Spotlight Case: Why a Genetic Test Is Sometimes Worth a Shot
A 45-year-old Caucasian man reported decreased vision for 3 years with insidious onset. The patient had no history of rheumatic joint disease, sarcoidosis, or other inflammatory disorders and had a negative purified protein derivative (PPD) 2 years prior. His best-corrected visual acuity (BCVA) was 20/40 OU.
Examination was remarkable for the absence of lacrimal enlargement or granulomas. He had no keratic precipitates (KP), posterior synechiae, or anterior-chamber cell or flare, and there was bilateral 2+ vitritis.
Fundus examination was remarkable for pale, ovoid lesions most prominent nasal to the optic disc (Figures 1 and 2). There was mild retinal vasculitis and an epiretinal membrane. Mild increased retinal thickness was evident on OCT (Figures 3 and 4). Fluorescein angiography (FA) and indocyanine green (ICG) angiography were performed, and demonstrated hypofluorescent areas (Figures 5-8).
A thorough laboratory workup was performed, including:
- Complete blood count (CBC)
- Erythrocyte sedimentation rate (ESR)
- Angiotensin-converting enzyme (ACE)
- Antinuclear antibodies (ANA)
- Rapid plasma reagin (RPR)
- Fluorescent treponemal antibody absorption (FTA-ABS)
- Chest X-ray (CXR)
- Tuberculosis (TB) PPD
All workup tests were negative. However, the patient tested positive for histocompatibility leukocyte antigen-A29 (HLA-A29) by genetic testing.
What’s your diagnosis?
The patient was diagnosed with birdshot chorioretinopathy.
Birdshot chorioretinopathy, a disease seen primarily in Caucasians, has a strong correlation with the HLA-A29 serotype.
An international consensus conference found that a diagnosis of birdshot chorioretinopathy requires:
- Bilateral disease
- At least 3 peripapillary birdshot lesions in 1 eye
- Low-grade anterior-segment inflammation (≤1+ cells)
- Low-grade vitreous inflammation (≤2+ haze)
Criteria supportive of birdshot chorioretinopathy diagnosis are:
- HLA-A29 positivity
- Retinal vasculitis
- Cystoid macular edema
A diagnosis of birdshot chorioretinopathy is excluded if any of the following are present:
- Keratic precipitates
- Posterior synechiae
- Infection, neoplasm, or concurrent inflammatory disease that can also cause multiple choroidal lesions
While considered only a supportive piece of evidence in the above consensus criteria, HLA-A29 positivity—rather than being required for diagnosis—has been found in 96% of birdshot chorioretinopathy patients. If a patient tests negative for HLA-A29, other causes of choroidal infiltrates, such as sarcoidosis, should be given strong consideration.
Although progressive visual loss is often inevitable in patients with birdshot chorioretinopathy, daclizumab has been shown effective by 1 group in 8 patients, despite some electroretinogram (ERG) deterioration. In fact, ERG has been found most useful for following the progression of birdshot chorioretinopathy, with abnormal findings in 70% of patients. One group study found that abnormalities in the 30 Hz flicker implicit times were predictive of recurrence of inflammation following immunosuppressive taper.
- Birdshot chorioretinopathy, seen almost always in Caucasians, has a very strong association with HLA-A29, although HLA typing is not technically required for diagnosis.
- Birdshot chorioretinopathy generally manifests with mild to moderate inflammation of the vitreous and anterior segment.
- Other causes of chorioretinopathy must be ruled out for proper diagnosis.
- ERG can be useful for following the progression of birdshot chorioretinopathy, including predicting successful taper from immunosuppression.
1. Brézin AP, Monnet D, Cohen JH, Levinson RD. HLA-A29 and birdshot chorioretinopathy. Ocul Immunol Inflamm. 2011;19(6):397-400. doi:10.3109/09273948.2011.619295.
2. 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(1):185-187.
3. Shah KH, Levinson RD, Yu F, et al. Birdshot chorioretinopathy. Survey Ophthalmol. 2005;50(6):519-541. doi:10.1016/j.survophthal.2005.08.004.
4. Sobrin L, Huang JJ, Christen W, Kafkala C, Choopong P, Foster CS. Daclizumab for treatment of birdshot chorioretinopathy. Arch Ophthalmol. 2008;126(2):186-191. doi:10.1001/archophthalmol.2007.49.
5. Comander, J, Loewenstein J, Sobrin L. Diagnostic testing and disease monitoring in birdshot chorioretinopathy. Semin Ophthalmol. 2011;26(4-5):329-336. doi:10.3109/08820538.2011.588661.
6. Zacks DN, Samson CM, Loewenstein J, Foster CS. Electroretinograms as an indicator of disease activity in birdshot retinochoroidopathy [published online July 10, 2002]. Graefes Arch Clin Exp Ophthalmol. 2002;240(8):601-607.
Dr. Reddy - None.
Mr. Mendel - None.
Dr. Hau - SEQUENOM: Speaker, Honoraria; THROMBOGENICS, INC: Other, Honoraria.
Dr. Choudhry - ALLERGAN, INC: Advisory Board, Speaker, Honoraria; BAUSCH + LOMB, INC: Advisory Board, Honoraria; BAYER HEALTHCARE: Consultant, Speaker, Honoraria; NOVARTIS: Advisory Board, Speaker, Grants, Honoraria; OPTOS PLC: Speaker, Honoraria.