June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
What are the smallest clinically visible drusen in aging and age-related macular degeneration (AMD)? A histology and fluorescein angiography study
Author Affiliations & Notes
  • Charles Dwight Evers III
    Ophthalmology and Visual Sciences, The University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, United States
  • Ling Chen
    The First Affiliated Hospital of Chongqing Medical University, Chongqing, Sichuan, China
  • Jeffrey D Messinger
    Ophthalmology and Visual Sciences, The University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, United States
  • Diogo Cabral
    Vitreous Retina Macula Consultants of New York, New York, New York, United States
    CEDOC - NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal
  • Rosa Dolz-Marco
    Unit of Macula, Clinica Oftalvist, Valencia, Spain
  • K Bailey Freund
    Vitreous Retina Macula Consultants of New York, New York, New York, United States
    Department of Ophthalmology, New York University Grossman School of Medicine, New York, New York, United States
  • Christine A Curcio
    Ophthalmology and Visual Sciences, The University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, United States
  • Footnotes
    Commercial Relationships   Charles Evers III None; Ling Chen None; Jeffrey Messinger None; Diogo Cabral None; Rosa Dolz-Marco Heidelberg Engineering, Novartis, Roche, Code C (Consultant/Contractor), Celltrion, IvericBIO, Novartis, Roche, Code F (Financial Support); K Bailey Freund Allergan, Bayer, Genentech, Heidelberg Engineering, Nidek, Novartis, Regeneron, Zeiss, Code C (Consultant/Contractor), Genentech, Code F (Financial Support); Christine Curcio Genentech/ Hoffman LaRoche, Heidelberg Engineering, Novartis, Code F (Financial Support), MacRegen Inc. , Code I (Personal Financial Interest)
  • Footnotes
    Support  Genentech/Roche
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 1021 – F0268. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Charles Dwight Evers III, Ling Chen, Jeffrey D Messinger, Diogo Cabral, Rosa Dolz-Marco, K Bailey Freund, Christine A Curcio; What are the smallest clinically visible drusen in aging and age-related macular degeneration (AMD)? A histology and fluorescein angiography study. Invest. Ophthalmol. Vis. Sci. 2022;63(7):1021 – F0268.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : High resolution optical coherence tomography (HR-OCT) provides unprecedentedly detailed views of retina and choroid. Small perturbations of retinal pigment epithelium-basal lamina-Bruch’s membrane band (RPE-BL-BrM) represent earliest stages of AMD. To inform the interpretation of HR-OCT-anchored multimodal imaging, we identified small drusen by histology and fluorescein angiography.

Methods : We surveyed Project MACULA (https://projectmacula.org/) an online resource of epoxy-resin histology of human donor eyes (N=54, aged-normal; N=24 early-intermediate AMD; N=13 geographic atrophy). Nodular drusen located between RPE- BL and inner collagenous layer of BrM were solid, globular, and homogeneously stained with toluidine blue. They lacked overlying basal laminar deposit (BLamD, between RPE and native BL) and basal mounds (soft drusen material within BLamD). Soft drusen material in any location was granular and light grayish brown. In images acquired with an oil immersion objective, base widths of single (non-confluent) nodular drusen were measured using FIJI. In one eye with non-exudative neovascular AMD, an area of punctate hyperfluorescence in late-phase fluorescein angiography (FA) 11 years before death (PMID 32247535) was mapped in histology.

Results : In 104 images from 43/92 eyes, small lesions included nodular drusen, 53 images; small soft drusen, 8; BLamD / basal mounds, 33; multilayer BLamD / BLinD-drusen, 10. The Figure shows that the range of nodular drusen (N=128) widths was 2.2 to 110 µm (median, 13.0 µm; interquartile range 7.7, 20.0 µm). In the eye with late phase FA, 91 similar-sized nodular drusen were found in an area with small circles of uniform fluorescence.

Conclusions : In two samples, 90% and 95% of nodular drusen (92% total) have base width <30 µm, a size just visible in color fundus photography (CFP; PMID 10365048). Results support reports that CFP reveals depigmentation over drusen and underestimates drusen dimensions, relative to histology and OCT (PMID 32568988, 33411474). The FA appearance is consistent with staining of individual drusen. Whether these deposits resemble cuticular drusen with “starry sky” angiograms needs further research (PMID 7525362, 10365048, 20924263, 28964580). Direct visualization of a sequence from numerous small drusen to soft drusen (PMID 17270675, 25905023) may be possible.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

 

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×