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Title: Peripapillary retinal nerve fibre layer thickness in individuals with epilepsy exposed to vigabatrin
Author: Clayton, L. M.
ISNI:       0000 0004 2731 1327
Awarding Body: University College London (University of London)
Current Institution: University College London (University of London)
Date of Award: 2011
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Background: The antiepileptic drug vigabatrin (VGB) is associated with the development of visual field loss in around 50% of exposed individuals. The mechanisms of VGB retinotoxicity are unknown, and there is continued debate as to the best methods of assessing visual function in VGB-exposed individuals, particularly in those unable to perform perimetry. Methods: 204 VGB-exposed individuals, 90 non-exposed individuals with epilepsy and 90 healthy controls participated. Individuals underwent visual field testing using Goldmann kinetic perimetry and peripapillary retinal nerve fibre layer (ppRNFL) imaging using optical coherence tomography (OCT). Results: A retrospective analysis of the evolution of vigabatrin associated visual field loss (VAVFL) in individuals continuing VGB showed progression of VAVFL in all individuals over a ten-year period. More VGB-exposed individuals were able to perform OCT compared to perimetry. Measures of ppRNFL thickness were found to be highly repeatable in this population. There was a strong correlation between ppRNFL thickness and visual field size suggesting that irreversible VAVFL may be related to loss of retinal ganglion cells (RGCs). Duration of VGB exposure, maximum daily VGB dose, male gender and the presence of a homonymous visual field defect were associated with ppRNFL thinning. The pattern of ppRNFL thinning suggested that ppRNFL loss progresses with increasing VGB exposure. Subtle ppRNFL thinning may occur in discrete areas after exposure to small amounts of VGB, whilst other ppRNFL areas appear to be resistant to large cumulative VGB exposure. The ppRNFL was significantly thinner in non-exposed individuals with epilepsy compared to healthy controls. Factors that may be associated with ppRNFL thinning included the presence of learning disability, MTLE with HS and longer duration of epilepsy. Conclusions: ppRNFL imaging using OCT provides a useful tool to assess VGB-exposed individuals, and can provide an accurate estimate of the extent of VAVFL in the absence of a reliable direct measure of the visual field. Understanding patterns of ppRNFL thinning associated with cumulative VGB-exposure may aid in the early detection of VGB toxicity. Pathophysiological mechanisms of VAVFL are unknown; however, pathology of RGC apparatus is evidently implicated.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available