Amantadine-Associated Corneal Edema Responsive To Drug Holiday And Dose Reduction: Considerations For Cataract And Refractive Assessment

To report suspected amantadine-associated corneal endothelial toxicity in Parkinson’s disease (PD), demonstrating that clinically significant corneal edema can present after years of therapy, consistent with a cumulative, dose-dependent effect. We describe the clinical course and the visual and pachymetric response to a brief drug holiday followed by dose reduction, emphasizing the importance of timely interdisciplinary coordination to stabilize the cornea and optimize ocular measurements before cataract or refractive surgery.

Tertiary care hospital eye center: a 56-year-old man with a 16-year history of PD under the care of Neurology, treated with deep brain stimulation (implanted 6 years earlier), levodopa/carbidopa, and amantadine (initiated 8 years prior). He was referred to Neuro-Ophthalmology for reduced vision and visual disturbances and then co-managed with the Cornea service and treating neurologist.

At initial Ophthalmology assessment, best corrected visual acuity (BCVA) was 20/60 in the right eye (OD) and 20/40 in the left eye (OS). The patient reported blurred vision and formed visual hallucinations consistent with PD; the hallucinations were felt to be unrelated to the reduced acuity. Slit-lamp examination revealed diffuse, centrally predominant, corneal edema with Descemet membrane folds (DMFs) without infiltrate or epithelial defect. The remainder of the ocular examination, including posterior segment, was unremarkable. Given the examination findings and long-term amantadine exposure (100 mg BID), drug-related endothelial dysfunction was suspected. In consultation with Neurology, amantadine was tapered to 100 mg daily for 5 days then stopped.

After 1 week following amantadine cessation, BCVA improved to 20/40 OD and 20/40 OS with residual discoid edema. Central corneal thickness (CCT) was 809 µm OD and 632 µm OS, Scheimpflug tomography confirmed edema, worse in OD. Due to worsening PD symptoms, amantadine was restarted at a reduced dose (100 mg once daily). Two weeks later, BCVA improved further to 20/30 OD and 20/25 OS, with marked reduction in corneal edema and DMFs. CCT decreased to 687 µm OD and 611 µm OS, and tomography showed interval improvement.  

- The temporal relationship between drug interruption/dose reduction and clinical improvement supported a diagnosis of amantadine-related corneal toxicity.

- Amantadine can cause late-onset, dose-dependent corneal endothelial dysfunction and corneal edema; medication review is essential in otherwise unexplained corneal swelling.

- For cataract and refractive planning, optimize the cornea first (delay keratometry/biometry until edema stabilizes) and coordinate promptly with Neurology.

- When discontinuation is not possible due to therapeutic benefit, individualized reduction may improve symptoms and vision while avoiding unnecessary corneal intervention.