Double-layer sign in neovascular age-related macular degeneration - do we treat?

Abstract

Neovascular age-related macular degeneration (nAMD) is managed medically with intravitreal anti-angiogenic therapy and monitored with optical coherence tomography (OCT) to detect exudation in retinal layers. One OCT feature suggesting early-stage macular neovascularization of choroidal origin (type 1 MNV) is two hyperreflective bands separated by a narrow hyporeflective band, called ‘double-layer sign’ (DLS). We report a clinicopathologic correlation of DLS. Comprehensive ophthalmologic examination and multimodal imaging were performed during a 9-year follow-up in the pseudophakic right eye of a woman presenting at age of 79 years with inactive subretinal fibrosis due to AMD and best-corrected visual acuity (BCVA) of 20/50. Two years later (7 years before death), BCVA was 20/200. Near-infrared reflectance (Figure 1A, left) with corresponding OCT B-scan through the fovea and optic nerve head (Figure 1A, right) shows a DLS nasal to a central fibrovascular scar (pink, orange and turquoise arrowheads) along with outer retinal tubulation (ORT, white arrowhead). These structures appear in a registered histologic section (Figure 1B). In the magnified OCT (Figure 1C), the upper hyperreflective band of the DLS (yellow arrowheads) corresponds to the RPE-basal lamina (RPE-BL) complex and is irregularly thickened. The lower hyperreflective band corresponds to Bruch’s membrane (BrM). Histology shows that the hyporeflective line separating these bands to create the DLS may correspond to type 1 MNV beneath basal laminar deposit (BLamD), a thickened extracellular matrix material (Figure D1; D2; E1 fuchsia asterisk, E2) or just thick BLamD without type 1 MNV (Figure 1D3, 1E2). With a 7-year interval between OCT and histology, BLamD was likely thinner at the time of imaging; however, a DLS was already visible at that early time-point. Our clinicopathologic correlation reinforces that while minimizing retinal exudation is critical to preserving photoreceptors, a DLS on OCT can indicate BLamD without type 1 MNV, which would not benefit from anti-angiogenic therapy.