Pathogenetic Risk Factors for Corneal Graft Rejection

NCT ID: NCT06281587

Last Updated: 2024-02-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

93 participants

Study Classification

OBSERVATIONAL

Study Start Date

2011-01-31

Study Completion Date

2019-01-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Graft Rejection

Study Design

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Observational Model Type

COHORT

Study Time Perspective

RETROSPECTIVE

Study Groups

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Group 1 - low-risk (LR) keratoplasty

if the patient was diagnosed with keratoconus and there were no concomitant complicating diagnoses (n = 42)

penetrating keratoplasty

Intervention Type PROCEDURE

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)

penetrating keratoplasty

Intervention Type PROCEDURE

replacement of the affected tissue with healthy donor tissue in diseases that disrupt the shape or transparency of the cornea.

Interventions

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penetrating keratoplasty

replacement of the affected tissue with healthy donor tissue in diseases that disrupt the shape or transparency of the cornea.

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* completeness of data and records

Exclusion Criteria

* no
Minimum Eligible Age

13 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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The S.N. Fyodorov Eye Microsurgery State Institution

OTHER_GOV

Sponsor Role lead

Responsible Party

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Alexander Romanov

Head of the Department

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Krasnodar, , Russia

Site Status

Countries

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Russia

References

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Inoue K, Tsuru T. ABO antigen blood-group compatibility and allograft rejection in corneal transplantation. Acta Ophthalmol Scand. 1999 Oct;77(5):495-9. doi: 10.1034/j.1600-0420.1999.770501.x.

Reference Type RESULT
PMID: 10551286 (View on PubMed)

Di Zazzo A, Kheirkhah A, Abud TB, Goyal S, Dana R. Management of high-risk corneal transplantation. Surv Ophthalmol. 2017 Nov-Dec;62(6):816-827. doi: 10.1016/j.survophthal.2016.12.010. Epub 2016 Dec 22.

Reference Type RESULT
PMID: 28012874 (View on PubMed)

Guilbert E, Laroche L, Borderie V. [Rejection of corneal allografts]. J Fr Ophtalmol. 2011 May;34(5):331-48. doi: 10.1016/j.jfo.2011.02.001. Epub 2011 Apr 14. French.

Reference Type RESULT
PMID: 21492957 (View on PubMed)

Hopkinson CL, Romano V, Kaye RA, Steger B, Stewart RM, Tsagkataki M, Jones MN, Larkin DF, Kaye SB; National Health Service Blood Transplant Ocular Tissue Advisory Group and Contributing Ophthalmologists (OTAG Study 20). The Influence of Donor and Recipient Gender Incompatibility on Corneal Transplant Rejection and Failure. Am J Transplant. 2017 Jan;17(1):210-217. doi: 10.1111/ajt.13926. Epub 2016 Jul 22.

Reference Type RESULT
PMID: 27412098 (View on PubMed)

Simon M, Fellner P, El-Shabrawi Y, Ardjomand N. Influence of donor storage time on corneal allograft survival. Ophthalmology. 2004 Aug;111(8):1534-8. doi: 10.1016/j.ophtha.2003.12.060.

Reference Type RESULT
PMID: 15288984 (View on PubMed)

Writing Committee for the Cornea Donor Study Research Group; Sugar A, Gal RL, Kollman C, Raghinaru D, Dontchev M, Croasdale CR, Feder RS, Holland EJ, Lass JH, Macy JI, Mannis MJ, Smith PW, Soukiasian SH, Beck RW. Factors associated with corneal graft survival in the cornea donor study. JAMA Ophthalmol. 2015 Mar;133(3):246-54. doi: 10.1001/jamaophthalmol.2014.3923.

Reference Type RESULT
PMID: 25322173 (View on PubMed)

Armitage WJ, Goodchild C, Griffin MD, Gunn DJ, Hjortdal J, Lohan P, Murphy CC, Pleyer U, Ritter T, Tole DM, Vabres B. High-risk Corneal Transplantation: Recent Developments and Future Possibilities. Transplantation. 2019 Dec;103(12):2468-2478. doi: 10.1097/TP.0000000000002938.

Reference Type RESULT
PMID: 31765363 (View on PubMed)

Yamaguchi T, Higa K, Tsubota K, Shimazaki J. Elevation of preoperative recipient aqueous cytokine levels in eyes with primary graft failure after corneal transplantation. Mol Vis. 2018 Sep 13;24:613-620. eCollection 2018.

Reference Type RESULT
PMID: 30262982 (View on PubMed)

Siebelmann S, Ramos SL, Matthaei M, Scholz P, Schrittenlocher S, Heindl LM, Bachmann B, Cursiefen C. Factors Associated With Early Graft Detachment in Primary Descemet Membrane Endothelial Keratoplasty. Am J Ophthalmol. 2018 Aug;192:249-250. doi: 10.1016/j.ajo.2018.05.010. Epub 2018 May 29. No abstract available.

Reference Type RESULT
PMID: 29858043 (View on PubMed)

Other Identifiers

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SNFyodorov

Identifier Type: -

Identifier Source: org_study_id

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