Double trouble: a patient with both HLA-B27 anterior uveitis and HLA-A29 birdshot chorioretinitis
© Haddad and Reddy; licensee Springer. 2014
Received: 2 July 2014
Accepted: 28 October 2014
Published: 26 November 2014
Birdshot chorioretinitis (BSCR) is a rare ocular inflammatory disorder associated with HLA-A29 and characterized by bilateral choroidal lesions, vitritis, macular edema, and retinal vasculitis. Ocular inflammation associated with HLA-B27 is typically a recurrent, unilateral, acute anterior uveitis (AAU) that is frequently associated with ankylosing spondylitis (AS). To date, there are no reports of patients with both HLA-A29-positive BSCR and HLA-B27 AAU/AS in the English literature.
A 50-year-old man with a history of bilateral anterior uveitis, vitritis, retinal vasculitis, and cream-colored depigmented oval choroidal lesions was found to be HLA-A29 and HLA-B27 positive. His lumbar spine and sacroiliac joint films revealed fusion of the spine, known as `bamboo spine' compatible with the diagnosis of ankylosing spondyloarthropathy. He had chronic ocular inflammation that was difficult to control with systemic steroids and immunomodulatory agents.
This is the only report of a patient with both HLA-A29-positive BSCR and HLA-B27-positive AS and associated anterior uveitis. The severity of his disease suggests that patients who test positive for both HLA-A29 and HLA-B27 carry a poor visual prognosis. Prompt diagnosis and treatment with local or systemic corticosteroids or steroid-sparing agents may control the disease.
KeywordsBirdshot chorioretinitis Ankylosing spondyloarthropathy Seronegative spondyloarthropathy Panuveitis Cystoid macular edema
Birdshot chorioretinitis (BSCR) is a rare ocular disorder characterized by bilateral choroidal lesions and chronic intraocular inflammation without anterior segment complications. A minimum of three discrete, round or oval, cream-colored foci of depigmentation is required for diagnosis. The lesions are most often one quarter to one half optic disc diameter in size and clustered around the disc, nearly always with involvement of the inferior and nasal peripapillary area. Exclusion criteria include keratic precipitates and posterior synechiae, which may form as a consequence of independent HLA-B27-related anterior uveitis .
In 2002, a 38-year-old male sought care for flashes and floaters, blurred vision, intermittent eye redness, and photophobia OU. Initial best corrected visual acuity was 20/20 OU with bilateral peripheral field constriction, vitritis, and choroidal lesions. At that time, he was diagnosed with bilateral panuveitis with cystoid macular edema (CME) and started on 40 mg oral prednisone daily and topical steroid and nonsteroidal anti-inflammatory drops. A laboratory workup included complete blood count, erythrocyte sedimentation rate, antinuclear antibodies, rapid plasma reagin, fluorescent treponemal antibody absorption test, angiotensin converting enzyme, chest X-ray, and toxoplasmosis serology - all of which were within normal limits. In 2004, his visual acuity deteriorated to 20/60 OU. A diagnostic vitrectomy was performed in the left eye and was negative for malignancy and infection. Vision failed to improve, despite bilateral cataract surgery, due to persistent bilateral vitritis, episodes of anterior uveitis, CME, and epiretinal membranes. He was treated only with steroid and nonsteroidal anti-inflammatory drops over this time period.
The patient provided consent for the report to be published.
In 1975, Ryan and Maumenee  used the descriptive term birdshot retinochoroidopathy to define a rare ocular inflammatory disease characterized by bilateral cream-colored ovoid spots densest around the optic nerve and nasally.
Classically, eyes with BSCR are quiet with no ciliary injection or anterior chamber inflammation. Common posterior segment findings include hyperpermeable capillaries with CME, narrowing of retinal arterioles, perivascular hemorrhages, vessel tortuosity, and optic disc swelling. HLA typing is a valuable diagnostic tool but not a requirement for diagnosis; it has a sensitivity of 96% and a specificity of 93% .
The required characteristics for the diagnosis of BSCR according to Levinson  are bilateral disease, the presence of at least three peripapillary `birdshot lesions inferior or nasal to the optic disc in one eye, low-grade anterior segment intraocular inflammation (defined as ≤1+ cells) and a low-grade vitreous inflammation (defined as ≤2+ vitreous haze). Birdshot lesions are defined as cream-colored, irregular or elongated, choroidal lesions with indistinct borders, the long axis of which is radial to the optic disc. The ocular inflammatory activity was assessed according to the Standardization of Uveitis Nomenclature Working Group. Supportive findings for the diagnosis of BSCR were: HLA-A29 positivity, retinal vasculitis, and CME. Exclusion criteria for the diagnosis of BSCR were the presence of keratic precipitates and posterior synechiae and the presence of infectious, neoplastic, or other inflammatory diseases that can cause multifocal choroidal lesions . Exacerbations and remissions characterize the course of the disease. Loss of visual acuity is due to CME, macular epiretinal membrane formation, macular hole, subretinal neovascular membrane, macular scar, and cataract .
Our patient with AS-related acute anterior uveitis (AAU) was given a diagnosis of BSCR based on the clinical exam and had HLA typing confirming HLA-A29 and HLA-B27 status. Over 90% of patients with AS are HLA-B27 positive, whereas only 6% to 8% of the general population is HLA-B27 positive. The primary ocular manifestation of AS is recurrent nongranulomatous acute anterior uveitis, which our patient reported. Acute anterior uveitis occurs in 25% to 40% of patients with AS .
Priem and Oosterhuis reviewed 62 patients with BSCR. In half of the patients followed for 5 years or more, visual acuity was maintained at 20/60 or better . More recent studies suggest that central visual acuity can be preserved long term in patients with BSCR. Tomkins-Netzer et al. found that 88% (n = 81) and 97% (n = 89) of the eyes maintained best corrected visual acuity and did not progress to permanent visual loss (<20/50) or severe visual loss (<20/200), respectively over 10 years . Our patient had uncontrolled ocular inflammation despite being on systemic steroids and immunomodulatory agents. Vision deteriorated to 20/200 OD and 20/80 OS with associated nerve pallor, epiretinal membranes, macular edema, and retinal atrophy. The severity of his disease suggests that patients who test positive for both HLA-A29 and HLA-B27 carry a poor visual prognosis, though delay to diagnosis and patient deferral of additional treatment are also contributing factors.
BSCR is generally considered to be an isolated ocular disorder. Few reports in the literature suggest a possible association with systemic illnesses including essential hypertension, cerebrovascular accidents, hearing loss, and cutaneous immune-mediated conditions such as vitiligo and psoriasis ,-.
To our knowledge, this is the only reported case of a patient with both HLA-A29-positive BSCR and HLA-B27-positive AS and associated anterior uveitis. Given the severity of his disease, we suspect that patients with this association develop inflammation that is difficult to control and have poorer visual prognosis than patients with BSCR alone. Prompt diagnosis and treatment with local or systemic corticosteroids or steroid-sparing agents may be of benefit.
ZH is a third-year ophthalmology resident at the University of Virginia and had completed a two-year vitreoretinal fellowship at the University of Virginia. AR is a uveitis and a medical retina specialist at the University of Virginia.
acute anterior uveitis
cystoid macular edema
The authors would like to acknowledge Drs. Kathryn Pepple, Paolo Silva, and Sophia Mirza Saleem who agreed to be peer reviewers for this manuscript.
- Levinson RD, Brezin A, Rothova A, Accorinti M, Holland GN: Research criteria for the diagnosis of birdshot chorioretinopathy: results of an international consensus conference. Am J Ophthalmol 2006, 141: 185–187. 10.1016/j.ajo.2005.08.025View ArticlePubMedGoogle Scholar
- Ryan SJ, Maumenee AE: Birdshot retinochoroidopathy. Am J Ophthalmol 1980, 89: 31–45. 10.1016/0002-9394(80)90226-3View ArticlePubMedGoogle Scholar
- Feltkamp TEW: Ophthalmological significance of HLA-associated uveitis. Eye 1990, 4: 839–884. 10.1038/eye.1990.133View ArticlePubMedGoogle Scholar
- Priem HA, Oosterhuis JA: Birdshot chorioretinopathy: clinical characteristics and evolution. Br J Ophthalmol 1988, 72: 646–659. 10.1136/bjo.72.9.646PubMed CentralView ArticlePubMedGoogle Scholar
- Van der Linden S, Van Der Heijde D, et al.: Ankylosing spondylitis. In Kelly's textbook of rheumatology. 6th edition. Edited by: Ruddy S, Harris ED, Sledge CB. Saunders, Philadelphia; 2001:1039–1053.Google Scholar
- Tomkins-Netzer O, Taylor SR, Lightman S: Long-term clinical and anatomic outcome of birdshot chorioretinopathy. JAMA 2014,132(1):57–62.Google Scholar
- Gasch AT, Smith JA, Whitcup SM: Birdshot retinochoroidopathy. Br J Ophthalmol 1999,83(2):241–249. 10.1136/bjo.83.2.241PubMed CentralView ArticlePubMedGoogle Scholar
- Gass JD: Vitiliginous chorioretinitis. Arch Ophthalmol 1981,99(10):1778–1787. 10.1001/archopht.1981.03930020652006View ArticlePubMedGoogle Scholar
- Heaton JM, Mills RP: Sensorineural hearing loss associated with birdshot retinochoroidopathy. Arch Otolaryngol Head Neck Surg 1993,119(6):680–681. 10.1001/archotol.1993.01880180100019View ArticlePubMedGoogle Scholar
- Rothova A, Berendschot TT, Probst K, van Kooij B, Baarsma GS: Birdshot chorioretinopathy: long-term manifestations and visual prognosis. Ophthalmology 2004,111(5):954–959. 10.1016/j.ophtha.2003.09.031View ArticlePubMedGoogle Scholar
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