Cumulative Effect of Risk Alleles in CFH , ARMS2 , and VEGFA on the Response to Ranibizumab Treatment in Age-related Macular Degeneration

Purpose Intravitreal ranibizumab injections currently are the standard treatment for neovascular age-related macular degeneration (AMD). However, a broad range of response rates have been observed, the reasons for which are poorly understood. This pharmacogenetic study evaluated the impact of high-risk alleles in CFH , ARMS2 , VEGFA , vascular endothelial growth factor (VEGF) receptor KDR , and genes involved in angiogenesis ( LRP5 , FZD4 ) on the response to ranibizumab treatment and on the age of treatment onset. In contrast to previous studies, the data were stratified according to the number of high-risk alleles to enable the study of the combined effects of these genotypes on the treatment response. Design Case series study. Participants A cohort of 420 eyes of 397 neovascular AMD patients. Methods The change in visual acuity (VA) between baseline and after 3 ranibizumab injections was calculated. Genotyping of single nucleotide polymorphisms in the CFH , ARMS2 , VEGFA , KDR , LPR5 , and FZD4 genes was performed. Associations were assessed using linear mixed models. Main Outcome Measures The VA change after 3 ranibizumab injections and the age of neovascular disease onset. Results After ranibizumab treatment, AMD patients without risk alleles in the CFH and ARMS2 genes (4.8%) demonstrated a mean VA improvement of 10 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, whereas no VA improvement was observed in AMD patients with 4 CFH and ARMS2 risk alleles (6.9%; P = 0.014). Patients with 4 high-risk alleles in CFH and ARMS2 were 5.2 years younger than patients with 1 or 2 risk alleles, respectively (63.5%; P