In addition to today’s resource, please review:
NAION: Diagnosis and Management. Ophthalmic Pearls, AUG 01, 2022
Nonarteritic anterior ischemic optic neuropathy (NAION) is the most common cause of acute optic nerve injury in individuals over 50 years old. Despite its frequency, several aspects of this disease, including its pathogenesis and effective treatments, remain unknown or unproven.
Although no treatment for NAION exists, a history and clinical examination, as well as additional investigations, are critical in ruling out life- or sight-threatening conditions that can mimic NAION.
Epidemiology
In the United States, the estimated annual incidence of NAION ranges from 2.3 to 10.2/100,000 for the population over 50 years old and 0.54/100,000 for all ages. This disease affects both sexes equally, and the mean age of onset is 66 years. White people are at higher risk of NAION than other ethnic groups.
Pathophysiology
The precise pathogenesis of NAION remains unclear, but it has been hypothesized that transient hypoperfusion of the short posterior ciliary arteries causes acute ischemia to the optic nerve head (ONH), resulting in axonal swelling. This swelling compromises the axoplasmic flow, which subsequently increases the axonal swelling, contributing to the compression of ONH microcirculation, exacerbating the ischemia. This vicious cycle creates a compartment syndrome, eventually leading to infarction and apoptosis of the retinal ganglion cells
Today, I review, link to, and excerpt from Mass General Brigham Newsroom‘s Weight Loss Drugs and Blindness: Is There a Link?
All that follows is from the above resource.
The popular prescription drug semaglutide (sold as Ozempic and Wegovy) has helped many patients with obesity or type 2 diabetes lose weight. Since their approval by the United States Food and Drug Administration (FDA) in 2019 and 2017, respectively, demand has skyrocketed for both drugs.
Emerging research from around the world shows that the active ingredient in both, however, may be linked to sudden blindness. Researchers have observed that patients prescribed semaglutide, the active ingredient in both drugs, had an increased risk of nonarteritic anterior ischemic optic neuropathy (NAION). NAION is a disease of the optic nerve that causes blindness. The optic nerve connects the eye to the visual part of the brain.
In one study, Joseph Rizzo, MD, a Mass General Brigham ophthalmologist, found that people with diabetes who had been prescribed semaglutide were more than 4 times more likely to be diagnosed with NAION than people with diabetes who didn’t take semaglutide. Those who were prescribed the drug and had overweight or obesity, he found, were more than 7 times more likely to receive the diagnosis than similar patients who didn’t take semaglutide. The research was published in JAMA Ophthalmology in July 2024.
“To be perfectly clear, I would not take my findings and use them to recommend that patients stop taking their medications,” says Dr. Rizzo. “Our finding was really the first possible significant negative finding with these drugs. Our finding may just merit extra caution in the consideration between doctors and patients about who might use this medicine.”
Dr. Rizzo sees patients with complex vision disorders at Mass Eye and Ear. He explains what NAION is and discusses research related to how semaglutide may trigger the condition.
How does semaglutide work for weight loss and diabetes treatment?
The marked effectiveness of semaglutide is due to multiple mechanisms of action on the body. Perhaps most importantly, semaglutide enhances release of the hormone insulin from the pancreas. Insulin allows sugar to move from the blood stream to cells throughout the body, where they convert sugar into energy. Achieving reduced levels of blood sugar is the main goal for managing diabetes.
Patients inject semaglutide under their skin once every week. Researchers are developing oral versions of this and similar other drugs.
“You essentially feel full without eating as much food as you normally would,” says Dr. Rizzo. “Patients who use these medications enjoy tremendous success and I am still impressed by the relative lack of complications from these medications.”
In addition to weight loss benefits, another Mass General Brigham study found that patients taking semaglutide were less likely to die from cardiovascular events and COVID-19. Researchers continue to advance our understanding of these medications and learn more about the health benefits and potential side effects.
What is NAION?
According to Dr. Rizzo, more than 1 million nerve fibers within the optic nerve relay visual signals from the eyes to the visual parts of the brain. Damaged fibers can disrupt the crucial eye-brain connection, leading to blindness.
According to the American Academy of Ophthalmology (AAO), NAION is the most common cause of sudden or severe (acute) optic nerve injury in people older than 50. That said, it is not commonly found among the general population, nor do doctors fully understand what causes it.
Dr. Rizzo likens the condition to a “stroke” of the optic nerve. NAION occurs suddenly without pain, and blindness occurs without warning. However, he tells patients not to take the term “stroke,” too literally. Typically, strokes and heart attacks occur from a blockage of blood flow through a main artery, restricting oxygen from reaching vital organs.
“There are so many vessels in the eye that it would be reasonable to think a stroke could never occur near the optic nerve,” says Dr. Rizzo. “If one of those vessels was blocked, blood and oxygen could probably reach the optic nerve through other, adjacent vessels.”
Damage to the optic nerve and subsequent blindness are permanent.
Why do researchers suspect a link between NAION and semaglutide?
A conversation with a group of trainees led Dr. Rizzo to investigate the popular weight loss drugs.
At Mass Eye and Ear, he regularly gathers trainees in the morning to review patient cases and discuss diagnoses and treatments. One morning, he mentioned a patient with NAION who happened to have taken semaglutide.
“I thought it was purely anecdotal, until a resident who had come up from the emergency room said, ‘Well, I just saw the same thing,’” he adds. “When I saw a third such case that next week, I knew this was too far out of the ordinary.”
Dr. Rizzo wanted to determine if the cases belonged to a larger, more troubling trend. He teamed up with his fellow Tatiana Hathway, MD, and several other trainees to analyze the records of 17,000 Mass Eye and Ear patients treated since the FDA first approved Ozempic.
They separated cases into two groups: patients with obesity or overweight and patients with diabetes. The researchers then distinguished cases by whether a patient had taken semaglutide or another weight loss drug, and whether NAION had occurred.
Their study evaluated more than 600 patients diagnosed with NAION over a 6-year span. All of these patients had been examined by Dr. Rizzo or one of the other Harvard Medical School neuro-ophthalmologists who see patients at Mass Eye and Ear.
Another group of researchers later published a study that also found a link between semaglutide and NAION. After reviewing records of about 37 million adults, they reported a small increase of NAION risk in patients with type 2 diabetes who took semaglutide.
While this risk is smaller than what Dr. Rizzo and team reported, the two studies together help patients understand the potential risk of NAION when taking semaglutide. Dr. Rizzo recommends speaking with your doctor to understand your risk if you’re concerned about the link between these drugs and vision loss.
Studying possible semaglutide eye side effects
Dr. Rizzo’s study is the first to associate semaglutide with NAION.
Not knowing exactly what causes NAION makes it even more difficult to understand the drug’s role in developing the condition.
“On the one hand, we’re committed to exploring a definitive cause-and-effect relationship,” says Dr. Rizzo. “On the other, we’re trying to understand how this class of medicine could possibly trigger the condition.”
Researchers around the world continue to study how weight loss drugs may be linked to eye conditions.
Another team reported that 9 patients taking semaglutide and tirzepatide (the active ingredient in Zepbound and Mounjaro) experienced side effects in their eyes, including NAION and two other eye conditions that could lead to vision loss. And another recent study found that patients who used these weight loss drugs for 6 months or longer had 2 times higher risk of developing neovascular age-related macular degeneration (nAMD). nAMD is an eye condition where abnormal blood vessels grow in the back of your eye and blur the center of your vision.
Researchers from around the world continue to publish a flurry of studies on this topic and report a range of findings. The differences among studies is primarily due to differences in methods that the researchers use to study the question.
Dr. Rizzo weighs some possible explanations as to how semaglutide and other weight loss drugs could affect the eyes.
Changes to blood sugar levels
The optic nerve needs oxygen and other nutrients, including sugar, from its surrounding blood vessels to function.
High levels of blood sugar can damage these vessels, compromising the health of the optic nerve. According to Dr. Rizzo, this is known to increase the risk of worsening of diabetic retinopathy, a complication of diabetes that affects your vision.
“For someone with type 2 diabetes, their body may be accustomed to having higher than normal blood sugar,” he says. “If those levels drop too quickly, the period of metabolic adjustment can make cells vulnerable to injury.”
But a rapid drop in blood sugar likely isn’t the mechanism associated with NAION, since most cases of blindness happen many months after starting the medication.
Reduced blood pressure
According to Dr. Rizzo, most neuro-ophthalmologists attribute NAION to reduced blood pressure (hypotension). When blood pressure drops too much, it can reduce the delivery of oxygen and other nutrients below a critical threshold that causes injury to the nerve fibers.
Semaglutide can lower blood pressure, which may be one reason researchers have linked this drug to NAION, Dr. Rizzo speculates.
“Changes in blood pressure and blood glucose are compelling factors, but do they explain the whole picture?” Dr. Rizzo says. “I don’t think so. It’s likely much more nuanced.”
