Comparative efficacy and safety of preserved versus preservative‐free beta‐blockers in patients with glaucoma or ocular hypertension: a systematic review

Abstract

Preservative‐free topical medications have been introduced for glaucoma care to reduce ocular adverse events associated with preservatives. This is a systematic review and meta‐analysis of randomized clinical trials (RCTs) comparing the efficacy and safety of beta‐blockers, or combination using beta‐blockers, with and without preservatives. PubMed, EMBASE and Web of Science were examined. Risk of bias was assessed using the Cochrane Handbook for Systematic Reviews. The primary outcome was change in intraocular pressure (IOP) from baseline to final follow‐up. Secondary outcomes included ocular and systemic side effects, and other clinical and quality of life outcomes. Of 242 records identified, seven RCTs (1125 patients) were included. The follow‐up period ranged from one to 12 months. Timolol was used in five studies, and two studies used a combination (timolol with bimatoprost or dorzolamide). The difference in mean change (MD) in IOP between the preservative‐free and the preserved drugs was statistically significant but not clinically relevant: (MD 0.29 mmHg, 95% confidence interval 0.07–0.51 mmHg, p = 0.010; moderate‐certainty evidence). Regarding adverse events: Level of evidence for all ocular surface outcome was low or very low and reported in few studies. No significant difference was observed on ocular surface symptoms. Tear break‐up time (TBUT) was better with preservative‐free drops (p < 0.001). Schirmer’s test was better in the preservative‐free group (p < 0.001). Level of evidence for all ocular surface outcomes was low or very low. There was no difference in other secondary outcomes. We found no clinically relevant difference in mean change in IOP between the preserved and the preservative‐free treatments. Data on adverse events used different methods and were incompletely reported. Although some measures of ocular surface health favoured preservative‐free medications, more evidence is needed. The increasing use of preservative‐free drops may be associated with better ocular surface and tolerability, but strong evidence from RCTs would be welcome.

Czy konserwanty poprawiają przepuszczalność powierzchni oka, a tym samym skuteczność terapii?

“…In the meta-analysis, the level of evidence for all ocular surface outcomes was low or very low and reported in only a few studies. No significant difference was observed in ocular surface symptoms [10].…”

“…The difference in mean IOP changes between preservative-free and preservative-containing formulations was statistically significant, but of no clinical importance (MD 0.29 mmHg; 95% confidence interval 0.07-0.51 mmHg; p = 0.010). In 6 out of 7 studies, slightly lower IOP was reported in patients using preservative-containing formulations [10].…”

Autophagy in glaucoma pathogenesis: Therapeutic potential and future perspectives

“…Glaucoma is a complex disease with no effective cure. Glaucoma is usually treated with prescription eye drops that function via different molecular mechanisms, including prostaglandin analogs (latanoprost, travoprost, bimatoprost, and tafluprost) ( Aihara, 2021 ), β-blockers ( Skov et al, 2021 ), α-adrenergic agonists ( Nocentini and Supuran, 2019 ), cholinergic inhibitors, carbonic anhydrase inhibitors ( Jansook et al, 2021 ) and cholinergic drugs ( Faiq et al, 2019 ). These eye drops reduce IOP by improving the outflow of AH through the trabecular drainage system or by reducing the volume of AH produced by the eye.…”

Rho Kinase (ROCK) Inhibitors for the Treatment of Glaucoma

“…Typically, medication is the preferred treatment choice for patients with glaucoma [ 18 ]. In recent decades, several small-molecule agents, such as cholinergic agents [ 19 , 20 ], beta-adrenergic agonists [ 21 , 22 ], alpha-adrenergic agonists [ 23 ], beta-blockers [ 24 , 25 ], carbonic anhydrase inhibitors [ 26 ], prostaglandin analogs [ 27 - 29 ], and Rho-associated coiled-coil protein kinase (ROCK) inhibitors [ 30 ], have been developed and used to treat glaucoma. These molecular agents can lower IOP by reducing the rate of AH formation, increasing the outflow of AH from the unconventional outflow pathway, or decreasing the outflow resistance of AH in the conventional outflow pathway [ 23 ].…”