Abstract
Background Omidenepag isopropyl (OMDI) eye drops are newly developed for glaucoma treatment. OMDI is a non-prostaglandin EP2 agonist with a mechanism of action distinct from other commonly used drugs, such as prostaglandin FP agonists. The aim of this study was to evaluate the long-term efficacy and safety of OMDI administered as first-line therapy for untreated primary open-angle glaucoma (POAG) over five years. Methods This retrospective study included one eye per patient. A total of 103 treatment-naïve, consecutive POAG eyes newly administered OMDI between December 2018 and March 2020 were included. Reasons for discontinuing OMDI due to adverse effects or other factors were analyzed. The primary outcome was change in intraocular pressure (IOP) over time, and secondary outcomes were visual field progression and rate of persistence with OMDI monotherapy. Pre- and posttreatment IOP and mean deviation (MD) in Humphrey visual field testing were analyzed using a mixed-effects model for repeated measures in IBM SPSS Statistics for Windows, Version 25.0 (Released 2017; IBM Corp., Armonk, NY, USA), with statistical significance set at p < 0.05. Kaplan-Meier analysis was performed to evaluate the persistence of OMDI monotherapy. Results Among 103 initial eyes, 13 cases were discontinued early (up to six months) due to adverse events (e.g., conjunctival hyperemia), and nine cases were lost to follow-up (e.g., transferred to another institution). In the remaining 81 eyes, over the five-year follow-up, 20 eyes (25%, 20/81) required additional glaucoma medications due to inadequate efficacy associated with visual field progression or structural changes. Two eyes underwent cataract surgery (one eye cataract surgery alone, one eye combined cataract surgery and microhook trabeculotomy). Median (IQR) IOP decreased significantly from baseline to one, two, three, four, and five years: 17 (15.5-18.5), 15 (13-16), 14 (13-15), 14 (13-16), 15 (13-16), and 14 (13-16) mmHg, respectively (p = 0.008, mixed-effects model). Five years after initiating OMDI, monotherapy remained feasible in 73% of cases (59/81). The visual field of these 59 eyes under OMDI monotherapy changed from -1.47 (-0.48 to -2.48) dB at baseline to -0.94 (-0.34 to -3.15) dB at five years, with no significant change in MD values (p = 0.34, mixed-effects model). No cases discontinued OMDI due to adverse events such as allergies after six months of treatment. Conclusions OMDI achieved sustained IOP reduction and demonstrated good tolerability over five years. This retrospective study suggests that OMDI may be a reliable first-line treatment option for glaucoma. These findings require confirmation in prospective multicenter trials.