One of the most common transplant procedures in humans today is penetrating keratoplasty 1,2 (more recognizable to patients as corneal transplant or graft). The main aims of a corneal graft are to improve vision, reduce pain and repair structural damage. A successful visual outcome depends on the long-term survival of the graft.

With careful management, corneal grafts can have a high success rate in the short-term. Yet, in contrast to many vascularised organ grafts where failures tend to occur within the first year post-transplant, the attrition rate for corneal grafts is typically slow, but inexorable. In many centres, the need for re-grafting a failed corneal transplant is one of the main indications for corneal transplantation 3 – utilizing donor corneas that could potentially have been donated to other patients, and further threatening an already short supply of donor corneas.

Corneal graft failure may occur as a result of bad donor tissue (primary failure) or due to early or late post-operative complications. However, one of the most common reasons for corneal graft failure is immunological corneal graft rejection 1,4 which occurs in around 30% of cases 5,6 Rejection can occur at any layer of the cornea, but the decisive factor for the survival of a corneal graft is the integrity of the corneal endothelium, a non-replicating monolayer of cells that is largely responsible for maintaining corneal clarity. Any factor that adversely affects this layer can result in endothelial rejection, usually accompanied by ‘deep’ stromal rejection, which can be difficult to manage effectively compared with epithelial (superficial) rejection. Effective prevention or treatment is essential as corneal graft rejection can result in serious, sometimes irreversible ocular damage. 7

There are a number of risk factors that can help to predict the likelihood of corneal graft rejection, these include:

Of these, neovascularisation within the normally avascular host cornea prevails as the most established and recognized risk factor 1,7 with an increased risk of rejection that ranges from 0–10% in avascular host corneas to 25–50% in severely vascularised host corneas.8

Symptoms of corneal revascularisation can range from asymptomatic and mild (with some patients noticing redness around the cornea) to severe (eye pain, tearing and photophobia, redness, contact lens intolerance after a few hours of wear, decreased vision). In particular, revascularisation in the cornea's visual axis can threaten visual function directly or through secondary hemorrhage, scarring or lipid deposition.