in ApoE(-) mice. CONCLUSIONS: ApoE(-) mice exhibit accumulation of EL 
particles at an earlier age and have more membrane-bounded material in BM than
control mice. This material has ultrastructural similarities to basal linear
deposit, which accumulates in age-related maculopathy.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 10892840 [PubMed - indexed for MEDLINE]

3195: Ophthalmology. 2000 Jul;107(7):1358-63.

Morphologic characteristics of disciform scarring after radiation treatment for
age-related macular degeneration.

Haas A, Prettenhofer U, Stur M, Hanselmayer R, Feigl B, Berghold A, Langmann G,
Faulborn J.

Department of Ophthalmology, Karl-Franzens-University, Graz, Austria.

OBJECTIVE: To investigate the influence of radiation therapy on the development
of disciform lesions in patients with age-related macular degeneration (AMD).
DESIGN: A prospective, nonrandomized, comparative trial (patient
self-controlled). PARTICIPANTS: Forty eyes with exudative AMD involving the
central fovea in 40 consecutive patients were enrolled in this study.
INTERVENTION: Radiation was administered to the posterior pole with an 8-mV
photon beam from a linear accelerator. A dose of 14.4 Gy, 1.8 Gy per day, five
fractions per week was delivered through a single port. MAIN OUTCOME MEASURES:
The visual acuity and the morphologic characteristics, demonstrated by fundus
photography, fluorescein, and indocyanine green angiography, were investigated
before treatment and every 3 months after treatment over a period of 24 months.
In 10 patients with bilateral disease the disciform lesions were compared.
RESULTS: Twenty five patients could be followed regularly over the period of 24
months. The disciform lesions occurring after radiation were classified in three 
types. Type I (10 patients) was characterized by being smaller than 2 DD in size,
with little fibrotic tissue underneath the retina, but pronounced retinal pigment
epithelial changes. Type II (seven patients) showed extensive growth of the
choroidal neovascularization (CNV) extending to and beyond the arcades with
angiographically active loops in the peripheral parts. Eight patients had type
III lesions develop characterized by a size greater than 2 DD but fewer than 6 DD
and by a different amount of fibrotic tissue, hemorrhage, and lipid. Type I
scarring was significantly associated with occult CNV without pigment epithelial 
detachments, whereas type II scarring was associated with classic CNV at the
initial presentation (P<0.05). CONCLUSIONS: Although no severe side effects have 
been reported after radiation therapy for AMD, a subgroup of patients may
experience extensive growth of CNV after radiation, causing greater functional
damage than occurs spontaneously.

Publication Types: 
    Clinical Trial
    Comparative Study
    Controlled Clinical Trial

PMID: 10889113 [PubMed - indexed for MEDLINE]

3196: Nat Genet. 2000 Jul;25(3):257-8.

ABCR expression in foveal cone photoreceptors and its role in Stargardt macular
dystrophy.

Molday LL, Rabin AR, Molday RS.

Department of Biochemistry and Molecular Biology, University of British Columbia,
Vancouver, British Columbia, Canada.

Mutations in the gene encoding ABCR are responsible for Stargardt macular
dystrophy. Here we show by immunofluorescence microscopy and western-blot
analysis that ABCR is present in foveal and peripheral cone, as well as rod,
photoreceptors. Our results suggest that the loss in central vision experienced
by Stargardt patients arises directly from ABCR-mediated foveal cone
degeneration.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10888868 [PubMed - indexed for MEDLINE]

3197: Hosp Pract (Minneap). 2000 Jun 15;35(6):41-50, 56-8.

Macular degeneration: the emerging genetics.

Lewis RA, Lupski JR.

Medical Scientist Training Program, Baylor College of Medicine, Houston, USA.

Discovery of the gene responsible for a recessive, early-onset maculopathy has
focused attention on a biomolecular pathway in which subtle metabolic flaws
become toxic to irreplaceable retinal cells. The pathway's identification points 
toward specific ways of intervening. Among patients with age-related macular
degeneration, carriers of single mutations in the same gene are proving to be
remarkably common.

Publication Types: 
    Review

PMID: 10884818 [PubMed - indexed for MEDLINE]

3198: Am J Hum Genet. 2000 Aug;67(2):487-91. Epub 2000 Jul 3.

Further evidence for an association of ABCR alleles with age-related macular
degeneration. The International ABCR Screening Consortium.

Allikmets R.

Departments of Ophthalmology and Pathology, Columbia University, New York, NY,
10032, USA. rla22@columbia.edu

Age-related macular degeneration (AMD) accounts for >50% of the registered visual
disability among North American and Western European populations and has been
associated both with environmental factors, such as smoking, and with genetic
factors. Previously we have reported disease-associated variants in the ABCR
(also called ABCA4) gene in a subset of patients affected with this complex
disorder. We have now tested our original hypothesis, that ABCR is a dominant
susceptibility locus for AMD, by screening 1,218 unrelated AMD patients of North 
American and Western European origin and 1,258 comparison individuals from 15
centers in North America and Europe for the two most frequent AMD-associated
variants found in ABCR. These two sequence changes, G1961E and D2177N, were found
in one allele of ABCR in 40 patients ( approximately 3.4%), and in 13 control
subjects ( approximately 0.95%). Fisher's two-sided exact test confirmed that
these two variants are associated with AMD at a statistically significant level
(P<.0001). The risk of AMD is elevated approximately threefold in D2177N carriers
and approximately fivefold in G1961E carriers. The identification of a gene that 
confers risk of AMD is an important step in unraveling this complex disorder.

PMID: 10880298 [PubMed - indexed for MEDLINE]

3199: Br J Ophthalmol. 2000 Jul;84(7):757-60.

Radiotherapy for age related macular degeneration causes transient lens
transparency changes.

Eter N, Wegener A, Schüller H, Spitznas M.

Department of Ophthalmology, Bonn University Medical Center, Bonn, Germany.
eter@uni-bonn.de

AIM: Evaluation of potential side effects of photon radiotherapy on the
transparency of the lens. METHODS: The anterior segments of 14 phakic eyes from
patients suffering from subfoveal neovascularisation as a result of age related
macular degeneration (AMD) were documented by Scheimpflug photography (Topcon
SL-45, Kodak Tmax 400) before the start of radiotherapy as well as 6 and 12
months afterwards. All negatives were evaluated by microdensitometry, and peak
heights for distinct layers of the lens were used for statistical comparison.
External beam radiotherapy (6 MeV photons) consisted of a total dose of 20 Gy,
delivered as 10 fractions of 2 Gy. RESULTS: Six and 12 months following
irradiation statistical comparison of the ratios in density change of lenses from
irradiated versus non-irradiated fellow eyes revealed statistically significant
(p</=0.05) loss of transparency of layers 5 and 7 of the nuclear region. In layer
1 (capsuloepithelial complex) the changes were close to significance. At the 12
month examination, however, all of these significant changes had disappeared.
CONCLUSION: Six months following radiotherapy for AMD, both the anterior
capsuloepithelial region and the nuclear layers showed precataractous changes. As
most of these significant differences had disappeared after 12 months, it is
obvious that these findings reflect acute radiation damage to the lens epithelial
cells and an ionising effect on the proteins of the lens nucleus. Long term
studies will have to be carried out to demonstrate whether or not this acute
radiation damage, which is expressed as a transient increase in light scattering 
of some layers of the lens, actually does lead to permanent transparency changes,
thus reflecting radiation cataractogenesis, and if so, after what time interval
and to what extent cataract occurs.

PMID: 10873989 [PubMed - indexed for MEDLINE]

3200: Br J Ophthalmol. 2000 Jul;84(7):682-6.

Comment in:
    Br J Ophthalmol. 2000 Jul;84(7):679-80.

Sorsby fundus dystrophy without a mutation in the TIMP-3 gene.

Assink JJ, de Backer E, ten Brink JB, Kohno T, de Jong PT, Bergen AA, Meire F.

Department Ophthalmogenetics, The Netherlands Ophthalmic Research Institute,
Netherlands.

AIMS: To examine a large family with an autosomal dominant fundus dystrophy and
to investigate whether or not mutations in TIMP-3 gene were involved. METHODS: A 
large family of 58 individuals with an autosomal dominant fundus dystrophy was
examined ophthalmologically. A DNA linkage analysis in the 22q12.1-q13.2 region
was performed. The TIMP-3 gene was screened for mutations in all five exons.
RESULTS: In this large family 15 individuals were affected. All other individuals
were found to be clinically unaffected. Pisciform flecks in the midperiphery and 
drusen-like deposits were the most typical ophthalmological finding in this
family and were encountered from the fifth decade on. Chorioretinal atrophy and
neovascularisation with disciform lesions characterised the disease from the
sixth decade on. Linkage analysis using an affected only analysis, showed a
maximum positive lod score of 3.94 at theta = 0.0 with marker D22S283. No
mutations possibly causing Sorsby fundus dystrophy were found in either the
exonic sequences, the promotor region, or the 3'UTR. CONCLUSION: The family in
this pedigree has an autosomal dominant fundus dystrophy, which is most probably 
Sorsby fundus dystrophy. Although, in the linkage analysis, significant positive 
lod scores were found with the region 22q12.1-q13.2, no causative mutations could
be identified in the TIMP-3 gene.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10873973 [PubMed - indexed for MEDLINE]

3201: Retina. 2000;20(3):251-6.

Comment in:
    Retina. 2001;21(2):191.

Intravitreal injection of tissue plasminogen activator and gas in subretinal
hemorrhage caused by age-related macular degeneration.

Krepler K, Kruger A, Tittl M, Stur M, Wedrich A.

Department of Ophthalmology, University of Vienna, Austria.

PURPOSE: To assess the efficacy and safety of intravitreal injection of
recombinant tissue plasminogen activator and sulfur hexafluoride gas for
displacement of subretinal hemorrhages in patients with age-related macular
degeneration. METHODS: The authors injected 25 microg of recombinant tissue
plasminogen activator and 0.5 mL sulfur hexafluoride gas intravitreally in 11
patients with subretinal hemorrhages of less than 3 weeks duration. Anatomic and 
functional results were evaluated. RESULTS: Displacement of subretinal blood was 
successful within the first week after surgery in 10 of 11 patients. This was
accompanied by visual improvement in eight patients. After 1 year, visual acuity 
was better than before surgery in five patients. Diagnosis of a choroidal
neovascularization by fluorescein angiography was possible in all patients, and
was treated with laser photocoagulation in five. The authors observed no adverse 
effects of treatment. CONCLUSION: Recombinant tissue plasminogen activator and
gas effectively displace subretinal blood in patients with age-related macular
degeneration. Randomized studies are necessary to prove the benefit of this
simple and safe method in patients with subretinal hemorrhage due to age-related 
macular degeneration.

Publication Types: 
    Clinical Trial

PMID: 10872929 [PubMed - indexed for MEDLINE]

3202: Retina. 2000;20(3):244-50.

Intravitreal triamcinolone acetonide in exudative age-related macular
degeneration.

Danis RP, Ciulla TA, Pratt LM, Anliker W.

Department of Ophthalmology, Indiana University School of Medicine, Indianapolis,
USA.

PURPOSE: To examine the effects of intravitreal injection of 4.0 mg triamcinolone
acetonide on the visual and clinical course of exudative age-related macular
degeneration. METHODS: A randomized clinical trial of a single injection of
triamcinolone acetonide into the vitreous cavity of experimental eyes at baseline
versus observation of untreated subjects was performed in 27 patients followed up
for 6 months. Inclusion criteria included exudative age-related macular
degeneration with subfoveal or occult choroidal neovascularization, and visual
acuity between 20/40 and 20/400. Examination, acuity assessment, fundus
photography, and fluorescein angiography were performed at baseline and at 3 and 
6 months after enrollment. LogMAR visual acuity was compared between groups by a 
repeated measures analysis of variance model. Masked assessment of photographic
studies was performed and groups were compared with Fisher's exact test. RESULTS:
Visual acuity was significantly better in the treated group compared with control
subjects at 3 and 6 months (P < 0.005). Fundus photography and angiography were
more likely to show stability or improvement at 3 and 6 months in the treated
group (P = 0.05). Intraocular pressure elevation was seen in 25% of treated
patients, but was controlled with topical medications. Progression of cataract
was more frequently seen in the treated group. CONCLUSIONS: Intravitreal
triamcinolone acetonide may provide short-term improvement in visual acuity and
fundus findings in exudative macular degeneration. These findings must be
considered preliminary and should be followed by multicenter, masked,
placebo-controlled trials with long-term follow-up.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 10872928 [PubMed - indexed for MEDLINE]

3203: Exp Eye Res. 2000 Apr;70(4):441-9.

A potential role for immune complex pathogenesis in drusen formation.

Johnson LV, Ozaki S, Staples MK, Erickson PA, Anderson DH.

Center for the Study of Macular Degeneration, Neuroscience Research Institute,
University of California, Santa Barbara 93106, USA.

Drusen are abnormal extracellular deposits that accumulate between the retinal
pigmented epithelium and Bruch's membrane and are commonly associated with
age-related macular degeneration. Our recent work has identified a number of
plasma proteins as molecular components of drusen. Of interest is the fact that
many of these drusen-associated molecules are acute phase reactant proteins and
some have established roles in mediating immune responsiveness. As immune and
inflammatory responses appear to play a role in the formation of other pathologic
age-related deposits, we examined the distribution of immunoglobulin molecules
and terminal complement complexes at sites of drusen deposition. Here, we report 
that concentrations of immunoglobulin G and terminal C5b-9 complement complexes
are present in drusen. In addition, we observe that retinal pigmented epithelial 
cells overlying or directly adjacent to drusen, as well as some within apparently
normal epithelia, exhibit cytoplasmic immunoreactivity for immunoglobulin and the
C5 component of complement. Taken together, these results suggest that drusen
biogenesis may be a byproduct of immune responsiveness, and they implicate immune
complex-mediated pathogenesis involving retinal pigmented epithelial cells as an 
initiating event in drusen formation.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.

PMID: 10865992 [PubMed - indexed for MEDLINE]

3204: Brain Res. 2000 Jun 30;869(1-2):39-48.

Depletion of intracellular zinc induces macromolecule synthesis- and
caspase-dependent apoptosis of cultured retinal cells.

Hyun HJ, Sohn J, Ahn YH, Shin HC, Koh JY, Yoon YH.

Department of Neurology, University of Ulsan College of Medicine, 388-1
Poongnap-Dong Songpa-gu, 138-040, Seoul, South Korea.

Although zinc deficiency may contribute to age-related macular degeneration
(ARMD), the pathogenic mechanism is as yet uncertain. In light of evidence that
cellular zinc depletion induces apoptosis in cortical neurons and thymocytes, in 
the present study, we examined the possibility that the same phenomenon occurs
also in retinal cells. Exposure of primary retinal cell cultures to 1-3 microM of
a cell membrane-permeant zinc chelator TPEN for 24 h induced
concentration-dependent death of neurons, photoreceptor cells, and astrocytes.
Addition of zinc or copper reversed TPEN toxicity to all cell components,
indicating the particular involvement of zinc chelation in cell death. Consistent
with apoptosis, oligonucleosomal DNA fragmentation and chromatin condensation
accompanied, and the protein synthesis inhibitor cycloheximide blocked the
TPEN-induced retinal cell death. During TPEN-induced retinal cell apoptosis,
cleavage/activation of procaspase-1, but little of procaspase-3, was observed.
Consistent with this finding, a broad-spectrum caspase inhibitor (zVAD-fmk) was
significantly more protective than a caspase-3-selective inhibitor (DEVD-fmk).
The present study has demonstrated that depletion of intracellular zinc is
sufficient to induce macromolecule synthesis- and caspase-dependent apoptosis of 
cultured retinal cells. In light of the possibility that zinc depletion may
contribute to the pathogenesis of ARMD, the current culture model may be a useful
tool for the investigation of the mechanism of zinc depletion-induced retinal
cell death.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10865057 [PubMed - indexed for MEDLINE]

3205: Ophthalmologica. 2000;214(4):289-91.

The apolipoprotein E epsilon4 allele is unlikely to be a major risk factor of
age-related macular degeneration in Chinese.

Pang CP, Baum L, Chan WM, Lau TC, Poon PM, Lam DS.

Department of Ophthalmology and Visual Sciences, Chinese University of Hong Kong,
Hong Kong. cppang@cuhk.edu.hk

Apolipoprotein E (ApoE) is a major transporter of lipids and cholesterol in the
nervous system. Age-related macular degeneration (ARMD), characterized by drusen 
containing lipids, was reported to show a lower frequency of the ApoE epsilon4
allele than control subjects. We sought to examine the association of this
polymorphism with ARMD in Hong Kong Chinese. Among 98 ARMD subjects, the
frequency of epsilon4 carriers showed a trend toward a decrease compared to
controls, but it was not significant (11.2 vs. 15.0%, p < 0.52). The association 
of epsilon4 with an apparent reduced risk of ARMD was reported previously in the 
exudative form of the disease, however among 39 exudative ARMD patients there was
also no significant difference in epsilon4 frequency (12.8%, p < 0.93). The lack 
of a statistically significant effect of epsilon4 may be due to the lower
frequency of epsilon4 in Chinese than Europeans. Thus we cannot exclude a
possible effect of this allele on ARMD risk, but we can conclude that this allele
is likely not a major factor influencing ARMD risk in the Chinese. Copyright 2000
S. Karger AG, Basel.

Publication Types: 
    Comparative Study

PMID: 10859513 [PubMed - indexed for MEDLINE]

3206: Ophthalmologica. 2000;214(4):240-5.

Indocyanine green angiography in Fundus flavimaculatus.

Schwoerer J, Secrétan M, Zografos L, Piguet B.

University Eye Department, Jules Gonin Hospital, Lausanne, Switzerland.

PURPOSE: To describe the characteristic findings of fundus flavimaculatus
(Stargardt disease) as seen on indocyanine green angiography. METHODS: Twelve
eyes of 6 consecutive patients with fundus flavimaculatus were studied by fundus 
color photographs, fluorescein angiography and indocyanine green angiography.
RESULTS: Indocyanine green angiography allowed visualization of small, clearly
demarcated areas in which hypofluorescence increased over time, leading
eventually to a large reticular pattern with small areas of normal-appearing
choroid encircled by a well-defined network of hypofluorescent curvilinear
lesions. These hypofluorescent flecks were present in all 12 eyes but
corresponded only partially to the yellow flecks visible on biomicroscopy of the 
fundus. The peripapillary area was well preserved on indocyanine green
angiography and the periphery did not show any visible abnormalities.
CONCLUSIONS: The hypofluorescent curvilinear areas visualized on indocyanine
green angiography form a reticular pattern that is similar to the polygonal shape
of the watershed zones between terminal choroidal arterioles, which supply the
choriocapillaris. These dark areas may reflect choriocapillaris defects secondary
to lysis of lipofuscin-engorged retinal pigment epithelial cells. The typical
lesions of fundus flavimaculatus thus seem to be situated in areas of least
vascular supply. Their absence in the peripapillary area, which benefits from
anastomotic vascular connections, would support this hypothesis. Copyright 2000
S. Karger AG, Basel.

Publication Types: 
    Comparative Study

PMID: 10859505 [PubMed - indexed for MEDLINE]

3207: J Biol Chem. 2000 Sep 1;275(35):27027-31.

A novel tissue inhibitor of metalloproteinases-3 mutation reveals a common
molecular phenotype in Sorsby's fundus dystrophy.

Langton KP, McKie N, Curtis A, Goodship JA, Bond PM, Barker MD, Clarke M.

Division of Oncology & Cellular Pathology, Pathology Section, University of
Sheffield, Medical School, Beech Hill Road, Sheffield, S10 2RX, United Kingdom.

Sorsby's fundus dystrophy (SFD) is a dominantly inherited degenerative disease of
the retina that leads to loss of vision in middle age. It has been shown to be
caused by mutations in the gene for tissue inhibitor of metalloproteinases-3
(TIMP-3). Five different mutations have previously been identified, all
introducing an extra cysteine residue into exon 5 (which forms part of the
C-terminal domain) of the TIMP-3 molecule; however, the significance of these
mutations to the disease phenotype was unknown. In this report, we describe the
expression of several of these mutated genes, together with a previously
unreported novel TIMP-3 mutation from a family with SFD that results in
truncation of most of the C-terminal domain of the molecule. Despite these
differences, all of these molecules are expressed and exhibit characteristics of 
the normal protein, including inhibition of metalloproteinases and binding to the
extracellular matrix. However, unlike wild-type TIMP-3, they all form dimers.
These observations, together with the recent finding that expression of TIMP-3 is
increased, rather than decreased, in eyes from patients with SFD, provides
compelling evidence that dimerized TIMP-3 plays an active role in the disease
process by accumulating in the eye. Increased expression of TIMP-3 is also
observed in other degenerative retinal diseases, including the more severe forms 
of age-related macular degeneration, the most common cause of blindness in the
elderly in developed countries. We hypothesize that overexpression of TIMP-3 may 
prove to be a critical step in the progression of a variety of degenerative
retinopathies.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10854443 [PubMed - indexed for MEDLINE]

3208: Eur J Hum Genet. 2000 Apr;8(4):286-92.

Mutations in the VMD2 gene are associated with juvenile-onset vitelliform macular
dystrophy (Best disease) and adult vitelliform macular dystrophy but not
age-related macular degeneration.

Krämer F, White K, Pauleikhoff D, Gehrig A, Passmore L, Rivera A, Rudolph G,
Kellner U, Andrassi M, Lorenz B, Rohrschneider K, Blankenagel A, Jurklies B,
Schilling H, Schütt F, Holz FG, Weber BH.

Institut für Humangenetik, Universität Würzburg, Germany.

Recently, the VMD2 gene has been identified as the causative gene in
juvenile-onset vitelliform macular dystrophy (Best disease), a central
retinopathy primarily characterised by an impaired function of the retinal
pigment epithelium. In this study we have further characterised the spectrum of
VMD2 mutations in a series of 41 unrelated Best disease patients. Furthermore we 
expanded our analysis to include 32 unrelated patients with adult vitelliform
macular dystrophy (AVMD) and 200 patients with age-related macular degeneration
(AMD). Both AVMD and AMD share some phenotypic features with Best disease such as
abnormal subretinal accumulation of lipofuscin material, progressive geographic
atrophy and choroidal neovascularisation, and may be the consequence of a common 
pathogenic mechanism. In total, we have identified 23 distinct disease-associated
mutations in Best disease and four different mutations in AVMD. Two of the
mutations found in the AVMD patients were also seen in Best disease suggesting a 
considerable overlap in the aetiology of these two disorders. There were no
mutations found in the AMD group. In addition, four frequent intragenic
polymorphisms did not reveal allelic association of the VMD2 locus with AMD.
These data exclude a direct role of VMD2 in the predisposition to AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10854112 [PubMed - indexed for MEDLINE]

3209: Proc Natl Acad Sci U S A. 2000 Jun 20;97(13):7154-9.

Biosynthesis of a major lipofuscin fluorophore in mice and humans with
ABCR-mediated retinal and macular degeneration.

Mata NL, Weng J, Travis GH.

Center for Basic Neuroscience and Department of Psychiatry, University of Texas
Southwestern Medical Center, Dallas, TX 75235-9111, USA.

Increased accumulation of lipofuscin in cells of the retinal pigment epithelium
(RPE) is seen in several forms of macular degeneration, a common cause of
blindness in humans. A major fluorophore of lipofuscin is the toxic bis-retinoid,
N-retinylidene-N-retinylethanolamine (A2E). Previously, we generated mice with a 
knockout mutation in the abcr gene. This gene encodes rim protein (RmP), an
ATP-binding cassette transporter in rod outer segments. Mice lacking RmP
accumulate A2E in RPE cells at a greatly increased rate over controls. Here, we
identify three precursors of A2E in ocular tissues from abcr-/- mice and humans
with ABCR-mediated recessive macular degenerations. Our results corroborate the
scheme proposed by C. A. Parish, M. Hashimoto, K. Nakanishi, J. Dillon & J.
Sparrow [Proc. Natl. Acad. Sci. USA (1998) 95, 14609-14613], for the biosynthesis
of A2E: (i) condensation of all-trans-retinaldehyde (all-trans-RAL) with
phosphatidylethanolamine to form a Schiff base; (ii) condensation of the amine
product with a second all-trans-RAL to form a bis-retinoid; (iii) oxidation to
yield a pyridinium salt; and (iv) hydrolysis of the phosphate ester to yield A2E.
The latter two reactions probably occur within RPE phagolysosomes. As predicted
by this model, formation of A2E was completely inhibited when abcr-/- mice were
raised in total darkness. Also, once formed, A2E was not eliminated by the RPE.
These data suggest that humans with retinal or macular degeneration caused by
loss of RmP function may slow progression of their disease by limiting exposure
to light. The precursors of A2E identified in this study may represent
pharmacological targets for the treatment of ABCR-mediated macular degeneration.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 10852960 [PubMed - indexed for MEDLINE]

3210: Gene Ther. 2000 Jun;7(11):978-85.

Experimental subretinal neovascularization is inhibited by adenovirus-mediated
soluble VEGF/flt-1 receptor gene transfection: a role of VEGF and possible
treatment for SRN in age-related macular degeneration.

Honda M, Sakamoto T, Ishibashi T, Inomata H, Ueno H.

Department of Ophthalmology, Faculty of Medicine, Kyushu University, Fukuoka,
Japan.

Accumulating evidence has shown the importance of vascular endothelial growth
factor (VEGF) in chorioretinal angiogenesis. However, whether or not VEGF is
indeed critical for the pathogenesis of subretinal neovascularization (SRN) in
adulthood, which is a serious complication of age-related macular degeneration,
has to be further investigated. We constructed an adenovirus expressing an entire
ectodomain of the human VEGF receptor/flt-1 fused to Fc portion of human IgG
(Adflt-ExR): this soluble receptor is secreted from Adflt-ExR-transfected cells. 
We studied the effect of Adflt-ExR on the formation of experimental SRN.
Experimental SRN was induced by intense photocoagulation on the retina in
pigmented rats and Adflt-ExR was injected into the femoral muscle. The formation 
of SRN assessed by fluorescein angiography was more significantly inhibited for 7
days in the Adflt-ExR-treated rats than in the control rats who received either
an adenovirus vector encoding LacZ gene or balanced salt solution (BSS). The
serum concentration of this soluble receptor increased for 7 days and thereafter 
gradually decreased. An immunohistochemical study disclosed the fibroblast cell
proliferation and inflammatory cell infiltration to be reduced in the
photocoagulation spot of Adflt-ExR-treated rats. VEGF plays a crucial role in the
formation of SRN and VEGF soluble receptor gene transfection can inhibit SRN.
This method will contribute to future gene therapy for age-related macular
degeneration.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10849558 [PubMed - indexed for MEDLINE]

3211: Ophthalmic Surg Lasers. 2000 May-Jun;31(3):198-202.

Retina tomography after vitrectomy for macular edema of central retinal vein
occlusion.

Sekiryu T, Yamauchi T, Enaida H, Hara Y, Furuta M.

Ohara General Hospital, Fukushima City, Fukushima Pref., Japan.

PURPOSE AND OBJECTIVE: To report retina tomography after vitrectomy for macular
edema in central retinal vein occlusion (CRVO). PATIENTS AND METHODS: Five
patients with macular edema caused by CRVO were examined using optical coherence 
tomography (OCT) through their clinical courses. RESULTS: The retinal thickness
through the fixation was reduced in all 5 eyes. Preoperatively, the retina
thickness at the foveola was more than 500 microm in three eyes and more than
1000 microm in 2 eyes. The retina thickness was reduced to 311+80 microm within
two weeks on average. Visual acuity was improved by two or more lines in 3 of 5
eyes. CONCLUSION: Vitrectomy is worthy of consideration when macular edemas are
prolonged in patients of CRVO. OCT is a useful instrument for management and
treatment of macular edema.

Publication Types: 
    Case Reports
    Comparative Study

PMID: 10847495 [PubMed - indexed for MEDLINE]

3212: Ophthalmic Surg Lasers. 2000 May-Jun;31(3):192-7.

Optical coherence tomography after laser photocoagulation for clinically
significant macular edema.

Rivellese M, George A, Sulkes D, Reichel E, Puliafito C.

Ophthalmology Department, New England Medical Center, Tufts University School of 
Medicine, Boston, MA 02111, USA.

BACKGROUND AND OBJECTIVE: To demonstrate the utility of optical coherence
tomography (OCT) for documenting an early response to laser photocoagulation in
clinically significant macular edema (CSME) secondary to diabetes. PATIENTS AND
METHODS: Five eyes of four patients were selected for review based on the
diagnosis of CSME. All eyes had a clinical diagnosis of CSME based on slit lamp
biomicroscopy. All eyes underwent focal/grid laser photocoagulation to areas of
retinal thickening detected by OCT and clinical exam. Pre and post-treatment
optical coherence tomograms were obtained for all patients. RESULTS: All eyes
selected for review had an early positive response to focal laser
photocoagulation. OCT was useful for demonstrating areas of retinal thickening
prior to laser treatment. Serial macular maps demonstrated the resolution of
retinal thickening after laser photocoagulation in all eyes. CONCLUSION: OCT is a
useful tool for evaluating and documenting CSME both before and after focal/grid 
laser photocoagulation. OCT is capable of detecting an early positive response to
photocoagulation for macular edema.

Publication Types: 
    Case Reports

PMID: 10847494 [PubMed - indexed for MEDLINE]

3213: Ophthalmic Surg Lasers. 2000 May-Jun;31(3):187-91.

Optical coherence tomography findings in diabetic macular edema before and after 
vitrectomy.

Giovannini A, Amato G, Mariotti C, Scassellati-Sforzolini B.

Clinica Oculistica dell'Universita di Ancona, Italy.

BACKGROUND AND OBJECTIVE: To assess the role of optical coherence tomography
(OCT) in the evaluation and follow-up after vitrectomy for diabetic macular
edema. MATERIALS AND METHODS: The 18 eyes of 12 patients affected by presumed
diabetic vitreous-induced macular edema underwent biomicroscopy with a Goldmann
contact lens, fluorescein angiography, and OCT. RESULTS: OCT revealed two
patterns of edema. The first group (15 eyes) was characterized by widespread
thickening of the neurosensory retina with an increased nonhomogeneous
reflectivity of the inner retinal layers; cystoid-like spaces of absent or
reduced reflectivity in the neurosensory retina were also present. In the second 
group (3 eyes), a cystoid macular edema with a dome-shaped foveal profile because
of a markedly increased retinal thickness in the foveal region was observed. The 
disappearance of the physiologic foveal profile was always seen. Biomicroscopy
revealed an increased reflex of the inner limiting membrane in the first group
and minimal alterations in the second one. Four patients (7 eyes) underwent
vitrectomy with posterior hyaloid removal. In 5 eyes, the patients experienced a 
visual improvement greater than two Snellen lines. The restoration of the normal 
foveal profile and the reduction of the retinal thickness on the OCT were evident
in all cases one month after surgery. CONCLUSION: OCT appears to be a useful tool
in the diagnosis and management of diabetic macular edema and in the monitoring
of the morphological changes after vitrectomy.

Publication Types: 
    Comparative Study

PMID: 10847493 [PubMed - indexed for MEDLINE]

3214: Ophthalmic Surg Lasers. 2000 May-Jun;31(3):182-6.

Optical coherence tomography for retinal thickness measurement in diabetic
patients without clinically significant macular edema.

Schaudig UH, Glaefke C, Scholz F, Richard G.

Department of Ophthalmology, Augenklinik und Poliklinik, Universitats-Krankenhaus
Eppendorf, Hamburg, Germany.

BACKGROUND AND OBJECTIVE: To evaluate the potential of optical coherence
tomography (OCT) as a screening method for retinal thickness measurements in
diabetic patients. PATIENTS AND METHODS: We used a previously described pattern
of six 5 mm OCT scans through the center of fixation in 45 diabetic patients
without clinically significant macular edema: 22 patients (group 1) had no
diabetic retinopathy (ETDRS classification); 18 (group 2) had nonproliferative
retinopathy; 5 patients with peripheral neovascularization did not enter
statistical analysis; 25 normal healthy subjects were used as a control group.
Retinal thickness was measured at five locations in each scan: in the fovea, at
the foveal rim, and outside the macula. Measurements were identified in
nonaligned images and taken from raw data A-scans. Locations were grouped into
hemispheres, quadrants and rings, and mean values tested for statistically
significant differences using Mann-Whitney U-Wilcoxon rank sum W test. RESULTS:
Differences in retinal thickness were found to be significant in the macula
(controls vs group 2 P = 0.0266), at the foveal rim (controls vs group 1 and 2: P
= 0.0386 and P = 0.0193), in the nasal and superior hemisphere (controls vs group
2: P = 0.0251 and P = 0.0187), and in the superior nasal quadrant (controls vs
group 1 and group 1 vs group 2: P = 0.0022 and P = 0.0462). CONCLUSIONS:
Significant differences of retinal thickness between patients with diabetic
retinopathy and normals can be detected by OCT even in the absence of clinically 
significant macular edema. Significant differences between diabetic patients with
and without retinopathy are most likely to be found in the superior nasal
quadrant.

Publication Types: 
    Comparative Study

PMID: 10847492 [PubMed - indexed for MEDLINE]

3215: Curr Opin Ophthalmol. 2000 Apr;11(2):94-100.

Latanoprost and cystoid macular edema: is there a causal relation?

Schumer RA, Camras CB, Mandahl AK.

Department of Ophthalmology, Mt. Sinai School of Medicine, New York, New York,
USA.

Published reports of the occurrence of cystoid macular edema (CME) in eyes being 
treated with latanoprost have led to concern regarding a possible causal relation
between the two. Review of all published cases (28 eyes in 25 patients), plus
another case reported here for the first time, indicates that all eyes had
independent risk for development of CME, so that definitive conclusions about a
causal relation cannot be established. In addition, controlled clinical trials
and experimental studies with latanoprost have given no indication that
latanoprost causes clinical CME. Pharmacokinetic considerations indicate that the
concentration of latanoprost expected in the posterior segment of the eye is too 
low to have a pharmacologic effect, and latanoprost is not known to exhibit
vasoactive or inflammatory properties. Nevertheless, reports of a possible
association between CME and latanoprost use must be given serious consideration, 
and in eyes that are at risk for CME, an increased level of surveillance for its 
development is recommended.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't
    Review

PMID: 10848227 [PubMed - indexed for MEDLINE]

3216: Eye. 2000 Apr;14 ( Pt 2):155-64.

Proton beam irradiation of subfoveal choroidal neovascularisation in age-related 
macular degeneration.

Flaxel CJ, Friedrichsen EJ, Smith JO, Oeinck SC, Blacharski PA, Garcia CA, Chu
HH.

Department of Ophthalmology, Loma Linda University Medical Center, California,
USA. flaxelcj@aol.com

PURPOSE: To assess the safety and potential toxicity of proton beam radiation in 
the treatment of subfoveal choroidal neovascular membrane (CNVM) due to
age-related manner degeneration (ARMD) in a prospective, non-randomised study.
METHODS: Forty-eight eyes of 46 consecutive patients with subfoveal CNVM due to
ARMD, not amenable to laser photocoagulation, were treated prospectively with a
single proton beam exposure. Two dose regimens were evaluated: 8 CGE (Cobalt Gray
Equivalent) and 14 CGE. Patients were followed for an average of 22.1 months
after proton beam treatment. RESULTS: At the 12 month follow-up, 44% of eyes in
the 8 CGE group and 75% of the eyes in the 14 CGE group had stabilized or
improved visual acuity. Complex size in the 8 CGE group as measured on standard
fluorescein angiography (FA), decreased or had no change initially but showed
less effect over time, while the eyes treated with 14 CGE maintained decreased
leakage over the follow-up period of 12 months. However, 11 eyes in the 14 CGE
group experienced radiation retinopathy, with the onset between 3 and 30 months. 
Seven of these 11 eyes have demonstrated some visual loss but only 1 eye
developed severe visual loss at 15 months after proton treatment. CONCLUSIONS: To
date, 14 CGE has suggested a favourable influence on visual function and growth
inhibition of CNVM. Proton beam irradiation appears to inhibit CNVM growth. The
14 CGE dose regimen appears to have a longer effect of CNVM growth than does 8
CGE, with overall stabilisation of visual function and growth inhibition.
Radiation retinopathy has developed over time, but severe visual loss has been
limited. On the basis of the incidence of radiation retinopathy, adjustments in
the total radiation dosage and/or fractionation of the dosage should be
considered.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 10845009 [PubMed - indexed for MEDLINE]

3217: Am Fam Physician. 2000 May 15;61(10):3035-42.

Comment in:
    Am Fam Physician. 2001 Jan 15;63(2):225.

Age-related macular degeneration: update for primary care.

Fong DS.

Southern California Permanente Medical Group, Baldwin Park, California, USA.

Age-related macular degeneration is the leading cause of severe vision loss among
the elderly. In this condition, central vision is lost, but peripheral vision
almost always remains intact. Affected persons rarely require canes or guide
dogs. The diagnosis of age-related macular degeneration is based on symptoms and 
ophthalmoscopic findings, and the disease can be classified into atrophic and
exudative forms. The two currently proven treatments are laser photocoagulation
and photodynamic therapy, but these measures are effective in only a small
fraction of eyes with the exudative form of macular degeneration. Vision
rehabilitation can help patients maximize their remaining vision and adapt so
that they can perform activities of daily living. Families need encouragement in 
providing support and helping patients adjust to being partially sighted.

PMID: 10839553 [PubMed - indexed for MEDLINE]

3218: Ophthalmic Physiol Opt. 2000 Mar;20(2):137-41.

Evidence for mild blue-yellow colour vision deficits immediately following
fluorescein angiography.

Sankeralli MJ, Chen JC, Metha AB, Mullen KT.

McGill Vision Research, Department of Ophthalmology, McGill University, Montreal,
Quebec, Canada.

AIMS: We have investigated the short term effects of fluorescein angiography on
the blue-yellow, red-green, and luminance contrast sensitivity of patients with
early age-related macular degeneration (ARMD). METHODS: Nine ARMD patients with
no exudative complications and a visual acuity of 20/60 or better in the tested
eye were selected. Cardinal colour directions for the isolation of the red-green,
blue-yellow and achromatic (luminance) visual mechanisms were determined for each
patient. Contrast sensitivity was measured in each cardinal colour direction
immediately before and 20 min after standard 20-flash fluorescein angiography.
RESULTS: A significant, albeit mild, reduction for blue-yellow contrast
sensitivity following angiography was observed (ANOVA, alpha = 0.05). Fluorescein
angiographic exposure had no significant effect on red-green or luminance
contrast sensitivity. CONCLUSION: Our results show that fluorescein angiography
causes at least a short term deficit selective to blue-yellow contrast
sensitivity in our patient group.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10829137 [PubMed - indexed for MEDLINE]

3219: Diabet Med. 2000 Apr;17(4):326-8.

Macular oedema with associated uveitis and cataract following presentation of
Type 1 diabetes mellitus in severe ketoacidosis.

Gordon D, Browne BH.

Department of Diabetes, Stobhill Hospital, Glasgow, UK.

We present a case of cystoid macular oedema presenting in a newly diagnosed
diabetic teenager. She had developed anterior uveitis prior to diabetes and
whether this contributed to the subsequent ocular complications remains
speculative. The macular changes resolved spontaneously over 6 months without the
use of grid laser photocoagulation.

Publication Types: 
    Case Reports

PMID: 10821301 [PubMed - indexed for MEDLINE]

3220: Br J Radiol. 2000 Mar;73(867):305-13.

External beam radiotherapy in exudative age-related macular degeneration: a
pooled analysis of phase I data.

Chakravarthy U, MacKenzie G.

Queen's University of Belfast, UK.

In recent years external beam radiotherapy (EBRT) has been proposed as a
treatment for the wet form of age-related macular degeneration (AMD) where
choroidal neovascularization (CNV) is the hallmark. While the majority of pilot
(Phase I) studies have reported encouraging results, a few have found no benefit,
i.e. EBRT was not found to result in either improvement or stabilization of
visual acuity of the treated eye. The natural history of visual loss in untreated
CNV of AMD is highly variable. Loss of vision is influenced mainly by the
presenting acuity, and size and composition of the lesion, and to a lesser extent
by a variety of other factors. Thus the variable outcome reported by the small
Phase I studies of EBRT published to date may simply reflect the variation in
baseline factors. We therefore obtained information on 409 patients treated with 
EBRT from eight independent centres, which included details of visual acuity at
baseline and at subsequent follow-up visits. Analysis of the data showed that
22.5% and 14.9% of EBRT-treated eyes developed moderate and severe loss of
vision, respectively, during an average follow-up of 13 months. Initial visual
acuity, which explained 20.5% of the variation in visual loss, was the most
important baseline factor studied. Statistically significant differences in loss 
of vision were observed between centres, after considering the effects of case
mix factors. Comparisons with historical data suggested that while moderate
visual loss was similar to that of the natural history of the disease, the
likelihood of suffering severe visual loss was halved. However, the benefit in
terms of maintained/improved vision in the treated eye was modest.

Publication Types: 
    Meta-Analysis

PMID: 10817048 [PubMed - indexed for MEDLINE]

3221: Arch Ophthalmol. 2000 May;118(5):681-8.

Prospective study of alcohol consumption and the risk of age-related macular
degeneration.

Cho E, Hankinson SE, Willett WC, Stampfer MJ, Spiegelman D, Speizer FE, Rimm EB, 
Seddon JM.

Department of Nutrition, Harvard School of Public Health, Boston, Mass, USA.
hpeyc@capecod.bwh.harvard.edu

OBJECTIVE: To describe the relationship between alcohol consumption and the
incidence of age-related macular degeneration (AMD). METHODS: We conducted a
prospective study among female nurses between 1980 and 1994 and among male health
professionals between 1986 and 1994. We included 32764 women and 29488 men who
were 50 years or older, without a diagnosis of AMD or cancer at baseline, and
added additional subjects to the analysis as they reached 50 years of age. Their 
alcohol intake was assessed at baseline and updated during follow-up evaluations 
using a validated semiquantitative food-frequency questionnaire. After separate
analyses for women and men, pooled estimates of the relationship of alcohol to
the risk of AMD were calculated. RESULTS: Age-related macular degeneration
associated with a visual acuity loss of 20/30 or worse, including the early and
dry and wet types, was diagnosed in 298 women (from 697498 person-years of
follow-up) and 153 men (229 180 person-years) by 1994, the end of follow-up.
After controlling for age, smoking, and other risk factors, the pooled relative
risks (RRs) and 95% confidence intervals (CIs) for AMD compared with nondrinkers 
were 1.0 (0.7-1.2) for drinkers who consumed 0.1 to 4.9 g/d of alcohol; 0.9
(0.6-1.4) for 5 to 14.9 g/d; 1.1 (0.7-1.7) for 15 to 29.9 g/d; and 1.3 (0.9-1.8) 
for 30 g/d or more. Among women, there was a suggestion of a modest increased
risk of the disease in drinkers who consumed 30 g/d or more (RR, 1.5; 95% CI,
1.0-2.4); this was limited to an increased risk of the early and dry form (RR,
2.0; 95% CI, 1.2-3.4). No specific type of alcohol provided protection against
AMD. CONCLUSION: This prospective study does not support an inverse relationship 
between moderate alcohol consumption and risk of AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 10815161 [PubMed - indexed for MEDLINE]

3222: Arch Ophthalmol. 2000 May;118(5):630-4.

Indocyanine green angiography of well-defined plaque choroidal neovascularization
in age-related macular degeneration.

Pece A, Bolognesi G, Introini U, Pacelli G, Calori G, Brancato R.

Department of Ophthalmology and Visual Sciences, Scientific Institute H San
Raffaele, University of Milano, Milan, Italy.

OBJECTIVE: To determine the natural course of well-defined plaque choroidal
neovascularization (CNV) using indocyanine green angiography. METHODS: Two
ophthalmologists, experts in macular diseases and indocyanine green angiography, 
examined 40 eyes with exudative age-related macular degeneration and a
well-defined plaque CNV using complete ophthalmoscopic evaluation, fluorescein
angiography, and indocyanine green angiography. The increase in the size of the
plaques was analyzed using multivariate analysis, in relation to the worsening of
visual acuity, with adjustment for age, sex, and length of follow-up. RESULTS:
Mean follow-up was 13.5 months (median, 11 months). Initial and final mean visual
acuity were 20/46 (median, 20/50) and 20/65 (median, 20/100), respectively. The
mean initial size of the plaque was 6.62 mm2 (median, 6.20 mm2), and the mean
final size was 10.40 mm2 (median, 9.76 mm2). The enlargement was statistically
significant (P<.001). CONCLUSIONS: We found that plaque CNV tends to become
larger with time, the enlargement reaching about 40% in 1 year of follow-up. The 
resulting loss of visual acuity, however, is not significant, and is slightly
correlated with the extension of the lesion; it also does not appear to be
directly related to sex.

PMID: 10815154 [PubMed - indexed for MEDLINE]

3223: Arch Ophthalmol. 2000 May;118(5):625-9.

Correlation of histologic 2-dimensional reconstruction and confocal scanning
laser microscopic imaging of choroidal neovascularization in eyes with
age-related maculopathy.

Grossniklaus HE, Cingle KA, Yoon YD, Ketkar N, L'Hernault N, Brown S.

Department of Ophthalmology, Emory University School of Medicine, Atlanta, GA,
USA. ophtheg@emory.edu

OBJECTIVE: To topographically localize vascular channels, macrophages, and
retinal pigment epithelium and other components of choroidal neovascularization
(CNV) associated with age-related maculopathy. METHODS: Two postmortem eyes with 
age-related maculopathy and CNV were evaluated. The formalin-fixed CNV complex
was excised and processed for confocal scanning laser microscopy including
immunostaining for factor VIII-related antigen and incubation with Ig fluorescein
isothiocyanate. After confocal microscopy, the specimens were serial step
sectioned, stained, and 2-dimensional topographic reconstructions were made. The 
confocal images were compared with the 2-dimensional reconstructions. RESULTS:
Both specimens contained central disciform scars surrounded by areas of intact
retinal pigment epithelium. The first specimen was more atrophic and contained
fewer choroidal neovascular channels than the second specimen. The topographic
arrangement of the CNV and retinal pigment epithelial changes in the confocal
images corresponded with the 2-dimensional reconstructions. Macrophages were
concentrated around areas of vascularization. CONCLUSION: Confocal scanning laser
microscopy of excised CNV simulates fluorescein angiography and topographic
localization of the components of CNV provides insight into the pathogenesis of
CNV.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 10815153 [PubMed - indexed for MEDLINE]

3224: Hum Mol Genet. 2000 May 22;9(9):1329-49.

A full genome scan for age-related maculopathy.

Weeks DE, Conley YP, Mah TS, Paul TO, Morse L, Ngo-Chang J, Dailey JP, Ferrell
RE, Gorin MB.

Department of Human Genetics, University of Pittsburgh Graduate School of Public 
Health, Pittsburgh, PA 15261, USA,

Age-related macular degeneration or age-related maculopathy (ARM) is a major
public health issue, as it is the leading cause of irreversible vision loss in
the elderly in the Western world. Using three diagnostic models, we have
genotyped markers in 16 plausible candidate regions and have carried out a
genome-wide screen for ARM susceptibility loci. A panel of 225 ARM families
comprising up to 212 affected sib pairs was genotyped for 386 markers. Under our 
most stringent diagnostic model, the regions with the strongest evidence of
linkage were on chromosome 9 near D9S301 and on 10 near D10S1230, with peak
multipoint heterogeneity LOD scores (HLOD) of 1.87 and 1. 42 and peak
GeneHunter-Plus non-parametric LOD scores (GHP LOD) of 1. 69 and 1.83. After
expanding our initial set of families to 364 ARM families with up to 329 affected
sib pairs, the linkage signal on chromosome 9 vanished, while the chromosome 10
signal decreased to a GHP LOD of about 1.0, with a SimIBD P -value of 0.008 under
the broadest diagnostic model with marker D10S1236. After error filtration, the
GHP LOD increased to 1.27 under our most stringent model and 1.42 under our
broadest model, peaking near D10S1236. This peak was seen consistently across all
three diagnostic models. Our analyses also excluded up to nine different
candidate regions and identified a few other regions of potential linkage,
suitable for further studies. Of particular interest was the region on chromosome
5 near D5S1480, where a reasonable candidate gene, glutathione peroxidase 3,
resides.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 10814715 [PubMed - indexed for MEDLINE]

3225: Can J Ophthalmol. 2000 Apr;35(3):127-33.

Difference between ophthalmologists' and patients' perceptions of quality of life
associated with age-related macular degeneration.

Brown GC, Brown MM, Sharma S.

Retina Vascular Unit, Wills Eye Hospital, Jefferson Medical College,
Philadelphia, Pa., USA. Gary0514@aol.com

BACKGROUND: There may be a wide disparity between the perceptions of patients and
those of their treating physicians concerning the quality of life associated with
a given state of health. Because of this potential for difference of opinion, we 
performed a study to evaluate patients' and ophthalmologists' perceptions of
quality of life, as measured by utility analysis, associated with visual loss
secondary to age-related macular degeneration (AMD). METHODS: Cross-sectional
study. Utilities were assessed, by means of both the time trade-off method and
the standard gamble method, for various degrees of theoretical visual loss
secondary to AMD for ophthalmologists-in-training and graduate ophthalmologists. 
These were compared to utilities for a known population of patients with actual
visual loss due to AMD. A utility of 1.0 is associated with perfect health,
whereas a utility of 0.0 is associated with death. RESULTS: With both the time
trade-off and standard gamble methods, the patients had lower mean utilities than
did the ophthalmologists for the same degrees of visual loss secondary to AMD.
The ophthalmologists were significantly less willing than the patients to trade
years of remaining life for perfect vision with the time tradeoff method (p < or 
= 0.01), and with the standard gamble method they were less willing than the
patients to take the risk of dying in return for perfect vision. Given the
scenario of counting fingers or worse vision in both eyes, the ophthalmologists
were willing to trade 3.3 of every 10 years of remaining life for perfect vision 
in both eyes, whereas the patients with actual vision of counting fingers or
worse in both eyes were willing to trade 6.0 of every 10 years of remaining life 
for this result. INTERPRETATION: When presented with the scenario of visual loss 
secondary to AMD, ophthalmologists substantially underestimated its effect on
patients' quality of life.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 10812481 [PubMed - indexed for MEDLINE]

3226: Ophthalmology. 2000 May;107(5):1015-8.

Macular translocation. American Academy of Ophthalmology.

[No authors listed]

OBJECTIVE: This document describes macular translocation surgery and examines the
evidence to answer four key questions about whether the surgery is effective in
treating visual loss from age-related macular degeneration, the technique that is
most effective, the complications that result from the procedure, and the
relationship of the volume of surgery to the number of complications. METHODS: A 
literature search that was conducted in September 1999 retrieved 21 relevant
citations, and the reference lists of these articles were consulted for
additional citations. Panel members reviewed this information, and a
methodologist reviewed and rated all articles as good, fair, or poor in quality. 
RESULTS: The published literature contains only information from case series,
which lack a control group and randomization. They describe a number of
approaches, all of which are evolving. Follow-up is limited and visual outcomes
vary widely. Serious intraoperative and postoperative complications are frequent,
with accompanying risk of visual loss. Surgical morbidity is also an important
factor. CONCLUSIONS: To date no strong evidence exists with which to answer
questions about the effectiveness of macular translocation surgery in treating
visual loss from age-related macular degeneration or about the most effective
technique. Published case series have reported a significant rate of
complications. There is no evidence to date to indicate that the complication
rate is related to the volume of surgery done. Randomized clinical trials are
needed to determine whether macular translocation is a safe and effective
treatment for visual loss from age-related macular degeneration.

PMID: 10811099 [PubMed - indexed for MEDLINE]

3227: J Nutr. 2000 May;130(5S Suppl):1516S-9S.

The Age-Related Eye Disease Study: a clinical trial of zinc and
antioxidants--Age-Related Eye Disease Study Report No. 2.

Age-Related Eye Disease Study Research Group.

The Age-Related Eye Disease Study includes a clinical trial of high dose
antioxidant and zinc supplements for age-related macular degeneration and a
clinical trial of high dose antioxidants for cataract. The clinical trials were
initiated largely because of the widespread public use in the United States of
commercially available pharmacological doses of vitamins and minerals to treat
these two eye conditions and the absence of definitive studies on the safety and 
efficacy of their use. This report focuses on the clinical trial of zinc and the 
possibility that this elderly study cohort, who were randomly assigned in a
factorial design to receive zinc, antioxidants and placebo, could be assessed for
zinc effects other than those currently addressed by the trial.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, U.S. Gov't, P.H.S.

PMID: 10801969 [PubMed - indexed for MEDLINE]

3228: Invest Ophthalmol Vis Sci. 2000 May;41(6):1498-506.

Retinal sensitivity to flicker modulation: reduced by early age-related
maculopathy.

Falsini B, Fadda A, Iarossi G, Piccardi M, Canu D, Minnella A, Serrao S, Scullica
L.

Istituto di Oftalmologia, Università Cattolica del S. Cuore, Rome, Italy.
md0571@mclink.it

PURPOSE: To evaluate retinal, cone-mediated flicker sensitivity (CFS) in
age-related maculopathy (ARM) by quantifying response gain and threshold of the
focal electroretinogram (FERG) to flicker modulation. METHODS: Nineteen patients 
with ARM (visual acuity > or =20/30) and 11 age-matched control subjects were
examined. Twelve patients had less than 20 soft drusen in the macular region and 
no hyper-/hypopigmentation (early lesion), whereas seven had more than 20 soft
drusen and/or focal hyper-/hypopigmentation (advanced lesion). Macular (18 degree
) FERGs were elicited by a sinusoidally flickering (41 Hz) uniform field (on a
light-adapting background) whose modulation depth was varied between 16.5% and
94%. Amplitude and phase of the response's fundamental harmonic were measured.
RESULTS: In both control subjects and patients with ARM, log FERG amplitude
increased with log stimulus modulation depth with a straight line (power law)
relation. However, the slope (or gain) of the function was, on average, steeper
in control subjects than in patients with either early or advanced lesions. Mean 
FERG threshold, estimated from the value of the log modulation depth that yielded
a criterion response, did not differ between control subjects and patients with
early lesions but was increased (0.35 log units) compared with control subjects
in those with advanced lesions. In both patient groups, but not in control
subjects, mean FERG phase tended to delay with decreasing stimulus modulation
depth. CONCLUSIONS: Retinal CFS losses can be detected in ARM by evaluating the
FERG as a function of flicker modulation depth. Reduced response gain and phase
delays, with normal thresholds, are associated with early lesions. Increased
response thresholds, in addition to gain and phase abnormalities, may reflect
more advanced lesions. Evaluating CFS by FERG may directly document different
stages of macular dysfunction in ARM.

PMID: 10798669 [PubMed - indexed for MEDLINE]

3229: Invest Ophthalmol Vis Sci. 2000 May;41(6):1309-15.

Visual function and subjective quality of life compared in subjects with acquired
macular disease.

Hazel CA, Petre KL, Armstrong RA, Benson MT, Frost NA.

Vision Sciences Research Institute, Aston University, Birmingham, United Kingdom.
hazelca@aston.ac.uk

PURPOSE: To determine the objective measures of visual function that are most
relevant to subjective quality of vision and perceived reading ability in
patients with acquired macular disease. METHODS: Twenty-eight patients with
macular disease underwent a comprehensive assessment of visual function. The
patients also completed a vision-related quality-of-life questionnaire that
included a section of general questions about perceived visual performance and a 
section with specific questions on reading. RESULTS: Results of all tests of
vision correlated highly with reported vision-related quality-of-life impairment.
Low-contrast tests explained most of the variance in self-reported problems with 
reading. Text-reading speed correlated highly with overall concern about vision. 
CONCLUSIONS: Reading performance is strongly associated with vision-related
quality of life. High-contrast distance acuity is not the only relevant measure
of visual function in relation to the perceived visual performance of a patient
with macular disease. The results suggest the importance of print contrast, even 
over print size, in reading performance in patients with acquired macular
disease.

Publication Types: 
    Comparative Study

PMID: 10798645 [PubMed - indexed for MEDLINE]

3230: Invest Ophthalmol Vis Sci. 2000 May;41(6):1291-6.

Allelic variation in the VMD2 gene in best disease and age-related macular
degeneration.

Lotery AJ, Munier FL, Fishman GA, Weleber RG, Jacobson SG, Affatigato LM, Nichols
BE, Schorderet DF, Sheffield VC, Stone EM.

Department of Ophthalmology, The University of Iowa College of Medicine, Iowa
City 52242, USA. edwin-stone@uiowa.edu

PURPOSE: To assess the allelic variation of the VMD2 gene in patients with Best
disease and age-related macular degeneration (AMD). METHODS: Three hundred
twenty-one AMD patients, 192 ethnically similar control subjects, 39 unrelated
probands with familial Best disease, and 57 unrelated probands with the
ophthalmoscopic findings of Best disease but no family history were screened for 
sequence variations in the VMD2 gene by single-strand conformation polymorphism
(SSCP) analysis. Amplimers showing a bandshift were reamplified and sequenced
bidirectionally. In addition, the coding regions of the VMD2 gene were completely
sequenced in six probands with familial Best disease who showed no SSCP shift.
RESULTS: Forty different probable or possible disease-causing mutations were
found in one or more Best disease or AMD patients. Twenty-nine of these
variations are novel. Of the 39 probands with familial Best disease, mutations
were detected in all 39 (33 by SSCP and 6 by DNA sequencing). SSCP screening of
the 57 probands with a clinical diagnosis of Best disease but no family history
revealed 16 with mutations. Mutations were found in 5 of 321 AMD patients (1.5%),
a fraction that was not significantly greater than in control individuals (0/192,
0%). CONCLUSIONS: Patients with the clinical diagnosis of Best disease are
significantly more likely to have a mutation in the VMD2 gene if they also have a
positive family history. These findings suggest that a small fraction of patients
with the clinical diagnosis of AMD may actually have a late-onset variant of Best
disease, whereas at the same time, a considerable fraction of isolated patients
with the ophthalmoscopic features of Best disease are probably affected with some
other macular disease.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 10798642 [PubMed - indexed for MEDLINE]

3231: J Am Geriatr Soc. 2000 Apr;48(4):375-80.

Binocular vision in older people with adventitious visual impairment: sometimes
one eye is better than two.

Faubert J, Overbury O.

Ecole d'Optométrie, Université de Montréal, Canada.

PURPOSE: To determine the effect of adventitious visual impairment (low vision)
on monocular and binocular spatial contrast sensitivity of older people. DESIGN: 
A between-within repeated measures design. PARTICIPANTS: Fifty-nine older adults 
between the ages of 50 and 96; 49 of the observers had age-related macular
degeneration (AMD). MEASURES: Visual acuity screening and spatial contrast
sensitivity. RESULTS: In almost half of the population with AMD, the sensitivity 
to spatial information, as measured by spatial contrast sensitivity, is worse
when both eyes are used than when the stimuli are viewed with only one eye. This 
"binocular inhibition" is not related to the contrast sensitivity of the better
eye or to acuities. Furthermore, this inhibition process is reflected primarily
in images with medium to low spatial frequency components (medium to large size
bars). CONCLUSIONS: These results have important implications for understanding
the functional impact of low vision in older people. They suggest that almost
one-half of older people with AMD view the world best using only one of their
eyes, whereas for the other half, there is an advantage to using binocular vision
for certain visual tasks.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10798462 [PubMed - indexed for MEDLINE]

3232: Cochrane Database Syst Rev. 2000;(2):CD002030.

Update in:
    Cochrane Database Syst Rev. 2001;(3):CD002030.

Photodynamic therapy for neovascular age-related macular degeneration.

Wormald R, Evans J, Smeeth L.

'Glaxo' Department of Ophthalmic Epidemiology, Institute of Ophthalmology (UCL)
and Moorfields Eye Hospital, City Road, London, UK, EC1V 2PD. r.wormald@ucl.ac.uk

BACKGROUND: In neovascular age-related macular degeneration, new vessels grow
under the retina, distorting vision and leading to scarring. This is further
exacerbated if the blood vessels leak. Photodynamic therapy, originally used in
cancer treatment, has been investigated as a way to treat the neovascular
membranes without affecting the retina. OBJECTIVES: The aim of this review is to 
examine the evidence for the safety and effectiveness of photodynamic therapy in 
the treatment of neovascular age-related macular degeneration. SEARCH STRATEGY:
We searched for trials in the Cochrane Eyes and Vision Group trials register
(available in the Cochrane Controlled Trials Register), the Cochrane Controlled
Trials Register, Medline and Embase. We used the Science Citation Index to search
for reports that cited identified relevant study reports. We contacted experts in
the field for further trials information, and we searched the reference lists of 
identified relevant studies for further trial reports. Searches were conducted in
December 1999. SELECTION CRITERIA: We included randomised trials of photodynamic 
therapy in people with choroidal neovascularisation due to age-related macular
degeneration. DATA COLLECTION AND ANALYSIS: Two reviewers extracted the data
independently. Meta analysis was not performed. MAIN RESULTS: One published trial
was identified. Outcome data were available at 12 months after the first
treatment. Patients received an average of 3.7 treatments. The relative risk of
losing three or more lines of visual acuity at 12 months comparing the
intervention with the control group was 0.72 (95% confidence interval 0.61 to
0.86). The relative risk of losing six or more lines of visual acuity at 12
months comparing the intervention with the control group was 0.62 (95% confidence
interval 0.44 to 0.87). Subgroup analyses suggest that the benefits may be
confined to people with no occult choroidal neovascularisation. REVIEWER'S
CONCLUSIONS: Photodynamic therapy in people with classic choroidal
neovascularisation due to age-related macular degeneration is effective in
preventing visual loss. This evidence is drawn from a subgroup analysis of 143
participants in one trial. Outcomes and potential adverse effects of this
treatment should be monitored closely. There is no evidence that photodynamic
therapy is beneficial for people with evidence of occult choroidal
neovascularisation. These people should be offered treatment in the context of a 
randomised trial.

Publication Types: 
    Review

PMID: 10796845 [PubMed - indexed for MEDLINE]

3233: Cochrane Database Syst Rev. 2000;(2):CD001775.

Ginkgo biloba extract for age-related macular degeneration.

Evans JR.

'Glaxo' Department of Ophthalmology Epidemiology, Institute of Ophthalmology
(UCL) and Moorfields Eye Hospital, City Road, London, UK, EC1V 2PD.
jennifer.evans@ucl.ac.uk

BACKGROUND: Ginkgo is used in the treatment of peripheral vascular disease and
'cerebral insufficiency'. It is thought to have several potential mechanisms of
action including increased blood flow, platelet activating factor antagonism and 
prevention of membrane damage caused by free radicals. Vascular factors and
oxidative damage are thought to be two potential mechanisms in the pathology of
age-related macular degeneration. OBJECTIVES: The objective of this review is to 
determine the effect of Ginkgo biloba extract on the progression of age-related
macular degeneration. SEARCH STRATEGY: The Cochrane Eyes and Vision Group
specialised register, the Cochrane Controlled Trials Register - Central, MEDLINE,
reference lists of identified trial reports, and the Science Citation Index were 
searched. The reviewer contacted Investigators of included studies for additional
information. The most recent searches were performed in February 2000. SELECTION 
CRITERIA: All randomised trials where Ginkgo biloba extract had been compared to 
control in people with age-related macular degeneration were included. DATA
COLLECTION AND ANALYSIS: The reviewer extracted data using a standardised form.
The data were verified with the trial investigator. MAIN RESULTS: One published
trial was identified. Although a beneficial effect was observed, as only 20
people were enrolled in the trial, and assessment of outcome was not masked, its 
results must be considered equivocal. Adverse effects and quality of life for
people with age-related macular degeneration have not been addressed. One
unpublished trial is awaiting translation and assessment. REVIEWER'S CONCLUSIONS:
The question as to whether people with age-related macular degeneration should
take Ginkgo biloba extract to prevent progression of the disease has not been
answered by research to date.

Publication Types: 
    Review

PMID: 10796819 [PubMed - indexed for MEDLINE]

3234: Cochrane Database Syst Rev. 2000;(2):CD000254.

Update in:
    Cochrane Database Syst Rev. 2002;(1):CD000254.

Antioxidant vitamin and mineral supplements for age-related macular degeneration.

Evans JR.

'Glaxo' Department of Ophthalmology Epidemiology, Institute of Ophthalmology
(UCL) and Moorfields Eye Hospital, City Road, London, UK, EC1V 2PD.
jennifer.evans@ucl.ac.uk

BACKGROUND: It has been proposed that antioxidants may prevent cellular damage in
the retina by reacting with free radicals produced in the process of light
absorption. OBJECTIVES: The objective of this review is to assess the effects of 
antioxidant vitamin and/or mineral supplementation on the progression of
age-related macular degeneration. SEARCH STRATEGY: The Cochrane Eyes and Vision
Group specialised registered, the Cochrane Controlled Trials Register - Central, 
MEDLINE, the Science Citation Index, and the reference lists of relevant articles
were searched. Investigators of included studies were contacted. The most recent 
searches were performed in December 1999. SELECTION CRITERIA: All randomised
trials comparing an antioxidant vitamin and/or mineral supplement (alone or in
combination) to control in people with age-related macular degeneration were
included. DATA COLLECTION AND ANALYSIS: The reviewer extracted data and assessed 
trial quality. Due to the small number of trials identified, and variable methods
of collecting and presenting outcome data, no statistical summary measure was
calculated. MAIN RESULTS: Four published, two unpublished and two ongoing trials 
were identified. Published trials to date have been small and results
inconsistent. Adverse effects and quality of life for people with age-related
macular degeneration have not been addressed. REVIEWER'S CONCLUSIONS: The
question as to whether people with age-related macular degeneration should take
antioxidant vitamin or mineral supplements to prevent progression of the disease 
has not been answered by research to date. The results of ongoing trials are
awaited.

Publication Types: 
    Review

PMID: 10796708 [PubMed - indexed for MEDLINE]

3235: Cochrane Database Syst Rev. 2000;(2):CD000253.

Update in:
    Cochrane Database Syst Rev. 2008;(1):CD000253.

Antioxidant vitamin and mineral supplementation for preventing age-related
macular degeneration.

Evans JR, Henshaw K.

'Glaxo' Department of Ophthalmology Epidemiology, Institute of Ophthalmology
(UCL) and Moorfields Eye Hospital, City Road, London, UK, EC1V 2PD.
jennifer.evans@ucl.ac.uk

BACKGROUND: Some observational studies have suggested that people who eat a diet 
rich in antioxidant vitamins (carotenoids, vitamins C and E) or minerals
(selenium and zinc) may be less likely to develop age-related macular
degeneration. OBJECTIVES: The aim of this review is to examine the evidence as to
whether or not taking vitamin or mineral supplements prevents the development of 
age-related macular degeneration. SEARCH STRATEGY: We searched the Cochrane Eyes 
and Vision Group specialised register, the Cochrane Controlled Trials Register - 
Central, MEDLINE, reference lists of identified reports and the Science Citation 
Index. We contacted investigators and experts in the field for details of
unpublished studies. The most recent searches were conducted in June 1999.
SELECTION CRITERIA: All randomised trials comparing an antioxidant vitamin and/or
mineral supplement (alone or in combination) to control were included. We
included only studies where supplementation had been given for at least one year.
DATA COLLECTION AND ANALYSIS: Both reviewers independently extracted data and
assessed trial quality. Currently there is only one published trial included in
the review so no data synthesis was conducted. MAIN RESULTS: One trial is
included in the review. This was a primary prevention trial in Finnish male
smokers with four treatment groups: alpha-tocopherol alone, beta-carotene alone, 
alpha-tocopherol and beta-carotene, placebo. The add-on maculopathy study was
conducted in a subset of the main trial cohort. 269 cases of maculopathy (14 late
stage age-related macular degeneration) were identified. There was no association
of age-related macular degeneration with treatment. REVIEWER'S CONCLUSIONS: There
is no evidence to date that people without age-related macular degeneration
should take antioxidant vitamin and mineral supplements to prevent or delay the
onset of the disease. The results of five large ongoing trials are awaited.

Publication Types: 
    Review

PMID: 10796707 [PubMed - indexed for MEDLINE]

3236: Retina. 2000;20(2):162-9.

Improvement of visual acuity over time in patients with bilateral geographic
atrophy from age-related macular degeneration.

Sunness JS, Applegate CA, Gonzalez-Baron J.

Lions Vision Research and Rehabilitation Center, Johns Hopkins University School 
of Medicine, Baltimore, Maryland, USA.

PURPOSE: To study the improvement in visual acuity over time in patients with
central scotomas. METHODS: In a prospective natural history study of geographic
atrophy (GA) from age-related macular degeneration (ARMD) with annual follow-up, 
36 patients with bilateral GA completed 3 years of follow-up. Protocol visual
acuity (VA) measurements were performed. Scanning laser ophthalmoscopy (SLO) was 
performed, and the areas of GA were measured from fundus photographs. RESULTS:
Six eyes of six patients with VA ranging from 20/80 to 20/500 had a VA
improvement of two or more lines (mean, 3.2 lines). This was found only in the
worse-seeing eyes of the patients and was contemporaneous with the deterioration 
in VA of the better-seeing eyes. Four of six eyes that improved in acuity had an 
improvement in the ability to find and hold the fixation target in an area of
seeing retina, as assessed by SLO at follow-up, and a fifth eye changed from one 
fixation site that had little functional retina to another site. CONCLUSIONS:
Spontaneous improvement in VA in eyes with bilateral GA and central scotomas may 
occur. It appears to be related to deterioration in VA of the better-seeing
fellow eye and is associated with improvement of fixation in the worse-seeing
eye. The worse-seeing eye of a patient with bilateral ARMD may have the potential
for better vision than measured VA indicates. This finding may have implications 
for the choice of patients in treatment trials, for interpretation of long-term
results, and for planning and assessment of low vision intervention.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 10783949 [PubMed - indexed for MEDLINE]

3237: Retina. 2000;20(2):143-50.

Comment in:
    Retina. 2001;21(5):563-4.

ICGA-guided laser photocoagulation of feeder vessels of choroidal neovascular
membranes in age-related macular degeneration. Indocyanine green angiography.

Desatnik H, Treister G, Alhalel A, Krupsky S, Moisseiev J.

Goldschleger Eye Institute, The Sheba Medical Center, Tel Hashomer, Israel.

PURPOSE: To report the ability of indocyanine green angiography (ICGA) with a
confocal scanning laser ophthalmoscope (SLO) to identify feeder vessels of
choroidal neovascular membranes (CNVM) secondary to age-related macular
degeneration (ARMD) and to show the feasibility of inducing complete closure of
the CNVM by photocoagulation targeted exclusively to the feeder vessels. METHODS:
Five consecutive patients with exudative ARMD in whom ICGA with the confocal SLO 
showed extrafoveal feeder vessels supplying choroidal neovascular nets had laser 
photocoagulation done only to the feeder vessels. In two patients, two separate
membranes were seen. RESULTS: Laser photocoagulation resulted in closure of the
feeder vessels and the CNVM in four patients. Complete closure was achieved with 
one treatment in one patient and with two treatments in three patients. In one
patient, two treatments failed to close the feeder vessel and the CNVM, but a
third, more intense laser treatment resulted in temporary closure of the feeder
vessel and CNVM, which recanalized 2 to 4 weeks later with development of a large
rip in the retinal pigment epithelium. In one patient, two separate CNVMs grew
from the edge of the laser scars, but they were not directly related to the
original CNVM and its feeder vessel, and were treated successfully. The same eye 
later developed subfoveal occult CNVM with gradual deterioration of visual
acuity. In the other four patients, visual acuity improved in two and was
unchanged in two. CONCLUSIONS: Indocyanine green angiography with the confocal
SLO can identify choroidal feeder vessels supplying CNVM secondary to ARMD. Laser
treatment to such extrafoveal feeder vessels, particularly in membranes that are 
large or subfoveal, may be effective in closing the feeder vessel and CNVM with
preservation of the fovea and central vision. More than one treatment may be
required, however, and failures and complications may be expected with this
treatment modality.

Publication Types: 
    Case Reports

PMID: 10783946 [PubMed - indexed for MEDLINE]

3238: Retina. 2000;20(2):134-42.

ICGA-guided laser photocoagulation of occult choroidal neovascularization in
age-related macular degeneration. Indocyanine green angiography.

Brancato R, Introini U, Bolognesi G, Pacelli G, Trabucchi G, Pece A.

Department of Ophthalmology and Visual Sciences, University of of Milan, and S.
Raffaele Hospital, Italy.

PURPOSE: To evaluate the efficacy of indocyanine green angiography (ICGA)-guided 
laser photocoagulation in eyes with fluorescein angiographic evidence of occult
choroidal neovascularization (O-CNV) in patients with age-related macular
degeneration (ARMD) with or without pigment epithelium detachment (PED). METHODS:
Eighty eyes of 79 consecutive patients with O-CNV underwent laser treatment of a 
clearly outlined extrafoveal ICGA hyperfluorescent area, presumed to be focal
CNV. Four types of presumed CNV were treated: Group 1 (20 eyes), CNV beneath the 
PED; Group 2 (23 eyes), CNV at the margin of the PED; Group 3 (10 eyes),
parapapillary CNV and PED; and Group 4 (27 eyes), macular CNV without PED. Median
follow-up was 17.5 months (range, 6-24 months). RESULTS: After 1 year, 15% of the
eyes in Group 1, 30% in Group 2, 100% in Group 3, and 52% in Group 4 had
obliteration of the presumed CNV. After 1 year, visual acuity was stable or
improved in 18% of Group 1, in 37.5% of Group 2, in 100% of Group 3, and in 73%
of Group 4. The remaining eyes worsened. CONCLUSIONS: Indocyanine green
angiography-guided laser treatment may improve or stabilize visual acuity in some
eyes with O-CNV. The best outcome is seen in eyes with presumed parapapillary
CNV, probably made up of choroidal telangiectases in many cases. The type and
location of the presumed CNV influence prognosis after laser treatment
considerably. A randomized, controlled clinical study appears necessary to
investigate the efficacy of ICGA-guided laser treatment in different types of
presumed CNV. The inclusion criteria for further trials need to be defined with
precision, as data from patients with different choroidal vascular abnormalities 
have been pooled until now.

Publication Types: 
    Clinical Trial
    Comparative Study

PMID: 10783945 [PubMed - indexed for MEDLINE]

3239: Retina. 2000;20(2):126-33.

Resolution of diabetic macular edema after surgical removal of the posterior
hyaloid and the inner limiting membrane.

Gandorfer A, Messmer EM, Ulbig MW, Kampik A.

Department of Ophthalmology, Ludwig-Maximilians-University, Munich, Germany.

PURPOSE: To evaluate the surgical results of pars plana vitrectomy with peeling
of the inner limiting membrane (ILM) in a preliminary series of 12 eyes with
diffuse diabetic macular edema. PATIENTS AND METHODS: Pars plana vitrectomy with 
peeling of the ILM was performed in 12 eyes with diffuse diabetic macular edema. 
In 10 eyes, the posterior hyaloid was attached and thickened. Six eyes had
undergone macular photocoagulation previously, and two other eyes had been
vitrectomized previously. Light and electron microscopy of the specimens obtained
during vitrectomy was performed. Visual acuity and retinal thickening were
monitored. RESULTS: Intraoperatively, the posterior hyaloid was found to be
thickened and completely attached to the macula in 10 eyes. Two previously
vitrectomized eyes showed a glistening reflex of the vitreoretinal interface but 
no premacular membrane. The posterior hyaloid and the ILM were removed from the
macula. Postoperatively, retinal thickening resolved or decreased in all eyes.
Visual acuity improved by at least two lines in 11 eyes. Best-corrected
postoperative visual acuity developed within 4 to 12 weeks. No recurrence or
deterioration of macular edema or epiretinal membrane formation were observed
during the entire period of review (mean, 16 months; range, 8-31 months). Light
and electron microscopy showed the presence of the ILM associated with sparse and
mostly single-layered fibrous astrocytes. CONCLUSION: Vitrectomy including
removal of the ILM leads to expedited resolution of diffuse diabetic macular
edema and improvement of visual acuity without subsequent epiretinal membrane
formation. Complete release of tractional forces and inhibition of
reproliferation of fibrous astrocytes seem to be prudent in the eyes of patients 
with diabetes and advanced vitreoretinal interface disease of the macula.

PMID: 10783944 [PubMed - indexed for MEDLINE]

3240: Retina. 2000;20(2):121-5.

Surgical treatment for severe diabetic macular edema with massive hard exudates.

Yang CM.

Ophthalmological Department, National Taiwan University Hospital, Taipei.

PURPOSE: Massive diabetic macular exudates respond poorly to conventional laser
treatment. The purpose of this study was to analyze the surgical results of eyes 
with massive hard exudates secondary to diabetic macular edema treated with
combined pars plana vitrectomy, posterior hyaloid removal, focal endolaser
treatment, and panretinal photocoagulation. METHODS: The author retrospectively
analyzed the surgical outcome of 13 consecutive eyes (11 patients) with massive
diabetic macular exudates. All patients had had at least one session of focal
and/or grid laser treatment without any effect. Pars plana vitrectomy, posterior 
hyaloid removal, focal macular endolaser treatment, and intraoperative panretinal
photocoagulation were performed. Postoperative visual acuity, evolution of
macular edema, and hard exudates were recorded. RESULTS: All 13 eyes showed
significant decreases in macular edema and hard exudates, a process that became
clinically obvious 3 months after the operation. Eleven eyes had improved vision 
of at least two lines during an average follow-up period of 14.8 months.
Intraoperative and postoperative complications included angle closure glaucoma
(one eye), persistent vitreous hemorrhage (two eyes), choroidal detachment (one
eye), intravitreal fibrin formation (one eye), epiretinal membrane formation (one
eye), and neovascular glaucoma (one eye). CONCLUSION: Combined surgery may offer 
an opportunity for improvement of vision and reduction of massive macular
exudates in patients with severe diabetic macular edema.

Publication Types: 
    Case Reports

PMID: 10783943 [PubMed - indexed for MEDLINE]

3241: FASEB J. 2000 May;14(7):835-46.

Drusen associated with aging and age-related macular degeneration contain
proteins common to extracellular deposits associated with atherosclerosis,
elastosis, amyloidosis, and dense deposit disease.

Mullins RF, Russell SR, Anderson DH, Hageman GS.

The University of Iowa Center for Macular Degeneration, Department of
Ophthalmology and Visual Sciences, The University of Iowa, Iowa City, Iowa 52242,
USA.

Age-related macular degeneration (AMD), a blinding disorder that compromises
central vision, is characterized by the accumulation of extracellular deposits,
termed drusen, between the retinal pigmented epithelium and the choroid. Recent
studies in this laboratory revealed that vitronectin is a major component of
drusen. Because vitronectin is also a constituent of abnormal deposits associated
with a variety of diseases, drusen from human donor eyes were examined for
compositional similarities with other extracellular disease deposits. Thirty-four
antibodies to 29 different proteins or protein complexes were tested for
immunoreactivity with hard and soft drusen phenotypes. These analyses provide a
partial profile of the molecular composition of drusen. Serum amyloid P
component, apolipoprotein E, immunoglobulin light chains, Factor X, and
complement proteins (C5 and C5b-9 complex) were identified in all drusen
phenotypes. Transcripts encoding some of these molecules were also found to be
synthesized by the retina, retinal pigmented epithelium, and/or choroid. The
compositional similarity between drusen and other disease deposits may be
significant in view of the recently established correlation between AMD and
atherosclerosis. This study suggests that similar pathways may be involved in the
etiologies of AMD and other age-related diseases.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 10783137 [PubMed - indexed for MEDLINE]

3242: J AAPOS. 2000 Apr;4(2):75-83.

Combined superior oblique muscle recession and inferior oblique muscle
advancement and transposition for cyclotorsion associated with macular
translocation surgery.

Freedman SF, Seaber JH, Buckley EG, Enyedi LB, Toth CA.

Department of Ophthalmology, Duke University, Durham, North Carolina 27710, USA.

PURPOSE: The purpose of this study was to evaluate the effects of oblique muscle 
surgery on the large-angle incyclotorsion resulting from macular translocation
surgery for severe age-related macular degeneration. METHODS: Patients undergoing
macular translocation (superiorly) at our institution from May 1996 until
November 1998 were included. In the Staged Group, strabismus surgery for
symptomatic incyclotorsion was performed after the macular translocation, and in 
the Combined Group, it was performed simultaneous with the macular translocation.
Cyclotorsion was quantified using Maddox rod testing. Surgery for incyclotorsion 
included superior oblique muscle recession combined with inferior oblique muscle 
advancement and transposition in the affected eyes. The minimum follow-up time
was 6 weeks. RESULTS: Fifteen patients (15 eyes) were included (ages 66-89
years). Nine eyes (Baseline Group) had macular translocation surgery before any
strabismus surgery; the mean postoperative incylotorsional angle was 33.4 +/-
18.3 degrees (range, 20-80 degrees) after a mean follow-up of 6.6 months. Four of
these eyes (Staged Group) underwent oblique muscle surgery for symptomatic
incyclotorsion, which reduced the mean incyclotorsion from 26.9 +/- 6.9 degrees
(range, 20-35 degrees) to 9. 9 +/- 7.9 degrees (range, 2.5-20 degrees)-a mean
reduction of 16.9 +/- 1.3 degrees (P =.00012), after a mean follow-up of 4.6
months. Six additional eyes (Combined Group) had simultaneous macular
translocation and oblique muscle surgery, with a mean postoperative
cyclotorsional angle of 14.0 +/- 6.7 degrees (range, 4-22.5 degrees), after a
mean follow-up of 3.75 months. CONCLUSION: Oblique muscle surgery is effective at
reducing the large degree of incyclotorsion resulting from macular translocation 
surgery and may be used either following or simultaneous with retinal surgery.

Publication Types: 
    Comparative Study

PMID: 10773805 [PubMed - indexed for MEDLINE]

3243: Ophthalmology. 2000 Apr;107(4):755-9.

Entoptic perimetry screening for central diabetic scotomas and macular edema.

Brown JC, Kylstra JA, Mah ML.

Department of Ophthalmology, The University of North Carolina School of Medicine,
Chapel Hill 27599-7040, USA.

OBJECTIVE: The aim of this study was to compare entoptic perimetry, using
conventional television, to Amsler grid and patient-reported visual loss for the 
detection of functional diabetic maculopathy and macular edema. DESIGN:
Observational case series. PARTICIPANTS: A single eye from each of 104
consecutive patients with diabetes in an academic retina clinic. INTERVENTION:
Each eye was screened by Amsler grid, entoptic perimetry, and Humphrey 10-2
threshold visual field testing (HVF 10-2; Humphrey Instruments Inc., San Leandro,
CA) in random order. Eyes were then examined clinically. MAIN OUTCOME MEASURES:
The presence or absence of new visual decline since the patient's last clinical
examination, the presence or absence of central visual field abnormalities using 
an Amsler grid, entoptic perimetry, HVF 10-2, and the presence or absence of
clinically significant macular edema (CSME). RESULTS: The sensitivities and
specificities for the detection of central diabetic scotomas as evidenced by HVF 
10-2 abnormalities were: subjective impression, 31 of 90 eyes (34.4%) and 11 of
14 eyes (78.6%); Amsler grid, 29 of 90 eyes (32.2%) and 13 of 14 eyes (92.9%);
and entoptic perimetry, 58 of 90 eyes (64.4%) and 11 of 14 eyes (78.6%). Entoptic
perimetry was statistically more sensitive than both subjective impression (P <
0.001) and Amsler grid (P < 0.001), but the specificities were statistically
indistinguishable. The sensitivities and specificities for the detection of CSME 
were: subjective impression, 6 of 24 eyes (25.0%) and 52 of 80 eyes (65.0%);
Amsler grid, 9 of 24 eyes (37.5%) and 59 of 80 eyes (73.8%); and entoptic
perimetry, 17 of 24 eyes (70.8%) and 44 of 80 (55.0%) eyes. These results are
also statistically significant, with entoptic perimetry being more sensitive and 
less specific than both subjective impression (P = 0.007 and P = 0.011,
respectively) and Amsler grid (P = 0.008 and P < 0.001, respectively) in this
subset of patients. CONCLUSIONS: Entoptic perimetry is 87% more sensitive than
the subjective impression of visual decline (P < 0.001) and 100% more sensitive
than Amsler grid (P < 0.001) for the detection of central scotomas in diabetic
patients. For the detection of CSME, entoptic perimetry is 183% more sensitive
than subjective impression (P = 0.007) and 89% more sensitive than Amsler grid (P
= 0.008). Hence, entoptic perimetry, performed using conventional television, has
the potential to be an effective, inexpensive, and widespread adjunct to
surveillance examinations for the early detection of diabetic maculopathy.

Publication Types: 
    Clinical Trial
    Comparative Study
    Controlled Clinical Trial

PMID: 10768339 [PubMed - indexed for MEDLINE]

3244: Ophthalmology. 2000 Apr;107(4):742-53; discussion 753-4.

Retinal choroidal anastomoses and occult choroidal neovascularization in
age-related macular degeneration.

Slakter JS, Yannuzzi LA, Schneider U, Sorenson JA, Ciardella A, Guyer DR, Spaide 
RF, Freund KB, Orlock DA.

Vitreous-Retina-Macula Consultants of New York, New York 10021, USA.
vrmny@aol.com

OBJECTIVE: This study was designed to identify the incidence of retinal choroidal
anastomoses in patients with occult choroidal neovascularization (CNV) and focal 
hot spots on indocyanine green (ICG) angiography, to identify the clinical and
angiographic features that would assist in their identification, and to determine
if the presence of these anastomotic lesions affect the outcome of laser therapy.
DESIGN: Combined prospective and retrospective cross-sectional study.
PARTICIPANTS: One hundred fifty consecutive patients with newly diagnosed occult 
CNV secondary to exudative age-related macular degeneration and focal hot spots
on ICG angiography were evaluated prospectively. In addition, a retrospective
review was performed on 79 eyes previously reported to have undergone laser
photocoagulation treatment with ICG guidance. METHODS AND TESTING: In all cases, 
stereo color and red-free photographs, and stereo fluorescein and digital ICG
angiograms were obtained for evaluation. MAIN OUTCOME MEASURES: Images obtained
by all four techniques were evaluated for the presence of a retinal choroidal
anastomosis. Associated clinical and angiographic findings were noted. In the
retrospective review, the success rate of laser treatment was correlated with the
presence or absence of a retinal choroidal anastomosis. RESULTS: Of the 150 eyes 
evaluated prospectively, 31 (21%) were found to have a retinal choroidal
anastomosis. Retinal choroidal anastomoses were found in 27% of patients with
associated serous pigment epithelial detachment (PED), whereas 13% were found in 
those without an associated elevation of the retinal pigment epithelium.
Seventy-one percent of eyes had multiple anastomotic connections. Ninety percent 
of eyes had at least one retinal vein involved in the anastomotic connection.
Clinical evidence of preretinal and intraretinal hemorrhage and cystic edema
coupled with angiographic evidence of intraretinal dye leakage were key features 
of retinal choroidal anastomoses. In the retrospective review, seven patients
were found to have retinal choroidal anastomoses with associated serous PED and
demonstrated a very low (14%) success rate for laser treatment. CONCLUSIONS:
Retinal choroidal anastomoses can present as a primary manifestation of the
exudative process in age-related macular degeneration. They may be seen in eyes
with and without detachment of the retinal pigment epithelium. Specific clinical 
and angiographic features have been identified that can aid in the diagnosis of
these vascular anomalies. Their presence represents a poor prognostic sign for
successful ICG-guided laser treatment.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10768338 [PubMed - indexed for MEDLINE]

3245: Am J Ophthalmol. 2000 Apr;129(4):547-9.

Improvement in macular function after retinal translocation surgery in a patient 
with age-related macular degeneration.

Potter MJ, Chang TS, Lee AS, Rai S.

Department of Ophthalmology, University of British Columbia, Vancouver, BC,
Canada. mpotter@interchange.ubc.ca

PURPOSE: To assess focal electroretinographic findings before and after retinal
translocation surgery in a patient with age-related macular degeneration. METHOD:
Case report. A 79-year-old man with a well-defined subfoveal choroidal
neovascular membrane from age-related macular degeneration underwent preoperative
and postoperative focal electroretinography. RESULTS: After retinal translocation
surgery, best-corrected Snellen visual acuity improved from 9/200 to 20/60. A
significant increase in mean foveal amplitude, from 0.08 microV to 0.16 microV (P
= 0.008) was recorded. CONCLUSION: Age-related macular degenerative changes in
visual acuity and foveal electroretinogram amplitude may be reversible after
retinal translocation surgery.

Publication Types: 
    Case Reports

PMID: 10764875 [PubMed - indexed for MEDLINE]

3246: Am J Ophthalmol. 2000 Apr;129(4):495-500.

Comparison of fluorescein angiography and indocyanine green angiography for
imaging of choroidal neovascularization in hemorrhagic age-related macular
degeneration.

Kramer M, Mimouni K, Priel E, Yassur Y, Weinberger D.

Department of Ophthalmology, Rabin Medical Center, Beilinson Campus, Petah Tiqva,
Israel.

PURPOSE: To compare fluorescein angiography and indocyanine green angiography for
imaging of choroidal neovascularization located under subretinal hemorrhage, in
age-related macular degeneration. METHODS: In a retrospective study, 30 eyes of
30 consecutive patients with hemorrhagic age-related macular degeneration were
evaluated with fluorescein angiography and indocyanine green angiography. In each
eye, areas of macular hemorrhage, choroidal neovascularization, and total lesion 
(hemorrhage plus choroidal neovascularization) were measured, and the choroidal
neovascularization was categorized as classic, occult, or mixed on fluorescein
angiography, and as hot spot, plaque, or combined lesion on indocyanine green
angiography. Results of the two techniques were compared for the ability to
identify a laser-treatable lesion. RESULTS: Fluorescein angiography showed
fluorescence in most cases (28, 93.3%). In 23 cases (76.6%), the fluorescence
pattern was compatible with occult choroidal neovascularization. Indocyanine
green angiography revealed defined patterns of fluorescence in 27 cases (90%): 12
hot spots, seven plaques, and eight combined hot spots and plaques. Twenty
lesions (66.6%) detected by indocyanine green angiography were considered
eligible for laser therapy. Nine of them (45%) were extrafoveal. CONCLUSIONS:
Indocyanine green angiography is beneficial for imaging choroidal
neovascularization located under subretinal hemorrhage. Choroidal
neovascularization demonstrated on indocyanine green angiography may be
considered eligible for laser treatment. Therefore, indocyanine green angiography
should be considered in cases of hemorrhagic age-related macular degeneration.

Publication Types: 
    Comparative Study

PMID: 10764859 [PubMed - indexed for MEDLINE]

3247: Am J Ophthalmol. 2000 Apr;129(4):487-94.

Comment in:
    Am J Ophthalmol. 2002 Jan;133(1):166.

Tomographic assessment of vitreous surgery for diabetic macular edema.

Otani T, Kishi S.

Department of Ophthalmology, Gunma University School of Medicine, Maebashi,
Gunma, Japan. otanito@akagi.sb.gunma-u.ac.jp

PURPOSE: To evaluate the retinal structure before and after vitrectomy for
diabetic macular edema and to assess the correlation between thickness of
neurosensory retina and best-corrected visual acuity. METHODS: Tomographic
features of 13 eyes (nine patients) with diabetic macular edema were
prospectively evaluated with optical coherence tomography before and after
vitrectomy. The foveal thickness (the distance between the inner retinal surface 
and the retinal pigment epithelium) and the retinal thickness (thickness of
neurosensory retina) were measured by optical coherence tomography preoperatively
and postoperatively. The correlation of the best-corrected visual acuity with
foveal and retinal thickness was determined. RESULTS: All 13 eyes had retinal
swelling with low intraretinal reflectivity. In addition to retinal swelling,
there were cystoid spaces in five (38%) of 13 eyes, a serous retinal detachment
in three (23%), and both cystoid spaces and serous detachment in three (23%). Six
months postoperatively, the mean foveal thickness significantly decreased from
630 +/- 170 to 350 +/- 120 microm (P <.01, paired t test) and the mean thickness 
of neurosensory retina decreased from 540 +/- 160 to 320 +/- 140 microm (P <.01, 
paired t test). A serous retinal detachment occurred transiently in 3 eyes.
Compared with the preoperative level, the postoperative best-corrected visual
acuity level improved by more than 2 lines in five of the 13 eyes (38%), remained
the same in seven eyes (54%), and decreased in one eye (8%). The postoperative
thickness of neurosensory retina at the fovea and best-corrected visual acuity
level at the sixth postoperative month had a strong negative correlation
(correlation coefficient, -0.76; P <.01, Spearmans rank test). CONCLUSIONS:
Vitrectomy was generally effective in treatment of diabetic macular edema.
Optical coherence tomography demonstrated the intraretinal changes of macular
edema and the process of edema absorption. During the process of macular edema
absorption, intraretinal fluid appeared to move into the subretinal space in some
cases. Best-corrected visual acuity improvement was greater in eyes with less
preoperative increase in thickness of neurosensory retina.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10764858 [PubMed - indexed for MEDLINE]

3248: Hum Genet. 2000 Feb;106(2):244-8.

Complex inheritance of ABCR mutations in Stargardt disease: linkage
disequilibrium, complex alleles, and pseudodominance.

Shroyer NF, Lewis RA, Lupski JR.

Program in Cell and Molecular Biology, Baylor College of Medicine, Houston, TX
77030, USA.

Stargardt disease is a recessively transmitted disease caused by mutations in the
ABCR gene. Linkage disequilibrium has recently been reported between a
polymorphism, 2828 A, and a common Western European founder mutation, 2588 C.
Here, we confirm this linkage disequilibrium in a North American population. We
also describe two complex alleles involving the 2828 A and 2588 C alterations and
suggest a possible order of clinical severity of mutations identified in trans to
the complex alleles. Finally, we report pseudodominance of Stargardt disease in a
family with the 2588 C mutation, further supporting a high frequency of carriers 
for ABCR mutations in our population.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 10746567 [PubMed - indexed for MEDLINE]

3249: Hum Mutat. 2000;15(4):301-8.

VMD2 mutations in vitelliform macular dystrophy (Best disease) and other
maculopathies.

White K, Marquardt A, Weber BH.

Institut für Humangenetik, Universität Würzburg, Würzburg, Germany.

Mutations in the gene VMD2 are associated with autosomal dominant vitelliform
macular dystrophy (Best disease). VMD2 is expressed in the retinal pigment
epithelium and codes for a 585 amino acid putative transmembrane protein with
undetermined functional properties. To date, 48 different mutations,
predominantly missense, have been described in Best disease families. These
mutations generally affect amino acids in the first 50% of the protein, and occur
in four distinct clusters possibly representing regions of functional importance.
VMD2 has also been investigated in other macular diseases. Mutations have been
documented in a significant percentage of patients with adult vitelliform macular
dystrophy (AVMD) and in a single case of "bull's-eye" maculopathy. Results of
analysis in two large series of individuals with age-related macular degeneration
(AMD) suggest that VMD2 does not play a major role in this prevalent disorder.
Copyright 2000 Wiley-Liss, Inc.

Publication Types: 
    Review

PMID: 10737974 [PubMed - indexed for MEDLINE]

3250: Curr Opin Ophthalmol. 2000 Feb;11(1):65-72.

Cystoid macular edema following cataract surgery.

Rossetti L, Autelitano A.

Clinica Oculistica, San Paolo Hospital, University of Milan, Italy.

Cystoid macular edema (CME) remains a troublesome problem after cataract surgery 
and other types of ocular surgical procedures. It is recognized as the most
frequent cause of decreased vision in patients following cataract surgery.
Although the disease was first described more than 40 years ago, its cause is
unclear, and all available therapeutic interventions, mainly based on theories
regarding the pathogenesis of the condition, are of doubtful effectiveness and
are still far from being satisfactory. Most published literature on the incidence
and treatment of CME consists of small, retrospective case series and cannot
provide reliable answers as to whether a given factor or intervention is
associated with the occurrence or outcome of the disease.

Publication Types: 
    Review

PMID: 10724830 [PubMed - indexed for MEDLINE]

3251: Arch Ophthalmol. 2000 Mar;118(3):401-4.

Dietary fat and fish intake and age-related maculopathy.

Smith W, Mitchell P, Leeder SR.

National Centre for Epidemiology and Population Health, Australian National
University, Australian Capital Territory. wayne.smith@anu.edu.au

OBJECTIVE: To assess whether dietary intake of fat or fish is associated with
age-related maculopathy (ARM) prevalence. DESIGN: Cross-sectional, urban
population-based study. PARTICIPANTS: People (N = 3654) aged 49 years or older.
MAIN OUTCOME MEASURES: Subjects with ARM were identified from masked grading of
retinal photographs. A 145-itemself-administered, semiquantitative food frequency
questionnaire was completed adequately by 88.8% of participants and was used to
assess intakes of dietary fat and fish. RESULTS: A higher frequency of fish
consumption was associated with decreased odds of late ARM (odds ratio for
frequency of consumption more than once per week compared with less than once per
month, 0.5). Subjects with higher energy-adjusted intakes of cholesterol were
significantly more likely to have late ARM, with an increased risk for late ARM
for the highest compared with the lowest quintile of intake (odds ratio, 2.7).
CONCLUSION: The amount and type of dietary fat intake may be associated with ARM.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10721964 [PubMed - indexed for MEDLINE]

3252: Arch Ophthalmol. 2000 Mar;118(3):351-8.

Hypertension, cardiovascular disease, and age-related macular degeneration.
Age-Related Macular Degeneration Risk Factors Study Group.

Hyman L, Schachat AP, He Q, Leske MC.

Department of Preventive Medicine, University Medical Center, Stony Brook, NY
11794-8036, USA. lhyman@uhmc.sunysb.edu

OBJECTIVES: To describe a case-control study of risk factors for neovascular and 
non-neovascular age-related macular degeneration (AMD) and to present findings on
associations with systemic hypertension and cardiovascular disease. METHODS:
Participants with and without neovascular and non-neovascular AMD were recruited 
from 11 ophthalmology practices in the New York, NY, metropolitan area.
Comprehensive data collection included (1) a standardized interview, (2) blood
pressure measurements, and (3) blood samples. Cases and controls were classified 
from fundus photograph gradings. Polychotomous logistic regression analyses were 
used to evaluate associations. RESULTS: Classification of 1222 sets of available 
photographs resulted in the inclusion of a neovascular case group (n = 182), a
non-neovascular case group (n = 227), and a control group (n = 235). Neovascular 
AMD was positively associated with diastolic blood pressure greater than 95 mm Hg
(odds ratio [OR] = 4.4), self-reported use of potent antihypertensive medication 
(OR = 2.1), physician-reported history of hypertension (OR = 1.8), use of
antihypertensive medication (OR = 2.5), combinations of self-reported and
physician-reported data on hypertension and its treatment (OR = 1. 7),
high-density lipoprotein level (OR = 2.3), and dietary cholesterol level (OR =
2.2). Non-neovascular AMD was unrelated to hypertension or cholesterol level. No 
associations were found between either AMD type and other definitions of
hypertension or other cardiovascular disease. CONCLUSIONS: These findings suggest
that neovascular AMD is associated with moderate to severe hypertension,
particularly among patients receiving antihypertensive treatment. They also
support the hypotheses that neovascular and non-neovascular AMD may have a
different pathogenesis and that neovascular AMD and hypertensive disease may have
a similar underlying systemic process.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 10721957 [PubMed - indexed for MEDLINE]

3253: Jpn J Ophthalmol. 2000 Mar-Apr;44(2):115-21.

Analysis of the metallothionein gene in age-related macular degeneration.

Sato M, Abe T, Tamai M.

Department of Ophthalmology, Tohoku University School of Medicine, Sendai, Japan.

PURPOSE: To analyze the expression of metallothionein in neovascular membranes in
patients with age-related macular degeneration (AMD) and to compare the findings 
in patients with proliferative diabetic retinopathy and proliferative
vitreoretinopathy with findings in normal retinal pigment epithelial (RPE) cells.
METHODS: Semiquantitative reverse transcriptase-polymerase chain reaction and
immunohistochemical examinations were performed. Sequence analysis was also
carried out. RESULTS: Expression of the metallothionein-II gene was not
statistically significant in proliferative membranes. Sequence analysis revealed 
that there were at least six polymorphisms in the metallothionein-II gene and
three in the metallothionein-IA gene. However, no amino acid substitution was
observed. Metallothionein expression was also observed by immunohistochemical
techniques in RPE cells of neovascular membranes in AMD patients. CONCLUSIONS:
Metallothionein was reported to be decreased in aged macular RPE and in some
monkey retina with early onset of macular degeneration. However, our results
suggest that the expression of the metallothionein-II gene in neovascular
membranes in patients with AMD may be controlled like other proliferating cells.

PMID: 10715376 [PubMed - indexed for MEDLINE]

3254: Ophthalmology. 2000 Mar;107(3):593-9.

Comparison between optical coherence tomography and fundus fluorescein
angiography for the detection of cystoid macular edema in patients with uveitis.

Antcliff RJ, Stanford MR, Chauhan DS, Graham EM, Spalton DJ, Shilling JS, Ffytche
TJ, Marshall J.

GKT Department of Ophthalmology, Rayne Institute, St Thomas' Hospital, London,
England.

PURPOSE: To compare optical coherence tomography (OCT) with fundus fluorescein
angiography (FFA) for the detection of cystoid macular edema (CME) in patients
with uveitis. DESIGN: Prospective comparative observational series. PARTICIPANTS:
One hundred twenty-one eyes of 58 patients with uveitis of varied causes (seven
patients were studied twice). TESTING: Patients with suspected CME underwent OCT 
scanning followed by FFA at the same visit. MAIN OUTCOME MEASURES: Detection and 
distribution of macular edema. RESULTS: One hundred eight eyes had similar
results on both OCT and FFA in that 67 eyes had CME and 41 eyes had no CME. In 10
eyes subretinal fluid was detected on OCT but not FFA. Five of these eyes had CME
on FFA but not OCT. Three other eyes had CME that was detected by FFA but not by 
OCT. Compared with FFA, the OCT sensitivity for detecting CME was 96% (including 
the eyes with subretinal fluid), and the OCT specificity was 100%. CONCLUSIONS:
OCT is as effective at detecting CME as is FFA but is superior in demonstrating
axial distribution of fluid.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 10711901 [PubMed - indexed for MEDLINE]

3255: Invest Ophthalmol Vis Sci. 2000 Mar;41(3):898-902.

TIMP-3, collagen, and elastin immunohistochemistry and histopathology of Sorsby's
fundus dystrophy.

Chong NH, Alexander RA, Gin T, Bird AC, Luthert PJ.

Department of Pathology, Institute of Ophthalmology, University College London,
England.

PURPOSE: Mutations in the tissue inhibitor of metalloproteinases-3 (TIMP-3) gene 
have previously been identified in patients with Sorsby's fundus dystrophy (SFD).
We evaluated the ocular distribution of TIMP-3 and other extracellular
constituents in SFD. METHODS: The eyes of an SFD donor with a confirmed TIMP-3
mutation were examined using histologic techniques demonstrating connective
tissue, calcium, and lipid. Immunohistochemical analyses were performed using
antibodies against TIMP-3, collagen type IV, V, and VI, laminin, fibronectin,
elastin, and fibrillin. Electron microscopy also was used. RESULTS: A subretinal 
pigment epithelium (sub-RPE) deposit similar to that previously described was
seen. A morphologically similar but different deposit was present internal to the
nonpigmented ciliary epithelium (NPCE). Both deposits contained collagens,
elastin, glycosaminoglycans, lipids, and calcium. Immunolabeling of TIMP-3 was
found in the basement membrane of the NPCE, Bruch's membrane, and choroidal
vessels in normal control subjects. In SFD, immunolabeling of TIMP-3 also was
present in the sub-RPE deposit and in the inner portion of the ciliary body
deposit. TIMP-3 immunoreactivity was more extensive in the SFD eye. The pattern
of elastin immunoreactivity was remarkably similar to that of TIMP-3. Electron
microscopy revealed a morphologically altered elastic layer of the Bruch's
membrane. CONCLUSIONS: Sub-RPE TIMP-3 immunoreactivity appears more extensive in 
SFD than in control subjects. There is also a correspondence between TIMP-3 and
elastin immunoreactivies, which invites speculation as to a link between the SFD 
TIMP-3 mutation and altered elastin processing. The accumulation of abnormal
material in SFD is more widespread than previously reported. In view of this, SFD
might be better termed Sorsby's ocular epitheliopathy.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10711711 [PubMed - indexed for MEDLINE]

3256: Invest Ophthalmol Vis Sci. 2000 Mar;41(3):892-7.

New ABCR mutations and clinical phenotype in Italian patients with Stargardt
disease.

Simonelli F, Testa F, de Crecchio G, Rinaldi E, Hutchinson A, Atkinson A, Dean M,
D'Urso M, Allikmets R.

Eye Clinic, Second University of Naples, Italy.

PURPOSE: To assess the mutation spectrum in the ABCR gene and clinical phenotypes
in Italian families with autosomal recessive Stargardt disease (STGD1) and fundus
flavimaculatus (FFM). METHODS: Eleven families from southern Italy, including 18 
patients with diagnoses of STGD1, were clinically examined. Ophthalmologic
examination included kinetic perimetry, electrophysiological studies, and
fluorescein angiography. DNA samples of the affected individuals and their family
members were analyzed for variants in all 50 exons of the ABCR gene by a
combination of single-strand conformation polymorphism analysis and direct
sequencing techniques. RESULTS: TenABCR variants were identified in 16 (73%) of
22 mutant alleles of patients with STGD1. Five mutations of 10 that were found
had not been previously described. The majority of variants represent missense
amino acid substitutions, and all mutant alleles cosegregate with the disease in 
the respective families. These ABCR variants were not detected in 170 unaffected 
control individuals (340 chromosomes) of Italian origin. Clinical evaluation of
these families affected by STGD1 showed an unusually high frequency of early
age-related macular degeneration (AMD) in parents of patients with STGD1 (8/22;
36%), consistent with the hypothesis that some heterozygous ABCR mutations
enhance susceptibility to AMD. CONCLUSIONS: Patients from southern Italy with
Stargardt disease show extensive allelic heterogeneity of the ABCR gene,
concordant with previous observations in patients with STGD1 from different
ethnic groups. Half the mutations identified in this study had not been
previously described in patients with STGD1. Screening of increasingly large
numbers of patients would help to determine whether this can be explained by
ethnic differences, or is an indicator of extensive allelic heterogeneity of ABCR
in STGD1 and other eye diseases. In 6 (55%) of 11 families, the first-degree
relatives of patients with STGD1 were diagnosed with early AMD, supporting the
previous observation that some STGD1 alleles are also associated with AMD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10711710 [PubMed - indexed for MEDLINE]

3257: Invest Ophthalmol Vis Sci. 2000 Mar;41(3):877-9.

Laser treatment and the mechanism of edema reduction in branch retinal vein
occlusion.

Arnarsson A, Stefánsson E.

Department of Ophthalmology, University of Iceland, Reykjavik.

PURPOSE: To test a hypothesis on the physiological mechanism of the disappearance
of macular edema after laser treatment. The hypothesis is based on the effect
grid laser treatment has on retinal oxygenation and hemodynamics. It predicts
that laser-induced reduction of macular edema is associated with shortening and
narrowing of retinal vessels in patients with branch retinal vein occlusion
(BRVO). METHODS: The study included 12 subjects, treated with argon laser
photocoagulation for BRVO and macular edema. Fundus photographs taken at the time
of diagnosis and again after laser treatment, were digitized, and diameter and
segment length of retinal vessels was measured using NIH-Image program. RESULTS: 
Macular edema disappeared or was dramatically reduced in all cases after laser
treatment. The diameter of occluded venules constricted to 0.81+/-0.02 (mean +/- 
SD, P = 0.019) of the prelaser diameter and adjacent arterioles constricted to
0.78+/-0.01 (P = 0.008). The laser treatment also led to shortening of the
affected vessels. The final segment length of the occluded venules was
0.95+/-0.17 (P = 0.005) of the length before treatment. The corresponding value
for the adjacent arterioles is 0.95+/-0.14 (P = 0.008). Control arterioles and
venules in the same fundus did not change in either length or width. CONCLUSIONS:
These results do not reject the authors' hypothesis that the disappearance of
macular edema in BRVO can be explained by the effect the laser photocoagulation
has on retinal oxygenation. Increased oxygenation causes vessel constriction and 
shortening and lower intravascular pressure, which reduces edema formation
according to Starling's law.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10711707 [PubMed - indexed for MEDLINE]

3258: Jpn J Ophthalmol. 2000 Jan-Feb;44(1):91-3.

Role of the vitreous in age-related macular degeneration.

Ondeş F, Yilmaz G, Acar MA, Unlü N, Kocaoğlan H, Arsan AK.

Ankara Hospital, Department of Ophthalmology, Cebeci, Turkey.

PURPOSE: To investigate the relationship between posterior vitreous detachment
(PVD) and age-related macular degeneration (AMD). METHODS: The condition of the
vitreous was examined by slit-lamp funduscopy and ultrasonography in 93 eyes of
50 patients with AMD (exudative or dry) and 100 eyes of 50 controls. RESULTS:
There was complete PVD in 31 of the 93 eyes (33.3%) of 50 patients with AMD and
the posterior vitreous was attached in 62 of these eyes (66.6%). In the control
group, in 50 eyes (50%) of 50 subjects there was posterior vitreous detachment.
The prevalence of PVD in eyes with macular degeneration was significantly lower
(P < .05). There was no statistically significant difference between the
exudative and the nonexudative groups in respect to PVD. CONCLUSIONS: PVD may
have a protective role against the development of AMD. Chronic vitreomacular
traction and/or continuous exposure to free radicals and cytokines may possibly
be one of the causes of AMD in eyes with attached vitreous.

Publication Types: 
    Comparative Study

PMID: 10698032 [PubMed - indexed for MEDLINE]

3259: Jpn J Ophthalmol. 2000 Jan-Feb;44(1):58-67.

Comparison of diclofenac and fluorometholone in preventing cystoid macular edema 
after small incision cataract surgery: a multicentered prospective trial.

Miyake K, Masuda K, Shirato S, Oshika T, Eguchi K, Hoshi H, Majima Y, Kimura W,
Hayashi F.

Miyake Eye Hospital, Nagoya, Japan.

PURPOSE: To compare a nonsteroidal topical solution (0.1% diclofenac) to a
steroidal topical solution (0.1% fluorometholone) in preventing cystoid macular
edema (CME) and disruption of the blood-aqueous barrier. METHODS: A
multicentered, prospective clinical trial was performed on eyes undergoing
phacoemulsification followed by implantation of a foldable acrylic intraocular
lens by the envelope technique. The presence and degree of cystoid macula edema
(CME) was determined by fluorescein angiography. A breakdown of the blood-aqueous
barrier was determined by laser flare-cell photometry. RESULTS: Five weeks after 
surgery, CME was present in 3 of 53 eyes (5.7%) receiving diclofenac and in 29 of
53 eyes (54.7%) receiving fluorometholone. This difference was statistically
significant (P < .001). The amount of flare in the anterior chamber at 3 days, 1,
2, 5, and 8 weeks after surgery was also significantly lower (P < .01-P < .001)
in the diclofenac group. The degree of flare at 3 days, 1, 2, 5, and 8 weeks
after surgery was significantly higher in eyes with CME (P < .001). CONCLUSIONS: 
These findings suggest that diclofenac effectively prevents CME following
cataract surgery and that CME is closely related to the breakdown of the
blood-aqueous barrier.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial

PMID: 10698027 [PubMed - indexed for MEDLINE]

3260: Retina. 2000;20(1):63-8.

Electron immunocytochemical analysis of posterior hyaloid associated with
diabetic macular edema.

Jumper JM, Embabi SN, Toth CA, McCuen BW II, Hatchell DL.

Vitreoretinal Service, Duke University Eye Center, Durham, North Carolina 27710, 
USA.

BACKGROUND: Tangential traction in the macula from a thickened posterior hyaloid 
of the vitreous has been implicated as a cause of diffuse diabetic macular edema.
Vitrectomy with peeling of the posterior hyaloid has been shown to reduce
retinovascular leakage and improve vision in select patients. We report a
clinicopathologic correlation using electron microscopy and electron
immunocytochemistry to characterize the membrane infiltrating the posterior
hyaloid in two such patients. METHODS: Two patients presented with vision loss
associated with diffuse diabetic macular edema and an attached, thickened, and
taut posterior hyaloid. The patients underwent vitrectomy with peeling of the
posterior hyaloid. The premacular posterior hyaloid specimens then were analyzed 
by electron microscopy with immunocytochemical staining for cytokeratin and glial
fibrillary acidic protein. RESULTS: Both posterior hyaloid specimens contained
collagen and a large cellular component. Immunogold labeling showed cells
positive for glial fibrillary acidic protein or cytokeratin. With double
labeling, no cells expressed both proteins simultaneously. Clinically, both
patients had vision improvement and macular edema resolution after surgery.
CONCLUSIONS: The thickened, taut posterior hyaloid observed in our patients with 
diabetic macular edema contained cells of glial and epithelial origin. This
cellular infiltration may contribute to abnormal vitreomacular adherence and
could play a role in the pathogenesis of macular edema in some patients with
diabetes.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, Non-P.H.S.
    Research Support, U.S. Gov't, P.H.S.

PMID: 10696750 [PubMed - indexed for MEDLINE]

3261: Ann Epidemiol. 2000 Feb;10(2):125-34.

Design of Physicians' Health Study II--a randomized trial of beta-carotene,
vitamins E and C, and multivitamins, in prevention of cancer, cardiovascular
disease, and eye disease, and review of results of completed trials.

Christen WG, Gaziano JM, Hennekens CH.

Department of Medicine, Brigham and Women's Hospital, Harvard Medical School,
Boston, MA, USA.

PURPOSE: To assess the balance of benefits and risks of supplementation with
beta-carotene, vitamin E, vitamin C, and multivitamins on cancer, cardiovascular 
(CVD), and eye diseases. DESIGN: Physicians' Health Study II (PHS II) is a
randomized, double-blind, placebo-controlled trial enrolling 15,000 willing and
eligible physicians aged 55 years and older. PHS II will utilize a 2 x 2 x 2 x 2 
factorial design to test alternate day beta-carotene, alternate day vitamin E,
daily vitamin C, and a daily multivitamin, in the prevention of total and
prostate cancer, CVD, and the age-related eye diseases, cataract and macular
degeneration. PRIOR RESULTS: The final results of the recently completed
Physicians' Health Study I (PHS I), a randomized, double-blind,
placebo-controlled trial in 22,071 healthy US male physicians, indicated that
beta-carotene supplementation (50 mg on alternate days) had no significant
benefit or harm on cancer or CVD during more than 12 years of treatment and
follow-up. In regards to cancer, there were possible benefits on total and
prostate cancer in those with low baseline levels assigned to beta-carotene, a
finding compatible with the Chinese Cancer Prevention Study for combined
treatment with beta-carotene, vitamin E, and selenium in a poorly nourished
population. Further, with respect to CVD, there were apparent benefits of
beta-carotene supplementation on subsequent vascular events among a small
subgroup of 333 men with prior angina or revascularization. The currently
available data from randomized trials of primary prevention are sparse and
inconsistent for vitamin E and non-existent for vitamin C and multivitamins. For 
eye diseases, namely cataract and age-related macular degeneration, there are no 
completed large-scale randomized trials of antioxidant vitamins. CONCLUSIONS: PHS
II is unique in several respects. PHS II is the only primary prevention trial in 
apparently healthy men testing the balance of benefits and risks of vitamin E on 
cancer and CVD. In addition, PHS II is the only primary prevention trial in
apparently healthy men to test the balance of benefits and risks of vitamin C,
multivitamins, as well as any single antioxidant vitamin, alone and in
combination, on cancer, CVD, and eye diseases. Finally, PHS II is the only trial 
testing a priori the hypotheses that beta-carotene and vitamin E may reduce the
risks of prostate cancer. Thus, PHS II will add unique as well as importantly
relevant and complementary information to the totality of evidence from other
completed and ongoing large-scale randomized trials on the balance of benefits
and risks of beta-carotene, vitamin E, vitamin C, and multivitamins alone and in 
combination on prevention of cancer, CVD and eye diseases.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.
    Review

PMID: 10691066 [PubMed - indexed for MEDLINE]

3262: Ophthalmology. 2000 Feb;107(2):375-85.

Infrared scanning laser tomography of macular cysts.

Beausencourt E, Remky A, Elsner AE, Hartnett ME, Trempe CL.

Schepens Eye Research Institute, Boston, Massachusetts 02114-2500, USA.

OBJECTIVE: To perform three-dimensional, noninvasive, quantitative analysis of
cystoid macular edema and macular cysts using infrared scanning laser tomography 
and to correlate findings with visual acuity (VA) as a basis for interventional
studies. DESIGN: Cross-sectional, nonrandomized study. PARTICIPANTS: Seventeen
patients (29-86 years of age) with macular cysts associated with a broad spectrum
of diseases. INTERVENTION: Confocal infrared imaging with scanning laser
tomography with the TopSS (790 nm) (Laser Diagnostic Technologies, San Diego, CA)
with digitized images was used to perform three-dimensional, quantitative
analysis of cysts in the central 5 degrees of the macula. MAIN OUTCOME MEASURES: 
Measurements of macular cyst number, area, volume, depth, slope, height of the
surrounding macular elevation, and correlation with VA. RESULTS: Scanning laser
tomography detected macular cysts in all patients. The number per patient ranged 
from 1 through 15. Cysts were accompanied by surrounding macular elevation in 16 
patients (mean macular height, 216 microm). The area covered by cysts in the
central 5 degrees was 0.087 to 0.969 mm2, and volume was 0.007 to 0.549 mm3.
Visual acuity was significantly poorer in patients with greater cyst area (P =
0.0007), cyst volume (P = 0.0009), macular thickening (P = 0.0002), and cyst
depth (P = 0.0013). Cyst number, average slope, and maximum slope, however, did
not correlate significantly with VA. Grouping of macular cysts according to
macular height and average cyst depth revealed that cysts in a more thickened
retina were significantly deeper, had steeper slopes, and corresponded to worse
VA. Macular height and average cyst depth were highly associated with each other,
suggesting that in eyes with surrounding macular edema, cysts were deeper and may
reflect more widespread tissue destruction. Individual confocal tomographic
images provided additional information. Neither ophthalmoscopy nor fluorescein
angiography delineated features such as retinal folds that suggested vitreous
traction or changes in deeper layers that suggested occult choroidal new vessels.
CONCLUSIONS: Infrared scanning laser tomography is a rapid and noninvasive
imaging method that provides quantitative analysis of macular cysts in addition
to qualitative information not seen clinically. Because poor VA is related to
severe involvement of the central retina, scanning laser tomography could provide
an objective outcome measure for interventional studies.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 10690842 [PubMed - indexed for MEDLINE]

3263: Br J Ophthalmol. 2000 Mar;84(3):244-50.

Macular degeneration: do conventional measurements of impaired visual function
equate with visual disability?

McClure ME, Hart PM, Jackson AJ, Stevenson MR, Chakravarthy U.

Division of Ophthalmology and Vision Science, The Queen's University of Belfast
and Royal Group of Hospitals, Belfast BT12 6BA, UK.

AIMS: To examine the relation between measures of vision and ability to perform
daily living tasks in those visually impaired with macular degeneration. METHODS:
A visual functioning index (daily living tasks dependent on vision: DLTV) was
used to evaluate patients' perception of their ability to perform vision
dependent tasks. Distance visual acuity, near visual acuity, reading speed, and
contrast sensitivity were measured in all patients. In addition, a new measure of
reading ability was derived, designated the reading index. This takes into
account both the size of the text read and the time to read it and is equivalent 
to the reading speed in words per minute divided by text size in M. RESULTS: The 
reading index was found to show best associations with the majority of items
within the DLTV. Stepwise regression identified the combination of reading index 
and distance visual acuity as having the best associations with DLTV items. The
present study also demonstrated that specific levels of vision as measured by
acuity, reading index, and contrast sensitivity corresponded with different
perceived amounts of difficulty in the performance of daily living tasks.
CONCLUSIONS: This study showed that reading index is valuable in predicting the
ability to perform daily living tasks and therefore may be useful in the visual
assessment of the visually impaired individual. In addition, this study
identified specific levels of vision at which individuals reported different
degrees of difficulty in performing daily living tasks.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10684832 [PubMed - indexed for MEDLINE]

3264: Br J Ophthalmol. 2000 Mar;84(3):239-43.

Clinicopathological correlation in exudative age related macular degeneration:
histological differentiation between classic and occult choroidal
neovascularisation.

Lafaut BA, Bartz-Schmidt KU, Vanden Broecke C, Aisenbrey S, De Laey JJ, Heimann
K.

University Eye Clinic, Joseph-Stelzmann- Strasse 9, D-50931 Cologne, Germany.

AIMS: To analyse the histopathology of classic and occult choroidal neovascular
membrane surgical specimens in age related macular degeneration. METHODS: 35
membranes, from a consecutive series of surgically removed choroidal neovascular 
membranes in age related macular degeneration, were classified as classic or
occult following the guidelines of the Macular Photocoagulation Study. Membranes 
with classic as well as occult components were considered as mixed membranes. The
membranes were serially sectioned and stained with haematoxylin and eosin, Masson
trichrome, periodic acid-Schiff, and phosphotungstic acid haematoxylin stain. The
correlation has been made in a masked fashion. RESULTS: 31 membranes (19 classic,
10 occult, and two mixed membranes) could be analysed histologically. 18 classic 
choroidal neovascular membranes had a major subretinal fibrovascular component
and 10 of these had an additional, minor fibrovascular component under the
retinal pigment epithelium. The 10 occult membranes contained a fibrovascular
component under the retinal pigment epithelium and the two mixed membranes
contained fibrovascular tissue on both sides of the retinal pigment epithelium.
Fibrin and remains of outer segments tended to occur at the lateral edges of
classic membranes and to cover the inner surface of occult membranes. CONCLUSION:
Classic choroidal neovascularisation in age related macular degeneration is
predominantly composed of subretinal fibrovascular tissue while occult choroidal 
neovascularisation is composed of fibrovascular tissue at the choroidal side of
the retinal pigment epithelium.

PMID: 10684831 [PubMed - indexed for MEDLINE]

3265: Am J Ophthalmol. 2000 Feb;129(2):264-7.

Optical cross-sectional observation of resolved diabetic macular edema associated
with vitreomacular separation.

Watanabe M, Oshima Y, Emi K.

Department of Ophthalmology, Osaka Rosai Hospital, Sakai-City, Japan.

PURPOSE: To describe the resolution of cystoid macular edema associated with
vitreomacular separation in a diabetic patient. METHODS: Case report. A
58-year-old man who had cataract surgery 3 years earlier developed diabetic
macular edema after panretinal laser photocoagulation. For a detailed fundus
examination, we performed neodymium: YAG (Nd:YAG) laser capsulotomy in the left
eye as the initial management. RESULTS: Two days after the laser capsulotomy,
fundus biomicroscopy and B-mode ultrasonography disclosed a vitreomacular
separation in the left eye that was not detectable preoperatively. Optical
coherence tomography through the macula disclosed a dramatic decrease in the size
of intraretinal cystoid spaces with an improvement of visual acuity. Scanning
retinal thickness analysis also confirmed the decrease of retinal thickness at
the macula with the resolution of cystoid macular edema. CONCLUSION: Resolution
of diabetic macular edema with subsequent visual recovery is potentially
associated with the vitreomacular separation in a patient after Nd:YAG laser
capsulotomy.

Publication Types: 
    Case Reports

PMID: 10682989 [PubMed - indexed for MEDLINE]

3266: Am J Ophthalmol. 2000 Feb;129(2):260-2.

A novel spontaneous missense mutation in VMD2 gene is a cause of a best macular
dystrophy sporadic case.

Palomba G, Rozzo C, Angius A, Pierrottet CO, Orzalesi N, Pirastu M.

Istituto di Genetica Molecolare, CNR, Alghero, Italy.

PURPOSE: To report the molecular characterization of a novel VMD2 mutation
causing a Best macular dystrophy sporadic case. METHODS: All family members
underwent ophthalmologic examination and genetic testing by single strand
conformation polymorphism analysis and direct sequencing of the VMD2 gene.
RESULTS: A single T to G transition at nucleotide 663 was identified in one of
the VMD2 gene copies of the patient, which results in a Cys to Trp substitution
at position 221 in the corresponding protein (C221W). Sequence analysis of the
VMD2 exon 6 of both parents of the patient did not reveal any mutation.
CONCLUSION: These data confirm the involvement of the VMD2 gene in Best macular
dystrophy onset, even in sporadic cases of the disease, pointing out the
relevance of molecular analysis in the diagnosis of this degenerative retinal
disease.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 10682987 [PubMed - indexed for MEDLINE]

3267: Am J Ophthalmol. 2000 Feb;129(2):205-14.

Location, substructure, and composition of basal laminar drusen compared with
drusen associated with aging and age-related macular degeneration.

Russell SR, Mullins RF, Schneider BL, Hageman GS.

University of Iowa Center for Macular Degeneration, Department of Ophthalmology
and Visual Sciences, The University of Iowa, Iowa City 52242-1091, USA.
steven-russell@uiowa.edu

PURPOSE: To determine whether basal laminar drusen differ in their location,
ultrastructure, or composition from drusen associated with aging and age-related 
macular degeneration. METHODS: A paraffin-embedded block from an eye of a patient
with basal laminar drusen was obtained. Sections were examined
immunohistochemically using a battery of antibodies and lectins directed against 
drusen-associated proteins and glycoconjugates, respectively. Thin sections were 
examined by electron microscopy and compared with eyes with age-related macular
degeneration. RESULTS: Drusen in the eye with basal laminar drusen are located
between the basal lamina of the retinal pigment epithelium and the inner
collagenous layer of Bruch membrane, just as they are in age-related macular
degeneration. Two distinct ultrastructural phenotypes are observed in the eye
with basal laminar drusen; their substructure is indistinguishable from drusen
phenotypes in age-related macular degeneration. Both basal laminar drusen and
drusen associated with age-related macular degeneration are bound by the lectins 
Ricinis communis agglutinin and Arachis hypogea agglutinin (after neuraminidase
digestion) and by antivitronectin, anti-HLA-DR, anti-serum amyloid P, and anti-C5
antibodies, but not by antibodies directed against basement membrane-associated
heparan sulfate proteoglycan, laminin, fibrinogen, or collagen type IV.
CONCLUSIONS: These data support the notion that cuticular or basal laminar drusen
are similar to, and perhaps indistinguishable from, drusen associated with
age-related macular degeneration and are not nodular or diffuse thickenings of
Bruch membrane, as previously suggested. Thus, we suggest basal laminar drusen is
a misnomer. This clinical phenotype should be identified as "early adult onset,
grouped drusen" or by the eponym "Gass syndrome." Features of basal laminar
drusen, such as uniform drusen size, clustered distribution, and angiographic
features, do not appear to be related to differences in drusen location,
composition, or substructure.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 10682974 [PubMed - indexed for MEDLINE]

3268: J Struct Biol. 2000 Feb;129(1):38-47.

Structure of abnormal molecular assemblies (collagen VI) associated with human
full thickness macular holes.

Knupp C, Munro PM, Luther PK, Ezra E, Squire JM.

Biological Structure and Function Section, Biomedical Sciences Division, London, 
SW7 2AZ, United Kingdom.

Transversely banded deposits with an approximately 100-nm periodicity have been
seen in association with a number of eye pathologies (e.g., age-related macular
degeneration). Recently such aggregates have also been discovered in the cortical
vitreous of a patient suffering from full thickness macular holes. The aggregates
in the vitreous were of sufficient size and regularity for us to attempt 3D
ultrastructural studies in the electron microscope. The molecules forming this
aggregate pack in a centered tetragonal unit cell of dimensions approximately 26 
x 26 x 180 nm. A real-space (r-weighted back projection) 3D reconstruction was
computed. The aggregate is discussed in terms of its possible protein
constituents. Collagen VI has been singled out as the most likely protein to form
the aggregate. Two alternative models for the molecular packing are proposed,
comprising aggregates of molecular tetramers or octamers. Understanding the
structure of these abnormal banded deposits in the eye should help to throw light
on the pathophysiological mechanisms of the diseases, including age-related
macular degeneration, in which they occur. Copyright 2000 Academic Press.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10675295 [PubMed - indexed for MEDLINE]

3269: Prog Retin Eye Res. 2000 Mar;19(2):205-21.

Oxidative damage and protection of the RPE.

Cai J, Nelson KC, Wu M, Sternberg P Jr, Jones DP.

Department of Biochemistry, Emory University School of Medicine, Atlanta, GA
30322, USA.

This review provides a model for the role of oxidative stress in the etiology of 
age-related macular degeneration (AMD). Epidemiological studies of diet,
environmental and behavioral risk factors suggest that oxidative stress is a
contributing factor of AMD. Pathological studies indicate that damage to the
retinal pigment epithelium (RPE) is an early event in AMD. In vitro studies show 
that oxidant treated RPE cells undergo apoptosis, a possible mechanism by which
RPE cells are lost during early phase of AMD. The main target of oxidative injury
seems to be mitochondria, an organelle known to accumulate genomic damages in
other postmitotic tissues during aging. The thiol antioxidant GSH and its amino
acid precursors protect RPE cells from oxidant-induced apoptosis. Similar
protection occurs with dietary enzyme inducers which increase GSH synthesis.
These results indicate that therapeutic or nutritional intervention to enhance
the GSH antioxidant capacity of RPE may provide an effective way to prevent or
treat AMD.

Publication Types: 
    In Vitro
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.
    Review

PMID: 10674708 [PubMed - indexed for MEDLINE]

3270: Invest Ophthalmol Vis Sci. 2000 Feb;41(2):513-7.

Multifocal electroretinogram in occult macular dystrophy.

Piao CH, Kondo M, Tanikawa A, Terasaki H, Miyake Y.

Department of Ophthalmology, Nagoya University School of Medicine, Japan.
piao@med.nagoya-u.ac.jp

PURPOSE: Occult macular dystrophy (OMD) is an unusual macular dystrophy
presenting with an essentially normal fundus and fluorescein angiography but with
progressive central visual loss. The authors studied the function of local
retinal areas in the posterior pole of patients with OMD using multifocal
electroretinograms (ERGs). METHODS: Multifocal ERGs were recorded using the
Visual Evoked Response Imaging System with 61 hexagonal elements within a visual 
field of 30 degrees radius from 8 OMD patients and 20 age-matched, normal
subjects. The amplitudes and implicit times of the patients and normal control
subjects were compared at the various retinal eccentricities. RESULTs. The
amplitudes of the multifocal ERGs in the OMD patients were markedly reduced in
the central 7 degrees of the fovea. The difference of the ERG amplitudes between 
OMD and normal subjects became smaller toward the peripheral retina. Most OMD
patients had slight but significantly delayed implicit times across the whole
testing field, and the differences between the OMD and the normal subjects did
not change with retinal eccentricity. CONCLUSIONS. Our results for multifocal ERG
amplitudes support the idea that OMD patients have localized retinal dysfunction 
distal to the ganglion cells in the central retina. The delayed implicit times
across the whole test field suggest that the retinal dysfunction has a broader
boundary than expected by ERG amplitudes and psychophysical perimetric results.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10670483 [PubMed - indexed for MEDLINE]

3271: Invest Ophthalmol Vis Sci. 2000 Feb;41(2):496-504.

Autofluorescence distribution associated with drusen in age-related macular
degeneration.

Delori FC, Fleckner MR, Goger DG, Weiter JJ, Dorey CK.

Schepens Eye Research Institute, Boston, Massachusetts 02114, USA.
delori@vision.eri.harvard.edu

PURPOSE: To determine whether drusen in patients with age-related maculopathy and
macular degeneration (ARM/AMD) are associated with focal changes in retinal
pigment epithelium (RPE) lipofuscin fluorescence. METHOD: A new autofluorescence 
imaging device was used to study lipofuscin distribution associated with
individual drusen in 20 patients with ARM/AMD. Paired monochromatic and
autofluorescence fundus images were used for detailed analysis of the topography 
of autofluorescence at specific sites containing drusen. In four eyes, image
analysis was used to compare the spatial distribution of the autofluorescence
with the location of drusen and to quantify the autofluorescence distribution
over individual drusen (54 drusen). REsuLTs. A specific pattern of
autofluorescence was frequently found to be spatially associated with hard drusen
and soft drusen between 60 and 175 microm in size. The pattern is characterized
by a central area of decreased autofluorescence surrounded, in most cases, by an 
annulus of increased autofluorescence. The location of this pattern was highly
correlated with the position of individual distinct drusen. The central low
autofluorescence focus was on average 16% below the surrounding background, and
the annulus, when present, was on average 6% more fluorescent than the
background. Soft drusen larger than 175 microm and confluent soft drusen show
either multifocal areas of low autofluorescence or a more heterogeneous
distribution. CONCLUSIoNs. Autofluorescence imaging permits measurement of RPE
lipofuscin at specific sites. RPE overlying drusen have altered autofluorescence,
suggesting changes in RPE health.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 10670481 [PubMed - indexed for MEDLINE]

3272: J Med Genet. 2000 Feb;37(2):83-7.

Genetic susceptibility to age related macular degeneration.

Yates JR, Moore AT.

Department of Medical Genetics, University of Cambridge, Box 134, Addenbrooke's
Hospital, Cambridge CB2 2QQ, UK.

Age related macular degeneration (AMD) is the leading cause of visual impairment 
in the elderly and a major cause of blindness in the developed world. The disease
can take two forms, geographic atrophy and choroidal neovascularisation. The
pathogenesis of AMD is poorly understood. There are undoubtedly environmental and
other risk factors involved and the adverse effect of smoking is well
established. Several studies have shown that genetic factors are important but
leave uncertainty about the magnitude and nature of the genetic component and
whether it varies with the type of AMD. Several hereditary retinal dystrophies
show similarities to AMD and these genes are potential candidate susceptibility
genes. Particular interest has focused on the ABCR gene which is responsible for 
autosomal recessive Stargardt macular dystrophy. It has been claimed that
heterozygotes for ABCR mutations are predisposed to AMD but the data are
conflicting. Studies of the genes responsible for autosomal dominant Sorsby
fundus dystrophy, Doyne honeycomb retinal dystrophy, and Best disease have given 
negative results. In one large AMD family, linkage has been reported to markers
in 1q25-q31. Recent data suggest that the ApoE epsilon4 allele may be associated 
with reduced risk of AMD. A better understanding of the genetic factors in AMD
would contribute to understanding the pathogenesis. If those at risk could be
identified it may be possible to modify lifestyle or develop novel therapies in
the presymptomatic stage to prevent disease or decrease its severity.

Publication Types: 
    Review

PMID: 10662806 [PubMed - indexed for MEDLINE]

3273: Br J Ophthalmol. 2000 Feb;84(2):158-64.

Coffee and doughnut maculopathy: a cause of acute central ring scotomas.

Kerrison JB, Pollock SC, Biousse V, Newman NJ.

Department of Ophthalmology, Emory University School of Medicine, Atlanta,
Georgia, USA.

AIMS: To report the clinical features of five patients with non-progressive
central ring scotomas of acute onset associated with excellent retained visual
acuity. METHODS: Complete neuro-ophthalmological examinations were performed.
Visual fields were performed by tangent screen, Goldmann, or Humphrey perimetry. 
In some cases further testing was carried out including fundus photography,
fluorescein angiography, ERG, VEP, and neuroimaging. RESULTS: The patients were
three women and two men whose ages ranged from 25 to 57 years. Four patients were
heavy caffeine consumers while the fifth patient experienced an episode of
hypotension. Vision loss was acute in all cases. The onset of vision loss was
bilateral/simultaneous in three cases, bilateral/sequential in one case, and
unilateral in one case. All affected eyes retained visual acuities of 20/25 or
better. Colour vision was subnormal in three of four cases. Visual field defects 
were characterised by a central ring scotoma having an outer diameter less than
10 degrees. Fundus examination demonstrated temporal optic nerve pallor in three 
patients (five of 10 affected eyes) and reddish, petaloid macular lesions in one 
patient. Good visual acuity was maintained for the duration of follow up in all
five patients. CONCLUSION: Central ring scotomas with excellent retained visual
acuity may present as an acute, bilateral syndrome in patients who are heavy
caffeine consumers. The configuration of visual field loss and its location,
combined with the presence of temporal pallor in five eyes, suggest that the
defect localises to the inner layers of the macula. While these cases could be
considered an expansion of the clinical spectrum of acute macular
neuroretinopathy, some may represent a distinct entity.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 10655191 [PubMed - indexed for MEDLINE]

3274: Br J Ophthalmol. 2000 Feb;84(2):150-3.

Visual and anatomical results of surgery for long standing macular holes.

Scott RA, Ezra E, West JF, Gregor ZJ.

Moorfields Eye Hospital, City Road, London EC1V 2PD.

AIMS: To determine the visual and anatomical outcome of surgery for long standing
idiopathic macular holes. METHODS: A retrospective review of 24 eyes of all 22
patients who underwent surgery for idiopathic full thickness macular holes (FTMH)
symptomatic for between 1 and 3 years. Postoperative follow up was for 6 months. 
Preoperative and postoperative visual acuities were recorded as well as the
presence of anatomical closure of the hole. RESULTS: The mean duration of
symptoms was 18.21 (SD 5.42) months). Anatomical closure of the FTMH was achieved
in 17 (70.8%) of the eyes at 6 months. The logMAR acuity of the group where
closure was achieved improved by a mean of 0.31, equivalent to a change of
Snellen acuity from 6/60 to 6/29. Where the hole remained open the acuity
deteriorated by a mean logMAR of 0.11 lines, equivalent to a change of Snellen
acuity from 6/60 to 5/60. Anatomical closure of the hole was associated with a
significantly improved acuity over non-closure (p<0.001). The degree of visual
improvement was independent of the preoperative visual acuity (Spearman
correlation coefficient 0.03, p=0.888), though preoperative acuity was related to
the final acuity (Spearman correlation coefficient 0.701, p<0.001). Over the
study period, six patients required cataract surgery, one patient developed
secondary glaucoma, and one a retinal detachment. CONCLUSIONS: Vitrectomy with
intraocular gas tamponade and postoperative posturing is a well tolerated and
effective intervention for long standing macular holes. Anatomical closure of the
macular hole is associated with a significant improvement in visual acuity.

PMID: 10655189 [PubMed - indexed for MEDLINE]

3275: Am J Ophthalmol. 2000 Jan;129(1):104-6.

Arteriovenous adventitial sheathotomy for the treatment of macular edema
associated with branch retinal vein occlusion.

Shah GK, Sharma S, Fineman MS, Federman J, Brown MM, Brown GC.

Retina Vascular Service, Wills Eye Hospital, Philadelphia, Pennsylvania, USA.

PURPOSE: To report arteriovenous adventitial sheathotomy for treatment of macular
edema associated with branch retinal vein occlusion. METHODS: Case reports with
review. Five eyes of five patients with best-corrected visual acuity of less than
20/200 secondary to branch retinal vein occlusion had pars plana vitrectomy and
arteriovenous adventitial sheathotomy and were followed postoperatively for a
mean of 6.5 years (range, 5 to 7 years). RESULTS: In four of five eyes, the
best-corrected visual acuity improved to 20/30 to 20/70. In the remaining eye,
visual acuity remained at finger counting secondary to macular ischemia.
CONCLUSION: Arteriovenous adventitial sheathotomy may be beneficial for select
patients with poor vision secondary to branch retinal vein occlusion.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10653427 [PubMed - indexed for MEDLINE]

3276: Am J Ophthalmol. 2000 Jan;129(1):27-32.

Scanning laser ophthalmoscope fundus perimetry before and after laser
photocoagulation for clinically significant diabetic macular edema.

Rohrschneider K, Bültmann S, Glück R, Kruse FE, Fendrich T, Völcker HE.

Department of Ophthalmology, University of Heidelberg, Germany.
Klaus_Rohrschneider@med.uni-heidelberg.de

PURPOSE: To prospectively evaluate functional and funduscopic changes after laser
treatment in patients with diabetic retinopathy and clinically significant
macular edema by scanning laser ophthalmoscope fundus perimetry. METHODS: Thirty 
eyes of 30 patients with clinically significant macular edema as a result of
diabetic retinopathy were prospectively examined before and at least 3 months
after focal laser treatment with automatic fundus threshold perimetry using the
scanning laser ophthalmoscope. Thresholds of light sensitivity were compared with
age-corrected normal values and correlated with corrected visual acuity and
subjective appraisal of visual function. RESULTS: In 30 eyes, fundus perimetry
lasted for 10.5+/-2.7 (mean+/-SD) minutes with 322+/-67 stimulus presentations
for each eye. Whereas eight eyes remained stable (< +/-1 dB change), 15 improved 
concerning mean deviation (MD) (3.1+/-1.7 dB) after focal laser treatment.
Stability of fixation remained the same after focal laser treatment (0.75+/-0.57 
degree). Laser scars showed marked loss of function (MD > 13 dB). CONCLUSIONS:
Although light sensitivity was reduced in areas of macular edema, there was no
correlation between the amount of edema and visual function. Fundus perimetry
allows the creation of exact maps of retinal dysfunction before and after laser
treatment. It may help in making management decisions in diabetic and nondiabetic
patients by offering a sensitive parameter in addition to visual acuity.

PMID: 10653409 [PubMed - indexed for MEDLINE]

3277: Ophthalmic Epidemiol. 2000 Mar;7(1):61-5.

Exposure to diagnostic x-rays and incident age-related eye disease.

Klein BE, Klein RE, Moss SE.

Department of Ophthalmology and Visual Sciences, University of Wisconsin Medical 
School, Madison, Wisconsin 53705-2397, USA.

OBJECTIVE. The purpose of this study was to evaluate whether a self-reported
history of computed tomography or other x-rays of the head were associated with
the incidence of age-related cataracts and maculopathy five years later. METHOD. 
A 5-year longitudinal follow-up of the Beaver Dam Eye Study cohort (n=3,684,
43-86 years at baseline). RESULTS. There was no evidence of a relationship
between the x-ray exposures and the incidence of nuclear or cortical cataracts,
or early maculopathy. There was a significant relationship to the incidence of
posterior subcapsular cataract after adjusting for age only. CONCLUSIONS. Adult
patients in whom medical conditions warrant diagnostic x-rays of the head appear 
to be at little or no increased risk of age-related cataract or maculopathy.
However, research efforts with more precise measures of x-ray exposure, longer
follow-up, and further attempts to define uncontrolled confounders are warranted.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 10652172 [PubMed - indexed for MEDLINE]

3278: Arch Ophthalmol. 2000 Jan;118(1):85-92.

Autosomal dominant hemorrhagic macular dystrophy not associated with the TIMP3
gene.

Ayyagari R, Griesinger IB, Bingham E, Lark KK, Moroi SE, Sieving PA.

W.K. Kellogg Eye Center, University of Michigan, Ann Arbor 48105, USA.
ayyagari@umich.edu

OBJECTIVE: To describe the ophthalmic and genetic findings of a large kindred
(UM:H389) with autosomal dominant hemorrhagic macular dystrophy. METHODS: The
disease state of family members was documented by dilated fundus examination,
electroretinography, color vision tests, fluorescein angiography, measurement of 
visual fields, biomicroscopy, gonioscopy, and intraocular pressure measurement.
Linkage and haplo-type analyses were carried out with markers flanking the Sorsby
fundus dystrophy TIMP3 (tissue inhibitor of metalloproteinase 3) gene locus, and 
mutation analysis was carried out by screening exon 5 of the TIMP3 gene. RESULTS:
This 4-generation pedigree with autosomal dominant hemorrhagic macular
degeneration has visual symptoms beginning in the sixth decade of life. Several
family members developed choroidal neovascular membrane formation in the macula
of both eyes. The phenotype overlaps that of Sorsby fundus dystrophy. Some of the
affected members have unusual zonularlike radial striations on the anterior lens 
capsule surface, and glaucoma or ocular hypertension has developed in 2 of them. 
Involvement of the TIMP3 gene was excluded by linkage, haplotype, and mutation
analyses. CONCLUSIONS: The phenotype of this family with autosomal dominant
macular dystrophy overlaps that of Sorsby fundus dystrophy. Exclusion of the
TIMP3 gene in this family indicates genetic heterogeneity for hemorrhagic macular
dystrophy. Anterior segment anomalies may occur with this condition, but
cosegregation has not yet been established. CLINICAL RELEVANCE: This study
broadens the spectrum of hemorrhagic macular dystrophy by identifying a family in
which the TIMP3 gene is not involved. Once the gene is cloned, we are eager to
learn whether this gene may be involved in age-related macular degeneration.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 10636420 [PubMed - indexed for MEDLINE]

3279: Arch Ophthalmol. 2000 Jan;118(1):47-51.

Utility values and age-related macular degeneration.

Brown GC, Sharma S, Brown MM, Kistler J.

Retina Vascular Unit, Wills Eye Hospital, Jefferson Medical College,
Philadelphia, PA, USA. gary0514@aol.com

OBJECTIVE: To ascertain the utility values associated with age-related macular
degeneration and varying degrees of visual loss. DESIGN: A cross-sectional study.
PARTICIPANTS: Eighty white patients with unilateral or bilateral age-related
macular degeneration in 1 or both eyes, and visual loss to a minimum of the 20/40
level in at least 1 eye. MAIN OUTCOME MEASURES: Utility values were measured in 5
groups according to the visual acuity in the better-seeing eye, 1 (20/20 to
20/25), 2 (20/30 to 20/ 50), 3 (20/60 to 20/100), 4 (20/200 to 20/400), and 5
(counting fingers to light perception), using the time trade-off and the standard
gamble methods. Conventionally assigned anchor utility values were 1.0 for
perfect health and 0.0 for death. RESULTS: The mean utility value for the total
group with age-related macular degeneration was 0.72 (95% confidence interval
[CI], 0.66-0.78) using the time trade-off method and 0.81 (95% CI, 0.76-0.86)
using the standard gamble method. Using the time trade-off method correlated with
the visual acuity in the better-seeing eye, the results were as follow: group 1, 
0.89 (95% CI, 0.82-0.96), group 2, 0.81 (95% CI, 0.73-0.89), group 3, 0.57 (95%
CI, 0.47-0.67), group 4, 0.52 (95% CI, 0.38-0.66), and group 5, 0.40 (95% CI,
0.29-0.50). Thus, those patients in group 1 were willing to trade 11% of their
remaining lifetime in return for perfect vision in each eye, whereas those in
group 5 were willing to trade 60% of their remaining lifetime in return for
perfect vision in each eye. CONCLUSION: Age-related macular degeneration causes a
substantial decrease in patient utility values and is highly dependent on the
degree of visual loss in the better-seeing eye.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10636413 [PubMed - indexed for MEDLINE]

3280: Invest Ophthalmol Vis Sci. 2000 Jan;41(1):267-73.

Psychophysical evidence for rod vulnerability in age-related macular
degeneration.

Owsley C, Jackson GR, Cideciyan AV, Huang Y, Fine SL, Ho AC, Maguire MG, Lolley
V, Jacobson SG.

Department of Ophthalmology, School of Medicine, University of Alabama at
Birmingham, USA.

PURPOSE: To determine whether there is rod system dysfunction in the central
retina of patients with age-related macular degeneration (AMD). METHODS:
Dark-adapted sensitivity (500-nm stimulus) and light-adapted sensitivity (600 nm)
were measured psychophysically at 52 loci in the central 38 degrees (diameter) of
retina in 80 patients with AMD, and results were compared with those from older
adult normal controls. All dark-adapted data were corrected for preretinal
absorption. RESULTS: Mean field dark-adapted sensitivity was significantly lower 
in AMD patients as a group than in normal subjects. Within the AMD group were
subsets of patients with normal mean dark- and light-adapted sensitivities;
reduced dark-adapted sensitivities without detectable light-adapted losses; both 
types of losses; and, least commonly, only light-adapted losses. Regional retinal
analyses of the dark-adapted deficit indicated the greatest severity was 2
degrees to 4 degrees or approximately 1 mm from the fovea, and the deficit
decreased with increasing eccentricity. CONCLUSIONS: These psychophysical results
are consistent with histopathologic findings of a selective vulnerability for
parafoveal rod photoreceptors in AMD. The different patterns of rod and cone
system losses among patients at similar clinical stages reinforces the notion
that AMD is a group of disorders with underlying heterogeneity of mechanism of
visual loss. Dark-adapted macula-wide testing may be a useful complement to the
more traditional outcome measures of fundus pathology and foveal cone-based
psychophysics in future AMD trials.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 10634630 [PubMed - indexed for MEDLINE]

3281: Invest Ophthalmol Vis Sci. 2000 Jan;41(1):248-55.

Autosomal dominant macular atrophy at 6q14 excludes CORD7 and MCDR1/PBCRA loci.

Griesinger IB, Sieving PA, Ayyagari R.

W.K. Kellogg Eye Center, University of Michigan, Ann Arbor 48105, USA.

PURPOSE: Localization of the gene responsible for autosomal dominant atrophic
macular degeneration (adMD) in a large pedigree UM:H785. METHODS: Standard
ophthalmologic examinations were performed. Microsatellite markers were used to
map the disease gene by linkage and haplotype analyses. RESULTS: The macular
degeneration in this family is characterized by progressive retinal pigment
epithelial atrophy in the macula without apparent peripheral involvement by
ophthalmoscopy or functional studies. Acuity loss progressed with age and
generally was worse in the older affected individuals. The rod and cone function 
remained normal or nearly normal in all tested affected members up to 61 years of
age. The phenotype in our family has characteristics similar to Stargardt-like
macular degeneration with some differences. Haplotype analysis localized the
disease gene in our adMD family to an 8-cM region at 6q14, which is within the
18-cM interval of STGD3 but excludes cone-rod dystrophy 7 (CORD7; centromeric)
and North Carolina macular degeneration and progressive bifocal chorioretinal
atrophy (MCDR1/PBCRA; telomeric). The mapping interval overlaps with that of
recessive retinitis pigmentosa (RP25). CONCLUSIONS: These results implicate at
least three genetically distinct loci for forms of macular degeneration that lie 
within a 30-cM interval on chromosome 6p11-6q16: CORD7, adMD, and MCDR1/PBCRA.
Because the critical interval for the adMD family studied overlaps with STGD3 and
RP25, these loci could be allelic.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 10634627 [PubMed - indexed for MEDLINE]

3282: Invest Ophthalmol Vis Sci. 2000 Jan;41(1):244-7.

ABCR gene analysis in familial exudative age-related macular degeneration.

Souied EH, Ducroq D, Rozet JM, Gerber S, Perrault I, Munnich A, Coscas G,
Soubrane G, Kaplan J.

INSERM U-393, Hôpital des Enfants-Malades, Paris, France.

PURPOSE: Identification of genetic factors in the pathogenesis of age-related
macular degeneration (AMD) is of crucial importance in this common cause of
blindness. Mutations in the Stargardt disease gene (ABCR) were previously
reported in patients with atrophic forms of AMD. The purpose of this study was to
analyze familial segregation of ABCR gene mutations in 52 unrelated multiplex
cases of exudative AMD. METHODS: A complete ophthalmological examination
including visual acuity measurement, fundus examination, and fluorescein
angiography (FA) was performed on each exudative AMD patient. The entire coding
sequence of the ABCR gene was analyzed using a combination of single-strand
conformation polymorphism and confirmatory sequencing of the exons showing an
abnormal pattern of migration. RESULTS: Six heterozygous missense changes were
identified. A lack of familial segregation was observed in 4 of 6 codon changes
(Arg943Gln, Val1433Ile, Pro1948Leu, and Ser2255Ile). Conversely, 2 codon changes 
cosegregated with the disease in 2 small families: Pro940Arg and Leu1970Phe.
CONCLUSIONS: The authors believe that segregation of the ABCR gene mutations with
familial cases of AMD has not yet been shown. The analysis of familial
segregation allowed the authors to exclude 4 of 6 codon changes as
disease-causing mutations. Furthermore, it was shown here that the ABCR gene may 
be rarely involved in exudative AMD, with at best 2 of 52 familial cases (4%)
related to this susceptibility factor.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10634626 [PubMed - indexed for MEDLINE]

3283: Br J Ophthalmol. 2000 Jan;84(1):40-7.

Subthreshold (retinal pigment epithelium) photocoagulation in macular diseases: a
pilot study.

Roider J, Brinkmann R, Wirbelauer C, Laqua H, Birngruber R.

Department of Ophthalmology, University of Regensburg, Regensburg, Germany.

BACKGROUND: Subthreshold (retinal pigment epithelium) photocoagulation is a new
photocoagulation method, which treats the retinal pigment epithelium (RPE) and
avoids damage to the neural retina. The initial results in this prospective pilot
study on various macular diseases are presented. METHODS: 12 patients with
diabetic maculopathy (group I), 10 with soft drusen (group II), and four with
central serous retinopathy (CSR) (group III) were treated and followed up for 1
year. Treatment was achieved using a train of repetitive short laser pulses (1.7 
micros) of a green Nd:YLF laser (parameters: 527 nm, 100 and 500 pulses,
repetition rate: 500 Hz, spot size: 160 microm, energies: 70-100 microJ). Laser
energy was based on the visibility of test lesions on fluorescein angiography
(50-130 microJ). Patients were examined at various times by ophthalmoscopy,
fluorescein and ICG angiography, and infrared imaging. RESULTS: After 6 months
hard exudates disappeared in six out of nine patients in group I and leakage
disappeared in six out of 12 diabetic patients. In group II drusen were less in
seven out of 10 patients. In group III serous detachment disappeared in three out
of four cases. Visual acuity was stable in all cases. None of the laser lesions
was clinically visible immediately. After 1 day most lesions were visible as
yellowish RPE depigmentation. After 3 months some of the lesions were visible as 
hyperpigmented areas but most were not. Fluorescein angiography showed leakage
only in the first week. Infrared imaging showed that most lesions can be
visualised in groups I and II after a period longer than 1 week as
hyperreflective areas. CONCLUSION: This study showed that subthreshold (RPE)
photocoagulation is effective in some cases of diabetic maculopathy, drusens, and
in CSR. Visibility of laser burns is not always necessary in the treatment of
macular diseases presented here. Infrared imaging is an effective and
non-invasive way of visualising subthreshold (RPE) laser burns.

PMID: 10611098 [PubMed - indexed for MEDLINE]
