Longitudinal changes in photopic OPs occurring with vigabatrin treatment

Abstract

Purpose: Vigabatrin (gamma-vinyl-GABA) is an antiepileptic drug successful in the management of infantile spasms. Photopic ERGs were tested in children followed longitudinally before and during vigabatrin treatment.

Methods: Subjects were 26 infants (age range 1.5-24 months, median 7.6 months) on vigabatrin treatment who had been tested on multiple visits (two to four visits; mean, three visits). Eighteen of these were assessed initially before starting vigabatrin therapy and eight were assessed within 1 week of initiation of the drug. ERGs were recorded at 6-month intervals. Standard ISCEV protocol with Burian-Allen bipolar contact-lens electrodes (standard flash 2.0 cd.s/m2) was used. Although ISCEV standards were followed, a higher flash intensity (set at 3.6 cd.s/m2) was chosen for single-flash cone assessment to provide a better definition of OPs. Photopic OPs were divided into categories of early OPs and late OP (OP4). Responses were compared with age corrected limits extrapolated from our lab control database.

Results: Results showed differential effects of vigabatrin on the summed early OP amplitudes versus the late OP (OP4) and cone b-wave amplitude. The early OPs showed significant decrease (p = 0.0005, repeated measures analysis of variance) after 6 months and remained decreased for the duration of treatment. There was no significant change seen in the late OP. The cone b-wave amplitude showed initial increase (p = 0.04) after 6 months, followed by a decrease after 18 months; a trend similar to that of the late OP.

Conclusion: Early photopic OPs were disrupted more than the late OP, suggesting relative deficit in the ON (depolarizing) retinal pathways.

Figure 1

Sample ERG traces: (left column) and percent deviation from control (right column) From top to bottom: mixed rod cone responses, cone isolated responses, photopic oscillatory potentials (late OP, black line; early OPs, grey line) and the 30-Hz flicker. (a) Subject 49, a 6-month-old child before and at approximately 6-month intervals during vigabatrin treatment. The last waveform is from data recorded from a 34-month-old control (with normal vision). (b) Subject 6, a 6-month-old child had been on vigabatrin 7 days and at approximately 6-month intervals during vigabatrin treatment. Numbers at the left of the series of traces shows length of time on vigabatrin. Time is shown in milliseconds. Positive electrical signals are in the upward direction. Vertical arrows and numbers represent 100 μV. The flash intensity for the photopic single flash cone responses is 3.6 cds/m² and the flicker flash intensity is 2.0 cds/m². For the flicker response the stimulus flash is at time 0. For all other responses the stimulus flash is at 20 ms. ^*Abnormal amplitude levels.

Figure 1

Sample ERG traces: (left column) and percent deviation from control (right column) From top to bottom: mixed rod cone responses, cone isolated responses, photopic oscillatory potentials (late OP, black line; early OPs, grey line) and the 30-Hz flicker. (a) Subject 49, a 6-month-old child before and at approximately 6-month intervals during vigabatrin treatment. The last waveform is from data recorded from a 34-month-old control (with normal vision). (b) Subject 6, a 6-month-old child had been on vigabatrin 7 days and at approximately 6-month intervals during vigabatrin treatment. Numbers at the left of the series of traces shows length of time on vigabatrin. Time is shown in milliseconds. Positive electrical signals are in the upward direction. Vertical arrows and numbers represent 100 μV. The flash intensity for the photopic single flash cone responses is 3.6 cds/m² and the flicker flash intensity is 2.0 cds/m². For the flicker response the stimulus flash is at time 0. For all other responses the stimulus flash is at 20 ms. ^*Abnormal amplitude levels.

Figure 2

(a–e) Mean ERG responses from children in the longitudinal vigabatrin study. Log relative amplitudes are plotted against length of time on vigabatrin (months). The error bars represent the standard deviation. Shaded areas represent lab normal ranges containing 95% of control data. (a) OP2+OP3 amplitude; (b) OP4 amplitude; (c) flicker amplitude; (d) cone b-wave amplitude; (e) photopic OP2 implicit time. Vertical arrows signify that the upward direction reflects increase in both amplitude and implicit time data. The flash intensity for the photopic single flash cone responses is 3.6 cds/m² and the flicker flash intensity is 2.0 cds/m².