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.

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.

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.

Neurotrophic keratopathy (NK) is a rare degenerative disease in which damage to the corneal nerves leads to corneal hypoesthesia or anesthesia. Neurotrophic corneal ulcers are notoriously difficult to treat and can lead to blindness. Corneal neurotization (CN) is a recent surgical technique aimed at restoring corneal sensation and may offer a definitive treatment in the wake of NK. Herein, we review the surgical techniques utilized in direct and indirect CN. Technical considerations, outcomes, current limitations and future perspectives are also discussed. This article highlights the key points of this promising procedure and biological aspects that will help provide the best treatment options for patients with severe NK.

We present a comprehensive review of existing literature on surgical corneal neurotization (SCN) as a treatment modality for neurotrophic keratopathy (NK) with an interim report of seven cases where SCN was performed using the indirect approach and followed up till 18 months postoperatively to look for improvement in ocular surface, corneal sensations, and nerve regeneration by using in vivo confocal microscopy (IVCM). A literature search was performed for publications with keywords \"corneal nerves,\" \"neurotization,\" \"esthesiometry,\" \"corneal anesthesia,\" and \"neurotrophic keratopathy.\" All literature available till December 31, 2020 was reviewed and included to describe NK and its management options, particularly SCN. NK is associated with absent or reduced corneal sensations and is managed using a step-ladder algorithm ranging from medical management for symptomatic relief to surgical corneal neurotization. Both direct and indirect approaches of SCN have a favorable outcome with reduced surgical morbidity in the indirect approach using sural nerve graft. Post neurotization, corneal sensation recovery may take up to 3-6 months, while nerve regeneration on confocal microscopy can take as long as 6 months-1 year.

OBJECTIVE: To report the feasibility and the successful outcomes of a pediatric neurotrophic keratopathy (NK) owing to congenital corneal anesthesia (CCA) treated with allogeneic serum eye drops obtained from the mother as the only therapy.
METHODS: A 18-month-old girl with generalized pain insensitivity presented with a large epithelial defect in the right eye (RE) and superficial punctate keratopathy (SPK) in the left eye (LE). Corneal sensitivity was completely absent in both eyes (BE). Peripheral serum eye drops obtained from the mother was prescribed and administered every 2 hours in BE. Two weeks after the beginning of treatment, compete healing of the epithelial defect in the RE was obtained, while the severity of the SPK in the LE markedly improved; in parallel, conjunctival hyperemia disappeared in BE. The treatment was continued over the course of 3 months with good tolerability and neither signs of recurrence of the epithelial defect nor other complications were noted.
CONCLUSIONS: Allogeneic serum eye drops obtained from the mother are effective in treating pediatric NK owing to CCA. This treatment may represent a readily available and inexpensive option when topical nerve growth factor is unavailable or corneal neurotization is not feasible.

Neurotrophic keratopathy is a degenerative disease in which damage to the corneal nerves leads to corneal hypoesthesia. Injuries to neurotrophic corneas are notoriously difficult to treat and have traditionally been approached with supportive management. However, recent progress in the field of corneal neurotization has given new direction for addressing nerve loss directly by stimulating new nerve growth onto the cornea from nearby sensory nerves transferred to the perilimbal region. Herein, we review the surgical techniques utilized in corneal neurotization, including direct transfers and the use of nerve grafts. Considerations in surgical approach, as well as factors that influence prognosis and outcomes of the surgical intervention are also discussed.

Neurotrophic keratopathy (NK) is a degenerative corneal disease produced by different factors, including infection, trauma, and neurogenesis, that lead to trigeminal nerve damage and impaired corneal sensitivity. Extensive epithelial breakdown, impaired corneal epithelial healing and corneal ulceration, stromal melting, and perforation are main NK features. The proliferation of the corneal epithelium is endogenously regulated by a balance between adrenergic cAMP-dependent and cholinergic cGMP-dependent pathways. A careful balance of epitheliotropic neuromediators and neurotrophic factors expressed by corneal nerves and epithelial cells, respectively, is required to maintain corneal homeostasis. Even in its early stages, NK can cause reduced vision secondary to epithelial disturbance. Diagnosing NK is challenging, requiring the acquisition of a thorough clinical history and a comprehensive neurological and ophthalmic examination. Following suspicion of a clinical NK diagnosis, corneal sensitivity must be assessed qualitatively with the wisp of the cotton-tipped applicator and quantitatively through Cochet-Bonnet esthesiometry (CBE). A myriad of therapies is used for NK, and new, more specific modalities are being developed and investigated. Medical treatment with topical recombinant human nerve growth factor and surgical treatment through corneal neurotization are promising therapies aiming to target NK pathophysiology. Coexistent ocular surface disorders must be managed concomitantly to improve its prognosis. This review describes the up-to-date knowledge of the molecular basis regarding the pathogenesis of NK, and the novel target-specific therapeutic approaches based on this molecular mechanism.

Background: Corneal neurotization is an innovative surgical approach for restoring corneal sensation, whereby the sensory functions of a normal donor nerve are rerouted to an anesthetic cornea. Many variations upon this basic surgical principal have been introduced and have proven successful in ameliorating corneal sensation in patients. It is unclear whether one surgical approach is superior to another, as each has advantages and disadvantages. Surgical approaches differ in the donor nerve selected and in whether a nerve graft is required. Surgical techniques have varied in the location, number and extent of incisions, methods of nerve coaptation, the number of surgeons required, the equipment and materials utilized and the duration of the procedure.Purpose: The current review provides an overview of developments in this nascent field. Methods: A review of all peer-reviewed publications on corneal neurotization was performed. The various approaches to corneal neurotization are compared and discussed.Conclusions: The least morbid, simplest, most expedient and successful surgical approaches will ultimately become the most utilized.