Advances in understanding and managing dry eye disease

PURPOSE: To present evidence from the literature and scientific meetings to support fundamental changes in concepts regarding the prevalence, pathogenesis, definition, diagnosis, management of dry eye disease (DED) and the prospects for the development of new, therapies. DESIGN: Analysis and clinical perspective of the literature and recent presentations. METHODS: Review and interpretation of literature. RESULTS: The tear film and ocular surface form an integrated physiologic unit linking the surface epithelia and secretory glands via a neural network. This sensory, driven network regulates secretory activity in quantity and composition, supporting the homeostasis of the system. The tear film forms a metastable covering be, tween blinks, subserving clear vision, and maintains the health and turnover of the ocular surface cells. Disturbance of intrinsic factors such as increasing age; hormonal balance; systemic or local autoimmune disease, or both; systemic drugs or extrinsic factors including topical medications; environmental stress; contact lens wear; or refractive surgery result in a final common pathway of events at the tear film and ocular surface, resulting in DED. Diagnosis of DED and the design of clinical trials for new drugs have been hampered by a lack of correlation between signs and symptoms and flawed endpoints; successful new drug applications likely will require new approaches, such as the use of objective biomarkers for disease severity. CONCLUSIONS: Recent advances in our knowledge of the causation of DED open opportunities for improving diagnosis and disease management and for developing new, more effective therapies to manage this widely prevalent and debilitating disease state.