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Manuel Hermann, Philipp Muether, Dzenita Smailhodzic, Anneke Den Hollander, Bernd Kirchhof, Sascha Fauser; Variants in the VEGFA gene and visual outcome after anti-VEGF treatment for neovascular age-related macular degeneration. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4120.
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To correlate the ocurrence of genetic variants of the VEGFA gene with visual outcome of anti-vascular endothelial growth factor (VEGF) treatment in patients with neovascular age-related macular degeneration (AMD).
In this prospective cohort study with a follow-up of 12 months we included 283 patients from 2 study centers. Initial treatment consisted in 3 monthly ranibizumab injections. On monthly follow-up visits additional series of 3 monthly ranibizumab injections were initiated if necessary on the basis of clinical retreatment criteria. Multivariate data analysis was used to determine the influence of 125 selected tagged single nucleotide polymorphisms (tSNPs) in the VEGFA gene on visual acuity (VA) outcome at 12 months.
Mean baseline VA was 0.64 ±0.36 logMAR (logarithm of the Minimum Angle of Resolution). Mean VA improved after 3 months by 0.08 ±0.29 logMAR and by 0.03 ±0.36 logMAR after 12 months. The only tSNPs significantly associated with visual outcome at 12 months with multiple correction were rs11603042 (P=0.032), rs307826 (P=0.047), and rs4576072 (P=0.002). For rs11603042 the presence of a T allele (TG or TT genotypes) lead to an increase of VA gain by mean 0.10 logMAR (95% confidence interval (CI), 0.01-0.18) when compared to the GG genotype. Concerning rs307826 the presence of a G allele (GA or GG genotypes) increased VA gain by mean 0.06 logMAR (95% CI, 0.01-0.16) when compared to the AA genotype. The largest effect was observed for the presence of a C allele (CT or CC genotypes) at the rs4576072 tSNP which lead to an increase in VA gain by mean 0.12 logMAR (95% CI, 0.03-0.21) when compared to the TT genotype.
Pharmacogenetic charcteristics may influence visual outcome in patients receiving anti-VEGF treatment for neovascular AMD. In patients with the T allele in tSNP rs11603042, the G allele in rs307826, and/or the C allele in rs4576072 visual outcome was significantly better at 12 months.
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