welcome to this program preventing inevitable blindness in the diabetic patient. This is part of a series on diabetic retinopathy, but also diabetic macular oedema and age related macular degeneration. So these other programs are also available. So my I'm Paul Chows and the topic I'm talking about today is the diagnosis, referral and management of diabetic retinopathy. I have a practice in Tacoma, Washington, and essentially all of the patients I see have diabetes. I'm across the street from a large endocrine practice. I'm also a professor, uh, of optometry at the Western University of Health Sciences. Diabetes is something about which I'm really passionate. Here are my disclosures. I've spoken for a whole number of different companies in the diabetes space and otherwise, but I've done my darndest to not be biased in any way. And this, uh, program is part of an educational grant that was provided by Regeneron. So we all know that diabetes rates are going up. The prevalence of diabetes is astounding. More than 30 million Americans now with it. So in 2012, it was about one in 10 people with diabetes Now in 2020 it was about one in nine by 2050 it's going to be somewhere between one and 3 to 1 in five patients. It's estimated by the year 2050 100 million Americans will have diabetes worldwide. Right now we're at about half of a billion. So it's really a prevalent problem, as we all know. So diabetic retinopathy as you know, all of us. And I care. No, it's the leading cause of new onset blindness in people of working age that is under the age of 70. About a third of patients with diabetes have some degree of diabetic retinopathy. Of course, not all diabetic retinopathy is created equal. We know that about 10% of these patients have what's called vision threatening or sight threatening diabetic retinopathy, And this generally refers to severe non proliferated disease proliferated diabetic retinopathy or diabetic macular oedema. Another just an interesting thing to be aware of. There's this huge pool of people with pre diabetes more than 90 million now, and somewhere between eight and 13% of those patients have signs that are suggestive of diabetic retinopathy. About 12% of people diagnosed with diabetes in the year 2018 reported some degree of visual disability including blindness. The majority of patients with retinopathy, as we know, have Type two diabetes. Because the majority of patients with diabetes have Type two diabetes. Studies say somewhere between 20 and 40% of patients have some degree of diabetic retinopathy at the diagnosis of Type two diabetes, so I'm using the lower figure about 20%. The estimated duration of type two diabetes by the time someone is diagnosed based on clinical parameters is six years. So we're not catching diabetes at an early time, so a lot of patients have it for multiple years before being diagnosed. And that's why a lot of patients show up with D R, sometimes diabetic macular oedema at the diagnosis of their disease. The biggest risk factor for diabetic retinopathy is really how long you've had the disease, as well as the overall blood glucose control over time. And that's the important message that I want to deliver today is that it doesn't matter what a patient's hemoglobin, a one c is the day you examine them. What matters is what has their hemoglobin, a one c been over the duration of their time living with diabetes, for instance, in the Diabetes Control and Complications trial. Uh, the A one c in the trial about a 10 year study did not account for the majority of diabetic retinopathy risk. It was only about 11% of the total risk. So again, this speaks to the notion that long term blood glucose exposure is what causes diabetic retinopathy. Prevalence of D R and D M in the DME in the United States is quite high. About eight million people are believed to have diabetic retinopathy, and this includes some patients that haven't been diagnosed with diabetes yet. It's about 25% of the total diabetes population. More than two million haven't been diagnosed with diabetic retinopathy rabbit, now more than two million of diabetic macular oedema, and about a third of those patients have not been diagnosed yet. So you can see data here from this is from a couple of years ago that just shows kind of the overall treatment rates of diabetic macular oedema and diabetic retinopathy in the United States, at least, so who gets diabetic? Retinopathy continued. So, of course, patients to get diabetes. So the best way to not go blind from diabetes is to not develop diabetes in the first place, and we have outstanding prospective trials that show us we can prevent people from developing Type two diabetes, even if they already have pre diabetes by intervening earlier on, So medications have been shown to be beneficial. But in particular, lifestyle modification, which amounts to walking 30 minutes a day, five days a week, can dramatically reduce the rate of developing type two diabetes. Put it off into the future. Patients that have diabetes a long time, as I've already said, are more likely to get retinopathy and patients that have not only bad hemoglobin a one C but also this newer metric of blood glucose control called time in range. And I'll talk more about that in a moment. So the most important point here is that it's the cumulative blood glucose exposure that leads to retinopathy, not what the As I said, the glucose control is Now. Patients with poorly controlled hypertension are more likely to get retinopathy patients that have other vascular complications, including renal disease as well as cardiovascular disease, including gum disease, periodontal disease, basically any complication of diabetes. If you look at it, it's associated with diabetic retinopathy, all of these comorbidities hang together as it were. This is just a notion that it's the long term blood glucose control that really matters. This is from the D. C, C T. And the follow up study called Edict. These are all patients with type one diabetes, and at the start of the trial, this is the 19 eighties. Patients have lousy blood glucose control. Their A one C was about 9% on average people in the intensively managed group they either took multiple shots of insulin or an insulin pump. They got their A one C down for about, you know, the 8 to 10 years they were enrolled in the study. After the study concluded, patients in the intensively controlled group continued to have far less diabetic retinopathy, diabetic kidney disease and diabetic neuropathy than the patients that had poorer control during the trial. And this is sometimes referred to as a legacy effect or metabolic memory. The notion is again it's important to get good blood glucose control. Good metabolic control, including blood pressure and blood lipids early on after the diagnosis of diabetes and the data is really disappointing in that regard. So a new study that just got published, called the Discover Trial, founded in the U. S. Only about half of patients five years after diagnosis of diabetes have a hemoglobin, a one C under 8% and this is all patients with Type two diabetes. So glucose time and ranges this kind of newer metric instead of or as an alternative to hemoglobin a one C, and it simply refers to the percentage of any given time period a day. But typically over a month or three months, 90 days kind of like an A one C is the patient's blood glucose in this relatively normal range between 70 and 180 mg per deciliter. Now 1 80 is clearly hi. But you know when you get above 1 80 that's when the risk of eye damage and renal damage really goes up. What's very interesting is that for any given time in range, there's a super wide variability in a patient's hemoglobin, a one C. So for a given time in range, let's say 60%. The A one C can range between seven and 12%. To put a finer point on this, it's been shown that people with the same hemoglobin A one C have widely or wildly different average blood glucose, as measured by a continuous glucose monitoring device. And it's possible that a patient with an A one C of 9% actually has better glucose control over time than a patient with an A one C of 7%. A one C is no longer the gold standard that we've always assumed it to be. The reason, time and range is important is that if you can decrease the time in range or if you do by about 10% the likelihood of getting diabetic retinopathy and progressing goes up 64%. Putting that on its head if you can improve the time in range 10%. So that's two about 2.5 hours a day, right 2.4 hours. That lowers the risk of getting diabetic retinopathy about 40% and it's totally independent of hemoglobin a one C. It's related to a one scene, but it's a separate predictive factor. So what do patients think about, you know, diabetes in their eyes? Most patients, you know, the majority, I think, are unaware that they really do need dilated eye examinations on a regular basis. They don't know how often they're supposed to get their eyes examined. And the most important problem. I think for a lot of patients, they don't realize the diabetic retinopathy is an asymptomatic disease, especially early on in its course. So I say the most common symptom of D. R is no symptoms whatsoever. And this is a really important point for patients to know, because if we catch it before you have symptoms, we can do a lot more to prevent significant vision loss. Long term. This is the critical message. Good vision on an eye chart or in your day to day life doesn't mean you have healthy eyes. We have to consistently remind patients all of us on the health care team about the asymptomatic nature of diabetic retinopathy and, to some degree, also diabetic macular oedema. That's why it's critically important to get your eyes examined on a regular basis. So these are the recommended examination intervals based on clinical practice guidelines from various groups. So for Type two diabetes, it's at diagnosis because I said, a lot of these patients have some degree of d r. When they're first diagnosed and then thereafter between every 1 to 2 years, depending on whether or not D R is detected at the baseline exam. And you might want to examine patients more frequently. Clearly, if they're retinopathy, looks like it's getting worse more rapidly. Or if a patient has a long term history of poor glycemic control over time, if they have renal disease. Let's say these are all risk factors for worsening diabetic retinopathy in Type one diabetes, because generally the onset of the disease is more acute. These patients can be seen about five years after diagnosis, and then every 1 to 2 years. Thereafter are generally the recommendations I'm a fan of every year because patients forget when it's, you know, when their last eye examination or dental examination was. So I think it's a really good idea to get patients on a routinized, you know, follow up when they developed diabetes. And there's lots of other things and expect people with diabetes in addition to diabetic retinopathy. When we're talking about the eyes, right cataract formation. Glaucoma rates are higher, ocular surface diseases higher, so we need to keep close watch on these patients. So what are some obstacles to diagnosing diabetic retinopathy and, you know, staging it appropriately. So you know, I'll lay a little blame on patients. You know. Only about two thirds of diabetes patients adhere to getting annual dilated exams. It's a little better if you go out to two years. Here are some other problems, though, that I frequently encounter in my diabetes centric practice. I've had patients come in and say, You know, I'm just here for an eye exam and I specifically asked every patient You have diabetes. No. And I've had patients tell me. At the very end of the example, I was just told that maybe I have a little bit of blood sugar problem and then you ask them about their blood glucose levels. And as it turns out, you know, they definitely have diabetes. So this is an issue. So we have to be explicit. I think upfront in the eye exam, you have diabetes. Do you have prediabetes? Some patients are not dilated by the eye care provider, and I think there's been an increased reliance on non Modry attic imaging by eye care providers like the Op does device, for instance, it's a great device. It's wonderful, but you don't really get the outstanding views that you get when you dilate the patient. You can even get better images taken when the patient's pupils are dilated. To that end, a lot of patients don't dilate adequately. So many patients with diabetes, especially long term, have autonomic neuropathy that affects the pupil dilation response. So sometimes you have to give these patients multiple rounds of drops to get the pupils dilated. We've all seen this than I care. Use of clinical impression rather than rigorous elements of staging diabetic retinopathy. I know you look in the eye if you see a lot of red stuff, right, if it looks bad, you're probably going to refer that patient out. But we really want to be more, uh, rigorous about staging diabetic retinopathy because it matters as to whether or not those patients would benefit from treatment. I think a lack of O. C. T. Is a problem, Um, many optometrist duo C T. But not all of us do. And then I think the other thing we don't do is look at the systemic risk factors like what is your history of metabolic control over time, Do you have other cardio? You know, other vascular diseases like heart disease and the like. There are risk factors for D R, and then the other one. I didn't mention it here, but it's been shown more recently to be really predictive of worsening. Retinopathy is untreated obstructive sleep apnea. So I think every patient needs to be asked about sleep disorders. Even in skinny patients with diabetes, there's a much higher prevalence of obstructive sleep apnea that contributes to all sorts of vascular problems. So what tools should the Tom Mattress used to diagnose diabetic retinopathy and help us stage it? So you need to do a dilated exam? I know that's been drilled into all of our heads. You need a condensing lens at the slit lamp. When 90 78 doctor die after a 68 Dr Lens, take a good look at the macula and look at it. Stereoscopic Lee. It's helpful to have a bio to look at retinopathy outside the posterior pole. There is evidence that I'll talk about in a second that shows that patients that have a lot of retinopathy outside the poster report kind of in the mid peripheral retina are far more likely to progress on to proliferate of retinopathy, agony, Oscar villains. Clearly, they look to look for iris or angle neo vascular ization. So here are my tips were using retinal imaging. So with a retinal camera, use red free imaging because it highlights vascular pathology. It's much easier to see micro aneurysms and hemorrhages neo vascular ization Irma even vein beating when you use a red free filter. And Whitefield imaging is again very helpful for accurately staging the degree of diabetic retinopathy. Spectral domain, O. C. T. And now swept source. O. C. T. Are really the most sensitive ways to detect diabetic macular oedema. And I know I'm not talking about DME specifically today, but it's been shown that about a third of patients have subclinical DME that's not detected on clinical examination, even by retina specialist. So O. C. T. Is an exquisitely sensitive way to pick up on subclinical DME. It's not going to be treated, but these patients are far more likely to progress on to a disease severity that requires treatment. OC to is another emerging technology that I'll speak more about in a second, and there are some other visual function measures like color contrast, sensitivity testing, which has been linked to diabetic retinopathy. Contrast. Sensitivity goes down in general and diabetic retinopathy. Macular pigment. Optical density is lower in people with diabetes, and it gets lower as the retinopathy gets worse and as the blood glucose control goes up. So this is something that I'm looking at my patients with diabetes on a routine basis. So diabetic retinopathy in the periphery. So let me put a finer point on it. You. Some literature citations that 10 to 12% of eyes. If you look at the peripheral retina, especially the mid peripheral retina, you're going to discover they have more severe diabetic retinopathy than you would have otherwise by simply looking at the posterior pole. So this is a study out of the Joslin Diabetes Center at Harvard University, and they showed that if patients had predominantly peripheral lesions, this means more hemorrhages. Micro aneurysms, you know, even neo vascular ization in Irma in the retinal periphery than they do in the posterior pole. Those patients are about Tripoli likely to develop a two step worsening in their diabetic retinopathy. Severity and a two step worsening is significant you know. Moreover, these patients were nearly five times more likely to develop proliferated diabetic retinopathy over a 1 to 2 year study duration. So I think it's important to look at the periphery whether you do it with what I field imaging or put on a B i o. To evaluate it, you need to look O. C. T again is the most sensitive way to detect diabetic macular oedema. And DME, we've got to remember, is the leading cause of vision loss and diabetes. It doesn't cause total blindness, like PDR can with traction retinal detachment, but they can really muck up somebody's quality of life and render them legally blind. So Jobs and Data says somewhere around a third to 40% of patients. I'm sorry of ODS deploy O C. T. Regularly in their practices. And so if you don't have an O. C. T in your practice, that's fine. I would encourage you to buy one or buy one second hand that's more affordable. I mean, that's what I've done over my practice history or work with another even optometrist that doesn't know CT that you can develop a collaborative relationship with. How about OC ta. So this is kind of this newer O. C. T modality that does, you know, imaging sequential be scans of the retina, and it actually tracks red blood cell movement through the vasculature. And it appears to be very sensitive, it picking up on things that you can't see with normal O. C. T. Or even with normal imaging, things like subclinical micro aneurysm formation you wouldn't have seen otherwise. And and the really other big thing, I think, is retinal non profusion. So faux viel ischemia is kind of the ugly stepsister of diabetic retinopathy, but it occurs in up to about 30% of patients with diabetic retinopathy, and it can cause some vision loss. So when OC to it's been shown that the deep capillary plexus so kind of the deeper layers of the retina, if there's a loss of blood vessel density in those layers and lots of blood flow, those patients are dramatically more likely to progress on to more severe diabetic retinopathy. And then here is just a statistic about micro aneurysms that couldn't be detected on clinical exam and capillary non profusion. You know, 11% more micro aneurysm detection in patients when they're subjected to O C. D A. Uh, 25% of patients had some degree of phobia ischemia or capillary dropout. It's non I a transgenic. It's relatively easy to do. It does take some time. That's the that's the issue. Here's just a beautiful example. I thought of neo vascular ization at the vitriol. Retinal interface using oc ta. So you see the photo on the left and you can see the faux Bulus vascular zones irregular. There are areas where there's capillary drop out, so we know that's a risk factor. But if you look specifically at the interface between the retina and vitreous, which is highlighted on the right, what you see there is blood vessels on the retinal surface growing into the vitreous. So that's neo vascular ization. And if you look at where it is on the image to the left, you know it's pretty close to the optic nerve. But it's more than a disc diameter away, so that would be considered neo vascular ization elsewhere. But this patient requires referral to a victory, a retinal specialist, Of course. Again, accurate grading is really the key to assessing your patient's risk of developing sight threatening retinopathy. A lot of people have diabetes. Some of those patients have retinopathy. Some have more severe retinopathy that can progress, and then some have really severe retinopathy. PDR, DME that can cause severe permanent vision loss. Here's the diabetic retinopathy severity scale that most of us use. The one in clinical practices on the top, right? So the patient has no d are they might have nonproliferation retinopathy, and that can be stratified as these are either mild, moderate or severe. And then if you get to a certain point, you get neo vascular ization and you have P. D. R. But for clinical trials, they typically well, you these more, uh, descriptive, more precise grading scales for retinopathy. So we see the early treatment diabetic retinopathy, study scale there in the middle and the modified E T D. R s, which was just developed to devised to talk about step changes. So when I'm going to talk about step changes now worsening or getting better, what we're really looking at is the modified E. T. D. R s scale. So with two step improvement would be going from level six for instance, severe nonproliferation retinopathy two steps better is to level four or moderate nonproliferation retinopathy and so on and so forth. I want you to pay attention, particularly to the modified e T D. R s Level five, which corresponds to E tdrs 47. Now that's not on the international scale. And what it corresponds to is moderately severe nonproliferation, diabetic retinopathy and the reason there is a reason that's important, that is, that these patients are more likely to benefit from intervention. So how do we diagnose severe N p. D. R. And, you know, the 4 to 1 rule that most of us have had drilled into our head in our clinical training? So if the patient has any one of these findings, they have by definition severe nonproliferation. Diabetic retinopathy. So it's more than 20 hemorrhages or micro aneurysms in all four retinal quadrants centered on the macula or and or significant vein beating so obvious prominent vein beating the sausage case looking veins in two or more quadrants, or Irma prominent Irma intra retinal micro vascular anomalies, which are thought to be kind of the germ bed for incipient proliferated disease. If you have any of that, that's prominent those patients need to be referred. And in the E. T. V. R s study, 50% or more of patients who have severe NPR go on and get PDR within a year. The more of the findings you have, the more likely it is you're going to progress. This is just kind of a graphic, graphic representation of what I said, but it scales it according to the degree of NPD are at baseline, so you can see patients with mild, non proliferated disease. The risk of developing PDR at a year is quite low. It's less than 5%. If you go out five years, it's still relatively low, a little bit above 20%. But in the people that have severe MPD are by year five, you know they're above 60% risk for developing PDR, and if they've got moderately severe, MPD are the risk is substantially higher. But even in moderate MP dear NPR, if you go out five years, 40% of those patients will progress on to proliferate of diabetic retinopathy. So some to always keep an eye on is the retinopathy moves past mild. The risk of significant vision loss goes up dramatically. So who would benefit from being referred earlier than we have to afford to a retina specialist? So the studies show that in general, optometrists, but not just us, general ophthalmologists and even retina specialists have a tendency to under grade the severity. He's diabetic retinopathy based on clinical exam. And the Comparator is an image reading center that's looking at multiple stereoscopic views of the retina. In recent evidence shows that anti digest therapy a flipper cept ran a bizarre map and to a lesser degree, Bevis is a mob can significantly improve nonproliferation, diabetic retinopathy, severity by two steps or more On that scale, I showed you. But especially when the diabetic retinopathy severity scale was level 47 on E. T. D. R s or worse. So that's moderately severe, NPR or worse. Those patients were the most likely to get a two step or more improvement in their diabetic retinopathy severity. So we'll look at some of the data with respect to that momentarily. So this again is kind of the e T. D. R s scale there is on the left and the ones who benefit the patients who benefit most from anti TNF therapy are people with Level 47 which is moderately severe. NPR or severe NPR, which is level 53. So what are the characteristics of moderately severe NPR? It's mild vein beating moderate Irma, not prominent Derma or severe hemorrhage in 2 to 3 quadrants. So it kind of my my fallback position is if I see vein beating and it's it's, you know, easy to detect that the patient I'm referring out. It's a sign of severe retinal ischemia. So let's look at an example of a two step improvement. So this is a patient that had DRS s severity level 53. So that severe NPR, which on the modified scale I know it's confusing with all these overlapping scales is Level six. Patient received antiviral therapy. I went back. Sorry if we see what happened there, step improvement to level four on the modified scale. Now they've only got moderate. NPD are so that's just an example. And some patients, you know about according to a third have a three step or more improvements. You can make a really big difference. So what are the treatments now for diabetic retinopathy available? So we all know about laser photo graduation. When is it used? PDR. And it has been used historically for diabetic macular oedema, although increasingly less so. Intra virtual steroids, we know, can be very effective, especially for anti V Jeff resistant or refractory diabetic macular oedema. And then antiviral therapies are now used for DMI for proliferated diabetic retinopathy and for moderately severe or severe. NPD are, in fact two of the agents. So it's a random. Is a mob in a flipper step? Have FDA approval to treat any level of diabetic retinopathy? But the patients who benefit the most are those who have more severe disease. So level 47 or above diabetic retinopathy Combination therapies are often used, especially when patients have PDR. So a little bit of lasers laid down some anti TNF therapy to try to get the best response. Minimize the amount of laser that patients need to be subjected to, and it's also used for diabetic macular oedema to some extent. And then, of course, there's surgical interventions like the trek to me, helpful in many patients with vitreous hemorrhage that have proliferated retinopathy in a patient that vitro macular traction doing attracted me can help alleviate the traction that is worsening. Diabetic macular oedema. All of these therapies have potential events. So I've had Prp. It's been a long time now, 1985 you lose your peripheral vision. I have terrible night vision. You lose your accommodation So those are the downsides It doesn't generally make you know it makes neo vascular ization go away, quote unquote. But it doesn't really cause a reversal of the diabetic retinopathy severity at earlier stages of disease with steroids, of course, you have the problem of cataract and increased I o. P. And developing glaucoma. But the anti digit therapies there can be an increased in i o p. It's typically transient. Some people, though, do have some sustained elevation in inter ocular pressure. So the retina specialist that I've worked with and lectured with always emphasized If you're an O. D co managing these patients getting anti digit therapy, make sure you check the interactive pressure every time you see them and, you know, treat glaucoma if it develops. And, uh, you know, let the rental specialists no, uh, the other issue is that you can get very low risk less than one in 1000 of India Phlebitis or retinal detachment. These things are very rare, but they can happen anytime you're introducing a foreign object or for an element into the eye. And then there is this possibility of an increased risk of arterial thrombosis. Symbolic events. They're called a a TPC events. Basically, these are blood clots, strokes, heart attacks and the like. There may be a slightly increased with a risk of these events with anti digit therapy. Patients with diabetes already have a slightly higher risk, so it's just something you need to evaluate closely, you know, in consultation with the patient and the retina specialist. So this is data from the diabetic macular oedema trials, the three on the left and then one proliferated retinopathy study using anti death therapy. So in Vivid and Vista, which used a flipper cept a lot of patients, about 30% had a two step or more improvement in their diabetic retinopathy severity scale. Now these are patients that already at DME in the Rise Ride trial, which used to run a bizarre MAB similar kind of finding in protocol t that compared, uh, devices. A Malbranque's is a map and a flipper step to each other. They all improve. Diabetic macular oedema a flipper cept was a little better than the other two agents. But again, in this trial patients a significant number at a reduction in their severity. And in protocol s of the of the diabetic retinopathy network the D r C r dot net diabetic retinopathy clinical research network trial. They showed that a flipper cept was non inferior to Prp for proliferated retinopathy, with about half of patients having at least a two step progression in their retinopathy. Severity. So what was Panorama? This isn't a flipper cept trial Looking for the first time in patients that didn't have DME. These are only patients that have level 47 moderately severe NPR or level 53 severe non proliferated diabetic retinopathy, no diabetic macular oedema. So patients were given a flipper cept or a sham injection. There were kind of two different. Uh, you know, uh, uh, injection rates every eight weeks or every 16 weeks. There was loading doses in each group and after year to the group. Getting it every 16 weeks continued on that same trajectory in terms of injections, no matter what level of retinopathy they had and the people that were getting it every eight weeks they had gotten more injections. They were treated prn by the retina specialist. If they met certain pre specified criteria for retinopathy severity. And the primary outcome is how many people, what percentage in each group get at least a two step improvement. And they're diabetic retinopathy. Severity scale. There was a secondary outcome, which I think is really interesting and important, and that was the percentage of eyes who went on to develop what they call the vision threatening complication. So that's either proliferated retinopathy or Iris rubio sis or anterior segment vascular ization. That's the vision threatening complication group, or and or center involved diabetic macular oedema that we all know can threaten vision. So here are the results of the six months, 12 month and basically 100 week, nearly two year trials in Panorama. So the sham group you had very few people that had a two step improvement or more from baseline in the every 16 week group. With a flipper step, you can see pretty consistent improvements in diabetic retinopathy. Severity at least two steps in about two thirds of patients now, Interestingly, the every eight week group. They did a little better at year 1 80% reduction in, uh in 80% improvement in diabetic retinopathy severity scale of two steps. But at year two they did less well. They did less well than the people getting it every 16 weeks. And so the question is, Why did that happen? So the Post talk analysis of Panorama showed that the retina specialists treating patients under graded in about 30% of eyes the severity of the patient's diabetic retinopathy. And so these patients were under treated so they actually did worse in year two. I think that's a really important message for those of us in optometry, because even retina specialist sometimes get it wrong. Okay, that's the key. This is the the secondary outcome, which was vision threatening complications or center involved diabetic macular oedema and on the far left. There you see those two things combined, and the bottom line is you get nearly an 80% reduction in developing one of these bad outcomes. If patients receive a flipper cept at either of the dosage regimens, most of these eyes that had a two step or more improvement 92% maintained at least a two step improvement after 100 weeks. So these are my key takeaways from Panorama, and I've already alluded to this pretty forcefully that even retina specialist under great diabetic retinopathy severity. And I think for those of us in optometry, if we don't have fluorescent angiography at our immediate disposal, it makes pragmatic sense to refer patients into a retina specialist. If we believe they have moderate MPD are or worse, because when we grade them as moderate, they might in fact have moderately severe or severe NPD are again. That's about 30% of the retina specialist under graded folks that had at least level 43 retinopathy in the in the Panorama trial. So I think it makes sense to refer patients a little earlier than we would have otherwise. Now, some retina specialist are going to treat. Some won't even if they get to Level 47 retinopathy. But the key is at least give the patient the benefit of being introduced to the retina specialist, who can then follow that patient in collaboration with you so that they are caught early. If they develop more severe disease. The other important point here, I think, is that antibiotic therapy can really turn back the clock on NPR severity. It can reduce the risk of these bad outcomes. But it may be better to give patients what I call defined interval treatment. So every 16 weeks, rather than relying on the retina specialist to decide whether or not the patient needs treatment, because those patients over two years actually ended up doing better. The other thing that's important. And this was presented in December virtually at the SRS meeting American Society of Retina Specialist. What was that? The people that benefitted from a flipper cept did so across a whole range of demographics. So it didn't matter what their hemoglobin, a one c was. It didn't matter what their b m I was or how long they had had diabetes. All of all of the patients in the trial, regardless of baseline characteristics, benefited from a flipper cept treatment, the really other turning this on its head. The other key finding here is that you can have a great human globe in a one C and in panorama. In fact, a lot of patients who went on to get proliferated retinopathy had a one CS of 6% when they were enrolled in the trial. It doesn't matter what their a one C is now. As I said earlier, They get to this level of severity. They need to be referred, regardless of their metabolic control or how long they've already had diabetes. Now a couple of examples just to help kind of cap this off. So this is somebody I saw? I said just last week. It's actually been about six weeks now, so it's a young man that came to my office with Type one diabetes. His last exam was five years earlier, and at that time somebody said, Yeah, you've got some early I damage but he kind of blew them off his last day. Once he was 9.1. So that's not very good. Even assuming a once, he's not totally accurate. It's probably not that good. He's taken a lot of insulin, so this is not something we focus on much, but he takes 150 units a day of insulin, so a normal person without diabetes makes about 30 to 40 units a day. So this guy has taken a lot of insulin. He's insulin resistant, or he's eating whatever he wants and just injecting more and more insulin to try to try to kind of compensate for the elevations and glucose. Now the reason that's important. Insulin stimulates veg F production. So we know patients. The more insulin they take, the higher the risk for them developing more severe retinopathy. I checked his blood sugar while he's in my chair because I don't want to write him a prescription for glasses if his blood sugars out of control, his a one. So as a one. C was high, but his blood glucose when he was sitting there was above 400. So not very good. The guys 2015. He has no visual symptoms whatsoever. So here are a couple of his images, and these specific images were taken because I'm using an AI an artificial intelligence algorithm to kind of double check myself now. So if we look at this image of the right eye, we see vein beating. We see. You know, there's a good amount of hemorrhage there vein beating and at least two quadrants. So, you know, at that point I see that he needs to be referred. He's got some cotton wool sports spot formation here in the nasal retina. Here's the other eye. Some hard exited formation there. Fair amount of Hammerjacks wouldn't say severe, but he's got vein beating. And then here's the left eye. We see some cotton wool spot formation, their nasal e. So, you know, I thought because of the vein beating, he's got severe nonproliferation retinopathy, but I sent these images into this AI algorithm that's through a company affiliated with U. C. L. A. It's called I nook and I'm not here, you know, hawking for their product. But what it came back with was a nice report that showed me and the patient, you know, within a couple of minutes that you've been graded as having severe nonproliferation retinopathy. I had already told him That's what I thought it was. But this is kind of a backup plan. And was he impressed? No, not at all. He said to me, I don't care. I'm not having any symptoms at all. Why don't I want to go to a retina specialist? What's he gonna do? And I said, Well, you know, he may offer you, uh, therapy, Antiviral therapy I explained what that was, he said, I don't want any part of that. And so sometimes you get these patients that no matter what you do, they won't listen to what you have to say to them. This was what finally worked, though I I showed him a picture of my own. I that has prp scar scars, like 3000 of them. And I told him, You know, I don't want you to end up on that road But here's the deal, my friend. You're standing at the edge of a cliff. Okay? Everything's fine now at the edge of the cliff, but you take one step forward, you're falling off the cliff and that finally sunk in. He kind of sat there in silence for about 30 seconds. It seemed like about an hour to me and he said, Okay, I'll go reaffirming And I did. And he ended up getting antibiotic therapy. Here's another example 58 year old female. I borrowed this case from a colleague, Diana Shechtman in Miami, who is an OD fabulously smart, great speaker to, uh so her patient was diagnosed with Type two diabetes and was referred by the PCP for the first dilated eye exam patients I met Foreman Lan test Listen to Paul and laboratory service that right? We see this all the time. Patients on this combination of drugs, a one C was not good. 10% and the blood glucose was for about 400 in her office, patient has some cataracts with visions down a little bit to die after myopic shift. Not all that uncommon. So here's an opt OSCE image and ultra wide field image of the right and left eye. So I ask you rhetorically, what stage of diabetic retinopathy does this patient have? So I'm gonna profess I'm not allowing you to magnify the image or to put it in red, free to see what's going on. But kind of when I look at this, I do some some hemorrhaging there, right? There's maybe a little bit of veined beating. So I would say, you know, this patient probably has moderate np. Er, maybe it's a little worse than that. The question is, would you refer this patient well now, knowing what I know, I certainly would. So I said moderate, uh, M P D r. When Diana sent this photo to me, and I solicited from her a case example where patients don't look that bad, but they really were bad. So here's an ultra wide field f a. So what do you see here? A lot of non profusion, right? So that's a start up. Forgetting proliferated. Diabetic retinopathy. All that dark stuff means the patients not getting blood supply to those areas of the retina. High risk. And here's the left eye. So we all know that's neo vascular ization that you wouldn't necessarily have seen if you'd only looked at the photograph. Neo vascular ization sometimes is very subtle. So that's the point. Here is that sometimes people will fool you so that you refer that patient. Yes, you would and should. So here's a real problem, and I'm going to make the point that the referral to a retina specialist is not accomplished by those of us in optometry until the patient actually keeps the appointment with the retina specialist and for for that matter, it's not really accomplished until the patient follows up with the retina specialist for whatever treatment regimen has been assigned to that patient. So lost to follow up, sometimes called fun a follow up. Non attendance affects a lot of people with D R and D M E. So in one trial, 25% of people getting anti DeGette therapy for diabetic macular oedema didn't go back for the follow up recommended follow up. Within the first year, they waited at least a year to go back. Well, we all know you need a series of injections, typically to get a good result in patients with PDR, whether they were treated with laser or with an TV. Jeff somewhere between a quarter and a half didn't come back for follow up within 1 to 2 years, as it turned out that people getting anti VHF therapy were much more likely to get traction retinal detachment when they didn't show up again. And that's because you need ongoing therapy with anti VHF for proliferated retinopathy. So the message here, I think to me is patients may really benefit from getting a combination of therapies. A little bit of Prp kind of quenched the neo vascular stimulus as well as the anti TNF therapy. Hopefully, they show up for more anti Geoff injections as they need them, but if they don't maybe not all is going to be lost. I'll show you an example of that. In a moment. The people that were most likely to not come back were people that were younger, not really that surprising people who were poorer, so lower socioeconomic status, African Americans, Latino Americans, Native Americans and those that had worse baseline visual acuity. So if you go in with bad vision, you get an individual therapy and it's still kind of lousy. Afterwards, you may be less motivated to return, right, So they actually tracked down a lot of these patients in one trial or one want to follow up study, and they showed that there were certain characteristics of those that were lost to follow up. So these were These were the reasons cited by the patients who actually didn't show up again when they finally tracked them down, they said I didn't have any connection with other people that have the same thing that I have so actually putting patients, you know, somehow in connection with each other. And you know, this is something that I think various entities could do, having a support group people to talk to you about your diagnosis might be really beneficial that was identified by these patients, more disease specific education. So a lot of people said they didn't really understand. You know what diabetic retinopathy was? So we got to do a good job explaining to them, and I think the picture is really worth 1000 words. So if you can show patients there, you know, ultra wide field images or their O. C. T. And then show them a normal I I think that's a really powerful way, you know, to motivate and educate patients. And then a lot of patients that were lost to follow up said they didn't have transportation, and maybe that goes hand in hand with being poorer. So we really got to do our best to try to make sure that these patients are able to get in to see retina specialist when it's indicated. The other thing that predicts lost to follow up, by the way, is chronic depression and having had a foot or uh, toe amputated as well as kidney disease. So if you have a patient with retinopathy you want to refer, you might want to ask about Do you feel depressed? Do you have you. Have you lost any toes from your diabetes? Is your renal function okay? Look at there. Look at their record and see if any of those things are true. And you want to follow up to those patients much more closely to make sure they get into the retina. Specialist. So you're just my example. This is a guy that I saw who came in with the vitreous hemorrhage and he said I just lost vision in this eye. You know? I thought it would get it go away, but it didn't. So I sent him into the retina specialist. He went and he had Prp and anti vet Geoff kind of in combination and, you know, about a year and a half later, that's what he looked like. So he went basically from basically blindness to about 2060 visual acuity. So he was asked to return for more anti digest therapy. Apparently he didn't. I saw him a few years later, and that's what happened. He got a traction retinal detachment, and now he's no light perception vision in that eye. So, again, I didn't do my job. I feel like making sure this person knew you know that he needed to follow up with the retina specialist. And I think we refer to rent a specialist when we think, well, you know that that baby is over on their side of the of the of the of the line. Now I don't wanna have to deal with it anymore, but really, because we are their primary eye doctors in optometry, I think following up with patients and encouraging them about the importance of getting follow up is a really good thing to do. Communication is critical, right? So this is a study out of U. C. San Francisco. A retina specialty practiced, and they looked at how often retina specialist, uh, and primary care physicians communicated with each other. And what they showed was that when patients were recommended to get an eye exam, if if the if the the primary care physician got a letter from the eye care provider and it was actually ophthalmologist in general, patients were more likely to get their eyes dilated when they were told to do so. But what was even more potent was the primary care physician or the endocrinologist or the internal medicine doctor sending a letter to the eye carrier provider, telling them this is the patient's treatment regimen. I really want to make sure that you help me take care of my patient, so we need bi directional communication and this is my bugaboo and optometry. I send letters. I'm writing 78 letters a day to PC PS about their patients with diabetes, even when they have no retinopathy, because that's what we need to do. But I rarely get letters back. And so I think it's something not to lay the blame on anybody I know PC PS and endocrinologists are busy, but if you can even have just a short follow up communication from that provider, it will help us in I care. Do a better job managing patients in conjunction with retina specialist, primary care physicians and endocrinologists all alike. So with that, I want to say thank you. I want to thank the people that you know allowed this program to be put on. I want to thank Regeneron for their support, and if you have any questions, my email address is there at the bottom. I'd be more than happy to answer questions. That's kind of what I live for. I'm passionate about diabetes. Thanks very much
