Systematic Reviews
Copyright ©The Author(s) 2023.
World J Diabetes. Jun 15, 2023; 14(6): 930-938
Published online Jun 15, 2023. doi: 10.4239/wjd.v14.i6.930
Table 1 Summary of the key characteristics of the included animal studies
Ref.
Country
Aim
Study design
Subject groups (number)
Insulin type and dose
Results
Nakamura et al[13], 2003JapanTo study the effect of the combination of FGLM-NH2 and IGF-1 on corneal epithelial wound healing in rats with diabetesAnimal4-wk-old male Sprague-Dawley Streptozocin-induced diabetic rats; 100 g (n = 20)FGLM-NH2 (1 mmol/L) and IGF-1 (1 μg/mL) 6 times per daySimilar wound healing processes were observed in normal rats and diabetic rats treated with FGLM-NH2 and IGF-1. Wound closure was significantly faster in diabetic rats treated with FGLM-NH2 and IGF-1 than in those treated with vehicle
Zagon et al[14], 2007United StatesTo determine TI normalizes delayed corneal wound healing in rats with diabetesAnimalMale Sprague-Dawley Streptozocin-induced diabetic rats; 165 g (38 diabetic rats; 11 nondiabetic rats)Bovine insulin 1, 2, or 5 U. Single drop (20 μL)TI normalizes corneal re-epithelialization in diabetic rats. No difference in efficacy of insulin dose of 1, 2, or 5 U and safe for cornea
Chen et al[15], 2013United StatesTo determine corneal nerve depletion in type 1 diabetes rats using corneal confocal microscopy and its relationship with TIAnimalFemale Swiss Webster Streptozocin-induced diabetic mice; 25-30 g (8 diabetic mice; 8 control)0.1 IU of regular U-100 Humulin (Lilly, Indianapolis, IN, United States) in 10 μL salineTI prevent depletion of nerve occupancy in the subbasal nerve plexus of the cornea without affecting systemic glycemic control
Yang et al[10], 2020ChinaTo investigate the relationship between TI and WnT/β-catenin signaling pathway in corneal epithelial healing and corneal nerve repair in diabetic miceAnimalStreptozocin-induced diabetic mice (6 to 8-year-old-male C57BL/6J mice)Human neural insulin (Lilly France S.A., Fegersheim, France). 3 μL QID (1 IU/mL)Insulin contributes to diabetic corneal epithelial wound healing and nerve injury healing via Wnt signaling, making it a potential protective factor for diabetic corneal epithelial wounds and nerve injuries
Table 2 Summary of the key characteristics of the included clinical studies
Ref.
Country
Aim
Study design
Subject groups (number)
Insulin type and dose
Results
Bastion and Ling[16], 2003MalaysiaTo determine whether TI improve healing rate of corneal epithelial erosion during vitreoretinal surgeryRetrospective reviewHuman (15 eyes of 14 patients underwent corneal debridement during vitreoretinal surgery)Actrapid HM, Novo Nordisk 1 U QID (50 UI/mL)Delayed epithelial healing in diabetic eyes compared with normal eyes. Diabetic eyes treated with TI had significantly smaller defect size than diabetic eyes treated with conventional therapy
Fai et al[3], 2017MalaysiaTo investigate the effect of 3 concentration of TI in corneal epithelial wound healing in postoperative patient with diabetesDouble blind randomized controlledHuman (32 eyes of 32 diabetic patient underwent corneal debridement during vitreoretinal surgery)Actrapid HM, Novonordisk 0.5, 1, 2 U QIDTI 0.5 U QID is most effective for corneal re-epithelialization in patients with diabetes after vitrectomy surgery as compared with placebo and higher concentrations. TI is safe for human ocular use
Aniah Azmi and Bastion[17], 2020MalaysiaTo determine the short-term effects of TI on symptoms and signs of dry eye disease in patients with diabetesRandomized, double-blind interventional studyHuman (320 eyes of 160 patients with diabetes for treatment of dry eyes)Actrapid HM, Novo Nordisk 1 U QID (25 UL/mL)Similar improvement in the Ocular Surface Disease Index score for TI 1 U QID and standard artificial tears in the treatment of dry eye in patients with diabetes
Quiroz-Mendoza et al[18], 2021MexicoTo compare the effect of TI and sodium hyaluronate in epithelial defects postoperative in patients with diabetesControlled human clinical trialHuman (36 eyes of 36 patients with diabetes who underwent corneal debridement during vitreoretinal surgery)Recombinant human insulin (Humulin® R, Eli Lilly and Company, Indiana, United States) 0.5 IU/drop QID (25 IU/mL)TI 0.5 IU/drops monotherapy and combined treatment with 0.15% sodium hyaluronate is effective in healing corneal epithelial defects after intraoperative corneal debridement in patients with diabetes. Adding sodium hyaluronate to TI did not provide additional benefit