VISICORT PI Prof Emeritus W. John Armitage of the University of Bristol on behalf of the CTFS II Study Group recently announced the publication of a novel corneal transplant follow-up study exploring whether tissue matching reduced the risk of rejection in corneal transplants. John kindly summarised the study and findings.
The cornea is the clear tissue at the front of the eye that lets in light and helps to focus images onto the retina at the back of the eye, enabling us to see. Damage or disease to the cornea can result in severe visual impairment and loss of vision. The only treatment option for many patients with these conditions is a corneal transplant with healthy tissue from a deceased donor. As with organ transplants, a corneal transplant may be recognized as ‘foreign’ by the patient’s immune system resulting in rejection of the transplanted tissue. While the overall success rate of corneal transplantation is generally high, there are certain conditions that can increase the risk of rejection, and immunological rejection is a leading cause of corneal transplant failure.
However, unlike organ transplants where tissue matching between donors and recipients reduces the risk of rejection, the evidence for a benefit of tissue matching in corneal transplantation is less clear cut. White blood cells carry certain markers, called human leucocyte antigens (HLA), which are an essential component of our immune system. Like blood groups, the HLA profile varies between individuals but shows far greater diversity. As with blood transfusion where blood groups are matched, tissue (HLA) matching between donors and recipients reduces the risk of rejection of transplanted organs. The two main groups of HLA thought to be relevant to corneal transplantation are HLA class I and HLA class II. There is some evidence to suggest that HLA class I antigen matching might be beneficial; but, for HLA class II matching, which is prioritized in kidney transplantation, studies have suggested a beneficial effect, no effect, or even a detrimental effect in corneal transplantation.
Most of the studies of tissue matching in corneal transplantation have relied on retrospective analyses of clinical outcome data often from a single centre. To investigate whether tissue matching is beneficial ideally requires a clinical trial where corneas with different degrees of tissue matching are randomized to patients. Our Corneal Transplant Follow-up Study II (CTFS II) was set up to investigate whether HLA class II matching reduced the risk rejection in corneal transplants. This was a randomized clinical trial where all the tissue typing for donors and recipients used DNA-based methodology to avoid the errors inherent in the serological methods used in previous studies. Transplants were followed for five years and the time to first rejection was the outcome measure. The study, which involved 31 hospitals in the UK, accrued 1133 transplants in 980 patients.
The results showed that HLA class II matching had no influence on the risk of rejection. However, the risk of rejection was shown to be higher in patients under 40 years old, in patients with higher numbers of preoperative risk factors, such as vascularized corneas, regrafts and glaucoma, and where a patient had cataract surgery after corneal transplantation. The lack of effect of HLA class II matching suggests that the way a recipient recognizes a corneal transplant as ‘foreign’ is different from organ transplants.
W John Armitage, on behalf of the CTFS II Study Group
Armitage WJ, Winton HL, Jones MNA, Downward L, Crewe JM, Rogers CA, Tole DM, Dick AD. 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. Br J Ophthalmol; 2020, doi: 10.1136/bjophthalmol-2020-317543