Longitudinal Study of Macular Preservation and Geographic Atrophy Progression in Age-Related Eye Disease Study 2

To investigate the natural history of macular tissue preservation in geographic atrophy (GA) by evaluating the relationship between the macular tissue integrity index (MTII) and best-corrected visual acuity (BCVA) over time.

Post hoc analysis of Age-Related Eye Disease Study 2 (AREDS2), a multi-center, randomized clinical trial.

Participants from the AREDS2 fundus autofluorescence ancillary study with nonsubfoveal GA.

Areas of GA were segmented by a deep learning algorithm and verified by expert graders. Macular tissue integrity index was defined as the percentage of the macula without GA within the central 1-mm and 3-mm circles. Baseline associations with BCVA were assessed, and longitudinal analyses evaluated GA progression, MTII loss, and BCVA decline over time.

Geographic atrophy area, MTII, and BCVA.

Two hundred forty-three eyes (194 participants) were included. The median follow-up was 2 years. At baseline, the mean GA area was 1.8 mm² (standard deviation 2.7), and the growth rate was 1.3 mm²/year. Baseline mean MTII in the 1-mm zone was 95.2% (standard deviation 9.1) with a decrease of 5.4%/year, and 87.3% (standard deviation 14.5) in the 3-mm zone with a decrease of 6.7%/year. Baseline mean BCVA was 76.4 letters (standard deviation 11.8; Snellen equivalent 20/30) with a 1.5-letter loss/year. Baseline MTII showed significant correlations with BCVA (1 mm: r = 0.17, P = 0.01; 3 mm: r = 0.14, P = 0.03), while GA area was not significantly associated with BCVA (r = -0.02, P = 0.71). Multivariable analysis showed that MTII in the 1-mm and 3-mm zones was associated with visual loss (both P < 0.0001). When eyes were stratified by MTII decline rate (stable/moderate/rapid), those in the rapid group showed numerically greater vision loss and GA growth.

This study characterizes the natural history of central macular preservation in GA using MTII. Results show moderate but significant associations with BCVA cross-sectionally and longitudinally. These findings suggest that MTII may offer complementary functional context for evaluating disease progression in GA, warranting further validation in clinical trial settings.

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.