New options address challenges of managing uveitic glaucoma

Uveitic glaucoma presents a treatment challenge because of the need to control two conditions. Furthermore, side effects of conventional treatments for uveitis-corticosteroids and systemic immunomodulatory agents-limit their use.

Fortunately, new treatments for uveitis are enabling safer and effective management of uveitic glaucoma, and others are on the horizon, said Terri Pickering, MD.

Speaking at the 23rd Annual Glaucoma Symposium during the 2019 Glaucoma 360 meeting, Dr. Pickering reviewed the etiology, diagnosis, and management of uveitic glaucoma. She is a clinical instructor, California Pacific Medical Center, San Francisco.

Dr. Pickering said there are multiple classification systems for uveitis, but it is most often categorized as infectious or non-infectious, and the latter group may be further divided according to whether it is associated with a systemic disorder.

With so many possible causes for uveitis, the work-up for a patient with intraocular in-flammation may seem daunting, but establishing the etiology is important to avoid overlooking a treatable cause for uveitis (i.e., infection) or a concurrent systemic disease that needs treatment. A targeted work-up is facilitated based on the patient’s demographics and findings from the history and physical examination.

“Identifying the cause for the uveitis can also help with counseling patients about their prognosis,” Dr. Pickering said.

She recommended, however, that all patients be tested for syphilis, which is considered “the great masquerader,” and have a chest X-ray or CT scan to look for sarcoidosis or tuberculosis.

Uveitis management

Dr. Pickering said glaucoma can develop in patients with uveitis through several path-ogenic pathways and may represent open-angle or closed-angle disease. Inflamma-tion control is critical, and steroids are the cornerstone of treatment for non-infectious uveitis.

The risk for intraocular pressure (IOP) elevation and other side effects, howev-er, create a need for steroid-sparing therapy.

“Furthermore, results of the Multicenter Uveitis Steroid Treatment (MUST) trial showed that systemic immunosuppressive therapy was superior to the use of the fluocinolone acetonide steroid implant for controlling uveitis over the long-term,” said Dr. Pickering.

Prednisone is still the mainstay for systemic immunosuppressive treatment of uveitis, but antimetabolites, alkylating agents, and T-cell inhibitors have been used as steroid-sparing therapy instead of or in combination with prednisone to limit steroid-induced adverse events.

Biologic therapy was first used to treat uveitis about 15 years ago.

“Now, the biologics are revolutionizing treatment of uveitis because compared with traditional immunomodulatory treatments, the biologics tend to be more effective, better tolerated, and easier to comply with because of a less frequent administration schedule,” Dr. Pickering said. “But as with everything, there are cons associated with the biologics.”

Dr. Pickering noted that the response to biologic treatment can be variable, there is potential for long-term toxicity, more long-term safety data are needed, and while the situation is improving, insurance coverage can be difficult to obtain.

“Methotrexate is still much less expensive,” Dr. Pickering added. Biologics may be most useful for treating uveitis in patients with HLA-B27 disease, Behçets disease, or juvenile idiopathic arthritis. In addition, they may be considered for patients who fail or cannot tolerate traditional immunomodulatory treatments.

Adalimumab (Humira, Abbvie), which is a tumor necrosis factor (TNF) antagonist, is the only biologic approved by the FDA for treating noninfectious uveitis. It is indicated for the treatment of noninfectious intermediate, posterior, and panuveitis in adults and pediatric patients 2 years of age and older.

Study results

Studies with adalimumab and other TNF antagonists showed benefit for improving uveitis control and decreasing steroid dependency. It appears that earlier treatment initiation is helpful for minimizing irreversible tissue damage.

However, there is evidence that efficacy may decline over time and compared to their use in treating systemic diseases, biologics may need to be given at a higher dose or more frequently to control uveitis, said Dr. Pickering.

“Combination treatment with a biologic and nonbiologic is also commonly done, but two biologics should not be used together because of toxicity and infection risk,” Dr. Pickering said.

Potential side effects of the TNF antagonists include infection or infection reactivation, malignancy development, particularly non-melanoma skin cancers, a lupus-type syn-drome, and a systemic drug sensitivity allergic reaction.

In addition, the TNF antago-nists are contraindicated in patients with advanced congestive heart failure, any type of demyelinating disease, and women who are pregnant or nursing. Patients on a TNF antagonist should not be given a live vaccine.

“In the interest of minimizing toxicity, most uveitis specialists will use a biologic in a pulse regimen, treating patients for two or three years and then try to stop the biologic,” Dr. Pickering said. “In the future we may see different classes of biologics emerge for the treatment of uve-itis because there are many potential targets in the eye, and there are some agents already in development."

Glaucoma management

Medical management is considered first-line of treatment for controlling IOP in eyes with uveitic glaucoma, although prostaglandins and laser trabeculoplasty should be avoided if the uveitis is not well controlled and alpha agonists should be avoided in children.

Ideally, surgery for glaucoma should be performed only after the eye has been quiet for at least three months.

“The problem is that surgical intervention is often indicated because of high IOP, and so there may not be the luxury of time,” Dr. Pickering said.

A glaucoma drainage device is considered the surgical intervention of choice for adults.

Dr. Pickering cautioned that cycloablative procedures can lead to phthisis, especially in the setting of active inflammation.

Goniotomy may be the best choice for surgical intervention in children and teens. Trabeculectomy should not be performed in the pediatric population, Dr. Pickering said.

Novel therapeutic target The gut microbiome has become a new target of interest for treating noninfectious au-toimmune uveitis based on the theory that it plays a key role in any disease involving the immune system.

Dr. Pickering explained that cross-reactive antigens of gut bacte-ria can trigger an autoimmune attack in the eye by activating T-cells that pass through the intestine and cross the blood-brain barrier.

“HLA-B27 shares a short peptide sequence with some bacterial molecules, and be-cause HLA-B27 disease accounts for 40% of anterior uveitis cases, treatments directed at the gut microbiome or T-cells open up a large avenue for potential future therapy based on the goal of restoring immune homeostasis,” she concluded.