Short-term Efficacy and Safety of Biological Tear Substitutes and Topical Secretagogues for Dry Eye Disease: A Systematic Review and Network Meta-analysis.

PURPOSE:The purpose of this study was to assess short-term efficacy and safety of tear promotion eye drops (biological tear substitutes and topical secretagogues) for treating dry eye disease. METHODS:Randomized controlled trials comparing short-term effects of biological tear substitutes or topical secretagogues versus placebo or other topical dry eye treatments in adults with dry eye disease were identified from the MEDLINE, Embase, Scopus, ClinicalTrials.gov , and World Health Organization International Clinical Trials Registry Platform databases. Pairwise meta-analysis and network meta-analysis were performed. Outcomes were ocular symptoms, ocular surface staining, tear break-up time, Schirmer test, and adverse events. The certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations approach. RESULTS:Thirty-nine randomized controlled trials (3693 patients) were eligible. Using artificial tears as a reference, autologous platelet lysate was the most effective treatment for lowering ocular surface disease index (unstandardized mean difference [USMD] -31.85; 95% confidence interval [CI]: -43.19 to -20.51) and platelet rich plasma showed the most reduction in corneal fluorescein staining scores (standardized mean difference -2.52; 95% CI: -3.23 to -1.82). Cord blood serum was the most effective treatment for increasing tear break-up time (USMD 2.67; 95% CI: 0.53-4.82), and eledoisin was superior to others in improving Schirmer scores (USMD 2.28; 95% CI: 0.14-4.42). Most interventions did not significantly increase ocular adverse events compared with artificial tears. CONCLUSIONS:Biological tear substitutes, including autologous serum, autologous platelet lysate, platelet rich plasma, and cord blood serum, might be the most effective treatment among tear promotion eye drops in relieving dry eye symptoms without increasing adverse events. However, there remains uncertainty around these findings because of low/very low certainty of evidence.