Corneal wounds may be helped in the future by topical insulin eyedrops if further research supports this intervention.

Corneal wounds may be helped in the future by topical insulin eye drops if further research supports this intervention. Photo: Daniel Grangaard, ODClick image to enlarge.

In two posters presented at ARVO 2024 in Seattle on Sunday, a new possible treatment was investigated for corneal wounds. The first was a retrospective review of patients with neurotrophic keratitis resistant to conventional treatment, while the second study, which was also retrospective in design, dealt with neurotrophic corneal ulcers.

In the first study, patients were classified into two groups: Group I received topical insulin therapy with 4 units per mL of concentration and Group II received conventional treatment.1 Of the 52 patients included in this cohort (52 eyes), 27 eyes were designated to Group I and 25 to Group II. Age range in Group I was from 55 to 68 years old and in Group II was 55 to 69 years old.

Mean time between diagnosis and start of treatment was longer in Group I than Group II and no differences were seen in baseline characteristics between the two groups. Re-epithelialization was achieved in 74% of Group I (20 eyes) and 64% in Group II (16 eyes). Mean time to re-epithelialization was also shorter in Group I than Group II, with rates of 32.3 days and 82.5 days, respectively. Final defect area was smaller in the insulin group as well, but no significant differences were seen between groups in visual acuity. There were also no observed differences in recurrences, complications and subsequent surgical interventions.

Based on these results, the study authors suggest that “the use of topical insulin was effective in accelerating epithelial defect closure in patients with refractory neurotrophic keratitis when compared to conventional treatment and may be highly advantageous due to its affordability and accessibility; however, it is not free of complications and recurrences.”1

Hopefully, they reason, “the use of insulin aims to support nerve regeneration and enhance the overall repair process in the affected eye. This approach holds potential for improving the outcomes and management of neurotrophic keratitis, offering a new avenue for treating this challenging eye condition.”1

Similarly, the second study presented also used insulin drops for treatment of refractory neurotrophic corneal ulcers in vivo and investigated cellular mechanisms underlying re-epithelialization of corneal epithelial wounds in vitro. Included were 20 eyes of 20 patients treated with topical insulin eye drops for neurotrophic corneal ulcers; corneal epithelial wound closure was monitored daily. As well, human primary limbal epithelial cells were incubated in serum-free medium either with or without different insulin concentrations, ranging from 0.05µg/mL to 150µg/mL, for 24 hours.

The researchers observed that all 20 eyes achieved complete corneal re-epithelialization after insulin standard treatment regimens (25U/mL or 0.5U/drop). However, outcomes were not enhanced by higher doses, instead appearing to induce corneal angiogenesis. After analysis, it was found that a significant dose-dependent effect of insulin on epithelial migration was most effective with lower doses (0.5µg/mL to 1.0µg/mL). Upregulation of genes FSCN2 and TSPAN1 was found, both of which are involved in cell migration. Conversely, downregulation was seen with cell adhesion molecules, including integrin subunits, after exposure to 1.0µg/mL to 5.0µg/mL of insulin. Even greater insulin doses (50µg/mL to 100µg/mL) induced a 2.5-fold upregulation of vascular endothelial growth factor A.

 It should be noted that in both of these studies, topical insulin treatment is not yet available, but both display the possible benefits and prospects for future use. The authors of the second study echo this sentiment, stating that “these findings may have important implications in treating neurotrophic keratopathy and epithelial wound healing defects.”2

Original abstract content @2024 Association for Research in Vision and Ophthalmology.

1. Graue-Hernandez EO, Anaya-Barragan F, Vera-Duarte GR, et al. Topical insulin for persistent corneal epithelial defects in neurotrophic keratopathy. ARVO 2024 annual meeting.

2. Zeisberg VEB, Zenkel M, Gießl A, et al. Insulin for treatment of neurotrophic ulcers: clinical evidence and potential mechanism. ARVO 2024 annual meeting.