Fixed Triple-Combination Bimatoprost/Brimonidine/Timolol Versus Separate Administration in Glaucoma: Randomized Clinical Trial

Abstract

Purpose: To compare the efficacy, tolerability, and persistence of a fixed triple combination (FTC) of bimatoprost 0.01%/brimonidine tartrate 0.15%/timolol maleate 0.5% with the same agents administered separately. Secondary outcomes included adverse effects, quality of life (QoL), and adherence. Methods: This randomized clinical trial included 46 patients with primary open-angle ( n = 36) or primary angle-closure glaucoma ( n = 10) requiring three or more hypotensive agents. After a washout period, participants were randomized to FTC twice daily or to bimatoprost 0.03% once, brimonidine 0.2%, and timolol 0.5% twice daily. Examinations at 1, 4, and 6 months included conjunctival hyperemia grading, tear break-up time, corneal staining, and validated questionnaires assessing QoL, ocular surface, and adherence. Results: Mean age was 65.0 ± 11.5 years; baseline mean deviation –11.94 ± 8.72 dB, and prior treatment 3.9 ± 2.5 years. Both regimens significantly reduced intraocular pressure (FTC group: 24.37 ± 5.92 to 15.42 ± 2.69 mmHg; unfixed group: 26.18 ± 6.79 to 14.53 ± 3.49 mmHg; P < 0.001), with no difference between groups. Hyperemia worsened ( P = 0.009), QoL declined ( P < 0.001), and adherence remained stable. Discontinuation reached 63%, mainly from disease progression (34.5%) and intolerance (27.6%). Survival analysis showed a 69.6% probability of treatment maintenance at 6 months. Among completers, 61.8% had worsening hyperemia ( P = 0.004), whereas discontinuers exhibited QoL decline ( P < 0.001). In FTC, the visual field deteriorated in the discontinued group (Δ–1.11; P = 0.025). Conclusions: Both regimens achieved similar efficacy but were associated with progressive hyperemia, reduced QoL, and low persistence, underscoring the limitations of multiple topical glaucoma therapy.