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Published on: September 3, 2020
Changes in the electroretinogram resulting from discontinuation of vigabatrin in children
Carol A Westall1, Rita Nobile, Sharon Morong
1Department of Ophthalmology, University of Toronto, The Hospital for Sick Children, Toronto, Ontario, Canada.
Insights
Discontinuation of vigabatrin treatment in children led to significant recovery in early wavelet amplitudes of photopic oscillatory potentials (OPs) in electroretinograms (ERGs). This suggests vigabatrin
Area of Science:
- Ophthalmology
- Neuroscience
- Pharmacology
Background:
- Vigabatrin, an antiepileptic drug, has been observed to induce changes in electroretinogram (ERG) responses in children.
- Oscillatory potentials (OPs) within ERGs show the most dramatic changes during vigabatrin treatment.
- The reversibility of these ERG changes upon drug discontinuation is key to distinguishing pharmacological effects from toxicity.
Purpose of the Study:
- To investigate the changes in ERG responses following the discontinuation of vigabatrin therapy in pediatric patients.
- To determine if vigabatrin-induced ERG alterations are reversible, indicating a non-toxic pharmacological effect.
Main Methods:
- Longitudinal ERG recordings were analyzed from 17 children who discontinued vigabatrin.
- Standard ERG protocols were employed, including photopic oscillatory potentials (OPs) using Burian-Allen bipolar contact-lens electrodes.
- Paired t-test was used to compare ERG amplitudes before and after drug discontinuation.
Main Results:
- Discontinuation of vigabatrin resulted in a dramatic increase in the amplitude of early wavelets of photopic OPs.
- Scotopic oscillatory potentials also demonstrated some degree of recovery after stopping the drug.
- The observed changes suggest a significant, reversible pharmacological effect rather than toxicity.
Conclusions:
- Reversible changes in oscillatory potentials, particularly photopic OPs, indicate a non-toxic pharmacological effect of vigabatrin.
- Vigabatrin's impact on GABAergic amacrine cells in the inner plexiform layer likely underlies the observed ERG alterations.
- Reduced OPs in children on vigabatrin may not necessarily be an indicator of retinal toxicity.
Abstract:
Electroretinograms (ERGs) have been recorded longitudinally in children before and during treatment with the antiepileptic drug vigabatrin for the past 3.5 years. Vigabatrin induced changes in ERG responses occur in children; the most dramatic changes occur in the oscillatory potentials. The purpose of this study was to identify changes in ERG responses associated with discontinuation of vigabatrin treatment. If vigabatrin-induced changes reverse after discontinuation of the drug we infer that the original change is not an indicator of toxicity. ERG data were analyzed from 17 children who discontinued vigabatrin therapy. The duration of treatment ranged from 5 to 52 months, the age for the first ERG ranged from 6 to 38 months (median 10 months). ERGs were tested using the standard protocol established by the International Society for Clinical Electrophysiology of Vision, with Burian-Allen bipolar contact-lens electrodes. In addition to standard responses we recorded photopic oscillatory potentials (OPs). During vigabatrin treatment OPs show a greater change than other ERG responses, with the early occurring wavelets from the photopic OPs showing the greatest change. With discontinuation of vigabatrin the amplitude of the early wavelets of the photopic OPs increased dramatically compared with amplitudes while taking the drug (paired t-test, p = 0.000075). The scotopic oscillatory potentials also show some recovery. Although changes in oscillatory potentials may occur with vigabatrin toxicity, a large change likely occurs with a non-toxic pharmacological effect of vigabatrin on GABAergic amacrine cells in the inner plexiform layer. Reduction of OPs in children on vigabatrin may not be related to toxicity.
