Cutting-Edge Science for Eye Health — Dr. Jeffrey Goldberg

0:00 that glaucoma is the number one cause of irreversible blindness in the world. And that I think is going to be the piece that we overturn. >> We have always said, "Hey, we got to prevent you from losing vision. We got to slow down the disease because once you've lost whatever vision you've lost, I can't get that back for you." And I think that is about to topple. >> We are about to get into vision restoration. at a level that has been totally unexpected and totally unprecedented. >> Dr. Jeffrey Goldberg, so nice to meet you. Thanks for making the time. >> Absolutely. Thanks for having me on. I'm really looking forward to it. >> I have so many questions for you. And as

0:46 usual, I am scratching my own itch. This is going to be a selfish conversation for yours truly in some respects because the way this whole thing came about is I put up a post on social media asking for cutting edge technologies or treatments related to presbopia which for those who don't recognize the term is a very fancy way of saying age related visual decline. If you're a word nerd like I am, Presbyterian, similar etmology, leadership of the elders, and I have noticed in the last year that my near work, my near vision has started to falter looking at books, looking at my iPhone, looking at supplement bottles.

1:33 And this has led to somewhat of a crisis of meaning for me because I have had my identity based on in some respects very very good eyesight and visual acuity for my entire life. And Andrew Huberman, mutual friend of ours, texted me and said, "I've got the guy. I know the guy." And listen to our interview, which I did. And for that reason, we're going to go all over the place. But I thought we would start where I had to start, which is supraanormal visual performance. And these are the notes I scribbled down from your conversation with Andrew. I recommend everyone listen to it. Goggles that reduce frame rate for basketball. And that was sort of left hanging a little bit. You guys didn't do you didn't do a deep dive on

2:19 it. So I want to start right there because of course there's preventing decline, there's maybe a restoring function and then there's going further and taking things as far as you can and nowhere are the stakes higher and the rewards greater perhaps than in professional sports. So could you take that and run with it in any way that makes sense? >> Yeah, sure, sure, sure. And yeah, Presby, vision of the old. So, I'll tell you just a funny side note. You know, we all get that. >> Mhm. >> I like you have, you know, gone my whole life without needing glasses until I hit around age 40. And when everyone hits around age 40, our lens inside the eye won't compress and reshape to focus up

3:06 close. So, your distance vision might still be great, but you just can't bring that focus in as tight. And I discovered it accidentally in myself because I was actually like in my house and someone I I found a pair of glasses in a closet. Like somebody must have just left them there. >> I see where this is going. >> And it turned out they were readers and I was we couldn't figure out who this they were. We're calling around friends and family. Fine. Nobody's claiming them. And then one day I just put them on like let's see how I look in glasses. And I look down at my phone and I'm like oh my god wait a second I can see a lot better. these readers on and then once you do it, you're addicted because good vision is pretty addicting, right? >> Yeah, for sure. >> Like you want to have good vision. So now I'm in them too and you know I'm I'm

3:53 pretending to look so young with you not wearing them right now but here they are just in case. Yeah, >> very common. Yeah, very very common. It raises a really cool question that you're raising which is we, you know, like as an eye doctor, I spent a lot of time and as a researcher spent a lot of time, we could come back to talking about like how do we prevent the sick from losing vision on all these big eye diseases. We could come back to that, but like there's a much bigger world of people who have pretty good vision. Maybe they need glasses, but they've got good vision. And how do we think about the difference? Not from sick to normal, but how do we think about the difference from normal to supra normal? And we know they're supernormal because when, for example, as you bring up, professional athletes get studied. >> Mhm. >> They have better vision. They have

4:39 better reflex time. They have sharper vision. You know, we talk about like 2020 vision. That means I can see at 20 ft what a quote normal person can see at 20 ft. So I have normal vision. But you can have 202 vision, which means you can see at 20 feet what normal people can see at 12 feet. Right? You've got better than norm. And it turns out like a lot of pro aletes have that. And then the next question becomes and you just kind of hinted at it right there. Can we train to supernormal vision? Can we like induce super? And almost no one studies that, but there are some really cool tools and toys that actually might have that effect. And so you brought up one of them. So we see like our cones inside

5:26 of our eyes. is, you know, we've got rods and cones. The cones, they've got a refresh rate around 30 to 60 frames per second, >> kind of like our computer screens do, right? If you actually subtract out a couple of frames, so if you put on some glasses that dim one out of every 30th of a second or they dim two out of every 30th of a sec, or push it three and now you're giving up visual data and I throw a basketball at you. >> If you've got your regular vision, you'll catch it. >> Yeah. But if I'm only giving you 90% of your vision or 80% or 70 or 60% of that vision, you might miss the ball.

6:12 >> Yeah. >> Right. But if we practiced and trained in those goggles where you've got to play basketball, throw and catch, shoot, whatever, throw baseball back and forth at 70% vision, and then we put you in the game back with 100% vision, right? you're going to be like better, faster, reflex time, >> all of that hand eye coordination. So, it's actually like some of these supra normal visual tactics are actually trainable and there's tools that athletes are using, but they're accessible to all of us. Yeah. >> All right. >> So, you can grab one of those. Tim, >> let's dig into this a little bit. I have a number of friends who have engineering shops and have played with sensory substitution experiments and all sorts of wild stuff. And in fact, I think

7:00 there are some folks at Stanford who uh David Eagleman comes to mind who's who've developed tools along these lines. We won't go down that route. Let me stick with vision for a second and just note that there are, for instance, indigenous groups in various parts of the Amazon. I've seen them in Brazil and in Peru as well, which use eye drops of various types. could be from a plant, could be from a toad for improving not near work but distance work. So let's just say using most of them use shotguns these days but some still use blow guns and arrows for hunting bow and arrows for hunting say monkeys right so there seems to be something to it now you could say ah that's a bunch of voodoo hoodoo nonsense but then you have eye

7:46 drops for as I understand it temporarily inducing more this isn't going to be the right term but flexibility in the lens I think is it pilocarpine >> it's actually The iris. >> The iris. There we go. >> Yeah. So, I don't know what they're using in the plants. Yeah. But we now have FDA approved eye drops. And what they actually do is they bring your pupil size down by having your iris constrict to a smaller circle. And it turns out that if you have refractive error, so you need glasses, you know, the shape of the front of your eye, the shape of your lens isn't perfect, you have a little bit of glasses or contacts or whatever to correct that, including if it's not focusing up to close. You can have reading glasses that change

8:32 that refractive, you know, that light coming into your eye so that you're focusing up at close. >> Mhm. If you come down to a pinhole, you actually kind of normalize the light so that it's as if it's all coming from infinity and you actually kind of correct refractive error. One of the ways we can tell if someone needs glasses is we have you read the eye chart and then we have you read the eye chart through a little pinhole, you know, a little device you stick in front of that eye and read through a pinhole. And if you can read better through the pinhole, you actually have better vision and could correct it with glasses. So now we could just give an eye drop that kind of makes your pupil closer to a pinhole and then it allows you to see without glasses near or far and in fact

9:19 people are kind of using it now for near vision for that presbopia you were talking about in the beginning. >> Yeah. for people listening and also for me frankly could you just give a vision 101 and in this case let's focus on the eye just so people understand the basic components of the eye and part of the reason I want to explore this is there are different levers you might be able to pull on to improve >> vision some of which might be structurally related but not all at least to the eye but could you just lay out the basic anatomy of the eye, the architecture. >> Absolutely. So, light comes in the front, goes through the clear window in the front of our eye called the cornea. You can have corneial diseases obviously

10:07 that block that light from coming through clearly, but if it's if it's healthy, that light comes through clearly. The cornea is curved on the front, and that curvature is actually responsible for curving most of the light into the back of the eye. Then the light goes through your pupil. So that's the iris, which is the brown and me, but brown, blue, hazel. So that's our iris. And the iris can open and close like we were talking about a minute ago. Comes through the middle of that, the open middle part of that. Goes through the lens. The lens does fine focusing, little focusing from far to near, that kind of thing. That's what we're saying stiffens as we age. So we can't go far to near as well as we get older. Kind of passing 40 years old typically. Then it goes through the gelatinous middle part

10:53 of the eye. We call it the vitrius after the lens is called the vitrius. That's where floaters are. People who get floaters, they're floating. It's like little concretions of proteins and stuff floating in the vitrius. It's a gel. As we get older, that gel turns to water, kind of shrinks up. Our eye doesn't shrink cuz it fills in with, you know, salt water, but the gel shrinks up >> and then the light hits the retina. And our retinas are what we call inverted. So the light actually passes through almost all of the retina and then it hits the rods and the cones and those are the photo receptors. They absorb the light like the photons of light. The rods are really really only good for nighttime vision. They're only good at like very low light. If you go into normal daytime vision sitting here in

11:39 the room, whatever, those are getting bleached out. You're not really using your rods too much. And next to them, the cones. Cones are great for color vision. They're great for bright lights. They're what we use most of the day. That's what you and I are using mainly right now. The rods and the cones collect all that light. They process it and transmogriphy it into electrical signals and those electrical signals are then propagated back forward through the retina. There's some internal processing layers in the retina. So, it's not just a layer of film. You're actually doing some computation right there in the retina. And then they hit what are called retinal ganglen cells. And those are the cells that then send a process across the surface of the retina. It's

12:25 an axon, but it's like a telephone wire. And that then goes back out the back of the eye into what we call the optic nerve. And that optic nerve connects the eye to the brain. So those retinal gang cells are collecting all the data and sending it all back through the optic nerve to the brain. And then of course the rest of that processing is happening in the brain. >> There we go. That was a great summary. Thank you very much. And I'll tell folks if if you thought that is a lot to remember, it is a lot to remember. But the point of it is as I as my own N of one am trying to consider different paths forward with Presbopia, whether it's glasses, yes, my readers do fix the problem, right? They do fix the problem. But I am a little concerned of increased

13:12 dependency and then increased magnification over time. I know there are arguments for and maybe some arguments against. But when I put up my social post, and I think people can identify with this, there was a lot of noise. There were some of the most hairbrained, insane, certainly potentially dangerous suggestions you can imagine. And then there were a few things that came up when I reached out to let me get this right is it vitro retininal surgeon and researcher who I happen to know and he sent me a number of white papers or I shouldn't say white papers more so studies and meta analyses and so on that I read up on and I thought to myself look at that surprise of surprises a few of the things that came up repeatedly in the hundreds of

13:58 responses to my post actually show up in the literature and there might be something to Um, and we'll definitely come to a number of those, but it can be very overwhelming for people to try to figure out what to do next. And the reason I wanted you to do that recap and then I'll stop giving my second TED talk of our conversation is that much like if someone complains of say brain fog and fatigue, a rose is a rose is a rose is not a rose in the sense that there can be many different factors and independent variables that contribute to that. So one person might have insulin insensitivity and trouble with glucose disposal. somebody else might have Lyme disease or some infectious disease that is contributing to metabolic dysfunction. I mean there's so many different

14:44 contributing factors that it helps to I think get a little thinly sliced. So in my case I have the stiffening of the lens. Please correct my terminology. I also have a really pretty sizable I had never seen it before. I did some really impressive imaging on the eye, but a huge neas on the back of my right eye that I need to keep an eye on. So, I'll be following up on that in 3 or 4 months. But I wanted to I suppose start with what are other ways to improve vision. Now, there are certain things I'm always looking for limited downside potential upside. So, for instance, I'm taking the A-Reds 2 supplement with luteine and various

15:31 other ingredients in it. I would say it's probably not going to help, but within my patient cohort of the the medical practices I work with, there are a few folks who claimed after 6 weeks that their vision really improved and they didn't need their readers even though technically mechanistically the AIDS 2 shouldn't have helped them. So whether it's placebo effect or not interesting outcome I know the plural of anecdote is not data but I was like ah okay sure I'll take the supplement. What are some other sort of cutting edge treatments or augmentations for improving vision? And I'll shut up in a second, but I've been very excited to talk to you. So, I'm like chopping at the bit here because as you mentioned, I mean, there's this sort of eye architecture brain interface and among professional athletes, just because I've

16:17 funded a lot of science in this area, lowdosese psychedelics also seem to improve visual acuity. So everyone from Aaron Rogers to very very high level athletes that I will not dox here report measurable performance improvements that they attribute to increased visual acuity. Well, it's it's probably not changing the anatomy of the eye. So what's going on? >> Yeah. >> Right. So I would just love you speak to any other means of supercharging visual perception. There are some things that we have a pretty decent sense on aids too and some of these supplements. You know, first of all, eating a lot of carrots is probably not going to actually do. So, great childhood get the kids to eat their vegetables. We we

17:03 definitely exercised that ourselves as parents. But, ids too clinically proven if you have moderate age related macular degeneration to slow down your vision loss. Does that mean it doesn't work at all if you have mild age related macular degeneration or if you have no age related macular degeneration? It might just be like we haven't done a study big enough to detect those effects and >> as you say like that's probably not going to hurt. So, you know, feel free if you want. We can't prove it's helping, but feel free. There are other supplements that have, you know, received some study that maybe suggest there isn't much going on there that again probably not going to hurt. Some patients take, you know, CoQ10, some

17:50 patients take GKO. There's actually maybe the hottest topic in supplement vitamin space right now internationally is actually vitamin B3 nicotinomide which has really been linked to a number of good potential you know kind of medical uses and is receiving a lot of study there's actually international clinical trials including one here in the US actually testing whether it could restore vision in certain eye diseases like glaucoma which is my specialty See, so definitely some hints in that direction. We already talked about some device elements and I think between vision training like we talked about earlier and also visual augmentation,

18:36 we're moving into augmented reality. And so training vision and visual reflex time, you know, almost certainly makes a difference in the activities you're training in. If you're training in basketball, will it also help you doing some weekend surfing? I don't know. But definitely can help move you from normal to to supernormal or help enhance improve what you're doing. And then there's all sorts of stuff that I'm going to be honest, Tim, we don't know because a it's kind of really new, really hot right now, like micro dosing certain psychedelics, things like that >> that we know act on the nervous system, including the brain, but the retina in

19:22 the back of the eye and the optic nerve that connects the retina to the brain. Those are developmentally an outgrowth from the brain. They are part of the brain. They are part of the central nervous system. And we barely know about how to influence the wiring, the plasticity. Are there drugs that we can give? You know, a lot of people have talked about gabapentin and drugs in that space. Obviously, micro doing LSD is a really hot area right now for like inducing plasticity. There's like actually great science showing in animal models and a little bit now in humans that you can actually reopen brain plasticity >> by dosing some of these drugs at appropriate doses. Obviously, we got to

20:09 be careful. We don't know what the right dose is yet, but it's really worth looking at because there's clear evidence that these are relevant and, you know, likely to have some effects. We just got to figure out, you know, a little bit more like how what's the right dose. By the way, when you're doing it, should you be doing some behavioral training like visual training? But these things act on the brain and about a third of our brain inside our skull is dedicated to processing vision. >> There's a lot there. All right. I I've been so I'm not just over caffeinated because I'm actually not really caffeinated. I might be over ketoned. I have quite a bit of ketone monaster in me at the moment. Putting that aside, I am right now, and this could make me seem like I'm in the tin foil hatwearing

20:55 crowd, but I had a number of companies reach out to me, not surprising, after I put up my social posts. Most of them didn't make any sense. A few of them seemed to make sense, and the people involved seem to have technical chops and also some pretty credible research backgrounds. And I'm not going to name the company X cuz I'm not done with my personal testing, but I have been testing at about 8 minutes a day. I don't know the right descriptor to use. I would say maybe visual perception training to distinguish it from and we can talk about this what I suppose some opthalmologists or optometrists might call visual education, right? to trying to improve the siliary muscle strength and so on around the eyes. Much like if

21:41 people are want to visual sort of the springs around a trampoline, right? But in this case, it's very quick flashes of blurry or not blurry circles and you need to identify what is more blurred and there are many permutations. It adapts to your successes and failures over time. And it could absolutely be placebo, but after about, you know, a month now of using it, I feel like my near vision has improved. And even the woman I'm dating has commented on this. And I'm still waiting. The jury is out. But this is just to say that I'd love to know what

22:27 you think of visual improvement that is not dependent on surgery or drops. Is there something to the various types of visual education? Is there something there or not? And then when we go maybe upstream a bit, if that's the right phrasing to use, to the brain, are there interesting approaches like limiting the frame rate or removing a number of frames that you think are at least plausibly interesting for enhancing performance? >> First of all, absolutely. And then it does get back to that idea of like visual training, reducing frame rate, training on visual perception. There's actually a fair amount of data

23:12 actually. There's so there's enough data to even say like there's elements that make it better. For example, if you do visual training where you're just showing yourself being shown these different objects, maybe they're getting smaller, dimmer, blurrier, etc. Your ability to train off of that is significantly better if it demands a behavioral outcome, a motor action. So, for example, you've got to point at the right one or choose something. And it's not just that you're mentally thinking that was the sharper image. It's actually the motor output of pushing a button or pointing at something or doing an activity that actually reinforces

23:58 the visual perception training. >> So, that's one great example. Another great example is after concussion. So concussion, traumatic brain injury, of course, very common in athletes because they're more likely to get into the head bumps and things like that. But but happens all the times in kids, >> military, very big problem. >> Military, it's actually like a very big issue. And the line in between mild concussion, severe concussion, traumatic brain injury, that's all on a spectrum, a continuum. And there's actually decent data from that group of people that if you get a concussion, actually visual symptoms are some of the more significant symptoms.

24:44 You know, ability to focus, ability to sleep, and vision are three of the big symptoms that people get in that concussion through TBI spectrum. And those can be debilitating, right? And kids are out of school, they're missing high school, you know, for weeks or longer. It can be really debilitating. Obviously, if you're older adult and you're in your job situation, really tough. And it turns out though that there are visual perception exercises that you can put patients through in those situations that in the limited clinical studies that have been done point to a positive effect of basically rehabbing like neuro rehabbing you back. Now that of course is back from injured to normal. But the idea that that can also induce the same kind of plastic

25:31 remodeling in our eye and brain and particularly the eye brain connection. >> Mhm. >> In patients who are starting from normal and trying to get themselves up to supra normal try to improve performance visual performance. You know, we've set up here a whole human performance laboratory really just to study these questions and the data rolling in make it look like, hey, there's something here. This is definitely worth chasing. What can someone search if they want to find something to read up on related to the concussion rehabilitation protocol? Because this type of visual training because there's a lot of nonsense floating around and charlatans out there. any particular search terms or

26:16 principal investigators or anything that people can search? >> I would say like, you know, if you want to sort of at least hit some of the science or science adjacent web resources, you're going to want to use a few technical terms in there like concussion, neuro rehab, neuro rehabilitation, plasticity, and then some of the terms you've already been using, you know, visual perception exercises. >> Mhm. And then look in these situations you got to look not just at the content but of the source right is this a dude on his blog or is this you know coming from a foundation or an institute or one of the academic centers or some of the choices like that. >> All right Jeeoff I would love to hop to another set of interventions and this is

27:04 in the device category. Red light in the morning for mitochondrial health question mark. violet light to reduce progression of nearsightedness in children. Is there an application of red light or violet light? To what extent do we have supporting data for using either of these? Do we have an idea of what best practices look like? Is it only for people with a disease state or can they be potentially used to preserve vision before vision loss? >> The disease state data is pretty good. And also the myopia control is pretty good data too. >> Just for a definition for folks, what's myopia? >> Myopia is nearsightedness. And you know it's it's an epidemic more common in

27:51 Asians or people of Asian heritage, but common in everyone. And kids can get nearsighted. If you're a little nearsighted, it might be annoying to wear glasses. If you get more severely nearsighted, it actually can lead to all sorts of problems inside the eye. you know, real severe vision loss even early in life. So, that's a big one. What was really shocking was it turns out that a small dose of daily red light can slow down progression of myopia in young people. We're talking about teens and younger even. >> So, what's even more shocking to me is that it also works with violet light. So how does it work with light at the two

28:37 ends of the visible spectrum? And definitely mitochondria are implicated. Mitochondria are the little like kind of powerhouses, energy sources inside the cell. They are big player in converting the sugar a cell takes in into energy that the cell can use for all of the cellular processes. So our bodies clearly need functioning mitochondria. In fact, one of the big features common across many neurodeenerative diseases of the eye and the brain is dysfunction of mitochondria. There's an FDA approved red light therapy for patients with macular degeneration, but there's good data that it may also be supportive or protective in other eye diseases. And we're talking

29:24 in small doses. Like this is not overwhelmingly bright lights and we're talking about minutes a day. You don't have to sit in front of it for two hours a day. So minutes a day. So it's exciting. The data suggests that the mechanism of action is kind of giving a little protective booster shot to our mitochondria so that they don't get dysfunctional. Whether that's dysfunctional just from normal use throughout the day or dysfunctional because you happen to have a disease that's getting in the way of those mitochondria. So now we don't know what the right dose is. We don't know what the right brightness is. All we know is that in these initial things that have been tested, initial brightness of how and how many minutes, three minutes a day, for example, there's a signal there. There's something working there. Should

30:10 we have everybody buying one on the internet right now, hopping on Amazon, spending 25 bucks, spending three minutes a day? You know, we don't have the data to support that. Yeah. >> Is it going to hurt? Probably not. Tim, it's a problem because we've got so many things that are like, "Oh, that looks promising and we just we need a little more science. We need a little more study." A friend of mine wanted me to write a blog post about you're this this may look I'm not a doctor. I don't play one on the internet. But the difference between sort of getting into science versus getting out of suffering in the sense that you know and I know just having been involved with the funding side, randomized control trials are expensive and they take a long time. But at the same time, if you take the advice of

30:57 every whackadoodle running around on the internet, you're going to have 600 different interventions, some of which could do a lot of damage, or you're going to get the wrong device. I've seen this also because I've talked about accelerated TMS and different types of brain stimulation for potentially addressing treatment resistant depression and Nolan Williams at Stanford has done a lot of great research related to that and you see these people on YouTube with DIY TMS and they've got the polarities reversed and I'm just like oh my god what are you doing your poor brain but I also want to preserve my vision as long as humanly possible and maybe you can disp spell a concern that I have and this is based on the fact that I have a lot of Alzheimer's and Parkinson's in my family and I'm able to be 34 some 2.5 times or

31:46 so more likely to develop Alzheimer's based on what we currently think we know than someone who is I guess 33. And it scares the hell out of me. And I've had conversations with aiologists who point out the correlation. I don't know how strong the signal is between hearing loss and onset or progression of dementia. Is there something similar for visual loss? >> Absolutely. Actually, one of our faculty here has done some of the really foundational research showing that correlation between vision loss and cognitive decline and the loss of input. Again, vision is our biggest input sense. that's driving a third of our brain is dedicated as I said to

32:31 processing and using that vision and interfaces with every other thing that we do. It also is a really critical piece around depression and mental health. Anxiety is vision. You know, the work that Andy Huberman had done on visual fear and how that plays into the fear and anxiety pathways as well as the depression pathways. And not only does visual decline accelerate cognitive decline, possibly in part because of how depression then plays in with cognitive. I mean, these things are all clearly related to each other. >> But also, remarkably, if you have low vision, let's say from something as simple and correctable as cataracts, a blurring of the lens that happens with age. If we all live to 100, we're all

33:17 going to need cataract surgery, some people younger, some people older. But if you do cataract surgery and restore vision in an older person who appears to be suffering is suffering with cognitive decline and or depression, you can reverse a significant amount of that decline in either of those domains. And so it just again it speaks to the interplay of vision with our mental health, our cognitive health. And this is this is long-term important stuff. >> Tell me if I'm interpreting this the wrong way, but it seems like this would lead to a strong proargument for wearing glasses instead of suffering in silence. I don't know, but that's that's what I

34:02 hear when I'm sort of trying to read between the lines. There's an important myth to dispel, especially when it comes to presbopia and wearing reading glasses. Between age 40 and around 60 or so, that lens stiffens and stiffens and stiffens and the first year you only need plus 1.25 glasses and then three years later you're like, ah, I need plus 1.5 plus 150s. Few years after that, you're moving up to the 2.0's. Eventually, you'll peak out at around 2.5 or 3.0's because that's the difference basically. That's the refractive, the glasses difference between viewing something at infinity, which from an optics perspective is actually just kind of like 3 ft away or further and viewing something at 14 in

34:48 like comfortable reading distance right in front of us. So 2.5 to three power of those readers is all you're going to need. >> But you're going to progress through those numbers whether you wear the readers or not. >> I see you're saying >> so where are the readers? >> I got it. Is it a a mistaken causality then where people believe because an optometrist said this to me a couple weeks ago and I was like well I assume you know what the hell you're talking about which is always a stupid assumption but that you develop increased dependence but it's actually just tracking along with the natural stiffening of the lens. In the case of presbopia >> it is and it's psychological dependence. It's just like what I went through as soon as I started wearing those readers by accident. I didn't think I needed them. I was still reading off my phone. It was fine. But as soon as I

35:34 experienced that extra crisp vision, I was like, "Well, I like that." >> Yeah. >> Or I got psychologically dependent cuz who doesn't want their best vision? >> Yeah, for sure. I'm going to keep saying this, it's going to get annoying cuz I'm like a sweaty palm fanboy like jumping all over you. But I was very excited to chat with you also because I mean the nose, the eyes, these are sort of direct paths into the brain in a sense. And for instance, I don't know, I don't expect you to track all things in all fields. That would be impossible. But Cognto therapeutics, it's a headset that is used and they have a lot of good data. I think they're either phase 2 or phase three. They've raised a ton of money and

36:21 it's a headset and they have these visors covering the eyes and then earpieces and it produces I want to say gamma waves in the brain. There's more to it but using flashing lights and this appears to I'm getting into the sort of deep end of my ignorance pool here cuz I'm pulling from memory but it appears to assist in the breakdown of beta amalloid plaque maybe tow as well. I'm not really sure. So, Houston flashing light to help people with conditions like Alzheimer's. I mean, it's kind of mindboggling, I guess, literally and metaphorically. That does come from from credible researchers. I wish I could cite them offhand, but it's going to take me too much time to find the the scientists involved, but that is one

37:08 that appears to be Ed Bdon and Lee Huait Sai out of MIT. >> I know them both. Fed was a graduate student here at Stanford when I was at Stanford. >> Oh, amazing. >> Yes. So, there you go. Are we going to see more of these devices and how far away are they? Because I'm seeing decline in my near relatives. I'm currently taking care of two relatives with severe cognitive decline. Scares the hell out of me. And some of them are 33, by the way, and I'm 34. So, I'm like, good God. Okay, if there's anything I can do, and I'm already doing quite a few things, but are there other devices that are sort of on the cusp of being available that you find interesting? >> Yeah, I think so. And input through the visual system and output through the visual system are both looking really

37:55 interesting these days. So you're talking about input like what can we stick in through the visual system to influence the rest of our brain brain wave activity plasticity like we were talking about before help preventing cognitive decline. There is very strong data for example that if you give the right amount of electrical activity of our neurons in the eye and the brain so the neurons in the brain talk to each other through electrical activity like little wires and too much activity is bad. I mean really too much activity epilepsy for example >> too little is clearly bad too. If you have a stroke then you've got no electrical activity in that area of your brain and it's just not working anymore. but providing kind of that sweet spot in

38:41 the middle of electrical activity. In addition to it participating in the processing of whatever that area of the brain does like in the retinence your vision obviously it also stimulates pathways like plasticity and responsiveness to the survival and growth factors. And we and others have shown that very clearly in animal research over the years that you need not just the right growth factors circulating around in the brain, but you also need the right levels of electrical activity so that the neurons are maximally responsive. >> Yeah. It's like weightlifting. You can have all the protein in the world, >> right? >> You need the stimulus. >> You got to have the right amount, right? You got to match that up.

39:26 >> So, it's really cool. Like we actually know in the eye the visual stimula. You were talking about flashes of light, but it turns out like different cells in our eye respond differentially to different stimuli. We have some cells that fire when the lights go on. We call those very creatively on cells. We have some cells that fire when the lights go off called off cells. We have some cells that are firing like between blue and yellow. Others that are differentiating between red and green. We have some cells that are in charge of motion detection in the eye and all that data has got to get back to the brain. But if we stimulate for example the motion direction sensitive retinal ganglion cells in our retinas in headsets where we devise cues you know basically

40:12 imagine you're flying through like kind of that star trek field of stars you know like you're going into hyperspace right and >> engage and you're going into h and all those stars speed up by you >> those are great stimuli for some of our direction sensitive cells in the eye and could those actually stimulate those cells to then like perform better or not degenerate in disease. And so we've been studying those kinds of questions. Cognitos engaged in that kind of work. And then how does that affect what's going on in the brain? Very reasonable that that's going to actually lead to specific patterns of activity, flexibility, plasticity that are going to change our brains. And the idea that some of that work can not happen only in

40:59 the academic world, but that people are excited about it and are funding the startup companies and taking that science into that kind of either health domain, health span domain or consumer domain like how do we get the normals protected against the future? There's a lot going on there on that's on the input side. >> Okay. Uh, I am going to just bookmark that for a second and I'm going to highlight a few things that I thought were of of interest and I'd like you to expand on from your conversation with Andy. So, glaucoma, you know, could you have a normal reading during the day but higher at night? And then the potential place of, you know, cannabis edibles. And my

41:45 question there was, do we know what compounds are responsible? Well, people are listening to me and they're like, what the hell are you talking about? So if that's enough of a cue, would you mind just discussing that? Because you know, big challenge with people who are trying to do the right thing. They're trying to get checkups. They're trying to get assessed. They're getting their blood work done, but maybe it's once a year and they had their blood draws, you know, the last one was at 8:00 a.m. and the next one was at 11:00 a.m. and lo and behold, their testosterone is really different. They freak out and this that and the other thing. So like timing matters, among other things. Could you just speak to glaucoma in that respect? >> Absolutely. So, let me just back up one step. Glaucom after Alzheimer's disease, glaucoma is the most common neurodeenerative

42:31 disease. It's the number one cause of irreversible vision loss in the world. It's a degeneration of that optic nerve connection from the eye to the brain. So those retinal ganglen cells that are collecting the data in the retina and their axon fibers, those telephone wires running down the optic nerve carrying that all the vision from the eye to the brain, they degenerate in glaucoma. If you take all comers, it's around 2% of people in an aging population that will have developed glaucoma. If you have a primary family member, a parent, a sibling, a child with glaucoma, your risk probably goes up to about 20%. And so it it runs in families, but just cuz your parent has it doesn't mean 100%

43:16 you'll have it. There are two main risk factors for glaucoma. One is increasing age, and we're all working desperately on correcting that one. We don't have a slam dunk treatment for that yet. The other main risk factor for glaucoma is actually increasing eye pressure. >> Yeah, >> if you have real high pressure, you're going to get glaucoma. But a lot of people with normallook eye pressure can also develop glaucoma. It's just like they were more susceptible. And the eye pressure isn't just the same number. We've got short-term variability and long-term variability. So long-term is like, you know, this month it might be whatever number. Next year it might be a little higher, a little lower. You know, you can vary through your life. But there's also this short-term variability. It actually varies in our dal cycle. So everybody has a dial cycle

44:05 where your circadian rhythm. Some of us like myself are night people and we love to be up at night and getting up in the morning isn't our favorite thing and other people are the opposite and all this stuff relates to our dural cycle our our circadian rhythm you know you can try to take melatonin and affect that but your eye pressure also varies by that and as you say like if I take your eye pressure in the morning and then the next week I take it in the afternoon and I say oh my god your pressure's gone up I got to take you to surgery well wait a second it might just be because I'm measuring at different times times. Now, you brought up like the most common question that I get asked. I'll tell you the most common question that I get asked by patients with glaucoma is, "Hey, can I take cannabis?" And you know, by the way, it's legal for medical use in many

44:51 states and frankly recreational use also in many states and certainly accessible in every state. >> Can I take cannabis? Cannabis, whether you smoke it or eat it in the brownie or take the chewy, it lowers your eye pressure. >> If you're using the version, which are available where you know you feel a little high from it, you get that good feeling. The problem is that it only really lowers the eye pressure kind of during that time that you're getting high. So, I tell patients like it works, but you'd have to be high 24/7, so maybe you should just use this eye drop instead. >> Do we know which compounds within

45:38 cannabis are responsible for the lowering of the eye pressure? >> There's actually data that both the THC's that do get you high and the others also that don't can have that effect. And there's some cool startup companies that have been working on trying to isolate now test in human patients >> the you know you don't get high versions of those compounds or chemically modifying them and by the way turning them into an eye drop. >> Mhm. >> So that it's really just treating the eye and make that really accessible. You don't want to be on your glaucoma treatment and not able to drive. So >> that would be a bummer. Trade-offs. >> It's got to be compatible with daily life for most patients, right? So, that does work. That does work. >> Yeah. The second most common question I get asked is, "Well, can't you just fix

46:25 my eye or give me stem cells or that kind of thing?" But number one is cannabis. >> Well, what's your answer to the stem cells? The magic stem cells. >> We're getting there on stem cells. Like, so if you've lost your retinal ganglen cell connection to the brain through the optic nerve, we're actually getting pretty good at growing retinal ganglen cells out of human stem cells like in the laboratory cell culture dish. And we're actually starting to make real progress, you know, in animal models to start showing that you can transplant them in. But I still tell patients like, don't go to some clinic that's telling you they'll give you stem cells and pay $18,000 of your hard-earned money. It is not ready for that yet. >> Go to Tijana and get a new pair of eyes. >> Exactly. Don't waste your money. >> Well, yeah, that'll be the least of your problems. Will be the money part. So,

47:11 let me circle back to the cannabis for a second. So, I don't consume much cannabis, but I have experimented with cannabis for chronic pain and specifically a number of back issues that I have and some of it's congenital. I have a transitional segment and a bunch of arthropathy and blah blah blah blah blah. And interestingly, a lot of folks, including people who are sort of credible and familiar with the literature, recommended CBD, but I did not find it to have a pain relieving effect that was sufficient for sleep until adding a little bit of THC, which I thought was actually pretty interesting. And I'm wondering if and this actually cycles back to our very short discussion of psychedelic compounds also because why why might psychedelics say improve visual acuity?

47:57 You can come up with a dozen plausible explanations. But when you look at say the depression outcomes with psychedelics, there people on many different in many different parties in terms of arguing why or how they exert their effect. One that I think is underemphasized is the anti-inflammatory effects which can be potent in some psychedelics and you can find studies where they look at anti-inflammatory just standard off-the-shelf anti-inflammatory effects on depression which can be substantial. Do we have any data to suggest that anti-inflammatories have any effect on vision or can in any subopul improve vision? >> Absolutely. Decades ago, there was a pretty hot focus on to what degree the

48:42 immune system might be playing a role particularly in eye diseases, including the common ones, macular degeneration, glaucoma. And then it was hard to pull that together in part I think because we didn't know as much about the immune system 20 30 years ago as we do today. And now we know a lot about what we call the innate immune system, which is not the part that learns about the flu virus and makes you immune the next time you get the flu virus, but just how our immune system interacts with our body normally >> and how it also might interact with our gut bacteria and then crossreact with our own body, things like that, right? And so it turns out now that we've got

49:28 this much deeper appreciation from the whole immunology crowd about how the immune system and in particular the innate immune system works. We're now revisiting in neurodeenerative diseases including glaucoma macular degeneration. And it turns out it is just packed with evidence that the immune system and innate immunity really play a role. Let me give you one example that is shocking. If you raise the eye pressure in a mouse, the retinal ganglen cells and the optic nerve will degenerate just like in human glaucoma. But in a really beautiful set of experiments that came from a woman, a professor at Harvard, Dongfang Chen, she

50:14 showed that if you raised the eye pressure in a mouse that was raised itself, grew up in a germfree environment and doesn't have kind of all the normal mouse dirty gut bacteria and therefore its immune system is at some level fundamentally different. You can raise the eye pressure in that mouse but the optic nerve won't degenerate. they won't get glaucoma damage. And then if you take the immune cells out of the first mouse and just put them back into the bloodstream of the second mouse, >> then the optic nerve will degenerate. >> Wow. So like the immune system is playing a huge role that was previously totally underappreciated and they're amazing drug therapy candidates that are now moving up through the pipeline in

51:00 towards human testing to test, hey, if we could like suppress the immune system, not totally suppress it, cuz by the way, we still want to be like attacking bacteria and viruses, but just suppress the little leg of that immune system that's attacking our body and leading to neurodeenerative disease. That's going to be off the charts. as you were talking about the microbiome and and so on. I was doing a bunch of reading for another interview I'll be doing shortly with the with the scientist and one of the stories and this is in animal models of course but looked at how and some people have heard through the grapevine one way or another how you could take the microbiome just for simplicity sake of say obese

51:46 mice and transplant that to lean mice and they get fat right or vice versa and I might getting some of the details wrong, but roughly you see some very interesting effects. However, if you sever the vagus nerve in those recipient mice, they do not exhibit those changes. And so then some of the questions that are kind of outstanding is well if that indicates that you could instead of using like ablation or severing something stimulation to achieve a similar effect then what can you start to do and then you have like hockey puck sized things that you put next to the liver that can you know via some

52:33 technological wizardry affect these things. But God, you know, I suppose that the more I look at a lot of these things, also with family with Alzheimer's and they might take something like theurin, which has on some level anti-inflammatory effects, I'm like, okay, well, and I don't want to be a onetrick pony with like the one thing I keep beating over the head, but it's like, okay, well, if we know that chronically inflamed like micro ga have all of these hosts or at least they're associated with a host of different neurodeenerative diseases and inflam ations associated with depression. To what extent can we mitigate these things? And we're sort of hitting a bunch of birds with one stone. Does that make any sense? Which is why I'm so interested in the possibility of using

53:20 devices. I'm so interested in nutritional ketosis, but also exogenous ketones. Brain loves this stuff. Also, the beta hydroxybutyrate, very potent anti-inflammatory. I'm just wondering, do you think that I am just too clever by half and I'm like missing the plot here? I just I feel like chronic inflammation, which is kind of like saying business or the arts, right? I mean, there are like a million different facets to inflammation. You need you need inflammation for a lot of reasons, but when it is pathological and chronic, it turns into a big issue. with rapid decline in eyesight, let's just say in glaucoma, how often is that comorbid with like metabolic syndrome or something like that when the decline is faster than say average?

54:07 >> The earliest data looking at, you know, let's say diabetes as a marker of a lot of patients with type 2 diabetes. It's associated with what we call metabolic syndrome, which is this cluster of high lipids, high blood pressure, insulin resistance, right? And so there was initial data suggesting that a little bit of diabetes might actually be like a little protective in glaucoma and then some of the followup like next set of studies suggested like no no maybe it's a little bit bad for your glaucoma and so the net net is it's probably not >> metabolic syndrome as a whole is probably not a huge difference but I'll tell you the place where those two are converging is one of the hottest topics in medical science today which is these

54:52 GLP1 receptor agonist which are going to have a huge effect on human health by reducing metabolic syndrome, overweight, obesity, etc. but also are looking very promising for neuroprotective y and I think it actually gets to that point you're trying to tease yourself like are you just kind of getting ahead of it but actually you're touching on I think where we're actually coming to as an understanding is where the science is going in the field which is this axis between the brain which you think of like well isn't that mostly inside my head but also the peripheral nerves that are going out to the whole rest of our body and the immune system and those two are talking to each other all the time.

55:39 And now we've got the microbiome and that gut axis is like a third leg of that stool because that's clearly also interacting with both the nervous system and the immune system in very specific ways. We're going to see a lot more of that really I think come together and understand more mechanisms. You know, is it going to be one day that we're all just kind of taking that like purified poop pill that we just swallow down and it changes our microbiome for the day and it protects us from Alzheimer's or glaucoma in the future? We're all hoping that's going to happen. We'd love that protection one day. >> Yeah. >> You know, should you buy the poop pill off the internet just yet? I'm not sure. Yeah, I don't think so. >> Yeah. Sri Lankan poop pills from like rural rural children. I'm in. Yeah. Be

56:26 careful with what's out there on the internet, guys. And I'm supporting a company, I might have to bleep this out, but called Holo Biome. And they're actually creating the most comprehensive library currently of gut microbiota because it's like what you can buy currently off the shelf. First of all, most of it's dead. It's like inert by the time you consume it. A lot of it doesn't actually get through your metabolism to where you want it to be. And it only represents maybe in some a few dozen like I don't know the right term is strains of bacteria whereas there's like thousands upon thousands. So there's so much to explore which is also very exciting. >> Let me give you one more idea of what what might be that ideal world on the way to that. >> Yeah. >> So you know we share microbiomes between

57:13 us. At Stanford med school years ago when I was there, we had a microbiology professor and he used to kind of tease the world is covered with a thin layer of poop because no matter how well you wash your hands after going to the bathroom, there's a couple bacteria that got on your hands or your belt buckle and your, you know, and then you shake hands or pat someone on the back. I don't want to increase anyone's anxiety. This episode is brought to you be by Purel. Right. >> There's a thin layer of poop. What we call clean and dirty, he used to say, is really just how thick that layer is. God. >> Okay. So, that joking aside, if you just shack up with someone who's got great

58:00 longevity and probably a great microbiome, >> Yeah. >> good chance you're going to absorb their microbiome. Maybe that'll be good for you. You know, so I they got to put that on the dating websites, you know, get your microbiome on that profile. >> Yeah, Craigslist microbiome casual encounters. So, this is going to be a bit of a hard left, but preservative free strips of tears for dry eye. Why? That was one of my notes from the conversation that you had with with Andrew. because I'm I'm also looking for just lowhanging fruit for people who are contending as we all do with aging eyes. Maybe you could speak to that and then I do have to ask about the blood serum for eye drops. Maybe you can hit that too.

58:47 >> Sure. So, look, actually the most common eye disease as we get older is actually dry eye. As we get older, we make fewer tears. We also make lower quality tears. are tiers at high quality have have a liquid phase like a water saltwater phase. There's also like an oily component to good high quality tiers and that oily component also kind of dissipates a little bit as we get older, gets less as we get older. So, we make fewer tears and lower quality tears. And a real simple over-the-counter solution for so many people is just put in some artificial teardrops. The thing is is that those little bottles come with preservatives so that you know when you use it all month, by the end of the

59:33 month it's not growing bacteria. And if you're just using a drop or two a day, fine. That's getting you by. Fine. Just buy those bottles. They're the cheapest. But if you're getting to the point where it's three, four, five, six times a day, you like, you know, maybe you work on the computer a lot, so you blink less and your eyes get drier, you want to use more of those. Then we usually recommend at that stage switch over to preservative free artificial tears because it turns out that preservative in those bottles of drops at a drop or two a day, fine. But if you're getting up to a lot of drops a day, the preservative is actually irritating and kind of inflammatory to the ocular surface. It actually kind of breaks down some of the cells on the surface of our eyes.

1:00:19 >> So at that point, we like to switch people to recommending the preservative free. Mh. >> They're the ones that usually they come in like a little strip of tiny little plastic. You break one off. It's got its own little cap on it. It's got this tiny little bubble of fluid that you can squeeze. It really tests if you've got bad fingers or bad, you know, by the way, if you've got bad vision, you're poking yourself in the eye with it. Anyway, that's what we recommend. Switch to preservative free. And then people who need more than that, we actually have drugs that for example reduce inflammation on the ocular surface to help the tear quality and quantity come bounce back a little bit. And then we also have drugs that contain growth factors,

1:01:05 things like nerve growth factor that are almost certainly also good for the surface. And when our eyes get dry, the surface, the reason it feels irritating is not just cuz it feels dry. It's actually because the surface starts to break down a little bit. >> And when you go to sleep every night and your eyelids are closed and nothing can evaporate, you know, it bounces back a little bit by morning. So, it kind of regenerates or rejuvenates. The ocular surface can regenerate pretty well every day. But at some point, your eyes are getting dry enough that you're having much more chronic problems. And that's where sometimes we can use what are called serum tears. So our blood serum, if you take out a blood, you know, like a tube of blood, you're getting your blood drawn. That tube of blood has your red blood cells carrying all your

1:01:50 oxygen. Your white blood cells, which is like your immune system, and then all just the liquid with the proteins in it. That's what we call the serum. That's the So you could take that tube, you spin the cells out, what's left is the serum. >> Let me ask a dumb question. Is that different from plasma? Are we talking >> serum and plasma? Yeah. Depending how you treat some of those proteins, that's serum and plasma. Let's just say you're spinning out the cells. >> Yep. >> And then you can take that serum, maybe you dilute it a little bit in some of that preservative free, you know, artificial tears. Maybe you just use it straight. Usually we dilute it a little bit. And we can give patients their own serum as artificial teardrops. And that serum is filled with really good juicy growth factors that help the surface

1:02:37 rejuvenate. And that's the principle of in some patients using serum tears. >> Maybe this is just a difference in terminology, but it makes me think of a plateletri plasma or platelet poor plasma. Are there experiments with different not sure concentrations or cocktails? >> Different cocktails. That's a great way to put it. Yeah. and plateletri plasma. Again, one of the reasons that that looks so rejuvenating for our bodies is again it's just like choa block full of growth factors. >> Mhm. >> And so I don't know, I'm sure somebody's testing this as another way to treat really severe dry eye or if your dry eye is so bad you're actually getting like kind of ulcers on the surface of your

1:03:24 eyes. some of the most severe cases might really benefit from like serum tears maybe platelet rich plasma would work too. So that's a hot area right now and again filled with growth factors. >> We talked about the importance of timing with say >> glaucoma exams things of that type. What are some other recommendations for perhaps avoiding common mistakes or filling gaps that are commonly unfilled? Any any recommendations to folks? >> Yeah, there's a bunch of things. First of all, get an exam. And if you have a family member or blood relative with eye disease, maybe get that exam even sooner. Take glaucoma as an example. If you got an exam and you're 40 and you don't have a family history and your

1:04:10 exam was normal, you don't have to come do that full exam every year. You could come back in five or 10 years, try it again. But especially as we get older now, half the people in the world need glasses. Half the people in the US need glasses. So you might be going into your local eye care provider, optometrist, getting your glasses checked each year or two anyway, just to see if you're still in the right prescription, and they can do the full exam, check for everything else, make sure nothing else looks suspicious, leave you in great shape. So getting that periodic eye exam, especially as we get older and more of those age related diseases like macular degeneration, glaucoma, etc. Obviously, if you have diabetes, you're supposed to get an eye exam every year just to make sure because if you've got diabetes and it's starting to affect the

1:04:55 retina inside your eye, we could get

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