The Efficacy and Safety of Varenicline Nasal Spray for the Management of Dry Eye Signs: A Systematic Review and Meta-analysis

Abstract

Background Dry eye disease (DED) is a disease caused by a reduced volume or deficient quality of tears and is treated mainly with tear supplementation. There is emerging evidence that nicotinic nasal sprays are effective for DED. Our systematic review and meta-analysis assessed the efficacy and safety of varenicline nasal spray (OC-01) for DED treatment utilizing the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. Methods Medline, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched. Only randomized controlled trials (RCTs) that evaluated the efficacy of OC-01 versus placebo were included. The mean change in the Schirmer test score from baseline on day 28 was the efficacy endpoint. Serious adverse events (SAEs), nonserious adverse events (NSAEs), and the rate of mortality were the safety endpoints. The standardized mean difference (SMD) was used for continuous outcomes, while the risk ratio (RR) was used to demonstrate dichotomous variables. Data pooling was performed using the inverse variance weighting technique. The certainty of evidence was rated using the GRADE approach. The risk of bias assessment was conducted using the Revised Cochrane risk of bias tool for randomized trials. Results Three RCTs (n = 1063) met the eligibility criteria. All RCTs had a low risk of bias. Meta-analysis found a statistically significant increase in the mean STS change from baseline on day 28 (SMD = 5.70, 95% CI 3.40 − 7.99 P < 0.00001, I2 = 99%). The pooled analysis found no significant difference between OC-01 and placebo in the frequency of SAEs (RR = 0.99, 95% CI 0.49–2.00, P = 0.98, I2 = 8%) or mortality (RR = 1.05, 95% CI 0.16–7.16, P = 0.96, I2 = 0%). However, OC-01 had a significant effect on developing NSAEs (RR = 1.88, 95% CI 1.51–2.34, P < 0.00001, I2 = 75%). Conclusion OC-01 had a highly significant increase in the efficacy endpoints but caused an increased frequency of NSAEs. OC-01 did not correlate with either SAEs or mortality. The RCTs included in our study had a low risk of bias assessment. Nevertheless, they were downgraded in multiple domains upon GRADE assessment.