Treatment of LSCD With DM

NCT ID: NCT05909735

Last Updated: 2026-01-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-11-30
• Study Completion Date: 2025-12-01

Brief 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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Visually significant partial LSCD

Patient with visually significant partial LSCD, as defined by a best corrected visual acuity of 20/100 or less, and partial LSCD on slit lamp exam with at least 25% of the limbus intact or at least 25% of the corneal surface covered with corneal epithelium will be enrolled in the first arm.

Group Type: EXPERIMENTAL

transplantation of a Descemet's Membrane corneal onlay, partial LSCD

Intervention Type: PROCEDURE

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.

Total/near-total LSCD with recurrent or persistent epithelial defects (PED)

Patient with visually significant total LSCD, as defined by a best corrected visual acuity of 20/100 or less, and total LSCD on slit lamp exam with over 25% of the limbus intact or less than 25% of the corneal surface covered with corneal epithelium; and a history of a persistent epithelial defect that has persisted over 2 weeks despite maximal medical therapy, or a history of recurrent epithelial erosions that occur more frequently than once a month; will be enrolled in the second arm.

Group Type: EXPERIMENTAL

transplantation of a Descemet's Membrane corneal onlay, total/near-total LSCD

Intervention Type: PROCEDURE

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

Arm 1:

• partial LSCD (involving less than 75% of the limbus, or <75% of the corneal surface)
• Visually significant (best-corrected visually acuity 20/100 or worse)

Arm 2:

• total/near-total LSCD with recurrent erosions or PEDs (involving more than 75% of the limbus, or more than 75% of the corneal surface)
• Visually significant (best-corrected visually acuity 20/100 or worse) PLUS
• Persistent epithelial defects last >2 weeks despite maximal medical therapy OR
• Recurrent erosions occuring at least once every month

Exclusion Criteria

• Pregnant women
• Prisoners (vulnerable population)
• Adults lacking capacity to consent (vulnerable population)
• Adults unable to sign consent due to non-english speaking or illiterate (vulnerable population)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Minnesota

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stephen Kaufman, MD

Role: PRINCIPAL_INVESTIGATOR

University of Minnesota

Locations

University of Minnesota

Minneapolis, Minnesota, United States

Countries

United States

Other Identifiers

OPH-2023-31727

Identifier Type: -

Identifier Source: org_study_id