Birdshot chorioretinopathy

Birdshot chorioretinopathy, now commonly named birdshot uveitis or HLA A29 uveitis, is a rare form of bilateral posterior uveitis affecting both eyes. It causes severe, progressive inflammation of both the choroid and retina. Affected individuals are almost exclusively Caucasian and usually diagnosed in the fourth to sixth decade of their lives.

Symptoms of this disorder include floaters, blurred vision, photopsia (flashing lights in eyes), loss of color vision and nyctalopia. In an eye examination, light colored spots on the retina are seen. Complete loss of visual acuity may happen The name of the condition comes from the small light colored fundus spots on the retina, scattered in a pattern like birdshot from a shotgun, but these spots might not be present in early stages.

Birdshot chorioretinopathy is a rare form of posterior uveitis and accounts for 1–3% of uveitis cases in general. Birdshot chorioretinopathy is thought to be an autoimmune disease. The disease has strong association with the human leukocyte antigen haplotype (HLA) A29, which is the strongest association between a disease and HLA class I documented (>99% of patients are HLA A29 positive by molecular testing and HLA A29 negative cases are controversial The disease affects typically middle aged or elderly caucasians. HLA A29 is less prevalent in Asia and no birdshot chorioretinopathy cases have been reported in Asia. When birdshot chorioretinopathy is suspected, a person is usually tested to determine if they are HLA A29 positive. Although previously HLA A29 testing was not considered necessary for definitive diagnosis, because HLA A29 is also common in the general healthy population (7%). An increasing number of specialists consider the presence of HLA A29 critical for diagnosis. Genetic variants near ERAP2 on chromosome 5 resulted in high mRNA and protein expression of this aminopeptidase in BSCR patients. ERAP2 is an aminopeptidase that, together with the closely related ERAP1, trims peptides in the endoplasmic reticulum and loads these peptides on HLA molecules for presentation to T cells of the immune system. ERAP HLA associations have also been reported in Ankylosing spondylitis and Behcet's disease, suggesting shared pathogenic pathways among these diseases. The combined Birdshot risk polymorphisms at 5q15 linked to ERAP1 and ERAP2 genes (T rs10044354 C rs2287987) are only observed in HLA A29 positive individuals in populations in which BU is "endemic", explaining why BU is reported merely in populations of Western European Ancestry (Spain, France, The Netherlands, Great Britain, but also non european countries such as Puerto Rico). Functional analysis of patient derived immune cells revealed that ERAP2 increases the abundance of peptides that specifically bind to HLA A29 and further supports that the antigen presentation pathway drives the etiology of BSCR.

Birdshot chorioretinopathy may show resistance to treatment. Immunosuppressant therapy along with oral corticosteroid has been somewhat effective in slowing down the progressive inflammation associated with the disorder, preserving visual integrity as much as possible. Long term use of such medications must be closely monitored, however, due to the discomforting and potentially debilitating and life threatening side effects. Immunosuppressive drugs such as the therapeutic monoclonal antibody daclizumab, ciclosporin, methotrexate and Adalimumab, sold under the trade name Humira, have proven to be effective treatment options for birdshot chorioretinopathy. Substantial reduction and even stabilization of both vitreous inflammation and retinal vasculitis have been evident via electroretinography, during daclizumab (IL 2 receptor blocker) therapy. This is also supported by the observation of elevated levels of IL 2 in the eyes of patients. Contraindications and adverse side effects are always a factor, as well. A corticosteroid implant surgically placed within the eye can be used for patients who are not able to achieve remission on or tolerate immunomodulatory therapy, or in cases where this option presents less of a burden on life than long term medical therapy.