Eight parallel-group studies (ten articles) were included in the review, all apparently RCTs (n=2,387, 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 IOPR did not differ significantly between the groups (WMD 0.24 mmHg, 95% CI: -0.57, 1.04). This finding had significant heterogeneity (p=0.00001, I2=91%). Subgroup and metaregression 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.
The risk of adverse effects (burning and stinging) did not differ significantly between the groups (RR 1.14, 95% CI: 0.61, 2.14) but a significantly lower risk of allergy was associated with timolol (RR 0.08, 95% CI: 0.01, 0.47, p=0.005).
One study reported a chronotropic effect with timolol (p=0.04, n=211).
Individual studies found that brimonidine was associated with a significantly improved between- or within-group outcome (respectively) for RNFL damage (n=41; p≤0.02), and contrast sensitivity (n=16, p≤0.046).
There was no obvious evidence of publication bias.