Topiramate is an increasingly popular medication used in the treatment of migraines, seizures, and other neurologic disorders. Its several mechanisms of action include enhancement of postsynaptic gamma-aminobutyric acid (GABA) receptor activity (an inhibitory neurotransmitter) and mild inhibition of carbonic anhydrase isoenzymes. The authors report an unusual side effect of topiramate, wherein the medication exaggerates a visual field defect that is caused by a lesion along the visual pathway. Failure to recognize this peculiar property of the drug may result in the erroneous presumption that the enlargement of a field defect is due to progression of a lesion rather than to the effect of topiramate.

A 46-year-old Caucasian woman was referred with both a nasal visual field defect and decreased visual acuity in the right eye. Her visual acuity (VA) had deteriorated from 20/30 on the right side as measured just two months earlier. A visual field at that time demonstrated a nasal defect of the right eye near fixation, with a mean deviation of - 13.8dB (Figure 1a). The visual field in the left eye was normal. She had undergone an MRI revealing a right orbital apical lesion, abutting the inferolateral portion of the optic nerve, measuring 10 X 5 X 5 millimeters (Figures 2a-2c).

The patient had a history of migraines and was taking topiramate 100mg daily for the prior 15 months as well as an oral contraceptive. The patient’s medical and ophthalmic history were otherwise unremarkable.

At presentation, her VA was 20/60 OD, 20/20 OS with a slight right afferent pupillary defect; color vision, extraocular movements, intraocular pressures, and anterior chamber depth were normal. Dilated funduscopic examination revealed blunted foveal light reflexes bilaterally, with normal optic nerves and retinal periphery.

A new visual field was performed; it revealed significant progression of the right visual field defect, with a mean deviation of -22.9dB (Figure 1b). A repeat MRI revealed that the tumor size was stable.

An optical coherence tomogram (OCT) of the macula revealed bilateral hyporeflective cystic changes with subfoveal disruption of the ellipsoid layer, the photoreceptor inner segment-outer segment junction, and the external limiting membrane (Figures 2d-2e). No chorioretinal folds were seen and there was no evidence of vitreomacular traction.

The fact that the patient had no other obvious cause of her bilateral cystoid maculopathy raised the suspicion that this finding was medication induced. While macular cystic changes have not specifically been reported in association with topiramate, use of this medication has been associated with both irreversible retinal pigment epithelial (RPE) pigmentary changes and electronegative electroretinograms, thought to occur from direct RPE insult [1]. Direct RPE injury itself can potentially result in fluid accumulation in the retina, with subsequent compromise of the outer retinal layers as seen on OCT.

Furthermore, the extent and rapid progression of the patient’s visual field defect seemed greatly out of proportion to the small and stable size of the orbital mass, despite the fact that the field defect corresponded anatomically to the exact location of the tumor. In one published report, the use of

topiramate was temporally associated with the onset of a new, clinically apparent visual defect that corresponded anatomically with a long-standing, stable cerebral lesion that had previously been asymptomatic; stopping the topiramate in that case resulted in marked resolution of the scotoma to a level the authors felt was the same as a baseline defect [2]. This published case suggests that, perhaps, topiramate’s potentiation of GABA activity may further inhibit already compromised neural tissue to worsen a small or previously unrecognized scotoma. For example, in our patient’s case, the orbital tumor might be only slightly compressing the optic nerve causing minimal symptoms alone, but topiramate’s inhibitory effect on neuronal firing may enhance the effect of the tumor on the nerve, exaggerating a small visual field defect into one that is much larger than expected based solely on the size of the lesion.

Accordingly, on the supposition that the patient’s maculopathy and rapidly expanding visual field defect were both idiosyncratic reactions to topiramate ingestion (albeit in the presence of a small orbital tumor abutting the optic nerve), the medication was discontinued.

Following cessation of topiramate, slow progressive improvement in the visual field defect was noted. Over the ensuing 6 months, the mean deviation of the visual field improved steadily with each subsequent visit, measuring sequentially -14.5, -10.7, -8.9, and finally -2.97 dB at 2 weeks, 1 month, 3 months, and 6 months following cessation of topiramate, respectively (Figures 1c-f). The visual acuity correspondingly improved to 20/30 OD.

The patient has remained stable with excellent vision and a small nasal field defect in the right eye, likely the actual field defect caused by the apical orbital tumor. The final OCT revealed decreased but persistent bilateral cystoid macular changes that may be irreversible. She has tolerated amitriptyline for migraine prophylaxis; the small apical orbital lesion continues to be followed with serial imaging studies, without further growth after 3 years of follow up.

Topiramate has been associated with a wide variety of ophthalmic side effects such as non-pupillary block angle-closure glaucoma with ciliochoroidal effusion and anterior rotation of the ciliary body and lens, “cellophane” maculopathy, retinal striae, pigmentary retinopathy, and visual field defects [3-6]. Most of these side effects resolve with cessation of the drug. In addition to these well-described side effects, based on this report and a previously published case, ophthalmologists should also be cognizant that topiramate may cause the expansion of a visual field defect that is caused by a lesion along the visual pathway. The enlargement of such a scotoma may be reversible with cessation of the drug, perhaps avoiding more invasive and unnecessary interventions which would otherwise not be indicated.

The patient provided written consent for the publication of this case and the use of the clinical images.

The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The authors received no financial support for the research, authorship, and/or publication of this article.