Genetic Susceptibility, Diet Quality, and Two-Step Progression in Drusen Size

PURPOSE. To investigate the relationship of growth in drusen size with genetic susceptibility and adherence to the alternate Mediterranean diet. METHODS. Participants in this analysis had complete ocular, genetic, and dietary data with mean follow-up time of 10.2 years in the Age-Related Eye Disease database. Maximal drusen size was graded on an ordinal scale and two-step progression was determined. A genetic risk score using variants associated with advanced AMD and derived from a stepwise regression model yielded 11 variants in 8 genes. Adherence to the alternate Mediterranean diet was assessed using a nine-component score based on intake of vegetables, fruits, legumes, whole cereals, fish, meat, nuts, alcohol, and monounsaturated-to-saturated fatty acids ratio. Multivariate Cox proportional hazards models were used. RESULTS. Among 3023 eligible eyes, 19% had drusen growth. In the stepwise selection, common and rare risk alleles for CFH Y402H, CFH rs1410996, CFH R1210C, C3 R102G, C3 K155Q, and ARMS2/HTRA1, as well as VEGF-A, TIMP3, NPLOC4, and HSPH1 variants were significantly associated with 2-step progression in drusen size, and the C2 E318D protective allele conferred decreased risk, adjusting for other covariates. A higher genetic risk score conferred a higher risk (hazard ratio per 1-unit increase, 2.68; 95% confidence interval, 2.23-3.23; P < 0.001), and a medium/high adherence to alternate Mediterranean diet score (4-9) tended to lower risk (hazard ratio, 0.83; 95% confidence interval, 0.680.99; P = 0.049), adjusting for all covariates. CONCLUSIONS. Genetic susceptibility was independently related to drusen growth. A Mediterranean-style diet with healthful nutrient-rich foods (fruits, vegetables, legumes and fish), may reduce enlargement of drusen, the hallmark of AMD.