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Changes in the ERG d-wave with vigabatrin treatment in a pediatric cohort

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Abstract

Purpose

Vigabatrin (VGB), a treatment for the childhood epilepsy, infantile spasms (IS), is implicated in visual field constriction. Electroretinograms (ERGs) are used as a substitute for visual field testing in infants. We use the VGB-associated ERG reduction (VAER), defined as reduction in age-corrected light adapted 30 Hz flicker amplitude from a pre-treatment measurement in the absence of other retinal defects, as an indicator of retinal toxicity resulting from VGB use. The d-wave ERG response is predominantly the result of OFF-bipolar cell depolarization response to light offset. The purpose of this study is to evaluate the ERG d-wave response as a marker for VAER toxicity in an infant population.

Methods

One hundred children with IS treated with VGB (median age at baseline: 7.6 months; range 1.7–38.4) were tested for the cone-OFF response elicited to a 250 cd s m2 flash with 200 ms duration (long flash ERG). Diagnosis of VAER requires baseline testing of the flicker ERG and at least one follow up ERG; Fifty-one patients fulfilled this criteria. Fifty-eight children received the long flash ERG at baseline. Thirteen retinally normal controls with a median age of 32 months (5.7–65) were also tested. Amplitude and implicit time of the d-wave response were measured manually.

Results

Longer duration of treatment was associated with reduced d-wave amplitude (ANOVA p < 0.05) in patients taking VGB. Nine patients demonstrated VAER during the course of the study. D-wave amplitude was reduced in the IS group with VAER compared to those without VAER (p < 0.05).

Conclusions

Vigabatrin associated retinal defects may be reflected in reduction of the cone d-wave amplitude.

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References

  1. Wheless JW, Ramsay RE, Collins SD (2007) Vigabatrin. Neurotherapeutics 4:163–172. doi:10.1016/j.nurt.2006.11.008

    Article  PubMed  CAS  Google Scholar 

  2. Harding G, Wild J, Robertson K et al (2000) Separating the retinal electrophysiologic effects of vigabatrin. Treatment versus field loss. Am J Ophthalmol 130:691

    Article  PubMed  Google Scholar 

  3. Lewis H, Wallace SJ (2001) Vigabatrin. Dev Med Child Neurol 43:833–835

    Article  PubMed  CAS  Google Scholar 

  4. Neal MJ, Cunningham JR, Shah MA, Yazulla S (1989) Immunocytochemical evidence that vigabatrin in rats causes GABA accumulation in glial cells of the retina. Neurosci Lett 98:29–32

    Article  PubMed  CAS  Google Scholar 

  5. Grove J, Schechter PJ, Tell G et al (1981) Increased gamma-aminobutyric acid (GABA), homocarnosine and beta-alanine in cerebrospinal fluid of patients treated with gamma-vinyl GABA (4-amino-hex-5-enoic acid). Life Sci 28:2431–2439

    Article  PubMed  CAS  Google Scholar 

  6. Grove J, Tell G, Schechter PJ et al (1980) Increased CSF gamma-aminobutyric acid after treatment with gamma-vinyl GABA. Lancet 2:647

    Article  PubMed  CAS  Google Scholar 

  7. Yang X-L (2004) Characterization of receptors for glutamate and GABA in retinal neurons. Prog Neurobiol 73:127–150. doi:10.1016/j.pneurobio.2004.04.002

    Article  PubMed  CAS  Google Scholar 

  8. Tomita T, Yanagida T (1981) Origins of the ERG waves. Vision Res 21:1703–1707

    Article  PubMed  CAS  Google Scholar 

  9. Sieving PA, Murayama K, Naarendorp F (1994) Push-pull model of the primate photopic electroretinogram: a role for hyperpolarizing neurons in shaping the b-wave. Vis Neurosci 11:519–532

    Article  PubMed  CAS  Google Scholar 

  10. Masland RH (2012) The neuronal organization of the retina. Neuron 76:266–280. doi:10.1016/j.neuron.2012.10.002

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  11. Frishman L (2006) Origins of the electroretinogram. In: Heckenlively JR, Arden GB (eds) Princ. Pract. Clin. Electrophysiol. Vis., 2nd edn. The MIT Press, Cambridge, pp 139–183

    Google Scholar 

  12. Marmor MF, Fulton AB, Holder GE et al (2009) ISCEV Standard for full-field clinical electroretinography (2008 update). Doc Ophthalmol 118:69–77. doi:10.1007/s10633-008-9155-4

    Article  PubMed  CAS  Google Scholar 

  13. Sergott RC, Westall CA (2011) Primer on visual field testing, electroretinography, and other visual assessments for patients treated with vigabatrin. Acta Neurol Scand Suppl 124:48–56. doi:10.1111/j.1600-0404.2011.01600.x

    Article  Google Scholar 

  14. Westall CA, Logan WJ, Smith K et al (2002) The Hospital For Sick Children, Toronto, longitudinal ERG study of children on vigabatrin. Doc Ophthalmol 104:133–149

  15. Spencer EL, Harding GFA (2003) Examining visual field defects in the paediatric population exposed to vigabatrin. Doc Ophthalmol 107:281–287

    Article  PubMed  CAS  Google Scholar 

  16. Moskowitz A, Hansen RM, Eklund SE, Fulton AB (2012) Electroretinographic (ERG) responses in pediatric patients using vigabatrin. Doc Ophthalmol 124:197–209. doi:10.1007/s10633-012-9320-7

    Article  PubMed  Google Scholar 

  17. Kondo M, Piao CH, Tanikawa A et al (2000) Amplitude decrease of photopic ERG b-wave at higher stimulus intensities in humans. Jpn J Ophthalmol 44:20–28

    Article  PubMed  CAS  Google Scholar 

  18. Sieving PA (1993) Photopic ON- and OFF-pathway abnormalities in retinal dystrophies. Trans Am Ophthalmol Soc 91:701–773

    PubMed  CAS  PubMed Central  Google Scholar 

  19. Seiple W, Holopigian K (1994) The “OFF” response of the human electroretinogram does not contribute to the brief flash “b-wave”. Vis Neurosci 11:667–673

    Article  PubMed  CAS  Google Scholar 

  20. Westall CA, Panton CM, Levin AV (1999) Time courses for maturation of electroretinogram responses from infancy to adulthood. Doc Ophthalmol 96:355–379

    Article  CAS  Google Scholar 

  21. R Core Team (2013) R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing, Vienna, Austria. http://www.R-project.org

  22. McCoy B, Wright T, Weiss S et al (2011) Electroretinogram changes in a pediatric population with epilepsy: is vigabatrin acting alone? J Child Neurol 26:729–733. doi:10.1177/0883073810390213

    Article  PubMed  Google Scholar 

  23. Hansen RM, Fulton AB (2005) Development of the cone ERG in infants. Invest Ophthalmol Vis Sci 46:3458

    Article  PubMed  PubMed Central  Google Scholar 

  24. Heim MK, Gidal BE (2012) Vigabatrin-associated retinal damage: potential biochemical mechanisms. Acta Neurol Scand 126:219–228. doi:10.1111/j.1600-0404.2012.01684.x

    Article  PubMed  CAS  Google Scholar 

  25. Wang Q-P, Jammoul F, Duboc A et al (2008) Treatment of epilepsy: the GABA-transaminase inhibitor, vigabatrin, induces neuronal plasticity in the mouse retina. Eur J Neurosci 27:2177–2187. doi:10.1111/j.1460-9568.2008.06175.x

    Article  PubMed  PubMed Central  Google Scholar 

  26. Maldonado RS, Izatt JA, Sarin N et al (2010) Optimizing hand-held spectral domain optical coherence tomography imaging for neonates, infants, and children. Invest Ophthalmol Vis Sci 51:2678–2685. doi:10.1167/iovs.09-4403

    Article  PubMed  PubMed Central  Google Scholar 

  27. Vardi N, Zhang LL, Payne JA, Sterling P (2000) Evidence that different cation chloride cotransporters in retinal neurons allow opposite responses to GABA. J Neurosci 20:7657–7663

    PubMed  CAS  Google Scholar 

  28. Varela C, Blanco R, De la Villa P (2005) Depolarizing effect of GABA in rod bipolar cells of the mouse retina. Vision Res 45:2659–2667. doi:10.1016/j.visres.2005.03.020

    Article  PubMed  CAS  Google Scholar 

  29. Duebel J, Haverkamp S, Schleich W et al (2006) Two-photon imaging reveals somatodendritic chloride gradient in retinal ON-type bipolar cells expressing the biosensor Clomeleon. Neuron 49:81–94. doi:10.1016/j.neuron.2005.10.035

    Article  PubMed  CAS  Google Scholar 

  30. Nawy S, von Gersdorff H (2011) Bipolar cells in the vertebrate retina: from form to function. Introduction. Vis Neurosci 28:1–2

    Article  PubMed  Google Scholar 

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Acknowledgments

This research was funded by Lundbeck LLC (Deerfield, IL) as an investigator-initiated study.

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Authors and Affiliations

  1. Department of Ophthalmology and Vision Sciences, The Hospital for Sick Children, Toronto, Canada

    Rachel Dragas, Carol Westall & Tom Wright

  2. Ophthalmology and Vision Science, University of Toronto, Toronto, Canada

    Carol Westall

Authors
  1. Rachel Dragas
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  2. Carol Westall
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  3. Tom Wright
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Correspondence to Tom Wright.

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Dragas, R., Westall, C. & Wright, T. Changes in the ERG d-wave with vigabatrin treatment in a pediatric cohort. Doc Ophthalmol 129, 97–104 (2014). https://doi.org/10.1007/s10633-014-9453-y

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  • DOI: https://doi.org/10.1007/s10633-014-9453-y

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