Investigation of genetic base in the treatment of age-related macular degeneration

Purpose To determine whether gene polymorphisms which are associated with age-related macular degeneration (AMD) influence treatments’ response and specifically the antioxidant supplementation in dry AMD patients, as well as the anti-vascular endothelial growth factor (anti-VEGF) therapy in neovascular AMD patients. Methods A total of 170 patients with dry AMD and 52 neovascular AMD patients were genotyped for the following single nucleotide polymorphisms (SNPs): rs1061170/Y402H in CFH gene, rs10490924/A69S in ARMS2 gene, rs9332739/E318D and rs547154/IVS10 in C2 gene, and rs4151667/L9H and rs2072633/IVS17 in CFB gene. Treatment response was evaluated by comparing visual acuity and optical coherence tomography between baseline and at the end of the treatment. Results Τhe CFH/Y402H variant was associated with the response to antioxidants in dry AMD patients. Carriers of one or two CFH risk alleles displayed a lower chance of responding compared to those with no risk allele. No association of antioxidants’ response and ARMS2/A69S genotype was identified. The analysis of the C2 and CFB genetic variants (protective SNPs) revealed that antioxidant supplementation was much more effective in protective SNP carriers. In neovascular AMD patients, the analysis indicated that Y402H homozygous patients were less likely to respond to anti-VEGF therapy compared to heterozygous. Regarding the ARMS2/A69S genotype, carriers of the risk variant experienced significantly worse treatment outcome compared to wild-type patients. Conclusion In AMD patients, the efficacy of the antioxidant supplementation and the anti-VEGF therapy appears to differ by genotype. The detection of genetic variants, associated with treatment responsiveness, could lead to improved visual outcomes through genotype-directed therapy.