Histology of Type 3 Macular Neovascularization and Microvascular Anomalies in Treated Age-Related Macular Degeneration
Purpose: To investigate intraretinal neovascularization and microvascular anomalies by correlating in vivo multimodal imaging with corresponding ex vivo histology in a single patient. Design: A case study comprising clinical imaging from a community-based practice, and histologic analysis at a unive...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-09-01
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| Series: | Ophthalmology Science |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S266691452300012X |
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| author | Andreas Berlin, MD, MS Diogo Cabral, MD Ling Chen, MD, PhD Jeffrey D. Messinger, DC Chandrakumar Balaratnasingam, MD, PhD Randev Mendis, MD Daniela Ferrara, MD, PhD K. Bailey Freund, MD Christine A. Curcio, PhD |
| author_facet | Andreas Berlin, MD, MS Diogo Cabral, MD Ling Chen, MD, PhD Jeffrey D. Messinger, DC Chandrakumar Balaratnasingam, MD, PhD Randev Mendis, MD Daniela Ferrara, MD, PhD K. Bailey Freund, MD Christine A. Curcio, PhD |
| author_sort | Andreas Berlin, MD, MS |
| collection | DOAJ |
| description | Purpose: To investigate intraretinal neovascularization and microvascular anomalies by correlating in vivo multimodal imaging with corresponding ex vivo histology in a single patient. Design: A case study comprising clinical imaging from a community-based practice, and histologic analysis at a university-based research laboratory (clinicopathologic correlation). Participants: A White woman in her 90s treated with numerous intravitreal anti-VEGF injections for bilateral type 3 macular neovascularization (MNV) secondary to age-related macular degeneration (AMD). Methods: Clinical imaging comprised serial infrared reflectance, eye-tracked spectral-domain OCT, OCT angiography, and fluorescein angiography. Eye tracking, applied to the 2 preserved donor eyes, enabled the correlation of clinical imaging signatures with high-resolution histology and transmission electron microscopy. Main Outcome Measures: Histologic/ultrastructural descriptions and diameters of vessels seen in clinical imaging. Results: Six vascular lesions were histologically confirmed (type 3 MNV, n = 3; deep retinal age-related microvascular anomalies [DRAMAs], n = 3). Pyramidal (n = 2) or tangled (n = 1) morphologies of type 3 MNV originated at the deep capillary plexus (DCP) and extended posteriorly to approach without penetrating persistent basal laminar deposit. They did not enter the subretinal pigment epithelium (RPE)–basal laminar space or cross the Bruch membrane. Choroidal contributions were not found. The neovascular complexes included pericytes and nonfenestrated endothelial cells, within a collagenous sheath covered by dysmorphic RPE cells. Deep retinal age-related microvascular anomaly lesions extended posteriorly from the DCP into the Henle fiber and the outer nuclear layers without evidence of atrophy, exudation, or anti-VEGF responsiveness. Two DRAMAs lacked collagenous sheaths. External and internal diameters of type 3 MNV and DRAMA vessels were larger than comparison vessels in the index eyes and in aged normal and intermediate AMD eyes. Conclusions: Type 3 MNV vessels reflect specializations of source capillaries and persist during anti-VEGF therapy. The collagenous sheath of type 3 MNV lesions may provide structural stabilization. If so, vascular characteristics may be useful in disease monitoring in addition to fluid and flow signal detection. Further investigation with longitudinal imaging before exudation onset will help determine if DRAMAs are part of the type 3 MNV progression sequence. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. |
| first_indexed | 2024-03-11T21:14:34Z |
| format | Article |
| id | doaj.art-198921117a03433db244ff39bc698b04 |
| institution | Directory Open Access Journal |
| issn | 2666-9145 |
| language | English |
| last_indexed | 2024-03-11T21:14:34Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ophthalmology Science |
| spelling | doaj.art-198921117a03433db244ff39bc698b042023-09-29T04:45:17ZengElsevierOphthalmology Science2666-91452023-09-0133100280Histology of Type 3 Macular Neovascularization and Microvascular Anomalies in Treated Age-Related Macular DegenerationAndreas Berlin, MD, MS0Diogo Cabral, MD1Ling Chen, MD, PhD2Jeffrey D. Messinger, DC3Chandrakumar Balaratnasingam, MD, PhD4Randev Mendis, MD5Daniela Ferrara, MD, PhD6K. Bailey Freund, MD7Christine A. Curcio, PhD8Department of Ophthalmology and Visual Sciences, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama; Department of Ophthalmology, University Hospital Wurzburg, Wurzburg, GermanyVitreous Retina Macula Consultants of New York, New York; NOVA Medical School Research, Universidade NOVA de Lisboa, Lisbon, PortugalDepartment of Ophthalmology and Visual Sciences, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama; The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, and Chongqing Eye Institute, Chongqing, ChinaDepartment of Ophthalmology and Visual Sciences, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AlabamaCentre for Ophthalmology and Visual Science, University of Western Australia, Perth, Western Australia, Australia; Lions Eye Institute, Nedlands, Western Australia, Australia; Department of Ophthalmology, Sir Charles Gairdner Hospital, Nedlands, Western Australia, AustraliaCanberra Retina Center, Canberra, AustraliaGenentech, South San Francisco, CaliforniaVitreous Retina Macula Consultants of New York, New York; Department of Ophthalmology, New York University Grossman School of Medicine, New York, New YorkDepartment of Ophthalmology and Visual Sciences, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama; Correspondence: Christine A. Curcio, PhD, 1670 University Boulevard Room 360, Birmingham, AL 35294-0019.Purpose: To investigate intraretinal neovascularization and microvascular anomalies by correlating in vivo multimodal imaging with corresponding ex vivo histology in a single patient. Design: A case study comprising clinical imaging from a community-based practice, and histologic analysis at a university-based research laboratory (clinicopathologic correlation). Participants: A White woman in her 90s treated with numerous intravitreal anti-VEGF injections for bilateral type 3 macular neovascularization (MNV) secondary to age-related macular degeneration (AMD). Methods: Clinical imaging comprised serial infrared reflectance, eye-tracked spectral-domain OCT, OCT angiography, and fluorescein angiography. Eye tracking, applied to the 2 preserved donor eyes, enabled the correlation of clinical imaging signatures with high-resolution histology and transmission electron microscopy. Main Outcome Measures: Histologic/ultrastructural descriptions and diameters of vessels seen in clinical imaging. Results: Six vascular lesions were histologically confirmed (type 3 MNV, n = 3; deep retinal age-related microvascular anomalies [DRAMAs], n = 3). Pyramidal (n = 2) or tangled (n = 1) morphologies of type 3 MNV originated at the deep capillary plexus (DCP) and extended posteriorly to approach without penetrating persistent basal laminar deposit. They did not enter the subretinal pigment epithelium (RPE)–basal laminar space or cross the Bruch membrane. Choroidal contributions were not found. The neovascular complexes included pericytes and nonfenestrated endothelial cells, within a collagenous sheath covered by dysmorphic RPE cells. Deep retinal age-related microvascular anomaly lesions extended posteriorly from the DCP into the Henle fiber and the outer nuclear layers without evidence of atrophy, exudation, or anti-VEGF responsiveness. Two DRAMAs lacked collagenous sheaths. External and internal diameters of type 3 MNV and DRAMA vessels were larger than comparison vessels in the index eyes and in aged normal and intermediate AMD eyes. Conclusions: Type 3 MNV vessels reflect specializations of source capillaries and persist during anti-VEGF therapy. The collagenous sheath of type 3 MNV lesions may provide structural stabilization. If so, vascular characteristics may be useful in disease monitoring in addition to fluid and flow signal detection. Further investigation with longitudinal imaging before exudation onset will help determine if DRAMAs are part of the type 3 MNV progression sequence. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.http://www.sciencedirect.com/science/article/pii/S266691452300012XAge-related macular degenerationDeep retinal age-related microvascular anomaliesHistopathologyType 3 macular neovascularizationVascular morphology |
| spellingShingle | Andreas Berlin, MD, MS Diogo Cabral, MD Ling Chen, MD, PhD Jeffrey D. Messinger, DC Chandrakumar Balaratnasingam, MD, PhD Randev Mendis, MD Daniela Ferrara, MD, PhD K. Bailey Freund, MD Christine A. Curcio, PhD Histology of Type 3 Macular Neovascularization and Microvascular Anomalies in Treated Age-Related Macular Degeneration Ophthalmology Science Age-related macular degeneration Deep retinal age-related microvascular anomalies Histopathology Type 3 macular neovascularization Vascular morphology |
| title | Histology of Type 3 Macular Neovascularization and Microvascular Anomalies in Treated Age-Related Macular Degeneration |
| title_full | Histology of Type 3 Macular Neovascularization and Microvascular Anomalies in Treated Age-Related Macular Degeneration |
| title_fullStr | Histology of Type 3 Macular Neovascularization and Microvascular Anomalies in Treated Age-Related Macular Degeneration |
| title_full_unstemmed | Histology of Type 3 Macular Neovascularization and Microvascular Anomalies in Treated Age-Related Macular Degeneration |
| title_short | Histology of Type 3 Macular Neovascularization and Microvascular Anomalies in Treated Age-Related Macular Degeneration |
| title_sort | histology of type 3 macular neovascularization and microvascular anomalies in treated age related macular degeneration |
| topic | Age-related macular degeneration Deep retinal age-related microvascular anomalies Histopathology Type 3 macular neovascularization Vascular morphology |
| url | http://www.sciencedirect.com/science/article/pii/S266691452300012X |
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