A Phase I Randomized Trial of Topical Insulin for Glaucoma: Safety and Efficacy Outcomes.

Purpose: Insulin is neuroprotective in mouse and nonhuman primate models of glaucoma. Here we evaluate the safety and efficacy of topical insulin in human patients with glaucoma. Methods: This prospective study of once-daily topical insulin for glaucoma was conducted in 2 parts: an open-label dose escalation phase evaluating low (100 units/mL) and high doses (500 units/mL), followed by a randomized masked trial comparing low- and high-dose topical insulin. The worse-affected eye served as the study eye while the contralateral eye served as a control. The primary endpoint was safety and tolerability, monitored by recording adverse events (AEs), intraocular pressure, and serum blood glucose and potassium levels. The secondary endpoints included structural and functional testing including visual acuity, 24-2 Humphrey visual field (HVF), OCT, and macular and peripapillary flavoprotein fluorescence (FPF). Results: Safety and tolerability were favorable for topical insulin at both doses, with no serious AEs. The most frequent AE was transient stinging, resolving almost immediately after application to the study eyes. Blood glucose levels remained consistently stable before and after insulin administration for all groups. In group 3, 5 of 15 study eyes showed an increase of average retinal nerve fiber layer (RNFL) thickness by ≥5 μm, compared with 0 of 12 fellow eyes from baseline to the 1-month visit ( Conclusions: The application of topical insulin proved safe and well-tolerated among patients with glaucoma. Notably, 1 month of topical insulin led to a significant, reversible increase in RNFL thickness, indicating evidence for pharmacodynamic effect at the retina after topical delivery. These data support study initiation to evaluate topical insulin's neuroprotective or neuroenhancement effects. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.