Directional Association Between Perilesional Fundus Autofluorescence and Geographic Atrophy Border Expansion.

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