Hello and welcome toe optimizing management and treatment strategies and diabetic eye disease. A case based study overview of new blindness prevention treatment strategies for diabetic retinopathy. I'm Jennifer Lim, professor of Ophthalmology, Marien Chunk chair and vice chair of ophthalmology at the University of Illinois at Chicago. I'm also the director of the Retina Service. I thank you for joining me today. Today we'll be discussing diabetes and importance of referral for diabetic retinopathy. Diabetes involves 415 million people today, and this is projected to increase to 642 million people by 2040. Diabetes is a leading cause of new blindness in the ages of 22 74 year old people. In addition, this increasing prevalence of diabetes comes with concomitant increase and the prevalence of diabetic retinopathy. It's very important that early intervention be performed in diabetic retinopathy in order to prevent visual loss and other complications such as progression to prolific tive diabetic retinopathy. In fact, the prevalence of proliferated diabetic retinopathy increases with e duration of diabetes for Type one diabetics. After 15 years duration, the prevalence is 30% for Type two diabetics receiving insulin after 15 years duration the prevalence is 15 to 20% and for those not on insulin, the prevalence is 5 to 10%. Nonetheless, patients can also develop not Onley, productive diabetic retinopathy, but obviously non proliferated diabetic retinopathy. It is very important that these patients be referred for timely diabetic retinopathy evaluations and treatment as needed. The path of physiology of diabetes causing diabetic retinopathy involves the fact that chronic hyperglycemia causes metabolic responses as listed here on the slide. These in turn lead to increase veg off production as well as micro vascular damage. Chronic subclinical inflammation can also concomitantly make this worse and thies to result in retinal capillary, leuco Stasis, endothelial damage and capillary closure. Combined with ischemia, which also increases veg F production, there is resultant breakdown of the inner blood retinal barrier causing diabetic macular Dema, as well as progression to prolific tive retinopathy and other findings of diabetic retinopathy. Diabetic retinopathy can be classified into diabetic macular Demas presence or absence, as well as by the presence or absence of non proliferated diabetic retinopathy and prolific tive diabetic retinopathy. Diabetic macular oedema is characterized predominantly by swelling in the central retina, and this typically accounts for most of the visual loss in patients with diabetic retinopathy, it can coexist with non proliferated disease as well as proliferated diabetic retinopathy. When we look at the classifications in terms of non proliferated or proliferated diabetic retinopathy, we're specifically looking at the microvascular changes present within the retina, and we will go into this categorization shortly. Non proliferated diabetic retinopathy can be categorized as to mild, moderate or severe. Over the years, this chronic micro vascular damage increases and typically with non proliferated diabetic retinopathy patients may not yet have significant visual loss until they developed diabetic macular oedema or more severe stages of diabetic retinopathy. Again, early referral for evaluation is extremely important in this stage. In prolific tive diabetic retinopathy, neo vascular ization of the retina has already occurred, and there is a very high risk of severe visual loss. So when we see a patient with diabetes who has no diabetic retinopathy, it is not necessary to refer to a retina specialist. But the patient must return for an annual eye examination. This must be a dilated retinal evaluation in patients with mild non proliferated diabetic retinopathy. Again, a referral to a reading specialist is not necessary, and these patients should be followed every 9 to 12 months. Of course, if the patient has diabetic macular Dema, that changes the follow a paradigm in the need for referral. In a patient with moderate non proliferated diabetic retinopathy, referrals should be considered. These patients are typically followed every 6 to 9 months as they have an increased risk for progression toe higher levels of non proliferated diabetic retinopathy and proliferated diabetic retinopathy. In a patient with severe non proliferated diabetic retinopathy, referral to a retina specialist should be made. These patients are typically followed by us every 3 to 4 months. The referral should be made to a retina specialist within 2 to 4 weeks. For a patient with proliferated diabetic retinopathy, referral is essential as thes patients must be followed closely and must receive treatment for high risk PDR. Again, referral is important as these patients can have severe visual loss without prompt treatment. So what constitutes mild non prolific diabetic retinopathy? While the presence of a least one micro aneurysm is required as shown here, this patient has not only micro aneurysms but also hard exit dates characterized by diabetic macular Dema. And here's a blow up of another patient with mild, and you can see a few micro aneurysms in the Cy but no significant macular oedema again. Such a patient should be seen every 9 to 12 months, and referral is not required in a patient with moderate, non proliferated diabetic retinopathy. You can see multiple blood hemorrhages, multiple micro aneurysms, and there may be the presence of Venus beating or Connell spots, essentially a moderate, non prolific diabetic retinopathy patient. His findings more than mild but less than severe, and these patients are typically re examined every 6 to 9 months, and referral is not required. If we look now at a patient with severe, non prolific diabetic retinopathy, classifications requires the presence of significant hemorrhages in four quadrants and these air in the e. T. DRS quadrant. So they're relatively posterior, and you can see here Ah, lot of hemorrhages out here and in the areas superior, nasal, inferior and temporally, and these extend out into the mid per free. Another classification for severe would be the presence of Venus beating into quadrants. And here's a slide showing Venus beating. You can see like bulbous changes here on the vein that causes beating of the wall of the vein. Another category is intra retinal micro vascular anomaly or Irma. The presence of Irma in one Quadrant would also classify the patient as having severe and PDR. And here on the floor scene, you can see the squiggly vessels characterizing an area of interesting all micro vascular anomaly. And clinically, of course, this would appear as squiggly vessels that air not elevated above the plane of the retina to distinguish it from neo vascular ization. So let's turn now to discuss some cases of different classifications of diabetic retinopathy and their treatment. Our first case is patient B. D. BD is a 74 year old woman with a history of diabetes for 25 years, on insulin for five years and history of several years of hypertension. Her visual acuity typically is 2025 in the right eye and 2030 in the left eye for follow up for several years. She's referred to me now with a history of ran, a busy mob being given in the right I once and 10 times in her left eye. She has a history on her records of severe non proliferated diabetic retinopathy in the right eye and moderate, non proliferated diabetic retinopathy in the left eye. She is 2030 in each eye. On examination, we see that she has severe, non prolific diabetic retinopathy in her right eye, and I made this diagnosis on the basis of hemorrhages in all four quadrants and Venus beating in one quadrant in her left eye. She has moderate, non proliferated diabetic retinopathy characterized by the presence of some hemorrhages as well as the Commonwealth spot is shown here on examination by O. C. T. We can see that the right I still has some macular oedema after she's been treated with Renna, Busy met once previously elsewhere, her left eye also has macular. Dema is shown here when the decision was to retreat her Now note that this is only one cut of the O. C. T. And when we make the decision to treat, we look at all of the cuts of the O. C. T. In both eyes and those cuts showed the presence of macular oedema. She comes back then in May 1 month after treatment in her vision is still 2030. We see that she still has severe NPD are in the bright i in the basis of the hemorrhages but she no longer has significant Idema involving this center area of the phobia. This far area here of oedema is far extra faux viel and does not qualify her for treatment for that oedema. And we follow the patients, right? I in contrast, her left eye with moderate, non prolific diabetic retinopathy was shown to have worsening of the macular Dema and therefore she was retreated with Rateb is a mob in this I One month later she returns and you can now see that the right eye has recurrent macular Dema so that I Xcaret treated the left eye has improving oedema but still is a de minus and requires re treatment by July. A month later, the right eye after receiving three Rateb is a mob injections has now moderately severe n p d r. I saw that there was a regression and the amount of the hemorrhage is seen in the retina. So she's now gone from severe and P. D. R. Two of moderately severe, so less severe in that right I her left eye has improvement in the Dema and has moderate NPD are but still requires treatment. So she returns in August and her vision is now 2025 in both eyes and we see that the right eye has far fewer hemorrhages than was present previously. So instead of severe in PDR, she is now classified is moderate, non proliferated diabetic retinopathy. This is after her three rent a busy mob injections in the right eye in the left eye. We see that there are some hemorrhages and cotton wool spots remaining and she remains moderate. NPD are and this is after 13 ran a busy mob injections in that I in the right eye in August of 2015 vision is 2025 there is no macular Dema present. So she's observed in her left eye. Theodore Emma is markedly improved after 13 ran a busy mab injections. She is, however, retreated with Brenna busy map as there is still residual oedema in that i. By October of 2015, her vision remains 2025 in each eye and the demon and the right eye remains under control and she stays at the level of moderate N p d. R. In the left eye. She has residual oedema and again requires re treatment with Ran a busy mob. Between November and December of 2015, Theodore Emma, in the right eye, remains under control. As shown here, you can see a beautiful faux viel contour and you can see on the some box of production some areas of hemorrhage remaining in that I, but not at the level of severe where she was at before she is still now moderate N P D r. As to the left eye, she's had 15 injections by November. Still has a demon is retreated, returns in December. The Dema looks worse, and so she is again retreated in that left eye between February and March again, she requires re treatment and the left eye for a Dema, but remained stable in her right eye. Let's look and see what she looked like in April of 2016, so this is a year later she's had four ran a busy Mab injections, requiring treatment here, as well as in the left eye, where she's had 19 and in appearance. You see that the hemorrhages are markedly decreased in this right eye compared to baseline, because she still has some hemorrhages is shown here. She is moderate. NPD are. She does have a few micro aneurysms as shown in the Phobia center, but she does not have a significant oedema in her left eye. She has now mild to moderate and PDR. You see that this left eye, which has received multiple injections as compared to the right eye, has had further regression of the level of retinopathy almost to the level of mild. But because there's still a hemorrhage, we call it moderates. This is very mild, moderate NPD are. Here's a nice example, just comparing April 2015 to April 2016 showing you further regression here of the levels of hemorrhage. And similarly, in the left eye, you can see the hemorrhage is much less, and also the cotton wool spots are fading away. Here's a blow up now off the right eye in 2021 when she has received a few more Prn injections of random is a mob, and we see that the hemorrhages, compared to 2015 are markedly decreased. There's only one little one left here versus all of these other hemorrhages that we're seeing previously, and in the left eye we see again marked regression compared to 2015 now to 2021 where she has almost no stigmata of the moderate NPR except for a mild hemorrhage here and that macular region. So I'd like to now discuss the fact that when you use an anti bed Jeff, you can indeed get regression of the level of diabetic retinopathy. And these findings have been seen repeatedly for different drugs as well as in different multi centered clinical trials. This was one of the first publications on the step improvement in diabetic retinopathy levels. This was performed by Dr Michael Ip in his group. Looking at the Ride and Rise Renna Biz Amev Data at month 24 and basically what they found was that compared to baseline, you could get a regression in the level of diabetic retinopathy, they found 20% had a regression of one step, 22% had a regression of two steps and 14% had a regression of three or more steps in diabetic retinopathy. And these air considered significant. Once you get to the level of 2 to 3 step improvement and diabetic retinopathy severity on the Converse side, looking at diabetic retinopathy worsening. Very few patients had worsening of even 12 or three steps, basically about 1% for each group. If we look at the vista and vivid study data a week 100 we see that for eyes that were given a flavor stepped, there was a marked improvement in the two and three step improvement in D. R. S s levels compared to the Comparator, which was laser. And if we look here a week 52 in Vivid and Vista, we see that this improvement of two steps occurred in about 30 to 33% of of patients, compared to 8 to 14% of patients were given laser bye Week 100. This improvement was maintained and again improved to about 33 to 37% off. Patients were given 2 mg Q eight of Flipper cept, or 30 to 37% of those given 2 mg Q four of a flea recep, compared to anywhere from 8 to 16% of patients given laser. If we look at the three step improvements we see again an improvement in the patients who were given a flavor cept compared to patients given laser and these differences were statistically significant. And these three step improvements occurred in about 14% on average, to about 20% on average, between the vista and the vivid eyes, compared to anywhere from 0 to 5% for patients who were given laser. So again, the anti vet Geoff caused an improvement in the diabetic retinopathy levels. If we look at the d. R C R studies, we see a similar trend for improvement in two steps and three steps in the D. R. S s levels. And you can see here for the eyes with improvement that these continued at three years, four years and five years, with about a third of eyes to 35% of eyes improving significantly. The slide here on the right shows a comparison off what happens over time in terms of improvement within an NPD, our group, and for levels 35 43 we see a 10% improvement for more severe levels, 47 to 53. We see a 40% improvement at one year. So basically the more severe the level of diabetic retinopathy. When it's treated with an anti veg F, there is a mawr large response in the percent that improve in D. R S s levels, most recently the boulevard study, which is a Phase two study using a novel drug which is a by specific antibody for us. Mm, it blocks not only veg f, but also anti pointing to also showed that there is an improvement in the D. R S s levels. If we look at the boulevard face to study results at week 24 we see that there's also an improvement in the two steps of DRS s severity. The boulevard study looked at Faris a mob which is a by specific novel antibody, which blocks not only veg f, but also Angie pointing to we see that for the lower dose of for us, um, ab 1.5 mg, 28% had a two step or more improvement in D. R. S s severity at 24 weeks for the higher dose, the 6 mg of a fleet receptor 39% improved to are more steps in the D. R. S s severity scale. So basically, no matter what anti veg a for looking at and even this by specific novel new drug, we do see an improvement in D. R. S s levels when we treat eyes with diabetic macular oedema. The Panorama study was a Phase three study that looked specifically at the ability of an anti veg F to cause regression of non proliferated diabetic retinopathy. Severity. The anti VHF looked at was the flavor Sepp, and this was dosed either 2 mg Q. 16 weeks after loading or 2 mg q eight and then transitioning to Pierre N in year two. And these were compared to sham treatments. And you can see here a clear difference in the proportion of patients who had a two step or more improvement from baseline in the D. R S s severity level. In fact, for the Flipper subgroups, this was about two thirds of the eyes that improved compared to basically 15% at one year at week 100. The improvement remained at about two thirds for the fixed dose ing to milligram Q 16 group, compared to 13% for the sham group. For the PRN Group, that's dropped a little bit going from to Q eight, where it reached even 80% at 52 weeks to about 50% in week 100. The bottom line is is that a flipper stopped, however, did achieve its end point and causing regression of the NPD are severity levels compared to sham. And so this leads us to consider the use of an anti veg A for treatment of the non productive diabetic retinopathy, uh, itself even in eyes without macular oedema. Now, interestingly, when we look at the panorama data, we see that not on Lee did we achieve regression of the NPD are severity. But we also had a protective effect of the anti V Jeff that is, there were less vision threatening complications which are defined by the presence of center involving diabetic macular oedema or the development of neo vascular ization, anti early or proliferated diabetic retinopathy. And we see here on this slide that the levels were decreased. That is, for the presence of a vision threatening complication of prolific diabetic retinopathy, or anterior segment neo vascular ization, or center, involving diabetic macular oedema from 58% down to 18% for the flavor cept fixed dozing or 20.5% for the flavor stepped prn Flex group. And this was significant at week 100 and so we can now not only drive back the level of the diabetic retinopathy severity, but we can also say that by using the anti bed Jeff, we can protect the patient from developing thes vision, threatening complications or developing center involved diabetic macular demon. So essentially we can halt the progression of diabetic retinopathy in a significant proportion of patients. Let's turn now to our second patient MP MPs, a 53 year old woman with a history of diabetes for 15 years and has a hemoglobin a one c V 8.6. She's a mild, my open, his best corrected acuity of 2020. She has moderate, non productive diabetic retinopathy with non center involved diabetic macular Dema, and was seen in June of 2016. She was asked to return within 6 to 9 months. She returned in April of 2017 with 2030 vision hemoglobin, a one, Steve 8.3 and on exam. This is what I saw. You can see that she has clearly developed neo vascular ization of the optic disc. Yet she has no macular Dema and she thought her vision was okay. So her left eye had 2025 vision at this time and unfortunately also had neo vascular ization of the disc. Her phobia was essentially flat in the center, although she has this area of non clinically significant as well as non center, involving diabetic macular Dema. So what do we do for this patient? Well, we have some options. We can either treater with laser and put in peer P to both eyes for this envy d or we can consider based on protocol. Esa's Wells The Clarity study the use of an anti veg F to treat the PDR itself. Remember, vision is good. She's 2030 in the right and 2025 on the left. So she was given these options and decided to go with the anti V Jeff. Now, when I decided to use the anti V Jeff on this patient with bilateral PDR, I made it very clear to her that follow up was going to be really important and that she must be compliant or she could go blind. So we went ahead and emphasizes I said the importance of follow up and also emphasized importance of glucose control and asked her to again try to get her hemoglobin a one C down to seven and to control her blood pressure as well as her cholesterol. So what happened to her? Well, one month after the anti veg, if she returns, her vision is 2030 in the right eye, 2025 on the left eye. And you can see here that the N V. D. Has essentially melted away in the right eye as well as in the left eye. Her level of retinopathy now in this Sy is moderate and PDR again. Few hemorrhage is here, and she has no center involved. DME. Similarly, in the left eye, no envy de feu hemorrhages that qualify her again is having moderate NPD are, without center involved diabetic macular Dema. Now, over the next 2 to 6 months, she has followed closely and is given Brandon busy mob when the PDR Rikers such that by December she has had four anti va Jeff injections in the right eye and three in the left eye, and her vision remains the same. 2013, the right eye, 2025 the left eye at month seven. When she presents she's now had a total of five injections in the right eye over six months and for injections in the left eye. Between months 13 and 17. She has now approved to 2020 and she's had a total of five injections in the left eye and six in the right eye. Importantly, however, her hemoglobin a one C, has now approved to 6.7. When previously it was 86 months ago and recall it baseline, it was over eight. So she's getting her systemic disease under better control. She's coming in and being very compliant, and her anti bed Jeff is caused a very, very nice regression of the neo vascular ization in each eye. But note here that we're not complacent. We're still seeing her frequently and following her very closely. And indeed, what has happened to her? PDR? Well, the right eye is now gone, from PDR to moderate. NPD are, and the left eye has gone from PD are too severe. N p d r. By the end of two years and she's 2020. So she's pretty happy we are still following her, and at three years look what we see. She has now had some recurrence of her new vascular ization in the right eye, although it remains at bay in the left eye. And with all this treatment she has never developed center involved macular oedema. She is getting the anti V Jeff, and she's receiving the protective effect in terms of the DME, and you could even see that the areas of non center involved DME in each. I have gone away, so it's really important to know that follow up is really, really key in these patients, long term as a neo vascular ization can recur. In fact, by September 2020 she had a total of eight injections in the right eye and six in the left eye. And you can see here that by November of 2020 she looks pretty good. There's basically nice regression of the neo vascular ization with some fibrosis present. So how does anti veg F stack up to Prp when treating patients with P. D. R. Well, for me, if I have a patient with PDR without significant involvement of traction rental detachment or other complications, but has PDR defined by N, B D or N B E alone as well as macular oedema for me that is a patient who is going to be treated with an anti veg F Now if the patient has PDR without DME, then I consider Do I use the rented is a mob or do I do prompt pure P? And so the DRC are actually has a protocol called protocol s It looked at patients who had PDR with her without macular oedema and randomize them to random is, um ever prompt prp and in fact, it two years when the reading center looked at the funders photographs and graded them, they found that there was no difference between the random is a map treated eyes and the prompt peer p treated eyes that is about a third of eyes had no PDR in the rented is a map group compared to 30% and the Prp group no significant difference in terms of the regress neo vascular ization it was about 23% in rented is a map 20 foreign prp again no significant difference in terms of eyes It had some neo vascular ization present it two years 42% in the rented is a map treated eyes and 46% in the peer p treated eyes. So again, no difference. And I think what this shows is is that you can get good control with the anti V Jeff compared to PRP. But you do need close follow up and in fact, a lot of people think you do appear p and you're done. It's actually not the case. Patients will need some re treatment with Pierre P in a significant proportion of eyes going forward at two years. There was another study, known as the Clarity Study, that looked specifically at patients who have proliferated diabetic retinopathy without macular oedema. And this is basically what our patient had. And this study looked at the drug of flavor cept and compared it to Pierre P. And basically they found that the A flavor step showed superior visual acuity results. That is, there were more eyes that had a ton, letter improvement and the flavor subgroup compared to the Pier P group. And there were fewer eyes that lost 10 or more letters in the flipper subgroup compared to the laser group. And they also showed a higher total regression off the productive diabetic retinopathy in the Flipper Step Group. Compared to the laser group for 30% difference. So this basically again supports the use of anti veg F for prolific diabetic retinopathy. Even without diabetic macular oedema, what about adverse events? So if we look at the DRC, our protocol that compared Renna biz a map to peer P, we see that there was no significant difference in the rates of complications of retinal tear, elevation of intraocular pressure or the need for cataract surgery. There was a slightly MAWR in percent of eyes that had inflammation in the pure P Group. Compared to the rent a busy map group, the numbers were small 4% versus 1%. And in terms of end up clematis, obviously you don't get end off limits from doing P R P and the brand of Islamic group. It was 0.5%. What about systemic adverse events? While looking at death of any cause, the need for hospitalization, serious adverse events or hypertension? There was no significant difference between the Rent abysmal treated group and the Prp treated group. Now let's look at the peripheral visual field difference. So in protocol asset two years, there was a difference in that the patients treated with ran a busy mob had markedly less loss of visual field compared to the eyes that retreated with Pierre P. And if we look at the DB changes, we see that the difference was 372 d B in favor of the red of is a mob versus prp Now. What happened, though, at the end of five years was that this peripheral visual field defect was no longer significantly better for rent a visit them than for peer P. That is the brand of Bizima buys also lost peripheral visual field. And so the question then is you know, is this just the natural history of prolific diabetic retinopathy which occurs even in the absence of laser? Let's look now specifically at the protocol s improvements and diabetic retinopathy severity levels. And we see it two years that 47% of eyes treated with random busy mob improved two or more steps and the d r severity on the fund s photos and this was essentially maintained 46% at five years, with treatment as needed in protocol s. Now there is no corresponding number for regression of the level of PDR in the laser group because you can't regress once you've had laser put in for PDR. It's just the way the classifications system is made. Let's look specifically now at the proportion of eyes who developed center involving diabetic macular oedema in protocol s between the peer p and the rent a busy mom groups. And here we see the same protective effect that is. There were far fewer eyes shown here in orange that developed clinically significant diabetic macular oedema. At the end of two years. That is, 9% compared toa eyes treated with pure P where the rate was 28% and this was significantly different. So let's turn now to our final patient. C G. C. G is a 47 year old man with Type two diabetes and hypertension. He has excellent control of his A one C at 6.6%. He has a history of moderate, non prolific diabetic retinopathy in the right eye and mild, non proliferated diabetic retinopathy in the left eye. And he presents to me, complaining of blurry vision in his right eye. He's 2040 in the right eye and 2025 in the left eye. Ah, flirting angiogram shows some leakage here, close to the nerve of the nerve as well as in the macular region. And in O. C. T shows the presence of faux viel center involving diabetic macular oedema as well as Jason DME. So we make a diagnosis of PDR with DME in the right eye. His left eye has moderate NPD are without DME So how do we treat him? Well, as I said earlier, if I see PDR with DME, I will pretty much choose an anti veg f treatment. So this is what we did. We gave him an anti veg off in the right eye and within a month you can see that there is some decrease in the level of macular Dema shown here adjacent and even in the faux viel center. But he still has persistent DME, so he is again retreated. After three treatments, you can see the oedema is less and these air two different cuts, but it's still present, so he needs additional treatment. I also like to do o c t a s on my patients. As you can see here, you can see areas of some non profusion and you can see the phobia lay vascular zone quite nicely. Of course, when you look at those c ts, you have to use the actual analysis program so that you can dive through the layers and see the different layers. We don't just look at one cut. So the left die now as a writer is being treated also has to be watching. This is really important. Remember he had moderate NPD are. We didn't treat him with an anti veg if he didn't want any treatment to try to stop any progression in the left eye because he felt he had no symptoms. So he comes back and now he has proliferated diabetic retinopathy in his left eye. And here's my clinical photo showing some tiny neo vascular ization of the disc as well Samen ve and some mild vitreous hemorrhages. Well, he also has some Venus beating present, but fortunately his retina still attached. But now he's also developed diabetic macular Dema. So now he warrants treatment with an anti veg F. So here is the O. C. T. A. Showing an increase favela vascular zone In some areas of capillary, drop out the corresponding oh CTS show Diabetic macular oedema So what is this risk of? NPD are progression? Well, I said he was moderate. NPD are so moderate. NPD are could be anywhere from level 43 to 47 we see that the risk of progression Thio any form of prolific tive diabetic retinopathy one year is anywhere from 12 to 26%. At five years it's 44 to 66%. And so we have to consider these risks in the patient and consider would we want to therefore treat a patient who has moderately severe and PDR level 47 for higher levels? Let's say they have severe MP dear. It's 44 to 50% will progress onto prolific diabetic retinopathy within one year, and it says HIAS, 75 to 81% in five years. So that is very important to realize. And that's why we see these patients more frequently based on the severity off the n p. D. R. If it's very severe, NPD are The rates are up to 75% for any PDR and 90% for any PDR at five years. So keep these numbers in mind and I put this here because my patient progressed. And this is why. Because the patient had moderate and P. D. R. And was in that unlucky group where he actually progressed to P. D. R. But fortunately because he was being followed closely, we picked it up and we're able to treat him. So let's see how he did so. His left eye after one treatment improved beautifully. His macular oedema went away and his envy d also regressed. His vision is now 2040. Let's go back to the right I, His right eye after four treatments within six months, has now improved to mild, non prolific diabetic retinopathy, although there's still some oedema. His left eye at this point, which has had one treatment, has improved to severe non proliferated diabetic retinopathy without significant phobia. Ledezma. So you can see here on the bottom that is right. I still has a Dema. His left eye does not have center involved the Dema, So I went ahead and treated the right eye, but not the left eye. 10 months after his first treatment in the left eye, the PDR remains regressed. Although he's still severe. NPD are as characterized by the presence of the hemorrhages but because he doesn't have center involved a demon. This I He didn't want further treatment and he was happy that his p. D. R was under control. His right eye has had a Dema and requires re treatment. So how do we put all this together? Protocol s show support. As I previously said, for patients who have proliferated diabetic retinopathy with macular oedema. It's important. However, when we choose this treatment to make sure that we have a patient who is likely to be compliant, that would be a patient who does not have a lot of co morbidity ease who has transportation and will most likely be able to return to the clinic on a monthly basis. We know from studies that if patients air noncompliant, the risk of progression and severe visual loss is quite high in patients with P d. R. And we don't wanna lose a patient to progression of proliferated diabetic retinopathy if they don't have follow up looking at protocol s if we separate out the patients who had diabetic Macular demon baseline shown in, uh the dark line here compared toa eyes that were treated with prp shown in the open circle lines. We see that the Rateb is, um, have treated eyes had a better improvement. Envision that is, they had anywhere from about 10 to 12 letter improvement at one year and almost nine letter improvement by two years. And this was in contrast to the pier P treated eyes where there wasn't an improvement. So why did they improve? Well, the answer is pretty obvious. It's because the random is a map Treated the diabetic macular Dema Aziz Well, Azad PDR and therefore the retina thinned out. So what happened to our patient? Well, 33 months later, in the right eye, after treatment and with continued treatment, we see that there is just a faint blush here of the area that he used to have N b d and the macula Now is quite nice. There's no leakage in the macula and the left eye. We see no NBD and no macular oedema. The right I basically to me looks like it's very, very moderate and mild moderate. NPD are with that little hemorrhage, and the left eye continues to have severe N p d r. 40 months later, the right eye has had continued treatment with Renna biz mob is needed for the diabetic macular Dema We see that the level of non proliferated diabetic retinopathy in the right eye is now to the level of mild. In contrast, the left eye is moving towards more severe and PDR with some areas of interesting all micro vascular anomalies developing and you can still see some hemorrhage here. This is because this I has not required significant treatment because there's no center involved. Diabetic macular demon, the left eye and the patient wishes on Lee to be treated when he has PDR. So how do we manage our patients with Severe and P D. R and D me? While I would recommend if a patient has severe and PDR with DME, Definitely consider and treat with anti veg F therapy. The anti veg, a full treat the DME and will also give you the improvement in the level of D r severity. And we know that this improvement in D R severity comes with it, with a lower rate for progression to proliferate diabetic retinopathy, of course, as well as a lower rate of progression to continued visual loss from macular oedema. Now, when I has only severe and PDR without a Dema. We know that the anti veg F can cause regression of the D r severity level and prevent therefore progression to DME prolific diabetic retinopathy, an anterior segment neo vascular ization. So consider an anti veg F in those patients. For a patient who has proliferated, diabetic retinopathy without or with DME compliance is really the key and trying to decide what treatment to use in these patients. However, if a patient has DME, I would say definitely use anti veg f in that patient and based on protocol s If you're worried about the PDR level and want to add laser that you could do that, there is no study right now that shows the benefit of doing that compared to an anti veggies alone. Um and that probably remains to be seen whether combination treatment is better than the anti veg F alone or laser alone. But again, compliance is the key in terms of how we based all of our treatments. I like to use the DRC, our studies as well as the multi centered clinical trials, as a basis for why I choose my treatment and to guide my therapy So I thank you for joining me today and look forward to seeing you at future Weber Nurse. Stay well and thanks for your attention. As thes cases have shown you, it's very important that these diabetic patients have a diabetic retinopathy evaluation. So I urge you to remember that at the very least, every diabetic should have an annual diabetic retinopathy examination. If you see patients with severe and PDR or PDR, please refer them promptly so that we can treat them and prevent visual loss for patients who have moderate and PDR or higher, thes patients can also be helped, and it's very important to go ahead and send them to a retina specialist so that they can get their treatment. Remember that these anti veg F drugs are currently available and can improve vision and can also reverse the level of diabetic retinopathy were fortunately, living in an era where we can actually improve visual. I don't like that last sentence. Let's see as thes three cases have shown us it's very important that patients with diabetes are evaluated and the diabetic retinopathy is diagnosed. An annual diabetic exam is mandatory for patients who have more severe levels of diabetic retinopathy such as moderate NPD are severe and PDR more frequent examinations are indicated. If the higher levels of diabetic retinopathy air seen proper Ferral is mandatory, that is, patients who have severe and p d r p d r should be seen within a week by I don't like that either. As thes three cases have shown us we can treat patients with diabetic retinopathy. Prompt examination is important for patients with severe and P. D. R and P. D R, as well as diabetic macular Dema. In order to prevent further visual loss. Annual diabetic examinations are mandatory for all of our patients, at the very least, for patients with more severe levels of non proliferated diabetic retinopathy, More frequent examinations air indicated we now are living in an era where we have anti veg F drugs that cannot Onley, treat the diabetic macular oedema and result in improvement in vision but can also reverse the level of diabetic retinopathy. Thus, it's really important that we see these patients so that we can treat them in a prompt manner and prevent further visual loss
