Genetics in neovascular age‐related macular degeneration susceptibility and treatment response to anti‐VEGF intravitreal injection: A case series study

Abstract Background To identify genotypes associated with neovascular age‐related macular degeneration (nAMD) and investigate the associations between genotype variations and anti‐vascular endothelial growth factor (VEGF) treatment response. Methods This observational, retrospective, case series study enrolled patients diagnosed with nAMD who received anti‐VEGF treatment in National Taiwan University Hospital with at least one‐year follow‐up between 2012 and 2020. A genome‐wide association study (GWAS) was conducted on enrolled patients and controls. Correlations between the genotypes identified from GWAS and the treatment response of functional/anatomical biomarkers, including visual acuity (VA), presence of intraretinal or subretinal fluid (SRF), serous or fibrovascular pigmented epithelium detachment (PED), and disruption of the ellipsoid zone (EZ), were analysed. Results In total, 182 patients with nAMD and 1748 controls were enrolled. GWAS revealed 16 single nucleotide polymorphisms (SNPs) as risk loci for nAMD, including seven loci in CFH and ARMS2/HTRA1 and nine novel loci, including rs117517872 and rs79835234( COPB2‐DT ), rs7525578( RAP1A ), rs2123738( LOC105376755 ), rs1374879( CNTN3 ), rs3812692( SAR1A ), rs117501587( PRKCA ), rs9965945( CNDP1 ), and rs189769231( MATK ). Our study revealed rs800292( CFH ), rs11200638( HTRA1 ), and rs2123738( LOC105376755 ) correlated with poor treatment response in VA ( P = 0.005), SRF ( P = 0.044), and fibrovascular PED ( P = 0.007), respectively. Rs9965945( CNDP1 ) was correlated with poor response in disruption of EZ ( P = 0.046) and serous PED ( P = 0.049). Conclusions Among the 16 SNPs found in the GWAS, four loci— CFH , ARMS2/HTRA1 , and two novel loci—were correlated with the susceptibility of nAMD and anatomical/functional responses after anti‐VEGF treatment.