Clinicopathologic Correlation of Retinal Angiomatous Proliferation Treated With Ranibizumab

Skalet, Alison H.; Miller, Audra K.; Klein, Michael L.; Lauer, Andreas K.; Wilson, David J.

doi:10.1097/iae.0000000000001672

Cited by 14 publications

(10 citation statements)

References 20 publications

(21 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The RPE monolayer underlying the lesion was disrupted; however, the inner portion of the Bruch membrane was intact. The histopathologic findings corresponded to an area of hyperreflectivity on SD-OCT imaging, confirming the reported tomographic appearance of MNV3 lesions ( Skalet et al, 2017 ).…”

Section: Introductionsupporting

confidence: 83%

Clinical Pathological Features and Current Animal Models of Type 3 Macular Neovascularization

Wei

Chen

et al. 2021

Front. Neurosci.

View full text Add to dashboard Cite

Type 3 macular neovascularization (MNV3), or retinal angiomatous proliferation (RAP), is a distinct type of neovascular age-related macular degeneration (AMD), which is a leading cause of vision loss in older persons. During the past decade, systematic investigation into the clinical, multimodal imaging, and histopathological features and therapeutic outcomes has provided important new insight into this disease. These studies favor the retinal origin of MNV3 and suggest the involvement of retinal hypoxia, inflammation, von Hippel–Lindau (VHL)–hypoxia-inducible factor (HIF)–vascular endothelial growth factor (VEGF) pathway, and multiple cell types in the development and progression of MNV3. Several mouse models, including the recently built Rb/p107/Vhl triple knockout mouse model by our group, have induced many of the histological features of MNV3 and provided much insight into the underlying pathological mechanisms. These models have revealed the roles of retinal hypoxia, inflammation, lipid metabolism, VHL/HIF pathway, and retinoblastoma tumor suppressor (Rb)–E2F cell cycle pathway in the development of MNV3. This article will summarize the clinical, multimodal imaging, and pathological features of MNV3 and the diversity of animal models that exist for MNV3, as well as their strengths and limitations.

show abstract

Section: Introductionsupporting

confidence: 83%

Clinical Pathological Features and Current Animal Models of Type 3 Macular Neovascularization

Wei

Chen

et al. 2021

Front. Neurosci.

View full text Add to dashboard Cite

show abstract

“…We think this is unlikely, because neo-capillaries may shrink after treatment, but they do not disappear. 56, 57 Further, our use of stepped sections may miss key details. Nevertheless, in all analyzed sections of this case, both BLamD and BrM were intact.…”

Section: Discussionmentioning

confidence: 99%

Histology of type 3 macular neovascularization and microvascular anomalies in treated age-related macular degeneration: a case study

Berlin

Cabral

Chen

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Additionally, it is always possible that anti-vascular endothelial growth factor treatment in our case rendered invisible downward projections from the DCP and any connections they might make with type 1 neovascularization, as suggested. We think this is unlikely, because neocapillaries may shrink after treatment but they do not disappear, as Sacconi et al also point out. This signifies either partial retraction, slowing of flow velocity below the threshold of OCTA detection or both.…”

mentioning

confidence: 85%

Optical Coherence Tomography Angiography and Corresponding Histology—Reply

2023

View full text Add to dashboard Cite

COMMENT & RESPONSEIn Reply Thank you very much for your interest in our recent publication. 1 We are happy to answer each of your questions in order.1. An injection was administered 8 weeks before optical coherence tomography angiography (OCTA) imaging and 8 weeks before date of death in the right eye. 2. Eight injections at about 8-week intervals were administered between OCTA imaging and date of death over 16 months. Before undergoing OCTA imaging, the patient had received 28 intravitreal injections over more than 3.5 years, indicating a chronic lesion with chronic changes. Substantial changes of the macular neovascularization structure in such a chronic complex are not likely. 3. We agree that connections between the deep capillary plexus (DCP) and the choriocapillaris are associated with advanced stages of disease. Choroidal contributions have been confirmed in surgical specimens 2 and in clinical imaging studies of treated eyes. 3 Thus we stated: "Our current findings do not exclude such a connection in general or in other cases." 1 We could have also said (but did not) that we did not see DCPoriginating vessels penetrate through basal laminar deposit (BLamD) and enter the sub-RPE-basal laminar (BL) space. As cited in the letter to the editor, Sacconi et al 4 described how DCP-originating flow signal extends past the RPE (and also BLamD) during periods of exudation. 4. Figure 1B of our article 1 shows a type 3 lesion with flow signal, positioned over calcified drusen that masquerade as a double layer sign. We chose to detail this lesion, and others in this case, in a separate manuscript. The type 3 lesion in Figure 1B spans a large area. As we state as a limitation, 1 our use of stepped sections may have missed connections between the retinal and choroidal circulations, and as mentioned above, may have also missed connections between the DCP and sub-RPE-BL space. Lack of serial sections is a trade-off we accepted in using epoxy resin embedding for high-resolution light microscopy covering a large area. However, in all analyzed tissue sections of the Figure 1B lesion, both BLamD and the Bruch membrane were intact. Furthermore, we did not see OCTA flow signal in the sub-RPE-BL space under this lesion, perhaps because we used volumetric projection artifact removal. This technique should reduce the chance of seeing spurious signal directly under type 3 neovascularization. This is especially important for accurate localization of flow in instances where the RPE-BL is not elevated by a hyporeflective structure, such as sub-RPE fluid or a calcific nodule. Sacconi et al, 4 who reported many treatment-naive eyes with flow signal in the sub-RPE-BL space, at the same time mentioned lack of pro-

show abstract

Clinicopathologic Correlation of Retinal Angiomatous Proliferation Treated With Ranibizumab

Abstract: In a patient with ARMD extensively treated with ranibizumab, color fundus photography, fluorescein angiography and SD-OCT images of RAP correlated histopathologically with a paucicellular intraretinal vascular complex.

Cited by 14 publications

References 20 publications

Clinical Pathological Features and Current Animal Models of Type 3 Macular Neovascularization

Clinical Pathological Features and Current Animal Models of Type 3 Macular Neovascularization

Histology of type 3 macular neovascularization and microvascular anomalies in treated age-related macular degeneration: a case study

Optical Coherence Tomography Angiography and Corresponding Histology—Reply

Contact Info

Product

Resources

About