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Two potentially distinct pathways to geographic atrophy in age-related macular degeneration characterized by quantitative fundus autofluorescence

Eye volume 37, pages 2281–2288 (2023)Cite this article

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Abstract

Background/Aims

To demonstrate two distinct pathways to geographic atrophy (GA) that originate from soft drusen/ pigment epithelial detachments (PEDs) and subretinal drusenoid deposits (SDDs), respectively, and are characterized by their final quantitative autofluorescence (qAF) levels.

Methods

23 eyes of 18 patients with GA underwent spectral-domain optical coherence tomography (SD-OCT) and qAF imaging on the qAF-ready Heidelberg Spectralis. 52 GA Regions-of-interest (ROIs), or clusters of adjacent lesions, were selected, and the ROIs were divided into groups by the dominant iAMD precursors on prior serial tracked SD-OCT scans. Mean qAF values and structural SD-OCT findings of groups were compared.

Results

Group 1 lesions (soft drusen/PED precursors, 18/52) were isolated, with lower mean qAF (35.88 ± 12.75 units); group 3 lesions (SDD precursors, 12/52) were multilobular, with significantly higher mean qAF (71.62 ± 12.12 units, p < 0.05). Group 2 lesions, (mixed precursors, 22/52) had intermediate mean qAF (58.13 ± 67.92 units). Significantly greater prevalence of split RPE/ Bruch’s membrane complex in SDD-associated GA, suggesting basal laminar deposit (BLamD), than in drusen-associated lesions was the major structural difference.

Conclusion

Quantitative autofluorescence (qAF) of GA lesions may reflect two distinct pathogenic pathways and structural outcomes, originating from soft drusen/PED and subretinal drusenoid deposits (SDDs), with the final qAF values lower or higher, respectively. Basal laminar deposit specifically in and adjacent to SDD-associated lesions may account for their greater autofluorescence. The potential importance of this paradigm is that it could direct, simplify and facilitate research on geographic atrophy by dividing the disease into two components that may be studied separately.

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Fig. 1: Quantitative autofluorescence (qAF) of Geographic Atrophy (GA) with soft drusen precursors.
Fig. 2: Quantitative autofluorescence (qAF) of Geographic Atrophy (GA) with subretinal drusenoid deposit (SDD) precursors and basal laminar deposit (BLamD).
Fig. 3: Soft drusen and subretinal drusenoid deposits (SDDs) evolving and progressing to geographic atrophy (GA) in the same eye over 8 years with residual basal laminar deposit (BLamD) in a 79-year-old female.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Funding

NIH R01 EY015520 (RTS), Macula Foundation (KBF). The sponsor or funding organization had no role in the design or conduct of this research.

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Authors and Affiliations

  1. Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Wei Wei, Marco Mazzola, Oscar Otero-Marquez, Yuehong Tong & R. Theodore Smith

  2. Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China

    Wei Wei

  3. Ophthalmology, University of Insubria Varese-Como, Viale Luigi Borri, Varese, Italy

    Marco Mazzola

  4. Department of Ophthalmology, Hôpital Intercommunal de Créteil Université, Créteil, France

    Eric Souied

  5. Ophthalmology, University Vita-Salute, Via Olgettina, Milan, Italy

    Giuseppe Querques

  6. Vitreous Retina Macula Consultants of New York, New York, NY, USA

    K. Bailey Freund

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Contributions

WW: acquisition of data, analysis and interpretation of data, manuscript preparation MM: acquisition of data, analysis and interpretation of data, manuscript preparation. OOM: analysis and interpretation of data, manuscript preparation. YT: analysis and interpretation of data, manuscript preparation. ES: analysis and interpretation of data, manuscript preparation. GQ: analysis and interpretation of data, manuscript preparation. KBF: design, acquisition of data, analysis and interpretation of data, manuscript preparation. RTS: design, acquisition of data, analysis and interpretation of data, manuscript preparation.

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Correspondence to R. Theodore Smith.

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Wei, W., Mazzola, M., Otero-Marquez, O. et al. Two potentially distinct pathways to geographic atrophy in age-related macular degeneration characterized by quantitative fundus autofluorescence. Eye 37, 2281–2288 (2023). https://doi.org/10.1038/s41433-022-02332-8

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