title: Modelling the risk of visual field loss arising from long-term exposure to the antiepileptic drug vigabatrin: a cross-sectional approach.
abstract: BACKGROUND
  The antiepileptic drug vigabatrin has been used widely since 1989, but has only been approved for use in the US since 2009. The risk:benefit of vigabatrin is generally predicated upon an assumed frequency of associated visual field loss (VAVFL) of approximately 31 %. This estimate is based upon relatively short-term usage (up to 4-5 years) and it is essential to determine whether the frequency of VAVFL increases with longer-term usage.
  
  
  OBJECTIVE
  The aim of this study was to model, from cross-sectional evidence, over greater ranges of treatment duration and cumulative dose than previously evaluated, the risk (frequency) of VAVFL with increasing exposure to vigabatrin.
  
  
  METHODS
  This was a retrospective cohort study undertaken in a regional hospital epilepsy clinic.
  
  
  METHODS
  The cohort comprised 147 consecutive patients treated with vigabatrin for refractory complex partial (focal) seizures, who had all undergone ophthalmological examination and who had undertaken perimetry, reliably, according to a standard and robust protocol. The visual field plots were evaluated masked to treatment duration and dose.
  
  
  METHODS
  The risk (frequency) of VAVFL with increasing exposure to vigabatrin was modelled, from the cross-sectional evidence, by standard and plateau logistic regression.
  
  
  RESULTS
  The cohort comprised 80 females and 67 males (mean age 40.3 years, standard deviation 13.7). The median duration of vigabatrin exposure was 7.9 years (interquartile range 3.6-11.0, range 0.2-16.1 years); 46 patients (31 %) had received vigabatrin for over 10 years. Eighty-seven patients (59 %) exhibited VAVFL; the proportion with VAVFL was higher in males (66 %) than females (54 %). The plateau model for duration and for cumulative dose exhibited a better fit than the standard model (both p < 0.001). The modelled frequency of VAVFL increased with increasing exposure up to approximately 6 years duration and 5 kg cumulative dose, and plateaued at approximately 76 % (95 % CI 67-85) and 79 % (95 % CI 70-87), respectively. Severity of VAVFL, classified in terms of the visual field index Mean Deviation, was not significantly associated with either duration or cumulative dose of therapy.
  
  
  CONCLUSIONS
  Clinicians and patients, in enabling informed choice, should be alert to the possible substantial increased risk:benefit for VAVFL with increasing long-term exposure to vigabatrin and the ensuing increased cost:benefit resulting from the necessary additional visual assessments.
authors.affiliation: Cardiff Centre for Vision Sciences, College of Biomedical and Life Sciences, Cardiff University, Maindy Road, Cardiff, Wales, CF24 4HQ, UK, wildjm@cardiff.ac.uk.
authors.forename: John M
authors.initials: JM
authors.lastname: Wild
authors.forename: David L
authors.initials: DL
authors.lastname: Fone
authors.forename: Saleh
authors.initials: S
authors.lastname: Aljarudi
authors.forename: Charlotte
authors.initials: C
authors.lastname: Lawthom
authors.forename: Philip E M
authors.initials: PE
authors.lastname: Smith
authors.forename: Robert G
authors.initials: RG
authors.lastname: Newcombe
authors.forename: Gareth D
authors.initials: GD
authors.lastname: Lewis
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D012189:Retrospective Studies; D018570:Risk Assessment; D013997:Time Factors; D020888:Vigabatrin / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D058609:Visual Field Tests; D014794:Visual Fields / Q000187:drug effects*
chemical_list: D000927:Anticonvulsants; D020888:Vigabatrin