Effectiveness of Intranasal Tear Neurostimulation for Treatment of Dry Eye Disease: A Meta-Analysis

INTRODUCTION: To assess the effectiveness and safety of intranasal tear neurostimulation in the treatment of dry eye disease. METHODS: We performed a meta-analysis of four databases from their inception to October 2022 without language restrictions. Randomized controlled trials and non-randomized controlled trials meeting the inclusion criteria were included in this review and were quality appraised. The risk of bias was evaluated by two independent reviewers using the Cochrane Collaboration Tool and Methodological Index for Non-Randomized Studies. The random-effect model or fixed-effect model was adopted to estimate the pooled effect sizes. RESULTS: Fifteen published studies consisting of 17 clinical trials with a total of 901 patients were analyzed. Schirmer II test scores were significantly higher after intranasal tear neurostimulation in patients with dry eye disease (mean difference = 14.12 mm, 95% confidence intervals (8.93, 19.31), P < 0.001). Intranasal tear neurostimulation increased the meibomian gland areas (mean difference = − 251.79 μm(2), 95% confidence intervals (− 348.34, − 155.23), P < 0.001), but no significant difference was found in meibomian gland perimeters before and after stimulation (mean difference = 3.72 mm, 95% confidence intervals (− 22.14, 29.59), P = 0.78). All adverse events were mild or moderate, and no serious adverse events were reported. CONCLUSIONS: This meta-analysis provides promising evidence for the controversial effectiveness of intranasal tear neurostimulation in the treatment of dry eye disease, along with useful information for guiding intranasal tear neurostimulation in future clinical trials. TRIAL REGISTRATION: This meta-analysis was registered on the Prospective Register of Systematic Reviews (PROSPERO) (CRD42021284214). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40123-022-00616-6.