June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
Atrophy, neovascularization, transdifferentiation, and gliotic invasion in age-related macular degeneration (AMD): histology of a clinically characterized eye
Author Affiliations & Notes
  • Ling Chen
    Department of Ophthalmology and Visual sciences, University of Alabama at Birmingham, Birmingham, Alabama, United States
    Zhongshan Ophthalmic Center, Sun yat-sen University, Guangzhou, China
  • Miaoling Li
    Department of Ophthalmology and Visual sciences, University of Alabama at Birmingham, Birmingham, Alabama, United States
    Zhongshan Ophthalmic Center, Sun yat-sen University, Guangzhou, China
  • Jeffrey Messinger
    Department of Ophthalmology and Visual sciences, University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Daniela Ferrara
    Genentech, South San Francisco, California, United States
  • Christine Curcio
    Department of Ophthalmology and Visual sciences, University of Alabama at Birmingham, Birmingham, Alabama, United States
  • K Bailey Freund
    Vitreous Retina Macula Consultants of New York, New York, United States
  • Footnotes
    Commercial Relationships   Ling Chen, None; Miaoling Li, None; Jeffrey Messinger, None; Daniela Ferrara, Genentech (E); Christine Curcio, MacRegen Code (I); K Bailey Freund, Allergan (C), Bayer (C), Genentech (C), Heidelberg Engineering (C), Novartis (C), Optovue (C), Zeiss (C)
  • Footnotes
    Support  The Macula Foundation, Heidelberg Engineering, Genentech
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 1812. doi:
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      Ling Chen, Miaoling Li, Jeffrey Messinger, Daniela Ferrara, Christine Curcio, K Bailey Freund; Atrophy, neovascularization, transdifferentiation, and gliotic invasion in age-related macular degeneration (AMD): histology of a clinically characterized eye. Invest. Ophthalmol. Vis. Sci. 2020;61(7):1812.

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

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Abstract

Purpose : We explored via histology an eye with advanced AMD meeting criteria for complete retinal and retinal pigment epithelial (RPE) atrophy (cRORA; PMID 31708275) with clinical history and multimodal imaging of drusen-related atrophy and types 1 and 2 macular neovascularization (MNV).

Methods : An 82-year-old white man had drusen at baseline, drusen-related atrophy at 2 years, type 1 and 2 MNV confirmed by fluorescein angiography and optical coherence tomography (OCT) at 4 years, followed by 3 years of anti-vascular endothelial growth factor treatment. Two months after the last clinic visit, the patient died. Eyes were preserved 8.33 hours after death. Submicrometer epoxy resin sections were stained with toluidine blue and evaluated by oil immersion microscopy.

Results : The borders of atrophy correlating to hypertransmission on in vivo OCT was bounded by descent of external limiting membrane, thin outer nuclear layer (ONL), and dyslamination of Henle fiber layer and ONL. A shallow irregular RPE elevation on OCT correlated to type 1 MNV with neo-capillaries and fibrocellular scar. Type 2 MNV covered the native RPE and was enveloped at the margins by RPE (Figure 1). In a continuous layer, RPE cells transdifferentiated from normal cells with spindle-shaped melanosomes to transitional cells with spindle-shaped and spherical melanosomes, then to “melanotic” cells with only spherical melanosomes; these entered the type 1 MNV and invaded the choroid. Retinal tissue (presumably Müller glia) contacted type 2 MNV, entered type 1 MNV, breached Bruch’s membrane, and invaded the choroid.

Conclusions : An envelopment of type 2 MNV by RPE was seen in clinical imaging and in histology. Transdifferentiation of RPE, gliosis and choroidal invasion by Müller cells are new aspects of atrophy complicated with MNV. cRORA enlarged during the follow-up period; whether this change is due to drusen, exudation, or both requires further analysis.

This is a 2020 ARVO Annual Meeting abstract.

 

Figure 1. Type 1 and 2 MNV: RPE envelops the margin of Type 2 MNV.
A. Section through the clinically evident MNV. Yellow framed area is in (B). B. Type 1 MNV is below the native RPE. Type 2 MNV covers the native RPE. RPE (teal) envelops the type 2 MNV at the left (red asterisks). BLamD has a defect at the right (pink). Green framed area is in (C). C. Three vessel lumens (red arrowheads) and pericytes (green) are seen.

Figure 1. Type 1 and 2 MNV: RPE envelops the margin of Type 2 MNV.
A. Section through the clinically evident MNV. Yellow framed area is in (B). B. Type 1 MNV is below the native RPE. Type 2 MNV covers the native RPE. RPE (teal) envelops the type 2 MNV at the left (red asterisks). BLamD has a defect at the right (pink). Green framed area is in (C). C. Three vessel lumens (red arrowheads) and pericytes (green) are seen.

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