Multiscale clinicopathologic correlation of canonical and non-canonical intraretinal neovascularization in age-related macular degeneration (AMD)

Abstract

Purpose : Purpose: Intraretinal macular neovascularization (MNV) is often preceded by hyperreflective foci (HRF) attributed to ectopic retinal pigment epithelium (RPE) and non-RPE. RPE migration may reflect a response to choroidal ischemia. We investigated with histology clinically documented HRF in fellow eyes, each with 3 MNV.

Methods : Methods: A white woman receiving anti-VEGF was monitored by optical coherence tomography (OCT) and angiography (OCT, dye-based) (OD, n=37; OS, n=6; last visits 3 and 2 months, respectively, before death). Eyes were recovered 4:05 hours after patient death at age 97 years. Eye-tracking (Heidelberg Engineering) aligned clinical and ex vivo imaging of the preserved eye prior to epoxy embedding for high-resolution light microscopic and transmission electron microscopic (TEM) investigation. Horizontally oriented 12 mm wide sections, 30 µm apart, were interleaved with 30 µm-thick slabs re-embedded for TEM.

Results :
Results: In OD, 2 MNV were investigated via TEM. In the first MNV, a hyperreflective triangle, with base-down and apex disrupting outer retinal and RPE layers correlated to an intraretinal vascular complex with numerous pericytes, ensheathed by collagenous material. Fully pigmented RPE distributed upward along this complex, entering but not contacting vessels. The complex rested on persistent basal laminar deposit overlying a completely calcified druse. Bruch’s membrane was intact. In the second MNV, a hyperreflective column atop a soft druse correlated to a column of RPE emerging from the top of intact RPE covering a lipid-rich druse. Cells at the column tip encircled a vessel dipping into the Henle fiber layer from the deep capillary plexus. Pericytes were not seen.

Conclusions :
Conclusion: The components and morphology of the first MNV resembled our recent description of treated type 3 MNV and added new observations of pericytes, and lack of penetration into the sub-RPE-BL space, which contained calcified drusen. The second MNV did not resemble the first MNV or others in either eye. It may represent another entity such as perifoveal exudative vascular anomalous complex (PEVAC; PMID 29079450), which is non-responsive to anti-VEGF. Recognition of different intraretinal MNV morphologies through clinicopathologic correlation may assist management decisions for neovascular AMD.

This is a 2021 ARVO Annual Meeting abstract.