Labial Mucosal Epithelium Grafting for Corneal Limbus Substitution

Not Applicable

Recruiting

• Conditions: Limbal Stem-cell Deficiency
• Interventions: Procedure: Labial mucosal epithelium grafting for corneal limbus substitution

• Registration Number: NCT04995926
• Lead Sponsor: The S.N. Fyodorov Eye Microsurgery State Institution

Brief Summary

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.

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 Timeline

• Study Start: 2021-07-01
• Study First Submitted: 2021-08-02
• Study First Submitted QC: 2021-08-02
• Study First Posted: 2021-08-09
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-20
• Last Update Posted: 2024-04-23
• Primary Completion: 2024-05-30
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 20

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Labial mucosa epithelium grafting for corneal limbus substitution.	Labial mucosal 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.

Primary Outcome Measures

Name	Time	Method
Anatomical success	12 months	Presence of a stable epithelium on the cornea and absence of conjunctivalization in the visual axis of the recipient eye

Secondary Outcome Measures

Name	Time	Method
Number of participants with improvement in corneal status	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.
Functional success	12 months	Improvement in near and/or distance visual acuity
Rate of complications	12 months	Intraoperative and postoperative complications on the recipient eye

Trial Locations

Locations (1)

The S. Fyodorov Eye Microsurgery Federal State Institution; 🇷🇺 Moscow, Russian Federation