What was then a little-known subspecialization has now become a specialization in and of itself, thanks largely to Miller’s research and leadership. It’s known as neuro-ophthalmology, and today, Miller is among the most senior authorities in the field he helped to define.
Miller’s research is focused on optic nerve damage that can occur from stroke, trauma, infection or tumor. In particular, he has been performing research on optic nerve stroke, also called non-arteritic anterior ischemic optic neuropathy, or NAION. This disorder can lead to vision loss or even blindness and is the most common cause of sudden optic nerve-related visual loss in older people. Currently, there is no treatment for it, but Miller and his colleagues are working to change that.
Through his years of research, Miller has now isolated three drugs that in the laboratory either reduce damage to the optic nerve after an attack of NAION or heal the nerve once damage has occurred. Recently, his research crossed an important threshold in the drug development cycle when he began trials in primate models, whose optic nerve is nearly identical to that of humans. It is the penultimate stage before human clinical trials. If all goes well, Miller may soon be able to test his NAION drugs in people who have been blinded by optic nerve stroke and perhaps other conditions as well.
“We have now identified three compounds that protect the optic nerves from various forms of damage, such as loss of blood supply from stroke,” Miller says. “The focus now is the dosage and frequency.”
Miller has also discovered other — what he calls “add-on” — drugs that could constitute a cocktail of drugs that might protect the optic nerve more than any one drug by itself. Importantly, he has shown that if doctors can get these drugs into a damaged optic nerve within five hours of a stroke, they can prevent permanent damage.
“If it’s a day later, then it might be too late,” Miller says.
It has taken decades of painstaking work for Miller to reach this important milestone, and a key aspect of his leadership in the field is to ensure that important research continues. Miller has mentored several of the next generation of leaders in neuro-ophthalmology. One of his newest protegees is Amanda Henderson, M.D., an assistant professor of ophthalmology who recently joined the NAION team at Wilmer.
“We’re working to pass the torch to others like Dr. Henderson to both help expand our base of knowledge and ensure there is a next wave of researchers looking into NAION,” Miller says.
Miller, Henderson and their colleagues have begun to test a new type of drug delivery system that is aimed at carrying their drugs to the damaged nerve cells in the eye and optic nerve.
They are using a nanoparticle drug delivery mechanism — called a dendrimer — in which drug molecules are attached to the nanoparticle. The dendrimer helps the drug get to places in the body it typically cannot reach without help, such as deep inside the eye and in the brain.
“Dendrimers can be given intravenously, rather than as an injection in the eye. They travel through the bloodstream and localize to the specific inflammation site,” Henderson says. “They go right to the problem area.”