Author’s Disclosure Block: Sohat Sharma, none; Rishav Singh, none; Michael Balas, none; David Mathew, none

Abstract Body
Purpose: This systematic review and meta-analysis aimed to assess the safety and efficacy of Omidenpag Isopropyl (OMDI) 0.002% in comparison to commonly used Prostaglandin F2alpha receptor (FP) agonists used in glaucoma management. Study Design: Systematic review and meta-analysis. Methods: The primary outcome was the incidence of ocular adverse events (AEs) in patients treated with OMDI compared to two control groups: (1) patients receiving Latanoprost 0.005%, and (2) patients receiving any FP agonists, including Latonoprost, Timolol, and Tafluprost. Only studies with control groups were included, and data from the longest follow-up period were used. The secondary outcome was the mean change in intraocular pressure (IOP) from baseline to the end of the follow-up period. Meta-analyses were conducted using a random-effects model, with pooled estimates calculated as risk ratios (RRs) for AEs and weighted mean differences (WMDs) for IOP changes, both presented with 95% confidence intervals (CIs). Results: Nineteen studies (n=5134 eyes) were included. The meta-analysis demonstrated a significantly higher incidence of ocular AEs in patients treated with OMDI compared to Latanoprost (RR=1.41, 95% CI 1.14-1.73) and all FPs (RR=1.16, 95% CI 1.02-1.32). Ocular discomfort (8.7% vs. 5.1%, P=0.02), corneal changes (2.7% vs. 0.9%, P=0.04), conjunctival hyperemia (7.7% vs. 3.7%, P=0.01), and uveitis (1.2% vs. 0%, P=0.02) were more common in the OMDI group. However, eyelash changes were more frequent in the FP group (3.0% vs. 0.3%, P<0.01). OMDI significantly reduced IOP from baseline (WMD=-3.82 mmHg, 95% CI -4.68 to -2.95), with no difference compared to Latanoprost (WMD=0.57 mmHg, 95% CI 0.00-0.15). Conclusion: OMDI 0.002% offers a viable alternative to traditional FPs in the management of IOP, particularly for patients where FPs may not be suitable or effective. While its ability to reduce IOP is slightly less potent than other FP agonists, clinicians must carefully consider the increased risk of adverse events associated with OMDI. Further research could help identify patient subgroups who may benefit most from OMDI treatment, potentially optimizing both safety and efficacy outcomes in clinical practice.