Purpose: To comprehensively review the efficacy and safety of OC-01 varenicline nasal spray versus vehicle nasal spray (VNS) in the treatment in dry eye disease (DED). Methods: A systematic review that included full-length randomized controlled studies (RCTs), as well as post hoc analyses of RCTs reporting new findings on OC-01 VNS treatment in three databases, PubMed, Scopus and Web of Science, was performed according to the PRISMA statement. The search period included studies published between December 2021 and September 2023. The Cochrane risk of bias tool was used to analyze the quality of the studies selected. Results: A total of 8 studies were included in this systematic review. OC-01 VNS treatment achieved higher improvement than vehicle in all reported variables. The mean differences between both groups were in favor of OC-01 VNS treatment and were as follow: eye dryness score base on a visual analogue scale (EDS-VAS) of -7.5 +/- 2.2 points [-11.6 to -5.6], Schirmer test (ST) with anesthesia of 6.6 +/- 2.3 mm [4.9 to 11.8] and total corneal fluorescein staining (tCFS) of -1.2 +/- 0.01 points [-1.2 to -1.1]. Similar improvements were reported with OC-01 VNS 0.03 mg and 0.06 mg. Adverse events (AEs) were 15.5 +/- 19.4 % [-13 to 80.5] higher in the OC-01 VNS group with an overall adherence > 93 %. Conclusions: OC-01 VNS improves dry eye symptoms and signs with a satisfactory tolerability. Therefore, OC-01 VNS seems to be a safe and effective treatment that could be recommended in patients with DED. This new treatment could be particularly useful in those patients who have difficulties with the administration of traditional topical therapies.
