Birdshot Retinochoroidopathy

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Article initiated by:

Ella Leung, MD

All contributors:

Ghazala D. O'Keefe, MD, Ella Leung, MD, Russell W. Read, MD, PhD, Vinay A. Shah M.D., Leo A. Kim, MD, PhD, Koushik Tripathy, MD (AIIMS), Alan Palestine, MD, Jennifer I Lim MD, Peter A.Karth, MD, Homaira Ayesha Hossain, MD

Assigned editor:

Homaira Ayesha Hossain, MD, Razek Georges Coussa, MDCM, MPhil, MEng

Review:

Assigned status Up to Date

 by Homaira Ayesha Hossain, MD on June 30, 2024.

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Contributing Editors:	add

Birdshot Retinochoroidopathy

Fundus Photo in Birdshot Retinochoroidopathy

DiseasesDB

32404

OMIM

605808

Birdshot retinochoroidopathy (also known as birdshot chorioretinopathy, vitiliginous chorioretinitis, or simply birdshot uveitis) is a chronic, bilateral, posterior uveitis with characteristic yellow-white lesions in the fundus. HLA-A29 is a strong genetic risk factor, and the disease has been hypothesized to be due to an autoimmune response to retinal S antigens. Patients may experience a gradual decline in visual acuity over time due to cystoid macular edema and retinal atrophy. Treatment typically begins with oral steroids but the vast majority should be treated with immunomodulatory therapy.

Disease Entity

Disease

Birdshot uveitis is characterized by yellow-white choroidal lesions that are clustered around the optic nerve and posterior pole, radiating towards the periphery. The lesions are ¼ to ½ optic disc diameter in size and nearly always involve the inferior and nasal peripapillary area in a pattern similar to the gunshot spatter from birdshot. The lesions can be diffuse, macula predominant, macula sparing, or asymmetric. The disease accounts for 1-2% of all types of uveitis and primarily affects Caucasian females between 40-60 years old. The early stage of the disease is characterized by retinal vascular leakage; the middle stage by prominent birdshot lesions; and the late stage by the presence of cystoid macular edema (84% in BSRC vs. 30% in other types of uveitis), vascular attenuation, RPE changes, optic nerve atrophy, and subretinal neovascularization. 

History

Birdshot uveitis was first described in 1949. The disease has been called:

• ‘la chorioretinite en tache de bougie’’ (Candle Wax Spot Chorioretinopathy) by Drs. Franceschetti and Bable in 1949
• Birdshot Retinochoroidopathy by Drs. Ryan and Maumenee in 1980
• Vitiliginious Chorioretinitis by Dr. Gass in 1981
• Salmon Patch Choroidopathy by Dr. Aaberg in 1981
• Rice Grain Chorioretinopathy by Dr. Amalric and Cuq in 1981

Risk Factors

Birdshot uveitis has the strongest human class I MHC correlation with any disease, with 80-98% of patients being HLA-A29 positive (vs. 7% in the general population). The presence of the gene is associated with a 50-224 times greater relative risk of developing the disease.

Pathophysiology

The pathophysiology is unclear but may be due to an autoimmune response to retinal S antigens; however, one study found no significant difference in the serum titers of anti-S Ag between controls and patients with Birdshot uveitis. An alternate theory is that an infectious agent stimulates T lymphocytes to express self-peptides. The inflammatory exudates may infiltrate the choroidal cleavage plane, undergo fibrosis, fuse the choroidal interstitium, and result in atrophic lesions.

Biopsy of an HLA-A29 positive eye found multiple foci of lymphocytes at various levels of choroid, surrounding retinal blood vessels, and prelaminar optic nerve head, which may indicate a disease primarily of the choroid with secondary involvement of the retina. 

Diagnosis

Diagnostic Criteria

An International Workshop held at UCLA in 2002 established a set of diagnostic criteria.

• Required Characteristics Included:
  • Disease in both eyes
  • ≥ 3 peripapillary birdshot lesions (cream-colored, irregular or elongated choroidal lesions with long axis radiating from optic disc)
  • ≤ 1+ anterior vitreous cells
  • ≤ 2+ vitreous haze

• Supportive Findings:
  • HLA-A29 positive
  • Retinal vasculitis
  • Cystoid macular edema (CME)

• Exclusion Criteria:
  • Keratic precipitates
  • Posterior synechiae
  • Other causes (i.e. infectious, neoplastic, inflammatory)

Signs and Symptoms

The most common symptoms include decreased vision (68%), floaters (29%), nyctalopia (25%), dyschromatopsia (20%), glare (19%), and photopsia (17%). Although BSRC is a primarily ocular disease, there have been some reported associations with systemic hypertension, skin malignancy, hearing loss, vitiligo, and mood disorders. The symptoms can be vague, and sometimes the patient notes that 'something is not right' and such cases need to be investigated with electroretinogram, blue on yellow visual field, and angiography (fluorescein and/or indocyanine green angiography) to detect activity of disease. Vision may be stable in such cases, despite the disease being active or recurrent.

Work Up

Late ICG in Birdshot with hypo-fluorescent atrophic lesions

Other causes of uveitis should be considered, including infectious, autoimmune, and masquerade syndromes. RPR/FTA-ABS, ACE, lysozyme, complete blood count (CBC), chest X-ray, and tuberculin purified protein derivative (PPD) or QuantiFERON Gold testing may be indicated.

The following may be used to help diagnose and monitor birdshot uveitis:

• Diagnosis
  • Treponema pallidium screening cascade
  • QuantiFERON TB Gold, T-spot TB, or PPD
  • Chest X-ray
  • HLA-A29 positive serology
• Monitoring
  • Fundus photos: The lesions may be very subtle and can be missed, especially in the presence of a blonde fundus. Lesions are more frequently nasal and inferior to the optic disc.
  • Fundus autofluorescence: This will denote hypo-autofluorescent atrophic areas in later stages of disease.
  • Fluorescein Angiography (FA): Initially, there will be hypofluorescent lesions with subtle late staining, however, ICGA is a better test for following lesions. FA is more useful for monitoring disease progression (i.e. cystoid macular edema, optic nerve head leakage, vasculitis)
  • Indocyanine Green (ICG): This test usually reveals more fundus lesions (well delineated hypocyanescent spots at mid phase and late phase) than is visible on either FA or on clinical examination.
  • ERG: This test is notable for prolonged 30Hz flicker implicit times. Unlike other types of uveitis, BSCR has markedly diminished b waves (Mueller and bipolar cells) than a waves (photoreceptors) and thus, one can see an "electronegative" ERG. Multifocal ERG may be more useful in long term monitoring of this disease .
  • Visual Fields: This test can demonstrate various defects including multiple foci of vision loss, arcuate cahnges, enlarged blind spot, or central defects depending on the duration and activity of disease.
  • Color and contrast sensitivity abnormalities
  • OCT: OCT can show decreased reflectivity of the macular photoreceptor bands on OCT and may also show cystoid macular edema.

Differential Diagnoses

Autoimmune (or Presumed Autoimmune)

• Sarcoidosis
• Acute Posterior Multifocal Placoid Pigment Epitheliopathy (APMPPE)
• Multiple Evanescent White Dot Syndrome (MEWDS)
• Multifocal Choroiditis and Panuveitis Syndrome (MCP)

Infectious

• Tuberculosis
• Syphilis

Masquerade

• Primary CNS Lymphoma

Management and Outcomes

Treatment

Most patients, if left untreated, will experience a progressive decline in visual function. This disease typically requires the early use of immunomodulatory therapy (IMT).

Acute flares: Steroids

• Oral Steroids—less than 15% remained symptom-free on <20mg/d
• Intravitreal Triamcinolone implant— ↓ CME and maintained BCVA, but patients eventually require cataract surgery or intraocular pressure lowering treatment

Chronic disease: Immunomodulatory Therapy

• Cyclosporine A
• Mycophenylate mofetil
• Azathioprine
• Methotrexate
• Adalimumab
• Infliximab

A Cyclosporine and Mycophenolate combination has shown good efficacy in a study.

Visual Prognosis

Approximately 97.5% of patients may have some visual symptom at baseline, with 44% having an abnormal visual field and 50-76% with abnormal EOG. Without treatment, 16-22% of patients will developed VA ≤ 20/200 over 10 years (versus 4% in other types of uveitis). With the use of IMT, visual acuity remained stable or improved in 78.6-89.3% while visual fields improved from a loss of 56-107° per year to a gain of 30-53° per year.