Changes in the electroretinogram resulting from discontinuation of vigabatrin in children

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.

Retinal Function in Rabbits Does Not Improve 4–5 Months after Terminating Treatment with Vigabatrin

“…Similar results have been reported by Krakow et al [23]. A recent study [24] has shown increased amplitudes in both photopic and scotopic oscillatory potentials after discontinuation of vigabatrin, but they interpret these changes as a non-toxic pharmacological effect of vigabatrin on GABAergic amacrine cells in the inner retina.…”

Characteristic retinal atrophy with secondary “inverse” optic atrophy identifies vigabatrin toxicity in children

“…20,21 For example, oscillatory potentials decrease in amplitude during drug treatment but recover after discontinuation of the drug, unlike the decrease in flicker amplitude, which is less likely to recover. 22 Most children in the HSC longitudinal study do not show the form of retinal nerve fiber layer atrophy described in these 3 more advanced cases of retinal toxicity. Of interest is the tendency, reported by the parents of these children, to stare straight ahead rather than look normally about their visual environment.…”

“…Because a variety of ERG parameters (amplitude and implicit time) change during vigabatrin treatment, the current studies are helping to clarify which of these changes represent nontoxic side effects and which correlate with drug toxicity. [20][21][22] Changes in oscillatory potential amplitude result, at least in part, from non-toxic changes. 22 Conversely, if the ERG, particularly the 30-Hz flicker response, decreases more than expected from intervisit variability, both the clinical assessment and the ERG are repeated within 3 months.…”

“…[20][21][22] Changes in oscillatory potential amplitude result, at least in part, from non-toxic changes. 22 Conversely, if the ERG, particularly the 30-Hz flicker response, decreases more than expected from intervisit variability, both the clinical assessment and the ERG are repeated within 3 months. If the reduction is maintained, the treating neurologist is informed of the likelihood of vigabatrin toxicity.…”

Vigabatrin

“…59 Numerous investigators have reported the prevalence in children to be well below that of adults, 91,96,98,99 suggesting a prevalence of approximately 20% in this younger population. The best data on infants 65,71,73,100 have established a prevalence of approximately 40%, with incidence of 16% as assessed by the highly sensitive electroretinogram (ERG) 30-Hz flicker amplitude. The prevalence of cone B-wave amplitude abnormalities, the other vigabatrin-specific ERG parameter that is sensitive and specific for the vigabatrin-induced defect, is about 20%, with an incidence of 4%.…”