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Lack of scientific rationale for use of valproic acid for retinitis pigmentosa
  1. Michael A Sandberg,
  2. Bernard Rosner,
  3. Carol Weigel-DiFranco,
  4. Eliot L Berson
  1. Berman-Gund Laboratory for the Study of Retinal Degenerations, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA
  1. Correspondence to Dr Michael A Sandberg, Berman-Gund Laboratory, Harvard Medical School, 243 Charles Street, Boston, MA 02114, USA; michael_sandberg{at}

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‘Therapeutic potential of valproic acid for retinitis pigmentosa,’ by Clemson et al,1 has significant flaws that militate against their conclusion that short-term valproic acid improved the vision of patients with retinitis pigmentosa.

The investigators should have performed a case–control study, comparing patients taking valproic acid with control patients matched for baseline field and acuity. This would have allowed for possible floor effects owing to the low baseline function of some of the treated patients (ie, who might be more likely to improve rather than decline over follow-up by chance variability) and avoided their use of historical rates of change drawn from different populations tested by others with different methods.

Statistical analyses should have been performed on patients, instead of eyes, unless controlling for the intraclass correlation between fellow eyes of the same patient. A reanalysis of their results by the signed-rank test for cluster-correlated data2 reveals weaker effects for visual-field improvement (eg, p =0.14 vs no change) and visual acuity improvement (eg, p=0.06 vs no change) in their cohort. In fact, none of the presented comparisons was statistically significant with this test.

The authors did not cite any published side effects of valproic acid (eg, constipation, diarrhoea, and hearing loss). Among patients with retinitis pigmentosa given valproic acid elsewhere, one reported to us a further impairment of hearing and no visual improvement after taking this drug for several weeks. Another showed a decline in retinal function while on this drug for 1 year.

We believe that the above-named paper by Clemson et al. does not provide a scientific rationale for the clinical trial that the authors recommend.



  • Competing interests None.

  • Provenance and peer review Not commissioned; internally peer reviewed.