Abstract Purpose: Through this systematic review, we evaluated the therapeutic potential of topical eye insulin in different concentrations to treat several surface ocular pathologies, including: persistent epithelial defects, diabetic keratopathy after a vitrectomy, neutrophic keratopathy and dry eye syndrome. We have consolidated through the data, what are the doses used, the methods of preparation for insulin, whether there are adverse effects and what would be the effectiveness of the eye drops with insulin. Methods: We carried out an extensive search including Pubmed, Cochrane Library, Scopus and Web Of Science. We found 43 relevant studies, after which we excluded duplicates, animal studies, case reports, we ended up with 14 studies to include in the article. Through the Newcastle-Ottawa scale for observational studies and the Jadad scale for randomized controlled trials, we investigated the methodological quality of these articles. Results: Within the review we included a significant number of 525 patients who used eye drops with insulin in concentrations from 0.5 to 2 U/ml, having an ocular benefit in corneal healing rates without adverse effects. The quality analysis of the included studies showed a NOS score of moderate-high quality, whereas the Jadad scale showed a high quality. Conclusions: Our systematic review demonstrates that patients with persistent epithelial defects, diabetic keratopathy following vitrectomy, neurotrophic keratopathy, and dry eye syndrome showed significant improvements in corneal healing rates. To gain a clearer understanding of the effectiveness of insulin eye drops, future research should include direct comparisons with autologous serum eye drops and amniotic membrane eye drops. These studies will help establish comprehensive clinical guidelines.

The authors have declared no competing interest.

This work described in this literature review was supported by the 5x1000 funds to Fondazione Banca degli Occhi del Veneto from the Italian Ministry of Health and the Italian Ministry of University & Research.

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