Longitudinal Ellipsoid Zone Integrity Dynamics in Eyes with Geographic Atrophy: A Two-Year Natural History Assessment

Abstract

Purpose : Ellipsoid zone (EZ) integrity is a recently recognized biomarker as a therapeutic target and prognostic factor for disease progression in eyes with dry age-related macular degeneration with geographic atrophy (GA). Understanding the natural course of EZ attenuation as a part of disease evolution is imperative for the analysis of newer interventions targeting EZ preservation. The purpose of this analysis was to evaluate longitudinal changes in the ellipsoid zone integrity in eyes with GA over a two-year period.

Methods : In this IRB-approved longitudinal retrospective study, a cohort eyes were included with dry AMD and GA that underwent SD-OCT assessments at baseline and after a 2-year interval. Utilizing a machine learning-enhanced multi-layer retinal segmentation platform, all baseline analyzable SD-OCT scans underwent comprehensive analysis for panmacular measures of EZ integrity, coupled with the identification of OCT-defined areas indicative of GA. Each scan was subsequently reviewed by a certified reader and any segmentation errors were corrected as necessary. Calculation of panmacular partial and total EZ attenuation (%) involved determining the percentage of the macular cube with EZ-RPE thickness ≤ 20 μm and EZ-RPE = 0 μm, respectively. GA-occupied areas, calculated based on regions exhibiting total attenuation of the retinal pigment epithelium (RPE) with associated outer retinal atrophy.

Results : In this analysis 550 eyes with dry AMD and GA were included in this analysis. The baseline mean panmacular total EZ attenuation and mean partial EZ attenuation are 16.12% and 28.03% respectively. The mean total EZ absolute change was +7.39% of the macular cube (~ 2.67 mm2) which reflected a proportional increase of approximately 117% growth over 2 years. Partial EZ attenuation demonstrated a similar absolute increase of +8.69% of the macular cube (~ 3.13 mm2) which corresponded to a proportional increase of approximately 57% over 2 years.

Conclusions : This study demonstrates the longitudinal assessment of EZ integrity changes over 2 years in eyes with underlying GA. Providing an understanding of the natural history of progressive EZ loss in GA will help to provide greater insights for clinical trial designs targeting EZ attenuation as an end point.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.