Efficacy and tolerability of fixed combination of Brimonidine 0.2%/Timolol 0.5% compared with fixed combination of Dorzolamide 2%/Timolol 0.5% in the treatment of patients with elevated intra-ocular pressure: a meta-analysis of randomised controlled trials

Methodological quality of the review: Low confidence

Author: Budengeri P, Cheng JW, Cai JP, Wei RL

Geographical coverage: Not reported

Sector: Glaucoma

Sub-sector: See above

Equity focus: None specified

Review type: Effectiveness review

Quantitative synthesis method: Meta-analysis

Qualitative synthesis method: Not applicable

Background: Medical management remains the keystone of glaucoma treatment. Therefore, it is important to select the simplest treatment regimen that achieves the most effective intra-ocular pressure (IOP) reduction.

Objectives: To evaluate the efficacy and tolerability of the fixed-combination Brimonidine 0.2%/Timolol 0.5% (FCBT) compared with the fixed-combination Dorzolamide 2%/Timolol 0.5% (FCDT) in the treatment of patients with elevated intraocular pressure (IOP).

Main findings: Both FCBT and FCDT can effectively lower IOP in patients with elevated IOP. There is no significant difference between the efficacy of FCBT and FCDT. FCBT affords an ocular comfort advantage compared with FCDT.

In this meta-analysis, seven studies involving 582 patients were included. With a weighted mean difference (WMD) of IOPR in diurnal mean of 0.44 mm Hg (95% CI, 0.00–0.88), the FCBT was as effective as FCDT in lowering IOP in patients with elevated IOP (P=0.05). The WMD of IOP reduction (IOPR) at peak was 0.65 mm Hg (95% CI, −0.06 to 1.35) (P=0.76), and there was no significant difference between FCBT and FCDT. FCBT caused burning/stinging in fewer patients than FCDT [pooled relative risk: 0.45 (95% CI, 0.29–0.70)].

Implications for further research: to evaluate the relative efficacy and tolerability of FCBT and FCDT in lowering IOP, further long-term studies are required. Outcome data for IOP reduction, IOP control, IOP response and adverse events should be included. The number of patients and the follow-up period should be increased.

Methodology: The Cochrane Library, PUBMED and EMBASE were searched for randomised controlled trials comparing FCBT with FCDT in patients with elevated IOP. The main efficacy measures were the IOPR, including diurnal mean IOPR and peak IOPR. The main tolerability measure was the individual adverse events. Authors extracted data of included studies using a customised form described in the Cochrane Handbook for Systematic Reviews. Quality assessment was conducted using the Jadad score. It was not clear from the review whether data extraction and quality assessment of included studies were conducted by two reviewers independently.

Authors conducted a statistical analysis using RevMan, using an intention-to-treat basis. Relative risk was estimated and WMD was calculated from continuous outcomes. Q statistic was used for all comparisons to evaluate heterogeneity of treatment effects between studies. Results were presented with 95% confidence intervals (CIs). To detect publication bias, asymmetry in funnel plots was visually examined.

Applicability/external validity:No methods were used either to assess the applicability/external validity of the results or to discuss how generalizable the results are.

Geographic focus:The review focused on all countries and it is not clear whether studies from low/middle-income countries were found.

Publication source: Budengeri P, Cheng JW, Cai JP, Wei RL. Efficacy and tolerability of fixed combination of Brimonidine 0.2%/Timolol 0.5% compared with fixed combination of Dorzolamide 2%/Timolol 0.5% in the treatment of patients with elevated intraocular pressure: a meta-analysis of randomised controlled trials. J Ocul Pharmacol Ther. 2013 Jun;29(5):474-9

Downloadable link: https://www.ncbi.nlm.nih.gov/pubmed/23379771

Summary of quality assessment: Overall, there is low confidence in conclusions about the effects of this study as important limitations were identified. The authors conducted a search on relevant databases, however manual searching and contacting experts/authors were not part of the search strategy. In the discussion section, authors noted avoiding language bias. In addition, it is not clear from the review if selection bias was avoided during study selection, and if data extraction and quality assessment were conducted by two reviewers independently.