Efficacy and safety of topical macrolides versus systemic tetracyclines for meibomian gland dysfunction–a systematic review and meta‐analysis

PURPOSE: To review the efficacy and safety of oral doxycycline antibiotics versus topical macrolides in the treatment of meibomian gland dysfunction (MGD). DESIGN: Systematic review and meta-analysis. METHODS: A comprehensive search of PubMed, Scopus, Embase, and ClinicalTrials.gov through December 2024 identified randomised controlled trials (RCTs) comparing oral tetracyclines with topical macrolides for MGD. Eligible studies reported outcomes related to tear film stability, meibomian gland function, ocular surface health, or symptom severity. Data extraction followed PRISMA guidelines and risk of bias was assessed using Cochrane methods. RESULTS: Among 3699 publications (1964-2024), six RCTs from distinct locations (374 patients) met inclusion criteria, describing only topical azithromycin and oral doxycycline. Treatment regimens were comparable: one month of topical azithromycin (1-1.5%, once to four times daily) versus three to 8 weeks of oral doxycycline (100-200 mg daily). Both treatments significantly improved MGD signs and symptoms. In pooled analyses, topical azithromycin showed superiority in reducing tear debris (odds ratio OR, 0.33; 95% confidence interval CI, 0.15-0.74); however, while the total symptoms score favoured azithromycin, the result was borderline (OR, 0.62; 95% CI, 0.38-1.00) and sensitivity-dependent. Subgroup analysis showed doxycycline was superior for corneal fluorescein staining (standardised mean difference SMD, 0.64; 95% CI, 0.22-1.05), whereas 1% azithromycin was superior for tear breakup time (mean difference MD, -1.40; 95% CI, -2.20 to -0.60) and dropout-causing adverse events (risk ratio RR, 0.07; 95% CI, 0.01-0.49). CONCLUSIONS: Both topical azithromycin and oral doxycycline are effective for MGD management. Topical azithromycin demonstrated a more favourable safety profile and may represent a useful therapeutic option, particularly for patients with low tolerance to systemic medications. However, further high-quality studies are needed to strengthen the evidence base.