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Antiepileptic Drugs and Visual FunctionAlberto Verrotti, MD, PhD*, Rossella Manco, MD*, Sara Matricardi, MD, PhD*,

Emilio Franzoni, MD†, and Francesco Chiarelli, MD*

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ntiepileptic drugs are known to result in visual distur-ances. A number of antiepileptic drugs have recentlyeen reported to result in various abnormalities of vision,articularly deficiencies in visual fields and color vision.oreover, there has been a marked improvement in

he diagnosis and understanding of the pathophysiol-gy of visual disturbance. This review collects evidenceor visual adverse effects induced by the older antiepi-eptic drugs (barbiturates, benzodiazepine, carbamaz-pine, valproic acid, ethosuximide, and phenytoin) andhe newer ones (vigabatrin, topiramate, tiagabine, le-etiracetam, lamotrigine, gabapentin, felbamate, andxcarbazepine). © 2007 by Elsevier Inc. All rightseserved.

errotti A, Manco R, Matricardi S, Franzoni E, Chiarelli. Antiepileptic drugs and visual function. Pediatr Neurol007;36:353-360.

ntroduction

In epileptic patients, visual disturbances are not rare.hese problems may be caused by either the epilepsy pere or by the anticonvulsant therapy used to control theeizures. Antiepileptic drugs may cause many adverseffects, and one of the most frequent is visual dysfunction,ecause the eye is very susceptible to the dose, duration,nd mechanisms of action of many antiepileptic drugs.n recent years, alterations of visual function have beenxtensively studied in epileptic patients treated with dif-erent antiepileptic drugs.

The objective of this literature review is to clarify theink between antiepileptic drugs and visual function dis-urbances.

rom the *Department of Pediatrics, University of Chieti, Chieti, Italy,nd the †Department of Pediatrics, University of Bologna,ologna, Italy.

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2007 by Elsevier Inc. All rights reserved.oi:10.1016/j.pediatrneurol.2007.03.001 ● 0887-8994/07/$—see front matter

ntiepileptic Drugs

arbiturates

Barbiturates enhance gamma-aminobutyric acid (GABA)-ediated increases in chloride conductances by prolonging

he duration of channel opening [1]. Very few reports haveeen shown on the correlation between barbiturates andisual function.Schwankhaus et al. [2] described a 37-year-old man

ith a history of seizures who developed periodic alter-ating nystagmus due to primidone/phenobarbital toxicity.he signs gradually resolved with discontinuation of therugs. No other reports are available.

enzodiazepines

The most common benzodiazepines used are clonaz-pam, diazepam, and lorazepam. These act at distinctllosteric binding sites on the GABAA receptor-chlorideonophore to enhance GABA-mediated increases in chlo-ide conductances [3]. Stafanous et al. [4] conducted atudy to verify the effect of long-term use of benzodiaz-pines on the eye and retina. Of 30 patients who under-ent full ophthalmoscopic examination, 19 complained of

rritation, blurred vision, or difficulty in reading, but nonead reduced visual acuities.For diazepam, cases of retinopathy, maculopathy, and

cute glaucoma associated with diazepam treatment haveeen reported [5,6].

Studies have shown an effect of lorazepam on visualerception. In a study of the effects of this drug oninocular vision, visual acuity, and accommodation,peeg-Schatz et al. [7] demonstrated that a single dose of

orazepam induces an esophoric oculomotor imbalance,mpaired fusional convergence, and divergence amplitudesbut without impairing visual acuity or accommodation).

ommunications should be addressed to:r. Verrotti; Department of Pediatrics; University of Chieti;spedale Policlinico; Via dei Vestini 5; 66100 Chieti, Italy.

-mail: averrott@unich.iteceived September 25, 2006; accepted March 22, 2007.

353Verotti et al: Antiepileptic Drugs and Visual Function

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Long-term benzodiazepine medication has little effectpon visual acuity and retinal function.

arbamazepine

Carbamazepine is a widely used antiepileptic drug forartial and generalized tonic-clonic seizures. Its mecha-ism of action is to inhibit high-frequency neuronal firingy blocking the voltage-gated sodium channels [8].Therapy with carbamazepine can cause nystagmus,

iplopia, and blurred vision [9]. These visual disturbancesay be caused by either therapeutic or toxic doses.chwartzman and Leppik [10] found that carbamazepine

nduced dyskinesia and ophthalmoplegia; in particular,ne case with ocular skew deviation and down-beatingystagmus was associated with a high therapeutic level,nd another case with systemic dyskinesia was related tooxic carbamazepine level. Moreover, Berchou and Rodin11] reported oculogyric crisis as an idiosyncratic reactionf carbamazepine.In a group of healthy volunteers, altered saccadic eyeovements and smooth pursuit eye movements after

arbamazepine administration were reported [12].Yuksel et al. [13] studied the effects of carbamazepine

n visual evoked potentials, after 1 year of treatment,isual evoked potentials P100 latencies were significantlyrolonged in correlation with serum drug levels. Patientsn that study also exhibited a significant increase of peakatencies of waves I-III-V and interpeak interval I-V,ompared with healthy controls. Thus, carbamazepine canause a slowing down of central impulse conduction. Datarom a previous study by our group [14] confirm theseesults, and suggest that central impulse conduction de-reases and synaptic transport is impaired in patientseceiving carbamazepine.

Recent studies [15,16] found color disturbances duringreatment with carbamazepine. Visual color perceptionas impaired, particularly in the blue-yellow axis. Theegative effect of carbamazepine upon color vision, botharacentral and central, is probably due to changes at theevel of retinal processing [17]. Generally, color vision is

sensitive indicator of antiepileptic drug-induced retinaloxicity, a sign of inhibitory influence in the retinaletwork and not related with the specific mechanism ofction of the drug.

Nousiainen et al. [18] investigated possible changes inontrast sensitivity, macular photostress, and brightnesscuity (glare) in patients with epilepsy treated with car-amazepine monotherapy. They evaluated 18 carbamaz-pine monotherapy patients treated for an average of 60onths and found no effect on contrast sensitivity and no

lteration in glare sensitivity.Carbamazepine seems to cause irreversible clinical

isual impairment. The effect on color perception suggests

retinal toxicity. s

54 PEDIATRIC NEUROLOGY Vol. 36 No. 6

lobazam

Clobazam is a benzodiazepine in which the imine groupn the fourth and fifth position of the diazepine ring isubstituted by an amide. It is better tolerated than otherenzodiazepines, it is highly effective, and it has a rapidnset of action [19]. This drug is used in first-linedjunctive therapy for refractory partial and generalizedeizures, for intermittent therapy, and for nonconvulsivetatus epilepticus [20]. A single case of retinopathy in aatient with a history of long-term use of clonazepam haseen reported [21], and reports of visual disturbancesollowing clonazepam are scarce.

thosuximide

Ethosuximide is one of the major therapeutic antiepi-eptic drugs for the management of absence seizures, buthe mechanism of action is not completely known. Prob-bly, it alters neurotransmitter release and also controlsodium conductance.

No adverse visual side effects are associated with thisntiepileptic drug, apart from diplopia, which can beonsidered a nonspecific visual effect [1].

elbamate

Felbamate is an antiepileptic drug that acts on bothxcitatory and inhibitory brain mechanisms by blockingurrents evoked by N-methyl-d-aspartate and by facilitat-ng GABAergic responses [22]. The adverse visual sideffects are diplopia and nystagmus [23]. An isolated casef reversible downbeat nystagmus and ataxia has beeneported following felbamate intoxication [24].

abapentin

Gabapentin is a cyclic GABAergic analog and acts as aABA agonist [25], but the GABAergic mechanism is not

ompletely known.In a study on 599 epileptic patients treated with oral

abapentin, adverse effects included blurred vision andiplopia [26]. In another study, changes in visual evokedotentials and an abnormal pattern of the electroretinog-aphy were found in patients treated with gabapentin [27];t has been suggested that an individual predisposition tooxic effects on the transmitter function of the optic nerveight be responsible.A recent study investigated the oral gabapentin treat-ent in symptomatic patients with the Heimann-ielschowsky phenomenon [28]. This phenomenon is aonocular, vertical nystagmoid movement characterized

y slow, coarse, pendular movement of variable amplituden an eye with profound visual loss. The origin of theserifts is unknown, but probably involves disruption of theusional vergence mechanism as the monocular visual

tabilization system. In this study, a 57-year old patient

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ith retinitis pigmentosa and a 12-month history ofertical oscillopsia was evaluated after 2 months of ther-py with gabapentin. The vertical nystagmoid movementn Heimann-Bielschowsky phenomenon was considerablyeduced and the visual acuity remarkably improved.

This antiepileptic drug probably can have an effect onisual pathways, influencing the function of the opticerve. This effect seems to be reversible.

amotrigine

Lamotrigine is an antiepileptic drug with a wide spec-rum of efficacy. It acts through the inhibition of voltage-ependent sodium channels and inhibits voltage-activatedalcium currents [29]. Lamotrigine influences the releasef excitatory neurotransmitters, particularly inhibiting glu-amate [30].

The effects on vision in patients receiving lamotrigineonotherapy were evaluated by Arndt et al. [31], in

linical and electrophysiologic investigations: no adverseffects on visual function were documented. Only theatients with a high dose of lamotrigine had an apparentisual field constriction comparable to vigabatrin retinop-thy, but the normalization of the visual field after doseeduction of lamotrigine suggests that retinal damage iseversible.

Lamotrigine treatment may also induce significant ele-ation of GABA levels in the brain; consequently, retinalABA levels may also be higher (as demonstrated forigabatrin). This mechanism of action can be explained byhe electrophysiologic changes observed after lamotrigineherapy. Among adverse effects, visual blurring is reportedy 23% of the patients receiving lamotrigine monotherapy32]. Diplopia and rotary nystagmus can occur in cases ofcute toxicity following lamotrigine overdose [33].

Lamotrigine causes symptomatic visual problems onlyery rarely.

evetiracetam

Levetiracetam is a new antiepileptic drug, very wellolerated, that has recently been proven effective in con-rolling refractory partial seizures in adults [34].

The main cellular mechanisms thought to account forhe antiseizure activities of the established antiepilepticrugs refer either to facilitating inhibitory GABAergiceurotransmission [35] and inhibiting excitatory glutamateeceptors [36] or to blocking voltage-gated Na� or Ca��hannels [37,38].

Levetiracetam seems to be an effective and well-olerated antiepileptic drug. No visual abnormalities haveeen described [39].

xcarbazepine

Oxcarbazepine is an antiepileptic drug indicated as

irst-line therapy for the treatment of partial and second- c

rily generalized tonic-clonic seizures [40,41]. Oxcarbaz-pine has properties similar to those of carbamazepine, butas a better tolerability profile. It blocks sodium channelsnd interrupts high-frequency repetitive firing of neurons42]. N-calcium channel blockade is expected to dampynaptic activity broadly [43]; opening of potassium chan-els and blockade of N-methyl-d-aspartate receptor-medi-ted activity could limit burst activity [44-46].

The most common adverse effects associated withxcarbazepine are related to the central nervous systemnd include diplopia [47]. Fisher et al. [48] reportedlurred vision in 10% of epilepsy patients studied. Zaccarat al. [49] demonstrated that oxcarbazepine induced subtlelterations, with saccadic and smooth-pursuit eye move-ents.Considering these data, oxcarbazepine seems to be a

afe antiepileptic drug, without important visual impair-ent. Oxcarbazepine is associated with significantly fewer

isual adverse effects than carbamazepine, another factorhat could suggest a switch from carbamazepine to oxcar-azepine.

henytoin

Phenytoin has effective anticonvulsant action and it isn effective compound for treating generalized tonic-lonic seizures [50,51] and status epilepticus [52,53].henytoin has been shown to modify sustained repetitiveiring by blockade of the voltage-gated sodium channel54,55].

In an investigation of phenytoin toxicity in healthyolunteers, both horizontal gaze-evoked nystagmus andertical gaze-evoked nystagmus were found [56]. Revers-ble external ophthalmoplegia was observed in one patientollowing oral administration of phenytoin [57].

The effect of phenytoin on color vision, as tested by thearnsworth-Munsell 100 Hue Test, spectral sensitivity,nd tritan screening plates, has been addressed in severaltudies [15,58]. Color perception was found to be im-aired, and the most significant abnormality detected wasn the blue-yellow axis. These findings support the dele-erious effect of phenytoin upon color vision discrimina-ion, most likely due to changes at the level of retinalrocessing. Furthermore, there was a significant correla-ion between signs of phenytoin-induced neurotoxicity andlue-yellow color vision deficiencies. The present reviewdentified no other reports of visual disturbances.

The visual impairment induced by phenytoin seems toe rare and is reversible.

iagabine

Tiagabine is a new-generation antiepileptic drug usedgainst refractory partial epilepsy [59]. It has a GABAergicction and increases GABA levels in the extracellular fluidf the brain and the cerebrospinal fluid [60]. Tiagabine can

ause blurred vision, diplopia, and nystagmus in associa-

355Verotti et al: Antiepileptic Drugs and Visual Function

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ion with overdose and neurotoxicity, as previously de-cribed [61,62].

One study compared visual function between groups ofatients treated with vigabatrin, tiagabine, and other anti-pileptic drugs [63]. In contrast to the findings withigabatrin, patients in tiagabine treatment had normallectroretinography, visual field, and ophthalmologicalunction. Differences in retinal drug concentrations be-ween vigabatrin and tiagabine might explain why tiaga-ine does not cause retinal injury. Another study, however,ound that patients treated with tiagabine developed visualield defects [64]. These conflicting findings may bettributable to methodological problems.

Acquired color vision deficit was examined with thearnsworth-Munsell 100 Hue Test in a recent study [65].f 20 patients receiving tiagabine monotherapy, 41% had

olor vision deficit, suggesting that tiagabine may interfereith color perception. They found no correlation with theose and the duration of the exposure and color visionefects [65].Tiagabine seems to affect color vision frequently; how-

ver, the effect generally is reversible after discontinuationf therapy.

opiramate

Topiramate is a sulfamate-substituted monosaccharidehat modulates the voltage-gated sodium and calciumhannels, blocks kainite/AMPA (i.e., kainite/�-amino-3-ydroxy-5-methyl-4-isoxazolepropionic acid) type of glu-amate receptors, and increases GABAergic inhibition66]. Topiramate may cause idiosyncratic ciliochoroidaletachment and ciliary body edema, leading to anteriorisplacement of the lens-iris diaphragm, lens thickening,nd acute angle-closure glaucoma.

Banta et al. [67] described a case of reversible bilateralngle-closure glaucoma in a 51-year-old man, whicheveloped 2 weeks after the beginning of topiramatereatment.

Nemet et al. [68] reported a case of bilateral acute anglelosure glaucoma in a 64-year-old woman 2 weeks aftereginning topiramate therapy. Topiramate was discontin-ed, and a gradual deepening of the anterior chamber andesolution of the choroidal edema were accompanied bymprovement of visual acuity and corneal clarity. Craigt al. [69] described two women who developed acuteyopia, one of whom also developed bilateral angle

losure glaucoma. Topiramate was discontinued, and an-erior chamber shallowing was seen in both patients. Thus,opiramate may be associated with ciliochoroidal effusionith forward displacement of the lens-iris diaphragm and

nterior chamber shallowing, resulting in acute myopiand angle-closure glaucoma.

Fraunfelder et al. [70] conducted a large study tovaluate adverse visual side effects associated with topi-

amate: 115 case reports were reviewed, with the conclu- r

56 PEDIATRIC NEUROLOGY Vol. 36 No. 6

ion that topiramate therapy caused abnormal vision (3ases), acute secondary angle-closure glaucoma (85ases), acute myopia (17 cases), and suprachoroidal effu-ions (9 cases). All findings were reversible. In manyatients, the first presenting symptom of acute secondaryngle-closure glaucoma was blurred vision [70]. Anotherase of acute myopia and acute angle-closure glaucoma inhe early stage of topiramate therapy that subsided rapidlyith prompt discontinuation was reported by Bhatta-

haryya and Basu [71].Topiramate is a very useful drug for the treatment of

pilepsy, but it is necessary to be aware of its important, ifeversible, adverse visual side effects: acute bilateralngle-closure glaucoma, acute myopia, and ciliochoroidaletachment.

alproic Acid

Valproic acid is a broad-spectrum antiepileptic drug thatas been in use as a first-line agent for both generalizednd partial seizures. Valproic acid blocks voltage-depen-ent sodium channels and modifies calcium and potassiumonductance [72]. Administration of valproic acid in-reases activity of GABA-synthetic enzyme glutamic acidecarboxylase and acts as an inhibitor of GABA transam-nase [73]. Valproic acid can suppress visual evokedotentials in rats, and also in human children, via aABAergic mechanism. Recently, our group found that

he patients treated with valproic acid showed a significantncrease in visual evoked potential P100 latencies evenfter 12 months of therapy, in presence of normal bloodevels of this antiepileptic drug [14].

Sorri et al. [74] recently investigated whether initialalproic acid monotherapy for the treatment of epilepsyauses visual field defects or other visual dysfunction. Allatients had normal contrast sensitivity function and noisual field defects such as develop with vigabatrin treat-ent, but valproic acid did induce abnormalities in color

ision. It has been demonstrated [15,17] that adolescentpilepsy patients treated with valproic acid or carbamaz-pine monotherapy develop deficits in color vision after ahort treatment period. The negative effects of valproiccid upon color vision discrimination is most likely due tohanges at the level of retinal processing.

In yet another group of patients, no visual field abnor-alities were found [75]. Only one case of a 25-year-oldoman treated with valproic acid and later with carbam-

zepine presented visual field defects similar to thoseescribed with vigabatrin. Genetic predisposition mayave been responsible for this particular case.All these data suggest that valproic acid sometimes hassubclinical effect on color vision that can be diagnosed

sing chromatic perimetry. This effect does not seem to be

are, but it is reversible.

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igabatrin

Vigabatrin is a structural analog of GABA whichetermines irreversible, specific inhibition of GABA-ransaminase [76,77]. It is associated with visual fieldonstriction and other visual disturbances [78].

Visual dysfunction became a pressing issue after alarm-ng reports began to appear in 1997 about irreversiblympaired visual fields in some patients on chronic vigaba-rin therapy. The mechanisms behind the visual fieldefects are still not known, but there is some indicationhat there may be a reduction in cones, which may be dueo dysfunction of GABAergic cells of the inner retina [79].igabatrin increases GABA levels and it enhances inhib-

tory neurotransmission in the brain; this could be theause of many adverse visual side effects: diplopia,ystagmus, peripheral visual field loss, changes in colorerception, reduced contrast sensitivity, and reduced ocu-ar blood flow [1]. Vigabatrin therapy is associated mainlyith a loss of visual field in approximately 40% of patients

80]. The field defects appear with differing levels ofeverity, but the common feature is a bilateral concentriconstriction with varying extents of temporal field preser-ation [81].Researchers at the Hospital for Sick Children (Toronto,

anada) evaluated 138 patients for evidence of possibleigabatrin toxicity and showed clinical findings of periph-ral retinal nerve fiber layer atrophy with relative sparingf the central or macular portion of the retina in threeatients, without any clinical disturbances [82]. One of thenitial reports about visual field defects was that of

ackenzie and Klistorner in 1998 [79]. They found that,lthough some patients reported the visual defects, mostere asymptomatic. Kalviainen et al. [83] conducted a

tudy with 19 patients on carbamazepine monotherapy and2 patients on vigabatrin monotherapy, all of whom werenalyzed with visual field testing. Of the patients onigabatrin, 41% showed asymptomatic concentric visualield defects, compared with 0% for carbamazepine.

The deficits seem to be irreversible. Appearance ofigabatrin-induced visual field loss in the central field outo 30° eccentricity is typically localized to bilateral nasal.verall prevalence is approximately 20 to 40%, and is

wice as high in men than in women [81,83,84]. A possibleelationship of visual changes with time on vigabatrin andith cumulative dose of the drug taken has been suggested

85,86]. Moreover, there is evidence that visual field losss less likely to occur after the first 4 years of continuousreatment [81]: in fact, several studies have reported atrong relationship between visual field defects, durationnd total dose of vigabatrin. Visual field defects were in aubstantial percentage progressive [87]. Long-term treat-ent with vigabatrin seems to selectively reduce retinal

one function [88].Besch et al. [89] investigated functional, morphological

nd electrophysiological changes in 20 epilepsy patients

reated with vigabatrin. Visual acuity, anterior and poste- p

ior segments, color vision, and dark adaptation thresholdsere normal in all patients. Eighteen patients presentedisual field constriction; they showed altered oscillatoryotentials waveforms in the ERG [89]. These data indicaten effect of vigabatrin on the inner retinal layers.

Another study, by Harding et al. [90], used an electro-hysiological approach with visual-evoked potential tech-ique to identify visual field defects in children treatedith vigabatrin who were unable to perform perimetry.he study sample was 39 children aged 3 to 15; of these,2 patients were examined by both the field-specifictimulus test and perimetry. A field-specific visual evokedotentials was developed with a central and peripheraltimulus, and electroretinography were performed. Theiagnostic performance of the field-specific stimulus testas compared with perimetry. The results indicate that

ield-specific visual evoked potentials technique is wellolerated by children older than 2 and that the technique isensitive and specific in identifying vigabatrin-associatederipheral field defects [90].A characteristic form of peripheral retinal atrophy or

inverse” optic disc atrophy can occur in a small numberf children treated with vigabatrin. These changes areccompanied by retinal dysfunction, and so discontinua-ion of vigabatrin should be strongly considered [82].

In a study using the Farnsworth-Munsell 100 Hue Testn patients who had undergone add-on treatment withigabatrin, 33% showed an impairment in color discrimi-ation [91]. (Similar findings by Sorri et al. [74] foralproic acid are discussed in that section.) The findingsuggest a retinal toxic damage affecting all chromaticathways [1].The natural history of the vigabatrin retinopathy re-ains unknown. In a retrospective analysis of patients

eceiving long-term vigabatrin, Kinirons et al. [92] foundhat vigabatrin toxicity-induced development of visualonstriction is unrelated to daily dose, duration of therapy,r cumulative dose. They concluded that field defects mayevelop within the first few years of therapy and possiblyemain stable thereafter [92].

Recently, Wild et al. [93] tried to quantify retinal nerveiber layer thickness and macular thickness in patientsxhibiting vigabatrin-attributed visual field loss, and toetermine the efficacy of these measures as markers of theetinal damage. This study involved patients with visualield loss, patients exposed to vigabatrin, patients receiv-ng carbamazepine or valproic acid monotherapy, andealthy subjects. For each participant, the eyes underwentwo digital imaging modalities: ocular coherence tomog-aphy and scanning laser ophthalmoscopy. The patientsxposed to vigabatrin who suffered from vigabatrin-nduced visual field loss had a significant reduction ofetinal nerve fiber layer thickness. These data suggesthat the ocular coherence tomography of the retinalerve fiber layer can identify vigabatrin-induced dam-ge [93]. Thus, when vigabatrin therapy is necessary for

atients with resistant epilepsy, visual field testing

357Verotti et al: Antiepileptic Drugs and Visual Function

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hould be performed at the start of treatment and ategular intervals thereafter [1].

Although many questions are still open (e.g., whenxactly in the course of treatment does the problemccur?), the possibility of vigabatrin-related visual fieldefects must be considered in every patient. This isarticularly important for pediatric patients who are un-ble to perform perimetry. The data concerning visualoxicity of vigabatrin should encourage physicians to limithe duration of treatment, not beyond its indication.

onclusions

In recent years, the effects of antiepileptic drugs onisual function have been extensively collected and stud-ed. Table 1 summarizes the main adverse visual sideffects of the antiepileptic drugs most commonly used.lobazam effects are included in the benzodiazepine.Much controversy remains concerning the prevalence,

everity, and clinical significance of most of these effects.uch uncertainty reflects in part the unresolved questionsertaining to the different mechanisms of action of thentiepileptic drugs. Among the commonly used antiepi-eptic drugs, the large majority are associated with nonse-ious visual adverse events, mild to moderate in intensity.hese adverse effects seem to be reversible after discon-

inuation of therapy.It must be stressed that new antiepileptic drugs are

pproved on the basis of controlled clinical trials in aimited number of patients. Although such trials enable us

able 1. The main adverse visual side effects of the antiepileptic d

Drug Adverse Visual Side Effects

arbiturates Periodic alternating nystagmusenzodiazepines Blurred vision, retinopathy, maculopathy, glaucom

oculomotor imbalance, impaired fusionalconvergence

arbamazepine Nystagmus, diplopia, blurred vision, dyskinesia,ophthalmoplegia, impaired color vision, abnormvisual evoked potentials

thosuximide Diplopiaelbamate* Diplopia, nystagmusabapentin* Blurred vision, diplopia, changes in visual evoked

potentialsamotrigine* Diplopia, rotary nystagmus, visual blurringevetiracetam* No adverse visual side effectsxcarbazepine* Diplopia, blurred vision, saccadic movementshenytoin Nystagmus, ophthalmoplegia, impaired color

perceptioniagabine* Blurred vision, nystagmus, diplopiaopiramate* Glaucoma, myopia, ciliochoroidal detachmentalproic acid Impaired visual evoked potentials, visual field

defects, deficits in color visionigabatrin* Visual field loss, diplopia, nystagmus, reduced col

discrimination, impaired visual evoked potentialreduced ocular blood flow, retinal atrophy

In the class of newer antiepileptic drugs.

o see the most common adverse effects of the new p

58 PEDIATRIC NEUROLOGY Vol. 36 No. 6

edication, it is only with postmarketing surveillance,hen the drug has had a large patient population exposure,

hat we can begin to appreciate the full adverse potential.Furthermore, except for carbamazepine and valproic

cid, there is little clear evidence-based information con-erning the older antiepileptic drugs. Many studies havenvolved only small numbers of patients, with differencesn age and type of epilepsy, and often with polytherapy.he possibility of adverse visual side effects in epilepsyatients should be kept in mind by physicians, and honestnd comprehensive information should be given to theatients.In particular, there is suggestive evidence about a strict

elation between visual changes and vigabatrin. This factust be considered by physicians and a careful ophthal-ological follow-up should be conducted at regular inter-

als after initiation of therapy with vigabatrin.

eferences

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viewed

Reversibility FrequencyStrength ofEvidence

eversible Very rare Faireversible Moderate Poor

eversible-irreversible, dose-related Moderate Fair

eversible Very rare Pooreversible, dose-related Very rare Pooreversible Very rare Poor

eversible, dose-related Rare Poor

nknown Very rare Pooreversible Rare Fair

eversible Frequent Pooreversible Rare Pooreversible Rare Fair

eversible-irreversible, dose-related Very frequent Good

rugs re

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