Amantadine Use as a Risk Factor for Corneal Edema: A Nationwide Cohort Study in Taiwan

Abstract

Purpose: To evaluate the association between amantadine use and corneal toxicity in a nationwide population.

Design: Retrospective cohort study of nationwide population-based administrative database.

Methods: This study analyzed data in the Taiwan Longitudinal Insurance Database for a group of 8195 patients diagnosed with Parkinson disease during a 15-year period (January 1, 1996 to December 31, 2010). A control group of 8195 patients without Parkinson disease was randomly matched with the Parkinson group by age, sex, and comorbidity index. The Kaplan-Meier method was used to calculate the cumulative incidence of corneal edema. Incident rate ratios and Cox proportional hazard regressions were estimated to compare the risk of corneal edema. The same methods were then used to compare the risk between patients with and without amantadine treatment.

Results: The incidence of corneal edema in the Parkinson group (123 patients; 1.50%) was significantly higher than that in the control group (82 patients; 1.0%) (P = .004). The incidence ratio for corneal edema in the Parkinson group vs the controls was 5.77. When the Parkinson group was further subgrouped by use and non-use of amantadine, the hazard ratio for corneal edema was 1.79 times higher in the amantadine subgroup. Analyses of the amantadine subgroup by cumulative dose revealed that the 30-day hazard ratio for corneal edema was 2.05 higher in patients given moderate doses (2000-4000 mg) of amantadine and 2.84 times higher in the subgroup of patients given high doses (>4000 mg).

Conclusions: Amantadine increases the risk of corneal edema in a dose-dependent manner.