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Visual field constriction

Accumulation of vigabatrin but not tiagabine in the retina

From the Epilepsy Unit, University Department of Medicine and Therapeutics (Drs. Sills, Butler, Forrest, and Brodie), Western Infirmary, Glasgow, Scotland; and Pharmacology and Therapeutics Unit, University Department of Clinical Neurology (Drs. Patsalos and Ratnaraj), Institute of Neurology, The National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.

Address correspondence and reprint requests to Dr. Graeme J. Sills, Epilepsy Unit, Department of Medicine and Therapeutics, Western Infirmary, Glasgow G11 6NT, Scotland; e-mail: g.j.sills{at}clinmed.gla.ac.uk

BACKGROUND: The antiepileptic drug (AED) vigabatrin (VGB) causes concentric visual field constriction. Anecdotal reports involving tiagabine (TGB) have implied that this may be a class effect of all AEDs with -aminobutyric acid (GABA)–related actions. We investigated the pharmacokinetic and pharmacodynamic profiles of VGB and TGB in rat brain and eye.

METHODS: Adult male rats (n = 8) were administered 0.9% saline (control), VGB (500 or 1,000 mg/kg), or TGB (5, 10, or 20 mg/kg). At 1 (TGB) and 4 hours (VGB) postdosing, the animals were killed, a blood sample was obtained, their brains were dissected into five anatomic regions, and the retina and vitreous humor were isolated from each eye. Samples were analyzed for GABA concentrations and the activity of the enzyme GABA-transaminase (GABA-T). Plasma and tissue drug concentrations were also determined.

RESULTS: VGB treatment produced a decrease in the activity of GABA-T and a rise in GABA concentrations in all tissues investigated. This effect was most pronounced in the retina. VGB concentrations were as much as fivefold higher in the retina than in the brain. TGB was without effect on GABA concentrations and activity of GABA-T. TGB concentrations were notably lower in the retina than in the brain.

CONCLUSIONS: Accumulation of VGB in the retina, with or without an increase in GABA, may be responsible for the visual field constriction reported clinically. In contrast, TGB had no effect on GABA concentrations and did not accumulate in the retina. These results suggest that TGB is unlikely to cause visual field defects in humans.

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