Abstract

PURPOSETo determine associations between macular drusen parameters derived from an automatic optical coherence tomography (OCT) algorithm, age-related macular degeneration (AMD) stage and genetic variants.\n\nMETHODSEyes classified as early or intermediate AMD with OCT imaging and genetic data were selected (n=239 eyes). Drusen area and volume measurements were estimated using the Zeiss Cirrus advanced retinal pigment epithelium (RPE) analysis algorithm in a 5mm diameter (perifoveal) zone centered on the fovea. Associations between drusen measurements and common genetic variants in the complement and high density lipoprotein (HDL) lipid pathways and the ARMS2 variant were calculated using generalized estimating equations and linear mixed models adjusting for age, sex, smoking, BMI, and education.\n\nRESULTSWhen compared to eyes with no measurable drusen, drusen area [≥] the median was independently associated with a higher number of risk alleles for CFH risk score, risk variants in C3 and ARMS2/HTRA1. Similar results were obtained for drusen volume. When all genes were analyzed in the same model, only CFH score and ARMS2/HTRA1 were associated with drusen measurements. HDL pathway genes were not significantly related to drusen parameters. Early and intermediate AMD stages were associated with OCT derived drusen area and volume.\n\nCONCLUSIONGenetic variants in CFH and ARMS2/HTRA1, commonly associated with advanced AMD, were independently associated with higher drusen burden determined by OCT in eyes with early and intermediate AMD. The automatic RPE algorithm using OCT provides a quantitative classification of non-advanced AMD. Drusen morphology and other OCT-derived sub-phenotypes are biomarkers that could provide early anatomic endpoints for clinical trials.