Investigative Ophthalmology & Visual Science Cover Image for Volume 65, Issue 7
June 2024
Volume 65, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2024
Histology of fundus autofluorescence (FAF) in multifocal geographic atrophy (GA) with thick choroid in age-related macular degeneration (AMD)
Author Affiliations & Notes
  • Christine A Curcio
    Ophthalmology and Vision Science, The University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, United States
  • Jeffrey Messinger
    Ophthalmology and Vision Science, The University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, United States
  • Andreas Berlin
    Ophthalmology and Vision Science, The University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, United States
  • Malia Michelle Edwards
    Wilmer Institute, Johns Hopkins University, Baltimore, Maryland, United States
  • D. Scott McLeod
    Wilmer Institute, Johns Hopkins University, Baltimore, Maryland, United States
  • Jacques Bijon
    Vitreous Retina Macula Consultants of New York, New York, New York, United States
  • K. Bailey Freund
    Vitreous Retina Macula Consultants of New York, New York, New York, United States
  • Footnotes
    Commercial Relationships   Christine Curcio Apellis, Astellas, Genentech, Boehringer Ingelheim, Osanni, Character Biosciences, Annexon, Code C (Consultant/Contractor), Heidelberg Engineering, Code F (Financial Support); Jeffrey Messinger None; Andreas Berlin None; Malia Edwards None; D. Scott McLeod None; Jacques Bijon None; K. Bailey Freund Genentech, Optovue, Zeiss, Heidelberg Engineering, Allergan, Novartis., Code C (Consultant/Contractor)
  • Footnotes
    Support  R01EY027948; Macula Foundation (NY); anonymous donor to UAB; Research to Prevent Blindness, Inc; EyeSight Foundation of Alabama; Dr. Werner Jackstädt foundation
Investigative Ophthalmology & Visual Science June 2024, Vol.65, 2284. doi:
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      Christine A Curcio, Jeffrey Messinger, Andreas Berlin, Malia Michelle Edwards, D. Scott McLeod, Jacques Bijon, K. Bailey Freund; Histology of fundus autofluorescence (FAF) in multifocal geographic atrophy (GA) with thick choroid in age-related macular degeneration (AMD). Invest. Ophthalmol. Vis. Sci. 2024;65(7):2284.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Interpretation of GA trial outcomes and patient selection for recently approved complement inhibitors would benefit from new data about subcellular, cellular, and tissue-level contributors to FAF signal. We investigated 2 eyes of 1 woman with bilateral multifocal GA and thick choroids, with in vivo multimodal imaging followed by histology.

Methods : In 6 clinic visits in 5 years, both eyes were imaged using optical coherence tomography (OCT), near infrared reflectance (NIR; Spectralis), plus 55° color and green FAF (Topcon). Best corrected visual acuity (OD, OS) was 20/80, 20/40 at presentation and 20/400, 20/100 at the last visit. Six years later, after patient death at age 93 years, eyes were recovered 5 hours postmortem and opened for preservation. OS was imaged ex vivo and prepared for high-resolution epoxy resin histology linked to OCT B-scans (PMID 37306417; 26255578). FAF intensities at 100, 500, and 1000 µm on either side of long atrophy borders was measured with ImageJ.

Results : Bilateral multifocal GA exhibited appearance, growth, and coalescence of atrophic spots associated with drusen, mostly calcified, best seen in color and FAF, and less so in NIR due to thick choroid. Histology of OS revealed dilated veins especially nasally, attenuated choriocapillaris, multiple calcified drusen with thick basal laminar deposit (BLamD), and a layer of stage 1 subretinal drusenoid deposit. Four FAF stages of drusen-driven atrophy (PMID 33217617) were apparent. In the outer junctional zone, FAF signal was highest at 100 µm, corresponding to thin and continuous RPE over thick BLamD and short or absent outer segments. In the inner junctional zone, a mottled low signal at 100 µm and negligible signal at 500-1000 µm corresponded to dissociated RPE and absent RPE, respectively. Strong hyperFAF within atrophy corresponded to islands of RPE and photoreceptors between expanding atrophic spots started at drusen.

Conclusions : In this eye, a hyperFAF border and stages 2-3 of drusen-driven atrophy corresponds to thin continuous RPE and loss of overlying outer segments that normally absorb incoming light. Thickened RPE in some locations increase the pathlength of light through fluorophores. Ongoing studies will quantify the relative contribution of RPE- and photoreceptor-specific modulators of FAF.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.

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