CORNEAL GRAFT

Advanced tissue typing techniques such as human leukocyte antigen (HLA) matching deserve greater attention as a potential means of increasing the survival of corneal grafts over the long term, according to John Armitage PhD, director of tissue banking at the University of Bristol, UK. “HLA matching in corneal transplantation remains a controversial issue, although I think it is now reasonably accepted, at least in Europe, that HLA class I matching is beneficial for the survival of grafts in penetrating keratoplasty procedures,” he told delegates attending the 2013 Congress of the Society of European Ophthalmology (SOE).

He added that a lot more research was needed to resolve questions relating to possible benefits or otherwise of HLA class II matching and understand more about the way HLA responses are modulated in the anterior chamber. A wide range of factors have been invoked over the years to explain the cornea’s immune-privileged status, including the absence of lymphatic and blood vessels in the corneal graft bed, the expression of Fas ligand on corneal cells, low-level expression of HLA antigens, the paucity of mature antigen-presenting macrophages or Langerhans cells, and the presence of immunomodulatory cytokines such as α-melanocyte–stimulating hormone and transforming growth factor in aqueous humour, among other reasons.

“Despite this relative immune privilege, I think what we know now is that all of these factors can be overridden by inflammatory responses, leading to rejection and graft failure,” he said. Prof Armitage said that there is actually little evidence to justify the oft-repeated mantra that corneal transplantation is the most successful of all organ transplants.

“If you look at penetrating keratoplasty data from the United Kingdom and compare it with first renal transplants, the first year survivals are very similar, but by the time we reach five years then corneal transplant survival at 73 per cent is worse than renal which had an 83 per cent survival rate,” he said. Around 34 per cent of these penetrating keratoplasty failures are caused by allograft rejection, said Prof Armitage.

“Even if the surgeons are able to control and reverse the rejection episodes, long-term survival is compromised, as shown by data from the Australian corneal graft registry. For grafts that have suffered one or more rejection episodes, the survival rate after 10 years is halved. Probably the reason for that is that with each rejection episode we tend to lose corneal endothelial cells and these cells can continue to be lost at an accelerated rate many years after the transplant,” he said. Prof Armitage said that there are several studies in the scientific literature showing that HLA class I matching reduces the risk of graft rejection.

“A more recent study in the UK found that matching for HLA class I antigens in bullous keratopathy patients reduced the risk of graft failure at five years by twoand- a-half-fold, which is quite a big impact. And Prof Thomas Reinhard’s group in Freiburg, Germany, has also shown that HLA matching reduced the risk of rejection even in apparently low-risk grafts,” he said.

Prof Armitage said that while contradictory results on the benefits of HLA matching have been obtained in previous trials, ongoing studies using modern DNA typing techniques should help to demonstrate that HLA typing has a positive role in reducing the rate of allograft rejection in both high- and low-risk patients.