Background and Objective: Corneal neurotization is a novel surgical technique used to restore corneal sensation in patients with neurotrophic keratopathy. Neurotrophic keratopathy is a disorder characterized by dysfunction of the ophthalmic division of the trigeminal nerve, which provides sensory innervation to the cornea. Without sensation, the cornea is at risk of infection, ulceration, perforation, and ultimately, vision loss. Corneal neurotization has emerged as an innovative technique to reinnervate anesthetized corneas by transferring a healthy donor nerve to the affected eye around the corneoscleral limbus. As the field of corneal neurotization rapidly grows, there is a need to synthesize the existing body of literature on corneal neurotization and identify important areas for further research. In this review, we will discuss neurotrophic keratopathy and its current management strategies, followed by an overview of corneal neurotization techniques, outcomes, surgical considerations, and future directions. Methods: PubMed and Google Scholar searches were conducted to retrieve and analyze relevant original papers and reviews on neurotrophic keratopathy and corneal neurotization up until April 2022.Key Content and Findings: Currently, numerous techniques for corneal neurotization exist, including direct nerve transfers, as well as indirect neurotization via interposition nerve grafts. So far, corneal neurotization has been shown to be highly successful in restoring corneal sensation, improving visual acuity,and improving corneal epithelial health. To date, there have been no significant differences in outcomes between direct versus indirect neurotization techniques, different donor nerves, or autologous versus allogeneic interposition grafts. However, there is some evidence that corneal neurotization procedures may be more successful in pediatric patients.Conclusions: Corneal neurotization shows great promise in treating neurotrophic corneas and represents the first management option to date that addresses the underlying pathophysiological mechanism of neurotrophic keratopathy by restoring corneal sensation. As the use of corneal neurotization continues to broaden, additional studies will become important to compare techniques in a systematic manner, with larger sample sizes, as well as standardized outcome measures and follow-up time.

Although amniotic membrane transplantation (AMT) has long been used as an essential surgical technique for ocular surface reconstruction, its role continues to evolve and expand. In the management of numerous ocular surface disorders, ranging from inflammatory to infectious, traumatic to neoplastic, the ability to perform AMT is a valuable addition to the skillset of any ophthalmologist. The purpose of this paper is to provide ophthalmologists with an updated, evidence-based review of the clinical indications for AMT in corneal and conjunctival reconstruction, reviewing its common and even experimental applications known to date. The methods of amniotic membrane preservation, the available commercial amniotic membrane products to date, and future directions for amniotic membrane use, including amniotic membrane extract eye drops (AMEED), are also discussed. It is paramount for ophthalmologists to stay up-to-date on the applications of AMT so as to effectively incorporate this versatile treatment modality into their practice,both in the operating room and in the clinic. By familiarizing the general ophthalmologist with its diverse applications, we hope to motivate general ophthalmologists to incorporate the use of AMT into their clinical practice, or provide guidance on how to recognize when referral to a corneal specialist for amniotic membrane application is prudent.

Background and Objective: Limbal stem cell deficiency (LSCD) describes the clinical condition when there is dysfunction of the corneal epithelial stem/progenitor cells and the inability to sustain the normal homeostasis of the corneal epithelium. The limbal stem cells are located in a specialized area of the eye called the palisades of Vogt (POV). There have been significant advances in the diagnosis and management of LSCD over the past decade and this review focuses on the pathophysiology of LSCD, its clinical manifestations, diagnosis, and causes.

Methods: Papers regarding LSCD were searched using PubMed to identify the current state of diagnosis and causes of LSCD published through to June 2022. 
Key Content and Findings: LSCD is clinically demonstrated by a whorl-epitheliopathy, loss of the POV, and conjunctivalization of the cornea. The diagnosis of this condition is based on clinical examination and aided by the use of impression cytology, in vivo confocal microscopy, and anterior segment optical coherence tomography (asOCT). There are many causes of LSCD, but those which are most common include chemical injuries, aniridia, contact lens wear, and Stevens-Johnson syndrome (SJS).

Conclusions: While this condition is most commonly encountered by corneal specialists, it is important that other ophthalmologists recognize the possibility of LSCD as it may arise in other co-morbid eye conditions.

Abstract: Corneal injuries and infections are the leading cause of blindness worldwide. Thus, understanding the mechanisms that control healing of the damaged cornea is critical for the development of new therapies to promptly restore vision. Innate lymphoid cells (ILCs) are a recently identified heterogeneous cell population that has been reported to orchestrate immunity and promote tissue repair in the lungs and skin after injury. However, whether ILCs can modulate the repair process in the cornea remains poorly understood. We identified a population of cornea-resident group 2 ILCs (ILC2s) in mice that express CD127, T1/ST2, CD90, and cKit. This cell population was relatively rare in corneas at a steady state but increased after corneal epithelial abrasion. Moreover, ILC2s were maintained and expanded locally at a steady state and after wounding. Depletion of this cell population caused a delay in corneal wound healing, whereas supplementation of ILC2s through adoptive transfer partially restored the healing process. Further investigation revealed that IL-25, IL-33, and thymic stromal lymphopoietin had critical roles in corneal ILC2 responses and that CCR2- corneal macrophages were an important producer of IL-33 in the cornea. Together, these results reveal the critical role of cornea-resident ILC2s in the restoration of corneal epithelial integrity after acute injury and suggest that ILC2 responses depend on local induction of IL-25, IL-33, and thymic stromal lymphopoietin.

Background: Because of its superficial anatomical localization, the cornea is particularly vulnerable to abrasive forces and various traumas, which can lead to significant visual impairments. Upon injury of the corneal epithelium, there are important changes that occur in the composition of the underlying extracellular matrix (ECM). Those changes are perceived by the integrins that recognize the ECM components as their ligand and activate different intracellular signalling pathways, ultimately leading to reepithelialisation and reorganization of the injured epithelium, both of which are necessary in order to restore the visual properties of the cornea. The goal of this study was to analyse the impact of the pharmacological inhibition of specific signal transduction mediators of integrin-dependant signalling pathways on corneal wound healing using both monolayers of hCECs and tissue-engineered human corneas (hTECs) as in vitro models.

Methods: hTECs were produced by the self-assembly approach and wounded with a 8-mm diameter biopsy punch. Total RNA and proteins were isolated from the wounded and unwounded hTECs to conduct gene profiling analyses and protein kinase arrays. The wounded tissues were then incubated with the WNK1 inhibitor WNK463 and wound healing was monitored over a period of 6 days. Control corneas were incubated with the vehicle alone (DMSO). The impact of WNK1 inhibition on hCECs monolayers was determined using a scratch wound assay.

Results: Gene profiling analyses and protein kinases arrays revealed important alterations in the expression and activity of several mediators from the integrin-dependent signalling pathways in response to the ECM changes taking place during corneal wound healing. Among these, WNK1 is considerably activated through phosphorylation during corneal wound healing. The pharmacological inhibition of WNK1 by WNK463 significantly reduced the dynamic of corneal wound closure in our hTECs and hCECs monolayers compared to their respective negative controls.

Conclusions: These results allowed the identification of WNK1 kinase as an important player for a proper healing of the cornea. Also, these results allowed for a better understanding of the cellular and molecular mechanisms involved in corneal wound healing and they may lead to the identification of new therapeutic targets in the field of corneal wounds.