Nonexudative Macular Neovascularization Supporting Outer Retina in Age-Related Macular Degeneration

Abstract

Purpose: Type 1 macular neovascularization (MNV) secondary to age-related macular degeneration (AMD) may sustain hypoxic and micronutrient-insufficient outer retinal cells compensatorily. We explored this hypothesis via histologic analysis of an eye with a shallow irregular retinal pigment epithelial elevation (SIRE) on OCT and good vision.Design: Case study and clinicopathologic correlation.Participant: A white woman with untreated nonexudative neovascular AMD and 20/30 visual acuity (left eye) and neovascular AMD (right eye), with 9 years' multimodal imaging before dying at 90 years of age.Methods: The left eye was preserved 6.25 hours after death and prepared for submicrometer epoxy resin sections and transmission electron microscopy aligned to clinical OCT B-scans. Inside and outside the MNV area, layer thicknesses, phenotypes, and vascular density of native choriocapillaris and neovessels were measured. Lengths of choriocapillaries and intervening gaps in the index eye and in early AMD eyes and healthy eyes with similar age (n ¼ 19 each) from the Project MACULA (Maculopathy Unveiled by Laminar Analysis) online histopathologic resource (http://projectmacula.cis.uab.edu/) were measured with custom software (Caps and Gaps).Main Outcome Measures: Descriptive features, vascular density, histologic and OCT layer thicknesses, and distribution of choriocapillaries and intervening gaps.Results: The SIRE correlated to a type 1 MNV that expanded slowly without evidence of exudation and with numerous choroidal vessels traversing Bruch's membrane defects, some visible on OCT. Tissue layers in and adjacent to the MNV area showed continuous RPE and characteristic AMD deposits. Capillary-like neovessels with fenestrations and caveolae resembling native choriocapillaris lined the retinal pigment epithelium (RPE) with a vascular density comparable with surrounding non-MNV areas. Relative to early AMD and healthy aged eyes, the index eye showed similar capillary lengths but larger gaps between vessels, indicating dropout. Outer nuclear layer thickness was preserved and showed less photoreceptor degeneration over areas of relative choriocapillaris health, including the type 1 MNV.Conclusions: Eyes with nonexudative type 1 MNV in AMD may progress to exudation, yet this stable MNV complex supported outer retinal structure for 9 years. Distinguishing features were numerous connecting vessels, high density of neovessels, continuous RPE, and slow growth. Maintaining beneficial type 1 MNV may be a therapeutic strategy. Ophthalmology 2020;127:931-947 ª 2020 by the American Academy of Ophthalmology Supplemental material available at www.aaojournal.org.Macular neovascularization (MNV), a major sight-threatening complication of age-related macular degeneration (AMD), occurs in 3 variants. 1 Type 1 MNV originates from the choroid and proliferates beneath the retinal pigment epithelium (RPE) and its basal lamina 2,3 (RPEþBL) and above the inner collagenous layer of Bruch's membrane (BrM). 4,5 When type 1 MNV extends anteriorly across the R...

Recognizing Atrophy and Mixed-Type Neovascularization in Age-Related Macular Degeneration Via Clinicopathologic Correlation

“…Types 1 and 2 MNV in this case both featured fibrovascular scar but differed in the location of vessels relative to RPE (near RPE for type 1, Fig. 5B) 9 and separated from it, for type 2). Type 1 and type 2 MNV are both choroid-originated and often occur together.…”

“…ChC density (proportion of BrM or RPE covered) in native ChC underneath MNV, ChC inside type 1 MNV, and native ChC underneath atrophy were assessed using a custom image J plugin. 9…”

Measuring the Contributions of Basal Laminar Deposit and Bruch's Membrane in Age-Related Macular Degeneration

“…This thinning is accompanied by breakthroughs of pre-NV buds to form type 1 MNV. 19,35,36 To definitively separate BLamD from BrM over a wide area, we studied many eyes with high-resolution and high-magnification tissue visualization techniques. Previous major surveys (> 100 eyes) of age-related macular pathology used light microscopy of paraffin embedded tissue supplemented by transmission electron microscopy of small tissue blocks.…”

“…imaging acquired before patient death, we investigate whether BLamD can be visualized with commercial OCT devices as a hyporeflective spitting of the RPE-BL-BrM complex, sometimes called the "double layer sign." Because 15% of eyes with early to intermediate AMD have nonexudative type 1 MNV, 19 distinguishing a double layer sign due to thick BLamD from MNV in vivo may ultimately assist management decisions. We confirm BLamD expansion as a major change to the RPE-BL-BrM complex in early AMD and the importance of thick BLamD as a risk factor for disease progression, especially in the central macula.…”

“…Descriptions of subretinal drusenoid deposits and nonexudative type 1 MNV in this eye have been reported. 19,31…”