title: Synergistic antiherpetic effect of acyclovir and mycophenolate mofetil following keratoplasty in patients with herpetic eye disease: first results of a randomised pilot study.
abstract: OBJECTIVE
  The main reasons for graft failure following penetrating keratoplasty in patients with herpetic eye disease are recurrence of herpetic disease and allograft rejection. In a randomised trial the effect of systemic acyclovir and mycophenolate mofetil (MMF) on these post-keratoplasty complications was evaluated.
  
  
  METHODS
  Patients with typical clinical findings of recurrent herpetic keratitis were enrolled in this single-centre study after contraindications to systemic immunosuppression were ruled out. In a prospective randomised trial 30 patients were treated in three groups. In group A patients received acyclovir 200 mg five times/day for 3 weeks. In group B patients were treated with acyclovir 200 mg five times/day for 1 year, and patients in group C received acyclovir 200 mg five times/day in combination with MMF 1 g twice daily for 1 year.
  
  
  RESULTS
  In group A 3 patients experienced seven herpes recurrences. One patient had a moderate and one further patient a severe allograft rejection. In group B three severe allograft rejections were observed. Herpes recurrences did not occur while receiving acyclovir prophylaxis, but only once after the prophylaxis had been stopped. In group C no herpes recurrence was observed, and only two mild allograft rejections occurred while being under combined acyclovir-MMF therapy. Another mild and one moderate allograft rejection were observed after cessation of MMF.
  
  
  CONCLUSIONS
  These results demonstrate that systemic acyclovir protects the grafts from recurrences of herpetic disease as long as it is administered at efficient doses. Simultaneously administered mycophenolate mofetil does not trigger herpes recurrences and protects the graft from severe allograft rejections, but mild, less dangerous immune reactions may still occur while receiving MMF. The combination of systemic acyclovir and mycophenolate mofetil therefore is recommended for patients at high risk for herpes recurrence and allograft rejections.
authors.affiliation: Eye Hospital, Heinrich Heine University, Moorenstrasse 5, 40225 Düsseldorf, Germany. klaus.mayer@uni-duesseldorf.de
authors.forename: Klaus
authors.initials: K
authors.lastname: Mayer
authors.forename: Thomas
authors.initials: T
authors.lastname: Reinhard
authors.forename: Alexander
authors.initials: A
authors.lastname: Reis
authors.forename: Adina
authors.initials: A
authors.lastname: Voiculescu
authors.forename: Rainer
authors.initials: R
authors.lastname: Sundmacher
mesh_terms: D000212:Acyclovir / Q000627:therapeutic use*; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D018259:Herpesvirus 1, Human / Q000502:physiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016849:Keratitis, Herpetic / Q000517:prevention & control* / Q000821:virology; D015948:Keratoplasty, Penetrating; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D010865:Pilot Projects; D011183:Postoperative Complications / Q000517:prevention & control* / Q000821:virology; D011446:Prospective Studies; D012008:Recurrence; D014775:Virus Activation / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D000212:Acyclovir