TFOS DEWS III: Digest.

This digest summarizes the interdisciplinary research in dry eye disease (DED) published since the 2017 TFOS DEWS II reports. It comprises 7 topics including Sex, Gender, and Hormones; Epidemiology; Pathophysiology; Tear Film; Pain and Sensation; Iatrogenic Dry Eye; and Clinical Trial Design and explores how each of these inform diagnostic methodology, disease subtype, and management of DED. Sex- and gender-related differences significantly influence the ocular surface due to hormones, sex chromosomes, sex-specific autosomal factors, epigenetics, care-seeking behaviors, and service use. Epidemiologic data reveal that DED prevalence varies by age and sex, influenced by diagnostic criteria and the multifactorial nature of the disease. New risk factors for DED include environmental, iatrogenicity, systemic diseases, and lifestyle domains. Pathophysiological distinctions between aqueous deficient and more evaporative forms of DED have been clarified, with the latter most commonly characterized by a muted inflammatory response at the ocular surface, meibomian gland dysfunction, and conceivably phenotypic changes in corneal epithelial cells. There is an expanding role for metabolic, hormonal, physical, neural and cellular stresses, including hyperosmolarity, mitochondrial stress, and neurogenic inflammation. Advancements in tear film research recommend new approaches to understanding DED pathogenesis and identifying biomarkers, such as microRNAs. Ocular pain perception is linked to structural integrity of corneal nerves, functional capacities of neurons, and activity of the central and peripheral nervous systems. Iatrogenic DED can result from medications, contact lenses, and surgical procedures. Clinical trials now emphasize aligning design and end points with DED subtypes and therapeutic mechanisms, with new therapeutics and trial designs under consideration.