Real-world effectiveness of topical insulin for neurotrophic keratopathy: retrospective case series of 29 eyes

OBJECTIVE: To evaluate the real-world effectiveness and safety of topical insulin (25 IU/mL) in patients with neurotrophic keratopathy (NK) across multiple etiologies. METHODS: We retrospectively reviewed 29 consecutive eyes of 28 patients with neurotrophic keratopathy treated with topical insulin at a single center. The primary outcome was complete epithelial healing for stages 2 and 3 NK; for stage 1, success was prespecified as improvement in corneal staining and epithelial integrity. Statistical analysis included survival analysis and multivariable logistic regression with Firth penalization. RESULTS: Twenty-nine eyes with a mean follow-up of 32.7 weeks were included. Most common etiologies were infectious (51.7%), including herpes simplex virus (24.1%) and varicella zoster virus (20.7%). Twenty-three eyes had stages 2 or 3 NK. Among eyes with stages 2 and 3 NK, complete epithelial healing occurred in 18/23 (78.3%, 95%; CI: 58.1-90.3%), with a median healing time of 33.5 days (IQR: 15.8-81.8). The cumulative healing rate at 8 weeks was 43.5%. Healing success was not significantly associated with defect size or etiology. Among 8 patients who discontinued insulin after healing, recurrence occurred in 1 case (12.5%) and resolved upon treatment resumption. One patient developed mild punctate keratopathy that resolved with continued therapy. CONCLUSIONS: Topical insulin demonstrated substantial healing efficacy for neurotrophic keratopathy across diverse etiologies, with a favourable safety profile and low recurrence rate. Although healing may be slower than FDA-approved alternatives, the dramatic cost difference suggests insulin may be a cost-effective first-line therapy for refractory cases. This represents one of the largest multietiological case series of insulin therapy for neurotrophic keratopathy reported to date.