Geographic atrophy: Understanding the relationship between structure and function

Antoine Huang; Zhichao Wu; Georg Ansari; Leon Von Der Emde; Maximilian Pfau; Steffen Schmitz-Valckenberg; Monika Fleckenstein; Tiarnán D L Keenan; Srinivas R Sadda; Robyn H Guymer; Chui Ming Gemmy Cheung; Usha Chakravarthy

doi:10.1016/j.apjo.2025.100207

Geographic atrophy: Understanding the relationship between structure and function

Asia Pac J Ophthalmol (Phila). 2025 May-Jun;14(3):100207. doi: 10.1016/j.apjo.2025.100207. Epub 2025 May 19.

Affiliations

¹ Singapore National Eye Centre, Singapore; Sorbonne Université, Paris, France.
² Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Australia; Ophthalmology, Department of Surgery, The University of Melbourne, Melbourne, Australia.
³ Department of Ophthalmology, University of Basel, Basel, Switzerland.
⁴ Department of Ophthalmology, University of Bonn, Bonn, Germany; Division of Epidemiology and Clinical Applications, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
⁵ Department of Ophthalmology, University of Basel, Basel, Switzerland; Department of Ophthalmology, University of Bonn, Bonn, Germany; Roche Pharmaceutical Research and Early Development, Translational Medicine Ophthalmology, Roche Innovation Center Basel, Basel, Switzerland.
⁶ Department of Ophthalmology, University of Bonn, Bonn, Germany; John A. Moran Eye Center, University of Utah, Salt Lake City, UT, USA.
⁷ John A. Moran Eye Center, University of Utah, Salt Lake City, UT, USA.
⁸ Division of Epidemiology and Clinical Applications, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
⁹ Doheny Eye Institute, Pasadena, CA, USA; Department of Ophthalmology, University of California - Los Angeles, Los Angeles, CA, USA.
¹⁰ Singapore National Eye Centre, Singapore; Singapore Eye Research Institute, Singapore; Duke-NUS Medical School, National University of Singapore, Singapore.
¹¹ Centre for Public Health, Queen's University Belfast, Belfast, United Kingdom. Electronic address: u.chakravarthy@qub.ac.uk.

PMID: 40398512
DOI: 10.1016/j.apjo.2025.100207

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.

Keywords: Age-related macular degeneration; Fundus autofluorescence; Geographic atrophy; Microperimetry; Structure-function correlation.

Publication types

Review

MeSH terms

Disease Progression
Fluorescein Angiography / methods
Geographic Atrophy* / diagnosis
Geographic Atrophy* / physiopathology
Humans
Tomography, Optical Coherence* / methods
Visual Acuity* / physiology
Visual Field Tests
Visual Fields* / physiology