A 29-year-old white female was referred by her internist due to sudden bilateral vision loss and nondescript eye pain during the last three days. The patient, who had never worn glasses, presented with an uncorrected acuity of 20/400 O.U. Interestingly, her pinhole acuity improved to 20/30- O.U., which relieved her greatly. Subsequent refraction revealed a myopic prescription of approximately -2.75DS O.D. and -3.25DS O.S. with resultant 20/25- acuity.
Biomicroscopically, she had a very narrow anterior chamber angle. Curiously, there was no iris bombé in either eye; rather, the anterior chamber angles in each eye were nearly flat, and there was mild diffuse corneal edema in both eyes. Intraocular pressure was 29mm Hg O.D. and 38mm Hg O.S. Gonioscopy revealed no angle structures in either eye. Not only did the patient have an apparently sudden myopic shift, but she also had bilateral angle closure. However, her age, myopic status, and lack of iris bombé seemed to preclude relative pupil block as the likely cause of angle closure.
Her medical history was very important in this case—she was a chronic migraine sufferer, and her internist had just started her on a migraine medication called Topamax (topiramate, Ortho-McNeil Neurologics). In this case, the patient had suffered from a medically-induced sudden myopic shift and angle closure due to Topamax. While this phenomenon seems to be well reported in the literature, interaction with optometric colleagues across the country underscores that it is not well-known; so, this month, we revisit and review some recent findings about Topamax-induced angle closure.
What is Topamax?
Topamax is a sulfamate-substituted monosaccharide originally developed and used as an anti-convulsant medication to prevent epileptic seizures. Since its development, however, researchers have identified additional applications. Topamax is occasionally used as an antidepressant. In children, it is indicated for the treatment of Lennox-Gastaut syndrome, a disorder that causes seizures and developmental delay.
It is also approved by the Food and Drug Administration for the prevention of migraines. This appears to be the most common indication for Topamax today.
Though not specifically FDA-approved for it, Topamax is also used off-label for the treatment of bipolar disorder, as well as bulimia, autism-spectrum disorder, psychological addiction in alcoholism, weight loss, post-traumatic stress disorder, obsessive-compulsive disorder, smoking cessation, idiopathic intracranial hypertension, neuropathic pain and cocaine dependence.1-4
Topamax can cause numerous adverse effects, including paresthesia (the most common side effect), fatigue, renal stone development, taste change (described as a “metallic” taste) and weight loss (leading to its use in treating obesity). There may also be difficulty with concentration, attention span and memory; this has lead some to humorously refer to the medication as “Dopamax.” Topamax is also a carbonic anhydrase inhibitor, which likely accounts for the taste perversion and the development of renal stones during treatment.
Topamax and Angle Closure
The most concerning adverse effect of Topamax for optometrists is the possibility of acute angle-closure glaucoma. Patients need not be at risk of angle closure prior to the use of Topamax for it to occur. In fact, angle closure from Topamax use can occur in younger patients and even children who otherwise would not be at risk.5-8
When angle closure occurs from Topamax use, it usually is seen relatively soon after starting the medication—often within the first month, and sometimes even after the first dose.
Also, the angle closure is typically bilateral, compared to the unilateral presentation of angle closure resulting from primary pupil block.9-16 Accompanying Topamax-induced angle closure is the acute onset of a myopic refractive shift, which, with angle closure, is an important diagnostic indication of this drug effect. It is not uncommon to see abrupt myopic shifts of four to five diopters or more, and the resultant change in acuity may be more symptomatic to the patient than the IOP effects from angle closure.17-20
The glaucomatous and angle closure mechanism occurring from Topamax use is not relative pupil block, but seems to be a sulfa-allergic response with resultant swelling and congestion, as well as effusion, detachment or forward rotation of the ciliary body.21-24 Topiramate-induced ciliochoroidal effusion with forward displacement of the lens-iris diaphragm causes extreme anterior chamber shallowing, resulting in angle-closure glaucoma.
In contrast to relative pupil block, there will be no iris bombé in Topamax-induced angle closure; rather, the chamber will be flat. Congestion of the ciliary body allows the lens zonules to become lax, and the resultant thickening of the lens as well as the forward rotation of the lens-iris diaphragm induces the myopic shift. Increased lens thickness contributes only minimally to anterior chamber shallowing and does not participate in the angle closure.24
Typically, cessation of Topamax results in resolution of the myopia and angle closure.9,10-12,14,15,17 Visual outcome is usually good and the episode resolves within days to weeks with little, if any, permanent damage. Beyond cessation of Topamax, the acute IOP rise can also be addressed with anti-glaucoma medications. Pilocarpine should be avoided, but virtually any other topical IOP-lowering medication is acceptable. More important, however, is the use of a strong cycloplegic, such as atropine, and an anti-inflammatory, such as prednisolone acetate 1%. These stabilize leaking vascular membranes, leading to reduced choroidal swelling, relaxation of the ciliary body and lens-iris diaphragm, deepening of the chamber with cessation of angle closure, and reversal of the myopic shift.9,10-12,14,15,17
Because there is no relative pupil block, laser peripheral iridotomy and miotics do not have any effect in Topamax-induced angle closure.6,11 But, argon laser iridoplasty, an iridoretraction procedure, has been helpful in managing refractory Topamax-induced angle closure, as it physically pulls the iris away from the trabecular meshwork.25-26 Clearly, Topamax-induced angle closure and myopic shift is a widely reported phenomenon; however, our conversations with optometric colleagues, primary care physicians and pharmacists demonstrate that it is not a well-known phenomenon in practice. So, we thought it important to reach out to colleagues to remind everyone that, in some cases, solving one problem can lead to another.
1. Walia KS, Khan EA, Ko DH, et al. Side effects of antiepileptics—a review. Pain Pract. 2004 Sep;4(3):194-203.
2. Spaeth GL, Mantravadi AV. Topiramate as treatment for alcohol dependence. JAMA. 2008 Jan;299(4):405.
3. Alore PL, Jay WM, Macken MP. Topiramate, pseudotumor cerebri, weight-loss and glaucoma: an ophthalmologic perspective. Semin Ophthalmol. 2006 Jan-Mar;21(1):15-7.
4. Guay DR. Oxcarbazepine, topiramate, zonisamide, and levetiracetam: potential use in neuropathic pain. Am J Geriatr Pharmacother. 2003 Sep;1(1):18-37.
5. Brandão MN, Fernandes IC, Barradas FF, et al. Acute myopia and angle closure glaucoma associated with topiramate use in a young patient. Arq Bras Oftalmol. 2009 Jan-Feb;72(1):103-5.
6. Stangler F, Prietsch RF, Fortes Filho JB. Bilateral acute angle closure glaucoma in a young patient receiving oral topiramate: case report. Arq Bras Oftalmol. 2007 Jan-Feb;70(1):133-6.
7. Lin J, Fosnot J, Edmond J. Bilateral angle closure glaucoma in a child receiving oral topiramate. J AAPOS. 2003 Feb;7(1):66-8.
8. Coats DK. Bilateral angle closure glaucoma in a child receiving oral topiramate. J AAPOS. 2003 Aug;7(4):303.
9. Boonyaleephan S. Bilateral acute onset myopia and angle closure glaucoma after oral topiramate: a case report. J Med Assoc Thai. 2008 Dec;91(12):1904-7.
10. Singh SK, Thapa SS, Badhu BP. Topiramate induced bilateral angle-closure glaucoma. Kathmandu Univ Med J (KUMJ). 2007 Apr-Jun;5(2):234-6.
11. Panday VA, Rhee DJ. Review of sulfonamide-induced acute myopia and acute bilateral angle-closure glaucoma. Compr Ophthalmol Update. 2007 Sep-Oct;8(5):271-6.
12. Chalam KV, Tillis T, Syed F, et al. Acute bilateral simultaneous angle closure glaucoma after topiramate administration: a case report. J Med Case Reports. 2008 Jan 8;2:1
13. Aminlari A, East M, Wei W, et al. Topiramate induced acute angle closure glaucoma. Open Ophthalmol J. 2008 Mar 28;2:46-7.
14. Izambart C, Rocher F, Zur C, et al. Topiramate and acute myopia with angle-closure glaucoma: case report and literature review. J Fr Ophtalmol. 2007 May;30(5):e11.
15. Levy J, Yagev R, Petrova A, et al. Topiramate-induced bilateral angle-closure glaucoma. Can J Ophthalmol. 2006 Apr;41(2):221-5.
16. Rhee DJ, Goldberg MJ, Parrish RK. Bilateral angle-closure glaucoma and ciliary body swelling from topiramate. Arch Ophthalmol. 2002 Dec;120(12):1775.
17. Guier CP. Elevated intraocular pressure and myopic shift linked to topiramate use. Optom Vis Sci. 2007 Dec;84(12):1070-3.
18. Rodríguez-Gómez D, Castro-Pérez A, Landaluce-Chaves ML,et al. Narrow-angle glaucoma and acute myopia from using topiramate as prophylactic treatment of migraine. Rev Neurol. 2007 Aug;45(4):254.
19. Desai CM, Ramchandani SJ, Bhopale SG, et al. Acute myopia and angle closure caused by topiramate, a drug used for prophylaxis of migraine. Indian J Ophthalmol. 2006 Sep;54(3):195-7.
20. Chen TC, Chao CW, Sorkin JA. Topiramate induced myopic shift and angle closure glaucoma. Br J Ophthalmol. 2003 May;87(5):648-9.
21. Ikeda N, Ikeda T, Nagata M, et al. Ciliochoroidal effusion syndrome induced by sulfa derivatives. Arch Ophthalmol. 2002;120(12):1775.
22. Sankar PS, Pasquale LR, Grosskreutz CL. Uveal effusion and secondary angle-closure glaucoma associated with topiramate use. Arch Ophthalmol. 2002 Dec;119(8):1210-1.
23. Medeiros FA, Zhang XY, Bernd AS, et al. Angle-closure glaucoma associated with ciliary body detachment in patients using topiramate. Arch Ophthalmol. 2003 Feb;121(2):282-5.
24. Craig JE, Ong TJ, Louis DL, et al. Mechanism of topiramate-induced acute-onset myopia and angle closure glaucoma. Am J Ophthalmol. 2004 Jan;137(1):193-5.
25. Sbeity Z, Gvozdyuk N, Amde W, et al. Argon laser peripheral iridoplasty for topiramate-induced bilateral acute angle closure. J Glaucoma. 2009 Apr-May;18(4):269-71.
26. Zalta AH, Smith RT. Peripheral iridoplasty efficacy in refractory topiramate-associated bilateral acute angle-closure glaucoma. Arch Ophthalmol. 2008 Nov;126(11):1603-5.