Determinants of Four-Year Visual Acuity Loss in Geographic Atrophy: An Analysis of Age-Related Eye Disease Study and Age-Related Eye Disease Study 2

Abstract

Purpose: To investigate the relationship between geographic atrophy (GA) progression and change in best-corrected visual acuity (BCVA) over 4 years and identify factors associated with faster BCVA loss.

Design: Secondary analysis of 2 randomized controlled clinical trials.

Participants: Age-Related Eye Disease Study (AREDS) and AREDS2 participants with GA secondary to nonexudative age-related macular degeneration.

Methods: Baseline and annual color fundus photographs were assessed for GA area and proximity to the foveal center. Best-corrected visual acuity was measured using Early Treatment Diabetic Retinopathy Study logarithm of the minimum angle of resolution (logMAR) charts. Analyses included BCVA change over 4 years, with the relationship of BCVA decline with GA progression and other baseline factors examined using multivariable linear mixed-effects models.

Main outcome measures: The primary outcome was BCVA change over 4 years. Secondary outcomes included BCVA change from baseline to years 1, 2, and 3.

Results: We included 1351 eyes from 994 participants, including 594 eyes from 464 participants with 4-year BCVA follow-up. Higher baseline BCVA, smaller baseline GA proximity to the foveal center, and greater GA growth rate were each independently associated with larger BCVA loss over 4 years (each P < 0.001). Among the 594 eyes with 4-year BCVA data, 69 eyes with a baseline BCVA < 40 letters (Snellen equivalent of 20/160 or worse) and 42 eyes with baseline GA located more than 1 mm from the foveal center did not experience significant BCVA loss over 4 years. In contrast, 483 eyes that met both criteria of baseline BCVA ≥ 40 letters and GA lesions involving or within 1 mm of the foveal center showed significant BCVA loss over 4 years (mean change = -11.33 letters [95% confidence interval = -12.80 to -9.84]), with faster GA progression associated with larger BCVA loss (P < 0.001).

Conclusions: In this cohort, eyes with GA involving or within 1 mm of the foveal center and a baseline BCVA of ≥ 40 letters appeared more likely to experience significant BCVA loss, suggesting these eyes may benefit more from therapies that slow GA progression. Our findings support a personalized approach to managing patients with GA, potentially guiding the design of future GA trials.

Financial disclosure(s): Proprietary or commercial disclosure may be found after the references.

Keywords: Age-related macular degeneration; Clinical trial; Geographic atrophy; Visual acuity.