Dataset Information

Efficacy of valproic acid for retinitis pigmentosa patients: a pilot study.

ABSTRACT:

Purpose

The purpose of this study was to examine the efficacy and safety of valproic acid (VPA) use in patients with retinitis pigmentosa (RP).

Patients and methods

This was a prospective, interventional, noncomparative case study. In total, 29 eyes from 29 patients with RP whose best-corrected visual acuities (BCVAs) in logarithm of the minimum angle of resolution (logMAR) ranged from 1.0 to 0.16 with visual fields (VFs) of ?10° (measured using Goldmann perimeter with I4) were recruited. The patients received oral supplementation with 400 mg of VPA daily for 6 months and were followed for an additional 6 months. BCVAs, VFs (measured with the Humphrey field analyzer central 10-2 program), and subjective questionnaires were examined before, during, and after the cessation of VPA supplementation.

Results

The changes in BCVA and VF showed statistically significant differences during the internal use of VPA, compared with after cessation (P=0.001). With VPA intake, BCVA in logMAR significantly improved from baseline to 6 months (P=0.006). The mean deviation value of the VF significantly improved from baseline to 1 month (P=0.001), 3 months (P=0.004), and 6 months (P=0.004). These efficacies, however, were reversed to the baseline levels after the cessation of VPA intake. There were no significant relations between the mean blood VPA concentrations of each patient and the changes in BCVA and VF. During the internal use of VPA, 15 of 29 patients answered "easier to see", whereas blurred vision was registered in 21 of 29 patients on cessation. No systemic drug-related adverse events were observed.

Conclusion

While in use, oral intake of VPA indicated a short-term benefit to patients with RP. It is necessary to examine the effect of a longer VPA supplementation in a controlled study design.

SUBMITTER: Iraha S

PROVIDER: S-EPMC4975153 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Efficacy of valproic acid for retinitis pigmentosa patients: a pilot study.

Iraha Satoshi S Hirami Yasuhiko Y Ota Sachiko S Sunagawa Genshiro A GA Mandai Michiko M Tanihara Hidenobu H Takahashi Masayo M Kurimoto Yasuo Y

Clinical ophthalmology (Auckland, N.Z.) 20160725

<h4>Purpose</h4>The purpose of this study was to examine the efficacy and safety of valproic acid (VPA) use in patients with retinitis pigmentosa (RP).<h4>Patients and methods</h4>This was a prospective, interventional, noncomparative case study. In total, 29 eyes from 29 patients with RP whose best-corrected visual acuities (BCVAs) in logarithm of the minimum angle of resolution (logMAR) ranged from 1.0 to 0.16 with visual fields (VFs) of ≤10° (measured using Goldmann perimeter with I4) were re ...[more]

PMID: 27536054

Similar Datasets

Project description:ImportanceThere are no approved drug treatments for autosomal dominant retinitis pigmentosa, a relentlessly progressive cause of adult and childhood blindness.ObjectivesTo evaluate the potential efficacy and assess the safety of orally administered valproic acid (VPA) in the treatment of autosomal dominant retinitis pigmentosa.Design, setting, and participantsMulticenter, phase 2, prospective, interventional, placebo-controlled, double-masked randomized clinical trial. The study took place in 6 US academic retinal degeneration centers. Individuals with genetically characterized autosomal dominant retinitis pigmentosa were randomly assigned to receive treatment or placebo for 12 months. Analyses were intention-to-treat.InterventionsOral VPA 500 mg to 1000 mg daily for 12 months or placebo.Main outcomes and measuresThe primary outcome measure was determined prior to study initiation as the change in visual field area (assessed by the III4e isopter, semiautomated kinetic perimetry) between baseline and month 12.ResultsThe mean (SD) age of the 90 participants was 50.4 (11.6) years. Forty-four (48.9%) were women, 87 (96.7%) were white, and 79 (87.8%) were non-Hispanic. Seventy-nine participants (87.8%) completed the study (42 [95.5%] received placebo and 37 [80.4%] received VPA). Forty-two (46.7%) had a rhodopsin mutation. Most adverse events were mild, although 7 serious adverse events unrelated to VPA were reported. The difference between the VPA and placebo arms for mean change in the primary outcome was -150.43 degree2 (95% CI, -290.5 to -10.03; P = .035).Conclusions and relevanceThis negative value indicates that the VPA arm had worse outcomes than the placebo group. This study brings to light the key methodological considerations that should be applied to the rigorous evaluation of treatments for these conditions. This study does not provide support for the use of VPA in the treatment of autosomal dominant retinitis pigmentosa.Trial registrationClinicalTrials.gov Identifier: NCT01233609.

Project description:BackgroundRetinal dystrophies constitute a group of diseases characterized by clinical variability and pronounced genetic heterogeneity. Retinitis pigmentosa is the most common subtype of hereditary retinal dystrophy and is characterized by a progressive loss of peripheral field vision (Tunnel Vision), eventual loss of central vision, and progressive night blindness. The characteristics of the fundus changes include bone-spicule formations, attenuated blood vessels, reduced and/or abnormal electroretinograms, changes in structure imaged by optical coherence tomography, and subjective changes in visual function. The different syndromic and nonsyndromic forms of retinal dystrophies can be attributed to mutations in more than 250 genes. Molecular diagnosis for patients with retinitis pigmentosa has been hampered by extreme genetic and clinical heterogeneity between retinitis pigmentosa and other forms of retinal dystrophies. Next generation sequencing (NGS) technologies are among the most promising techniques to identify pathogenic variations in retinal dystrophies.PurposeThe purpose of this study was to discover the molecular diagnosis for Brazilian patients clinically diagnosed with a retinitis pigmentosa pattern of inheritance by using NGS technologies.Materials and methodsSixteen patients with the clinical diagnosis of retinitis pigmentosa were included in the study. Their DNA was sequenced in a panel with 132 genes related to retinal dystrophies using the Illumina® platform. Sequence analysis and variation calling was performed using Soft Genetics®, NextGene, and Geneticist Assistant software. The criteria for pathogenicity analysis were established according to the results of prediction programs (Polyphen 2, Mutation taster and MetaCore™) and comparison of pathogenic variations found with databases.ResultsThe identified potentially pathogenic variations were all confirmed by Sanger sequencing. There were 89 variations predicted as pathogenic, but only 10 of them supported the conclusion of the molecular diagnosis. Five of the nine patients were autosomal dominant RP (56%), two (22%) were autosomal recessive RP, and two (22%) were X-linked RP. Nine of the 16 patients (56%) had probably positive or positive results.ConclusionThe Next Generation Sequencing used in this study allowed the molecular diagnosis to be confirmed in 56% of the patients and clarified the inheritance pattern of the patient's retinal dystrophies.

Dataset Information

Efficacy of valproic acid for retinitis pigmentosa patients: a pilot study.

Purpose

Patients and methods

Results

Conclusion

Publications

Efficacy of valproic acid for retinitis pigmentosa patients: a pilot study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets