Efficacy of Perfluorohexyloctane for the Treatment of Patients With Dry Eye Disease: A Meta-Analysis

Introduction: To systematically review the evidence from randomized controlled trials that evaluate the efficacy and safety of perfluorohexyloctane in the treatment of dry eye disease. Methods: Literature search was conducted on PubMed and Scopus in April 2024 with the search strategy ("perfluorohexyloctane" or "NOV03" or "semifluorinated alkane") and "dry eye". Extension and paired-eyes study were excluded. The risk of bias was assessed using the Cochrane Risk of Bias Tool. Forest plots and a summary of findings were prepared for total corneal fluorescein staining (tCFS), tear film break-up time (TFBUT), eye dryness score (EDS), and Ocular Surface Disease Index (OSDI). Results: The pooled standardized mean difference (SMD) for tCFS after 8 weeks of treatment was -0.53 (95% CI, -0.68 to -0.38; P<0.001), indicating a significant improvement in patients treated with perfluorohexyloctane. The between-study heterogeneity was moderately high (I2=52.0%). No significant differences in TFBUT were observed (SMD=0.05; 95% CI, -0.16 to 0.25; P=0.654). Regarding symptoms, patients treated with NOV03 had significantly lower EDS compared to controls (SMD=-0.49; 95% CI, -0.66 to -0.32; P<0.001), with moderately high heterogeneity (I2=71.1%). Conversely, the pooled SMD of OSDI was -0.13 (95% CI, -0.43 to 0.17; P=0.412), indicating no significant difference. Conclusion: Perfluorohexyloctane is an effective and safe alternative for the treatment of evaporative dry eye disease due to MGD that can significantly reduce tCFS and eye dryness symptoms. More well-designed non-sponsored randomized clinical trials are required to investigate the impact on other ocular surface parameters.