Abstract Purpose To measure the progression of geographic atrophy (GA) in subjects with age‐related macular degeneration (AMD) in a natural history study. Methods We analysed fundus autofluorescence (FAF) images using a semiautomatic method (RegionFinder) to quantify the GA area in a monocentric study. Three independent graders analysed each eye. Patient visits were scheduled at baseline, 12, 24 and 48 weeks. The primary endpoint was the progression of GA area per eye. Potential correlations with clinical and imaging‐based parameters were analysed. Results The annual GA progression rate was 1.16 mm 2 /year (95% CI: 0.76–1.56; p < 0.001), with faster growth in eyes with larger baseline lesions ( R 2 = 0.74). After square root transformation, the progression rate was 0.34 mm/year (95% CI: 0.26–0.43; p < 0.001), and the size dependency was reduced (adjusted R 2 = 0.16). Multivariable mixed‐effects models identified a significant association between larger GA lesion sizes per eye and the number of smoking pack‐years ( p = 0.017), the presence of perilesional hyperautofluorescence ( p = 0.044) and a multifocal configuration of the GA lesions ( p = 0.038). Intermediate AMD in the fellow eye was significantly associated with faster GA progression ( p = 0.041). Conclusion GA progression in AMD is significantly influenced by baseline lesion size and a larger number of smoking pack‐years is associated with larger GA lesions. The marked variability between individuals underscores the multifactorial nature of GA dynamics. Quantitative FAF analysis is a reliable method for assessing lesion progression and may inform risk‐based monitoring strategies.
Valmaggia et al. (2026) studied this question.