Early Detection of Diabetic Retinopathy in Optometry
Mark Dlugoss:
By year 2050, the Centers for Disease Control and Prevention predict the number of Americans living with the complications of diabetic retinopathy will reach 14.6 million individuals. This is an increase from 7.7 million in the year 2010.
Hi, this is Mark Dlugoss, Senior Contributing Editor of Ophthalmology 360. And in recognition of April being National Retina Awareness Month, Ophthalmology 360 wants to highlight some clinical points associated with the early detection of diabetic retinopathy. Joining me to share his expertise on the subject is, Paul Chous, OD of Chous Eye Care Associates in Tacoma, Washington. Welcome, Dr. Chous, and thank you for providing some time.
Dr. Chous:
Thank you so much. I’m really thrilled to have the opportunity to do this. Diabetes is my whole world. I have diabetes, I’ve had it for 55 years now. Had diabetic retinopathy in my early twenties and now I have a practice that emphasizes diabetes, eye care and education. So it’s really something that I’m passionate about. Thanks so much for having me.
Mark Dlugoss:
Great. Well, before we start, let’s begin with, most people know in the optometric in community know who you are, but in case there are a few that don’t, let’s begin with a brief bio of yourself, including your education, training, clinical background, and obviously your clinical interest are diabetic retinopathy. But go ahead and introduce yourself.
Dr. Chous:
You got it. So I was an undergrad at Brown University and then ran out of money and transferred to UC, Irvine. I was a California resident. And then I went on and got a Master’s Degree in Political Philosophy, of all things, at UC Berkeley. Developed proliferative diabetic retinopathy, lost vision in my right eye first. I had PRPE vitrectomy surgery, was able to finally get my master’s degree, but my retina specialist said to me, “You know, you ought to think about maybe going into eyecare. You’d know all the best specialists and you really seem to be interested in diabetes.”
I did that. When I became an optometrist I worked in a private practice as an associate and the person who hired me was referring all the patients with diabetes to see me. And even if he had already examined their eyes because he knew I was really passionate about patient education. Ultimately my own endocrinologist about 30 miles away said, “Paul, why don’t you move down here to Tacoma and I’ll send all my patients with diabetes to you.” He had worked with me for a number of years, thought that I did a great job and sent timely letters to him to let him know what the status of the patients were.
So that’s where I am now for about the last 23 years in a practice across the street from a big endocrinology clinic. And pretty much what I do all day long is see folks with diabetes and pre-diabetes, a number of whom have diabetic retinopathy.
Mark Dlugoss:
Well. Let’s start off with the whole subject of diabetic retinopathy and clinical studies have maintained that early detection and management of diabetic retinopathy can reduce the risk of vision loss for diabetics by 95%. Well, as we all know, the comprehensive eye exam is an effective way to detect the signs of the disease. What clinical protocol should optometrists consider in conducting a comprehensive eye exam for diabetic retinopathy?
Dr. Chous:
Yeah. It’s such an important question. So what I tell my colleagues, it seems like in the last decade we’ve had this move towards using ultra-wide field imaging and not dilating patients. It’s good, especially in the time of a pandemic, to get patients in and out of your exam space quickly. But I would advocate for dilating every patient with diabetes. So you get a great stereoscopic look at the macula using a 3D fundus lens to look at the macula to help you detect macular edema.
I also am a fan of imaging, and particularly with red-free filters because it does highlight retinal vascular abnormalities. I’ve even started using fundus autofluorescence because it actually does show more microaneurysm formation. So I’m an advocate for using as many tools as you have at your disposal. And recently I’ve been using ERG to help me decide which patients are more likely to progress on to need treatment.
And the main thing I would say optometrist is, “Act as if every patient you see with diabetes and even pre-diabetes has diabetic retinopathy and you have to prove to yourself that in fact they do not.” So I’m a big advocate for technology, but also clinical exam, patient education and prevention is where it’s at. Talk to patients about what they can do to lower their risk of developing DR and if it does develop, how to prevent it from turning into a site threatening stage that requires more aggressive treatment.
And when they need treatment, of course work closely, I’m a fan of working with retina specialists because I got a lot of them in my community, so I work really closely with them to get patients in when they need treatment.
Mark Dlugoss:
Okay. Now there’s been a lot of clinical data over the years supporting the importance of metabolic control in managing diabetic retinopathy. What does the early data recommend in the management of DR?
Dr. Chous:
So every study that’s been done shows two things. That if you have better glycemic control but also blood pressure control and to a lesser extent control of dyslipidemia, the patients are less likely to develop diabetic retinopathy and have it get worse. In addition, there’s this other important phenomenon that I don’t think enough eye care professionals, both in optometry and ophthalmology, may be familiar with.
And that’s the notion of what’s called metabolic memory. That is if you get good control early on after diagnosis of diabetes, despite going down the toilet as it were, as time goes by, there’s a protective feature that lasts for decades after early tight control. And conversely, if you have bad control for the first eight to 10 years and suddenly you get great control, you remain for the rest of your life with diabetes at elevated risk for developing diabetic retinopathy and site threatening diabetic retinopathy.
Mark Dlugoss:
Recent clinical data has suggested that tighter blood glucose control is of little or no benefit once the severity of diabetic retinopathy is beyond that moderate level. Can you elaborate what this newest data has reported?
Dr. Chous:
Yeah, and this is really interesting. It comes primarily from the PANORAMA trial, which looked at using aflibercept specifically for patients with moderately severe or severe non-proliferative diabetic retinopathy without macular edema. So level 47 or 53 on the DRSS. And what was shown in this trial was even patients with fabulous control and entry into the study, people with A1C values under 6% were equally likely, in fact a little more likely, to progress onto proliferative retinopathy or anterior segment neovascularization or diabetic macular edema.
Now, Protocol W looked at kind of a similar patient population, found the same thing that having tighter control once retinopathy has developed onto beyond moderate NPDR, it was really of no value whatsoever. Neither was having a lower BMI or tighter blood pressure control. So the idea here is that the horse is already out of the barn. And there’s a really interesting slide from the ASRS, American Society of Retina Specialists, that just surveyed what are your treatment preferences for patients with severe NPDR?
And the answer was tell patients to get better glycemic control and watch them closely. So there are a lot of reasons to get improved glycemic control to protect maybe your kidneys and your cardiovascular status, but vis-a-vis diabetic retinopathy, once you get to level 47 retinopathy, unfortunately improving glucose control seems to be of no benefit. That’s my take home message.
Mark Dlugoss:
Do these findings change the paradigm of how eye care professionals address and manage in a diabetic retinopathy, especially in the management of its progression?
Dr. Chous:
Yeah, I think they do. And so again, I think we, in eyecare, need to remember, look beyond just the retina at the entire patient and encourage them to get tight glucose control, blood pressure control early on, talk about retinal protective drugs. And there’s a number of those that we use commonly to take care of patients with diabetes like ACE inhibitors, angiotensin receptor blockers. I know we’re not prescribing those in eyecare, but we can communicate with the PCP or the endocrinologist about the protective effects on the retina.
And the other thing, and I’ve alluded to this in my last answer is, we maybe should be thinking about treating at least some of these high risk patients with severe NPDR, with anti-VEGF therapy or possibly emerging therapies. There are a couple of companies working on topical administration that might relieve the burden on both the patient and the retina specialist for treating severe NPDR. And so I think the paradigm has shifted towards treating patients earlier than we would’ve here to four.
Mark Dlugoss:
Okay. So what does the clinical data say regarding relationship between early detection of diabetic retinopathy and the preventive interventions of say, cardio, renal and vascular diseases?
Dr. Chous:
Yeah, it’s a great question. It’s really important. So what the data shows is even when patients have mild non-proliferative diabetic retinopathy, their risk for a major adverse cardiovascular event. And that’s generally defined as needing a coronary artery bypass graft, or a stent placement, or having an MI, or a stroke, or being hospitalized for heart failure. So even with a few microaneurysms, the risk of that happening goes up about 30 to 70% compared to an age-matched patient with diabetes but without any diabetic retinopathy.
Once you develop proliferative diabetic retinopathy or macular edema, the risk of stroke and heart attack goes up about two to three-fold, risk of stent and cabbage surgery goes up dramatically. So what this alludes to is the fact that I think we and eyecare need again to look at the entire patient. And I just spoke in Norway last month and we were talking about diabetic retinopathy therapies and my statement there was it’s nice to prevent somebody from losing their vision and that’s what all of our goals are in eyecare, but it doesn’t really matter if your patient dies prematurely from a prevental cardiovascular or renal cause.
And we now have wonderful medications that can dramatically lower the risk of these bad cardiovascular and renal outcomes. Drugs like the SGLT2 inhibitors, the Flosin’s, they’re on television all the time. The glucagon-like peptide-1 receptor and antagonist drugs, Ozempic is in that class. These drugs dramatically lower the risk of major adverse cardiovascular events.
And I think that all of us in eyecare need to inform our patients about these because as it turns out, there’s a wonderful paper written in this journal called Cardiovascular Diabetology. It’s a group of diabetologist’s around the world, but mostly in Europe, the US and Australia, saying that about two thirds of patients who are on metformin monotherapy remain at extremely high cardiovascular risk. And that’s because they’re not being treated aggressively enough. So we’re having unnecessary deaths.
And so I think it’s incumbent on all of us, and this is what the authors called for, was for healthcare providers in every discipline, including eye care to educate our patients and their primary care docs about these wonderful agents that unfortunately are expensive, but they really do lengthen lifespan, lower the risk of these cardiovascular events. And that’s really what costs the most money in diabetes care. It’s renal failure, it’s major cardiovascular surgeries, and then blindness and amputations as well.
Mark Dlugoss:
When it comes to vascular complications uncovered while managing diabetic retinopathy and the preventive interventions of… Wait, I’ve read the wrong paragraph, I’m sorry.
Dr. Chous:
No, you’re good.
Mark Dlugoss:
When it comes to vascular complications uncovered while managing diabetic retinopathy, what are the newer interventions that eye care professionals should know and understand?
Dr. Chous:
Yeah, I answered my own question there already, didn’t I? But I think that the two big ones, let’s start with the basics. The stuff that’s cheap and it’s generic ACE inhibitors and ARB drugs, most patients over age 40 with type two diabetes, probably most with type one should be on a statin drug. The data shows no matter how low your LDL cholesterol is, if you’re on a statin at a population level, your risk of a early cardiac death goes way down.
Beyond that, these other two really important new classes of diabetes agents, the SGLT2s and the GLP1s. And so now routinely in my notes to the PCP, if my patient comes in, particularly if they’re on Metformin alone or if they’re on one of these older sulfonylurea drugs like glipizide or glyburide that we know based on the data, do increase the risk of bad cardiovascular outcomes. I’ll just include something like as you know these newer agents have been shown to be cardioprotective, our mutual patient already has had an MI or has heart failure.
And these SGL2 drugs cut the risk of heart failure, a hospitalization by about 40%, and the risk of end stage renal disease by 50%. In Europe now they’ve been approved as first line therapy for diabetes. And I think we’re a little behind the mark in terms of getting patients in the United States on these cardiorenal protective agents. So that’s my spiel about that.
Some of these physicians have sent me letters saying, “Can I have your business cards? Because I’d like that, it’s actually helped grow my practice.” I’ve had some pushback from PCPs that have said, “Don’t tell my patient and don’t tell me what drugs to use.” And my only retort to that is, “Look, I work for the patient. I have diabetes myself. My goal is I’m trying to keep our patient alive longer and have them have a healthier, more productive life.”
And so you win the battles you can win. And in my community at least, most of the PCPs that are diabetes savvy and the endocrinologists as well, welcome it when I raise the possibility of putting patients on these cardiorenal protective directs.
Mark Dlugoss:
You mentioned technology earlier and so when the optical coherent tomography, or OCT, was introduced in 1991, how has OCT changed the way eye care professionals diagnose and manage retinal diseases, especially diabetic retinopathy?
Dr. Chous:
I think it’s been a game changer. In my career, I graduated in 1991 from CAL and we didn’t have OCT. Even at that point digital retinal cameras were at their infancy. So it’s really changed the way I manage my patients. And so I just get some pushback from my OD colleagues about this. But when I have a patient with diabetes, especially a baseline exam, they’re already dilated. I’m looking at their fundus, I’m imaging them, it takes 10 seconds to do an OCT. I’m doing it as a baseline so that I have something to compare with in the future.
And like every provider that uses OCT, I’m often amazed at how many different diagnoses you uncover by doing routine OCTs on any patient. But people with diabetes seem to have a higher preponderance of that retinal membranes, which also increases the risk of diabetic macular edema. I just think it allows me to flag those patients if they don’t need referral now, need to be followed more closely so that we can get them before they lose a lot of vision and get them in to see the retina specialist.
Mark Dlugoss:
It’s very important, as you mentioned that you do it for a baseline. It’s been going on in glaucoma for a long while, so why not do it in retina?
Dr. Chous:
I think so, so what people tell me is, “Well, I’m not going to get paid if I don’t have a diagnosis.” All right, so what? You already paid for the device, it doesn’t take that long to do. I would encourage my colleagues throughout eyecare just to do a baseline OCT and maybe in intervals thereafter, especially if you’re patient’s at higher risk.
Mark Dlugoss:
So the evolution of OCT has come a long way. We’ve discussed you with the introduction of wide field imaging OCT, or OCT angiographic. This has vastly improve how retina diseases are diagnosed. What are the clinical benefits of these new technologies and how do images improve eye care professionals approach to treating and managing diabetic retinopathy?
Dr. Chous:
Yes.
Mark Dlugoss:
It’s a [inaudible 00:16:32] question there?
Dr. Chous:
No. I’ll break the question into two parts. So let’s talk about ultra-wide field imaging. So the data from all the major studies now is saying that about 30% of diabetic retinopathy lesions are beyond the seven standard fields that we typically image and examine in a clinical exam. In about 10 to 12% of patients, depending on what study you look at, if you consider the retinal mid-periphery, even the periphery as well, about 10 to 12% of patients, their diabetic retinopathy severity will be worse than what you thought it was, at least one level worse.
And that’s important because if I think a patient is moderate NPDR and they’ve actually got moderately severe or severe NPDR, and I’ve had this happen, if you see neovascularization elsewhere out in the mid-periphery, that changes the whole dynamic with regard to me sending the patient to retina specialists for fluorescein angiography and the like. So I think it’s really important to look at the retinal mid-periphery and periphery.
Now, let’s talk about OCTA for a moment. I think it’s wonderful. What it does seem to demonstrate is diabetic retinopathy much earlier than we would have detected it before. So you can see capillary loss, you can see subclinical microaneurysm formation that you may not see on clinical exam or even with a standard fundus photograph, even in with a red-free in black and white. And so that’s good because you’re identifying the disease earlier.
My only qualm about it is what do I do with that information? I can tell the patient, “Yeah, I’m seeing on this specialized test, you’ve got early signs of diabetic retinopathy. It doesn’t require treatment.” And I guess my mantra has been, “Well, let’s see if we can improve your glucose control even more than you’re doing now.” If they don’t have severe disease and talk about maybe various strategies to get their metabolic control improved from where it is now. So it’s good to identify it earlier. It does again flag those patients that might need more careful follow up.
And the other thing OCTA does quite well, I think better than fluoresce angiography in talking to retina specialists, is it allows you to identify what I call the ugly stepsister of diabetic retinopathy. And that’s macular ischemia. So studies say somewhere between eight and maybe as high as 30% of patients have diabetic macular ischemia, they have reduced visual acuity. Now we don’t have treatment for it now, but it’s at least nice to know if your patient’s 20, 25, 20, 30 and you don’t see macular edema, there may be something else going on.
And OCTA allows us, I think, very beautifully to visualize changes in the Foveal Avascular Zone and macular ischemia in particular.
Mark Dlugoss:
So what do you see the technology heading to? This might be a little bit broad question, but where do you see the technology heading regarding OCT? It’s been a dynamic tool.
Dr. Chous:
I think we’re seeing it already. I don’t have the highest resolution OCT in the world because I bought mine a decade ago and it keeps getting doubles in its ability to image and get great resolution it seems every few years. I think we’re going to get better and better resolution. We’ll be able to probably to use artificial intelligence with OCTA and OCT as well as retinal imaging writ large to help us pick up on abnormalities that maybe we as clinicians don’t identify right off the bat.
So I’m test-driving one of the AI programs in my practice and so far my sense is that I’ve picked up on everything the AI picked up on, but it’s nice to have that fallback position. And in a few patients that had severe disease, I’ve told them, “You’ve got severe non-proliferative disease,” let’s say, “or even NPDR and I did this AI program on you too and here’s what the report says. It says you have site threatening diabetic retinopathy.” It helps back up my position in terms of patient counseling, but I think it’s going to get better and better.
I know a lot of my colleagues in eyecare have expressed worry to me that AI will replace us. And my answer is I don’t think that’s going to happen. I think patients want to talk to another human being to get counsel about what they do. And the other thing is, right now at least the AI is not perfect. It’s going to get better and better no doubt. But I think what we and eye care have to do is more than just simply detect DR, we have to stage it accurately. We have to have predictive tools to tell us who’s going to get worse, who’s going to benefit from earlier intervention.
And now it’s all really being worked out right now. The most amazing thing to me, I’m consulting to one clinical trial in diabetic retinopathy using a topical, is that to be eligible for the study, all they do is they consider the seven standard fields. So a patient might have neovascularization out in the mid-periphery, in fact have proliferative diabetic retinopathy, but they’re not staged by the image reading centers as having proliferative diabetic retinopathy because it’s not in the posterior poll.
I think we need to change the parameters around which we enroll patients in clinical trials. That’s just the way it is now. And so in this one study, these are all patients being screened by retina specialists. 75% of patients are failing the screening when their images are sent to the Wisconsin Reading Center because their retinopathy isn’t severe enough in the seven standard fields.
Well, that’s kind of nonsense to me because if the patient has more severe disease, we want to be able to account for that and enroll those patients in trials that might benefit them. That’s been an epiphany for me in the last six months working with a group of retina specialists on this trial, is just stuff that gets excluded because our definitions of DR, what’s important are from 30 years ago, maybe 40 years ago now.
Mark Dlugoss:
With the new clinical information about the management of diabetic retinopathy supplemented by improved OCT technologies, how can the optometrists improve their co-management of diabetic retinopathy with not only the retina specialists, but maybe their primary care physicians as well?
Dr. Chous:
Yeah, I think it circles back to everything we’ve talked about in this conversation thus far, right? In terms of the PCP and endocrinologist, it’s just letting them know because sometimes they don’t, but if a patient has diabetic retinopathy, their cardiovascular risk is higher. So patient talked to me, he is not on an ACE inhibitor, suggested the patient ask you about that. Those sorts of things. And so I get more referrals from PCPs and endocrinology now than I ever have in my career because they know that I’m an advocate for the patient and I want to help them do the best possible job for the mutual patient. And any optometrist or ophthalmologist can do that.
Now, in terms of eyecare, what the technology lets us do, I think is identify things earlier, make more appropriate referrals. And what I’ve realized, and this comes right out of the PANORAMA Trial that had all retina specialists grading patients that even retina specialists sometimes misgrade diabetic retinopathy. It’s just what happens.
So there was about a 30% undergrad in PANORAMA. Patients had worse retinopathy than what the clinician thought they had and so patients were undertreated in this ongoing two year study using aflibercept for a diabetic retinopathy. And when the patients are undertreated, they don’t do as well. And so I think, look, we’re all on the same team. We all need to work together. And I think if optometrists particularly can develop closer working relationships with retina specialists, that’s a good thing or even a general ophthalmologist that’s passionate about retinal disease.
I want all of my colleagues in ophthalmology to know we want to do the best job we can to make sure our patients do well. We want to work with you. We’re not adversaries in any way, shape or form. Patients get better care when we all work together. That’s my view.
Mark Dlugoss:
We’ve presented some good information in the management of diabetic retinopathy today. Are there any clinical pearls you would like to share with optometrists about the points we’ve discussed today?
Dr. Chous:
I think one of the key things, and when I lecture on diabetes at optometry meetings, I always talk to patients, sorry, to my audience about assuming retinopathies there until you prove that it’s not, using red-free imaging. If you’ve got these newer technologies at your disposal, and I’m starting to become a bigger fan of electrophysiology, helping me determine how sick the retina is like we do in glaucoma, you do structural testing with OCT, but you’re also looking at functional parameters. Well, and that’s what a visual field is essentially.
So I think it’s good if you can marry structure and function, that’s an advantage. Any other pearls? Here’s the real deal. We know that about 50 plus percent of American adults either have diabetes or pre-diabetes. And you alluded to that statistic right off the bat. It’s going to be a doubling of diabetic retinopathy in the US. By 2050, the same year you said 14 million people with DR there’s going to be a billion people worldwide with diabetes.
And then the United States, it’s a hundred million. We’re sitting at about close to 40 million now. It’s an epidemic problem. My real caveat would be, not caveat, my pearl, for all my colleagues in eyecare is you’re not going to go blind from diabetes if you don’t get diabetes in the first place. So if you can educate your patient about lifestyle strategies to not get diabetes, and it’s a lot of stuff you don’t normally think about.
Eat a plant-based diet, get at least seven hours of sleep a night, but not more than nine because there’s a sweet spot for sleep duration that lowers the risk of developing type two diabetes. Turning off your cell phone, your computer monitor within a couple of hours of going to bed because melatonin is suppressed by blue light emitted by your screen and that mucks up your REM sleep, you lose about 11 minutes of REM sleep a night. And that’s been directly associated with a higher risk of diabetic retinopathy, diabetes in general, but also age-related macular degeneration.
So I think sleep is a hot topic now. There’s tens of thousands of studies looking at sleep disorders, on effects on systemic disease, but also eye disease. So I try to talk to my patients about diet, sleep, moving their bodies around, get off your rear end, walk around, carry some lightweights and just move around because you’re going to burn more calories, you’re going to be more insulin sensitive if you do that. Try to stay away from the middle aisle of a grocery store where there’s Captain Crunch cereal and Coca-Cola beverages.
Try to stay on the ends of the grocery store, try to get more plant food in your diet. Try to eat more variety of plant food. I know I’m going on too long about this, but I’m a big advocate for prevention. Prevention beats cure in my book, although I’m not doing laser and injecting people’s eyes. So maybe cures better than prevention if I’m sitting on the other end of the spectrum as an ophthalmologist.
Mark Dlugoss:
That’s some good advice though. I just learned something from you there. So in closing, what’s your take home message for optometrists when it comes to the early detection and management of diabetic retinopathy?
Dr. Chous:
So again, half of your patients have either diabetes or pre-diabetes. And some studies say as high as like 12% of people with pre-diabetes already have diabetic retinopathy. So I think it begs the question, do they have pre-diabetic retinopathy? No, they have end organ disease because they’ve already got the disease. So it’s really interesting, and this is based on data from a number of clinical trials. By the time a patient’s diagnosed with type two diabetes based on the prevalence of retinopathy, which doesn’t happen overnight, the average patients had diabetes more than six years by the time they received their diagnosis.
And that’s why somewhere between 20 and 40% of patients have DR right at the diagnosis of the disease. A lot of docs tell me, “I don’t see a lot of retinopathy at diagnosis.” “Look harder,” is what I would tell him because it’s actually, excuse me, it’s pretty prevalent. I had a gentleman came in yesterday, just diagnosed macular edema in his left eye, little bit of vision loss. He’s got macular edema, he just got diagnosed and put on therapy for his diabetes. So clearly he didn’t develop it last month, he’s had it for a while.
Mark Dlugoss:
Well, thank you, Dr. Chous, I really appreciate your time on this and I think you provided us with some really good information about diabetic retinopathy. Thank you so very much.
Dr. Chous:
Mark, it’s been a joy talking to you. Thanks so much for having me on.
Mark Dlugoss:
Okay, take care.
Dr. Chous:
You too.
