Highly active antiviral and immunosuppressive combination therapy with acyclovir and mycophenolate mofetil following keratoplasty in patients with herpetic eye disease

BACKGROUND: Herpes simplex virus (HSV) infection is the most common cause of corneal blindness in developed countries. Penetrating keratoplasty is the only therapeutic option for visual rehabilitation in patients with severely scarred corneas. Recurrence of the underlying disease and allograft rejection (AR) are the common causes of graft failure. Systemic immuno-suppression with cyclosporin A is contraindicated due to the risk of HSV recurrence. The potent immunosuppressive properties of mycophenolate mofetil (MMF) have already been shown clinically. By reducing the intracellular guanosid-pool MMF inhibits the proliferation of lymphocytes. As these quanosin-nucleosides also act as competing substrates to acyclovir at the viral DNA-polymerase, a synergistic effect of MMF and acyclovir might be expected. The aim of this study was to evalute the efficacy and safety of a double-drug regimen with MMF and acyclovir in the prevention of acute allograft rejection and HSV recurrence following corneal transplantation. METHODS: Patients following penetrating keratoplasty due to herpetic eye disease have been treated with MMF 1 g twice dialy and acyclovir 5 x 200 mg/day for one year. Primary efficacy variables have been the number of acute AR and recurrence of herpetic disease per patient and time. The number of adverse events has been documented for safety analysis. RESULTS: Fifteen patients have been enrolled. The average follow up period was 9.1 (+/- 5.2) months. No graft opacifications have been seen. With two AR and no recurrence of herpetic disease the efficacy ofthis therapeutic regimen was supperior compared with historical control groups. CONCLUSION: In this first study on the efficacy and safety of a double drum regimen with acyclovir and MMF for the control of acute corneal AR and HSV-recurrenct following keratoplasty in patients with herpetic eye disease, the combination therapy has been shown to be a safe and highly efficient protocol for graft protection.