Intraretinal hyperreflective foci: Pathophysiology, imaging features, and clinical implications across retinal diseases

Intraretinal hyperreflective foci (IHRF) are a common but pathologically diverse optical coherence tomography (OCT) finding, increasingly recognized as a hallmark of retinal disease activity. IHRF have been described in age-related macular degeneration (AMD), where they may represent migrating retinal pigment epithelium cells, in diabetic retinopathy, retinal vein and artery occlusions, pachychoroid spectrum disorders, inherited retinal dystrophies, and ocular inflammatory diseases. Their appearance reflects a spectrum of underlying processes, including inflammatory cell recruitment, lipid or proteinaceous material deposition, and degenerative tissue remodeling. Advances in OCT technology and multimodal imaging have refined the characterization of IHRF, enabling correlations with histopathology, cytokine profiles, and genetic risk variants. Across diseases, their presence, number, distribution, and temporal evolution have been linked to structural progression, functional decline, and treatment response—serving as early indicators of atrophy or neovascularization in AMD, markers of inflammation and therapeutic responsiveness in vascular retinopathies, and predictors of recurrence or complication in pachychoroid disease. This review provides a comprehensive synthesis of the current literature on IHRF, summarizing their proposed histopathological correlates, multimodal imaging features, molecular associations, prognostic significance, and potential role as biomarkers in a wide range of retinal disorders.