June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Corneal Transplant Follow-up Study II (CTFS II) - HLA class II matching does not reduce risk of allograft rejection in high-risk penetrating keratoplasty
Author Affiliations & Notes
  • John Armitage
    Clinical Sciences, University of Bristol, Bristol, United Kingdom
  • Mark Jones
    NHS Blood and Transplant, Bristol, United Kingdom
  • Helen Winton
    Clinical Sciences, University of Bristol, Bristol, United Kingdom
  • Chris Rogers
    Clinical Sciences, University of Bristol, Bristol, United Kingdom
  • Derek Tole
    Bristol Eye Hospital, Bristol, United Kingdom
  • Andrew D Dick
    Clinical Sciences, University of Bristol, Bristol, United Kingdom
  • Footnotes
    Commercial Relationships John Armitage, None; Mark Jones, None; Helen Winton, None; Chris Rogers, None; Derek Tole, None; Andrew Dick, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 4358. doi:
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      John Armitage, Mark Jones, Helen Winton, Chris Rogers, Derek Tole, Andrew D Dick; Corneal Transplant Follow-up Study II (CTFS II) - HLA class II matching does not reduce risk of allograft rejection in high-risk penetrating keratoplasty. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4358.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: The role of HLA matching in corneal transplantation remains controversial. We designed an observational, prospective, longitudinal clinical trial (ISRCTN25094892) to determine the influence of HLA class II matching on the risk of allograft rejection in high-risk, HLA class I matched penetrating keratoplasties (PK).

Methods: Patients at increased risk of rejecting corneal allografts were registered for the study after giving informed consent and placed on a waiting list held by NHS Blood & Transplant (NHSBT). Tissue typing used DNA methodology to avoid the errors inherent in serological typing. All corneas were stored by organ culture for up to 4 weeks and had a minimum endothelial cell density of 2200 cells/mm². When corneas from a tissue-typed donor became available, the HLA type was compared with those of patients on the waiting list. Patients matched at HLA class I (≤2 mismatches) were identified and then the corneas allocated by cohort minimization to patients in this group with 0, 1 or 2 HLA class II mismatches. Patients were followed for 5 years. The primary outcome measure was time to first rejection episode. Data were analyzed both by univariate and multiple regression methods (Cox proportional hazards). The level of significance was set at p<0.05. Survival estimates and relative risks (RR) are quoted with 95% confidence intervals (95% CI).

Results: Recruitment closed with 1137 transplants. The overall rejection-free survival at 5 years was 60% (95% CI 56, 63; n=1072). Univariate Kaplan-Meier rejection-free survivals for 0, 1 and 2 HLA class II mismatches were, respectively, 60% (95% CI 51, 67; n=180), 63% (95% CI 57, 67; n=480), and 57% (95% CI 51, 62; n=412) (p=0.4). This lack of influence of HLA class II was confirmed in the Cox regression model (p=0.2). Recipient age had a major influence on rejection with recipients ≤40 years having a 3-fold greater risk of rejection than those over 60 years (RR 2.9, 95% CI 1.8, 4.7; p<0.0001). The next most influential factor was the number of preoperative risk factors. Recipients with ≥3 preoperative risk factors were at >2-fold higher risk of rejection than those with no risk factors (RR 2.3, 95% CI 1.5, 3.7; p=0.0004).

Conclusions: Matching for HLA class II did not reduce the risk of rejection in high risk PK matched for HLA class I.

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