Thursday, September 3, 2015

Vigabatrin and visual field defects

Riikonen R, Rener-Primec Z, Carmant L, Dorofeeva M, Hollody K, Szabo I, Krajnc
BS, Wohlrab G, Sorri I. Does vigabatrin treatment for infantile spasms cause
visual field defects? An international multicentre study. Dev Med Child Neurol.
2015 Jan;57(1):60-7.



The aim of this study was to examine whether vigabatrin treatment had caused visual field defects (VFDs) in children of school age who had received the drug in infancy.


In total, 35 children (14 males, 21 females; median age 11y, SD 3.4y, range 8-23y) were examined by static Humphrey perimetry, Goldmann kinetic perimetry, or Octopus perimetry. The aetiologies of infantile spasms identified were tuberous sclerosis (n=10), other symptomatic causes (n=3), or cryptogenic (n=22).


Typical vigabatrin-attributed VFDs were found in 11 out of 32 (34%) children: in one out of 11 children (9%) who received vigabatrin for <1 year (group 1), in three out of 10 children (30%) who received vigabatrin for 12 to 24 months (group 2), and in seven out of 11 children (63%) who received vigabatrin treatment for longer than 2 years (group 3). VFDs were mild in five and severe in six children. Patients with tuberous sclerosis were at higher risk of VFDs (six out of 10 children). The mean cumulative doses of vigabatrin were 140.5, 758.8, and 2712g in group 1, 2, and 3, respectively.


VFDs were found in 34% of the cohort of children in this study. The rate of VFD increased from 9% to 63% as duration of treatment increased. The results of this study showed that the risk-benefit ratio should always be considered when using vigabatrin.

Commentary:  Chiron C, Dulac O. Analysis of vigabatrin treatment causing visual field
defects in infantile spasms. Dev Med Child Neurol. 2015 Jan;57(1):9-10.

...However, these suggestions require some precision to be applied in clinical practice. The first pitfall would be to discourage vigabatrin prescription in newly diagnosed infantile spasms. To date no other drug proved to be efficient on symptomatic epileptic spasms except hormonal therapy at high doses, which demonstrated lower efficacy than vigabatrin in tuberous sclerosis and equivalent efficacy at 1 year in other causes. Potentially life-threatening adverse events of steroids have also to be considered when compared to vigabatrin retinal toxicity. Finally, the subjective impact of vigabatrin-related VFL is exceptionally assessed in the reports: in fact very few patients complain of such peripheral VFL. Except for driving, VFL seldom alters quality of life, and in no case would the impact be comparable to the cognitive deterioration caused by persisting or relapsing infantile spasms.
The second pitfall would be to underestimate the required vigabatrin dose <36mg/kg/day proved to be inefficient randomly compared to the usual 100–150mg/kg/day, and the lowest effective dose has yet to be determined. Interestingly, the daily dose of vigabatrin was found positively correlated to the severity of VFL: in Riikonen et al.'s study five of the nine patients receiving at least 1500mg/day provided five of the six severe VFL cases.
The third and still unsolved question is the optimal treatment duration regarding the risk of relapse of refractory infantile spasms and cognitive deterioration after vigabatrin termination. Infantile spasms relapse is maximum within the first year of treatment, but may occasionally occur some years later after vigabatrin withdrawal and be untreatable, particularly in focal cortical dysplasia and tuberous sclerosis. In other cases, it seems possible not to exceed 6 months’ treatment.
The risk of vigabatrin needs, therefore, to be balanced against that of alternative therapy and of the disease, including severe relapse determined by aetiology.

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