The Immunobiology of Dry Eye Disease: A Review of the Pathogenesis, Regulation and Therapeutic Implications

Abstract

Dry eye disease (DED) is increasingly recognized as a condition driven by immune dysregulation at the ocular surface (OS). Chronic inflammation, mediated by aberrant activation of both innate and adaptive immune pathways, underlies disease progression and symptom persistence. Neuroimmune interactions further amplify OS inflammation, contributing to epithelial damage and impaired homeostatic regulation. This review summarizes current literature on the immunopathogenesis of DED, highlighting the complex interplay of molecular mechanisms of innate and adaptive immune activation, neuroimmune-mediated inflammation, and emerging molecular and cellular biomarkers. In addition, we examine existing and emerging therapeutic strategies that target these immune-molecular pathways, including precision immunomodulatory approaches, to inform future management of DED. By integrating mechanistic insights with clinical findings, this review aims to provide a comprehensive overview of the molecular mechanisms underlying the dysregulated immune response associated with DED.