In the present study, we investigated the association between susceptible genetic variants to age-related macular degeneration (AMD) and response to as-needed intravitreal aflibercept injection (IAI) therapy for exudative AMD including both typical neovascular AMD and polypoidal choroidal vasculopathy (PCV) over 12-months. A total of 234 patients with exudative AMD were initially treated with 3 monthly IAI and thereafter as-needed IAI over 12 months. Seven variants of 6 genes including ARMS2 A69S (rs10490924), CFH (I62V:rs800292 and rs1329428), C2-CFB-SKIV2L(rs429608), C3 (rs2241394), CETP (rs3764261) and ADAMTS-9 (rs6795735) were genotyped for all participants using TaqMan technology. After adjusting for age, gender, baseline BCVA and AMD subtype, A (protective) allele of C2-CFB-SKIV2L rs429608 was associated with visual improvement at 12-month (P = 0.003). Retreatment was associated with T(risk) allele of ARMS2 A69S (P = 2.0 × 10-4; hazard ratio: 2.18:95%CI: 1.47-3.24) and C(risk) allele of CFH rs1329428 (P = 2.0 × 10-3; hazard ratio: 1.74:95%CI: 1.16-2.59) after adjusting for the baseline confounders. The need for additional injections was also associated with T allele of ARMS2 A69S (P = 1.0 × 10-5) and C allele of CFH rs1329428 (P = 3.0 × 10-3) after adjusting for the baseline confounders. The variants of ARMS2 and CFH are informative for both physicians and patients to predict recurrence and to quantify the need for additional injections.
Genetic factors associated with response to as-needed aflibercept therapy for typical neovascular age-related macular degeneration and polypoidal choroidal vasculopathy.