Eyeworld

EW NEWS & OPINION 24 June 2017 by Liz Hillman EyeWorld Staff Writer corticosteroid pills after 2 years improved visual function. 7 The effects and side effects of the two treatments, however, were different. Retisert, for example, resulted in higher risk for cataract and glauco- ma. Conventional systemic therapy resulted in more cases of infections that required a prescription. The use of immunomodulato- ry drugs for systemic treatment of noninfectious uveitis, as Dr. Foster advised, has increased in recent decades. 8 An article published in 2000, which included Dr. Foster as a coauthor, acknowledged that corticosteroids might not be the best treatment for patients, depending on the severity of their disease and the potential for steroid-related side effects. This, Jabs et al. wrote, "supports the rationale for immu- nosuppressive drugs (for example, antimetabolites, T-cell inhibitors, and alkylating agents) being used in management of these patients." 9 In July 2016, the U.S. Food and Drug Administration (FDA) approved Humira (adalimumab, AbbVie, North Chicago) as the first non-corticosteroid for treatment of noninfectious uveitis. A randomized, placebo-controlled trial to evaluate the safety and efficacy of adalim- umab (an anti-tumor necrosis factor alpha, anti-TNF-alpha) published in September 2016 found that it "con- trolled multiple aspects of uveitic inflammation and was associated with a lower risk of uveitic flare and a longer time to a flare than was placebo." 10 There were, however, more adverse events, some serious, associated with adalimumab use vs. placebo, including respiratory tract infections and allergic reactions. granulomatous, anterior uveitis that responds to steroid therapy with- out relapse upon tapering steroid drops, then the case doesn't need to be referred to a uveitis specialist. However, if the patient relapses several times, if it's granulomatous (has what Dr. Foster called greasy, "mutton-fat" keratic precipitates indicative of possible systemic dis- ease), and if it's posterior uveitis, it's a referable case. However, Dr. Foster said it doesn't have to be referred if the physician wants to continue managing the case, but co-managing might be key. "Hook up with someone in their locality who is a uveitis specialist, or if there is no such person, hook up with a hematologist or rheuma- tologist to co-manage the patient and not get stuck in first gear with steroids endlessly. Move past that and engage with a person who is very comfortable and knowledgeable about the use of immunomodula- tory drugs," he said. "That person doesn't know about the eye. They're going to be dependent on the ophthalmologist to communicate carefully and frequently with them about how it's going with respect to the eye. The eye doctor isn't going to feel comfortable doing drug man- agement—that will be the task of the hemotherapist." What's new In 2011, a study published by the National Eye Institute found that the slow-release, implantable cor- ticosteroid drug Retisert (Bausch + Lomb, Bridgewater, New Jersey) and conventional systemic treatment of the patient's immune system with it is typically classified based on what part of the uvea—the layer between the sclera and the retina— is affected. 6 Chronic, recurrent, or posterior uveitis are more vision threatening than anterior uveitis, said Dr. Foster, who is also presi- dent and CEO of the Massachusetts Eye Research & Surgery Institution, Waltham, Massachusetts. Uveitis can result in vision-threatening complications such as glaucoma and cystoid macular edema, cataract, and retinal detachment, among others. Fortunately, most cases of uve- itis are curable. "There are certain cases that are not [curable] and the patient is dependent on medication forever, but in the vast majority, if they're treated in a particular way that the immune system can be retrained how to behave correctly, eventually the patient can be off everything and achieve remission. It takes a while—it takes a minimum of 2 years to accomplish that—but it's possible," Dr. Foster said. Diagnosing uveitis starts with taking an internist-style history. Dr. Foster said the review of systems, going from head to toe and asking the patient questions, can result in more diagnostic leads than a battery of laboratory tests. The exam should include more than just the slit lamp examination. "We emphasize to our fellows that they should take a look at what they can actually see with the room lights on—the hair, the skin, the ears, the fingertips, the joints—then move on with the slit lamp exam- ination," he said. The history and examination should allow one to come up with a differential diagnosis list to choose the appropriate laboratory tests. One test that should not be overlooked is an antibiotics test for the possibil- ity of late or secondary syphilis. Dr. Foster said over the course of a year, they'll pick up several cases of syph- ilis presenting in recurrent ocular inflammation that the patient might have forgotten to mention. If this test is positive, penicillin is curative. Other testing, Dr. Foster said, is predicated on the review of systems history and features observed on the eye exam. Most cases of noninfectious uveitis treatment begin with corti- costeroids. Dr. Foster said if it's non- With it accounting for up to 15% of blindness in the U.S., uveitis remains an important issue—and most types are curable U veitis is kind of the "poor stepchild" of ophthalmol- ogy, said Charles Stephen Foster, MD, clinical pro- fessor of ophthalmology, Harvard Medical School, Boston, and founder and president of the Ocular Immunology and Uveitis Foundation. Few ophthalmologists got into this field of medicine wanting to specialize in an internal medical issue, Dr. Foster explained, adding that of the more than 100 residency programs in the U.S., only a fraction have a fellowship-trained uveitis specialist on the faculty to educate those in training about the disease. "It's not a glamorous area of medicine. The patients aren't falling down and kissing your hands the day after surgery. It's a slug-it-out kind of tedious medicine," Dr. Foster said, noting that most physicians treat patients who exhibit noninfec- tious inflammation of the uvea with "steroids and more steroids," which come with a host of negative side effects and should not be a long- term solution. When one considers that uveitis is the third leading cause of prevent- able blindness in the world—fifth in the U.S.—it suggests there should be more of a focus on treatment of these patients. 1,2 In the U.S., uveitis accounts for 10–15% of cases of blindness. 3 According to analysis published in 2016 based on data from claims from a commercially in- sured population, there are 121 non- infectious uveitis cases per 100,000 adults—in this population, that's a prevalence of less than 0.1%. 3 Yet estimates in the U.S. suggest uveitis accounts for 10–15% of blindness. 4 In 1996 the cost of uveitis-related blindness in the U.S. was estimated to be $242.7 million—and that was more than 2 decades ago. 5 The basics There are many different causes for the various forms of uveitis—au- toimmune dysfunction, infection, medication, trauma, and more—and Calling attention to uveitis: The basics and the latest research " … in the vast majority [of cases], if they're treated in a particular way that the immune system can be retrained how to behave correctly, eventually the patient can be off everything and achieve remission. " —Charles Stephen Foster, MD

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