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Johns Hopkins Pediatric

Deciphering the Complexities of a Rare Disease

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Jennifer Thorne, right, has been treating Meredith Cross, who has birdshot chorioretinitis, since 2012

Uveitis is a broad term that describes inflammation inside the eye. Birdshot chorioretinitis is a progressive type of uveitis characterized by inflammatory deposits in the retina and choroid. The deposits have a scattered appearance reminiscent of birdshot, hence the name.

Birdshot, as it is familiarly known, is an autoimmune disease that occurs when the body’s immune system mistakenly attacks healthy tissue. First described in 1980 by A. Edward Maumenee, M.D., former director of the Wilmer Eye Institute, Johns Hopkins Medicine, it affects slightly more women than men, typically in their middle years. Untreated, the inflammation can lead to vision loss, including loss of visual field, night vision, color vision, contrast and central visual acuity.

Jennifer Thorne, M.D., Ph.D., the Cross Family Professor of Ophthalmology at the Johns Hopkins University School of Medicine and chief of the Division of Ocular Immunology at Wilmer, specializes in treating patients with uveitis and is an authority on birdshot. She says that while there’s much to learn about the disease, she’s seeing more patients diagnosed earlier — and that can be vision-saving.

“Over the last 10 to 20 years, ophthalmologists have increasingly been more aware of this as a diagnosis and referring patients earlier, so we’re seeing them at a younger age, which is really fantastic,” says Thorne.

One of the challenges in diagnosing the disease is that early symptoms — which may include trouble with night vision and peripheral vision as well as color and contrast — can be very subtle. (More significant symptoms may include floaters, flashing lights and vibrating vision, which Thorne says can be quite distressing for patients.)

To complicate matters, says Thorne, there might not be obvious signs that ophthalmologists can see inside the eye.

“They may be able to see inflammation in the vitreous cavity, but they may not see the spots, so there ends up being a lot of symptoms with very little evidence of inflammation inside the eye, so patients may experience a delay in diagnosis,” she says.

A variety of tests are used to diagnose birdshot, including visual acuity and visual field tests as well as imaging tests such as indocyanine green (ICG) angiography, fluorescein angiography, optical coherence tomography (OCT) and, more recently, OCT-angiography.

High doses of oral steroids and intravitreal steroids can help control the disease, but particularly with oral steroids, the doses required are too high to be maintained long term. For this reason, treatment typically includes an immunosuppressant drug to allow for tapering of the steroid and continued control of the disease. Birdshot is a chronic disease, however, and close monitoring of patients is important to catch and treat flare-ups before damage to vision can occur.

Thorne says that while there is a genetic predisposition to the disease — nearly all patients with birdshot test positive for the HLA-A29 gene — not everyone who has the gene will develop birdshot.

“It’s something that I’m very interested in,” says Thorne, who collaborates with colleagues at Harvard University and the University of California, Los Angeles, as well as in France, to study the disease.

“The HLA-A29 gene affects approximately 8% of Caucasians and about 4% of African Americans in the United States — a whole lot more than the amount of birdshot we observe,” Thorne says. “So there’s clearly more to it than just that marker.”

Because birdshot is a rare disease, conducting many studies quickly can be challenging. One area of research interest is subtypes of genes that appear to be associated with birdshot. Another is how proteins are produced that lead to the disease in some people who are HLA-A29 positive but not in others.

Thorne is also interested in data showing that a group of patients was able to achieve drug-free remission, but she cautions that those conclusions must be taken with a grain of salt.

“When you look back retrospectively at something, you’re not doing the same thing for every patient, so it’s possible that patients that remain on the drug could in fact come off the drug safely, or not,” she says. “So, that proportion of successful remissions could be higher, but it could also be lower.”

Because the initial data suggest that this was possible, however, Thorne advocates for a more systematic approach to patient care for those with birdshot.

“Hopefully, in time, we’ll be able to look at it again and see if the trend is increasing,” she says. “If the trend suggests that we’re more likely to get remissions, that tells us that perhaps we’re on the right track.”

Recently, Thorne and her colleagues have been exploring the interplay between visual acuity and visual field, (clarity of vision and the total area one can see). They want to understand how that correlates with duration of the disease and with risk factors.

Thorne hopes the lessons she and her colleagues are learning will not only help inform treatment of birdshot but will also help expand knowledge about uveitis in general. She’s upbeat about the strides that have already been made in understanding and treating birdshot.

“Given the fact that the disease wasn’t optimally described until the early 1980s, I think it’s been pretty impressive what has been able to be done in this period of time,” she says.

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