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.

Figures

Figure 1

Sample ERG traces (left column) and percent deviation from control (right column). From top to bottom: mixed rod cone responses, scotopic OPs, cone isolated responses, photopic oscillatory potentials and the 30-Hz flicker. In the right column, 4th graph from the top (photopic OPs) the percent deviation is shown for the late OP (black line) and early OPs (gray line). (a) subject 5, a child who began vigabatrin at 5 months of age and had ERG testing at approximately 6-month intervals during vigabatrin treatment and after vigabatrin treatment (labeled age off). The last waveform (gray ERG trace) is data recorded from a 30-month-old control (with normal vision). (b) subject 61, 14 months of age for his first ERG recorded. By this time he had been on vigabatrin for 5 months. He was tested at approximately 6-month intervals and again after discontinuation of vigabatrin. The last waveform (gray ERG trace) is data recorded from a 36-month-old control (with normal vision) The numbers at the left of the series of graphs shows length of time on vigabatrin. Time is shown in milliseconds. Positive electrical signals are in the upward direction. Vertical arrows and numbers represent microvolts. For the top four graphs stimulus onset was at time 20 ms. For the flicker response the stimulus flash is at time 0. *Abnormally reduced amplitude levels.

Figure 1

Sample ERG traces (left column) and percent deviation from control (right column). From top to bottom: mixed rod cone responses, scotopic OPs, cone isolated responses, photopic oscillatory potentials and the 30-Hz flicker. In the right column, 4th graph from the top (photopic OPs) the percent deviation is shown for the late OP (black line) and early OPs (gray line). (a) subject 5, a child who began vigabatrin at 5 months of age and had ERG testing at approximately 6-month intervals during vigabatrin treatment and after vigabatrin treatment (labeled age off). The last waveform (gray ERG trace) is data recorded from a 30-month-old control (with normal vision). (b) subject 61, 14 months of age for his first ERG recorded. By this time he had been on vigabatrin for 5 months. He was tested at approximately 6-month intervals and again after discontinuation of vigabatrin. The last waveform (gray ERG trace) is data recorded from a 36-month-old control (with normal vision) The numbers at the left of the series of graphs shows length of time on vigabatrin. Time is shown in milliseconds. Positive electrical signals are in the upward direction. Vertical arrows and numbers represent microvolts. For the top four graphs stimulus onset was at time 20 ms. For the flicker response the stimulus flash is at time 0. *Abnormally reduced amplitude levels.

Figure 2

Mean ERG responses from the 17 children. Log relative amplitudes are plotted against length of time on vigabatrin (months). Black lines represent mean ERG amplitude. The error bars represent the standard deviation. Shaded areas represent lab normal ranges containing 95% of control data. (a) rod-cone a-wave amplitude, (b) mixed rod-cone b-wave amplitude, (c) scotopic sum of OPs (d) cone a-wave amplitude, (e) cone b-wave amplitude responses, (f) flicker amplitude data, (g) photopic sum of OPs, (h) photopic OP2 implicit time, (i) flicker implicit time, (j) photopic sum of early OPs, (k) photopic OP4 amplitude. Upward direction reflects increase in both amplitude and implicit time data. (i) flicker implicit time, (j) photopic sum of early OPs, (k) photopic OP4 amplitude. Upward direction reflects increase in both amplitude and implicit time data.

Figure 2

Mean ERG responses from the 17 children. Log relative amplitudes are plotted against length of time on vigabatrin (months). Black lines represent mean ERG amplitude. The error bars represent the standard deviation. Shaded areas represent lab normal ranges containing 95% of control data. (a) rod-cone a-wave amplitude, (b) mixed rod-cone b-wave amplitude, (c) scotopic sum of OPs (d) cone a-wave amplitude, (e) cone b-wave amplitude responses, (f) flicker amplitude data, (g) photopic sum of OPs, (h) photopic OP2 implicit time, (i) flicker implicit time, (j) photopic sum of early OPs, (k) photopic OP4 amplitude. Upward direction reflects increase in both amplitude and implicit time data. (i) flicker implicit time, (j) photopic sum of early OPs, (k) photopic OP4 amplitude. Upward direction reflects increase in both amplitude and implicit time data.