Vigabatrin visual field defects

Visual field defects associated with various antiepUeptic drugs (carbamazepine, diazepam, gabapentin, pheny-toin, tiagabine, and vigabatrin) have been reviewed (19). The true frequency is unknown, but in a retrospective study in 158 patients with partial epilepsy visual field defects were detected in 21 (13%) 13 patients had concentric visual field constriction without subjective spontaneous manifestations. Of these 13 patients, 9 were taking vigabatrin. 

Vigabatrin is used mainly in the treatment of refractory partial seizures and infantile spasms. Weight gain and mostly transient sedation are its most common adverse effects, but visual field defects are the main cause for concern and severely restrict its use. 

Severe symptomatic visual field constriction, affecting mostly the peripheral fields and without loss of visual acuity, was first reported in 1997 in three patients who had taken vigabatrin for 2-3 years (17), and reports continue to appear (18-24). Electrophysiological investigations suggested damage to the outer retina, and there was no recovery for up to 12 months after withdrawal. Over 50 other cases of visual field defects (including asymptomatic cases) were published thereafter, and 28 were known to the manufacturer before the initial publication (SEDA-21, 78) (SEDA-22, 92). 

Visual field defects have been commonly reported in patients taking vigabatrin (10-30%) (27,28), although if asymptomatic cases are included, the incidence may be as high as 40% (29) or even 60% (30). In an observational cohort study the prevalence was relatively low, at 0.8% of 7228 patients (31) however, this result was challenged as a probable underestimate, because of the use of a questionnaire to elicit the diagnosis (12-14). These different... 

Expert review of 25 cases of visual field defects reported to the manufacturer suggested that in 13 of the patients the visual field loss could not be assigned to an alternative known cause and had to be ascribed to vigabatrin (11). In an open extension study in Japan, 29 of 99 patients treated with vigabatrin for 2.7-6.7 years had visual field defects attributed to vigabatrin (11). 

Of 20 consecutive patients treated with vigabatrin 12 had visual field constriction, severe in four and sjmpto-matic in two (33). Visual field defects were more common in patients who were also taking valproate. Although most reports concerned adults, children may also be affected (34). 

In a randomized monotherapy trial in newly diagnosed epilepsy, seven of 32 patients who were stiU taking vigabatrin after 3-9 years had concentrically constricted visual fields, and the defect was rated as severe in two (35). Of the seven patients with field defects, five had reduced oscillatory potentials and two also had abnormal a and b waves in rod and cone electroretinography. In contrast, none of the 20 patients who were stiU taking carba-mazepine had abnormal visual fields. There is also preliminary evidence that a pre-existing visual field defect increases susceptibility to vigabatrin-induced visual field constriction. 

The efficacy and adverse effects of steroids and vigabatrin in children with infantile spasms have been reviewed (38). The authors found a high rate of visual field defects and concluded that although vigabatrin is efficacious it does not seem to be more effective than steroids or corticotrophin, and that the benefits of vigabatrin do not justify the associated risks of possible irreversible visual changes. 

The prevalence of visual field constriction associated with vigabatrin has been evaluated in 91 children aged 5.6-18 years (39). There were visual field defects in 17,... 

A 41-year-old man who had taken vigabatrin for 2 years in doses of 3-6 g/day developed bilateral concentric visual field defects, with greater loss in the nasal fields. Vigabatrin was withdrawn. Later he had a cardiopulmonary arrest and died. At postmortem there was peripheral retinal atrophy with loss of ganghon cells, severe in the peripheral retina and less severe in the maculae. 

In a cohort study of 99 patients taking vigabatrin, the prevalence of visual field defects increased significantly with increasing total vigabatrin dose. The prevalence ranged from four of 51 patients who had been exposed to 1 g/day or less to six of 8 patients taking a total dose of 3-5 g/day (28). 

Although in a 10-year-old girl a severe visual field defect was said to have reversed after withdrawal (59), repeat confirmatory testing was not performed before the withdrawal of vigabatrin and the pattern of constriction was suggestive of an artefact related to inadequate compliance with the testing procedure (J Wild, personal communication, 1999). 

Of 12 vigabatrin-treated patients with visual field defects re-examined 2-10 years after vigabatrin withdrawal, all stiU had visual field defects (28). In five cases there was apparent worsening. Exceptional cases of reversible visual field defects have been reported in children (61). However, perimetry assessment in children is burdened with multiple methodological problems that usually preclude reliable results. 

Wild JM, Martinez C, Reinshagen G, Harding GF. Characteristics of a unique visual field defect attributed to vigabatrin. Epilepsia 1999 40(12) 1784-94. 

Manuchehri K. Visual field defect associated with vigabatrin. Method of estimating prevalence was inappropriate. BMJ 2000 320(7246) 1403. ... 

Spence SJ, Sankar R. Visual field defects and other ophthal-mological disturbances associated with vigabatrin. Drug Saf 2001 24(5) 385 04. 

Kalviainen R, Nousiainen I. Visual field defects with vigabatrin epidemiology and therapeutic implications. CNS Drugs 2001 15(3) 217-30. 

Midelfart A, Midelfart E, Brodtkorb E. Visual field defects in patients taking vigabatrin. Acta Ophthalmol Scand 2000 78(5) 580-4. 

Nousiainen I, Mantyjarvi M, Kalviainen R. No reversion in vigabatrin-associated visual field defects. Neurology 2001 57(10) 1916-17. 

Wilton LV, Stephens MD, Mann RD. Visual field defect associated with vigabatrin observational cohort study. BMJ 1999 319(7218) 1165-6. 

Kalviainen R, Nousianen I, Nikoskelainen A, Partanen J, Partanen K, Mantijarvi M, Riekkinen PJ. Visual field defects associated with initial vigabatrin monotherapy as compared with initial carbamazepine monotherapy. Epilepsia 1998 39(Suppl. 2) 5. 

Versino M, Veggiotti P. Reversibility of vigabatrin-induced visual-field defect. Lancet 1999 354(9177) 486. 

Kramer G, Ried S, Landau K, Harding GFA. Vigabatrin reversibility of severe concentric visual field defects after early detection and drug withdrawal—a case report. Epilepsia 2000 41(Suppl Florence) 144. 

Adverse effects of vigabatrin include sedation, dizziness and behavioural changes similar to those seen with phenytoin. Vigabatrin may cause irreversible visual field defects, which limits its use. 

Vigabatrin Sedation, weight gain, agitation, confusion, psychosis, visual field defects with long-term use (possibly irreversible)... 

In a study of vigabatrin-induced visual fields loss in 753 patients, a subset of 341 subjects were studied with both static perimetry and Goldmann kinetic perimetry [361 ]. Of this subset, 258 were taking vigabatrin, of whom 16% had moderate visual field defects and 3 % had severe defects. There was a weak correlation between the severity of visual field constriction and visual symptoms. 

Sergott RC, Bittman RM, Christen EM, Sagar SM. Vigabatrin-induced peripheral visual field defects in patients with refractory partial epilepsy. Epilepsy Res 2010 92(2-3) 170-6. 

Sorri I, Brigell MG, Malyusz M, Mahlamaki E, de Meynard C, Kalviainen R. Is reduced omithine-5-aminotransferase activity the cause of vigabatrin-associated visual field defects Epilepsy Res 2010 92(1) 48-53. 

Until now, the incidence ofvigabatrin-asso-ciated retinal toxicity in Asian populations has not been studied. In 18 Chinese patients, 8 men and 10 women, who had taken vigabatrin for 13 months to 5 years, mean dosage 1581 mg/day, there were significant bilateral visual field defects in 20 eyes, and 80% showed a concentric pattern, compared with none in the control group [433 ]. 

Brodie MJ. Binasal visual field defects are not specific to vigabatrin. Epilepsy Behav 2009 16(3) 521-6. 

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