thank you for listening to this program entitled Optimizing Management and Treatment Strategies in age related Macular Degeneration. We're going to talk through some cases and discuss some new data regarding the treatment of executive, and my name is Rishi Singh from Cleveland Clinic in Cleveland, Ohio. First, I want to start off with some really great news. Uh, the use of anti V e g f for anti vascular endothelial growth factor Therapy has really reduced the progression legal blindness in the world. And here you can see a study that was done in Sweden, Israel, Britain and the US, which shows a significant reduction in the level of legal blindness of the past two years during the anti Bgf era. And that's a responsibility or a commitment because of all of you who are probably listening to this program now between optometrist, ophthalmologist and retina specialist. We've all done a great job of referring these patients appropriately, trying to get them in for treatment and obviously resulting in a significant improvement in the reduction of legal blindness in this population. We realized that anti B G F therapy has become a mainstay in multiple disease states, including central retinal vein occlusion or diabetic retinopathy and retinopathy. Prematurity and wet are exited of age related macular degeneration. So how do we optimize the visual benefits for patients with neo vascular M. D? You know, neo vascular MB therapy has now been around for almost 15 years, and we've learned a lot through some of the studies of what the optimal treatment should look like. And here is my take on what the optimal treatment should look like. A list of early diagnosis and treatment. To ensure the improved outcomes, it should start off with the initiation of treatment with loading doses to help maximize visual acuity. In the early phases, we should be able to titrate and personalize the treatment approach for each patient. The match, the level of need, and we should be able to sustain this therapy over long periods of time. And we use visual function and morphological parameters on the CT to guide our treatment decisions in order for this to occur. So this is sort of my take on how we can optimally treat these patients, and I'll talk about the data that supports each of these pillars in the next upcoming slides, one of the real ways that this has improved. Our ability to treat patients has been the detection of this disease in our population, and imaging has evolved from colors from the photography to fluorescent angiography. We have the ability for funding auto fluorescence, which we incredibly helpful for those patients, especially with geographic atrophy or the end stage form of dry or non exhibited A M D. But we also have things like E. T, which have been very helpful at monitoring and managing patients with exited max deterioration in our populations over time. And lastly, we have optical coherence tomography angiography, or O C. T. A, which allows us to look at the retinal vessels without using a die and looking at the structural changes in those patients over time. In addition, we've known that we can see significant response to treatment with a few anti bgf injections. On the left side, you see a patient as almost a complete response with very little fluid after the injections are given and on the right side you can see another great response from anti V Jeff treatments in response to this fluid that's present within the retina, and that improvement over time. So here's a case we'll talk through and the patient has multiple compartments of fluid. We have both internal fluid, sub retinal fluid and sub RP fluid, and the question here becomes is which of these plays a role in our decision making and what parameters should be looking at to determine if there's truly success in treating these patients in our hands. And so let's talk about some of these individually. Internal fluid is a hallmark of specific types of neo vascular allegiance. It commonly occurs with a Pickman empathy. Let attachment and associate with aggressive lesion types, and it's responsible for poor vision. Seen in eyes with neo vascular station, it's one of the negative prognosticators to the visual outcomes. If you see persistent I ref over time, and what we found essentially from some of the studies is that valid point, which is that while there was no significant difference in the fluid early on, if you look at the total fluid compartments when you broke the fluid out into separate compartments, you saw that internal fluid early on and the ability not to dry the retina because of this presence of fluid resulted in lesser visual gains in comparison to those patients who had no fluid early on. In the course of the study, there's almost a two letter differential here in those patients within this this view one post talk analysis and in addition, interational early fluid had significant roles with regards to roll difficulty in driving. So these are patients who obviously need to get around and drive and obviously need to determine, you know, having the ability to have some independence. And what you can see is that early international fluid really had an impact with regards to their visual outcomes over the course of the study and obviously, their visual functional questionnaire outcomes as well. Again, you can see why that's important, because those with phobia I r f had significantly worse outcomes than those with no I R f over time. And here you can see those patients have lost vision with mobile I R f. In comparison to those patients, were totally bone dry, had better visual acuity, outcomes of almost a line division at one year. In addition, we know that from some other trials, like the harbour analysis again. You see that, uh, that the I R F present and here in the Green showed you a worsened visual outcome in person of those patients who are again bone dry during the course of the study, let's start off with the case to maybe he'll he'll illustrate some of these points from the studies. This is an 87 year old female with Nebraska AMG treatment for the past five years. She's receiving random is a mob as a PRN treatment. She has great monthly follow up. She comes to see me no matter what the weather is or what the situation is. Her visual acuity has been decreasing in her left eye, and she's count fingers as you can see in both eyes right now. And here you can see the presence of her changing her left. I received some hemorrhage present, and here you can see that same change left eye, which a large pigment apathy detachment is present. There is some oval fluid presence is somewhat of fluid and internal fluid as well We planted giving your random is a map injection, and she was treated with that over the course of the study. But the real question becomes is what is this uh, this pigment episode attachment which I just showed you. That picture is thought to be the most difficult morphology to treat within neo vessel AMG. So what is the difference in these drugs? And actually, this is a study that I did with my former fellow Yasha Modi, where we looked at the response of each of the pigment of the detachment to all three drugs, a vast and Lucentis and Alia to compare what the treatment outcome was in those patients. And we use this polynomial fit algorithm which essentially is where we are using the R p as a line and following the RP line for depression or elevation in those patients, determine what the responses. And here you can see the results, which was that the flippers left arm had a greater reduction in the ped height in comparison to the other two drugs. Arguably, this was certainly biased because of the fact that the flavor patients were given, uh, the were pre selected to have those who had higher P E. D s, the retrospective series. We didn't have the ability to not influence the investigators. Some of the investigators felt like they had a better response to PDS and therefore they gave them the highest PDS to the Flipper set patients. Nonetheless, you can see a nice improvement in the current height as a result of getting those injections. And here again, the cube volume. And here's just one example of a patient with all that follow up over time, where you see a nice improvement in the pigment of the detachment as well as in visual acuity. Over the course of almost two years, for this patient was treated for WebMD. This patient, actually the one I mentioned to you in the case, actually had 11 anti V E G F injections with 2015 50 vision at the end of the study. Again, I think that's an important and impressive outcome, given their presenting visual acuity of counting fingers due to that new bleed you saw. And here's just a comparison showing you before and after and again before and after on the T as well. I'll show you that I said permit there. This is case to this patient who is 2100 vision, uh, pressures 15 millimeters. Mercury can see a large pigment of the attachment present some rental fluid and maybe some interesting fluid present as well. And you can see after six months after five anti B e g F injections, this patient is now 2025 has a little bit of separate all food resolution that's left over and and some IRA and software, but otherwise didn't really quite well. Edit Year one has good vision and has maintained again good vision over time. Year two has 2030 vision with some internal fluid present but not too bad again able to maintain good vision over the course or your 3 2070 vision. Now you can see some macular atrophy forming. You see that atrophy, which is a sub elimination change within the O. C. T. Where you can see some changes from that as well. And the right I was then initiated as well. During this course of the study, due to wet change as well, and you can see continual treatment, the patient has led to 2030 vision the right 2100 vision left again, uh, continual evaluation and management. And at five years now, this patient is 2070 vision left and 2030 in the right again this is starting off at counting fingers on the left, which I think is a very, very impressive outcome for these patients over time. And here's just my EMR showing you the graph of those patients over time showing you that there's really a nice improvement in this graph with regards to the retinal thickness during the course of treatment, albeit that there were some times where there were ups and downs. The goal of the majority of time was to get the downs present there so they could at least show that there was a benefit of treating this patient over time. This gets back to, I think, to some of our our averages or durability challenges with these drugs, and I showed you this patient where I saw essentially monthly. She was happy to come in every month as an as needed basis. But that's tough to do for all patients. And so what we need to do is really evaluate what the durability is of some of the drugs we have available right now. So this is anchor Marina Harbor Cat. If you want to, they should a mean number of 10.2 injections, a range from 6.6 to 12.3 injections over a one year period. And again, you really get a sense of, like, where the higher, uh, you need a high number of injections to already get a good clinical outcome. And this was seen actually in the, uh, seven up study where patients actually followed after really intensive therapy over a seven year period. And what you see here is that after that year four that their vision sort of drops off a lot because they weren't seen as intensively. They lacked the enthusiasm coming back, and they never got treated as much, and therefore they lost vision over time, had the same problem after two years of intensive therapy, looking at your five, where people were allowed to sort of do whatever they want to do in practice. You see a lot of patients that didn't come back probably and didn't get their injections on time, and you see a lot of detriment to their vision. As a result of this course, This was actually a really interesting finding that one of my med students had, and I was super impressed that she was able to pick this out and what she said was, Well, why don't we look at the five year outcomes and see what's the relationship with things like visual acuity or even a number of injections over a five year period? And here you can see the result of that five year injection time framework shows you that there's a linear relationship between the mean number of injections and the visual outcome in patients for more than five years. It's really important to remember that that long term outcomes are really based upon the injection frequency. And so we've done a much better job, I think, educating our colleagues that this is something we need to pay attention to in order for them to have the greatest success in treating patients in neo vascular. And so just to summarize my talk today, what is the optimal treatment in patients with neo vascular AMG? Well, it depends a lot on you, US optometrist or ophthalmologist and partnership with retina specialist. Getting these patients into practice and being evaluated and referred for this condition, and in particular where optometrists and ophthalmologists come into play, is in the early diagnosis and treatment to ensure that we achieve that the top visual outcomes that we can get with these patients. We need to see them earlier with good vision. They need to be promptly referred within 2 to 3 days of their diagnosis for evaluation and management, because earlier we get them into our practices, the more faster we can deliver the anti V E G F injections and again that will allow for the visual function and the morphological improvements to occur on the faster in those patients without having significant long term detriment. In addition, we know that loading doses do help, and there's been some studies have compared loading doses with and without the study and found benefit and loading dose ng the patient and finally tie trading the treatment interval between determining, uh, you know what interval you're going to see the patient back at and do a treat and extend paradigm or something else. Hi trading and for each patient is really vitally important and finally sustaining therapy to maintain early visual gains. It's a partnership with a patient to make sure they understand the need to come back at a regular basis in order to be treated and monitored
