title: A lack of clinically apparent vision loss among patients treated with vigabatrin with infantile spasms: The UCLA experience.
abstract: BACKGROUND
  Vigabatrin (VGB) is one of two FDA-approved medications for treatment of infantile spasms. Despite demonstrated efficacy, its use has been curtailed by reports indicating a substantial risk of VGB-associated visual field loss (VAVFL). As these reports have conflicted with our clinical observations in routine practice, we systematically reviewed the experiences of patients treated with VGB at UCLA to estimate the prevalence of clinically apparent VAVFL.
  
  
  METHODS
  Patients with video-EEG-confirmed infantile spasms evaluated at our center between February 2007 and February 2014 were retrospectively identified. Among patients with VGB exposure, we documented relevant clinical factors and determined the duration of therapy, peak dosage, and cumulative dosage. Based on a review of serial neurologic and ophthalmologic reports and aided by electroretinography (ERG) assessments when available, we ascertained whether each patient had evidence of clinically apparent vision impairment (i.e., recognized by a neurologist or ophthalmologist during any follow-up visit) and whether or not the vision loss was attributed to VGB exposure (i.e., evidence of bilateral, symmetric, and peripheral visual field loss), either by the treating physician or on retrospective review by the study team.
  
  
  RESULTS
  During the study period, 257 patients with video-EEG-confirmed infantile spasms were identified. One hundred and forty-three (56%) patients received VGB. Although visual loss of any cause was common among patients with (31%) and without (32%) VGB exposure, there were no cases in which visual field defects were plausibly linked to VGB. We estimate that the risk of clinically significant VAVFL does not exceed 3.2% (95% CI upper bound). Vision loss was never characterized as exclusively peripheral and was always better explained by other causes (e.g., hemianopsia following hemispherectomy and cortical vision impairment after hypoxic ischemic encephalopathy). Precise quantitative exposure data were available for 104 (73%) patients treated with VGB, among whom the median duration of treatment was 8.6 (IQR: 3.7-16.2) months, the median peak dosage was 141.5 (IQR: 104.8-166.0) mg/kg/day, and the median cumulative dosage was 314 (IQR: 140.8-645.7) grams.
  
  
  CONCLUSIONS
  We found that the risk of clinically apparent vision loss is quite low among young children treated for infantile spasms. Our estimate of risk contrasts with prior studies and likely reflects our ascertainment of vision loss without the aid of perimetry or serial ERG, the short treatment duration, and the relatively young age of our patients. In the treatment of infantile spasms, risk-benefit assessment should consider both the low prevalence of ERG-identified VAVFL among patients with brief (<6-9months) exposure and the very low prevalence of clinically apparent VAVFL in this population.
authors.affiliation: School of Medicine, University of California, San Francisco, San Francisco, CA, USA.
authors.forename: Madeline D
authors.initials: MD
authors.lastname: Schwarz
authors.affiliation: School of Medicine and Health Sciences, George Washington University, Washington, DC, USA.
authors.forename: Menglu
authors.initials: M
authors.lastname: Li
authors.affiliation: Division of Pediatric Neurology, Mattel Children's Hospital and David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: Jackie
authors.initials: J
authors.lastname: Tsao
authors.affiliation: Division of Pediatric Neurology, Mattel Children's Hospital and David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: Raymond
authors.initials: R
authors.lastname: Zhou
authors.affiliation: School of Medicine, University of California, San Francisco, San Francisco, CA, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
authors.forename: Yvonne W
authors.initials: YW
authors.lastname: Wu
authors.affiliation: Division of Pediatric Neurology, Mattel Children's Hospital and David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; Department of Neurology, Mattel Children's Hospital and David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: Raman
authors.initials: R
authors.lastname: Sankar
authors.affiliation: Division of Pediatric Neurology, Mattel Children's Hospital and David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: Joyce Y
authors.initials: JY
authors.lastname: Wu
authors.affiliation: Division of Pediatric Neurology, Mattel Children's Hospital and David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. Electronic address: shussain@mednet.ucla.edu.
authors.forename: Shaun A
authors.initials: SA
authors.lastname: Hussain
mesh_terms: D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use*; D002140:California / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004569:Electroencephalography; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D015995:Prevalence; D012189:Retrospective Studies; D018570:Risk Assessment; D013036:Spasms, Infantile / Q000188:drug therapy*; D013997:Time Factors; D020888:Vigabatrin / Q000009:adverse effects / Q000627:therapeutic use*; D014786:Vision Disorders / Q000139:chemically induced* / Q000453:epidemiology; D058609:Visual Field Tests
chemical_list: D000927:Anticonvulsants; D020888:Vigabatrin
keywords: Epileptic spasms; Peripheral; Retina; Vision loss; West syndrome