Noninfectious uveitis is a sight-threatening, immune-mediated intraocular inflammatory disorder. Posterior uveitis can involve the retina, choroid, vitreous, and optic nerve. Uveitis can result from heterogeneous numerous etiologies, including infectious, autoimmune causes, and tumoral-mimicking uveitis. Infectious and tumoral causes need specific treatment. Primary or secondary autoimmune disorders of posterior ocular segment require anti-inflammatory treatment to prevent from visual loss.
Uveitis is responsible for ~10% of the visual handicap.
Immunodepressive treatment is required in sight-threatening noninfectious posterior uveitis. Nowadays, corticosteroid therapy remains the first-line conventional treatment for active, noninfectious uveitis. Corticosteroids could be administered by peri or intra-ocular injection, using intravitreal implant, or systemically. The limit od intra-ocular steroid are side effects as secondary glaucoma and a short time therapeutic activity needing re-injection or bilateral injection for bilateral chronic uveitis. Therefore, posterior chronic bilateral uveitis is still nowadays treated with an oral steroid such as prednisone. If the daily dose threshold is greater than ~0.2 mg/kg/d of prednisone, a combination of immunosuppressive or immunomodulator drugs is indicated, both for their own immunosuppressive and steroid-sparing capabilities.
Immunosupressive agents, conventionally used in its indication, can be categorized into 3 main classes: T-cell inhibitors (cyclosporine, tacrolimus), antimetabolites (azathioprine, methotrexate, mycophenolate mofetil, leflunomide), and alkylating agents (cyclophosphamide, chlorambucil). All had been shown efficient in severe uveitis. Side effects include increased risk of infection, hematologic toxicity, sterility, and secondary malignancy. Moreover, immunosuppressive drugs can exhibit selective tissue toxicity as renal toxicity induced by cyclosporine treatment.
The risk of severe side effects of immunosuppressive drugs has led to the evaluation of the therapeutic benefit of immunomodulator drugs such as polyclonal antibodies and interferon alpha. The therapeutic benefit of INFa in Behcet’s disease was recently documented in a meta-analysis of both systemic disease control and uveitis control. The frequency of ocular attacks was significantly reduced compared with the pretreatment observation period, and there was a significant steroid-sparing effect. A randomized prospective study has been done using 3 arms - with only steroids systemic therapy - with only inf alpha systemic therapy – under only observation, for 4 months, in the chronic noninfectious posterior uveitis associated to macular edema. The main criteria was the central foveal thickness, an objective, reproductible parameter measured through optical coherence tomography, a noninvasive tool. The results will be presented in the conference.
Trial Randomized multicentric trial. Code number P051032. Biomedical research Phase II with individual direct benefit.. Promotor: Assistance Publique des Hôpitaux de Paris.
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