Topiramate-induced bilateral angle-closure glaucoma

Topiramate-induced bilateral angle-closure glaucoma Jaime Levy, MD; Ronit Yagev, MD; Alena Petrova, MD; Tova Lifshitz, MD ABSTRACT • RÉSUMÉ Case report: We present an interventional case report of a rare occurrence of acute angle-closure glaucoma in a 35-year-old woman presenting 1 week after start of oral topiramate therapy for depression. Intraocular pressure measured 57 mm Hg OD and 56 mm Hg OS, and bilateral shallow anterior chamber and closed angles were observed. Ultrasound disclosed ciliochoroidal detachment, a closed angle with a forward shift of the lens, and swollen ciliary processes. Topiramate treatment was stopped. Antiglaucoma treatment was started and quickly tapered. After 5 days, examination showed deep anterior chambers and normal intraocular pressures with no medication. Comments: Topiramate use can result in acute bilateral angle-closure glaucoma, which is usually reversible if the drug is discontinued. Patients starting topiramate therapy need to be informed of this potential risk. Observation : Nous faisons état d’une intervention pour un cas rare de glaucome aigu par fermeture de l’angle, survenu une semaine après le début d’un traitement au topiramate par voie orale. Une femme de 35 ans s’est présentée avec une douleur et une vision floue aux deux yeux, qui durait depuis plusieurs heures, une semaine après avoir entrepris un traitement au topiramate par voie orale pour soigner une dépression. La pression intraoculaire était de 57 mm Hg OD et 56 mm Hg OS. À l’examen, nous avons observé que la chambre antérieure des deux yeux était peu profonde et les angles, fermés. L’ultrason a révélé un décollement ciliochoroïdien, un angle fermé avec déplacement de lentille vers l’avant et des procès ciliaires enflés. Le traitement au topiramate a été arrêté. Un traitement antiglaucomateux a été entrepris et rapidement sevré. Après 5 jours, l’examen a fait voir une chambre antérieure profonde et des pressions intraoculaires normales sans médicament. Commentaires : Le topiramate peut entraîner un glaucome aigu par fermeture de l’angle qui s’avère ordinairement réversible si l’on cesse le médicament. Il faut informer les patients qui commencent un traitement au topiramate de ce risque potentiel.

From the Department of Ophthalmology, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer-Sheva, Israel Originally received Mar. 14, 2005 Accepted for publication Aug. 26, 2005 Correspondence to: Dr. Jaime Levy, Department of Ophthalmology, Soroka University Medical Center, P.O. Box 151, Beer-Sheva 84101, Israel; fax +972-8-640-3927; [email protected] This article has been peer-reviewed. Can J Ophthalmol 2006;41:221–5

Topiramate-induced angle-closure glaucoma—Levy et al

T

opiramate (Topamax; Ortho-McNeil Neurologics, Inc., Titusville, NJ) is an oral sulfamate medication used primarily for seizure treatment that also demonstrates preliminary efficacy in the treatment of bipolar disorders and pain control of migraine.1 Since July 2001, when Banta et al2 first reported a case of secondary angle-closure glaucoma associated with topiramate use, several cases of ocular side effects associated with topiramate have been published.

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A

Fig. 1—Slit-lamp photograph of the right eye at presentation revealing shallowing of the anterior chamber.

B

The presenting symptom in the majority of patients was blurring of vision.3 We herein present a rare case of acute angle-closure glaucoma in a patient presenting 1 week after starting oral topiramate therapy, and we review reports of topiramate-associated ocular side effects. CASE REPORT

A 35-year-old woman presented to the emergency department with a 6-hour history of bilateral eye pain and blurry vision. Her medical history was notable for noninsulin-dependent diabetes mellitus and depression. Her ocular history was unremarkable, she had never worn glasses, and she denied ocular disease within the family. Her medications included oral topiramate at 50 mg twice daily, which she had started 1 week before initial examination. At presentation her visual acuity was 20/200 OU. In both eyes, slit-lamp examination revealed conjunctival chemosis and injection, corneal edema, and markedly shallow anterior chamber (Fig. 1). Intraocular pressure measured 57 mm Hg OD and 56 mm Hg OS. Gonioscopy revealed closed angles. Pupils were reactive and lenses were clear. Hazy view of the optic nerve revealed normal cup:disc ratios of 0.2 in both eyes. A-scan and B-scan ultrasonography revealed anterior chamber depth of 0.8 mm OU and 360° ciliochoroidal detachment in both eyes (Fig. 2A). Ultrasound biomicroscopy demonstrated a closed angle with a forward shift of the lens, and swollen ciliary processes (Fig. 3).

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Fig. 2—A. B-scan ultrasound of the left eye at the time of initial examination showing choroidal effusions (arrow). B. Repeat B-scan ultrasound of the left eye 5 days after presentation demonstrating resolution of the uveal effusion.

The diagnosis of bilateral angle-closure glaucoma was made. The patient was treated with 0.1% dexamethasone sodium phosphate, brimonidine tartrate, 0.5% timolol maleate, latanoprost, 250 mg oral acetazolamide 4 times per day, and 120 mL oral glycerol. Her pressures eventually decreased to 32 mm Hg OD and 30 mm Hg OS. On the following day, the anterior chambers were still shallow in both eyes. Refraction was unsuccessful because of the persistence of corneal edema. After consultation with the patient’s psychiatrist, topiramate treatment was stopped. Antiglaucoma treatment was rapidly tapered and stopped. Five days after presentation, her vision returned to 20/20 OU. Manifest refraction revealed emmetropia. Slit-lamp examination showed clear


corneas and deep anterior chambers of 2.4 mm. Her intraocular pressures were 13 mm Hg OD and 14 mm Hg OS without medication. Gonioscopy revealed open angles without synechiae in both eyes. Repeat B-scan ultrasound revealed resolution of the ciliochoroidal effusion (Fig. 2B). COMMENTS

Topiramate is a sulfamate-substituted monosaccharide. Several mechanisms elicit its antiseizure effect:4 a state-dependent blocking of sodium channels; enhanced GABA(γ-aminobutyric acid)-mediated chloride fluxes across the postsynaptic membrane; positive modulation of GABA-A receptors; kainite inhibition activating AMPA (α-amino-3-hydroxy-5methylisoxazole-4-propionic acid) receptors; and a mild effect from carbonic anhydrase inhibition. Topiramate is also used in the management of migraine, depression, and neuropathic pain.3 Offlabel, it has gained popularity as a weight-reduction agent and for treating bipolar disorders.3 The following side effects have been observed with topiramate therapy, according to the World Health Organization classification system: abnormal vision, acute secondary angle-closure glaucoma, acute myopia, and suprachoroidal effusions.3 Since September 2001 when Ortho-McNeil Pharmaceuticals sent out a safety alert to healthcare professionals indicating 23 cases of acute angle-closure glaucoma related to topiramate use,5 more than 100 cases of ocular side effects have been reported. The majority of reported adverse events have occurred in female patients (up to 89%).6 Although the median age for all patients was 36 years,3 ocular side effects have also been reported in children.7 Acute elevation of intraocular pressure usually occurred within the first 3 weeks of start of topiramate therapy, and patients were typically taking topiramate doses within the normal therapeutic range.3,8 In only a few cases was the presentation unilateral. Management of topiramate-related acute pressure elevation requires cessation of the drug after consultation with the prescribing physician. Antiglaucoma medication may be needed initially during the first hours or days until the pressure returns to normal values. If unrecognized as a drug-related event, cases of permanent vision loss can occur.3 Acute myopia up to –8.75 diopters has also been described after starting topiramate.3,9 The pathophysiology of this phenomenon remains unclear, and

Fig. 3—Ultrasound biomicroscopy of the right eye obtained at initial examination showing ciliary body swelling (CB), uveal effusions (*), and a closed angle (arrow); (S = sclera).

several theories have been proposed to explain the underlying mechanism. Some authors suggest that forward displacement of the lens is caused by supraciliary effusion, which has been better characterized with ultrasound biomicroscopy.1,2,9–11 Fluid accumulation in the supraciliary space with ciliary body detachment is the main factor producing anterior rotation of the ciliary body. This rotation pushes the iris anteriorly and closes the angle. A small change in lens thickness has been noted, which may result from effusion-induced forward displacement of the lens–iris diaphragm, causing reduced zonular tension. Fluid movement in choroidal effusion could be related to drug-induced changes in membrane potential associated with topiramate. The finding of effusion in only a few patients taking topiramate, however, suggests that it is an idiosyncratic reaction. Other authors postulate that acute myopia could be caused by lenticular swelling, forward rotation of the lens–iris diaphragm, allergic ciliary body swelling causing increased curvature of the lens surfaces, and (or) a spasm of accommodation.3,8 In these reports, the induced myopia was related to lens thickening in 87% of cases and to anterior lens displacement in 13%. Ciliary body edema results in exaggerated relaxation of the zonules, with lens thickening and anterior movement of the entire lens. Finally, topiramate’s weak inhibition of carbonic anhydrase or an effect mediated by prostaglandin has also been suggested as causative of the myopia.10


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Table 1—Drugs reported to cause acute bilateral angle-closure glaucoma

Table 2—Other reported causes of acute bilateral angle-closure glaucoma

Adrenergic agonists

Ocular diseases/procedures

Ephedrine Epinephrine (adrenaline) Phenylephrine

Salbutamol (albuterol) Noncatecholamine adrenergic agonists

Amphetamine Dextroamphetamine Methamphetamine Phendimetrazine

Pilocarpine Cholinergic agents

Acetylcholine Carbachol Atropine Cyclopentolate Disopyramide Homatropine Ipratropium Bromide Tropicamide Acetazolamide Cotrimoxazole (trimethoprimsulfamethoxazole) Hydrochlorothiazide Topiramate Dexfenfluramine Fluoxetine Fluvoxamine Imipramine Maprotiline Paroxetine Venlafaxine

Anticholinergics

Sulfa-based drugs

Antidepressants

Warfarin Antihistamines

Brompheniramine Chlorpheniramine Dexbrompheniramine Dexchlorpheniramine Dimethindene Pheniramine Triprolidine Cimetidine Ranitidine Candesartan cilexetil

Histamine H2-receptor antagonists Angiotensin-converting enzyme (ACE) inhibitors 12

Note: Data from Tripathi et al and MEDLINE search (US National Library of Medicine and National Institutes of Health).

Since rechallenging at lower doses does not cause recurrence of myopia, allergic hypersensitivity is unlikely. Because the mechanism of angle closure does not involve pupillary block, pilocarpine or peripheral

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Blepharoplasty Cataract surgery Ciliary body epithelial cysts of the pars plicata Vogt-Koyanagi-Harada disease Herpes zoster Laser treatment for retinopathy of prematurity Microhaemangiomas of the iris Nd:YAG laser iridotomy Spherophakia Weill-Marchesani syndrome Other Alagille's syndrome General anesthesia HIV infection Watching soap opera13 Labor Leukemic orbital infiltration Myelodysplastic syndrome Snake bite Systemic lupus erythematosus Tonic pupils post-coronary artery bypass graft 12

Note: Data from Tripathi et al and MEDLINE search (US National Library of Medicine and National Institutes of Health).

iridotomy are usually ineffective.3 Unlike other antidepressant drugs such as the selective serotonin reuptake inhibitor medications that can also cause bilateral acute angle-closure glaucoma in predisposed patients with narrow angles, topiramate-associated angle closure can occur in normal eyes with open angles. Other reported causes of acute bilateral angle-closure glaucoma are presented in Tables 1 and 2. Other sulfa-derivative drugs, including acetazolamide, hydrochlorothiazide, and sulfamethoxazole, have been noted to cause similar complications. Although acetazolamide has been reported to cause bilateral acute angle-closure glaucoma by the same mechanism, this reaction has not been reported after a single dose of acetazolamide, but only after a sensitizing dose in the past or repeated dosing.2 Furthermore, in the majority of reported cases of topiramate-associated high intraocular pressure, acetazolamide treatment was administered. Ocular examination before starting topiramate use cannot identify eyes at risk. At present it seems that


acute bilateral angle-closure glaucoma with forward displacement of the lens–iris diaphragm and anterior chamber shallowing is an idiosyncratic reaction. It is important that physicians be aware of the possible ocular side effects after initiating topiramate use, principally during the first weeks. It is also advisable to alert patients to the possibility of blurred vision, eye pain, or headache and the need to seek immediate ophthalmic examination in these events. The authors have no proprietary interest in any of the materials or techniques used in this study.

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5. Hulihan J. Important drug warning [letter]. Available: http:// www.fda.gov/medwatch/SAFETY/2001/topamax_deardoc. PDF (accessed 2001 Sep 13). 6. Thambi L, Kapcala LP, Chambers W, Nourjah P, Beitz J, Chen M, Lu S. Topiramate-associated secondary angleclosure glaucoma: a case series. Arch Ophthalmol 2002;120: 1108. 7. Lin J, Fosnot J, Edmond J. Bilateral angle closure glaucoma in a child receiving oral topiramate. JAAPOS 2003;7:66–8. 8. Fraunfelder FW, Fraunfelder FT. Adverse ocular drug reactions recently identified by the National Registry of Drug-Induced Ocular Side Effects. Ophthalmology 2004;111: 1275–9. 9. Craig JE, Ong TJ, Louis DL, Wells JM. Mechanism of topiramate-induced acute-onset myopia and angle closure glaucoma. Am J Ophthalmol 2004;137:193–5. 10. Rhee DJ, Goldberg MJ, Parrish RK. Bilateral angle-closure glaucoma and ciliary body swelling from topiramate. Arch Ophthalmol 2001;119:1721–3. 11. Sankar PS, Pasquale LR, Grosskreutz CL. Uveal effusion and secondary angle-closure glaucoma associated with topiramate use. Arch Ophthalmol 2001;119:1210–1. 12. Tripathi RC, Tripathi BJ, Haggerty C. Drug-induced glaucomas: mechanism and management. Drug Saf 2003;26: 749–67. 13. Laidlaw A, Bloom P. Soap gets in your eyes. West Engl Med J 1990;105:120. Key words: topiramate, bilateral angle-closure glaucoma, treatment


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