What are the ocular side effects of vigabatrin?

Ocular Side Effects of Vigabatrin

Vigabatrin causes irreversible bilateral concentric peripheral visual field defects in approximately 30-40% of adult patients, representing the most serious and common ocular adverse effect that mandates regular vision monitoring for all patients receiving this medication. 1

Primary Ocular Toxicity: Visual Field Defects

The characteristic visual field defect is specific and severe:

• Bilateral concentric constriction within a 30° radius from fixation, consisting of nasal loss extending in an annulus over the horizontal midline with relative sparing of the temporal field 1
• The prevalence in adults is approximately 30%, though experts suspect it may be even more common, potentially affecting up to 40% of patients 1
• The defect is irreversible—neither recovery nor progression has been confirmed after drug withdrawal 1
• Asymptomatic visual field loss is extremely common, with studies showing that 8 of 12 patients (67%) with documented visual field constriction had no visual symptoms 2

Pathophysiology and Retinal Dysfunction

The mechanism involves cone and amacrine cell dysfunction in the retina:

• Electroretinography demonstrates abnormalities of cone function in adults, with loss of oscillatory potential responses suggesting impairment of highly GABAergic amacrine cells 1, 3
• Retinal cone system dysfunction is the primary pathologic finding, with reduced inner retinal cone response documented on ERG 3
• Four of ten patients tested electrophysiologically showed abnormal ERGs, five had abnormal electro-oculograms (EOG), and three had delayed visual evoked potentials (VEPs) 2

Additional Ocular Side Effects

Beyond visual field defects, vigabatrin causes multiple other ocular complications:

• Blurred vision occurs commonly (≥5% of patients in clinical trials) 4
• Diplopia (double vision) is reported in ≥5% of patients 4
• Nystagmus occurs in ≥5% of patients 4
• Corneal microdeposits are visible on slit-lamp examination in nearly all patients treated with amiodarone (note: this citation 1 refers to amiodarone, not vigabatrin—the evidence provided does not support corneal findings specific to vigabatrin)
• Compromised retinal microvascular perfusion and reduced pulsatile ocular blood flow have been documented in vigabatrin-treated epilepsy patients 5

Central Visual Dysfunction

Recent evidence demonstrates that vigabatrin toxicity is diffuse, affecting both peripheral and central vision:

• Disturbances in color perception, contrast sensitivity, and short-wavelength automated perimetry have been identified in patients receiving vigabatrin 5
• Two patients complained of blurred vision with abnormal ERGs despite normal VEPs and minimal findings on clinical ophthalmology examination 3
• Clinical ophthalmologic findings may include narrowed retinal arteries, surface wrinkling retinopathy, and abnormal macular reflexes 3

Critical Monitoring Requirements

Because confrontation testing does not reliably identify the defect, formal perimetry is mandatory:

• Adults and children with cognitive age >9 years should undergo visual field examination with Goldmann perimeter (I1e or I2e isopter and I4e or V4e isopter) or Humphrey field analyzer before vigabatrin is prescribed and ideally every six months 1
• For children aged <9 years, field-specific visual evoked potential techniques to assess peripheral vision are being evaluated but are not yet routinely available 1
• Electroretinography performed according to international standards may be useful in children when visual field testing is not feasible 1

Relationship to Duration and Dose

The temporal relationship between vigabatrin exposure and visual field defects remains unclear:

• The relation between duration of exposure to vigabatrin and development of the field defect is not known 1
• Visual symptoms may develop 2 to 40 months after starting the drug 3
• Current evidence suggests that the defect is unlikely to develop if perimetry gives normal results after more than three years of treatment 1

Common Pitfalls in Management

Several critical errors must be avoided:

• Do not rely on patient symptoms alone—asymptomatic visual field loss is the norm, not the exception 2
• Do not use confrontation testing as a screening tool—it does not reliably identify vigabatrin-associated visual field defects 1
• Do not assume ERG abnormalities predict visual field defects—in pediatric studies, there was no significant association between any ERG parameter and visual field defects 6
• Do not automatically withdraw vigabatrin in well-controlled patients—the decision requires careful risk-benefit analysis, particularly for infantile spasms where vigabatrin remains the drug of choice 1

Risk-Benefit Considerations

The continued prescription of vigabatrin requires individualized assessment:

• Vigabatrin remains the drug of choice for infantile spasms, and limited data suggest it could be withdrawn without relapse in infants who have been spasm-free for six months 1
• For refractory complex partial seizures, if seizures do not improve enough within 3 months in adults (or 2-4 weeks in infants with infantile spasms), vigabatrin should be discontinued 4
• Children taking vigabatrin whose seizures are well controlled should not automatically have the drug withdrawn 1
• Children who have or are at risk of developing visual defects due to other causes (e.g., surgery) should be prescribed vigabatrin with extreme caution 1