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Br J Ophthalmol. 2020 Feb 12. pii: bjophthalmol-2019-315623. doi: 10.1136/bjophthalmol-2019-315623. [Epub ahead of print]

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.

Author information

Department of Ophthalmology, Copenhagen University Hospital, Rigshospitalet-Glostrup, Glostrup, Denmark.
Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
Department of Neurosciences, Psychology, Drug Research and Child Health (NEUROFARBA), University of Firenze and AOU Careggi, Florence, Italy.
Centre for Public Health, Queen's University Belfast, Belfast, Northern Ireland, UK.
Department of Ophthalmology, Copenhagen University Hospital, Rigshospitalet-Glostrup, Glostrup, Denmark



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.


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.


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.


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 numberCRD42019139692.


drugs; glaucoma; intraocular pressure; ocular surface

Conflict of interest statement

Competing interests: None declared.

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