mycophenolic-acid and Scleritis

Ocular inflammations such as uveitis and scleritis can lead to significant visual impairment if not treated properly. To limit potentially sight-threatening complications, good control of the inflammation in the acute phase is necessary. Corticosteroids have been the mainstay of ocular therapies for many years, but high doses of corticosteroids, which are required to maintain quiescence in severe uveitis, can be associated with many systemic and ocular complications. In order to limit steroid side-effects, classic immunosuppressant and immunobiologic agents have been widely used as steroid-sparing agents. In this review, we summarise the immunosuppressive drug therapy utilised in the treatment of ocular inflammatory diseases.

Topics: Adrenal Cortex Hormones; Azathioprine; Cyclosporine; Enzyme Inhibitors; Immunosuppressive Agents; Methotrexate; Mycophenolic Acid; Scleritis; Uveitis

To evaluate the usefulness of mycophenolate mofetil (MMF) (CellCept, Roche, Nutley, NJ), an antimetabolite immunosuppressant with a selective antiproliferative effect on T and B lymphocytes, for the treatment of scleritis.. Retrospective, noncomparative case series.. Eight patients with scleritis treated with MMF in a tertiary referral center.. Review of the clinical records of patients evaluated at the National Eye Institute and prescribed MMF for the treatment of scleritis.. Control of scleral inflammation, the ability to taper prednisone or other immunosuppressive medications, and adverse events were recorded for each patient. Mycophenolate mofetil was determined to be an effective steroid-sparing agent if the daily prednisone dosage could be reduced by 50% or more and was determined to be an effective adjunctive immunosuppressive agent if the scleral inflammation was controlled in patients with active scleritis.. Four patients with diffuse anterior scleritis, two with necrotizing scleritis with inflammation, one with nodular anterior scleritis, and one with nodular anterior and posterior scleritis, were identified. Mycophenolate mofetil administration was initiated as a steroid-sparing agent in 4 patients with controlled scleritis and as an additional immunosuppressive agent in 4 patients with active scleritis receiving concomitant treatment with prednisone and cyclosporine or methotrexate. In 3 of the 4 patients started on MMF as a steroid-sparing agent, the scleritis remained controlled while the prednisone dosage was tapered by more than 50%. One of the patients started on MMF as a steroid-sparing agent had recurrent scleritis, and each of the patients with active scleritis continued to have persistent scleral inflammation requiring additional immunosuppressive therapy. Adverse effects recorded in 4 of the 8 patients included a rash, gastrointestinal symptoms, paresthesias, and laboratory evidence of hepatotoxicity and renal toxicity.. Although MMF maybe be useful as a steroid-sparing agent, it was not effective as an adjunctive immunosuppressive agent in patients with active scleritis in our small, tertiary referral series. The adverse effects encountered with the use of MMF in this study cannot be attributed conclusively to MMF and are more likely complications of the multiagent systemic immunosuppressive therapy required for the treatment of recalcitrant scleritis.

Topics: Adult; Drug Evaluation; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Retrospective Studies; Scleritis

To assess the usefulness of mycophenolate mofetil (MMF) (Cellcept, Roche), a potent selective uncompetitive and reversible inhibitor of ionisine monophosphate dehydrogenase involved in purine synthesis, as an immunosuppressive and steroid-sparing agent in the management of ocular inflammatory disease.. Open-label, prospective, uncontrolled pilot study.. Eleven patients with uncontrolled ocular inflammation.. Mycophenolate mofetil, at a dosage of 1 g twice daily, was given in conjunction with steroids, as a steroid-sparing agent, or as an additional agent with cyclosporine (CsA), or instead of CsA or azathioprine.. The inflammatory response, side effects, and toxicity were monitored.. The addition of MMF to immunosuppressive regimens led to the improvement in symptoms and the ability to reduce the dose of prednisone in most patients. Ten of 11 patients showed a favorable response to MMF, with few side effects noted.. These findings suggest that MMF is a useful immunosuppressive drug for controlling ocular inflammation with minimal side effects.

Topics: Adult; Aged; Enzyme Inhibitors; Female; Humans; Immunosuppressive Agents; IMP Dehydrogenase; Male; Middle Aged; Mycophenolic Acid; Panuveitis; Pilot Projects; Prospective Studies; Safety; Scleritis; Treatment Outcome

Infectious scleritis is a rare but important cause of scleral inflammation. It is usually associated with an underlying ocular (prior ocular surgery or trauma) or systemic risk factor. A 53-year-old apparently systemically healthy woman presenting with spontaneous-onset pain, redness and watering in the left eye for 10 days was diagnosed with culture-proven

Topics: Anti-Bacterial Agents; Autoimmune Diseases; Cefazolin; Diagnosis, Differential; Female; Glucocorticoids; Granulomatosis with Polyangiitis; Humans; Immunosuppressive Agents; Middle Aged; Mycophenolic Acid; Polymyxin B; Pseudomonas aeruginosa; Pseudomonas Infections; Scleritis; Tropanes

To compare mycophenolate mofetil (MMF) to methotrexate (MTX) as corticosteroid-sparing therapy for ocular inflammatory diseases.. Retrospective analysis of cohort study data.. Participants were identified from the Systemic Immunosuppressive Therapy for Eye Diseases Cohort Study. Demographic and clinical characteristics were obtained via medical record review. The study included 352 patients who were taking single-agent immunosuppression with MTX or MMF at 4 tertiary uveitis clinics. Marginal structural models (MSM)-derived statistical weighting created a virtual population with covariates and censoring patterns balanced across alternative treatments. With this methodological approach, the results estimate what would have happened had none of the patients stopped their treatment. Survival analysis with stabilized MSM-derived weights simulated a clinical trial comparing MMF vs MTX for noninfectious inflammatory eye disorders. The primary outcome was complete control of inflammation on prednisone ≤10 mg/day, sustained for ≥30 days.. The time to success was shorter (more favorable) for MMF than MTX (hazard ratio = 0.68, 95% confidence interval: 0.46-0.99). Adjusting for covariates, the proportion achieving success was higher at every point in time for MMF than MTX from 2 to 8 months, then converges at 9 months. The onset of corticosteroid-sparing success took more than 3 months for most patients in both groups. Outcomes of treatment (MMF vs MTX) were similar across all anatomic sites of inflammation. The incidence of stopping therapy for toxicity was similar in both groups.. Our results suggest that, on average, MMF may be faster than MTX in achieving corticosteroid-sparing success in ocular inflammatory diseases.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Female; Glucocorticoids; Humans; Immunosuppressive Agents; Infant; Inflammation; Male; Methotrexate; Middle Aged; Mycophenolic Acid; Prednisone; Retrospective Studies; Scleritis; Uveitis; Visual Acuity

To analyze the visual outcome, systemic associations, effectiveness of treatment, and predicting features of 104 scleritis patients.. Retrospective case series.. One hundred four patients treated for scleritis at the University Medical Centers of Groningen and Utrecht, The Netherlands.. The clinical records of 104 patients diagnosed with scleritis between 1992 and 2011 at the University Medical Centers of Groningen (n = 64) and of Utrecht (n = 40) were analyzed retrospectively.. Loss of visual acuity, ocular complications, related systemic disease, type of treatment, time to treatment success, and predictive features.. Mean age ± standard deviation (SD) was 51.5 ± 13.6 years, and 63 (60.6 %) patients were female. Mean follow-up ± SD was 38.2 ± 33.8 months. A loss of more than 2 lines of Snellen acuity was observed in 23 patients, 3 of whom had a final visual acuity of no light perception. In general, patients with necrotizing scleritis (n = 15) had a poorer outcome. Ocular complications were observed in 88 (84.6%) patients. Underlying systemic disease was identified in 34 (32.7%) patients. Steroid-sparing immunosuppressive medication was used in 47 patients, 36 of whom were treated with methotrexate (MTX). This treatment was successful in 17 (47.2%) patients over the course of a mean ± SD of 103.7 ± 83.7 weeks. Mycophenolate mofetil was the treatment in 10 patients, and in 5 of these patients, treatment success was achieved in a mean ± SD of 65.3 ± 37.4 weeks. Treatment with tumor necrosis factor α (TNF-α) antagonists led to treatment success in a mean ± SD of 32.6 ± 21.8 weeks in 5 of the 11 treated patients. Patients with loss of visual acuity or those treated with steroid-sparing immunosuppressive drugs more often had an underlying associated disease, bilateral scleritis, and a longer duration of symptoms at presentation.. Scleritis is a severe ocular inflammatory disease often associated with ocular complications. In this population, roughly half of the patients were treated with systemic immunosuppressive medication. Mycophenolate mofetil and TNF-α antagonists can be used in case of MTX failure. Tumor necrosis factor α antagonists seemed to be more effective than MTX. Within this group, an underlying associated disease, bilateral scleritis, and a longer duration of symptoms at presentation were predictive features for a more severe disease course.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Methotrexate; Middle Aged; Mycophenolic Acid; Retrospective Studies; Risk Factors; Scleritis; Treatment Outcome; Tumor Necrosis Factor-alpha; Visual Acuity; Young Adult

To determine the effectiveness and corticosteroid (CS) sparing capabilities of mycophenolate mofetil (MMF) in the treatment of chronic non-infectious, non-necrotizing scleritis.. A retrospective chart review of patients treated for scleritis at the Institute of Ophthalmology and Visual Science at New Jersey Medical School was performed. Only those patients taking MMF for greater than or equal to six consecutive months were included. Main outcome measures were rate of inflammation control, CS, and MMF discontinuation, as well as visual acuity and side effects.. Twenty-two patients (32 eyes) were included in the study. Mean ± SD age was 53.5 ± 13.3 years. Twenty (91%) patients had previously failed some form of immunomodulatory therapy. After 6, 12, 18, and 24 months of consecutive MMF treatment, 91-100% of patients achieved inflammation control. Mean time to resolution of inflammation was 2.8 months, while mean duration of inflammation control was 14.8 months. CS sparing was achieved in 100% of patients at each time point, with mean starting CS dose decreased by 91% at final visit. Vision was stable or improved in 24 (75%) eyes. Fourteen (64%) patients reported side effects including leucopenia (n = 7), gastrointestinal upset (n = 4), abnormal liver function tests (n = 3), and abnormal renal function tests (n = 2). None required hospitalization or medical treatment. Four (18%) patients discontinued MMF due to side effects (n = 3) and treatment ineffectiveness (n = 1).. MMF is an effective and well-tolerated therapy that can successfully reduce inflammation and decrease CS use in the treatment of chronic non-infectious, non-necrotizing scleritis.

Topics: Adrenal Cortex Hormones; Aged; Chronic Disease; Female; Gastrointestinal Diseases; Humans; Immunosuppressive Agents; Kidney Function Tests; Leukopenia; Liver Function Tests; Male; Middle Aged; Mycophenolic Acid; Retrospective Studies; Scleritis; Treatment Outcome; Visual Acuity

To evaluate enteric-coated mycophenolate sodium (EC-MPS) as a corticosteroid-sparing agent in the treatment of autoimmune scleritis.. A retrospective, interventional, noncomparative review of EC-MPS use in patients with autoimmune scleritis.. Seven eyes of 5 patients (all female; median age: 47 years, range: 20-55 years) with inflammatory scleral disease were treated with EC-MPS. The mean follow-up duration was 16.4 months (range, 12-20 months). EC-MPS was started at 360 mg twice daily. The mean time to treatment success was 1.6 months (range, 1-3 months). The mean prednisolone dosage at the onset of EC-MPS was 24 mg daily (range, 15-30 mg), and this was reduced to 6.5 mg daily (range, 0-10 mg) as inflammation control was achieved. No severe adverse events except for 1 patient with transient knee pain were reported; the incidence of adverse events after using EC-MPS was 1/6.83 person-years. There was no recurrence of scleral inflammation during the follow-up period.. EC-MPS can be used as a corticosteroid-sparing agent to safely suppress inflammatory autoimmune scleritis.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Autoimmune Diseases; Female; Follow-Up Studies; Glucocorticoids; Humans; Immunosuppressive Agents; Middle Aged; Mycophenolic Acid; Prednisolone; Retrospective Studies; Scleritis; Tablets, Enteric-Coated; Treatment Outcome; Young Adult

To evaluate mycophenolate mofetil as a single noncorticosteroid immunosuppressive treatment for noninfectious ocular inflammatory diseases.. Retrospective cohort study.. Characteristics of patients with noninfectious ocular inflammation treated with mycophenolate mofetil at 4 subspecialty clinics from 1995 to 2007 were abstracted by expert reviewers in a standardized chart review of every eye at every visit. Main outcomes measured were control of inflammation, corticosteroid-sparing effects, and discontinuation of mycophenolate mofetil (including the reasons for discontinuation). Survival analysis was used to estimate the incidence of outcomes, and to identify risk factors for each.. Among 236 patients (397 eyes) treated with mycophenolate mofetil monotherapy, 20.3%, 11.9%, and 39.8% had anterior uveitis, intermediate uveitis, and posterior uveitis or panuveitis respectively; 14% had scleritis; 7.6% had mucous membrane pemphigoid; and 6.4% had other ocular inflammatory diseases. By Kaplan-Meier estimation, complete control of inflammation--sustained over consecutive visits spanning at least 28 days--was achieved in 53% and 73% of patients within 6 months and 1 year respectively. Systemic corticosteroid dosage was reduced to 10 mg of prednisone or less, while maintaining sustained control of inflammation, in 41% and 55% of patients in 6 months and 1 year respectively. Twelve percent of patients discontinued mycophenolate mofetil within the first year because of side effects of therapy.. Given sufficient time, mycophenolate mofetil was effective in managing ocular inflammation in approximately half of the treated patients. Treatment-limiting side effects were observed in 12% of patients and typically were reversible.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Child; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Pemphigoid, Benign Mucous Membrane; Prednisone; Retrospective Studies; Risk Factors; Scleritis; Treatment Outcome; Uveitis; Visual Acuity

To evaluate the association between scleritis and systemic disease in a non-university, non-tertiary referral practice and to describe our experience with scleritis treatment.. Retrospective chart review.. The medical records of patients with scleritis between 2001 and 2007 were reviewed for associated systemic disease.. In our series of 86 patients with scleritis, 55 patients (64.0%) had isolated scleritis while 31 patients (36.0%) had associated systemic-disease. Twenty-six patients (83.9%) with systemic disease had diagnosed systemic disease at the time of initial scleritis presentation, while 5 patients (16.1%) were diagnosed following systemic work-up. Those diagnosed after systemic work-up were more likely to have systemic vasculitic disease as opposed to a rheumatic or infectious disease. Patients with and without associated systemic disease were likely to require systemic therapy at similar rates (93.5% and 92.7%, respectively). Five patients with steroid-refractory scleritis were treated with infliximab (Remicade; Centocor Inc, Horsham, Pennsylvania, USA) and all responded without evidence of adverse effect. Seven patients were treated with mycophenolate mofetil (CellCept; Roche Laboratories, Nutley, New Jersey, USA), of which three improved.. The association between scleritis and systemic disease in a community-based referral practice may be lower than in tertiary referral or university-based centers. Although thorough systemic disease evaluation is warranted in scleritis patients, most patients with associated systemic disease will have such a diagnosis prior to the development of scleritis. The need to institute aggressive systemic therapy cannot be predicted by the presence of an associated systemic disease. Infliximab and mycophenolate mofetil are useful additions to the scleritis practitioner's armamentarium for steroid-refractory scleritis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents; Antibodies, Monoclonal; Autoimmune Diseases; Child; Community Health Services; Female; Herpes Zoster; HIV Infections; Humans; Infliximab; Male; Middle Aged; Mycophenolic Acid; Referral and Consultation; Retrospective Studies; Sarcoidosis; Scleritis; Young Adult

To compare the relative effectiveness and side effect profiles of antimetabolite drugs in the treatment of noninfectious ocular inflammation.. Retrospective cohort study.. A total of 257 patients with inflammatory eye disease seen in a single-center, academic practice and treated with an antimetabolite as a first-line immunosuppressive agent from 1984 to 2006.. Data recorded included demographics, antimetabolite and prednisone doses, use of other immunosuppressive drugs, response to therapy, and side effects associated with drug use.. Ability to control ocular inflammation and to taper prednisone to

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antimetabolites; Azathioprine; Child; Female; Glucocorticoids; Humans; Inflammation; Male; Methotrexate; Middle Aged; Mycophenolic Acid; Prednisone; Retrospective Studies; Scleritis; Uveitis

To evaluate the outcomes of treatment with mycophenolate mofetil in patients with scleritis and uveitis refractory to or intolerant of methotrexate.. Retrospective noncomparative case series.. Eighty-five patients with scleritis and/or uveitis who failed with or did not tolerate methotrexate and were subsequently treated with mycophenolate mofetil between 1998 and 2006.. We reviewed medical records of patients who were treated with mycophenolate mofetil after methotrexate intolerance or failure at one tertiary uveitis referral practice. We recorded dose and duration of methotrexate and mycophenolate mofetil therapy, inflammation grade, Snellen visual acuity (VA), use of other immunomodulatory therapy, and adverse events. Multivariate logistic regression was used to identify factors associated with inflammation control.. Control of inflammation, steroid-sparing effect, VA, and adverse effects were assessed.. Inflammation was controlled with mycophenolate mofetil in 47 patients (55%), with 5 achieving durable remission off all medication. In multivariate logistic regression analysis that adjusted for gender and age, the odds of inflammation control were lower for patients with scleritis (odds ratio [OR], 0.19; 95% confidence interval [CI], 0.04-0.93; P = 0.04) than for patients without scleritis. Among patients without scleritis, the odds of inflammation control were lower for patients with juvenile idiopathic arthritis (JIA)-associated uveitis (OR, 0.14; CI, 0.02-0.81, P = 0.03) compared to patients without JIA-associated uveitis. Eight of the 11 patients (73%) who were taking concomitant prednisone were able to taper their dose to <10 mg daily. Visual acuity declined in a greater percentage of patients who were unresponsive to mycophenolate mofetil (29%) compared with that of patients who responded to mycophenolate mofetil (9%). Side effects requiring discontinuation of mycophenolate mofetil occurred in 18 patients (21%).. Mycophenolate mofetil was effective in controlling inflammation in approximately half of the patients who had previously failed with or did not tolerate methotrexate. The odds of inflammation control were less in patients with the diagnoses of scleritis and JIA.

Topics: Adolescent; Adult; Child; Child, Preschool; Confidence Intervals; Female; Folic Acid Antagonists; Humans; Immunosuppressive Agents; Male; Methotrexate; Middle Aged; Mycophenolic Acid; Odds Ratio; Retrospective Studies; Scleritis; Treatment Failure; Treatment Outcome; Uveitis; Visual Acuity

To evaluate treatment outcomes with mycophenolate mofetil in patients with inflammatory eye disease.. Retrospective case series.. Eighty-four consecutive patients with inflammatory eye disease treated with mycophenolate mofetil at an academic referral center.. Medical records were reviewed for treatment with mycophenolate mofetil. Dose of mycophenolate mofetil, response to therapy, dose of prednisone, use of other immunosuppressive drugs, and side effects associated with the use of mycophenolate mofetil were recorded.. Ability to control ocular inflammation with mycophenolate mofetil and to taper prednisone to < or =10 mg daily, and incidence of treatment-related side effects.. Of the 84 patients treated with mycophenolate mofetil, 61% had uveitis, 17% had scleritis, 11% had mucous membrane pemphigoid, and 11% had orbital or other inflammatory disease. Forty-three percent of patients treated with mycophenolate mofetil had been treated with at least one other immunosuppressive drug previously. The median dose of prednisone at the start of mycophenolate mofetil therapy was 40 mg, and 82% of the patients were considered a treatment success, as judged by the ability to control the inflammation and taper prednisone to < or =10 mg daily. Median time to treatment success was 3.5 months. Mycophenolate mofetil therapy was discontinued due to insufficient efficacy at a rate of 0.10 per person-year (PY) and due to side effects at a rate of 0.08/PY. The most frequent side effect was gastrointestinal upset, with a rate of 0.19/PY.. These data suggest that mycophenolate mofetil may be an effective corticosteroid-sparing agent in the treatment of inflammatory eye disease with a manageable side effect profile.

Topics: Adolescent; Adult; Aged; Child; Conjunctival Diseases; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Orbital Pseudotumor; Pemphigoid, Benign Mucous Membrane; Prednisone; Retrospective Studies; Scleritis; Treatment Outcome; Uveitis

The value of immunosuppressive drugs for the therapy of scleritis patients is unclear. The authors investigated the indications and effects of immunosuppression in a group of patients with scleral inflammation.. Retrospective study of patients treated for scleritis (n = 87) or episcleritis (n = 18). The demographic factors, clinical symptoms, visual outcome, course of inflammation, ocular complications resulting from inflammation, topical and systemic antiinflammatory medication, and associated systemic diseases were analysed.. Only one patient with episcleritis, but 37 with scleritis presented with ocular complications (P = 0.003). The vision was impaired in 15 patients with scleritis, but not in episcleritis patients (P = 0.022). In the group of patients with episcleritis, only those with frequent relapses required more than topical antiinflammatory drugs, especially systemic non-steroidals. In contrast, systemic therapy was indicated in all of the scleritis patients. Ocular complications were found more often in patients with necrotising (n = 7/10) or posterior scleritis (n = 10/11) than in those with diffuse (9/39) or nodular (11/27) scleritis. Compared with the other patients, associated systemic autoimmune diseases were more common in patients with necrotising scleritis (P = 0.03). The need for immunosuppression was associated with vision-threatening complications (glaucoma, uveitis, peripheral ulcerative keratitis) (P < 0.01), systemic autoimmune disease, and necrotising and posterior form of scleritis (P < 0.01). Quiescence of scleritis was obtained in 59 of the scleritis patients, and improvement of inflammation was achieved in further 21. In 26 patients, scleritis did not improve with systemic steroid or non-steroidal treatment, but with immunosuppression.. Scleritis is often associated with life-threatening systemic diseases and vision-threatening ocular complications. In patients with severe scleritis, especially with the posterior and necrotising form, improvement can often be achieved with immunosuppression.

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Autoimmune Diseases; Azathioprine; Cyclosporine; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Methotrexate; Middle Aged; Mycophenolic Acid; Retrospective Studies; Scleritis; Treatment Outcome

To report the first known case of bilateral scleritis in a patient with hypocomplementemic urticarial vasculitis.. Interventional case report.. Medical and ophthalmic history, results of physical and ophthalmic examinations, laboratory data, and histologic and immunopathologic examination were reviewed and results recorded.. A 67-year-old man who presented with eye redness and pain, rash, arthralgia, and malaise was found to have hypocomplementemic urticarial vasculitis. Treatment with high-dose oral corticosteroids and mycophenolate mofetil resulted in the resolution of the rash and scleritis.. Ocular involvement may be a helpful clue in the diagnosis of this uncommon syndrome.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Antibodies, Antinuclear; Complement C3; Complement C4; Glomerulonephritis, Membranoproliferative; Glucocorticoids; Humans; Male; Mycophenolic Acid; Prednisone; Scleritis; Urticaria