Pathogenetic Risk Factors for Corneal Graft Rejection

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.