Hello and welcome to this program on diabetes and primary care specialists. Perspective on the prevention off advanced diabetic retinopathy, which many of us look at as inevitable blindness in the diabetic patient. I don't think it's inevitable, and I'm going to show you some very exciting new data today, and I hope that that will prompt better care of people with diabetes. We've been talking about screening for diabetes, diabetic retinopathy for many years and haven't really done a good job with it. And we hope to change that. My name is Vivian Fonseca and professor of medicine and assistant dean for clinical research at Tulane University in, UH, New Orleans, Louisiana, and this program has been brought to you by M. C L C M E, which stands for multi modular, curriculum based learning and CMI. But what it means is that there are many modules to these programs. You will be hearing more from other specialists. I'm going to give you the perspective off and endocrinologist, which I am, But also I interact a lot with primary care physicians looking after many people with diabetes, and we wanna make sure that our patients get the best possible care and prevent complications of diabetes, particularly advanced blah, retinopathy and blindness. So, as you know, well, diabetes associated with serious systemic co mobility's retinopathy. It's the leading cause of blindness under the age of 65. Ah, large proportion of patients have some retinopathy. In fact, after a few years of diabetes, almost all have at least background retinopathy. That's a hallmark of diabetes, but not all progress to the advanced stage. And we need to recognize who does and who doesn't, and so that they get the appropriate treatment to prevent progression. Diabetes also associated with net property, neuropathy, coriander diseases, etcetera. And, uh, the reason I mentioned the other complications is that these often travel together. If you have a patient who has neuropathy symptoms, it's very likely that they're going to have retinopathy as well, so make sure they know that and get their screening done. And one of the strongest predictors of future complications is duration of diabetes, and you need to emphasize that to your patients. So let's focus on the I and the complications off the diabetes and the I include obviously diabetic retinopathy, which is very specific to diabetes. You don't get this if you don't have diabetes. And also diabetic macular oedema, which is not totally specific. But the pattern off the disease is certainly far, far more common in people with diabetes, particularly in type two. Uh, I don't know why people with type to get more macular oedema that die pipe one get more proliferate written novelty. And there are other eye complications that are not very specific, with more common in people with diabetes such as cataract and glaucoma. And patients need a comprehensive evaluation off all these things. So, as I pointed out, diabetes leading cause of new onset blindness after a certain age, macular degeneration comes in a za cause. But certainly in younger people, it is very serious to lose vision. And I still see people with diabetes losing their vision because they haven't really had the screening and referrals in care. And patients fear blindness. If you ask people with diabetes what they fear most about the disease, they say they feel going blind Aziz compared to heart disease. And, uh, this is the ice losing eyesight is the worst thing that can happen to any patient now. Obviously this is very closely related to diabetes control as well as duration of disease. So you see you, those within a one c greater than 7.5. We have diabetes for more than eight years have over 50% chance of having written apathy. And sadly, this is not an uncommon ah scenario in clinical practice. We all have a lot of patients who have a one. C is greater than 7.5 for more than eight years. Uh, at the prevalence in type one is after 15 years, about 30% have. But if you really look for a little background is present, perhaps even in more among people with type two, receiving insulin is also very high, and even among those not receiving insulin, you do get some. It's not that insulin causes the disease. It perhaps, is a marker of greater disease severity and probably poorer diabetes control, for which you're using the insulin. So let's look at the path of physiology. Why do you get written up with you there multiple things that go wrong when you have chronic hyperglycemia, you get, uh, a number of metabolic responses. We know about things like, uh, Polly, all pathways activated so you get so bit all accumulation, that's more in the lens. You get location and products and downstream, uh, sort of a one C that because in in various tissues, that leads to oxidative stress active, activating other, uh, proteins like protein kinase C that sets off inflammation and sets off growth factors on Veysel, dilator, Zen Veysel, active substances. Part of this is related to s Chemie A that comes from micro vascular damage and material damage. Capillaries close thes very small blood vessels. Closing the response to ischemia is to have new vessels grow around it. And the leading biochemical process to stimulate growth of new vessels is what we call vascular endothelial growth factor off. Jeff, This has been recognized for a long time and has been associate ID. And I'll show you data about its association with people with diabetes and at this breaks down the blood blood retinal barrier. You get leakage and you also get growth. You get growth of new blood vessels that are not normal than not well supported in the layers of off the retina, and they tend to bleed. So you get either bleeding or more commonly, you get a Dema due to leakage your fluid in the retina and you can see that. So here's a retinal capillary, and it has very little fluid as you keep getting more and more fluid. Uh, and the you get chronic accumulation and swelling off the layers on the layer gets pushed forward to patient, gets blurred vision, and I'll show you a little more detail of that. You also get weakening of the blood vessel ball. What's called micro aneurysms. You can see this very easily within opt alma scope, and you get lipid deposits as well. As you know, These people have a lot of high polyp anemia as well, and eso we their various stages and we'll go into more detail what, in a simple terms, you have background or non proliferated retinopathy. As you can see on the left. These little micro aneurysms occur after a few years. But the important thing about recognizing these is they can progress and the progression takes you into various stages. One of which is this oedema, and you can see this with a technique called OCR optical coherence tomography. You see this lifting up the layer of the retina and leakage of the fluid around and you get profited right now. But do you see these new vessels, then? Uh, like a bunch of fruit that's not well supported there. And they tend to break and bleed and you get bleeding. And then ultimately, uh, patients lose their vision because of bleeding into the victories. So how do we make a diagnosis? We need to get the image of the retina. And, uh, in the past, we'd all be doing up Thomas Cope exams. That was a bit cumbersome and challenging to do. You have to dilate the retina. And there are now multiple ways to get retinal images. And this can be done through telemetry and other, uh, easy to use techniques like that as a screening tool. And then people who have some abnormality can go for more sophisticated testing with a retinal specialist. So color funders photography is a very well established technique. Now and now you have these newer techniques that show you the image of the retina and you can actually see is a normal one. And if you have some swelling underneath you to this fluid accumulation, the retina gets push forward the layers there I push forward. It's very easy to see with this technique. Some ophthalmologists use Florissant and geography. They inject the dye and you can see where the fluid is leaking out. You can see whether there are new blood vessels, and that helps them target laser treatment. At least they used to use it a lot when Lazo was used almost exclusively as the treatment. It's being used less and less now for reasons we will discuss. So a lot of people have this oedema if you have diabetes for more than 20 years, about 28% of patients have this macular oedema, and it loses patient for the patient on it. Ultimately, it becomes irreversible and leads onto blindness. But many people get a warning because they're losing vision and they will come to see a non opthamologist or their doctor quickly. So what can we do? Even people who don't yet have symptoms can have some degree of Dema or some productive right now, but the particularly in the periphery, which is why we need to dilate the pupils and we should refer patients to a specialist for that. Most people I asymptomatic, but they can lose vision suddenly, if they have bleeding. Yes, what macular oedema does to you? It's a kind of blurry vision. You look at these letters some parts, places you'll see, uh, double some. You'll see little bits of the, uh, blanked out, depending on where the Deem A is, because it's very patchy. So the guidelines are very clear. People with Type one diabetes after they've had diabetes for 3 to 5 years should have an eye exam and then yearly after that in Type two. Because we don't know when the disease really started, you need to have it at the time of diagnosis and then annually. There are some particular situations right of pregnancy because pregnancy is associated with rapid improvement in control, particularly, mostly young women with type one uh, you get a worsening, a transient worsening of the red novelty, so that's well recognized. And we recommend that every pregnant type one has a quick eye exam. And now there's some, uh, there have been some reports with GOP one receptor agonists and other drugs like that, which might affect it, So we need to, uh, maybe make sure that patients have an eye exam before they embark on such therapies. Unfortunately, there a lot of gaps in ophthalmic care. Many patients are not getting their eye exam done annually when they should. And, uh, there's this data is a little out of date, but there's There's been more recent data also suggesting the pattern is still the same. Ah, lot of people have not had good education about their eyes. They're not affected. They're not informed about retinopathy screening. About 40% of people reported that they hadn't had a dilated eye exam in the previous 12 months, and a smaller percentage have visual impairment, which means a lot of people don't know that they have written novelty, and this occurs across the board. This is a very sad statistic. It hasn't changed in many years. This is in an insured population, uh, with commercial insurance, Medicare, Medicaid, a little bit more testing in the Medicare population because people who are older, perhaps a little bit more conscious about their eyes and have other visual problems. So they go to the doctor. So not much changed in in a few years, and it hasn't changed since then. Unfortunately, so many people, uh huh, did not have time we follow up. About half the patients go have one examine and they don't go for follow up. They are aware that they have written up with the and we need to do at this kind of testing because it's important, uh, for as I will show you to pick it up early, you also need to treat the hyperglycemia, which is a key modifiable risk factor. There's also evidence that good blood pressure control will slow the progression of retinopathy and lipid Hyperloop anemia. And there's some data with vibrates to suggest that they might actually have a beneficial effect. Eso If you control the lipids well, you might prevent this. As I mentioned, telemedicine has been a big boost to screening. We use it in our in our diabetes clinic. There's a machine there. People go, have sit in front of it and not clicks the button. There. The the image is sent to an ophthalmologist who reads it, and it's not perfect. It's not as good ascending the patient to the ophthalmologist, but it allows us to say you're okay. You can wait a year or you need to be seen quickly, and that's pretty good uh, agreement between seeing the ophthalmologist in person and the sensitivity could be improved. They're getting better with the photographs, but it's better than not doing the exam it all. So let's now look at how we can change things. Well, first of all, I mentioned diabetes control and you know very well from the D. C. C. T. And now we've learned also from a court and others that good control of diabetes, uh, slows the progression off retinopathy and may prevent it. A good diagnostic evaluation might do that. So, funders photography is the gold standard. It helps us assess. Severity helps with treatment decisions. Now, this way, once the patient goes to the ophthalmologist, they will have better photographs than with telemedicine. They'll get kind of pictures like this. And here you see very clearly on the right hand side, the prolific of retinopathy. So they have been a number of studies. One of them establishing front of photography is the e. T. D. R. S study on it established method for doing the 16 images for, uh, for I seven fields. Peoples are dilated. You have skilled retinal photographers, and they are able to quantify who's going. You know what stage the patient is that and there are various severity scales saying you got mild disease, very severe disease in between the two, based on what has seen a little bit of subjectivity there. But now a number off criteria have been put in place to allow opthamologist to quantify where exactly the patient is and tell you when a patient is getting better or getting worse based on these numbers. And this, uh, Ossetia's well has helped a lot with early recognition off oedema. So the Ophthalmology Association has recently released guidelines on what to do with diabetes. I'm not going to go into detail about this other than more or less, It tells us, uh, everybody should be screen and it it really helps ophthalmologists in what degree of follow ups it? No, right now, but the your mind right now, but he once a year. But if you got high risk, couple of live right now, but you need to see the patient back within one or two months, so that kind of guidance helps the ophthalmologist. And here's a broad summary of the same thing. High risk. You see the patient very quickly if you got no retinopathy and annual eye exam is good enough. And people who have macular oedema need to be followed up closely because of treatment that I'll tell you about. So here's some examples I'm gonna grown through very quickly years mild written apathy is you could Seymore little dot and blood hemorrhages. This is moderate. And then here's somebody with what we call non proliferating, written up with the no blood vessels, but they've got a lot of abnormalities in their vessels. Uh, and you're a little bit more moderate. And if you do a Florissant angiography, you can see a number of these abnormalities, and here you see some fluid on the O. C. T. Yes, more severe proliferate, non proliferate. They don't have new vessels yet, but they're getting a lot, a little bit of bleeding into the eye and years more severe. And then finally, you end up with very severe disease. So what do we do next? What is the multi model management? And I think it's good for us to understand this even if you're in primary care so that you know what's going to be done with your patient in the past. It was simple. They would do laser. But that wasn't very good because laser burned parts of the retina and it didn't quite get to us. They couldn't put a laser on the optic nerve and the macula. So a lot large part of the I wasn't optimally treated, so the disease may have continued to progress and, uh, things started and many people ended up with the tract amis and blindness. Then things started changing, with little better quality lasers, opening up arteries, doing starting medical therapies on some new protocols and with these anti veg F drugs that became available as well, a steroids. So for many years, we used next megazone in the eye and new ways of giving that were developed. And now we have multiple drugs that affect Jeff. And I'm going to show you very briefly how you can actually improve a patient's vision. So here is ah, some background data to this. This was in the New England Journal in 1994. Very good scientific background for what we're doing today. If you measure of interest, fluid and artifice, fluid veg F levels, they're extremely high in people with mild disease or no disease, it's almost zero. And here you have levels going up 2030 times in people with retinopathy. So this is another studies showing the same thing. People with macular oedema without proliferation also have elevations invade. Jeff, there are extremely high levels on highly six, statistically significant. And what is interesting is, if you use this e TDRs scale, the higher you are in the scale. The higher your your bed. Jeff left. I don't want to give you the impression that Jeff is the only mediator. There are multiple other things that we don't have time to go into today. Uh, some of these are drugs. Have bean tried, Some have failed, some others are in development. So this is an interesting field. We're trying to address, uh, DME through multiple mechanisms. And some are non specific treatments like steroids, for example, pressing inflammation. So people used to inject steroids into the I. Then came an implant that pushed this little pellet like thing into the eye where had worked for several months. And you can see the reduction in the, uh, oedema in this population, Aziz, compared to sham patients. So there was a a good benefit from steroids, but it led to problems. There's when you give steroids. As you know, you get more cat track and if you're giving the steroid into the eye, cataract rates were extremely hot. So people started targeting VHF, which has been implicated in a wide variety of diseases, including age related macular degeneration, which in a way is very similar in its manifestations to written apathy and diabetic macular oedema and what was really compared to laser. What was quite striking with the early studies that were published it showed an improvement envision never before had been seen. Patients will be referred because they had blurred vision and tear retinopathy. And now we're include improving their visual acuity. So there and a number of agents became available. So N. I h. Launched a very big study that was has been published in the New England Journal a few years ago, looking at comparative effectiveness off three different anti veg F drugs now, and I just want to show you a summary off the results. Over one year, there were differences, some what appeared to be better than than others. The differences are not huge. So long as you give patient is getting some treatment, you can see the mean. This is main change in visual acuity. Letters course for patients to go up three like off rather go down three lines on the vision box, which we all are very familiar with is a big deal. They really feel quite quite better. So there's subtle differences between drugs but any drug treatment addressing where Jeff is useful and years it in for the, uh, scores over a longer period of time. And if U. S so if you go from 2032 to 2040 20 baseline 2050 that's a pretty bad, uh, vision. And in half the people there, they get us very striking benefit so and they see this benefit within three months. You see, on the right hand side a two step improvement on the left hand side of three step improvement here they're talking about improvement in E T E. R s severity schools. So you're some more studies showing a similar kind of things improvement in visual outcomes. And this is for both proliferated retinopathy as well as macular demon. You you see a very striking picture reduction in it that you can see in oedema on the funders photograph and you see it here on the coma. Grammas. Well, so people started using this about 345 years ago quite extensively for macular oedema seeing good results. But then the question came up. It should be be treating patients earlier instead of rushing to treat them when they've already got proliferated. Changes? What if we treated them early? Would it mean that the disease wouldn't progress? And they need less injections? So a new study has bean recently completed, called Panorama. This is a double mass randomized prospective study looking at one of these, uh, anti V Jeff's agents athlete, except when people with moderate retinopathy years the scores which fairly moderately severe, not very advanced. And over 24 weeks, the endpoint was improving it two steps in the score. So what was done is that three groups of patients one got a sham injection with no, with nothing put in. One group got 2 mg every 16 weeks on. Then I repeated 16 weeks and one guard it at eight weeks, and they were followed for 24 weeks. And then there was continued follow up for two years. And here you see the very striking improvement group One who had a three monthly a monthly doses on then, uh, they were then quarterly, uh, and then ah, group to got it. There wasn't There was a slight difference between the two. Very strikingly different from, uh from from the from the sham group. And if you combine them all about a 60% of patients had a two step improvement. Where is only 6% headed with in this sham group? If you look at patients improved from baseline, Uh uh, that was perhaps a little bit, uh, less severe. 15% in the sham group got ah benefit, whereas 65 to 80% of people in the treatment group that I had this kind of benefit. So if you look at it combined at 24 weeks, 58% got better. Treatment was stopped by then, but still people continue to improve by 80% had an improvement at the end of one year in those getting it every eight weeks and 65% in those getting it every 16 weeks. And after two years there was still a benefit that was seen so less frequent injections, Uh, but still getting a benefit over a long period of time. And also what is important is you prevent the further progression to proliferated retinopathy, which was a secondary endpoint. And you see that 20% of people in the in the sham group progress where it was only 4% in group one and 2.4% in those getting it more frequently every eight weeks. On a progression off you combine both the to, uh, it's 40% progress with shame, and only 10% got either, uh, macular oedema of progress off productive right novelty so very striking benefit. And in the years, a summary of the results vision threatening complications reduced by 82 to 85% compared to sham injection at one year and 62% at one at week. 100 and and a significant reduction in advance oedema in these patients. So in conclusion, anti vigil therapies have improved patient outcomes, including improving vision and slowing progression of the red novelty thes several drugs. Now that I approved that target, the veg F pathway, and for specifically for diabetic retinopathy, both proliferated as well as macular oedema, and we can address retinopathy both in advanced and moderate stage. Uh, for us looking after the every day care of people with diabetes, it's very important to recognize that this treatment is available and we need to be able to get this treatment of patients quickly. And to achieve that, we need proper referral to retinal specialist for every patient who has moderate or severe nonproliferation apathy. And how are we going to recognize those patients? Well, it's only through screening, so we screen all our patients, recognize who has a problem and make sure that they get to the right specialist, Thank you very much.
