Macular Degeneration: Goldenberg-Cohen N

Chowers I, Meir T, Lederman M, Goldenberg-Cohen N, Cohen Y, Banin E, Averbukh E, Hemo I, Pollack A, Axer-Siegel R, Weinstein O, Hoh J, Zack DJ, Galbinur T. · Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. · Mol Vis. · Pubmed #19065273 links to  free full text

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

Chowers I, Cohen Y, Goldenberg-Cohen N, Vicuna-Kojchen J, Lichtinger A, Weinstein O, Pollack A, Axer-Siegel R, Hemo I, Averbukh E, Banin E, Meir T, Lederman M. · Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Hebrew University School of Medicine, Jerusalem, Israel. · Mol Vis. · Pubmed #18852870 links to  free full text

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

Weinberger D, Lichter H, Goldenberg-Cohen N, Priel E, Bahar I, Yassur Y, Axer-Siegel R. · Department of Ophthalmology, Rabin Medical Center, Beilinson Campus, Petah Tiqva, Israel. · Retina. · Pubmed #12172105 No free full text.

Abstract: PURPOSE: To evaluate alterations in the retinal vasculature overlying pigment epithelial detachments (PED) in exudative age-related macular degeneration (ARMD) using indocyanine green and fluorescein angiography. METHODS: Forty-one patients (41 eyes) with a clinical diagnosis of exudative ARMD with PED underwent simultaneous fluorescein and indocyanine green angiography, also under high (10 degrees ) magnification. Vascular abnormalities in the retina were compared between patients with vascularized (n = 34, group 1) and nonvascularized (n = 7, group 2) PED on indocyanine green angiography and correlated with the size of the PED and the presence of serous retinal detachment. RESULTS: In all, 67 vascular abnormalities were found by indocyanine green angiography and only 22 by fluorescein angiography; this finding was statistically significant (P < 0.0001). The finding of retinal vasculopathy (32 patients in group 1 and two patients in group 2) was directly correlated with the presence of choroidal neovascularizations (P = 0.002). There was also a direct correlation between the presence of choroidal neovascularization and size of the PED (P = 0.03). The number of retinal vascular findings was not significantly correlated with serous elevation of the retina. CONCLUSIONS: Retinal vasculopathies may be observed in eyes with PED and are detectable by indocyanine green and fluorescein angiography.