Study of long-term visual function and plasma biomarkers in patients with epilepsy receiving Vigabatrin

Michael, Kaleena Bulan (2022) Study of long-term visual function and plasma biomarkers in patients with epilepsy receiving Vigabatrin. PhD thesis, University of Glasgow.

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Vigabatrin is a highly effective adjunctive treatment for adults with refractory epilepsy and for infantile spasms. After gaining its license in Europe in 1989, it was used widely with much success until 1997 when reports of permanent visual fields defects were observed in some patients. The use of Vigabatrin had fallen in Europe since, where significant number of patients were denied this treatment leading to inadequate seizure control, poorer quality of life and greater risk of death and injury. In the US, Vigabatrin was made available for their patients in 2009 involving costly and extensive monitoring programme of visual function. The result of long-term monitoring is varied, partly due to the mixed methods used for examination of visual function. Our centre previously completed one of the largest international studies investigating Vigabatrin associated retinal toxicity, differentiating the pathological from physiological effects of Vigabatrin on vision and to document pre-existing visual field defects in 25% of patients with epilepsy. More than 2 milliseconds timing delay on the peripheral retina on WF-mfERG was found to be a sensitive and specific indicator of Vigabatrin associated retinal toxicity.

28 subjects were examined in this study. The effect of Vigabatrin use (current versus previous) on their visual function and retinal structures with the Optical Coherence Tomography (OCT) was assessed. Subjects were also stratified based on the presence of >2ms peripheral timing delay to uncover specific patterns in their visual tests.

The results showed a strong relationship between >2ms peripheral timing delay with higher volume of the inner retinal microstructures based on the OCT (p<0.05). These changes are also predictive of their perimetry scores (p<0.05). OCT retinal nerve fibre layer however appear to have poor correlation with mfERG results making it an unsuitable biomarker. Several retinal microlayers appear be affected, suggesting VaRT to be more diffuse and widespread than previously believed. Sub-group analyses showed no difference in the concentration of serum Taurine and Ornithine in the current or previous user groups or those with and without the mfERG >2ms peripheral timing delay. We propose that OCT macula volume analysis to be a promising method to detect and monitor for presence of VaRT. Development of a customised analytical algorithm involving retinal auto-segmentation could help us progress in developing a practical and reliable tool for the detection and monitoring of VaRT.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Subjects: R Medicine > R Medicine (General)
Colleges/Schools: College of Medical Veterinary and Life Sciences
Supervisor's Name: Parks, Dr. Stuart and Keating, Dr. David
Date of Award: 2022
Depositing User: Theses Team
Unique ID: glathesis:2022-82953
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 14 Jun 2022 13:03
Last Modified: 14 Jun 2022 13:17
Thesis DOI: 10.5525/gla.thesis.82953

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