Amantadine Use as a Risk Factor for Corneal Edema: A Nationwide Cohort Study in Taiwan.
OBJECTIVE
To evaluate the association between amantadine use and corneal toxicity in a nationwide population.


METHODS
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.
Department of Ophthalmology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Health Management Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Po Yen
PY
Lee
Department of Public Health and Environmental Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Hung Pin
HP
Tu
Department of Ophthalmology, Changhua Christian Hospital, Changhua, Taiwan.
Chang Ping
CP
Lin
Department of Ophthalmology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Cheng Hsien
CH
Chang
Department of Ophthalmology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Ophthalmology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan.
Kai Chun
KC
Cheng
Department of Ophthalmology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Chia Ching
CC
Lin
Department of Ophthalmology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address: shiuhlianghsu@gmail.com.
Shiuh Liang
SL
Hsu
D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D000547:Amantadine / Q000009:adverse effects* / Q000627:therapeutic use; D000978:Antiparkinson Agents / Q000009:adverse effects / Q000627:therapeutic use; D003315:Cornea / Q000000981:diagnostic imaging / Q000187:drug effects*; D015715:Corneal Edema / Q000139:chemically induced / Q000175:diagnosis / Q000453:epidemiology*; D016208:Databases, Factual; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy; D011159:Population Surveillance / Q000379:methods*; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D017678:Sex Distribution; D013624:Taiwan / Q000453:epidemiology; D055815:Young Adult
D000978:Antiparkinson Agents; D000547:Amantadine