Case Report: Topiramate Induced Myopia Essay

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Case Report: Topiramate Induced Myopia Essay

G.Srinivasagopalan Gopalsamy, Murali Mohan Mohan, Sudhakar Sankar

Tamilnadu, India

Abstract

Topiramate (sulfamate-substituted monosaccharide) is a broad spectrum newer anti-convulsant. It is also used in prophylaxis of migraine, cluster headache, bipolar affective disorder, post traumatic stress disorder, post herpetic neuralgia , relapse prevention in alcohol dependence syndrome, add on treatment for antipsychotic induced weight gain.Case Report: Topiramate Induced Myopia Essay. Acute Myopia and angle closure glaucoma are some of the rare side effects of topiramate. This case highlights the development of myopia in a middle aged patient with alcohol dependence syndrome while he was on topiramate therapy.

Keywords: Topiramate, alcohol dependence syndrome, angle closure glaucoma, myopia.

INTRODUCTION

Topiramate is a sulfamate substituted monosaccharide, a broad spectrum anticonvulsant acting on voltage dependent sodium channels, enhancement of gamma amino butyric acid (GABA), decrease in glutamate and inhibition of carbonic anhydrase. We (the psychiatrists) use topiramate to treat migraine, cluster headache, bipolar affective disorder, post traumatic stress disorder, post herpetic neuralgia , relapse prevention in alcohol dependence syndrome, add on treatment for antipsychotic induced weight gain¹. Some of the rare side effects of topiramate are acute myopia and angle closure glaucoma. We report a case of topiramate induced transient myopia in a patient who had been started on topiramate for relapse prevention in alcohol dependence syndrome.

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CASE REPORT

A 35 year old married male, lower middle socio economic status from rural background, working in a private company presented to the outpatient services of our department of psychiatry with 10 years history of alcohol use amounting to dependence and two weeks history of blurred vision and headache. Patient was diagnosed as a case of alcohol dependence syndrome – uncomplicated withdrawal state (F10.30) as per International Classification of Diseases (ICD) â€‘10 criteria. He was admitted for detoxification and on eliciting history; it was found that he had been commenced on oral topiramate 50 mg/day 3 weeks previously by a private psychiatrist for his alcohol use.Case Report: Topiramate Induced Myopia Essay. The patient had no history of hypertension, diabetes or glaucoma, he had never worn glasses and there was no history of injury to eyes or head and no history of withdrawal seizures. He was referred to department of ophthalmology for blurred vision. Ophthalmic opinion on the day of admission suggested refractive errors bilaterally with left eye myopia of -2.5 diopters and right eye myopia of -3.5 diopters with shallow anterior chamber and normal pupils and lens on slit lamp examination and normal intra ocular pressure on tonometry. After this ophthalmologic report, topiramate was stopped immediately by us thinking that it could have induced myopia. Other routine investigations were normal and detoxification with oral lorazepam and thiamine supplementation continued along with motivation enhancement sessions by psychologist. Patient reported gradual clinical improvement in his vision. Repeat ophthalmologic consultation on the 7^th day of admission showed significant improvement in visual acuity and refraction with left eye – myopia of 0.75 diopters and right eye – myopia of 0.75 diopters .Because of our early intervention, angle closure glaucoma was averted in our case.

DISCUSSION

The most frequently reported side effects for Topiramote are dizziness, mental slowing, somnolence, ataxia, impaired concentration and confusion². Most of these are transient and observed during the initial weeks of therapy and can be reduced by slow titration of the dose. Anorexia and mild weight loss has been observed during the therapy. Metabolic acidosis, and nephrolithiasis are the other reported side effects. WHO Causality Assessment³ suggests abnormal vision, acute secondary angle closure glaucoma, acute myopia and suprachoroidal effusions are complications of Topiramate therapy. This case highlights and aims to raise awareness that topiramate can cause acute myopia and angle closure glaucoma. Both are reversible with immediate discontinuation of the drug⁴. Various authors have also reported these serious complications due to topiramate^[4][5][6]. The mechanism for topiramate induced angle closure glaucoma is by ciliochoroidal effusion with forward displacement of the lens – iris diaphragm and anterior chamber shallowing, resulting in acute myopia and angle closure glaucoma^4]. Case Report: Topiramate Induced Myopia Essay. Topiramate’s weak carbonic anhydrase inhibitor activity and prostaglandin mediated effects have also been postulated as possible mechanisms⁷. Acute myopia up to -9.0 diopters can occur in a matter of hours after starting topiramate, but might take weeks to fully resolve. Whenever a case of myopia with angle closure glaucoma and a shallow anterior chamber is encountered, ciliochoroidal effusion syndrome induced by drugs should be considered in the differential diagnosis. Drug induced myopia has also been associated with promethazine, spironolactone, tetracycline, corticosteroids etc.⁵. Pupils should not be dilated to prevent further angle closure and possible rise in pressure. Paediatric and developmentally delayed patients who have been started on topiramate should be closely monitored during the first 2 weeks of treatment. It is important for the clinician to educate the patients about this serious adverse effect while prescribing topiramate and advise them to report immediately in the event of visual disturbance.

REFERENCES

1V. Shivakumar, N. Jayaram, N. P. Rao, and G. Venkatasubramanian, ‘Successful Use of Add – on Topiramate for Antipsychotic – Induced Weight Gain’, Indian J Psychol Med, 34 (2012), 85-6.

2Y. Mikaeloff, A. de Saint-Martin, J. Mancini, S. Peudenier, J. M. Pedespan, L. Vallee, J. Motte, M. Bourgeois, A. Arzimanoglou, O. Dulac, and C. Chiron, ‘Topiramate: Efficacy and Tolerability in Children According to Epilepsy Syndromes’, Epilepsy Res, 53 (2003), 225-32.

3S. A. Zaki, ‘Adverse Drug Reaction and Causality Assessment Scales’, Lung India, 28 (2011), 152-3.

4J. E. Craig, T. J. Ong, D. L. Louis, and J. M. Wells, ‘Mechanism of Topiramate-Induced Acute-Onset Myopia and Angle Closure Glaucoma’, Am J Ophthalmol, 137 (2004), 193-5.

5T. C. Chen, C. W. Chao, and J. A. Sorkin, ‘Topiramate Induced Myopic Shift and Angle Closure Glaucoma’, Br J Ophthalmol, 87 (2003), 648-9. Case Report: Topiramate Induced Myopia Essay.

6H. A. Sen, H. S. O’Halloran, and W. B. Lee, ‘Case Reports and Small Case Series: Topiramate-Induced Acute Myopia and Retinal Striae’, Arch Ophthalmol, 119 (2001), 775-7. Case Report: Topiramate Induced Myopia Essay.

7C. M. Desai, S. J. Ramchandani, S. G. Bhopale, and S. S. Ramchandani, ‘Acute Myopia and Angle Closure Caused by Topiramate, a Drug Used for Prophylaxis of Migraine’, Indian J Ophthalmol, 54 (2006), 195-7.

Topiramate is a sulfamate-substituted monosaccharide mainly used to treat epilepsy in children and adults and for prophylaxis of migraine. This article describes a case of topiramate induced acute transient myopia. The underlying mechanism and management is discussed.

Case presentation

A 34-year-old female complained of sudden onset of blurred vision, 9 days prior to this she had commenced topiramate therapy for migraine prophylaxis. Visual acuity was reduced to 6/36 right eye and 2/60 left eye. Examination revealed ocular anatomical and myopic refractive changes which resolved quickly following discontinuation of the drug.

Conclusion

Ophthalmologists need to be aware of the potential ocular side effects of topiramate. Although relatively rare prompt recognition is key so appropriate management can be instituted.

Case presentation

A 34-year-old female complained of sudden onset of blurred vision. She attended her optician who noted a large myopic shift from –1.00/+0.50 × 90 right eye, −0.75/+0.25 × 95 left eye to –3.50/+0.50 × 90 right eye, −3.50/+0.25 × 95 left eye. Oral topiramate treatment had been commenced for migraine prophylaxis 9 days prior to the onset of her symptoms at a dose of 25 mg once daily (OD), increased 7 days later to 50 mg OD. On examination Snellen visual acuity with her glasses on was 6/36 right eye, 2/60 left eye, with full new myopic correction vision was 6/6 bilaterally. Both eyes were white and quiet but anterior chambers were shallow and the iris and lens were bowed forward. Intraocular pressures (IOP) were 18 mHg and Gonioscopy revealed 360° Shaffer Grade 1.Case Report: Topiramate Induced Myopia Essay. No choroidal effusions were seen by indirect ophthalmoscopy but B-scan showed a small separation between the choroidal and scleral layers bilaterally in keeping with small effusions. Given the patient had discontinued the topiramate therapy herself and as IOPs were normal no treatment was instituted. At review 2 days later vision with her glasses on had improved to 6/9 right eye, 6/36 left eye. The anterior chambers were deep, IOP normal and the iris and lens had returned to a normal position and configuration. Two weeks later repeat Gonioscopy showed 360^oShaffer Grade 4 angles, B-scan ultrasound showed resolution of the choroidal effusions and refraction was –0.75/+0.50 × 100 right eye, −0.75/+0.50 × 90 left eye, with this correction vision was 6/5 bilaterally.

Discussion

As well as epilepsy and migraine topiramate has also been used to treat depression, neuropathic pain, as a weight reduction agent and for bipolar disorder. Case reports on ocular side effects of this drug date back to 2001 [1]-[3]. In September 2001 Ortho-McNeil Pharmaceuticals sent out a safety alert to healthcare professionals indicating 23 cases of secondary angle-closure glaucoma related to topiramate use based on post-marketing experience in more than 825,000 patients. (Hulihan J: Important drug warning [letter]. Available at: http://www.fda.gov/medwatch/SAFETY/2001/topamax_deardoc.PDF).

The majority of reported adverse events have occurred in female patients (up to 89%) [4]. Ocular side effects have also been reported in children [5]. In the “certain” category of the World Health Organisation classification system adverse ocular side effects associated with topiramate include abnormal vision, acute IOP elevation, acute myopia (up to 8.75 dioptres), diplopia, nystagmus and shallow anterior chamber with angle-closure. “Probable/likely” include blepharospasm, myokymia, oculogyric crisis, suprachoroidal effusions and “possible” are congenital ocular abnormalities, periorbital oedema and scleritis [6]. High frequency ultrasound biomicroscopy, anterior segment ocular coherence tomography and B-scan ultrasound have helped establish and document the underlying mechanism of the myopia and angle-closure glaucoma [7]-[9] – uveal effusions and ciliary body oedema result in antero-lateral rotation of the ciliary body, anterior displacement of the lens-iris diaphragm which contributes to the myopic shift, anterior chamber shallowing and secondary appositional angle closure. Case Report: Topiramate Induced Myopia Essay. The effusion and oedema also lead to relaxation of the lens zonules resulting in thickening of the lens further narrowing the angle. Though the exact mechanism is unclear the fluid movement leading to effusions is thought to be related to drug induced changes in membrane potential [8]. In reported cases of angle-closure glaucoma topiramate doses varied from 50 mg or less to 100 mg or more, 5 reported cases were precipitated within hours after doubling the dose, 85% of cases occurred in the first 2 weeks of treatment with the drug [10].

Fraunfelder et al [10] advise the following management strategy for topiramate-associated angle-closure glaucoma:

Stoppage of the drug in the first instance, the prescribing doctor should be consulted.

Medical therapy such as oral medications and aqueous suppressants should be given.

Laser iridotomy or peripheral iridectomy are not helpful as topiramate angle closure is not pupil block related.

Topical miotics may be contraindicated as they could precipitate a relative pupil block.

Topical cycloplegic agents may be given as they possibly lower IOP by retracting ciliary processes.

Care should be taken with acetazolamide as it is also a sulfa-based drug and has been reported to cause angle-closure glaucoma in a similar manner to topiramate [11].

In this case the topiramate induced anatomical changes stopped short of inducing angle-closure glaucoma. The rapid onset of visual loss secondary to the myopia is understandably distressing to the patient and it is helpful to be able to provide some guidance on prognosis – as the mean plasma elimination half life of the drug is about 21 hours [12], rapid visual recovery usually occurs although in some cases it can take several weeks [10]. If unrecognised as a drug-related event serious outcomes could occur (7 cases of permanent visual loss following angle-closure glaucoma have been reported) [10]. Ocular examination before starting topiramate cannot identify eyes at risk [8]. Patients commencing topiramate should therefore be advised to immediately report any symptoms of eye pain or blurred vision especially in the first few weeks of treatment. Case Report: Topiramate Induced Myopia Essay.

Case presentation

Conclusion

Ophthalmologists need to be aware of the potential ocular side effects of topiramate. Although relatively rare prompt recognition is key so appropriate management can be instituted.

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Case presentation

A 34-year-old female complained of sudden onset of blurred vision. She attended her optician who noted a large myopic shift from –1.00/+0.50 × 90 right eye, −0.75/+0.25 × 95 left eye to –3.50/+0.50 × 90 right eye, −3.50/+0.25 × 95 left eye. Oral topiramate treatment had been commenced for migraine prophylaxis 9 days prior to the onset of her symptoms at a dose of 25 mg once daily (OD), increased 7 days later to 50 mg OD. On examination Snellen visual acuity with her glasses on was 6/36 right eye, 2/60 left eye, with full new myopic correction vision was 6/6 bilaterally. Both eyes were white and quiet but anterior chambers were shallow and the iris and lens were bowed forward. Intraocular pressures (IOP) were 18 mHg and Gonioscopy revealed 360° Shaffer Grade 1.Case Report: Topiramate Induced Myopia Essay. No choroidal effusions were seen by indirect ophthalmoscopy but B-scan showed a small separation between the choroidal and scleral layers bilaterally in keeping with small effusions. Given the patient had discontinued the topiramate therapy herself and as IOPs were normal no treatment was instituted. At review 2 days later vision with her glasses on had improved to 6/9 right eye, 6/36 left eye. The anterior chambers were deep, IOP normal and the iris and lens had returned to a normal position and configuration. Two weeks later repeat Gonioscopy showed 360^o Shaffer Grade 4 angles, B-scan ultrasound showed resolution of the choroidal effusions and refraction was –0.75/+0.50 × 100 right eye, −0.75/+0.50 × 90 left eye, with this correction vision was 6/5 bilaterally.

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Discussion

As well as epilepsy and migraine topiramate has also been used to treat depression, neuropathic pain, as a weight reduction agent and for bipolar disorder. Case reports on ocular side effects of this drug date back to 2001 [1-3]. In September 2001 Ortho-McNeil Pharmaceuticals sent out a safety alert to healthcare professionals indicating 23 cases of secondary angle-closure glaucoma related to topiramate use based on post-marketing experience in more than 825,000 patients. (Hulihan J: Important drug warning [letter]. Available at: http://www.fda.gov/medwatch/SAFETY/2001/topamax_deardoc.PDF).

The majority of reported adverse events have occurred in female patients (up to 89%) [4]. Ocular side effects have also been reported in children [5]. In the “certain” category of the World Health Organisation classification system adverse ocular side effects associated with topiramate include abnormal vision, acute IOP elevation, acute myopia (up to 8.75 dioptres), diplopia, nystagmus and shallow anterior chamber with angle-closure. “Probable/likely” include blepharospasm, myokymia, oculogyric crisis, suprachoroidal effusions and “possible” are congenital ocular abnormalities, periorbital oedema and scleritis [6]. High frequency ultrasound biomicroscopy, anterior segment ocular coherence tomography and B-scan ultrasound have helped establish and document the underlying mechanism of the myopia and angle-closure glaucoma [7-9] – uveal effusions and ciliary body oedema result in antero-lateral rotation of the ciliary body, anterior displacement of the lens-iris diaphragm which contributes to the myopic shift, anterior chamber shallowing and secondary appositional angle closure. The effusion and oedema also lead to relaxation of the lens zonules resulting in thickening of the lens further narrowing the angle.Case Report: Topiramate Induced Myopia Essay. Though the exact mechanism is unclear the fluid movement leading to effusions is thought to be related to drug induced changes in membrane potential [8]. In reported cases of angle-closure glaucoma topiramate doses varied from 50 mg or less to 100 mg or more, 5 reported cases were precipitated within hours after doubling the dose, 85% of cases occurred in the first 2 weeks of treatment with the drug [10].

Fraunfelder et al [10] advise the following management strategy for topiramate-associated angle-closure glaucoma:

Stoppage of the drug in the first instance, the prescribing doctor should be consulted.

Medical therapy such as oral medications and aqueous suppressants should be given.

Laser iridotomy or peripheral iridectomy are not helpful as topiramate angle closure is not pupil block related.

Topical miotics may be contraindicated as they could precipitate a relative pupil block.

Topical cycloplegic agents may be given as they possibly lower IOP by retracting ciliary processes.

Care should be taken with acetazolamide as it is also a sulfa-based drug and has been reported to cause angle-closure glaucoma in a similar manner to topiramate [11].

In this case the topiramate induced anatomical changes stopped short of inducing angle-closure glaucoma. The rapid onset of visual loss secondary to the myopia is understandably distressing to the patient and it is helpful to be able to provide some guidance on prognosis – as the mean plasma elimination half life of the drug is about 21 hours [12], rapid visual recovery usually occurs although in some cases it can take several weeks [10]. If unrecognised as a drug-related event serious outcomes could occur (7 cases of permanent visual loss following angle-closure glaucoma have been reported) [10]. Ocular examination before starting topiramate cannot identify eyes at risk [8]. Case Report: Topiramate Induced Myopia Essay.Patients commencing topiramate should therefore be advised to immediately report any symptoms of eye pain or blurred vision especially in the first few weeks of treatment.

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Conclusion

Ophthalmologists need to be aware of the potential ocular side effects of topiramate. Although relatively rare prompt recognition is key so appropriate management can be instituted and visual outcomes maximised.

Author contribution

SG is the sole author of this work. SG was instrumental in the medical care of the patient, analysed and interpreted the patient data, performed the literature search and case write-up.

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References

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