Innovations in Intraocular Pressure and Closed Loop Drug Delivery Systems

On Tech and Vision Podcast with Dr. Cal Roberts

In 2012, Christine Ha won the third season of Masterchef, after having lost her vision in her twenties. Since her win, she has opened two restaurants in Houston, adapting to the challenges the pandemic still poses to restaurateurs in order to meet the needs of her community. In a similarly innovative way, Max Ostermeier, CEO and Founder of Implandata Ophthalmic Products out of Hannover Germany, has reimagined the remote management and care of patients with glaucoma. Max and his team developed the EyeMate system, a microscopic implantable device and micro sensor that measures intraocular pressure throughout the day. The EyeMate sends eye pressure data to an external device and uploads it to their eye doctor’s office for analysis. This game changing technology allows people with glaucoma to bypass regular trips to the ophthalmologist’s office to measure their eye pressure, key data in maintaining their eye health. We revisit a conversation with Sherrill Jones, who lost her sight due to glaucoma, in which she shares how difficult it was to adhere to compliance protocols. Max believes the EyeMate will evolve to be part of a closed loop drug delivery system; that is, when the EyeMate registers a high pressure, medications could automatically be released into the patient’s eye, which could improve outcomes significantly. We dig into issues of compliance and closed loop systems by considering diabetes. We talk to occupational therapist Christina Senechal who has managed her diabetes for 27 years, and Dr. Carmen Pal, who specializes in internal medicine, endocrinology, diabetes and metabolism in Lighthouse Guild’s Maxine and John M. Bendheim Center for Diabetes Care. 

Podcast Transcription

Ha: A dish that has a lot of memory for me is in Vietnamese is called thit kho, which means braised pork with egg. And it was actually a dish that I cooked in the finale of master chef in my season, because it was kind of a tribute to my mom.

Roberts: That’s Christine Ha, two-time restaurant tour, and winner of the third season of master chef in the US in 2012.

Ha: It was actually a dish that I grew up eating quite often. She was a working mom. So she would make this dish that use very inexpensive ingredients. You know, at the time, pork belly was cheap. And it was simple to make. It was just a matter of like adding fish sauce, some sugar, coconut water, garlic, shallot, onion. Both my parents are from Vietnam, and they came here in 1975 as refugees right after the Vietnam War.

I went to college and I missed a lot of the home cooking that my mom used to do. When I was growing up. She actually passed away when I was 14 and never taught me how to cook and never left recipes behind. So it was really about a nostalgia for my childhood foods. And I went and got cookbooks and read the recipes and just kind of by trial and error taught myself how to cook in the kitchen.

Roberts: Mastering her mother’s home cooking got harder, as Christine began to lose her vision in her 20s due to an autoimmune condition called neuromyelitis optica or NMO. But she kept working at her craft.

Ha: And then, like, decided to try out for Master Chef.

Every episode Christine’s dishes were innovative, beautifully plated, and always delighted the judges. Gordon Ramsay told her she cooks like an angel. And every week, her star kept rising.

Ha: And then because I won that season, then it sort of launched my culinary career as well. So I wrote a cookbook called Recipes From My Home Kitchen after winning Master Chef, which went on to be a New York Times bestseller. And then since then, I’ve also opened two restaurants in Houston, the first one called the Blind Goat, and the second is called Xin Chao, which means hello in Vietnamese.

Roberts: While the pandemic has been hard on restaurateurs, like Christine, she has found ways to keep the doors open.

Ha: So it’s just a matter of figuring out how to adapt as quickly as possible to serve and meet the needs of other people, whether it’s staff, you know, the landlord, people in the community, people who want to still have a good meal in spite of everything. We just had to figure out how to make it work. There is opportunity and you just have to kind of think outside of the box and figure out what new ways to think or do things and what new needs are, are need to be met. And that’s how you survive.

Roberts: Thinking outside the box, finding opportunities, and doing things in new ways for patients with blindness or vision loss is what this podcast is all about. As glaucoma patients know, glaucoma management has always required many trips to the doctor’s office, since that has been the only place where one can measure intraocular eye pressure. And for some, the pandemic made those trips more challenging. Enter Max Ostermeier, CEO and founder of Implandata Ophthalmic Products out of Hannover, Germany. Max Ostermeier and his team have invented the Eyemate system, which introduces remote management and care of glaucoma. 

What Max Ostermeier and his team have developed is a microscopic implantable device that rests in someone’s eye and measures the pressure throughout the day. The information is automatically downloaded to a handheld device to the patient uses and then uploaded to the doctor’s office for analysis. This is truly game changing technology. And I’m delighted to have Max as my guest. So Max, where did this idea come from?

Ostermeier: My personal interests are really because I have also some glaucoma cases in the family. So, I’m certainly also a candidate for developing Glaucoma at that point of time. And then I realized that there’s not too much change in measuring eye pressure for the last 50 years. 50 years back Dr. Goldman invented the golden applanation tonometry and this is still the gold standard. It’s the method as pointed out, which can be only performed at a doctor’s office, but doesn’t tell you what’s going on in the patient’s real life. And I thought, you know, there must be a better way to understand what’s going on with a patient in between office visits. To better understand if the therapy of a patient is really working and the pain point for a patient is, they take eyedrops on a daily basis to lower your eye pressure. But they don’t get any feedback at all. As a potential patient, it’s very bothering. And I think it’s also very bothering for patients who have already glaucoma.

Roberts: So go back in time with us go way back in time with us. So what were you doing before you started doing this?

Ostermeier: Actually, I just exited another company, a medical device startup company. Then I became aware of a technology, which was initially developed for automotive applications, tire pressure sensors. And I thought, hmm, that’s interesting, you know, because it has to be wireless. And maybe you can utilize the same kind of technology platform to measure pressure inside the human body. And that was kind of the starting point. So we started the research project with Fraunhofer Institute, which is an Applied Research Institute in Germany, and tried to miniaturize the tire pressure sensors to make it small enough that it can also fit into a human body. And that was a quite, quite challenging effort. It took us really years to get there because it has to be small enough, it has to be accurate enough, it has to be long term robust, and as I said it has to be extremely small so that it will also fit in a patient’s eye. These really have been very challenging years. And point of times, you know, we were close to give up because we thought we’d never get there. But we have been always encouraged by ophthalmologists, because they said it’s an important need to could address with such kind of technology.

Roberts: So, there’s several pressures within the body that are important to measure. Obviously, blood pressure, probably is the one that’s most common that people know. There’s also intracranial pressure, the pressure within the brain. And this technology, though, could be used to measure blood pressure, or it could be used to intracranial pressure, couldn’t it?

Ostermeier: Absolutely, absolutely. In the end it’s a platform. It’s a technology platform consisting of a very tiny MEMS micro system with capacitive pressure membranes integrated. It’s telemetric means there is no better insight, it’s powered from the outside by RFID. So basically, what you are doing, you are applying a very weak magnetic field, which the MEM system is getting activated. And right, it’s in moments, a measurement is taken and sent to the outside, you can use it for measuring any pressure in the body, you know, if it’s eye pressure, if it’s intracranial pressure, if it’s pressure in blood vessels, and even into your heart.

Roberts: So, the big idea, to me is the idea that technology like this empowers someone to care for themselves, outside of the doctor’s office. And so that there is actually more information than measurement of in this case, eye pressure. But this idea that it could be done better at home, than it can be done in a doctor’s office. That, to me is the revolutionary idea. It’s not that we’re looking for something that’s inferior to what can be done in a doctor’s office, we’re not looking at something that could be done equally as well as in the doctor’s office, we’re looking at something that can be done better by the patient at home than the doctor can do it at his or her office.

Ostermeier: That’s absolutely correct, and I give you a very nice example. You know our products the eyemate system is earmarked for ophthalmic use means for glaucoma patients, and we have done already close to 80 patients in last year. During the most intense lockdown period. We did a small study, so we included 35 patients into that study. 

So, patients perform self-measurements at home and connected to patients with the eye doctors. And as you may know glaucoma patients are typically elderly patients so they are among the most vulnerable people the situations like we had last year with Corona and so they have been asked to stay out of the doctor’s office and stay at home. But at the same time, they have an eye disease which the pressure is too high can damage the optic nerve. So, what we found out is step by step remote patient monitoring and management at 1/3 of that 35 patients. 

The therapy was adjusted remotely because it was found out that the pressure is too high and sets the current medication does not work anymore for the patient. And so as a medication was adjusted remotely, and equally important, the rest of the patients, that two thirds of the patients, the therapy, effectiveness was confirmed. And that’s also important in times where patients cannot see their eye doctors in eye doctors don’t know what’s going on if the patients. 

So, I think that’s a very nice example that data is acquired at the patient under normal life conditions at home, and the data is sent to the doctor’s office, and the doctor can really take a close look. And early on at just therapy when he finds out that applied therapy is not effective anymore. And I think that’s really a big game changer. Because right now, as pointed out, a patient sees his eye doctor maybe every few weeks or every few months. And in between the office visits, a doctor has no understanding at all, what’s going on with the patient, how effective is the therapy, how adherent is a patient to the therapy, and it’s all unknown. And then you have these cases he knows the patient shows up at the doctor’s office, the pressure seems to be normal. But since the last visit, the visual field deteriorated and sends a guessing story, you know, and then the doctor thinks, oh, what’s happening with that patient? Why is that? He has normal pressure. But he said he’s progressing. Why is that? And that’s really the biggest challenge for eye doctors today is that they really don’t know what’s going on in the rest of the maybe 361 days during the year while the patient is not at the doctor’s office.

Roberts: Last season, we talked about remote visual field testing, and the ability to get that quality of testing they wouldn’t get in the doctor’s office again, get at home and remotely. I think what we’ve learned from the Coronavirus pandemic is there besides efficacy, safety is important, too. And so this ability that people could get tested, not only tested well but get tested safely in their home and not have the challenges of going to a crowded area or going to a doctor’s office, that becomes important, too. Now we add the measurement of the pressure to the visual field and two of the most important diagnostics involved in glaucoma now get done in the patient’s home.

Ostermeier: I think that’s fantastic. You know, because I think this is really the real disruption. And then when you combine that with really big data, and AI, you know, so that AI supported tools are really analyzing that data, and gives the eye doctor an alert, because the eye doctor is not really able to look after patients all the time and look at every single data point. And so, this has to be computer assisted. And I think that’s a huge benefit. That this is done by digitalization in AI supported tools. And then if there’s something going the wrong direction, the eye doctor will get an alert and the patient will get an alert. But if everything is fine, that runs in the background. And I think that’s really what we’ll see in the next 10 years. There’s a major disruption, this kind of home monitoring of important physiological parameters, so that therapy can really be personalized big time, I think it’s really going to be a huge step forward in managing glaucoma patients.

Roberts: So, we talk a lot about AI or artificial intelligence. And it’s not always clear what it does and what it means. But here’s a very clear example. So, for example, the pressure inside someone’s eye varies in the course of a day. So, what a computer can do is with multiple measurements through the day, it can learn what the normal variation is in that person’s eye. Then, when something different happens, the computer can say, oh my gosh, this is not the usual pattern that we see in this person’s eye. This is something that we need to bring to the doctor’s attention. That is artificial intelligence in a very basic area, but a very important and useful area.

Ostermeier: Absolutely. And you know, you could go even further, maybe you find a pattern by which you know, okay, so this kind of pattern, you have to apply this medication, or it’s this pattern, maybe do to do surgery early on. So I think it’s all to kind of  will drive. See the therapy of a patient in the long run and more data you gather the more reliable you can really make predictions and also make risk predictions because there’s also we know, there’s a lot of patients having high pressures, but they are not progressing. I think it’s amazing how less still is unknown in glaucoma. There’s still a lot of discussions going on. What’s really responsible for the deterioration of the optic nerve? Is it really high pressures? Is it fluctuation? Is it high mean pressures? Is it peak pressures? So that’s still not really clear. And I think our system could be an extremely important tool to really fully understand why certain patients are progressing and others not.

Roberts: So, in that way, you’re talking about the importance of big data. What big data does is it takes all the information from a lot of people, look for what the trends are, and then look at the outcomes. And as Max was saying, that if you have enough people who after a certain change occurs, then get a certain outcome, or need a certain kind of medication or benefit from a certain medication, then what we’re learning from this term big data is how can you influence individuals on the basis of what happens to large groups of people?

Ostermeier: Absolutely right. And I think, in that regard, also, kind of our business model changed. In the beginning, we thought, okay, we are going to sell devices. I think in the future, we are going to sell data and information. You start with something and you end up somewhere else.

Roberts: Right. So, you’re also working as technology was changing dramatically. And so that I remember seeing your original device, it must be close to 10 years ago. And look at the size of the device today compared to what you showed me 10 years ago. So, you had to grow as technology miniaturized.

Ostermeier: Absolutely. In the semiconductor industry, and we are using parts out of the semiconductor industry the last 10 years, changed so much now, we’ve altered mobile devices, Internet of Things, components get smaller and smaller. And the challenge is, you know, for a medical product, you cannot change key components so quickly, because it always comes with cost and has an impact on your regulatory paths. So you have to carry on with a certain design for a period of time. But I think now we are at the stage you know, with authorization that the sensors get so small that they can also be injected instead of doing a surgery rehabilitation sometimes are very, in the very near future, they can be injected and then you can address any glaucoma patients at any disease stage.

Roberts: That’s great. Now, many of the patients with glaucoma, many of the patients that we care for here at Lighthouse Guild have impaired vision. And if someone has impaired vision, what are the particular challenges in order to use equipment like yours, if they can’t see the equipment.

Ostermeier: So basically, it’s totally, totally simple to use. And once you get the sensor in your eye, you can take either on demand measurement by simply keeping a device in front of your eye close to it close to your eye. And that can be done by any patient, even if they are already visually impaired. We are also integrating right now the external reader device for the powering enforcer read out of the sensor into glasses so that patients don’t have to do anything at all. So that data is really completely automatically collected to the patient without any patient interaction needed. So I think user convenience is very important as that you’re talking about patients have already some loss of eyesight and are already visually impaired. So it’s very important that patients are able to really easily and comfortably can use our system.

Roberts: So, I’ve seen how far you’ve come in these last 10 years. It’s remarkable. And I congratulate you and I’m so thrilled that I’ve been able to watch this journey with you over the past 10 years. So, where do you go from here?

Ostermeier: We got a CE mark. And we are right now preparing a first very careful and cautious market launch in Europe in certain European countries. With early adopting eye centers to do also some market validation. We have done extensive validation of the technology in regard of safety and performance. And now we want to start with our first market validation. And most importantly, just a few weeks ago, we obtained FDA breakthrough device designation, which I think is a significant advantage because on the one hand FDA kind of confirms that you’re addressing an important and currently unmet need. And that will insure an expedited market authorization process in the US, too.  

Also in the US, we have a long way to go because it’s a class three product. So, that means we have to do a PMA. And so we will start our first pilot study in the US and then followed by a pivotal study, and hopefully, then product will be available in the next four to five years, although in the US, but it’s already now available in Europe. I think it’s still an unanswered question, how much impact continual measurement of eye pressure and remote management of patients does have. In theory, everyone agrees that more information, better information, remote care, results in better outcome. But I think peers still want to see the proof. And that’s also something that you want to accomplish in the next two, three years in Europe. 

So, I think we have still a lot of things in front of us. But we are very thrilled because I think, times have never been so good as these days with all the digital things going on, remote patient monitoring, and so on and so on. As I said, it’s a great time to work on such a technology.

Roberts: Treatments for glaucoma require rigorous adherence, and patient compliance to those treatment regimens can fluctuate for any number of very human reasons. We spoke with Sherrell Jones, who lost her vision to glaucoma for our episode on telehealth.

Jones: I knew I had glaucoma, but the rapidness of it attacked me really fast. I didn’t faithfully use the drops in the beginning because I thought other things could help. Being a mom and a wife and the struggles of the world dealing with people. I also suffer with high blood pressure. And I didn’t know if my pressures up it also affected my eyes as well. So, a lot of that came from having my high blood pressure.

Roberts: Life makes it hard to stay in compliance with glaucoma treatments, as Sherelle makes clear. So technological advancements like Max Ostermeier’s, which makes it easier for patients to stay in compliance with the regimens for managing glaucoma, would be a huge relief for patients like Sherelle. I asked him, what is the future of the eyemate system?

Ostermeier: And I’m pretty sure in 10 years from now, we will see something like that, you know, a device, which is releasing active ingredients. At every time the pressure is too high. You know, there is already sustained release drug devices, but they are just releasing drugs over time. And it would be fantastic if the drug is only released when the pressure is too high. And I think we’ll see something like that, I think in the next 10 years.

Roberts: So, we have something like that for diabetes. 

Ostermeier: Right.

Roberts: I want to stop the tape here. Because, in my conversation with Max Ostermeier, I brought up the analogy to diabetes. But it’s worth spending a few more minutes talking about it. Like glaucoma, diabetes requires patients to manage their disease by staying in compliance with medical protocols.

Sensashal: I was on two different types of insulins at the time. I was on a long-lasting insulin which acted as a base of medicine to keep my blood sugars at, hopefully a consistent level.

Roberts: Occupational therapist Christina Senashal was diagnosed with diabetes 27 years ago, at the age of 12. She describes what managing the disease required back then.

Sensashal: So, I would have to take that insulin out of the refrigerator. Let it warm up for probably 15 minutes. Because it was a mixture, you had to mix the contents inside. And you can only do that once it was warmed up. And then you put the syringe inside the vial and you had to draw up your dose. And then I had to take a second shot… So basically, I was an absolute slave to my diabetes. It was, it was just awful.

Pal: Diabetes is complex. The patient with diabetes would have to estimate their carbohydrates. They have to count their carbs, they have to estimate how much insulin, they have to calculate how much insulin they think they need based on that. They need to calculate how much insulin do they need based on their glucose levels, and then they have to arrive to a final number. So quite a number of steps. Error prone, and it is an estimate.

Roberts: Dr. Carmen Pal specializes in internal medicine, endocrinology, diabetes and metabolism in Lighthouse Guild’s Maxine and John M Bendheim Center for Diabetes Care.

Pal: It is also painful as well, which is quite important, especially when someone has to test their glucose, maybe even as many as four times a day, or perhaps more.

Sensashal: My doctors encouraged me to test four times a day.  There was a period in my life where I was super hyper vigilant. And I would test it 13 times a day. And I remember my fingers were just awfully sore. It was a very labor-intensive disease to manage.

Pal: In diabetes, there has been a lot of progress. There have been a lot of developments.

Roberts: Developments, like more advanced insulins, better glucose monitoring systems and insulin pumps, drug delivery systems that are fixed to the body. So patients don’t have to take shots the old fashioned way.

Pal: And the patient is still certainly struggles with a lot of challenges. And, of course, it is important to fit all this into many times a busy schedule, whether that’s someone who has a busy professional life or is busy in terms of caring for themselves, or perhaps caring for others.

Sensashal: My Compliance is still a daily battle. I’m a mom now, a wife. And I know there’s times now where it’s like nine o’clock, 10 o’clock at night, I’m exhausted, I’ve had a full day at work. And my insulin pump starts beeping and says you have zero units remaining. And I’m like, Ah, I just want to go to bed!  I’m so tired! But I can’t, I don’t have that luxury of saying no.

Pal: The fact that algorithms actually were developed which help the patient manage their glucose, take away some of that burden of the patient, making calculations all the time estimating their carbs and calculating their bolus. That is a relief for patients. The patient still remains a key component in the management of their glucose levels. And the patient is still announcing when they will have a meal announcing when they plan to exercise. That is still key. The algorithm will also be based on an estimate. But depending on the accuracy with which the algorithms are created, this approach may be more precise. And again, it is quite beneficial that the patient does not have to feel responsible for trying to play the role of the pancreas, which is a little bit of an unfair to task to ask of them.

Roberts: The closed loop monitoring and drug delivery system is exciting, and for many, liberating. However, as with many cutting-edge medical advancements, access to these compliance enhancing devices is dictated by insurance coverage.

Sensashal: The next generation of insulin pumps today use continuous glucose monitoring. But right now, my health insurance won’t pay for that until October, because I have to meet some deductible. So, I’m stuck with doing it the old-fashioned way doing continuous glucose monitoring with my insulin pump.

Roberts: So we can think of diabetes as an analogy to glaucoma. Like Christina, glaucoma patients have strict protocols they need to follow to be in compliance. But unlike with diabetes, no one has yet developed a closed loop system to monitor conditions in the eye and then deliver necessary medications. But Max Ostermeier sees one on the horizon. Let’s get back to our conversation. So we have something like that for diabetes. Okay, so explain how could this be similar?

Ostermeier: It would be really similar correct delivery system. We’ve got MEMs or nanotechnologies involved, you know, there’s already kind of nano pumps, so they are so small that they are 10,000th of a human hair. So, there are really extremely small systems. And so, this will be also kind of telemetrically powered and every time the pressure sensor gives a signal so that the eye pressure is beyond a critical level, then that pump would release eyedrops into a patient’s eye and that would be a IUP driven, it would not be just releasing eyedrops over time it would just release when the eye pressure has reached a critical level.

Roberts: So, super exciting because of the precision with which you can then be treating the person. The other thing that it does, is that it takes the burden of treatment, partially away from the patient, because the pump is now releasing the medicine without the patient having to put drops in their eyes, and so that their care of their eyes now starts to happen automatically without patient involvement.

Ostermeier: Absolutely.  You know, I was amazed when I learned how small the amount of active ingredient is for this sustained-release device which was approved last year by the FDA.  It’s less than what you have in one drop which is applied on a daily basis.

So you don’t need a lot of medication.  With it you can run such a system for months and months before you have to do a refill.

Roberts:  And then this also feeds into this idea of health equity because the more than can be done outside the doctor’s office, then the more patients that each doctor can care for while giving good quality, therefore the more people who can get great care and then we start making great care available to everyone.

Ostermeier: Absolutely.

Roberts:  Like we mentioned earlier, Max Ostermeier’s pressure-sensing technology could have uses beyond ophthalmology.  to measure blood pressure, intercranial pressure in the brain and heart pressure.  In a future iteration of this work, Max Ostermeier predicts that his sensors will trigger the release of drugs.  If it works well, it could create more than just a closed loop.  It could create a positive feedback loop.

Imagine that the system can measure positive outcomes over time and then tune itself to respond with even more nuance, improving with artificial intelligence and big data, how treatment happens for glaucoma.

Positive feedback loops like these also inspire innovators like Max Ostermeier and Christine Ha.

Ostermeier: I think when we started the project I never thought that it would take us so much time and so much effort and facing so many challenges.  But, I think what really helped is that we got a lot of endorsement from eye doctors.  And the most fulfilling thing for me is how well and accepted and received the product is with patients.  As pointed out we have done now close to 80 patients, and I’m amazed at how fast patients really took that and integrated that into their lives.  That’s really the most exciting part for me.

Ha:  I always say that the greatest rewards in life come with the greatest challenges.  And yes, operating two restaurants, and especially opening one during the pandemic, these were definite challenges.  But I feel like I’m starting to see the light at the end of the tunnel.  And, if anything, I feel like I can take on pretty much any challenge now because we’re able to survive that pandemic.

Embrace your mistakes.  You only get better if you learn to accept your mistakes and try to figure out and problem solve, okay, how can I prevent this from happening next time?  Or what do I need to change in order to be successful in this goal that I have?

Secondly, celebrate all of the small victories you have.  So, each time you accomplish something small, you should give yourself a pat on the back and celebrate it.  Because these are all achievements that will add up to the bigger accomplishment.

Roberts:  Max Ostermeier has done incredible work developing the Eyemate system.  Innovating on traditional glaucoma care, chucking the status quo, overcoming challenges, and bringing patients a new resource, one that addresses their needs and reduces their burdens while improving the quality of their care.  And when the closed loop drug delivery system is ready, it will change the game again.

Christine Ha has been similarly tenacious and innovative.  First, in overcoming her vision loss to win MasterChef.  And secondly in adapting her restaurants in Houston to offer her community warmth and comfort and a bit of economic resilience during the pandemic.

In On Tech and Vision, we love the creative spark that happens when a challenge becomes an opportunity.  It’s when a life-altering solution appears after someone like Christine Ha and  Max Ostermeier refuses to accept the world they’ve inherited and challenges norms with a new, bold way of thinking and wins.

I’m Dr. Cal Roberts and this is On Tech & Vision.  Thanks for listening.

Did this episode spark ideas for you?  Let us know at podcasts@lighthouseguild.org.  And if you liked this episode please subscribe, rate and review us on Apple Podcasts or wherever you get your podcasts.

I’m Dr. Cal Roberts.  On Tech & Vision is produced by Lighthouse Guild.  For more information visit www.lighthouseguild.org.  On Tech & Vision with Dr. Cal Roberts is produced at Lighthouse Guild by my colleagues Jaine Schmidt and Annemarie O’Hearn.  My thanks to Podfly for their production support.