Long-Term Natural History of Treatment-Naïve Geographic Atrophy in Age-Related Macular Degeneration

Purpose: To evaluate the long-term fundus autofluorescence-based growth rate (GR) of treatment-naïve patients with geographic atrophy (GA) in age-related macular degeneration. Methods: We conducted a prospective, single-center, observational study between February 2013 and September 2024 at the Department of Clinical Neuroscience, Karolinska Institutet, and St. Erik Eye Hospital, Stockholm/Solna, Sweden. Clinical examination and fundus autofluorescence were performed in patients with GA owing to dry age-related macular degeneration. The area and the absolute and square root transformed GR were analyzed every 6 months. Results: We examined 432 eyes and enrolled 204 eyes (111patients). The median follow-up was 21 months (minimum-maximum, 5-123). Of 73 fovea-sparing, 22 eyes converted to foveal-involving over a median of 24 months. The mean growth for the total cohort was 1.597 mm2/y and 0.264 mm/y after square root transformation. Bilateral (1.621 mm2/y; 0.267 mm/y), multifocal (1.961 mm2/y; 0.322 mm/y), and fovea-sparing (1.987 mm2/y; 0.234 mm/y) lesions showed significantly faster growth when analyzed in isolation. In a mixed statistical model that controlled for bilaterality, only fovea status remained a significant influencer on the square root transformed GR (P < 0.001). Conclusions: In this long-term GA cohort, an influence of lesion characteristics on GRs can be observed. Fovea sparing, multifocality, and bilaterality showed faster growth, depending on the statistical model. Patients presenting with one or more of these lesion characteristics hold a high potential for benefit of future treatments because a growth slow down may be more likely to be achieved. In fovea-sparing cases, functional preservation may be possible. Translational relevance: By analyzing the data of one of the most extensive geographic atrophy patient cohorts in the Nordics, this study establishes a dataset on the long-term treatment-naïve growth dynamics. It provides a reference for upcoming preclinical treatment developments and clinical trial end points.