Purpose: To further define the structural OCT features described as the “double-layer sign” suggestive of subclinical, nonexudative macular neovascularization (NE-MNV) in asymptomatic eyes with age-related macular degeneration (AMD). Design: Cross-sectional observational study. Participants: Participants with large drusen (>125 μm) secondary to AMD in at least 1 eye. Methods: Participants in a “discovery” cohort, with known NE-MNV identified on swept-source (SS) OCT angiography (OCTA) and the “double-layer sign” on structural spectral-domain OCT (SD-OCT) imaging, were used to identify characteristic features of this sign. These features were then assessed by masked grading in an “evaluation” cohort of AMD eyes with large drusen to determine the predictive values for NE-MNV. Main Outcome Measures: Description of OCT features associated with an increased risk of NE-MNV and their diagnostic and predictive performance. Results: The discovery cohort of 4 eyes revealed that in retinal pigment epithelium (RPE) elevations with a greatest transverse linear dimension of 1000 μm or more, an irregular RPE layer with a height of predominantly less than 100 μm, and a nonhomogenous internal reflectivity as characteristic features of the double-layer sign when NE-MNV was present. We term these collective features as a shallow, irregular RPE elevation (SIRE). Features on OCT images from 233 eyes in the evaluation cohort that were associated significantly with NE-MNV when the RPE elevation was more than 1000 μm in length were: height of the RPE elevation, overall flat or variable morphologic features, RPE layer irregularity, and nonhomogeneous reflectivity (all P ≥ 0.032). Twenty-four eyes (10.3%) were identified with a SIRE. On SS-OCTA imaging, 6 of the 233 eyes were found to have definite NE-MNV, and all 6 graded positively for SIRE (sensitivity, 100%). The absence of SIRE was identified in 209 of 227 eyes without NE-MNV (specificity, 92.1%). The positive predictive value for SIRE was 25% and the negative predictive value was 100%. Conclusions: Eyes whose OCT images display a SIRE sign are at higher risk of having subclinical NE-MNV. SIRE can be used as a screening tool on routine structural OCT imaging. More frequent follow-up and diligent home monitoring is recommended for those with SIRE.
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