The structure of the eye is highly organized and complex (Figure 1), reflecting the high degree of specialization that is required to support its function. The integrity and transparency of the ocular media (aqueous, lens, and vitreous), which refract, transmit, and sense light, are critical to optimal visual function. Any distortion of the visual axis — from the cornea through the anterior chamber, lens, and vitreous body to the retina (Figure 1) — by inflammatory processes within the eye can adversely affect vision. Uveitis or uveoretinitis is a general term referring to inflammation of the retina and uvea (the pigmented vascular coat of the eyeball, consisting of the choroid, ciliary body, and iris). Uveitis is categorized on an anatomical basis as anterior, intermediate, or posterior, or as panuveitis if it involves both the anterior and posterior parts of the eye.
Noninfectious uveitis is believed to be autoimmune or immune-mediated (1). Although the distinction between autoimmune and immune-mediated causality canbe blurry, the former is generally believed to be driven by aberrant immune recognition of self, whereas the latter is primarily an innate inflammatory reaction triggered by environmental (microbial) or autologous (tissue damage) “danger” signals. Uveitis, especially if untreated, can result in significant visual deficit and blindness. In the United States alone, uveitic diseases of noninfectious origin have an incidence of 52.4 per 100,000 and a prevalence of 115.3 per 100,000, and are believed to account for about 10% of legal blindness (2).
Some uveitic diseases are confined to the eye, such as sympathetic ophthalmia and birdshot retinochoroidopathy. Others are part of a generalized systemic syndrome in which the eye is one of several organs involved. Examples include anterior uveitis associated with juvenile idiopathic arthritis or ankylosing spondylitis, posterior uveitis in Behçet disease (which also involves skin and mucosal tissues), Vogt-Koyanagi-Harada (VKH) disease (which also targets melanocytes of the skin), and ocular sarcoidosis (part of systemic sarcoidosis, a multisystem inflammatory granulomatous disease that also targets the lymph nodes, lungs, and skin) (1, 3) (Table 1). However, many cases of noninfectious uveitis do not fall under a defined classification and are referred to as “idiopathic.” Patients with noninfectious uveitis frequently exhibit immune responses targeted to ocular antigens such as uveal melanin and proteins involved in its metabolism, retinal arrestin (formerly known as the 48-kDa retinal soluble antigen [S-Ag]), inter-photoreceptor retinoid inding protein (IRBP), and recoverin (4, 5). Although it is unclear whether these immune responses represent the etiological cause or an epiphenomenon of autoimmunization to the products of tissue breakdown (especially in diseases where the initial trigger may be microbial; see Table 1), they are believed to fuel progression of the disease. Diseases in this group tend to have strong MHC associations (6), which is believed to indicate an autoimmune etiology, because MHC molecules select and present antigens for recognition by T cells.