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

• Published in: British journal of ophthalmology Vol. 106; no. 1; p. 42
• Main Authors: Armitage, W John, Winton, Helen L, Jones, Mark N A, Downward, Lewis, Crewe, Julie M, Rogers, Chris A, Tole, Derek M, Dick, Andrew D
• Format: Journal Article
• Language: English
• Published: England 01-01-2022
• Subjects: Allografts; Cataract; Corneal Transplantation; Follow-Up Studies; Graft Rejection - prevention & control; Graft Survival; Histocompatibility Testing; Humans; Keratoplasty, Penetrating; HLA class II; HLA matching; allograft rejection; corneal transplantation; immunological rejection
• ISSN: 1468-2079
• DOI: 10.1136/bjophthalmol-2020-317543

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).
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.
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).
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.
ISRCTN25094892.