Tear cytokines and their relevance as biomarkers in ocular surface inflammatory diseases

Abstract Ocular surface disorders (OSDs) are complex, multifactorial diseases, often coexisting and with overlapping symptoms leading to discomfort and visual compromise. OSD is driven by chronic inflammation and its pathogenesis involves multiple ocular surface structures such as the cornea, conjunctiva, lacrimal glands, and meibomian glands. Diagnosing and monitoring disease progression based on clinical features is crucial for effective treatment implementation. However, achieving a differential diagnosis solely through clinical features can be challenging. The evaluation of biomarkers can facilitate disease diagnosis, aid in classification, and offer insights into disease progression and treatment effectiveness. There remains an unmet clinical need for biological tools to manage ocular surface diseases (OSDs). Tear fluid serves as a readily accessible source of biological material that has undergone extensive analysis in the quest for biomarkers related to OSD. Numerous studies have contributed to the extensive catalog of biomarkers found in tear fluid for OSD. The objective of this review is to provide a comprehensive and up-to-date overview of the most pertinent biomarkers for various OSDs, with a specific focus on quantitative analyses and their correlations with clinical parameters. To achieve this objective, we conducted a review of the PubMed database from January 2013 to June 2023, including original articles that investigated tear cytokines in various OSD pathologies. These studies unveiled a dysregulated interplay of pro- and anti-inflammatory cytokines within these disease pathologies. Pro-inflammatory interleukins (IL-1β, IL-2, IL-8, and IL-17), tumor necrotic factor (TNF-α), interferon-gamma (IFN-γ), as well as IL-4, IL-5, and IL-13 (Th2 pathway), and chemokines such as CCL5, IP-10 (CXCL10), and CX3CL, appear to represent similar inflammatory mechanisms in OSD pathologies. The cytokines identified through tear fluid analysis can aid in categorizing the disease as either pro-inflammatory or pro-fibrotic based on its severity, or they may serve as potential targets for intervention. This, in turn, can facilitate the planning of appropriate management strategies. The integration of biomarker testing into clinical settings holds the potential to advance personalized medicine and represents the next significant step in managing OSD.