Dry eye disease beyond tear deficiency: inflammation, biomarkers, genetics and precision medicine

Dry eye disease (DED) is a prevalent multifactorial ocular surface disorder that is associated with instability of the tear film, hyperosmolarity, inflammation, and abnormality of the neurosensory epithelium. Previously thought of as a passive outcome of poor tear production, DED is now recognized as a complex and heterogenous disease involving multiple interacting pathophysiological mechanisms. Inflammation plays an important role in DED, with significant implications on visual performance and quality of life across the globe. Recent advances have improved our understanding of the molecular pathogenesis of DED. Tear hyperosmolarity triggers innate and adaptive immune responses that consist of proinflammatory cytokine release, activation of matrix metalloproteinases, inflammasome, and involvement of the ICAM-1/LFA-1 signaling pathway. These mechanisms lead to chronic inflammation and progression of disease of the ocular surface. Simultaneously, biomarker studies have identified tear cytokines, inflammatory mediators, and multi-marker panels as potential tools for disease diagnosis, patient stratification and treatment monitoring, although their clinical utility requires further validation. Recent studies on systems biology and multi-omics have highlighted the intricate interactions between genetic, molecular, and environmental factors, providing further insight into disease heterogeneity. The growing focus on mechanism-based treatment methods is aided by developments in targeted therapies, such as immunomodulators and new drug delivery systems. The future of DED management will potentially be based on the analysis of biomarkers, genomic data, and clinical phenotypes to support precision medicine. However, further clinical validation is needed to establish whether these approaches can improve individualized diagnosis, treatment selection, and long-term patient outcomes.