June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Histology of cells suggestive of inflammation in treated neovascular age-related macular degeneration (AMD), a clinicopathologic correlation
Author Affiliations & Notes
  • Christine A. Curcio
    The University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, United States
  • Jeffrey D. Messinger
    The University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, United States
  • CHANDRAKUMAR Balaratnasingam
    University of Western Australia Centre for Ophthalmology and Visual Science, Perth, Western Australia, Australia
  • Randev Mendis
    Canberra Retina Center, Canberra, Australian Capital Territory, Australia
  • Daniela Ferrara
    Genentech Inc, South San Francisco, California, United States
  • K. Bailey Freund
    Vitreous Retina Macula Consultants of New York, New York, New York, United States
  • Andreas Berlin
    The University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, United States
  • Footnotes
    Commercial Relationships   Christine Curcio Apellis, Code C (Consultant/Contractor), Astellas, Code C (Consultant/Contractor), Boehringer Ingelheim, Code C (Consultant/Contractor), Genentech/ Roche, Code F (Financial Support); Jeffrey Messinger None; CHANDRAKUMAR Balaratnasingam None; Randev Mendis None; Daniela Ferrara Genentech/ Roche, Code E (Employment); K. Bailey Freund Genentech, Code C (Consultant/Contractor), Zeiss, Code C (Consultant/Contractor), Heidelberg Engineering, Code C (Consultant/Contractor), Allergan, Code C (Consultant/Contractor), Bayer, Code C (Consultant/Contractor), Novartis, Code C (Consultant/Contractor); Andreas Berlin None
  • Footnotes
    Support  Genentech/ Roche; Macula Foundation
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 2955. doi:
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      Christine A. Curcio, Jeffrey D. Messinger, CHANDRAKUMAR Balaratnasingam, Randev Mendis, Daniela Ferrara, K. Bailey Freund, Andreas Berlin; Histology of cells suggestive of inflammation in treated neovascular age-related macular degeneration (AMD), a clinicopathologic correlation. Invest. Ophthalmol. Vis. Sci. 2023;64(8):2955.

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

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Abstract

Purpose : To assess the inflammatory potential of drusen and subretinal drusenoid deposits (SDD), cells were documented by histology in the intraretinal, subretinal and sub retinal pigment epithelium (RPE)-basal lamina (BL) compartments in a single case of neovascular age-related macular degeneration (AMD).

Methods : Two eyes of a white woman receiving numerous intravitreal anti-vascular endothelial growth factor injections for type 3 neovascularization secondary to AMD were prepared for high-resolution histology. Eye-tracked spectral-domain optical coherence tomography (OCT) imaging applied to the donor eyes linked in vivo imaging to histology. Cells (n=334) were counted on 199 glass slides. Cells with numerous RPE organelles were considered RPE-originated. Cells with sparse RPE organelles were considered non-RPE phagocytes, as were macrophages and giant cells.

Results : Both eyes had centrally located soft drusen, most with calcific nodules, and abundant SDD. RPE-derived cells were common in the retina (n=125) and subretinal space (n=73); some corresponded to hyperreflective foci documented by in vivo OCT. In the same compartments, cells with sparse RPE organelles were infrequent (n=5 in both). The sub-RPE-BL space had many RPE-derived cells (n=87) and non-RPE phagocytes (n=49). The latter included macrophages and giant cells. Over drusen, RPE morphology smoothly transitioned from the adjacent layer up the sloping sides into the retina.

Conclusions : Numerous sub-RPE-BL cells comport with a known role of inflammation in choroidal neovascularization and the presence of bioactive lipids in drusen and aged Bruch’s membrane. Most subretinal and intraretinal cells were RPE-derived and transdifferentiated; some manifest as hyperreflective foci. Comparing these compartments with regard to infiltrating non-RPE phagocytes, drusen are strongly associated with inflammatory cells while SDD is not. Due to processing-related retinal detachment in this case, this finding should be investigated in a larger clinical series, especially with high-resolution OCT technologies that resolves cells.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

 

Cells associated with end-stage drusen. Arrowheads: brown, RPE. Blue, macrophage. Yellow, giant cell. Pink asterisk, basal laminar deposit (BLamD). BrM, Bruch’s membrane. ChC, choriocapillaris. HFL, Henle fiber. IS, inner segments. ONL; outer nuclear. OPL, outer plexiform. OS, outer segments.

Cells associated with end-stage drusen. Arrowheads: brown, RPE. Blue, macrophage. Yellow, giant cell. Pink asterisk, basal laminar deposit (BLamD). BrM, Bruch’s membrane. ChC, choriocapillaris. HFL, Henle fiber. IS, inner segments. ONL; outer nuclear. OPL, outer plexiform. OS, outer segments.

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