Topical Insulin Safe and Effective for Refractory PEDs

Topical insulin can be reasonably considered as an accessible option for refractory PEDs, particularly in clinical settings where other biological or regenerative therapies are unavailable, unaffordable or contraindicated. Photo: Alan Kwok, OD/BostonSight. Click image to enlarge. Corneal persistent epithelial defects (PEDs) are generally defined as defects that fail to show significant healing within two weeks despite standard supportive treatment. These represent severe conditions potentially associated with significant visual impairment; they may develop in the setting of different conditions, most commonly neurotrophic keratopathy and severe ocular surface diseases, such as dry eye disease. Increasing attention has been directed toward topical insulin as a potential regenerative treatment for refractory PEDs.Researchers in Italy recently evaluated the clinical outcomes of insulin eye drops in a retrospective real-world cohort of eyes with refractory PEDs, with particular emphasis on time to complete reepithelialization, longitudinal wound-healing dynamics, visual outcomes and recurrence rates. Complete reepithelialization was achieved in 44 of 45 eyes (97.8%) treated with topical insulin for refractory PEDs, with a median time to closure of 29 days.“The longitudinal analysis demonstrated a biphasic healing pattern, characterized by rapid early reduction of the epithelial defect followed by progressive deceleration over time. Reepithelialization was accompanied by a significant improvement in BCVA, while structural sequelae and recurrence rates remained very low,” the study authors wrote in their paper. “Treatment was uniformly well tolerated, and no treatment-related adverse events were recorded.”This retrospective study, which was published in Ophthalmology and Therapy, included 45 eyes from 43 consecutive patients (mean age 64.6 years) with refractory PEDs treated with topical insulin (1IU/mL) four times daily. The most common etiology was chronic ocular surface diseases (62.2%), followed by neurotrophic keratopathy (37.8%).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. Median BCVA improved from 2.0 to 1.0 logMAR at epithelial closure. 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.The researchers suggested that the proportion of eyes presenting with stromal scarring (26.7%) and corneal neovascularization (13.3%) at the last follow-up likely reflects the long-term sequelae of the chronic epithelial breakdown that preceded treatment, rather than complications of insulin therapy itself. No patient experienced treatment intolerance, ocular discomfort upon instillation or other adverse events directly attributable to the eye drops.Beyond clinical efficacy, topical insulin can offer practical advantages in real-world settings and may influence its positioning within the therapeutic algorithm of refractory PEDs.“Insulin is universally available as an inexpensive molecule, can be compounded by hospital pharmacies into stable ophthalmic formulations, and does not require donor-derived material, blood sampling or complex regulatory pathways for tissue procurement,” the researchers noted. “This translates into shorter time intervals between prescription and treatment initiation, improved continuity of supply and a markedly reduced economic burden on both patients and healthcare systems.”The study concluded that prospective, randomized, controlled studies will be necessary to definitively establish the role of topical insulin in the therapeutic algorithm of PEDs, including its dosing schedule, treatment duration and the potential indications for maintenance therapy.Click here for the journal source. Lixi F, Mancini A, Rossi C, et al. Topical insulin for corneal persistent epithelial defects: a multicenter retrospective study. Ophthalmol Ther. July 3, 2026. [Epub ahead of print]. This article was developed by the editorial staff in conjunction with experts in the field. In the process, AI may have been among the editorial tools used to meet the goals of human editors, who approved all content.