A strong association between birdshot chorioretinopathy and HLA-A29 expression has been well established.1 In fact, some have suggested that HLA-A29 expression is essential to make the diagnosis of birdshot chorioretinopathy. Such a strong association makes accurate HLA-A29 subtyping quite important in patients suspected of having this entity. Herein, we describe two patients with birdshot chorioretinopathy in whom initial testing for HLA-A29 expression using antibody-based methods was negative and subsequent testing using more sensitive and specific PCR-based techniques was positive.

Case 1

A 45-year-old Caucasian man with a history of psoriatic skin lesions presented with worsening vision, floaters, and nyctalopia affecting both eyes for 2 months prior to presentation. Best corrected visual acuity was 20/25 in each eye. Intraocular pressures were normal bilaterally. Anterior segment examination revealed 1+ cell and flare in the anterior chamber and 2+ cell in the anterior vitreous in each eye. Posterior segment examination revealed diffuse vitreous inflammation, mild disc oedema, diffusely dilated retinal veins and multiple yellow-white choroidal lesions in the mid- and far-periphery of each eye (fig 1). Fluorescein angiography showed leakage from the optic disc and retinal vessels bilaterally. Extensive laboratory evaluation, including serum FTA-ABS and RPR titres, serum ACE and lysozyme levels, chest x ray, and antibody testing for HLA-A29 expression, were unrevealing. Clinical suspicion of birdshot chorioretinopathy remained high, however, so repeat testing for HLA-A29 expression using PCR-based techniques was performed and found to be positive.

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Figure 1 Red-free photographs of the right (A) and left (B) fundi of Case 2 showing multiple yellow-white choroidal lesions inferior to the optic disc characteristic of birdshot chorioretinopathy.

Case 2

A 39-year-old Caucasian woman was seen with best-corrected visual acuity 20/25+1 in the right eye and 20/30+2 in the left eye. Intraocular pressures were normal bilaterally. Anterior segment examination was unremarkable. Posterior segment examination revealed scattered vitreous cells and multiple yellow-white choroidal lesions in the mid- and far-periphery of each eye (fig 2). Extensive laboratory evaluation, including serum FTA-ABS and RPR titres, serum ACE and lysozyme levels, and chest x ray were unrevealing. Antibody-based HLA-A29 testing was negative on two separate occasions. Clinical suspicion of birdshot chorioretinopathy remained high, however, so PCR-based testing for the HLA-A29 expression was requested and found to be positive.

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Figure 2 Red-free photographs of the right (A) and left (B) fundi of Case 1 showing scattered yellow-white choroidal lesions inferior, nasal and superior to the optic disc characteristic of birdshot chorioretinopathy.

Although the precise pathogenesis of birdshot chorioretinopathy is unknown, the vast majority of patients express HLA-A29, and the presence of this class I antigen confers a markedly elevated relative risk for developing the disease.1 2 In addition, HLA-A29 transgenic mice have been shown to develop a spontaneous retinopathy similar to birdshot chorioretinopathy.3 Among patients with this entity, almost all express subtype 2 of the HLA-A29 antigen.1 2 Accordingly, in populations where the prevalence of HLA-A29 subtype 2 expression is low, birdshot chorioretinopathy is correspondingly less frequent.4 Accurate testing for HLA-A29 expression is therefore essential for establishing an accurate diagnosis and treatment plan in patients with clinical features consistent with this disease.

Historically, HLA testing was performed using antibody-based methods. PCR-based techniques for HLA subtyping have emerged more recently, however, and have been shown to be more sensitive and specific than antibody-based approaches, including testing for HLA-A29 expression.5 6 While our report represents the first description of false negative antibody-based HLA-A29 testing, similarly false negative outcomes have been reported in patients tested for HLA-B27 expression.7 Such findings suggest that PCR-based subtyping should be considered in patients with characteristic birdshot chorioretinopathy, particularly when antibody-based methods produce an unexpected negative result.