Nascent type 3 neovascularization in age-related macular degeneration

PURPOSE: To describe the preclinical and very early stages of type 3 neovascularization using multimodal retinal imaging to expand our understanding of the pathogenesis of this disorder and potentially to prevent late treatment. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients diagnosed with treatment-na\uefve type 3 neovascularization in the setting of age-related macular degeneration were identified at 4 retina referral centers. Inclusion criteria were: patients older than 55 years with at least 1 OCT and OCT angiography (OCTA) examination before the onset of clinically active type 3 neovascularization (i.e., preclinical stage). METHODS: Patients underwent a complete ophthalmologic examination including at least OCT and OCTA at the baseline and preclinical stage examinations, and dye angiographies when available. Demographics and clinical findings were analyzed. MAIN OUTCOME MEASURES: Description of multimodal imaging features of nascent type 3 neovascularization. RESULTS: Fifteen eyes (15 patients; mean age, 83 \ub1 9 years) were included. At the baseline, mean BCVA was 0.32 \ub1 0.17 logarithm of the minimum angle of resolution and central macular thickness was 313 \ub1 50 \u3bcm. Preclinical (i.e., prebaseline) structural OCT illustrated the presence of intraretinal hyperreflective foci (HRF) at the site of type 3 neovascularization development in all patients. These foci were characterized by hyperfluorescence on dye angiography and by detectable flow on OCTA, identified with either the avascular slab (20%) or with both the deep retinal capillary plexus (DCP) and avascular slabs (80%). Typically, HRF with detectable flow on OCTA were characterized by the absence of intraretinal exudation (or very mild microcystic changes) until the lesion progressed from the DCP into the retinal pigment epithelium (RPE) and sub-RPE space. Of note, in 1 patient we observed the complete resolution of HRF despite the presence of OCTA flow and dye angiography hyperfluorescence detected at the preclinical stage examination. CONCLUSIONS: Hyperreflective foci on structural OCT may represent early intraretinal neovascularization originating from the DCP, namely nascent type 3 neovascularization; these lesions can progress to active type 3 neovascularization or more rarely may regress without functional impairment. An advanced multimodal imaging approach is useful in detecting nascent type 3 lesions, which should be followed up carefully and treated as soon as possible if flow progresses to the RPE and sub-RPE space to prevent progression to late stages