Although commonly used, oral corticosteroids alone are ineffective in treating optic neuritis, a debilitating inflammation of the optic nerve, and actually increase a person’s risk for future attacks, according to a large National Eye Institute-supported clinical trial published today in the New England Journal of Medicine.
This unexpected finding calls into question the benefit of treating related demyelinating neurological diseases, such as multiple sclerosis, with oral corticosteroids. Demyelinating diseases are characterized by progressive damage to the lipid sheaths that insulate nerve fibers.
Most neurologists and ophthalmologists now treat optic neuritis with oral corticosteroids, based on anecdotal reports that these anti-inflammatory agents improve patient recovery.
The Optic Neuritis Treatment Trial, which involved over 450 patients at 15 clinical centers nationwide, is the first randomized clinical trial to evaluate corticosteroid therapy for optic neuritis.
"This is a very significant finding," said HHS secretary Louis W. Sullivan, M.D. "It highlights the critical importance of conducting research on the effectiveness of commonly used therapies that have not been fully and rigorously scientifically evaluated, as well as newly developed treatments."
Optic neuritis affects more than 25,000 Americans each year, primarily women between ages 18 and 45. People with the disease have rapid vision loss and usually have ocular pain. If left untreated, some patients regain normal vision after several months of gradual improvement, but most are left with at least some visual deficit. Because a significant number of people who have an initial attack of optic neuritis later develop multiple sclerosis, many physicians consider optic neuritis as a precursor or manifestation of the disease.
The Optic Neuritis Treatment Trial randomly assigned patients to one of three treatment groups: oral corticosteroids (prednisone), intravenous (methylprednisolone) followed by oral corticosteroids (prednisone), and placebo. Trial patients had no previous history of optic neuritis in the eye being treated.
Trial investigators found that 27 percent of people taking oral prednisone had at least one new attack of optic neuritis during a follow-up period, which for some patients was as long as two years. In contrast, patients in the intravenous group had a 13 percent rate of new attacks, and those given a placebo had a 15 percent rate of subsequent optic neuritis. Few patients had immediate serious side effects from the treatments.
The researchers also reported no differences in how rapidly patients in the oral group regained their vision compared to the placebo group, or in either group’s long-term visual recovery.
"We believe based on our results that there is no role for oral prednisone alone in the treatment of patients with initial episodes of optic neuritis," said Roy Beck, M.D., professor of ophthalmology at the University of South Florida and the study chairman.
The researchers found, however, that patients in the group given both intravenous and oral corticosteroids recovered their vision about two weeks sooner than those receiving a placebo. At a six-month follow-up examination, they also had slightly better contrast sensitivity, visual fields, and color vision than placebo patients. However, the patients receiving intravenous treatment did not have superior visual acuity to those given a placebo.
Because intravenous therapy proved marginally effective in the follow-up examination, trial investigators stated that physicians should weigh the therapy’s potential benefits against the small risk of serious adverse effects, patient inconvenience, and the cost of treatment (particularly if hospitalization is required, as it was during this clinical trial). Since the intravenous regimen was generally well-tolerated, outpatient therapy may be feasible.
Since the eye is such an excellent model for brain research, the trial’s findings may have implications for corticosteroid treatment of other demyelinating neurological diseases. "Nearly 40 percent of sensory input to the brain originates in the eye," said Carl Kupfer, M.D., director of the National Eye Institute.”Vision research not only reveals the dynamics of ocular disease but its results may also be applied to many disorders that affect the brain.”
Corticosteroids are currently used to treat multiple sclerosis. But, according to Dr. Beck, their effects have not been properly studied in multiple sclerosis patients. "Since there is ample evidence that optic neuritis is often the first manifestation of multiple sclerosis," said Dr. Beck, "the results of our study indicate that oral corticosteroids may not be efficacious in treating patients with multiple sclerosis."
The National Eye Institute is one of the National Institutes of Health, an agency of the Public Health Service within HHS.
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- Beck RW, Cleary PA, Anderson MM Jr, Keltner JL, Shults WT, Kaufman DI, Buckley EG, Corbett JJ, Kupersmith MJ, Miller NR, et al. A Randomized, Controlled Trial of Corticosteroids in The Treatment of Acute Optic Neuritis. The Optic Neuritis Study Group. N Engl J Med. 1992 Feb 27. PubMed