Efficacy and safety of topical macrolides versus systemic tetracyclines for meibomian gland dysfunction-a systematic review and meta-analysis
In brief
Topical azithromycin cuts tear debris risk by two thirds versus oral doxycycline
In six randomized trials involving 374 patients, eye drops of azithromycin reduced the presence of tear debris to about one-third of that seen with oral doxycycline. The drops also lowered symptom scores modestly and caused far fewer drop-out-forcing side effects, though doxycycline was better for corneal staining. The findings support azithromycin as a safer first-line option, but larger trials are still needed.
- Journal
- Acta ophthalmologica (Q1)
- Published
- 17 July 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Margarita Safir, Clara C Chan, Joshua C Teichman, Itamar Arbel, Ruth Lapid-Gortzak, Camiel J F Boon, et al.
- PMID
- 42464955
- DOI
- 10.1111/aos.70196
Why clinicians should know about it
- Picked for Family Practice (top studies of the week, 19 July 2026).
- Picked for Ophthalmology (top studies of the week, 19 July 2026): Topical macrolides vs systemic tetracyclines for meibomian gland dysfunction
Abstract
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.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.