Topiramate Induced Bilateral Angle-Closure Glaucoma: Low Dosage in a Short Time

Introduction

Topiramate is a sulfamate-substituted monosaccharide. ¹ Topiramate, a drug used as the prophylaxis of migraine with or without aura in adult patients who have not responded or are intolerant to the other standard therapies, is also being used for many types of epilepsies, essential tremor, peripheral neuropathies, post-traumatic stress disorder, loss of weight, and insomnia.^2,3 Among drugs, sulphonamide and its derivatives have been documented as causing transient myopia, ciliary body edema, uveal effusions, and anterior rotation of the lens-iris diaphragm causing secondary acute angle closure glaucoma ⁴ (AACG). AACG induced by topiramate occurred predominantly in women. We reported a female patient of bilateral AACG and acute progressive myopia due to topiramate, which is a drug used for migraine prophylaxis.

Case Report

A thirty-six-year-old woman presented with severe headache and ocular pain associated with a blurred vision for the last 3 hours. The biomicroscopic examination showed conjunctival hyperemia, narrowing of the anterior chamber, and diffuse corneal edema in both eyes. The pupils were widely dilated, and the lenses were clear. İntraocular pressure (IOP) with applanation tonometer was 68 mmHg in the right eye and 70 mmHg in the left eye. Gonioscopy revealed closed angles with absence of angle structures. Undilated funduscopic examination findings were normal with a cup-to-disk ratio of 0.3 and a healthy neuroretinal rim. Refractive error was −6.00 diopters, and visual acuity was 20/400 in both eyes. B-scan ultrasonography revealed suprachoroidal effusion in both eyes. A-scan biometry revealed an axial length of 22.21 mm in the right eye and 22.31 mm in the left eye, while the respective anterior chamber depths were 1.75 and 1.72 mm. Lens thickness was 4.73 and 4.81 mm in the right and left eye, respectively. The patient had no past history of glaucoma but had a history of migraine and was prescribed 25 mg of topiramate acetate on initial examination for 1 day before the onset of these symptoms. The patient took only 2 doses of medication. With these clinical features, the diagnosis of topiramate-induced bilateral AACG was made. The therapy with topiramate was immediately discontinued. The patient was intravenously treated with mannitol 20% (5 mL/kg), oral acetazolamide tablets 250 mg thrice daily, and timolol maleat/dorzolamide hydrochloride ophthalmic solution and brimonidine tartrate eye drops topically twice a day in both eyes. Topical 1% prednisolone acetate and cyclopentolat eye drops were started. She was reviewed the next day with examination findings remaining unchanged, her vision improved to 20/200, and the IOP was 33 mmHg in the right eye and 36 mmHg in the left eye. On the 1 week of the treatment, visual acuity, gonioscopic, ultrasonographic and myopic findings returned to normal. IOP was 11 mmHg in both eyes maintained with only topical 0.5% timolol maleate. On the arrival of the patient's 1st day, 3rd day, 1st week, and 2nd month, clinical findings are demonstrated in Table 1.

Discussion

Bilateral simultaneous secondary AACG has been reported secondary to drugs, general anesthesia, snake bite, Vogt-Koyanagi-Harada syndrome, and microspherophakia. ⁵ Although the exact mechanism remains unclear, topiramate, an oral sulpha-derivative medication, is known to cause ciliochoroidal effusion, which leads to forward rotation of the ciliary body and displacement of the lens-iris diaphragm, with resultant AACG and myopic shift. ⁶ The molecular mechanism of this serious side effect is not yet clear, but the idiosyncratic reaction currently remains the most shared hypothesis. ⁷ The acute pressure elevation usually occurred in the first 2 weeks (ranged from 1 to 49 days, with a mean of 7 days from the onset of therapy) after starting topiramate therapy. Some cases were precipitated within hours when the dose was doubled. ¹ In the presented case, topiramate was initiated for migraine prevention several hours before the onset of acute findings. The patient had only taken 2 doses of topiramate. In the reported cases of glaucoma, the dose of topiramate varied from 50 mg or less (47% of cases), to 50–75 mg (33% of cases), and 100 mg (13%) to more than 100 mg (7%) and this adverse event at the increase of the dose. ¹ However, there have been reports of angle closure glaucoma with plasma topiramate levels less than therapeutic levels. ³ Our patient was given a minimum therapeutic dosage of 25 mg for only 2 days, which suggests that the ocular side effects were not dose dependent.

Management of topiramate-associated AACG is included in the following steps: Topiramate should be stopped as soon as possible. Maximum anti-glaucomatous medical therapy was administered, including oral medications and aqueous suppressants. Lazer iridotomy or peripheral iridectomy may not be helpful in the treatment for angle closure caused by topiramate, as the precipitating mechanism is not pupillary block. Topical miotics are contraindicated in such cases, because their usage may aggravate a relative pupillary block and worsen the signs and symptoms.^1,8 Based on these rules, we administered topical and systemic antiglaucomatous treatment. Topical 1% prednisolone acetate was also given to reduce inflammation within the suprachoroidal space, and topical cyclopentolat was prescribed thrice a day to relax the ciliary muscle and displace the lens-iris diaphragm posteriorly to relieve the angle closure. In our case, stopping topiramate and controlling the IOP medically resulted in rapid resolution of the bilateral angle closure without any intervention.

Topiramate is a drug that has potential for the treatment of migraine as seen in this patient. However, topiramate treatment may result in AACG and acute myopia, which are usually reversible when the drug is discontinued. Final visual acuity is usually good, and this disorder generally resolves within a few weeks. If unrecognized as a drug-related event, serious outcomes could occur (ie, 7 cases of permanent vision loss reported). ¹

Ophthalmologists will have to be aware of this potential complication, as they may be the first ones to see patients with these symptoms. Due to the potential ophthalmic serious adverse effects of topiramate, patients should be warned when prescribed topiramate. Our patient was only on 25 mg once a day for 2 days, which suggests that the reaction is not a dose-dependent toxicity. This case report illustrates AACG, and acute myopia occurs even with low doses of topiramate.

Based on our knowledge, this is the first reported case of topiramate-induced bilateral AACG and myopia, where a patient shows severe side effects in such a short time and a low dosage (25 mg of topiramate once a day for 2 days).