Biologics for the Treatment of Noninfectious Uveitis
Biologics for the Treatment of Noninfectious Uveitis
Noninfectious uveitis is a potentially sight-threatening ocular disorder and variable therapeutic strategies have been proposed. Biologic therapies were introduced as a new option for patients with uveitis refractory to the conventional therapy using corticosteroids and immunosuppressive agents, and 10 years have passed since the initiation. In this review, the author summarizes current articles on the assessment of therapeutic application of biologics for refractory uveitis including other autoimmune diseases. Although some results are based on investigation with insufficient clinical trials, especially in biologics, the majority of biologics indicate preferable outcomes on refractory uveitis, with remarkable promise to increase the possibility of long-term remissions.
Uveitis is one of the leading causes of visual impairment and is responsible for 5 to approximately 20% of legal blindness in western countries and approximately 25% of blindness in the developing world. Noninfectious uveitis has an unknown etiology and variable ocular inflammatory disorders accompanied by anomalous immune processes are included in this entity. As well as other autoimmune disorders, corticosteroids and immunosuppressive agents (i.e., cyclosporine [CSA], methotrexate [MTX], azathioprine and mycophenolate mofetil) have been provided for treatment of immune-mediated uveitis. However, these conventional therapies did not lead to satisfactory outcomes for some active uveitis, including the management of adverse effects. Pathogenesis of ocular inflammation has been more clearly understood by studies using clinically relevant animal models and analysis of ocular specimens obtained from patients. Roles of cytokines and chemokines, costimulatory molecules, cell adhesion molecules and oxygen-free radicals have all been implicated in the pathogenesis. After the advent of molecular biology techniques in the early 1990s, several biologics have been proposed for treatment of ocular inflammation. The aim of biologic therapy is to regulate the inflammatory process, potentially by offering more specific targeted suppression of immune effector responses that damage tissue and, at present, more biologics are available for treatment of uveitis. In this review, the literature is summarized, describing current assessments in the progressing fields, under headings that relate to the specific targets of these biologics. A systematic literature search was carried out using PubMed and Embase databases, with the search terms of 'human uveitis', 'biologics' and 'treatment', limited to after January 2008. Bibliographies of the retrieved literature were searched manually, and reports of randomized clinical trials preferentially selected.
Abstract and Introduction
Abstract
Noninfectious uveitis is a potentially sight-threatening ocular disorder and variable therapeutic strategies have been proposed. Biologic therapies were introduced as a new option for patients with uveitis refractory to the conventional therapy using corticosteroids and immunosuppressive agents, and 10 years have passed since the initiation. In this review, the author summarizes current articles on the assessment of therapeutic application of biologics for refractory uveitis including other autoimmune diseases. Although some results are based on investigation with insufficient clinical trials, especially in biologics, the majority of biologics indicate preferable outcomes on refractory uveitis, with remarkable promise to increase the possibility of long-term remissions.
Introduction
Uveitis is one of the leading causes of visual impairment and is responsible for 5 to approximately 20% of legal blindness in western countries and approximately 25% of blindness in the developing world. Noninfectious uveitis has an unknown etiology and variable ocular inflammatory disorders accompanied by anomalous immune processes are included in this entity. As well as other autoimmune disorders, corticosteroids and immunosuppressive agents (i.e., cyclosporine [CSA], methotrexate [MTX], azathioprine and mycophenolate mofetil) have been provided for treatment of immune-mediated uveitis. However, these conventional therapies did not lead to satisfactory outcomes for some active uveitis, including the management of adverse effects. Pathogenesis of ocular inflammation has been more clearly understood by studies using clinically relevant animal models and analysis of ocular specimens obtained from patients. Roles of cytokines and chemokines, costimulatory molecules, cell adhesion molecules and oxygen-free radicals have all been implicated in the pathogenesis. After the advent of molecular biology techniques in the early 1990s, several biologics have been proposed for treatment of ocular inflammation. The aim of biologic therapy is to regulate the inflammatory process, potentially by offering more specific targeted suppression of immune effector responses that damage tissue and, at present, more biologics are available for treatment of uveitis. In this review, the literature is summarized, describing current assessments in the progressing fields, under headings that relate to the specific targets of these biologics. A systematic literature search was carried out using PubMed and Embase databases, with the search terms of 'human uveitis', 'biologics' and 'treatment', limited to after January 2008. Bibliographies of the retrieved literature were searched manually, and reports of randomized clinical trials preferentially selected.
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