This paper reports results from a phase 2 trial evaluating oral valproic acid for treating autosomal dominant retinitis pigmentosa.

Study design

This was a multicenter, prospective, interventional, double-masked, randomized controlled trial of 90 patients with genetically characterized autosomal dominant retinitis pigmentosa. Patients were given oral valproic acid (500–1,000 mg daily) or a placebo. The primary outcome measure was the change in visual field area (assessed by the III4e isopter) on semiautomated kinetic perimetry at 12 months.

Outcomes

Patients in the valproic acid arms had significantly more visual field loss compared with patients in the placebo group. The difference in visual field area between groups was −150.43 degree² (P=0.035). Most adverse events were deemed mild.

Limitations

The study was limited to patients with autosomal dominant retinitis pigmentosa.

Clinical significance

This study found that valproic acid made the isopter III4e visual field deteriorate faster than those in the placebo group. This in in contrast to an earlier, smaller trial, that found valproic acid to be beneficial for this group of patients.

In an excellent accompanying editorial, Brian P. Brooks, MD, and Brett Jeffrey, PhD, offer their opinion on the methodological insights that can be gleaned from this trial. They astutely mention that had the V4e isopter been used as a primary outcome instead of the III4e isopter, this study would have likely reported a statistically significant positive result.