Pathogenetic Risk Factors for Corneal Graft Rejection

February 24, 2024 updated by: Alexander Romanov, The S.N. Fyodorov Eye Microsurgery State Institution

Pathogenetic Risk Factors for Corneal Graft Rejection in Penetrating Keratoplasty Patients

There are many predictors that may influence the development of corneal graft rejection after penetrating keratoplasty. In our study investigators analysed the results of keratoplasty and the risk factors for graft rejection.

Investigators analysed data from 493 patients who underwent penetrating keratoplasty between 2011 and 2019. Keratoplasty outcomes were followed up at subsequent clinic visits until December 2021. Then, 93 medical records were selected (taking into account the completeness of the medical records) and divided into two groups based on the primary diagnosis that was an indication for keratoplasty: high-risk and low-risk patients. Investigators then estimated the survival time (clear graft) of the corneal graft using Kaplan-Meier statistical survival analysis. Investigators also investigated the factors that influence corneal graft opacity.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The pathogenesis of corneal graft rejection (CGR) is complex and is associated with numerous risk factors related to the donor, recipient and surgical technique.

Donor-related factors. These include AB0 and HLA incompatibility. Compared to corneal transplantation from a male donor to a male recipient, corneal transplantation from a male donor to a female recipient is associated with HR (high risk) CGR. Factors such as the method of storage of the donor cornea, sex mismatch between recipient and donor, and cause of death of the donor are not thought to have a significant impact on the outcome of keratoplasty. However, storage of donor tissue in organ culture medium for 7 days or more may reduce the incidence CGR.

Recipient-related factors. The most important risk factor for corneal graft rejection is the degree of corneal neovascularization (CNV) in the recipient. Another risk factor is rekeratoplasty. The presence of chronic diseases - herpes keratitis, uveitis, atopic dermatitis - also increases the risk of immune reactions. Dry eye syndrome (DES) and a history of glaucoma increase the risk of keratoplasty rejection. The presence of antibodies after rejection of other previously transplanted organs and blood transfusions can significantly increase the risk of rejection. Low limbal stem cell counts due to degradation of the limbal palisades of Vogt may lead to poor re-epithelialisation and development of corneal damage in the post-operative period.

Surgical factors. It has been observed that penetrating keratoplasty (PKP) has a lower graft survival rate than lamellar keratoplasty (LKP).

The aim of this study was to analyse the results of keratoplasty and to identify the risk factors for post-operative opacities of the corneal graft.

The study was conducted in accordance with the ethical standards of the authors' institutions and the Declaration of Helsinki (revised in 2013) and was approved by the Local Biomedical Ethics Committee of the The S.N. Fyodorov Eye Microsurgery State Institution no. 1 from 11.09.2019. Written informed consent was not required for participation in the study. The study was retrospective and patient data were anonymised.

Study design and groups The data of patients (n = 493) with corneal surgeries performed in " ISTC "Eye Microsurgery" named after Acad. S.N. Fedorov" Krasnodar for the period from 2011 to 2019. The results of keratoplasty were tracked at the patients' subsequent visits to the clinic until December 2021. Thus, the study included data from 8 years of postoperative follow-up of the patients.

In the next step, 93 medical records were selected from the entire cohort of patients who underwent penetrating keratoplasty (PKP), taking into account the completeness of data and records. These cases were divided into two groups without randomisation according to the primary diagnosis that indicated keratoplasty:

  • Group 1 - low-risk (LR) keratoplasty - if the patient was diagnosed with keratoconus and there were no concomitant complicating diagnoses (n = 42);
  • Group 2 - high-risk (HR) keratoplasty - in the presence of corneal dystrophy (pseudophakic bullous keratopathy, primary dystrophy), corneal inflammatory pathology (erosions, corneal ulcers, corneal fistulas,leucoma), complicated keratoconus, CGR or rekeratoplasty (n = 51).

Pharmacological management postoperative Antibiotics, antiseptics, keratoprotectors and Lubricating Eye Drops and gels were used for postoperative pharmacological management.

Methods of clinical evaluation of keratoplasty outcomes In the overall cohort group, recipient-related factors (ophthalmological and somatic status), primary and concomitant diagnoses, type of keratoplasty and postoperative complications were assessed.

In the next step, diagnostic data of the patients' ophthalmological examinations were obtained from electronic medical records and archives: examination and consultation by an ophthalmologist, refractometry, keratometry, visometry, tonometry, endothelial cell density (ECD), Schirmer test, optical coherence tomography (OCT) of the anterior segment, as well as graft characteristics and incidence of postoperative complications.

In groups 1 and 2, the assessment of graft transparency at each visit and signs of CGR, if present, were recorded in the medical records. CGR (or postoperative graft opacity) was defined if rekeratoplasty was performed and the loss of central graft transparency caused visual impairment for at least three consecutive months, if the patient's database or medical record mentioned the development of CGR as a diagnosis or postoperative complication. Stages of data analysis: 0 - at hospital admission before keratoplasty, 1, 3, 6, 9, 12 months after surgery. The anatomical results of keratoplasty (clear graft or postoperative graft opacity) in the cohort group and in groups 1 LR and 2 HR - were evaluated during the follow-up period of 8 years.

Study Type

Observational

Enrollment (Actual)

93

Contacts and Locations

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

Study Locations

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

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

corneal inflammatory pathology (erosions, corneal ulcers, corneal fistulas,leucoma), complicated keratoconus, CGR or rekeratoplasty

Description

Inclusion Criteria:

  • completeness of data and records

Exclusion Criteria:

  • no

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

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Group 1 - low-risk (LR) keratoplasty
if the patient was diagnosed with keratoconus and there were no concomitant complicating diagnoses (n = 42)
Procedure: penetrating keratoplasty
replacement of the affected tissue with healthy donor tissue in diseases that disrupt the shape or transparency of the cornea.
Group 2 - high-risk (HR) keratoplasty
in the presence of corneal dystrophy (pseudophakic bullous keratopathy, primary dystrophy), corneal inflammatory pathology (erosions, corneal ulcers, corneal fistulas,leucoma), complicated keratoconus, CGR or rekeratoplasty (n = 51)
Procedure: penetrating keratoplasty
replacement of the affected tissue with healthy donor tissue in diseases that disrupt the shape or transparency of the cornea.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cohort group Kaplan-Meier survival analysis (clear graft engraftment)
Time Frame: 2011-2019
Investigators used Kaplan-Meier survival analysis to evaluate the survival (clear graft) of the corneal graft in this cohort.
2011-2019

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

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)

January 1, 2011

Primary Completion (Actual)

January 1, 2019

Study Completion (Actual)

January 1, 2019

Study Registration Dates

First Submitted

January 31, 2024

First Submitted That Met QC Criteria

February 24, 2024

First Posted (Actual)

February 28, 2024

Study Record Updates

Last Update Posted (Actual)

February 28, 2024

Last Update Submitted That Met QC Criteria

February 24, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • SNFyodorov

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

It is not yet known if there will be a plan to make the iPad available.

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 Graft Rejection

Clinical Trials on penetrating keratoplasty

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Albania

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe