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Vigabatrin, tiagabine, and visual fields
  1. MC Lawden
  1. Department of Neurology, Leicester Royal Infirmary, Leicester LE1 5WW, UK; lawden01{at}

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    A retinotoxic class effect of GABAergic antiepileptic drugs seems unlikely

    The paper by Krauss et al (this issue, pp 339–343)1 helps to settle a controversy that has been simmering in the epilepsy world for several years.1 Initial reports that vigabatrin use was associated with irreversible visual field defects evoked scepticism. Various voices held that such visual field defects were not uncommon in patients with epilepsy and might be associated with epilepsy itself rather than from specific drug treatment. Evidence has now accumulated to convince all but the most sceptical that the antiepileptic drug vigabatrin, an irreversible inhibitor of GABA transaminase, has a strong tendency to produce visual field constriction by a toxic effect on the retina, although the precise mechanism by which it does so has yet to be identified. It is not clear either why a small minority of patients develop visually disabling field constriction while in most subjects visual field defects are mild and asymptomatic or indeed completely undetectable. It does not appear that such visual defects are produced by the majority of antiepileptic drugs in mainstream use—most comparative studies have compared patients taking vigabatrin with those taking carbamazepine, sodium valproate or phenytoin. It remains possible that other less widely used drugs might have similar toxic effects and attention has focused particularly on those drugs whose pharmacological effect is exerted upon the GABAergic system.

    A single case of visual field constriction associated with prolonged treatment with the GABA agonist drug progabide has been reported,2 but this drug is not in widespread use. Of all the antiepileptic drugs tiagabine is closest to vigabatrin in its mode of action. Tiagabine blocks the reuptake of GABA at the synapse, thus increasing its availability, an effect that vigabatrin achieves by reducing its breakdown. If retinal toxicity were a class effect of drugs increasing the effect of GABA at retinal synapses then tiagabine would appear the most likely candidate to exert a similar action. It was, therefore, somewhat alarming when Beran et al3 reported that they had detected visual field defects similar to those associated with vigabatrin in 6 of 12 patients exposed to tiagabine. Although these results were first announced at the Third European Congress on Epileptology in Warsaw in 1998, they have not yet been published in full and are therefore difficult to evaluate. Nousiainen et al,4 who had earlier demonstrated a high frequency of visual field defects in vigabatrin monotherapy patients, failed to find any such defects in 15 patients treated with tiagabine monotherapy.

    Krauss et al,1 performed static perimetry, kinetic perimetry, and electroretinography (ERG) on 12 patients treated with tiagabine and compared the results with 32 vigabatrin treated and 14 control patients. None of the tiagabine treated patients displayed any abnormality of visual field and their ERG results did not diverge from normal. By contrast, 53% of the vigabatrin treated patients had field defects and all had abnormal ERG results. Although patient numbers remain small (only 11 of the tiagabine treated patients were able to produce reliable visual fields), these results, taken with those of Nousiainen et al,4 indicate that visual field constriction is at worst a much rarer side effect of tiagabine than vigabatrin, and at best may not occur with the drug. A class effect of GABAergic drugs causing retinal damage now seems unlikely.

    A retinotoxic class effect of GABAergic antiepileptic drugs seems unlikely

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