Tacrolimus (FK506) in failed cyclosporin A therapy in endogenous posterior uveitis.
Tacrolimus (FK506) is effective in Japanese endogenous posterior uveitis (EPU), but there is limited data on its role in refractory EPU where cyclosporin A (CsA) toxicity/resistance develops. This open prospective clinical study aimed to assess the efficacy and adverse effects of low-dose FK506 therapy in western patients with refractory EPU where CsA resistance or toxicity has developed. Patients with CsA resistant/toxic EPU were started on low-dose (< 0.10 mg/kg/day) FK506 therapy. Immunosuppressive efficacy was assessed by visual acuity, binocular indirect ophthalmoscopy (BIO) scores, and change in clinical features. Adverse effects were assessed by routine biochemical tests (including serum creatinine) and symptoms. Seven patients (13 eyes), aged (mean +/- SD) 37.5 +/- 14.8 years, were recruited with previous CsA nephrotoxicity as the main indication and prior duration of EPU of (mean +/- SD) 13.1 +/- 7.3 years. Behçet's disease was the commonest diagnosis. FK506 therapy was maintained at 0.06 +/- 0.02 mg/kg/day, trough level of 8.7 +/- 1.8 ng/ml, in combination with low-dose prednisolone (0.11 +/- 0.04 mg/kg/day) in all patients for a mean duration of 8.7 months (range 1.0-17.7). From baseline (for 11 eyes with meaningful follow-up), visual acuity was maintained in nine eyes and BIO score improved in nine eyes. No major adverse effects developed, with only a 7.5 +/- 6.5% maximum increase in serum creatinine in patients with previous CsA-induced nephrotoxicity. Minor adverse effects (especially mild hyperglycaemia and neurological symptoms) were common and usually well tolerated, except for two patients in whom drug withdrawal was necessary, thus producing therapeutic failure. Low-dose FK506 is effective in refractory EPU as CsA-rescue therapy, and should be considered earlier in the evolution of refractory EPU.
Department of Ophthalmology, University of Aberdeen Medical School, Scotland, UK.
D J
DJ
Kilmartin
J V
JV
Forrester
A D
AD
Dick
D000328:Adult; D016572:Cyclosporine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004351:Drug Resistance; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D009883:Ophthalmic Solutions; D009887:Ophthalmoscopy; D011446:Prospective Studies; D012449:Safety; D016559:Tacrolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D017211:Treatment Failure; D015866:Uveitis, Posterior / Q000188:drug therapy*; D014792:Visual Acuity
D007166:Immunosuppressive Agents; D009883:Ophthalmic Solutions; D016572:Cyclosporine; D016559:Tacrolimus