 All right. Hello everybody. Can you hear me okay? All right. My name is Rebecca Genscher, and I am a fourth-year medical student as Adam mentioned. I'm at Rutgers Robert Wood Johnson Medical School in New Jersey and today I'm going to be talking a little bit about trans-courney electrical simulation, which is a technology that I learned a lot more about while doing about six months of research at Will's Eye Hospital. And I'm just going to give you a brief overview of the technology and some of its applications. So in terms of the history, electrical treatments have been explored sort of throughout the ages. We know that there's some evidence to support that the ancient Greeks were using these electrical currents to treat diseases as early as 1st century AD and maybe even in BC times. And this is an example here. This is a torpedo fish, which exerts some amount of electrical current, which was used to treat patients with headache long, long time ago. There were also applications of similar types of electrical treatments, going in patients with arthritis and pain relief and an improving circulation. So once we sort of got past that initial sort of wonder with, oh, there's natural producers of electricity and we started making our own electricity, we started to replace those sort of natural producers with man-made devices. Once we developed static electrical currents and pulse electrical current that could be applied directly to the skin, the treatments moved along this way as well. And once we got to the early 20th century, sort of an about face, people started to say, oh, this electrotherapy is quack medicine. We have, you know, we have drugs that we can take. We have analgesics that are up and coming on the market. Why would I take an electrical shock when I could take a pill? And as we continued on in time, some understanding, increased understanding of the neurochemical pathways and the neurochemical compounds and how those relate to different types of electrical stimulation sort of became more apparent and people started to, again, begin to accept these treatments. And we get to the modern day where we have lots of examples of these types of treatments, such as transcutaneous electrical nerve stimulation, which is used for pain relief. We have deep brain stimulators for Parkinson's. We have cochlear implants, et cetera. So one of these novel types of electrical stimulation used as a therapeutic modality is called transcorneal electrical stimulation. And this is pretty new probably within the last 10, 15 years that this has been sort of tested and developed. So the idea is you're delivering a low voltage signal that goes directly across the pornea into the retina. You're resulting in a, it's a noninvasive way of stimulating the retina directly. So you're sort of bypassing the traditional light activation pathway where light causes a change of those photons into electrical signal. You're instead getting a direct electrical signal to the retina. And in some initial studies looking at PET scans, what's been found is that there's some activation of some of the same types of the brain that are activated in traditional light signaling. And here you can just see this is the PET scans during light signal, and this is PET scans during transcorneal electrical stimulation treatment. And you can see some of the same areas in the visual cortex lighting up, and some of these secondary visual areas as well. So what does the device look like? Well, it comes in sort of two flavors. The initial development was looking more at this contact lens type electrode, sort of modeled after what we used for the electroretinogram. And this is a gold electrode that's applied directly to the cornea. And you can see there's a lot of surface area to cover the cornea, a lot of sort of potential for problems. So as time has gone on and we've gotten better technology, we've moved on to more of this silver type electrode, which is just a very thin wire that sits right on the lower lid and essentially just grazes the inferior limbis of the cornea, delivering the electrical signal equally as effectively and with a much less corneal contact. In terms of potential risks of transcorneal electrical stimulation, it's really not too bad. It's very well tolerated. Most complaints are minor. People complain of a little bit of a foreign body sensation, like having an eyelash in your eye. And some of the potential risks that we really pay attention to are corneal abrasions and corneal agarosis. These are a little more serious complications that we want to make sure to deal with. Corneal agarosis, in case you're not familiar, sort of this brownish gray darkening of the cornea and sclera that can happen with repeated exposure to silver particles. And as I mentioned, these electrodes are coated with a silver particle that can sometimes be released into the eye. Most of these effects are totally mitigated and even prevented by just being really careful to wash out the eye with a buffered saline solution after each treatment. And most protocols include this as a standard operating procedure. So I'm going to talk just very briefly about some of the preclinical work that's been done in TES, which has been in the area of retinitis pigmentosa. And just a general overview, retinitis pigmentosa is a degenerative disease. We know that it affects the rods and the cones, essentially results in a loss of the outer nuclear layer of the retina, which is the layer of those photoreceptor nuclei. First, you start with some impairment of your night vision and your dark adaptation as you're losing your rods. And then as that progresses, you get tunnel vision and you ultimately develop central vision loss. And this progression happens somewhat predictably over the years. There are some ongoing trials. They've looked at retinal implants. They've looked at different types of gene therapy. But basically, there's no definitive treatment that's FDA approved that's sort of commonly accepted. So this is an area where really better treatments are needed and something like trans-corneal electrical stimulation, which is non-invasive and as I'm going to show pretty soon, seems to target those photoreceptors directly, might be able to be a benefit to patients. So this group out of Japan, Morimoto, they sort of got the whole excitement going for this type of treatment. And they looked at the Royal College of Surgeons rat strain, which was a model developed for retinitis pigmentosa. And first, they injured the optic nerves and they wanted to see what happened to the retinal ganglion cells. And they found that with applying the trans-corneal electrical stimulation, those rat cells, they survived longer than the patients who had not been treated with trans-corneal electrical stimulation. Sorry, the rats who had not been treated with trans-corneal electrical stimulation. In another set of experiments, which was done a few years later, they looked at causing direct damage to the retina. So exposing the retina to light, what happens to the photoreceptors? And again, they found that the rats that were treated with trans-corneal electrical stimulation, those photoreceptors, although they were injured, survived longer than the ones that had not been exposed to the treatment. And they also delayed the loss of retinal function in these rats. And then in another series of experiments, they considered, you know, sort of, is there anything beyond the direct effects on the optic nerve and on the photoreceptors themselves, sort of going further up into the brain that's going on with this treatment? And what they found is that there was some increase in these regulatory growth factors, these neurotrophic factors. So there may actually be some sort of neuroprotective effect induced by the treatment. So this was all pretty exciting. And there were a couple of groups who put together some very small clinical trials. I'm not even sure I would call them clinical trials. But looking at a few patients, one study looked at NAION and traumatic optic neuropathy, and they found some improvement in visual acuity. They didn't find any improvement in any of the other measures that they looked at. Another study in a very small study in three patients looked at patients with long-standing retinal artery occlusion and found some improvement in their visual acuity as well. So again, although these were underpowered studies, not randomized, it gave us some initial sort of propulsion for getting people interested in this treatment and thinking about whether it might be effective for some other types of applications. So this is sort of the big trial in looking at TES. This was done by Shatz et al. in 2011, and they looked at a sham-controlled prospective study. So half of the patients got sham treatment, which was just the electrodes were replaced, but no treatment was applied, and half of the subjects received the TES treatment, and 24 patients with retinitis pigmentosa. And what they found was that when you look at... These are four example patients here who had retinitis pigmentosa. When they looked at their baseline visual fields and compared after 16 weeks of treatment, they found some increases in the area on the kinetic visual field. And these increases or sort of expanding areas here you can see a little bit. Didn't really follow a clear pattern, but they definitely found a numerical increase in those areas. And again, this just shows increase in visual field area. Numerically, this is the treatment group here, and this is the control. This is sort of a low treatment group. You can see that those... That visual field area was increasing over time, so we're essentially getting back some visual field. And then they also looked at the scotopic B-wave amplitude and found that that was increasing as well for the patients who had treatment. And essentially what we found is that treatment was well tolerated. There were improvements in the visual field, again, as we showed with the kinetic area. And as I mentioned, the scotopic B-wave amplitude increased. And this just tells you that these patients were better able to adapt in the dark. And so, again, kind of trying to pull back to this hypothesis that there may be some effects from the transcorneal electrical stimulation on the retina and on the optic nerve itself. But there may also be some downstream effect on expression of neurotrophic factors. All of these sort of small experiments and clinical trials have been trying to dig at this hypothesis. So just to give you a summary of sort of where things are going, there's a lot of clinical trials going on in this area. A lot of these are completed, so it'll be interesting to see their results coming down the pipeline. A few of these studies are in retinitis pigmentosa. There's another study here which looked at a whole host of retinal diseases. And then this study is the one that I was sort of peripherally involved in during my time at Wills. And they were actually looking at patients who had combat-induced trauma to their eye and also NAION. And then this study down here is actually pretty exciting because they're doing it in the UK. It's a multi-center study. It's the first for transcorneal electrical stimulation to really get a good safety profile of the device and understand, you know, if these sort of effects that we saw in these early trials are, you know, really, really coming true. So I'd just like to acknowledge the group that I worked with at Wills, and thank you for your time. Any questions? So it isn't fascinating the area that's interesting. It is. It is. Japan took off with that. We immediately saw, and it was a lot of choreography. I mean, there was a lot of crazy stuff going on. I was really interested in this. The first time I realized that I went into a Japanese bathhouse and accidentally got into one of their waters in which they... I said, yeah, we use that all the time for rejuvenation. The people who are careful is going to kill somebody. Yeah. They are. They've been into it for a long period of time. But there is evidence. I know that some of our people have looked at this and apparently the general feeling on the car... The idea is that you'll get a little pickup from this. There seems to be some sort of ideal window of treatment, especially for other diseases. There was another more recent study that I didn't talk about here where they looked at patients with retinal artery occlusion and they actually didn't find much benefit when it was much further downstream from when the initial occlusion was discovered. But some of those early studies found some benefit and the difference between the two was the time after the artery occlusion was discovered. So if you treat sooner, you might be able to take care of some not functioning but haven't completely died. Whereas if you wait too long, your window may be gone and you may not be able to get the treatment. They also call that one TES, but it's transcranial. So how well can you keep such a... Yeah, so that's sort of tricky because if you're... So the phosphine level, basically, you're testing to see how much current you need to deliver or how much stimulation you need to deliver for the patient to detect a signal to the retina that is as though there were light coming in. And if they're at 150% of that level, then they're going to feel like there's light coming in. So, so far, I mean, my experience with the patients that were in the study at Wills is that there may be some ability to detect that they're in whichever group. But there's not really a way to avoid that. If somebody can come up with some idea, that would be wonderful. But it's the closest that we could get to a sort of placebo-controlled or sham-controlled. It's a big issue. So these visual fields and other percepts are going to be very suggestive? Yes, absolutely. Yeah, so the Traumatic Optic Neuropathy Study is a DOD grant. And actually, while I was there, we had applied for another grant looking at TBI, which I thought was really interesting. Unfortunately, it didn't get funded, but we'll see they might keep pursuing it somewhere else. All right, so our next two presenters, we'll first hear from Nate Lamberg, who's a fourth-year student here at the University of Utah. Nate is originally from Logan, Utah, where he studied business...