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Review
. 2024 Oct 5;8(6):709-718.
doi: 10.1177/24741264241276929. eCollection 2024 Nov-Dec.

Imaging-Guided Classification of Neovascularization in Neovascular Age-Related Macular Degeneration: Progress to Date

Giovanni Staurenghi  1 , Eric H Souied  2 , Tomohiro Iida  3 , David R Chow  4 , Armin Wolf  5 , Roberto Gallego-Pinazo  6 , Francesco Viola  7   8 , Peter K Kaiser  9
Affiliations
Review

Imaging-Guided Classification of Neovascularization in Neovascular Age-Related Macular Degeneration: Progress to Date

Giovanni Staurenghi et al. J Vitreoretin Dis. .

Abstract

Purpose: To review the evolution of terminology describing the classification of lesions in neovascular age-related macular degeneration (nAMD) based on retinal imaging technologies. Methods: A review of the current and historical literature on imaging-guided classification of neovascularization in nAMD was performed. Results: Imaging-guided classification of neovascularization in nAMD facilitates an understanding of the pathological mechanisms and disease progression. Neovascularization classification has evolved with advances in imaging technologies, from earlier classifications based on neovascularization patterns assessed by fluorescein angiography to multimodal imaging patterns, resulting in varied descriptions of lesions depending on the techniques used. Until recently, there has been a lack of consensus regarding the clinical features of choroidal neovascularization lesion types as a result of the imaging modalities initially used to define them; a recent consensus on classification has the potential to simplify and clarify descriptions of neovascularization in nAMD. The use of multimodal imaging techniques will improve lesion identification and has the potential to individualize treatment plans and improve outcomes. Conclusions: Widespread adoption of a consensus-based, image-guided classification system for neovascular lesions in nAMD and the appropriate imaging techniques used to identify them will aid clinical research and could potentially improve patient outcomes by individualizing treatment plans in the future.

Keywords: age-related macular degeneration; choroidal neovascularization; fluorescein angiography; imaging; indocyanine green angiography; macular neovascularization; multimodal imaging; neovascularization; optical coherence tomography angiography.

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Conflict of interest statement

Dr. Wolf received funds from Bayer, Novartis, Sandoz, and Zeiss. Dr. Chow received consultancy fees from Bayer and Roche, research support from Opthea and RegenxBio Inc, and payment or honoraria for lectures or educational activities from Aviceda Therapeutics and Apellis Pharmaceuticals. Dr. Souied provided expert support for AbbVie, Apellis Pharmaceuticals, Bayer, Novartis, Roche, and Teva. Dr. Viola received consultancy fees, grants, and support for attending meetings and/or travel and participation on a data safety monitoring board or advisory board from Bayer, Novartis, and Roche. Dr. Kaiser received consultancy fees from Alcon, Allergan, Bayer, Bausch + Lomb, Biogen Idec, Clearside Biomedical, Coherus BioSciences, Genentech/Roche, Astellas, Novartis, Ocular Therapeutix, Oculis, Ocuphire Pharma, Regeneron Pharmaceuticals Inc, and RegenxBio Inc. Dr. Staurenghi received consultant/advisor fees from AbbVie, Annexon Bioscience, Apellis Pharmaceuticals, Bayer HealthCare Pharmaceutical, Boehringer Ingelheim, Genentech, Iveric Bio, and OraPharma Inc; consultant/advisor fees and grant support from Optos Inc and RetinAI; grant support from Quantel Medical; consultant/advisor fees, lecture fees/speakers bureau and grant support from CenterVue, Inc, Heidelberg Engineering, Hoffman La Roche, and Novartis Pharmaceuticals; lecture fees/speakers bureau and grant support from Carl Zeiss Meditec; consultant/advisor fees and lecture fees/speakers bureau from Medscape; lecture fees/speakers bureau and grant support from Nidek Inc; and patents/royalty from Ocular Instruments Inc. Dr. Gallego-Pinazo received consultancy fees from Apellis Pharmaceuticals and Carl Zeiss AG, consultancy fees and research support from Novartis and Roche, and research support from Ionis, Iveric Bio, Janssen, and Opthea. Dr. Iida received consultancy fees from Bayer Yakuhin Ltd., Chugai Pharmaceutical Co, Janssen Pharmaceutical K.K., Kyowa Kirin, Nippon Boehringer Ingelheim Co, Ltd, Novartis, and Senju Pharmaceutical Co, Ltd; study funding and article processing charges from Bayer AG (Leverkusen, Germany); funding for editorial support and medical writing from Bayer Consumer Care AG (Basel, Switzerland); study funding from Regeneron Pharmaceuticals Inc; grant funding from Alcon Japan, AMO Pharma Ltd, HOYA, Nidek, Novartis, Santen Pharmaceutical, Senju Pharmaceutical Co Ltd, and Topcon Healthcare; payment or honoraria for lectures from Alcon Japan, Bayer Yakuhin Ltd, Canon Inc, Chugai Pharmaceutical Co, Nidek, Nikon, Novartis, Otsuka Pharmaceutical Co, Ltd, Santen Pharmaceutical, Senju Pharmaceutical Co, Ltd; and Topcon; patent from Topcon; and other financial rewards from Kyowa Kirin.

Figures

Figure 1.
Figure 1.
Literature search flow diagram. *Keywords: “choroidal neovascularization” AND “review” / “neovascular age-related macular degeneration” / “geographic atrophy” / “differential diagnosis” / “optical coherence tomography” / “treatment response” / “subtypes” / “diagnosis” / “classification” / “fluorescein angiography” / “spectral domain optical coherence tomography” / “choroidal neovascularization subtype / “lesion” AND “optical coherence tomography angiography” / “optical coherence tomgography” / “indocyanine green angiography” / “infrared reflectance inaging” / “Type 1/2/3 choroidal neovascularization lesion” AND “optical coherence tomography” / “fluorescein angiography” / “optical coherence tomography angiography” / “quiescent CNV” AND “optical coherence tomography” / “optical coherence tomography angiography” / “double layer sign” AND “ spectral domain optical coherence tomography” AND “neovascular age-related macular degeneration” / polypoidal choroidal vasculopathy lesion” AND “optical coherence tomography/ optical coherence tomography angiography” / “reticular pseudodrusen” AND “infrared reflectance imaging”.
Figure 2.
Figure 2.
Evolution of classification of neovascularization lesions. *According to the unified classification of neovascularization proposed by Spaide et al, the term CNV is inaccurate in the context of type 3 neovascular lesions and should be replaced with MNV. Abbreviations: CNV, choroidal neovascularization; FA, fluorescein angiography; ICGA, indocyanine green angiography; MNV, macular neovascularization; RPE, retinal pigment epithelium; TAP, Treatment of Age-Related Macular Degeneration with Photodynamic Therapy; OCT, optical coherence tomography; OCTA, optical coherence tomography angiography; PCV, polypoidal choroidal vasculopathy; RAP, retinal angiomatous proliferation; RVAC, retinal vascular anomalous complex.
Figure 3.
Figure 3.
Type 1 MNV. Left image: Fibrovascular PED. (A) Color image shows increased pigmentation in the macular area with macular thickening and retinal hemorrhages. (B) Fundus autofluorescence indicating mottled hyperautofluorescence of the macular area with subretinal fluid. (C) FA shows the presence of an occult neovascular lesion. (D) ICGA shows hypofluorescence coincident with the fibrovascular PED. (E) En face structural tomographic image shows the tangled vascular network surrounded by a wide hyporeflective halo. (F) OCT structural image with flow overlay shows the presence of flow signal within the PED but absence of flow signal within the subretinal hyperreflective material. (G) Structural OCT scan through the foveal center indicates the presence of subretinal hyperreflective material overlying a fibrovascular PED with the RPE showing no disruption. Right image: LLUS. (A) Infrared reflectance image shows pigmentary changes in the macular region. (B) FA indicating mild pigmentary changes in the macular region. (C) FA shows the correspondence of the previously described signs with no evidence of vascular leakage. (D) ICGA shows thickened choroidal vessels with anastomosis between the superior and inferior veins. (E) En face OCT angiography proves the presence of a neovascular network. (F) Structural OCT scan shows a shallow, irregular RPE elevation corresponding to the neovascular lesion with no structural evidence of active or past exudation. Abbreviations: FA, fluorescein angiography; ICGA, indocyanine green angiography; LLUS, late leakage of underdetermined source; OCT, optical coherence tomography; PED, pigment epithelial detachment; RPE, retinal pigment epithelium.
Figure 4.
Figure 4.
Type 2 MNV. (A) Color image shows decreased tessellation of the macular region with thickening and subretinal fibrinous material. (B) FA shows increased autofluorescence at the margins of the hypofluorescent lesion. (C) FA shows the presence of a classic neovascular lesion. (D) ICGA shows the presence of a tangled network of neovessels. (E) En face OCT angiography proves the presence of a dense neovascular network. (F) Structural OCT scan shows an RPE elevation associated with subretinal hyperreflective material and subretinal fluid. Abbreviations: FA, fluorescein angiography; ICGA, indocyanine green angiography; MNV, macular neovascularization; OCT, optical coherence tomography; RPE, retinal pigment epithelium.
Figure 5.
Figure 5.
Type 3 MNV. (A) Color image with intraretinal flame hemorrhage. (B) Midphase FA with intraretinal leakage. (C) Intermediate ICGA with typical leakage; other MNVs do not usually leak ICG dye. (D) OCT with intraretinal fluid without neurosensory retinal detachment. (E) RPE detachment with interruption and evident type 3 neovascularization. (F and G) FA and ICGA of an RPE detachment with typical position of a type 3 neovascularization in the center of the detachment. (H–K) Indirect signs, such as the disappearance of RPE detachment, after intravitreal injection of anti-VEGF resulting from the lack of new neovascular tissue under the RPE. Abbreviations: anti-VEGF, antivascular endothelial growth factor; FA, fluorescein angiography; ICG, indocyanine green; ICGA, indocyanine green angiography; MNV, macular neovascularization; OCT, optical coherence tomography; RPE, retinal pigment epithelium.
Figure 6.
Figure 6.
Type 1 and type 2 MNV. (A) Color image shows decreased tessellation of the macular region with thickening and some degree of subretinal fibrinous material. (B) FA shows a minimally (<50%) classic neovascular lesion. (C) ICGA shows the presence of a tangled network of neovessels. (D) En face OCTA proves the presence of a dense neovascular network at the level of the avascular external retina slab. (E) En face OCTA proves the presence of a dense neovascular network at the level of the sub-RPE layer slab. (F) Structural OCT scan shows an RPE elevation with a focal disruption in close proximity to an overlying subretinal fibrovascular material associated with subretinal fluid. Abbreviations: FA, fluorescein angiography; ICGA, indocyanine green angiography; MNV, macular neovascularization; OCT, optical coherence tomography; OCTA, optical coherence tomography angiography; RPE, retinal pigment epithelium.
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