Morphologic and Microvascular Differences Between Macular Neovascularization With and Without Subretinal Fibrosis

Abstract

Purpose: To evaluate morphologic and microvascular differences between eyes with and without subretinal fibrosis (SF) caused by neovascular age-related macular degeneration (nAMD).

Methods: Patients with nAMD with a minimum history of 12 months of anti-VEGF treatment were prospectively included in this cross-sectional study. Patients were imaged using standard imaging, swept-source optical coherence tomography angiography for quantitative microvascular analysis and polarization-sensitive OCT as an ancillary method for automated SF segmentation. The presence of reticular pseudodrusen, hyperreflective foci (HRF), and outer retinal tubulation (ORT) were also evaluated.

Results: Sixty eyes of 60 participants (37 female) with nAMD and a mean 3.1 (±2.7)-year history of anti-VEGF treatment were included, 20 (33%) of which were diagnosed with SF. Eyes with SF had a higher prevalence of ORT (P < 0.001) and a lower prevalence of HRF (P = 0.004) than eyes without SF. Fifty eyes were analyzed quantitatively for microvascular biomarkers. Eyes with SF had a larger greatest vascular caliber (P = 0.001) and greatest linear diameter (P = 0.042), a larger microvascular neovascularization (MNV) area (P = 0.026), larger vessel area (P = 0.037), higher number of vessel junctions (P = 0.025), longer total vessel length (P = 0.027), higher number of vessel endpoints (P = 0.007), and higher endpoint density (P = 0.047).

Conclusions: This multimodal imaging approach demonstrated in vivo microvascular and morphological differences in eyes with and without SF. Eyes with SF tend to have larger MNV lesions with thicker vessels and are often associated with the presence of ORT.

Translational relevance: This study points out imaging biomarkers in patients with SF, which may help identifying high-risk patients.

Figure 1.

Post processing steps for quantitative microvascular analysis using optical coherence tomography angiography. The initial choriocapillaris en face map (a) does not show a clear border between the MNV and the surrounding choriocapillaris network. An individualized slab was chosen for every MNV lesion (b) with the anterior border aligned with the anterior border of the MNV complex and the posterior border aligned with Bruch's membrane. After manual delineation (c) of the MNV complex and Angiotool analysis, the program displays the vessels (highlighted in red) and junctions (highlighted as blue dots) as an overlay (d).

Figure 2.

Right eye of a patient with type 2 MNV and subretinal fibrosis. Color fundus photography (a), polarization-sensitive optical coherence tomography (PS-OCT) en face intensity image with segmented subretinal fibrosis shown in blue (b), PS-OCT intensity B-scan with segmented retinal pigment epithelium in red (c), OCTA en face image showing the MNV complex (d) and OCTA B-scan with flow highlighted in red (e) are presented. The location of the en face images is highlighted by a white dotted square in (a) and the location of B-scans is highlighted by dotted white lines in (b) and (d). The yellow-whitish material in (a), clinically diagnosed as subretinal fibrosis, overlaps with the area of automatically segmented fibrosis in PS-OCT (b).

Figure 3.

Color fundus photographs (a,e), choriocapillaris en face OCTA slabs (b,f), manually delineated MNV complexes (c,g) and Angiotool analysis results (d, h) are displayed. The top row (a-d) shows a typical example of a MNV lesion without SF. The bottom row (e-h) shows a typical case of a MNV lesion with SF.