ArticleInvestigative ophthalmology & visual science2012
Corneal neurotoxicity due to topical benzalkonium chloride.
Article in Investigative ophthalmology & visual science, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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.
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Who cites it
67 citing papers in PubMed, 1 synthesis or guideline pooled it, 145 citations in OpenAlex.
- TFOS Lifestyle: Impact of cosmetics on the ocular surface.The ocular surface · 2023Pooled it
- A 6-month study comparing efficacy, safety, and tolerability of the preservative-free fixed combination of tafluprost 0.0015% and timolol 0.5% versus each of its individual preservative-free components.Advances in therapy · 2014Trial
- The safety of besifloxacin ophthalmic suspension 0.6 % used three times daily for 7 days in the treatment of bacterial conjunctivitis.Drugs in R&D · 2013Trial
- Review
- Blocking IL-6 trans-signaling mitigates benzalkonium chloride-induced inflammation, oxidative imbalance, ER stress, and barrier disruption in human corneal epithelial cells.Eye and vision (London, England) · 2026Article
- A novel rat model of neurotrophic keratopathy complicated with limbal stem cell deficiency induced by trigeminal ophthalmic branch injury.BMC ophthalmology · 2026Article
- Unseen Consequences: The Expanding Burden of Iatrogenic Dry Eye Disease in Surgical and Cosmetic Practice.Turkish journal of ophthalmology · 2026Review
- Aging and Corneal Nerve Health: Mechanisms of Degeneration and Emerging Therapies for the Cornea.Cells · 2025Review
- Review
- Clinical Benefits of Preservative-Free Treatment for Glaucoma with a Focus on Preservative-Free Latanoprost.Ophthalmology and therapy · 2025Review
- Microstructural alterations of the trigeminal ganglion in chronic ocular surface pain patients: A diffusion MRI study.NeuroImage · 2025Article
- Calcitonin Gene-Related Peptide Ameliorates Experimental Dry Eye Disease.Investigative ophthalmology & visual science · 2025Article
- Deep Corneal Nerve Plexus Selective Damage in Persistent Neurotrophic Corneal Epithelial Defects Detected by In Vivo Multiphoton Confocal Microscopy.Investigative ophthalmology & visual science · 2025Article
- Emerging Treatments for Persistent Corneal Epithelial Defects.Vision (Basel, Switzerland) · 2025Review
- Current and Emerging Therapeutic Strategies for the Management of Neurotrophic Keratitis.Drugs · 2025Review
- Non-contact confocal calcium imaging ofBiomedical optics express · 2025Article
- Hyaluronate Protects From Benzalkonium Chloride-Induced Ocular Surface Toxicity.Translational vision science & technology · 2024Article
- The PRAMOS Study: PRostaglandin Analogues Monotherapy-Awareness Survey on Ocular Surface Involvement.Ophthalmology and therapy · 2024Article
- Interaction and Transport of Benzalkonium Chlorides by the Organic Cation and Multidrug and Toxin Extrusion Transporters.Drug metabolism and disposition: the biological fate of chemicals · 2024Article
- Aprepitant Restores Corneal Sensitivity and Reduces Pain in DED.Translational vision science & technology · 2024Article
7 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
purposeThe aim of this study was to determine and characterize the effect of topical application of benzalkonium chloride (BAK) on corneal nerves in vivo and in vitro.
methodsThy1-YFP+ neurofluorescent mouse eyes were treated topically with vehicle or BAK (0.01% or 0.1%). Wide-field stereofluorescence microscopy was performed to sequentially image the treated corneas in vivo every week for 4 weeks, and changes in stromal nerve fiber density (NFD) and aqueous tear production were determined. Whole-mount immunofluorescence staining of corneas was performed with antibodies to axonopathy marker SMI-32. Western immunoblot analyses were performed on trigeminal ganglion and corneal lysates to determine abundance of proteins associated with neurotoxicity and regeneration. Compartmental culture of trigeminal ganglion neurons was performed in Campenot devices to determine whether BAK affects neurite outgrowth.
resultsBAK-treated corneas exhibited significantly reduced NFD and aqueous tear production, and increased inflammatory cell infiltration and fluorescein staining at 1 week (P < 0.05). These changes were most significant after 0.1% BAK treatment. The extent of inflammatory cell infiltration in the cornea showed a significant negative correlation with NFD. Sequential in vivo imaging of corneas showed two forms of BAK-induced neurotoxicity: reversible neurotoxicity characterized by axonopathy and recovery, and irreversible neurotoxicity characterized by nerve degeneration and regeneration. Increased abundance of beta III tubulin in corneal lysates confirmed regeneration. A dose-related significant reduction in neurites occurred after BAK addition to compartmental cultures of dissociated trigeminal ganglion cells. Although both BAK doses (0.0001% and 0.001%) reduced nerve fiber length, the reduction was significantly more with the higher dose (P < 0.001).
conclusionTopical application of BAK to the eye causes corneal neurotoxicity, inflammation, and reduced aqueous tear production.
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Registered trials
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.