Birdshot uveitis: current and emerging treatment options

Abstract

Birdshot chorioretinopathy is a relatively uncommon subtype of idiopathic posterior uveitis with distinct clinical characteristics and a strong genetic association with the Human Leukocyte Antigen (HLA)-A29 allele. The diagnosis remains clinical and is based on the presence of typical clinical features, including multiple, distinctive, hypopigmented choroidal lesions throughout the fundus. The long-term visual prognosis of this disorder, however, remains guarded - central visual acuity can be preserved until late in the disease and it is not uncommon for patients to receive inadequate immunosuppressive treatment, leading to a poor long-term outcome in which peripheral retinal damage eventually leads to visual deterioration. Birdshot chorioretinopathy has proven a particularly attractive area of study within the field of uveitis, as it is a relatively easily defined disease with an associated human leukocyte antigen haplotype. Despite this, however, the immune mechanisms involved in its pathogenesis remain unclear, and some patients continue to lose retinal function despite therapy with corticosteroids and conventional immunosuppressive agents. Laboratory research continues to investigate the underlying mechanisms of disease, and clinical research is now being driven to improve the phenotyping and monitoring of this condition as, in the era of so-called personalized medicine, it is becoming increasingly important to identify patients at risk of visual loss early so that they can be treated more aggressively with targeted therapies such as the newer biological agents. This approach requires the formation of collaborative groups, as the relative rarity of the condition makes it difficult for one center to accumulate enough patients for worthwhile studies. Nevertheless, results obtained with newer therapies, such as biological agents directed against particular cytokines or cell-surface receptors, demonstrate ever improving control of the inflammation in refractory cases, providing hope that the outlook for visual function in this condition can only improve.

Keywords: HLA-A29; Th17 cells; birdshot chorioretinopathy; interleukin antagonists; monoclonal antibodies; retinal vasculitis.

Figure 1

Fundus photographs (A–C) of patients with HLA-A29 positive birdshot chorioretinopathy demonstrating heterogeneity of fundal appearances.

Figure 2

A patient with long-standing birdshot chorioretinopathy who developed a central choroidal neovascular membrane associated with a dramatic drop in visual acuity.

Figure 3

Fundus fluorescein angiograms demonstrating (A) central and (B) peripheral retinal vasculitis associated with birdshot chorioretinopathy.