Treatment of Mixed Dry Eye Disease with Topical Azithromycin: A Prospective Controlled Pilot Study

Background: This study evaluated the efficacy of topical azithromycin ophthalmic solution (Azyter^®, 15 mg/g) as second-line treatment for mixed dry eye disease (DED), given the drug's known non-antimicrobial anti-inflammatory and immunomodulatory properties. Methods: In this pilot, prospective, controlled, non-randomized interventional study, fifteen patients with mixed DED refractory to first-line treatment received topical azithromycin for 30 days (twice daily for 3 days, then once daily for 27 days); ten healthy individuals served as controls. Clinical evaluation was performed before and after treatment in the study group and once in controls, and included the Dry Eye Questionnaire-5 (DEQ-5), Schirmer test, non-invasive tear break-up time (NITBUT, Sirius PLUS corneal topography), tear meniscus height (TMH; Sirius PLUS corneal topography), Efron scale grading of blepharitis, meibomian gland dysfunction (MGD), and conjunctival hyperemia; Oxford-scale grading of corneal fluorescein staining, and corneal epithelial thickness (swept-source anterior segment optical coherence tomography, AS-SS-OCT). Results: After treatment, DEQ-5 scores improved significantly (p < 0.001) and no longer differed from controls. Schirmer test and NITBUT values increased significantly (p = 0.003 and p = 0.027, respectively), becoming comparable to controls. Blepharitis, MGD, and corneal fluorescein staining scores also improved significantly (p < 0.001, p < 0.001, p = 0.002), as did maximum corneal epithelial thickness (p = 0.037). Conclusions: In this pilot cohort, second-line treatment of mixed DED with topical azithromycin significantly improved disease symptoms and signs, supporting its potential as a treatment option. Larger randomized studies are needed to confirm these findings and determine the optimal treatment regimen and duration.