How has high-resolution multimodal imaging refined our understanding of the vasogenic process in type 3 neovascularization?

How Has High-Resolution Multimodal Imaging Refined Our Understanding of the Vasogenic Process in Type 3 Neovascularization? J. Donald M. Gass defined a terminology for neovascularization in macular diseases that is based on the anatomical location of the neovessels. He proposed the term “Type 1 neovascularization” to describe neovascularization confined to the sub-retinal pigment epithelium (RPE) space, showing minimal late leakage on fluorescein angiography (FA). The term “Type 2 neovascularization” denoted neovascularization proliferating above the RPE in the subneurosensory space. These neovessels have penetrated the basement membrane/RPE complex or have gained access to the subretinal space through an existing break in the basement membrane/RPE such as a chorioretinal scar. Type 2 neovascularization actively proliferates beneath the neurosensory retina, and there is active leakage associated with dye pooling into the subneurosensory and intraretinal spaces on FA. In 1992, Hartnett et al first described a retinal angiomatous lesion associated with age-related macular degeneration (AMD) drusen causing retinal pigment epithelium detachment (PED). In the original description, the authors found on FA that a feeding retinal arteriole dipped toward the RPE, forming an angiomatous lesion in the outer retina that had a sub-RPE component. Indocyanine green video angiography in PEDs with hot spots allowed Kuhn et al to confirm the localization of the retinal angiomatous lesions in the outer retina and to identify, in the vast majority of these cases, an anastomosis between the choroidal and retinal vasculature. Subsequently, Yannuzzi et al coined the term retinal angiomatous proliferation to define this specific form of neovascularization secondary to AMD and believed that it originated within the deep retinal layers. Gass et al proposed instead that what was described as retinal angiomatous lesion or retinal angiomatous proliferation actually originates as occult choroidal neovascularization (CNV) that erodes through the RPE forming an occult retinal choroidal anastomosis (RCA) early in its evolution. Because of the controversial pathogenesis, Freund et al recently proposed to use the term “Type 3 neovascularization” to refer to this peculiar form of neovascular AMD that has a predilection for the neurosensory retina. The term Type 3 neovascularization encompasses both Yannuzzi’s and Gass’ hypotheses regarding the origin of the intraretinal component of this proliferative process and complements Gass classic anatomical classification of neovascularization as Type 1 (sub-RPE) CNV and Type 2 (subneurosensory) CNV. The advent of high-resolution multimodal imaging technologies including spectral domain optical coherence tomography with eye tracking and simultaneous (real-time eye tracked) high-speed FA and/or indocyanine green angiography has enabled unprecedented in vivo analysis of retinal lesions. By means of multimodal imaging, we recently described, in vivo, one possible origin for Type 3 neovascularization. However, according to Yannuzzi et al, there may be at least three variants of the vasogenic process seen in Type 3 neovascularization: 1) initial focal retinal proliferation and progression, 2) focal retinal proliferation with preexisting or simultaneous choroidal proliferation, and 3) initial focal choroidal proliferation and progression. Considering the controversial pathogenesis and the possibility of different variants of this peculiar form of neovessels, what has high-resolution multimodal imaging taught us about the vasogenic sequence in Type 3 neovascularization and its behavior compared with other lesion types? High-resolution multimodal imaging has helped confirm that, in many cases, the early appearance of Type 3 neovascularization is characterized by an intraretinal vascular complex emanating from the deep capillary plexus often associated with adjoining telangiectatic vessels (Figure 1). In some of these eyes, high-density spectral domain optical coherence tomography raster scans fail to show any apparent defect in Supported in part by The Macula Foundation, Inc. None of the authors have any conflicting interests to disclose. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (www.retinajournal.com).