Abstract
Purpose :
Genetic susceptibility and modifiable factors including the Alternate Mediterranean Diet (aMeDi) are associated with rate of progression to advanced stages of AMD. (Merle B, Am J Clin Nut 2015; 102:1196-1206, Seddon J. IOVS 2017; 58: 6513-6528). In this study, we investigated the relationship of growth in drusen size in earlier stages of AMD with genetic susceptibility and the aMeDi.
Methods :
Subjects 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 2 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 aMeDi was assessed using a 9-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 to assess associations between drusen growth and the genetic and nutritional variables.
Results :
Among 3023 eligible eyes, 587 (19.4%) had drusen growth. In the stepwise selection, common and rare risk alleles for CFH Y402H, CFH rs1410996, CFH R1210C, C3 R102G, C3 K155Q, VEGF-A, ARMS2/HTRA1, 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. Participants with a high genetic risk score had higher risk, (HR per 1 standard deviation increase = 1.64, 95% CI: 1.49-1.80; P<0.001), and subjects with a medium/high adherence to aMeDi score (4 to 9) tended to have a lower risk (HR 0.83, 95% CI: 0.68-0.99; P=0.049), adjusting for all covariates.
Conclusions :
Genetic susceptibility involving the complement, immune and other biologic pathways was independently related to drusen growth, after adjusting for other AMD risk factors. A diet rich in healthful nutrient-rich foods including fruits, vegetables, legumes and fish, as in the Mediterranean diet, may reduce enlargement of drusen, the hallmark of early stages AMD. Knowledge of both nature and nurture -modifiable factors and genetic susceptibility-may identify subjects at higher risk of early disease progression who could benefit from preventive measures.
This is a 2020 ARVO Annual Meeting abstract.