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© 2015 Wiley Periodicals, Inc. Primary open-angle glaucoma is the most common optic neuropathy and an important cause of irreversible blindness worldwide. The optic nerve head or optic disc is divided in two parts: a central cup (without nerve fibers) surrounded by the neuroretinal rim (containing axons of the retinal ganglion cells). The International Glaucoma Genetics Consortium conducted a meta-analysis of genome-wide association studies consisting of 17,248 individuals of European ancestry and 6,841 individuals of Asian ancestry. The outcomes of the genome-wide association studies were disc area and cup area. These specific measurements describe optic nerve morphology in another way than the vertical cup-disc ratio, which is a clinically used measurement, and may shed light on new glaucoma mechanisms. We identified 10 new loci associated with disc area (CDC42BPA, F5, DIRC3, RARB, ABI3BP, DCAF4L2, ELP4, TMTC2, NR2F2, and HORMAD2) and another 10 new loci associated with cup area (DHRS3, TRIB2, EFEMP1, FLNB, FAM101, DDHD1, ASB7, KPNB1, BCAS3, and TRIOBP). The new genes participate in a number of pathways and future work is likely to identify more functions related to the pathogenesis of glaucoma.

© 2014 Macmillan Publishers Limited. All rights reserved. Glaucoma is characterized by irreversible optic nerve degeneration and is the most frequent cause of irreversible blindness worldwide. Here, the International Glaucoma Genetics Consortium conducts a meta-analysis of genome-wide association studies of vertical cup-disc ratio (VCDR), an important disease-related optic nerve parameter. In 21,094 individuals of European ancestry and 6,784 individuals of Asian ancestry, we identify 10 new loci associated with variation in VCDR. In a separate risk-score analysis of five case-control studies, Caucasians in the highest quintile have a 2.5-fold increased risk of primary open-angle glaucoma as compared with those in the lowest quintile. This study has more than doubled the known loci associated with optic disc cupping and will allow greater understanding of mechanisms involved in this common blinding condition.

Objective: To study associations between aspirin use and early and late aging macula disorder (AMD). Design: Population-based cross-sectional European Eye Study in 7 centers from northern to southern Europe. Participants: In total, 4691 participants 65 years of age and older, collected by random sampling. Methods: Aspirin intake and possible confounders for AMD were ascertained by a structured questionnaire. Ophthalmic and basic systemic measurements were performed in a standardized way. The study classified AMD according to the modified International Classification System on digitized fundus images at 1 grading center. Nonfasting blood samples were analyzed in a single laboratory. Associations were analyzed by logistic regression. Main Outcome Measures: Odds ratios (ORs) for AMD in aspirin users. Results: Early AMD was present in 36.4% of the participants and late AMD was present in 3.3% of participants. Monthly aspirin use was reported by 1931 (41.2%), at least once weekly by 7%, and daily use by 17.3%. For daily aspirin users, the ORs, adjusted for potential confounders, showed a steady increase with increasing severity of AMD grades. These were: grade 1, 1.26 (95% confidence interval [CI], 1.08-1.46; P

Objective: To investigate whether dietary nutrients can reduce the genetic risk of early age-related macular degeneration (AMD) conferred by the genetic variants CFH Y402H and LOC387715 A69S in a nested case-control study. Methods: For 2167 individuals (>= 55 years) from the population-based Rotterdam Study at risk of AMD, dietary intake was assessed at baseline using a semiquantitative food frequency questionnaire and genetic variants were determined using TaqMan assay. Incident early AMD was determined on fundus photographs at 3 follow-up visits (median follow-up, 8.6 years). The synergy index was used to evaluate biological interaction between risk factors; hazard ratios were calculated to estimate risk of early AMD in strata of nutrient intake and genotypes. Results: Five hundred seventeen participants developed early AMD. Significant synergy indices supported the possibility of biological interaction between CFH Y402H and zinc, beta-carotene, lutein/zeaxanthin, and eicosapentaenoic/docosahexaenoic acid (EPA/DHA) and between LOC387715 A69S and zinc and EPA/DHA (all P < .05). Homozygotes of CFH Y402H with dietary intake of zinc in the highest tertile reduced their hazard ratio of early AMD from 2.25 to 1.27. For intakes of beta-carotene, lutein/zeaxanthin, and EPA/DHA, these risk reductions were from 2.54 to 1.47, 2.63 to 1.72, and 1.97 to 1.30, respectively. Carriers of LOC387715 A69S with the highest intake of zinc and EPA/DHA reduced their risk from 1.70 to 1.17 and 1.59 to 0.95, respectively (all P trends

Purpose: Vascular endothelial growth factor (VEGF) is an important regulator of angiogenesis and a target for inhibition therapy in wet age-related macular degeneration (AMD). The purpose of this study was to examine whether genetic variation in the VEGF gene is associated with AMD and, especially, with its wet end stage. Design: Prospective population-based cohort study. Participants: Four thousand two hundred twenty-eight participants aged 55 years and older. Methods: AMD was classified according to a modified International Classification System using fundus color images. Genotypes and haplotypes were determined for 3 functional VEGF single nucleotide polymorphisms (SNPs): C-2578A, G-1154A, and G-634C. Cox proportional hazards regression analyses were used to investigate possible associations between the individual SNPs and incident AMD. The Haplo.Stats program was used to test the associations between VEGF gene haplotypes and incident AMD. Main Outcome Measure: AMD Results: Of 4228 participants at risk for incident early and late AMD for whom blood specimens were available for VEGF genotyping, incident early AMD developed in 514 and incident late AMD developed in 89 (35 dry and 54 wet) after a mean follow-up of 7.4 years. None of the SNPs showed a significant association with incident early or late AMD, especially not with incident wet AMD. Haplotype analyses also detected no associations. Conclusions: The a priori hypothesis that 3 common SNPs in the VEGF gene would be a risk factor for AMD, especially the wet form, could not be confirmed. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology 2008; 115:1899-1903 (C) 2008 by the American Academy of Ophthalmology.

Purpose: To determine the incidence of open–angle glaucoma (OAG) in a general elderly Caucasian population. Methods: Participants (n=3842) of the prospective population–based Rotterdam Study, aged 55 years and older and at risk for incident OAG, underwent at baseline and follow–up the same ophthalmic examination including measurement of intra–ocular pressure, visual field testing and stereo optic disc photography. The diagnosis of probable or definite OAG was made with an algorithm based on optic disc parameters and on glaucomatous visual field loss, independent of the intra–ocular pressure. The incidence was calculated in incidence rates and 5–year risks. Results:After a mean follow–up time of 6.5 years, probable or definite OAG developed in 87 persons. The 5–year risk rose threefold till 3.2% in men between ages 55 and 80 years and one and a half times till 2.3% in women. The odds ratio for men versus women was 1.3 (95% confidence interval: 0.9–2.0) Bilateral OAG occurred five times more often after than before age 75. In participants with prevalent OAG in one eye, the 5–year risk of OAG in the fellow eye was five times higher than in fellow eyes of non–OAG eyes. Only 37% of the incident cases received treatment for OAG. Conclusions:The incidence of OAG rose with age and more in men than in women. Bilateral incident OAG occurred more frequently among the eldest participants. The majority of the new cases was unaware of having OAG.