Uveitis in Kids Linked With Risk of Cataracts Over 20 Years

Children with uveitis appeared to have an increased risk of developing cataracts over 20-year follow-up, according to a retrospective cohort study.

Among over 45,000 children, uveitis was associated with a higher risk of cataracts during 20-year follow-up compared with never having the condition (HR 17.17, 95% CI 12.90-22.80), reported Chun-Ju Lin, MD, of China Medical University Hospital in Taichung City, Taiwan, and colleagues in JAMA Network Open.

“The main point we want doctors to take away from our study is the heightened awareness of cataract risk among children with uveitis,” Lin and co-author Alan Hsu, MD, also of the China Medical University Hospital, told MedPage Today in an email. “Consequently, clinical practice should emphasize increased vigilance in monitoring these at-risk children for cataract development, as the timely diagnosis and management of pediatric cataracts are crucial to [improving] visual outcomes.”

A Kaplan-Meier analysis revealed an approximate 8% incidence of cataracts among those with uveitis over the 20-year period, versus about a 0% to 1% incidence among those without uveitis (log-rank P<0.001).

Although the risk of cataracts after uveitis is well-documented in adults, few studies have focused exclusively on the pediatric population or used such a large dataset, the study authors pointed out.

The increased cataract risk began as soon as 1 month after an initial episode of uveitis, a finding that Dilraj Grewal, MD, a specialist in vitreoretinal pathology and uveitis at Duke Eye Center in Durham, North Carolina, found surprising. “Typically, we don’t see cataract development that rapidly unless the inflammation was already longstanding at the time of diagnosis,” he told MedPage Today.

“It might have been helpful if the authors had looked at how many of the eyes that were diagnosed with cataract underwent cataract extraction,” Grewal said. “Mild cataracts may not cause visual symptoms … particularly in children, and cataract extraction often serves as a surrogate to quantify those cataracts that were visually significant.”

Much of the risk for cataracts was apparently driven by the use of steroid eye drops and immunosuppressive agents. A history of steroid eye drops in children with uveitis was associated with a nearly 30-fold increased risk of cataracts (HR 29.51, 95% CI 14.56-59.70), whereas no history of steroid eye drops was tied to a more than 16-fold increased risk (HR 16.49, 95% CI 11.92-22.70). Increased cataract risk was seen with prednisolone drops (HR 26.42, 95% CI 12.39-56.20) and dexamethasone drops (HR 13.34, 95% CI 1.74-102.60).

A history of receiving immunosuppressive agents within 3 months of a first episode of uveitis was also linked to an increase in cataract risk (HR 26.52, 95% CI 16.75-41.90), but an association with cataract risk was also seen among patients with uveitis who did not have a history of immunosuppressive agents (HR 17.69, 95% CI 11.39-27.40). Of note, the increased risk was less pronounced among patients who received certain immunosuppressives, such as methylprednisolone and triamcinolone, but far higher in those who received methotrexate (HR 20.52, 95% CI 6.42-65.62).

“The implication that methotrexate may be associated with a higher risk of cataract development than prednisolone and triamcinolone is surprising and needs to be investigated further,” Grewal noted. Also, the study did not include children prescribed biologics such as adalimumab (Humira) and infliximab (Remicade), “which are now increasingly used in the management of pediatric uveitis and, with a rapid onset of action, allow for a quicker discontinuation of steroids,” he pointed out.

In terms of anatomic location, panuveitis (HR 42.16, 95% CI 5.77-308.20) and anterior uveitis (HR 17.37, 95% CI 12.71-23.70) were associated with the highest risks of cataract development.

Grewal was surprised by the finding that posterior uveitis was associated with the lowest increase in risk of cataracts (HR 9.44, 95% CI 1.18-75.58), because “these eyes often have more severe inflammation requiring longer duration of therapy, often with higher steroid doses.”

Of note, Lin and colleagues also observed a higher cataract risk among children with uveitis who had increased levels of C-reactive protein and leukocyte count, which “further emphasizes the important role that inflammation may potentially play in the pathophysiology between uveitis and cataract formation,” Hsu and Lin told MedPage Today.

They also reported a lower risk for cataract development among children who had undergone intraocular surgeries compared with those who didn’t have surgeries, possibly due to the confounding effects of medication. “Specifically, certain anti-inflammatories, like topical nonsteroidal anti-inflammatories … might have mitigated inflammation within the intraocular structures caused by the procedures, potentially leading to a reduced risk of cataract development,” they posited.

When analyzing the association between comorbidities and cataracts, the researchers found that juvenile arthritis was associated with an increased risk of developing cataracts (HR 59.31, 95% CI 8.23-427.60), as was asthma (HR 6.65, 95% CI 2.32-19.04).

All age groups and all racial and ethnic groups of children with uveitis appeared to have elevated risk of cataracts, according to a subgroup analysis.

This study used data primarily from the U.S. Collaborative Network within TriNetX, an international health research platform, from January 2002 through December 2022. A total of 22,687 children with uveitis and 22,687 without uveitis were enrolled in the study. In both groups, mean age was 10.3 years, and 54-55% were boys.

Lin and colleagues acknowledged several limitations to their study, including a lack of information on dosage and frequency of immunosuppressive medications and steroid drops. Furthermore, medication adherence, an important challenge among pediatric patients, could not be assessed.

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