Advancing Health and Longevity by Analyzing the Retina with Manjot Gill, MD

Erin Spain, MS: They say the eyes are the window to the soul, but new research suggests that eyes, specifically the retina, may offer a window into how well we are aging and give unique insights and understanding about overall health Here to discuss this topic as well as the use of human AI partnerships in ophthalmology care and medical research is Dr. Manjot Gill, a Northwestern medicine retina specialist. She's the Vice Chair of Clinical Performance and Professor in the Department of Ophthalmology and Professor of Medical Education at Northwestern University Feinberg School of Medicine. She's also a member of the Human Longevity Laboratory within the Potocsnak Longevity Institute at Feinberg, where a group of scientists are conducting a longitudinal cross-sectional study that investigates the relationship between chronological age and biological age across different organ systems and aims to validate interventions that may reverse or slow down the process of aging. Welcome to the show, Dr. Gill. 

Dr. Manjot Gill: Thank you so much, Erin. Happy to be here. 

Erin Spain, MS: Well, in a previous episode of this podcast, we talked about the launch of the Human Longevity Laboratory, but can you refresh our memories a little bit and describe the vision behind the laboratory and this study, and what makes Northwestern Medicine's approach to understanding and extending healthy aging so unique. 

Dr. Manjot Gill: We are really very excited about the Human Longevity Lab. This was really conceived by, by, uh. Dr. Douglas Vaughn and he has really spent his career researching, aging and particularly super ages. So what we are doing is approaching the study of aging in a very multidisciplinary very methodical scientific fashion to really look at aging in various different organs across various organ systems in a longitudinal fashion, and to really try and understand the relationships between chronologic age and biologic age, within and across individuals, but also across people of different socioeconomic different geographic backgrounds. And really look at this , in a very scientific fashion, in the hopes of trying to understand aging much better. And then also in the hopes of trying to come up with interventions that may be able to slow down the aging process. 

Erin Spain, MS: Again, this is a unique study. There's so much longevity research that seems to be taking place. There's a lot of sort of pop culture, longevity things happening in the media. Can you talk about the rigor that's involved with this study and how it's different maybe than some of the other things that we hear out there in the media? 

Dr. Manjot Gill: Yeah. I'm really glad you brought that up, Erin, because that really is, I think, what sets apart our lab and what we are doing because we are really looking at this in a truly scientific fashion in terms of patient recruitment and, um. extracting all of the data in a, you know, multidisciplinary approach. We are looking at various biometrics as well as cognitive function, cardiovascular function, pulmonary function we're doing retinal imaging, obviously, and genomic testing. So really trying to gather data in a very standardized fashion across all of our subjects that are recruited. And then eventually longitudinally follow these patients to look for the trajectory of their aging. So this is, I think what really is unique is that we're not really focusing on one organ system. We're looking at multiple organ systems and looking at the relationship of aging across various organ systems and studying how that may be different. Because that is one thing that we really actually don't understand is, is aging the same across different organs? Does your brain age at a different age than your heart? And is that similar within individuals or are there different time points in one's lifetime where one organ system may age quicker than others? 

Erin Spain, MS: Your work revolves around using the retina to study biological aging. Previous research, you've actually found the retina to be a pretty good marker of certain diseases. Can you tell me about that? 

Dr. Manjot Gill: This really is part, a larger field, an emerging field known as oculomics, where we are utilizing the retina as a biomarker for systemic disease. This is what really got me very excited and this is largely the focus of my research. The retina is an extension of the brain. It has similar embryologic backgrounds as brain tissue, and so we may be able to gather insights about brain health by imaging the retina and looking at the various layers of the retina as well as the vasculature of the retina, and seeing if that is a reflection of what may be hap in blood vessels within the brain. In a similar note the circulation of the retina also communicates with the circulation in the rest of the body. So various cardiovascular diseases may also manifest themselves within the retinal vasculature. So that's another way in which we can study both disease and the aging process. We actually have found signals in a variety of disease states. Long COVID being one of them. We looked at a population of long COVID patients and compared them to age match controls and did in fact find that patients with long CO. Did have decreased blood flow in their retinas. So this is the first finding that we've actually found that there are biologic signals and physiologic signals in patients with long COVID. So this may help not only in the detection of patients at long with long COVID OVID, being able to follow them now with a physiologic marker, but also may provide insights into what the cause is for long COVID and come up with interventions. In a similar vein we looked at a population of patients who were at risk for heart failure, who did not have established heart failure, but did carry a risk for heart failure because of a variety of systemic risk factors. And we did also find that compared to age match control eyes, those patients at risk did in fact have decreased blood flow in one layer of their retina. So that. Speaks to the power that the retina may have, and by looking at the vasculature and the retina, we may be able to detect those patients that are at risk prior to the onset of heart failure. So what we're doing specifically in the Human Longevity Lab with respect to the retina and aging, is capturing fundus images, retinal images with a camera, and getting really high quality retinal images, and then running it through an AI model where we're comparing it to millions of other retinal images and being able to render a biologic age to the retina. And this is based on the color of the retina. Various features such as pigmentary changes, other age related changes, and largely based on blood vessels. So then we will ascertain a biologic age, and then we can compare that to a patient's chronologic age. 

Erin Spain, MS: What can you tell me about some of the preliminary data that you've found so far? Is there a large gap sometimes between the biological and chronological age of the retina? 

Dr. Manjot Gill: So we certainly can see this. You know, the majority of the patients that we have studied so far actually have their biological age rather than their chronologic age. And that largely may just be driven by the patient selection. Gathering mostly younger, healthier subjects. Where I think we will start to see some gaps is as one's chronology, age advances, and then certainly if they're afflicted with more systemic diseases such as diabetes and hypertension. And I also think what we will also find is that we're gonna have a trajectory where one may see that there is kind of a gap between chronologic age and biological age. But then that gap starts to narrow as one ages. So there may be, you know, what we find through our study is that there are critical periods where there is a gap and potential for interventions where we can actually slow that trajectory of aging. 

Erin Spain, MS: Are there current treatments that could possibly do that, or is this something that would be in the future that you would have to look into? 

Dr. Manjot Gill: As you had mentioned earlier, this is such a hot area right now so there's a lot of things that are purported to slow down the aging process. I think one of the things that's been talked about has been metformin. I still think that is, you know, relatively inconclusive. I think there's a lot of excitement surrounding the GLP one agonists with respect to, you know, not only their impact on diabetes, but on metabolic syndrome as a whole. You can imagine if they're helpful in helping one's weight and obesity, hypertension, diabetes that would also have a positive effect potentially on slowing down the aging process. So I certainly think there could be some area of interest there. Other things such as, healthy diet, lifestyle stress reduction, mindfulness. In fact, we're running a small clinical trial right now through the Longevity Lab, looking at mindfulness intervention over the course of two months. And so it'll be interesting to see these various measures that we take before and after. If there is in fact any change and I think this is what we're all gonna be learning is not only about various interventions, what may show some promise, but also are these curves even malleable. Can we even alter the trajectory of aging? Because everything that is out there right now is largely anecdotal, but nothing is really studied in a truly scientific fashion, and that's exactly what we are doing. And this is what sets apart our lab from uh, anywhere else in the world. 

Erin Spain, MS: And what's also nice is that participants in this study are able to gain some information about their own health and possibly make some changes, which is different from some other studies. 

Dr. Manjot Gill: Absolutely right. we're not purporting to be offering preventative care per se, but certainly in the course of evaluation, if an abnormality of some type is detected. You know, for example, I read all the color retinal images, and if we find something, you know, a patient may be a glaucoma suspect, then we certainly do reach out and make sure that the patients will get the appropriate care. 

Erin Spain, MS: You mentioned that you use an AI model when looking at these images. How new is using AI technology with the retina and how do you partner with these outside companies to make this happen? 

Dr. Manjot Gill: So this was interesting when we first launched the Longevity Lab a few years ago . An area of interest of mine is how are we going to leverage the power of the retina and bring this into this whole model of aging? And so, kind of looking through the literature I came across an industry partner, Toku Eyes. And they have developed this model where by looking at color, images of the retina are able to ascertain a biological age. And so we have since partnered with Toku and like I said, this field is just continuing to grow and expand not only in the area of longevity, but just in terms of systemic health as a whole. 

Erin Spain, MS: You're an expert in this area and you've been using your own human eyes to look at these images for years, but now to really have this sort of advanced supercomputing power under your belt, what does that mean to you? 

Dr. Manjot Gill: You're absolutely right. You know, obviously I chose the field of ophthalmology and retina specifically because I feel that vision and sight is so precious but now that we can actually use this. This tissue, the retina, to get insight not only into systemic disease, which you know, we have been in terms of, diabetes and hypertension. But now to really gather insights into what may drive disease, what may drive aging. And then really the key is in terms of prevention. How do we? Prevent and intervene at a much earlier stage. So the retina may offer unique insights that other organs in the body are not able to because of the fact that it is so readily accessible and readily visualized. 

Erin Spain, MS: You recently co-authored a nature communications paper about a large language AI model that enhances how clinicians and researchers mine medical literature to help you more efficiently conduct reviews of literature mining. Tell me about this study and how that kind of plays into everything that you're doing here. 

Dr. Manjot Gill: This was a multidisciplinary paper and essentially it is looking at using large language models to conduct literature searches. And so I served as a control and selected papers that I felt were the most relevant and topical in a particular area of interest. And what we found is that the large language models were equally effective in terms of selecting those papers that the model felt were the most relevant in terms of a literature search. So this really is very exciting because it takes a lot of kind of the manual task out uh, when we're conducting literature reviews, 

Erin Spain, MS: In this particular model, this is not chat, GPT. This is a model that is specifically designed for medical researchers. 

Dr. Manjot Gill: correct? Yes. It was actually, uh, designed by a researcher at Northwestern. 

Erin Spain, MS: Where could you possibly see AI being used in other areas of ophthalmology? 

Dr. Manjot Gill: You know, in terms of patient care being able to help the physician in terms of, you know, diagnostic. Therapeutic interventions being able to help with image interpretation. I know there's been some work that's been done in radiology to semi automate the interpretation of radiographic images. Ophthalmology, you know. As we know it is very image heavy, and so there may be a utility there as well in detecting patterns in images as well. We can use this as a recruitment tool for clinical trials to identify patients who may be amenable to certain therapies by screening their images. I actually just did a study that looked at large language models, chat, GPT and Gemini. And we fed them publicly available color photographs. So this is not patient identified data. This was publicly available dataset, and had it screened for referable diabetic retinopathy and found that the large language models were equally if not more effective than some of the FDA-approved AI screening devices that are out there. And so this just goes to show how powerful this is. So eventually we could say that, you know, we could use that as a proof of concept that we can try and create these own large language models. Help us interpret images within our own health systems. 

Erin Spain, MS: You mentioned clinical trials. This is another area that you are very active in and you have been working on some other age-related eye conditions and had some pretty exciting results from clinical trials so far. Can you just talk to me about that And, your commitment to finding better solutions and treatments for patients. 

Dr. Manjot Gill: So this is really how we push our field forward is through clinical trials with scientific rigor and doing it in a very methodical way. So, you know, I was very pleased that I was the principal investigator on one of the second generation therapies for macular degeneration, which has now since been FDA approved and is in widespread usage across the country, across the world for wet macular degeneration. But we have such a high treatment burden with our therapies in that they are effective, but as long as the patient keeps getting the drug. And so this can be very, you know, cumbersome for patients as well as for the practices to have some of these patients coming in every month. So we're always looking for newer drugs that may have different mechanisms of action as well as different platforms of delivery that would allow for these drugs to be utilized less frequently. So the most recent clinical trial that we concluded looked at a different delivery platform rather than injection of medication into the eye, but implantation of a sustained release device where the drug can be released into the eye over a prolonged period of time and therefore not needing repeat treatment for between six to nine months? 

Erin Spain, MS: If you could offer some advice to listeners about healthy aging, especially when it comes to the eyes, what are some things that everybody could start implementing if they're interested in aging healthily? 

Dr. Manjot Gill: I think that's the thing that I probably get asked the most as, you know, as an ophthalmologist, as a retina specialist. So I would say there's several things. UV protection is so vitally important. We know that UV associated damage can accelerate cataract formation also as a risk factor for macular degeneration. So, wearing sunglasses, wearing a hat, particularly if you are light skinned and blue eyed is extremely important. Secondly, a good diet. You know, I always tell patients that whatever's good for your heart is good for your eyes, and there's been so much evidence about the Mediterranean diet there's also evidence that has been looked at with macular degeneration and the benefit of Mediterranean diet on slowing the progression of macular degeneration. In addition, some patients, depending on whether they have macular degeneration and a more advanced form, would benefit from vitamin supplementation. Particularly an AREDS two formulation has been shown in clinical trials to slow the progression of macular degeneration. This is not for all patients. So this really would be under the direction of the advice of your ophthalmologist if you had a certain stage or degree of macular degeneration. Otherwise, if you wanna take a good multivitamin that would certainly suffice. And then other lifestyle factors particularly smoking similar to UV damage smoking, we know can accelerate macular degeneration because of the free radical formation and all the negative effects that it can have in the eye. So, if patients are. Smokers, you know, really counsel them to encourage them to cut back or to quit smoking in general. 

Erin Spain, MS: A decade from now, what breakthroughs do you hope we will be talking about when it comes to using the retina as a biomarker of aging and overall health? 

Dr. Manjot Gill: I feel we are on sort of the precipice of some real change in terms of how we think about disease, how we and especially how we approach and manage patient care. So what I envision, and I hope it's not too distant into the future, is being able to walk into your, either your primary care's office or you know, into a Walgreens getting a retinal scan done. And then by entering a variety of kind of basic data about your diet, your lifestyle, how frequently you exercise what medications you're on, that you would get kind of a risk stratification of your risk, future risk for either diabetes, high blood pressure, heart disease, stroke and then, not so much being able to detect these early, but to really give you tangible information on how you can intervene to really slow or minimize the onset of these chronic conditions. And then hand in hand with that is by being able to do that, by preventing the onset of disease, not just detecting disease, but preventing the onset of disease. This is really how we are going to be able to. Increase one's health span and not just lifespan, but really health span. So I think that really is the secret to longevity. 

Erin Spain, MS: Thank you so much Dr. Gill, for being on the podcast and sharing all these exciting new developments with the retina. I appreciate your time today. 

Dr. Manjot Gill: Thank you so much, Erin. It was a pleasure. 

Erin Spain, MS: Thanks for listening. Please click the bell to receive notifications about our latest episodes and follow us on social media @NUFeinbergMed to stay up to date with our latest research findings. 

Physicians who listen to this podcast may claim continuing medical education credit after listening to an episode of this program.

Target Audience

Academic/Research, Multiple specialties

Learning Objectives

At the conclusion of this activity, participants will be able to:

1. Identify the research interests and initiatives of Feinberg faculty.
2. Discuss new updates in clinical and translational research.

Accreditation Statement

The Northwestern University Feinberg School of Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

Credit Designation Statement

The Northwestern University Feinberg School of Medicine designates this Enduring Material for a maximum of 0.25 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

American Board of Surgery Continuous Certification Program

Successful completion of this CME activity enables the learner to earn credit toward the CME requirement(s) of the American Board of Surgery’s Continuous Certification program. It is the CME activity provider's responsibility to submit learner completion information to ACCME for the purpose of granting ABS credit.

Disclosure Statement

Manjot Gill, MD, has received payment for consulting from Regeneron and Genentech, Inc. Course director, Robert Rosa, MD, has nothing to disclose. Planning committee member, Erin Spain, has nothing to disclose. FSM’s CME Leadership, Review Committee, and Staff have no relevant financial relationships with ineligible companies to disclose.

All the relevant financial relationships for these individuals have been mitigated.