A role for methotrexate in the management of non-infectious orbital inflammatory disease.

AIM: To evaluate the clinical usefulness of methotrexate for patients with non-infectious orbital inflammatory disease who fail to respond to systemic corticosteroids and/or orbital irradiation. METHODS: The medical records of patients with non-infectious orbital inflammatory disease who were treated with methotrexate at Oregon Health Sciences University between June 1993 and June 2000 were examined. Methotrexate was administered at a median maximum dose of 20 mg per week (range 15-25 mg per week) in conjunction with folate supplementation. Patients were followed with regular ophthalmic examinations, as well as serum liver enzyme levels and blood cell counts. Clinical signs of regression of the orbital inflammation, visual acuity, dosage and duration of methotrexate therapy, requirement for concurrent corticosteroid administration, and adverse drug reactions were recorded. RESULTS: The study cohort included 14 patients (24 eyes) with diagnoses including non-specific orbital inflammation (n=7), Tolosa-Hunt syndrome (n=1), thyroid orbitopathy (n=3), Wegener's granulomatosis (n=1), sarcoidosis (n=1), and Erdheim-Chester disease (n=1). In all cases, methotrexate was commenced as a corticosteroid sparing agent. 10 patients (71%) completed a 4 month therapeutic trial of methotrexate. Median duration of treatment for the nine (64%) patients who experienced clinical benefit was 25 months (range 10-47 months). Six responders were ultimately able to cease methotrexate, including the single patient who required concurrent long term corticosteroid therapy. Complications included fatigue, gastrointestinal disturbance, hair thinning and mild, reversible serum liver enzyme elevation. Two patients (14%) discontinued treatment because of adverse effects. CONCLUSION: Methotrexate is a well tolerated immunosuppressive medication which may benefit patients with recalcitrant non-infectious orbital inflammatory disease.

Synoviocytes synthesize, bind, and respond to basic fibroblast growth factor.

Rheumatoid arthritis (RA) is a systemic disease characterized by the destructive proliferation of synovial tissue. It has been suggested that this proliferative lesion resembles a malignancy. Although polypeptide growth factors have been implicated in malignant cell growth, their role in the pathogenesis of proliferative but non-neoplastic diseases such as RA has not been extensively studied. We tested the hypothesis that the synoviocyte itself may be a source of growth factor activity. We demonstrated that culture supernatants from synoviocytes obtained from patients with RA, osteoarthritis, and traumatic joint disease contain mitogenic activity. This activity has biologic properties identical to those of basic fibroblast growth factor (bFGF). Specifically, the mitogenic activity is synergistic with insulin and binds to heparin-agarose, but elutes with 2.0M NaCl. In addition, synoviocyte extracts contain a peptide with a molecular weight of approximately 16,000, which reacts with antibody specific for bFGF. Cultured synoviocytes express the bFGF gene, express receptors for bFGF, and proliferate in response to bFGF. We conclude that bFGF derived from the synoviocytes themselves may play a role in stimulating their proliferation in an autocrine manner in disease states such as RA.

Effects of a fish oil dietary supplement on endotoxin-induced ocular inflammation.

We compared the effects of fish oil versus corn oil dietary supplements on two rabbit models of uveitis induced by either intravenous (IV) or intravitreal (IVT) Escherichia coli endotoxin. Addition of fish oil to a standard diet consistently diminished the rise in aqueous humor prostaglandin E2 levels 24 hours after IVT endotoxin injection or 3 hours following IV endotoxin injection. Aqueous humor thromboxane B2 levels following IV or IVT endotoxin injection were also lower in rabbits fed a fish oil supplemented diet. However, the fish oil diet resulted in only a modest attenuation of increases in ocular vascular permeability following either IVT or IV endotoxin injection. Fish oil supplementation inconsistently reduced leukocyte infiltration into the anterior chamber following IVT endotoxin. In contrast to the reported ability of fish oil dietary supplements to reduce corneal inflammation, these models of anterior uveal inflammation do not seem to be altered in a clinically significant manner.