Vision loss studies aim to optimize future care for patients with juvenile idiopathic arthritis-related uveitis

Uveitis associated with juvenile idiopathic arthritis can result in significant vision loss. Systemic immunosuppressive therapy may protect against that outcome. Identifying predictors of ocular complications and vision loss may help to select patients who can best benefit from aggressive medical treatment.

Key Points

Baltimore-Researchers aiming to define predictors of vision loss in patients with juvenile idiopathic arthritis (JIA)-associated uveitis are hoping to use that information for identifying at-risk individuals who may be appropriate candidates for early aggressive therapy, said Jennifer E. Thorne, MD, PhD, at Current Concepts in Ophthalmology.

"JIA is estimated to have an incidence of 2 to 14 cases per 100,000 children per year, and about 30% of patients with JIA who are antinuclear antibody (ANA)-positive, irrespective of the type of arthritis, develop chronic anterior uveitis," said Dr. Thorne, associate professor of ophthalmology and epidemiology, The Wilmer Eye Institute, The Johns Hopkins Medical Institutions, Baltimore.

"Chronic, nongranulomatous anterior uveitis is the most common type of uveitis in children with JIA, and diagnosis may be delayed because it usually is insidious in onset and asymptomatic," she said. "Screening criteria that aim to reduce the interval between uveitis onset and discovery have been in place for more than 17 years and have been recently updated in 2006. However, even with these efforts, development of ocular complications and vision loss remains a significant problem."

The majority of children were girls (73%) and white (85%). The patients had a median number of three involved joints; the majority had persistent oligarticular-type JIA (80%) and were ANA-positive (70%). The most frequent type of uveitis was anterior uveitis (87%), although about 1 in 8 children had anterior and intermediate uveitis, and the uveitis was bilateral in 71% of children.

"About half of the patients had uveitis for more than 6 years before presenting to our tertiary care center," Dr. Thorne said.

Review of ocular complications showed that two out of three children had at least one complication at presentation to the Wilmer Eye Institute, with the most common findings being cataract (22%), band keratopathy (32%), posterior synechiae (28%), anterior chamber (AC) cells ≥0.5%, and AC flare ≥1+ (44%). Almost half of the eyes presented with active uveitis as defined using the Standardization of Uveitis Nomenclature criteria. Presenting vision was 20/50 or worse in more than one-third of eyes and 20/200 or worse in one-fourth.

Multivariate statistical analyses identified prior surgery, presence of AC flare, and posterior synechiae as risk factors for poor vision. Immunosuppressive treatment was found to have a statistically significant protective effect for some visual acuity outcomes.

"One plausible hypothesis would be that patients receiving aggressive therapy with methotrexate might have relatively more severe disease and therefore be destined to have poorer vision," Dr. Thorne said. "However, after controlling for other variables, in our series, treatment with methotrexate had a strong protective effect against vision impairment (20/50 or worse vision) at presentation."

The leading causes of poor vision were presence of cataract, central band keratopathy, and glaucoma, she said.

"At least the vision loss in patients with cataract and central band keratopathy may be reversible," Dr. Thorne said.

During follow-up, the rate of vision loss to 20/50 or worse was 10% per eye-year, which parallels the rate seen in adults with uveitis. Findings at presentation that were independent risk factors for vision loss included ANA-positive status, posterior synechiae, AC flare, abnormal IOP, and active inflammation. The causes of vision loss during follow-up were similar with the exception that hypotony was responsible for causing more blindness in eyes over time.

Defining treatment candidates

Currently, Dr. Thorne and colleagues are developing a uveitis severity score that could be used to identify children who would particularly benefit from aggressive medical therapy. Initial analyses are being performed using the retrospective data from the Wilmer Eye Institute cohort of 75 children. However, the investigators hope ultimately to test their findings in a larger sample of patients using retrospective data from a multicenter study including 175 children with JIA uveitis. Eventually they hope to validate the severity score in a prospective manner.

Clinical findings at presentation being considered initially to calculate the severity score include peripheral band keratopathy, AC flare 3+ or greater, posterior synechiae, and abnormally low or high IOP. With the patients divided into two groups based on a predetermined cut-off score, analyses are investigating the score's predictive value based on its correlations with various clinical features, including visual acuity, ocular complications, and rate of vision loss.

In addition, the researchers will be investigating whether there is any difference in outcome between children with a given severity score who are treated with methotrexate and their counterparts who did not receive immunosuppressive therapy.