Efficacy and Safety of Topical Insulin Eye Drops for Corneal Epithelial Defects: A Systematic Review, Meta-Analysis, and Grading of Recommendations Assessment, Development, and Evaluation Assessment

Objectives: The aim of this study was to review and meta-analyze the efficacy and safety of topical insulin eye drops (TIED) in treating corneal epithelial defects (CED).
Methods: We registered the protocol in PROSPERO (CRD420251051879). A systematic literature search on PubMed, Cochrane, ScienceDirect, Scopus, and Google Scholar until May 2025 was done to identify controlled comparative studies. Outcomes of interest include time to complete re-epithelialization, re-epithelialization rate, treatment failure, recurrence, and adverse events. We performed meta-analysis using a random-effects model and assessed the certainty of evidence for each result using Grading of Recommendations Assessment, Development, and Evaluation (GRADE) assessment. Results: Seven studies involving 238 patients were included in the analysis. TIED significantly shortened re-epithelialization time (mean difference [MD] –1.20 days [−1.71–−0.69], p<0.0001) and accelerated the healing rate (MD +0.26 mm2/h [0.10–0.42], p=0.002). In addition, TIED significantly reduced the risk of treatment failure (risk ratio [RR] 0.30 [0.16–0.57], p=0.003) and recurrence (RR 0.25 [0.11–0.56], p=0.0007) compared to conventional treatments, with no adverse events reported. GRADE assessments indicated very low to low certainty of evidence.
Conclusion: TIED may speed corneal healing, cut failures and recurrences, and is well-tolerated and inexpensive. Robust randomized controlled trials are still needed to nail down the optimal dosing, long-term safety, and its role in CED management.

Keywords: Corneal epithelial defect, Corneal wound healing, Ocular surface disease, Topical insulin