Video Preventing “Inevitable” Blindness in the Diabetic Patient—Optimizing Management and Treatment Strategies for Diabetic Macular Edema Play Pause Volume Quality 1080P 720P 576P Fullscreen Captions Transcript Chapters Slides Preventing “Inevitable” Blindness in the Diabetic Patient—Optimizing Management and Treatment Strategies for Diabetic Macular Edema Overview Hi. I'm Charles Wykoff, a medical and surgical retina specialist here with you. Discuss diabetic macular Dema in the context of diabetic eye disease, optimizing management and treatment strategies. I'm a medical and surgical running specialists from Houston, Texas. As you know, there are two major forms of diabetic retinopathy that contribute to vision loss and ultimately, blindness among patients with diabetes, DME is illustrated at the top and proliferated. Diabetic retinopathy is illustrated at the bottom the day we're going to focus on DME or diabetic macular oedema. This is a disease state where there is breakdown of the normal retinal vasculature. The inner blood retinal barrier breaks down and the fluid that is normally contained within the normal retinal vasculature leaks out, filled out into the normal retinal tissue, distorting retinal architecture and ultimately causing vision loss. Remember the DME of the number one cause of blindness among patients with diabetes and therefore the number one cause of blindness among all people in working age groups occur across our country, a very common path biology that we deal with regularly. Today I want to talk about four major concepts related to DME, and we'll go through each of these chapters separately. The first is to talk about management of the different DME subtypes, their eyes with non center involved. DME Center involved DME with visual loss in the middle and center involved DME without visual loss on the right, let's take the first of these categories in this O. C. T. Image at the bottom, right or optical coherence tomography. There, these air essentially cross sectional images of the retina and in the center you have a color funders photograph. You could see the phobia will dip as illustrated here on the bottom, right is completely preserved. This patient is 2020 and completely asymptomatic. But as you see on the O. C. T heat map at the bottom left, you can see there's this large area of swelling denoted by the white and the red areas of thickening. This is essentially a topographical map that shows you where the thickened area is when this area involved the central phobia here, that is when patients often become symptomatic. A wide field flourishing angiogram here shows relative preservation of the blood vessel throughout the retina. One thing that can happen in diabetic retinopathy is you could get steamy, a or retinol non profusion where the normal blood vessels actually die. We're not seeing very much of that in this case. We'll see more of that future cases. But what you are seeing our multifocal areas of bright spots, these air areas where the dye is leaking out of the normal blood vessels, showing that breakdown of the normal blood retinal barrier and is that DI leaks out that is essentially showing accumulation of fluid, which causes DME. When we think about how to manage a patient like this, we actually have to go all the way back to the 19 eighties to a landmark trial that is still valuable. The clinical practice today called the E. T. D. R s or the early treatment Diabetic retinopathy study. What we learned in that study was that the appropriate application of macular laser reduces the risk of moderate vision loss by about 50% and critically, that benefit of focal laser was independent of baseline visual acuity. What was the baseline visual acuity for the patients in the each of US trial? Well, the majority had 2040 or better vision, with just 7% having vision worse than 2063. How does that compare with all of our recent pharmaceutical trials looking at anti veg F agents and cortical steroid options for the management of DME? Well, there's a striking difference. All of our pharmaceutical options to date, except for one trial called DRC Protocol V that we'll talk about later today, have had visual acuity is on average in the range of 2050 to 2080 much worse than the eyes and the dressed study. Therefore, in many cases, vocal laser can be used. Till today. I applied focal laser to this I and has been stable here through one years. And in fact this I have been stable for many years with preserve central vision and in fact, to date, no recurrence of their DMI. What about center involved DME with vision loss. In this context, the most common treatment are injections of pharmaceuticals. Inside, the vitreous cavity is illustrated in the middle of the bottom here, which causes resolution of that fluid. Most of these agents that we use are proteins that target and inhibit the function of vascular. And if you're a growth factor, however, you can also use corticosteroids to inject inside of the eye, which have a broader anti inflammatory effect. But the goal here is to cause resolution of the fluid. You can see this in a patient of mine that improved from 2018 to 2032 with multiple injections over many years. We have multiple phase three and large prospective studies beyond phase three trials demonstrating the value of anti veg F agents. CR CR Net Protocol T is probably the most widely referenced of these because it is the Onley study to date directly. Compare our three commonly used anti Veg F agents listed there at the top left so flavor step over to the map and ran a busy map. What we saw is that patients with good visual acuity 2040 or better on the left. All three of these agents from vision Perspective performed similarly among patients with 2050 or worse, vision is shown on the rights patients treated with a flipper cept appeared to do meaningfully better than patients treated with the other two agents. When an atomic perspective, there was a slightly different story in DRC. Our protocol t critically. The key point here is that Bevis is a map and Blue appeared to be a worst drying agent independent of baseline visual acuity, and among patients with worse vision is shown on the right Flipper ship again appeared to be a stronger agent. I mean, leading to improved rhymes compared Thio Davis is a map, especially, but also some numerical differences and improvement compared to run a business map. Now I want to talk about a key point. Earlier treatment in this population leads to better outcomes, and we've seen this from many different angles. First, one of the first large phase three data sets analyzed for DME use the population of patients illustrated in white here that were sham injections. In other words, they receive no therapy for their DME, and that was compared to monthly anti the Jeff Injections with Ran a busy man What you saw through the first two years in the dark parts of these graphs through here was about 10 to 13 letters gained, with monthly Aunt of Egypt dozing compared to very little visual acuity, change with observation, but then critically, in this gray zone, what happened was the control arm of sham patients now switched over and receive monthly anti V Jeff dozing, and they do gain a little bit of vision. They gain about 4 to 5 letters, but they never achieve where the other arms achieve. With initiation of monthly dozing two years earlier, we saw a very similar effect in the Phase three Vista vivid trial. This crowd had a different structure in that there was rescue criteria. Eyes here in, um, purple randomized toe vocal macular laser. But then they could escape and receive a flipper ship anti veg F dozing if they lost visual acuity. So how did those eyes do? Well, by necessity, they lost visual acuity here on average, 10 to 11 letters at the time of initiation of anti veg F a flipper Sepp dozing. And then, once you initiated the anti V Jeff treatment, you can see they gained a tremendous amount of vision 13 to 17 letters. But if you look at their absolute visual cue to gain, it was only 3 to 6 letters again, substantially below where they probably would have been if they had initiated anti by Jeff Therapy. From the beginning, the laid treatment leads the sub optimal outcome. We have seen this also in the DRC on that protocol I data set, in which patients with better visual acuity at Baseline they tend to gain less absolute vision. But in fact, ultimately they have better visual function. So while they're gaining fewer letters because they started with better visual acuity, they ultimately have better visual acuity. So overall, a key concept is to diagnoses. Patients early get them into treatment early so that they can maintain optimal visual function. Long term, you do not wanna wait until your patients are symptomatic or have blurry vision to think about. DME. You want to think about DME early in all, patients with diabetes make sure they're receiving their appropriate screening. What about patients with good central visual acuity? And yet center involved the M E, as shown in this case on the right. The only trial to analyze these patients is DSL Protocol B, which randomized patients to initial anti veg F therapy with a Clipper ship also known as I, Leah or initial Mac, your laser focal laser or observation through two years, there was no difference in the rates of patients who lost substantial visual acuity, but the lingering question has been our their patients that should be treated earlier, even if their vision is good and they're asymptomatic. This recent publication looked carefully at that. Observe baseline factors that predicted more likely progression to vision, loss and the need for treatment in this clinical trial. Patients were Onley given anti v Jeff therapy when they were randomized observation. Once they had lost about 10 letters of vision. And what we saw was that about a third of the observation arm ultimately did lose vision and received a flipper Sepp dozing when we looked at the baseline factors that correlated with an increased need for anti veggie therapy because vision was lost, three factors stood out thicker retinas, worst diabetic retinopathy, severity and the need for fellow I treatment In the context of all three of these clinical factors, those eyes had a 65% chance of losing vision and receiving a flipper Sepp anti veg F dozing. And so the take home message here is that when you have thicker retinas is shown in this I when you have more severe diabetic retinopathy, for example, um uh, moderately severe to severe NPD are or when the fellow I is already receiving DME treatment, any of these factors are present, and especially when all of these factors are present, we need to consider earlier intervention. Here's a clinical example that demonstrates this. This patient was asymptomatic. They were 2022 2025 both eyes, you could see the mild gamy they're on their left I with some slight architectural distortion. Fortune angiography did not show substantial retinal non profusion and showed these areas of leakage around the macula on the left eye of interest to write. I also had some mild leakage and I observed this patient for a year because remember, they're asymptomatic. And as long as we're being followed carefully, we have good data that we do not need to treat them early unless we see some progression when their vision is excellent. But here, by one year and three months, the patient has become symptomatic. They have lost a little bit of vision. Now they're 2030 and you can see their architectural distortion is getting worse. So I initiated. Bevis is a map dozing here. I gave them four treatments with this is a map. The fluid did not go away and therefore I switched them. What we believe to be a sort superior drying agent of Flipper cept I treat the monthly with a flavor cept and you can see now the retina has been dried here by the end of the first year, and now I begin a treat and extend protocol where I'm lengthening the intervals between each of the doses. And now I'm out that four months. In between each treatment, the patient is essentially 2020 and very happy with resolution of their DMI. Here's another clinical example that tells a slightly different story you can see again. There's relatively mild gamy, with some preservation of the phobia contour. This patient had very minimal symptoms. But when we do a forcing angiogram, this is why looking at the vasculature is so important. Uh, much more important to look the vascular in addition to the anatomy than just looking at the anatomy alone on O. C. T. Because here you could see these extensive areas of leakage. So, in fact, this patient didn't just have DME. They also had high risk proliferated diabetic retinopathy, a condition that can progress rapidly if left untreated. So even though this patient is 2020 and relatively asymptomatic, they receive treatment right away. I performed anti veg up injections and once the retina was stabilized from a d. M E perspective, I applied peripheral retinal laser or PRP. Let's switch to the third chapter, the intersection of DME and diabetic retinopathy. Here's another clinical case. This is a patient of mine that was symptomatic with substantial vision loss 2080. You can see dramatic architectural distortion here with DME, you could see resolution of that fluid repeated anti V Jeff injections through three years of dozing. And then I transitioned to an observation protocol to see if they would remain stable and what happened. Six months later, they developed proliferated diabetic retinopathy. You could see the area of the pasteurization here, even though the DME itself has not occurred. This is a phenomenon that we have seen repeatedly now in prospective trials here shown data from the Endurance Extension Study as well as the open label extension study following Vista and vivid and ride and rise phase three trials respectively. The key point is that over 1 to 2 years of follow up after decreasing the dose ing frequency with anti veg Jeffs during the phase three trials, you could see that about a third of eyes will experience diabetic quit not but the severity worsening many of these progressing to proliferated disease. So the silicone point is that even if GM is welcome rolled and we begin to decrease our anti veg F dozing frequency, we must be careful because he PDR can often initiate. At that time, we saw this also in the five year DRC, our Protocol T analysis in which on the far right you can see that the portion of patients with P. D. R or those treated with PDR has increased from about 24% of two years to, um, approximately 35% at five years. So what did I do with this patient? Developed, proliferated diabetic retinopathy. Why did what I often do, which is combination therapy. I treat them both with farmer pharmacologic anti by Jeff Dozing as well as applying panel on the photo coagulation into the periphery. Let's not talk about the long term management of DME for our final chapter. Here's another symptomatic patient 21 60 substantial visual acuity loss in the right eye. They're treated over the course of three years. The visual acuity improves to 2025. This is the home run. The patient is very happy. And what did we do? Should we continue our anti V Jeff dozing? Or should we stop in this case? Initially, I observe the patient to see if they would be stable. You can see through about six months to follow up. They are relatively stable, but in the second six months you can see that the DME begins to recur and they begin the need dose ing approximately every 6 to 8 weeks. Is that dozing frequency after multiple years of treatment? Common. And the answer is yes. We have two large extension studies that have demonstrated this. This is the open label extension which demonstrated that in years, 3 to 5 of DME management, about 25% of eyes will likely not need ongoing regular anti V Jeff dozing. But the translation of that is that 75% of patients will require on anti veg F dozing long term with an average annual eyes injection frequency of about 3 to 4 shots per year. The endurance extension studies showed the same thing through the 3rd and 4th years of management. We saw that the proportion of patients requiring ongoing anti Jeff dozing was about 75% again, with a annual eyes dozing frequency of 3 to 4 injections per year. We also saw during this time period that the visual acuity gains achieved during the initial core phase three trials through the first three years were maintained in years 4 to 5, with endurance so in summary from a long term outcome perspective. UH, a small minority of patients, maybe 25 to 30% may be able to remain stable after achieving a stable macula with frequent anti V, Jeff does saying. But the remainder of the majority of patients will likely require ongoing anti V Jeff dozing for either DME and or diabetic retinopathy with an average annual eyes injection frequency of about 3 to 5 injections per year. Thank you. Published January 26, 2021 Created by
