The effect of antiepileptic drugs on visual performance.

Visual disturbances are a common side-effect of many antiepileptic drugs. Non-specific retino- and neurotoxic visual abnormalities, that are often reported with over-dosage and prolonged AED use, include diplopia, blurred vision and nystagmus. Some anticonvulsants are associated with specific visual problems that may be related to the mechanistic properties of the drug, and occur even when the drugs are administered within the recommended daily dose. Vigabatrin, a GABA-transaminase inhibitor, has been associated with bilateral concentric visual field loss, electrophysiological changes, central visual function deficits including reduced contrast sensitivity and abnormal colour perception, and morphological alterations of the fundus and retina. Topiramate, a drug that enhances GABAergic transmission, has been associated with cases of acute closed angle glaucoma, while tiagabine, a GABA uptake inhibitor, has been investigated for a potential GABAergic effect on the visual field. Only mild neurotoxic effects have been identified for patients treated with gabapentin, a drug designed as a cyclic analogue of GABA but exhibiting an unknown mechanism while carbamazepine, an inhibitor of voltage-dependent sodium channels, has been linked with abnormal colour perception and reduced contrast sensitivity. The following review outlines the visual disturbances associated with some of the most commonly prescribed anticonvulsants. For each drug, the ocular site of potential damage and the likely mechanism responsible for the adverse visual effects is described.

Regional variability in visual field sensitivity during hypercapnia.

PURPOSE: Previous investigations have demonstrated a relative vascular autoregulatory inefficiency of the inferior compared to the superior retina in healthy subjects breathing increased CO(2). The purpose of this study was to determine whether the superior and inferior visual field sensitivities of healthy eyes are similarly affected during mild hypercapnia. DESIGN: Experimental study. METHODS: Visual field analysis (Humphrey Field Analyser; SITA standard 24-2 program) was carried out on one randomly selected eye of 22 subjects (mean age, 27.7 +/- 5 years) during normal room air breathing and isoxic hypercapnia. The Student paired t-tests were used to compare the visual field indices mean deviation (MD) and pattern standard deviation (PSD) for each breathing condition. A secondary, sectoral analysis of mean pointwise sensitivity was performed for each condition. In each case a P value of <.01 was considered statistically significant (Bonferroni corrected). RESULTS: Visual field MD was -0.23 +/- 0.95dB during room air breathing and -0.49 +/- 1.04dB during hypercapnia (P =.034). Sectoral pointwise mean sensitivity deteriorated by 0.46dB (P =.006) in the upper visual hemifield during hypercapnia, whereas no significant difference was observed for the lower hemifield (P =.331). CONCLUSIONS: The upper visual hemifield exhibited a significantly greater degree of deterioration in pointwise visual field mean sensitivity compared to the lower hemifield during hypercapnic conditions. This suggests that the upper visual hemifield and hence inferior retina is more susceptible to insult during hypercapnia than the superior retina in healthy individuals. A regional susceptibility of inferior retinal function to altered vascular or metabolic effects may account for the earlier and more frequent inferior nerve fibre damage associated with glaucomatous optic neuropathy.

Epilepsy patients treated with antiepileptic drug therapy exhibit compromised ocular perfusion characteristics.

PURPOSE: Reduced cerebral blood flow and decreased cerebral glucose metabolism have been identified in patients with epilepsy treated with antiepileptic drug (AED) therapy. The purpose of this study was to determine whether ocular haemodynamics are similarly reduced in patients with epilepsy treated with AEDs. METHODS: Scanning laser Doppler flowmetry was used to measure retinal capillary microvascular flow, volume, and velocity in the temporal neuroretinal rim of 14 patients diagnosed with epilepsy (mean age, 42.0 +/- 0.9 years). These values were compared with those of an age- and gender-matched normal subject group (n = 14; mean age, 41.7 +/- 0.3 years). Student's unpaired two-tailed t tests were used to compare ocular blood-flow parameters between the epilepsy and normal subject groups (p < 0.05; Bonferroni corrected). RESULTS: A significant reduction in retinal blood volume (p = 0.001), flow (p = 0.003), and velocity (p = 0.001) was observed in the epilepsy group (13.52 +/- 3.75 AU, 219.14 +/- 76.61 AU, and 0.77 +/- 0.269 AU, respectively) compared with the normal subject group (19.02 +/- 5.11 AU, 344.03 +/- 93.03 AU, and 1.17 +/- 0.301 AU, respectively). Overall, the percentage mean difference between the epilepsy and normal groups was 36.31% for flow, 28.92% for volume, and 34.19% for velocity. CONCLUSIONS: Patients with epilepsy exhibit reduced neuroretinal capillary blood flow, volume, and velocity compared with normal subjects. A reduction in ocular perfusion may have implications for visual function in people with epilepsy.

Patients treated with vigabatrin exhibit central visual function loss.

PURPOSE: To investigate visual function in the central 10 degrees in patients who have undergone vigabatrin (VGB) antiepileptic drug (AED) therapy with the aim of identifying a clinical regimen for assessing central visual function. METHODS: The sample comprised 12 epilepsy patients (mean age, 38.6 +/- 11.7 years) who had been treated with VGB (either as monotherapy or polytherapy). A number of central visual-function tests were carried out for each eye, including high-contrast LogMAR visual acuity, short-wavelength automated perimetry (SWAP 10-2), spatial contrast sensitivity (CSV-1000), and Farnsworth-Munsell (FM) 100-hue colour discrimination. RESULTS: The group mean cumulative VGB dose was 5,086 +/- 3,245 g. The average SWAP 10-2 mean deviation (MD) for the group was -3.24 +/- 3.23 dB; 14 eyes of eight patients showed defects (range, -1.62 to -9.46 dB). The square root of the group mean total error score for FM 100-hue was 7.42 +/- 3.84; nine eyes of five patients were classified as abnormal with an unsolved colour axis suggestive of complex drug interactions. For contrast sensitivity, 15 eyes of eight patients yielded abnormal results in one or more spatial frequencies. Defects were more prominent at higher spatial frequencies. Overall, four patients had defects in all three visual-function tests, six patients had mixed defects, and two patients were normal. CONCLUSIONS: Visual-function deficits in epilepsy patients treated with VGB are present in the central 10 degrees of the retina. We recommend a battery of investigations, including SWAP 10-2 and spatial contrast sensitivity testing, to assess central visual function.

Neurotoxic effects of GABA-transaminase inhibitors in the treatment of epilepsy: ocular perfusion and visual performance.

Vigabatrin is a GABA (gamma-aminobutyric acid) transaminase inhibitor that elicits an antiepileptic effect by enhancing inhibitory neurotransmission in the brain. Vigabatrin has been previously associated with concentric peripheral visual field loss and visual electrophysiological abnormalities. Recently, visual function deficits of the central retina have been identified in a proportion of patients receiving vigabatrin; these include disturbances in colour perception, contrast sensitivity and short-wavelength automated perimetry. Consequently, it is suggested that vigabatrin-associated retinal toxicity is diffuse inducing subtle central visual dysfunction and more severe peripheral visual defects. Reductions in cerebral blood flow and cerebral metabolic rate for glucose occur in epilepsy patients receiving antiepileptic drug therapy. Despite the known cerebral haemodynamic alterations in epilepsy and the visual consequences of vigabatrin therapy, ocular blood flow has only recently been investigated in this group. We present findings from a series of novel investigations that identify compromised retinal microvascular perfusion and pulsatile ocular blood flow (POBF) in epilepsy patients. The reduction in POBF was exacerbated in epilepsy patients treated with vigabatrin compared to conventionally treated epilepsy patients. A number of theories are presented to explain compromised ocular blood flow in vigabatrin treated epilepsy patients, and the possibility of a GABAergic mechanism of toxicity is discussed.