Therapeutic potential of valproic acid in advanced glaucoma: A pilot study

PURPOSE: Oral valproic acid (VPA) used as an anticonvulsant has been shown to improve contrast threshold sensitivities in patients receiving it on long-term. This study aimed to evaluate the efficacy of oral VPA in improving visual function in eyes with advanced stage glaucoma. METHODS: In this prospective randomized study, 31 patients (n = 31 eyes) with advanced stage glaucoma (with an intraocular pressure <16 mmHg) in at least one eye received oral VPA 500 mg once a day for 3 months and 33 patients (n = 33 eyes) continued on glaucoma therapy. Patients were followed up at 3 and 12 months (to evaluate the legacy effect of the drug). Blood VPA concentrations were measured at 3 months. Following parameters were assessed at baseline, 3 months and 12 months: log of the minimum angle of resolution (LogMAR) visual acuity, mean deviation on visual fields, and multifocal electroretinogram (ERG). RESULTS: Median LogMar visual acuity in the VPA group improved from 0.3 at baseline to 0.18 and 0.18 at 3 and 12 months, respectively (P < 0.01). In comparison, the median visual acuity in control group at baseline was 0.18 and showed neither worsening nor improvement over 3 and 12 months (P = 0.56). The improvement in VPA group was significant compared to the control group (P < 0.01; Wilcoxon Signed-rank test). An improvement in one line was experienced in 11 out of 31 eyes in the VPA group compared to 1 out of 33 eyes among controls (P = 0.003). No significant improvement was noted in the mean deviation, and the multifocal ERG (Latency and amplitudes) in the VPA-treated patients. The average blood VPA concentration measured at 3 months of therapy was 26 ± 8.9 μg/ml (range 8–55 μg/ml) which is much lower than that achieved during anticonvulsant therapy. None of the patients complained of any adverse effects that required stopping VPA therapy. CONCLUSION: A 3 months oral VPA therapy results in some improvement in visual acuity in a subgroup of eyes with advanced glaucoma and the effect was seen to persist 9 months after the drug was stopped.