tacrolimus and Uveitis--Posterior

To evaluate the responsiveness of the Vision core module 1 (VCM1) vision-related quality of life (VR-QOL) questionnaire to changes in visual acuity in patients with posterior and intermediate uveitis and to validate its use as a clinical end point in uveitis.. Logarithm of the minimum angle of resolution visual acuity and VR-QOL using the VCM1 questionnaire were prospectively recorded in 37 patients with active posterior segment intraocular inflammation before starting systemic immunosuppression with ciclosporin, tacrolimus or the anti-tumour necrosis factor (TNF) agent, p55TNFr-Ig, and again 3 months later. Spearman analysis was used to correlate improvements in visual acuity and VR-QOL between baseline and 3 months.. The correlation between changes in visual acuity and VR-QOL was moderate to good for the worse eye (r = 0.47, p = 0.003), but poor for the better eye (r = -0.05, p = 0.91). The responsiveness indices effect size and standardised response mean were 0.57 and 0.59, respectively, showing that the VCM1 questionnaire is moderately responsive to immunsosuppressive therapy for active uveitis.. Changes in VR-QOL measured with the VCM1 questionnaire correlated moderately well with changes in the worse eye visual acuity, suggesting that the VCM1 is a valid instrument for monitoring response to treatment in uveitis.

Topics: Adult; Aged; Cyclosporine; Female; Health Status Indicators; Humans; Immunosuppressive Agents; Male; Middle Aged; Quality of Life; Severity of Illness Index; Surveys and Questionnaires; Tacrolimus; Treatment Outcome; Tumor Necrosis Factor-alpha; Uveitis, Intermediate; Uveitis, Posterior; Visual Acuity

To compare the efficacy and tolerability of tacrolimus and cyclosporine therapy for noninfectious posterior segment intraocular inflammation and to evaluate their effect on peripheral blood CD4(+) T-cell phenotype and activation status.. Thirty-seven patients who required second-line immunosuppression for posterior segment intraocular inflammation were enrolled in this prospective randomized trial of tacrolimus vs cyclosporine therapy. The main outcome measures were visual acuity, binocular indirect ophthalmoscopy score, adverse effects, and quality of life. In addition, peripheral blood CD4(+) T-cell phenotype and activation status were evaluated by flow cytometry before treatment and at 2, 4, and 12 weeks using CD69, chemokine receptor (CCR4, CCR5, and CXCR3), and intracellular cytokine (tumor necrosis factor alpha, interferon-gamma, and interleukin 10) expression.. Thirteen patients (68%) taking tacrolimus and 12 patients (67%) taking cyclosporine responded to treatment. Cyclosporine therapy was associated with a higher incidence of reported adverse effects. Mean arterial pressure and serum cholesterol level were significantly higher at 3 months in the cyclosporine group than the tacrolimus group. No significant difference was detected with regard to effect on quality of life or CD4(+) T-cell phenotype.. Tacrolimus and cyclosporine were similar with regard to efficacy for posterior segment intraocular inflammation, but the results suggested a more favorable safety profile for tacrolimus therapy.

Topics: Adult; Antigens, CD; Antigens, Differentiation, T-Lymphocyte; Blood Pressure; CD4-Positive T-Lymphocytes; Cholesterol; Cyclosporine; Cytokines; Female; Flow Cytometry; Humans; Immunophenotyping; Immunosuppressive Agents; Lectins, C-Type; Lymphocyte Activation; Male; Middle Aged; Prospective Studies; Quality of Life; Tacrolimus; Treatment Outcome; Uveitis, Intermediate; Uveitis, Posterior; Visual Acuity

To assess the efficacy and side effects of tacrolimus, a potent immunosuppressive macrolide antibiotic, in the treatment of sight-threatening uveitis.. A clinical study of tacrolimus in patients who required systemic immunosuppression for control of uveitis, but were refractory to cyclosporine.. Six patients with uveitis were treated: three had Behçet disease, one had microscopic polyangiitis, one had pars planitis, and one had idiopathic retinal vasculitis.. Patients with sight-threatening uveitis refractory to cyclosporine were treated with tacrolimus.. Intraocular inflammation, visual acuity (VA), neovascularization. Adverse effects of tacrolimus were documented.. The posterior uveitis remained controlled in all patients while they were taking tacrolimus. Five of the six patients showed improvement, defined as improvement of two or more lines of Snellen acuity or a decrease in the binocular indirect ophthalmoscopy score (P < 0.05, Sign test). One patient with Behçet disease showed a marked improvement in best-corrected VA from 1/60 to 6/24. Two patients with Behçet disease showed a modest improvement in VA in the affected eye and had no disease activity in the other eye. The patient with microscopic polyangiitis was symptomatically improved, and there was no progression of the posterior uveitis. The patient with pars planitis had an improvement in VA from 6/18 to 6/9. The patient with retinal vasculitis showed partial regression of neovascularization on tacrolimus. Side effects were less troublesome than with cyclosporine.. Tacrolimus (FK506) has a useful role as an immunosuppressive agent for the treatment of sight-threatening uveitis in patients who did not respond to cyclosporine either because of lack of therapeutic effect or unacceptable adverse effects.

Topics: Adolescent; Adult; Cyclosporine; Female; Fundus Oculi; Humans; Immunosuppressive Agents; Male; Middle Aged; Safety; Tacrolimus; Uveitis, Posterior; Vision, Binocular; Visual Acuity

PURPOSE. To evaluate the effects of intravitreal injection of liposomes encapsulating tacrolimus (FK506) on experimental autoimmune uveoretinitis (EAU) in Lewis rats. METHODS. Liposomes containing tacrolimus were prepared by reverse-phase evaporation vesicles. EAU was induced in Lewis rats by subcutaneous injection of interphotoreceptor retinoid-binding protein R16 peptide emulsified in adjuvant. Ten days later, rats were intravitreally injected with saline, tacrolimus, tacrolimus-loaded liposomes, or unloaded liposomes. Clinical signs of inflammation and ocular histologic sections were observed and graded. Retinal function was evaluated by electroretinography (ERG). Tacrolimus concentration was determined in the vitreous body and serum by ELISA. Ocular biodistribution of rhodamine-conjugated liposomes containing tacrolimus (tacrolimus-Rh-lip) was analyzed with a laser scanning confocal microscope. To evaluate the systemic effect of intravitreally injected tacrolimus, delayed-type hypersensitivity (DTH) and lymphocyte proliferation assay (LPA) responses were detected. RESULTS. Treatment of EAU with intravitreal injection of liposomal tacrolimus significantly reduced intraocular inflammation and markedly inhibited the development of EAU, as determined in clinical and histopathologic analyses. No toxic effects could be detected as evaluated by ERG. The concentration of tacrolimus in ocular fluids remained for as long as 14 days after liposomal injection of tacrolimus. Confocal microscopy showed a transretinal distribution of the liposomal particles. DTH and LPA responses were not impaired in liposomal tacrolimus-treated rats. CONCLUSIONS. Intravitreal injection of liposomal tacrolimus was highly effective in suppressing the process of EAU without any side effects on retinal function or systemic cellular immunity. This treatment may represent a new option for the management of intraocular inflammation.

Topics: Animals; Autoimmune Diseases; Disease Models, Animal; Electroretinography; Female; Hypersensitivity, Delayed; Immunosuppressive Agents; Injections; Liposomes; Lymphocyte Activation; Microscopy, Confocal; Rats; Rats, Inbred Lew; Retinitis; T-Lymphocytes; Tacrolimus; Uveitis, Posterior; Vitreous Body

Topics: Cyclosporine; Humans; Immunosuppressive Agents; Randomized Controlled Trials as Topic; Tacrolimus; Uveitis, Intermediate; Uveitis, Posterior

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.

Topics: Adult; Cyclosporine; Drug Resistance; Female; Humans; Immunosuppressive Agents; Male; Ophthalmic Solutions; Ophthalmoscopy; Prospective Studies; Safety; Tacrolimus; Treatment Failure; Uveitis, Posterior; Visual Acuity