Dataset Information

Recognizing Atrophy and Mixed-Type Neovascularization in Age-Related Macular Degeneration Via Clinicopathologic Correlation.

ABSTRACT: Purpose:We explored via multimodal imaging and histology an eye with mixed-types 1 and 2 macular neovascularization (MNV) and complete retinal pigment epithelium (RPE) and outer retinal atrophy (cRORA) in age-related macular degeneration. Methods:An 82-year-old white man was followed 7 years by optical coherence tomography and treated with intravitreal anti-vascular endothelial growth factor for 3 years. At the last clinic visit, visual acuity was stable at 20/50. Two months later the patient died, and eyes were preserved at 8.33 hours after death. Submicrometer epoxy resin sections of osmicated tissue were stained with toluidine blue and evaluated by oil immersion microscopy. Results:A shallow irregular RPE elevation on optical coherence tomography correlated with type 1 MNV with fibrocellular scar and neocapillaries (close to RPE), at a density similar to underlying native choriocapillaris (0.37 vs. 0.42). Type 2 MNV covered the native RPE and was enveloped at the margins by RPE, without neocapillaries. Native RPE cells transdifferentiated from age-normal to melanotic and entered type 1 MNV and choroid. Some photoreceptors persisted over MNV. The cRORA initiated at a collapsed druse, expanded during follow-up, and exhibited low choriocapillaris density (0.05). Conclusions:An eye with maintained vision on 3 years of anti-vascular endothelial growth factor therapy had type 1 MNV sustaining RPE. Type 2 MNV enveloped by RPE was visible in optical coherence tomography and histology. Persistence of photoreceptors and RPE over MNV contrasted with drusen-associated cRORA. Translational Relevance:Vision during long-term anti-vascular endothelial growth factor treatment persists by MNV partially preserving outer retinal cells and by RPE enveloping type 2 MNV.

SUBMITTER: Chen L

PROVIDER: S-EPMC7422865 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Recognizing Atrophy and Mixed-Type Neovascularization in Age-Related Macular Degeneration Via Clinicopathologic Correlation.

Chen Ling L Li Miaoling M Messinger Jeffrey D JD Ferrara Daniela D Curcio Christine A CA Freund K Bailey KB

Translational vision science & technology 20200707 8

<h4>Purpose</h4>We explored via multimodal imaging and histology an eye with mixed-types 1 and 2 macular neovascularization (MNV) and complete retinal pigment epithelium (RPE) and outer retinal atrophy (cRORA) in age-related macular degeneration.<h4>Methods</h4>An 82-year-old white man was followed 7 years by optical coherence tomography and treated with intravitreal anti-vascular endothelial growth factor for 3 years. At the last clinic visit, visual acuity was stable at 20/50. Two months later ...[more]

PMID: 32855855

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Project description:PURPOSE:In an eye with geographic atrophy (GA) secondary to age-related macular degeneration, we correlated ex vivo histologic features with findings recorded in vivo using optical coherence tomography (OCT), near-infrared reflectance imaging, and fundus autofluorescence. METHODS:In the left eye of an 86-year-old white woman, in vivo near-infrared reflectance and eye-tracked OCT B-scans at each of 6 clinic visits and a baseline fundus autofluorescence image were correlated with high-resolution histologic images of the preserved donor eye. RESULTS:Clinical imaging showed a small parafoveal multilobular area of GA, subfoveal soft drusen, refractile drusen, hyperreflective lines near the Bruch membrane, subretinal drusenoid deposit (reticular pseudodrusen), and absence of hyperautofluorescent foci at the GA margin. By histology, soft drusen end-stages included avascular fibrosis with highly reflective cholesterol crystals. These accounted for hyperreflective lines near the Bruch membrane in OCT and plaques in near-infrared reflectance imaging. Subretinal drusenoid deposit was thick, continuous, extracellular, extensive outside the fovea, and associated with distinctive retinal pigment epithelium dysmorphia and photoreceptor degeneration. A hyporeflective wedge corresponded to ordered Henle fibers without cellular infiltration. The external limiting membrane descent, which delimits GA, was best visualized in high-quality OCT B-scans. Retinal pigment epithelium and photoreceptor changes at the external limiting membrane descent were consistent with our recent histologic survey of donor eyes. CONCLUSION:This case informs on the extent, topography, and lifecycle of extracellular deposits. High-quality OCT scans are required to reveal all tissue features relevant to age-related macular degeneration progression to GA, especially the external limiting membrane descent. Histologically validated signatures of structural OCT B-scans can serve as references for other imaging modalities.

Project description:Purpose: Age-related macular degeneration (AMD) is one of the leading causes of blindness, and choroidal neovascularization (CNV) in AMD can lead to serious visual impairment. Gene expression profiling of human ocular tissues have a great potential to reveal the pathophysiology of AMD. This study aimed to identify novel molecular biomarkers and gene expression signatures of AMD. Methods: We analyzed transcriptome profiles in retinal-choroid tissues derived from donor patients with AMD in comparison with those from healthy controls using a publicly available dataset (GSE29801). We focused on the EFEMP1 gene, which was found to be differentially upregulated in AMD, especially in wet AMD eyes. Serological validation analysis was carried out to verify the expression of EFEMP1 in 39 wet AMD patients and 39 age- and gender-matched cataract controls, using an enzyme-linked immunosorbent assay (ELISA). We then investigated the role of EFEMP1 in angiogenesis through in vitro experiments involving EFEMP1 overexpression (OE) and knockdown in human umbilical vein endothelial cells (HUVECs). Results: An increase in EFEMP1 expression was observed in the retinal-choroid tissues of eyes with AMD, which was more significant in wet AMD than in dry AMD. In addition, there was a significant increase in serum fibulin-3 (EFEMP1 encoded protein) concentration in patients with wet AMD compared with that in the controls. Tube formation and proliferation of EFEMP1-OE HUVECs increased significantly, whereas those of EFEMP1 knockdown HUVECs decreased significantly compared with those of the control. Additional extracellular fibulin-3 treatments did not increase tube formation and proliferation of wildtype and EFEMP1 knockdown HUVECs, indicating that the proangiogenic properties of EFEMP1 are of cell origin. We also found that vascular endothelial growth factor expression in HUVECs was upregulated by EFEMP1 overexpression and downregulated by EFEMP1 knockdown. Conclusion: Our findings demonstrate EFEMP1 as a novel biomarker for CNV in AMD, providing a new target for the development of wet AMD-directed pharmaceuticals and diagnostics.

Dataset Information

Recognizing Atrophy and Mixed-Type Neovascularization in Age-Related Macular Degeneration Via Clinicopathologic Correlation.

Publications

Recognizing Atrophy and Mixed-Type Neovascularization in Age-Related Macular Degeneration Via Clinicopathologic Correlation.

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