Twelve studies involving 3048 patients with open-angle glaucoma or ocular hypertension were included in the meta-analysis comparing timolol with prostaglandin analogs «Li N, Chen XM, Zhou Y ym. Travoprost compared with...»1. Participants received either travoprost, other prostaglandin analog or timolol.
Ocular hyperaemia was the most common side-effect of prostaglandin analogues. The combined results suggested that travoprost 0.004 % caused a higher percentage of ocular hyperaemia than timolol 0.5 % (OR = 6.76, 95 % CI 4.93-9.25, P < 0.00001), or latanoprost 0.005 % (OR = 2.03, 95 % CI 1.49-2.75, P = 0.00001) and travoprost 0.0015 % (OR = 1.64, 95 % CI 1.32-2.04, P = 0.00001). However, there was no statistically significant difference between travoprost 0.004 % and bimatoprost 0.03 % (OR = 0.65, 95 % CI 0.42.1.00, P = 0.05) in hyperaemia.
There was an increased incidence of pigmentation with travoprost 0.004 % when compared to timolol 0.5 % (OR = 11.06, 95 % CI 2.07-59.08, P = 0.005). There was no statistically significant difference between travoprost 0.004 % and latanoprost 0.005 % (OR = 0.74, 95 % CI 0.38-1.46, P = 0.4) in iris pigmentation.
Travoprost 0.004 % caused a higher percentage of eyelash changes than timolol 0.5 % (OR = 38.81, 95 % CI 20.65-72.93, P < 0.00001). There was also an increased incidence of eyelash changes with travoprost 0.004 % than latanoptost 0.005 % (OR = 3.82, 95 % CI 2.50-5.84, P < 0.00001), or travoprost 0.0015 % (OR = 1.79, 95 % CI 1.40-2.27, P < 0.00001).
In another meta-analysis comparing latanoprost with timolol in patients with open-angle glaucoma «Zhang WY, Po AL, Dua HS ym. Meta-analysis of rando...»2, latanoprost caused hyperaemia and iris pigmentation more often than timolol (RR = 2.20, 95 % CI 1.33-3.65). The number needed to harm was 21 (CI 14-42) when compared to timolol. Moreover, of 478 patients who were treated with latanoprost, 21 (4.39 %) developed iris pigmentation. In contrast, none of the patients treated with timolol showed this effect (0/387). Four studies compared systemic adverse reactions to timolol versus latanoprost, such as their effects on systolic blood pressure and heart rate. Timolol caused slowing of heart rate after 3 or 6 months of treatment, and this returned to the baseline level after switching to latanoprost.
In a systematic review comparing timolol with brimonidine (α2 adrenergic agonist), prostaglandin analogs (travoprost, latanoprost), other β adrenergic antagonists, and placebo «Boland MV, Ervin AM, Friedman DS ym. Comparative e...»3 there was a twofold increase in the odds of participant drop out due to drug-related adverse events among participants randomized to timolol versus betaxolol (OR. 2.40; 95 % CI, 1.04-5.53, five trials), and the odds of dropping out were lower among participants randomized to timolol when compared to those receiving brimonidine (OR, 0.21; 95 % CI 0.14-0.31, three trials). As to the comparison of timolol with prostaglandin analogs, participants receiving either travoprost or latanoprost had six times the odds and twice the odds (OR, 6.76, CI 4.93-9.25 and OR 2.03, CL 1.49-2.75), respectively, of dropping out of the study due to conjuctival hyperemia, compared to patients receiving timolol. Both drugs also significantly increased iris pigmentation (travoprost OR 11.06, CI 2.07-59.08 and latanoprost OR 8.01, Cl 1.87-34.30).
Subjects on timolol (beta-blocker) were less likely to drop out of studies due to side effects than those on brimonidine (alpha-adrenergic agonist), latanoprost (prostaglandin analog), travoprost (prostaglandin analog), or betaxolol (beta-blocker).
Comment: The side effects of porostaglandin analogs are usual but local while the side effects of betablockers are more systemic and may be severe.