The review concluded that all six commonly used drug combinations containing timolol could effectively lower intra-ocular pressure in patients with primary open-angle glaucoma and ocular hypertension. The authors' conclusions were based on the evidence but the relatively small sample sizes for some drug combinations, uncertain heterogeneity and uncertainty regarding the appropriateness of the synthesis should be considered.

To evaluate the intra-ocular pressure-lowering effect of commonly used fixed-combination drugs containing 0.5% timolol.

Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE and PubMed were searched between January 1998 and September 2011. Search terms were reported. Google and Yahoo were searched. Reference lists of retrieved articles were handsearched.

Randomised controlled trials (RCTs) of 2% dorzolamide/0.5% timolol twice daily, 1% brinzolamide/0.5% timolol twice daily, 0.2% brimonidine/0.5% timolol twice daily, 0.005% latanoprost/0.5% timolol once daily, 0.004% travoprost/0.5% timolol once daily and 0.03% bimatoprost/0.5% timolol once daily in patients (at least 85% of trial population) diagnosed with primary open-angle glaucoma or ocular hypertension were eligible for inclusion. Trials had to report at least one time point between one and three months. The intervention had to be given after a wash out period. Relevant outcomes were absolute and relative reductions from baseline in intra-ocular pressure.

The included trials were of patients with mean baseline intra-ocular pressure in the range 22 to 30.2 mmHg. The proportion of patients with primary open-angle glaucoma or ocular hypertension ranged from 90% to 100%. Mean patient ages ranged from 56.1 to 68 years. Trials were undertaken in various countries that included USA, Australia, Brazil and Greece. Study duration ranged from four to 812 weeks.

Two reviewers independently undertook study selection.

Quality assessment was undertaken using the Delphi list of quality items such as randomisation, blinding and withdrawals to give a maximum score out of 18. Higher scores indicated better quality.

Two reviewers independently undertook quality assessment.

Data were extracted on an intention-to-treat basis and used to calculate absolute and relative reductions from baseline in intra-ocular pressure, together with 95% confidence intervals (CIs).

Two reviewers independently extracted these data.

Random-effects meta-analysis was used to calculate pooled estimates of intra-ocular pressure and 95% CIs. Mixed-effects meta-regression was used to estimate weighted mean differences (WMDs) and 95% CIs for different drug combinations. The Ι² statistic was used to assess statistical heterogeneity. Egger’s weighted regression test was used to assess publication bias.

Forty-one RCTs with 53 arms were included in the review (5,261 patients, range 14 to 533 patients). The mean quality score was 16.2 (range 13 to 18). No publication bias was found.

Relative reductions for mean diurnal intra-ocular pressure were 34.9% for travoprost/timolol (95% CI 33.0 to 36.8%; seven RCTs), 34.3% for bimatoprost/timolol (95% CI 33.2 to 35.4%; one RCT), 33.9% for latanoprost/timolol (95% CI 32.5 to 35.2%; 12 RCTs), 32.7% for brinzolamide/timolol (95% CI 28.3 to 37.1%; two RCTs), 29.9% for dorzolamide/timolol (95% CI 27.4 to 32.4%; 18 RCTs) and 28.1% for brimonidine/timolol (95% CI 23.2 to 32.9%; four RCTs).

Latanoprost/timolol was statistically significantly better at lowering intra-ocular pressure than dorzolamide/timolol (WMD 3.8, 95% CI 0.8 to 6.7) and brimonidine/timolol (WMD 5.9, 95% CI 2.5 to 9.4). Travoprost/timolol was statistically significantly better at lowering intra-ocular pressure than dorzolamide/timolol (WMD 3.3, 95% CI 2.2 to 4.5) and brimonidine/timolol (WMD 7.0, 95% CI 2.5 to 11.6). Other results were presented in the review.

All six commonly used fixed-combination drugs containing timolol could effectively lower intra-ocular pressure in patients with primary open-angle glaucoma and ocular hypertension. Latanoprost/timolol and travoprost/timolol possibly achieved the best effects.

Inclusion criteria for the review were clearly defined and three relevant databases were searched. Publication bias was assessed and was not detected. Attempts were made to reduce reviewer error and bias throughout the review. Quality assessment was undertaken using a standard checklist that indicated that most of the evidence was good quality.

Data were combined using meta-analysis. Statistical heterogeneity was not reported, which made it difficult to determine the suitability of data for pooling. Fourteen crossover trials were included but it was not clear whether they were synthesised using appropriate methods as insufficient information was provided. The authors noted that evidence for bimatoprost/timolol and brinzolamide/timolol was based on only two papers.

Overall the authors' conclusions were based on the evidence but the relatively small sample sizes for some drug combinations, uncertain heterogeneity and uncertainty regarding the appropriateness of the synthesis should be considered.

Practice: The authors did not state any implications for practice.

Research: The authors stated that further research of bimatoprost/timolol and brinzolamide/timolol was needed.

Shanghai Rising-Star Program; Shanghai Municipal Natural Science Foundation; National Natural Science Foundation of China.

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.