Corneal Epithelial Allograft From Living-related Donor for LSCD

A Non-randomized Controlled Clinical Trial of Epithelial Allograft Transplantation From Living-related Donors for the Treatment of Limbal Stem Cell Deficiency

The purpose of the study is to explore whether femtosecond laser-assisted corneal epithelial allograft from living-related donor is more effective than limbal conjunctival allograft from living-related donor for ocular surface reconstruction in patients with limbal stem cell deficiency (LSCD).

Study Overview

• Status: Completed
• Conditions: Limbal Stem Cell Deficiency
• Intervention / Treatment: Procedure: Corneal epithelial allograft; Device: Femtosecond laser; Procedure: Limbal conjunctival allograft; Device: Diamond knife

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Zhongshan Ophthalmic Center, Sun Yat-sen Univerisity

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 80 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. LSCD secondary to ocular burns, with the duration of disease of at least 24 months at the time of screening visit;
2. Presence of superficial neo-vascularization affecting at least 2 cornea quadrants and involving central cornea;
3. Having a human leukocyte antigen (HLA)-matched living-related donor (≥4/6 HLA-A/B/DR matched);
4. Informed consent signed by patient or legal guardian. Having the ability to comply with study assessments for the full duration of the study.

Exclusion Criteria:

Recipients:

1. LSCD of mild degree, with less than 2 quadrants of neo-vessel invasion and without central cornea involvement;
2. LSCD by ocular surface disorders other than ocular burn;
3. Eyelids malposition;
4. The center corneal thickness<450µm, the depth of corneal opacity > 150µm;
5. High myopia with a spherical equivalent of -15.0 D or less;
6. Corneal or ocular surface infection within 30 days prior to study entry;
7. Ocular surface malignancy;
8. Uncontrolled diabetes with most recent Hemoglobin A1c greater than 8.5%;
9. Renal failure with creatinine clearance< 25ml/min;
10. Alanine aminotransferase > 40IU/L, or aspartate aminotransferase > 40IU/L;
11. Platelet levels < 150,000 or > 450,000 per microliter;
12. Hemoglobin < 12.0 g/dL (male) or < 11.0 g/dL (female);
13. Prothrombin time > 16s and activated partial thrombin time > 35s in patients not accepting anticoagulant therapy; An international normalized ratio greater than 3 in patients accepting anticoagulant therapy;
14. Pregnancy (positive test) or lactation;
15. Participation in another simultaneous medical investigation or clinical trial;
16. Severe cicatricial eye disease; Conjunctival scarring with fornix shortening;
17. Ocular comorbidities that affect the prognosis of transplantation, such as advanced glaucoma or retinal diseases;
18. Severe dry eye disease as determined by Schirmer's test < 2mm at least in one eye;
19. Any medical or social condition that in the judgment of the investigator would interfere with or serve as a contraindication to adherence to the study protocol or ability to give informed consent;
20. Signs of current infection, including fever and treatment with antibiotics;
21. Active immunological diseases;
22. History of allo-limbal transplantation, penetrating keratoplasty or anti-glaucoma filtering surgeries.

Donors:

1. Cornea diseases (epithelial defects, neovascularization, etc.);
2. Eyelids malposition;
3. The center corneal thickness<450µm, the depth of corneal opacity > 150µm;
4. High myopia with a spherical equivalent of -15.0 D or less;
5. Corneal or ocular surface infection within 30 days prior to study entry;
6. Ocular surface malignancy;
7. Uncontrolled diabetes with most recent Hemoglobin A1c greater than 8.5%;
8. Renal failure with creatinine clearance< 25ml/min;
9. Alanine aminotransferase > 40IU/L, or aspartate aminotransferase > 40IU/L;
10. Platelet levels < 150,000 or > 450,000 per microliter;
11. Hemoglobin < 12.0 g/dL (male) or < 11.0 g/dL (female);
12. Prothrombin time > 16s and activated partial thrombin time > 35s in patients not accepting anticoagulant therapy; An international normalized ratio greater than 3 in patients accepting anticoagulant therapy;
13. Pregnancy (positive test) or lactation;
14. Participation in another simultaneous medical investigation or clinical trial;
15. Severe cicatricial eye disease; Conjunctival scarring with fornix shortening;
16. Ocular comorbidities that affect the prognosis of transplantation, such as advanced glaucoma or retinal diseases;
17. Severe dry eye disease as determined by Schirmer's test < 2mm at least in one eye;
18. Any medical or social condition that in the judgment of the investigator would interfere with or serve as a contraindication to adherence to the study protocol or ability to give informed consent;
19. Signs of current infection, including fever and treatment with antibiotics;
20. Active immunological diseases;
21. History of allo-limbal transplantation, penetrating keratoplasty or anti-glaucoma filtering surgeries.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Cornea epithelial allograft; Femtosecond laser assisted corneal epithelial allograft from live relatives in the treatment of limbal stem cell deficiency (LSCD)	Procedure: Corneal epithelial allograft; A living-related donor's epithelial flap, equal in area to the recipient's diseased cornea bed, will be created using femtosecond laser technology. This corneal epithelial allograft is then ready for transplantation on the recipient's disease eye, following removal of the recipient's scarred and diseased epithelium.; Device: Femtosecond laser; A commercial femtosecond laser to create a particular shaped graft for transplantation
ACTIVE_COMPARATOR: Limbal conjunctival allograft; Diamond knife assisted limbus conjunctival allograft from live relatives in the treatment of limbal stem cell deficiency (LSCD)	Procedure: Limbal conjunctival allograft; A 3- to 5- clock hour limbal-conjunctival allograft will be obtained from the living-related eye. This is then ready for transplantation on the recipient's disease eye following removal of the recipient's scarred and diseased epithelium.; Device: Diamond knife; A diamond knife to create a particular shaped limbal graft for transplantation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Restoration of corneal surface in the recipient	Restoration of a completely epithelized, stable, and avascular corneal surface in the recipient	1 year
Restoration of corneal surface in the donor	Restoration of a completely epithelized, stable, and avascular corneal surface in the donor	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Uncorrected and best-corrected visual acuity of recipients and donors	To assess changes of uncorrected and best-corrected visual acuity using ETDRS chart.	1 year
Corneal power, astigmatism and aberration of recipients and donors	To measure changes of corneal power, astigmatism and aberration using autorefractor keratometer and wavefront aberrometer respectively.	1 year
Corneal sensation of recipients and donors	To measure corneal sensation using Cochet-Bonnet esthesiometer.	1 year
Corneal thickness of recipients and donors	To measure corneal thickness using Anterior Segment Optical Coherence Tomograph (AS-OCT).	1 year
Density of stromal nerve and stromal keratocytes of recipients and donors	To measure density of stromal nerve and stromal keratocytes using in vivo confocal microscopy	1 year
Reconstruction of limbal palisades of Vogt of recipients	To assess reconstruction of limbal palisades of Vogt using in vivo confocal microscopy.	1 year
Corneal graft rejection of recipients	To assess corneal graft rejection using slit-lamp microscopy.	1 year
Corneal haze of recipients and donors	To assessing corneal haze using in vivo confocal microscopy	1 year

Collaborators and Investigators

• Sponsor: Chunxiao Wang

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 27, 2017
• Primary Completion (ACTUAL): November 13, 2019
• Study Completion (ACTUAL): November 13, 2019

Study Registration Dates

• First Submitted: July 12, 2017
• First Submitted That Met QC Criteria: July 12, 2017
• First Posted (ACTUAL): July 14, 2017

Study Record Updates

• Last Update Posted (ACTUAL): February 28, 2020
• Last Update Submitted That Met QC Criteria: February 27, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Other Study ID Numbers: 2017KYPJ057

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No