Efficacy and Safety of Brinzolamide as Add-On to Prostaglandin Analogues or β-Blocker for Glaucoma and Ocular Hypertension: A Systematic Review and Meta-Analysis

Background: Brinzolamide as a carbonic anhydrase inhibitor could be combined with other intraocular pressure (IOP) lowering drugs for glaucoma and ocular hypertension (OHT), but the efficacy was controversial. So, this study was used to assess the efficacy and safety of brinzolamide as add-on to prostaglandin analogues (PGAs) or β-blocker in treating patients with glaucoma or OHT who fail to adequately control IOP. Methods: We searched PubMed, Embase, MEDLINE, Cochrane Library, and clinicaltrials.gov from inception to October 4, 2018. Randomized controlled trials of brinzolamide as add-on to PGAs or β-blocker for glaucoma and OHT were included. Meta-analysis was conducted by RevMan 5.3 software. Results: A total of 26 trials including 5,583 patients were analyzed. Brinzolamide produced absolute reductions of IOP as an adjunctive therapy for patients with glaucoma or OHT. Brinzolamide and timolol were not significantly different in lowering IOP as add-on to PGAs (9 am: P = 0.07; 12 am: P = 0.66; 4 pm: P = 0.66). Likewise, brinzolamide was as effective as dorzolamide in depressing IOP (9 am: P = 0.59; 12 am: P = 0.94; 4 pm: P = 0.95). For the mean diurnal IOP at the end of treatment duration, there were no statistical differences in above comparisons (P > 0.05). Compared with brimonidine (b.i.d.), there was a significant reduction of IOP in brinzolamide (b.i.d.) at 9 am (P < 0.0001); however, the difference was cloudy in thrice daily subgroup (P = 0.44); at 12 am, brinzolamide (b.i.d.) was similar to brimonidine (b.i.d.) in IOP-lowering effect (P = 0.23), whereas brimonidine (t.i.d.) led to a greater effect than brinzolamide (t.i.d.) (P = 0.02). At 4 pm, brinzolamide (b.i.d.) was superior IOP-lowering effect compared with brimonidine (b.i.d.) (P = 0.0003); conversely, the effect in brinzolamide (t.i.d.) was lower than brimonidine (t.i.d.) (P < 0.0001). For the mean diurnal IOP, brinzolamide was lower in twice daily subgroup (P < 0.00001); brimonidine was lower in thrice daily subgroup (P < 0.00001). With regard to the safety, brinzolamide and dorzolamide had a higher incidence of taste abnormality; moreover, brinzolamide resulted in more frequent blurred vision; dorzolamide resulted in more frequent ocular discomfort and eye pain. Timolol resulted in more frequent blurred vision and less conjunctival hyperemia. Brimonidine resulted in more frequent ocular hyperemia. As to other adverse events (AEs) (conjunctivitis, eye pruritus, foreign body sensation in eyes, and treatment-related AEs), brinzolamide was similar to other three active comparators. Conclusions: Brinzolamide, as add-on to PGAs or β-blocker, significantly decreased IOP of patients with refractory glaucoma or OHT and the AEs were tolerable.