Directional Association Between Perilesional Fundus Autofluorescence and Geographic Atrophy Border Expansion

The purpose of this study was to evaluate the directional association between perilesional fundus autofluorescence (FAF) intensity and geographic atrophy (GA) border expansion.

This study included 102 untreated fellow eyes from the MAHALO clinical trial with FAF images at baseline and 6 months. FAF intensity was normalized within each eye and analyzed within two perilesional zones (0-250 µm and 0-500 µm). The highest and lowest 25% of normalized intensity were defined as hyperautofluorescence (hyperAF) and hypoautofluorescence (hypoAF), respectively. A relative density metric (sector value minus eye-level mean) was calculated for each clock-hour sector. GA border expansion was quantified using Euclidean distance mapping. Associations between FAF density and sector-wise GA expansion were assessed using linear mixed-effects models. Sensitivity analyses using 20% and 30% thresholds and subgroup analysis of unifocal lesions were performed.

Across all conditions, higher hyperAF density was not associated with greater extent of GA border expansion and showed consistently negative regression slopes (all P < 0.001). In contrast, higher hypoAF density was significantly associated with greater GA expansion, with uniformly positive regression slopes across all ring sizes and thresholds (all P < 0.001). These findings were consistent in eyes with unifocal lesions and across sensitivity analyses.

GA expansion is not preferentially directed toward regions of higher hyperAF but rather, is associated with hypoAF-dominant areas. These findings suggest that GA progression may be related to spatial changes in perilesional autofluorescence (AF) patterns, although the underlying biological mechanisms require further investigation.