Dataset Information

Quantitative assessment of choriocapillaris flow deficits and type 1 macular neovascularization growth in age-related macular degeneration.

ABSTRACT: During the past 15 years, new treatment paradigms for neovascular age-related macular degeneration (nvAMD) have evolved due to the advent of intravitreal anti-vascular endothelial growth factor (VEGF) therapy and rapid advances in retinal imaging. Recent publications describe eyes with type 1 macular neovascularization (MNV) as showing more resistance to macular atrophy than eyes with other lesion types. We sought to explore whether the perfusion status of the native choriocapillaris (CC) surrounding type 1 MNV influences its pattern of growth. To evaluate this effect, we analyzed a case series of 22 eyes from 19 nvAMD patients with type 1 MNV exhibiting growth on swept-source optical coherence tomography angiography (SS-OCTA) over a minimum follow-up of 12 months. We observed an overall weak correlation between type 1 MNV growth and CC flow deficits (FDs) average size (τ = 0.17, 95% CI [- 0.20, 0.62]) and a moderate correlation with CC FD % (τ = 0.21, 95% CI [- 0.16, 0.68]). Type 1 MNV was located beneath the fovea in most of the eyes (86%) and median visual acuity was 20/35 Snellen equivalent. Our results support that type 1 MNV recapitulates areas of CC blood flow impairment while serving to preserve foveal function.

SUBMITTER: Cabral D

PROVIDER: S-EPMC10220043 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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Quantitative assessment of choriocapillaris flow deficits and type 1 macular neovascularization growth in age-related macular degeneration.

Cabral Diogo D Fradinho Ana C AC Zhang Yi Y Zhou Hao H Ramtohul Prithvi P Ramakrishnan Meera S MS Pereira Telmo T Wang Ruikang K RK Freund K Bailey KB

Scientific reports 20230526 1

During the past 15 years, new treatment paradigms for neovascular age-related macular degeneration (nvAMD) have evolved due to the advent of intravitreal anti-vascular endothelial growth factor (VEGF) therapy and rapid advances in retinal imaging. Recent publications describe eyes with type 1 macular neovascularization (MNV) as showing more resistance to macular atrophy than eyes with other lesion types. We sought to explore whether the perfusion status of the native choriocapillaris (CC) surrou ...[more]

PMID: 37236984

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Project description:Loss of choriocapillaris (CC) in advanced age-related macular degeneration (AMD) is well documented but changes in early AMD have not been quantified. Postmortem eyes from donors with clinically documented early AMD were examined in choroidal whole mounts to determine the area, pattern, and severity of CC loss. Choroids from postmortem human eyes without AMD (n = 7; mean age = 86.1) and from eyes with a Grade 2 clinical classification of early AMD (n = 7; mean age = 87) were immunolabeled with Ulex europaeus agglutinin (UEA) lectin-FITC to stain blood vessels. Whole mounts were imaged using confocal microscopy and image analysis was performed to determine the area of vascular changes and density of vasculature (percent vascular area, %VA). All areas evaluated had a complete RPE monolayer upon gross examination. In age-matched control eyes, the CC had broad lumens and a homogenous pattern of freely interconnecting capillaries. The mean %VA ± standard deviation in submacula of control subjects was 78.1 ± 3.25%. In eyes with early AMD, there was a significant decrease in mean %VA to 60.1 ± 10.4% (p < 0.0001). The paramacular %VA was not significantly different in eyes with or without AMD. The area of submacular choroid affected by CC dropout was 0.04 ± 0.09 mm2 in control eyes. In eyes with early AMD, the mean area affected by CC dropout was significantly increased (10.4 ± 6.1 mm2; p < 0.001). In some cases, incipient neovascular buds were observed at the border of regions with CC dropout in early AMD choroids. In conclusion, UEA lectin-labeled choroidal whole mounts from donors with clinically documented early AMD has provided a unique opportunity to examine regional changes in vascular pathology associated with choriocapillaris. The study demonstrated attenuation of submacular CC in early AMD subjects but no vascular pathology was observed outside the submacular region. While the affected area in some eyes was quite extensive histologically, these changes may not be detectable clinically using standard in vivo imaging.

Project description:PurposeTo detect and quantify choroidal neovascularization (CNV) in patients with age-related macular degeneration (AMD) using optical coherence tomography (OCT) angiography.DesignObservational, cross-sectional study.ParticipantsA total of 5 normal subjects and 5 subjects with neovascular AMD were included.MethodsA total of 5 eyes with neovascular AMD and 5 normal age-matched controls were scanned by a high-speed (100 000 A-scans/seconds) 1050-nm wavelength swept-source OCT. The macular angiography scan covered a 3 × 3-mm area and comprised 200 × 200 × 8 A-scans acquired in 3.5 seconds. Flow was detected using the split-spectrum amplitude-decorrelation angiography (SSADA) algorithm. Motion artifacts were removed by 3-dimensional (3D) orthogonal registration and merging of 4 scans. The 3D angiography was segmented into 3 layers: inner retina (to show retinal vasculature), outer retina (to identify CNV), and choroid. En face maximum projection was used to obtain 2-dimensional angiograms from the 3 layers. The CNV area and flow index were computed from the en face OCT angiogram of the outer retinal layer. Flow (decorrelation) and structural data were combined in composite color angiograms for both en face and cross-sectional views.Main outcome measuresThe CNV angiogram, CNV area, and CNV flow index.ResultsEn face OCT angiograms of CNV showed sizes and locations that were confirmed by fluorescein angiography (FA). Optical coherence tomography angiography provided more distinct vascular network patterns that were less obscured by subretinal hemorrhage. The en face angiograms also showed areas of reduced choroidal flow adjacent to the CNV in all cases and significantly reduced retinal flow in 1 case. Cross-sectional angiograms were used to visualize CNV location relative to the retinal pigment epithelium and Bruch's layer and classify type I and type II CNV. A feeder vessel could be identified in 1 case. Higher flow indexes were associated with larger CNV and type II CNV.ConclusionsOptical coherence tomography angiography provides depth-resolved information and detailed images of CNV in neovascular AMD. Quantitative information regarding CNV flow and area can be obtained. Further studies are needed to assess the role of quantitative OCT angiography in the evaluation and treatment of neovascular AMD.

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

Quantitative assessment of choriocapillaris flow deficits and type 1 macular neovascularization growth in age-related macular degeneration.

Publications

Quantitative assessment of choriocapillaris flow deficits and type 1 macular neovascularization growth in age-related macular degeneration.

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