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The Topographical Relationship between Visual Field Loss and Peripapillary Retinal Nerve Fibre Layer Thinning Arising from Long-Term Exposure to Vigabatrin

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Abstract

Background

The antiepileptic drug vigabatrin is associated with characteristic visual field loss (VAVFL) and thinning of the peripapillary retinal nerve fibre layer (PPRNFL); however, the relationship is equivocal.

Objective

The aim of this study was to determine the function–structure relationship associated with long-term exposure to vigabatrin, thereby improving the risk/benefit analysis of the drug.

Methods

A cross-sectional observational design identified 40 adults who had received long-term vigabatrin for refractory seizures, who had no evidence of co-existing retino-geniculo-cortical visual pathway abnormality, and who had undergone a standardized protocol of perimetry and of optical coherence tomography (OCT) of the PPRNFL. Vigabatrin toxicity was defined as the presence of VAVFL. The function–structure relationship for the superior and inferior retinal quadrants was evaluated by two established models applicable to other optic neuropathies.

Results

The function–structure relationship for each model was consistent with an optic neuropathy. PPRNFL thinning, expressed in micrometres, asymptoted at an equivalent visual field loss of worse than approximately − 10.0 dB, thereby preventing assessment of more substantial thinning. Transformation of the outcomes to retinal ganglion cell soma and axon estimates, respectively, resulted in a linear relationship.

Conclusions

Functional and structural abnormality is strongly related in individuals with vigabatrin toxicity and no evidence of visual pathway comorbidity, thereby implicating retinal ganglion cell dysfunction. OCT affords a limited measurement range compared with perimetry: severity cannot be directly assessed when the PPRNFL quadrant thickness is less than approximately 65 µm, depending on the tomographer. This limitation can be overcome by transformation of thickness to remaining axons, an outcome requiring input from perimetry.

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Author information

Author notes

  1. Saleh Aljarudi

    Present address: Dhahran Eye Specialist Hospital, Dhahran, 7500, Saudi Arabia

Authors and Affiliations

  1. College of Biomedical Sciences, Cardiff University, Maindy Road, Cardiff, CF24 4HQ, UK

    John M. Wild, Saleh Aljarudi & Carlo Knupp

  2. Alan Richens Unit, Welsh Epilepsy Centre, University Hospital of Wales, Heath Park, Cardiff, CF14 4XW, UK

    Philip E. M. Smith

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  1. John M. Wild
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Correspondence to John M. Wild.

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Funding

SA was supported by an unrestricted grant from the Ministry of Higher Education, Kingdom of Saudi Arabia. The latter had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation of the manuscript.

Conflicts of interest

John M. Wild, Saleh Aljarudi, Philip E.M. Smith and Carlo Knupp declare that they have no conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with ethical standards of the Local Research and Ethics Committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study had approval from the Local Research and Ethics Committee. For this type of study, formal consent is not required.

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Wild, J.M., Aljarudi, S., Smith, P.E.M. et al. The Topographical Relationship between Visual Field Loss and Peripapillary Retinal Nerve Fibre Layer Thinning Arising from Long-Term Exposure to Vigabatrin. CNS Drugs 33, 161–173 (2019). https://doi.org/10.1007/s40263-018-0583-8

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