Visionary Innovation: Advancing Pediatric Eye Care with Technology & Education

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Daniel Simon, MD (Host): Hello, everyone. Thank you for listening to another episode of Science@UH. I am your host, Dr. Dan Simon, and today I am happy to be joined by Dr. Faruk Orge, the William R. and Margaret E. Althans Chair in Pediatric Ophthalmology, Director of the Center for Pediatric Ophthalmology and Adult Strabismus at Rainbow Babies & Children's Hospital and University Hospitals Eye Institute. Dr. Orge is also a Professor of Ophthalmology in Pediatrics at Case Western Reserve University School of Medicine. Welcome, Faruk.

Faruk Orge, MD (Guest): Thank you for having me, Dan. It is indeed a pleasure to be here with you, and I have been a fan of your podcast, so again, it's an honor.

Daniel Simon, MD (Host): Well, Faruk, you know, in reading your bio, it's obviously incredibly impressive. And one of the things I think that we all like to know about is how did you get interested in ophthalmology in the first place? I mean, what led you to the eye?

Faruk Orge, MD (Guest): I was a little lucky in one sense that my father is an ophthalmologist, and, I've been exposed to his work and his patient care since middle school. So I think that's the biggest influence, but during the medical school I really tried to fall in love with other departments and divisions and, other fields. And, when I went back to the… which happened to be my last rotation was in ophthalmology and went back to that then seems like it just felt home and then the rest is history.

Daniel Simon, MD (Host): Wow. So, one of the things that's very interesting about your research is the incredible inventor component of it. A lot of intellectual property and patents and glaucoma devices and 3D ultrasound, biomicroscopy, drug delivery platforms and others. Tell us a little bit about - how did you transition from clinician only to a discovery innovator, especially on the new technology side?

Faruk Orge, MD (Guest): Maybe I'll start with the first exposure to the research aspect. And after medical school and before the residency, I did two years of research fellowship. And during this time, I was exposed to new technology, inocular ultrasonography and other cutting edge imaging modalities at that time. And my focus in research during those years were on broader aspect of glaucoma, telemedicine, and online education in pediatric ophthalmology and retinal vascular diseases. Having spent dedicated time from bench to clinical application allowed me to have a better sense of understanding on the full array of research and their impact on patient care. But the love of ultrasound work that I did in 1990s allowed me to be a better clinician. And as I applied ultrasonography on my patients personally, and as a frequent user, I could see the limitations and possibilities, but I could finally act on them after I joined UH, and met great people to make that happen. It is the environment, and I remember distinctly that I think when the first UH Ventures were formed, they were actually having talks and reaching out to departments about, do you have any ideas? And, that was the first connection I have to say on giving the ideas and, trying to realize that.

So over the years, just for the ultrasound, we came up with a new concept of acquiring images and collaging them together to make them three dimensional, then quickly partnered with the Case Western Reserve engineers to apply sophisticated software and artificial intelligence for higher quality semi-automated imaging. And then we kept coming up with new tools to expand on this concept that is not available anywhere else in the world at this point. And then I can maybe just expand on the others?

Daniel Simon, MD (Host): Yeah, no, I think that's really terrific. You know, one of the things that might be helpful to our listeners is to understand a little bit about your role as principal investigator on some multi center national international clinical studies. Can you tell us a little bit about these and perhaps also comment on the challenges of doing research in the pediatric population in children. It's sort of, you're obviously consenting parents, guardians and then obviously have participating children. So I think we'd like to hear about that.

Faruk Orge, MD (Guest): Sure. And you know this better than anyone else, and doing any research has responsibilities for us. We have to make sure that it's a safe environment. We do the research for the right reason, at the right time, for the right people and with the appropriate oversight. That has to be in the center of any clinical research in particular that we do. That bar is even more so raised when you're taking care of or doing research with pediatric population. And even further one step is when you're really doing research in neonates, any research that we do not only goes through stringent oversight by Department of Ophthalmology, but also pediatrics. And then neonatology gets involved as well when we take care of or do research on neonates and we have done quite a bit of them.

Yes, we have been a part of the National Eye Institute funded multicenter national studies and continue to do so for various pediatric eye diseases, such as amblyopia or lazy eye, strabismus, also known as misalignment of the eyes, for pediatric cataracts, pediatric glaucoma. And right now we are building international research communities to study common and shared problems such as myopia, which is nearsightedness. And a fact that the current pediatric generation is showing the highest rates of increase in nearsightedness globally.

So with global experts we are putting our minds together to help slow down this progression rate through medications and contact lens use, as well as new technologies in glasses and exposure to certain wavelengths of lights. It's just amazing that when you go outside your own angle and your individual clinical expertise and start doing research with other clinicians, researchers in different institutions and, around the world, you get to learn quite a bit and you get their expertise. And that actually comes back to help us in the clinic as well. So that has been fantastic.

Daniel Simon, MD (Host): Let me ask you a question. You know, we hear a lot about advances on the hearing side with cochlear implants being able to really transform the way we treat deafness, even new gene therapies for certain congenital forms of deafness. We hear about gene therapy for potentially retinitis pigmentosa, a little bit about artificial retinas. Can you bring our listeners up to date on where is that space in eye right now with respect to artificial retina and gene therapies?

Faruk Orge, MD (Guest): Sure. And actually, another fun fact that a lot of people don't know is that the first FDA approved gene therapy in humans was actually to do with the eyes. It was first performed on a dog with a similar condition called Leber's congenital amaurosis. So then using the CRISPR technology, this was applied to humans with great success, and that opened the door for gene therapy for every field.

So, eye is a very accessible organ and has elements from all three stem cells. And because it's transparent, easy to see, even in micron level, and detecting these changes and that accessibility makes it a very amenable target organ… there are even chips have been placed in the eye and that allows people to see. So these different modalities, including stem cells, gene therapies and, uh, these electronics literally integrated into the eye has been looked at and continues to be looked at in the eye. So, the ophthalmology world, I dare to say leads the group in that.

Daniel Simon, MD (Host): Wow, that's really exciting. I do remember seeing some of those first videos. I think it was out of Penn, right, that did gene therapy for the eye and having people be able to navigate, you know, a reasonable, simple obstacle course, but who never could see before. And so it was impactful to me when I saw it.

You've initiated some very innovative teaching platforms in pediatric ophthalmology. Can you tell us about them? I mean, obviously this is an elite of an elite specialty, so it's impossible to get into adult ophthalmology programs and then to do pediatric fellowships is even harder. So tell us about these new education platforms for pediatric ophthalmology.

Faruk Orge, MD (Guest): Gladly. I have to say I've been blessed to have many mentors and teachers in my life, which includes my father, as I mentioned, who is an ophthalmologist as well. I have seen the impact of inspiring teaching firsthand as a student in many levels. My efforts have been simply to give back. Some of what I have received over the years, but was lucky to be in a newer era that we could further amplify the teaching in a global scale.

We not only broadcasted the first ever ophthalmic webinar here at UH in 2011… and I know this was the first one because I was tasked by the national organizations for ophthalmology and pediatric ophthalmology to first do this…but we also created the biggest online educational library in pediatric ophthalmology with visibility by millions of users from 215 countries.

With this platform, we came up with interactive simulators. So not only the digital components of what we do just similar to what we are doing right now, the podcasts and different videos and written content that you can get, but we wanted to do something more interactive. That was the simulators. And the idea was to really give a different platform for people to learn very hard concepts and like examination techniques that we utilize every day. And after we did this and started doing this in 2005, and because of the success of these simulators allowed us to receive a 5 million donation from the Knights Templar Eye Foundation, and to form a virtual reality platform through our national organization, the American Academy of Ophthalmology.

Through this platform now, we can teach examination and treatment techniques on very vulnerable NICU babies via virtual reality simulators. This will help us to tackle significant diseases such as retinopathy of prematurity, which is the leading cause of preventable blindness in children worldwide. Again, the impact of that is we are trying to bring the gaming industry that is in the forefront of many of the technology at this point, to medicine and that interaction that people innately do already and allow people to learn in their own pace without causing any complications or stress on the patients on the techniques and the treatments so they get to practice as much as they want. And then now apply that to their patients and it's just been an amazing field at this point.

Daniel Simon, MD (Host): You know, that's really incredible and your work related to ultrasound and then developing three dimensional interpretations of two dimensional imaging seems like it's made for AI. Tell us a little bit about maybe, where is AI going in your field towards helping clinicians understand what they're actually seeing when they're evaluating these babies.

Faruk Orge, MD (Guest): AI is a hot topic like any other field in medicine and ophthalmology is no different from that. In ophthalmology, we do do a lot of imaging and I really mean a lot of imaging. It's there are techniques called optical coherence tomography. You can, again, see up to micron level. This technology allows us to scan the eyes in detail. In a second, you can do 3,000 scans. This technology is amazing. On top of that, there is ultrasonography on top of that, there is many other photography, angiography, and similar technology being done. So one aspect of that has been always, can you look into this data and bring these pictures together? And utilizing that, can you teach it to a machine platform that the machine can tell us as an expert, on what's going on in the back of the eye or different portions of the eye? Actually two of the modalities for diabetic retinopathy, so changes in the back of the eye due to diabetes, is one way to really understand that not only the disease process, but the impact on the eye.

And our patients who have diabetes needs to be seen by eye doctors. But the idea is, can we maybe take pictures and AI could help us with that. There is actually now available AI technology; clinically available that we can use and some studies say they're better than the experts in many ways.

Same goes along with glaucoma, looking at the nerve. So not only you can actually make it more efficient, more accessible, but it's amazing when you start doing AI and AI is very novice to this. Doesn't know like us and can come up with new algorithms.

For example, when I look at the back of the eye, I can't tell if this is a female eye or a male eye, AI can tell us that. It's just amazing that it's doing, understanding or seeing things that we don't really understand how but bringing new information that we didn't have before. So imaging is a portion of that.

The other portion is the big data that we all deal with. There is a big consortium, not only countries do this, the entire data, EHR pours into a system. In ophthalmology we have these big data systems and making sense of that, understanding the algorithms on the effectiveness of the treatment, the disease process, and the trends on what's changing in people's interactions. So really the sky's the limit. Obviously there, and there's this teaching aspect of that on what we're doing, the impact. I think the AI will continue to revolutionize what we do. It will increase the communication and the publication and the quality of that, and allow us to look much faster on big data and make these correlations more efficiently.

But we have to be careful as we all know, if the data is put in wrong, so if you have the wrong data that the AI is looking or learning from, then the outcome will be different. So that's the challenge we're looking into. And, another challenge is the personal information.

So who owns the picture of the eye and are we able to share that with different platforms? And this has all been discussed.

Daniel Simon, MD (Host): Wow. It's incredibly exciting. And I think as a specialty of a very limited number of highly expert physicians; it's great to think that potentially these tools would allow you to reach more babies worldwide. I mean, you mentioned that retinitis of prematurity is the leading cause of preventable blindness worldwide. I mean, I'm only a cardiologist, I certainly didn't know that. Tell us a little bit for the listeners what's the prevailing view, what is the pathophysiology of that and how would it potentially be prevented or treated?

Faruk Orge, MD (Guest): It is a very segmented group. Examining the eye is not easy and I'll step one back. So what's causing this? And the eyes, just like any other organ continues to develop in the mother's womb. And the vascular portion that feeds the eye is fully matured when we're about full term. So, when we're born prematurely, when the baby is born prematurely, the vessels are not fully grown yet. We know that. But now, because they're in a different environment, they're not in the mother's womb, now they're exposed to different elements like oxygen and different processes, along with the normal vessel growth, abnormal vessels grow as well.

And if the baby is small enough or mature enough, the likelihood of these abnormal vessels causing a problem and making them go blind is very high. That's why every week we're in the neonatal ICU with our team, watching for these kids to make sure they don't go blind. And an expert needs to really not only do this quickly and efficiently because these are very vulnerable babies, very tiny babies, that if you even look at them at a different angle, they'd stop breathing.  Let alone you're trying to examine a very small organ and trying to make sense of if there is an abnormal vessel growing in there or not. So it takes some time to really learn these concepts. We have, our fellowship is one year and it takes a little bit more than even a year to really feel comfortable taking care of the ROP babies.

Now, when you're in sub-Saharan Africa and you don't not only have the appropriate tools to examine the baby, but you don't have the expertise to really understand the process, it becomes very difficult. And that's what we're seeing. And there are continents that actually falling behind or have been behind. They don't, it's not even in their radar. And unfortunately, the babies are, going blind every day. Our efforts - was try to close the gap between what we know and where they are and through different organizations and technology. And, again, imaging and AI and these virtual platforms has been a game changer, is going to be that so we don't have to physically be there but we can share the knowledge with them, what we know about this process and teach them very efficiently.

Daniel Simon, MD (Host): Well, thank you so much. This has been so inspiring to me to hear from you. It's been also an honor and a privilege to watch you over the years. You've really flourished here and you bring so much expertise to Rainbow and to UH. Thank you for taking the time to speak with us today, Dr. Orge.

To learn more about research at university hospitals, please visit uhhospitals.org/UHresearch. Thank you.

Faruk Orge, MD (Guest): Thank you.