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Understanding immune mechanisms of noninfectious intraocular inflammation via animal models, and the relatively more restricted insights that can be achieved through studies in humans, continues to generate successful immunotherapies. This translational conduit elaborates immunopathogenic mechanisms, and illuminates further prospects of tailored therapies and biomarkers of disease activity and prognosis. More recently, our increased understanding has moved on from the success of previous biologic therapies, such as anti-TNF and IFN-α treatments, revealing other possible avenues to target; for example, Th17 cells, immune cell migration and the use of T-regulatory and dendritic cells to induce immunological tolerance. We now recognize that the ocular environment is endowed with many regulatory mechanisms but is hardly privileged in as much as ocular inflammation remains prevalent. Nevertheless, future therapeutic and diagnostic developments will harness our understanding of the local immunoregulatory networks to not only restrain immune-mediated damage, but also to restore homeostasis and neuronal function. This article attempts to crystallize our understanding of local immune regulation and immune mechanisms leading to intraocular inflammation. [ABSTRACT FROM AUTHOR]

Despite a lack of robust evidence, anti-TNF therapies are in wide use for the treatment of noninfectious ocular inflammatory diseases. There is a clear rationale, based on mechanistic and preclinical efficacy data, for their use in posterior segment intraocular inflammation. However, their increasing use for other indications has been largely extrapolated from the benefit observed in autoinflammatory and autoimmune systemic diseases. Given their cost and the potential for significant adverse events, this review highlights the evidence for their continued use, possibilities for switching anti-TNF agents, and ways of reducing the risk of therapy. [ABSTRACT FROM AUTHOR]

Glucocorticoids remain the first-line treatment for a range of autoimmune and allergic diseases. However, 30% of patients fail to achieve disease control at tolerable systemic doses and continue to have an increased immune response with poor clinical outcome. This steroid refractory (SR) phenotype has previously been attributed to enhanced expression of inactive glucocorticoid receptor isoforms and cytokine-mediated suppression of glucocorticoid (GC) signaling, in particular by interleukin-2. These mechanisms are discussed, with emphasis on recent evidence for the role of the CD4+CD25intand GC-induced T regulatory cell subsets in perpetrating SR disease. [ABSTRACT FROM AUTHOR]

Orbital involvement in chronic lymphocytic leukemia (CLL) is highly unusual and most commonly involves hemorrhage or soft tissue infiltration in advanced disease. We report a case of rapid onset bilateral orbital muscle infiltration as the presenting feature of early stage CLL. In addition, we demonstrate clinico-pathological correlation with an identical chronic B-cell lymphocytic infiltrate in both orbit and bone marrow, with good response of the orbital disease to local radiotherapy. [ABSTRACT FROM AUTHOR]