Vigabatrin-associated visual field constriction: A review

1 February 2006
Volume 07, Issue 1

Up to half of patients using this antiepileptic drug experience visual field loss.

Introduction

Until the mid-1980s the treatment of epilepsy was based upon a small number of long-established drugs such as phenytoin and carbamazepine. Vigabatrin (γ-vinyl-GABA: VGB) was the first of the new antiepileptic drugs to be introduced, a group that now has nine members. It was first synthesised in 1974 and licensed for clinical practice in the UK in 1989. VGB was also the first antiepileptic drug whose mode of action was known from the outset; it irreversibly inhibits the enzyme GABA-transaminase, which breaks down GABA (γ-aminobutyric acid), one of the major inhibitory transmitters in the brain and retina. This in turn increases availability of GABA within the central nervous system and increases inhibitory as compared to excitatory tone, reducing the likelihood of propagation of paroxysmal epileptic neuronal activation. VGB was soon established as a powerful antiepileptic drug that could be used, usually adjunctively with other older drugs, to treat epileptic seizures of focal onset, with or without secondary generalisation. Although its role in epilepsy management is now much diminished in view of its propensity to cause visual field constriction, it still has a role in the treatment of infantile spasms and for patients with focal epilepsy unresponsive to other drugs.

Initially the side-effects of VGB were believed to be uncommon and mostly minor. Sedation was never a major problem, in contrast to most of the older drugs, and although psychiatric disturbances were occasionally provoked, these can occur with any antiepileptic drug and indeed may sometimes be a paradoxical consequence of successful seizure control. Concerns arose when it was shown in preclinical toxicity studies that VGB was associated with the appearance of microvacuolation (intramyelinic oedema) in the white matter of mice, rats and dogs (Butler et al. 1987, Graham 1989), but no such lesions have ever been found in monkeys or in human cases at autopsy (Pedersen et al. 1987).

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