TY - JOUR
T1 - Inflammatory cell activity in treated neovascular age-related macular degeneration
T2 - A histologic case study
AU - Berlin, Andreas
AU - Messinger, Jeffrey D.
AU - Ramtohul, Prithvi
AU - Balaratnasingam, Chandrakumar
AU - Mendis, Randev
AU - Ferrara, Daniela
AU - Freund, K. Bailey
AU - Curcio, Christine A.
N1 - Funding Information:
Supported by Genentech/Hoffman LaRoche, The Macula Foundation, Inc., New York, NY; Dr. Werner Jackstädt-foundation (AB); unrestricted funds to the Department of Ophthalmology and Visual Sciences (UAB) from Research to Prevent Blindness, Inc., and EyeSight Foundation of Alabama. Purchase of the slide scanner was made possible by the Carl G. and Pauline Buck Trust. The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Publisher Copyright:
© 2023 Lippincott Williams and Wilkins. All rights reserved.
PY - 2023/11/1
Y1 - 2023/11/1
N2 - Background:Imaging indicators of macular neovascularization risk can help determine patient eligibility for new treatments for geographic atrophy secondary to age-related macular degeneration. Because type 1 macular neovascularization includes inflammation, we assessed by histology the distribution of cells with inflammatory potential in two fellow eyes with age-related macular degeneration.Methods:Two eyes of a White woman in her 90's with type 3 macular neovascularization treated with antivascular endothelial growth factor were prepared for high-resolution histology. Eye-tracked spectral domain optical coherence tomography applied to the preserved donor eyes linked in vivo imaging to histology. Cells were enumerated in the intraretinal, subretinal, and subretinal retinal pigment epithelium (RPE)-basal lamina compartments on 199 glass slides. Cells with numerous organelles were considered to RPE-derived; cells with sparse RPE organelles were considered non-RPE phagocytes.Results:Both eyes had soft drusen and abundant subretinal drusenoid deposit. In the retina and subretinal space, RPE-derived cells, including hyperreflective foci, were common (n = 125 and 73, respectively). Non-RPE phagocytes were infrequent (n = 5 in both). Over drusen, RPE morphology transitioned smoothly from the age-normal layer toward the top, suggesting transdifferentiation. The sub-RPE-basal lamina space had RPE-derived cells (n = 87) and non-RPE phagocytes (n = 49), including macrophages and giant cells.Conclusion:Numerous sub-RPE-basal lamina cells of several types are consistent with the documented presence of proinflammatory lipids in drusen and aged Bruch's membrane. The relatively compartmentalized abundance of infiltrating cells suggests that drusen contents are more inflammatory than subretinal drusenoid deposit, perhaps reflecting their environments. Ectopic RPE occurs frequently. Some manifest as hyperreflective foci. More cells may be visible as optical coherence tomography technologies evolve.
AB - Background:Imaging indicators of macular neovascularization risk can help determine patient eligibility for new treatments for geographic atrophy secondary to age-related macular degeneration. Because type 1 macular neovascularization includes inflammation, we assessed by histology the distribution of cells with inflammatory potential in two fellow eyes with age-related macular degeneration.Methods:Two eyes of a White woman in her 90's with type 3 macular neovascularization treated with antivascular endothelial growth factor were prepared for high-resolution histology. Eye-tracked spectral domain optical coherence tomography applied to the preserved donor eyes linked in vivo imaging to histology. Cells were enumerated in the intraretinal, subretinal, and subretinal retinal pigment epithelium (RPE)-basal lamina compartments on 199 glass slides. Cells with numerous organelles were considered to RPE-derived; cells with sparse RPE organelles were considered non-RPE phagocytes.Results:Both eyes had soft drusen and abundant subretinal drusenoid deposit. In the retina and subretinal space, RPE-derived cells, including hyperreflective foci, were common (n = 125 and 73, respectively). Non-RPE phagocytes were infrequent (n = 5 in both). Over drusen, RPE morphology transitioned smoothly from the age-normal layer toward the top, suggesting transdifferentiation. The sub-RPE-basal lamina space had RPE-derived cells (n = 87) and non-RPE phagocytes (n = 49), including macrophages and giant cells.Conclusion:Numerous sub-RPE-basal lamina cells of several types are consistent with the documented presence of proinflammatory lipids in drusen and aged Bruch's membrane. The relatively compartmentalized abundance of infiltrating cells suggests that drusen contents are more inflammatory than subretinal drusenoid deposit, perhaps reflecting their environments. Ectopic RPE occurs frequently. Some manifest as hyperreflective foci. More cells may be visible as optical coherence tomography technologies evolve.
KW - age-related macular degeneration
KW - drusen
KW - epithelial mesenchymal transition
KW - histopathology
KW - macrophages
KW - microglia
KW - optical coherence tomography
KW - reticular pseudodrusen
KW - retinal pigment epithelium
KW - subretinal drusenoid deposits
KW - type 3 macular neovascularization
UR - http://www.scopus.com/inward/record.url?scp=85175422833&partnerID=8YFLogxK
U2 - 10.1097/IAE.0000000000003881
DO - 10.1097/IAE.0000000000003881
M3 - Article
C2 - 37490776
AN - SCOPUS:85175422833
SN - 0275-004X
VL - 43
SP - 1904
EP - 1913
JO - Retina
JF - Retina
IS - 11
ER -