Rationale:
Topiramate may be associated with higher glaucoma incidence via carbonic anhydrase inhibition. with several observational studies showing elevated risks relative to non-users. Relative risks versus other antiseizure medications (ASMs) and variations by sex or indication remain unclear. This study evaluates glaucoma incidence in topiramate initiators compared to valproate or lamotrigine users among patients with epilepsy or migraine.
Methods:
We conducted a retrospective active-comparator, new-user cohort study using electronic primary health care records from the IQVIA Medical Research Data among patients with epilepsy or migraine who initiated topiramate, valproate, or lamotrigine. Patients with prior ASM use, limited washout period and follow-up, or pre-existing glaucoma were excluded. The outcome was incident glaucoma during up to one-year follow-up, censored at glaucoma occurrence, death, discontinuation, switch, or study end (September 30, 2023). Covariates included age, sex, race, lifestyle factors, history of diseases such as diabetes and hypertension, and prior use of medications, like steroids. We used propensity score-based inverse probability weighting to balance characteristics and applied crude and weighted Cox models to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). We refitted weights and models for subgroups by sex, age, and indication.
Results:
Topiramate was associated with higher glaucoma risk versus valproate (adjusted HR 2.66, 95% CI 1.12-6.32) and lamotrigine (adjusted HR 3.57, 95% CI 1.76-7.26). Risks were elevated in females (vs. valproate: HR 5.31, 95% CI 1.48-19.08; vs. lamotrigine: HR 5.73, 95% CI 2.38-13.79) and epilepsy patients (vs. valproate: HR 2.23, 95% CI 1.04-4.76; vs. lamotrigine: HR 5.08, 95% CI 2.32-11.14), but not in males or in migraine patients.Conclusions:
Compared to valproate and lamotrigine, topiramate use substantially increases the risk of glaucoma particularly in females and epilepsy patients, while showing no significant association in males or in migraine patients. These findings may inform targeted ophthalmologic monitoring in high-risk groups and use of alternative ASMs.
Funding:
No funding was received to support this work.