Study Reveals New Safety Signals of Oxymetazoline Eye Drops for Blepharoptosis

Researchers hypothesize that the observed association—not causation—between oxymetazoline eye drop use and vitreoretinal complications may involve its repetitive daily use, “leading to incremental traction over time secondary to constant micro-fluctuations in aberrant pupillary dynamics.” Photo: Marlon Demeritt, OD, and Diana Shechtman, OD. Click image to enlarge. It’s been about six years since the FDA approved the first topical agent indicated for the short-term treatment of blepharoptosis (oxymetazoline hydrochloride ophthalmic solution 0.1%; Upneeq, RVL Pharmaceuticals). Thousands of doctors have since prescribed the medication, providing a plethora of data on its real-world use in the FDA Adverse Event Reporting System (FAERS). Researchers recently analyzed that database to characterize the safety profile of oxymetazoline ophthalmic solution, with particular emphasis on detecting potential adverse events not captured in preapproval trials or listed on the product label. Its findings raise both reassurance and caution about the use of the eye drops for acquired blepharoptosis.Researchers queried FAERS for reports from July 2020 through April 2025. After automated and manual deduplication and limiting to reports listing oxymetazoline ophthalmic solution as the primary suspect, 306 individual patients with 658 adverse drug events were included. The cohort was predominantly female (262 patients, 85.6%) with a median age of 61. Oxymetazoline nasal spray and phenylephrine ophthalmic solution served as negative controls, while pilocarpine eye drops were used as a positive control.The results confirmed label-listed localized reactions, including the following: ocular surface disease (129 reports; 34.5%), conjunctival hyperemia (43; 11.5%), temporary blurred vision (33; 8.8%), instillation site pain (27; 7.2%) and headache (32; 8.6%). Importantly, the data also revealed novel safety signals not listed on the product label, which involved vitreoretinal events (12 reports; 3.2%) including retinal detachment (three; 0.8%), posterior vitreous detachment (three; 0.8%), vitreous floaters (three; 0.8%) and vitreous hemorrhage (three; 0.8%). The researchers also identified reports of mydriasis in 21 patients (5.6%), and systemic blood pressure increases were reported in six patients (1.6%). A decreased therapeutic effect over time was also observed in a small subset of patients (five reports, 1.3%). Six reports met criteria for serious outcomes (disability, hospitalization or intervention to prevent impairment), including one hospitalization for hypertensive emergency and three cases of persistent disability related to retinal detachment or visual impairment. The pilocarpine positive-control analysis showed nine reports of retinal detachment, while negative controls did not show similar vitreoretinal signals.“Although causality cannot be definitively established due to the spontaneous nature of FAERS reporting,” wrote the researchers in their paper, “the presence of statistically robust signals highlights clinically relevant patterns that merit closer mechanistic and epidemiologic investigation.”When discussing the potential mechanism of vitreoretinal complications in oxymetazoline users—which were not described in clinical trials—the researchers highlighted one case report that described “a healthy female experiencing new-onset floaters within hours after administering an oxymetazoline eye drop on the second day of use.” They explained that she was found to have “hemorrhagic posterior vitreous detachment with retinal detachment despite no personal or family risk factors, and normal examination of the retina and vitreous just three months prior.” The authors of that report had proposed “a possible relationship with oxymetazoline eye drop to dynamic changes in pupillary size and iris-lens mechanics, leading to vitreoretinal traction.”In conclusion, the authors summarize, “The findings confirm previously known local ocular effects of ocular surface disease, conjunctival hyperemia, blurred vision, instillation site pain and headache, as well as introduce new associations with vitreoretinal complications, systemic hypertension, mydriasis and reduced therapeutic response over time.” They reiterate that while these signals don’t prove causation, and that the absolute number of vitreoretinal events was minimal (12 reports), “their consistency and strength of association warrant further investigation and increased clinical awareness, particularly in patients with pre-existing retinal pathology or cardiovascular disease.” The authors advise clinicians, “Retinal evaluation and patient education surrounding new visual symptoms or systemic changes could mitigate risks.”Click here for the journal source. Azzam DB, Hong JD, Chen TH, et al. Safety analysis of oxymetazoline eye drops for blepharoptosis using the FDA Adverse Event Reporting System. Ophthalmic Plast Reconstr Surg. April 2026. [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.