Abstract
Vigabatrin is an antiepileptic drug for the treatment of partial seizures. The anticonvulsant effect is achieved by irreversible inhibition of the enzyme GABA-transaminase which catalyses the inactivation of GABA. Vigabatrin has been associated with visual field loss and electrophysiological abnormalities. The purpose of the study was to determine any alterations in normal volunteers of the visual field and the visual electrophysiology resulting from a short exposure to vigabatrin. A three-way, double-blind study of placebo, carbamazepine and vigabatrin was undertaken at baseline and on days two, four and nine. Seven subjects completed all three cycles and 14 subjects (six females and eight males; mean age 27.3 years SD 6.7) completed at least one cycle. Static threshold automated perimetry comprised Humphrey Visual Field Analyzer Programs 30-2 and 30/60-2. Electro-oculography and electroretinograms were performed with undilated pupils using the Medelec Ganzfeld stimulator GS2000. The visual field was unaffected by placebo, carbamazepine or vigabatrin. The group mean amplitudes and latencies for the scotopic ERG, 30Hz flicker ERG and the oscillatory potentials remained unchanged for any cycle. The group mean photopic ERG b-wave latency increased from baseline (p < 0.05); no significant change occurred with carbamazepine or placebo. The group mean Arden Index for vigabatrin decreased from baseline to day 9 (p <; 0.01); no significant differences were present for carbamazepine or placebo. Vigabatrin has a rapid effect on both the photopic ERG and the EOG; however, the changes merely reflect alterations in retinal GABA levels secondary to concomitant blocking of GABA transaminase by existing vigabatrin therapy.
Similar content being viewed by others
References
Anon. Sabril Data Sheet. ABPI Data Sheet Compendium of Data Sheets and Summaries of Product Characteristics (1998-1999). Association of the British Pharmaceutical Industry.
Arezzo JC, Schroeder CE. Litwak MS, Steward DL. Effects of vigabatrin on evoked potentials in dogs. Br J Clin Pharmacol 1989; 27: 53S–60S.
Ben-Menachem E, Persson LI, Schechter PJ et al. The effect of different vigabatrin treatment regimens on CSF biochemistry and seizure control in epileptic patients. Br J Clin Pharmacol 1989; 27: 79S–85S
Butler WH, Ford GP, Newberne JW. A study of the effects of vigabatrin on the central nervous system and retina of Sprague Dawley and Lister-Hooded rats. Toxicol Pathol 1987; 15: 143–8.
Dawson W.W., Trick G.L., Litzkow CA. Improved electrode for electroretinography. Invest. Ophthalmol. Vis., Sci 1979; 18: 988–91.
Duckett T. Brigell M, Ruckh S. Electroretinographic changes are not associated with loss of visual function in pediatric epileptic patients following treatment with vigabatrin. Invest. Ophthalmol. Vis. Sci 1998; 39(4): S973, May 10-15.
Eke T, Talbot J.F., Lawden M.C. Severe persistent visual field constriction associated with vigabatrin. BMJ 1997; 314: 180–81.
Gibson JP, Yarrington JT, Loudy DE, Gerbig CG et al. Chronic toxicity studies with vigabatrin: a GABA-transaminase inhibitor. Toxicol Pathol 1990; 18: 225–38.
Graham D. Neuropathology of vigabatrin. Br J Clin Pharmacol 1989; 27: 43S–45S.
Gram L, Klosterskov P, Dam M. Gamma-vinyl GABA: a double-blind placebocontrolled trial in partial epilepsy. Ann Neurol 1985; 17: 262–6.
Haegele KD, Schecter PJ. Kinetics of the enantiomers of vigabatrin after an oral dose of the racemate or the active 5-enantiomer. Clin Pharmacol Ther 1986; 40: 581–86.
Harding G.F.A., Jones L.A., Tipper V.J., Betts T.A., Mumford J.P. Electroretinogram, pattern electroretinogram & visual evoked potential assessment in patients receiving vigabatrin. Epilepsia 1995; 36: (3), 30.
Harding G.F.A. Severe persistent visual field constriction associated with vigabatrin. Four possible explanations exist. BMJ 1997; 7, 314, (7095): 1694.
Harding G.F.A., Wild J.M, Robertson K.A., Edson A., Barber C., Lawden M., Betts T. Electrooculography, ERGs, multifocal ERGs and VEPs in epileptic patients showing visual field disorders. Electroenceph. Clin. Neurophysiol 1997; 103, (1): 96.
Harding G.F.A., Wild J.M, Robertson K.A., Lawden M., Betts T.A., Barber CM., Barnes P.M.F. EOGs, ERGs, VEPs and Multifocal ERGs in epileptic patients showing visual field constriction. EEG Journal 1999; (in press)
Kälväinen R, Aikiä M, Mervaala E at al. Vigabatrin versus carbamazepine monotherapy in newly diagnosed patients with epilepsy. Archives of Neurology 1995; 52: 989–96.
Krauss G.L., Johnson M.A., Miller N.R. Vigabatrin-associated retinal cone system dysfunction. Electroretinogram and ophthalmic findings. Neurology 1998; 50: (3), 614–8.
Lawden M.C., Eke T., Degg C., Harding G.F.A., Wild J.M. Visual field defects associated with vigabatrin therapy. Journal of Neurology, Neurosurgery and Psychiatry. (In Press).
Marmor ME, Zrenner E. Standard for clinical electrooculography. Documenta Ophthalmologica 1993; 85:115–24.
Marmor ME, Zrenner E. Standard for clinical electroretinography. Documenta Ophthalmologica 1994; 89: 199–210.
Mumford J.P. Tolerability and Safety Profile of Vigabatrin. In: Reviews in Contemporary Pharmacotherapy-Vigabatrin 1995; 6, (9): 477–83.
Neal MJ, Cunningham JR, Shah MA, Yazulla S. Immunocytochemical evidence that vigabatrin in rats cause GABA accumulation in glial cells of the retina. Neurosci. Lett. 1988; 98, 29–32.
Patsalos PN, Duncan JS. The pharmacology and pharmacokinetics of vigabatrin. In: Reviews in Contemporary Pharmacotherapy-Vigabatrin 1995; 6, (9): 447–56.
Pow.., Rogers.. GABA transamination regulates neuronal glutamate content in the retina, Neuroreport 1996; 7, 2683–6.
Schecter PJ. Clinical pharmacology of vigabatrin. Br J Clin Pharmacol 1989; 27: 19S–22S.
Vles JSH, van den Heyden AMGH, Ghijs A et al. Vigabatrin in the treatment of infantile spasms. Neuropediatrics 1993; 24: 230–1.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Harding, G., Robertson, K., Edson, A. et al. Visual electrophysiological effect of a GABA transaminase blocker. Doc Ophthalmol 97, 179–187 (1998). https://doi.org/10.1023/A:1002045223358
Issue Date:
DOI: https://doi.org/10.1023/A:1002045223358