Retinal Pigment Epithelial Detachment: Molecular Mechanisms, Multimodal Imaging Classification, and Clinical Management Across the Spectrum of Macular Disease

Pigment epithelial detachment (PED) represents a critical structural finding across the spectrum of chorioretinal diseases, occurring in 63-80% of eyes with neovascular age-related macular degeneration and frequently in central serous chorioretinopathy, polypoidal choroidal vasculopathy, and inflammatory conditions. This review provides a comprehensive analysis of current multimodal imaging techniques in the diagnosis and management of PEDs. We examine the role of various imaging modalities including optical coherence tomography (OCT), OCT angiography (OCTA), en face OCT, fluorescein angiography (FA), indocyanine green angiography (ICGA), infrared imaging (IR), and fundus autofluorescence (FAF) in evaluating PEDs. Each imaging modality provides unique insights: OCT reveals characteristic structural changes and quantitative biomarkers (height, volume, prechoroidal cleft); OCTA demonstrates type 1-4 MNV localisation; en face OCT visualises internal architecture; FA shows leakage patterns; ICGA identifies choroidal hyperpermeability; IR assists RPE evaluation; and FAF highlights dysfunction patterns. The integration of these imaging techniques has enhanced our understanding of PED pathophysiology-hydrostatic imbalance, RPE pump failure, Bruch's alterations-and improved classification into drusenoid, serous, fibrovascular, and haemorrhagic subtypes. This review particularly emphasises how advanced OCT/OCTA has advanced our knowledge of PED natural history, treatment response (anti-VEGF/PDT), and complications (RPE tears). We also discuss future directions in AI-driven classification and imaging biomarkers for personalised therapeutic approaches. The synergistic use of multimodal imaging represents a cornerstone in PED management, enabling precise diagnosis, risk stratification, and tailored treatment strategies.