Deconstructing White Dot Syndromes - Multimodal Imaging in Uveitis (MUV) Taskforce: Report 11

PURPOSE: The term white dot syndromes (WDS) has historically grouped multiple non-infectious posterior uveitis (NIPU) entities based on a similar funduscopic appearance of "white dots." Despite decades of use, the clinical relevance of this umbrella terminology has been questioned. This perspective critically examines whether WDS remains a valid conceptual and diagnostic construct in the era of advanced retinal and choroidal imaging. DESIGN: Perspective review. METHODS: Critical interpretation of the available literature on imaging and current pathophysiological evidence, combined with observations collected using cutting edge imaging technology (structural high-resolution OCT, OCT angiography, and indocyanine green ICG angiographyICGA) for six of the NIPU classically considered as WDS: multiple evanescent white dot syndrome (MEWDS), multifocal choroiditis with panuveitis(MFCPU), punctate inner choroiditis (PIC), acute posterior multifocal placoid pigment epitheliopathy (APMPPE), serpiginous choroiditis (SC), and birdshot chorioretinitis (BSCR). RESULTS: Although these diseases share some overlapping clinical features, multimodal imaging reveals profound differences, with each entity having distinct anatomic features on multimodal imaging. OCT and OCTA demonstrate distinct patterns of tissue involvement-from photoreceptor/RPE injury in MEWDS, to Bruch's membrane disruption in MFCPU and PIC, to profound choriocapillaris ischemia in APMPPE and SC, and deep stromal choroidal infiltration in BSCR. ICGA further differentiates these entities by choroidal perfusion characteristics, distinguishing true vascular non-perfusion from other inflammatory reactions leading to tissue damage. Imaging-based hypotheses of immunopathogenesis suggest that these entities may arise from different immunopathogenic pathways-transient outer retinal inflammation (MEWDS), possible antigenic exposure from structural disruptions (MFCPU/PIC), primary inflammatory inner choroidal vascular occlusive process (APMPPE), a possible autoimmune or autoinflammatory choroidal ischemic mechanism (SC), and a likely HLA-A29-associated autoimmune response affecting the inner retina and choroid (BSCR) CONCLUSIONS: The label white dot syndromes, originally based on appearance alone, does not take into consideration major biological and prognostic differences among these NIPU. Current imaging-guided hypotheses of Immunopathogenesis suggest that these conditions should no longer be grouped under a single classification. A paradigm shift toward disease-specific terminology is warranted to improve diagnostic precision, guide management, and reflect presumed pathophysiological diversity.