Advances in the diagnosis and immunotherapy for ocular inflammatory disease (original) (raw)
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Biologic Therapy For Ocular Inflammatory Diseases: An Update
Uveitis comprehends a wide and heterogeneous group of intraocular inflammatory conditions potentially sight-threatening and variable therapeutic strategies have been proposed. Classical treatment with steroids and conventional immunosuppressive agents is often used as first-step. However, a number of patients may not respond properly or tolerate these medications with well-known side effects. Over the last two decades, advances in the understanding of the pathogenesis of autoimmune uveitis, as well as improved biotechnology, have enabled the development of a new class of drugs called biologics, which provide selective targeting of the immune mediators of the inflammation cascade. Biologic therapies were introduced as a new option for patients with autoimmune rheumatic conditions refractory to conventional therapy and due to their success have posteriorly been used in ophthalmology to treat ocular inflammatory disorders. These new agents may potentially provide more effective and less toxic treatment than conventional therapy. Biologic therapies include a wide variety of drugs with different mechanisms of action, including monoclonal antibodies against cell surface markers, cytokines and their receptors, or recombinant forms of natural inhibitory molecules. Although some results are based on investigations with insufficient clinical trials, the majority of biologics indicate preferable outcomes on refractory uveitis, with remarkable promise to increase the possibility of long-term remission. The development of these new drugs is one of the most revolutionary advances in recent years, and the promise of shifting paradigms makes it an exciting time for uveitis specialists worldwide. Keywords: Uveitis; Ocular Inflammation; Biologics; Cytokines; Immunomodulation
Biologic agents in inflammatory eye disease
Journal of ophthalmic & vision research, 2011
Non-infectious uveitis is a potentially sight threatening disease. Along the years, several therapeutic strategies have been proposed as a means to its treatment, including local and systemic steroids, immunosuppressives and more recently, biologic agents. The introduction of biologics can be defined as a new era: biologic therapies provide new options for patients with refractory and sight threatening inflammatory disorders. The availability of such novel treatment modalities has markedly improved the therapy of uveitis and considerably increased the possibility of long-term remissions. This article provides a review of current literature on biologic agents, such as tumor necrosis factor blockers, anti-interleukins and other related biologics, such as interferon alpha, for the treatment of uveitis. Several reports describe the efficacy of biologics in controlling a large number of refractory uveitides, suggesting a central role in managing ocular inflammatory diseases. However, the...
Biologics in non-infectious uveitis past, present and future
Annals of Eye Science, 2021
Our increase in knowledge of the pathophysiology of non-infectious uveitis (NIU) and other immune-mediated diseases has been mirrored over the last two decades by the expansion of therapeutic options in the realm of immunosuppressive medications. Principal among these advances is the emergence of biologics, which offer the promise of targeted therapy and the hope of reduced toxicity when compared to corticosteroids and "standard" immunosuppression. Among the biologics, monoclonal antibodies blocking tumor necrosis factor alpha (TNF-α) have been shown to be a very effective therapeutic target for uveitis and many associated systemic inflammatory diseases. Multiple TNF blockers have shown benefit for uveitis, and in 2016, adalimumab became the first biologic and non-corticosteroid immunosuppressive to obtain Food and Drug Administration (FDA) approval in the treatment of NIU. Although effective, TNF blockers are not universally so, and safety concerns such as infection and demyelinating disease must be carefully considered and ruled out prior to their use, especially in patients with intermediate uveitis with which multiple sclerosis is a known association. Ongoing study has identified novel targets for regulation in the treatment of immune-mediated and inflammatory diseases. Interferons, interleukin and Janus kinase inhibitors in addition to antibodies targeting T cell and B cell activation highlight the expanding field of treatment modalities in NIU. Ongoing study will be required to better determine the safety and efficacy of biologics in the armamentarium of immunosuppressive treatments for NIU.
ABSTRACT Uveitis is the third most common cause of blindness in developed countries. Considering the systemic and local complications of long-term corticosteroid therapy and the intolerance due to side effects and ineffectiveness of conventional chemotherapy, use of biologic response modifiers is a reasonable alternative in the treatment of non-infectious uveitis and persistent uveitic macular edema. The majority of the evidence presented here comes from open uncontrolled analyses. Based on these studies, tumor necrosis factor alpha inhibitors, especially infliximab and adalimumab, have been shown to be effective in the treatment of non-infectious uveitis in numerous studies. More research is necessary, particularly multi-center randomized clinical trials, to address the choice of biologic response modifier agent and the length of treatment as we employ biologic response modifiers in different types of uveitis and persistent uveitic macular edema.
Optimising drug therapy for non-infectious uveitis
International ophthalmology, 2018
Uveitis encompasses a wide variety of sight-threatening diseases characterized by intraocular inflammation. It is often classified as infectious and non-infectious uveitis. Unlike infectious uveitis, a distinct infectious agent cannot be identified in non-infectious uveitis and disease origin is usually autoimmune, drug related, or idiopathic. Non-infectious uveitis can often have a relapsing-remitting course, making it difficult to treat, and poses a significant challenge to ophthalmologists. The autoimmune nature of non-infectious uveitis warrants the use of anti-inflammatory and immunomodulatory agents for disease control. However, a subset of patients has persistent or recurrent ocular inflammation despite appropriate treatment, stressing the need for newer therapies aimed at more specific inflammatory targets such as tumour necrosis factor (TNF) alpha agents, anti-interleukin agents, and anti-interleukin receptor agents. This article discusses the various medical options availa...
Inflammation & Allergy-Drug Targets, 2013
Ocular inflammatory disorders constitute a sight-threatening group of diseases that might be managed according to their severity. Their treatment guidelines experience constant changes with new agents that improve the results obtained with former drugs. Nowadays we can make use of a five step protocol in which topical, periocular and systemic corticosteroids remain as the main therapy for non-infectious uveitis. In addition, immunosuppresive drugs can be added in order to enhance the anti-inflammatory effects and to play the role of corticosteroid-sparing agents. These can be organized in four other steps: cyclosporine and methotrexate in a second one; azathioprine, mycophenolate and tacrolimus in a third step; biological anti-TNF drugs in fourth position; and a last one with cyclophosphamide and chlorambucil. In the present review we go through the main characteristics and complications of all these treatments and make a rational of this five-step treatment protocol for non-infectious posterior uveitis.
Biological agents in the treatment of uveitis
Advances in Bioscience and Biotechnology, 2013
Recently, a new class of drugs obtained by a biological process and therefore defined as "biologics" has been successfully used in the treatment of immunemediated rheumatic diseases. These drugs target different pro-inflammatory cytokines including tumor necrosis factor-α, interleukin-1 and interleukin-6, or immune effector cells including B and T lymphocytes. Their use has been then extended to different forms of uveitis resistant to standard therapy in small uncontrolled trials, with general and unexpected efficacy. The present review analyzes the literature on treatment of uveitis with the biologics currently available for the treatment of inflammatory rheumatic diseases. We used PubMed search engine as the main source of information. Among the papers included in the reference list, a particular emphasis was given on articles published during the last 5 years.
Immunotherapeutic approaches in ocular inflammatory diseases
Archivum immunologiae et therapiae experimentalis
This comprehensive review discusses immunotherapeutic approaches to ocular inflammatory diseases, updates information provided in the literature, and presents clinical experiences with an emphasis on autoimmune uveitis at the National Eye Institute, United States. Current medical and surgical therapeutic approaches, including medications such as corticosteroids, anti-metabolites, alkylating agents, calcineurin and purine synthesis inhibitors, biologics as well as some anti-infectious agents, are reviewed along with new modalities and experimental approaches. Most immunosuppressive therapies have significant adverse effects. Physicians must be familiar with the pharmacology of the available drugs and aware of the philosophies behind the treatment.