TACROLIMUS (FK506) IN FAILED CYCLOSPORINE-A THERAPY IN ENDOGENOUS POSTERIOR UVEITIS

Tacrolimus (FK506) is effective in Japanese endogenous posterior uveit is (EPU), but there is limited data on its role in refractory EPU wher e cyclosporin A (CsA) toxicity/resistance develops. This open prospect ive 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. I mmunosuppressive efficacy was assessed by visual acuity, binocular ind irect ophthalmoscopy (BIO) scores, and change in clinical features. Ad verse effects were assessed by routine biochemical tests (including se rum creatinine) and symptoms. Seven patients (13 eyes), aged (mean+/-S D) 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. Behcet's disease was the commonest diagnosis. FK506 therap y was maintained at 0.06+/-0.02 mg/kg/day, trough level of 8.7+/-1.8 n g/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 10-17.7) Fr om 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 neurologic al symptoms) were common and usually well tolerated, except for two pa tients in whom drug withdrawal was necessary, thus producing therapeut ic failure. Low-dose FK506 is effective in refractory EPU as CsA-rescu e therapy, and should be considered earlier in the evolution of refrac tory EPU.