The Structure-Function Link of Ellipsoid Zone Integrity and Outer Retinal Features with Visual Acuity in Dry AMD

Background/Objectives: The purpose of this study was to evaluate associations between quantitative ellipsoid zone (EZ) integrity metrics derived from spectral-domain OCT (SD-OCT) and visual outcomes, including clinically meaningful visual acuity (VA) loss, in dry age-related macular degeneration (AMD). Methods: This single-center retrospective image-analysis cohort included 351 eyes from 351 patients with intermediate AMD or atrophic changes. Macular SD-OCT scans were analyzed using a certified-reader-validated machine learning-based segmentation platform to delineate the EZ, retinal pigment epithelium (RPE), and Bruch's membrane (BM). EZ metrics included EZ-RPE thickness (i.e., outer segment thickness) and EZ attenuation, defined as partial attenuation (EZ-RPE thickness of ≤20 µm, abnormal outer segment thinning)) or total attenuation/loss (0 µm). Drusen volume was quantified from the RPE-BM compartment. VA was converted to ETDRS letters. Associations between baseline OCT metrics and baseline VA, Year 2 VA, and ≥15-letter VA loss were assessed using nonparametric testing, linear regression, and ANCOVA. Results: Greater EZ-RPE thickness and lower EZ attenuation were associated with better baseline VA (all p < 0.001), and EZ metrics remained significant in cross-sectional regression models. Among 188 eyes with Year 2 follow-up, 38 (20%) experienced ≥15-letter VA loss. These eyes had significantly lower baseline EZ-RPE thickness (i.e., abnormal outer segment thinning) and greater EZ attenuation than eyes without such loss (all p < 0.001). In ANCOVA models, EZ metrics remained associated with Year 2 VA (all p < 0.001), whereas drusen volume was not. Conclusions: Quantitative EZ integrity metrics were associated with cross-sectional and longitudinal visual outcomes in dry AMD. EZ-RPE thickness and EZ attenuation may serve as clinically relevant OCT biomarkers reflecting photoreceptor integrity and risk of meaningful VA loss.