Visual field defects in patients taking vigabatrin

Abstract

ABSTRACT.Purpose: To investigate visual field loss in patients on long-term treatment with the antiepileptic drug vigabatrin, recently reported to cause visual disturbances. Methods: Eighteen patients taking vigabatrin for 0.5-9.5 years were examined with automated perimetry up to 60ae from fixation using the Humphrey Field Analyser. Five patients with epilepsy receiving other medications served as controls. Patients found to have a visual field defect underwent ophthalmologic examination. Results: Among the 18 patients in the vigabatrin group, visual field defects categorised as mild were revealed in 6 right eyes (33%) and 8 left eyes (44.4%), while defects categorised as severe were found in 9 right eyes (50%) and 8 left eyes (44.4%). The majority of the defects (66.7% in the right eye) were peripheral constriction with nasal predominance. The location of the defects was confirmed in 8 patients also tested with Kowa AP340 perimetry. Conclusion: According to our results, visual field defects among the patients on vigabatrin therapy may occur more frequently than previously recognised. V igabatrin (VGB) is an effective antiepileptic drug acting as a relatively specific irreversible inhibitor of gammaaminobutyric acid (GABA) transaminase. Inhibition of this enzyme produces an elevation of GABA concentrations in the brain associated with anticonvulsant effect (Mattson et al. 1994;Petroff et al. 1996aPetroff et al. , 1996bAvanzini et al. 1997). No abnormalities in central nervous system conduction related to VGB treatment in humans have been observed (Mauguière et al. 1997). In the vertebrate retina, GABA is one of the most important inhibitory transmitters (Berman 1991).Currently, VGB has been used for more than 12 years for treatment of partial seizures (Marson et al. 1997). It was found to be less effective, but better tolerated than carbamazepine, which is the first-choice drug for the treatment of partial epilepsies (Chadwick 1999). Recently, several reports have documented persistent visual field defects in patients with long-term use of VGB, either as monotherapy or concurrently with other antiepileptic drugs (Blackwell et al. 1997;Eke et al. 1997;Harding 1997;Wilson & Brodie 1997;Wong et al. 1997;Williams & Brennan 1997;Krauss et al. 1998;Ruether et al. 1998;Daneshvar et al. 1999;Kälviäinen et al. 1999;Wilton et al. 1999). According to these, VGB seems to increase the risk of a unique and specific pattern of bilateral, mainly asymptomatic visual field constriction (Kälviäin-en et al. 1999). The incidence of these visual field defects was recently found to be substantially higher than previously assumed. A frequency as high as 40% (9% mild, 31% severe) among patients on VGB monotherapy has been reported (Kälviäinen et al. 1999). Any clear risk factors regarding age, duration of the treatment, the dosage or the cumulative amount of VBG consumed during the treatment were not found (Kälviäinen et al. 1999;Daneshvar et al. 1999). Unfortunately, irreversible visual field defects after cessation of the VGB therapy...

Relationship between the area of isopters and Vigabatrin dosage during two years of observation

“…Besch and colleagues have observed sparing of the temporal field in VGB patients using static perimetry [26]. Nasal predominance of the VF constriction was also observed by Midlefart in regard to static perimetry within 60 degrees of eccentricity [6] and by Daneshvar [27]. Kinirions and colleagues observed concentric constriction in 52.7% of the cohort [19], Newman in 20% of examined patients [3] but they used mean radial degree of III4e [19] or I4e [3] as an indicator.…”

“…In clinical practice most of the patients treated with VGB are examined with static perimetry within 60° [6] or 30° [7] or 24° [8] of eccentricity. However, there is lack of validated scoring system for analysing supra-threshold screening programmes and unacceptable poor reliability indices have been observed while examining epilepsy patients with full threshold automated static perimeter [3,9].…”

Modelling the topography of absolute defects in patients exposed to the anti-epileptic drug vigabatrin and in normal subjects using automated static suprathreshold perimetry of the entire 80° visual field

“…In contrast to kinetic perimetry this method is almost examiner-independent. Previous publications, referring to static techniques, are usually restricted to the central field less than 30°for static threshold [6,23,[29][30][31][32] and less than 60°for suprathreshold perimetry [6]. It is well-known that extreme periphery of the visual field is influenced by the anatomical variation.…”

“…The visual field loss associated with vigabatrin is a bilateral and clinically symmetrical constriction which manifests in varying levels of severity and which, until the late stages, is more pronounced nasally than temporally [8][9][10][11][12].…”

“…Examination of the peripheral field by automated threshold static perimetry has, in general, received little attention [4,6,12,21,25], and has only rarely been used for the investigation of the so-called vigabatrin-attributed visual field loss (VAVFL) [26].…”