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Valproic acid worse than placebo as treatment for retinitis pigmentosa
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In a prospective trial, patients treated with oral valproic acid for autosomal dominant retinitis pigmentosa had worse visual field outcomes than patients treated with placebo.
Valproic acid (VPA) is an approved treatment for epilepsy, bipolar disorder, migraine headache and pain management. It has several and potentially severe adverse effects.
Among other effects, it upregulates growth factor gene expression and could potentially enhance ganglion cell survival by increasing levels of brain-derived neurotrophic factor and nerve growth factor in the retina.
Because no approved treatment exists for retinitis pigmentosa (RP), the administration of VPA was attempted, with positive short-term benefits. However, longer-term effects remained controversial.
In this new trial, 90 participants were recruited in six major U.S. universities and randomized to receive VPA treatment or placebo over 1 year. The primary outcome measure was the change in kinetic perimetry visual field area (VFA) over the 52 weeks of the study, as assessed by the III4e isopter, which provides greater sensitivity to detect short-term change in RP. Secondary outcomes included changes in VFA by the I4e and V4e isopters and static perimetry volumetric measurements at the full field and central 30° field.
While minimal visual field change occurred in the placebo group, significant worsening was observed in the group treated with VPA. No significant adverse events were reported.
“This study does not provide support for the use of VPA in the treatment of autosomal dominant retinitis pigmentosa,” the authors concluded. – by Michela Cimberle
Disclosure: Birch reports grants and personal fees from Foundation Fighting Blindness during the conduct of the study and grants from Nightstar, Applied Genetic Technologies Corp., Ionis Pharmaceuticals, Regeneron, 4D Molecular Therapeutics and Second Sight Medical Products outside the submitted work. Please see the study for the other authors’ financial disclosures.
Perspective
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Barbara Reiss, OD, FAAO
VPA is a fatty acid used to treat epilepsy, schizophrenia and bipolar disorder. Its mechanism of action is not completely understood, but because of its effect on neurotransmitters, gene expression and inflammation, some researchers believed that it had potential for treating RP. In 2010, a small retrospective observational study indicated a possibility that VPA could improve visual acuity and visual field in people with autosomal dominant RP.
The current study is a multicenter, prospective, interventional, placebo-controlled, randomized clinical trial. Patients were given oral VPA or a placebo for 12 months. In this study, those taking VPA had greater visual field loss than the control group, indicating that with rigorous study, VPA is not a treatment for RP.
This study demonstrates the need for prospective randomized controlled clinical trials, particularly for treatment of diseases like RP for which there is no cure. The early reports (based on a small, poorly controlled retrospective study) showed great promise. VPA, like most drugs, is not without side effects. Clinicians must be able to evaluate studies to make the best possible treatment decisions for their patients.
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