Abstract
PURPOSE: This review explores the complex relationship between anatomical alterations and functional consequences in geographic atrophy (GA), the advanced non-neovascular form of age-related macular degeneration. We examine the natural history, progression patterns, structural biomarkers, functional assessments, and structure-function correlations in GA. METHODS: Experts contributed specialized knowledge on GA pathophysiology, imaging biomarkers, and functional assessment methods. We synthesized an understanding of the relationship between structural changes (including fundus autofluorescence patterns, optical coherence tomography markers, and novel biomarkers) and functional outcomes (visual acuity, microperimetry, reading performance, and patient-reported outcomes), drawing from authors' research expertise and relevant literature. RESULTS: While GA is defined by visible areas of outer retinal atrophy, the structure-function relationship is complex and often discordant. Visual acuity incompletely reflects the functional impact of GA, as it may remain preserved until foveal involvement occurs. Microperimetric assessments reveal functional deficits extending beyond visible atrophic borders, with varying degrees of correlation between structural and functional metrics. Different fundus autofluorescence patterns demonstrate distinct functional implications and progression rates. Recent innovations in imaging and visual function testing offer enhanced characterization of disease progression. CONCLUSIONS: The complex relationship between structural and functional measures in GA reflects underlying pathophysiological mechanisms and has important implications for clinical trial endpoints and patient management. Multimodal assessment incorporating both structural and functional parameters is essential for the comprehensive evaluation and management of GA, particularly as novel therapeutic approaches emerge.