Macular Tissue Integrity Index: a Novel Biomarker for Geographic Atrophy (GA)

Abstract

Purpose : The measurement of geographic atrophy (GA) enlargement on fundus autofluorescence (FAF), a standard outcome in clinical trials, often fails to delineate the critical central macular region and its structure-function relationship. We propose a targeted approach in monitoring GA progression within the central macula, highlighting the limited benefit of including GA expansion beyond the 3mm perifoveal zone. This study introduces a biomarker based on tissue integrity in the 1mm and 3mm areas around the fovea, providing a novel approach to understand the functional changes in GA. The present study aims to explore how macular tissue integrity index correlates with best-corrected visual acuity (BCVA) and low-luminance visual acuity (LLVA).

Methods : Manual planimetry was used to delineate non-GA areas on Heidelberg FAF from 20 baseline scans from a GA clinical trial (GSK 341) (figure 1). OCT images were used to confirm GA status within the fovea. The area of non-GA within 1mm and 3mm circles around the center of the fovea was measured as a percentage to define the macular tissue integrity index. Correlation between the index and BCVA and LLVA was analyzed.

Results : The median GA area was 5.23 mm² (range 0.88-9.64 mm²), with sub foveal GA in 11 (55%) and multifocal GA in 10 (50%). The integrity index ranged from 0-96% in the 1mm zone and 9-95% in the 3mm zone.
In the 1 mm area, the integrity index was significantly correlated with BCVA (r² = 0.36, p-value = 0.005) but did not correlate with LLVA (r² = 0.04, p-value = 0.38). Conversely, in the 3mm subfield, we observed opposite correlation patterns, with BCVA (r² < 0.01, p-value = 0.89) and LLVA (r² = 0.22, p-value 0.04).

Conclusions : The dichotomy in visual correlations highlights the importance of considering the specific functional roles of different retinal regions when assessing conditions like GA. The contrasting correlations in our study between macular integrity and visual acuity within the 1mm and 3mm foveal zones are likely due to the different distributions of rods and cones. Further research with a larger sample and longitudinal data is needed for validating the macular tissue integrity index's role in GA monitoring.

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

 

Figure 1: Representative FAF image graded for area of intact macular tissue within the central 1 and 3 mm.