Birdshot Retinopathy 

Birdshot retinochoroidopathy (BSRC) is an uncommon chronic posterior uveitis characterized by vitritis and multiple ovoid spots, which are orange to cream in color and hypopigmented. These spots are mainly distributed in the posterior pole and in the mid periphery of the retina. The classic presentation is described to "resemble the pattern seen with birdshot in the scatter from a shotgun."

Birdshot retinochoroidopathy was first described by Franceschetti and Bable in 1949. In 1980, Ryan and Maumenee coined the term birdshot.^[1] Gass described birdshot retinochoroidopathy as vitiliginous choroiditis because of the similarities of the fundus lesion to cutaneous vitiligo.

Birdshot retinochoroidopathy may indeed represent a clinical disease that has only recently come into existence, and one may wonder what factors from recent times have allowed it to emerge, such as a new strain of virus, an environmental factor, or some yet unrecognized participant in the development of this disease.

The cause for birdshot retinochoroidopathy is unknown. A strong link to the presence of the human leukocyte antigen A29 (HLA-A29) molecule exists, suggesting that the disease may result from an inherited immune dysregulation. Multiple case series report 80-93.1% HLA-A29 positivity for patients with birdshot retinochoroidopathy, with a relative risk ratio from 50 to 224. This is the strongest HLA association with any known disease.^[2]

LeHoang and coauthors reported a series of European patients in which all patients who were HLA-A29 positive with birdshot retinochoroidopathy expressed the HLA-A29 type 2 subtype.^[3] Both the HLA-A29 type 1 subtype and the HLA-A29 type 2 subtype respond to serologic tests but migrate differently on 1-dimensional electrofocusing gel electrophoresis. Their results suggested that the HLA-A29 type 2 subtype is the risk factor for birdshot retinochoroidopathy and that the HLA-A29 type 1 subtype actually may be protective against developing the disease. However, Levinson and coauthors found that both subtypes were associated with disease in patients in the United States.^[4]

Nussenblatt and colleagues also found a link with human leukocyte antigen B12 (HLA-B12), which has been confirmed by several other authors.^[5] The link to HLA-B12 is less strong, with a relative risk ratio from 2.7 to 7. Most individuals who are HLA-A29 or HLA-B12 positive do not have birdshot retinochoroidopathy, which obviously implies that other factors are required to provoke the onset of the disease.

Pathogenesis

Class I major histocompatibility (MHC) molecules play an important regulatory role in the immune response. Retinal autoimmunity may play an important role in the pathogenesis of the development of the intraocular inflammation activity for individuals who are HLA-A29 positive because of a genetic immune regulation.

Strong in vitro cell-mediated responses to various retinal autoantigens, including self-antigen (S-Ag) and interphotoreceptor retinoid-binding protein (IRBP), have been observed in patients with birdshot retinochoroidopathy. Autoreactive T cells produce interleukin 2 (IL-2) in response to autoantigens, but, during disease quiescence or during therapy with cyclosporine, IL-2 levels are not detectable.

The precise mechanism that might lead to this retinal autoimmunity is unknown. Further research is necessary to reveal the immune mechanism that leads to this rare condition.

Many theories have been proposed to explain the genesis of autoimmunity in the genetically predisposed individual.

• Receptor mechanism and concomitant infection: MHC antigen provides a specific cell marker for binding of an infectious microorganism, such as Borrelia burgdorferi and Coxiella burnetii.
• Common embryologic origin: The retina and the pineal gland share a common embryological origin. Experimental studies show that animals immunized with S-Ag and IRBP develop pinealitis in addition to experimental autoimmune uveitis (EAU).

Frequency

United States

Birdshot retinochoroidopathy is a rare disease. There are few reports that address the incidence of birdshot retinochoroidopathy. In the United States, one uveitis clinic reported 7 out of 600 patients (1.2%) with this diagnosis. Since and including 1980, 59 cases have presented to the National Eye Institute (NEI).

International

In Europe, at 14 eye clinics, only 102 cases of birdshot retinochoroidopathy were diagnosed from 1980-1986.

Mortality/Morbidity

Birdshot retinochoroidopathy is a potentially blinding disease. Although some ophthalmologists describe patients with birdshot retinochoroidopathy in whom the disease process runs a relatively benign course, where good visual acuity is preserved with minimal therapy, many patients experience a severe course with loss of functional vision, with permanent macular pathology secondary to uncontrolled inflammation and undertreated macular edema. The author strongly believes that if the disease process of a patient with birdshot retinochoroidopathy demonstrates the ability to cause significant inflammation (particularly if significant vasculitis is present) or vision-affecting macular edema, then it is imperative that treatment options be pursued aggressively to control the disease process.

Race

Most patients are of Caucasian background.

Sex

Gender preference is not clear, as some studies showed predilection for women, but other studies showed no significant sexual predilection.

Age

Birdshot retinochoroidopathy typically occurs during the middle age, presenting at an average age of 50 years, with an age range of 35-70 years.