Photo Credit: yogenyogeny

The following is a summary of “Neuroretinal and RPE changes and susceptibility to Age-Related Macular Degeneration: insights from the longitudinal Alienor Study,” published in the January 2025 issue of Ophthalmology by Larsen et al. 

Researchers conducted a retrospective study to assess the associations between macular layer thicknesses measured by spectral-domain OCT (SD-OCT) and incident age-related macular degeneration (AMD) and AMD polygenic risk scores (PRS).  

They analyzed data from 653 participants of the Alienor study with biennial eye imaging from 2009 to 2024. Macular layer thicknesses of 8 distinct layers and 3 compound layers were segmented from SD-OCT imaging. Total and pathway-specific PRS were calculated using summary statistics from prior AMD genome-wide association studies. Cox proportional hazard models were used to examine associations between macular layer thicknesses and incident intermediate and advanced AMD. Linear mixed models were applied to assess the relationship between macular layer thicknesses and PRS.  

The results showed that the mean age of the 653 participants at the first OCT examination was 82.2 ± 4.2 years, with 61.3% being women. In multivariate models, thicker retinal pigment epithelium (RPE) – Bruch’s Membrane (BM) complex in the 1 mm central circle was linked to incident intermediate AMD (Hazard ratio (HR) = 1.13 for 1 μm increase; P_FDR= 8.08 x 10-4). Incident advanced AMD was associated with thicker RPE-BM complex in both the central circle (HR = 1.09; P_FDR = 0.005) and inner circle (1 mm – 3 mm) (HR = 1.28; P_FDR = 1.61 x 10-5). RPE-BM complex thickening in the inner circle was more marked in individuals with higher total PRS (ß = 0.06 μm/year for 1 standard deviation increase, P_FDR = 1.61 x 10-10), higher complement pathway PRS (ß = 0.04 μm/year, P_FDR = 3.23 x 10-5), higher lipid pathway PRS (ß = 0.03 μm/year, P_FDR = 3.74 x 10-4), and ARMS2 (ß = 0.03 μm/year, P_FDR = 0.002). Additionally, high total PRS and complement-specific PRS were linked to a thinner photoreceptor segment layer (PSL) at baseline and thinning of the outer nuclear layer.  

Investigators concluded that RPE-BM complex thickening played a significant role in the pathophysiology of AMD, with further longitudinal studies needed to assess its value and PSL thinning for clinical follow-up. 

Source: aaojournal.org/article/S0161-6420(25)00003-X/fulltext