Effect of phenytoin on retinal ganglion cells in acute isolated optic neuritis

Phenytoin has been shown to reduce the peripapillary retinal nerve fiber layer (pRNFL) loss in optic neuritis (ON). We evaluated the effects of phenytoin on retinal ganglion layers and visual outcomes of newly diagnosed acute ON.

A randomized, placebo-controlled trial was conducted in a tertiary referral eye hospital and patients with the first episode of typical demyelinating ON, without any history of multiple sclerosis were randomly assigned to phenytoin or placebo. The thickness of ganglion cell-inner plexiform layer (GCIPL) measured by optical coherence tomography (OCT) was considered as the primary outcome.

One patient in the phenytoin group developed severe cutaneous rashes that progressed to Stevens-Johnson syndrome (SJS)/toxic epidermal necrosis (TEN), and further allocation of patients to the phenytoin group was stopped, and finally fifteen participants were included in the phenytoin group. Fifty-one patients were enrolled to the placebo group, from which four were excluded. Both visual acuity and field were not significantly different between the control and phenytoin groups after 1 and 6 months. Mean 3- and 6-mm macular GCIPL thicknesses decreased after 6 months to 73.6 ± 14.1 and 57.9 ± 7.5 μm, respectively, in the phenytoin group and to 71.6 ± 15.7 and 55.6 ± 6.6 μm, respectively, in the placebo group with no significant differences between the two groups (P = 0.77 and P = 0.26, respectively, linear multilevel model).

Phenytoin is not probably safe and effective as neuroprotection after acute ON. Further investigation with other sodium channel inhibitors could be considered.