Sunir J. Garg

BASICS

DESCRIPTION

• Chronic, bilateral, posterior uveitis

• The characteristic lesions are yellow-white spots at the level of the choroid that “radiate” from the optic nerve.

• Over 90% of patients are HLA-A29 positive.

EPIDEMIOLOGY

Incidence

Very rare eye disease

Prevalence

• In the population, it affects <1/200,000

• It affects 1% of patients in uveitis clinics and 5–7% of all patients with posterior uveitis.

RISK FACTORS

• Most common in Caucasian patients

• Equal male/female distribution

• Mean age of onset ∼50 years old

Genetics

• No strong familial association (although disease has been reported in monozygotic twins)

• Very strong association with HLA-A29 allele (birdshot has the highest association between HLA class I alleles and any disease)

• 90% of patients with disease have HLA-A29 compared with 7% of general population.

GENERAL PREVENTION

None

PATHOPHYSIOLOGY

• Likely autoimmune process

• Some similarities between birdshot and murine models of retinal S-antigen-induced uveitis

ETIOLOGY

Autoimmunity, likely involving type IV hypersensitivity

COMMONLY ASSOCIATED CONDITIONS

None known

DIAGNOSIS

HISTORY

• Gradual, painless vision loss

• Floaters are common.

• Symptoms are usually bilateral.

• Nyctalopia, peripheral visual field constriction, abnormal color vision, photopsias, and photophobia may also occur.

PHYSICAL EXAM

• The eyes are usually painless and appear white and noninflamed.

• The anterior segment has no to mild inflammation.

• A mild to moderate diffuse vitreitis is common.

• The characteristic lesions are cream colored hypopigmented spots in the choroid with relatively indistinct borders.

• These lesions are suggestive of scattering of “birdshot” from a shotgun.

• The choroidal spots may not appear until later in the disease course, delaying diagnosis.

• Cystoid macular edema (CME) is a common cause of decreased visual acuity.

• Retinal vasculitis involving veins and arteries is sometimes seen, as is optic disc edema.

DIAGNOSTIC TESTS & INTERPRETATION

Lab

• None are absolutely required for diagnosis; however, HLA-A29 is a reliable marker of disease (∼95% specificity and sensitivity).

• Must rule out other treatable causes of posterior uveitis, including syphilis, tuberculosis, lyme disease, ocular lymphoma, and sarcoidosis.

Imaging

Initial approach

• Fluorescein angiography (FA) shows early hypofluorescence and late hyperfluorescence of choroidal lesions, as well as hyperfluorescence of the disk, vascular leakage, and CME (when present).

• Indocyanine green angiography (ICGA) often demonstrates more lesions than seen on either clinical exam or FA. ICG shows early hypofluorescence of choroidal lesions.

• Optical coherence tomography (OCT) can be useful to detect macular edema.

• Electroretinograms (ERG) are often abnormal, typically showing a decrease in both photopic and scotopic amplitudes; Initially, B-wave may be affected more than the A-wave.

• Peripheral visual field testing may show constriction.

Follow-up & special considerations

• FA useful to monitor amount of inflammation and to follow response to therapy

• OCT useful to evaluate patients for macular edema, and for evaluating response to treatment

Pathological Findings

There are limited reports in the literature; however, lymphocytic aggregates in the choroid and retinal vasculature have been noted.

DIFFERENTIAL DIAGNOSIS

• White dot syndromes (acute posterior multifocal placoid pigment epitheliopathy, multifocal choroiditis and panuveitis, multiple evanescent white dot syndrome, AZOOR)

• Infectious posterior uveitis (tuberculosis, syphilis, and presumed ocular histoplasmosis syndrome)

• Masquerade syndromes (leukemia and ocular lymphoma)

• Sarcoidosis

TREATMENT

MEDICATION

First Line

• Ocular and systemic steroids have been the mainstay of therapy; however, the typical chronicity of this disease warrants consideration of nonsteroidal immunomodulatory therapy early in the disease course.

• Dramatic improvement of ocular inflammation can often be seen with systemic steroids (prednisone 1 mg/kg per day); however, long-term toxicity of steroids limits this approach.

• Cyclosporine, mycophenolate mofetil, azathioprine, cyclophosphamide, and methotrexate have all been used as nonsteroidal immunomodulatory therapies.

Second Line

• Periocular and intravitreal triamcinolone acetate has been used to treat severe inflammation and/or macular edema.

• More recently, use of antitumor necrosis factor alpha drugs and intravenous immunoglobulin has been reported.

ADDITIONAL TREATMENT

Issues for Referral

• Management of birdshot retinochoroidopathy often requires referral to a uveitis and/or retina specialist.

• Consultation with a rheumatologist or hematologist may be required when immunomodulatory agents are used.

SURGERY/OTHER PROCEDURES

• As with other types of ocular inflammation, cataract formation may be accelerated in patients with birdshot; cataract surgery is best delayed until the patient is free of inflammation for at least 3 months.

• Glaucoma filtration or shunting surgery may be required in some patients with uncontrolled glaucoma.

• In the near future, implantable drug delivery devices may play a major role in the treatment of this disease.

IN-PATIENT CONSIDERATIONS

Initial Stabilization

Pulse intravenous steroids may be considered in severe cases with profound bilateral vision loss.

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS

The course of birdshot is often progressive over a number of years, with intermittent exacerbations of disease activity; therefore, patients should be monitored closely by a specialist familiar with the treatment of the disease.

Patient Monitoring

• Visual acuity may be normal until late in the disease course.

• Careful biomicroscopic examination should be undertaken at regular intervals.

• Ancillary testing such as FA, ICGA, OCT, peripheral visual field testing and ERG testing should also be taken at regular intervals to monitor disease activity.

PATIENT EDUCATION

• Patients should be aware of the chronic progressive nature of birdshot chorioretinopathy, and the associated need for close monitoring and long-term treatment of the disease.

• Patients should also be aware that a variety of immunomodulatory treatments are available, and not be discouraged if one treatment modality is insufficient to treat their disease.

PROGNOSIS

• Because of the chronic progressive nature of the disease, visual prognosis is guarded over time.

• Patients often need to be treated with immunomodulatory agents that have side effects.

• Visual function can often be impaired to a greater extent than the visual acuity indicates.

COMPLICATIONS

• CME is the most common cause of decreased visual acuity.

• Epiretinal membranes (ERM) are also common.

• Glaucoma may be seen in up to 20% of patients and is likely a secondary effect from systemic and ocular steroid treatments.

• Choroidal neovascular membranes (CNVM) can occur in areas of chronic choroidal inflammation.

• Retinal neovascularization is uncommon, but can result from retinal vascular inflammation and secondary retinal ischemia.

• Optic nerve atrophy is rare, but has been reported.

ADDITIONAL READING

• Ryan SJ, Maumenee AE. Birdshot retinochoroido- pathy. Am J Ophthalmol 1980;89(1):31–45.

• Jap A, Chee SP. Immunosuppressive therapy for ocular diseases. Curr Opin Ophthalmol 2008;19(6):535–540.

• Monnet D, Brézin AP. Birdshot chorioretinopathy. Curr Opin Ophthalmol 2006;17(6):545–550.

• Kiss S, Anzaar F, Foster SC. Birdshot retinochoroidopathy. Int Ophthalmol Clin 2006;46(2):39–55.

• Shah KH, Levinson RD, Yu F, et al. Birdshot chorioretinopathy. Surv Ophthalmol 2005;50(6):519–541.

CODES

ICD9

363.20 Chorioretinitis, unspecified

CLINICAL PEARLS

• Chronic, progressive, bilateral posterior uveitis

• Characteristic peripapillary choroidal lesions and associated vitreitis are usually present. Choroidal lesions are often delayed in onset.

• Very strong association with HLA-A29

• Common cause of decreased visual acuity is cystoid macular edema.

• Electroretinograms are usually abnormal.

• Patients are often initially responsive to steroids but often require maintenance with nonsteroidal immunomodulatory agents.