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Review
. 2025 May-Jun;14(3):100207.
doi: 10.1016/j.apjo.2025.100207. Epub 2025 May 19.

Geographic atrophy: Understanding the relationship between structure and function

Antoine Huang  1 , Zhichao Wu  2 , Georg Ansari  3 , Leon Von Der Emde  4 , Maximilian Pfau  5 , Steffen Schmitz-Valckenberg  6 , Monika Fleckenstein  7 , Tiarnán D L Keenan  8 , Srinivas R Sadda  9 , Robyn H Guymer  2 , Chui Ming Gemmy Cheung  10 , Usha Chakravarthy  11
Affiliations
Review

Geographic atrophy: Understanding the relationship between structure and function

Antoine Huang et al. Asia Pac J Ophthalmol (Phila). 2025 May-Jun.

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.

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Conflict of interest statement

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ansari Georg: Recipient of funding from F. Hoffmann-La Roche and iCare/CenterVue Maximilian Pfau: Employee of F. Hoffmann-La Roche; Funding from iCare/CenterVue Steffen Schmitz-Valckenberg: Reports grants or contracts from AlphaRET, Apellis, Bayer, Carl Zeiss MediTec, eyeDNA, Formycon, Galimedix, Katairo, LaScience, Novartis, Perceive Therapeutics, Roche, SparingVision; personal fees from Apellis, Roche, Vertex Pharmaceuticals; speaker honoraria from Apellis; and non-financial support from Carl Zeiss Meditec and Heidelberg Engineering, outside the submitted work Srinivas Sadda: Consultant/Advisor for 4DMT, Abbvie/Allregan Inc., Alexion, Sanofi, Alnylam Pharmaceuticals, Amgen Inc., Apellis Pharmaceuticals, Inc., Astellas, Bayer Healthcare Pharmaceuticals, Biogen MA Inc., Boehringer Ingelheim, Carl Zeiss Meditec, ONL Therapeutics, Catalyst Pharmaceuticals Inc., CharacterBio, iCare/Centervue Inc., GENENTECH, Ocular Therapeutics, Eyepoint, Heidelberg Engineering, Hoffman La Roche, Ltd., Iveric Bio, Janssen Pharmaceuticals Inc., Nanoscope, Notal Vision Inc., Novartis Pharma AG, Optos Inc., Oxurion/Thrombogenics, Oyster Point Pharma, Regeneron Pharmaceuticals Inc., Samsung Bioepis, Topcon Medical Systems Inc.; Recipient of honoraria for speaking from Carl Zeiss Meditec, Heidelberg Engineering, Nidek Incorporated, Novartis Pharma AG, Topcon Medical Systems Inc., Roche; Research Instruments from Carl Zeiss Meditec, Heidelberg Engineering, Optos Inc., Nidek, Topcon, iCare/Centervue, Intalight Robyn H. Guymer: Reports participation in advisory boards for Apellis, Roche/Genentech, Bayer, Novartis, Belite Bio, Boehringer Ingelheim Pharmaceuticals, Character Bioscience, Janssen, AbbVie, Astellas, Retinai, Sitala, Kriya, Ocular Therapeutix, Complement Therapeutics, Pulse Sight Chui Ming Gemmy Cheung: grants, personal fees and non-financial support from Bayer and Novartis; grants from Roche and GlaxoSmithKline; non-financial support from Allergan and Topcon, outside the submitted work Usha Chakravarthy: None relevant to the current paper. Consultancy payments from Annexon, Apellis, Aviceda, Eyepoint, Exonate, Isarna, F. Hoffman La Roche, Nanoscope, Ocular Therapeutix, Unity Biotechnology; Data and Safety Monitoring Committee for Adverum If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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