PURPOSE: To assess the efficacy and safety of perfluorohexyloctane ophthalmic solution (NOV03; investigated under United States Investigational New Drug application; approved in the United States as MIEBO [perfluorohexyloctane ophthalmic solution]) once-daily, twice-daily, or 4 times daily compared with hypotonic saline solution (0.6%) for the treatment of dry eye disease (DED) associated with Meibomian gland dysfunction (MGD).

DESIGN: Multicenter, randomized, double-masked, saline-controlled phase 3 study.

PARTICIPANTS: Adults with a history of DED, total Meibomian gland dysfunction score of ≥3, tear film break-up time of ≤5 seconds, Schirmer test score of ≥5 mm, total corneal fluorescein staining (tCFS) score of ≥4 to ≤11 (National Eye Institute scale), and Ocular Surface Disease Index score of ≥25 in ≥1 eye (the same eye).

METHODS: Eligible participants were randomized 1:1 to perfluorohexyloctane or saline 4 times daily for 8 weeks.

MAIN OUTCOME MEASURES: Co-primary efficacy end points were change from baseline at day 57 in tCFS score and visual analog scale (VAS) eye dryness score.

RESULTS: A total of 597 participants were randomized; 303 to perfluorohexyloctane and 294 to saline. Perfluorohexyloctane demonstrated statistically significant improvements compared with saline in change from baseline at day 57 for tCFS score (least squares mean difference [LSMD], -0.97; 95% confidence interval [CI], -1.40 to -0.55; P < 0.001) and VAS eye dryness score (LSMD, -7.6; 95% CI, -11.8 to -3.4; P < 0.001). Statistically significant treatment effects were also observed for tCFS score and VAS eye dryness score at day 15. The most common ocular adverse events were blurred vision (3.0% in perfluorohexyloctane group; 1.0% in saline group) and eye redness (1.3%; 1.4%, respectively).

CONCLUSIONS: In adults with DED associated with MGD, perfluorohexyloctane demonstrated statistically significant and clinically meaningful improvements in signs and symptoms of DED compared with hypotonic saline at day 57, with a favorable safety and tolerability profile.