Association between Pre-diagnostic Macular Thickness With Risk of Age-related Macular Degeneration

PURPOSE: To determine whether specific pre-diagnostic macular thickness are associated with an increased risk of age-related macular degeneration (AMD). METHODS: A total of 40,078 UK Biobank participants without baseline AMD who underwent optical coherence tomography (OCT) imaging were included. Macular thickness measurements were obtained via OCT across nine subfields of the Early Treatment Diabetic Retinopathy Study. Latent Profile Analysis (LPA) was employed to classify distinct pre-diagnostic macular thickness profiles, while cox proportional hazards models were utilized to estimate hazard ratios (HRs) between the identified profiles. RESULTS: Two distinct pre-diagnostic macular thickness profiles were identified. Compared to profile 1 (n = 31,942), profile 2 (n = 8,136) was characterized by thinner inner and outer superior subfields, alongside thicker central and other outer subfields. Profile 2 was associated with significantly increased AMD risk compared to profile 1 (HR, 1.59; 95% confidence interval [CI], 1.32-1.90; P < 0.001). After adjustment for all covariates, the observed association persisted (HR, 1.39; 95% CI, 1.16-1.67; P < 0.001). CONCLUSION: Distinct pre-diagnostic macular thickness patterns are associated with elevated AMD risk. These findings provide novel insights into potential early macular structural changes prior to AMD diagnosis, and may serve as novel biomarkers for early identification of AMD.