Meta-analysis Compares Safety and Efficacy of Omidenepag to Prostaglandins

Ocular discomfort, photophobia and conjunctival hyperemia are potential side effects of omidenepag use but the drug is less likely than a prostaglandin to induce orbitopathy (pictured, OS) following chronic use. Whether transient or permanent, side effects may deter patients from using their medication. Clinicians should counsel patients about the expected onset and duration of any potential symptoms and monitor tolerance.  Photo: Luai Tabaza, MD/eyerounds.org. Click image to enlarge.  Prostaglandin analogs are among the most effective medications for reducing intraocular pressure in glaucoma patients, but they are associated with certain side effects, such as conjunctival hyperemia, excessive eyelash growth, skin and iris hyperpigmentation and prostaglandin-associated periorbitopathy (PAP). Since these adverse effects can lead to patient nonadherence, Canadian researchers recently investigated the efficacy and safety of a drug with lower incidence of PAP but IOP-reducing effects comparable to latanoprost—omidenepag isopropyl (OMDI) 0.002%, an E-prostanoid subtype 2 (EP2) agonist. In their recent American Journal of Ophthalmology paper, they reported evidence supporting OMDI as a suitable alternative to traditional prostaglandin analogs with some distinct advantages, but noted that OMDI agents have less IOP-lowering efficacy.Researchers screened 358 studies reporting ocular adverse events and IOP change data for the two drug classes. The meta-analysis included 17 of these studies (3,294 eyes; five randomized controlled trials, seven retrospective cohort studies and five prospective cohort studies). Most were uncontrolled and had variable follow-up periods. Mean patient age was approximately 60 years, and 45% of patients were male.The researchers reported the following findings: Four studies reported no significant differences in IOP reduction between EP2 agonists and prostaglandin analogs.All studies showed significant IOP reductions from baseline with the use of omidenepag.Some ocular adverse events (discomfort, photophobia, hyperemia) may be higher in OMDI-treated patients than in those treated with prostaglandin analogs.The researchers also found that conjunctival hyperemia and corneal changes were significantly greater with omidenepag use, but this same group experienced fewer eyelash and eyelid or orbital side effects than those treated with prostaglandin analogs.“OMDI represents a promising advancement in the glaucoma treatment landscape, demonstrating IOP-lowering efficacy comparable to FP receptor agonists while minimizing PAP and cosmetic concerns that can impact adherence,” the researchers explained in their paper. “By offering a distinct mechanism of action, OMDI broadens therapeutic options, particularly for patients who are intolerant or refractory to conventional prostaglandin analogs.” Clinicians should nevertheless be mindful of  its higher incidence of mild ocular AEs such as conjunctival hyperemia and ocular irritation, they cautioned.In the US, omidenepag isopropyl is marketed as Omlonti by Santen; the manufacturer was not involved in this study.Click here for the journal source. Sharma S, Singh R, Balas M, Mathew DJ. Safety and efficacy of omidenepag isopropyl for elevated intraocular pressure: A systematic review and meta-analysis. Am J Ophthalmol. July 24, 2025. [Epub ahead of print]. This article was developed by the editorial staff in conjunction with experts in the field. In the process, AI may have been among the editorial tools used to meet the goals of human editors, who approved all content.