The natural history of Vigabatrin associated visual field defects in patients electing to continue their medication

Abstract

Purpose To determine the natural history of visual field defects in a group of patients known to have Vigabatrin-associated changes who elected to continue the medication because of good seizure control. Methods All patients taking Vigabatrin alone or in combination with other antiepileptic drugs for at least 5 years (range 5-12 years) were entered into a visual surveillance programme. Patients were followed up at 6-monthly intervals for not less than 18 months (range 18-43 months). In all, 16 patients with unequivocal defects continued the medication. Following already published methodology (Eye 2002; 16;567-571) monocular mean radial degrees (MRDs) to the I/4e isopter on Goldmann perimetry was calculated for the right eye at the time of discovery of a visual field defect and again after not less than 18 months follow-up. Results Mean right eye MRD at presentation was 36.981 (range 22.25-51.0), compared to 38.401 (range 22.5-49.75) after follow-up; P ¼ 0.338 unpaired t-test. Only one patient demonstrated a deterioration in visual field during the study period and discontinued treatment. Conclusion Established visual field defects presumed to be due to Vigabatrin therapy did not usually progress in spite of continuing use of the medication. These data give support to the hypothesis that the pathogenesis of Vigabatrin-associated visual field defects may be an idiosyncratic adverse drug reaction rather than dose-dependent toxicity.

Safety and Tolerability of Antiepileptic Drug Treatment in Children with Epilepsy

“…This is a point of major concern since GVG is effective, and well tolerated, in the treatment of infantile spasms but the visual defect is asymptomatic and indefinable in the infantile spasms age group. It is still unclear if GVG-related visual field defects may represent an idiosyncratic adverse effect [130] rather than result from dose-dependent toxicity. [63] Its exact pathophysiological mechanisms remain unclear, but the site of toxicity could be the inner layer of retina, where GVG causes irreversible inhibition of GABA aminotransferase.…”

“…Although a correlation with total GVG load seems to exist, [63] a dose-dependent mechanism has been questioned. [130] As most responses to GVG treatment are obtained within the initial 3 weeks, non-responders will have little risk, if any, of developing a visual field defect if the drug is promptly withdrawn. In responders, it has been This material is the copyright of the original publisher.…”

Vigabatrin

“…As already discussed, given the extreme range of doses and duration of therapy that have been shown to be associated with the defect, and given that many patients do not develop the defect even after years and many kilograms of cumulative drug administration, it is clear that this is not a simple dose-related toxicity. Best and Acheson, 118 among others, 112,119 have proposed the pathophysiology of injury to be an idiosyncratic adverse drug reaction based on the prevalence (30 -40%), distal appearance, lack of progression, and lack of remission. The defect has been shown not to progress following discontinuation of drug, and not to begin after discontinuation.…”

“…The defect has been shown not to progress following discontinuation of drug, and not to begin after discontinuation. 112,118,119 Notably, many patients in several studies with very long vigabatrin exposure at high doses have completely normal fields (Aventis 4020, unpublished clinical study). The defect may represent an idiosyncratic adverse drug reaction, as opposed to a strict dose-or duration-dependent toxicity.…”

Delayed, rapid visual field loss in a patient after ten years of vigabatrin therapy

“…4,5 Prospective studies of patients with established vigabatrinassociated VFL suggest that the field defect is stable and irreversible and does not progress further with continued treatment. 2,3 However, observation periods are usually shorter than the one reported here. On the basis of this evidence, guidelines from the Royal College of Ophthalmologists suggest six monthly visual field screening for the first 5 years of treatment and yearly screening thereafter.…”