• Written By: Michael Vaphiades, DO
    Neuro-Ophthalmology/Orbit

    Six-month results from this phase 2 randomized study shows that the anti-seizure drug phenytoin protects against retinal nerve fiber layer (RNFL) loss in acute optic neuritis. However, it’s unclear if the neuroprotective benefits will result in substantially better vision or less disability in the future.

    This is the first proof-of-concept study supporting preservation of axons with early use of phenytoin. Experimental studies suggest sodium channel inhibition may be neuroprotective because sodium-filled inflamed nerve cells lead to an influx of calcium and ultimately, cell death.

    Phenytoin can be loaded rapidly to achieve therapeutic serum concentrations within days; an important property because experimental studies suggest that neuroprotection for relapses should be started as early as possible during the phase of acute inflammatory injury (an inflammatory penumbra that corresponds to about the first 2 weeks of a clinical episode), and then potentially sustained until beyond the period of active inflammation, which can be detected for a median of 2 months after symptom onset.

    In this study, 86 patients who experienced an episode of  acute optic neuritis within 2 weeks were randomized to receive oral phenytoin or placebo for 3 months. At 6 months, mean RNFL thickness decreased by 16.69 µm in the phenytoin group compared to 23.79 µm in the placebo group (P=0.021). Macular volume also significantly improved in treated patients (P=0.005).

    The two groups showed no difference in visual acuity, contrast sensitivity, visual evoked potential latency or amplitude, color vision or lesion length.

    Similar proportions of patients in both groups had adverse events. Ten subjects in the phenytoin group discontinued treatment due to skin rashes.

    These results are encouraging. Additional studies could also investigate potential benefits in preventing lesions throughout the central nervous system in patients with multiple sclerosis. However, will patients see better in 10 to 20 years if treated with phenytoin early in the disease process? I think that is the big question that remains unanswered.