Article Text

Download PDFPDF
Efficacy and safety evaluation of benzalkonium chloride preserved eye-drops compared with alternatively preserved and preservative-free eye-drops in the treatment of glaucoma: a systematic review and meta-analysis
  1. Anne Hedengran1,2,
  2. Alvilda T Steensberg2,
  3. Gianni Virgili3,
  4. Augusto Azuara-Blanco4,
  5. Miriam Kolko1,2
  1. 1Department of Ophthalmology, Copenhagen University Hospital, Rigshospitalet-Glostrup, Glostrup, Denmark
  2. 2Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark
  3. 3Department of Neurosciences, Psychology, Drug Research and Child Health (NEUROFARBA), University of Firenze and AOU Careggi, Florence, Italy
  4. 4Centre for Public Health, Queen's University Belfast, Belfast, Northern Ireland, UK
  1. Correspondence to Professor Miriam Kolko, Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark; miriamk{at}


Background/aims This systematic review compared the efficacy and safety of benzalkonium chloride (BAK)-preserved eye-drops with alternatively preserved (AP) and preservative-free (PF) eye-drops.

Methods PubMed, EMBASE and MEDLINE were searched for randomised controlled trials in June and October 2019. Study selection, data extraction and risk of bias assessment were made by two independent reviewers using the Cochrane Handbook. Studies on prostaglandin analogue or beta-blocker eye-drops and patients with glaucoma or ocular hypertension were included. Primary outcome was change in intraocular pressure (IOP). Secondary outcomes were safety measures as assessed in original study.

Results Of 433 articles screened, 16 studies were included. IOP meta-analysis was conducted on 13 studies (4201 patients) ranging from 15 days to 6 months. No significant differences between BAK versus PF and AP were identified (95% CI −0.00 to 0.30 mm Hg, p=0.05). Meta-analyses revealed no differences between BAK versus AP and PF with regards to conjunctival hyperaemia (risk ratio (RR) 1.05, 95% CI 0.91 to 1.22, 3800 patients, 9 studies), ocular hyperaemia (RR 1.31, 95% CI 0.96 to 1.78, 2268 patients, 5 studies), total ocular adverse events (RR 1.03, 95% CI 0.88 to 1.20, 1906 patients, 5 studies) or tear break-up time (mean difference 0.89, 95% CI −0.03 to 1.81, 130 patients, 3 studies). Diverse reporting on safety measures made comparison challenging. Risk of bias was assessed as high or unclear in many relevant domains, suggesting potential selective reporting or under-reporting.

Conclusion No clinically significant differences on efficacy or safety could be determined between BAK versus AP and PF. However, there were substantial uncertainties on safety.

PROSPERO registration number


  • glaucoma
  • drugs
  • ocular surface
  • intraocular pressure

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


  • Contributors All authors contributed to study design, drafting of manuscript and data interpretation. MK and AA-B initiated the systematic review. AH and ATS performed study selection, data extraction and risk of bias assessments. GV performed all meta-analyses. All authors contributed to and approved the final manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data included in this systematic review is extracted from published articles. No additional data has been supplied for the authors.