Changes in tear fluid composition in dry eye disease: a literature review

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Abstract
Background. The global prevalence of dry eye disease (DED) continues to rise. Alterations in the composition of the tear film are a key factor in the development of this condition. In recent years, a growing body of evidence has emerged on the underlying mechanisms of DED pathogenesis, driven by increasing interest in tear fluid as a material for clinical and diagnostic studies. Purpose: to outline the main research directions concerning tear biomarkers of DED, as well as their role in prognosis, development of novel treatment approaches, and monitoring therapeutic effectiveness. Materials and methods. A literature search was conducted in PubMed for articles published from 2000 to 2024. The selection was carried out using a comprehensive sampling method with the following keywords: tear, dry eye disease, Sjögren’s syndrome, biomarkers, cytokines, oxidative stress, enzymes, extracellular vesicles, microRNAs, NETosis. A total of 60 articles were included in the review. Results. Literature data on tear composition changes in DED indicate the presence of both general inflammatory alterations and disease-specific features. The review summarizes findings on tear content changes involving oxidative stress markers, apoptosis-related factors, proteases and their inhibitors, cytokines, lipids, and nucleic acids. Tear hyperosmolarity is a hallmark of DED, contributing to the enhancement of inflammation, recruitment of neutrophils into the tear film, and the formation of neutrophil extracellular traps (NETs). Elevated levels of inflammation markers such as matrix metalloproteinase-9, lactoferrin, myeloperoxidase, and elastase are indicative of disease severity. Differences in tear composition between Sjögren-related and non-Sjögren DED have diagnostic potential. Furthermore, tear microRNAs show promise as severity markers and differential diagnostic tools in DED. Conclusion. Available literature convincingly demonstrates that tear components can serve as biomarkers for diagnostic, prognostic, and therapeutic monitoring purposes in dry eye disease. The investigation of DED biomarkers paves the way for personalized approaches to the treatment of this condition.

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