Spotlight Case: Why a Genetic Test Is Sometimes Worth a Shot

  • author profile pictureAshvini K. Reddy, MD
  • author profile pictureThomas A. Mendel, PhD

Case history

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).

Figure 1: Fundus right eye - Hyperemic optic nerve with pale lesions scattered within macula and periphery

Figure 2: Fundus left eye - Hyperemic optic nerve with pale lesions scattered within macula and periphery

   

Figure 3: OCT right eye - ERM increased retinal thickness and preservation of foveal contour OU

Figure 4: OCT left eye - ERM increased retinal thickness and preservation of foveal contour OU

   

Figure 5: FA right eye - Disc staining with retinal vasculitis and scattered areas of retinal staining

Figure 6: FA left eye - Disc staining with retinal vasculitis and scattered areas of retinal staining

   

Figure 7: ICG right eye - Indocyanine green angiography demonstrating hypofluorescent choroidal lesions

Figure 8: ICG left eye - Indocyanine green angiography demonstrating hypofluorescent choroidal lesions

   

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. 

Discussion

Birdshot chorioretinopathy, a disease seen primarily in Caucasians, has a strong correlation with the HLA-A29 serotype.[1

An international consensus conference[2] 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.[3] If a patient tests negative for HLA-A29, other causes of choroidal infiltrates, such as sarcoidosis, should be given strong consideration.[1]

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.[4] In fact, ERG has been found  most useful for following the progression of birdshot chorioretinopathy, with abnormal findings in 70% of patients.[5] One group study found that abnormalities in the 30 Hz flicker implicit times were predictive of recurrence of inflammation following immunosuppressive taper.[6]
 

Take-home points

  • 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.

 

References

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.

 

Financial disclosures

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.

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