title: Retinal nerve fibre layer thinning is associated with drug resistance in epilepsy.
abstract: OBJECTIVE
  Retinal nerve fibre layer (RNFL) thickness is related to the axonal anterior visual pathway and is considered a marker of overall white matter 'integrity'. We hypothesised that RNFL changes would occur in people with epilepsy, independently of vigabatrin exposure, and be related to clinical characteristics of epilepsy.
  
  
  METHODS
  Three hundred people with epilepsy attending specialist clinics and 90 healthy controls were included in this cross-sectional cohort study. RNFL imaging was performed using spectral-domain optical coherence tomography (OCT). Drug resistance was defined as failure of adequate trials of two antiepileptic drugs to achieve sustained seizure freedom.
  
  
  RESULTS
  The average RNFL thickness and the thickness of each of the 90° quadrants were significantly thinner in people with epilepsy than healthy controls (p<0.001, t test). In a multivariate logistic regression model, drug resistance was the only significant predictor of abnormal RNFL thinning (OR=2.09, 95% CI 1.09 to 4.01, p=0.03). Duration of epilepsy (coefficient -0.16, p=0.004) and presence of intellectual disability (coefficient -4.0, p=0.044) also showed a significant relationship with RNFL thinning in a multivariate linear regression model.
  
  
  CONCLUSIONS
  Our results suggest that people with epilepsy with no previous exposure to vigabatrin have a significantly thinner RNFL than healthy participants. Drug resistance emerged as a significant independent predictor of RNFL borderline attenuation or abnormal thinning in a logistic regression model. As this is easily assessed by OCT, RNFL thickness might be used to better understand the mechanisms underlying drug resistance, and possibly severity. Longitudinal studies are needed to confirm our findings.
authors.affiliation: Department of Clinical and Experimental Epilepsy, NIHR University College London Hospitals Biomedical Research Centre, UCL Institute of Neurology, London, UK Neuroscience Department, Polytechnic University of Marche, Ancona, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Balestrini
authors.affiliation: Department of Clinical and Experimental Epilepsy, NIHR University College London Hospitals Biomedical Research Centre, UCL Institute of Neurology, London, UK.
authors.forename: Lisa M S
authors.initials: LM
authors.lastname: Clayton
authors.affiliation: Department of Clinical and Experimental Epilepsy, NIHR University College London Hospitals Biomedical Research Centre, UCL Institute of Neurology, London, UK.
authors.forename: Ana P
authors.initials: AP
authors.lastname: Bartmann
authors.affiliation: Department of Clinical and Experimental Epilepsy, NIHR University College London Hospitals Biomedical Research Centre, UCL Institute of Neurology, London, UK.
authors.forename: Krishna
authors.initials: K
authors.lastname: Chinthapalli
authors.affiliation: Department of Clinical and Experimental Epilepsy, NIHR University College London Hospitals Biomedical Research Centre, UCL Institute of Neurology, London, UK.
authors.forename: Jan
authors.initials: J
authors.lastname: Novy
authors.affiliation: Department of Clinical and Experimental Epilepsy, NIHR University College London Hospitals Biomedical Research Centre, UCL Institute of Neurology, London, UK.
authors.forename: Antonietta
authors.initials: A
authors.lastname: Coppola
authors.affiliation: Department of Clinical and Experimental Epilepsy, NIHR University College London Hospitals Biomedical Research Centre, UCL Institute of Neurology, London, UK.
authors.forename: Britta
authors.initials: B
authors.lastname: Wandschneider
authors.affiliation: Department of Clinical and Experimental Epilepsy, NIHR University College London Hospitals Biomedical Research Centre, UCL Institute of Neurology, London, UK.
authors.forename: William M
authors.initials: WM
authors.lastname: Stern
authors.affiliation: Department of Neuro-Ophthalmology, National Hospital for Neurology and Neurosurgery, London, UK.
authors.forename: James
authors.initials: J
authors.lastname: Acheson
authors.affiliation: Department of Clinical and Experimental Epilepsy, NIHR University College London Hospitals Biomedical Research Centre, UCL Institute of Neurology, London, UK.
authors.forename: Gail S
authors.initials: GS
authors.lastname: Bell
authors.affiliation: Department of Clinical and Experimental Epilepsy, NIHR University College London Hospitals Biomedical Research Centre, UCL Institute of Neurology, London, UK Stichting Epilepsie Instellingen Nederland, Heemstede (SEIN), Heemstede, The Netherlands.
authors.forename: Josemir W
authors.initials: JW
authors.lastname: Sander
authors.affiliation: Department of Clinical and Experimental Epilepsy, NIHR University College London Hospitals Biomedical Research Centre, UCL Institute of Neurology, London, UK.
authors.forename: Sanjay M
authors.initials: SM
authors.lastname: Sisodiya
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D000069279:Drug Resistant Epilepsy / Q000473:pathology*; D005260:Female; D006801:Humans; D008607:Intellectual Disability / Q000150:complications; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009412:Nerve Fibers / Q000473:pathology; D055351:Retinal Neurons / Q000473:pathology*; D041623:Tomography, Optical Coherence; D020888:Vigabatrin / Q000009:adverse effects / Q000627:therapeutic use; D014794:Visual Fields
chemical_list: D000927:Anticonvulsants; D020888:Vigabatrin