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Fundus autofluorescence and optical coherence tomography biomarkers associated with the progression of geographic atrophy secondary to age-related macular degeneration



To investigate the impact of qualitatively graded and deep learning quantified imaging biomarkers on growth of geographic atrophy (GA) secondary to age-related macular degeneration.


This prospective study included 1062 visits of 181 eyes of 100 patients with GA. Spectral-domain optical coherence tomography (SD-OCT) and fundus autofluorescence (FAF) images were acquired at each visit. Hyperreflective foci (HRF) were quantitatively assessed in SD-OCT volumes using a validated deep learning algorithm. FAF images were graded for FAF patterns, subretinal drusenoid deposits (SDD), GA lesion configuration and atrophy enlargement. Linear mixed models were calculated to investigate associations between all parameters and GA progression.


FAF patterns were significantly associated with GA progression (p < 0.001). SDD was associated with faster GA growth (p = 0.005). Eyes with higher HRF concentrations showed a trend towards faster GA progression (p = 0.072) and revealed a significant impact on GA enlargement in interaction with FAF patterns (p = 0.01). The fellow eye status had no significant effect on lesion enlargement (p > 0.05). The diffuse-trickling FAF pattern exhibited significantly higher HRF concentrations than any other pattern (p < 0.001).


Among a wide range of investigated biomarkers, SDD and FAF patterns, particularly in interaction with HRF, significantly impact GA progression. Fully automated quantification of retinal imaging biomarkers such as HRF is both reliable and merited as HRF are indicators of retinal pigment epithelium dysmorphia, a central pathogenetic mechanism in GA. Identifying disease markers using the combination of FAF and SD-OCT is of high prognostic value and facilitates individualized patient management in a clinical setting.

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Fig. 1: Illustration of the registration procedure.
Fig. 2: Pairwise comparison of mean and 95% confidence intervals.


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The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

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Authors and Affiliations



US-E, SMW, and PTAB designed the research; GSR, CG, HB, and PTAB acquired and analyzed the data; MF and MA provided technical support; US-E, GSR, CG, HB, and SMW contributed to critical revision of the article; US-E provided resources, supervised the project and gave final approval for submitting; SMW provided resources and supervised the project; PTAB wrote the article.

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Correspondence to Ursula Schmidt-Erfurth.

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Competing interests

US-E serves as a consultant to Genentech, Heidelberg Engineering, Kodiak, Novartis, RetInSight, and Roche—all unrelated to this study. SMW serves as a consultant to Novartis and receives research support from Bayer and Genentech—all unrelated to this study. PTAB, GSR, MF, CG, HB, and MA declare no conflict of interests.

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Bui, P.T.A., Reiter, G.S., Fabianska, M. et al. Fundus autofluorescence and optical coherence tomography biomarkers associated with the progression of geographic atrophy secondary to age-related macular degeneration. Eye 36, 2013–2019 (2022).

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