Podcast: Dr. Mark Bullimore Part 2

I recently sat down with Dr. Mark Bullimore to discuss his perspective on myopia management.

You can check out our full conversation here, or by searching "EyeCode Media" in your favorite podcast app.

Read the transcript here:

Chris: [00:00:00] If, if we transition you, you made the comment of, okay. If there's one in 20. Infiltrates that wind up being MK and 10 to 15% of those wind up with vision loss. Then you've got to look at the idea of this, which is the second part of my question that I wanted to have you kind of delve in a little bit more on is.

[00:00:19] Alright. Well, what is the actual like numbers needed to treat? If we can reduce your risk of myopic maculopathy from a minus six down to a minus five by 40% preserving that one diopter. How many of those minus six patients or who would have been a minus six patient, had we not intervened? Would we need to intervene on to save that one doctor?

[00:00:40] Did you?

[00:00:43]Mark: [00:00:43] yeah. So there is, so you've seen a couple of sort of glimpses pieces of data. So you've seen the safety data, but, you know, and you've seen a little bit of the data on risk of. Myopic maculopathy as a function

[00:01:00] Chris: [00:01:00] of levels. It's not published

[00:01:02] Mark: [00:01:02] yet. Well, there's the stuff that's under review.

[00:01:04] So let me, let me, let me sort of join the pieces together. so first of all, you're very sophisticated in so much, you, you mentioned number needed to treat, so, the number of kids that you would need to treat to slow myopia. By, I mean, by an amount to sort of produce that, that benefit is actually very low it's in the single digits.

[00:01:30]yeah. so let me, let me pull up. That's

[00:01:34] Chris: [00:01:34] pretty powerful

[00:01:35] Mark: [00:01:35] then. yes. And your number

[00:01:37] Chris: [00:01:37] needed to harm is actually quite high based on the data. You've just,

[00:01:41]Mark: [00:01:41] yeah. so

[00:01:42] Chris: [00:01:42] compelling stuff, because the, I mean, this is the kind of stuff that makes people really say, like when they people say now a standard of care.

[00:01:52] I, I, I think, yeah, it's part of my care. I don't know that it's standard of care, but if you get into the point of saying number needed to treat of less than 10, that's pretty significant.

[00:02:03] Mark: [00:02:03] Yeah. yeah, so, I mean, there are, I guess sort of general numbers. That's

[00:02:10] Chris: [00:02:10] why I wanted John

[00:02:20] hello and welcome to the Chris Wolfe podcast on EyeCode Media. Today's conversation is part two with Mark Bullimore and we're discussing specifically the incidents of infections in child, in children who wear contact lenses, has some of his literature related to that. And also, the literature related to the amount of vision that we can preserve by reducing overall myopia, which is super compelling. And actually he gets into data that hasn't been published yet. So the data that I've seen sort of scratches that surface. And he was able to answer ideas of things like number needed to treat and number needed to harm, and really bring those two ideas together based on his evaluation of all of the evidence that is available to us. So it was a really great conversation for me because I, I, it, it helped, it helped me wrap my mind around the full impact of what we're doing with myopia management. And, and so I'm really grateful for Mark to be on and discuss that. And so please enjoy our conversation as always be sure to subscribe to the podcast, write a review and share it with your friends and support those who support us.

[00:03:32] We've been providing myopia control treatments in our practice for years. If you've been listening to the podcast for awhile, CooperVision has received FDA approval of its innovative. My site one day contact lens. This will be the cornerstone of a comprehensive myopia management approach to be offered by Cooper vision. This daily wear single use contact lens is the first and only FDA approved product clinically proven to slow the progression of myopia. When initially prescribed for children eight to 12 years old. And when compared to children in the control group, wearing a single vision one day contact lens, check out the show notes for all the specific prescribing details and to get more information about this lens and how you can begin to offer it to your practice.

[00:04:14] Mark: [00:04:14] This has been fun aside jet sort of a territory here.

[00:04:18] Chris: [00:04:18] Yeah. Yeah. So I, I think, that's, there's kind of two questions that I want to pick your brain about and one is not to be, Is because I think if, if, well, one, if I can understand the data better and where the actual data is coming in, how you find those

[00:04:33] Mark: [00:04:33] like one, it would be the

[00:04:35] Chris: [00:04:35] 40% of saving one diopter of myopia.

[00:04:38] How do we get there and to the infection stuff. So if I can, and I've read that, I've read both of those, papers that you've put out. but maybe, and I'm not, and I'm not opposing you in this. I'm just thinking the better I can understand it. The more convincing

[00:04:52] Mark: [00:04:52] I can be to other people.

[00:04:54]Chris: [00:04:54] because I know there's a lot of people that are just like, you know, they still think kind of cleanses and kids not going to do it.

[00:04:59] They still think myopia management, not really that helpful longterm or short term, it's more, it's more effort than it's worth it. So. In my effort to try to make sure that I'm communicating as effectively as possible to people and trying to also tell them about the evidence, but then kind of, I think the evidence guides us into why it's important, the better job I can do explaining the evidence,

[00:05:22] Mark: [00:05:22] the better job I think, or the more people will say,

[00:05:25] Chris: [00:05:25] yeah, this is important.

[00:05:26] So those are kind of the questions, like how do we get, how did you get to that

[00:05:29] Mark: [00:05:29] point to be able to say, yes,

[00:05:30] Chris: [00:05:30] this is how the evidence shows us that, kind of lenses in kids are safe. Can you

[00:05:36] Mark: [00:05:36] tell me about that? Yeah. So those are two great examples of sort of, you know, me sitting in my, my computer and trying to pull things together.

[00:05:47] Now, the other thing I talk about, you know, being a industry funded academic, you know, both of those pursuits were really stimulated by interactions with industry or people coming to me and saying, Hey, Could you put something together. So let's talk about the safety aspect and, you know, before I give you the long history, let me give you the sort of disclaimer.

[00:06:14]you know, people might regard me as a hired gun and, you know, a keyboard, you know, have keyboard we'll we'll, we'll we'll travel. but. Yeah, my, my brand, my reputation as an academic is the thing that's most important to me. So if somebody says, can you say this? And I I'm going to say, well, if the evidence supports it.

[00:06:41] Yeah. so, you know, pulling information together, is. Is important, but you know, I have the freedom to come up with whatever, whatever answer, you know, I'm led to. So, in the case of safety of contact lenses in children, so I, you know, I've done some work on a contact lens infections and epidemiology I've been involved in, focus night and days.

[00:07:14]pivotal study, which involved, you know, almost 10,000 patients and yeah. Looking at the rates of infections and classifying, what was serious, what was amongst those? So I, I had a little bit of involvement there. And then in again, just before I had left, by the time you were a. Graduating from optometry school in the, you know, 2008, I had done a study that was commissioned by, Bausch and Lomb and Paragon to look at the safety of, overnight orthokeratology.

[00:07:55] And in that particular instance, essentially, you know, overnight orthokeratology or CRT had been approved. Without age restrictions, basically, for the temporary reduction of myopia, but then, unexpectedly in the eyes of the FDA. it started to be used a lot in children because we were learning that it could slow my OPA progression.

[00:08:18] And at the same time, there was a whole slew of, case reports out of the far East. Mainly showing that we were getting some serious infections in children. so the FDA said, hang on a minute, you know, they have a mechanisms. Yeah. We need you to do a post-market study, to provide some data on safety and children.

[00:08:37]so we, we, we had done that study and again, you know, it was a company sponsored study and it sort of gets criticized, in some quarters for been, you know, unreliable. In that regard, but you know, we're dealing with the FDA. Okay. They have badges and guns. Okay. The government. All right. and you know, it's my academic reputation on the line.

[00:09:03] We did the study. The data are what they are. So anyway, so about. Five years ago, Gary Osborne from CooperVision said, Hey, Mark, you know, would you be able to write a white paper on the safety of, contact lenses in children? And this was the sensibly to support the product development of my site.

[00:09:26] And, you know, as part of either a submission to the FDA, but in terms of educating practitioners, We're going to get asked about this. What did the data say? Okay. What do the, what do the papers say? So, again, you know, off I go, how many page papers can I find that have followed a meaningful number of children for a meaningful number of time, amount of time, to contribute to some estimate estimate of the, the.

[00:09:58] The safety of, contact lenses in children. So I was able to identify a number of, prospective studies. Most of them. related to my OPO or there was a big paper out of a high state, Jeff Arlene on self-esteem and contact lens wear. So, you know, you put all the data together and you sort of like, it looks, it looks pretty good.

[00:10:19] And at the same time, or just previously the clay study group, or a group of largely women, optometry academics had done a similar study. You see my research assistants just, Similar retrospective study, looking at the rates of infections or the rates of adverse events in different ice groups. And they basically came to the same conclusion I did, on the, the prospective studies that actually children are, the safest teenagers are, have a high rate of infections and then college age people, I don't call them adults, college age students, have an even higher rate of infections.

[00:10:59] So the kids are the safest in part, probably because there's, adult supervision, you know, and the kids listen to their parents at that age. teenagers, less. So college age, you know, And

[00:11:18] Chris: [00:11:18] they also have a history. If I'm asked another question I would wonder is they also now have a history of things being okay.

[00:11:24] Right. If they started wearing contacts when they're eight and they were fine. And then now they're 16. Oh, I've had eight years of history. Everything's fine.

[00:11:34] Mark: [00:11:34] Yeah.

[00:11:35] Chris: [00:11:35] Did you find that, do you find that in the evidence

[00:11:38] Mark: [00:11:38] beyond what you're just describing? I mean, you see that, I think all the time and you probably see it in your practice.

[00:11:43]you know, it's, you know, there's a bias, there is a biological aspect to infections that we still don't fully understand. but we do know that, you know, if somebody gets a corneal infiltrative event, and I'll use that as a catch-all that may or may not be infectious they're four times as likely to get a subsequent one than somebody who hasn't had one before.

[00:12:06] So there's a, an innate sort of risk. I mean, I, I was, one of my, master's students. This is going back. 20 years. at OSU, we did a study. We were looking at corneal swelling where these new Silicon hydrogels with overnight wear. I wore the, what was it? The Bausch and Lomb lens, the pure vision lens.

[00:12:27] Yup. First night I slept in pure vision. I woke up with a red eye infiltrating. Okay. Right over the contact lens clinic, contact lens lab, let every a second year student take a look at it. You know, this is what an infant, this is. Yeah. This is what it looks like. Okay. So, again, that's part of the joys of being in a teaching institution or an academic institution.

[00:12:53] You, you basically, you could, you could take somebody out of the research lab like myself in this case and sort of say. There you go

[00:13:04] Chris: [00:13:04] back up on that again, because you know, when I was, when I was being trained and it's not something I think about nearly as much anymore, but you know, there's, there is this proportion of the, of the population in my experience that, that tends to have reactions like that to a silicone hydrogel lens.

[00:13:17] It's not, it's not a ton, maybe five to 10% in my experience, but,

[00:13:21] Mark: [00:13:21] Yeah.

[00:13:22] Chris: [00:13:22] Yeah. So, but that seems to be less of an, I guess from a contact lens company standpoint, it seems to be that most contact lens companies aren't concerned about that because they say they seem to be moving everything. There's some companies that almost exclusively just have Silicon hydro gel offerings as least at least in a monthly standpoint.

[00:13:43] Mark: [00:13:43] So. Yeah, it's it's, you know, I mean, you know, again, the Silicon hydrogels story is an interesting one in so much that we thought it was going to be a panacea or, overnight where, and then for baby work, but, you know, the evidence is quite clear that. Even with daily wear Silicon hydrogen lenses, you get a, a higher incidence of these little ditzels, than you do with conventional hydrogen.

[00:14:10] Okay. It's the nature of the material. Now, there are other advantages in the material, but yeah, that alone stops it from being a clear, you know, Stops. Everybody stops everybody from moving to Silicon hydrogels. but yeah, so it's that, that there's some good things and bad things. Now, as I said, with those little peripheral vessels, that kind of infiltrate of events that we see more commonly with Silicon hydrogels that generally innocuous.

[00:14:43] Okay. you know, you take the person out of the lens for a few days. You. Because you're a naturally conservative guy. You treated with a topical antibiotic, you know, even put a steroid on Saturday. Do you want them to feel more comfortable? you do what you do, you'll be the doctor and then you move up.

[00:15:02]but you know, it happens and, you know, I was certainly working. I was supposed to child for that, based on one night of overnight wear and. But the other thing that is really sort of, I would say, revolutionized safety and, you know, really makes it very attractive, in, in anybody, but children particular is go into daily disposables.

[00:15:26] Yeah. So, you know, one of the keys, things that's attractive about my site is that it is a daily disposable lens. And, you know, we know that sleeping in the lens is probably the number one risk factor for, or increasing rates of infections. But. Things related to solutions and cases, sort of two and three, if you can get those three things out of it, the way you're likely to have better safe safety, of a contact lens.

[00:16:00]I would say the third, the other thing that that's pretty equally important is that, you know, you can now in any of your patients, you know, they can call a number if. they got a problem. So, you know, I would say if I was seeing patients, you know, if you have a painful red eye, you need to reach out to me right away so we can address it.

[00:16:24] And as your doctor, I'm, I'm available to you, you know what the, what the, you know, I think if you say painful red eye, you're going to see some uncomfortable red eyes as well. But again, you can nip it in the bud. You can, you're an associate can. See it and deal with it right away before, you know, there's a risk of it being more serious.

[00:16:47] Chris: [00:16:47] Well, and that's in the literature that you looked at and reviewed. what were those numbers like when you said, cause you, cause I think that's a great point too. I mean, I think those are the four big ones that I think about is obviously sleeping in lenses, cases, solution responses or solution, improper tests.

[00:17:04] And then also how, quick somebody gets in to see those,

[00:17:08] Mark: [00:17:08] if you

[00:17:09] Chris: [00:17:09] mitigate that, what's the numbers, for, for kids in context.

[00:17:12]Mark: [00:17:12] so basically, you know, In, in all of the studies I reviewed, there was not any cases of microbial keratitis in eight to 12 year olds. now, and that represents probably over 2000 years of wear now.

[00:17:31] And the recently published, blink study, which, you know, three year study, high state and Houston randomizing kids too. Two different strengths of bifocals are a single vision lens. They did have one, case of presumed microbial. Keratitis. But, you know, if it was, if, if you look at the details of that case and they presented it, at the Academy meeting as part of the general safety profile, it was pretty iffy.

[00:18:01] Okay. If

[00:18:02] Chris: [00:18:02] he, if he, as in, they were just being overly cautious or if he is

[00:18:07] Mark: [00:18:07] peripheral

[00:18:08] Chris: [00:18:08] infiltrate that. Had a little overlying staining and they just called

[00:18:12] Mark: [00:18:12] it microbial keratitis. That was kind of you, you, you, you narrowed it, it was a relatively small, peripheral, you know? so one of the, one of the things, you know, hindsight's 20, 20 or 2015, One of the things that, while in acknowledged, he said, you know, they didn't go into this study expecting to see these things.

[00:18:35] So they didn't have a classification scheme in place. So. so basically they had the data safety and monitoring committee reviewing these adverse events. And there were three optometrists, three clinicians on that group who sort of made a decision on this. But yeah, it was a peripheral infiltrate, I think, based on its size, it wouldn't have met the criteria for probable MK and some of the studies that I've been involved with.

[00:19:04] So, you know, the ortho case study that we, you know, that we did. you know, even before we started reviewing cases, we had a criterion for what was probable and K what was possible and K, and what was, what was not,

[00:19:21] Chris: [00:19:21] can you, can you do, if you have that off the top of your head, like, cause again, I'm not a, I'm not a researcher.

[00:19:26] Mark: [00:19:26] I think it's really cool. And it would be the same things that you would look at. So basically, to be probable I'm K. You need to have an infiltrate. That's at least one millimeter in diameter, overline, stain in, pain, greater than mild. So, you know, it can't be just discomfort that it has to be pain.

[00:19:51]and then one or one of the three, you know, purulent discharge and IC reaction or shit. What's the third one. or a positive culture, I think. So if you look at different studies, they typically use that construct, right. And then they will just below that, have a sort of possible MK that fails to meet all of those criteria.

[00:20:17] So they might not be big enough. there wasn't that much pain, you know, there wasn't. Really any sort of nasty discharge, AC reaction or whatever, but you thought it was still probably or might be it. So typically, you know, so if you take all infiltrates, okay. All infiltrative events in soft lenses, one in 10 or one in 20, typically be classified as, and K.

[00:20:47] Now again, you know, you have the ability to treat the, be cautious. You treat them all the same. Right. And that was something that we went back and forth with the FDA in that court, that ortho case study, because they said, you know, treatment, if the treatment was consistent with MK, then that was like, you think it's like, okay, because Chris Wolf is going to reach for the same antibiotic.

[00:21:16] Whether it's he thinks it's MK or he thinks it's not MK. All right. I mean that's so we have the ability to treat. We treat. Okay. so with the treatments, like, you know, isn't a good indication of what the practitioner thinks, but generally as you've probably already figured out when you're, when you're doing these studies, either prospectively or retrospectively, you don't let the clinician decide you don't let the clinicians treatment dictate.

[00:21:46] You have, an independent panel of three to five people who look up the case and say, you know, What is it? Okay. And it's like a, what do you call him? A more mortality morbidity conference, in a hospital, which they have on a regular basis. Okay. Who died? All right. what, what are we, what are we saying here?

[00:22:09]yeah, you want to, because you want to. You want transparency, but you want to get ahead of anything that might be coming down the pike. So, so yeah, those are the things that you look for. And, you know, the challenge in the blink study is they didn't have a construct that could, they have gone to a shine paper or a Baltimore paper or a Charmaz paper and said, let's use what they did.

[00:22:34] Yeah. But they, you know, they had one case. Okay. But yeah, it was pretty, it was. And it was the same actually in, if in the, my site retrospective study, they had, you know, it wasn't my site lenses. but the FDA wanted a large retrospective, practice by sample of, young, soft lens. Whereas, and to, to S to get another estimate of what the incidents of, microbial keratitis might be.

[00:23:02] And again, if you dig into those data, I think they had two cases of MK, but, you know, they were pretty soft, you know? and yeah, the other thing that, you know, you have to, remember is that my phone, my, It's all good. It's all good. I was just telling me there's another podcast for me to listen to, but the, you know, the other thing is, you know, you've got this basket of infiltrates and know a small proportion of those will be classified as MK.

[00:23:35]and of those, a small proportion will lead to vision loss. So typically, you know, between five and 15%. Of MK leads, division Wells. So that's an important thing. When we talk about, place in safety, in the context of, vision saved by reducing the risk of macula or whatever, not, you know, just cause you've got something that is an MK.

[00:24:06] It doesn't mean no that's vision loss. And again, some people lose it. Oh. You know, patients got MK. And part of that comes from the, you know, ophthalmologists or optometrists who work in a hospital who see the real train wrecks. Part of it is just misconception that people say MK, vision loss. Right. even in the most.

[00:24:28] Conservative of cases or conservative of studies, you know, it's 15%, but when you look at other studies, it's four or 5% and you know, again, what kind of lenses where these people were in what kind of care systems where they use in, when was this? Yeah. Did they

[00:24:51] Chris: [00:24:51] get into ended? They did, is that study being done by a tertiary care center that.

[00:24:55] Is seeing the train wrecks and not in primary care that is taking care of a majority of them

[00:25:00] Mark: [00:25:00] before they get, I mean, some of our best studies have been done in Australia where optometrists weren't treating these things. And, you know, the time that the studies were done, you know, in the late nineties, the, you know, the anything that was, you know, Any corneal infection was going to be seen at one of these hospitals or one of these tertiary centers or whatever.

[00:25:27]so chances are that they were not only capturing the, the, the mild ones, but also the extreme. And if anything, you probably did see more severe cases because of the seven. If you do the studies. As part of, you know, prospectively like the blink study and, you know, you end up with, you know, 300 kids wearing self lenses for three years.

[00:25:53] So that's, you know, that's as big a sample you would get outside of an FDA. Post-market surveillance study, you know, that's, that's a, that's a huge data, so yeah, you're going to see shit. And, but generally, you know, you would not expect even in that number of cases to see perhaps more than one case of MK or.

[00:26:16] Possible MK. And you certainly wouldn't expect to see any vision loss in part, because it's extremely rare. And in part, because these kids are in a study and they are kids, they're getting sort of, there's more caution, there's more care involved. And perhaps, you know, somebody, buying contact lenses online as a young adult and, you know, No paying too much attention to things.

[00:26:41] So w

[00:26:42] Chris: [00:26:42] well, let me transition that into, because I do want to be respectful of your time is that if, if we transition you, you made the comment of, okay. If there's one in 20. Infiltrates that wind up being MK and 10 to 15% of those wind up with vision loss. Then you've got to look at the idea of this, which is the second part of my question that I wanted to have you kind of delve in a little bit more on is.

[00:27:07] All right. Well, what is the actual like numbers needed to treat? If we can reduce your risk of myopic maculopathy from a minus six down to a minus five by 40% preserving that one diopter. How many of those minus six patients or who would have been a minus six patient, had we not intervened? Would we need to intervene on to save that one doctor?

[00:27:27] Did you?

[00:27:30]Mark: [00:27:30] yeah. So there is, so you've seen a couple of sort of glimpses pieces of data. So you've seen the safety data, but, you know, and you've seen a little bit of the data on risk of. Well, I think maculopathy as a function of levels,

[00:27:48] Chris: [00:27:48] it's not published

[00:27:49] Mark: [00:27:49] yet. Well, there's, there's stuff that's on the review.

[00:27:52] So let me, let me, let me sort of join the pieces together. so first of all, you're very sophisticated in so much, you, you mentioned number needed to treat, so, the number of kids that you would need to treat to slow myopia. By, I mean, by an amount to sort of produce that, that benefit is actually very low it's in the single digits.

[00:28:18]yeah. so let me, let me pull up

[00:28:22] Chris: [00:28:22] pretty powerful then.

[00:28:24] Mark: [00:28:24] Yes.

[00:28:24] Chris: [00:28:24] And your number needed to harm is actually quite high based on the data. You've just,

[00:28:29]Mark: [00:28:29] yeah. so

[00:28:30] Chris: [00:28:30] this is compelling stuff because I mean, this is the kind of stuff that makes people really say like when they people say now a standard of care, I think, yeah.

[00:28:41] It's part of my care. I don't know that it's standard of care, but if you get into the point of saying number needed to treat of less than 10, that's pretty significant.

[00:28:50] Mark: [00:28:50] Yeah. yeah, so I'm in there. I get to sort of throw some general numbers that you saw around

[00:28:57] Chris: [00:28:57] John.

[00:28:58]Mark: [00:28:58] I'm just pulling up the Piper here so I can actually give you the numbers. So, so one of the things, and again, this was, this was something that was requested or by, by CooperVision, young lady in the UK called Elizabeth llama. Who's an optometrist and is sort of, in charge of, medical affairs in Europe.

[00:29:16] She said, Hey, you know, would it be possible for you to compare. The risk of vision loss, associated with wearing contact lenses with the benefit of preventing vision loss associated remote control. And she asked me this two, three years ago, and like so many things I didn't have the answer right away.

[00:29:39]And I thought, you know, you know, my interested in, let me think about that. Let me think about it. I thought about it. I thought about it some more and you know, the challenge was that you had to come up, you had to compare data on the incidents of monocular infection, and the incidents of vision loss in a young kid.

[00:30:03]wearing contact lenses with the potential prevention of visual impairment, somewhat down the road associated with a diopter of myopia control. And I, it took me a long while to figure out how to put those pieces together because they were, you know, you initially you're comparing apples and oranges.

[00:30:23] Okay. You've got. Data on risk, based on incidents and you've got data on, you know, risk of prevalence additional. So, so let me, let me go back to your, The issue of, that you asked about number needed to a trait. So this, this paper was submitted, for publication about two weeks ago. it took a long time and went through a number of iterations.

[00:30:47] And, you know, for example, you know, I, you know, there were things I wasn't. Comfortable about, and I needed to think about some more. There was just my own inertia. the sort of often takes over and I, you know, I put things aside and it takes me a while to get back to them. but then as often happens, I'll have a little bit of an aha moment where it's like, Oh yeah, no, the answers here.

[00:31:13] I, and then I flurry of activity and you throw it out to coalesces again. And it's like, Hey guys. Yeah. so where are we? I'm just looking here at number needed to treat. So, so just to put it in context, so we're familiar with the ocular hypertension treatment study, where they found that if you put a person on. I like you're hypertensive for five years, you could reduce the incidence of glaucomatous field loss or optic nerve changes, from 10

[00:31:51] Chris: [00:31:51] to 5%.

[00:31:53] Mark: [00:31:53] So one in 21 in 20. So you need to treat people for five years to prevent one case. So

[00:32:03] Chris: [00:32:03] obviously tree changes. I want to interject because I think some of our listeners may not fully.

[00:32:08] Think through this all the time. Like you, you obviously do, but that number would change, obviously, if you're, if you're scaling your treatment based on risk factors. So patients that have thin corneas

[00:32:20] Mark: [00:32:20] higher, IOP's

[00:32:21] Chris: [00:32:21] more suspicious nerves, family history, right? Like if there risks,

[00:32:26] Mark: [00:32:26] if you keep believing that, Chris, no, you don't think so.

[00:32:29] I'm being facetious. Yes. It probably, it probably does.

[00:32:35] Chris: [00:32:35] I'm not saying that to diminish what you're

[00:32:37] Mark: [00:32:37] saying. I agree that number, but that number needed to treat is 20 patients for five years. So the whole cohort, a hundred patient years in order to, prevent one case. And that's the provide one case of.

[00:32:54] Glaucoma early glaucoma

[00:32:56] Chris: [00:32:56] and we've accepted that we've accepted that that's that's okay.

[00:32:59] Mark: [00:32:59] Yeah. It's, it's become standard of care because we have, in most cases, cheap innocuous therapies, you know, to do that. but you know, when you get to my age, you, you come into contact with decisions to sort of treat.

[00:33:14] So, you know, my cholesterol is a little high. Okay. Am I one in 300?

[00:33:20] Chris: [00:33:20] One in 300 for a statin, you know, that

[00:33:24] Mark: [00:33:24] it's actually probably okay. Because, you know, I worked with ophthalmologists who think about these things as physicians, but yeah, no, the, the numbers for statins. So let me, let me just, where are we?

[00:33:42]this is probably not the best document to look at cause everything's segregated. I'm just trying to find the, the table with the number needed to treat for myopia. So,

[00:33:56]so you can then do the same mass and I'm sorry to keep you on.

[00:34:01] Chris: [00:34:01] No, it's good. I'll I'll cut this all out

[00:34:05] Mark: [00:34:05] right off

[00:34:06] Chris: [00:34:06] the

[00:34:06] Mark: [00:34:06] top of your head, the number. Needed to treat okay. To prevent five years of visual impairment. Okay. In, in somebody who's destined to be a minus six is about five. So the number needed to treat, to prevent one year.

[00:34:31]is actually, you know, fifth of that. So it's almost a one-to-one ratio. So the benefits, at least according to our calculations are, you know, incredibly favorable, in terms of, you know, so five years of vision impairment, you typically need to treat five patients. in order to get that benefit.

[00:34:54] Now, the review is my Savage stat, but I've got some pretty smart people. Who've already looked at it either as coauthors or as, collaborators who, now, so. Take on the, on the contact lens side. Okay. So if you consider a let's consider a medium risk contact lens, where the incidents, the annual incidences of MK is five cases per 10,000 patients.

[00:35:19] Okay. So that's a high-end for daily work. All right. You, yeah, through the same math, math, and you come up with the number needed to harm. Okay. The number of patients you need to expose for five years of contact lens, wear to produce five years of vision loss. so it's the other side of that coin. The numbers are 190.

[00:35:46] Okay. So you're looking at five versus one 90. The number needed to treat is five. The number needed to harm is 190. So the, the. The needle is firmly pointing towards the, you know, the benefits outweigh and, Oh, have I lost you, Chris?

[00:36:13] I'll keep talking. the number, the number needed to, You're back. I'm back.

[00:36:17] Chris: [00:36:17] Sorry. So you were, I got this. So you were saying the number of patients that needed to harm would be what?

[00:36:24]Mark: [00:36:24] 190. So you, so basically, to, to, to save five years of visual vision loss

[00:36:34] Chris: [00:36:34] from.

[00:36:36] Mark: [00:36:36] For vision loss from contact lenses.

[00:36:39] Okay. So you would need to treat so, or you would need to expose, 190 patients to five years of contact lens wear in order to produce five years of. Vision loss. And I'm saying vision loss, because the criteria for vision loss in those contact lens studies is typically either 20, 40, or two to line loss.

[00:37:06] Okay. And the other costs, the other caveat is that's why, so, like the old spin and early joke, our risk one. if you don't know the joke, I'll tell you it offline. the, So when you, however you look at this, even, even if you go to ortho, K and you assume a very high level of risk of microbial, keratitis, it's still, the odds are still firmly in favor of.

[00:37:37] Yeah, sorry. The scales are clearly tipped in favor of the benefits of myopia control far outweigh the risks. Okay. So, you know, I may end up having my pants down on this one, once this goes through review. but I really don't think so in terms of how you look at these data and again, you know, why, why haven't we figured this out before?

[00:38:03] Well, I had to, first of all, develop a construct to sort of compare, and I'll send you the paper. So you can, you can look at it and sort of go through, on, come back to me with more questions. you know, I had to develop a construct, so you could actually compare the risks of vision loss from.

[00:38:24] Contact lens wear with the risk of vision, loss of vision gained from lowering the levels of myopia. but also, you know, we've only recently got good data on the relationship between visual impairment and myopia level. you know, and there's still really only a couple of studies out there. so for it, you know, and the data I'm going to show you the data in a minute, Yeah, made sure I've where are we?

[00:38:50] It might be a vision impairment. I'm going to show you, the data are I, use frequency.

[00:39:03]all right. so let me, I'm going to share my screen, just to show you a graph here or a couple of graphs.

[00:39:10] Chris: [00:39:10] Let me allow you to share it.

[00:39:11] Mark: [00:39:11] Yeah, I'm just, I'm just making sure I got the graphs readily available because you know, like many of my spreadsheets is there's a, it's a train wreck. in terms of a draw, a graph, then I draw another graph. Okay. So you see my screen now. Okay. So this is, let's go to this.

[00:39:32] So these are data from, 15,000 patients across multiple studies in Rotterdam. And basically I've replied to dead data. The Piper, the Piper, this is from is cooled. so people can find this online, the association of axial length with risk of uncorrectable visual impairment in the Europeans, but basically they have in that paper, graphs that show that, and you've probably seen these presented by me and other people, showing the, the cumulative risk of vision impairment is a function of age for different levels of axial length and different levels of myopia.

[00:40:17] So this paper is publicly available and it's, you know, if you're willing to go through and it's fairly accessible, you can, you can be impressed by the, the data. But what I did was I said, okay, let's, replot it. In terms of level of myopia. And what you see here as a set of exponential curves for different age groups.

[00:40:38] But when again, you put them on a log scale, those curves are a straight lines and a remarkably parallel. that is to say the relationship between cumulative risk of visual impairment and level of myopia is remarkably consistent across. Different age groups. Okay. So obviously the risk increases with age, the risk increases with level of myopia.

[00:41:06] So you can do a multiple regression and come up with an equation that will give you the risk of visual impairment as a function of age, the myopia. So that's something we do in that paper. And we, it that,

[00:41:22] Chris: [00:41:22] can I ask you one more question? They're actually the, a case where, where, amount of myopia and myopic maculopathy are sort of, they, are not cause and effect, but they're sort of co-variants together where there, whereas the case that even if we re, so maybe patients are more at risk for developing more myopia, but also a separate risk at the same time that they're going to be developing myopic.

[00:41:45] Maculopathy where even if we reduced. That

[00:41:50] Mark: [00:41:50] they saw. So what, I'm, what I'm showing you.

[00:41:53] Chris: [00:41:53] So that's, that's the other thing I think might people might,

[00:41:56] Mark: [00:41:56] well, these data are agnostic in terms of the cause of visual impairment. So this isn't a big macular degeneration. This is loss of vision. Okay. So obviously myopic maculopathy is a big component here, but so is detachment.

[00:42:13]glaucoma is probably a huge feature here as well. But it's probably Malbec. Maculopathy, what's really driving this because as we sort of talked about, early on each traditional diopter of myopia increases your risk of myopic maculopathy by about 67% looking at these curves, each additional diopter of myopia increases your risk of visual impairment regardless of age by that 30%.

[00:42:42] Okay. So. The other thing I wanted to show you is, you know, this is one study. these are the same data here. but in the last year there was a paper by one of my collaborators, published on French people, which essentially shows nearly identical data. So these are, these are French individuals, the dotted line at the top.

[00:43:08] They're over 60. These are. French myopes under 60. and they agreed pretty well with the, very well, I think with, the Dutch data. So we've got some independent, support for here, but it's only these recent data. The look at visual impairment and eye disease as a function of level of myopia that really allow us to quantify what the potential benefit is regarding.

[00:43:39]like, the potential benefit of myopia control. So we can see here on these, these graphs and others, the relationship between level of myopia. And visuall