MS Speaks

Seizure Drug May Help in MS Eye Disease

Phenytoin shows promise for slowing neurodegeneration in optic neuritis.

by Kristina Fiore
Staff Writer, MedPage Today

The seizure drug phenytoin may improve degenerative eye disease in patients with multiple sclerosis, researchers reported.

In a small phase II study, MS patients with optic neuritis who were on the drug had better preservation of retinal thickness and macular volume than those on placebo, although visual outcomes were similar.


The findings by Raj Kapoor, MD, of the National Hospital for Neurology and Neurosurgery in London, and colleagues are to be reported at the American Academy of Neurology annual meeting next week. An abstract for the late-breaking study was released Thursday.

Some early studies have shown that the partial blockade of voltage-gated sodium channels may be neuroprotective. Phenytoin being a sodium channel blocker, as well as a drug with an established safety record, Kapoor and colleagues randomized 86 MS patients with acute optic neuritis to the agent at 4 mg/kg/day or to placebo for 3 months.

They measured retinal nerve fiber layer (RNFL) thickness and macular volume at baseline and 6 months using optical tomography. They also measured visual function via logMAR, low contrast acuity, and color perception, along with optic nerve imaging and visual evoked potentials.

The primary outcome was RNFL thickness in the affected eye at 6 months.

Ultimately, five patients were lost to follow-up, so 81 were assessed for the intention-to-treat comparison.

Kapoor and colleagues found that patients in the phenytoin group had 30% less damage to the nerve fiber layer compared with placebo, with RNFL thickness that was 7.15 mcm higher in the drug group (P=0.02).

The volume of the macula was 34% higher in those on phenytoin compared with placebo, with a 0.20 mm3 greater volume among patients in the active group (P=0.005).

However, there were no differences in visual outcomes between the two groups.

Still, they concluded that phenytoin protects the RNFL and the macula from neurodegeneration in acute optic neuritis, raising the possibility that blockage of voltage-gated sodium channels may be neuroprotective in relapses of MS in general.

Kapoor said in a statement that if the findings are confirmed in larger studies, it may lead to a treatment to prevent nerve damage and blindness in MS.

Shlomo Shinnar, MD, PhD, of Montefiore Medical Center in New York, who was not involved in the study, was not immediately convinced of the utility of the drug in this condition.

"Over the years, phenytoin has been reported to have a wide range of effects in a variety of disorders. Most have not been confirmed," Shinnar said in an email to MedPage Today.

He agreed with Kapoor that the result needs confirmation in a more definitive study. In addition, he noted that the lack of a difference in actual vision means that the clinical significance of the finding remains unclear.

"As we continue to search for disease modifying/neuroprotective agents, our enthusiasm for preliminary findings is tempered by a long history of promising agents that subsequently more definitive trials did not find to be effective," Shinnar said.

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Kapoor and Shinnar disclosed no financial relationships with industry.