effects side ocular induced-Drug • 7 t Pa r

acid has no effect on retinal function. There are nine cases in the National Registry of mydriasis being caused by this agent, but this is unproven.

Valproic acid has many ocular teratogenic effects, especially myopia. Glover et al reviewed the ‘fetal anticonvulsant syndrome’. Boyle et al (2001) reported decreased corneal sensation and severe dry eyes in a child with a fetal valproate syndrome. While intracranial hypertension has been associated with these drugs, this remains unproven.

References and Further Reading

Bayer AU, Thiel HJ, Zrenner E, et al. Color vision tests for early detection of antiepileptic drug toxicity. Neurology 48(5): 1394–1397, 1997.

Bellman MH, Ross EM. Side effects of sodium valproate. BMJ 1: 1662, 1977. Boyle NJ, Clark MP, Figueiredo F. Reduced corneal sensation and severe dry eyes in a child with fetal valproate syndrome. Eye 15: 661–662, 2001. Filteau MJ, Leblanc J, Lefrancoise S, Demers MF. Visual and auditory hal-

lucinations with the association of bupropion and valproate. Can J Psychiatry 45: 198–199, 2000.

Glover SJ, Quinn AG, Barter P, et al. Ophthalmic findings in fetal anticonvulsant syndrome. Ophthalmology 109: 942–947, 2002.

McEvoy GK (ed). American Hospital Formulary Service Drug Information 87, American Society of Hospital Pharmacists, Bethesda, pp 1042–1045, 1987.

McMahon CL, Braddock SR. Septo-optic dysplasia as a manifestation of valproic acid embryopathy. Teratology 64: 83–86, 2001.

Remler BF, Leigh RJ, Osoria I, et al. The characteristics and mechanisms of visual disturbances associated with anticonvulsant therapy. Neurology 40: 791–796, 1990.

Scullica L, Trombetta CJ, Tuccari G. Toxic effect of valproic acid on the retina. Clinical and experimental investigation. In: Acta XXV Concilium Opthalmologicum, Blodi F, et al (eds), Proceedings of the XXVth International Congress of Ophthalmology, Vol. 2, Rome, May 4–10, 1986, Kugler & Ghedini Publishers, 1988.

Uddin S. Drug-induced pseudotumor cerebri. Clin Neuropharmacol 26: 236–238, 2003.

Generic name: Topiramate.

Proprietary name: Topamax.

Primary use

Topiramate is a novel agent used to treat patients with various types of epilepsy and migraine headaches. It is used off-label as a ‘magic’ weight-reduction medication, in bipolar disorder and in clinical depression.

Ocular side effects

Systemic administration

Certain

1.Acute glaucoma (mainly bilateral)

2.Anterior chamber shallowing

3.Ocular hyperemia

4.Increased intraocular pressure

5.Mydriasis

6.Suprachoroidal effusions

7.Visual field defects

8.Non-specific ocular irritation a. Ocular pain

9.Decreased vision

10. Acute myopia (up to 6–8.5 diopters)

11. Nystagmus

12. Diplopia

13. Palinopsia

Probable

1. Myokymia

2. Blepharospasm

3. Oculogyric crisis

4. Uveitis

Possible

1. Periorbital edema

2. Scleritis

3. Retinal bleeds

Ocular teratogenic effects

Possible

1. Ocular malformations

Clinical significance

Banta et al first reported a case of uveal effusion and secondary angle closure glaucoma associated with topiramate. This has now developed into a well-recognized syndrome. This usually occurs­ within the first 2 weeks after starting topiramate therapy. In some cases, it develops within hours after doubling the dosage. Almost all cases are bilateral acute secondary angle-closure glaucoma. The syndrome may include the typical findings of acute glaucoma, including acute ocular pain, headache, nausea and vomiting, papillary changes, hyperemia, corneal edema, cataract, retinal and vascular accidents, visual field defect and, if not recognized soon enough, blindness. A few cases of scleritis have been reported but this may be more common than recognized since the glaucoma-induced hyperemia may mask the signs of scleritis. Suprachoroidal effusions have been reported by Rhee et al (2001) and others and should be looked for as the cause of the glaucoma. These effusions cause a forward rotation of the cilliary processes and therefore angle closure. These effusions along with the acute pressure elevation may cause uveitis.

Topiramate is a sulfa drug, a class that is known to cause transient myopia. Acute myopia up to 8.5 diopters may occur in a matter of hours after starting this drug; however, it may take a number of weeks to resolve once the drug is discontinued. Causation is not fully known, but includes lenticular swelling, forward rotation of the iris and lens diaphragm, cilliary body swelling causing increased curvature of the lens surface, and spasms of ­accommodation. Evans (2006) reported two well-documented cases with multiple positive rechallenge and clearly a positive dose reponse curve of reversible palinopsia after taking topiramate. ­Diplopia and nystagmus are seen primarily in high dosages and the mechanism is unknown. However, other neurologic muscular ­defects such as myokymia, oculogryric chrisis, and blepharospasms have been reported. Foroozan and Buono (2003) reported a single case of homonomous hemianopia. Vaphaiades and Mason (2004) reported a single case of bilateral pigmentary retinopathy due to this drug. There are no cases of either in the National Registry.

Recommendations (Fraunfelder, Fraunfelder and Keates)

1. The patient should stop the medication in concert with the prescribing physician since dropping the drug by as little as 50 mg may exacerbate the preexisting systemic disease.

2. Institute maximum medical therapy for glaucoma, including topical ocular cycloplegic agents along with topical betablockers and oral pressure lowering agents.

3. Laser iridotomy or peripheral iridectomy are probably not beneficial as they do not resolve the supra choroidal effusions.

4. Topical ocular miotics are probably contraindicated since they may precipitate a relative papillary block.