Evidence map›Paper›PMID 42000941›Full record

ArticleJournal of neurology2026

Corneal edema: an underrecognized safety risk of amantadine.

David Croteau, Anne Tobenkin, Vicky Chan, Natalie Branagan, Julie Goldrich, Emily Freilich, Allen Brinker

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Article in Journal of neurology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

David CroteauU.S Food & Drug Administration, Division of Pharmacovigilance I, Office of Surveillance and Epidemiology Center for Drug Evaluation and Research, 10903 New Hampshire Avenue, Silver Spring, MD, 20993, USA. david.croteau@fda.hhs.gov.ORCID http://orcid.org/0000-0002-5561-6940
Anne TobenkinU.S Food & Drug Administration, Division of Pharmacovigilance I, Office of Surveillance and Epidemiology Center for Drug Evaluation and Research, 10903 New Hampshire Avenue, Silver Spring, MD, 20993, USA.
Vicky ChanU.S Food & Drug Administration, Division of Pharmacovigilance I, Office of Surveillance and Epidemiology Center for Drug Evaluation and Research, 10903 New Hampshire Avenue, Silver Spring, MD, 20993, USA.
Natalie BranaganU.S. Food & Drug Administration, Division of Neurology 1, Office of Neuroscience, Office of New Drugs, Center for Drug Evaluation and Research, 10903 New Hampshire Avenue, Silver Spring, MD, 20993, USA.
Julie GoldrichU.S. Food & Drug Administration, Division of Neurology 1, Office of Neuroscience, Office of New Drugs, Center for Drug Evaluation and Research, 10903 New Hampshire Avenue, Silver Spring, MD, 20993, USA.
Emily FreilichU.S. Food & Drug Administration, Division of Neurology 1, Office of Neuroscience, Office of New Drugs, Center for Drug Evaluation and Research, 10903 New Hampshire Avenue, Silver Spring, MD, 20993, USA.
Allen BrinkerU.S Food & Drug Administration, Division of Pharmacovigilance I, Office of Surveillance and Epidemiology Center for Drug Evaluation and Research, 10903 New Hampshire Avenue, Silver Spring, MD, 20993, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

objectivesTo characterize a large case series of corneal edema associated with amantadine and to disseminate the information on that safety risk. MATERIALS AND

methodsFor this retrospective pharmacovigilance case series, we searched the FDA Adverse Event Reporting System (FAERS) and the medical literature for case reports of corneal edema associated with amantadine. After the application of corneal edema case definition criteria, case reports were assessed for a drug-event causal association between amantadine and corneal edema development.

resultsWe identified 54 cases of corneal edema reported or published since the 1990s with reasonable evidence of a causal association with amantadine prescribed for Parkinson's disease or other neuropsychiatric indications. The median amantadine total daily dose was 200 mg (range, 100-400 mg). Corneal edema developed after a median exposure of 12 months (range, 0.6-120 months) with most cases occurring within 24 months of amantadine initiation. There was no apparent relationship between reported total daily dose or exposure duration and corneal edema frequency or severity. The median age at corneal edema development was 61 (IQR, 50.0-64.5; range, 8-82). Corneal edema was bilateral in all cases. In eight cases, corneal grafts were either performed (n = 6) or planned (n = 2). Amantadine was permanently discontinued in all but two cases where the amantadine dose was reduced, and topical corticosteroid treatment was initiated. DISCUSSION: Corneal edema is an important yet underrecognized safety risk associated with chronic amantadine use, particularly among patients with Parkinson's disease. Based on our findings, the Warnings and Precautions section of the United States Prescribing Information of all amantadine products was amended.

Indexed as

AmantadineAntiparkinson AgentsCorneal EdemaAdolescentAdultAgedAged, 80 and overChildFemaleHumansMaleMiddle AgedParkinson DiseasePharmacovigilanceRetrospective StudiesYoung AdultAmantadineAntiparkinson AgentsAmantadineCase seriesCorneal edemaParkinson’s disease

Identifiers

PMID42000941

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.