The cornea is the most commonly transplanted human tissue. It is estimated that globally over 65000 corneal transplants are being performed each year. 1 Over 16 000 corneal transplants were performed in the UK alone since 2005. 2 The cornea is largely considered to be an immune privileged site. There are several attributes that contribute to this notion such as the compact architecture of the corneal stroma, which is believed to retard migration of immune cells; the physiological bloodeaqueous barrier that prevents any immunogenic mediators and cells entering the ocular tissue; 3 the relative lack of lymphatics and blood vessels; the presence of unique factors within the ocular fluids like transforming growth factor-b, calcitonin gene-related peptide, melanocyte stimulating hormone and vasoactive intestinal peptide and cortisol binding globulin, 4e6 which contribute to immune modulation/anterior chamber associate immune deviation wherein antigen introduced in to the anterior chamber results in antigen specific suppression of delayed hypersensitivity; 7 mucosal tolerance induced by conjunctiva associated lymphoid tissue, 8 and constitutive expression of Fas ligand which promotes apoptosis in cells bearing Fas such as lymphocytes. 9 Notwithstanding the above, immune mediated graft rejection is the single most important cause of graft failure. Although the 1-year survival rate is around 87%, it steadily falls thereafter. 10 The reported rate of rejection varies widely in several studies and ranges from 2.3% to 68%. 11 The highest incidence of rejection is in the first 1e3 years after transplantation (29% and 43%) but can occur very late. A rate of 21% e29% is reported at 15 years. 12 13

Following penetrating keratoplasty (PKP), graft rejection can occur in any of the three main corneal layers, in isolation or in different combinations. The most common and most sight threatening one is endothelial graft rejection which is characterised by limbal injection, cells in the anterior chamber, keratic precipitates on the graft (not the host rim) and oedema of the graft. The Khodadoust line, an endothelial rejection line of keratic precipitates, is a classical sign but not always present. It usually starts from the (inferior) periphery of the graft, sometimes close to an inciting stromal vessel and migrates towards the centre of the graft in a sinuous manner leaving segmental stromal oedema in its wake. When it is irreversible, endothelial rejection leads to diffuse corneal oedema, bullous keratopathy and eventually graft opacity.