Clinical Study on the Treatment of Mixed Component Cornea for High Risk Keratoplasty

Suppression of Graft Rejection Using Mixed Component Cornea in the High-risk Keratoplasty，A Randomized Controlled Trial.

Because of the immunologically privileged nature of the cornea, the graft rejection rate is less than 10% for low-risk keratoplasty. But when the cornea performed 2 or more quadrants of corneal neovascularization after ocular trauma or infection, the graft rejection rate is more than 65%, it is called high-risk keratoplasty.

This study will observe the graft survival of high-risk corneal transplantation using mixed component cornea from different donors.

Study Overview

• Status: Recruiting
• Conditions: Corneal Transplantation
• Intervention / Treatment: Procedure: Limbal transplantation combined with central penetrating keratoplasty; Procedure: Limbal transplantation combined with central penetrating keratoplasty

Detailed Description

Ocular trauma or infection lead to corneal limbal stem cell deficiency and central corneal opacification which could only be treated by central penetrating keratoplasty and limbal transplantation, but the rejection rate is very high. In clinical, we found that limbal transplantation combined with central penetrating keratoplasty from different donors can keep the graft transparent for a long time, this result also be found in organ transplantation, multiple donor organ transplantation could reduce rejection risk in liver and kidney transplantation. Therefore, it is speculated that there are different MHC antigens from different donors, which cause different reactions after transplantation. Because there are a large number of Langerhans cells， abundant blood vessels and lymphatic in the limbal, so the rejection occurs early and severely. Continuous and intense limbal rejection leads to the depletion of recipient T cells, lead to the immune tolerance of another donor's central corneal tissue. In this project, central penetrating keratoplasty and limbal transplantation from different donors will be carried out and the graft survival of high-risk corneal transplantation will be observed in clinical, to find a new method for high-risk corneal transplant patients.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ting Huang, MD, PHD; Phone Number: 86-13552338050; Email: qingerdong@126.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Recruiting
      • Zhongshan Ophthalmic Center, Sun Yat-sen University
      • Contact: Ling Jin; Phone Number: 86-20-87334687; Email: lingjin41@yahoo.com
      • Principal Investigator: Ting Huang, MD, PHD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Central corneal opacity involving full layer
• Corneal neovascularization in two or more quadrants
• Patients must be willing and able to return for scheduled follow-up examinations for 12 months after surgery
• Ages：18 -70 Years

Exclusion Criteria:

• Central corneal opacity not involving the endothelial layer
• Less than two quadrants of corneal neovascularization
• History of Stevens-Johnson syndrome or Sjogren's syndrome
• Severe eyelid and conjunctival scar
• Loss of vision in contralateral eye
• Pregnant and lactating women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Single graft corneal transplantation; Limbal transplantation combined with central penetrating keratoplasty from single donors.	Procedure: Limbal transplantation combined with central penetrating keratoplasty; Limbal transplantation combined with central penetrating keratoplasty with single donor cornea; Procedure: Limbal transplantation combined with central penetrating keratoplasty; Limbal transplantation combined with central penetrating keratoplasty with mixed component cornea
Experimental: Dual graft corneal transplantation; Limbal transplantation combined with central penetrating keratoplasty from different donors.	Procedure: Limbal transplantation combined with central penetrating keratoplasty; Limbal transplantation combined with central penetrating keratoplasty with single donor cornea; Procedure: Limbal transplantation combined with central penetrating keratoplasty; Limbal transplantation combined with central penetrating keratoplasty with mixed component cornea

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The rate of corneal graft rejection at 12 months	The rejection index of corneal transplantation will be observed by slit lamp after surgery	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The changes of best corrected visual acuity	Best corrected visual acuity in different point will be compared with preoperative	Before surgery, 1 week, 1 month, 3 months, 6 months, 12 months
The changes of corneal thickness depth	Corneal thickness depth will be measured by anterior segmental OCT and compared with preoperative	baseline (Before surgery), 1 week, 1 month, 3 months, 6 months, 12 months
Reconstruction of corneal limbal	Confocal microscopy will be used to define whether the structure of corneal limbal has reconstructed	baseline (Before surgery), 1 week, 1 month, 3 months, 6 months, 12 months
Endothelial Cell Density	Endothelial Cell Density will be measured by specular microscope to evaluate the loss of endothelial cells	baseline (Before surgery), 1 week, 1 month, 3 months, 6 months, 12 months
The rate of presence of goblet cells containing conjunctival epithelium on the corneal surface by impression cytology	Detects whether conjunctival epithelial and goblet cells have invaded the corneal surface by impression cytology, to observe the reconstruction of limbal function	baseline (Before surgery), 1 week, 1 month, 3 months, 6 months, 12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intraocular pressure	Intraocular pressure will be measured by non contact tonometer as safety index	Before surgery, 1 week, 1 month, 3 months, 6 months, 12 months

Collaborators and Investigators

• Sponsor: Zhongshan Ophthalmic Center, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): August 18, 2020
• Primary Completion (Anticipated): July 1, 2023
• Study Completion (Anticipated): July 1, 2023

Study Registration Dates

• First Submitted: July 22, 2020
• First Submitted That Met QC Criteria: July 28, 2020
• First Posted (Actual): July 29, 2020

Study Record Updates

• Last Update Posted (Actual): February 24, 2022
• Last Update Submitted That Met QC Criteria: February 22, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Penetrating keratoplasty; High-risk corneal transplantation; Limbal transplantation
• Other Study ID Numbers: 2020KYPJ111

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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