Various etiologies, including diabetic keratopathy (DK), dry eye disease (DED), and neurotrophic keratopathy (NK), can disrupt corneal homeostasis, exacerbating corneal epithelial defects. Topical insulin has emerged as a promising therapy for promoting corneal wound healing and addressing underlying pathologies. This review systematically evaluates the efficacy of topical insulin across different corneal disorders. A literature review was conducted across the PubMed, Google Scholar, and Scopus research databases. The search resulted in a total of 19 articles, consisting of clinical trials, retrospective studies, and case reports. In DK, topical insulin accelerates corneal wound healing post-vitreoretinal surgery with lower concentrations showing higher outcomes when compared to conventional therapy, possibly due to improved epithelial stem cell migration. In comparison, the dry-eye disease results are inconclusive regarding patient-reported outcomes and corneal staining. For NK, topical insulin accelerates corneal wound healing and restores corneal nerve sensation. Other persistent epithelial defect (PED) etiologies that have been treated with topical insulin are infection, immune-mediated, mechanical and chemical trauma, and chronic ocular surface alterations. Although individual mechanisms for the benefits of topical insulin for each of these etiologies have not been studied, the literature demonstrates that topical insulin is efficacious for PEDs regardless of etiology. Future clinical trials need to be conducted to further evaluate optimal dosing, duration, and use of topical insulin for the restoration of the corneal surface.

Compounded insulin eye drops were prepared at 1 IU/mL from commercially available subcutaneous insulin by dilution in saline solution or artificial tears. Physicochemical characterization and in vitro tolerance testing in human and conjunctival cells were followed by a 28-day short-term stability study under various conditions. The formulations were isotonic (280-300 mOsm/L), had a pH close to neutral (7-8), medium surface-tension values (<56 MN/m-1), and low (≈1 mPa·s) and medium (≈5 mPa·s) viscosities (compounded normal saline solution and artificial tear-based preparation, respectively). These values remained stable for 28 days under refrigeration. Microbiological stability was also excellent. Insulin potency remained in the 90-110% range in the compounded formulations containing normal saline solution when stored at 2-8 °C for 28 days, while it decreased in those based on artificial tears. Although both formulations were well tolerated in vitro, the compounded insulin diluted in a normal saline solution exhibited better cell tolerance. Preliminary data in humans showed that insulin in saline solution was an effective and safe treatment for persistent corneal epithelial defects. Compounded insulin eye drops diluted in normal saline solution could, therefore, constitute an emergent therapy for the treatment of persistent corneal epithelial defects.

Corneal epithelial defects are one of the most common ocular disorders. Restoring corneal integrity is crucial to reduce pain and regain function, but in cases of neurotrophic or desensitized corneas, healing can be significantly delayed. Treating neurotrophic corneas is challenging for ophthalmologists, and surgical intervention is often indicated to manage refractory cases that are unresponsive to medical therapy. Over the last decade, as more expensive therapeutics reach the market, topical insulin has returned to the forefront as an affordable option to improve corneal wound healing. There is still a paucity of data on the use and the efficacy of topical insulin, with no consensus regarding its indications, preparation, or posology. Here we review the literature on topical insulin for corneal and ocular surface pathologies, with a focus on the current evidence, its mechanisms of action, and its safety profile. Additionally, we share our experience in the field and provide a potential framework for future research.

Background: Insulin and insulin-like growth factor (IGF)-1 receptors are present in ocular tissues such as corneal epithelium, keratocytes, and conjunctival cells. Insulin plays a crucial role in the growth, differentiation, and proliferation of corneal epithelial cells, as well as in wound healing processes in various tissues. Purpose: This review explores the potential role of topical insulin in the treatment of ocular surface diseases. Specifically, it examines its impact on corneal nerve regeneration, sub-basal plexus corneal nerves, and its application in conditions like corneal epithelial defects, dry eye disease, and diabetic keratopathy. Methods: The review analyzes studies conducted over the past decade that have investigated the use of topical insulin in ocular surface diseases. It focuses on indications, drug preparation methods, side effects, efficacy outcomes, and variations in insulin concentrations and dosages used. Results: While off-label use of topical insulin has shown promising results in refractory corneal epithelial defects, its efficacy in dry eye disease is yet to be demonstrated. Variations in concentrations, dilutions, and dosing guidelines have been reported. However, limited data on ocular penetration, ocular toxicity, and systemic side effects pose challenges to its widespread utility. Conclusion: This review synthesizes findings from ocular investigations on topical insulin to assess its potential applicability in treating ocular surface and corneal diseases. By highlighting indications, preparation methods, side effects, and efficacy outcomes, it aims to provide insights into the current status and future prospects of using topical insulin in ophthalmic practice.

Neurotrophic keratopathy is a corneal disease characterized by impaired corneal innervation. It can lead to corneal epithelial defects, ulcerations, and perforations. Topical insulin has been shown to be effective in treating this disorder. Insulin is a growth factor that can promote corneal epithelial cell proliferation and migration. In addition, it can also inhibit corneal epithelial cell apoptosis. Topical insulin has previously been found to enhance corneal wound healing. This article reviews the current understanding of the mechanism of action of topical insulin in the treatment of neurotrophic keratopathy.

BACKGROUND: Diabetic keratopathy (DK) occurs in 46%-64% of patients with diabetes and requires serious attention. In patients with diabetes, the healing of corneal epithelial defects or ulcers takes longer than in patients without diabetes. Insulin is an effective factor in wound healing. The ability of systemic insulin to rapidly heal burn wounds has been reported for nearly a century, but only a few studies have been performed on the effects of topical insulin (TI) on the eye. Treatment with TI is effective in treating DK.
OBJECTIVE: To review clinical and experimental animal studies providing evidence for the efficacy of TI to heal corneal wounds.
METHODS: National and international databases, including PubMed and Scopus, were searched using relevant keywords, and additional manual searches were conducted to assess the effectiveness of TI application on corneal wound healing. Journal articles published from January 1, 2000 to December 1, 2022 were examined. The relevancy of the identified citations was checked against predetermined eligibility standards, and relevant articles were extracted and reviewed.
RESULTS: A total of eight articles were found relevant to be discussed in this review, including four animal studies and four clinical studies. According to the studies conducted, TI is effective for corneal re-epithelialization in patients with diabetes based on corneal wound size and healing rate.
CONCLUSIONS: Available animal and clinical studies have shown that TI promotes corneal wound healing by several mechanisms. The use of TI was not associated with adverse effects in any of the published cases. Further studies are needed to enhance our knowledge and understanding of TI in the healing of DK.

BACKGROUND: Topical insulin can promote and accelerate corneal regeneration, even in eyes with serious comorbidities, and offers several benefits over other treatment options.
OBJECTIVE: The aim of this study is to evaluate the effect of topical insulin in treatment of recurrent epithelial corneal erosion.
METHODS: Patients with recurrent epithelial erosions were included in a prospective non-randomized hospital-based study, divided into two groups, one of them received persistent epithelial defects (PEDs) conventional treatment and the other received the same treatment with insulin eye drops 4 times/day. All patients were examined carefully by slit lamp. Patients during the 1st, 2nd, 3rd, and 4th weeks as well as after 2 months. Demographics, etiology, therapy, comorbidities, and the healing time of PED were performed.
RESULTS: Area shows significant improvement after 2 weeks (p = 0.006), 2 months (p = 0.046), and 3 months (p = 0.002) in group II (cornetears gel and topical insulin) as compared to group I (cornetears gel). The recurrence was statistically significant decreased with cornetears gel and topical insulin (group II) by 0.0%, as compared to cornetears gel (group I) by 3 patients (21.4%).
CONCLUSIONS: Topical insulin can promote corneal reepithelization in recurrent epithelial erosion and decreases recurrence in these cases. Other advantages include excellent tolerance, availability, and cost-effectiveness.

The Purpose is to identify, through a systematic literature review, the current evidence regarding the effectiveness of topical insulin treatment in ocular surface pathologies. A literature search was implemented in Medline (Pubmed), Embase and Web Of Science medical indexing databases by using keywords such as \"insulin\" AND \"cornea\" OR \"corneal\" OR \"dry eye\" in published papers in English or Spanish within the last eleven years (2011-2022). Nine papers were identified with 180 participants from the United States, Spain, Ireland, Canada, Portugal and Malaysia, with persistent refractory epithelial defects and secondary to vitrectomy, whose extension of the lesion was from 3,75mm2 to 65.47mm2. The preparation was dissolved with artificial tears and the insulin concentration ranged from 1 IU/ml to 100 IU/ml. In all cases, the resolution of the clinical picture was complete with a healing time from 2.5 days to 60.9 days, the latter being a secondary case to a difficult-to-control caustic burn. Topical insulin has been effective for the treatment of persistent epithelial defects. The intermediate action and low concentrations showed a shorter resolution time in neurotrophic ulcers and induced during vitreoretinal surgery.

BACKGROUND: Scarring is a common but difficult to manage consequence of acne vulgaris. The intricate balance between the degradation of collagen and its inhibition is disturbed during the formation of acne scars. We mostly rely on invasive, non-topical modalities for the treatment of acne scars which may not be indicated in all patients. There is also a need for maintainence therapies after these procedures.
METHODS: The topical agents can be utilized as individual therapy, in combination with other modalities or delivered through assisted technology like iontophoresis. Retinoids have long been tried to prevent and treat acne scars. Tacrolimus and glycolic acid are among the newer sole agents that have been explored. Ablative lasers like Er:YAG, CO2 and Microneedling are being used in combination with topical agents like silicone gel, plasma gel, lyophilized growth factors, platelet rich plasma, insulin, and mesenchymal stem cells. These procedures not only increase the permeability of the topical agents but also concomitantly improve acne scars. Iontophoresis has proven beneficial in increasing the delivery of topical estriol and tretinoin.
CONCLUSIONS: There is lack of evidence to support the widespread use of these topical agents, and therefore, there is need for further well designed studies.

OBJECTIVE: Aim of this study was to evaluate the effect of topical intranasal insulin on healing of nasal mucosa in a rat model.
METHODS: Forty-eight Wistar rats, weighing between 250 and 300 g and aged 10-12 weeks were used and randomized into two equal groups. 1.9 mm curette was introduced through the left nostril and 1.9 mm mucosa from the left nasal septum was curetted. Postoperatively, animals in the control group received 1 mL of physiologic saline, 3 times a day in a nasal irrigation fashion. Animals in the experimental group received 1 mL of 5 IU/mL regular insulin in saline solution. Subjects were sacrificed after 5, 10, and 15 days and macroscopic and histomorphometric evaluations were performed.
RESULTS: There were no mucosal synechiae and septal perforation macroscopically. Histological examination revealed that the defect size reduction was 21% in the saline group versus 56% in the insulin group on the fifth day (p = 0.006). There was 62% defect reduction in the saline group versus 79% in the insulin group on the 10th day (p = 0.034). On the 15th day, only 67% of saline group animals had complete defect closure, whereas 100% of animals treated with insulin had complete closure (92% vs 100% mucosal defect reduction, p = 0.036). Both edema and inflammation were less in the insulin group on 15th day (p = 0.006; p = 0.023, respectively).
CONCLUSIONS: The results from this study support the safety and efficacy of topical insulin on wound healing in the literature. This study could guide further experimental studies that examine human sinonasal wound healing.