title: Nasal retinal nerve fiber layer attenuation: a biomarker for vigabatrin toxicity.
abstract: OBJECTIVE
  To investigate whether nasal peripapillary retinal nerve fiber layer (RNFL) attenuation is associated with visual field loss attributed to the anti-epileptic drug vigabatrin.
  
  
  METHODS
  Prospective cross-sectional observational study.
  
  
  METHODS
  Twenty-seven individuals with focal-onset epilepsy exposed to vigabatrin and 13 individuals with focal-onset epilepsy exposed to non-GABAergic anti-epileptic drug monotherapy.
  
  
  METHODS
  At one visit, suprathreshold perimetry of the central and peripheral field (3-zone, age-corrected Full Field 135 Screening Test) and threshold perimetry of the central field (Program 30-2 and the FASTPAC strategy) were undertaken using the Humphrey Field Analyzer (Carl Zeiss Meditech, Dublin, CA). At a second visit, ocular coherence tomography was undertaken for the right eye using the 3.4 RNFL thickness protocol of the StratusOCT (Carl Zeiss Meditech).
  
  
  METHODS
  The magnitude, for each individual, of the RNFL thickness, averaged across the 4 oblique quadrants, and for each separate quadrant.
  
  
  RESULTS
  Of the 27 individuals exposed to vigabatrin, 11 (group I) exhibited vigabatrin-attributed visual field loss, 15 exhibited a normal field, and 1 exhibited a homonymous quadrantanopia (group II). All 13 individuals exposed to non-GABAergic therapy had normal fields (group III). All individuals in group I exhibited abnormal average and nasal quadrant RNFL thicknesses in the presence of a normal temporal quadrant thickness. Most also exhibited additional RNFL attenuation in either the superior or inferior quadrant, or both. Four individuals in group II exhibited an identical pattern of RNFL attenuation suggesting that nasal RNFL thinning is a more sensitive marker for vigabatrin toxicity than visual field loss. None of the 13 individuals in group III exhibited nasal quadrant RNFL attenuation.
  
  
  CONCLUSIONS
  Vigabatrin-attributed visual field loss is associated with a characteristic pattern of RNFL attenuation: nasal quadrant thinning and normal temporal quadrant thickness with, or without, superior or inferior quadrant involvement. Nasal attenuation may precede visual field loss. Ocular coherence tomography of the peripapillary RNFL should be considered in patients previously exposed to vigabatrin. It should also be considered at baseline and follow-up in those commencing vigabatrin for treatment of epilepsy or in trials for anti-addiction therapy. The pattern of RNFL thinning seems to be a useful biomarker to identify vigabatrin toxicity.
authors.affiliation: Welsh Epilepsy Unit, University Hospital of Wales, Cardiff, Wales, United Kingdom.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Lawthom
authors.forename: Philip E M
authors.initials: PE
authors.lastname: Smith
authors.forename: John M
authors.initials: JM
authors.lastname: Wild
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000009:adverse effects*; D001369:Axons / Q000187:drug effects / Q000473:pathology*; D015415:Biomarkers; D002220:Carbamazepine / Q000627:therapeutic use; D003430:Cross-Sectional Studies; D004828:Epilepsies, Partial / Q000188:drug therapy; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000473:pathology*; D041623:Tomography, Optical Coherence; D020888:Vigabatrin / Q000009:adverse effects*; D014786:Vision Disorders / Q000139:chemically induced / Q000175:diagnosis*; D058609:Visual Field Tests; D014794:Visual Fields / Q000187:drug effects*
chemical_list: D000927:Anticonvulsants; D015415:Biomarkers; D002220:Carbamazepine; D020888:Vigabatrin