August 2016

Vogt-Koyanagi-Harada syndrome (VKH) is a bilateral, diffuse granulomatous uveitis associated with neurological, audiovestibular, and dermatological systems. The primary pathogenesis is T-cell-mediated autoimmune response directed towards melanocyte or melanocyte-associated antigens causing inflammation of the choroidal layer. This phenomenon usually leads to diffuse inflammatory conditions throughout most parts of eye before ocular complications ensue. The diagnosis is achieved mainly by clinical features according to the revised diagnostic criteria of VKH published in 2001, without confirmatory serologic tests as a requirement. However, ancillary tests, especially multimodal imaging, can reliably provide supportive evidence for the diagnosis of early cases, atypical presentations, and evaluation of management. Prompt treatment with systemic corticosteroids and early non-steroidal immunosuppressive drug therapy can lessen visually threatening ocular complications and bring about good visual recovery. Close monitoring warrants visual stabilization from disease recurrence and ocular complications. This article review aims not only to update comprehensive knowledge regarding VKH but also to emphasize three major perspectives of VKH: immunogenetics as the major pathogenesis of the disease, multimodal imaging, and therapeutic options. The role of anti-vascular endothelial growth factor therapy and drug-induced VKH is also provided.

Scleritis is an inflammatory process of the sclera and adjacent tissues with a wide spectrum of clinical presentations and co-morbidities. Careful clinical history taking, detailed ocular examination, and appropriate investigation for likelihood of an underlying systemic disease are essential for diagnosis. Treatment can be quite challenging in some cases. Conventional therapy with corticosteroids and immunosuppressive agents may not be sufficient to control ocular inflammation in refractory patients. In such cases new therapeutic agents, which have a more targeted and sustained effect on the immune response, so-called biologic response modifiers, are being used. This review focuses on both diagnosis and therapeutic options including traditional and emerging therapies of non-infectious scleritis.

Allergic eye disease, as in most forms of atopy, ranges in severity among individuals from immediate hypersensitivity to a severe and debilitating chronic disease. Dendritic cells play a key role in stimulating pathogenic T cells in allergen re-exposure, or secondary responses. However, molecular cues by dendritic cells underpinning allergic T cell response levels and the impact that this control has on consequent severity of allergic disease are poorly understood. Here, we show that a deficiency in thrombospondin-1, a matricellular protein known to affect immune function, has subsequent effects on downstream T cell responses during allergy, as revealed in an established mouse model of allergic eye disease. More specifically, we demonstrate that a thrombospondin-1 deficiency specific to dendritic cells leads to heightened secondary T cell responses and consequent clinical disease. Interestingly, whereas thrombospondin-1-deficient dendritic cells augmented activity of allergen-primed T cells, this increase was not recapitulated with naïve T cells in vitro. The role of dendritic cell-derived thrombospondin-1 in regulating secondary allergic T cell responses was confirmed in vivo, as local transfer of thrombospondin-1-sufficient dendritic cells to the ocular mucosa of thrombospondin-1 null hosts prevented the development of augmented secondary T cell responses and heightened allergic eye disease clinical responses. Finally, we demonstrate that topical instillation of thrombospondin-1-derived peptide reduces T cell activity and clinical progression of allergic eye disease. Taken together, this study reveals an important modulatory role of dendritic cell-derived thrombospondin-1 on secondary allergic T cell responses and suggests the possible dysregulation of dendritic cell-derived thrombospondin-1 expression as a factor in allergic eye disease severity.

Uveitis is a common and serious complication of juvenile idiopathic arthritis. Up to 75% of all cases of anterior uveitis in childhood are associated with juvenile idiopathic arthritis. Despite the remarkable progress in early detection and treatment of inflammation, vision-threatening complications of uveitis still occur in almost 60% of patients. Structural complications include band keratopathy, maculopathy (macular edema, macular cysts, and epiretinal membrane), glaucomatous optic neuropathy, and cataracts. The management of complications in juvenile idiopathic arthritis is usually complex and requires early surgical intervention. In this paper, we review the general concepts of common ocular complications seen in patients with JIA-associated uveitis, with special attention to the recent diagnostic and preferred treatment approaches at the Massachusetts Eye Research and Surgery Institution. Received 9 March 2015; revised 30 September 2015; accepted 30 October 2015; published online 14 January 2016.