BMJ Open Ophthalmology (Sep 2021)

Impact of benzalkonium chloride-preserved and preservative-free latanoprost eye drops on cultured human conjunctival goblet cells upon acute exposure and differences in physicochemical properties of the eye drops

  • Steffen Heegaard,
  • Anne Hedengran,
  • Miriam Kolko,
  • Tor P Utheim,
  • Darlene A Dartt,
  • Goran Petrovski,
  • Olivia Müllertz,
  • Zaynab Ahmad Mouhammad,
  • Josefine Freiberg,
  • Richárd Nagymihály,
  • Jette Jacobsen,
  • Susan Weng Larsen,
  • Jeffrey Bair

DOI
https://doi.org/10.1136/bmjophth-2021-000892
Journal volume & issue
Vol. 6, no. 1

Abstract

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Objective To investigate the short-term impact on human conjunctival goblet cell (GC) survival and mucin release of acute exposure to benzalkonium chloride (BAK) preserved and preservative-free (PF) 0.005% (w/v) latanoprost (LT) eye drops, and to compare the eye drops’ physicochemical properties.Methods and analysis Primary GC cultures were established from human conjunctival donor tissue. The impact of eye drops on GC survival was assessed using a lactate dehydrogenase assay. Mucin release was evaluated through mucin-specific immunostaining. pH value, osmolality, drop mass and surface tension for all LT eye drops were measured.Results After application with PF-LT for 30 min (min), the GC survival was maintained compared with control (p=0.9941), while all BAK-LT eye drops reduced survival with approximately 30% (p<0.02). Following application with PF-LT for 30 min, mucin was found around the GC nucleus, as seen in the vehicle control, indicating no secretion. In contrast, BAK-LT caused diffuse staining of mucin, similar to the secretagogue histamine, indicating stimulation of secretion. The pH value of the BAK-LT and PF-LT eye drops were 6.0–6.9 and 6.8, respectively. The osmolality was 258–288 mOsm/kg for the BAK-LT eye drops and 276 for PF-LT eye drops. The mean drop mass was 26–31 mg for the BAK-LT eye drops and 30 mg for PF-LT. The surface tension was lower for all BAK-LT eye drops (31.1–32.1 mN/m) compared with PF-LT (42 mN/m).Conclusion PF-LT compared with various branded and generic LT preparations containing BAK are less cytotoxic when applied to cultured GCs.