Efficacy and safety of preservative-free versus preserved timolol eye drops in glaucoma: A randomized crossover study

BACKGROUND: The efficacy and safety of preservative-free timolol (PF-timolol) vs preserved timolol (P-timolol) have not been compared in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OHT). METHODS: In this randomized, crossover, single-center study, patients received PF-timolol twice daily or P-timolol once daily for 6 weeks, followed by crossover to the alternate treatment for 6 weeks. The primary endpoint was the change in intraocular pressure (IOP) between treatment groups. Secondary endpoints were tear film breakup time (TBUT), superficial punctate keratopathy (SPK) score, conjunctival hyperemia, systemic vital signs, and patient-reported symptoms. RESULTS: Thirty-four patients (mean age 58.1 years; male 50%) were enrolled. At baseline, mean IOP was 13.6 ± 2.7 mmHg (right eye, OD) and 13.4 ± 2.7 mmHg (left eye, OS). At week 6, PF-timolol led to a greater reduction in IOP in the OD vs P-timolol (-1.3 ± 1.5 mmHg vs -0.2 ± 1.2 mmHg; p = 0.004), whereas no significant difference was observed in the OS ( p = 0.08). At week 12, the mean IOP did not differ between the two groups for both eyes. TBUT increased in the PF-timolol group but decreased in the P-timolol group ( p = 0.006), and the change from baseline favored PF-timolol ( p = 0.001). The SPK score decreased significantly more in the OD in the PF-timolol group than P-timolol group (-0.4 ± 0.8 4 vs 0.2 ± 1.1; p = 0.03). S ystemic vital signs remained stable throughout the study. Patient-reported symptoms were comparable between groups. CONCLUSION: PF-timolol eye drops achieved a greater IOP reduction at week 6 but showed comparable efficacy to P-timolol by week 12, while providing additional advantages in ocular safety outcomes and subjective tolerability. PF-timolol offers an effective and safer option for glaucoma management, particularly in patients sensitive to preservatives.