Christopher Reiman, MD, Vitreoretinal Surgeon at Cincinnati Eye Institute, Clinical Governance Board and Director of Vitreoretinal Fellowship at University of Cincinnati, talks about a new treatment for the dry form of age related macular degeneration.
Can you explain what age-related macular degeneration is and what’s happening that a person starts to lose their vision?
RIEMANN: Age-related macular degeneration makes up about half of the patients that a vitreoretinal specialist would see on a given day. It’s the leading cause of visual loss amongst American senior citizens over age 50 and affects one out of three people over the age of 65. It comes in two forms. There’s a dry form and a wet form. The wet form of macular degeneration is the less common form and is marked by the presence of abnormal blood vessel growth, bleeding, and leakage inside the eye, and exudation and lipids seeping into areas where they don’t belong, causing damage and scarring. It’s typically treated with injections in the eye and only affects 10 to 20% of the patients that have macular degeneration, but it’s responsible for a significant amount of visual loss. The dry macular degeneration is by far more common with 80 to 90% of patients having it. Many of those patients don’t have severe visual loss, but some do. The visual loss from the dry macular degeneration comes from an atrophic withering away of normal pigmented structures in the back of the eye that can cause significant loss of vision, especially centrally. The main problem with dry macular degeneration is that there’s no treatment for it. Other than some vitamins that will slightly reduce the rate of visual loss, there’s no treatment that’s been shown to actually stabilize vision in patients that have dry age-related macular degeneration with geographic atrophy, which is the more severe form of the disease. And there’s no treatments that have been shown to actually improve vision.
When you have this condition with no real treatment for it, what do you do?
RIEMANN: You take vitamins which slows it down a little in some patients, but not too much. You adapt and do the best you can, get magnifiers to make things larger, and get stronger readers so you can hold things closer and make them larger. Ultimately, you find somebody else to drive for you and listen to audio tapes instead of reading. It can be a huge problem in terms of your quality of life.
What are you and your colleagues investigating with this trial?
RIEMANN: The trial is a super interesting and exciting project where we’re studying the retinal pigment epithelial cells. These are the cells that are defective in the severe dry age-related macular degeneration patients. We’re taking a slurry of those cells and injecting them into the space under the retina where they’re missing. You can almost think of it as a cell replacement therapy. The cells are differentiated retinal pigment epithelial cells. They physically and chemically look like the cells that are missing in the body and derived from pluripotential cells that are derived from discarded, ethically sourced invitro fertilization embryos.
So, when you do that injection, what’s taking place in the eye and in the body?
RIEMANN: The way vision works in the eye is you have the retina, which is a direct outgrowth of the brain, and it has photoreceptors in it. When those photoreceptors are activated by a beam of light that hits them, they cause a chemical reaction that results in a nerve impulse that’s sent to the brain. Our brain then interprets those nerve impulses into what we understand to be vision. Every time a photoreceptor is activated by light, that photoreceptor is off and it has to be recycled back into the on position biochemically. The retina sits on a structure called a retinal pigment epithelium, and the retinal photoreceptors interdigitate with the retinal pigment epithelium. There is this exchange of what we call photoreceptor outer segments where the spent ones from the photoreceptors get put into the retinal pigment epithelium, recycled, reprocessed, and then put back into the photoreceptors in order to continue being able to see. Those retinal pigment epithelial cells are the ones that are missing and damaged in the dry age-related macular degeneration patients with geographic atrophy. So, with this up-region cell replacement therapy, we can take those cells and replenish them.
Are you finding that they are working and growing? How are they replenishing?
RIEMANN: So, they are non-dividing cells. That’s important because whenever you inject foreign cells into the human body, there’s a chance that they divide and potentially cause tumors and cancers. These do not divide, so there’s a chance that there is rejection. The interesting thing about the eye is the eye is considered an immunologically privileged place. Within the eyeball, the extension of the blood-brain barrier is the blood-ocular barrier. So, if you were to take these same cells and inject them under your skin, there would be an immune response and a rejection. But because the eye is such an immunologically privileged place, these cells can survive as if they belong there from the start. It’s very interesting.
What are you finding in patients?
RIEMANN: So, it’s a phase one trial and what we’ve seen is some patients is no loss of vision. That in and of itself is a victory because the natural history of the disease is progressive visual loss because the geographic atrophy expands over time. When Sheri first started noticing the effect of her therapy, she called and she was crying tears of joy. It blew us away! Sheri’s not the only patient that’s had this promising improvement in vision. But again, it’s way too early to make any kind of conclusions about whether or not this works. There are all sorts of exciting phase one trial results that end up not panning out in phase two and phase three and that don’t end up getting FDA approved and don’t end up being the therapy of the future that everybody hopes for. But in this case, there are several patients where we’re seeing a signal which we haven’t seen before with this disease and it makes us very hopeful and very excited.
Can you explain how you go about injecting the cells? Are patients knocked out or are they just numbed?
RIEMANN: The cell injection happens in the operating room. It’s a surgical procedure. There are two different routes that we’re exploring to get the cells where they need to be. One of them is called vitrectomy approach. If you think of the eye like this, looking up at the ceiling, we enter the eye with instruments and remove the gelatinous material that fills the back of the eye. Then, we take a superfine polyamide cannula and inject the cells through the retina into the sub-retinal space. The other approach that we’re really excited about is the suprachoroidal approach, where we actually don’t do a vitrectomy. We snake a specially designed lubricious cannula between the outer layers of the eye to the back of the eye and then drive the needle from the outside in. It’s on a screwdriver and the patient’s anesthetized and don’t feel anything. It is local anesthesia and patients are awake for it. We drive it through the deeper layers into the dub-retinal space. So, we’re evaluating both of those approaches.
I know you are in Phase 1 of the trial, but what is the next step?
RIEMANN: What we’re going to do is let these patients cook for a little bit and really see what the data has to tell us. If the data continues to look as good as it’s looking, then we would proceed into phase two trials. If phase two trials look good, then we would probably modify the procedure to decide on the retinotomy approach versus the suprachoroidal approach to get the cells and do a phase three trial. If the results look as good as they’re looking now and the safety profile that we seem to think looks pretty good bears out in these later phase trials, then it would be submitted to the FDA for approval and brought to market.
Did Sheri have any other options? Was she going to go blind if she didn’t try something?
RIEMANN: There are always other options. Not everybody goes blind, but many do, especially with the kind of disease that meets the inclusion criteria for this trial. There are some other clinical trials like gene therapies and so on. So, there’s always options. But in Sheri’s case, she chose this trial because she liked the idea of replacing what was missing. She was awake during the whole surgery. We do 95% of retinal surgeries and ophthalmic surgeries under local anesthesia, where the patient gets sedation which puts them to sleep for about 30 seconds. In that 30-second period, we give them an injection of local anesthetic, just like the dentist can numb your teeth. Then, they wake up from being asleep, but their eye is numb, or really half of their face is numb, and they can’t see anything. The surgeries are very well tolerated.
Interview conducted by Ivanhoe Broadcast News.
END OF INTERVIEW
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