Uveitis refers to a collection of ocular inflammatory diseases that can have diverse causes and present in many ways. It is one of the most challenging disorders for ophthalmologists to diagnose and treat — especially in children, where it is more likely to cause chronic inflammation and subsequent visual impairment.
Numerous causes for pediatric uveitis exist, but autoimmune disorders are by far the most common, including juvenile idiopathic arthritis (JIA), sarcoidosis, HLA-B27-associated uveitis and tubulointerstitial nephritis and uveitis syndrome (TINU). Children also develop infectious uveitis at higher rates than adults. Because diagnoses and prognoses differ among anterior, intermediate, posterior and panuveitis, anatomic classification of uveitis is helpful.
There are fewer than 100 dedicated uveitis specialists in the U.S. The National Eye Institute-funded MUST (Multicenter Uveitis Steroid Treatment) network is a consortium of international uveitis specialists who participate in hypothesis-driven, randomized clinical trials to determine evidence-based treatment regimens for uveitis and the sequelae of inflammation.
Personalizing Uveitis Diagnosis
Stephen J. Kim, M.D., and Sapna Gangaputra, M.D., are specialists at Vanderbilt Eye Institute’s recently established Uveitis Center. Both are fellowship-trained in uveitis, commit the majority of their time to treating the condition and are participating members of the MUST network. While the center provides uveitis care to both adults and children, Kim and Gangaputra have a special interest in pediatric uveitis.
Some pediatric uveitis-related diseases have clinical diagnoses that can be detected on exam and require little laboratory analysis. In other cases, the patient has already been diagnosed with an autoimmune disorder by a rheumatologist before they come to the center. Often, the etiology is unknown.
“Because uveitis-related diseases are so heterogeneous, precise diagnosis is critical”
“Because uveitis-related diseases are so heterogeneous, precise diagnosis is critical,” Kim said. “If children don’t receive appropriate intervention as early as possible, they’ll suffer vision loss from structural damage.”
At the Vanderbilt Uveitis Center, personalized diagnostic testing is used to determine the cause of each child’s uveitis. In addition to the standard eye exam, Kim and Gangaputra use a personalized workup including bloodwork, imaging and polymerase chain reaction (PCR) analysis of intraocular fluid to detect and diagnose infectious causes of uveitis. PCR analysis can be done in real time in the center’s laboratory, which speeds the diagnostic workup.
Treating Pediatric Uveitis with Biologics
Standard local treatments for intermediate, posterior and panuveitis are corticosteroid drops, injections or fluocinolone acetonide implants. The Uveitis Center is focusing on systemic treatment using immunosuppressive medications including biologics. Biologics, primarily infliximab and adalimumab, have been shown to be effective in treating various subtypes of uveitis, especially in more treatment-resistant cases.
“We tackle noninfectious chronic uveitis in children by placing patients on systemic immunosuppression early, thereby minimizing their exposure to corticosteroids and their side effects,” said Kim. “Biologics are very specific; they inhibit a specific signal in the inflammatory cascade and result in better control and better outcomes in many cases.”
“You use the tools in your armament that you’re most comfortable with, and many ophthalmologists aren’t comfortable using biologics,” Gangaputra said. “We have used these drugs and we’re confident they work. We’ve seen children respond well, become more comfortable and regain quality of life.”
Kim and Gangaputra are interested in the microbiome as it relates to uveitis. “In children with uveitis, there is some concern as to whether their diets help or hurt their response to treatment,” Gangaputra said. “If harmful bacteria in the gut can be identified, we may treat these patients differently. While no human uveitis studies have been done yet, animal studies have shown improved intraocular inflammation.”
“We’re just getting started in studying the microbiome as it relates to inflammatory eye disease,” Kim said. “There’s a lot we have left to learn.”