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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction Atrophic acne scars pose significant cosmetic and psychological challenges for individuals. Various treatment modalities have been explored, including fractional CO2 laser therapy and topical insulin, which have shown promising efficacy in scar remodelling and tissue regeneration. The objective of the study is to evaluate the effectiveness and safety of a novel therapy utilizing a combination of fractional CO2 laser and topical insulin in treating atrophic acne scars. Methods A total of 19 patients with atrophic acne scars in Palembang were enrolled in this study. The treatment regimen included a combination of fractional CO2 laser therapy and topical insulin application. Treatment sessions were performed once every two weeks for two months. Scar severity was assessed using validated scales, and patient satisfaction and adverse events were recorded. Results The combination of fractional CO2 laser and topical insulin therapy demonstrated promising results in treating atrophic acne scars with significant developments in all outcome variables (Goodman and Baron score, visual analog scale, and quality of life index in dermatology). Significant improvements in scar severity and patient satisfaction scores were observed at the end of the treatment period (at six weeks), with minimal reported adverse events. There is no significant result for random blood sugar with topical insulin influencing blood sugar systemic. Conclusion A combination of fractional CO2 laser and topical insulin therapy has been proven effective in treating acne atrophic scars. This treatment option shows promise for managing acne atrophic scars due to its effectiveness and safety. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The diabetic foot ulcer is the precursor for diabetic foot and it is the most common sequel that occurs following any trauma or infection in a diabetic individual. The diabetic foot ulcers most commonly occur at the distal ends of the extremities because this is the area with the vascularity is the least as a result of microangiopathy that has occurs in in diabetes mellitus. The study was started after the ethical clearance was secured from the institution's ethical clearance committee. Following this the patients who came to the surgical outpatient department and the subspecialties of surgery that dealt with diabetic foot ulcers where well explained regarding the study. After they give informed consent to participate in the study, a thorough physical examination and history was taken based on a pre-defined questionnaire that was semi felt field. We noted that when insulin was used it reduced the size of the wound at a faster rate as compared to the conventional normal saline dressings. Also the quality of granulation tissue and the per cent reduction of the ulcer size was far better in the insulin group. We did not note any adverse effects as a result of insulin use in the test group. [ABSTRACT FROM AUTHOR]

Background: Topical insulin can promote and accelerate corneal regeneration, even in eyes with serious comorbidities, and offers several benefits over other treatment options. Aims: 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%). Conclusion: 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. [ABSTRACT FROM AUTHOR]

Objective: To study the efficacy of topical Insulin with microneedling compared to microneedling alone in atrophic acne scars. Study Design: Prospective, split face, comparative study. Place and Duration of Study: Department of Dermatology, Combined Military Hospital, Gujranwala Pakistan, from Jan to Jul 2021. Methodology: Fifty patients with atrophic acne scars from the dermatology outpatient department were selected. The right half of the face was treated with microneedling with Dermapen, keeping the needle depth at 2 mm, along with 40 units of Insulin, while the left half was treated with microneedling alone. The sessions were repeated at monthly intervals for a total of 3 sessions. Goodman and Baron’s quantitative scar scale was assessed at the beginning and then one month after the last (3rd) session, and improvement was measured. Results: Pre-treatment Goodman and Barons quantitative score mean on the right half was 20.44±3.54 whereas on the left half was 20.62±3.23. Post-procedure Goodman and Baron’s quantitative grading scale mean score on the right half was 9.78±2.88 while on the left half, 10.54±2.27. The improvement in mean global scores on the right and left halves was 10.66±2.11 and 10.08±1.88, respectively. The paired sample t-test showed a significant difference (p

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 (−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.

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). Conclusion: 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. [ABSTRACT FROM AUTHOR]

Background: Eighty percent or more of teenagers will experience acne. The acne scars left behind by acne vulgaris are irreversible. Up to 95% of people with acne vulgaris may experience scarring, yet this issue has received little attention from researchers. Depending on the study, acne scars affect between 1% and 11% of the population. Lasers have great potential as a therapeutic tool, but it has been difficult to get desirable clinical results because of the inherent trade-off between efficiency and safety, especially with the first generation of ablative lasers. Current research suggests that topical insulin may be effective in reducing the appearance of acne scars. Increased VEGF is produced after topical insulin activates PI3K/AKT pathways. Unlike the crisscross pattern typical of scar tissue, the collagen fibres generated and developed in normal skin more closely resemble a "basket weave. ". Objective: Assessment of possible role of topical insulin and fractional laser in the treatment of acne scars. Methods: PubMed, Google Scholar, and Science Direct were scoured for information about: Acne scars, fractional laser therapy and topical insulin. The authors also reviewed additional sources, but only the most up-to-date or comprehensive study between April 2004 and April 2021 was included. There are no translation resources available, thus non-English documents are out. Dissertations, conference papers, and oral presentations were not included since they do not constitute "important scientific discoveries.". Conclusion: It's possible that post-acne scars can be effectively treated with either topical insulin or fractional laser. Larger controlled studies are needed to confirm the effectiveness of insulin as a novel anti-scarring medication. [ABSTRACT FROM AUTHOR]

Introduction: 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. Review: 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. Conclusion: There is lack of evidence to support the widespread use of these topical agents, and therefore, there is need for further well designed studies. [ABSTRACT FROM AUTHOR]

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.

Aim: Study of effects of topical insulin in wounds of diabetic patients Materials and method: Patients attending hospital for illness and requiring treatment for diabetic ulcer was admitted and 12 hourly dressing was done by topical insulin application under aseptic precautions, blood sugar level pre and post dressing was monitored. 50 patients were included in this study. In 50 Percent of the sample size in diabetic patients on HAI dressing was done by topical insulin application(30ml 0.9% Normal saline +30IU of insulin) and in rest of the study population of diabetic patients on HAI dressing was done by conventional dressing method(Normal saline only). The Assessment of appearance of Granulation, disappearance of slough and reduction in wound size was compared at day 1 day 7 and day 21 between topical insulin dressing and conventional dressing. Results: The mean age of the control group was 59.85±6.36, as indicated in Table (1), whereas the mean age of the study group was 56.87±8.2. Male participation in the trial was 52% in the control group and 80% in the experimental group. We examined blood glucose levels before and after the administration of topical insulin to determine that it did not impact the blood glucose level. The initial wound sizes in our study groups were 6.8±0.1 and 2.5±0.7cm2 for the control and study groups, respectively. The NS Group took 47.58±0.3 days to recover, whereas the insulin Group required 28.2±0.7 days. The mean score for the NS group and the study group on day 0 was 9.31±0.3 and 88.32±0.2, respectively. On day 14, the mean PUSH score for the two groups was 6.92±0.5 and 1.71±0.2, respectively. At day 21, the NS group had a score of 5.93±0.8, whereas the insulin group had a score of 0.82±0.2. Conclusion: Our findings demonstrated that topical insulin is both efficacious and safe for various wound types in diabetes individuals. When topical insulin groups were compared to normal wound dressing, statistically significant variations in wound healing rate were seen. [ABSTRACT FROM AUTHOR]

Background: Current management of diabetic foot ulcer consists of an effective systemic and local therapy. Despite these measures infection control has been found to be inadequate leading to amputation in as high as 28.4% of these patients. Recent studies have shown local hyperglycaemia at the wound site as a cause of poor wound healing. Aim: To compare the rate of wound healing following topical insulin and conventional dressing in patients with diabetic foot ulcer. Material and Methods: All patients with diabetic foot ulcer above 18 years of age had undergone appropriate debridement and regular conventional dressing till the wounds were deemed clean. Subsequently, the patients were randomised into either Group A which received topical insulin dressing or Group B which received normal saline dressing. Ulcer size was measured once a week in both the groups till 12 weeks or complete re-epithelization of the wound. Random blood glucose levels were measured 10 minutes before and 1 hour after application of topical insulin in Group A patients. Results: A total of 66 patients were included in the study and randomised into two groups (33 each). The demographic, biochemical and ulcer characteristics were comparable between the groups. The rate of wound healing in group A was 48.97±6.54mm2/day and in the group B was 41.62±5.84mm2/day (p-value 0.05). Mean blood glucose levels pre and post insulin dressing was 139.87±14.20 mg/dl and 139.47±15.50 mg/dl respectively. Conclusion: The wounds, which are treated with topical insulin, have healed faster than those receiving conventional dressings with normal saline. [ABSTRACT FROM AUTHOR]

Aims: The role of insulin in the regulation of energy metabolism, protein synthesis, proliferation, migration, secretion by keratinocytes, endothelial cells, and fibroblasts suggests that its presence is essential for wound healing (WH). The present study aims to explore the opportunities and limitations of topical insulin (TI) formulations. Methods: To obtain a complete picture of the challenges of the local insulin formulation a chronological review of previous publications in electronic databases was performed, applying data collection and selection criteria. Results: The opportunity of topically applied insulin has shown active interest over time. According to studies, regular and isophane insulin are suitable for local use, but currently there is no consensus on the appropriate concentration. Insulin can be incorporated into cutaneous liquid, semisolid, and solid dosage forms, either by itself, or by prior nano-or microencapsulation methods. The most important limiting factors to be evaluated are the stability of the peptide and the sterility of the obtained products. Conclusion: Examination of the balance of opportunities and limitations of TI formulations, it can be concluded that the range of applicable technological methods is wide. A high-quality, safe, and efficacious form of TI would have great value from a socio-economic point of view. [ABSTRACT FROM AUTHOR]

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., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Moin et al.)

Objective: To study the efficacy of topical Insulin with microneedling compared to microneedling alone in atrophic acne scars. Study Design: Prospective, split face, comparative study. Place and Duration of Study: Department of Dermatology, Combined Military Hospital, Gujranwala Pakistan, from Jan to Jul 2021. Methodology: Fifty patients with atrophic acne scars from the dermatology outpatient department were selected. The right half of the face was treated with microneedling with Dermapen, keeping the needle depth at 2 mm, along with 40 units of Insulin, while the left half was treated with microneedling alone. The sessions were repeated at monthly intervals for a total of 3 sessions. Goodman and Baron's quantitative scar scale was assessed at the beginning and then one month after the last (3 rd) session, and improvement was measured. Results: Pre-treatment Goodman and Barons quantitative score mean on the right half was 20.44±3.54 whereas on the left half was 20.62±3.23. Post-procedure Goodman and Baron's quantitative grading scale mean score on the right half was 9.78±2.88 while on the left half, 10.54±2.27. The improvement in mean global scores on the right and left halves was 10.66±2.11 and 10.08±1.88, respectively. The paired sample t-test showed a significant difference (p<0.001) in the scores of both the right and the left halves. Conclusion: Microneedling alone and combined with Insulin effectively treats atrophic acne scars. [ABSTRACT FROM AUTHOR]

Objectives: In this prospective study we aim to demonstrate the effect of small doses of topical long acting insulin ( zink insulin ) application in wound healing. Methods: Thirty eight patients were studied in our private outpatient clinic between the years 2009 to 2011 , long acting insulin ( zinc insulin ) was used to avoid the hypoglycemic effect of insulin . Results: From a total of 38 patients, 20(52.6%) were males and 18(47.4%) were females. The median age was 49 years with a mean age of 35.11±11.543 years. There were different causes of the wounds, 21(55.3%) patients had previous operations leading to the wound, 9(23.7%) developed chronic wounds after burns, and 8(21.0%) had a wound due to trauma. The wounds were distributed in different sites of the body. In the trunk 24(63.2%) patients, in the extremeties 11(28.9%) patients and in the breast 3(7.9%). All the wounds were previously dressed with saline. The sizes of the wounds varied, minimum wound size was 1cm and maximum was 16cm with a mean of 6.32±4.319cm. 13(34.2%) of the wounds were infected, 18(47.4%) had allergy to stitches , 4(10.5%) had unhealthy granulation tissue and 3(7.9%) were covered with tough fibrin. These wounds were prepared prior to the study by giving antibiotic, removing the stitches, excising bad granulation tissue and removing fibrin. Soluble Insulin injection was prepared at a concentration of 1- Unit/10ml distilled water, then injected superficially in the inside of the wounds of the patient, and the effect was observed. The time range of saline-insulin treated wound closure was 15 days with a mean of 7.13±4.461 days. All patients had an excellent outcome and their wounds closed in a short time without any complications. Conclusion: Topical insulin application leads to acceleration of wound healing. The duration of wound healing and outcomes in our study were excellent. This depends on many factors also which should be taken seriously like wound infection of the wound and size. [ABSTRACT FROM AUTHOR]

The use of topical insulin therapy for promotion of second intention healing has been investigated in a case study following removal of a soft tissue sarcoma in a Bearded Dragon (Pogona Vitticeps). Topical Insulin therapy appears to be beneficial in promoting second intention healing in Pogona Vitticeps although consideration is needed when using on sites associated with neoplasia. A preferred suitable dressing medium for reptiles has been identified for future use. More research is needed through practical application of current studies into wound management in reptiles to be able to improve the management of future cases such as this. [ABSTRACT FROM AUTHOR]

Abstract Background Compared with mammals, wound healing in reptiles is characterized by reduced wound contraction and longer healing times. The aim of this study is to describe the clinical and histopathological effects of topical insulin on second-intention healing of experimentally induced wounds in skin without dermal bony plates of Trachemys scripta elegans exposed to daily variations in ambient temperature and in an aquatic environment. Forty-four healthy adult females were assigned to two groups: Group 1 (n = 24) was used to assess clinical features such as wound contraction; Group 2 (n = 20) was used for histological evaluation and morphometric analysis. Topical porcine insulin (5 IU/ml diluted in glycerol) was applied daily 1 week. For each control time (2, 7, 14, 21 and 28 days post-wounding), re-epithelisation and wound remodelling were evaluated histologically and the number of main inflammatory cells (heterophils, macrophages, lymphocytes and fibroblasts) was scored. Results Mean wound contraction was higher in the insulin-treated group at each time point and differences were significant at day 28 (P

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.

Introduction: Diabetes mellitus is one of the most common metabolic disorders affecting a large part of our population. Apart from its effect on all organ systems, these metabolic derangements affect other processes in the body as well. Diabetic wounds are difficult to treat with conventional treatments. Delayed wound healing has led to increased morbidity and mortality in the population. Increased blood glucose leads to ineffective angiogenesis and less collagen deposition. In various studies long acting insulin zinc suspension has been shown to augment wound healing without any harmful effects. Objectives: To find out the advantages of topical insulin in the management of diabetic foot ulcers. Study Design: Observational study. Setting: Plastic Surgery and General Surgery Department, Baqai Medical University Karachi. Period: January 2014 to December 2016. Material and Methods: Patients visiting the Surgical OPD with diabetes mellitus and concomitantly having foot ulcers were included in the study. Diabetics having blood glucose levels of 110-130 gm/dl and ulcers measuring more than one cm on the dorsum of the foot were included in the study. All patients having foot ulcers were treated by daily topical spray of 1cc saline mixed with 5 units of insulin. This treatment was continued for 12 weeks or till the time ulcer was completely healed (whichever was earlier) and ulcer size was measured weekly. Ulcer size and depth before and after treatment was measured. Results: We had a total of 65 participants, among them there were 52 males and 13 females presenting with diabetic foot ulcer. Around 87.6% (n=57) patients had type 2 diabetes mellitus whereas 12.3% (n=8) patients had type 1 diabetes mellitus. Upon examination of the patient the location, size and depth of the ulcer was measured as well. These parameters were measured before and after treatment by topical insulin spray. Right foot ulcers were present in 64.6% of the patients and 35.38% patients had left foot ulcers. The mean size and depth of ulcer was 5.1 ± 1.1 cm2 and 8.7 ± 0.12 mm respectively. After treatment the mean size and depth of ulcer was found to be 1 ± 0.04cm2 and 1.4 ± 0.12mm respectively. Conclusion: There was significant improvement after treatment of diabetic foot ulcers with topical insulin spray. The wound size and depth were considerably decreased. This treatment had more promising results than conventional treatment methods for diabetic foot ulcers. [ABSTRACT FROM AUTHOR]

Background: Compared with mammals, wound healing in reptiles is characterized by reduced wound contraction and longer healing times. The aim of this study is to describe the clinical and histopathological effects of topical insulin on second-intention healing of experimentally induced wounds in skin without dermal bony plates of Trachemys scripta elegans exposed to daily variations in ambient temperature and in an aquatic environment. Forty-four healthy adult females were assigned to two groups: Group 1 (n = 24) was used to assess clinical features such as wound contraction; Group 2 (n = 20) was used for histological evaluation and morphometric analysis. Topical porcine insulin (5 IU/ml diluted in glycerol) was applied daily 1 week. For each control time (2, 7, 14, 21 and 28 days post-wounding), re-epithelisation and wound remodelling were evaluated histologically and the number of main inflammatory cells (heterophils, macrophages, lymphocytes and fibroblasts) was scored. Results: Mean wound contraction was higher in the insulin-treated group at each time point and differences were significant at day 28 (P < 0.0001). Histologically, these clinical findings were associated with better re-epithelisation, inflammatory response, collagen synthesis and remodelling of the wounds. Morphometrically, insulin-treated wounds had significantly higher mean counts of heterophils (day 7), macrophages (days 2, 7 and 14) and fibroblasts (days 14 and 21), whereas lymphocyte counts were significantly lower at day 21. These results demonstrate that topical insulin modifies the inflammatory response of turtle skin up-regulating inflammatory cells at early stages and promoting wound healing. Conclusions: Topical insulin is a potentially useful therapy in skin wounds of Trachemys scripta and should be evaluated in non-experimental wounds of turtles and other reptiles. [ABSTRACT FROM AUTHOR]

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., Aim: 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., Conclusion: 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., Competing Interests: Conflict-of-interest statement: Bastion MLC received fees for serving as a speaker and/or an advisory board member for Novartis, Alcon, and Santen. She received fees for serving as a speaker for Bayer, Lumibird, and Allergan. She has received research funding from Alcon, Novartis, Santen, TRB Chemedica, IDB healthcare, and National University of Malaysia. She is an employee of the National University of Malaysia. Wan Abdul Halim WH received travel funding from Santen. She is also a key opinion leader for Oculus GMBH. She is an employee of Universiti Kebangsaan Malaysia. Leong CY and Naffi AA have no conflict of interest to disclose., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

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 3,75mm 2 to 65.47mm 2 . 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., (Copyright © 2023 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.)

The process of wound healing is a dynamic event during which the stages of fibroplasia, angiogenesis, and re-epithelization perfectly take place.The aim of this study is to compare the effects of wound irrigation by normal saline and topical insulin application, which we frequently use in clinical practice, on wound healing. The study covers a total of 20 male rats -10 for the insulin group and 10 for the control group. The first group received topical insulin application while the second group had irrigation by normal saline. The macroscopic outlook, collagen production, and wound contraction rates in the animals wounds were checked at the end of day 20. The rate of wound closing was found to be higher in the topical insulin group than the NS group at all times. Further, the period of complete wound closing was shorter than the insulin group. Histopathological analysis revealed that the ulceration and inflammation were localized in the subepithelial field in the skin cross-sections of the insulin group and that there was a significant increase in collagen bundles. Thus, we think that insulin can be an alternative to normal saline application specifically in chronic wounds related to diabetes and post-op wound care. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the effects of insulin on the healing of acute traumatic tympanic membrane (TM) perforations by observing the duration of perforation closure clinically and by examining the TM thickness, fibroblastic reaction, neovascularization and collagenization histologically. In all, 24 adult healthy guinea pigs were used. TM perforations, about 2 mm in diameter were made in the pars tensa of each ear. The perforations in the right ears of the guinea pigs (study group) were treated with 1 IU of regular insulin (Humulin-R® 100 IU/ml, Lilly) daily topically. The left ears of the guinea pigs (control group) were treated with saline solution daily. The treatments were continued until the each perforation closed. The animals were examined with otomicroscopy at first, third, fifth and seventh days. TM specimens were obtained after the animals were decapitated under deep anesthesia by an intraperitoneal injection of sodium pentobarbital (0.5 ml/100 g) 3 and 7 days after wounding. Histologically, the epithelial and mucosal layers were examined. Finger-like projections, the edema of the LP, neovascularization of LP, fibroblastic activity of LP, inflammatory cell presence of LP, collagenization ratios of LP were evaluated. In the study group; LP fibroblastic reaction positivity and LP collagenization positivity was significantly higher than the control group ( P < 0.001 and P < 0.05). Topical insulin treatment may be more beneficial in the treatment of atrophic membrane, which is a sequel of perforation, when tried in various dosages and time intervals. [ABSTRACT FROM AUTHOR]

Various researches have reported that the application of topical insulin improves wound healing. Considering the lack of a quantitative comprehensive research on this matter, we conducted a meta-analysis of clinical research and experimental animal studies. Prospective and randomized controlled trials of PubMed, Embase, and Cochrane Library were conducted using appropriate search strategies to compare the effectiveness of topical application of saline and insulin on wounds. The standardized mean difference was calculated as follows: wound healing time, wound healing rate, wound area, and the percentage of wound contraction. Each study used the Cochrane risk-of-bias tool and RevMan 5.3 software to create aggregated assessments and forest plots. The quality of evidence was evaluated in accordance with the methods of the Grading of Recommendations, Assessment, Development and Evaluation working group. Four clinical and nine animal studies eligible for inclusion were included in the meta-analysis. The assessments for clinical studies were as follows: wound healing time, -2.48 [-3.44, -1.51] and wound healing rate, 22.23 [18.17, 26.28]. Meanwhile, for animal studies, the following assessments were noted: wound healing time, -1.27 [-1.75, -0.79]; wound contraction rate, 15.91 [13.88, 17.95]; and wound area, -19.3 [-21.16, -17.44]. For the measurement of the following results, only one animal study was performed, pericyte recruitment of microvessels. Based on the analysis, it can be preliminarily judged that application of topical insulin can aid wound healing.

Overall, major burn wounds may require special care and long-term hospitalization as they not only bring complications from the wound itself, but may also compromise the immune system, or even other organs. Previous studies have indicated that topical insulin cream shortened wound closure time in second-degree burns in rats. Transplanted adipose-derived stem cells (AD-MSCs) have been developed as an alternative to treat burns and to accelerate the healing process. The aim of the present study is to investigate the effect of topical insulin gel, associated with AD-MSCs intradermal administration to heal second-degree burn wounds in rat models who were subjected to second-degree dorsal burns. The models were divided into four groups (n = 10 per group): placebo gel (C), topical insulin gel (TI), topical insulin gel and adipose-derived mesenchymal stem cells (TIMSCs) and placebo gel and adipose-derived mesenchymal stem cells (CMSCs). Wounds were assessed on a daily basis and histological evaluations were made on 5 animals from each group on the seventh and fourteenth day. There was a significant macroscopic decrease in burn wound areas in the Control (P = 0.0083), TIMSCs and CMSCs (P = 0.042) groups between the seventh and fourteenth days. The TI treatment did not show any significant change (P > 0.05) throughout this same period. The histological analysis showed significant granulation tissue formation in CMSCs and TIMSCs (P = 0.02235) treatments during the experimental period. According to the results, intradermal administration of allogenic AD-MSCs in experimental second-degree burns for short periods of time in the rat model has contributed to reducing the inflammatory phase duration, improving wound re-epithelialization, tissue granulation and wound contraction, as well as increasing collagen deposition., Competing Interests: None., (IJBT Copyright © 2020.)

Purpose: To determine the effect of topical insulin of 3 concentrations [0.5, 1, and 2 units per drop 4 times per day (QID)] on postoperative corneal epithelial wound healing in diabetic patients., Design: A double blind randomized controlled hospital-based study involving diabetic patients with postoperative corneal epithelial defect after vitreoretinal surgery., Methods: Diabetic patients were randomized to 3 different concentrations of topical insulin (DTI 0.5, DTI 1, and DTI 2) or placebo in the control group (DNS). Primary outcome measure was the rate of corneal epithelial wound healing (mm² per hour) over pre-set interval and time from baseline to minimum size of epithelial defect on fluorescein stained anterior segment digital camera photography. Secondary outcome measure was any adverse effect of topical insulin. Follow-up was 1 month., Results: Thirty-two eyes of 32 patients undergoing intraoperative corneal debridement with resultant epithelial defect (8 eyes per group) were analyzed. DTI 0.5 was superior to other concentrations achieving 100% healing rate within 72 hours of treatment compared with 62.5% in DNS, 75% in DTI 1, and 62.5% in DTI 2. Statistically, DTI 0.5 achieved significant results (P = 0.036) compared with the diabetic control group (DNS) in terms of mean rate of corneal epithelial wound healing from maximum to minimum defect size. No adverse effect of topical insulin was reported., Conclusions: Topical insulin 0.5 units QID is most effective for healing corneal epithelial defect in diabetic patients after vitrectomy surgery compared with placebo and higher concentrations. Topical insulin is safe for human ocular usage., (Copyright 2017 Asia-Pacific Academy of Ophthalmology.)