Tear Proteomics and Insights into Lacrimal Drainage Disorders: Lacriome Paper 8

To synthesize and evaluate current evidence from tear proteomic and cytokine profiling studies in lacrimal drainage disorders, with a primary focus on primary acquired nasolacrimal duct obstruction. This review aims to identify diagnostic biomarkers, elucidate underlying immunopathogenic mechanisms, and explore translational opportunities to improve clinical management and surgical outcomes.

Fifteen peer-reviewed studies were systematically reviewed, encompassing proteomic, immunoassay, and cytokine analyses of tear fluid from adult and pediatric patients with nasolacrimal duct obstruction. Included investigations comprised pre- and post-surgical cohorts, subgroup analyses by age, sex, and systemic disease status, and multiple analytical platforms such as mass spectrometry, ELISA, and multiplex bead-based assays. Studies were evaluated for methodological rigor, reproducibility, and clinical applicability.

Across the included studies, a consistent upregulation of inflammatory cytokines-particularly IL-6, IL-8, TNF-α, IFN-γ, and VEGF-A-was observed in primary acquired nasolacrimal duct obstruction patients compared to controls. Proteomic alterations involving antimicrobial, stress-response, and epithelial repair proteins (e.g. S100A8/A9, prolactin-inducible protein, lipocalin-1) were recurrently reported. Distinct cytokine patterns were noted in pediatric and diabetic subgroups, while diurnal variation influenced cytokine expression in control eyes. Post-dacryocystorhinostomy cohorts demonstrated partial normalization of IL-1β and IL-6 levels, correlating with improved tear osmolarity, meniscus dynamics, and patient-reported outcomes. Proteomic findings further implicated systemic inflammation, hormonal modulation, and mucosal barrier dysfunction in primary acquired nasolacrimal duct obstruction pathogenesis.

Tear proteomics has revealed a reproducible inflammatory and immune signature in lacrimal drainage disorders, positioning tear fluid as a valuable, noninvasive biospecimen for diagnosis, monitoring, and precision-based management. Emerging biomarker panels hold potential to stratify disease severity, predict surgical success, and guide individualized therapy. Future work should prioritize multicenter validation, standardized sampling protocols, and integration with advanced analytical and AI-driven diagnostic platforms.