There have been some reports in academic journals about the use of Valproic acid (VPA) in Retinitis Pigmentosa (RP). We thought we can review the current status of these trials and evaluate where we stand in the outcomes.
What is Valproic acid?
Valproic acid is in a class of medications called anticonvulsants. It may be used alone or with other medications to treat certain types of seizures. It is also used to treat mania in people with bipolar disorder (manic-depressive disorder; a disease that causes episodes of depression, episodes of mania, and other abnormal moods). It is also used to prevent migraine headaches, but not to relieve headaches that have already begun.
Valproic acid may cause serious or life threatening damage to the liver and is most likely to occur within the first 6 months of therapy. The risk of developing liver damage is greater in children who are younger than 2 years of age. Valproic acid may cause serious or life-threatening damage to the pancreas. This may occur at any time during your treatment. (source)
Warning: This medication may cause significant side-effects/complications. It should NOT be taken without a physician's consent and prescription, while being under regular review of the physician.
Results from clinical trials:
We looked up PubMed to review publications on the subject 'Valproic acid' and 'Retinitis Pigmentosa'. This search found 11 publications.
The earliest publication referencing this topic was published in the British Journal of Ophthalmology (BJO) in January 2011 titled "Therapeutic potential of valproic acid for retinitis pigmentosa". Dr Kaushal (who was then affiliated with the University of Massachusetts Medical School in Worcester, Massachusetts) and his team conducted this study on 13 RP eyes before and after treatment with VPA, with the average treatment time being 4 months. They primarily evaluated changes in visual fields (VF) using Goldmann Kinetic Perimetry. Nine eyes had improved VF with treatment, two eyes had decreased VF and two eyes experienced no change, with an overall average increase of 11%. Assuming typical loss in VF area without treatment, this increase in VF was found to be statistically significant (p<0.02). 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, which was significant (p<0.02) assuming no loss in acuity without treatment. Importantly, though VPA is known to have significant side effects as mentioned above, in this study, the side effects were reported to be mild and well tolerated. Based on their data, the authors concluded that treatment with VPA may be of a therapeutic benefit to patients with RP, and suggested that a placebo-controlled clinical trial will be necessary to assess the efficacy and safety of VPA for RP. They authors hypothesized a benefit in patients with autosomal-dominant RP (to know more about inheritance patterns of RP, click here), where VPA may act as a chaperone for rhodopsin.
But the response from the academics was swift. Most thought that the results were not spectacular enough to ask patients to take medications that have a possibility of such significant side-effects. Two groups commented in BJO, with one saying, "the conclusions...concerning valproic acid are premature", while the other group noted there is "lack of scientific rationale for use of valproic acid for retinitis pigmentosa". Another comment noted "VA treatment may be harmful in non-dominant forms of retinitis pigmentosa", noting significant negative outcomes in the 3 patients he attempted to treat with VPA after the above paper.
This study was followed by results of a study in BJO in July 2013 from University of Florida, College of Medicine, Gainesville, by Dr Bhalla et al, where they attempted to determine the long-term efficacy and safety of VPA in patients with pigmentary retinal dystrophies. This study was conducted on 31 patients, evaluating among others, visual acuity, visual fields with Goldmann VF tracings and the side effects. The main outcomes of the study indicated some decrease in visual fields in 5 patients, decline in visual acuity in 22 patients after almost 15 months of follow-up. Twelve patients reported negative side effects related to the use of VPA. The authors advised caution in the use of VPA in patients with pigmentary retinal dystrophies.
Another study on the use of VPA in RP was published in Ophthalmology And Therapy in November 2012 by Dr Mahesh Shanmugham and his colleagues from Sankara Eye Hospital, Bangalore, India. In this prospective, nonrandomized trial, 10 patients (20 eyes) with RP were treated with oral VPA for 3 months. Visual acuity and visual field changes using Humphrey visual field analyzer were recorded. The results showed mean visual acuity significantly improved from a pretreatment value of 20/72 (logMAR 0.560 ± 0.488) to 20/65 (logMAR 0.513 ± 0.422) after 3 months of treatment (P = 0.006). Vision improved by at least one line or more in 10 eyes, and remained stable in the other 10 eyes. Visual field improvement was noted in nine eyes (p < 0.05), with another nine showing no significant field change, while visual fields could not be recorded in 2 eyes due to poor vision. The authors conclude that short-term (3-month) treatment with VPA improved vision and visual field of patients with RP.
Recently, a comparative non-randomized study conducted at the Dr RP Center for Ophthalmic Sciences, AIIMS, New Delhi, evaluating efficacy of oral VPA on visual function in patients with RP was published in Journal of Ocular Pharmacology Therapy. Conducted by Prof Atul Kumar and his associates, they evaluated the outcomes of treatment with oral VPA in 30 RP patients (60 eyes). Fifteen patients received oral VPA for a period of 1 year, while the other group of the remaining 15 patients received no treatmentand thus served as controls. The effect of VPA on visual function was evaluated by the effect on visual acuity, multifocal electroretinography (mfERG), and visual evoked response (VER), while side effects of oral VPA were also monitored. At the 1-year follow-up, 14 of 15 patients in treatment group had improvement in median best corrected visual acuity. In contrast, there was a slight decrease in median BCVA in the control (no treatment) group. There was also a statistically significant increase in improvement in amplitude and latency/implicit time in mfERG and VER in this group (P<0.001), while the control group did not demonstrate any such improvement. The authors concluded that VPA appears to have a positive effect on the visual functions in RP patients, while suggesting that long-term studies evaluating the dose modifications, genetic analysis, and change in visual fields are required.
What should a patient of RP do?
We believe that there is no conclusive evidence to support or reject the treatment potential of VPA in RP at this time.
Considering that none of the studies so far have indicated significant side-effects or complications from the use of VPA, it may be concluded that this drug has not demonstrated significant worsening in patients with autosomal-dominant form of RP, in a medically-monitored, controlled environment (such as under the supervision of a physician in a clinical trial). Considering this outcome, it may be suggested that those patients, who have been specifically told that they have autosomal-dominant form of RP (usually suggested by the inheritance pattern - best to consult your doctor or a geneticist) may consider taking a course of VPA, but STRICTLY on the recommendation of your doctor and under the care of a licensed physician.
Note: The above article is information collated from sources referenced in the article. Nothing in the article should be construed as a recommendation for or against use of VPA as potential treatment in patients with RP. Our conclusion/recommendation is not equivalent to medical consultation or recommendation, and does not create any semblence of a doctor-patient relationship. We are not responsible for any actions and/or outcomes in reference to this article. Readers have a choice to read this article of their own free will.
What is Valproic acid?
Valproic acid is in a class of medications called anticonvulsants. It may be used alone or with other medications to treat certain types of seizures. It is also used to treat mania in people with bipolar disorder (manic-depressive disorder; a disease that causes episodes of depression, episodes of mania, and other abnormal moods). It is also used to prevent migraine headaches, but not to relieve headaches that have already begun.
Valproic acid may cause serious or life threatening damage to the liver and is most likely to occur within the first 6 months of therapy. The risk of developing liver damage is greater in children who are younger than 2 years of age. Valproic acid may cause serious or life-threatening damage to the pancreas. This may occur at any time during your treatment. (source)
Warning: This medication may cause significant side-effects/complications. It should NOT be taken without a physician's consent and prescription, while being under regular review of the physician.
Results from clinical trials:
We looked up PubMed to review publications on the subject 'Valproic acid' and 'Retinitis Pigmentosa'. This search found 11 publications.
The earliest publication referencing this topic was published in the British Journal of Ophthalmology (BJO) in January 2011 titled "Therapeutic potential of valproic acid for retinitis pigmentosa". Dr Kaushal (who was then affiliated with the University of Massachusetts Medical School in Worcester, Massachusetts) and his team conducted this study on 13 RP eyes before and after treatment with VPA, with the average treatment time being 4 months. They primarily evaluated changes in visual fields (VF) using Goldmann Kinetic Perimetry. Nine eyes had improved VF with treatment, two eyes had decreased VF and two eyes experienced no change, with an overall average increase of 11%. Assuming typical loss in VF area without treatment, this increase in VF was found to be statistically significant (p<0.02). 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, which was significant (p<0.02) assuming no loss in acuity without treatment. Importantly, though VPA is known to have significant side effects as mentioned above, in this study, the side effects were reported to be mild and well tolerated. Based on their data, the authors concluded that treatment with VPA may be of a therapeutic benefit to patients with RP, and suggested that a placebo-controlled clinical trial will be necessary to assess the efficacy and safety of VPA for RP. They authors hypothesized a benefit in patients with autosomal-dominant RP (to know more about inheritance patterns of RP, click here), where VPA may act as a chaperone for rhodopsin.
But the response from the academics was swift. Most thought that the results were not spectacular enough to ask patients to take medications that have a possibility of such significant side-effects. Two groups commented in BJO, with one saying, "the conclusions...concerning valproic acid are premature", while the other group noted there is "lack of scientific rationale for use of valproic acid for retinitis pigmentosa". Another comment noted "VA treatment may be harmful in non-dominant forms of retinitis pigmentosa", noting significant negative outcomes in the 3 patients he attempted to treat with VPA after the above paper.
This study was followed by results of a study in BJO in July 2013 from University of Florida, College of Medicine, Gainesville, by Dr Bhalla et al, where they attempted to determine the long-term efficacy and safety of VPA in patients with pigmentary retinal dystrophies. This study was conducted on 31 patients, evaluating among others, visual acuity, visual fields with Goldmann VF tracings and the side effects. The main outcomes of the study indicated some decrease in visual fields in 5 patients, decline in visual acuity in 22 patients after almost 15 months of follow-up. Twelve patients reported negative side effects related to the use of VPA. The authors advised caution in the use of VPA in patients with pigmentary retinal dystrophies.
Another study on the use of VPA in RP was published in Ophthalmology And Therapy in November 2012 by Dr Mahesh Shanmugham and his colleagues from Sankara Eye Hospital, Bangalore, India. In this prospective, nonrandomized trial, 10 patients (20 eyes) with RP were treated with oral VPA for 3 months. Visual acuity and visual field changes using Humphrey visual field analyzer were recorded. The results showed mean visual acuity significantly improved from a pretreatment value of 20/72 (logMAR 0.560 ± 0.488) to 20/65 (logMAR 0.513 ± 0.422) after 3 months of treatment (P = 0.006). Vision improved by at least one line or more in 10 eyes, and remained stable in the other 10 eyes. Visual field improvement was noted in nine eyes (p < 0.05), with another nine showing no significant field change, while visual fields could not be recorded in 2 eyes due to poor vision. The authors conclude that short-term (3-month) treatment with VPA improved vision and visual field of patients with RP.
Recently, a comparative non-randomized study conducted at the Dr RP Center for Ophthalmic Sciences, AIIMS, New Delhi, evaluating efficacy of oral VPA on visual function in patients with RP was published in Journal of Ocular Pharmacology Therapy. Conducted by Prof Atul Kumar and his associates, they evaluated the outcomes of treatment with oral VPA in 30 RP patients (60 eyes). Fifteen patients received oral VPA for a period of 1 year, while the other group of the remaining 15 patients received no treatmentand thus served as controls. The effect of VPA on visual function was evaluated by the effect on visual acuity, multifocal electroretinography (mfERG), and visual evoked response (VER), while side effects of oral VPA were also monitored. At the 1-year follow-up, 14 of 15 patients in treatment group had improvement in median best corrected visual acuity. In contrast, there was a slight decrease in median BCVA in the control (no treatment) group. There was also a statistically significant increase in improvement in amplitude and latency/implicit time in mfERG and VER in this group (P<0.001), while the control group did not demonstrate any such improvement. The authors concluded that VPA appears to have a positive effect on the visual functions in RP patients, while suggesting that long-term studies evaluating the dose modifications, genetic analysis, and change in visual fields are required.
What should a patient of RP do?
We believe that there is no conclusive evidence to support or reject the treatment potential of VPA in RP at this time.
Considering that none of the studies so far have indicated significant side-effects or complications from the use of VPA, it may be concluded that this drug has not demonstrated significant worsening in patients with autosomal-dominant form of RP, in a medically-monitored, controlled environment (such as under the supervision of a physician in a clinical trial). Considering this outcome, it may be suggested that those patients, who have been specifically told that they have autosomal-dominant form of RP (usually suggested by the inheritance pattern - best to consult your doctor or a geneticist) may consider taking a course of VPA, but STRICTLY on the recommendation of your doctor and under the care of a licensed physician.
Note: The above article is information collated from sources referenced in the article. Nothing in the article should be construed as a recommendation for or against use of VPA as potential treatment in patients with RP. Our conclusion/recommendation is not equivalent to medical consultation or recommendation, and does not create any semblence of a doctor-patient relationship. We are not responsible for any actions and/or outcomes in reference to this article. Readers have a choice to read this article of their own free will.
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