ArticleOphthalmology and therapy2026
Comparative Effectiveness of Timolol-Based Fixed-Combination Regimens for Glaucoma: a Retrospective Cohort Study Using Target Trial Emulation Framework.
Article in Ophthalmology and therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
introductionGlaucoma is a leading cause of irreversible blindness, and many patients ultimately require escalation beyond monotherapy to maintain adequate intraocular pressure control. Although timolol-based fixed-combination therapies are widely used, real-world evidence comparing their long-term effectiveness across different drug classes remains limited. This study was conducted to compare long-term outcomes among prostaglandin analog (PGA)/timolol, carbonic anhydrase inhibitor (CAI)/timolol, and α-agonist (AA)/timolol regimens.
methodsWe emulated a hypothetical open-label pragmatic trial using Taiwan's National Health Insurance Research Database, and included patients with incident glaucoma between 2011 and 2021 who initially received monotherapy and subsequently initiated a timolol-containing fixed-combination therapy with PGA, CAI, or AA. Propensity score-based overlap weighting was applied to balance baseline covariates, and Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). The primary outcome was treatment failure, defined as the initiation of additional topical anti-glaucoma medication, incisional surgery or laser treatment, or a diagnosis of blindness. Patients were followed from fixed-combination therapy initiation until occurrence of treatment failure, death, or 31 December 2021.
resultsAfter weighting, the cohorts included 5714 (PGA/timolol versus CAI/timolol), 5070 (PGA/timolol versus AA/timolol), and 18,654 (AA/timolol versus CAI/timolol) patients. PGA/timolol initiation was associated with a lower rate of treatment failure compared with CAI/timolol (HR: 0.85, 95% CI 0.80-0.91) and AA/timolol (HR: 0.87, 95% CI 0.81-0.93). PGA/timolol also reduced the need for additional medications and intraocular pressure-lowering procedures compared with other regimens. CAI/timolol and AA/timolol showed no significant difference in treatment failure rates (HR: 0.97, 95% CI 0.94-1.00).
conclusionsIn a nationwide real-world setting, PGA/timolol demonstrated superior long-term effectiveness compared with both CAI/timolol and AA/timolol, resulting in lower treatment failure rates and reduced need for additional medications or procedures. These findings suggest that PGA/timolol may be associated with the most favorable long-term effectiveness among timolol-based fixed combinations.
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