Eight parallel-group studies (ten articles) were included in the review, all apparently RCTs (2,387 patients, range 40 to 774) and all published in English. Seven studies reported adequate allocation concealment and double blinding; withdrawal rates ranged from nil to 18% (where stated) and eight studies reported using ITT analysis or carrying the last observation forwards.
Timolol versus brimonidine (eight studies):When all studies were combined, the mean intraocular pressure reduction did not differ significantly between the groups (WMD 0.24mmHg, 95% CI -0.57 to 1.04). This finding had significant heterogeneity (p=0.00001, Ι²=91%). Subgroup and meta-regression analyses of efficacy outcomes suggested that studies with at least 100 participants, which were those more likely to have adequate allocation concealment, slightly favoured brimonidine.
Adverse effects: The risk of adverse effects (burning and stinging) did not differ significantly between the groups (RR 1.14, 95% CI 0.61 to 2.14) but a significantly lower risk of allergy was associated with timolol (RR 0.08, 95% CI 0.01 to 0.47, p=0.005).
One study reported a chronotropic effect with timolol (p=0.04, 211 patients).
Other outcomes: Individual studies found that brimonidine was associated with a significantly improved between- or within-group outcome for retinal nerve fibre layer damage (41 patients; p≤0.02), and contrast sensitivity (16 patients, p≤0.046).
There was no obvious evidence of publication bias.