Multilayer atrophy progression in eyes with geographic atrophy secondary to age-related macular degeneration

Abstract

Purpose : To quantify photoreceptor degeneration beyond retinal pigment epithelium (RPE) atrophy in eyes with non-exudative advanced age-related macular degeneration (AMD) and assess its relationship with RPE-atrophy progression.

Methods : Longitudinal spectral-domain optical coherence tomography (SD-OCT) volume scans (121 B-scans across 30°x25°) from the prospective, natural-history Directional Spread in Geographic Atrophy study [DSGA; NCT02051998]) were segmented with a custom deep-learning pipeline. En-face maps of the descent of the external limiting membrane (ELM), the ellipsoid zone (EZ) and the boundary of RPE-atrophy were generated. The average Euclidean distance between the RPE-atrophy boundary and the ELM descent or EZ loss boundary were computed for each eye and visit as quantitative measures of photoreceptor degeneration. Statistical analyses were performed using mixed-models.

Results : A total of 153 eyes of 93 patients with a median (IQR) age of 78.3 years (72.5, 82.8) and area of RPE-atrophy of 8.25 mm2 (3.93, 15.44) at baseline were included in this analysis. In the vast majority of eyes, the average ELM-descent boundary position was slightly internal to the RPE-atrophy boundary at a median distance of -3.43 µm (-28.62, 74.41 [minus indicating position within PRE-atrophy]). In contrast, the position of the EZ-loss boundary was highly variable among patients and exceeded RPE-atrophy margins by a median of 429.38 µm (210.48, 726.08). Over time (median follow-up of 1.1 years [0.56, 1.97]), the average square-root RPE-atrophy progression rate was (estimate [95% CI]) 0.29 mm/year [0.24 – 0.33]. The relative position of the EZ-loss boundary was markedly associated with future progression rates (+0.16 mm/year per mm of distance between the EZ-loss and RPE-atrophy boundary [0.08 – 0.25]). The distance between the EZ-loss and RPE-atrophy boundary at the final visit was strongly correlated to its baseline value (R²=0.870).

Conclusions : Marked alterations of photoreceptor laminae, which spatially exceeded RPE-atrophy, were detectable and quantifiable. The degree of photoreceptor degeneration outside of RPE atrophy varied markedly between eyes, but was correlated within eyes over time. The distance between the EZ loss boundary and RPE atrophy may be applied (1) for refined patient stratification and (2) to identify potentially beneficial treatment effects beyond RPE-atrophy progression.

This is a 2020 ARVO Annual Meeting abstract.