American Academy of Ophthalmology Web Site: www.aao.org
A Shot in the Dark?
Beverly Uccello* was meeting up with her longtime golfing partners for an afternoon of early spring practice. "This will be the year we finally win the league title,?" she thought as she headed to the course. But as they started to play, she was surprised by how rusty she had become over the winter. She was having difficulty reading the greens, and she could not distinguish the red flag from the background of grass behind it. As she got close to the green, she had to ask one of her partners to stand by the pin. When she got home, she realized that she had been in denial, for she had been having episodes of blurry vision and difficulty differentiating her colors for a while.
We Get a Look
When we saw Ms. Uccello, a 48-year-old Caucasian with a nine-month history of progressive clouding of the central vision in her right eye, she told us that "the left eye sees light brighter - than the right and that certain objects had started to look "gray and dull."
The initial exam revealed a BCVA of 20/20 in her right eye and 20/25 in the left. Ishihara color vision was 6/8 in her right eye and 5/8 in the left. The anterior segment exam was normal. She also was found to have bilateral disc edema and +1 vitreous cells. Her posterior fundus appeared normal. At this point, we started a uveitis workup.
There was nothing remarkable about her RPR, FTA-ABS, Lyme titers, ANA, serum protein, electrophoresis, C-reactive protein, ESR, ACE, liver function tests and chest x-ray.
A Humphrey visual field revealed an enlarged blind spot in each of her eyes. A brain MRI was obtained, and it was significant for several nonspecific, nonenhancing, periventricular white matter lesions. With the positive ocular and radiological findings, the diagnosis was presumed intermediate uveitis secondary to multiple sclerosis and associated optic nerve edema. On physical exam there were no other neurological symptoms. At this point, she was referred to neuro-ophthalmology.
On the next visit, the clinical exam was unchanged except for worsening visual fields. Ms. Uccello was started on oral prednisone and one month later she had subjective improvement and decreased vitreous cells in both eyes. The prednisone was subsequently tapered. On follow-up visits, Ms. Uccello's exam seemed to be unchanged, including the persistent bilateral disc edema and +1 vitreous cells.
After minimal improvement with treatment and given the chronicity of the disease, she was lost to follow-up.
What's Your Diagnosis?
No Longer Lost to Follow-Up
More than a year later, Ms. Uccello reappeared. She had seen an optometrist, who told her that the decrease in visual acuity was not refractive in nature and urged her to follow-up with her ophthalmologist.
Repeat exam showed visual acuity of 20/80 in her right eye and 20/50 in the left; color vision was 5/8 in her right eye and 4/8 in the left. She had disc edema and +1 vitreous cells bilaterally. Her visual fields had worsened, with generalized depression and further enlargement of her blind spot in the right eye and peripheral constriction in the left. Repeat uveitis workup was again unremarkable. At this point she was referred to a retina clinic, where it was found that her visual acuity had worsened to 20/200 in her right eye and 20/60 in the left.
A fundus exam revealed multifocal, yellow, ovoid lesions radiating from the optic nerve bilaterally at the level of the retinal pigment epithelium with sheathing of the retinal vasculature and bilateral macular edema. A fluorescein angiogram revealed normal fill time in both eyes, bilateral inferior vascular inflammation, optic nerve edema and leakage, and cystoid macular edema.
The abnormal MRI of the previous year had been suggestive of MS. Additional test results included normal lumbar puncture and unchanged brain MRI. Continued follow-up indicated no evidence of new systemic neurologic disease, a criterion for the diagnosis of MS. The patient's clinical findings progressed to the diffuse radiating chorioretinal lesions consistent with birdshot chorioretinopathy (BSCR) and a positive HLA-A29 test further confirmed the diagnosis.
BSCR is a rare disorder first described 25 years ago by Maumenee and Ryan. They named the condition for its clinical appearance; the lesions bearing a resemblance to a blast from a shotgun. Around the same time, Gass also described the condition, giving it the moniker "vitiligenous chorioretinopathy." This name is more descriptive of the lesions themselves, which resemble the skin of a patient with vitiligo.
The namesake fundus lesions may be yellow to orange in color. They can vary in size and shape but are typically round or elliptical. The lesions are usually up to one-half disc diameter and often reside inferior and nasal to the optic disc.1,2 Their presence is usually bilateral and can be asymmetric. Of note, the lesions may not be present until years after the initial symptoms.1
This disorder predominantly affects females, and the age of onset ranges from 15 to 79, with a mean age of 53.1 Patients often present with blurred or distorted vision. Sometimes the subjective vision loss is much worse than is appreciated on exam. In a report of 13 subjects, 12 reported blurred vision despite recorded visual acuity of 20/20.1 Nyctalopia, photopsias, paracentral scotomas, floaters and color distortion have also been described.
Ocular inflammation is present as moderate vitritis.1,2 Retinal vasculitis also is commonly seen and usually is limited to the posterior fundus. Anterior segment involvement is usually very mild or absent. Decreased visual acuity early on in the disease is attributed to macular edema. Persistent inflammation and optic disc edema can lead to optic atrophy and subsequent permanent visual loss.
BSCR has a strong association with the HLA-A29 allele. Several studies have shown that more than 95 percent of BSCR patients are HLA-A29 positive. HLA-A29 subtype 1 seems to be protective against the disease, while patients who have BSCR belong to subtype 2.3
Diagnostic tools commonly used in the diagnosis of BSCR include a visual field, electroretinogram, fluorescein angiogram, indocyanine green angiogram and optical coherence tomography.
The visual fields may show enlargement of the blind spot, central or paracentral scotomas, or any constriction of the peripheral vision.
The electroretinogram typically has a preserved a-wave, representing the photoreceptor layer, which is relatively undisturbed. The b-wave, however, shows diminished amplitude and an increased latency time, which would represent damage specific to the inner neural retina. ERG is routinely used to follow BSCR patients on therapy for evidence of progression. In advanced stages, patients can progress to night blindness with a nonrecordable ERG.3
The fluorescein angiogram may demonstrate the breakdown of the inner blood retinal barrier secondary to inflammation, which results in the leakage of fluorescein from the retinal vessels and capillaries. Initially, the lesions may show early hypofluorescence and late hyperfluorescence.1 In patients with associated CME and optic disc edema secondary to BSCR, the FA shows late hyperfluorescence in the macular region and the optic nerve.
With ICG angiograms, the lesions are more numerous and can be identified earlier in the disease process than with fluorescein angiograms or indirect ophthalmoscopy. The lesions are typically hypofluorescent, as a result of choroidal nonperfusion secondary to choroidal inflammation.1,2 In short, an ICG angiogram is essential in following the choroidal inflammation, while a FA is critical in monitoring the presence of retinal vascular inflammation.
The OCT is often used in addition to the FA to objectively assess the degree of CME and the treatment response.
The differential diagnosis includes infectious causes such as syphilis, Lyme disease, tuberculosis, toxoplasmosis and presumed ocular histoplasmosis syndrome. Noninfectious etiologies include the other white dot syndromes, such as multifocal evanescent white dot syndrome, multifocal choroiditis with panuveitis, acute posterior multifocal placoid pigment epitheliopathy and serpiginous choroiditis. Other entities to consider are posterior scleritis, Harada??‚??„?s disease, sympathetic ophthalmia, pars planitis and the masquerade syndromes.
BSCR is a rare disorder with a variety of clinical presentations. Currently there is no consensus on the best course of therapy. It is an autoimmune disease with an inflammatory component and a variety of anti-inflammatory medications can be used to treat it. Initial treatment can involve corticosteroids - either oral prednisone, periocular triamcinolone (transeptal and sub-Tenon's) or intravitreal triamcinolone?€which have been effective in reducing CME, optic disc edema and vitritis.
In patients with recurrent chronic disease, immunomodulation therapy should be considered. These medications may include cyclosporine, methotrexate, mycophenolate mofetil, azathioprine, tacrolimus and daclizumab.
Ms. Uccello was started again on oral prednisone and given a one-time dose of sub-Tenon's triamcinolone, which resulted in improved acuity and decreased vitreous cells bilaterally. She also began immunosuppressive therapy with methotrexate. At the last visit, three months after starting treatment, she was on a slow taper of oral prednisone daily, and methotrexate weekly. With a BCVA of 20/40 in both eyes, she told us, "I'm starting to see normally."
* Patient name is fictitious.
1 Shah, K. H. et al. Surv Ophthalmol 2005;50:519??‚??€œ541.
Drs. Mauro and Pennock are residents at Nassau University Medical Center, N.Y. and Stony Brook University Hospital, N.Y. Dr. Huang is clinical professor of retina and uveitis at the latter hospital.