Background and Objective: Limbal stem cell deficiency (LSCD) is characterized by the insufficiency of limbal stem cells to maintain the corneal epithelium. Severe cases of LSCD may be treated with limbal transplantation from healthy autologous or allogeneic limbal tissue. Multiple cell-based therapies have been studied as alternative treatments to improve success rates and minimize immunosuppressive regimens after allogeneic transplants. In this review, we describe the success rates, and complications of different cell-based therapies for LSCD. We also discuss each therapy’s relative strengths and weaknesses, their history in animal and human studies, and their effectiveness compared to traditional transplants.

Methods: PubMed was searched for publications using the terms LSCD, cell-based therapy, cultivated limbal epithelial transplantation (CLET), cultivated oral mucosal epithelial transplantation (COMET),and mesenchymal stem cells from 1989 to August 2022. Inclusion criteria were English language articles.Exclusion criteria were non-English language articles.

Key Content and Findings: current cell-based therapies for LSCD are CLET and non-limbal epithelial cells. Non-limbal epithelial cell methods include COMET, conjunctival epithelial autografts, and mesenchymal stem/stromal cells (MSCs). Moreover, several alternative potential sources of non-limbal cells have described, including induced pluripotent stem cells (iPSCs), human embryonic stem cells (hESCs),human dental pulp stem cells, hair follicle bulge-derived epithelial stem cells, amniotic membrane epithelial cells, and human umbilical cord lining epithelial cells.

Conclusions: Cell-based therapies are a promising treatment modality for LSCD. While CLET is currently the only approved cell-based therapy and is only approved in the European Union, more novel methods have also been shown to be effective in human or animal studies thus far. Non-limbal epithelial cells such as COMET are also an alternative treatment to allogeneic transplants especially as a surface stabilizing procedure. iPSCs are currently being studied in early phase trials and have the potential to revolutionize the way LSCD is treated. Lastly, cell-based therapies for restoring the limbal niche such as mesenchymal stem cells have also shown promising results in the first human proof-of-concept study. Several potential sources of non-limbal cells are under investigation.

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.

Background and Objective: Nearly 30 years have passed since limbal stem cell deficiency (LSCD) was first identified by pioneers and given clinical attention. LSCD remains a difficult disease to treat. It can potentially lead to blinding. At present, understanding of limbal stem cells (LSCs) has deepened and various treatment options for LSCD have been devised. The objective of this review is to summarize basic knowledge of LSCD and current treatment strategies.

Methods: PubMed search was performed to find studies published in English on LSCs and LSCD including original reports and reviews. Literatures published from 1989 to 2022 were reviewed.
Key Content and Findings: LSCs are enigmatic stem cells for which no specific marker has been discovered yet. Although LSCD is not difficult to diagnose, it is still challenging to treat. An important advancement in the treatment of LSCD is the provision of guidelines for selecting systematic surgical treatment according to the patient’s condition. It is also encouraging that stem cell technologies are being actively investigated for their potential usefulness in the treatment of LSCD.

Conclusions: Although various treatment options for LSCD have been developed, it should be kept in mind that the best chance of treatment for LSCD is in the early stage of the disease. Every effort should be made to preserve as many LSCs as possible in the early treatment of LSCD.

Abstract: Cornea serves as the partial front barrier and major light reflection organ of the eye. The integrity of corneal surface is essential for ocular function. Injuries or congenital diseases could significantly destruct the homeostasis of the ocular surface, especially the microenvironment of limbal epithelial stem cells (LESCs), and will eventually cause dysfunction of corneal regeneration and diminish of LESCs. The loss of LESCs by different reasons are named limbal stem cell deficiency (LSCD), which is one of the leading cause of vision loss worldwide. To restore the corneal surface, LESC transplantation in the form of tissue or cell cultures is currently a viable and promising method to treat LSCD. In this review, we aim to introduce the characters and niche of LESCs, and discuss different aspects of its application in cornea surface reconstruction.