It is important for all ophthalmologists to be able to recognize birdshot chorioretinopathy (BCR), which is a rare, chronic, bilateral, posterior uveitis strongly associated with the human leukocyte antigen (HLA)-A29 gene. This is because the diagnosis of BCR is easily missed, and continued misdiagnoses may often follow. This article offers guidelines for the evaluation and treatment of BCR, many of which can also be applied toward a general approach for other forms of uveitis.
The name of this condition is derived from BCR’s characteristic feature, which consists of choroidal, hypopigmented, round to oval (occasionally linear) infiltrates (Figure 1). The most frequent symptoms are common to many disorders and include floaters (whirling, strobe, or flashing lights), nyctalopia, blurry vision, difficulty with color vision, and difficulty appreciating contrast. These symptoms can be very problematic for BCR patients, even when they have 20/20 or better vision in bot h eyes, because they make reading, driving and other visual tasks difficult. Adding difficulty to the evaluation, the birdshot lesions can be subtle, and the vitreous inflammation can be very mild.
Courtesy Ralph D. Levinson, MD
Figure 1. This 48-year-old male patient with birdshot chorioretinopathy presented with floaters and photopsia but no other complaints. The round to oval, yellow, hypopigmented birdshot lesions are more subtle than most textbook illustrations, but they are important to recognize.
Several features help in making the diagnosis of BCR. Almost all patients reported in the literature have been Caucasian. Keratic precipitates are rarely, if ever, seen, and posterior synechiae and iris nodules do not develop. At most, there is mild anterior segment inflammation. It is unclear if BCR patients with cataracts have them as a result of inflammation, the age of the patient, or the steroids used to treat the disease.
Vitritis is usually 2+ vitreous haze and cells or less. Retinal vasculitis can include vascular sheathing, though it often does not. Occlusive arteriolitis is not seen. Cystoid macular edema (CME), epiretinal membranes, and even optic nerve involvement can also be seen, and CME is the most common cause of decreased vision. About 95% of patients are HLA-A29 positive, but so are 7% to 9% of Caucasians, so a positive HLA-A29 test does not necessarily confirm the diagnosis. Case in point, HLA-A29 positive individuals with biopsy-proven sarcoidosis that mimics birdshot chorioretinopathy have been reported.
The diseases most commonly confused with BCR are sarcoidosis or lymphoma. Multifocal choroiditis with panuveitis or old Vogt-Koyanagi-Harada disease can result in hypopigmented choroidal lesions, but these usually are easy to differentiate by their specific morphology and the history, when available. Infections or neoplasia may have to be ruled out. Retinal findings in late BCR can mimic retinitis pigmentosa, and the differential diagnosis of pseudoretinitis pigmentosa must be considered, including entities such as late syphilis. Although the disease tends to be chronic with exacerbations, some specialists think it can be biphasic with an early, more active, inflammatory phase involving vasculitis and active vitritis and a later, low-grade, chronic phase with minimal vasculitis and vitritis.
There are various adjunctive examinations that have been used to follow patients with BCR. This is important, because symptoms and visual function often correlate poorly with the Snellen visual acuity test, so treatment cannot be guided by visual acuity alone. Tests that have been used to follow patients include fluorescein angiography or ocular coherence tomography (OCT) for evaluating macular edema, electrophysiology testing, which some advocate for following therapy, Humphrey or Goldman visual fields, color vision testing, and indocyanine green (ICG) angiography to find changes in the birdshot lesions or evidence of active choroidal vasculitis.
As in any form of uveitis, treatment for specific indications such as CME, vitritis, or retinal vasculitis is indicated. On the other hand, some individuals with mild disease may require no treatment. It is possible, though, that these people would still benefit from treatment, but since this is a long-term disease, one must consider the risks of long-term therapy for each patient. Patients who already have irreversible retinal or optic nerve damage receive little or no benefit from treatment.
In the absence of overt active inflammation (i.e., active vitritis, vasculitis, macular edema, or optic nerve involvement), it is unknown whether there may still be a long-term, low-grade inflammatory process that can result in diffuse retinal damage. What is also unknown is the mechanism by which a proportion of patients develop severe panretinal degenerative findings and whether these findings are truly inflammatory or due to early injury or whether treatment will ameliorate or prevent them. Recent reports which indicate that treatment alters electrophysiology and visual fields imply that treatment also improves retinal function, at least in some individuals. However, no prospective or other long-term studies have yet been undertaken to determine whether long-term therapy in the absence of active inflammation or CME, regardless of electrophysiology findings, is always indicated.
The treating physician generally begins therapy with either systemic corticosteroids (e.g., oral prednisone) or local corticosteroids (posterior sub-Tenons or intravitreal injections). A new form of local therapy is the Retisert fluocinolone implant, which has both strong proponents opponents. Compelling arguments for the fluocinolone implant include the fact that it is remarkably effective for CME, although there are no published reports detailing its use in BCR, and that it may avoid the need for systemic therapy. On the other hand, it is risky to place the implant surgically, and the corticosteroid from the implant is associated with ocular complications including cataracts (universal) and severe and prolonged glaucoma. In addition, some uveitis specialists feel that immunosuppressive therapy may induce long-term remissions, although this remains controversial.
While corticosteroids can be effective in treating uveitis, they are often not a good long-term strategy to pursue because of toxicities and side effects. Many patients will require immunomodulatory, corticosteroid-sparing agents. Indeed, there is some limited evidence that treatment with immunosuppressive agents may prevent vision loss from macular edema. Cyclosporine has been used for many years, but there are concerns about elevated blood pressure and limited renal reserves, particularly in older patients. This is important, as the average age of BCR onset is 50 years or older. Furthermore, no study has compared cyclosporine to anti-metabolites (e.g., methotrexate, mycophenolate or azathioprine), alkylating agents (e.g., cyclophosphamide), or biological agents (e.g., tumor necrosis factor [TNF] inhibitors such as infliximab or agents that inhibit the effects of interleukins such as daclizumab).
The ophthalmologist should be prepared to discuss all possible treatment options with the patient and a rheumatologist in order to determine which treatment will yield the fewest adverse side effects or toxicities of concern to that particular patient. The ophthalmologist should also prompt the rheumatologist to help monitor the patient for potential problems with the medications.
Monnet D, Brezin AP, Holland GN, et al. Longitudinal cohort study of patients with birdshot chorioretinopathy. I. Baseline clinical characteristics. Am J Ophthalmol. 2006;141(1):135-142.
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||Thorne JE, Jabs DA, Peters GB, Hair D, Dunn JP, Kempen JH. Birdshot retinochoroidopathy: ocular complications and visual impairment. Am J Ophthalmol. 2005;140(1):45-51. |
The author discloses that he has received a grant from Bausch & Lomb for use toward educational presentations related to birdshot chorioretinopathy. He has no proprietary interest in any of the procedures or products discussed in this article.