Functional antigen matching in corneal transplantation: matching for the HLA-A, -B and -DRB1 antigens (FANCY) – study protocol

BACKGROUND: Penetrating keratoplasty can commonly restore vision in corneal blindness. However, immunological graft reactions may induce irreversible graft failure in a substantial percentage. Repeat keratoplasties in turn are associated with increased risk of graft failure and possibly irreversible blindness. Topical as well as systemic immunosuppressants are administered for prophylaxis. However, severe adverse effects limit long-term usage. By contrast, matching for transplantation antigens might be effective for a long time. METHODS: FANCY is a prospective, controlled, randomised, double-blind, multi-centre clinical trial with two parallel arms. The primary objective is to evaluate superiority of the proposed HLA matching strategy in comparison to random graft assignment with respect to the primary endpoint ‘time to first endothelial graft rejection’. Relevant inclusion criteria are age over 18 years and waiting for penetrating or endothelial lamellar keratoplasty. The most important exclusion criteria are abuse of medication and/or drugs and an anticipated waiting time for an HLA match longer than 6 months. After randomisation, patients either receive a HLA-matched graft (experimental intervention) or a random graft (control intervention). The calculated sample size is 620 patients. The trial started in 2009 with a recruitment period of 24 months. A total of 654 patients were included during this time. DISCUSSION: The primary goal of FANCY is to assess whether histocompatibility matching is feasible and effective in the broad clinical routine. However, during the course of the trial, the landscape of keratoplasty changed due to the rise of Descemet Membrane Endothelial Keratoplasty (DMEK). Nowadays, immune reactions are confined mostly to the ‘high-risk’ subgroups. If we would design FANCY in 2014, we would narrow down the inclusion criteria to include only the high risk patients and accept longer waiting times for a matching donor here. TRIAL REGISTRATION: The unique identifying number of the FANCY trial is NCT00810472.