Evaluating the efficacy of topical tea tree oil versus preservative-free azithromycin in the treatment of dry eye disease associated with meibomian gland dysfunction: A randomized controlled trial focusing on tear interleukin levels.

PURPOSE: Meibomian gland dysfunction (MGD) is a leading cause of dry eye disease (DED) and is associated with ocular surface inflammation characterized by elevated tear cytokines. METHODS: In this single-masked, randomized, parallel-group clinical trial, 50 adults with meibomian gland dysfunction (MGD)-associated dry eye disease were randomized (1:1) to receive topical tea tree oil (TTO) gel or preservative-free azithromycin 1% eye drops for 4 weeks, in addition to preservative-free lubricants. Six participants were lost to follow-up, leaving 44 participants who completed the 4-week assessment. Clinical outcomes included tear break-up time (TBUT), Schirmer I test, Ocular Surface Disease Index (OSDI), Dry Eye-Related Quality of Life Score (DEQS), meibomian gland dysfunction grading, and tear interleukin-8 (IL-8) and interleukin-17 (IL-17) concentrations measured at baseline and week 4. Between-group post-treatment comparisons were adjusted for baseline values using analysis of covariance. RESULTS: Both groups demonstrated significant post-treatment improvement in all clinical parameters (P < 0.001). The TTO group exhibited greater improvement in DEQS (median 10 vs 35; P < 0.001), TBUT (median 11 vs 8 s; P < 0.001), Schirmer I test (mean 14 ± 2 vs 9 ± 2 mm; P < 0.001), and achievement of MGD Grade 0 (63.6% vs 9.1%; P < 0.001). Post-treatment IL-17 concentrations were significantly lower in the TTO group (mean 27 ± 1 vs 44 ± 1 pg/mL; P < 0.001), whereas IL-8 reduction was more pronounced in the azithromycin group. Multivariable regression identified TTO treatment as an independent predictor of greater clinical improvement and IL-17 reduction. CONCLUSIONS: Tea tree oil was associated with greater short-term improvement in clinical outcomes than preservative-free azithromycin in patients with MGD-associated dry eye disease, particularly regarding tear film stability, meibomian gland function, and reduction of IL-17 concentrations. CLINICAL TRIALS REGISTRATION: The trial was registered at ClinicalTrials.gov (Identifier: NCT06921525).