A systematic review based on 16 studies on patients with glaucoma or ocular hypertension (OHT) found no evidence of statistically significant differences in IOP or safety between benzalkonium chloride (BAK)-preserved eye drops, preservative-free and alternatively preserved prostaglandin analogue and beta-blocker eye-drops.

IOP was 0.15mm Hg lower in the BAK group than in the other groups, but this difference was not statistically significant or clinically relevant. Meta-analyses also revealed no differences with regards to conjunctival hyperemia, ocular hyperemia, total ocular adverse events or tear break-up time. The review noted that tolerability of eye drops with or without preservatives was generally reported as good.

Overall, the included studies varied substantially in study design and measuring methods, making comparisons challenging and questionable. According to the researchers, lack of statistically significant differences in adverse effects should be interpreted with caution, as it could be due to the variability in the reporting of side effects and not necessarily from the lack of toxic effect induced by BAK.

The researchers recommend longer clinical studies with standardized measurements and grading guidelines when assessing safety of eye drops to more accurately compare safety to fully identify any potential differences between preservation methods.

Hedengran A, Steensberg AT, Virgili G, et al. 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. Br J Ophthalmol. February 12, 2020. [Epub ahead of print].