In a recent case series study, researchers investigated potential ophthalmic complications associated with the use of the antidiabetic drugs semaglutide and tirzepatide. The retrospective case series examined 9 patients who developed vision-related complications—nonarteritic anterior ischemic optic neuropathy, bilateral papillitis, and paracentral acute middle maculopathy—while using these medications.
The researchers, led by Bradley J. Katz, MD, PhD, of the John A. Moran Eye Center, Department of Ophthalmology & Visual Sciences, Department of Neurology at the University of Utah Health in Salt Lake City, conducted a retrospective review of patients who developed ophthalmic complications while using semaglutide or tirzepatide. Cases were identified through neuro-ophthalmologists' reports via the North American Neuro-Ophthalmology Society (NANOS) listserv and queries to the National Registry of Drug-Induced Ocular Side Effects. Patients were included if they had documented vision loss following initiation of semaglutide or tirzepatide; or diagnosis of optic neuropathy, maculopathy, or other ocular ischemic events. Researchers also included patients whose follow-up data was available to assess progression.
Patients were excluded if they had preexisting optic neuropathy not related to diabetes, if they used multiple systemic medications known to impact optic nerve health, or if their medical records were insufficient for case evaluation.
Among the 9 patients analyzed (mean age 57.4 years, range 37 to 77 years), 7 cases of nonarteritic anterior ischemic optic neuropathy (NAION), 1 case of bilateral papillitis, and 1 case of paracentral acute middle maculopathy were identified, according to their recent article in JAMA Ophthalmology.
Patients displayed varying degrees of vision loss and optic nerve abnormalities. Some exhibited atypical features such as sequential ischemic optic neuropathy and progressive visual field loss. Notably, 1 patient developed NAION in 1 eye shortly after starting semaglutide and experienced vision loss in the fellow eye upon reintroducing the drug. Another patient developed bilateral optic disc swelling while using semaglutide.
The researchers proposed that rapid glycemic control induced by these medications may have contributed to the observed ophthalmic events. Indeed, previous research has linked abrupt reductions in blood glucose levels with worsening diabetic retinopathy and optic nerve changes. Another potential mechanism could involve GLP-1 receptors in the retina: vasoconstriction and decreased retinal perfusion secondary to metabolic changes, or mitochondrial function in retinal ganglion cells that leads to increased susceptibility to ischemic events. The precise mechanisms remain unclear, however.
Limitations of the study included selection bias, the absence of a control group, and reliance on historical data.
“In this case series study, it was not possible to determine if there is a causal link between these drugs and the ophthalmic complications reported,” the researchers concluded. However, they detailed guidance that was recently released by the American Academy of Ophthalmology:
In response to the retrospective study and its accompanying editorial, the American Academy of Ophthalmology has issued a press release for clinicians prescribing and patients using semaglutide. The Academy has not recommended that patients stop using semaglutide, but rather, that patients experiencing vision loss while taking semaglutide should stop the drug and contact the physician prescribing the medication. The Academy has also suggested that a postmarketing surveillance study might better inform physicians and patients about the safety of semaglutide. Because of the association of semaglutide with temporary worsening of diabetic retinopathy, the increased incidence of diabetic macular edema, and the concern that rapid correction of hyperglycemia could induce papillitis, physicians prescribing this medication to their patients with [type 2 diabetes] should consider a drug regimen that more gradually lowers the HbA1C level.
Full author disclosures can be found in the publish research.
