ArticleTransactions of the American Ophthalmological Society2012
In vitro and in vivo experimental studies on trabecular meshwork degeneration induced by benzalkonium chloride (an American Ophthalmological Society thesis).
Article in Transactions of the American Ophthalmological Society, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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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.
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Who cites it
40 citing papers in PubMed, 67 citations in OpenAlex.
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- Changing from preserved, to preservative-free cyclosporine 0.1% enhanced triple glaucoma therapy: impact on ocular surface disease-a randomized controlled trial.Eye (London, England) · 2023Trial
- Efficacy and Toxicity Evaluation of Bepotastine Besilate 1.5% Preservative-Free Eye Drops Vs Olopatadine Hydrochloride 0.2% Bak-Preserved Eye Drops in Patients with Allergic Conjunctivitis.Clinical ophthalmology (Auckland, N.Z.) · 2023Trial
- Tolerability in Glaucoma Patients Switched from Preserved to Preservative-Free Prostaglandin-Timolol Combination: A Prospective Real-Life Study.Clinical ophthalmology (Auckland, N.Z.) · 2022Trial
- Photothermal conversion hydrogel based mini-eye patch for relieving dry eye with long-term use of the light-emitting screen.International journal of nanomedicine · 2019Trial
- Selective laser trabeculoplasty: adverse effects of prior topical anti-glaucoma medication.Eye (London, England) · 2026Observational
- Clinical Microbial Contamination of Multidose Brimonidine: A Prospective Comparison of Benzalkonium Chloride and Purite® Preservatives.Journal of ophthalmology · 2026Article
- Preservative-Free Gel-Formulated Glaucoma Therapies: Learning from the Past, Looking to the Future.Advances in therapy · 2025Review
- Effects of Benzalkonium Chloride, a Preservative in Topical Drugs, on the Barrier Function of Human Corneal Epithelial Cells.Translational vision science & technology · 2025Article
- Clinical Benefits of Preservative-Free Treatment for Glaucoma with a Focus on Preservative-Free Latanoprost.Ophthalmology and therapy · 2025Review
- Association Between Preserved Glaucoma Eye Drops Exposure and Glaucoma Surgery Occurrence: A Nationwide 10-Year Outcome Study.Ophthalmology and therapy · 2025Article
- Very High Molecular Weight Hyaluronic Acid as an Enhanced Vehicle in Therapeutic Eye Drops: Application in a Novel Latanoprost Formulation for Glaucoma.Bioengineering (Basel, Switzerland) · 2025Review
- Development of Cell Culture Platforms for Study of Trabecular Meshwork Cells and Glaucoma Development.Tissue engineering and regenerative medicine · 2024Review
- 24-Hour Evaluation of the Effectiveness and Tolerability of Preservative-Free Tafluprost-Timolol Fixed Combination in Open-Angle Glaucoma or Ocular Hypertensive Patients Previously Treated with Preserved Latanoprost.Clinical ophthalmology (Auckland, N.Z.) · 2024Article
- Role of Inflammation in Canine Primary Glaucoma.Animals : an open access journal from MDPI · 2023Review
- Comparison of In Vitro Corneal Permeation and In Vivo Ocular Bioavailability in Rabbits of Three Marketed Latanoprost Formulations.European journal of drug metabolism and pharmacokinetics · 2023Article
- Favorable effect of ripasudil use on surgical outcomes of microhook ab interno trabeculotomy.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2023Article
- Ocular Tolerability of Bimatoprost 0.1 mg/mL Preservative-Free versus Bimatoprost 0.1 mg/mL with Benzalkonium Chloride or Bimatoprost 0.3 mg/mL Preservative-Free in Patients with Primary Open-Angle Glaucoma.Journal of clinical medicine · 2022Article
- Efficacy, Safety and Patient-Reported Outcomes with Preservative-Free (PF) Tafluprost or PF-Dorzolamide/Timolol Compared with Preserved Latanoprost: A Prospective Multicenter Study in Korean Glaucoma Patients with Ocular Surface Disease.Pharmaceuticals (Basel, Switzerland) · 2022Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeLong-term antiglaucomatous drug administration may cause irritation, dry eye, allergy, subconjunctival fibrosis, or increased risk of glaucoma surgery failure, potentially due to the preservative benzalkonium chloride (BAK), whose toxic, proinflammatory, and detergent effects have extensively been shown experimentally. We hypothesize that BAK also influences trabecular meshwork (TM) degeneration.
methodsTrabecular specimens were examined using immunohistology and reverse transcriptase-polymerase chain reaction. A trabecular cell line was stimulated by BAK and examined for apoptosis, oxidative stress, fractalkine and SDF-1 expression, and modulation of their receptors. An experimental model was developed with BAK subconjunctival injections to induce TM degeneration. Mass spectrometry (MS) imaging assessed BAK penetration after repeated instillations in rabbit eyes.
resultsTrabecular specimens showed extremely low densities of trabecular cells and presence of cells expressing fractalkine and fractalkine receptor and their respective mRNAs. Benzalkonium in vitro induced apoptosis, oxidative stress, and fractalkine expression and inhibited the protective chemokine SDF-1 and Bcl2, also inducing a sustained intraocular pressure (IOP) increase, with dramatic apoptosis of trabecular cells and reduction of aqueous outflow. MS imaging showed that BAK could access the TM at measurable levels after repeated instillations.
conclusionBAK enhances all characteristics of TM degeneration typical of glaucoma-trabecular apoptosis, oxidative stress, induction of inflammatory chemokines-and causes degeneration in acute experimental conditions, potentially mimicking long-term accumulation. BAK was also shown to access the TM after repeated instillations. These findings support the hypothesis that antiglaucoma medications, through toxicity of their preservative, may cause further long-term trabecular degeneration and therefore enhance outflow resistance, reducing the impact of IOP-lowering agents.
Indexed as
Identifiers
23818734PMC3671366W2109656527What OpenQuestion holds
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.