Abstract
Purpose :
To assess the safety and efficacy of topical insulin on neuroprotection and neuroenhancement in glaucoma.
Methods :
The study, approved by the institutional review board at Stanford University School of Medicine and listed on Clinicaltrials.gov (NCT#05206877), enrolled glaucoma patients after obtaining informed consent. One eye per patient with the worse glaucomatous damage on Humphrey visual field (HVF) testing was determined to be the study eye. Group 1 and 2 participants (n=5 for each group) received 1 drop of sterile human recombinant insulin (Humulin R, Eli Lilly) at 100 units/ml (4 units per drop, group 1) or 500 units/ml (20 units per drop; Group 2) daily for five days in clinic. Blood glucose levels were measured in Groups 1-2 prior to each instillation and 2 hours after instillation. Group 3 participants (n=20) were randomly assigned (1:1) to either dose to self-administer one drop daily for 28 consecutive days. Safety was monitored by adverse events (AEs), intraocular pressure, serum HgbA1C, blood glucose and potassium levels. Secondary efficacy endpoints included visual acuity, slit lamp exam, HVF, optical coherence tomography (OCT) measured at baseline, 1 month (end of treatment) and 2 months (washout).
Results :
Twenty-two patients diagnosed with glaucoma were enrolled in one or more of the study sub-groups. All 10 patients completed all visits in groups 1 and 2; 18 participants completed all study visits for group 3. Both insulin doses were safe and well tolerated with no serious AEs. There were no significant change to serum electrolytes, glucose levels or HbA1c in all patients. Twenty eyes experienced a mild short-lasting stinging after drop instillation. A significant proportion (5 out of 15) study eyes vs. 0 out of 12 fellow eyes demonstrated improvement of at least 5 µm of RNFL thickness measured by OCT from baseline to month 1 visit (p = 0.0473, Fisher’s exact test). The increase in retinal nerve fiber layer (RNFL) was found to be associated with ganglion cell complex (GCC) thickening in those eyes. Further subgroup analysis did not reveal any significant differences between the two dosing regimens.
Conclusions :
The use of topical insulin was safe and well tolerated in patients with glaucoma. Given the structural effect demonstrated in Group 3 which suggests possible neuroprotective function, broader efficacy studies are warranted.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.