Limbal Stem Cell Deficiency

The goal of this non-interventional, observational study is to describe the natural history, clinical course, and management patterns of subjects with limbal stem cell deficiency (LSCD).

This study will enroll subjects with qualifying limbal stem cell deficiency (LSCD). All subjects will receive CSB-001 investigational drug in either one or both study eyes. The study is comprised of two identical phases (Dosing Phase I and II) of test article dosing separated by a 31- to 40-day period, the Dosing Holiday, where no test article is administered. Dosing Phase II is followed by an observational, noninterventional phase (Observation Phase).

Background Intact corneal epithelium is important for the defense on the ocular surface, and the function of limbal stem cells is crucial to maintain its integrity. Certain chronic eye diseases, such as glaucoma, require long-term medication use. However, glaucoma patients often exhibit corneal punctate erosions and ocular surface inflammation. In cases where medication has been used for an extended period, patients may even show symptoms similar to limbal stem cell deficiency. Understanding how glaucoma medications affect the function of corneal limbal stem cells is a critical clinical issue. Objectives To evaluate the effect of glaucoma and anti-glaucoma agents on corneal epithelial and limbal epithelial thickness as a surrogate of limbal stem cell function, and to understand the association between tear fluid proteome and limbal function in glaucoma patients. Methods We planned to include 90 subjects with glaucoma, and analyze the absolute thickness and variation of corneal epithelium and limbal epithelium. Tear fluid samples will be collected and proteomic analysis will be performed to elucidate the association between protein. Anticipated Results To elucidate the impact of different types and cumulative doses of glaucoma medications on the thickness of the corneal epithelium and limbal epithelium, and to understand the relationship between limbal function and tear proteomics in glaucoma patients. The expected results may help develop early detection methods for changes in corneal and limbal epithelial function and provide valuable insights for future research on drug design and the protection of limbal stem cells.

The study " Autologous cultured corneal epithelium (CECA) for the treatment of corneal lesions associated with limbal stem cell deficiency" is the first clinical trial of this product manufactured at the LOEX laboratory. The culture of corneal epithelium strives to produce a reconstructed tissue with the therapeutical aim of treatment of limbal stem cell deficiency. The study is a phase I/phase II study with the goal to evaluate safety and efficacy of the CECA graft for the treatment of human patients suffering from limbal stem cell deficiency. The trial is open to all genders. The inclusion of 5 minors is planned.

CLET is a published treatment for the management of corneal failure due to extensive LSCD. Due to our previous studies on this novel treatment, the regulatory agency of Spain "Agencia Española de Medicamentos y Productos Sanitarios (AEMPS)" authorized our institution (IOBA-University of Valladolid) to perform this kind of therapy (CLET) in a case-by-case base following the Special Situation Medicines Policy Procedure in Spain. Upon approval of the permanent authorization patients will be included as specified by AEMPS.The objective of this study is to perform a protocolized treatment and follow up so that results can be reported to the scientific community.

Objectives The transparent surface of the eye, called the cornea, plays a crucial role in transmitting light to the retina and in protecting the eye. On its external surface, the cornea is composed of a constantly renewing multistratified epithelium. This mechanism is fueled by stem cells located in the limbus (the transition zone between the cornea and the sclera). Limbal Stem Cell Deficiency (LSCD) is characterized by a decrease or cessation of epithelial renewal and neovascularization of the cornea. Consequently, the cornea loses its integrity and transparency. This visually impairing condition is currently in a therapeutic impasse as only autologous limbal or allogeneic corneal grafts are viable options, but they pose significant risks to patients. Studies have shown that the oral cavity contains stem cells that can be isolated, cultured, and transdifferentiated into limbal stem cells (LSCs). However, to date, these studies are limited, and no protocol has been validated. In this study, the advantage of the accessibility of the oral cavity is used to develop a protocol for differentiating cells from the oral mucosa into limbal stem cells (LSCs) for use in a future clinical trial with patients. Methodology This prospective monocentric study will be conducted on patients from the ophthalmology department of the Montpellier University Hospital who have an indication for conjunctival reconstruction. After obtaining consent from the patients, cells from the oral wall will be sent to the tissue bank of the Montpellier University Hospital, where they will be cultured. Finally, the transdifferentiation steps will be analyzed by the "Eye" research team at the Institute of Neuroscience in Montpellier, which is collaborating on the project. The investigators have established objective factors to assess the success of the developed protocol based on the literature : (i) \> 3% of stem cells in primary cultures, (ii) \<10% aborted colonies, (iii) Expression of LSC markers (Pax6, Krt14, p63).

To investigate the effect of ocular surface reconstruction and assess the safety in cultivated oral mucosal epithelial cell sheet transplantation (COMET) regarding patients with cicatricial change of ocular surface.