mycophenolic-acid and Uveitis--Posterior

To study the effectiveness of mycophenolate mofetil (MMF) as first-line therapy combined with systemic corticosteroids in acute uveitis associated with Vogt-Koyanagi-Harada (VKH) disease. The outcomes in this group were compared with those of another group of patients with VKH disease who were treated with corticosteroid monotherapy or with delayed addition of immunomodulatory therapy.. This prospective study included 19 patients (38 eyes) diagnosed with acute uveitis associated with VKH disease.. The mean follow-up period was 27.0 ± 11.1 months (range 16-54 months). Corticosteroid-sparing effect was achieved in all patients. The mean interval between starting treatment and tapering prednisone to 10 mg or less daily was 5.1 ± 1.2 months (range 3-7 months). Ten (53%) patients discontinued treatment without relapse of inflammation. The mean time observed of treatment was 17.3 ± 11.9 months (range 3-41.5 months). Visual acuity of 20/20 was achieved by 38% of the eyes in the corticosteroid group and by 74% in the corticosteroid + MMF group (p < 0.001). Recurrent inflammation of ≥3 times was reduced significantly (p = 0.0383) in the corticosteroid + MMF group (3%) as compared to corticosteroid group (18%). Development of all complications was significantly higher in the corticosteroid group (43%) compared with the corticosteroid + MMF group (8%) (p < 0.001). None of the eyes in the corticosteroid + MMF group developed 'sunset glow fundus'.. Addition of MMF as first-line therapy to corticosteroids in patients with acute uveitis associated with VKH disease leads to significant reduction in recurrences of uveitis and development of late complications and significantly improves visual outcome.

Topics: Acute Disease; Administration, Oral; Adolescent; Adult; Child; Coloring Agents; Drug Therapy, Combination; Female; Fluorescein Angiography; Follow-Up Studies; Glucocorticoids; Humans; Immunosuppressive Agents; Indocyanine Green; Infusions, Intravenous; Male; Methylprednisolone; Mycophenolic Acid; Ophthalmoscopy; Prednisone; Prospective Studies; Secondary Prevention; Treatment Outcome; Uveitis, Posterior; Uveomeningoencephalitic Syndrome; Visual Acuity; Young Adult

The severity of disease and the side-effects of long-term corticosteroid treatment support the rationale for other immunosuppressive drugs in the management of uveitis. Mycophenolate mofetil (MMF) is a selective inhibitor of ionosine monophosphate dehydrogenase and exerts its major effects by modulation of the function of T and B lymphocytes. This study was undertaken to evaluate the clinical effect of MMF in the control of intermediate and posterior uveitis.. A retrospective study of 18 consecutive patients with intermediate or posterior uveitis treated with MMF was performed. Activity of intraocular inflammation was graded according to the guidelines of the international uveitis study group before and during treatment with MMF. Furthermore, the ability of MMF treatment to reduce the steroid dosage and/or substitute other immunosuppressive agents with unacceptable side-effects (cyclosporin A, tacrolimus, azathioprine) was evaluated.. The indication for treatment with MMF in all 18 patients (age range: 11-73 years) was either poor control of ocular inflammation by the previous immunosuppressive therapy or unacceptable side-effects of this therapy. The daily MMF dose was 2 g and therapy was combined with cyclosporin A and/or prednisolone. One patient received MMF monotherapy. Corticosteroids were discontinued in 4 patients and the steroid dose could be reduced in 14 patients following MMF therapy. Marked resolution of ocular inflammatory activity occurred in 13 patients. The most frequently observed side-effects of MMF were myalgia, fatigue, headache and gastrointestinal problems.. MMF was effective in disease control in the majority of patients with intermediate and posterior uveitis and proved to be a useful second line immunosuppressant for refractory intraocular inflammatory disease with an acceptable profile of side-effects.

Topics: Adolescent; Adult; Aged; Child; Cyclosporine; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; IMP Dehydrogenase; Male; Middle Aged; Mycophenolic Acid; Prednisolone; Retrospective Studies; Treatment Outcome; Uveitis, Intermediate; Uveitis, Posterior

To assess the effects of mycophenolate mofetil (MMF) therapy on T helper cell activation status, using CD69 expression and cytokine profile with flow cytometry in relation to clinical activity in uveitis.. Patients with posterior or intermediate uveitis treated with MMF (n = 10), patients with active uveitis not treated with MMF and receiving no or minimal therapy (n = 10), and healthy volunteers (n = 21) had peripheral blood lymphocyte immunofluorescence analysis for T helper cell (CD4, CD3) markers, activation status (CD69), and intracellular cytokine (interleukin [IL]-2, interferon [IFN]-gamma, and IL-4) levels. Patients were compared before and during MMF therapy in relation to T helper cell activation and clinical activity.. Patients with active uveitis not treated with MMF and receiving no or minimal therapy had increased frequency of CD69-positive CD4 T cells (10.5% +/- 4.6%, P = 0.0007) compared with healthy volunteers (3.3% +/- 2.7%). Of all patients receiving MMF therapy, only patients with moderate to severe uveitis activity in the pre-MMF treatment group (n = 5; 15.5% +/- 5.0%, P = 0.004) had increased frequency of CD69-positive CD4 T cells compared with healthy volunteers. During MMF therapy, a significant reduction in frequency of CD69-positive CD4 T cells occurred in patients with prior moderate to severe uveitis activity (to 8.9% +/- 3.8%, P = 0.04). Levels of CD69-positive CD4 T cells in patients who had had inactive or mildly active disease (n = 5) before and during MMF therapy were comparable with levels in healthy volunteers. No significant changes in cytokine levels were found between the patient and control groups. A significant association between changes in frequency of CD69-positive CD4 T cells and changes in visual acuity (P = 0.008) and changes in vitreal haze (binocular indirect ophthalmoscopy score; P = 0.01) was observed in MMF-treated patients with prior moderate to severe uveitis activity.. Reduction in uveitis activity during MMF therapy correlates with reduction in frequency of peripheral blood CD69-positive CD4 cells. The frequency of CD69-positive CD4 T cells is a measure of activity in posterior uveitis and may guide adequate immunosuppression.

Topics: Adult; Antigens, CD; Antigens, Differentiation, T-Lymphocyte; CD4-Positive T-Lymphocytes; Flow Cytometry; Humans; Immunosuppressive Agents; Interferon-gamma; Interleukins; Lectins, C-Type; Lymphocyte Activation; Mycophenolic Acid; Uveitis, Intermediate; Uveitis, Posterior