GRAFT REJECTION

The growing popularity of posterior lamellar keratoplasty techniques in recent years has led to a significant reduction in the risk of graft rejection after corneal transplants, according to researchers at the 2013 Congress of the European Society of Ophthalmology (SOE). “The primary reason for graft failure after penetrating keratoplasty (PKP) remains immune rejection, but thanks to the introduction of techniques such as Descemet’s stripping automated endothelial keratoplasty (DSAEK), and Descemet’s membrane endothelial keratoplasty (DMEK) we are now seeing a much better survival rate for these grafts in addition to improved visual outcomes,” Bjoern Bachmann MD, FEBO, told delegates. Dr Bachmann said that even though keratoplasty is renowned as the most successful form of solid organ transplantation, there is a graft failure rate of 20 per cent after five years in low-risk keratoplasty, with immune rejection the main cause. By comparison, the most recent data for DSEK procedures shows a downward trend in graft rejection rates of 7.5 per cent after one year and 12 per cent after two years.

Dr Bachmann cited the recent study by Price et al. which showed that DMEK had a graft rejection rate of one per cent at both one and two years, compared to PKP which had a rejection rate of 14 per cent at one year and 18 per cent at two years. “This shows that overall DMEK had a 15-fold lower risk of rejection than DSEK and a 20-fold lower risk than PKP,” he said. In his own clinical experience, Dr Bachmann said he had encountered only one DMEK rejection episode and that was a patient that had undergone the lamellar procedure after a previous PKP.

Dr Bachmann noted that when graft rejection does occur in DSAEK or DMEK procedures, the clinical signs are different from those typically found with PKP. “In a lot of patients we see only quite subtle inflammatory signs. One recent study found that 35 per cent of such cases were asymptomatic with the diagnosis obtained only after routine examination. “Other signs to watch for are isolated precipitates in almost 70 per cent of cases, diffuse corneal oedema in 11 per cent and combined precipitates and oedema in around one-fifth of patients,” he said. Endothelial rejection can present with an endothelial rejection line (Khodadoust line) that often begins at a vascularised portion of the peripheral graft-host junction and progresses, if untreated, across the endothelial surface over several days, said Dr Bachmann. The predominant cells are lymphocytes and macrophages that damage endothelial cells as the line moves across the endothelium. Such lines are more commonly associated with PKP procedures and are rarely found in lamellar keratoplasty, he said. The process leading to graft rejection is complex and multifactorial, said Dr Bachmann. The immune cascade begins when lymphatic vessels allow the transport of antigen-presenting cells from the graft bed to the regional lymph node in which they induce the activation and clonal expansion of alloantigen-specific T cells. These activated T cells subsequently migrate to the graft bed and initiate graft rejection, he said.

Dr Bachmann added that the lack of sutures in minimally-invasive DMEK procedures may also play a role in helping to reduce graft rejection rates, as sutures are known to induce corneal angiogenesis and lymphangiogenesis, which contribute to subsequent graft rejection. In addition, the graft transferred during DMEK does not contain corneal stroma and therefore probably lacks donor derived antigen presenting cells. These cells are important for the initiation of a donor specific alloimmune response. The fact that DMEK induces less disruption to the blood-aqueous barrier compared to PKP is also likely to play a role in the reduced rejection rate, he said.