Comparison of Efficacy and Ocular Surface Assessment Between Preserved and Preservative-Free Brimonidine/Timolol Fixed-Combination Eye Drops in Glaucoma Patients: A Parallel-Grouped, Randomized Trial

Abstract

The objectives of the study were to compare the efficacy and safety using ocular surface assessment between preserved and preservative-free brimonidine/timolol fixed-combination eye drops in glaucoma or ocular hypertension patients. Methods: This study was designed as a prospective, multicenter (three institutions), investigator-masked, parallel-grouped randomized clinical trial. The primary outcomes were corneal and conjunctival staining score, ocular surface disease index (OSDI) score, drug tolerance, and adherence rates at 12-week visits. The secondary outcomes were corneal and conjunctival staining score, OSDI score at 4-week visits and intraocular pressure (IOP), tear-film break-up time (TBUT), and bulbar/limbal hyperemia score at the 4- and 12-week visits. For safety assessment, best-corrected visual acuity (BCVA), systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and physical examination at 4 and 12 weeks and adverse events during the whole study period were analyzed. Results: Overall, 59 patients were enrolled and randomized into each group (29 preserved and 30 preservative-free). At the endpoint, 5 patients in the preserved group and 2 patients in the preservative-free group dropped out, leaving 24 and 28 patients in the preserved and preservative-free groups, respectively. Baseline characteristics showed no significant difference between the groups including age and sex. At the 12-week visit, intra-group change of OSDI scores did not change significantly compared to the baseline scores in both preserved and preservative-free groups (p = 0.791, 0.478, respectively). On the contrary, the corneal staining score and the conjunctival staining score showed a significant increase compared to the baseline score in the preserved group (p = 0.015, 0.009, respectively). Regarding drug satisfaction, higher proportions of patients in the preservative-free group reported convenience of installation (p = 0.002). Also, stinging and burning sensations in drug tolerance showed better results in the preservative-free group with a significant difference (p = 0.011). Safety assessment regarding systemic side effects such as SBP, DBP, and HR showed similar results between the preserved and preservative-free groups (p = 0.711, 0.232, 0.666, respectively). Conclusions: Preservative-free brimonidine/timolol showed comparable efficacy and safety, better corneal and conjunctival staining score with convenience of installation, and lower stinging and burning sensation. It is expected to be a proper treatment option for patients with glaucoma or ocular hypertension.