Topical Insulin for Corneal Persistent Epithelial Defects: A Multicenter Retrospective Study

INTRODUCTION: The purpose of this study was to evaluate the clinical outcomes of insulin eye drops in a real-world cohort of eyes affected by corneal persistent epithelial defects (PEDs) refractory to conventional therapy. METHODS: This retrospective study included consecutive patients with refractory PEDs treated with topical insulin (1 IU/mL) four times daily. Clinical end points were: time to complete reepithelialization, cumulative probability of closure, longitudinal changes in defect area, postclosure complications, recurrence, and changes in best-corrected visual acuity (BCVA). RESULTS: A total of 45 eyes from 43 patients (mean age 64.6 ± 15.6 years) were included. The most common etiology was chronic ocular surface diseases (62.2%) followed by neurotrophic keratopathy (37.8%). Complete epithelial closure was achieved in 44 of 45 eyes (97.8%), with a median time to closure of 29 days (95%CI 24-38). The cumulative probability of complete reepithelialization was 20.0% at 14 days, 53.3% at 30 days, 90.5% at 60 days, and 95.3% at 90 days. A biphasic healing pattern was observed, with marked early reduction of the defect area progressively slowing over time (p < 0.001). Median BCVA improved from 2.0 to 1.0 logMAR at epithelial closure (p < 0.001). Two eyes (4.4%) experienced PED recurrence: one case regressed after first-line treatment while the other case progressed to corneal melting and ultimately required Gundersen flap surgery. No treatment-related adverse events were recorded. CONCLUSIONS: Topical insulin may represent a safe, effective, and accessible therapeutic option for refractory PEDs, achieving high rates of complete reepithelialization with concomitant visual improvement and low short-term recurrence in a heterogeneous real-world cohort.