One or more lesions in ON mean increased risk for MS

Ten-year data from the Optic Neuritis Treatment Trial also found the risk was greater in women and patients without swollen optic discs.

Patients with acute optic neuritis who have one or more brain lesions on baseline MRI have a more than 50% chance of progressing to multiple sclerosis over a period of 10 years, according to long-term results of a major study.

The Optic Neuritis Study Group (ONSG) found that higher numbers of lesions do not seem to affect the risk of progression.

“This new information will allow ophthalmologists to have a more sophisticated discussion about the relative risks of developing multiple sclerosis in the patient with optic neuritis,” Barrett Katz, MD, an ONSG investigator and chair of the ophthalmology department at the George Washington University, told Ocular Surgery News.

Researchers in the Optic Neuritis Treatment Trial (ONTT) study group followed 388 patients who experienced optic neuritis between 1988 and 1991. Patients were followed for 10 to 13 years to determine the likelihood of developing multiple sclerosis (MS). The trial, funded by the National Eye Institute, was led by Roy W. Beck, MD, PhD, of the Jaeb Center for Health Research in Tampa.

Previous 5-year study outcomes revealed a 30% overall risk of developing MS after acute optic neuritis. Ten-year outcomes determined an overall risk of 38%; 12-year outcomes determined 40%. In the most recent data, 160 patients who had one or more typical lesions on baseline MRI had a 56% risk of developing MS; in those without lesions the risk was 22%.

ONSG authors said such data are a “critical input for estimating a patient’s 10-year multiple sclerosis risk and for weighing the benefit of initiating prophylactic treatment at the time of acute optic neuritis or other initial demyelinating events in the central nervous system.”

Source: The Optic Neuritis Study Group

Participants, methods

At study enrollment, the mean age of patients was 31.7 years; 77% of patients were women, 87% were white, 13% were black, 2% were Hispanic and 0.5% were Asian.

MRI of the brain was performed on 351 patients at 15 clinical centers upon enrollment. Tests were graded at a central reading center by a standardized protocol. The presence of brain T-2 signal lesions of 3-mm diameter or greater were documented and counted.

Standardized neurological examinations were performed at enrollment, after 6- and 12-month intervals and then yearly until 1997. From 1997 to 2002, telephone contact was made with patients semiannually, and neurological examinations were conducted when possible.

Study criteria defined patients as having MS if a clinical examination documented a new neurological deficit, consistent with a patient report of neurological symptoms of at least 24 hours’ duration, and separated by at least 4 weeks from the initial optic neuritis event. To qualify, a deficit must have been attributed to demyelination in the central nervous system, not in the optic nerve.

Of 388 patients, 336 had complete follow-up diagnosis of multiple sclerosis or at least 10 years of follow-up; 145 patients developed MS, and 243 did not develop MS.

Outcomes

“The most potent predictor of multiple sclerosis in our study was the presence of white matter lesions on the baseline MRI scan of the brain. The presence of one such lesion at least 3 mm in diameter more than doubled the 10-year risk of multiple sclerosis,” the authors said.

One or more lesions increased a patient’s risk by 56% (P <>

Multiple lesions detected on baseline MRI were not a significant risk factor.

“The risk of multiple lesions was not significantly higher than it was with a single lesion (58% vs. 51%),” the researchers noted.

Additionally, the presence of one or more lesions did not signify that the patient was destined to develop MS. More than 40% of patients who presented with lesions did not develop the disease.

Patients who developed MS were diagnosed at a median of 3 years after enrollment. Dr. Katz said that of these patients who developed the disease, two-thirds exhibited no MS-related neurological disabilities.

Among patients who were not diagnosed with MS by 5 years, the risk for developing MS in the next 5 years was 27% in patients with detected lesions, and 7% in patients with no detected lesions.

In total, 191 patients did not present with lesions. Study authors noted several trends from this cohort, which reduced the risk of developing MS.

Male patients or patients who had significant swelling of the optic disc had a lower incidence of developing MS. Other ON factors that contributed to a smaller risk of developing the disease were painless visual loss, lack of light perception, hemorrhage of the optic disc or surrounding retina and retinal exudates.

Implications

Study authors reported that the outcomes of the study hold clinical significance.

“They [outcomes] reaffirm the prognostic value of an MRI scan of the brain performed at the time of initial episode of acute optic neuritis,” the authors wrote.

Single lesions within a 3-mm diameter can predict the tendency to develop MS, but multiple lesions do not increase the risk.

These outcomes also highlight the importance of an ophthalmic examination for patients whose MRI of the brain is normal. Ophthalmoscopy can identify features that MRI cannot, such as optic disc swelling, hemorrhages and exudates, which are associated with a very low risk of developing MS.

This study was published in the Archives of Ophthalmology.

For Your Information:

• Barrett Katz, MD, MBA, is a professor of ophthalmology, neurology and neurosurgery and chair of the ophthalmology department at The George Washington University. He can be reached at 2150 Pennsylvania Ave. NW, Washington, DC 20037; (202) 741-2825; fax: (202) 741-2821; e-mail: bkatz@mfa.gwu.edu.
• Roy W. Beck, MD, PhD, lead investigator of the ONTT, can be reached at the Optic Neuritis Study Group Coordinating Center, Jaeb Center for Health Research, 15310 Amberly Drive, Suite 350, Tampa FL 33647; (813) 975-8690; fax: (813) 975-8761; e-mail: ontt@jaeb.org.

Reference:

• The Optic Neuritis Study Group. High- and low-risk profiles for the development of multiple sclerosis within 10 years after optic neuritis. Arch Ophthalmol. 2003;121:944-949.