NCT05909735

Treatment of LSCD With DM

Treatment of Limbal Stem Cell Deficiency With Descemet's Membrane

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 19 (actual)
• Sponsor: University of Minnesota · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Limbal Stem Cell Deficiency (LSCD) is a blinding disease that accounts for an estimated 15-20% of corneal blindness worldwide. Current treatments are limited. Traditional corneal transplantation with penetrating keratoplasty (PKP) is ineffective in treating these patients. Without a healthy population of limbal stem cells (LSC) to regenerate the corneal epithelium, standard corneal transplants will not re-epithelialize and will rapidly scar over or melt. The limbal niche is the microenvironment surrounding the LSCs that is critical for maintaining their survival and proliferative potential under physiologic conditions. Extracellular signals from the microenvironment are critical to the normal function and maintenance of pluripotent stem cells. Identifying an effective niche replacement is thus an important focus of limbal stem cell research and critical for advancing treatments for LSCD. Descemet's membrane (DM), an acellular, naturally occurring, basement membrane found on the posterior surface of the cornea, is a promising niche replacement. DM is routinely isolated and transplanted intraocularly with associated donor corneal endothelium for treatment of diseases like Fuchs' dystrophy and corneal bullous keratopathy that specifically affect DM and corneal endothelium. However, its application on the ocular surface has not been explored. DM is optically clear and highly resistant to collagenase digestion. This makes it very attractive as a long-term corneal on-lay and niche replacement on the surface of the eye. The anterior fetal banded layer of DM shares key compositional similarities with limbal basement membrane, which is a major component of the limbal niche. These similarities include limbus-specific extracellular matrix proteins such as collagen IV that is restricted to the α1, α2 subtypes, vitronectin, and BM40/SPARC. Of these, vitronectin and BM40/SPARC are known to promote proliferation of LSCs and induced pluripotent stem cells (iPSC) in culture. Because of this, DM is a promising biological membrane for establishing a niche-like substrate on the corneal surface in patients with LSCD. The purpose of this pilot study is to investigate the clinical efficacy of using DM as a corneal on-lay to promote corneal re-epithelialization in partial LSCD.

Conditions

• Limbal Stem-cell Deficiency
• Congenital Aniridia

Interventions

Type	Name	Description
PROCEDURE	transplantation of a Descemet's Membrane corneal onlay, partial LSCD	The worst seeing eye of these patients (or a randomized eye if vision is equal bilaterally) will be treated with superficial keratectomy to remove any pannus and debride the central corneal epithelium, followed by transplantation of a Descemet's membrane corneal onlay. Patient will be followed for 6 months and evaluated for improvement in visual acuity and improvement in limbal stem cell deficiency, and monitored for adverse events.
PROCEDURE	transplantation of a Descemet's Membrane corneal onlay, total/near-total LSCD	The worst seeing eye of these patients (or a randomized eye if vision is equal bilaterally) will be treated with superficial keratectomy to remove any pannus and debride the central corneal epithelium, followed by transplantation of a Descemet's membrane (DM) corneal onlay. Patient will be followed for 6 months and evaluated for improvement in visual acuity, limbal stem cell deficiency, and persistent epithelial defects/recurrent erosions, and monitored for adverse events.

Timeline

• Start date: 2023-11-30
• Primary completion: 2025-12-01
• Completion: 2025-12-01
• First posted: 2023-06-18
• Last updated: 2026-01-08

Locations

1 site across 1 country: United States