A small group of patients with severe Graves' eye disease experienced rapid improvement of their symptoms — and improved vision — following treatment with the drug rituximab(利妥昔). Inflammation(发炎,红肿) around their eyes and damage to the optic nerve(视神经) were significantly reduced. The same patients had not previously1 responded to steroids(甾体), a common treatment for Graves' eye disease. Raymond S. Douglas, M.D., Ph.D., an oculoplastics specialist who recently joined the faculty2 of the U-M Kellogg Eye Center, reports on the potential of the drug in the online October issue of Ophthalmology. Douglas reviewed the progress of six patients he treated while on the faculty of the University of California at Los Angeles.
Graves' eye disease is an autoimmune disease(自身免疫病) that causes inflammation and fatty deposits in the eye muscles and connective tissue surrounding the eye. Among the symptoms are pronounced(显著的,明白的) bulging3 eyes(突眼), retracted4 eyelids5(眼睑), dry eyes, and, in severe cases, loss of vision. Women are more likely than men to develop the disease.
The study suggests that rituximab is a potentially effective new treatment for the most severe forms of Graves' eye disease. "These patients had already received the maximum level of steroid(类固醇) treatment," says Douglas. "Treatment with rituximab calmed inflammation, stopped progression of the disease, and saved the patients from having to undergo surgery."
Rituximab has been used to treat patients with other autoimmune diseases, including rheumatoid(患风湿病的) arthritis6(关节炎) and in non-Hodgkin's B-cell lymphoma. The drug works by depleting7(耗尽,空竭) B cells—the body's normal antibody-producing cells—that appear to go awry8(扭曲的,走样的) in autoimmune diseases.
Collaborating9 with Terry J. Smith, M.D., the Frederick G.L. Huetwell Professor of Ophthalmology and Visual Sciences, Douglas has helped to explain the process by which the immune system attacks the orbital tissue in Graves' eye disease. In an earlier study, the researchers reported that B cells play a pivotal role in the inflammatory process in Graves' eye disease.
In the current study, Douglas observed improvement among the patients, four of whom were women, as early as four weeks following the first infusion10(输液,灌输) of rituximab. Researchers also observed that the positive results were sustained 4 to 6 months after treatment.
"Treatment of the inflammatory component11 of Graves' eye disease has not advanced appreciably12(相当大地) over several decades," says Douglas. High-dose steroids, sometimes in combination with orbital radiation, are still the first line treatment. But, says Douglas, "These are imperfect options because inflammation often recurs13 when the treatment ends." He is hopeful that rituximab can offer sustained improvement. Douglas observes that the results from a small case series must be viewed with some caution. But given the substantial benefits for patients treated with rituximab, he sees good reason to proceed with a large-scale clinical trial to test this promising14 new drug.