Welcome to this program on critical advances in mitigating progression of diabetic eye disease. I'm Vivian fonseca from Tulane University in New Orleans. I'm really very pleased to be speaking to you in conjunction with the American diabetes Association Annual meeting which as you know is virtual this year. But I hope you enjoyed this virtual program and I will be talking about the importance of prompt referral prompt anti VHF therapy in order to prevent vision loss associated with diabetic retinopathy and the other diabetes complications in the uh huh. We're going to talk about integrating new therapeutic advances in diabetic eye disease and bringing together specialists in ophthalmology and associated specialties with what we are doing on the front lines of diabetes management. This is a CMI certified uh webcast symposium jointly provided by the University of Massachusetts Medical School and CMI Education Resources LLC. A commercial support has been provided by a grant from Regeneron. I didn't encourage you to go to the website that you see on the screen there and have a look at some of the other webcast, many of which are about diabetes that are available on this site. Now. We have a very exciting program today and I'm delighted to have an outstanding group of presenters. Rishi Singh is a staff physician, an ophthalmologist at the Cleveland clinic. Uh Also joining us uh as part of a multi disciplinary approach to this uh disease state is dr Powell chow's who's an optometrist. Uh He's also diabetes educator. So an optometrist who focuses on diabetes uh and he's in Tacoma Washington and also Charles Wycoff who is an associate professor of clinical ophthalmology in Houston at the Weill Cornell Medical College uh and works there out of Houston. So the entire symposium and additional diabetes cmI is available on diabetes gas dot com. You can download power points from this program from that uh website and you can also send in questions uh about diabetes management to I. Q. And A. By cmi dot com. Which is also a very useful website resource. So you're my disclosures and uh including grants and consulting. And let me move on to talk about diabetic retinopathy. As you know, diabetes is associated with so many serious comorbidities uh that affect our patient population very seriously. I always wonder about the reliability of statistics about diabetic retinopathy because it depends so much on the duration of the disease, the degree of control at what time point in the patients natural history. You're actually studying it to determine prevalence. If you take a population that's had the disease a long time and uh is older. You're going to see a lot lot more diabetic retinopathy. In fact some mild diabetic retinopathy changes occur in almost every person with diabetes because it's so hard to get good glycemic control every day over many years. So, what are we talking about here? We're talking about retinopathy when we use the term we imply that is the retina itself that's affected. But sometimes just in front of the retina you can get fluid leakage, which we'll talk about in more detail. Uh Oedema, just like you get in the legs, it's occurring in the eye. And we call that diabetic macular oedema. They're sort of related in a way. Macular oedema is a little bit more common in Type two diabetes than in Type one. We also have an increased risk of cataracts compared to people without diabetes, but it's not specific. You can get cat tractors, you know, even if you don't have to. And and the same applies to glaucoma, where there is a somewhat increased risk Overall diabetic retinopathy and diabetic eye disease is the leading cause of new onset blindness. And people aged 20-74. This has been known for for a long time. It really hasn't changed very much. And people with diabetes who read about the disease and worry about it are really scared of blindness. They're more frightened of going blind than dying from heart disease, which were so focused on in preventing in our in our patient populations, the leading killer. Yet people are just as worried if not more about going blind. And uh the patients are really fear about this. And they say that's the worst thing that could happen to now. When we look at the prevalence and uh patients with retinopathy. As I pointed out to you, two things matter duration of the disease and glycemic control. And so this is a eight year period. But if you go even longer you will find uh even well controlled people have an increased risk of retinopathy because they there are some natural processes of the disease that occur even with small changes in glycemic control that affect a wide range of path of physiological ATM. And here is uh sort of overview of some aspects of the uh path of physiology. Uh you get microvascular changes and in material abnormalities that lead to capillary closure and ischemia and that induces a response by itself to have new vessels form to overcome this. And those new vessels, as you know, are liable to bleed. You also have chronic hypoglycemia inducing secondary metabolic changes, including activating the soviet all pathway that's really very operative in in the lens of the eye application and products and activation of protein kinase C. That are probably more active in the retina, reactive oxygen species. Changes in addition molecules and nitric oxide and all of these actually impact. Where Jeff, in some kind of way, VHF stands for vascular industrial growth factor. Uh and there's an interplay between all these conditions that lead to a breakdown of the blood retinal barrier and leakage. So you get new vessels forming and leakage of fluid. So the major components of retinopathy of the proliferation and macular oedema. So let me focus a little bit on VHF, which we have known for probably about 25 30 years now to be very uh involved in the process of diabetic retinopathy. If you look at Jeff uh levels mainly studies have looked at vitreous fluid and actress fluid as well as in the blood, but blood is less sensitive to it within the i if you have no proliferated disease, your levels of wages are very low. But as you start getting active levels, you have higher and higher levels of Jeff and the vet Geoff level in the vitreous fluid has been linked very closely with the severity of diabetic retinopathy using a scoring system called E. T. D. R. S, which I will talk to you briefly about in a moment. So Jeff has been implicated in in a wide range of of retinal disease, age related macular degeneration, diabetic retinopathy, retinopathy of prematurity, etcetera. So all of these have been treated with a definite, but when Jeff is not the only mediator, there are other abnormalities that I pointed out earlier to you involved with macular oedema, some which I didn't mention that might be maybe important. Uh Some of the other newer newly described uh uh side of kinds that affect blood vessel flow and blood leakage and a very early abnormality is the parasite loss, which leads to loss of the support of the blood uh of the blood vessels and contributes to hypoxia. So what we see when we examine the i is this loss of support. So this out Pao ching, so called micro aneurysms. The little dots that we looked at when we use a fund a scope. And you sometimes see oedema which is uh leakage from the capillaries due to breakdown of the of the blood vessels, lots of the of the cells there. And you get accumulation of fluid and swelling in there and there's some degree of uh deposition of life of proteins that are seen. So when we uh we use these changes to classify diabetic retinopathy, uh you see your a three different stages uh microvascular damage leading to non proliferation retinopathy. You see these small dots there uh there are no major new blood vessels yet. But this patient clearly has diabetic retinopathy. And this is a process that's going on right through the body. You can see it in the eye because that's visible, but it's also occurring in the kidney. And you will often find patients with diabetic retinopathy also have diabetic nerve property. They also have a neuropathy and cardiovascular disease and all these changes are occurring in those organs as well. Another aspect is this swelling in the eye and you can see that it's in a very central location close to the macula and this is going to affect central vision. And you can see this uh demography and I'll discuss that in more detail. Uh and this can a car even in the early stage before you get new blood vessel formation. Or when you get prolifically written apathy as well, which you see on the on the right hand side, which is the very late stage you're getting. These new blood vessels that are not well supported within the layers of the retina and they begin to bleed. And it's the large bleeding into the vitreous that leads to a sudden visual loss. So how do we make this diagnosis? And we need to get an image of the retina? And we used to do it a lot before we just simple Fanta Skopje, but that's not very precise and it misses a lot. And we have developed modern ways to uh to recognize this now, a simple thing and a simple tool that I believe needs to be expanded a lot is simple photography at the point of care and this can be done uh anywhere and sent on uh to an ophthalmologist for reading through telemedicine. People are working on uh uh techniques to uh use simple things like uh bluetooth with smartphones to upload the images. And in fact uh there are a number of studies going on looking at artificial intelligence to read these until somebody that an ophthalmologist needs to look at this picture because the sheer volume of patients with diabetes that makes it challenging to get everybody's Iceland, I just showed you a picture of that fancy image. You see that that some of our colleagues in ophthalmology are using uh it's called optical coherence tomography. Uh on the top you see a normal retinal layer, it's like taking a slice through there, uh no edema there. And below you see this boy labour fluid. Uh this is clear Oedema that's accumulating in one part of the retina, obviously that's not normal. And if you're dependent on the rods and cones in this area, looking at a particular image is going to be distorted and not surprising because you've got fluid in there. Another tool that we used to use a lot of and has limitations and uh is still used but not to the same extent is fluorescent angiography where you inject a dye and you get a much better image of the actual capillaries and the tree that you see. So the same patient that you're seeing here on the left hand side, you're seeing the image year of the blood vessels directly themselves. So we need to know that this can be done and we can't do it in primary care or offices. So we need to refer them uh to get down. These wonderful tools are available in most ophthalmology clinics, but patients need to be referred. They need to have a dilatation of the of the eye so that a good picture can be taken. And patients are often asymptomatic. But as I pointed out, vision loss can occur suddenly and very severely and that's often very difficult and challenging to manage. So we need to prevent that by regular examinations. Some people do get symptoms and the symptoms of dems are quite striking. You start getting blood vision occasionally double vision, that that would be very distressing and patients would come to you. But sometimes people just get a little patchy vision loss and they say, well, you know, it's not quite right but I'm getting older and that's the way it looks like they might ignore that. Uh And that is dangerous. So there are a lot of gaps in ophthalmic care for people with diabetes. If you look at statistics even among bell insured patients, a large number are not getting uh the uh the screening as recommend A recent cross sectional data. Uh this particular data is a little over now, but it's still true today. Over 40% of patients had not been to heaven. I examine the previous 12 months and they've got macular demon. Uh The patients don't remember that they had been informed that their eyes could be affected. Of course it's starting all diabetes education classes. But that's often done in a hurry. And patients are focused on their treatment and measuring their blood sugar, giving their injections. They don't remember these little details that they've got to go every year for an eye exam. And a large number of people have my visual impairment that they've ignored and just thought that they need better reading glasses and not got diabetic written out. So as a result, patients with sometimes vision threatening, written out buddy don't go for follow up exams. They don't get examined and they are unaware that they could suddenly lose their vision. So what can we do to make a difference? Uh clearly hyperglycemia is a key modifiable risk factor that we are managing in our clinics and that's in our hands still and will not be done by the ophthalmologist. So we have a role in that it's the same with hypertension management. There's some uh evidence to suggest that uh a wrasse innovation might help more than other blood pressure agents, but we're using that for kidney disease anyway. We need to manage the lipids, not just the LDL, which is important for the uh prevention of heart disease. But there's also intriguing data with the fibroids uh on lipids uh to lower triglycerides. And they have been shown to have some small effect on on slowing written off of the progression, but they're not approved for that indication. The key thing that we need to do to get the patients to have those wonderful new tests is an annual exam with referral to an appropriate person. A retina specialist who can actually diagnosed and then get on and treat. I mentioned the role of telemedicine. Uh It has improved access to care. Uh There's a lot of data to suggest that it's very cost effective can be done in a wide variety of settings. Uh many uh patients who are challenged with finding the time to go for another clinic appointment can do it when they come to the clinic. We use it in in several places uh where patients may not otherwise go and as a result we identify who's got a problem. And there's a good agreement between retinal screening uh done this way and the sophisticated our exam, you do miss a few. Some of the picture is not very good. But we can identify those patients and make sure they go for an exam. So what evaluation, what else can be done? You have the colorful funders photography either in your office or the ophthalmologist office. It's the gold standard uh for evaluating patients. It has c implications for severity follow up recommendations and treatment conditions. And here is a a good example of a nice color photograph showing when you focus in on the right hand side. You've got these new vessels. These could bleed any day. You shouldn't be waiting. These people need treat now. The early treatment of diabetic retinopathy studies, all study done many years ago had a standardized protocol for photography And they did this seven field 30° images, 16 images for. It's a standard procedure that's still done uh in all trials that are done today because they have a well established grading uh uh criteria, but it does require a skilled retinal photographer. This cannot be done in a primary care. What you need is a multidisciplinary team. You need this multi model management system using multiple clinicians, multiple agents. And you will be hearing about some of these, particularly some of the newer therapies. Even the older therapy, steroids and laser is still done today but is somewhat destructive. And uh we want to stay away from that. We have new drugs and you'll hear more details just to introduce you to the the anti VHF uh, inhibitors. There are three on the market, uh um mainly monoclonal antibodies against Jeff, different types of antibodies. The uh individual trials have been done to get them approved and uh there was even a comparative trial that was published a few years ago uh with the large number of uh ophthalmologists around the country intervening, identifying some differences in the success rate between these. But even so they all work to some degree. So I think the most important thing is to get the patients to have this therapy or have the advantage of this therapy to work and patience. See responses very quickly. So if you use this E. T. D. R. S severity is called more than three step worsening or improvement is considered significant. We don't want our patients to have worsening. We want to see an improvement and you can see a three step improvement in a large proportion of patients with these new therapies within three months. You don't see that that much. With laser therapy, laser therapy stops progression. But here you're seeing an improvement in vision. Uh Certainly three step is very significant, but some patients will notice even a two step improved. So Andy major therapies have increased patient outcomes. Uh Let us to identify retinopathy, identify progression both of macular oedema and retinopathy. And with the approval of these new drugs, we now have other methods to address. Right now. We need to manage this early uh get patients to be seen appropriately have the appropriate imaging so that they can be treated. Thank you. And now I'd like to hand it over to my ophthalmology colleagues to talk to you about specific details about these therapies.