Comparison of Preservative-Free and Preserved Latanoprost in Primary Open-Angle Glaucoma: A Randomized Crossover Study

Objective: To compare the effects of Preservative-free (PF) and benzalkonium chloride (BAK)-preserved latanoprost on intraocular pressure (IOP), objective ocular surface signs, and subjective symptoms in patients with primary open-angle glaucoma (POAG). Methods: A prospective, randomized, crossover study was conducted with 29 POAG patients. Participants were randomized to receive either PF or BAK-preserved latanoprost for two months, followed by a crossover to the alternative formulation for another two months. IOP, tear break-up time (TBUT), conjunctival staining, and patient-reported symptoms were assessed at baseline and after each treatment period. Results: IOP was significantly and comparably reduced by both formulations (PF: from 16.49 ± 3.89 to 15.05 ± 2.55 mmHg, P = 0.007; preserved: from 15.60 ± 3.79 to 13.79 ± 3.53 mmHg, P < 0.001). However, BAK-preserved latanoprost significantly shortened TBUT (from 7.23 ± 2.37 to 6.07 ± 2.40 s, P = 0.007) and worsened conjunctival staining (from 0.31 ± 0.60 to 0.69 ± 0.71, P = 0.013), whereas PF latanoprost maintained tear film stability (TBUT: from 5.61 ± 2.19 to 5.22 ± 2.26 s, P = 0.337) and improved conjunctival staining (from 0.76 ± 0.83 to 0.31 ± 0.60, P = 0.003). Subjective symptoms including burning (PF: 0.34 ± 0.81 vs. preserved: 1.21 ± 1.17, P = 0.001), stinging (0.14 ± 0.35 vs. 0.79 ± 0.79, P < 0.001), and pruritus (0.21 ± 0.41 vs. 0.50 ± 0.64, P = 0.030) were markedly lower with the PF formulation. After crossover, patients switching from preserved to PF latanoprost showed improvements in burning (P = 0.012) and photophobia (P < 0.001). Conclusion: PF latanoprost provides equivalent IOP-lowering efficacy to BAK-preserved latanoprost while offering significant advantages in ocular surface health and symptom tolerability. These findings support PF formulations as a preferred first-line option for glaucoma management to enhance treatment tolerability and patient's quality of life.