Rituximab in the Treatment of Scleritis and Non-Infectious Orbital Inflammation

Inclusion Criteria: * Patients with non-infectious scleritis or idiopathic orbital inflammatory disease requiring chronic immunosuppressive treatment for disease control. * Intolerance, failure to respond to, or inability to taper below prednisone \> 10mg/day in addition to one systemic immunosuppressive (such as methotrexate, azathioprine, mycophenolate mofetil, cyclosporine, cyclophosphamide, or chlorambucil). * Patients must be on a stable dosage of prednisone and at least one steroid-sparing agent in the 30 days prior to screening/enrollment. * Active disease will be defined using physician judgment and supported by patient and physician global ocular disease assessment of \> 5 cm on a 10cm visual analog scale anchored by the words "Inactive Eye Disease" at 0 cm point and "Extremely Active Eye Disease" at the 10cm point. Investigator discretion may apply in some cases. * Selected patients who are on biological agents such as TNF blockers etanercept, infliximab and adalimumab with ongoing ocular disease are acceptable. There will be an 8 week washout period of etanercept and a 12 week washout period for infliximab and adalimumab before patients are dosed with rituximab. * In patients with concomitant systemic autoimmune diseases including RA, SLE, Sjogrens, Wegener's granulomatosis the systemic disease must be sufficiently stable and not life threatening to allow tapering of steroids and/or immunosuppressive agents thus allowing assessment of ocular effect of rituximab. * Adults of both genders \> 18 years old. There is no upper age limit as long as there are no other disqualifying health conditions. * Have had a recent (\<3 months old) PPD skin test and are considered eligible according to the tuberculosis (TB) screening, eligibility assessment, and prevention rules defined in Appendix C. * Screening laboratory test results should be acceptable to the Investigator prior to placing a patient on study drug. * Must have a chest radiograph within 3 months prior to first infusion with no evidence of malignancy, infection or fibrosis. * Adequate renal function as indicated by normal BUN and creatinine levels. Exclusion Criteria: * Untreated thyroid disease * Organ threatening systemic disease as evidenced by rapidly progressive glomerulonephritis, pulmonary hemorrhage or respiratory failure, seizures or psychosis, progressive neuropathy or myopathy General Safety \& Laboratory Exclusion Criteria Patients will be excluded from the study based on the following criteria: * Hemoglobin: \< 8.5 gm/dL * Platelets: \< 100,000/mm * AST or ALT \>2.5 x Upper Limit of Normal unless related to primary disease. * Positive Hepatitis B or C serology (Hep B Surface antigen and Hep C antibody) * History of positive HIV (HIV conducted during screening if applicable) * Treatment with any investigational agent within 4 weeks of screening or 5 half-lives of the investigational drug (whichever is longer) * Receipt of a live vaccine within 4 weeks prior to randomization * Previous Treatment with Rituximab (MabThera® / Rituxan®) * History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies * History of recurrent significant infection or history of recurrent bacterial infections * Known active bacterial, viral, fungal, mycobacterial, or other infection (including tuberculosis or atypical mycobacterial disease, but excluding fungal infections of nail beds) or any major episode of infection requiring hospitalization or treatment with i.v. antibiotics within 4 weeks of screening, or oral antibiotics within 2 weeks prior to screening * Unstable steroid dose in the past 4 weeks * Lack of peripheral venous access * History of drug, alcohol, or chemical abuse within 6 months prior to screening * Pregnancy (a negative serum pregnancy for all women of childbearing potential at screening and negative urine pregnancy test prior to each infusion) or lactation * Concomitant or previous malignancies, with the exception of curatively resected non-melanoma skin carcinomas or carcinoma in situ of the cervix * History of psychiatric disorder that would interfere with normal participation in this protocol * Significant cardiac or pulmonary disease (including obstructive pulmonary disease) * Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications * Inability to comply with study and follow-up procedures