Causality assessment · Causality: well established

Topiramate and Acute angle-closure glaucoma: is the FAERS signal real?

n=597 co-reports · PRR 68.7 · ROR 69.2

Topiramate side-effect profile All assessments See in the full list

A written Bradford Hill assessment of one drug–event pair. The grade is a judgement about the signal, not a statement that this drug causes this event in any one person; FAERS counts are reports, not rates.

Causality: well established

Topiramate ↔ Acute angle-closure glaucoma

n=597 co-reports · PRR 68.7 · ROR 69.2 Ocular pain / secondary angle-closure (related terms): further co-reports

Topiramate, used for epilepsy, migraine prevention, and weight management, has a distinctive and well-documented ocular toxicity: a secondary acute angle-closure glaucoma that develops within days to weeks of starting or increasing the dose. It is caused by drug-induced effusion into the ciliary body and lens, which pushes the iris forward and closes the angle — a mechanism quite different from primary angle-closure. The presentation mimics a neurological event (severe headache, eye pain, blurred vision), which is a recognised diagnostic trap, and it resolves when the drug is withdrawn. The FDA labeling carries a specific warning, and it is treated as a medical emergency because vision can be permanently lost if unrecognised. The very high PRR reflects how characteristic and unusual this reaction is.

Regulatory basis: topiramate prescribing information (secondary angle-closure glaucoma warning). Established topiramate-induced acute myopia/angle-closure literature.

Bradford Hill viewpoint	Status	Note
Temporality (necessary)	met	Develops within days–weeks of starting or dose increase
Strength	met	PRR 69, one of the largest ocular signals on the page
Consistency	met	Replicated across case series and the prescribing information
Specificity	met	The secondary (ciliary-effusion) mechanism is characteristic of topiramate
Biological gradient	partial	More common at higher doses/rapid titration, but reported at standard doses
Plausibility	met	Ciliary-body effusion pushing the iris forward is a defined mechanism
Coherence	met	Coheres with the label warning and the classic secondary-closure picture
Experiment	met	Prompt drug withdrawal reliably reverses it — a consistent dechallenge
Analogy	met	Analogous to other sulfonamide-derived carbonic-anhydrase-inhibitor ocular effects

This page's own qualitative read, not an automated/citation-gated assessment.

✓ Trial evidence found — topiramate vs placebo (NCT01110434), N=66

Term (as recorded)	Topiramate (n=40)	Placebo (n=26)
Changes in vision (non-serious, eye disorders)	4	0

Visual symptoms cluster on the topiramate arm and not on placebo even in a very small trial, directionally consistent with the drug's ocular toxicity — though the specific term tracked here is generic visual change, not angle-closure, which is rare and usually diagnosed outside trial settings. View on ClinicalTrials.gov →