Neuroretinal and RPE changes and susceptibility to Age-Related Macular Degeneration: insights from the longitudinal Alienor Study

We assessed the associations of macular layer thicknesses, measured using spectral-domain OCT (SD-OCT), with incident age-related macular degeneration (AMD) and AMD polygenic risk scores (PRS). Population-based cohort study PARTICIPANTS: 653 participants of the Alienor study, with biennial eye imaging from 2009 to 2024. Macular layer thicknesses of eight distinct layers and three compound layers were automatically segmented based on SD-OCT imaging of the macula. Total and pathway specific PRS were calculated from previous AMD genome-wide association studies summary statistics. Associations of macular layer thicknesses with incident intermediate and advanced AMD were analyzed using time-dependent Cox proportional hazards models. Associations of macular layer thicknesses with PRS were assessed using linear mixed models. Incident intermediate and advanced AMD based on fundus colour photographs and SD-OCT. Mean age at first OCT examination of the 653 participants was 82.2 ± 4.2 years and 61.3 % were women. In multivariate adjusted models, incident intermediate AMD was associated with thicker retinal pigment epithelium (RPE) - Bruch's Membrane (BM) complex in the 1 mm central circle (Hazard ratio (HR)= 1.13 for 1 μm increase; P These results highlight the importance of RPE-BM complex thickening in the pathophysiological sequence of AMD. Further longitudinal studies are needed, in particular to determine the value of RPE-BM thickening and PSL thinning measured using SD-OCT for the clinical follow-up of AMD patients.