Autoimmune uveitis: clinical, pathogenetic, and therapeutic features

Abstract

Autoimmune uveitis (AU), an inflammatory non-infectious process of the vascular layer of the eye, can lead to visual impairment and, in the absence of a timely diagnosis and suitable therapy, can even result in total blindness. The majority of AU cases are idiopathic, whereas fewer than 20 % are associated with systemic diseases. The clinical severity of AU depends on whether the anterior, intermediate, or posterior part of the uvea is involved and may range from almost asymptomatic to rapidly sight-threatening forms. Race, genetic background, and environmental factors can also influence the clinical picture. The pathogenetic mechanism of AU is still poorly defined, given its remarkable heterogeneity and the many discrepancies between experimental and human uveitis. Even so, the onset of AU is thought to be related to an aberrant T cell-mediated immune response, triggered by inflammation and directed against retinal or cross-reactive antigens. B cells may also play a role in uveal antigen presentation and in the subsequent activation of T cells. The management of AU remains a challenge for clinicians, especially because of the paucity of randomized clinical trials that have systematically evaluated the effectiveness of different drugs. In addition to topical treatment, several different therapeutic options are available, although a standardized regimen is thus far lacking. Current guidelines recommend corticosteroids as the first-line therapy for patients with active AU. Immunosuppressive drugs may be subsequently required to treat steroid-resistant AU and for steroid-sparing purposes. The recent introduction of biological agents, such as those targeting tumor necrosis factor-α, is expected to remarkably increase the percentages of responders and to prevent irreversible sight impairment. This paper reviews the clinical features of AU and its crucial pathogenetic targets in relation to the current therapeutic perspectives. Also, the largest clinical trials conducted in the last 12 years for the treatment of AU are summarized and critically discussed.

MC5r and A2Ar Deficiencies During Experimental Autoimmune Uveitis Identifies Distinct T cell Polarization Programs and a Biphasic Regulatory Response

“…This may be explained by the possibility of differential expression of the receptors by immune cell subtypes1011. In addition, these distinct responses may reflect the heterogeneity of uveitis in the human population32.…”

The use of biologic agents in the management of uveitis

“…Ocular involvement in BD involves explosive attacks of severe inflammation with severe retinal complications, including haemorrhage, thrombosis and macular disease. In JIA, band keratopathy, posterior synechiae and ocular hypertension can occur, while long‐term complications of sarcoid uveitis include CME …”

“…Proposed theory of a pathogenic mechanism of autoimmune uveitis, adapted from Prete et al . and Caspi et al .…”

“…A stepladder approach is currently recommended, depending on the severity of uveitis. 20 The first stage is to gain early and rapid control of ocular inflammation to reduce the risk of Figure 1 Proposed theory of a pathogenic mechanism of autoimmune uveitis, adapted from Prete et al 15 and Caspi et al 16 Retinal antigen-specific T cells that have escaped central elimination in the thymus are activated via antigen presentation. Biologic targets here include abatacept and rituximab.…”

Immunological and pathological investigations in equine experimental uveitis

“…The onset of AU is thought to be related to an aberrant T cell-mediated immune response, triggered by inflammation and directed against retinal or cross-reactive antigens (Prete et al 2015). ERU is mediated by an autoaggressive Th response directed against several retinal proteins such as S-antigen, interphotoreceptor-retinoid binding protein (IRBP) and cellular retinaldehyde-binding protein (CRALBP).…”