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Valproic acid at half normal dose shows benefit in patients with retinitis pigmentosa
Results of a preliminary clinical analysis suggest that valproic acid may be an effective treatment for photoreceptor loss associated with retinitis pigmentosa.
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Valproic acid at half the indicated dosage showed potential efficacy in the treatment of retinitis pigmentosa, a study showed.
Results of the retrospective chart review indicated that treatment with 500 mg of valproic acid, or VPA, had a therapeutic benefit to patients with retinitis pigmentosa. Some patients were switched during the study to a 750-mg dose, but most patients stabilized at 500 mg, study author Shalesh Kaushal, MD, PhD, said.
Increase in visual fields
Nine of 13 eyes involved in the study had improved visual fields with treatment, two eyes had decreased visual fields and two eyes experienced no change, which resulted in an overall average increase of 11% in area of functioning retina. This increase in visual fields was statistically significant (P < .02), assuming typical loss in visual fields area without treatment. An average decrease (0.172) in the logMAR scores was seen in these 13 eyes, which translates to a positive change in Snellen score of approximately 20/47 to 20/32. This was also significant (P < .02), assuming no loss in acuity without treatment.
Patients received a daily VPA dose of 500 mg, which is approximately half the dosage prescribed for other indications. Several patients who tolerated the drug well switched to 750 mg. Tiredness (10%) and stomach irritation (13%) were the most commonly reported adverse effects.
“At the 750-mg dose, we saw a nice effect with [retinitis pigmentosa] with essentially zero toxicity,” Dr. Kaushal told Ocular Surgery News. “It was at the 750-mg dose that the patients experienced improvement in [retinitis pigmentosa] vs. stabilization with the 500-mg dose.”
All eyes included in the study were examined before and after treatment with VPA, which lasted between 2 and 6 months (average: 4 months). Investigators used digitized Goldmann kinetic perimetry tracing to define visual fields for each eye. Snellen visual acuity values at 20 feet were converted to logMAR scores, the authors said in the study, published in the British Journal of Ophthalmology.
Age of patients ranged from 16 years to 56 years (mean: 36 years), with five men included. More than 85% of patients had a family history or reported genotyping to suggest an autosomal-dominant form of retinitis pigmentosa.
Assessing negative effects
The investigators used a conservative approach to determine any negative effects of VPA on the patient’s visual fields. A negative effect was indicated by net loss in visual fields from baseline greater than 2%. Without any treatment, the natural progression of retinitis pigmentosa includes a potential for significant short-term deterioration in visual fields. Of the 13 eyes examined, two experienced worsening of their visual fields. No abnormal liver function or blood chemistries were noted in the study sample.
“VPA offers a new potential therapy for [retinitis pigmentosa], a tragic blinding disease with no good treatment options. The results of our preliminary clinical analysis in conjunction with the prior in vitro data suggest that VPA may be an effective treatment for photoreceptor loss associated with [retinitis pigmentosa],” the authors said.
This treatment is being studied in children, Dr. Kaushal said. The dosage used in the pediatric study is half the dose normally given to children for the treatment of seizures.
Plans for a randomized, placebo-controlled clinical trial using the 750-mg dose are underway to assess the efficacy and safety, Dr. Kaushal said. – by Cassandra A. Richards
Reference:
- Clemson CM, Tzekov R, Krebs M, Checchi JM, Bigelow C, Kaushal S. Therapeutic potential of valproic acid for retinitis pigmentosa [published online ahead of print July 20, 2010]. Br J Ophthalmol. doi:10.1136/bjo.2009.175356.
- Shalesh Kaushal, MD, PhD, can be reached at the Department of Ophthalmology, University of Massachusetts Medical School, 381 Plantation St., Biotech 5, Suite 250, Worcester, MA 01605; 508-334-9074; e-mail: Shalesh.Kaushal@umassmemorial.org.
