Amantadine-induced corneal edema – A reversible cause of visual blurring in Parkinson’s disease

Dear Editor, Amantadine is one of the common drugs used in Parkinson’s disease (PD), primarily to control dyskinesia and gait issues. Here, we describe a patient with PD who developed visual blurring from bilateral corneal edema, which improved after stopping amantadine. Amantadine-induced corneal edema can occur after variable duration of exposure and is characterized by alteration in corneal endothelial cell density and morphology. Clinicians should be aware of this potentially reversible entity to avoid further complications and recommend yearly ophthalmological examination in patients on amantadine. A 63-year-old female, a follow-up patient with PD for the last 4 years and currently on Levodopa (600 mg/day), pramipexole (1 mg/day), and amantadine (300 mg/day), developed insidious onset, painless, progressive blurring of vision for the last 1 month. Clinical examination revealed bilateral corneal edema, which resolved in 3 weeks after stopping amantadine [Figure 1].Figure 1: Bilateral Corneal edema (right eye 1a, left eye 1b) that resolved after stopping amantadine (right eye 2a, left eye 2b)Amantadine can cause corneal edema due to idiosyncratic reactions or dose-dependent cumulative toxicity on the corneal endothelial cells.[1,2] A two-year post-marketing surveillance study found a relative risk (RR) of 1.7 [95% confidence interval (CI): 1.1–2.8] for developing corneal edema among amantadine users with a frequency of 0.27%.[3] Female gender, higher daily dose (>100 mg/day), and use of multiple dopaminergic medications are possible risk factors.[1] Besides its use in treating parkinsonism, amantadine has been observed to cause corneal edema when prescribed for fatigue, ataxia, tardive dyskinesia, primary progressive freezing of gait, depression, and bipolar affective disorder.[1] Characteristically, it affects the central cornea, commonly bilaterally asymmetric and associated with reduced endothelial cell count, without any signs of endothelial guttata, anterior chamber inflammation, or deep stromal vessels. The presence of any of these red flags suggests an alternative diagnosis such as Fuchs’ endothelial dystrophy, posterior polymorphous corneal dystrophy, iridocorneal endothelial syndrome, Herpes Simplex Virus (HSV) keratitis, or interstitial keratitis.[4] The duration of exposure to amantadine in the reported cases varied widely, from 25 days to several years.[4] Our patient was on amantadine for 1 year to control her dyskinesia. PD patients on amantadine have shown a significant decrease in endothelial cell density (ECD), a reduction in the percentage of hexagonality of the cells (EH), and an increased coefficient of variation (CoV), as evidenced by specular microscopy and measuring mean central corneal subbasal nerve fiber layer density (SNFLD).[5,6] Commonly, this issue resolves within a month of stopping amantadine, but neglected cases may require keratoplasty, as prolonged corneal edema from chronic amantadine exposure can be irreversible. Therefore, clinicians should be aware of this potentially reversible complication for patients on amantadine who complain of gradually progressive visual blurring and recommend yearly ophthalmological checkups in all patients on amantadine. Acknowledgement We acknowledge the patient and her caregiver for their support. Author contribution Research project: Conception: JG, HK Organization: JG Execution: JG, SM, NS Manuscript preparation: Writing of the first draft: JG Review and Critique: HK Ethical compliance statement The authors confirm that the approval of an institutional review board/ patient consent was not required for this work. We also confirm that the patient has given written informed consent for the publication of her images. We confirm that we have read the journal’s position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.