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Man reports acute onset of blurred, tunnel vision
Bilateral angle closure and elevated IOP were observed.
A 35-year-old Caucasian man with a medical history of migraine headaches presented to the emergency room for acute onset of blurred vision and tunnel vision that began when he woke up in the morning. In addition to blurred vision, he complained of a mild headache with a pressure sensation behind his eyes. He denied eye pain, nausea and vomiting.
A week before presentation, he was seen by a neurologist for persistent headaches and started on topiramate 25 mgby mouth twice a day. The night before presentation, his dose of topiramate was increased to 50 mg by mouth twice a day. He was also followed closely by a psychiatrist for depression, anxiety and ADHD, taking mirtazapine, diazepam, diclofenac and methylphenidate. There was no history of ocular trauma, eye disease or need for spectacle correction. He never had surgery before. Medication allergies included gabapentin and tramadol, which cause tinnitus. The patient was adopted and had no known family history of eye disease. He used marijuana occasionally and denied current smoking and alcohol use.
Examination
Source: Huan Meng Mills, MD, and Michael Cooper, MD, PhD
Visual acuity was 20/300 bilaterally without correction at distance but 20/20 bilaterally at near. IOP was 40 mm Hg in the in the right eye and 41 mm Hg in the left eye. Pupils were 5 mm, round and sluggish bilaterally without afferent pupillary defect. Extraocular motions were full bilaterally without pain. Confrontational visual fields were mildly constricted bilaterally. Slit lamp exam of bilateral eyes revealed no conjunctival injection, clear corneas, trace anterior chamber inflammation and clear lenses. The anterior chamber was diffusely shallow bilaterally with anterior displacement of the iris and lens (Figures 1a and 1b). The patient had grade 0 narrowing of angles by the van Herick method in both eyes (Figures 1c and 1d). Gonioscopy revealed 360° appositional angle closure bilaterally without peripheral anterior synechiae (Figure 1e). Dilated fundus exam of both eyes revealed pink and healthy optic nerves with a 0.4 cup-to-disc ratio. The remainder of the fundus exam was unremarkable except for macular striae bilaterally.
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Drug-induced bilateral angle closure
The features of bilateral angle closure, elevated IOP and myopic shift in a young emmetropic patient who recently started topiramate are most consistent with a drug-induced mechanism for angle closure. This syndrome must be distinguished from pupillary block resulting from anatomic narrow angles. Primary angle closure glaucoma due to pupillary block is more commonly unilateral in comparison to our patient who presented with bilateral elevated pressure. Our patient also lacked risk factors for narrow angles, including Asian descent, female gender, hyperopic refraction and older age with development of cataracts.
Management
It is important to distinguish topiramate-associated bilateral angle closure from pupillary block because the management differs greatly. The most important initial step in the treatment of topiramate-associated angle closure is discontinuation of the medication. We consulted with the patient’s neurologist, who agreed with discontinuation of topiramate. In the emergency department, we administered acetazolamide 500 mg IV and topical pressure-lowering drops including timolol 0.5%, dorzolamide 2% and brimonidine 0.2%. Our patient was discharged home on oral acetazolamide 500 mg twice a day, dorzolamide 2%/timolol 0.5% twice a day and brimonidine 0.2% three times a day. Pilocarpine is usually administered in the treatment of pupillary block, but this is contraindicated in the treatment of topiramate-associated angle closure because it can worsen the ciliochoroidal effusion and cause more anterior displacement of the lens-iris diaphragm. In addition, pilocarpine induces ciliary muscle contraction, which leads to thickening of the lens and further shallowing of the anterior chamber.
Instead of pilocarpine, the patient was given dilating and cycloplegic agents, including tropicamide 1%, cyclopentolate 1% and phenylephrine 2.5%. Cycloplegic agents help decrease the IOP by paralyzing the ciliary muscle to increase zonular tension, decrease lens thickness and cause posterior rotation of the lens-iris diaphragm. The patient was discharged on cyclopentolate 1% both eyes three times a day for cycloplegia and prednisolone acetate 1% both eyes four times a day to treat mild anterior chamber inflammation. Because topiramate-associated angle closure is not caused by a pupillary block mechanism, a peripheral iridotomy is contraindicated.
Macula OCT images obtained 2 days after initial presentation highlight macular striae (Figures 2a and 2b). The exact etiology of the striae is unknown, but Natesh and colleagues hypothesized that topiramate causes alterations in sodium and chloride channels, which cause fluid shifts in the vitreous and choroid. The folds in the retina are likely due to a combination of vitreomacular traction and choroidal effusion. Anterior segment OCT further confirmed the gonioscopy findings of iridotrabecular apposition bilaterally (Figures 2c and 2d). Ultrasound biomicroscopy is another useful image modality that can help visualize the anterior displacement of the lens-iris diaphragm caused by a combination of ciliochoroidal effusion and anterior ciliary body rotation.
Discussion
Topiramate is a sulfa-derivative medication used primarily in the treatment of epilepsy and prevention of migraine headaches. Less common indications include bipolar disorder, depression, neuropathic pain, alcohol dependence, post-traumatic stress disorder and inducement of weight loss. The exact mechanism of the medication is unknown, but it is thought to inhibit carbonic anhydrase and augment GABA activity. The half-life of the medication is 21 hours for the immediate-release form and 56 hours for the extended-release form.
In 2004, Fraunfelder and colleagues analyzed 115 new spontaneous case reports of possible adverse ocular events associated with topiramate. In this case series, 86 patients had acute onset glaucoma. Of these 86 patients, 83 had bilateral acute onset glaucoma. In addition, 17 of these patients had acute bilateral myopia and nine patients had suprachoroidal effusions. Approximately 85% of adverse events occurred within the first 2 weeks of initiating the medication, and five cases occurred several hours after doubling the dose. The adverse effects were not dose dependent, and 47% of patients had adverse effects with a dose of 50 mg or less.
The key to preventing permanent vision damage is early recognition of the syndrome and prompt discontinuation of the medication. The diagnosis of topiramate-associated angle closure can often be made by taking a detailed history. Clinical symptoms of bilateral elevated IOP, angle closure and acute myopia are typical for topiramate-associated ocular toxicity. On examination, the anterior chamber is often diffusely shallow with forward rotation of the lens-iris diaphragm. Macular striae are also a common funduscopic finding. IOP usually normalizes within a few days after cessation of the topiramate, but myopia can take up to a few weeks to resolve completely. The visual outcome is usually excellent if the drug is discontinued promptly and medical management is initiated early to lower the eye pressure. Prolonged elevated IOP and angle closure can lead to permanent optic nerve damage and vision loss.
Clinical course continued
One day after the initial presentation, the patient’s vision improved slightly to 20/200 in the right eye and 20/150 in the left eye. IOP improved to 20 mm Hg in the right eye and 19 mm Hg in the left eye on topical drops and oral acetazolamide. Over the next week, IOP remained low, and acetazolamide and topical drops were slowly discontinued. Vision slowly improved, and 12 days after initial presentation, the patient’s vision returned to baseline at 20/30 in the right eye and 20/25 in the left eye without correction. Final best corrected visual acuity was 20/20 in both eyes, and manifest refraction revealed less than half a diopter of refractive error in both eyes. IOP was 10 mm Hg in both eyes off of drops. Examination revealed deep and quiet anterior chambers, and repeat gonioscopy revealed open angles with ciliary body visible 360° bilaterally. The macula striae also resolved over a 2-week period. We anticipate the patient will do well and have no residual visual deficits.
- References:
- Fraunfelder FW, et al. Ophthalmology. 2004;doi:10.1016/j.ophtha.2003.04.004.
- Lan YW, et al. Int Ophthalmol. 2018;doi:10.1007/s10792-017-0740-y.
- Murphy RM, et al. J Glaucoma. 2016;doi:10.1097/IJG.0000000000000270.
- Natesh S et al. Oman J Ophthalmol. 2010;doi:10.4103/0974-620X.60018.
- Ritch R, et al. Ophthalmology. 2003;doi:10.1016/S0161-6420(03)00563-3.
- For more information:
- Huan Meng Mills, MD, and Michael Cooper, MD, PhD, can be reached at New England Eye Center, Tufts University School of Medicine. 800 Washington Street, Box 450, Boston, MA 02111; website: www.neec.com.
- Edited by Alison J. Lauter, MD, and Sarah E. Thornton, MD. They can be reached at the New England Eye Center, Tufts University School of Medicine, 800 Washington St., Box 450, Boston, MA 02111; website: www.neec.com.