Purpose To describe a study to determine the influence of HLA class II matching on allograft rejection of high-risk, full-thickness corneal transplants.
Methods A prospective, longitudinal, clinical trial (ISRCTN25094892) with a primary outcome measure of time to first clinically determined rejection episode. Tissue typing used DNA-based techniques. Corneas were allocated to patients with ≤2 human leucocyte antigen (HLA) class I antigen mismatches by cohort minimisation to achieve 0, 1 or 2 HLA class II (HLA-DR) antigen mismatches. Transplants were to be followed up at 6 months and then annually on the anniversary of surgery for 5 years. Power calculations estimated a sample size of 856 transplants to detect a 0.1 difference in probability of rejection at 1 year between HLA class II matched and mismatched transplants at the 5% level of significance with 80% power.
Results To allow for loss to follow-up, 1133 transplants in 980 patients were accrued to the study between 3 September 1998 and 2 June 2011. 17% of transplants had 0 HLA-DR mismatches. The most frequent indication was bullous keratopathy, accounting for 27% of transplants and 54% of the transplants were regrafts. Median waiting time for a matched graft was 3 months. Donor and recipient characteristics were distributed evenly across the study groups.
Conclusion Recruitment to the CFS II has closed with 1077/1133 transplants meeting all the study criteria. Follow-up has been completed and final analysis of the data has started.
Trial registration number ISRCTN25094892 andUKCRNID9871, Pre-results.
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Contributors WJA is the principal investigator with overall responsibility for the study, study design, data analysis and interpretation, drafting and revising paper. HLW and JMC are the study co-ordinators, liaising with participating surgeons, contributed to drafting and review of paper. MNAJ did the statistical analysis and interpretation, contributed to drafting and review of paper. CAR statistical advice and interpretation, contributed to drafting and review of paper. DMT is the corneal transplant surgeon, advised on clinical aspects of the study, recruited patients for the study, contributed to the drafting and review of the paper. ADD is the ophthalmologist and specialist in ocular immunology, advised on clinical and immunological aspects of the study and data interpretation, contributed to drafting and review of paper.
Funding The study was funded principally by the National Eye Research Centre (grant no. SCIAD036) with start-up funding from the NHS Executive South and West Research and Development Directorate (grant no. R/14/09/06).
Competing interests None declared.
Patient consent Detail has been removed from this case description/these case descriptions to ensure anonymity. The editors and reviewers have seen the detailed information available and are satisfied that the information backs up the case the authors are making.
Ethics approval South West Research Ethics Committee favourable opinion: MREC/97/6/8 National Research Ethics Service: IRAS Project ID 11351.
Provenance and peer review Not commissioned; externally peer reviewed.
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