Ophthalmic Complications Observed After Use of GLP-1 Agonists

Though it was not possible to determine causality, a retrospective case series identified nine patients who developed ophthalmic complications during treatment with semaglutide (Ozempic, Wegovy) or tirzepatide (Mounjaro, Zepbound).

A survey of neuro-ophthalmologists turned up seven cases of nonarteritic ischemic anterior optic neuropathy (NAION), one case of bilateral papillitis, and one case of paracentral acute middle maculopathy (PAMM), reported Bradley J. Katz, MD, PhD, of the John A. Moran Eye Center at the University of Utah Health in Salt Lake City, and colleagues in JAMA Ophthalmology.

“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 authors concluded. “In some cases, we hypothesize that rapid correction of hyperglycemia induced by these drugs, rather than a toxic effect of the drugs, could be associated with the ophthalmic complications reported.”

Co-author Judith Warner, MD, also of the John A. Moran Eye Center, told MedPage Today that “people with diabetes on these medications will need to have an increased level of surveillance, especially early.”

While the disorders are uncommon, “use of these medications is dramatically increasing in the U.S.,” she noted.

Previous reports have linked semaglutide to a higher risk of NAION, and rapid weight loss with bariatric surgery or drugs to a possible increased risk of diabetic retinopathy. The American Academy of Ophthalmology and the North American Neuro-Ophthalmology Society have advised patients who suffer vision loss while taking semaglutide to stop the therapy and seek eye care.

The impetus for the new report was a patient at the University of Utah Health who developed NAION 1 day after starting semaglutide. The authors queried members of the North American Neuro-Ophthalmology Society about similar cases, and “lo and behold, these surfaced,” Warner said.

NAION often occurs in people over 50 who suddenly have painless vision loss, she said. “The vision loss is usually as bad as it’s going to be the day it occurs. Then often there’s a small amount of recovery — a line or two of the eye chart — and maybe a little bit of improvement of the field of vision.”

The condition appears to be triggered when the optic nerve swells, choking off its blood supply because the nerve’s pathway out of the eye is too small, she explained. This could happen when glucose levels dip quickly when a person is rapidly controlling their diabetes, she added.

In an accompanying commentary, David Maberley, MSc, MD, of the University of Ottawa in Ontario, and colleagues noted that epidemiologic studies have produced conflicting findings about possible links between GLP-1 receptor agonists and NAION.

“It is estimated that by 2030, 30 million GLP-1 [receptor agonist] prescriptions will have been dispensed in the U.S. Despite the rarity of NAION, the large number of users of these drugs can translate to a significant number of NAION cases,” they wrote. “Future epidemiologic studies with robust methods are urgently needed to accurately quantify this risk.”

Diabetic papillitis refers to optic nerve swelling with normal vision in a patient with diabetes and typically isn’t symptomatic, Warner said. “It is almost never in both eyes at the same time, but can happen in one eye and then the other. Sometimes it turns into NAION.”

In the case of papillitis in the new report, “a patient got her blood sugar under great control, lost a bunch of weight, and then she got this optic nerve swelling. Then it happened to the other eye,” Warner said. “Fortunately for her, she didn’t actually lose any vision.”

PAMM is a blood flow disorder related to the retina. “It typically affects the central vision, and is irreversible. This is probably more related to the worsening of diabetic papillitis,” Warner noted.

What should eye doctors do in light of the case series and other reports? “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,” the authors wrote.

The nine patients included in this case series had a mean age of 57.4 (range 37-77), and 56% were women. All patients were initially seen in a community setting. Of the seven with NAION, four were taking semaglutide, and three were taking tirzepatide. Six had at least one vascular risk factor — hypertension, hyperlipidemia, and/or type 2 diabetes — and five had bilateral optic nerve swelling.

The authors noted that other drugs have been linked to NAION, including erectile dysfunction medications (possibly because they can cause nocturnal hypertension), the anti-arrhythmic drug amiodarone, and the hepatitis/cancer drug interferon alfa. None of the patients in this report were taking those drugs.

Please enable JavaScript to view the

comments powered by Disqus.