Efficacy and Safety of Preservative-Free versus Preserved Latanoprost in Glaucoma and Ocular Hypertension: A Systematic Review and Meta-analysis

Muhammad Alfatih; Christina Wunardi; Dillan Cunha Amaral; Ricardo Noguera Louzada; Hashem Abu Serhan

doi:10.1097/IJG.0000000000002698

Efficacy and Safety of Preservative-Free versus Preserved Latanoprost in Glaucoma and Ocular Hypertension: A Systematic Review and Meta-analysis

J Glaucoma. 2026 Feb 13. doi: 10.1097/IJG.0000000000002698. Online ahead of print.

Authors

Muhammad Alfatih¹, Christina Wunardi², Dillan Cunha Amaral³, Ricardo Noguera Louzada³, Hashem Abu Serhan⁴

Affiliations

¹ Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
² Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia.
³ Faculty of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro 21941-617, RJ, Brazil.
⁴ Department of Ophthalmology, Hamad Medical Corporation, Doha, Qatar.

PMID: 41842582
DOI: 10.1097/IJG.0000000000002698

Abstract

Précis: In this meta-analysis of 10 randomized controlled trials involving 1,880 eyes, preservative-free latanoprost (PFL) demonstrated comparable intraocular pressure-lowering efficacy to preserved latanoprost (PL), but with significantly lower risk of ocular surface hyperemia, supporting its use in patients with sensitivity to preservatives.

Purpose: To review the efficacy and safety of preservative-free latanoprost (PFL) versus preserved latanoprost (PL) for glaucoma and ocular hypertension.

Methods: The protocol was registered in PROSPERO (CRD420251027099) and performed the literature search on PubMed, Scopus, CENTRAL, ScienceDirect, and Google Scholar in March 2025 to find eligible randomized controlled trials (RCTs). Outcomes of interest include IOP reduction and ocular adverse events (OAEs). Risk of bias was evaluated using Cochrane RoB 2.0. The meta-analyses were executed in Rstudio.

Results: The search yielded 591 records, of which 10 studies involving 1,880 patients from the USA, India, South Korea, and various European countries were included in this study. Meta-analyses showed a significantly greater mean IOP reduction with PL compared to PFL at 2 weeks (MD=0.43 mmHg, 95% CI: 0.05-0.81), with no significant difference at 4, 6, and 12 weeks (MD=0.03 mmHg, 95% CI: -0.31-0.37; MD=0.14 mmHg, 95% CI: -0.20-0.48; and MD=0.22 mmHg, 95% CI: -0.15-0.59, respectively). In terms of safety, PFL was associated with a significantly lower risk of ocular surface hyperemia (RR=0.66, 95% CI: 0.51-0.85) and and a lower-though not statistically significant-risk of overall OAEs (RR=0.81, 95% CI 0.66-1.00). GRADE assessment constitute to low to moderate certainty of evidence.

Conclusion: PFL have comparable IOP-lowering efficacy compared to PL, with superior ocular tolerability. These findings support the use of PFL as a suitable alternative to PL, particularly in patients sensitive to preservatives.

Keywords: Glaucoma; intraocular pressure; latanoprost; ocular adverse events; ocular hypertension; preservative-free.