Inside Frank Bruni’s Revolutionary Medical Trial
Patients of NAION were told they’d slowly become blind and that there was no hope to salvage their sight—until now.
On Friday, New York Times columnist Frank Bruni published a moving essay about his diagnosis of nonarteritic anterior ischemic optic neuropathy, commonly referred to as NAION—or, as Bruni writes, “more colloquially called ‘a stroke of the eye.’”
Bruni writes of feeling hopeless and afraid in the wake of his diagnosis—but while he grapples with the chance that he could go blind, his doctor offers some hope.
“This is bad, isn’t it?” I asked Dr. Moazami.
“This is bad,” she answered, then added, after an awkward pause: “I’m sorry. I have nothing to offer you.” But wait, there was one thing: a clinical trial of an experimental treatment, and she could tell me how to get into it—if I wanted to go that route. I did. So I soon added a new, time-consuming dimension to my already busy life. I became an ophthalmological guinea pig.
Bruni elected to take part in the world’s largest clinical trial of NAION, which is in the midst of testing a groundbreaking injection of RNA that could delay, maybe even stop, the progression of a disease that can eventually rob its patients of sight.
Marc Dinkin is the director of neuro-ophthalmology at Weill Cornell Medical College at New York Presbyterian. He’s the principal site investigator for clinical trials there—which are part of a group of others that are being run with patients around the country, one of whom is Bruni.
“I’ve received about 50 phone calls today alone,” he told The Daily Beast about the surge in interest in the condition since Bruni published his column. Dinkin said that while it’s not a super rare disease, it’s one that’s much less common than other visual ailments that typically strike the 50+ age group. “It’s received a lot less [media] exposure, partly because its estimated annual incidences is anywhere between two and 10 cases per 100,0000. The incidence in the population is less than glaucoma and macular degeneration.”
Bruni might have singlehandedly vaulted NAION into the public consciousness with his piece, and it’s something that Dinkin thinks is important, particularly given the growing elderly population of this country.
NAION’s origin story is murky. Scientists believe it occurs overnight, when the optic nerve in the eye faces lower blood flow from decreased blood pressure.
The optic nerve is the part of the eye that transmits impulses from the retina nestled at the back of the eye to the brain. It acts as a visual information transmitter, informing the brain about an image’s brightness, contrast, and more. What we see, in other words, is thanks to the optic nerve—which means any damage to it is detrimental to our sight function.
Bruni describes waking up one morning and seeing what he described variously as a “blob of petroleum jelly” and “a thick, dappled fog.” Dinkin said the two aspects of Bruni’s description—the morning onset and the sudden blurriness in vision—are key indicators that a person might be showing signs of NAION.
But how has a dip in blood pressure created blurry vision? That Bruni and neuro-ophthalmologists both refer to the sudden fuzziness in sight as an “eye stroke” is indicative of what doctors believe is going on. A traditional stroke happens when plaque blocks an artery, blocking blood flow to the brain.
“This isn’t the same as that,” Dinkin said, emphasizing that there is no link with the majority of patients with artery blockages.
It’s normal for our blood pressure to drop at night—our body is at rest, and it doesn’t require the intensity to do daily activities because, well, we’re not doing anything. If our blood pressure gets too low, our bodies are programmed to regulate it, sort of like a pressure equalizer to make sure damage to the sensitive optic nerve isn’t done.
With patients who get NAION, however, their blood pressure gets low—and the regulation part of the process to stop it from damaging the optic nerve doesn’t kick in. “What we think is that certain people have trouble with auto-regulation of blood vessels to the optic nerve head when blood pressure gets lower in the the middle of the night,” Dinkin explained. “For most of us, [lower blood pressure] dilates and opens up to allow blood to flow to optic nerve. In certain people of a certain age, the ability to do that is not great.”
The actual causes of NAION are not quite understood. “Some people have an anatomical disposition for that lack of blood flow and the swelling that happens with it,” he noted. Others have an optic nerve more poised for NAION than others—a little “cup” that lives behind the optic nerve might be smaller than normal, making it easier for nerves to crowd around the optic nerve, therefore priming it for an “eye stroke” by preventing dilation of blood flow to the optic nerve when blood pressure gets low.
Theories abound as to the risk factors that could make certain people more susceptible to NAION outside being over 50. One surprising factor is high blood pressure—which might seem odd given the fact that what made the optic nerve spaz in the first place was low blood pressure. “Chronic high blood pressure probably damages tiny vessels to the head, making them narrower or worse, affecting autoregulation,” Dinkin explained. Sleep apnea appears to play a role: Episodes of low oxygen with sleep apnea make it more likely that those who suffer from it are bringing in less oxygenated blood to help relieve low blood pressure at night. And high blood pressure and sleep apnea are both related to vascular risk factors in the modern era that are exacerbated by fast food, rising obesity, diabetes, and rising hypertension—all of which, combined with older age, could lead the optic nerve’s regulation system to fizzle and fail.
Treatment, too, isn’t clear cut right now. NAION currently doesn’t have a cure, a lot of which has to do with the fact that NAION’s instigators remain a mystery: “We really don’t know what factors predisposes [a person] to it,” Dinkin said.
So doctors tackle it in various ways, depending on individual conditions. Because many patients tend to have high blood pressure, Dinkin will often recommend they take their pressure-lowering medication in the morning to avoid suffering more damage to the optic nerve. Patients who are on a phosphodiesterase inhibitor—often found in medications for erectile dysfunction like Viagra—seem to be linked to NAION as well, so Dinkin said there are often discussions about trying to pull back on the pills. Some have tried steroids like cortisol, which hasn’t shown any real effects. Still others simply do nothing.
All of which is frustrating. After all, this is a disease that comes in the stealth of night, doesn’t have warning signs, and goes from an innocuous annoyance to steadily removing the power to see in its patients, whose strongest treatment plans are limited to avoiding certain pills at certain times.
But there’s beginning to be hope, thanks to experimental clinical trials that are taking audacious steps to salvaging the sight of those afflicted with NAION.
Over the past couple years, Dinkin and a team of researchers around the world have collaborated with the pharmaceutical company Quark along with the Neuro-Ophthalmology Research Disease Investigator Consortium, or NORDIC, to recruit NAION patients like Bruni and figure out a potential treatment plan that involves cutting-edge science—and perhaps could one day lead to a cure.
The revolutionary treatment involves an injection of RNA into the eye, which goes on a guerilla mission to find proteins and genes.
Dinkin described the Quark trial as an injection (into the eye) of a molecule called a “small interfering RNA” which targets the gene responsible for making a certain protein called caspase 2. Since this protein is involved in the pathways responsible for cell death, the hope is that blocking it will allow more of the nerve cells that form the optic nerve to survive NAION.”
Dinkin described the molecule as a “small interfering RNA,” whose role is to inhibit gene expression—in other words, the expression of genes that could result in sight loss like NAION. The small interfering RNA targets the gene responsible for making a protein called caspase 2. Since this protein is involved in the pathways responsible for cell death, the hope is that blocking it will allow more of the nerve cells that form the optic nerve to survive NAION, Dinkin said—potentially salvaging a patient's vision.
Dinkin said the injection is the type that could change the game for the disease that, until now, has been frustratingly obtuse in its formation and seemingly hopeless in treatment. The Quark and NORDIC initiatives are teaming up with hospitals around the country to enroll over 500 subjects over the next few years, seeking patients who have noticed their symptoms at the most two weeks out (later and it could be too late for the interfering RNA to halt NAION’s progression).
And the clinical trials are rigorous: Not only is there a placebo test but also a “sham” injection along with a range of doses being administered to see how patients respond.
Dinkin said that while it’s too early to know what the outcome will be—results aren’t expected for another two years—he believed that it would mark the beginning of a potential cure for the disease.
“We don’t yet know the results of the trial,” he said. “But we’re hopeful it will make a difference and that we will finally have a proven treatment to offer our patients with NAION.”