(Sabril) is used in combination with other anti-epileptic drugs for the
treatment of epilepsy and is specifically indicated as monotherapy for
the treatment of infantile spasms (West's syndrome)1. It increases
the concentration of gamma-amino butyric acid (GABA) in the brain and retina
and as a result its use is associated with a number of CNS and ocular side-effects.
field defects (VFDs) in patients on treatment have been reported since
1989. Severs symptomatic bilateral visual field constriction was found
first in 1997 in three patients who had been on vigabatrin for two to three
years on a dosage of 2G-4G daily2. Other case reports followed3-6
which described patients on concurrent treatment with other anti-epileptics.
However visual field defects have also come to light in asymptomatic patients
on vigabatrin7 and it is suggested that these may be relatively
common8. As it is now thought that approximately one third of
patients receiving the drug may have VFDs9, the indications
for the use of vigabatrin have been revised and the manufacturers Aventis
Pharma (formerly Hoechst) have issued guidelines for visual field screening10.
relation between visual field defects and vigabatrin cannot be assumed
as the mechanism may be multifactorial. Retinal changes and visual field
disorders have also been associated with other drugs used in the treatment
of epilepsy such as phenytoin, diazepam and carbamazepine11,
all of which may be used in conjunction with vigabatrin and VFDs themselves
may be related to a history of complex partial seizures. However the pattern
of visual field loss appears to be unique to vigabatrin. The issue is further
complicated as visual field testing is often unreliable in patients who
may have cognitive defects associated with chronic epilepsy.
current "MIMS" advises that 'visual fields should be tested before and
during therapy and that patients should report new visual problems'.
Committee on the Safety of medicines (CSM) and the Medicines Control Agency
(MCA) have issued new advice (Nov 1999) saying that 'vigabatrin therapy
should only be initiated by an epilepsy specialist and the drug is only
indicated when all other appropriate antiepileptic drug combinations have
proved ineffective or poorly tolerated. Vigabatrin should not be initiated
as monotherapy (except for West's syndrome). The maximum recommended dose
of vigabatrin has been educed to 3g daily and the drug is not recommended
for patients with pre-existing visual field defects.'
retinal arterioles, surface wrinkling retinopathy and abnormal macular
reflexes have been described in one small series12.
atrophy has been observed in some patients with severe visual field constriction4,5.
asymmetric binasal visual field loss between 30 and 40 degrees.
irreversible concentric visual field loss (with some sparing of the temporal
is usually after months or years of vigabatrin treatment in previously
asymptomatic patients. VFDs appear irreversible even after discontinuation
Arden index within the normal range or at the lower limit of normal2,12.
Increase of photopic a wave latency and b wave latency. Reduced amplitude
of b wave and 30Hz flicker and also oscillatory potentials12,13,14.
may be a risk factor, but age, body weight and duration of epilepsy have
not been identified as risk factors to date15. A total dose
of 1500 grams or more has been found to correlate significantly with the
severity of VFDs16.
taking vigabatrin should undergo a visual field examination by the following
methods to exclude the possibility of visual field loss:
suprathreshold 2 or 3 zone perimetry (Humphrey 120 point or Octopus 07)
to at least 45 radius eccentricity, or
kinetic perimetry (IIIe and I4e or I2e stimuli, as appropriate).
visual field should be obtained before starting treatment.
assessments every 6 months for three years which can then be extended to
annually in patients who have no defect detected.
the responsibility of the prescribing doctor to discuss with the patient
or the patient's relatives the implications of any side-effects.
must be informed of any abnormalities in visual field tests and should
be advised that the long-term course is still unknown, although progression
of defects after stopping the drug has not been reported to date.
degree of visual field constriction may be severe and have practical consequences
for the patient, the potential risk of a visual field defect developing
against the potential benefit of seizure control needs to be assessed.
should be alerted to report any abnormalities in their vision.
present a particular difficulty as formal perimetry cannot reliably be
undertaken on children below the developmental age of about 9 years or
on those with behavioural problems associated with their epilepsy.Confrontation
testing in younger children is unreliable. At present no validated method
is available for detection of VFD's in children who are not able to perform
conventional perimetry. Standard ERG or VEP techniques are not practical
as screening tools in young children for whom vigabatrin represents an
unknown risk, although focal techniques currently being developed may prove
useful in time and the CSM recommended the use of field-specific VEPs to
identify possible peripheral losses17. Despite these difficulties,
vigabatrin remains the drug of choice for monotherapy in children with
West's syndrome for whom early control of seizures is beneficial.
are still many unanswered questions concerning the relation between vigabatrin
and visual field defects. Evaluation of the clinical situation is difficult
when it comes to assessing the potential risk to the patient, particularly
where children are concerned. It is a mater for the prescribing paediatrician
or neurologist to weigh up the dangers of potential side-effects against
seizure control and to instigate screening for VFDs.
the additional workload that visual field screening for patients on vigabatrin
will add to already overburdened eye departments, accurate visual field
monitoring will help to provide much needed evidence and also enable a
more informed decision on whether to initiate or continue treatment with
Marion Roussel Ltd, vigabatrin data sheet (ABPI data sheet compendium,
T, Talbot JF, Lawden MC. Severe persistent visual field constriction associated
with Vigabatrin. BMJ 1997;314:180-1
Harding G, Wild J, Robertson K, Edson E, Barber C, Lawden M, et al. Elector
oculography, E.R.Gs, multi-focal E.R.G's and VEP's in epileptic patients
showing visual field disorders. Electroenceph Clin Neurophysiol 1997;103:96.
Wilson EA, Brodie MJ. Severe persistent visual field constriction associated
with vigabatrin. BMJ 1997;314:1693-1694
Wong ICK, Mawer GE, Sander JWAS. Reaction might be dose dependent. BMJ
Blackwell N, Hayllar J, Kelly G. Patients taking vigabatrin should have
regular visual field testing. BMJ 1997;314:1693-1694
MacKenzie R, Klistorner A. Severe persistent visual field constriction
associated with vigabatrin. BMJ 1998;316:233
Rao GP, Fat AF, Kyle G, Leach JO, Chadwick DW, Batterbury M. Study is needed
of visual field defects associated with any long-term anti-epileptic drugs.
Lawden MC, Eke T, Degg C, Harding GF, Wild JM. Visual Field Defects associated
with vigabatrin therapy. J Neurol Neurosurg Psychiatry 1999 Dec;67(6):716-22
Guidelines for Visual Field Screening. Aventis Pharma Ltd. Jan 2000.
Harding GFA. Four possible explanations exist. BMJ 1997;314:1693-1694
Krauss GL, Johnson MA, Miller NR. Vigabatrin associated cone system dysfunction:
electoretinogram and ophthalmological findings. Neurology 1998 50(3):614-8
Harding GFA, Jones LA, Tipper VJ, Betts TA, Mumford JP. Electro-retinogram,
pattern electoretinogram and visual evoked potential assessment in patients
receiving vigabatrin. Epilepsia 36:S108 1995
Duckett T, Brigell MG, Ruckh S. Electoretinographic changes are not associated
with loss of visual function in pediatric epileptic patients following
treatment with vigabatrin. Invest Ophathlmol Vis Sci 1998;39:S973
Wild JM, Martinez C, Reinshagen G, Harding GF. Characteristics of a unique
visual field defect attributed to vigabatrin. Epilepsia 1999 Dec;40(12):1784-94
Manuchehri K, Goodman S, Siviter L, Nightingale S. A controlled study of
vigabatrin and visual abnormalities. Br J Ophthalmol 2000;84:499-505
Harding GFA, Robertson K, Holliday I, Jones L. Field-specific visual evoked
potentials for assessment of peripheral field defect in a paediatric population.
Journal of Physiology 1999,518P:171P