Postmarketing Surveillance of Corneal Edema, Fuchs Dystrophy, and Amantadine Use in the Veterans Health Administration

Abstract

Retrospective examination of a large national medical database revealed that amantadine was temporally associated with a small proportion of patients diagnosed with corneal edema or Fuchs dystrophy. Although additional studies are needed to confirm the risk of corneal edema with amantadine, the development of corneal edema in persons prescribed amantadine warrants clinical attention. In such a situation, physicians may consider stopping amantadine to see if the edema subsides.

Ketamine-Associated Corneal Edema

“…In a postmarketing surveillance study between 2005 and 2006, 36 (0.27%) of 13,137 patients prescribed amantadine by the United States Veterans Health Administration pharmacy developed either corneal edema or decompensated Fuchs endothelial dystrophy compared with a background prevalence of at least 13 in 200,000 (0.0065%). 7,9 Given these cases and ours, it is possible that corneal endothelial NMDA receptors are important in maintaining corneal clarity.…”

“…4 Several case reports have described corneal edema in patients prescribed amantadine, also an NMDA antagonist. [5][6][7] NMDA receptors have been demonstrated in the corneal endothelium via immunocytochemical and real-time polymerase chain reaction. 8 Jeng et al 6 described 3 patients who developed bilateral corneal edema and significant endothelial cell loss following long-term use of amantadine.…”

Bilateral corneal edema associated with amantadine

“…1 It has a variety of effects on the brain, influencing dopamine, monoamine oxidase and N-methyl-d-aspartate receptors, and has been investigated for several neuropsychiatric conditions. 2 It is indicated as a treatment for Parkinson disease, as well as for drug-induced extrapyramidal adverse effects.…”

“…2 It is indicated as a treatment for Parkinson disease, as well as for drug-induced extrapyramidal adverse effects. 1 Off-label uses include treatment of attention-deficit/hyperactivity disorder and fatigue associated with multiple sclerosis,…”

“…1 As most of these cases had been diagnosed as idiopathic corneal edema or Fuchs endothelial corneal dystrophy, a failure to associate the onset with drug use is evident, which leads us to believe that the complication may be underreported.…”