NEW PROPOSAL FOR THE PATHOPHYSIOLOGY OF TYPE 3 NEOVASCULARIZATION AS BASED ON MULTIMODAL IMAGING FINDINGS

Purpose: To investigate the imaging characteristics of early Type 3 neovascularization and propose a new pathophysiologic sequence for early disease. Methods: Patients were evaluated with a comprehensive ophthalmologic examination to include fundus photography, optical coherence tomography, optical coherence tomography angiography, fluorescein angiography, and volume-rendered optical coherence tomography angiography. Relevant literature was also reviewed. Results: There were 10 eyes of 9 patients who had a mean age of 87 (range 79-93) years and 7 were women. The patients were seen to have distributed areas of cystoid macular edema, not necessarily contiguous with areas of fluorescein or optical coherence tomography angiographic evidence of neovascularization, which colocalized with each other. Areas of hemorrhage were not necessarily contiguous with observed neovascularization. In some patients, massive amounts of edema were imaged, although the associated neovascular invasion was small and did not reach deeper portions of the retina. These findings were readily responsive to intravitreal injections of anti-vascular endothelial growth factor (VEGF) medication. Review of published literature showed conflicting pathophysiologic proposals, which did not abide with contemporaneous imaging findings. Conclusion: Type 3 neovascularization likely grows in response to increased cytokine levels, particularly VEGF, in a permissive environment. Elevated levels of VEGF have been shown to cause hemorrhage, edema, and telangiectasis in the macula, suggesting some of the manifestations of Type 3 neovascularization are related to increased tissue VEGF levels and not necessarily to the neovascularization alone. A proposal based on imaging and histopathologic findings and known physiologic effects of VEGF is presented.