Our patient was a 30-year-old obese female with a history of asthma and myopia who presented with a 1-day history of blurry vision and pain in both eyes. Her review of systems was positive for nausea and vomiting. She denied ocular trauma or ocular surgeries.

On the patient’s initial exam performed at an outside hospital, her IOP was noted to be in the mid-50s mm Hg bilaterally. She was started on timolol, brimonidine and latanoprost and subsequently transferred to our medical center.

MEDICAL HISTORY AND OCULAR EXAM

In our initial assessment of the patient, history revealed that she had recently been started on a combined phentermine-topiramate tablet by her weight loss specialist within the past few weeks. She denied other medication use.

Our ocular exam showed the following:

• Distance VA: counting fingers at 1 foot OD, counting fingers 6 feet OS
• Pupils: 5-mm mid-fixed, minimally reactive OU
• IOP: 37 mm Hg OD, 39 mm Hg OS (after administration of timolol, brimonidine, latanoprost)
• Lensometry: -2.50 D sphere OU

Her anterior segment demonstrated mild bilateral lid edema, 2+ conjunctival injection OU, 3+ anterior basement membrane dystrophy (ABMD) with severe punctate corneal erosions OU, a severely uniformly shallow anterior chamber OU, clear lens OU and no visible angle structures on gonioscopy OU.

Her posterior segment showed a cup-to-disc ratio of 0.3 OD and 0.25 OS with small cups and intact rims, as well as clear vitreous, normal macula, vessel caliber and periphery OU.

DIFFERENTIAL DIAGNOSIS

In this patient presenting with acute angle closure, our suspected diagnosis was topiramate-induced acute angle closure. Other less likely diagnoses (considering the patient’s history and exam findings) included acute primary angle closure, lens-induced secondary angle closure (such as lens subluxation or phacomorphic glaucoma), posterior segment or ciliary body mass, and choroidal effusion or hemorrhage.

Given the high suspicion for topiramate-induced acute angle closure, we obtained an ultrasound biomicroscopy (UBM) image (Aviso A/B/UBM, Quantel Medical AG). This image demonstrated bilateral edematous and forwardshifting ciliary body and narrow angles, confirming our diagnosis (Figure 1).

TOPIRAMATE-INDUCED ACUTE ANGLE CLOSURE

FDA-approved for seizure therapy in 1996 and migraine treatment in 2004, topiramate is a sulfa-derived monosaccharide that functions via multiple mechanisms, including blockage of sodium channels, activation of postsynaptic GABA receptors and weak inhibition of carbonic anhydrase.¹ Its off-label uses include bipolar disorder, depression, idiopathic intracranial hypertension and neuropathic pain.²

The weight-loss side effect of topiramate was first noted in the psychiatric literature in 1999 and stood in contrast to the weight gain seen with other commonly prescribed psychiatric medications.

In 2012, the combined phentermine-topiramate was approved as a treatment for weight loss. A typical starting dose is 3.75 mg-23 mg, which can be increased to 7.5 mg-46 mg after the first 14 days of therapy.^3,4

First reported in 2012, topiramate-induced acute angle closure typically presents within the first 2 weeks of starting topiramate. Angle closure is thought to occur due to drug-induced changes in cellular membrane potential, leading to edema and forward displacement of the ciliary body. This both places pressure on the vitreous body and leads to a forward shift of the lens-iris diaphragm into the anterior chamber, narrowing and often closing the angle.^5-8

Topiramate-induced acute angle closure presents with eye pain, redness, blurry vision and often nausea and vomiting. Exams show decreased visual acuity, a mid-dilated pupil, high IOP, shallow chamber and narrow or closed angles on gonioscopy. Diagnosis can be made by observing ciliary body effusion and forward rotation on UBM.

Additionally, autorefraction can confirm the presence of a myopic shift due to forward movement of the lens, and A-scan measurements can confirm a reduced anterior chamber depth.⁹ Management of topiramate-induced acute angle closure consists of topiramate cessation and medical IOP control, with care taken to assess for glaucomatous neuropathy with visual field examinations and nerve fiber layer assessment.

Other classes of medications that can result in acute angle closure include sulfa drugs such as hydrochlorothiazide and sulfadiazine, tricyclic antidepressants, selective serotonin reuptake inhibitors, benzodiazepines and illicit drugs such as ecstasy.¹⁰

BACK TO OUR PATIENT

Our patient was counseled to stop phenterminetopiramate. She was started on acetazolamide, brimonidine, dorzolamide-timolol, Rhopressa (Aerie Pharmaceuticals)-latanoprost, atropine, prednisolone acetate, moxifloxacin (as prophylaxis for her corneal epithelial findings) and an oral prednisone taper. Subsequent examinations revealed stabilization and improvement of her IOP as well as new epithelial defects, wherein bandage contact lenses were placed.

Quantitative nerve fiber layer assessment of the retinal nerve fiber layer and optic nerve head (ONH) using Cirrus HD-OCT (Cirrus Model 5000, Carl Zeiss Meditec AG) was obtained and showed no significant thinning of the nerve tissue OU (Figure 2).

The current patient care plan is to continue to taper her IOP drops, acetazolamide and prednisone, continue follow-up with the cornea service for her ABMD and to obtain a visual field once her vision improves and her ocular surface normalizes.ement of her IOP as well as new epithelial defects, wherein bandage contact lenses were placed.

THE TAKE-HOME

The ophthalmologist should take care to review a patient’s systemic medications, understanding that topiramate, which can be prescribed for a variety of reasons including weight loss, is a well-documented cause of acute angle closure. OM

REFERENCES

1. 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;38:2639-2648.
2. Joshi AK, Pathal AH, Patwardhan SD, Kulkami AN. A rare case of topiramate-induced secondary acute angle closure glaucoma. J Clin Diagn Res. 2017;11:ND01-ND03.
3. Gordon A, Price LH. Mood stabilization and weight loss with topiramate. Am J Psychiatry. 1999;156:968-969.
4. Smith S, Meyer M, Trinkley K. Phentermine/Topiramate for the treatment of obesity. Ann Pharmacother. 2013;47:340-349.
5. Schear NJ, Rowan AJ, Wiener JA, et al. Drug-induced myopia: a transient side effect of topiramate. Epilepsia. 1990;31:643.
6. Aminlari A, East M, Wei W, Quillen D. Topiramate induced acute angle closure glaucoma. Open Ophthalmol J. 2008;2:46-47.
7. Gubbay SS. The occurrence of drug-induced myopia as a transient side effect of topiramate. Epilepsia. 1998;39:451.
8. Banta JT, Hoffman K, Budenz DL, Ceballos E, Greenfield DS. Presumed topiramate-induced bilateral acute angle-closure glaucoma. Am J Ophthalmol. 2001;132:112-114.
9. Aref A, Achiron A, Akkara J. Drug-induced acute angle closure glaucoma. Last updated June 21, 2019. https://eyewiki.aao.org/Druginduced_Acute_Angle_Closure_Glaucoma#Management_and_prevention . Accessed Oct. 13, 2019.
10. Lachkar Y, Bouassida W. Drug-induced acute angle closure glaucoma. Curr Opin Ophthalmol. 2007;18:129-133.

About the Author

Claire Kiernan, MD, is an assistant professor of ophthalmology at Hamilton Eye Institute in Memphis, Tenn. Contact her at ckiernan714@gmail.com.

Dr. Kiernan reports no financial disclosures.