Birdshot Retinochoroidopathy

From EyeWiki
Original article contributed by: Ella Leung, MD
All contributors: Ella Leung, MD, Peter A.Karth, MD and Vinay A. Shah M.D.
Assigned editor: Peter A.Karth, MD
Review: Assigned status Up to Date by Peter A.Karth, MD on October 17, 2015.



Birdshot Retinochoroidopathy
Classification and external resources

Fundus Photo in Birdshot Retinochoroidopathy

OMIM 605808
DiseasesDB 32404


Birdshot retinochoroidopathy (also known as birdshot chorioretinopathy or vitiliginous chorioretinitis) is a chronic, bilateral, posterior uveitis with characteristic hypopigmented lesions. 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. One-fifth of patients will will improve without treatment, but the majority will experience a gradual decline in visual acuity to ≤20/200 over 10 years due to cystoid macular edema and retinal atrophy[1]. Treatment includes oral or intravitreal steroids for acute flares and immunomodulatory therapy for chronic disease.

Disease Entity

Disease

Birdshot retinochoriodopathy (BSRC) is characterized by its hypopigmented choroidal lesions ¼ to ½ optic disc diameter, clustered around the optic nerve, radiating towards the periphery, nearly always involving 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, primarily affecting 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)[2], vascular attenuation, RPE changes, optic nerve atrophy, and subretinal neovascularization. 

History

Birdshot Chorioretinopathy 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

BSRC 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)[3]. The presence of the gene is associated with a 50-224x greater relative risk of developing the disease[4]

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 BSCR[5]. 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+ 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[6]

Diagnosis

Diagnostic Criteria

An International Workshop held at UCLA in 2002 established a set of diagnostic criteria[7].

  • 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 (+)
    • Retinal vasculitis
    • Cystoid Macular Edema (CME)
  • Exclusion Criteria:
    • Keratic precipitates
    • Posterior synechaie
    • 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%)[8]. Although BSRC is a primarily ocular disease, there have been some reported associations with systemic hypertension, skin malignancy, hearing loss, vitiligo, and mood disorders.

Work Up

Late ICG in Birdshot with hypo-fluorescent atrophic lesions
The diagnosis is primarily clinical. However causes of uveitis and infections should be ruled out, and RPR/FTA-ABS, ACE, lysozyme, complete blood count (CBC), chest X-ray, and tuberculin purified protein derivative (PPD) may be indicated. 

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

  • HLA-A29+ serology
  • Fundus photos
  • Autofluorescence fundus photos-- hypo-autofluorescent atrophic areas
  • Fluorescein Angiography (FA)-- initial hypofluorescent lesions with subtle late staining, more useful for monitoring disease progression (i.e. cystoid macular edema, optic nerve head leakage, vasculitis)
  • Indocyanine Green (ICG)-- may reveal more fundus lesions (early hypofluorescent spots that become isofluorescent or hypofluorescent in the late phase)
  • ERG - prolonged 30Hz flicker implicit times. Unlike in other types of uveitis, BSCR has markedly diminished b waves (Mueller and bipolar cells) than a waves (photoreceptors)
  • EOG - abnormal
  • Best Corrected Visual Acuity 
  • Visual Fields - various defects including multiple foci, arcute, enlarged blind spot, and central defect
  • Color and contrast sensitivity abnormalities
  • OCT - decreased reflective macular photoreceptor bands on OCT[9]
  • Amsler grid - may have metamorphopsia

Differential Diagnoses

White Dot Syndromes

  • Acute Posterior Multifocal Placoid Pigment Epitheliopathy (APMPPE)
  • Serpiginous Choroidpathy
  • Multiple Evanescent White Dot Syndrome (MEWDS)
  • Multifocal Choroiditis and Panuveitis Syndrome (MCP)
  • Punctate Inner Choroidopathy (PIC)
  • Acute Zonal Occult Outer Retinopathy (AZOOR)
  • Diffuse unilateral subacute neuroretinitis

Infectious

  • Tuberculosis
  • Syphilis
  • Ocular Histoplasmosis Syndrome

Non-Infectious

  • Vogt-Koyanagi-Harada syndrome (VKH)
  • Sympathetic Ophthalmia
  • Masquerade syndromes (i.e. lymphoma)
  • Pars Planitis
  • Posterior Scleritis    – Sarcoidosis

Management and Outcomes

Treatment

About 20% may achieve remission without treatment; however, most patients will experience recurrent exacerbations. The disease eventually becomes unresponse to steroids alone and requires the early use of immunomudulatory therapies (IMTs).

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 excision or intraocular pressure lowering treatment

Chronic disease: Immunomodulatory Therapy

  • Cyclosporine A-- 1st line therapy (initially 3mg/kg/d --> 5mg/kg/d
  • Mycophenylate mofetil– 1st line therapy (1g/d --> 3g/d)
  • Azathioprine
  • Methotrexate
  • Daclizumab


Future Treatments being investigated include daclizumab and IV immunoglobulin therapy, both of which have shown success in preserving or improving VA [10] .

Visual Prognosis

Approximately 97.5% of patients may have some visual symptom at baseline[11], with 44% having an abnormal visual field[12] and 50-76% with abnormal EOG[13]. 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 IMTs, visual acuities remain stable or improved in 78.6-89.3%[14] while visual fields improved from a loss of 56-107° per year to a gain of 30-53° per year[15].

References

  1. Rothova A, Berendschot TT, Probst K, et al. Birdshot chorioretinopathy: longterm manifestations and visual prognosis. Ophthalmology. 2004;111(5): 954-959.
  2. Rothova A, Berendschot TT, Probst K, van Kooij B, Baarsma GS. Birdshot chorioretinopathy: long-term manifestations and visual prognosis. Ophthalmology. 2004 May;111(5):954-9.
  3. Kiss S, Anzaar F, Stephen Foster C. Birdshot retinochoroidopathy. Int Ophthalmol Clin. 2006 Spring;46(2):39-55.
  4. American Academy of Ophthalmology. "Birdshot Retinochoroidopathy." Section 9: Intraocular Inflammation and Uveitis. Singapore, 2011-2012. 152-155.
  5. LeHoang P, Cassoux N, George F, Kullmann N, Kazatchkine MD. Intravenous immunoglobulin (IVIg) for the treatment of birdshot retinochoroidopathy. Ocul Immunol Inflamm. 2000 Mar;8(1):49-57.
  6. Gaudio PA, Kaye DB, Crawford JB. Histopathology of birdshot retinochoroidopathy.Br J Ophthalmol. 2002 Dec;86(12):1439-41.
  7. Levinson RD, Brezin A, Rothova A, Accorinti M, Holland GN. Research criteria for the diagnosis of birdshot chorioretinopathy: fckLR results of an international consensus conference. Am J Ophthalmol. 2006 Jan;141(1):185-7.
  8. Rothova A, Berendschot TT, Probst K, van Kooij B, Baarsma GS. Birdshot chorioretinopathy: long-term manifestations and visual prognosis. Ophthalmology. 2004 May;111(5):954-9.
  9. Monnet D, Brézin AP, Holland GN, Yu F, Mahr A, Gordon LK, Levinson RD. Longitudinal cohort study of patients with birdshot chorioretinopathy. I. Baseline clinical characteristics. Am J Ophthalmol. 2006 Jan;141(1):135-42.
  10. LeHoang P, Cassoux N, George F, Kullmann N, Kazatchkine MD. Intravenous immunoglobulin (IVIg) for the treatment of birdshot retinochoroidopathy. Ocul Immunol Inflamm. 2000 Mar;8(1):49-57.
  11. Monnet D, Brézin AP, Holland GN, Yu F, Mahr A, Gordon LK, Levinson RD. Longitudinal cohort study of patients with birdshot fckLR chorioretinopathy. I. Baseline clinical characteristics. Am J Ophthalmol. 2006 Jan;141(1):135-42.
  12. Gordon LK, Monnet D, Holland GN, Brézin AP, Yu F, Levinson RD. Longitudinaol cohort sudy of patients with birdshot chorioretinopathy, IV: Visual field results at baseline. Am J Ophthalmol. 2007 Dec;144(6):829-837. Epub 2007 Oct 15.
  13. Gasch AT, Smith JA, Whitcup SM. Birdshot retinochoroidopathy. Br J Ophthalmol. 1999 Feb;83(2):241-9.
  14. Kiss S, et al. Long-term follow-up of patients with birdshot retinochoroidopathy treated with corticosteroid-sparing systemic immunomodulatory therapy. Ophthalmology. 2005 Jun;112(6):1066-71.
  15. Thorne JE, Jabs DA, Kedhar SR, Peters GB, Dunn JP. Loss of visual field among patients with birdshot chorioretinopathy. Am Jo Ophthalmol. 2008 Jan;145(1):23-28. Epub 2007 Nov 12