DM Corneal Onlay Transplant for Limbal Stem Cell Deficiency

Overseen By Meaghyn Kramer, BA

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Minnesota

Disqualifiers: Pregnancy, Prisoners, Consent incapacity, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

Duration: Immediate post-operative period

20 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the DM Corneal Onlay Transplant treatment for Limbal Stem Cell Deficiency?

The effectiveness of similar treatments, like simple limbal epithelial transplantation (SLET), shows promise in treating limbal stem cell deficiency by improving visual acuity and maintaining a stable corneal surface. Additionally, allogeneic limbal transplants have been shown to integrate well into the corneal surface and improve vision, suggesting potential benefits for the DM Corneal Onlay Transplant. ^{1 2 3 4 5}

Is the DM corneal onlay transplant safe for humans?

The Descemet Membrane Endothelial Keratoplasty (DMEK), which involves similar techniques, is generally considered safe, but it can lead to significant loss of donor cells. This suggests that while the procedure is safe, there are risks related to the health of the donor tissue. ^{6 7 8 9 10}

How is the DM corneal onlay treatment different from other treatments for limbal stem cell deficiency?

The DM corneal onlay treatment is unique because it involves placing a thin layer of tissue (Descemet's membrane) onto the cornea to help restore its function, which is different from traditional corneal transplants that replace larger sections of the cornea. This approach may offer a more targeted and less invasive option for patients with limbal stem cell deficiency. ^{6 7 11 12 13}

What is the purpose of this trial?

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.

Research Team

Stephen Kaufman, MD

Principal Investigator

University of Minnesota

Eligibility Criteria

This trial is for people with Limbal Stem Cell Deficiency (LSCD), a condition that can cause blindness, who have significant vision loss (20/100 or worse). It's suitable for those with partial LSCD affecting less than 75% of the corneal surface and those with more severe cases involving over 75%, experiencing frequent erosions or persistent defects despite treatment.

Inclusion Criteria

My eye condition affects less than 75% of the corneal surface and my vision is 20/100 or worse.

I have severe eye surface damage with frequent pain or vision worse than 20/100 despite treatment.

Exclusion Criteria

Pregnant women

Prisoners (vulnerable population)

I am unable to make medical decisions for myself.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Descemet's membrane as a corneal on-lay to promote corneal re-epithelialization in partial LSCD

Immediate post-operative period

1 visit (in-person) for the procedure

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of corneal neovascularization, epitheliopathy, graft retention, and visual improvement

24 weeks

Visits at week 1, month 1, month 3, and month 6

Treatment Details

Interventions

• Descemet's Membrane corneal onlay

Trial Overview The study tests transplanting Descemet's Membrane (DM) onto the eye's surface as a potential new treatment. DM may serve as a replacement 'niche' to support limbal stem cells in patients with partial or near-total LSCD, aiming to promote healing and improve vision.

Participant Groups

Group I: Visually significant partial LSCD Experimental Treatment 1 Intervention

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 II: Total/near-total LSCD with recurrent or persistent epithelial defects (PED) Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

University of Minnesota

Lead Sponsor

Trials

1,459

Recruited

1,623,000+

Findings from Research

The novel simple limbal epithelial transplantation (SLET) technique was evaluated in four patients with total unilateral limbal stem cell deficiency, showing promising results with a completely avascular corneal surface in two patients after 6 months.

No serious complications were reported from the surgery, indicating that SLET is a safe option for treating limbal stem cell deficiency, although one patient experienced issues with graft adherence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of surgical outcomes of limbal transplantation using simple limbal epithelial transplantation technique in patients with total unilateral limbal deficiency. Queiroz, AG., Barbosa, MM., Santos, MS., et al.[2017]

A novel limbal transplantation technique was successfully performed on six patients with limbal stem cell deficiency, resulting in a completely healed and stable corneal surface within 6 weeks, maintained for an average of 9.2 months.

Visual acuity significantly improved in 66.6% of the patients, demonstrating the technique's efficacy while requiring less donor tissue and avoiding the need for specialized cell expansion laboratories.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Simple limbal epithelial transplantation (SLET): a novel surgical technique for the treatment of unilateral limbal stem cell deficiency. Sangwan, VS., Basu, S., MacNeil, S., et al.[2022]

Decellularised human limbus (DHL) maintains essential structural and biochemical properties of the limbal niche, including key basement membrane proteins, making it a promising carrier for limbal epithelial stem cell (LESC) transplantation.

The decellularisation process effectively removed DNA and immune cells from the DHL, demonstrating its safety and lack of cytotoxicity, which is crucial for successful transplantation outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Generation and characterisation of decellularised human corneal limbus. Spaniol, K., Witt, J., Mertsch, S., et al.[2018]

Allogeneic limbal transplantation (ALT) was performed on 22 patients with limbal stem cell deficiency (LSCD), resulting in successful integration of the transplanted tissue into the cornea, as confirmed by anterior segment optical coherence tomography (AS-OCT).

Post-surgery, patients experienced a significant improvement in visual acuity, with scores improving from an average of 2.06 to 1.44 logMAR over a mean follow-up period of 19 months, indicating the efficacy of ALT in treating LSCD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic Limbal Transplants Integrate into the Corneal Surface and Lead to an Improved Visual Acuity. Kesper, C., Heinzelmann, J., Viestenz, A., et al.[2023]

The deep anterior lamellar limbo-keratoplasty (DAL-LK) technique effectively managed bilateral limbal stem cell deficiency (LSCD) with corneal scarring in two patients, resulting in significant visual acuity improvements (20/80 and 20/60) over follow-up periods of 2.5 and 3 years, respectively.

DAL-LK offers a safer, single-stage solution for LSCD by simultaneously transplanting corneal stroma and limbal stem cells, preserving the host endothelium and eliminating the risk of rejection, which is a common issue with traditional methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep anterior lamellar limbo-keratoplasty for bilateral limbal stem cell deficiency with corneal scarring in chemical injury sequelae: Two case reports. Jain, N., Kate, A., Basu, S.[2023]

The use of a novel blunt instrument for preparing donor corneas in Descemet membrane endothelial keratoplasty improved visibility of the donor tissue without causing structural damage, as confirmed by transmission electron microscopy.

Endothelial cell loss was lower in the group using the new instrument (63 cells/mm²) compared to the traditional method (116 cells/mm²), suggesting that this tool may help minimize tissue loss during graft preparation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Instrument to Enhance Visualization of Descemet Membrane During Graft Preparation for DMEK Surgery. Menzel-Severing, J., Salla, S., Plum, WJ., et al.[2017]

In a study of 100 Indian eyes undergoing Descemet Membrane Endothelial Keratoplasty (DMEK), the procedure demonstrated safety and effectiveness, with 57.6% of patients achieving a Best Spectacle Corrected Visual Acuity (BSCVA) of ≥20/25 after three months.

The mean endothelial cell loss was 26.92%, which is considered acceptable, and complications were relatively low, with only 8% experiencing partial graft detachment and one case of primary graft failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of Descemet Membrane Endothelial Keratoplasty (DMEK) Using Surgeon's Prepared Donor DM-Roll in Consecutive 100 Indian Eyes. Basak, SK., Basak, S., Pradhan, VR.[2022]

In a study comparing two graft implantation techniques for Descemet membrane endothelial keratoplasty (DMEK) involving 40 patients, the technique using a DMEK injection cartridge resulted in a significantly longer insertion-to-attachment time and lower initial correct graft orientation compared to a standard lens injection cartridge.

Despite differences in insertion technique, both groups showed no significant differences in central corneal thickness, endothelial cell count, or best spectacle-corrected visual acuity after 12 months, indicating that while the technique may affect initial graft placement, it does not impact long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Flushing Versus Pushing Technique for Graft Implantation in Descemet Membrane Endothelial Keratoplasty. Siebelmann, S., Janetzko, M., König, P., et al.[2021]

In a study involving 15 human eye bank eyes, a new technique for transplanting Descemet's membrane (DM) was developed, which successfully maintained low levels of astigmatism post-surgery, averaging only 1.0 D.

The transplanted DM retained an intact endothelial cell layer with minimal cell death (3.4%), indicating that the procedure is effective and preserves the health of the donor tissue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transplantation of Descemet's membrane carrying viable endothelium through a small scleral incision. Melles, GR., Lander, F., Rietveld, FJ.[2022]

In a study of 40 patients undergoing Descemet's membrane endothelial keratoplasty (DMEK) for Fuchs' endothelial dystrophy, the learning curve showed that the last 13 procedures (33%) did not require rebubbling, indicating improved surgical proficiency over time.

After 3 months, 86% of the patients achieved a visual acuity of 0.5 or better, demonstrating that DMEK is a safe and effective procedure for restoring vision in patients with endothelial dysfunction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The learning curve for Descemet membrane endothelial keratoplasty performed by two experienced corneal surgeons: a consecutive series of 40 cases. Wubbels, RJ., Remeijer, L., Engel, A., et al.[2020]

Descemet's membrane endothelial keratoplasty (DMEK) significantly improved visual acuity in patients with endothelial cell decompensation, with a final mean LogMAR visual acuity of 0.32 after surgery compared to 0.87 preoperatively, indicating effective visual rehabilitation.

Despite a notable complication rate of transplant dislocation in 31% of cases, the overall safety profile was strong, with no serious complications like elevated intraocular pressure or endophthalmitis reported, supporting DMEK as a gold standard treatment for endothelial diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical results after Descemet membrane endothelial keratoplasty]. Yoeruek, E., Bayyoud, T., Röck, D., et al.[2012]

In a study involving 10 human cadaver eyes and 1 patient, Descemet membrane endothelial keratoplasty (DMEK) successfully maintained the position of the transplanted donor Descemet membrane after a 30-minute air-fill, indicating effective surgical technique.

The patient achieved excellent visual acuity of 20/20 one week post-transplant, demonstrating that DMEK can provide rapid visual rehabilitation for corneal endothelial disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Descemet membrane endothelial keratoplasty (DMEK). Melles, GR., Ong, TS., Ververs, B., et al.[2022]

Descemetectomy, which involves the targeted removal of Descemet's membrane, is proposed as a new treatment option for endothelial diseases like Fuchs endothelial dystrophy, potentially reducing the need for corneal transplants.

This approach offers a promising alternative to transplantation, addressing the growing demand for human corneal transplants while providing a direct intervention for specific corneal conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Descemetectomy : An alternative to transplantation?] Bramann, EL., Schröder, K., Schrader, S., et al.[2018]

References

1. Brazil pubmed.ncbi.nlm.nih.gov

Assessment of surgical outcomes of limbal transplantation using simple limbal epithelial transplantation technique in patients with total unilateral limbal deficiency. [2017]

2. England pubmed.ncbi.nlm.nih.gov

Simple limbal epithelial transplantation (SLET): a novel surgical technique for the treatment of unilateral limbal stem cell deficiency. [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

Generation and characterisation of decellularised human corneal limbus. [2018]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Allogeneic Limbal Transplants Integrate into the Corneal Surface and Lead to an Improved Visual Acuity. [2023]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Deep anterior lamellar limbo-keratoplasty for bilateral limbal stem cell deficiency with corneal scarring in chemical injury sequelae: Two case reports. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Instrument to Enhance Visualization of Descemet Membrane During Graft Preparation for DMEK Surgery. [2017]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Outcomes of Descemet Membrane Endothelial Keratoplasty (DMEK) Using Surgeon's Prepared Donor DM-Roll in Consecutive 100 Indian Eyes. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Flushing Versus Pushing Technique for Graft Implantation in Descemet Membrane Endothelial Keratoplasty. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Transplantation of Descemet's membrane carrying viable endothelium through a small scleral incision. [2022]

10. England pubmed.ncbi.nlm.nih.gov

The learning curve for Descemet membrane endothelial keratoplasty performed by two experienced corneal surgeons: a consecutive series of 40 cases. [2020]

11. Germany pubmed.ncbi.nlm.nih.gov

[Clinical results after Descemet membrane endothelial keratoplasty]. [2012]

12. United States pubmed.ncbi.nlm.nih.gov

Descemet membrane endothelial keratoplasty (DMEK). [2022]

13. Germany pubmed.ncbi.nlm.nih.gov

[Descemetectomy : An alternative to transplantation?] [2018]