Neovascular age-related macular degeneration (nAMD) is the leading cause of vision loss in the elderly. The gold standard of nAMD treatment is intravitreal injections of vascular endothelial growth factor (VEGF) inhibitors. Genetic factors may influence the response to anti-VEGF therapy and result in a high degree of response variability. The aim of the study was to evaluate the association of the polymorphisms in genes related to the complement system (rs2285714-CFI, rs10490924-ARMS2, rs2230199-C3, rs800292-CFH, and rs6677604-CFH) with nAMD its clinical features and optical coherent tomography (OCT) biomarkers of treatment response to anti-VEGF therapy. Genotyping by allele-specific PCR was performed in 193 AMD patients and 147 age-matched controls. A prospective study of the dynamics of changes in OCT biomarkers during aflibercept treatment included 110 treatment-naive patients. Allele T rs10490924 was associated with the increased risk of nAMD. For both rs800292 and rs6677604, carriage of the A allele was protective and decreased the nAMD risk. Associations of rs2230199 with central retinal thickness (CRT) and intraretinal cysts were revealed. The height of pigment epithelium detachment and the height of neuroretinal detachment were significantly higher in carriers of the minor allele of rs2285714, both at baseline and during treatment. The reduction of CRT was associated with higher CRT at baseline and the presence of the T allele of rs2285714. By the end of one-year follow-up the patients homozygous for the minor allele rs2285714 had significantly higher odds of the presence of anastomoses and loops and active neovascular membrane. Furthermore, minor allele carriers had decreased levels of complement factor I level in aqueous humor but not in the plasma, which may be due to the influence of rs2285714 on tissue-specific splicing. Our results suggest that the severity of AMD macular lesions is associated with rs2285714 and rs2230199 polymorphisms, which could be explained by their high regulatory potential. Patients with the minor allele of rs2285714 respond worse to antiangiogenic therapy.

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