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C.A. Westall, S. Morong, M. Abdolell; Repeated Measures Assessment of Vigabatrin Dosage on ERG Responses in Children With Infantile Spasms . Invest. Ophthalmol. Vis. Sci. 2003;44(13):4250.
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Purpose: Vigabatrin is associated with visual field and electroretinogram (ERG) abnormalities. Visual fields cannot be conducted reliably in infants. Reductions in cone b-wave amplitude and 30 Hz flicker are predictors of vigabatrin-toxicity but confounding factors, such as difference in vigabatrin dose, hamper prediction ability. The purpose of this study is to determine how daily dose and cumulative dose of vigabatrin affects ERG responses. Methods: ERGs were performed on 26 children with infantile spasms on repeated visits before and during vigabatrin therapy at six month intervals. All were tested over a one-year period and ten were tested over two years. Mean age at first ERG was 8.74 months (sd. = 5.7 months). Standard ISCEV protocol with Burian -Allen bipolar contact-lens electrodes (standard flash 2.0 cd.s/m2) was used. The cone response was also recorded at 3.5 cd.s/m2. Responses were age corrected. The effect of actual daily dosage and cumulative dosage on ERG responses was investigated using repeated measures Analysis of Variance (ANOVA) (SAS statistical software). ERG responses included in this analysis were standard flash and cone b-wave amplitude, flicker amplitude and flicker implicit time. In addition components of the three major photopic OP responses were included; specifically mean amplitude of the early (first two OPs), amplitude of the late OP (third OP) and implicit time of the first major OP. Vigabatrin dose was calculated as g/kg body weight. Results: Actual daily dose of vigabatrin was associated with change in amplitude of some ERG components. A quadratic trend accounted for change in cone b-wave amplitude (p=0.0342) and flicker amplitude (p=0.0105); the amplitude was maximum for intermediate vigabatrin dose. A linear trend accounted for change in amplitude of the early OPs with higher doses associated with lower amplitude. Cumulative dosage was associated with reduction in amplitude of the early OPs. Conclusions: The linear reduction in amplitude of the early OPs with increasing dosage of vigabatrin may be related to a GABAergic effect resulting from GABA accumulation in the amacrine cells. The quadratic relationship, whereby higher daily dosage of vigabatrin results in reduction of cone and flicker amplitudes, may be important in the understanding of vigabatrin toxicity. For the flicker response the reduction at higher dosages is more marked than for the cone response. The study continues to ensure that adequate data describing cumulative dosage are acquired for further testing of these models.
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