5 · Factors delaying or impairing healing
Benzalkonium chloride (BAK) — toxic preservative
Review — modulators of corneal healing › 5 · Factors delaying or impairing healing › Benzalkonium chloride (BAK) — toxic preservative
Benzalkonium chloride (BAK) — toxic preservative
Quaternary ammonium detergent, 0,004–0,02 % in numerous multidose eye drops
Oxford I–III
Negative · Strong
Present · to be eliminated
Mechanism (anti-healing / toxic)Surfactant that solubilizes membranes and disrupts tight junctions → loss of epithelial barrier function, ↓goblet cell density, tear film instability, oxidative stress, pro-inflammatory cytokines and apoptosis (epithelium, limbal stem cells, nerves, keratocytes). Dose- and duration-dependent effect: delays/inhibits epithelial closure and worsens persistent epithelial defects (PEDs).
Clinical contextDecisive in patients on chronic/multiple preserved eye drops (glaucoma), frequent dosing, pre-existing dry eye/PED, contact lens wearers. Switching to preservative-free formulations is a standard corrective measure.
"Dosage" of exposureCumulative toxicity = number of preserved drops/day × chronicity. Goal: minimize/eliminate exposure.
Level of evidenceOxford I–II (mechanistic + clinical comparative studies; II–III for delayed healing as an endpoint) · Scale: Strong (epithelial toxicity).
| Status | Approved preservative (FDA/EMA/ANSM) but under growing regulatory pressure — recommendations favoring preservative-free formulations, especially in glaucoma/chronic surface disease. France (ANSM) and the EU have led the shift toward preservative-free formulations. |
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Key studies: BAK-induced barrier disruption (human epithelial cells); BAK toxicity to epithelium + trigeminal neurons (2019) — PMID 31707104; review "Ocular BAK exposure," Eye 2021 — PMID 34262161; limbal stem cell toxicity (Sci Rep 2025) — PMID 40210649.
See also: Gabison E. “Corneal wound-healing agents”. In: SFO 2023 Report — Médicaments et biothérapies en ophtalmologie, chapter 21. Full text, open access (in French).