Combined effects of genetic and non‐genetic risk factors affect response to ranibizumab in exudative age‐related macular degeneration

Purpose To investigate whether genetic and non‐genetic risk factors influence 12‐month response to ranibizumab treatment for exudative age‐related macular degeneration ( AMD ). Methods A cohort of 94 Caucasian patients with unilateral exudative AMD received intravitreal ranibizumab. After a three‐injection loading phase, a PRN regimen was followed. Patients were genotyped for three single‐nucleotide polymorphisms: CFH rs1061170, ARMS 2 rs10490924 and C3 rs2230199. Non‐genetic risk factors [choroidal neovascularization ( CNV ) phenotype, smoking habit, hypertension and body mass index] were considered. The selected end‐point was the 12‐month variation of number of ETDRS letters. Results Complement factor H ( CFH ) risk alleles, smoking history and arterial hypertension each independently influenced treatment response, with worse 12‐month BCVA outcomes (p = 0.036, 0.037, 0.043, respectively). A significant cumulative effect of these risk factors was also observed: patients homozygous for the CFH risk alleles and with a positive smoking history showed a mean loss of 8.0 ETDRS letters (p = 0.010). Patients with CFH risk alleles, smoking history and hypertension had a mean loss of 13.9 ETDRS letters (p = 0.013). CNV phenotypes did not influence visual outcomes, nor were they associated with other genetic/non‐genetic risk factors. Conclusions Complement factor H risk alleles, smoking history and hypertension affect the mid‐term response to ranibizumab in exudative AMD .