Double layer sign in chorioretinal diseases: Clinical significance and implications from multimodal imaging.

The double-layer sign (DLS) is an emerging optical coherence tomography (OCT) biomarker of growing diagnostic and prognostic relevance in retinal and chorioretinal diseases, including age-related macular degeneration, pachychoroid spectrum disorders. Multimodal imaging, particularly OCT angiography (OCTA), has enhanced our ability to characterize DLS and its role in disease progression and treatment response. DLS is identified as a separation between the retinal pigment epithelium (RPE) and Bruch's membrane, with overlapping phenotypic presentations including flat irregular pigment epithelial detachment (FIPED) and shallow irregular retinal pigment epithelial elevation. These signs are often associated with vascularized lesions that demonstrate increased DLS thickness, irregular contours, and heterogeneous reflectivity. OCTA offers superior sensitivity and specificity for detecting subclinical macular neovascularization compared to dye-based angiography, which may underestimate nonexudative neovascularization. Additionally, indocyanine green angiography remains crucial for identifying branching vascular networks and polypoidal lesions, especially in polypoidal choroidal vasculopathy. In pachychoroid diseases, such as chronic central serous chorioretinopathy, the presence of FIPED/DLS can indicate underlying neovascularization, which may benefit from combination therapy with anti-vascular endothelial growth factor agents. We discuss the multimodal imaging characteristics, prognostic significance, and clinical relevance of DLS across various retinal and chorioretinal disorders.