Correlation Between RPE Aperture and Photoreceptor Integrity in Non-Neovascular AMD: A Longitudinal Study Using OCT and 3D Morphological Analysis

Purpose: The purpose of this study was to investigate longitudinal morphological changes of retinal pigment epithelium (RPE) apertures within pigment epithelial detachment (PED) and their association with photoreceptor integrity in non-neovascular age-related macular degeneration (AMD). Methods: This retrospective analysis included 22 eyes from 21 patients with RPE apertures within PED. During a mean follow-up of 11.4 ± 5.8 months, optical coherence tomography (OCT) with 3D volumetric analysis was used to measure RPE aperture diameter/area, PED dimensions, and areas of ellipsoid zone (EZ) loss and outer nuclear layer (ONL) thinning. Correlation and multivariate regression analyses were performed. Results: RPE apertures significantly enlarged in diameter and area, accompanied by progressive EZ loss and ONL thinning (all P ≤ 0.001). PED height (P = 0.018) and volume (P = 0.031) decreased, whereas PED width increased (P = 0.019). RPE aperture size showed strong cross-sectional and longitudinal correlations with photoreceptor damage (r up to 0.942 and 0.928, respectively, all P < 0.001, remaining significant after false discovery rate [FDR] correction). Multivariate regression demonstrated that change in RPE aperture diameter was independently associated with concurrent changes in EZ loss (β = 1.009, P < 0.001) and ONL thinning (β = 0.679, P = 0.001). Additionally, a larger baseline aperture diameter was an independent factor associated with greater visual acuity decline (P = 0.015). Conclusions: RPE apertures enlarge over time and are closely associated with worsening photoreceptor damage, supporting RPE aperture progression as a dynamic biomarker of ongoing photoreceptor degeneration in non-neovascular AMD. Translational Relevance: Quantitative OCT-based assessment of RPE aperture expansion enables clinically applicable monitoring of photoreceptor degeneration and visual risk in non-neovascular AMD.