Genetic markers of the effectiveness of anti-VEGF therapy in age-related macular degeneration

Objective. To systematically review and critically appraise current evidence on genetic markers associated with the efficacy of anti-VEGF therapy in neovascular age-related macular degeneration (nvAMD).

Methods. A literature analysis covering the period 2005–2025 was performed, including candidate gene studies, meta-analyses, and genome-wide association studies (GWAS). Genetic variants in CFH, ARMS2/HTRA1, VEGFA, KDR, IL8, and SIRT1 genes were examined.

Results. The most reproducible associations with anti-VEGF response were found for CFH rs1061170 (Y402H), ARMS2 rs10490924, IL8 rs4073 (-251A/T) и VEGFA rs699947 polymorphisms. According to meta-analyses, carriage of the CFH rs1061170 risk allele is associated with reduced functional response (pooled OR=1.34, 95 % CI 1.10–1.63). However, the effect size is modest, results differ between European and Asian populations, and large RCTs have not confirmed the clinical utility of single SNPs. None of the studied markers possess sufficient predictive value for standalone use in routine practice.

Conclusion. Genetic markers associated with anti-VEGF therapy efficacy in nvAMD show moderate and heterogeneous effects. The development of polygenic prognostic models combining multiple SNPs with clinical and imaging parameters is a promising direction.

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