Jessica Mendall
North Middlesex University Hospital NHS Trust, London, UK
Introduction
Birdshot chorioretinopathy (also known as birdshot retinochoroidopathy, vitiliginous chorioretinitis or birdshot uveitis) is a cause of chronic and bilateral posterior uveitis. It is characterised by yellow-white hypopigmented fundus lesions, and results in a gradual decline in visual acuity over time.
The disease was first described as “candle wax spot chorioretinopathy” in 1949 by two ophthalmologists, Franceschetti and Babel, referring to a case of a 65-year-old woman who presented with discrete hypopigmented lesions (1). It was not until 1980 that two other ophthalmologists, Ryan and Maumenee, used the term “birdshot” to describe the scatter pattern of cream-coloured retinal lesions seen in the condition that resemble the pattern seen when pellets are fired from a shotgun (2).
Birdshot chorioretinopathy is responsible for approximately 2% of all cases of uveitis (2,3). The aetiology is unclear, but it is hypothesised to result from an autoimmune response to retinal S antigens (1).
Risk factors
HLA-A29 is a strong genetic risk factor for birdshot chorioretinopathy. More than 95% of patients with the disease are HLA-A29 positive compared to 7% of the general population (4,5). The disease is also typically seen in middle-aged Caucasian patients and appears to be more common in females (6).
Presentation
The characteristic symptoms are an insidious impairment of central vision (68% of patients report subjectively ‘blurred’ vision), floaters in 29% of cases, nyctalopia in 25%, dyschromatopsia in 20%, glare in 19% and photopsia in 17% (7).
Regarding the signs, up to 83% of cases demonstrate a mild vitritis on examination, without snow banking or snowballs (8). The early stages of the disease involve retinal vascular leakage, and in the middle stages, the prominent birdshot lesions appear. These lesions are usually bilateral oval cream-coloured ill-defined choroidal lesions clustered around the optic nerve, posterior pole and mid-periphery, that usually spare the macula. The lesions are usually one quarter to half the optic disc diameter in size, and as the lesions become more advanced, they become well-delineated atrophic spots.
In the late stages of the disease, cystoid macular oedema (CMO) is common (present in 84% of cases of birdshot chorioretinopathy compared to 30% in other types of uveitis), and this is the leading cause of vision loss in birdshot chorioretinopathy (7). Other late-stage signs include optic nerve atrophy, retinal pigment epithelium changes and vascular attenuation. Aside from CMO, other major complications include cataract (present in 60% of cases), glaucoma (19%) and choroidal or retinal neovascularisation (14%) (7).
Diagnosis
Because it is a rare disease, and the characteristic ‘birdshot’ spots are not always visible in the early stages (they may not appear until eight years after symptoms are first reported), birdshot chorioretinopathy can often be missed or misdiagnosed (9).
A set of diagnostic criteria were defined in 2002 at an International Workshop held at UCLA (9). Essential characteristics are: (a) bilateral disease; (b) three or more characteristic peripapillary birdshot lesions (cream-coloured, irregular or elongated choroidal lesions with long axis radiating from the optic disc); (c) low-grade anterior chamber inflammation (no more than 1+ cells); and (d) low grade vitreous inflammation (no more than 2+ vitreous haze). Supportive findings are: (a) HLA-A29 positivity; (b) retinal vasculitis; and (c) CMO. Exclusion criteria include (a) keratic precipitates; (b) posterior synechiae; and (c) other causes (i.e. infectious, inflammatory and neoplastic).
Important differential diagnoses that need to be ruled out are autoimmune causes (such as sarcoidosis and white dot syndromes including Multiple Evanescent White Dot Syndrome (MEWDS) and Acute Posterior Multifocal Placoid Pigment Epitheliopathy (APMPPE)), infections (including tuberculosis and syphilis) and neoplasm (primary CNS lymphoma).
Investigations
There are several useful investigations for diagnosing and monitoring the disease. Fundus autofluorescence will often show hypo-autofluorescent atrophic areas in the late stages of the disease. Fluorescein angiography (FA) characteristically shows early hypofluorescence with late hyperfluorescence due to leakage, disc staining and CMO. Indocyanine green angiography shows well-defined oval hypofluorescent spots and will likely reveal more lesions than are visible on FA or clinical examination. The characteristic findings on electroretinography are prolonged 30 Hz flicker times. Visual fields can demonstrate various visual defects including central defects, multiple foci of vision loss and enlarged blind spots. Finally, Ocular Coherence Tomography shows reduced reflectivity of the macular photoreceptor bands and may also show CMO.
Management
Treatment usually begins with steroids, either in the form of oral steroids or an intravitreal corticosteroid implant. With prolonged use of the latter, patients are likely to require cataract surgery or treatment to lower intraocular pressure.
A majority of patients will require systemic immunomodulatory therapy to manage chronic disease, and this is the mainstay of treatment. Commonly used steroid-sparing drugs are ciclosporin, mycophenolate mofetil, methotrexate, azathioprine and TNF-alpha blockers (10,11). A combination of cyclosporin and mycophenolate mofetil has shown good efficacy (12).
Prognosis
Birdshot chorioretinopathy is a progressive disease, with the potential for significant visual loss if left untreated. However, despite irreversible peripheral retinal damage, in many patients, central vision can be well-preserved. The development of visual loss to 20/50 or worse, and to 20/200 or worse, are 13% and 4%, respectively (13). Those who receive long-term immunosuppression maintain better peripheral visual fields compared to patients who only receive short-term treatment (14).
Conclusion
To summarise, birdshot chorioretinopathy is a rare cause of chronic bilateral posterior uveitis with a strong HLA-A29 genetic association. It involves the development of characteristic yellow-white hypopigmented fundus lesions. If untreated, acute flares can cause CMO and potentially blindness, hence it is an important differential to consider in patients presenting with bilateral posterior uveitis.
References
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