Investigating the effects of antiepileptic drugs on the electrophysiology of vision

The principal aim of this work was to examine the effects of antiepileptic drugs (AEDs) on vision. Vigabatrin acts by increasing GABA at brain inhibitory synapses by irreversibly binding to GABA-transaminase. Remacemide is a novel non-competitive NMDA receptor antagonist and fast sodium channel inhibitor that results in the inhibition of the NMDA receptors located in the neuronal membrane calcium channels increasing glutamate in the brain. Vigabatrin has been shown to cause a specific pattern of visual field loss, as one in three adults taking vigabatrin have shown a bilateral concentric constriction. Remacemide has unknown effects on vision. The majority of studies of the effects of AEDs on vision have not included the paediatric population due to difficulties assessing visual field function using standard perimetry testing. Evidently an alternative test is required to establish and monitor visual field problems associated with AEDs both in children and in adults who cannot comply with perimetry. In order to test paediatric patients exposed to vigabatrin, a field-specific visual evoked potential was developed. Other tests performed on patients taking either vigabatrin or remacemide were electroretinograms, electro-oculograms, multifocal VEPs and perimetry. Comparing these tests to perimetry results from vigabatrin patients the field specific VEP was found to have a high sensitivity and specificity, as did the 30Hz flicker amplitude. The modified VEP was also found to provide useful results in vigabatrin patients. Remacemide did not produce a similar visual field loss to vigabatrin although macular vision was affected. The field specific VEP is a useful method for detecting vigabatrin associated visual field loss that is well tolerated by young children. This technique combined with the ERG under light adapted (30Hz flicker) condition is presently the superior method for detecting vigabatrin-attributed peripheral field defects present in children below the developmental age of 9. The effects of AEDs on vision should be monitored carefully and the use of multifocal stimulation allows for specific areas of the retina and visual pathway to be monitored.

Investigation into visual defects attributed to Vigabatrin

Vigabatrin (VGB) is a transaminase inhibitor that elicits its anitepileptic effect by increasing GABA concentrations in the brain and retina. - Assess whether certain factors predispose patients to develop severe visual field loss. - Develop a sensitive algorithm for investigating the progression of visual field loss. - Determine the most sensitive clinical regimen for diagnosing VGB-attributed visual field loss. - Investigate whether the reports of central retinal sparing are accurate. The investigations have resulted in a number of significant findings: - The anatomical evidence in combination with the pattern of visual field loss suggests that the damage induced by VGB therapy occurs at retinal level, and is most likely a toxic effect. - The quantitative algorithm, designed within the course of this investigation, provided increased sensitivity in determining the severity of visual field loss. - Maximum VGB dose predisposes patients to develop severe visual field loss. - The SITA Standard algorithm was found to be as sensitive and significantly faster, in diagnosing visual field defects attributed to VGB, when compared to the Full Threshold algorithm. The Full Threshold was found to be the most repeatable between visits. - The normal SWAP 10-2 database provided an effective method of differentiating SWAP defects. - SWAP, FDT and the mfERG have increased sensitivity in detecting visual field loss attributed to VGB. The pattern of visual field loss from these investigations suggests that VGB produces a diffuse effect across the retina including subtle central abnormalities and more severe peripheral defects. - Abnormalities detected using the mfERG have suggested that VGB adversely affects the photoreceptors Müller, amacrine and ganglion cells in the retina. An urgent review of the manufacturers recommended maximum dose for VGB is required.