Labial Mucosal Epithelium Grafting for Corneal Limbus Substitution

April 20, 2024 updated by: Boris Malyugin, The S.N. Fyodorov Eye Microsurgery State Institution

Efficiency and Safety of Labial Mucosal Epithelium Grafting for Corneal Reepithelization in Patients With Bilateral Non-immunogenic Limbal Stem Cell Deficiency

Earlier approaches for cornea reepithelization in patients with bilateral LSCD included allogeneic corneal limbus grafting from postmortem donor or livingrelated relatives with concomitant systemic immunosuppression (Cheung and Holland, 2017) and cultivated oral mucosal epithelial transplantation (COMET) (Nishida et al., 2004).

The novel surgical technique for corneal re-epithelization were described by Liu et al. (2011) and Choe et al. (2019). In both clinical studies, the autologous labial mucosal epithelium graft was transplanted as a surrogate corneal limbus for purpose of treatment the LSCD. Authors reported positive outcomes in terms of anatomical success and corneal status improvement.

The purpose of the study is to evaluate the feasibility of the novel surgical intervention in clinical use.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Earlier approaches for cornea reepithelization in patients with bilateral LSCD included allogeneic corneal limbus grafting from postmortem donor or livingrelated relatives with concomitant systemic immunosuppression (Cheung and Holland, 2017) and cultivated oral mucosal epithelial transplantation (COMET) (Nishida et al., 2004).

The novel surgical technique for corneal re-epithelization were described by Liu et al. (2011) and Choe et al. (2019). In both clinical studies, the autologous labial mucosal epithelium graft was transplanted as a surrogate corneal limbus for purpose of treatment the LSCD. Authors reported positive outcomes in terms of anatomical success and corneal status improvement.

Lip oral mucosa is a promising autologous source of epithelial cell for the trial because it has similar histological characteristic as the normal corneal. In particular, lip oral mucosal epithelium is stratified squamous and nonkeratinized.

The indicated histological and molecular features of the lip oral mucosal epithelium predetermined the use of labial mucosal epithelial graft for treatment patients with bilateral LSCD.

The purpose of the study is to confirm the validity of the hypothesis about the possibility of re-epithelialization diseased cornea using labial mucosal epithelium graft as a surrogate limbus in patients with bilateral LSCD.

Study Type

Interventional

Enrollment (Estimated)

20

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Russian Federation
      • Moscow, Russian Federation, 127473
        • Recruiting
        • The S. Fyodorov Eye Microsurgery Federal State Institution
        • Contact:
        • Contact:
        • Principal Investigator:
          • Boris E. Malyugin, MD PhD Prof.
        • Sub-Investigator:
          • Mikhail G. Kataev, MD PhD Prof.
        • Sub-Investigator:
          • Olga P. Antonova, MD PhD
        • Sub-Investigator:
          • Maria A. Zakharova, MD PhD
        • Sub-Investigator:
          • Maksim Y. Gerasimov, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Man or woman 18 years and older.
  • Signed informed consent, given by the participant or his/her legal representative.
  • Ability to understand Russian spoken and written language.
  • Sanitated oral cavity.
  • Bilateral limbal stem cell deficiency diagnosed by two or more symptoms during slit-lamp examination: corneal conjunctivalization, absence of palisades of Vogt, superficial corneal neovascularization, recurrent or persistent corneal epithelium erosion.
  • Bilateral limbal stem cell deficiency non-immunogenic etiology (burns, irradiation, contact lens related, etc.).
  • Best-corrected visual acuity less than 0.3 (6/18 Snellen chart)
  • Intraocular pressure in normal range.
  • Schirmer's test I more than 5 mm.

Exclusion Criteria:

  • Inability to give signed informed consent.
  • Age under 18 years.
  • Pregnancy and/or breastfeeding.
  • Hormonal contraceptives intake.
  • History of allergic reactions to antibiotics, glucocorticosteroids, remedies for treatment dry eye syndrome, medications for local and general anesthesia.
  • Participation in other clinical trials.
  • Systemic immunosuppression intake.
  • Diagnosed neoplastic process or treatment for it.
  • Positive tests for infectious: HIV, syphilis, Hepatitis B, Hepatitis C.
  • Any medical, psychiatric and/or condition, including cachexia, or social conditions that the investigator believes would interfere with or contraindicate adherence to the research protocol or the ability to provide signed informed consent.
  • Immune-mediated limbal stem cell deficiency (Stevens-Johnson syndrome, ocular cicatricial pemphigoid and other.), unknown and/or inherited etiology.
  • Best-corrected visual acuity more than 0.3 (6/18 Snellen chart)
  • Ocular burns earlier than 12 months.
  • Keratoplasty earlier than 12 months.
  • Limbal grafting (from postmortem or living-related donors).
  • Keratoprosthetic device or history of its implantation.
  • Cellular therapy for treatment of limbal stem cell deficiency.
  • Cellular transplantation for treatment of limbal stem cell deficiency.
  • Active ophthalmic infection.
  • Symblepharon, ectropion, trichiasis, lagophthalmos and/or other lid and/or conjunctival fornixes abnormalities.
  • Surgery on ocular adnexa earlier than 9 months.
  • Corneal stromal thickness less than 300 mkm.
  • Dry eye with Schirmer test I less than 5 mm and/or keratinized ocular surface.
  • Uncontrolled glaucoma and/or presents of a glaucoma drainage device.
  • Retinal defunctioning (no light perception and/or retinal detachment).
  • Absence of the electric activity of the optic nerve and/or retina.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Labial mucosa epithelium grafting for corneal limbus substitution.
Surgery for treating limbal stem cell deficiency using a strip of the lip oral mucosa with trimmed off the substantia propria and grafted as a circular corneal limbus substitute.
Procedure: Labial mucosal epithelium grafting for corneal limbus substitution
Labial mucosa epithelium grafting for corneal limbus substitution will be used to treat limbal stem cell deficiency by way of corneal surface re-epithelization

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Anatomical success
Time Frame: 12 months
Presence of a stable epithelium on the cornea and absence of conjunctivalization in the visual axis of the recipient eye
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants with improvement in corneal status
Time Frame: 12 months

A composite score for the corneal disease status (Campbell et. al., 2019) of the patients will be obtained throughout the study using the following 4 criteria in points according to the grades (grade 0, grade 1 - mild, grade 2 - moderate, grade 3 - severe):

  1. corneal staining: 0 - no punctuate staining, 1 - superficial punctate keratopathy (SPK) less than 50% of the corneal surface, 2 - SPK more than 50% of the corneal surface, 3 - epithelial defect;
  2. conjunctivalisation: 0 - absent, 1 - <25% of corneal surface, 2 - 25-50% of corneal surface, 3 - >50% of corneal surface;
  3. corneal neovascularization: 0 - absent, 1 - confined to corneal periphery, 2 - extending to pupil margin, 3 - extending beyond pupil margin into central cornea;
  4. corneal opacification: 0 - clear cornea, iris details clearly visualized, 1 - partial obscuration of iris details, 2 - iris details poorly seen with pupil margin just visible, 3 - complete obscuration of iris and pupil details.
12 months
Functional success
Time Frame: 12 months
Improvement in near and/or distance visual acuity
12 months
Rate of complications
Time Frame: 12 months
Intraoperative and postoperative complications on the recipient eye
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The S.N. Fyodorov Eye Microsurgery State Institution

Investigators

  • Principal Investigator: Boris E Malyugin, MD PhD Prof, The S. Fyodorov Eye Microsurgery Federal State Institution

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 1, 2021

Primary Completion (Estimated)

May 30, 2024

Study Completion (Estimated)

December 31, 2025

Study Registration Dates

First Submitted

August 2, 2021

First Submitted That Met QC Criteria

August 2, 2021

First Posted (Actual)

August 9, 2021

Study Record Updates

Last Update Posted (Actual)

April 23, 2024

Last Update Submitted That Met QC Criteria

April 20, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 517062021

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

We plan to share Clinical Study Report, present and publish results of the study.

IPD Sharing Time Frame

During the study and after.

IPD Sharing Access Criteria

upon request

IPD Sharing Supporting Information Type

  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Limbal Stem-cell Deficiency

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Myanmar

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe