mycophenolic-acid and Uveitis

Acute granulomatous tubulointerstitial nephritis (GTIN) is a rare finding in renal biopsy. Differential diagnosis is facilitated when GTIN is associated with granulomatous bilateral anterior uveitis (GBAU). Nevertheless, differentiation between a rare form of granulomatous tubulointerstitial nephritis and uveitis syndrome (TINU) and sarcoidosis can be challenging. We report a case of biopsy-proven GTIN with concomitant GBAU, leading to a dead-end diagnosis. We discuss workup and propose a diagnostic algorithm based on a literature review. We also report a successful treatment of ophthalmologic and renal relapse using mycophenolate mofetil.

Topics: Acute Disease; Humans; Mycophenolic Acid; Nephritis, Interstitial; Uveitis; Uveitis, Anterior

Immunosuppressants are prescribed for pediatric uveitis in cases of severe involvement affecting the prognosis for vision or life, in cases of recurrent or chronic uveitis to achieve corticosteroid sparing, or in cases of corticosteroid resistance. Immunosuppressants used in children include antimetabolites (methotrexate, mycophenolate mofetil, azathioprine), cyclosporine, tacrolimus, and biologics, including infliximab, adalimumab, anakinra, canakinumab, and tocilizumab. The mechanisms of action and indications of the various immunosuppressants are described in this review.

Topics: Adalimumab; Child; Humans; Immunosuppressive Agents; Infliximab; Mycophenolic Acid; Uveitis

Patients with POAG have lower corneal endothelial cell density than healthy controls of the same age. This may be attributed to mechanical damage from elevated IOP and toxicity of glaucoma medications.. Mycophenolic acid was detected in all cats. The dose 10 mg/kg given q12h for 1 week was tolerated (n = 3). The efficacy of MMF as an immunosuppressant and long-term safety in cats of this dosage regimen is unknown.. T

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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

Juvenile localized scleroderma (jLS) and juvenile systemic sclerosis (jSS) are both orphan diseases, with jLS around 10 times more frequent than jSS. In recent years the time gap between the appearance of symptoms and diagnosis has become significantly shorter. This review focuses on the new classifications of jSS and jLS, and on the developments and adaptations of the outcome measures for certain organ involvements whereby progress has been made regarding pediatric patients.

Topics: Antibodies, Monoclonal, Humanized; Child; Glucocorticoids; Humans; Immunosuppressive Agents; Methotrexate; Microscopic Angioscopy; Mycophenolic Acid; Scleroderma, Localized; Scleroderma, Systemic; Skin; Thermography; Tomography, Optical Coherence; Ultrasonography, Doppler; Uveitis

Mycophenolate mophetil (MMP) is a potent immunomodulatory drug that inhibits the function of T and B lymphocytes. It is used successfully in the treatment of recurrent noninfectious uveitis in adults and children. MMF can be used alone or in combination with other immunomodulatory drugs (biologics or calcineurin inhibitors) for moderate and severe cases of anterior, intermediate and posterior uveitis. It can also be used for treatment of patients with scleritis and ocular cicatricial pemphigoid.

Topics: Humans; Immunity, Cellular; Immunosuppressive Agents; Mycophenolic Acid; Prodrugs; Treatment Outcome; Uveitis

To identify advances in immunosuppressive therapy of ocular diseases since 2007.. The biologics in current use include antitumour necrosis factor-alpha agents (infliximab, etanercept and adalimumab), cytokine receptor antibodies (daclizumab) and interferon-alpha2a. They are effective and comparatively well tolerated options in the treatment of refractory uveitis in both adults and children in the short term, except for etanercept. Daclizumab had a favourable outcome in treating birdshot chorioretinopathy but not in Behcet's disease. The uncertainty of their long-term results, their high costs as well as the necessity for repeated intravenous infusions in the case of infliximab limit their widespread use. Mycophenolate mofetil is another efficacious, fairly well tolerated and less costly immunosuppressant. It has the additional advantage of an oral formulation. T cell inhibitors, cyclosporine and tacrolimus, were found to be useful steroid-sparing drugs in allergic eye disease and dry eyes. A number of studies on less invasive sustained ocular drug delivery systems, including episcleral implants, nanospheres, and cyclodextrin particles, were conducted on animals with encouraging results.. The armamentarium of immunosuppressive agents is constantly expanding and augurs well for the safe and effective treatment of ocular inflammation.

Topics: Adalimumab; Anti-Inflammatory Agents; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Daclizumab; Etanercept; Humans; Immunoglobulin G; Immunosuppressive Agents; Infliximab; Interferon alpha-2; Interferon-alpha; Mycophenolic Acid; Receptors, Tumor Necrosis Factor; Recombinant Proteins; Uveitis

Mycofenolate mofetil (MMF-Cellcept) is an immunomodulatory drug utilized extensively in transplant medicine. The efficacy of regimes including Cellcept in preventing allograft rejection, and in the treatment of rejection, is now firmly established. The immunosuppressive actions of this drug enabled the investigation for the beneficial effects in autoimmune diseases. We review the evidence for the contribution of MMF in autoimmunity in animal models of systemic lupus erythematosus (SLE), mercury induced autoimmune glomerulonephritis, diabetes mellitus, experimental autoimmune uveoretinitis, and experimental allergic encephalitis. MMF has an influence on the T and B cell pathways. It is immunosuppressive and anti-inflammatory.

Topics: Animals; Autoimmune Diseases; Diabetes Mellitus, Experimental; Disease Models, Animal; Immunosuppressive Agents; Inflammatory Bowel Diseases; Mycophenolic Acid; Retinitis; Uveitis

Oral corticosteroids remain the main therapeutical choice in patients with uveitis not responding to topical treatment, however their chronic use can be very toxic, especially for bones (osteoporosis or growth retardation). Immunosuppresive agents are used as corticosteroid sparing agents and/or as agents able to control refractory uveitis in sight threatening uveitis. Cyclosporin A is very efficacious but is nephrotoxic, in particular in old people. Methotrexate is well tolerated in young people, is not carcinogenic but not very active. Azathioprine is well tolerated but it's carcinogenic effect and its delayed action are helpful in chronic uveitis of old women. Cyclophosphamide and intravenous steroids are helpful for emergencies. Chlorambucil is toxic and carcinogenic but might lead to an increased rate of remission and might be useful as a short treatment. In any case, a careful and regular follow-up in collaboration with a competent internist is mandatory.

Topics: Adult; Aged; Antimetabolites; Antineoplastic Agents, Alkylating; Azathioprine; Child; Chlorambucil; Cyclophosphamide; Female; Humans; Immunosuppressive Agents; Methotrexate; Mycophenolic Acid; Uveitis

To evaluate the outcomes of uveitic macular edema at 6 and 12 months in patients treated with methotrexate or mycophenolate mofetil.. Subanalysis of a block-randomized, observer-masked, multicenter clinical trial.. Patients were enrolled in the First-line Antimetabolites as Steroid-sparing Treatment (FAST) Uveitis Trial between August 2013 and August 2017.. Patients were randomized to oral methotrexate 25 mg weekly or mycophenolate mofetil 1.5 g twice daily for 12 months, along with a corticosteroid taper. In addition to standardized clinical examination, all patients underwent spectral-domain OCT imaging at each visit. At the 6-month primary end point, patients who achieved treatment success continued the same treatment for a subsequent 6 months, and treatment failures switched to the other treatment group.. Prespecified 6-month primary outcome and 12-month outcomes of central subfield thickness and visual acuity.. Of 216 patients in the FAST Trial, 42 eyes (30 patients) in the methotrexate group and 55 eyes (41 patients) in the mycophenolate group had uveitic macular edema. Baseline median central subfield thickness was 359 μm and 342 μm in the methotrexate and mycophenolate groups, respectively. At 12 months, for those who stayed on the same treatment, macular thickness decreased from baseline by 30.5 μm (interquartile range [IQR], -132.3 to 4.0) and 54 μm (IQR, -95.5 to -4.5) in the methotrexate and mycophenolate groups, respectively (P = 0.73). In patients who switched treatment at 6 months, macular thickness decreased from baseline by 12.5 μm (IQR, -32.3 to -0.5) and 50 μm (IQR, -181.0 to -10.0) in the methotrexate and mycophenolate groups, respectively (P = 0.34). At 12 months, 7 of 19 eyes (37%) on methotrexate had resolution of macular edema compared with 15 of 25 eyes (60%) on mycophenolate (P = 0.10). For those who switched treatments, 8 of 17 eyes (47%) on methotrexate and 6 of 11 eyes (55%) on mycophenolate had resolution of macular edema (P = 0.92).. Treatment with methotrexate or mycophenolate mofetil for uveitic macular edema results in similar improvements in macular thickness at 6 and 12 months. At 12 months, approximately half of eyes in each antimetabolite group still had persistent macular edema.

Topics: Antimetabolites; Enzyme Inhibitors; Humans; Immunosuppressive Agents; Macular Edema; Methotrexate; Mycophenolic Acid; Steroids; Tomography, Optical Coherence; Treatment Outcome; Uveitis

To evaluate changes in health-related and vision-related quality of life (VRQoL) among patients with noninfectious uveitis who were treated with antimetabolites.. Secondary analysis of a randomized controlled trial.. Patients with noninfectious uveitis from India, the United States, Australia, Saudi Arabia, and Mexico.. From 2013 through 2017, 216 participants were randomized to receive 25 mg weekly oral methotrexate or 1.5 g twice daily oral mycophenolate mofetil. Median changes in quality of life (QoL) were measured using Wilcoxon signed-rank tests, and differences between treatment groups were measured using linear mixed models, adjusting for baseline QoL score, age, gender, and site. Among Indian patients, VRQoL scores from a general scale (the National Eye Institute Visual Function Questionnaire [NEI-VFQ]) and a culturally specific scale (the Indian Visual Function Questionnaire [IND-VFQ]) were compared using Pearson correlation tests.. Vision-related QoL (NEI-VFQ and IND-VFQ) and health-related QoL (HRQoL; physical component score [PCS] and mental component score [MCS] of the Medical Outcomes Study 36-Item Short Form Survey [SF-36v2]) were measured at baseline, the primary end point (6 months or treatment failure before 6 months), and the secondary end point (12 months or treatment failure between 6 and 12 months).. Among 193 participants who reached the primary end point, VRQoL increased from baseline by a median of 12.0 points (interquartile range [IQR], 1.0-26.1, NEI-VFQ scale), physical HRQoL increased by a median of 3.6 points (IQR, -1.4 to 14.9, PCS SF-36v2), and mental HRQoL increased by a median of 3.0 points (IQR, -3.7 to 11.9, MCS SF-36v2). These improvements in NEI-VFQ, SF-36v2 PCS, and SF-36v2 MCS scores all were significant (P < 0.01). The linear mixed models showed that QoL did not differ between treatment groups for each QoL assessment (NEI-VFQ, IND-VFQ, PCS SF-36v2, and MCS SF-36v2; P > 0.05 for all). The NEI-VFQ and IND-VFQ scores for Indian participants were correlated highly at baseline and the primary and secondary end points (correlation coefficients, 0.87, 0.80, and 0.90, respectively).. Among patients treated with methotrexate or mycophenolate mofetil for uveitis, VRQoL and HRQoL improved significantly over the course of 1 year and did not differ by treatment allocation. These findings suggest that antimetabolites could improve overall patient well-being and daily functioning.

Topics: Administration, Oral; Adult; Aged; Enzyme Inhibitors; Female; Health; Health Status; Humans; Immunosuppressive Agents; Male; Methotrexate; Middle Aged; Mycophenolic Acid; Prospective Studies; Quality of Life; Sickness Impact Profile; Surveys and Questionnaires; Uveitis; Vision, Ocular

Methotrexate and mycophenolate mofetil are commonly used immunomodulatory therapies for achieving corticosteroid-sparing control of noninfectious uveitis, but there is uncertainty about which drug is more effective.. To compare the effect of methotrexate and mycophenolate for achieving corticosteroid-sparing control of noninfectious intermediate uveitis, posterior uveitis, and panuveitis.. The First-line Antimetabolites as Steroid-sparing Treatment (FAST) uveitis trial screened 265 adults with noninfectious uveitis requiring corticosteroid-sparing immunosuppressive therapy from 9 referral eye centers in India, the United States, Australia, Saudi Arabia, and Mexico between August 22, 2013, and August 16, 2017. Follow-up ended on August 20, 2018.. Patients were randomized to receive oral methotrexate, 25 mg weekly (n = 107), or oral mycophenolate mofetil, 3 g daily (n = 109).. The primary outcome was treatment success at 6 months, which was defined as having control of inflammation in both eyes, no more than 7.5 mg prednisone daily and less than or equal to 2 drops of prednisolone acetate 1%, and no treatment failure due to safety or intolerability. Patients underwent follow-up to 12 months while receiving the same treatment or switched to the other antimetabolite, depending on their 6-month outcome.. Among 216 patients who were randomized (median age, 38 years; 135 (62.5%) women), 194 (89.8%) completed follow-up through 6 months. Treatment success occurred in 64 (66.7%) patients in the methotrexate group vs 56 (57.1%) in the mycophenolate group (difference, 9.5% [95% CI, -5.3% to 21.8%]; odds ratio [OR], 1.50 [95% CI, 0.81 to 2.81]; P = .20). Among patients with posterior uveitis or panuveitis, treatment success was achieved in 58 (74.4%) in the methotrexate group vs 42 (55.3%) in the mycophenolate group (difference, 19.1% [95% CI, 3.6% to 30.6%]; OR, 2.35 [95% CI, 1.16 to 4.90]; P = .02); whereas among patients with intermediate uveitis treatment success occurred in 6 (33.3%) in the methotrexate group vs 14 (63.6%) in the mycophenolate group (difference, -30.3% [95% CI, -51.6% to 1.1%]; OR, 0.29 [95% CI, 0.08 to 1.05]; P = .07; P for interaction = .004). Elevated liver enzymes were the most common nonserious laboratory adverse event, occurring in 14 patients (13.0%) in the methotrexate group and 8 patients (7.4%) in the mycophenolate group.. Among adults with noninfectious uveitis, the use of mycophenolate mofetil compared with methotrexate as first-line corticosteroid-sparing treatment did not result in superior control of inflammation. Further research is needed to determine if either drug is more effective based on the anatomical subtype of uveitis.. ClinicalTrials.gov Identifier: NCT01829295.

Topics: Adult; Anti-Inflammatory Agents; Drug Therapy, Combination; Enzyme Inhibitors; Female; Humans; Immunosuppressive Agents; Liver Function Tests; Male; Methotrexate; Middle Aged; Mycophenolic Acid; Prednisolone; Uveitis

To conduct a Bayesian analysis of a randomized clinical trial (RCT) for non-infectious uveitis using expert opinion as a subjective prior belief.. A RCT was conducted to determine which antimetabolite, methotrexate or mycophenolate mofetil, is more effective as an initial corticosteroid-sparing agent for the treatment of intermediate, posterior, and pan-uveitis. Before the release of trial results, expert opinion on the relative effectiveness of these two medications was collected via online survey. Members of the American Uveitis Society executive committee were invited to provide an estimate for the relative decrease in efficacy with a 95% credible interval (CrI). A prior probability distribution was created from experts' estimates. A Bayesian analysis was performed using the constructed expert prior probability distribution and the trial's primary outcome.. A total of 11 of the 12 invited uveitis specialists provided estimates. Eight of 11 experts (73%) believed mycophenolate mofetil is more effective. The group prior belief was that the odds of treatment success for patients taking mycophenolate mofetil were 1.4-fold the odds of those taking methotrexate (95% CrI 0.03-45.0). The odds of treatment success with mycophenolate mofetil compared to methotrexate was 0.4 from the RCT (95% confidence interval 0.1-1.2) and 0.7 (95% CrI 0.2-1.7) from the Bayesian analysis.. A Bayesian analysis combining expert belief with the trial's result did not indicate preference for one drug. However, the wide credible interval leaves open the possibility of a substantial treatment effect. This suggests clinical equipoise necessary to allow a larger, more definitive RCT.

Topics: Adolescent; Adult; Anti-Inflammatory Agents; Antimetabolites; Bayes Theorem; Female; Humans; Immunosuppressive Agents; Male; Methotrexate; Mycophenolic Acid; Uveitis; Young Adult

To compare the relative effectiveness of methotrexate and mycophenolate mofetil for noninfectious intermediate uveitis, posterior uveitis, or panuveitis.. Multicenter, block-randomized, observer-masked clinical trial.. Eighty patients with noninfectious intermediate, posterior, or panuveitis requiring corticosteroid-sparing therapy at Aravind Eye Hospitals in Madurai and Coimbatore, India.. Patients were randomized to receive 25 mg weekly oral methotrexate or 1 g twice daily oral mycophenolate mofetil and were monitored monthly for 6 months. Oral prednisone and topical corticosteroids were tapered.. Masked examiners assessed the primary outcome of treatment success, defined by achieving the following at 5 and 6 months: (1) ≤0.5+ anterior chamber cells, ≤0.5+ vitreous cells, ≤0.5+ vitreous haze and no active retinal/choroidal lesions in both eyes, (2) ≤10 mg of prednisone and ≤2 drops of prednisolone acetate 1% a day, and (3) no declaration of treatment failure because of intolerability or safety. Additional outcomes included time to sustained corticosteroid-sparing control of inflammation, change in best spectacle-corrected visual acuity, resolution of macular edema, adverse events, subgroup analysis by anatomic location, and medication adherence.. Forty-one patients were randomized to methotrexate and 39 to mycophenolate mofetil. A total of 67 patients (35 methotrexate, 32 mycophenolate mofetil) contributed to the primary outcome. Sixty-nine percent of patients achieved treatment success with methotrexate and 47% with mycophenolate mofetil (P = 0.09). Treatment failure from adverse events or tolerability was not different by treatment arm (P = 0.99). There were no differences between treatment groups in time to corticosteroid-sparing control of inflammation (P = 0.44), change in best spectacle-corrected visual acuity (P = 0.68), or resolution of macular edema (P = 0.31).. There was no statistically significant difference in corticosteroid-sparing control of inflammation between patients receiving methotrexate or mycophenolate mofetil. However, there was a 22% difference in treatment success favoring methotrexate.

Topics: Administration, Oral; Adult; Female; Humans; Immunosuppressive Agents; Macular Edema; Male; Methotrexate; Middle Aged; Mycophenolic Acid; Uveitis; Visual Acuity; Young Adult

Mycophenolate mofetil (MMF) has gained acceptance as an immune modulatory agent in the treatment of autoimmune disorders such as uveitis. It represented a major advance, although optimal use may be limited, in particular, by gastrointestinal (GI) side effects in up to 50 % patients. This prospective study was undertaken to evaluate the effect of conversion from mycophenolate mofetil (MMF) to an enteric-coated mycophenolate sodium (EC-MPS).. Within a cohort of 143 patients treated with MMF we prospectively followed 19 individuals who developed gastrointestinal side effects. Because of limited treatment alternatives, conversion to an enteric-coated mycophenolate sodium (EC-MPS) was undertaken. A standardised questionnaire (GSRS) was completed by each patient regarding GI adverse events, at predefined intervals during the study.. The spectrum of underlying disorders included uveitis (n = 16) and ocular cicatricial pemphigoid (n = 3) that were initially treated with MMF (1000 mg BID). All patients could be kept on EC-MPS treatment and followed with a mean follow-up of 44 weeks (median +/- 12). The maximum of scores on GSRS was reached at baseline (conversion to EC-MPS) in all but 3 patients. However, GSRS scores improved significantly between baseline and visit 4 (3 months) and remained stable further on (p < 0.03). In all but one (uveitis) patient the underlying disorders were under control demonstrating the similar efficacies of MMF and EC-MPS treatments.. The use of EC-MPS appears to be a valid treatment option in ocular autoimmune disorders. In particular. patients with gastrointestinal problems may profit from a significantly reduced frequency of adverse events.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Autoimmune Diseases; Drug Administration Schedule; Female; Gastrointestinal Diseases; Humans; Male; Mycophenolic Acid; Treatment Outcome; Uveitis

Topics: Adult; Humans; Immunosuppressive Agents; Mycophenolic Acid; Uveitis

Adalimumab in combination with other disease-modifying antirheumatic drugs (DMARD) such as methotrexate has a proven efficacy in the management of paediatric non-infectious uveitis. However, many children experience significant intolerance to methotrexate while on this combination, leaving a dilemma for clinicians for choosing the subsequent therapeutic roadmap. Continuation of adalimumab monotherapy might be an alternative feasible option under such settings. This study aims to investigate the efficacy of adalimumab monotherapy in paediatric non-infectious uveitis.. Children with non-infectious uveitis on adalimumab monotherapy (from August 2015 to June 2022) following intolerance to accompanying methotrexate or mycophenolate mofetil were included in this retrospective study. Data were collected at the initiation of adalimumab monotherapy and at three monthly intervals until the last visit. The primary outcome was to evaluate disease control on adalimumab monotherapy as determined by the proportion of patients who had less than a 2-step worsening in uveitis (as per SUN score) and no additional systemic immunosuppression during follow-up. Secondary outcome measures were visual outcome, complications and side-effect profile of adalimumab monotherapy.. Data was collected for 28 patients (56 eyes). The most common uveitis type and course were anterior and chronic uveitis respectively. Juvenile idiopathic arthritis-associated uveitis was the most common underlying diagnosis. During the study period, 23 (82.14%) of the study subjects met the primary outcome. On Kaplan-Meier survival analysis 81.25% (95% CI; 60.6-91.7%) children maintained remission at 12 months on adalimumab monotherapy.. Continuation of adalimumab monotherapy is an effective therapeutic option for the treatment of non-infectious uveitis in children who are intolerant to the combination of adalimumab and methotrexate or mycophenolate mofetil.

Topics: Adalimumab; Antirheumatic Agents; Child; Humans; Methotrexate; Mycophenolic Acid; Retrospective Studies; Uveitis

Mycophenolate mofetil (MMF) is an immunosuppressive agent widely applied in various autoimmune diseases, including autoimmune uveitis, a sight-threatening autoimmune disease mainly affecting the eyes. However, the mechanisms of action are not comprehensively understood. To investigate the potential impact of MMF on uveitis, we generated single-cell RNA sequence data from normal, experimental autoimmune uveitis (EAU) and MMF-treated EAU mice. We observed that some EAU-induced transcriptional changes were reversed by MMF treatment. Transcriptional data indicated that MMF may have a general inhibitory effect on the activation of immune cells during EAU. Each immune cell type showed a different response to MMF treatment. Pseudotime analysis showed that MMF treatment partly reversed the increased differentiation tendency from naïve to effector phenotypes of T and B cells in EAU. The reduced proportion of T-helper (Th)1 and T-helper (Th)17 cells after MMF treatment was confirmed using flow cytometry. MMF treatment downregulated the EAU-associated upregulation of several molecules (such as Cebpd, Pim1, Furin, Bhlhe40, and Hif1a) that promote pathogenic cytokine production by T helper (Th)-1 and Th17 cells. Abnormally enhanced immunoglobulin production, antigen processing, and presentation ability of B cells may also be inhibited by MMF treatment. In addition to T and B cells, MMF treatment countered EAU-induced transcriptional changes in other immune cells to different degrees. Overall, our findings provide novel insights into the mechanisms underlying MMF treatment and indicate that the therapeutic effect of MMF is not driven by a single molecule.

Topics: Animals; Autoimmune Diseases; Disease Models, Animal; Immunosuppressive Agents; Mice; Mice, Inbred C57BL; Mycophenolic Acid; Th17 Cells; Transcriptome; Uveitis

To report the clinical profile of Behcet's disease and its management with immunosuppressants and biologics in a cohort of 25 patients from a tertiary eye care center in South India.. This was a retrospective, observational study. Records of 45 eyes of 25 patients between January 2016 and December 2021 were retrieved from the hospital database. Complete ophthalmic evaluation and systemic examination by the rheumatologist with appropriate investigations had been done. Results were analyzed using Statistical Package for the Social Sciences (SPSS) software.. Males (19, 76%) were found to be more affected than females (6, 24%). Mean age of presentation was 27.68 ± 11.08 years. Twenty patients had bilateral involvement (80%), and unilateral involvement was seen in five patients (20%). Seven eyes of four patients (16%) had isolated anterior uveitis, out of which one patient had unilateral and three patients had bilateral involvement. Twenty-six eyes of 16 patients (64%) had posterior uveitis, out of which six patients had unilateral and 10 had bilateral involvement. Twelve eyes of seven patients (28%) had panuveitis, out of which two patients had unilateral and five had bilateral involvement. Hypopyon was seen in five eyes (11.1%) and posterior synechiae in seven eyes (15.55%). Posterior segment findings included vitritis (24.44%), vasculitis (17.78%), retinitis (17.78%), disc hyperemia (11.11%), and disc pallor (8.89%). Steroids alone were given in five patients (20%) and intravenous methylprednisolone (IVMP) was given in four patients (16%). Immunosuppressive agents along with steroids were given in 20 patients (80%), of which azathioprine alone was given in seven patients (28%), cyclosporin alone was given in two patients (8%), mycophenolate mofetil alone was given in three patients (12%), combination of azathioprine and cyclosporin was given in six patients (24%), and combination of methotrexate and mycophenolate mofetil was given in one patient (4%). Biologics were given in 10 patients (40%) - adalimumab in seven patients (28%) and infliximab in three patients (12%).. Behcet's disease is an uncommon uveitis in India. Addition of immunosuppressants and biologics to conventional steroid therapy gives better visual outcomes.

Topics: Adolescent; Adult; Azathioprine; Behcet Syndrome; Biological Products; Cyclosporins; Female; Humans; Immunosuppressive Agents; Male; Mycophenolic Acid; Retrospective Studies; Steroids; Uveitis; Young Adult

Experience with mycophenolate in uveitis due to Behçet syndrome (BS) is limited. Twelve patients with panuveitis or posterior uveitis who were started mycophenolate were included. Data on demographic characteristics, therapies, ocular attacks, and adverse events were extracted from patient charts. Seven patients with BS uveitis were prescribed mycophenolate for remission induction, of which 6 were refractory/intolerant to conventional immunosuppressives. Mycophenolate was combined with anti-TNFs in 3 patients, resulting in no further ocular attacks. Mycophenolate had to be stopped in the fourth patient due to adverse events. The remaining 3 patients continued to have ocular attacks and were switched to other agents without any drop in visual acuity. Among the 5 patients who were prescribed mycophenolate for maintenance, 2 were relapse free, but 3 experienced ocular attacks. One patient had an exacerbation of mucocutaneous lesions, and 2 experienced adverse events. Mycophenolate monotherapy may not be adequate for remission induction of refractory BS uveitis, but it can be a safe and effective alternative when combined with a biologic agent. It may also be an option for maintenance therapy.

Topics: Behcet Syndrome; Humans; Immunosuppressive Agents; Mycophenolic Acid; Retrospective Studies; Uveitis

Topics: Humans; Immunosuppressive Agents; Methotrexate; Mycophenolic Acid; Uveitis

Topics: Cost-Benefit Analysis; Drug Costs; Enzyme Inhibitors; Humans; Immunosuppressive Agents; Methotrexate; Mycophenolic Acid; Uveitis

To evaluate the therapeutic effect and safety profile of next generation mycophenolate sodium (MPS), which is different from mycophenolate mofetil with an enteric-coated formulation, in corticosteroid-refractory non-infectious inflammatory uveitis (CRU) patients.. Prospective, uncontrolled, open-label interventional case series. Forty consecutive patients at a tertiary uveitis referral centre received 6 months of oral MPS as the treatment regimen with follow-up 12 months. The main outcome measures were best-corrected visual acuity (BCVA), inflammatory index, steroid-sparing effect of tapering prednisone to ≤10 mg daily and side effects.. Mean age of enroled patients was 49 (49 ± 13) years and 29 (72.5%) were female. Thirty-six (90.0%) had bilateral disease. There were 0 (0%) anterior uveitis, 2 (5.0%) intermediate uveitis, 22 (55.0%) posterior uveitis, and 16 (40.0%) panuveitis. Vogt-Koyanagi-Harada disease was the most common diagnosis (17/40, 42.5%), followed by idiopathic panuveitis (8/40, 20%) and idiopathic retinal vasculitis (5/40, 12.5%). LogMAR BCVA improved from 0.9 (SD = 0.09) to 0.31 (SD = 0.08) after 6 months of MPS with good steroid-sparing effect (p = 0.012). Further maintenance in LogMAR BCVA was evident after MPS discontinuation from 6th month to 12th month, from 0.31 (SD = 0.08) to 0.33 (SD = 0.07), respectively (p = 0.81). MPS was the only immunosuppressive drug needed to reach quiescent state in 29 patients (72.5%). The drug-related safety profile was satisfactory.. MPS is an effective steroid-sparing drug for the treatment of CRU. The effect seen was not only during the 6 months of therapy, but also extended to 12 months to maintain BCVA and inflammation control. The side effects were acceptable.

Topics: Adrenal Cortex Hormones; Adult; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Prospective Studies; Retrospective Studies; Treatment Outcome; Uveitis; Visual Acuity

Topics: Antibiotics, Antineoplastic; Child; Drug Therapy, Combination; Female; Follow-Up Studies; Glucocorticoids; Humans; Mycophenolic Acid; Nephritis, Interstitial; Panuveitis; Time Factors; Uveitis

The non-infectious uveitis, a serious vision-threatening disease is the fourth most common cause of blindness in working population of the developed world. Various antimetabolites are applied in corticosteroid-sparing therapy also in Poland but their efficacy was not compared in our country. The aim of our study was to compare mycophenolate mofetil and azathioprine in terms of therapeutic effect of the antimetabolites in Polish patients with this disease.. The comparative, retrospective study included data of 61 patients admitted to Independent Public University Eye Hospital between January 2009 and January 2017, treated with antimetabolites for non-infectious uveitis. 31 patients received mycophenolate mofetil, 30 patients - azathioprine. In the assessment of corticosteroid-sparing efficacy, among others changes in visual acuity, the duration of the disease and therapy, incidence of ophthalmologic complications, adverse systemic side effects were determined.. The corticosteroid-sparing therapy was more often effective, and an improvement of visual acuity more frequent in patients treated with mycophenolate mofetil than in these receiving azathioprine (84% patients vs. 60%, and 27% patients vs. 13%, respectively); these differences were statistically significant (p<0.05).. Results of our study showing better therapeutic efficacy when applied mycophenolate mofetil seems promising approach for treatment of non-infectious posterior uveitis and panuveitis. In the first study, there was different duration of the disease before drug administration (10.5 years vs. 7.14 years in the azathioprine and mycophenolate mofetil therapy, respectively, p<0.05) and limited number of patients assessed, thus it is desirable to examine more Polish patients treated with the antimetabolites.

Topics: Adult; Aged; Antimetabolites; Azathioprine; Female; Humans; Male; Middle Aged; Mycophenolic Acid; Poland; Uveitis; Young Adult

Topics: Adrenal Cortex Hormones; Antimetabolites; Humans; Immunosuppressive Agents; Inflammation; Methotrexate; Mycophenolic Acid; Uveitis

To discover whether retinal vessel oxygen metabolism is affected in uveitis associated with Vogt-Koyanagi-Harada (VKH) disease.. 41 patients with VKH disease (82 eyes) and 12 healthy subjects (24 eyes) matched in age and gender were prospectively evaluated. Retinal oxygen saturation and vessel calibre were measured with a non-invasive spectrophotometric retinal oximeter (Oxymap T1).. In healthy controls, mean arteriolar oxygen saturation (%) was 93.8±5.9 and venular saturation was 60.1±5.8. In acute VKH uveitic phase associated with exudative retinal detachment (n=12), arteriolar and venular oxygen saturation values were 104.7±7.8 and 67.9±7.7, respectively, and both are significantly higher than the healthy group (p<0.001; p=0.001, respectively). In patients with VKH disease who recovered after immunosuppressive therapy and restored normal anatomy without 'sunset glow fundus' (n=13), oximetry values were 96.4±9.6 and 61.6±7.5, respectively, similar to healthy controls. In patients with 'sunset glow fundus' and chorioretinal atrophy (n=16), saturation levels were 88.6±7.8 and 50.0±13.1, respectively, significantly lower than healthy controls (p=0.02; p=0.003, respectively). These patients also had significantly smaller diameter of retinal arterioles and venules compared with controls (p=0.035; p=0.001, respectively).. Retinal oxygen metabolism is altered in uveitis associated with VKH disease. Oxygen saturation profile is abnormal in acute uveitic phase of the disease and returns to normal in those who recover with normal fundus appearance, but not in eyes that suffer permanent anatomical damage with 'sunset glow fundus' and chorioretinal atrophy. Retinal oximetry may be of value in evaluating vascular and metabolic aspects of posterior uveitis.

Topics: Adolescent; Adult; Antibiotics, Antineoplastic; Coloring Agents; Drug Therapy, Combination; Fluorescein Angiography; Fundus Oculi; Glucocorticoids; Humans; Indocyanine Green; Male; Middle Aged; Mycophenolic Acid; Ophthalmoscopy; Oximetry; Oxygen; Prospective Studies; Retinal Vessels; Tomography, Optical Coherence; Uveitis; Uveomeningoencephalitic Syndrome; Visual Acuity; Young Adult

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 highlight the rare but life-threatening infective consequences of immunosuppression or biologic treatment for sight-threatening uveitis.. Retrospective case series of four immunosuppressed patients with uveitis complicated by sepsis.. The affected patients were all treated using prednisolone 10 mg/day or greater, together with oral immunosuppression (2 mycophenolate mofetil, 1 azathioprine + ciclosporin, 1 methotrexate) and, in one case, infliximab. All patients survived following intensive treatment.. Life-threatening infection is a rare but important risk in immunosuppressed patients with uveitis. Complete protection is not possible and prophylaxis regimens are of unproven efficacy. Patients should understand the risks before agreeing to a course of treatment.

Topics: Adult; Aged; Azathioprine; Bacteremia; Cyclosporine; Drug Therapy, Combination; Female; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Klebsiella Infections; Male; Methotrexate; Middle Aged; Mycophenolic Acid; Pneumocystis Infections; Prednisolone; Retrospective Studies; Uveitis

To report the efficacy of mycophenolate mofetil (MMF) as adjunctive therapy for the treatment of multiple sclerosis (MS)-associated uveitis.. In this retrospective, interventional case series, patients with MS-associated uveitis who were treated by MMF as an adjunct therapy to systemic corticosteroid were studied. Patients' demographics, clinical course, response to treatment, and complications were assessed.. A total of 30 eyes of 15 patients with a mean age of 34.5 ± 8.3 years were studied. In three patients (20%), onset of uveitis preceded the diagnosis of MS. The course of MS was relapsing-remitting in 11 patients (73.3%) and secondary progressive in four patients (26.7%). At 1 year after institution of MMF, all the patients were on oral prednisolone ≤ 7.5 mg/day, all eyes were quiet without macular edema, and 53.3% of eyes gained visual improvement. Supplemental periocular and intraocular injections were needed during the first 6 months after starting MMF therapy. The systemic adverse effects were transient and minor in severity.. MMF had beneficial effects on vision and intraocular inflammation with an acceptable safety profile.

Topics: Adolescent; Adult; Chemotherapy, Adjuvant; Enzyme Inhibitors; Female; Fluorescein Angiography; Glucocorticoids; Humans; Male; Middle Aged; Multiple Sclerosis; Mycophenolic Acid; Prednisolone; Retrospective Studies; Tomography, Optical Coherence; Treatment Outcome; Uveitis; Visual Acuity; Young Adult

To evaluate the effectiveness and safety of mycophenolate mofetil (MMF) as first-line therapy combined with systemic corticosteroids in initial-onset acute uveitis associated with Vogt-Koyanagi-Harada (VKH) disease.. This prospective study included 38 patients (76 eyes). The main outcome measures were final visual acuity, corticosteroid-sparing effect, progression to chronic recurrent granulomatous uveitis and development of complications, particularly 'sunset glow fundus'.. The mean follow-up period was 37.0 ± 29.3 (range 9-120 months). Visual acuity of 20/20 was achieved by 93.4% of the eyes. Corticosteroid-sparing effect was achieved in all patients. The mean interval between starting treatment and tapering to 10 mg or less daily was 3.8 ± 1.3 months (range 3-7 months). Twenty-two patients (57.9%) discontinued treatment without relapse of inflammation. The mean time observed off of treatment was 28.1 ± 19.6 months (range 1-60 months). None of the eyes progressed to chronic recurrent granulomatous uveitis. The ocular complications encountered were glaucoma in two eyes (2.6%) and cataract in five eyes (6.6%). None of the eyes developed 'sunset glow fundus', and none of the patients developed any systemic adverse events associated with the treatment.. Use of MMF as first-line therapy combined with systemic corticosteroids in patients with initial-onset acute VKH disease prevents progression to chronic recurrent granulomatous inflammation and development of 'sunset glow fundus'.

Topics: Acute Disease; Administration, Oral; Adolescent; Adult; Child; Disease Progression; Drug Therapy, Combination; Enzyme Inhibitors; Female; Fundus Oculi; Glucocorticoids; Humans; Inflammation; Injections, Intravenous; Male; Methylprednisolone; Mycophenolic Acid; Prednisone; Prospective Studies; Recurrence; Uveitis; Uveomeningoencephalitic Syndrome; Visual Acuity

To assess the efficacy and tolerability of mycophenolate sodium (MPS) in the therapy of children with chronic non-infectious uveitis.. Retrospective analysis of 23 children with chronic uveitis, treated with MPS, with a follow-up of at least 6 months. The main outcome measures were time to uveitis reactivation and corticosteroid-sparing effect under MPS treatment. The secondary outcome measures were best-corrected visual acuity (BCVA) and treatment-related side effects.. From 23 patients included in the study, 2 patients had anterior uveitis, 19 had intermediate uveitis and 2 had panuveitis. The probability of reactivation-free survival after MPS initiation was estimated as 65% at both 1 and 2 years. The probability of discontinuing systemic corticosteroids after 1 year of treatment was 39% and after 2 years 51%. The probability to taper corticosteroids to a daily dosage of ≤0.1 mg/kg after 1 and 2 years was 62% and 85%, respectively. BCVA improved or remained stable in 96% of eyes after 1 year of therapy. Treatment-related side effects were found in nine children (rate: 0.17/patient-year). No therapy discontinuation because of side effects was needed.. Our data suggest that MPS is useful and well tolerated in children with chronic uveitis. MPS seems to be an effective drug for the treatment of chronic non-infectious uveitis of childhood and may be preferred as a first-line steroid-sparing agent in this form of uveitis.

Topics: Adolescent; Antibiotics, Antineoplastic; Child; Chronic Disease; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Male; Mycophenolic Acid; Retrospective Studies; Time Factors; Treatment Outcome; Uveitis; Visual Acuity

The aim of this study was to describe a single-center experience in the treatment and follow-up of cystoid macular edema patients. Clinical records of all patients with cystoid macular edema followed up in the Rheumatologic and Ophthalmological Unit of our center between 1993 and 2013 were retrospectively evaluated. The outcome was assessed by visual acuity and optical coherence tomography status during follow-up. Comparisons were made by Fisher's exact test (p < 0.05 significant). In this study 16 eyes in 9 patients were analyzed. Our study includes mainly post-uveitic (78 %) cases with a high prevalence of human leukocyte antigen B51 (67 %). Systemic immunosuppressive therapy was prescribed in 87 % of cases. The most frequently used drugs were cyclosporine, interferon-α, and infliximab. The first two molecules appeared respectively the most used as the first option and the one with the longest survival on treatment. Interferon-α was the most effective drug in contrasting visual acuity loss compared to the majority of drugs, but significantly more effective than mycophenolate (p = 0.01) in reducing macular edema. At the end of follow-up, 50 % of patients showed a significant visual loss, while 88 % did not present macular edema. In our small cohort, interferon-α is the most promising drug in contrasting visual acuity loss in cystoid macular edema. Visual prognosis remains severe in these patients.

Topics: Adult; Cohort Studies; Cyclosporine; Female; Follow-Up Studies; HLA-B51 Antigen; Humans; Immunosuppressive Agents; Infliximab; Interferon-alpha; Macular Edema; Male; Middle Aged; Mycophenolic Acid; Prevalence; Retrospective Studies; Tomography, Optical Coherence; Treatment Outcome; Uveitis; Visual Acuity

To determine whether patients with juvenile systemic granulomatous disease (JSGD) (Blau syndrome) and uveitis have a characteristic ocular phenotype.. Clinical and imaging data were collected retrospectively from patients attending the Regional Combined Paediatric Rheumatology and Ocular Inflammatory Service, Bristol Eye Hospital. General demographic information, laterality of the uveitis, age at onset, anatomical classification and course of the uveitis, clinical phenotype and specific NOD2 mutation were recorded for each patient.. Seventeen eyes from nine patients (five males; four females) were included in the study. Mean age at the disease onset was 15 months, range 1-84 months. Eight patients had bilateral uveitis. Anterior uveitis was present in five eyes, intermediate uveitis in two eyes, and there were 10 eyes with panuveitis, manifesting as multifocal choroiditis. Appearance of optic disc included indistinct disc margins in six eyes, optic nerve head pallor in six eyes, optic disc vessel sheathing in four eyes, and there was peripapillary hypo/hyperpigmentation in 13 eyes accompanied with characteristic peripapillary nodular excrescences. Among NOD2 mutations, the p.R334W was the most commonly detected (n: four cases), and three patients carried novel variants, the p.E338D and p.D390V variants in one patient, and the p.H520Y and p.Q809K variants in two different patients.. Chronic bilateral panuveitis and a nodular peripapillary appearance in childhood onset uveitis are characteristic features of JSGD, which support the need for an appropriate genetic NOD2 analysis.

Topics: Age of Onset; Arthritis; Child, Preschool; Female; Glucocorticoids; Humans; Immunosuppressive Agents; Infant; Male; Methotrexate; Mutation; Mycophenolic Acid; Nod2 Signaling Adaptor Protein; Optic Nerve; Phenotype; Prednisolone; Retina; Retrospective Studies; Sarcoidosis; Synovitis; Uveitis; Visual Acuity

To report the outcomes of pars plana vitrectomy with epiretinal membrane (ERM) peel, with or without internal limiting membrane peel, in patients with uveitis.. Retrospective interventional case series of patients undergoing pars plana vitrectomy with ERM peel between January 2005 and March 2012. Sixteen consecutive patients (16 eyes) were identified, with a minimum postoperative follow-up of 6 months. Visual acuity, anatomical outcomes, perioperative control of inflammation, and complications were assessed.. The mean age at surgery was 47.3 years (range, 14-68 years), with a mean duration of ERM at surgery of 21.3 months (3-84 months). At 6 months, visual acuity improved in 31.25% of eyes, stabilized in 31.25%, and was worse in 37.5%. The causes of reduced visual acuity postoperatively included severe preexisting macular pathology and unoperated cataract.. Pars plana vitrectomy with ERM peel in eyes with uveitis may improve or stabilize visual acuity, especially in eyes with macular traction, but in the absence of traction, outcomes are variable and unpredictable. Prevention of ERM formation by aggressive control of inflammation is important.

Topics: Adolescent; Adult; Aged; Azathioprine; Drug Therapy, Combination; Endotamponade; Epiretinal Membrane; Female; Follow-Up Studies; Glucocorticoids; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Prednisolone; Retrospective Studies; Tomography, Optical Coherence; Uveitis; Visual Acuity; Vitrectomy; Young Adult

Subretinal fibrosis and uveitis syndrome is a rare, potentially devastating, posterior uveitis of unknown aetiology, characterised bilaterally by initial multifocal choroiditis with later progressive subretinal fibrosis. We report a rare case of unilateral subretinal fibrosis and uveitis syndrome. To date, there are only two case reports of unilateral disease. Our patient presented with unilateral blur and was found to have reduced visual acuity. A Bartonella profile was positive and a diagnosis of Bartonella posterior uveitis was made. Several positive ocular findings in the anterior chamber and on fundoscopy consistent with the syndrome were found. When steroid therapy alone could no longer control active inflammation, the immunosuppressive agent mycophenolate was added. Over time subretinal fibrosis became established sparing the macula and associated complications occurred, but with mycophenolate, at four years, our patient's visual acuity had improved and remains stable. Moreover, four years after her initial presentation, her condition remains strictly unilateral.

Topics: Adolescent; Bartonella Infections; Female; Fibrosis; Humans; Immunosuppressive Agents; Mycophenolic Acid; Retina; Syndrome; Treatment Outcome; Uveitis; Visual Acuity

Macular edema represents a major cause of visual loss in uveitis and its adequate management is crucial for the maintenance of useful vision in patients with uveitis. Corticosteroid is the first choice for UME treatment.Long term and sustained release implantation is the newest administration for medical therapy. The immunosuppressant such as cyclosporine, methotrexate, azathioprine and mycophenolate mofetil can be used specially for chronic and intractable UME. Moreover, these years, some newly developed biological agents, for example, anti-VEGF, interferon-α, anti-TNF and acetazolamide will provide new options for UME pharmacotherapy.

Topics: Acetazolamide; Adrenal Cortex Hormones; Angiogenesis Inhibitors; Antibodies, Monoclonal, Humanized; Azathioprine; Bevacizumab; Cyclosporine; Humans; Immunosuppressive Agents; Macular Edema; Methotrexate; Mycophenolic Acid; Tumor Necrosis Factor-alpha; Uveitis; Vision Disorders

To assess the safety and efficacy of noncorticosteroid triple immunosuppressive therapy in the treatment of refractory chronic noninfectious childhood uveitis.. Subjects were retrospectively selected from a database. Patients were included if they were diagnosed with chronic, noninfectious uveitis at 16 years of age or under and treated with triple immunosuppressive therapy for at least 6 months (following failure of a combination of 2 immunosuppressants). Patient demographics, diagnoses, duration of uveitis, drug dosages, active joint inflammation, and ophthalmologic data were recorded. Efficacy outcomes for triple therapy were recorded at 6 months.. Thirteen patients with bilateral uveitis were included. Using Standardized Uveitis Nomenclature (SUN) criteria, at 6 months only 11 eyes (42%) had a 2-step improvement in anterior chamber cell inflammation (n = 26). In addition, 2 patients required additional oral corticosteroid treatment. There were 4 significant infectious adverse events during a total of 21.9 patient-years (PY) on triple therapy (0.18 events per PY).. In this group of children with refractory uveitis, addition of a third immunosuppressive agent did not confer substantial benefit in redressing ocular inflammation and was associated with significant infections in a minority of patients.

Topics: Adolescent; Child; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; Male; Methotrexate; Mycophenolic Acid; Retrospective Studies; Tacrolimus; Treatment Outcome; Uveitis

To evaluate the outcomes of changing immunosuppressive therapy for noninfectious uveitis after failure.. Retrospective cohort study.. Patients with noninfectious uveitis managed at 2 tertiary uveitis clinics in the United Kingdom and Australia.. Participants with a history of using immunosuppressive therapy were identified in clinics, and notes were reviewed by doctors trained in uveitis therapy. Each treatment episode/course (starting or changing a therapy) was identified, and demographic details, clinical characteristics, drug used (second-line immunosuppressive agent [ISA] or biologicals), and drug doses were obtained.. For each treatment episode, the reasons for changing therapy, corticosteroid-sparing effects, and control of inflammation were determined.. A total of 147 patients were identified who underwent 309 different treatment episodes. Fifty-five percent of patients eventually required a change in treatment after their first treatment episode/course. Forty-five episodes involved switching from one ISA to another, with 50% to 100% of these patients achieving "success" (prednisolone ≤10 mg and sustained control) with the new ISA. A combination of ISAs were used in 53 episodes, with "success" being achieved in 50% to 71% of these patients. Biological agents were used in 45 episodes, the most common one being infliximab, which achieved success in 80% of patients.. Our data suggest that control of inflammation can be achieved after switching or combining ISAs.

Topics: Adolescent; Adult; Aged; Azathioprine; Child; Child, Preschool; Cohort Studies; Cyclosporine; Drug Substitution; Female; Humans; Immunosuppressive Agents; Male; Methotrexate; Middle Aged; Mycophenolic Acid; Prednisolone; Retrospective Studies; Treatment Failure; Treatment Outcome; Uveitis; Visual Acuity; Young Adult

In human, autoimmune uveitis is a leading cause of visual disability and ranks with diabetic retinopathy as a major source of blind registrations in developed countries. Since most cases of non-infectious uveitis are considered to be autoimmune or at least immune-mediated, the management of such patients has rested on appropriate immunosuppression. Some patients, however, despite maximal immunotherapy, fail to respond or are seriously intolerant of the drug therapies. Since its establishment 20 years ago, the model of experimental autoimmune uveoretinitis has served as a useful template for novel therapeutic approaches. The aim of our study was to compare the efficacy of mycophenolate mofetil and cyclophosphamide and golimumab treatment in the mouse model of experimental autoimmune uveitis. The intensity of intraocular inflammation was evaluated histologically in the treatment and control groups. Experimental autoimmune uveitis has been induced in mouse strain C57BL/6 by subcutaneous application of interphotoreceptor retinoid binding protein in complete Freund's adjuvant and pertussis toxin. The treatment was commenced on the day of uveitis induction. Cyclophosphamide was applied intraperitoneally in a single dose (100 mg/kg), mycophenolate mofetil intraperitoneally daily (30 mg/kg or 50 mg/kg), golimumab subcutaneously weekly (70 mg/kg). Sham intraperitoneal injection of a placebo (aqua pro injectione) and untreated mice with experimental autoimmune uveitis served as controls. The results show statistically significant suppression of experimental uveitis both with mycophenolate mofetil and with cyclophosphamide, and thus support its use in human medicine.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antibodies, Monoclonal; Cyclophosphamide; Disease Models, Animal; Inflammation; Mice; Mice, Inbred C57BL; Mycophenolic Acid; Uveitis

To assess the long-term efficacy of mycophenolate mofetil (MMF) in uveitic cystoid macular edema (CMO).. Thirty-eight uveitis patients with CMO treated with MMF with a follow-up of at least 5 years were analyzed. The patients were divided into two groups: group A, 24 patients with CMO that had occurred before initiation of MMF; group B, 14 patients who developed CMO for the first time during MMF.. In group A, a complete remission of CMO without recurrences was observed in 12 of 24 patients (50%, rate: 0.12/patient-year). In group B, CMO occurred in 7 patients (50%) despite standard dosage of MMF, and in 7 patients (50%) during MMF dose reduction.. The results show that MMF is not always sufficiently effective as a long-term treatment for uveitic macular edema. Moreover, in some uveitis patients MMF cannot prevent new development of CMO.

Topics: Adolescent; Adult; Aged; Child; Female; Humans; Immunosuppressive Agents; Macular Edema; Male; Middle Aged; Mycophenolic Acid; Recurrence; Treatment Outcome; Uveitis; Visual Acuity; Young Adult

To evaluate effectiveness and safety of mycophenolate mofetil (MMF) monotherapy in paediatric autoimmune uveitis.. We reviewed medical records of patients, 18 years of age or younger, with autoimmune uveitis treated with MMF at our practice from 2005 to 2009. The dose and duration of MMF therapy, inflammation status, visual acuity, previous immunomodulatory therapies, and adverse effects were recorded. In addition, the following subgroups were defined: (1) Durable Disease Control: patients whose uveitis remained quiescent for at least 2 years on MMF monotherapy, with no more than two flare-ups successfully treated with an increase in MMF dosage and/or a short course (<1 month) of corticosteroids; (2) Short-term Inflammation Control: patients whose uveitis remained quiescent for less than 2 years, with no more than one flare-up successfully treated with an increase in MMF dosage and/or a short course of corticosteroids, or who initially achieved inflammation control but discontinued MMF because of significant adverse effects.. A total of 38 out of 52 patients (73.1%) obtained inflammation control following 2 months of MMF monotherapy, achieving ≤ 0.5+ grading in anterior chamber cell/flare and vitreous haze. In the cross-sectional analysis, 25 patients (48.1%) met the criteria for Durable Disease Control, and 13 others (25.0%) qualified for Short-term Inflammation Control. Visual acuity remained stable or improved in 94.2% of the study population. Six patients (11.5%) discontinued MMF because of significant adverse effects, the most common of which was gastrointestinal disturbances.. MMF monotherapy appears to be an effective and safe treatment in paediatric autoimmune uveitis.

Topics: Adolescent; Child; Child, Preschool; Female; Gastrointestinal Diseases; Humans; Immunosuppressive Agents; Male; Mycophenolic Acid; Retrospective Studies; Uveitis; Visual Acuity

Short-term studies have shown mycophenolate mofetil (MMF) to be a useful immunosuppressive agent for the treatment of intraocular inflammation. The aim of our study was to assess the long-term efficacy and tolerability of MMF in patients with chronic non-infectious uveitis, as well as to analyze disease course following discontinuation of therapy.. This is a retrospective case series on 60 uveitis patients treated with MMF with a follow-up period of at least 5 years. The main outcome measures were: control of inflammation, corticosteroid-sparing potential, side-effects, ability to stop/taper MMF treatment because of effective control of inflammation and relapse rate after therapy discontinuation.. Control of intraocular inflammation (efficacy of MMF), defined as inactive disease under prednisolone dose of ≤ 10 mg daily, was achieved in 43 of 60 patients (72%) after 1 year of MMF treatment at a rate of 0.72 per patient-year (PY), and in 45 of 55 patients (82%) after 2 years therapy (rate: 0.41/PY). An improvement (3 lines) or stabilization of visual acuity was observed in 49 patients (82%), and a worsening in 11 patients (18%, 95% CI: 10-30%). The probability of discontinuing prednisolone, estimated by the Kaplan-Meier method, was 40% after 5 years therapy. The probability of discontinuing mycophenolate mofetil due to efficacy was 33% after 5 years treatment. Recurrences of uveitis occurred in six of 21 patients (29%, rate: 0.11/PY) after MMF discontinuation due to efficacy. The treatment was stopped because of inefficacy in 12 patients (rate: 0.05/PY) and because of side-effects in four patients (rate: 0.02/PY). The rate of adverse effects during MMF therapy was 0.17/PY.. Our data show that mycophenolate mofetil is generally effective and well tolerated in the treatment of chronic non-infectious uveitis.

Topics: Adolescent; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Child; Chronic Disease; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Recurrence; Retrospective Studies; Treatment Outcome; Uveitis; Visual Acuity; Young Adult

To survey the practice of uveitis experts in the management of uveitic cataract and cystoid macular oedema (CMO).. A structured questionnaire containing two clinical scenarios was sent to members of the International Uveitis Study Group (IUSG). The questionnaire surveyed both respondents' current practice and their perception of the supporting clinical evidence.. For uveitic cataract, 70% required a 3-month inflammation-free period before surgery, and 76% gave a prophylactic preoperative systemic corticosteroid. For uveitic CMO, 87% gave corticosteroids, usually orally. Preferred second-line agents were methotrexate (39%), cyclosporin (24%), azathioprine (17%), and mycophenolate (7%). Respondents suggested the evidence underlying their decisions was either absent or relatively weak (levels III or IV), and in most cases personal experience was a factor.. This survey highlights areas of consensus and variation among uveitis experts in managing uveitic cataract and CMO, and emphasizes the need for further clinical trials to establish the best practice.

Topics: Adrenal Cortex Hormones; Adult; Anti-Bacterial Agents; Azathioprine; Cataract; Cataract Extraction; Cyclosporine; Expert Testimony; Female; Health Care Surveys; Health Knowledge, Attitudes, Practice; Humans; Macular Edema; Male; Methotrexate; Middle Aged; Mycophenolic Acid; Ophthalmologic Surgical Procedures; Surveys and Questionnaires; Uveitis; Young Adult

To study the efficacy of systemic steroids (SS) associated with mycophenolate mofetil (MMF) for the control of juxta/sub-foveal uveitic choroidal neovascularization (CNV) unresponsive to the traditional immunosuppressive agents. Patients with juxta/sub-foveal uveitic CNV unresponsive to the traditional immunosuppressive drugs were treated with SS and MMF. The study was designed as a prospective, consecutive, open-label, interventional case series. Visual gain and loss were defined as improving or worsening of two or more lines of best-corrected visual acuity (BCVA), respectively. CNV size outcome was dichotomized as "increased" or "stable/reduced", if increased >200 μm(2), or reduced ≥ 200 μm(2) or not modified by 200 μm(2), respectively. Nine cases (12 eyes) have been considered; ages ranged from 27 to 56 years. The mean follow-up time was 18.2 ± 2.9 months (min: 14 months, max: 23 months). At base-line, the mean BCVA was 0.3 ± 0.17, improving up to 0.57 ± 0.25 and to 0.63 ± 0.22 (P < 0.001, paired t-test) at the 6 and 12-month follow-ups, respectively. At the last follow-up, all the patients had stable/improved BCVA (P < 0.0001, Fisher's exact test) and stable/reduced lesion size (P < 0.0001, Fisher's exact test). None of the patients complained of any severe adverse event during the treatment. The combination of SS and MMF seems to be a promising strategy in order to control uveitic CNVs unresponsive to the traditional immunosuppressive agents. Further studies are needed to validate the data of this case series.

Topics: Administration, Oral; Adult; Choroidal Neovascularization; Drug Therapy, Combination; Female; Fluorescein Angiography; Glucocorticoids; Humans; Immunosuppressive Agents; Injections, Intravenous; Male; Methylprednisolone; Middle Aged; Mycophenolic Acid; Prednisolone; Salvage Therapy; Uveitis; Visual Acuity

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

A discrete subpopulation of steroid refractory (SR) CD4(+) T cells has recently been identified in patients with SR ulcerative colitis (UC). The purpose of this study was to test whether this subpopulation is also present in patients with clinically defined SR uveitis. As interleukin (IL)-2 experimentally mediates the SR phenotype, the combined effects of dexamethasone (Dex) and a range of IL-2 targeting immunosuppressive agents were also investigated.. Peripheral blood mononuclear cells (PBMCs) from 27 patients with uveitis and 4 normal volunteers were cultured for 5 days with CD3-CD28 beads. In vitro steroid refractivity or responsiveness was determined by the presence or absence of a subpopulation of SR CD4(+) cells (as previously reported for UC) that continued to proliferate or not in the presence of Dex. The patients were concurrently classified by a masked investigator as having clinically SR (threshold for disease reactivation, >or=10 mg prednisone daily) or steroid sensitive (SS) disease.. There was 78% (21/27) agreement between the in vitro and clinical classifications of SR and SS disease (kappa coefficient = 0.56, P = 0.002). This finding corresponds to a positive predictive value of 90% and a negative predictive value of 71%. In normal volunteers, basiliximab, daclizumab, and AG490 achieved an equivalent augmentation of CD4(+) cell suppression in combination with Dex.. As in UC, patients with SR uveitis have a subpopulation of SR CD4(+) cells that are a potential target for intervention with anti-IL-2 therapies, including inhibitors of JAK/STAT signaling. The identification of SR T cells also has potential clinical application as a biomarker for SR disease.

Topics: Adult; Aged; CD4-Positive T-Lymphocytes; Dexamethasone; Drug Resistance; Drug Therapy, Combination; Female; Flow Cytometry; Glucocorticoids; Humans; Immunosuppressive Agents; Interleukin-2; Lymphocyte Activation; Male; Methotrexate; Middle Aged; Mycophenolic Acid; Prednisone; Uveitis; Young Adult

Mycophenolate mofetil (MMF) is a relatively new immunomodulatory agent. The experience of MMF in inflammatory eye diseases is limited to a few case series. We report our experience of MMF in eight patients with uveitis. Control of inflammation was achieved in all patients. No patient had adverse side effects. Our study indicates that MMF is a safe and effective immunomodulatory agent.

Topics: Adult; Aged; Female; Follow-Up Studies; Humans; Immunologic Factors; India; Male; Middle Aged; Mycophenolic Acid; Treatment Outcome; Uveitis; Young Adult

To evaluate the long-term safety and efficacy of Mycophenolate Mofetil (MMF) for the control of cystoid macular oedema (CMO) secondary to noninfectious uveitis (NU).. The medical records of 19 consecutive patients with inflammatory CMO treated with MMF were retrospectively reviewed. Patient demographics, best corrected visual acuity (BCVA), fluorescein angiography (FA), and optical coherence tomography (OCT) findings were evaluated.. There were eight females and 11 males with a mean age of 32.9 +/- 8.9 years. After a 1-year follow-up, 18/19 patients (31 eyes, 96.9%, P < 0.05) no longer had signs of CMO, as per their FA and OCT findings; the mean central foveal thickness (CFT) was 167.2 +/- 12.8 microm. At the last follow-up, only 3/19 patients, all affected by Behçet panuveitis, had recurrences of CMO. Mean BCVA improved from 0.34 +/- 0.14 SD at baseline to 0.65 +/- 0.2 SD at last follow-up.. MMF was safe and effective in controlling CMO and in reducing the uveitis relapse rate in patients not responding to traditional immunosuppressants. Further case-controlled studies are mandatory to validate those preliminary results.

Topics: Adult; Anti-Inflammatory Agents; Disease Progression; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; Macular Edema; Male; Methylprednisolone; Mycophenolic Acid; Prednisone; Time; Treatment Outcome; Uveitis

To critically assess potentially carcinogenic effects of immunosuppressive therapy in the ocular inflammation setting.. Focused evidence assessment.. Relevant publications were identified by MEDLINE and EMBASE queries and reference list searches.. Extrapolation from transplant, rheumatology, skin disease, and inflammatory bowel disease cohorts to the ocular inflammation setting suggest that: 1) alkylating agents increase hematologic malignancy risk and cyclophosphamide increases bladder cancer risk, but less so with < or =18 months' duration of therapy and hydration, respectively; 2) calcineurin inhibitors and azathioprine probably do not increase total cancer risk to a detectable degree, except perhaps some other risk factors (uncommon in ocular inflammation patients) might interact with the former to raise risk; 3) tumor necrosis factor (TNF) inhibitors may accelerate diagnosis of cancer in the first six to 12 months, but probably do not increase long-term cancer risk; and 4) changes in risk with methotrexate, mycophenolate mofetil, and daclizumab appear negligible, although nontransplant data are limited for the latter agents. Immunosuppression in general may increase skin cancer risk in a sun exposure-dependent manner.. Use of alkylating agents for a limited duration seems justifiable for severe, vision-threatening disease, but otherwise cancer risk may be a relevant constraint on use of this approach. Antimetabolites, daclizumab, TNF inhibitors, and calcineurin inhibitors probably do not increase cancer risk to a degree that outweighs the expected benefits of therapy. Monitoring for skin cancer may be useful for highly sun-exposed patients. Data from ocular inflammation patients are needed to confirm the conclusions made in this analysis by extrapolation.

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antimetabolites; Azathioprine; Daclizumab; Databases, Factual; Humans; Immunoglobulin G; Immunosuppressive Agents; Inflammation; Longitudinal Studies; Methotrexate; Mycophenolic Acid; Neoplasms; Risk Factors; Tumor Necrosis Factor-alpha; Uveitis

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

Topics: Adolescent; Anti-Inflammatory Agents, Non-Steroidal; Humans; Male; Mycophenolic Acid; Nephritis, Interstitial; Syndrome; Uveitis

To evaluate the efficacy and tolerance of mycophenolate mofetil (MMF) for the treatment of noninfectious uveitis using the methods of analysis advocated by the Standardization of Uveitis Nomenclature (SUN) Working Group, and to compare this with other SUN-compliant reports of immunosuppression in ocular inflammation.. Retrospective case series. MEDHODS: A predefined data set was retrospectively obtained from the case notes of 100 consecutive uveitis patients treated with MMF at a single academic referral center between April 1, 2000 and August 1, 2006. These data were then analyzed in accordance with SUN recommendations. The main outcome measures were: 1) rate of tapering oral prednisone to 10 mg daily, 2) requirement for alternative second-line immunosuppressive therapy, and 3) rate of MMF dose discontinuation because of side effects.. In this large cohort with noninfectious persistent, chronic, or recurrent uveitis, there was an 84.6% probability of achieving a prednisone dose of < or =10 mg daily after one year of MMF treatment. Alternative second-line immunosuppressive therapy was introduced at a rate of 0.18 per patient-year (PY) and MMF was discontinued because of intolerance at a rate of 0.09/PY, predominantly because of gastrointestinal upset. This corroborates the findings of the only previous SUN-compliant study of MMF in ocular inflammation and is comparable to the rates of treatment success and intolerance we have recently reported for tacrolimus.. This data generates concordant evidence with other SUN-compliant studies supporting the use of MMF in uveitis.

Topics: Administration, Oral; Adolescent; Adult; Aged; Anti-Inflammatory Agents; Child; Cohort Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Guideline Adherence; Humans; Immunosuppressive Agents; Longitudinal Studies; Male; Medical Records; Middle Aged; Mycophenolic Acid; Practice Guidelines as Topic; Prednisone; Retrospective Studies; Treatment Outcome; Uveitis

Mycophenolate mofetil (MMF) is a new immunosuppressive agent that effectively controls the intraocular inflammation in adults.. To assess the efficacy of MMF in uveitis in children and to analyse the possible side effects.. A retrospective analysis was carried out on 17 children (32 eyes) with intraocular inflammation treated with MMF and followed up at the University Eye Hospital Tuebingen, Tuebingen, Germany, between 2000 and 2005. All children had chronic non-infectious uveitis and received MMF for at least 6 months. All patients were given steroids or other immunosuppressive agents before initiating treatment with MMF.. 17 children (10 boys and 7 girls) with a mean age of 8 (range 2-13) years at the onset of uveitis were examined. The average duration of follow-up after initiation of MMF was 3 (range 2-5) years. A steroid-sparing effect was achieved in 88% of the patients. The oral prednisolone was successfully discontinued in 41% children and reduced to a daily dose of < or =5 mg in 47% of the children. 24% of the patients remained relapse-free during the treatment, but a reduction in the relapse rate was observed in all other patients except one. Visual acuity was increased or maintained in 13 children (76%). Mild side effects (headache, rash, gastrointestinal discomfort) occurred in 7 patients (41%) and were the cause of discontinuation of MMF in 1 patient.. The results of our study are encouraging and suggest that MMF is an effective agent also in the treatment for uveitis in children, with marked steroid-sparing potential and an acceptable side effect profile.

Topics: Adolescent; Age of Onset; Anti-Inflammatory Agents; Child; Child, Preschool; Chronic Disease; Drug Administration Schedule; Female; Glucocorticoids; Humans; Immunosuppressive Agents; Male; Mycophenolic Acid; Prednisolone; Recurrence; Retrospective Studies; Treatment Outcome; Uveitis; Visual Acuity

Topics: Child; Humans; Immunosuppressive Agents; Mycophenolic Acid; Practice Guidelines as Topic; Uveitis

We evaluated the outcomes of patients with different forms of chronic uveitis treated with mycophenolate mofetil (MMF) as an immunomodulatory and steroid-sparing agent. The multi-system side effects that arise after long-term treatment with corticosteroids and other immunosuppressants prompted us to use MMF. MMF is a selective inhibitor of inosine monophosphate dehydrogenase, thus blocking purine synthesis via the de novo pathway preferentially used by T and B lymphocytes.. Between 1998 and 2003, 106 patients were treated for uveitis (anterior n=26, intermediate n=51, posterior n=23, panuveitis n=6) with MMF at a dose of 1g twice daily. Treatment duration was at least 6 months (n=10), in most cases greater than 12 months (n=77) and in 25 cases between 24 months and 41 months, when the present retrospective evaluation was undertaken. Patient charts were analysed according to a standardized evaluation protocol.. In 95 patients MMF was combined with prednisolone at a dosage of 2.5-10 mg per day. In 8 patients MMF was used as a monotherapy, and in 3 cases one further systemic immunosuppressant was required. The number of recurrences during MMF treatment was none or one in 92 patients, two in 6 cases and three or more in 8 patients. In none of the patients had MMF been stopped at the time of data analysis. The most frequently observed side effects were gastrointestinal upset (15%), followed by headache (9.3%), fatigue (5.7%), eczema (5%), and hair loss (3.5%). Other side effects were sporadic. Most of these phenomena were transitory. Forty-two patients experienced no side effects at all. In 4 patients MMF was judged ineffective due to failure to reduce the number of recurrences of severe inflammation compared with the previous therapeutic regime, or indeed occurrence of persistent macular oedema.. Our results show that MMF is an effective immunosuppressant in patients with uveitis. We provide evidence that MMF controls the disease in the majority of patients with an acceptable profile of side effects.

Topics: Adolescent; Adult; Aged; Child; Chronic Disease; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; IMP Dehydrogenase; Male; Middle Aged; Mycophenolic Acid; Prednisolone; Retrospective Studies; Treatment Outcome; Uveitis

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

Mycophenolate mofetil (MMF) has been used successfully in patients with various forms of uveitis not responsive to other immunosuppressants. Nevertheless, for these patients neither recommendations for optimal dosage of MMF nor data concerning drug exposure of MMF are available.. To describe the results of the therapeutic drug monitoring (TDM) of MMF trough concentrations in a cohort of patients with uveitis, with the aim of optimizing the dosage of this drug, by maintaining a target concentration to achieve adequate immunosuppression with a minimal risk of therapeutic failure or toxicity.. This study describes the results of monitoring trough plasma concentrations of MMF in 12 patients with uveitis during a mean period of 21.4 months. Patients included one with Stevens-Johnson syndrome, one with Graves-Basedow's disease, one with Behcet's disease, one with idiopathic thrombocytopenic purpura and the rest with idiopathic uveitis. All patients were treated with steroids and additional therapy prior to treatment with MMF.. Pharmacokinetic monitoring of mycophenolic acid (MPA) was performed with 108 trough plasma samples using an EMIT assay. Mean daily MMF dose was 24.5 +/- 6.3 mg/kg and mean trough MPA concentration was 2.9 +/- 1.9 microg/mL. Therapy was effective in 10 patients (83%). There were few side-effects: diarrhoea, excitement, agitation and cough that disappeared with daily dose reduction of MMF.. MMF was effective in the majority of patients with uveitis with an acceptable profile of side-effects. TDM of MMF in patients with uveitis is clinically practicable and may help to optimize individual immunosuppressive therapy. We estimated that MMF dosages in the range of 0.5-1.5 g/day might be sufficient for treating uveitis and we recommend an initial target range of 2-4 microg/mL, which included 50% of our results. Randomized controlled trials are essential to confirm the efficacy of MMF in uveitis.

Topics: Adult; Aged; Child; Drug Monitoring; Enzyme Multiplied Immunoassay Technique; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Uveitis

An 11-year-old boy with recurrent nephritis due to tubulointerstitial nephritis associated with uveitis (TINU syndrome) was treated with cyclosporin A (CSA) to induce sustained remission. CSA was introduced as a steroid-sparing drug because of extreme obesity (body mass index 32 kg/m(2)). Although the boy did not complain of any clinical symptoms, eye inspection after 7 months revealed bilateral disk edema with retinal bleeding and the patient developed cerebrospinal hypertension. Pseudotumor cerebri was diagnosed by measuring the intracranial pressure (31 cm H(2)O) and normal computer tomography and brain magnetic resonance imaging. Cessation of CSA therapy and treatment with mycophenolate mofetil led to resolution within 12 weeks.

Topics: Adrenal Cortex Hormones; Child; Cyclosporine; Humans; Immunosuppressive Agents; Magnetic Resonance Imaging; Male; Mycophenolic Acid; Nephritis, Interstitial; Pseudotumor Cerebri; Tomography, X-Ray Computed; Uveitis

Topics: Humans; Immunosuppressive Agents; Mycophenolic Acid; Sarcoidosis; Skin Diseases; Uveitis

To evaluate the outcomes of early versus late immunomodulatory treatment (IMT) in patients with HLA-B27-associated chronic uveitis.. Seventy-two patients (114 eyes) with HLA-B27-associated chronic uveitis received IMT at the Ocular Immunology & Uveitis Service of the Massachusetts Eye and Ear Infirmary and were evaluated retrospectively. Main outcome measures were visual acuity, control of inflammation, number of flare-ups and steroid-sparing effect.. The median time between diagnosis and start of IMT was 3.05 years. Accordingly, patients were divided into two groups: group A comprised those in whom initiation of IMT was within the first 3 years (36 patients), and in group B initiation of IMT was more than 3 years from the initial diagnosis (36 patients). Control of inflammation was achieved in 29 patients (80.5%) of the early-treated group and in 33 patients (91.6%) of the late-treated group. A steroid-sparing effect was achieved for 13 (81.25%) of the 16 and for 11 (73.33%) of the 15 patients who were on systemic steroid in the early- and late-treated groups respectively. The mean follow-up for the early-treated group was 2.14 years and for the late-treated group, 3.46 years.. Immunomodulatory therapy is an effective treatment for severe HLA-B27 uveitis that fails to respond to conventional steroid treatment, regardless of the timing of its initiation. However, introduction of IMT within 3 years of the disease onset prevents the adverse effects of steroids (cataract, glaucoma) and reduces the likelihood of repeated recurrences of the uveitis.

Topics: Adult; Azathioprine; Chronic Disease; Cyclophosphamide; Cyclosporine; Drug Therapy, Combination; Female; Follow-Up Studies; HLA-B27 Antigen; Humans; Immunosuppressive Agents; Male; Mycophenolic Acid; Retrospective Studies; Treatment Outcome; Uveitis

To assess whether the previously demonstrated short-term efficacy of the immunosuppressant mycophenolate mofetil (MMF; CellCept, Roche) is maintained in the long-term management of refractory uveitis.. The study was an open-label, non-comparative retrospective series of 14 patients with refractory uveitis and treated with MMF for a mean of >33 months. Mycophenolate mofetil was given at a dosage of 1 g (oral) twice daily. Indications included prednisolone reduction, additive agent with cyclosporin, or replacement therapy (azathioprine or methotrexate). The intraocular inflammatory response, side-effects, and toxicity were monitored.. Intraocular inflammation remained under control in 10 patients, unchanged in three and deteriorated in one patient. Transient side-effects included tiredness, headache and dizziness (one patient each, lasting less than 2 weeks from the time of MMF introduction). Mycophenolate mofetil was stopped in one patient because of absence of prolonged clinical improvement. Vision improved in 25% (7 eyes), did not change in 50% (14 eyes), but was reduced in 25% (7 eyes).. Mycophenolate mofetil is safe for long-term usage and is recommended for treatment of refractory panuveitis or posterior uveitis with uncontrolled inflammation despite high prednisolone maintenance dosage (>15 mg/day) or toxicity or lack of efficacy of other immuno-suppressive agents. However, MMF is less effective for refractory uveitis unresponsive to azathioprine.

Topics: Adult; Aged; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Retrospective Studies; Safety; Treatment Outcome; Uveitis; Visual Acuity

TINU syndrome probably is a frequently overlooked disease where uveitis occurs in association with acute tubulointerstitial nephritis. Diagnostic criteria have been published recently.. In this retrospective case series the charts of four consecutive patients with TINU syndrome (follow-up 36, 23, 17, and 12 months, respectively) were analysed, including comorbidity and complications, and the literature was reviewed.. Two patients were treated with methotrexate or ciclosporin A and mycophenolate mofetil. In one patient autoimmune thyroiditis was known. During the follow-up, symptoms indicative of rheumatoid arthritis were observed. Because of her uveitis she required methotrexate therapy. Three patients were obese (mean BMI 32.2 kg/m (2)). Ocular complications were posterior synechiae (two patients) and papillary and macular oedema (three patients). One patient developed cerebrospinal hypertension under ciclosporin A treatment which resolved after discontinuation of therapy.. Patients with definite TINU syndrome frequently suffer from other diseases and associated immune phenomena. The course of the disease can vary considerably. Complications do occur, despite overall good prognosis. Regional and systemic steroids may be sufficient; frequently steroid sparing immunosuppressives are necessary at least temporarily. Patients with this multiorgan disease do need to be followed by a paediatrician or a medical specialist.

Topics: Adolescent; Arthritis, Rheumatoid; Autoimmune Diseases; Child; Cyclosporine; Female; Follow-Up Studies; Humans; Male; Methotrexate; Mycophenolic Acid; Nephritis, Interstitial; Patient Care Team; Syndrome; Thyroiditis, Autoimmune; Treatment Outcome; Uveitis

Severe forms of uveitis can often only be managed sufficiently with systemic immunosuppression. All available drugs are known for their relative high rate of side-effects. Mycophenolate mofetil (MMF), an immunosuppressant successfully used in management after organ transplantation and many autoimmune diseases, has shown remarkably less side-effects when used for various forms of uveitis in monotherapy or in combination with corticosteroids. The aim of this multicenter-study was to investigate if monotherapy with MMF is effective in various forms of uveitis.. Ten patients with anterior uveitis (n = 3), intermediate uveitis (n = 2), panuveitis (n = 4) and retinal vasculitis (n = 1) were treated in a prospective study with 2 x 1 g MMF daily. Previous immunosuppression had been discontinued because of side-effects or ineffectivity in all patients. In these patients MMF was given in addition to the other immunosuppressant at the beginning of treatment.. The follow-up time ranged from 1 to 12 months (mean 4.5 months). Under therapy with MMF (monotherapy in 4 patients, additional prednisolone in 5 patients and additional metotrexate in 1 patient) 8 patients remained free of recurrences. In one female patient depression of inflammation activity was only achieved after cessation of therapy with Cyclosporin A in combination with MMF and a switch to methotrexate. Another patient with a bilateral uveitis was free of recurrences in only one eye, the second eye did not develop recurrence due to the additional corticosteroid treatment. Side-effects were diarrhoea in one patient and probably gastrointestinal problems in another (leading to cessation of therapy in both patients) and in another case nausea, vomitus and alopecia 10 months after beginning therapy.. MMF as a new immunosuppressant stopped inflammation or drastically reduced the rate of recurrences in 8 out of 10 patients with uveitis which was previously not brought under control by other immunosuppressants. The side-effects were tolerable in comparison with other immunosuppressive agents. More patients, longer follow-up times and a comparative study with Cyclosporin A are required to assess the long-term therapeutical success.

Topics: Adult; Aged; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Prospective Studies; Recurrence; Treatment Outcome; Uveitis

Topics: Humans; Immunosuppressive Agents; Mycophenolic Acid; Uveitis

The authors investigated mucosal tolerance therapy as a treatment for autoimmune conditions, including uveitis. Although nasal antigen administration was unable to suppress the disease when given to primed animals, previous studies of experimental autoimmune uveoretinitis (EAU) have shown that nasal antigen administration can maintain disease suppression when combined with oral cyclosporin A. This study aimed to determine whether mucosal tolerance can be induced when EAU is suppressed with mycophenolate Mofetil (MM) and whether tolerance can be maintained when immunosuppression with MM is stopped.. Lewis rats were immunized with retinal extract, and then they received either oral MM 7 to 20 days after immunization or retinal extract intranasally in combination with oral MM on days 7 to 20. Thereafter, weekly nasal administration of the antigen was given until the termination of the experiment at day 38. One group of control animals received the drug vehicle orally and phosphate-buffered saline intranasally. Clinical and histologic changes were assessed along with changes in immune status including delayed-type hypersensitivity, antibody responses to retinal antigens, and flow cytometric phenotyping of infiltrating ocular leukocytes.. EAU was delayed, but not prevented, by a short-term course of MM (7-20 days after immunization). Tolerance to the retinal extract could not be induced during MM treatment by nasal retinal extract administration. Despite the delay in onset of EAU in MM and in MM- and nasal antigen-treated animals, profound target organ damage occurred as seen in untreated controls with EAU. However, fluoroscein-activated cell sorter analysis of retinal leukocytic infiltrate indicated that there was a reduced macrophage recruitment at all time points, whereas lymphocyte infiltration was reduced in proportion to the overall reduction in leukocyte infiltration during therapy.. Nasal retinal antigen administration does not induce tolerance or maintain disease suppression when combined with MM therapy during the effector stage of the (auto)immune response. MM therapy delays disease onset, but target organ damage occurs when therapy is stopped, despite a marked inhibition of macrophagemonocyte infiltration into the chorioretina.

Topics: Animals; Autoantigens; Autoimmune Diseases; Female; Flow Cytometry; Hypersensitivity, Delayed; Immunity, Mucosal; Immunosuppression Therapy; Immunosuppressive Agents; Leukocyte Count; Macrophages; Monocytes; Mycophenolic Acid; Nasal Mucosa; Rats; Rats, Inbred Lew; Retina; Retinitis; T-Lymphocytes; Uveitis

Topics: Acute Disease; Adult; Anti-Inflammatory Agents, Non-Steroidal; Female; Humans; Mycophenolic Acid; Nephritis, Interstitial; Uveitis

Mycophenolate mofetil (MM), an inhibitor of purine metabolism, was found to effectively inhibit the development of experimental autoimmune uveoretinitis (EAU) induced by S-antigen (SAg) in Lewis rats. MM completely inhibited EAU development in the majority of rats when administered daily, on days 0-13, at a dose of 30 mg kg-1 day-1. The drug was less effective, however, when given on days 7-20: minimal disease inhibition was achieved with the drug at 30 mg kg-1 day-1, although at 60 mg kg-1 day-1 the drug inhibited EAU development in most treated rats during the period of its administration. MM also completely inhibited in most treated rats the development of EAU adoptively transferred by SAg-sensitized lymphocytes, thus depicting its capacity to inhibit the efferent limb of the immune response. Treatment with MM also suppressed the cellular and humoral immune responses against SAg, with a good correlation being observed between the inhibition of these responses and suppression of EAU in the different groups of rats. MM is currently being examined for its immunosuppressive effects in humans and the data recorded here thus suggest this compound may be useful in treatment of immune-mediated uveitic conditions.

Topics: Animals; Autoantibodies; Autoimmune Diseases; Female; Immunosuppressive Agents; Lymphocyte Activation; Lymphocyte Transfusion; Male; Mycophenolic Acid; Purines; Rats; Rats, Inbred Lew; Uveitis