Ophthalmology

Tearful from Topiramate: A Case of Bilateral Secondary Angle Closure Glaucoma

We present the case of an adult male with bilateral eye pain and visual changes. He is ultimately found to have bilateral acute angle closure glaucoma secondary to topiramate toxicity.

Acute angle closure glaucoma is a common ocular emergency. Rapid diagnosis, immediate intervention, and appropriate referral directly correlate with patient outcome and morbidity. Secondary acute angle closure glaucoma is more commonly a unilateral diagnosis.10 This is an unusual case of bilateral acute angle closure glaucoma.

Case
A 72-year-old male with a history of migraines presented to the ED with bilateral vision loss and eye pain for two days. He was driving cross country when he developed a migraine headache and decreased vision. The pain was localized behind his eyes and worse on the right side. He described this as being different from his normal migraine. Initially, he presented to a rural hospital. A CT scan of his head was negative for an acute intracranial abnormality. The patient was treated symptomatically with an oral analgesic medication, which mildly improved his symptoms, and he was discharged.

The following morning, he woke and immediately noticed decreased vision in both eyes, photophobia, large visual field defects as well as redness and tearing in both eyes, with his right eye being more affected than his left. At this time, he presented to the ED at a large academic center. Further history revealed he wore glasses for reading but no contacts and had no previous ophthalmologic conditions or surgeries. He mentioned he was started on topiramate the week prior as a prophylactic medication for his chronic migraines.

His systemic vitals were within normal limits, but the patient’s eye exam was concerning for acute ocular pathology. His visual acuity was decreased with 20/150 OD and 20/50 OS. His intraocular pressure (IOP) was increased bilaterally, 39 mmHg on the right and 35 mmHg on the left. He had no pain with extraocular movements and full ocular range of motion bilaterally. However, the patient had multiple visual field defects in both eyes. His right eye was found to have a mid-dilated minimally reactive pupil, and both eyes appeared injected, cloudy, and tearful. The remainder of his physical exam — including cranial nerves, gross systemic sensation, and motor function — remained intact.

Based on his history and physical exam, he was diagnosed with bilateral acute angle closure glaucoma, and treatment was initiated to decrease his IOP.

Pathophysiology
Angle closure glaucoma occurs when there is narrowing of the anterior chamber angle. A normal angle allows for aqueous humor to drain out of the anterior chamber of the eye. When the angle is narrowed, accumulation of this fluid causes increased IOP and damage to the optic nerve. Normal IOP is approximately 8-21 mmHg. In acute angle closure glaucoma, pressures are often greater than 30 mmHg.5

The two main types of acute angle closure glaucoma are primary and secondary. Primary occurs due to genetic susceptibility and the intrinsic characteristics of the eye, whereas secondary occurs as a result of an external event causing the angle to close (for example, a mass or hemorrhage in the posterior aspect of the eye pushing the angle closed, or as in the patient described above, an adverse drug reaction driving the acute angle closure glaucoma).5

Patients presenting with acute angle closure glaucoma can often have decreased visual acuity and describe seeing halos around lights that are associated with severe headache, eye pain, nausea, and vomiting. On physical exam, these patients commonly have conjunctival injection, corneal clouding, a shallow anterior chamber, and a mid-dilated pupil that reacts poorly to light. Dilation of the eye will cause worsening symptoms, whether it is physiologic from poorly lit areas or pharmacologic with dilating drops. Typically, acute angle glaucoma affects one eye and rarely occurs bilaterally.5

This patient had a recent addition of topiramate to his medication regimen as a migraine prophylaxis medication. Topiramate, more commonly known as Topamax, is a sulfa derivative used traditionally as an antiepileptic or for migraine prophylaxis. Recently, it has also become a popular medication to treat alcohol and drug dependence, eating disorders, PTSD, depression, and weight loss. Its mechanisms of action are as follows: It blocks voltage dependent sodium channels, antagonizes an NMDA glutamate receptor, enhances the effects of GABA at its nonbenzodiazepine receptors, and weakly inhibits carbonic anhydrase in the central nervous system.4,8

Common adverse effects of topiramate include metabolic acidosis, weight loss, cognitive impairment, paresthesia, fatigue, depression, and mood lability. Rare complications include kidney stones, acute myopia, and secondary acute angle closure glaucoma as seen in our patient.6

The mechanism by which topiramate causes acute glaucoma is thought to be through forward displacement of the lens-iris diaphragm from ciliochoroidal effusion, which causes anterior chamber shallowing and eventually a backup of aqueous humor.6 This causes an increase in IOP, which results in the pain and physical exam findings as described above.2,3

Other more common precipitating factors of acute angle closure glaucoma include dimly lit areas that cause physiological mydriasis and other drugs such as antihistamines, antidepressants, bronchodilators, cough/cold and flu medications, and other anticonvulsants.5

Management and Case Conclusion
Management for acute angle closure glaucoma in the ED revolves around decreasing the IOP caused by excess aqueous humor.5 Once the diagnosis is made by history and physical exam, steps can be initiated to rapidly decrease the pressure inside the eye and preserve vision. This includes a combination of patient positioning, topical eye drops, and systemic medications.

The patient should be positioned to lie flat on their back, which helps to displace the lens posteriorly. Administration of intravenous acetazolamide (500 mg) can further reduce the production of aqueous humor. Also, 1 to 2 grams of IV mannitol can be considered to reduce the volume of aqueous humor. Topical eye drops include a beta blocker such as timolol, an alpha 2 agonist such as apraclonidine or brimonidine, prostaglandin analogues such as latanoprost, and pupillary constricting agents like pilocarpine, repeated every 30-60 minutes until the pressure has decreased. In addition to the above measures, it is important to treat pain, nausea, and vomiting, as these symptoms can further increase IOP.5,7

The previously mentioned treatment should be initiated by the ED or the ophthalmologist, if at a facility with in-house ophthalmology. Further management depends on the type of glaucoma. For primary acute angle closure glaucoma, definitive management consists of peripheral iridectomy performed by an ophthalmologist. This allows for fluid to flow between the anterior and posterior chambers without increasing the IOP. In contrast, secondary acute angle closure glaucoma does not require this procedure.9 Secondary acute angle closure glaucoma should be treated symptomatically with the medications above as well as cessation of the inciting medication or removal of the secondary cause of glaucoma.1

Prognosis for this condition is dependent on how long the IOP remains elevated. The longer it goes without treatment, the more likely the patient will have irreversible damage to the optic nerve, resulting in permanent vision loss.7

Our patient began treatment and returned for follow-up in three days with ophthalmology. At that time, his IOP had normalized to OD 14 mmHg and OS 9 mmHg. He reported improvement in his vision as well as resolution of his pain.

Take-Home Points

  • Screen for ocular pathology when assessing a patient with headache complaints.
  • With ocular complaints, the five vital signs of the eye can rapidly assist in identifying the correct diagnosis: (1) visual acuity; (2) ocular pressure; (3) visual fields; (4) pupil examination; and (5) extraocular motility.
  • Acute angle closure glaucoma presents as a painful red eye often associated with headache, nausea, and vomiting. The eye will appear injected, with a cloudy cornea and mid-dilated mildly reactive pupil. The anterior chamber will appear shallow, and there will be an increased intraocular pressure on tonometry.
  • Glaucoma treatment should be initiated in the ED by decreasing intraocular pressure with systemic IV acetazolamide and topical eye drops including a beta blocker, alpha agonist, prostaglandin analog, and topical pilocarpine.
  • Topiramate is a sulfa-derived medication. One of its rarer adverse reactions is bilateral secondary acute angle closure glaucoma.
  • Don’t forget to ask about recent medication changes, especially in patients with unique clinical presentations.

References

  1. Banta JT, Hoffman K, Budenz DL, Ceballos E, Greenfield DS. Presumed topiramate-induced bilateral acute angle-closure glaucoma. Am J Ophthalmol. 2001 Jul;132(1):112-4.
  2. Craig JE, Ong TJ, Louis DL, Wells JM. Mechanism of topiramate-induced acute-onset myopia and angle closure glaucoma. Am J Ophthalmol. 2004 Jan;137(1):193-5.
  3. Desai CM, Ramchandani SJ, Bhopale SG, Ramchandani SS. Acute myopia and angle closure caused by topiramate, a drug used for prophylaxis of migraine. Indian J Ophthalmol. 2006 Sep;54(3):195-7.
  4. Pinto-Gouveia C, Bernardes L, Renca S. Topiramate-associated acute bilateral angle-closure glaucoma. J Clin Psychopharmacol. 2022;42(3):320-321.
  5. Khazaeni B, Khazaeni L. Acute closed angle glaucoma. In: Post TW, ed. StatPearls NCBI NLM NIH gov books, 2022. Accessed May 15, 2022.
  6. Lan YW, Hsieh JW. Bilateral acute angle closure glaucoma and myopic shift by topiramate-induced ciliochoroidal effusion: case report and literature review. Int Ophthalmol. 2018 Dec;38(6):2639-2648.
  7. Murray D. Emergency management: angle-closure glaucoma. Community Eye Health. 2018; 31(103):64.
  8. Schachter SC. Antiseizure medications: Mechanism of action, pharmacology, and adverse effects. In: Post TW, ed. UpToDare; 2022. Accessed May 15, 2022.
  9. van Issum C, Mavrakanas N, Schutz JS, Shaarawy T. Topiramate-induced acute bilateral angle closure and myopia: pathophysiology and treatment controversies. Eur J Ophthalmol. 2011 Jul-Aug;21(4):404-9.
  10. Weizer J. Angle-closure glaucoma. In: Post TW, ed. UpToDate; 2021. Accessed May 15, 2022.

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