Phakic Eyes with History of Trabeculectomy May Develop CME after Prostaglandin EP2 Receptor Use

Glaucoma management has many avenues available to reduce intraocular pressure (IOP). While prostaglandin F receptor agonists, like latanoprost, are a mainstay, they can result in adverse effects, such as prostaglandin-associated periorbitopathy, limiting tolerability of the traditional prostaglandin analogs (PGAs). Omidenepag isopropyl (OMDI), however, is a selective EP2 receptor agonist that provides potent IOP reduction, but with a known risk factor of cystoid macular edema (CME) in pseudophakic and phakic eyes.A group of researchers were interested in clarifying the safety profile of OMDI, as they explain in their paper published in JAMA Ophthalmology. To do so, medical records were retrospectively reviewed, including 836 patients with phakic eyes who received 0.002% OMDI; 86 of these patients had trabeculectomy in their history. A small set of six patients (eight eyes; median age 52.5 years) with prior trabeculectomy and surgical iridectomy developed CME, all occurring between six to 11 months after initiation of OMDI. Follow-up for periods for patients varied, with it being less than six months in 366 patients, six to less than 12 months in 419 and 12 or more months in 51.  The mechanism behind OMDI-induced macular edema remains unclear, but neuroinflammation is recognized as a critical factor in disrupting the blood-retinal barrier, contributing to CME pathogenesis. Photo: Oliver Kuhn-Wilken, OD. Click image to enlarge. After CME onset, baseline visual acuities with correction declined by zero to three lines. Treatment for CME also varied, with three eyes receiving topical NSAIDs, two needing systemic corticosteroids and three recovered by merely discontinuing the drug without further therapy needed. After the edema resolved, visual acuity ranged from 20/20 to counting fingers at 28 to 91 days after OMDI discontinuation. Post-resolution follow-up after CME ranged from 5.5 to 12 months, with no recurrences during this time.The development of CME in OMDI usage with previous surgery may have to do with surgically created channels between the anterior and posterior segments facilitating posterior drug distribution, thus possibly increasing retinal exposure to OMDI, leading to CME, the authors explain. As well, previous trabeculectomy may have altered the blood-retinal barrier’s integrity, with ocular tissue then being predisposed to be influenced by low concentrations of medication in its microenvironment.The investigators warn clinicians that, “while OMDI’s efficacy in IOP reduction and minimal prostaglandin-associated periorbitiopathies may make it appealing for younger patients, the observed CME complications in this series underscore the potential importance of careful patient selection, particularly in cases with extensive treatment histories and likely warrant monitoring for the possibility of CME when initiating OMDI.”1To combat this, they suggest that “routine OCT monitoring may facilitate early detection of CME, even in asymptomatic patients, allowing timely treatment and potentially better visual recovery.”1In an invited commentary to the original study—also published in JAMA Ophthalmology—the commentators point out that the original study does not provide information about intraoperative complications or early or late postoperative complications in the participants who had previous surgery. As the commentator authors explain, absence of this information limits the study’s conclusions, since these complications remain plausible contributions to chronic blood-retinal barrier dysfunction.They also add that the lack of CME development during prior prostaglandin therapy should be highlighted, suggesting a unique pharmacologic vulnerability to OMDI.Similar to the original authors of the paper, the commentators believe “this observation underscores the importance of individualized risk assessment in younger patients after filter surgery when considering novel therapies, such as OMDI. Close monitoring for CME with OCT and a low threshold for discontinuing OMDI in the event of macular thickening are recommended.”2 Click here for the journal source and here for the commentary. 1. Cheng MH, Hwang DK, Liu CJL. Prostaglandin EP2 receptor and cystoid macular edema in phakic posttrabeculectomy eyes. JAMA Ophthalmol. August 7, 2025. [Epub ahead of print].2. Zur D, Rachmiel R. Omidenepag isopropyl-associated cystoid macular edema after trabeculectomy. JAMA Ophthalmol. August 7, 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.