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
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We welcome the recent meta-analysis by Hedengran and co-workers in the British Journal of Ophthalmology (BJO).1 This study compared the efficacy and safety of benzalkonium chloride (BAK)-preserved eye drops with alternatively preserved (AP) and preservative-free (PF) eye drops. The meta-analysis was conducted on 16 studies that range from 15 days to 6 months of study duration. Change in IOP in BAK vs AP and PF groups was meta-analysed as the primary outcome. Conjunctival hyperaemia, ocular hyperaemia, total ocular adverse effects (AE), and TBUT were also meta-analysed. The authors found no evidence of significant change in IOP and conjunctival hyperaemia between BAK vs AP and PF treatment groups. The authors concluded that the main reason for detecting no clinical differences between the groups was related to the lack of long-term clinical studies on the safety of BAK vs AP and PF eye drops. We are in consensus with Kontas AG et al., comments on the deficiencies of this meta-analysis.
We do not agree to the conclusion, “BAK-containing and PF medications do not differ with respect to tolerability and therapy outcome”. We would like to direct the authors and readers to our recently published study in the journal, Clinical and Experimental Ophthalmology (CEO), which involved the randomised evaluation of the inflammatory effects of PF vs BAK and PF vs polyquad (PQ)-preserved eye drops in naïve glaucomatous patients over the period of 24 months.2 We p...Show More
In their review and meta-analysis, Hedengran and coworkers1 report no relative therapeutic benefit of preservative-free (PF) therapies over benzalkonium chloride (BAK)-preserved ones. Should the costlier PF medications therefore be abandoned, or should we question this conclusion?Show More
Ten of the 16 comparative trials analysed were of short duration, (between 15 and 90 days), the longest taking 6 months. Once-a-day medication was used in each trial, yet the dose response curve for BAK toxicity shows that each additional drop of BAK-containing medication doubles the likelihood of lissamine green corneal staining2 and increases the risk of early failure of glaucoma surgery.3 BAK toxicity is slow in onset increasing over time, due to its continual accumulation within ocular tissues.3 Thus, inconsistencies between experimental studies, which document the harmful effects of BAK and clinical trials, which do not, likely relate to the timing, dosing and duration of glaucoma therapy.4 Two to 12 week trials comparing BAK with alternatively preserved eyedrops, or PF formulations have shown no convincing differences in ocular tolerability, yet the benefits from switching from once-a-day preserved to PF therapy, accrue several months later.4 Longer term transition to alternatively preserved, or PF formulations improves tolerability, and there is good evidence that substituting PF tafluprost for BAK-containing latanoprost significantly improves tolerability.3 So sh...