Researchers say more children with arthritis than previously recognized may be at high risk for a devastating eye condition called uveitis, which causes blindness in up to 45 percent of cases.

Their study, which was published in the June 2010 issue of Arthritis & Rheumatism, has the potential to change eye-screening recommendations for kids with juvenile idiopathic arthritis (JIA), who often get uveitis as a complication of their disease.

Uveitis is the inflammation of the middle layer of the eye, which houses the colored iris and the lens.

In children, the most common disease associated with uveitis is JIA – approximately 1 in 8 diagnosed with arthritis will also develop the eye condition.

The condition often has no symptoms in its early stages, when it is most treatable. That’s why catching it early, with frequent eye screenings, is critical for saving sight.

Current guidelines, published in 2006 in the journal Pediatrics, recommend eye exams every three months for children diagnosed with juvenile arthritis before age 6 who also test positive for anti-nuclear antibodies, or ANAs. From four to seven years after diagnosis, the recommended frequency of screening drops to every six months; and after seven years, experts recommend eye screening once each year.

But the current study has called those guidelines into question, suggesting that kids diagnosed with JIA before age 5 should get quarterly eye exams until seven years after their diagnoses, instead of just four.

The researchers also stressed that gender appears to play a greater role in the development of uveitis than previously realized. Girls who were diagnosed with arthritis before age 2 comprised the highest risk group of all children in the study.

Traudel Saurenmann, MD, the study’s lead author and head of the Pediatric Rheumatology Unit at University Children's Hospital in Zürich, Switzerland, says she wanted to better understand risk factors associated with the development of uveitis because the condition can be difficult to recognize.

Dr. Saurenmann and her international team analyzed data on more than 1,000 children with a diagnosis of JIA who had been followed for many years through the Hospital for Sick Children in Toronto, Canada. Of the 1,081 patients with juvenile arthritis included in the study, 142, or 13.1 percent, eventually developed uveitis.

“This is the largest cohort of patients from a single center reported so far,” Dr. Saurenmann says, adding that a large patient population is one of the only reliable ways to spot patterns of risk factors related to a disease.

One of those patterns was related to age. “Age at diagnosis of juvenile arthritis was a much more important factor than we had previously thought,” she says.

Other red flags related to gender – girls seemed to be more susceptible to uveitis than boys, and to the presence of antinuclear antibodies (ANAs), in the blood. ANAs are proteins that may signal an autoimmune attack on the body.

Researchers found that nearly half of the girls in the study who were ANA positive and between the ages of 1 and 2 at the onset of JIA went on to develop uveitis at some point in their lives. Their risk was about three times, or 300 percent, higher than any other group in the study.

But that risk decreased with each year of age, dropping to just a 10 percent chance of getting uveitis if a girl was diagnosed by age 7 or later. Boys did not have the same risk connected to age and ANA in their blood.

Another significant finding of the study was that with only a couple of exceptions, the specific kind of arthritis a child had, called their subtype, didn’t seem to influence the risk of developing uveitis.

Previously, experts had believed that subtype had a lot to do with whether or not kids would go on to develop the eye condition. Kids with oligoarthritis, for example, in which four or fewer joints are affected during the first six months, were previously thought to be in greatest danger.

Not so, researchers say.

“Now we were faced with the fact that in our cohort the subtype of JIA did not influence the risk of getting uveitis, but the major factors were the age at diagnosis of JIA and sex,” Dr. Saurenmann says. 

“Girls had a higher risk the younger they were at the diagnosis,” she continues. “The age association in girls was so strong that the risk of getting uveitis was even significantly higher in girls who were 1 year old at diagnosis of JIA than in 2-year-olds.”

Researchers say age is likely to be a factor because younger immune systems that haven’t fully matured may be more susceptible to autoimmune diseases.

But they don’t yet know why there are differences between boys and girls.

“As a rule women tend to be more affected by autoimmune diseases than men and it has therefore been discussed whether hormonal factors may play a role. However, in young children sex hormones are not produced to a significant amount,” Dr. Saurenmann says.

Edward Sills, MD, chief of pediatric rheumatology at Johns Hopkins Children's Center in Baltimore, Md., weighed in on the significance of the study.

"I am familiar with and applaud the study. It emphasizes important points,” Dr. Sills says. But he also cautions that kids who fall outside of these apparent high-risk categories, those who are older, male or who may be ANA negative, aren’t off the hook when it comes to eye screening.

Dr. Sills says that for now, it’s clear what parents should do. “The single most important step is for parents to have the child seen on a regular basis, at least twice a year or more frequently in the higher risk groups, by an ophthalmologist, not an optometrist, for slit lamp exams (lighted microscopic views of the eye) of the uveal tract,” he says. “Early diagnosis, which slit lamp surveillance provides, will minimize or prevent any adverse effects of uveitis and, likely, maintain normal vision."

Dr. Saurenmann agrees. “The earlier the diagnosis of uveitis is made and effective treatment begun, the fewer the complications and the better the long-term outcome of uveitis,” she says.