Design: multicentre, randomised, double-blind, parallel-group superiority trial across 25 centres, ANCOVA on the primary endpoint
Population: 219 Chinese patients with open-angle glaucoma or ocular hypertension needing further pressure reduction after a four-week washout; mean age 44.8 years (SD 15.7), 59.1% male
Primary outcome: change from baseline in mean diurnal intraocular pressure at three months
Effect: reduction 6.56 ± 3.44 mmHg vs 5.36 ± 2.94 mmHg; adjusted difference −1.312 mmHg (95% CI −2.010 to −0.696); ocular adverse events 20.0% vs 26.6%, conjunctival hyperaemia 2.7% vs 8.3%

Adding timolol to a prostaglandin is routine; whether it should come as a fixed preservative-free combination or a second bottle is a question about adherence and surface toxicity as much as pressure. A multicentre randomised, double-blind trial across 25 Chinese centres enrolled 219 patients with open-angle glaucoma or ocular hypertension who still needed more pressure reduction after a four-week washout, and randomised them 1:1 to preservative-free tafluprost/timolol fixed combination or preservative-free tafluprost alone, once daily for three months.

Mean diurnal intraocular pressure — averaged across 08:00, 10:00 and 16:00 — fell by 6.56 ± 3.44 mmHg on the combination and 5.36 ± 2.94 mmHg on monotherapy. Adjusted for baseline, the between-group difference was −1.312 mmHg (95% confidence interval −2.010 to −0.696), establishing superiority by the trial's prespecified criterion. Responder rates at the ≥15%, ≥25% and ≥30% reduction thresholds were all higher on the combination. Ocular adverse events were less frequent on the combination (20.0% against 26.6%), driven by conjunctival hyperaemia, which occurred in 2.7% against 8.3%.

The hyperaemia difference is the part that will matter in clinic, since prostaglandin-associated redness is a common reason patients quietly stop treatment. Two caveats belong with it. The participants were young for a glaucoma trial — mean age 44.8 years — so this is not a cohort representative of typical open-angle glaucoma, and three months is short. And timolol remains timolol: the asthma, chronic obstructive pulmonary disease, bradycardia and heart block contraindications apply exactly as they do to the separate drops.

Screen for asthma, chronic obstructive pulmonary disease, bradycardia and heart block before any fixed combination containing timolol.
Consider the fixed combination where prostaglandin-associated hyperaemia is limiting adherence.
Teach punctal occlusion; it reduces systemic beta-blocker absorption and costs nothing.
Count the bottles a patient is on — fewer bottles is a real adherence intervention in its own right.
Do not extrapolate three-month pressure data to long-term field preservation.

Why it matters

The fixed combination reduced the side effect that most often ends prostaglandin treatment, rather than adding one.

The statistics, in plain English

A 1.3 mmHg additional reduction is real but modest, and the confidence interval (−2.01 to −0.70) tells you the plausible range: at best two millimetres, at worst under one. Whether that matters depends entirely on the starting pressure and the target. The lower adverse event rate on the combination is unusual for an added drug and is driven by less hyperaemia, which is probably a dilution effect on the prostaglandin rather than a protective action of timolol. At three months this trial can say nothing about visual field outcomes, which is what the pressure reduction is for.