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Farshad Abedi, Sanj Wickremasinghe, Andrea J. Richardson, FM Amirul Islam, Robyn Guymer, Paul N. Baird; Gene Variants in the HTRA1 and ARMS2 genes and Outcome of Anti-VEGF Treatment in Neovascular AMD. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2931. doi: https://doi.org/.
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To determine the contribution of genetic variants of known Age-related Macular Degeneration (AMD) risk associated genes with outcome of anti-vascular endothelial growth factor (anti-VEGF) treatment in neovascular AMD
Patients were recruited through public clinics at the Royal Victorian Eye and Ear Hospital, Melbourne. A total of 224 patients received intravitreal anti-VEGF (ranibizumab or bevacizumab) injections for untreated subfoveal choroidal neovascularisation (CNV) secondary to AMD and were followed over 12 months. Data relating to patient demographics, lesion characteristics, visual acuity (VA), using the Early Treatment Diabetic Retinopathy Study (ETDRS) charts, and number of injections, were collected. A total of 17 single nucleotide polymorphisms (SNPs) in known AMD genes (C3, LOC387715/ARMS2, CFH, HTRA1, CFHR, C2/BF and F13B) were genotyped and assessed for association using multivariate analysis adjusted for age, smoking status, baseline VA, number if injections, lesion type and size. Following Bonferroni correction, a significant p-value=0.003.
Mean age of patients was 78±6.7 years with a baseline VA of 51±17 ETDRS letter scores. Mean change in VA was +6.8±12.3, +5.1±13.4 and 3.3±14.9 letters at 3, 6 and 12 months, respectively. Patients received 4.2±1.1 and 6.4±2.3 injections in the first 6 and over 12 months, respectively. The AA genotype at rs11200638 (HTRA1 promoter SNP) predicted a better outcome of +7 and +9 letters after 6 (p= 0.003) and 12 months (p<0.0001), respectively. Similarly, the CC genotype at rs3793917 (LOC387715/ARMS2) was associated with increased VA outcome of +7 letters after 6 (p=0.006) and 12 months (p=0.001), whereas the TT genotype at rs10490924 (LOC387715/ARMS2) predicted a poorer VA response of -7 and -8 letters at 6 (p=0.004) and 12 months (p=0.001).
Two SNPs, in the HTRA1 gene and LOC387715/ARMS2 gene, were associated with a significantly better VA outcome, whereas SNP rs10490924 in the LOC387715/ARMS2 gene was associated with a significantly poorer VA outcome for anti-VEGF treatment in neovascular AMD. These findings may indicate differing roles for variants in these 2 closely linked genes as well as providing potential avenues for pharmacogenetic interventions.
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