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Corneal Transplant Follow-up Study II: a randomised trial to determine whether HLA class II matching reduces the risk of allograft rejection in penetrating keratoplasty

Armitage, WJ; Winton, HL; Jones, MNA; Downward, L; Crewe, JM; Rogers, CA; Tole, DM; (2020) Corneal Transplant Follow-up Study II: a randomised trial to determine whether HLA class II matching reduces the risk of allograft rejection in penetrating keratoplasty. British Journal of Ophthalmology 10.1136/bjophthalmol-2020-317543. (In press). Green open access

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Abstract

PURPOSE: A randomised trial to test the hypothesis that human leucocyte antigen (HLA) class II matching reduces the risk of allograft rejection in high-risk penetrating keratoplasty (PK). METHODS: All transplants were matched for HLA class I antigens (≤2 mismatches at the A and B loci) and corneas were allocated to patients by cohort minimisation to achieve 0, 1 or 2 HLA class II antigen mismatches. The corneal transplants (n=1133) were followed for 5 years. The primary outcome measure was time to first rejection episode. RESULTS: Cox regression analysis found no influence of HLA class II mismatching on risk of immunological rejection (HR 1.13; 95% CI 0.79 to 1.63; p=0.51). The risk of rejection in recipients older than 60 years was halved compared with recipients ≤40 years (HR 0.51; 95% CI 0.36 to 0.73; p=0.0003). Rejection was also more likely where cataract surgery had been performed after PK (HR 3.68; 95% CI 1.95 to 6.93; p<0.0001). In univariate analyses, preoperative factors including chronic glaucoma (p=0.02), vascularisation (p=0.01), inflammation (p=0.03), ocular surface disease (p=0.0007) and regrafts (p<0.001) all increased the risk of rejection. In the Cox model, however, none of these factors was individually significant but rejection was more likely where≥2 preoperative risk factors were present (HR 2.11; 95% CI 1.26 to 3.47; p<0.003). CONCLUSIONS: HLA class II matching, against a background of HLA class I matching, did not reduce the risk of allograft rejection. Younger recipient age, the presence of ≥2 preoperative risk factors and cataract surgery after PK all markedly increased the risk of allograft rejection. TRIAL REGISTRATION NUMBER: ISRCTN25094892.

Type: Article
Title: Corneal Transplant Follow-up Study II: a randomised trial to determine whether HLA class II matching reduces the risk of allograft rejection in penetrating keratoplasty
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1136/bjophthalmol-2020-317543
Publisher version: https://doi.org/10.1136/bjophthalmol-2020-317543
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
URI: https://discovery.ucl.ac.uk/id/eprint/10117322
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